efficient reduction of electron-deficient alkenes enabled

doi.org/10.26434/chemrxiv.12380330.v2

Efficient Reduction of Electron-Deficient Alkenes Enabled by aPhotoinduced Hydrogen Atom TransferXacobe Cambeiro, Natalia A. Larionova, Jun Miyatake Ondozabal

Submitted date: 01/06/2020 • Posted date: 02/06/2020Licence: CC BY-NC-ND 4.0Citation information: Cambeiro, Xacobe; Larionova, Natalia A.; Miyatake Ondozabal, Jun (2020): EfficientReduction of Electron-Deficient Alkenes Enabled by a Photoinduced Hydrogen Atom Transfer. ChemRxiv.Preprint. https://doi.org/10.26434/chemrxiv.12380330.v2

Direct hydrogen atom transfer from a photoredox-generated Hantzsch ester radical cation to electron-deficientalkenes has enabled thedevelopment of an efficient formal hydrogenation under mild, operationally simple conditions. The HAT-drivenmechanism, key to circumventthe problems associated with the low electron affinity of alkenes, is supported by experimental andcomputational studies. The reaction is appliedto a variety of cinnamate derivatives and related structures, irrespective of the presence of electron-donatingor electron-withdrawingsubstituents in the aromatic ring and with good functional group compatibility.

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Efficient reduction of electron-deficient alkenes enabled by a photoinduced hydrogen atom transfer

Natalia A. Larionova, Jun Miyatake Ondozabal and Xacobe C. Cambeiro*

Department of Chemistry, School of Biological and Chemical Sciences, Queen Mary University of London. Mile End Rd, London E1 4NS (UK). * [email protected]

Direct hydrogen atom transfer from a photoredox-generated Hantzsch ester radical cation to electron-deficient alkenes has enabled the

development of an efficient formal hydrogenation under mild, operationally simple conditions. The HAT-driven mechanism, key to circumvent

the problems associated with the low electron affinity of alkenes, is supported by experimental and computational studies. The reaction is applied

to a variety of cinnamate derivatives and related structures, irrespective of the presence of electron-donating or electron-withdrawing

substituents in the aromatic ring and with good functional group compatibility.

Introduction

The hydrogenation of C-C multiple bonds and related reductive

transformations are among the most important processes in

chemical industry.1 In particular, transfer hydrogenation,

which avoids the use of hydrogen gas, is of much practical

interest in both industrial and laboratory settings, and the

development of new methods and strategies is of continued

importance.2

The recent fast development of photocatalysis has resulted in

the discovery of a wide variety of reductive, oxidative and

redox-neutral transformations.3 Photocatalytic reduction

methods have been explored in a number of instances, and

actually some of the pioneering research in photocatalysis

dealt with the formal hydrogenation of alkenes using a

dihydropyridine (N-benzyl 1,4-dihydronicotinamide, BNAH) as

the reductant.4 However, this early work was handicapped by

a very narrow substrate scope ―the reaction only worked on

extremely electron-deficient alkenes bearing at least two

electron-withdrawing groups (Scheme 1A).5 This is attributed

to the low electron affinity of alkenes, which results in direct

electron transfer reductions being difficult. For other

functional groups, similar limitations have been overcome by

activating the substrate with Lewis or Brønsted acid additives

or co-catalysts, which make it more electron-deficient.6

However, to the best of our knowledge, such strategies have

not been successfully applied to the formal hydrogenation of

alkenes.7 On a different approach, reduction could be forced

by using catalytic systems with increased reductive power, for

example by the exploitation of two-photon excited states8 or

combining electro- and photocatalysis.9 Nevertheless, the

possible reduction of other functional groups under these very

strongly reducing conditions limits the scope of such

strategies. One recent report has described the application of

a two-photon strategy for the formal hydrogenation of 1,2-

diarylethylenes by sequential electron and proton transfer

reactions (Scheme 1A).10

Finally, an alternative strategy to achieve the reduction of

alkenes circumventing the issue of their low electron affinity

would be to exploit hydrogen atom transfer (HAT) reactions.11

Thus, a catalytic system capable of promoting the transference

of a H atom to an alkene would provide an easy route for their

reduction without requiring highly reducing potentials

(Scheme 1B). HAT is frequently invoked in light-promoted

hydrofunctionalisation,12 always in a termination step where

an organic radical abstracts a H atom from radical cations of

dihydropyridines, such as Hantzsch ester (HE), or other

donors.13,14 However, methodologies using HAT into a stable,

closed-shell compound have not been reported to date. Herein

we report an efficient and operationally simple reduction of

cinnamate derivatives under mild conditions, initiated by HAT

from a photoredox-generated Hantzsch ester radical cation.

Scheme 1. Strategies for the photoreduction of alkenes promoted by visible light

Results and discussion

We started our investigation by studying the reduction of

methyl cinnamate (1a) as a model substrate with combinations

of known photocatalysts and potential hydrogen atom

donors13 (summary in Table 1, entries 1-5). Gratifyingly, we

found that [Ir(ppy)2(dtbbpy)]PF6 (Ir1) was indeed capable of

promoting the reaction with either iPr2NEt, 1,4-

dihydronicotinamide (BNAH) or Hantzsch ester (HE) as the

reductant and H atom donor, with HE providing quantitative

yield (entry 1). Other similar photocatalysts such as Ru(bpy)3Cl2

and Ir(ppy)3 did not provide virtually any conversion to 2a.15

Application of these conditions to the more electron-rich

substrate 1b resulted initially in a significant erosion of the

yield (entry 6). Nonetheless, re-optimisation of the reductant

to substrate ratio (entry 7) and concentration (entry 8) brought

the yield back to satisfactory levels (91%, entry 8). As expected,

control experiments in the absence of the Ir photocatalyst

(entry 9) or in the dark (entry 10) showed that both are

essential for the reaction to proceed. It is worth noting that the

reduced form of Ir1 is not predicted to be a strong enough

reductant to perform a SET to 1a (E½(Ir1) = ‒1.51 V (MeCN),3d

E½(1a) = -1.87 V, see below for further discussion).

Table 1. Summary of reaction optimisation.a

Entry Substrate Conditions Yield (%)b

1 1a 50 mM, Ir1 2.5 mol%, HE (1 equiv) 100

2 Ru(bpy)3Cl2 as the catalyst 1

3 Ir(ppy)3 as the catalyst 2

4 EtNiPr2 as the reductant 36

5 BNAH as the reductant 42

6 1b As entry 1 64

7 HE (2 equiv) 70

8 12.5 mM, HE (2 equiv) 91

9 1b No photocatalystc 1

10 Darkd 0

Ir1: [Ir(ppy)2(dtbbpy)]PF6. a Reactions run with substrate 1 (0.1 mmol), reductant

(see table) and catalyst (2.5 mol%) at RT in MeOH, following general procedure B

(see ESI). b Yield determined by 1H NMR using an internal standard. c Reaction

performed at 50 mM concentration of 1b. d Reaction performed at 25 mM

concentration of 1b.

Then, we set out to explore the substrate scope and limitations of

our method (Table 2). The photoreduction worked to high yields

with a wide variety of cinnamate derivatives bearing different

substituents on the aryl ring (2a-u). Electron-donating MeO group

was tolerated at all three possible positions (2b-d), as well as

electron-withdrawing CF3 (2e-g). Likewise, no steric influence on

reaction yield was apparent from substitution at the ortho- position

(2k-m). The reaction was compatible with halogen substituents (2h-

j, 2l-2n), although a lower yield for I (2n) may suggest a competing

reduction of the C‒I bond. In the case of Br, para-substituted

compound (2h) was only obtained in moderate yield, in contrast

with the good results for the ortho- and meta- analogues (60% and

97%, respectively, for 2j and 2i).

Table 2. Substrate scope and limitations.a

a Unless stated otherwise, reactions were run with substrate 1 (0.2 mmol,

0.025 M), HE (2 equiv) and catalyst Ir1 (2.5 mol%) following general procedure B

(see ESI). Yields are of isolated product unless otherwise noted. b NMR yield in

this case was significantly higher (89%). c Yield determined by 1H NMR using an

internal standard. d The ethyl ester was used in this case instead of methyl. e

Starting from the corresponding ethyleneglycol acetal. f MeCN was used as the

solvent.

The reaction tolerated unprotected alcohols (2p), carboxylic acids

(2r) and amines, even when containing free NH bonds (2t and 2u),

although phenol and aniline provided decreased yields (2o and 2s).

Aldehyde-substituted product 2q could be obtained by performing

the reaction with the corresponding ethyleneglycol acetal, which

was deprotected in situ during work-up.

Replacing the aryl group in the cinnamate ester structure for

heterocycles such as pyridyl or furyl resulted in low yields of product

(2v-w) and the reaction did not proceed at all in the absence of an

aromatic group (2x).

Scheme 2. Mechanistic elucidation of the HAT-based photoreduction. a Experiments performed at 0.01 mM concentration of Ir1 in a quartz cuvette. b Conditions as in Table 2. c Reduction

potentials are in MeCN vs. saturated calomel electrode (SCE). 1a, [1aHα]• and [1aHβ]• are calculated by DFT (M06-2X/631+G(d,p), see ESI for details). d Relative energies respect of

independent starting materials (M06-2X/6-31+G(d,p), see ESI for details).

Moving away from the methyl cinnamate structure,

cinnamonitrile (2y) and coumarin (2aa) were both efficiently

reduced under our reaction conditions Finally, our method

worked well for the reduction of a tetrasubstituted alkene

(2ab), highlighting its robustness with respect to steric

hindrance.

To probe the mechanism of the reaction we decided to

perform a series of additional experiments, summarised in

Scheme 2. Firstly, Stern-Volmer quenching experiments

(Scheme 2A) showed fluorescence quenching by HE to

significantly outcompete quenching by substrate 1a (quencher

rate coefficient kq(HEH)/kq(1a) ≈ 13).16 This confirmed our

expectation that the reaction likely starts with a reductive

quenching of the excited catalyst [Ir1]* by HE to give the

reduced form of the catalyst [Ir1]‒ together with formation of

the Hantzsch ester radical cation [HE]•+.17

Then, we explored the use of deuterium labelling (Scheme 2B)

to assess the possibility of the reduction proceeding through a

sequence of electron and proton transfer events, as previously

proposed for related alkene photoreductions.4,5,10 The

photoreduction of 1a using MeOD instead of MeOH led to

formation of product 2a with 9% incorporation of deuterium

at the β-position and 44% at α (out of an expected maximum

of 50%). Conversely, the same reaction in MeOH with 4,4-d2-

HE resulted in 2a with 25% deuteration exclusively at α. These

results are in clear contrast with those previously reported for

reductions based on consecutive electron and proton

transfer.18 The extent of deuterium incorporation in these

experiments combined with the marked regioselectivity

strongly supports a mechanism where the α-H would be

incorporated by a HAT from a HE derivative, while the β-H

would come from the solvent. The incomplete deuteration

may be attributed to adventitious H2O, and some extent of H/D

exchange between the reagents and solvent during the

reaction.

With these data in hand, we contemplated two distinct

possible mechanisms –either: (a) The reaction is initiated by

SET to give, after protonation, an intermediate radical species,

which is in turn transformed into the final product 2 by HAT

from [HE]•+; or (b) the reaction is initiated by HAT from [HE]•+

to 1a, giving an intermediate radical species, which is then

transformed into 2a by consecutive SET and H+ transfer.

Interestingly, as mentioned above, while the role of [HE]•+ as a

H atom donor is frequently proposed in the literature, its

involvement is always mentioned in termination steps,

reacting with another radical intermediate (i.e. type a

mechanisms).12 Mechanisms of the type b where [HE]•+

transfers a H atom to a ground state, closed shell species are

absent from the literature. However, comparison of the

reduction potentials suggests that the reduced catalyst [Ir1]‒ is

not a strong enough reductant to engage in a direct SET with

cinnamate derivatives, which would be a requirement of type

a mechanisms (reduction potentials in MeCN referenced to

SCE: E½(Ir1) = ‒1.54 V,3d E½(1a) = ‒1.87 V,19 Scheme 2C). To assess

the feasibility of type b mechanism, we resourced to DFT

modelling of the reaction (M06-2X/6-31+G(d,p), see ESI for

details).20 Pleasingly, we could find transition states for the

HAT step from [HE]•+ to either position α or β of 1a, both of

which are predicted to be readily accessible energetically (ΔG‡

= 14.9 and 19.0 kcal/mol for α and β, respectively, Scheme 2D).

Moreover, computed reduction potentials of the resulting

radicals to their corresponding carbanions were consistent

with their easy reduction by [Ir1]‒ (E½(1aHα) = ‒1.43 V, Scheme

2C).21,22

All this evidence, thus, provides support for a mechanism as

depicted in Scheme 2E, where excitation of Ir1 by visible light

enables it to oxidise HE to its radical cation [HE]•+.

Subsequently, [HE]•+ transfers a H atom to the alkene 1a giving

place to a benzylic radical [1aHα]•, which is finally further

reduced by SET from [Ir1]‒ and protonated to give the reduced

product 2a.

Conclusions

In conclusion, we have developed a simple method for the

photoreduction of olefins which enables the use of moderately

electron-deficient, synthetically meaningful substrates with

good functional group compatibility. Our mechanistic

investigations support a hydrogen atom transfer to the

substrate as the key step which enables the reduction to

proceed without requiring the generation of a very highly

reducing medium. We believe this unprecedented mode of

substrate activation offers new opportunities for photoredox

transformations by enabling the generation of radical

intermediates that otherwise are not easily accessible.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We gratefully acknowledge Queen Mary University of London

for partially funding this research. NAL thanks the European

Commission for an MSCA fellowship (Project LIONCAT). JMO

thanks QMUL for a PhD scholarship. This research utilised

Queen Mary's Apocrita HPC facility, supported by QMUL

Research-IT. http://doi.org/10.5281/zenodo.438045.

Notes and references

1 J. A. Kent, T. V. Bommaraju and S. D. Barnicki, Eds., Handbook of Industrial Chemistry and Biotechnology, Springer International Publishing, 2017.

2 (a) D. Wang and D. Astruc, Chem. Rev., 2015, 115, 6621–6686; (b) L. Lloyd, in Fundamental and Applied Catalysis, eds. M. Twigg and M. Spencer, Springer US, 2011, pp. 73–117.

3 (a) R. C. McAtee, E. J. McClain and C. R. J. Stephenson, Trends Chem., 2019, 1, 111–125; (b) L. Marzo, S. K. Pagire, O. Reiser and B. König, Angew. Chem. Int. Ed., 2018, 57, 10034–10072; (c) C. R. J. Stephenson, T. P. Yoon and D. W. C. MacMillan, Eds., Visible Light Photocatalysis in Organic Chemistry, Wiley-VCH, Weinheim, 2018; (d) C. K. Prier, D. A. Rankic and D. W. C. MacMillan, Chem. Rev., 2013, 113, 5322–5363.

4 (a) C. Pac, Y. Miyauchi, O. Ishitani, M. Ihama, M. Yasuda and H. Sakurai, J. Org. Chem., 1984, 49, 26–34; C. Pac, M. Ihama, M. Yasuda, Y. Miyauchi and H. Sakurai, J. Am. Chem. Soc., 1981, 103, 6495–6497.

5 Similarly, a few cases of formal hydrogenation of alkylidene malonates have been reported: (a) R. C. Betori and K. A. Scheidt, ACS Catal., 2019, 9, 10350–10357. (b) R. C. Betori, B. R. McDonald and K. A. Scheidt, Chem. Sci., 2019, 10, 3353–3359; (c) B. R. McDonald and K. A. Scheidt, Org. Lett., 2018, 20, 6877–6881.

6 Selected papers: (a) E. Speckmeier, P. J. W. Fuchs and K. Zeitler, Chem. Sci., 2018, 9, 7096–7103; (b) T. Rossolini, J. A. Leitch, R. Grainger and D. J. Dixon, Org. Lett., 2018, 20, 6794–6798; (c) K. N. Lee, Z. Lei and M. Y. Ngai, J. Am. Chem. Soc., 2017, 139, 5003–5006; (d) M. Nakajima, E. Fava, S. Loescher, Z. Jiang and M. Rueping, Angew. Chem. Int. Ed., 2015, 54, 8828–8832; (e) L. J. Rono, H. G. Yayla, D. Y. Wang, M. F. Armstrong and R. R. Knowles, J. Am. Chem. Soc., 2013, 135, 17735–17738.

7 Y. Nakano, M. J. Black, A. J. Meichan, B. A. Sandoval, M. M. Chung, K. F. Biegasiewicz, T. Zhu and T. K. Hyster, Angew. Chem. Int. Ed., 2020, DOI: 10.1002/anie.202003125.

8 For a review on multi-photon excitation, see: (a) F. Glaser, C. Kerzig and O. S. Wenger, Angew. Chem. Int. Ed., 2020, 2–21. For selected recent papers, see: (b) M. Giedyk, R. Narobe, S. Weiß, D. Touraud, W. Kunz and B. König, Nat. Catal., 2020, 3, 40–47; (c) T. U. Connell, C. L. Fraser, M. L. Czyz, Z. M. Smith, D. J. Hayne, E. H. Doeven, J. Agugiaro, D. J. D. Wilson, J. L. Adcock, A. D. Scully, D. E. Gómez, N. W. Barnett, A. Polyzos and P. S. Francis, J. Am. Chem. Soc., 2019, 141, 17646–17658; (d) C. Kerzig and O. S. Wenger, Chem. Sci., 2019, 10, 11023–11029.

9 (a) N. G. W. Cowper, C. P. Chernowsky, O. P. Williams and Z. K. Wickens, J. Am. Chem. Soc., 2020, 142, 2093–2099; (b) H. Kim, H. Kim, T. H. Lambert and S. Lin, J. Am. Chem. Soc., 2020, 142, 2087–2092.

10 (a) T. Horngren, M. S. Taylor, M. Czyz and A. Polyzos, 2020, ChemRxiv: 10.26434/chemrxiv.12235928.v1. For a related pioneering report, see: (b) D. R. Arnold and A. J. Maroulis, J. Am. Chem. Soc., 1977, 99, 7355–7356.

11 (a) L. Capaldo, L. L. Quadri and D. Ravelli, Green Chem. 2020, DOI: 10.1039/D0GC01035A; (b) L. Capaldo and D. Ravelli, Eur. J. Org. Chem., 2017, 2056–2071;

12 Selected examples: (a) K. A. Margrey and D. A. Nicewicz, Acc. Chem. Res., 2016, 49, 1997-2006; (b) D. A. Nicewicz and D. S. Hamilton, Synlett, 2014, 25, 1191–1196. For selected papers, see: (c) J. Dong, X. Wang, Z. Wang, H. Song, Y. Liu and Q. Wang, Chem. Commun., 2019, 55, 11707–11710; (d) C. P. Seath, D. B. Vogt, Z. Xu, A. J. Boyington and N. T. Jui, J. Am. Chem. Soc., 2018, 140, 15525–15534; (e) S. Sumino, M. Uno, T. Fukuyama, I. Ryu, M. Matsuura, A. Yamamoto and Y. Kishikawa, J. Org. Chem., 2017, 82, 5469–5474; (f) C. Wang, K. Harms and E. Meggers, Angew. Chem. Int. Ed., 2016, 55, 13495–13498.

13 (a) P. Z. Wang, J. R. Chen and W. J. Xiao, Org. Biomol. Chem., 2019, 17, 6936–6951; (b) J. Hu, J. Wang, T. H. Nguyen and N. Zheng, Beilstein J. Org. Chem., 2013, 9, 1977–2001; (c) Y. Nakano, K. F. Biegasiewicz and T. K. Hyster, Curr. Opin. Chem. Biol., 2019, 49, 16–24.

14 HE has also been applied as a hydride donor in organocatalytic transfer hydrogenation reactions: (a) C. Zheng and S. L. You, Chem. Soc. Rev., 2012, 41, 2498–2518; (b) S. G. Ouellet, A. M. Walji and D. W. C. Macmillan, Acc. Chem. Res., 2007, 40, 1327–1339.

15 E/Z isomerisation of 1a was observed as a significant side-reaction, particularly with Ir(ppy)3. For related isomerisations, see: ; (a) J. B. Metternich and R. Gilmour, J. Am. Chem. Soc., 2015, 137, 11254–11257; (b) K. Singh, S. J. Staig and J. D. Weaver, J. Am. Chem. Soc., 2014, 136, 5275–5278.

16 The degree of quenching by 1a was very small, being difficult to differentiate from experimental error. It is reasonable to assume that at least some quenching takes place, which was consistent with the observation of Z-1a in small amounts by 1H NMR at early stages of the reaction (see ESI for details).

17 This has been frequently proposed in related transformations: (a) A. Trowbridge, D. Reich and M. J. Gaunt, Nature, 2018, 561, 522–527; (b) L. Qi and Y. Chen, Angew. Chem. Int. Ed., 2016, 55, 13312–13315.

18 For example in ref. 4(a), photoreduction of dimethyl fumarate by BNAH catalysed by Ru1 in MeOD gave 59% d2- and 37% d-dimethyl succinate, with only 4% non-deuterated product, while reaction with 4,4-d2-BNAH in MeOH gave 6% mono- and 94% non-deuterated product. Similar numbers were reported for dimethyl maleate.

19 Calculated value. Compare to ‒1.98 V experimental in MeOH, see: T. Shiragami, H. Ankyu, S. Fukami, C. Pac, S. Yanagida, H. Mori and H. Fujita, J. Chem. Soc. Faraday Trans., 1992, 88, 1055–1061.

20 Y. Zhao and D. G. Truhlar, Theor. Chem. Acc., 2008, 120, 215-241.

21 Calculated reduction potential for the isomeric radical [1aHβ]•, obtained from H addition on the β position, was E½(1aHβ) = -0.72 V.

22 Method for calculating reduction potentials: H. G. Roth, N. A. Romero and D. A. Nicewicz, Synlett, 2016, 27, 714-723.

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1

Efficient reduction of electron-deficient alkenes through

photoinduced hydrogen atom transfer

Supporting Information

Natalia A. Larionova, Jun Miyatake Ondozabal and Xacobe C. Cambeiro*

School of Biological and Chemical Sciences, Queen Mary University of London,

E1 4NS, London, United Kingdom. E-mail: [email protected]

Table of content

General Considerations .......................................................................................................... 2

Synthesis of Starting Material ................................................................................................ 4

Photoreduction and Characterization ................................................................................... 11

NMR Yields ......................................................................................................................... 18

Mechanistic Studies ............................................................................................................. 26

Computational Details ......................................................................................................... 28

References ............................................................................................................................ 37

Spectra.................................................................................................................................. 40

2

General Considerations

All experiments were performed under inert atmosphere in dry microwave vials.

Anhydrous solvents were purchased or collected from a MBRAUN SPS-800 solvent

purification system. Commercially available starting materials and photocatalysts were used as

purchased.

The photocatalytic reactions were performed in a tin container with aluminium foil and

strips of LED lights wrapped around the inner walls. The reaction tubes were held in place

using a plastic rack that sat at the top of the reactor. A thermometer was placed in a tube filled

with either water or paraffin oil at the centre of the reactor to monitor the temperature. The

reactor temperature was kept at room temperature by passing a stream of compressed air. The

top of the reactor was covered with a lid fashioned with cardboard/foil and holes were made

where appropriate (Figure S1).

Figure S1. Photographs of the reactor used for photocatalytic reactions.

LED strips, connectors, power supply and wireless IR remote were purchased from

superbrightleds.com. Specifications of the LED strips: Outdoor RGBW LED strip lights –

weatherproof 12V LED tape light with white and multicolour LEDs – 380 Lumens/ft. – natural

white (WFLS-RGBNW60X3-WHT).

NMR data was obtained from a Bruker Avance III 400 spectrometer. All spectra are

recorded at 303K and reported in ppm unless otherwise stated. Chemical shifts ( values) are

reported in ppm. Coupling constants are reported in Hz and multiplicities abbreviated as

follows: s (singlet); d (doublet); t (triplet); q (quartet); br (broad); m (multiplet); dd (doublet of

doublets); ddd (doublet of doublet of doublets); dt (doublet of triplets); td (triplet of doublets);

app (apparent).

GC-MS analyses were performed using Agilent Technologies GC6890N/MS5973. An

Agilent J&W HP-5MS capillary column of 30 m x 0.32 mm, film thickness 0.25 µm was used.

The oven temperature was programmed to start at 40 ℃ (hold for 1 minute) and increase at

3

20 ℃ min-1 to 300 ℃ (hold for 5 minutes). The carrier gas was helium at a flow rate of 2.0 mL

min-1. Data was processed using MSD ChemStation Data Analysis software.

High-resolution mass spectra were obtained using an Acquity H Class UPLC

instrument interfacing though an electrospray ionization (ESI) LockSpray source to a High

Definition Mass Spectrometer Synapt G2Si, both from Waters Corporation. The sample was

separated by reverse phase using a Waters BEH C18 column (2.1x 50 mm, 1.7 µm). The mobile

phases were water + 0.1% formic acid (A), and acetonitrile + 0.1% formic acid (B) using a

gradient of 2% B to 98% B in 8 minutes. The column temperature was 60 ℃. Data were

acquired and analysed using MassLynx v4.1.

IR spectra were recorded on a Perkin Elmer Spectrum 65 FT-IR spectrometer or an

Agilent Technologies Cary 630 FT-IR and are reported in frequency of absorption at the peak

maximum (cm–1). Data were acquired and analysed using Perkin Elmer Spectrum

v10.00.00.0018.

4

Synthesis of Starting Material

General Procedure A for the Synthesis of Methyl Cinnamate Derivatives1

Monomethyl malonate was synthesised from commercially available starting materials

following reported methodology.2 To a solution of malonic acid monomethyl ester (0.89 g; 7.5

mmol) in pyridine (2 mL) containing a catalytic amount of piperidine (0.045 mL) was added

5.0 mmol of the aldehyde derivative. The reaction mixture was refluxed until TLC analysis

indicated total consumption of the aromatic aldehyde (2-6 hours). Then, after cooling at room

temperature, water (ca. 10 mL) was added, the pH was adjusted to 7.0 with 20% aq. HCl and

the aqueous phase was extracted with ethyl ether (3*20 mL). The organic extracts were joined,

dried over anhydrous sodium sulphate and concentrated under reduced pressure.

(E)-methyl p-methoxycinnamate (1b)

Compound 1b was prepared following general procedure A. The

crude product was purified by column chromatography (silica gel,

n-hexane:EtOAc, 9:1) to afford a white solid, 48% yield. 1H NMR

(400 MHz, CDCl3) δ 7.65 (d, J = 16.0 Hz, 1H), 7.48 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz,

2H), 6.31 (d, J = 16.0 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H). 13C NMR (101 MHz, CDCl3) δ

167.92, 161.55, 144.68, 129.87, 127.29, 115.43, 114.48, 55.53, 51.72. The analytic data are in

agreement with the literature.3

(E)-methyl m-methoxycinnamate (1c)

Compound 1c was prepared following general procedure A. The crude

product was purified by column chromatography (silica gel, n-

hexane:EtOAc, 9:1) to afford a colourless oil, 65% yield. 1H NMR (400

MHz, CDCl3) δ 7.66 (d, J = 16.0 Hz, 1H), 7.30 (t, J = 7.9 Hz, 1H), 7.12

(d, J = 7.6 Hz, 1H), 7.05-7.04 (m, 1H), 6.94 (dd, J = 8.1, 2.3 Hz, 1H), 6.43 (d, J = 16.0 Hz,

1H), 3.83 (s, 3H), 3.81 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.44, 160.0, 144.87, 135.84,

129.97, 120.84, 118.19, 116.22, 113.08, 55.36, 51.78. The analytic data are in agreement with

the literature.4

5

(E)-methyl o-methoxycinnamate (1d)

Compound 1d was prepared following general procedure A. The crude


hexane:EtOAc, 9:1) to afford a colourless oil, 88% yield. 1H NMR

(400 MHz, CDCl3) δ 8.00 (d, J = 16.2 Hz, 1H), 7.51 (dd, J = 7.7, 1.7

Hz, 1H), 7.35 (ddd, J = 8.4, 7.5, 1.7 Hz, 1H), 6.98 – 6.94 (m, 1H), 6.92 (d, J = 8.3 Hz, 1H),

6.53 (d, J = 16.2 Hz, 1H), 3.89 (s, 3H), 3.80 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 13C NMR

(101 MHz, CDCl3) δ 13C NMR (101 MHz, CDCl3) δ 167.87, 158.33, 140.23, 131.50, 128.85,

123.32, 120.68, 118.26, 111.14, 55.41, 51.52. The analytic data are in agreement with the

literature.5

(E)-methyl p-trifluoromethyl cinnamate (1e)

Compound 1e was prepared following general procedure A. The



(400 MHz, CDCl3) δ 7.70 (d, J = 16.1 Hz, 1H), 7.66 – 7.61 (m, 4H), 6.51 (d, J = 16.0 Hz, 1H),

3.83 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 166.98, 143.13, 137.91, 132.99 (q, J = 32.5 Hz),

128.33, 126.02 (q, J = 3.8 Hz), 123.96 (q, J = 272.4 Hz), 120.53, 52.06. 19F NMR (377 MHz,

CDCl3) δ -62.90. The analytic data are in agreement with the literature.6

(E)-methyl m-trifluoromethyl cinnamate (1f)

Compound 1f was prepared following general procedure A. The crude


hexane:EtOAc, 9:1) to afford a white solid, 41% yield. 1H NMR (400

MHz, CDCl3) δ 7.75 (s, 1H), 7.72-7.68 (m, 2H), 7.63 (d, J = 7.7 Hz,

1H), 7.51 (t, J = 7.8 Hz, 1H), 6.50 (d, J = 16.1 Hz, 1H), 3.82 (s, 3H). 13C NMR (101 MHz,

CDCl3) 166.98, 143.14, 135.32, 131.5 (q, J = 32.8 Hz),131.18, 129.58, 126.79 (q, J = 3.7 Hz),

124.73 (q, J = 3.8 Hz), 123.91 (q, J = 273.0 Hz), 119.93, 51.99. 19F NMR (377 MHz, CDCl3)

δ -62.96. The analytic data are in agreement with the literature.5,7

6

(E)-methyl o-trifluoromethyl cinnamate (1g)

Compound 1g was prepared following general procedure A. The crude



MHz, CDCl3) δ 8.06 (dq, J = 15.8, 2.2 Hz, 1H), 7.71-7.69 (m, 2H), 7.57 (t, J = 7.6 Hz, 1H),

7.48 (t, J = 7.6 Hz, 1H), 6.41 (d, J = 15.8 Hz, 1H), 3.83 (s, 3H). 13C NMR (101 MHz, CDCl3)

δ 166.66, 140.47 (d, J = 2.2 Hz), 133.53 (d, J = 1.8 Hz), 132.24, 129.73, 129.17 (q, J = 30.4

Hz), 128.05, 126.32 (q, J = 5.6 Hz), 124.05 (q, J = 273 Hz), 122.34, 52.07. The analytic data

are in agreement with the literature.8 19F NMR (377 MHz, CDCl3) δ -58.98.

(E)-methyl o-bromomethyl cinnamate (1j)

Compound 1j was prepared following general procedure A. The crude


hexane:EtOAc, 9:1) to afford a yellow oil, 83% yield. 1H NMR (400

MHz, CDCl3) δ 8.05 (d, J = 15.9 Hz, 1H), 7.62-7.58 (m, 2H), 7.34-7.30 (m, 1H), 7.24 – 7.20

(td, J = 7.7, 1.6 Hz, 1H), 6.39 (d, J = 15.9 Hz, 1H), 3.82 (s, 3H). 13C NMR (101 MHz, CDCl3)

δ 166.71, 143.07, 134.39, 133.39, 131.21, 127.73, 127.71, 125.29, 120.63, 51.81. The analytic

data are in agreement with the literature.9

(E)-methyl o-methylcinnamate (1k)

Compound 1k was prepared following general procedure A. The crude



MHz, CDCl3) δ 7.98 (d, J = 15.9 Hz, 1H), 7.56 – 7.54 (m, 1H), 7.30 – 7.19 (m, 3H), 6.36 (d,

J = 15.9 Hz, 1H), 3.81 (s, 3H), 2.44 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.43, 142.51,

137.63, 133.36, 130.79, 130.04, 126.40, 126.35, 118.84, 51.64, 19.75. The analytic data are in


(E)-methyl o-fluoromethyl cinnamate (1l)

Compound 1l was prepared following general procedure A. The crude



MHz, CDCl3) δ 7.82 (d, J = 16.2 Hz, 1H), 7.53 (td, J = 7.6, 1.7 Hz, 1H), 7.38 – 7.33 (m, 1H),

7.16 (td, J = 7.6, 0.9 Hz, 1H), 7.10 (ddd, J = 10.6, 8.3, 1.0 Hz, 1H), 6.54 (d, J = 16.3 Hz, 1H),

7

3.82 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.25, 161.40 (d, J = 253.8 Hz), 137.5 (d, J =

3.2 Hz), 131.76 (d, J = 8.8 Hz), 129.10 (d, J = 2.8 Hz), 124.49 (d, J = 3.6 Hz), 122.50 (d, J =

11.9 Hz), 120.44 (d, J = 6.7 Hz), 116.23 (d, J = 22.3 Hz), 51.79. 19F NMR (377 MHz, CDCl3)

δ -114.42. The analytic data are in agreement with the literature.5,11

(E)-methyl o-chloromethyl cinnamate (1m)

Compound 1m was prepared following general procedure A. The crude



MHz, CDCl3) δ 8.10 (d, J = 16.0 Hz, 1H), 7.62 (dd, J = 7.3, 2.2 Hz, 1H), 7.43-7.41 (m, 1H),

7.33 – 7.27 (m, 2H), 6.44 (d, J = 16.0 Hz, 1H), 3.83 (s, 3H). 13C NMR (101 MHz, CDCl3) δ

166.72, 140.40, 134.81, 132.51, 130.98, 130.05, 127.52, 127.01, 120.36, 51.68. The analytic

data are in agreement with the literature.5

(E)-methyl o-iodomethyl cinnamate (1n)

Compound 1n was prepared following general procedure A. The crude



MHz, CDCl3) δ 7.90 (d*, J = 15.8 Hz, 1H), 7.90 (dd*, J = 8.0, 1.1 Hz, 1H), 7.56 (dd, J = 7.8,

1.6 Hz, 1H), 7.38-7.34 (m, 1H), 7.05 (td, J = 7.7, 1.6 Hz, 1H), 6.32 (d, J = 15.8 Hz, 1H), 3.83

(s, 3H). *Signals partially overlap. 13C NMR (101 MHz, CDCl3) δ 166.62, 147.85, 140.01,


the literature.12

(E)-methyl p-hydroxycinnamate (1o)

Compound 1o was prepared following general procedure A. The



(400 MHz, CDCl3) δ 7.64 (d, J = 16.0 Hz, 1H), 7.44 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.6 Hz,

2H), 6.31 (d, J = 16.0 Hz, 1H), 5.06-5.02 (m, 1H), 3.80 (s, 3H). 13C NMR (101 MHz, CDCl3)

δ 168.01, 157.69, 144.66, 130.12, 127.52, 116.02, 115.51, 51.80. The analytic data are in

agreement with the literature.13,14

8

(E)-methyl p-(hydroxymethyl)cinnamate (1p)

Compound 1p was prepared according to the procedure reported

in the literature from commercially available methyl 4-

formylcinnamate.15 The crude product was purified by column

chromatography (silica gel, n-hexane:EtOAc, 3:1) and recrystallized from benzene to afford a

white solid, 78% yield. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 16.0 Hz, 1H), 7.52 (d, J =

8.1 Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 6.44 (d, J = 16.0 Hz, 1H), 4.72 (d, J = 5.8 Hz, 2H), 3.81

(s, 3H). OH peak was not observed. 13C NMR (101 MHz, CDCl3) δ 167.59, 144.61, 143.35,


literature.16

(E)-methyl p-carboxylcinnamate (1q)

Compound 1q was prepared following general procedure A. The

crude product was purified by column chromatography (silica

gel, n-hexane:EtOAc, 3:1) to afford a white solid, 35% yield. 1H

NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.4 Hz, 2H), 7.73 (d, J =

16.1 Hz, 1H), 7.62 (d, J = 8.4 Hz, 2H), 6.55 (d, J = 16.1 Hz, 1H), 3.83 (s, 3H). 13C NMR (101

MHz, DMSO-d6) δ 166.77, 166.38, 143.24, 138.06, 132.08, 129.70, 128.43, 120.14, 51.62.

The analytic data are in agreement with the literature.17,18

(E)-methyl p-(1,3-dioxolan-2-yl)cinnamate (1r)

Compound 1r was prepared following general procedure A from

4-(1,3-dioxolan-2-yl)benzaldehyde synthesised according to the

literature.19 The crude product was purified by column

chromatography (silica gel, n-hexane:EtOAc, 5:1) to afford a

white solid, 57% yield. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 16.0 Hz, 1H), 7.54 (d, J =

8.3 Hz, 2H), 7.50 (d, J = 8.3 Hz, 2H), 6.45 (d, J = 16.0 Hz, 1H), 5.83 (s, 1H), 4.14 – 4.03 (m,

4H), 3.81 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.46, 144.45, 140.22, 135.35, 128.22,

127.14, 118.51, 103.32, 65.51, 51.87. HRMS (ESI) m/z calc. for C13H14O4, [MH+]: 235.0970,

found: 235.1001. IR (neat): 2950, 2887, 1706, 1171, 823 cm-1.

9

(E)-methyl p-(n-butyl)aminomethylcinnamate (1t)

Compound 1t was prepared according to the procedure

reported in the literature (a yellow oil, 81% yield).20 1H

NMR (400 MHz, CDCl3) δ 7.65 (d, J = 16.1 Hz, 1H),

7.44 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.38 (d, J = 16.1 Hz, 1H), 3.75 (s, 5H), 2.58

(t, J = 7.1 Hz, 2H), 1.62 (br s, 1H, NH), 1.49 – 1.42 (m, 2H), 1.36 – 1.27 (m, 2H), 0.87 (t, J =

7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 167.48, 144.68, 143.25, 133.04, 128.56, 128.15,

117.27, 53.69, 51.62, 49.19, 32.22, 20.46, 14.01. HRMS (ESI) m/z calc. for C15H21NO2,

[MH+]: 248.1651, found: 248.1637. IR (neat): 2957, 2930, 1717, 1637, 1166 cm-1.

(E)-methyl p-dimethylaminomethylcinnamate (1u)

Compound 1u was prepared according to the procedure reported

in the literature (a yellow oil, 65% yield).21 1H NMR (400 MHz,

CDCl3) δ 7.68 (d, J = 16.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H),

7.33 (d, J = 8.0 Hz, 2H), 6.42 (d, J = 15.9 Hz, 1H), 3.80 (s, 3H), 3.42 (s, 2H), 2.24 (s, 6H). 13C

NMR (101 MHz, CDCl3) δ 167.50, 144.70, 141.60, 133.29, 129.55, 128.09, 117.42, 64.02,

51.66, 45.42. HRMS (ESI) m/z calc. for C13H17NO2, [MH+]: 220.1338, found: 220.1360. IR

(neat): 2950, 2819, 2770, 1718, 1636, 1165 cm-1.

(E)-methyl 3-(pyridin-2-yl)acrylate (1v)

Compound 1v was prepared following general procedure A. The crude



MHz, CDCl3) δ 8.66-8.64 (m, 1H), 7.73 – 7.67 (m, 2H), 7.42 (d, J = 7.8 Hz, 1H), 7.28-7.25

(m, 1H), 6.93 (d, J = 15.7 Hz, 1H), 3.82 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.37,

153.06, 150.32, 143.70, 136.89, 124.39, 124.37, 122.12, 51.99. The analytic data are in


(E)-methyl 3-(thiophen-2-yl)acrylate (1w)

Compound 1w was prepared following general procedure A. The crude



MHz, CDCl3) δ 7.50 – 7.46 (m, 1H), 7.43 (d, J = 15.7 Hz, 1H), 6.61 (d, J = 3.4 Hz, 1H), 6.47-

6.46 (m, 1H), 6.32 (d, J = 15.8 Hz, 1H), 3.79 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.64,

10


the literature.3

(E)-2-Styrylpyridine (1z)

Compound 1z was prepared according to the procedure reported in the

literature.23 The crude product was purified by column chromatography

(silica gel, n-hexane:EtOAc, 95:5) to afford an off-white solid, 31% yield.

1H NMR (400 MHz, CDCl3) δ 8.62-8.60 (m, 1H), 7.68 – 7.62 (m, 2H), 7.60 – 7.57 (m, 2H),

7.40 – 7.36 (m, 3H), 7.32 – 7.28 (m, 1H), 7.18 (d*, J = 16 Hz, 1H), 7.16-7.13 (m*, 1H). *Signals

partially overlap. 13C NMR (101 MHz, CDCl3) δ 155.80, 149.84, 136.82, 136.67, 132.88,


literature.24

11

Photoreduction and Characterization

General procedure B for photocatalytic reduction of alkenes

Substrate (0.2 mmol), Hantzsch ester (2 eq., 0.4 mmol) and [Ir(dtbbpy)(ppy)2]PF6 (2.5 mol%)

were weighted out into a microwave vial equipped with a magnetic stirrer. Dry methanol (8

mL) was added and the vial was quickly capped. The mixture was degassed with argon for 10

minutes and the septum was covered with parafilm. The vial was placed in a photoreactor and

irradiated under blue light for 16 hours. Thereafter, the mixture was transferred to a round

bottom flask, the vial washed with Et2O and the solvent was evaporated.

Work-up A: 5 mL of HCl in Et2O (1.0-1.7M) was added to the residue and filtered through a

packed layer of silica. The solution was neutralized with a saturated NaHCO3 solution and the

extracted organic layer washed with water. The organic phase was dried over MgSO4, filtered

and concentrated in vacuo.

Work-up B: 0.5 mL of HCl in Et2O (1.0-1.7M) was added to the residue and filtered through a

packed layer of silica. The solution was neutralized with NaHCO3 powder, filtered and

concentrated in vacuo.

Method for crude NMR Analysis: An internal standard, either 1,3,5-trimethoxybenzene (0.33

eq.) or 1-bromo-4-nitrobenzene (1 eq.) was dissolved with CDCl3 in a volumetric flask. 1 mL

of the stock solution was added to the crude mixture and the resulting sample was analysed by

NMR. Spectra were referenced to 1,3,5-trimethoxybenzene peak at 6.09 ppm as the residual

CDCl3 was hard to identify unless otherwise stated.25

Methyl 3-phenylpropanoate (2a)

Synthesised according to general procedure B and the crude mixture

obtained after the first evaporation was directly purified by flash column

chromatography (n-hexane/ethyl acetate, 98:2). The desired product was

obtained as a colourless oil (87% yield). 1H NMR (400 MHz, CDCl3) δ 7.32 – 7.28 (m, 2H),

7.23-7.20 (m, 3H), 3.68 (s, 3H), 2.98-2.94 (m, 2H), 2.66-2.62 (m, 2H). 13C NMR (101 MHz,

CDCl3) δ 173.46, 140.64, 128.63, 128.39, 126.39, 51.73, 35.83, 31.07. The observed results

are in accordance with the literature values.26

12

Methyl 3-(4-methoxyphenyl)propionate (2b)

Synthesised according to general procedure B/work-up B and the

resulting oil was purified by flash column chromatography (n-

hexane/ethyl acetate, 95:5). The desired product was obtained as

a pale-yellow oil (61% yield). 1H NMR (400 MHz, CDCl3) δ 7.12 (d, J = 8.7 Hz, 2H), 6.83

(d, J = 8.7 Hz, 2H), 3.78 (s, 3H), 3.67 (s, 3H), 2.91-2.88 (m, 2H), 2.62-2.58 (m, 2H).

13C NMR (101 MHz, CDCl3) δ 173.55, 158.23, 132.73, 129.36, 114.06, 55.39, 51.71, 36.15,

30.24. The observed results are in accordance with the literature values.27

Methyl 3-(3-methoxyphenyl)propanoate (2c)

Synthesised according to general procedure B/work-up A and the


hexane/ethyl acetate, 95:5). The desired product was obtained as a pale-

yellow oil (85% yield). 1H NMR (400 MHz, CDCl3) δ 7.23-7.18 (m,

1H), 6.80-6.74 (m, 3H), 3.79 (s, 3H), 3.68 (s, 3H), 2.95-2.91 (m, 2H), 2.65-2.61 (m, 2H). 13C

NMR (101 MHz, CDCl3) δ 173.46, 159.87, 142.28, 129.64, 120.75, 114.20, 111.74, 55.29,

51.78, 35.76, 31.13. The observed results are in accordance with the literature values.28

Methyl 3-(2-methoxyphenyl)propanoate (2d)


desired product was obtained as a pale-yellow oil (98% yield). 1H NMR

(400 MHz, CDCl3) δ 7.20 (td, J = 7.8, 1.6 Hz, 1H), 7.15 (dd, J = 7.4,

1.5 Hz, 1H), 6.90-6.84 (m, 2H), 3.83 (s, 3H), 3.67 (s, 3H), 2.97-2.93 (m, 2H), 2.64-2.60 (m,

2H). 13C NMR (101 MHz, CDCl3) δ 173.95, 157.60, 130.03, 128.94, 127.72, 120.55, 110.33,

55.29, 51.61, 34.15, 26.25. The observed results are in accordance with the literature values.29

MS(EI) m/z 194.00 [M+].

Methyl 3-(4-(trifluoromethyl)phenyl)propanoate (2e)



hexane/ethyl acetate, 95:5). The desired product was obtained as a

colourless oil (71% yield). 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 2H), 7.31 (d, J

= 8.0 Hz, 2H), 3.67 (s, 3H), 3.01 (t, J = 7.7 Hz, 2H), 2.65 (m, 2H). 13C NMR (101 MHz,

CDCl3) δ 173.01, 144.73 (d, J = 1.3 Hz), 128.85 (q, J = 32.4 Hz), 128.79, 125.59 (q, J = 3.8

13

Hz), 124.39 (q, J = 271.9 Hz), 51.86, 35.31, 30.79. The observed results are in accordance with

the literature values.30 19F NMR (377 MHz, CDCl3) δ -62.43.

Methyl 3-(3-(trifluoromethyl)phenyl)propanoate (2f)



hexane/ethyl acetate, 95:5). The desired product was obtained as a pale-

yellow oil (86% yield). 1H NMR (400 MHz, CDCl3) δ 7.48-7.39 (m,

4H), 3.68 (s, 3H), 3.01 (t, J = 7.7 Hz, 2H), 2.68-2.64 (m, 2H). 13C NMR (101 MHz, CDCl3) δ

172.82, 141.53, 131.90 (d, J = 1.1 Hz), 130.99 (d, J = 32.0 Hz), 129.09, 125.20 (q, J = 3.8 Hz),

124.29 (q, J = 272.2 Hz), 123.37 (q, J = 3.8 Hz), 51.86, 35.48, 30.82. 19F NMR (377 MHz,

CDCl3) δ -62.64.The observed results are in accordance with the literature values.31

Methyl 3-(3-(trifluoromethyl)phenyl)propanoate (2g)



hexane/ethyl acetate, 95:5). The desired product was obtained as a

yellow oil (68% yield). 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.9

Hz, 1H, HAr), 7.47 (t, J = 7.3 Hz, 1H, HAr), 7.36-7.30 (m, 2H, HAr), 3.70 (s, 3H, OMe), 3.16-

3.12 (m, 2H, CH2Ar), 2.65-2.61 (m, 2H, CH2CO). 13C NMR (101 MHz, CDCl3) δ 173.11

(C10), 139.37 (d, J = 1.5 Hz, C7), 132.11 (C5), 131.09 (C6), 128.74 (q*, J = 29.8 Hz, C2), 126.64

(C4), 126.27 (q, J = 5.8 Hz, C3), 124.67 (q*, J = 273.6 Hz, C1), 51.87 (C11), 35.77 (d, J = 1.0

Hz, C9), 27.96 (d, J = 1.8 Hz, C8). *Only the two central peaks of the quartet were visible. 19F

NMR (377 MHz, CDCl3) δ -59.82. MS (EI) m/z 233.05 [MH+], 232.05 [M+]. IR (neat): 1738,

1312, 1151, 1107 cm-1.

Methyl 3-(3-bromophenyl)propionate (2i)

Synthesised according to general procedure B and the crude mixture

obtained after the first evaporation was directly purified by flash column

chromatography (n-hexane/ethyl acetate, 95:5). The desired product was

obtained as a colourless oil (97% yield). 1H NMR (400 MHz, CDCl3) δ

7.35-7.33 (m, 2H), 7.18-7.11 (m, 2H), 3.68 (s, 3H), 2.92 (t, J = 7.7 Hz, 2H), 2.64-2.60 (m, 2H).

13C NMR (101 MHz, CDCl3) δ 173.09, 142.96, 131.55, 130.21, 129.60, 127.12, 122.67, 51.85,

35.49, 30.66. The observed results are in accordance with the literature values.32

14

Methyl 3-(2-bromophenyl)propanoate (2j)


desired product was obtained as a yellow oil (68% yield). 1H NMR (400

MHz, CDCl3) δ 7.55-7.53 (m, 1H), 7.28 – 7.22 (m, 2H), 7.09 (ddd, J =

8.0, 6.5, 2.6 Hz, 1H), 3.69 (s, 3H), 3.10-3.06 (m, 2H), 2.69-2.65 (m, 2H). 13C NMR (101 MHz,

CDCl3) δ 173.18, 139.86, 133.04, 130.57, 128.23, 127.71, 124.48, 51.80, 34.04, 31.56. The

observed results are in accordance with the literature values.32

Methyl 3-(o-tolyl)propanoate (2k)



(400 MHz, CDCl3) δ 7.14 (s, 4H), 3.69 (s, 3H), 2.97-2.93 (m, 2H), 2.62-

2.58 (m, 2H), 2.33 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 173.60, 138.74, 136.10, 130.44,

128.62, 126.57, 126.27, 51.77, 34.56, 28.47, 19.35. The observed results are in accordance with

the literature values.33

Methyl 3-(2-fluorophenyl)propanoate (2l)



(400 MHz, CDCl3) δ 7.23 – 7.16 (m, 2H), 7.07 – 6.98 (m, 2H), 3.67 (s,

3H), 2.98 (t, J = 7.7 Hz, 2H), 2.66-2.62 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 173.26,

161.30 (d, J = 245.2 Hz), 130.72 (d, J = 4.8 Hz), 128.24 (d, J = 8.1 Hz), 127.44 (d, J = 15.6

Hz), 124.19 (d, J = 3.6 Hz), 115.43 (d, J = 21.9 Hz), 51.76, 34.33 (d, J = 1.4 Hz), 24.73 (d, J =

2.7 Hz). The observed results are in accordance with the literature values.27 19F NMR (377

MHz, CDCl3) δ -118.59.

Methyl 3-(2-chlorophenyl)propanoate (2m)


desired product was obtained as a yellow oil (85% yield). 1H NMR

(400 MHz, CDCl3) δ 7.35-7.33 (m, 1H), 7.26 – 7.24 (m, 1H), 7.21 –

7.13 (m, 2H), 3.68 (s, 3H), 3.09-3.05 (m, 2H), 2.67-2.64 (m, 2H). The

observed results are in accordance with the literature values.34 13C NMR (101 MHz, CDCl3)

δ 173.27 (C9), 138.17 (C6), 134.10 (C1), 130.59 (C2), 129.71 (C3), 128.00 (C4), 127.05 (C5),

15

51.79 (C10), 33.90 (C8), 29.09 (C7). MS (EI) m/z 198.00 [M+]. IR (neat): 2951, 1736, 1436,

1158, 1053, 751 cm-1.

Methyl 3-(4-(hydroxymethyl)phenyl)propanoate (2p)


desired product was obtained as yellow solids (81% yield).

1H NMR (400 MHz, CDCl3) δ 7.29 (d, J = 8.1 Hz, 2H), 7.19 (d,

J = 8.0 Hz, 2H), 4.65 (s, 2H), 3.67 (s, 3H), 2.97-2.93 (m, 2H), 2.64-2.60 (m, 2H). OH peak was

not observed. 13C NMR (101 MHz, CDCl3) δ 173.45, 140.05, 139.05, 128.57, 127.39, 65.17,

51.75, 35.77, 30.71.The observed results are in accordance with the literature values.35

4-(3-methoxy-3-oxopropyl)benzoic acid (2q)

Synthesised according to general procedure B and the crude

mixture obtained after the first evaporation was purified by flash

column chromatography DCM:EtOAc:AcOH, 95:4:1) and

concentrated. The residue was dissolved in EtOAc and washed

with brine. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The

desired product was obtained as a white solid (56% yield). 1H NMR (400 MHz, CDCl3) δ 8.04

(d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 3.68 (s, 3H), 3.03 (t, J = 7.7 Hz, 2H), 2.69-2.65

(m, 2H). 13C NMR (101 MHz, CDCl3) δ 173.09, 171.56, 147.08, 130.67, 128.65, 127.55,


Methyl 3-(4-formylphenyl)propanoate (2r)

Synthesised according to general procedure B/work-up B using 1r

as the starting material and the desired product was obtained as a

pale-yellow oil (83% yield). 1H NMR (400 MHz, CDCl3) δ 9.98

(s, 1H), 7.81 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 3.68 (s,

3H), 3.04 (t, J = 7.7 Hz, 2H), 2.70-2.66 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 192.01,

172.95, 147.91, 134.99, 130.18, 129.13, 51.87, 35.11, 31.12. The observed results are in

accordance with the literature values.37

16

Methyl 3-(4-((butylamino)methyl)phenyl)propanoate (2t)

Synthesised according to general procedure B and the

crude mixture obtained after the first evaporation was

directly purified by flash column chromatography (n-

hexane/acetone, 9:1). The desired product was

obtained as a yellow oil (73% yield). 1H NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.0 Hz, 2H,

H7), 7.14 (d, J = 8.1 Hz, 2H, H8), 3.74 (s, 2H, H5), 3.66 (s, 3H, H13), 2.95-2.91 (m, 2H, H10),

2.63-2.59 (m, 4H, H4 and H11), 1.67 (br. s, 1H, NH), 1.53-1.45 (m, 2H, H3), 1.38-1.29 (m, 2H,

H2), 0.90 (t, J = 7.3 Hz, 3H, H1). 13C NMR (101 MHz, CDCl3) δ 173.45 (C12), 139.21 (C9),

138.54 (C6), 128.42 (C7), 128.39 (C8), 53.84 (C13), 51.69 (C4), 49.28 (C5), 35.83 (C11), 32.28

(C3), 30.70 (C10), 20.58 (C2), 14.11 (C1). HRMS (ESI) m/z calc. for C15H23NO2, [MH+]:

250.1807; found: 250.1831. IR (neat): 2958, 2930, 1738, 1438, 1155 cm-1.

Methyl 3-(4-((dimethylamino)methyl)phenyl)propanoate (2u)

Synthesised according to general procedure B and the crude

mixture obtained after the first evaporation was directly

purified by flash column chromatography (n-hexane/acetone,

9:1). The desired product was obtained as a yellow oil (67%

yield). 1H NMR (400 MHz, CDCl3) δ 7.21 (d, J = 8.1 Hz, 2H, H4), 7.14 (d, J = 8.1 Hz, 2H,

H5), 3.66 (s, 3H, H10), 3.38 (s, 2H, H2), 2.95-2.91 (m, 2H, H7), 2.64-2.60 (m, 2H, H8), 2.22 (s,

6H, H1). 13C NMR (101 MHz, CDCl3) δ 173.47 (C9), 139.4 (C6), 136.85 (C3), 129.41 (C4),

128.25 (C5), 64.13 (C2), 51.70 (C10), 45.41 (C1), 35.83 (C8), 30.72 (C7). HRMS (ESI) m/z calc.

for C13H19NO2, [MH+]: 222.1494; found: 222.1488. IR (neat): 2950, 2770, 1738, 1148, 1021

cm-1.

3-Phenylpropanenitrile (2y)

Synthesised according to general procedure B/work-up B and the desired

product was obtained as a yellow oil (83% yield).

1H NMR (400 MHz, CDCl3) δ 7.36 – 7.21 (m, 5H), 2.96 (t, J = 7.4 Hz, 2H), 2.62 (t, J = 7.4

Hz, 2H). Spectrum referenced to diethyl ether (Et2O) peak at 1.21 ppm as the residual CDCl3

was hard to identify.38

13C NMR (101 MHz, CDCl3) δ 138.19, 129.04, 128.40, 127.40, 119.25, 31.75, 19.51.

The observed results are in accordance with the literature values.39

17

Chroman-2-one (2aa)

Synthesised according to general procedure B using acetonitrile as the solvent

and the crude mixture obtained after the first evaporation was directly purified

by flash column chromatography (n-hexane/acetone, 95:5). The desired product was obtained

as a yellow oil (84% yield, NMR purity = 81%; 16% of Hantzsch pyridine, 4% of starting

material and 1% of Et2O). 1H NMR (400 MHz, CDCl3) δ 7.28-7.24 (m, 1H), 7.21-7.19 (m,

1H), 7.10 (td, J = 7.4, 1.1 Hz, 1H), 7.06-7.04 (m, 1H), 3.03-2.99 (m, 2H), 2.81-2.78 (m, 2H).

Spectrum referenced to diethyl ether (Et2O) peak at 1.21 ppm as the residual CDCl3 was hard

to identify.38 13C NMR (101 MHz, CDCl3) δ 168.64, 152.14, 128.39, 128.12, 124.50, 122.75,


Ethyl 2-cyano-3,3-diphenylpropanoate (2ab)

Synthesised according to general procedure B/work-up A and the crude

mixture was purified by flash column chromatography (n-hexane/ethyl

acetate, 98:2). The desired product was obtained as a white solid (93%

yield). 1H NMR (400 MHz, CDCl3) δ 7.39 – 7.23 (m, 10H), 4.74 (d, J =

8.6 Hz, 1H), 4.25 (d, J = 8.6 Hz, 1H), 4.10 (qd, J = 7.1, 1.6 Hz, 2H), 1.09 (t, J = 7.1 Hz, 3H).

Spectrum referenced to ethyl acetate (EtOAc) peak at 1.26 ppm as the residual CDCl3 was hard

to identify.38 13C NMR (101 MHz, CDCl3) δ 165.11, 139.43, 138.85, 128.98, 128.95, 128.31,

127.93, 127.90, 127.76, 115.87, 62.95, 51.18, 43.65, 13.79. The observed results are in

accordance with the literature values.41

18

NMR Yields

Ethyl 3-(4-bromophenyl)propionate (2h)

Synthesised according to general procedure B and the crude yield

was determined by 1H NMR (30% yield) using 1,3,5-

trimethoxybenzene as internal standard.

Crude 1H NMR

SM: starting material

IS: Internal standard

HP: Hantzsch pyridine

19

Methyl 3-(2-iodophenyl)propanoate (2n)

Synthesised according to general procedure B and the crude yield was

determined by 1H NMR (46% yield) using 1,3,5-trimethoxybenzene as

internal standard.

Crude 1H NMR




20

Methyl 3-(4-hydroxyphenyl)propanoate (2o)




Crude 1H NMR




21

Methyl 3-(4-aminophenyl)propanoate (2s)




Crude 1H NMR




22

Methyl 3-(pyridin-2-yl)propanoate (2v)


determined by 1H NMR (25% yield) using 1-bromo-4-nitrobenzene as

internal standard.

Crude 1H NMR



HE: Hantzsch ester


23

2-Phenethylpyridine (2z)


determined by 1H NMR (44% yield) using 1-bromo-4-nitrobenzene as

internal standard. Spectra were referenced to Hantzsch ester peak at 2.20

ppm as the residual CDCl3 was hard to identify.42

Crude 1H NMR



HE: Hantzsch ester


24

Methyl 3-(furan-2-yl)propanoate (2w)


obtained by 1H NMR (16% yield) using 1,3,5-trimethoxybenzene as

internal standard.

Crude 1H NMR



HE: Hantzsch ester


25

Ethyl butyrate (2x)


obtained by 1H NMR (not detected) using 1-bromo-4-nitrobenzene as

internal standard.

Crude 1H NMR



HE: Hantzsch ester


26

Mechanistic Studies

Deuterium Labelling Studies

Hydrogenation of methyl cinnamate was performed according to general procedure B with

non-deuterated/deuterated Hantzsch esters. The results of these studies are summarized in

Table S1:

Table S1. Deuterium Labelling Experiments. N HE solvent Yield, % D incorporation, %

E-SM Z-SM Product α-d β-d

1

MeOD 0 0 100 9 44

2

MeOH 0 0 100 25 0

4,4’-Dideuterio-2,6-dimethyl-3,5-dicarboethoxy-1,4-dihydropyridine (4,4’-d2-HE)

4,4’-d2-HE was prepared according to the procedure reported in the

literature.43 A mixture of ethyl acetoacetate (4.25 mL, 33.3 mmol),

d2-paraformaldehyde (0.5 g, 16.7 mmol) and ammonium acetate (1.93

g, 25 mmol) was heated at 70°C in a water bath for 10 min. and then allowed to cool down to

room temperature. Cold water (30 mL) was added and the resulting mixture was stirred for 10

minutes and filtered. The precipitate was recrystallised from EtOH (25 mL) to afford the pure

deuterated Hantzsch ester 4b as a pale yellow solid (0.94 g, 22%). 1H NMR (400 MHz,

CDCl3) δ 5.21 (br s, 1H), 4.16 (q, J = 7.1 Hz, 4H), 2.19 (s, 6H), 1.28 (t, J = 7.1 Hz, 6H). The

analytic data are in agreement with the literature.43

27

Stern-Volmer quenching studies

Stern-Volmer studies were conducted with methyl cinnamate (1a) and Hantzsch ester.

Standard solutions of 1a, Hantzsch ester and [Ir(dtbbpy)(ppy)2]PF6 were prepared in DMF. The

samples contained 0.01 mM Ir photocatalyst solution and varying quencher concentrations

were prepared in 3 mL quartz cuvettes, equipped with Suba-Seal septa, and degassed with

argon for 10 minutes. The cuvettes were irradiated at 450 nm and the emission intensity was

measured at 575 nm (two times) using an Agilent Eclipse Fluorescence Spectrophotometer.

Data were acquired and analysed using Cary Eclipse Scan Application v1.2. The ratio of I0/I

was plotted as a function of the quencher concentration (I0 = emission intensity of the

photocatalyst in isolation at the specified wavelength; I = observed intensity as a function of

the quencher concentration). These results show that the photocatalyst is readily quenched only

by Hantzsch ester.

Table S2. Stern-Volmer quenching study of Hantzsch ester and methyl cinnamate (1a).

[Hantzsch ester],mM I (average) Io/I

0 436.741 1

0.5 380.4695 1.1479

1 346.2595 1.261311

2 313.057 1.395085

3.2 282.0585 1.548406

4 258.6745 1.688381

Figure S2. Stern-Volmer quenching study of Hantzsch ester and methyl cinnamate (1a).

y = 0.1613x + 1.0541R² = 0.9802

y = 0.0121x + 0.9895R² = 0.1056

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

0 1 2 3 4 5 6 7

I0 /I

[Q], mM

Hantzsch ester

methylcinnamate

[Methyl cinnamate],mM I (average) Io/I

0 440.3755 1

0.5 403.83 1.090497

1 478.6915 0.843612

2 444.1135 1.077858

3.2 454.9835 0.976109

4 424.1305 1.072744

5 397.7035 1.066449

6.1 378.15 1.051708

28

Computational Details

Methods. All calculations were performed using Gaussian 09.d01.44 All geometry

optimisations were performed using the M06-2X functional45 with 6-31+G(d,p) basis set

and SMD solvation model for MeOH or MeCN (for reduction potentials).46 Harmonic

vibrational frequencies were calculated with the same method and used to confirm the

nature of stationary points (minima or transition states) and to determine Gibbs free

energies (at 25 °C). Absolute half reaction reduction potentials were determined from the

difference of Gibbs free energies between oxidised and reduced form of the compound of

study in MeCN, applying equation 1,47 with 𝑛𝑒 = 1 and ℱ = 23.061. Relative potentials

were calculated using the reference values for SHE (Eabs(SHE) = 4.281 V) and SCE

(ESHE→SCE = ‒0.141 V in MeCN) reported by Isse and Gennaro.48

𝐸½𝑜 = −

Δ𝐺𝑜

𝑛𝑒ℱ (1)

Geometries and energies of minima and transition states:

1a

MeOH MeCN E = -537.3398988 Hartree E = -537.3415877 Hartree

G = -537.199653 Hartree G = -537.201648 Hartree

C 3.681316 0.975162 -0.000143 C 3.680758 0.977176 -0.000252

C 2.313735 1.243123 -0.000037 C 2.312405 1.242569 -0.000089

C 1.378151 0.198183 0.000096 C 1.378202 0.196311 0.000082

C 1.842963 -1.127666 0.000152 C 1.845937 -1.128576 0.000107

C 3.207401 -1.393998 0.000053 C 3.211146 -1.392690 -0.000050

C 4.130948 -0.344260 -0.000100 C 4.133189 -0.341472 -0.000232

H 4.392897 1.795382 -0.000253 H 4.390613 1.798785 -0.000389

H 1.961017 2.271385 -0.000064 H 1.957546 2.270041 -0.000099

H 1.138050 -1.953796 0.000290 H 1.142069 -1.955555 0.000258

H 3.554835 -2.422786 0.000105 H 3.560155 -2.420858 -0.000023

H 5.195785 -0.557694 -0.000174 H 5.198288 -0.552951 -0.000352

C -0.048619 0.540794 0.000170 C -0.050173 0.536487 0.000229

C -1.078729 -0.319317 -0.000078 C -1.080246 -0.322655 0.000175

H -0.276572 1.606555 0.000428 H -0.282246 1.601326 0.000390

H -0.957949 -1.397803 -0.000369 H -0.958276 -1.401136 -0.000004

C -2.461209 0.189383 0.000029 C -2.465281 0.192678 0.000370

O -2.791547 1.365387 0.000257 O -2.788154 1.365526 0.000285

O -3.353376 -0.807690 -0.000193 O -3.356083 -0.808823 -0.000099

C -4.736348 -0.422810 -0.000150 C -4.735969 -0.421461 -0.000346

H -4.963898 0.160524 -0.894798 H -4.965404 0.163984 -0.893358

29

H -5.298471 -1.354959 -0.000412 H -5.302808 -1.350982 -0.000731

H -4.963966 0.160059 0.894785 H -4.965849 0.163515 0.892859

[1a]•‒



C 3.720784 0.938386 -0.000093 C 3.720572 0.941570 -0.000082

C 2.370357 1.250340 -0.000052 C 2.370646 1.251864 -0.000054

C 1.365117 0.239841 -0.000007 C 1.362517 0.240139 -0.000021

C 1.825387 -1.109586 -0.000002 C 1.828538 -1.110958 -0.000015

C 3.181839 -1.409966 -0.000045 C 3.185479 -1.408341 -0.000044

C 4.150021 -0.398138 -0.000091 C 4.154328 -0.395817 -0.000079

H 4.453201 1.742252 -0.000128 H 4.451472 1.746958 -0.000108

H 2.058622 2.293035 -0.000056 H 2.058184 2.294508 -0.000058

H 1.105949 -1.923592 0.000034 H 1.110420 -1.926220 0.000013

H 3.492487 -2.452308 -0.000041 H 3.497259 -2.450527 -0.000038

H 5.207875 -0.641771 -0.000124 H 5.212385 -0.637802 -0.000101

C -0.015807 0.601671 0.000029 C -0.017215 0.595894 0.000003

H -0.235091 1.668823 0.000022 H -0.244627 1.661513 0.000005

C -1.108962 -0.279728 0.000070 C -1.110014 -0.284242 0.000018

H -0.957949 -1.397803 -0.000369 H -0.958276 -1.401136 -0.000004

C -2.461209 0.189383 0.000029 C -2.465281 0.192678 0.000370

O -2.791547 1.365387 0.000257 O -2.788154 1.365526 0.000285

O -3.353376 -0.807690 -0.000193 O -3.356083 -0.808823 -0.000099

C -4.736348 -0.422810 -0.000150 C -4.735969 -0.421461 -0.000346

H -4.963898 0.160524 -0.894798 H -4.965404 0.163984 -0.893358

H -5.298471 -1.354959 -0.000412 H -5.302808 -1.350982 -0.000731

H -4.963966 0.160059 0.894785 H -4.965849 0.163515 0.892859

[1aHα]•



C -3.722892 0.964886 -0.001894 C -3.720284 0.968842 -0.013061

C -2.371179 1.271295 -0.002525 C -2.367529 1.271221 -0.019111

C -1.386419 0.246613 -0.000835 C -1.385443 0.243708 -0.006966

C -1.837626 -1.100016 0.001475 C -1.840840 -1.101628 0.011161

C -3.194901 -1.394899 0.002069 C -3.199115 -1.392602 0.017428

C -4.147128 -0.370352 0.000402 C -4.148542 -0.365229 0.005422

H -4.455981 1.766658 -0.003177 H -4.450959 1.772615 -0.022698

30

H -2.046329 2.308883 -0.004286 H -2.039248 2.307561 -0.033369

H -1.114816 -1.910848 0.002754 H -1.119618 -1.913746 0.020380

H -3.517000 -2.432455 0.003833 H -3.524272 -2.428997 0.031750

H -5.206465 -0.607998 0.000886 H -5.208452 -0.599685 0.010356

C -0.008980 0.587242 -0.001421 C -0.006804 0.579821 -0.012752

H 0.268216 1.636558 -0.003245 H 0.276252 1.627479 -0.025206

C 1.076444 -0.432082 0.000549 C 1.078589 -0.439552 -0.004218

H 1.013721 -1.100837 -0.870845 H 1.019272 -1.108374 -0.875373

C 2.460154 0.164054 0.001324 C 2.461671 0.165515 0.009614

O 2.723982 1.350986 0.006683 O 2.716806 1.349654 0.051946

O 3.398132 -0.784814 -0.003924 O 3.401469 -0.784480 -0.027192

C 4.762397 -0.332609 -0.002032 C 4.761505 -0.327170 -0.011950

H 5.368452 -1.236711 -0.006448 H 5.374035 -1.226519 -0.046117

H 4.960538 0.264492 -0.894360 H 4.959115 0.301128 -0.882938

H 4.960873 0.255952 0.895879 H 4.961882 0.234568 0.902772

H 1.012655 -1.097867 0.874263 H 1.006553 -1.104985 0.869003

[1aHβ]•



C 3.547436 -0.377408 -0.571412 C 3.669479 -0.436393 -0.435029

C 2.430244 -1.144125 -0.233473 C 2.495418 -1.158335 -0.208446

C 1.294570 -0.539615 0.310495 C 1.334531 -0.510243 0.220245

C 1.287833 0.847525 0.503257 C 1.364347 0.877062 0.412362

C 2.402278 1.613941 0.167968 C 2.534539 1.599719 0.187971

C 3.536304 1.002446 -0.371519 C 3.692166 0.943640 -0.237580

H 4.425945 -0.860279 -0.989921 H 4.564921 -0.954350 -0.766355

H 2.441729 -2.220205 -0.388968 H 2.480865 -2.234224 -0.364374

H 0.404579 1.324160 0.924080 H 0.463464 1.390120 0.743706

H 2.386882 2.688239 0.328226 H 2.544176 2.674438 0.345084

H 4.405478 1.598958 -0.632785 H 4.604493 1.505715 -0.413632

C 0.062629 -1.357991 0.669435 C 0.048311 -1.280441 0.469891

H 0.310372 -2.423094 0.608691 H 0.234935 -2.347047 0.292174

C -1.047918 -1.052697 -0.271831 C -1.043022 -0.812407 -0.425746

H -1.011540 -1.409720 -1.295467 H -0.933890 -0.891106 -1.502196

C -2.157681 -0.212486 0.116951 C -2.253444 -0.215307 0.100698

O -2.301985 0.295816 1.226660 O -2.497604 -0.051464 1.289042

O -3.045235 -0.034133 -0.878232 O -3.107448 0.150738 -0.875486

C -4.180579 0.785642 -0.570518 C -4.332040 0.748305 -0.437879

H -4.777443 0.811198 -1.480713 H -4.886696 0.982934 -1.345184

H -4.754075 0.345189 0.248203 H -4.898249 0.048905 0.181799

31

H -3.857165 1.793064 -0.298988 H -4.130845 1.660053 0.129420

H -0.247691 -1.132356 1.694106 H -0.264467 -1.163241 1.512203

[1aHα]‒



C -3.752379 0.927041 -0.079233 C -3.755521 0.925048 -0.059442

C -2.416628 1.273225 -0.116253 C -2.420560 1.275919 -0.053089

C -1.353853 0.290991 -0.042889 C -1.354997 0.293744 -0.003569

C -1.819882 -1.075654 0.065866 C -1.819704 -1.077786 0.046373

C -3.172121 -1.394365 0.103377 C -3.171372 -1.400951 0.039477

C -4.173273 -0.415911 0.032270 C -4.174515 -0.422896 -0.014861

H -4.498545 1.718663 -0.138340 H -4.502934 1.716580 -0.099397

H -2.139446 2.323390 -0.202058 H -2.145000 2.329371 -0.088582

H -1.091797 -1.881918 0.116873 H -1.089588 -1.882666 0.088339

H -3.455094 -2.443417 0.186596 H -3.452625 -2.453011 0.077046

H -5.226008 -0.677914 0.059541 H -5.226591 -0.688323 -0.019958

C -0.009165 0.637765 -0.077129 C -0.011212 0.643069 -0.005042

H 0.282716 1.680043 -0.166428 H 0.285319 1.687350 -0.027977

C 1.068599 -0.402673 -0.009774 C 1.069948 -0.394576 0.043708

H 1.065329 -1.115326 -0.852292 H 1.029765 -1.115560 -0.791107

C 2.460532 0.160765 0.061834 C 2.465733 0.174234 0.037129

O 2.759748 1.312976 0.321493 O 2.770265 1.344326 0.139109

O 3.393349 -0.773695 -0.175979 O 3.389727 -0.795707 -0.087059

C 4.760645 -0.348855 -0.082034 C 4.755956 -0.368282 -0.076289

H 5.357306 -1.231870 -0.305339 H 5.350487 -1.274221 -0.186140

H 4.962100 0.439709 -0.810080 H 4.949621 0.313770 -0.907327

H 4.976201 0.010612 0.926545 H 4.994215 0.127966 0.867371

H 0.987611 -1.050186 0.884661 H 1.024873 -1.035347 0.944946

[1aHβ]‒



C 3.692713 -0.334255 0.265570 C 3.669572 -0.298006 0.300086

C 2.561809 -1.133831 0.076755 C 2.557896 -1.120857 0.092098

C 1.305841 -0.564444 -0.155627 C 1.296774 -0.577601 -0.172545

32

C 1.208649 0.833718 -0.193590 C 1.174701 0.819090 -0.228321

C 2.334156 1.636049 -0.018032 C 2.280555 1.643929 -0.034321

C 3.583551 1.054320 0.215917 C 3.535427 1.087690 0.235569

H 4.657191 -0.798783 0.453007 H 4.637986 -0.742335 0.514171

H 2.656205 -2.217274 0.114374 H 2.671471 -2.202046 0.141742

H 0.235926 1.290683 -0.363580 H 0.193941 1.246272 -0.429112

H 2.238066 2.717813 -0.059263 H 2.166633 2.723428 -0.088373

H 4.460324 1.679179 0.360094 H 4.396452 1.730226 0.395570

C 0.074694 -1.428982 -0.385501 C 0.079310 -1.460519 -0.407916

H -0.174194 -1.374110 -1.454648 H -0.182586 -1.380891 -1.472558

C -1.140709 -1.050715 0.416737 C -1.142114 -1.118053 0.402265

H -1.215051 -1.373092 1.451246 H -1.220324 -1.461351 1.429779

C -2.115005 -0.232560 -0.089327 C -2.108576 -0.266501 -0.099860

O -2.205228 0.281756 -1.255040 O -2.165692 0.287382 -1.230253

O -3.139758 0.073237 0.825573 O -3.157460 -0.013054 0.804506

C -4.285124 0.725257 0.297961 C -4.186872 0.830550 0.328767

H -4.971003 0.853202 1.137748 H -4.905631 0.923670 1.146578

H -4.038295 1.706246 -0.119196 H -3.811161 1.824632 0.063450

H -4.770695 0.120599 -0.475744 H -4.690454 0.406857 -0.547089

H 0.357967 -2.471753 -0.193473 H 0.388848 -2.501420 -0.243115

HE

E = -783.60137 Hartree

G = -783.39199 Hartree

C -1.220169 1.594897 -0.000074

C -1.258591 0.234902 -0.000104

C 0.000000 -0.611607 -0.000417

C 1.258591 0.234902 -0.000106

C 1.220169 1.594897 -0.000061

H 0.000000 3.247637 0.000048

H -0.000002 -1.278285 0.871534

N 0.000000 2.235356 -0.000245

H 0.000003 -1.277701 -0.872829

C 2.398771 2.524861 0.000152

H 3.023170 2.357219 0.880383

H 3.023291 2.357456 -0.880042

H 2.060261 3.563011 0.000262

C -2.398771 2.524861 0.000126

H -3.023498 2.357197 -0.879867

H -3.022962 2.357477 0.880557

33

H -2.060261 3.563011 -0.000138

C -2.541752 -0.462597 0.000072

O -3.662040 0.038398 0.000488

O -2.377625 -1.799685 -0.000241

C 2.541752 -0.462598 0.000029

O 3.662041 0.038397 0.000231

O 2.377625 -1.799685 -0.000054

C -3.576470 -2.584145 -0.000062

H -4.168034 -2.373727 -0.893809

H -3.245928 -3.621727 -0.000435

H -4.167461 -2.374186 0.894172

C 3.576469 -2.584146 0.000114

H 3.245927 -3.621728 0.000040

H 4.167886 -2.373937 -0.893780

H 4.167609 -2.373978 0.894201

HE•+

E = -783.3994389 Hartree

G = -783.192259 Hartree

C -1.226440 1.620027 -0.012816

C -1.250487 0.243379 0.006084

C 0.000000 -0.546856 0.002477

C 1.250486 0.243381 0.006147

C 1.226434 1.620030 -0.012734

H -0.000001 3.241389 -0.048316

H -0.000019 -1.251945 0.854389

N -0.000002 2.220645 -0.026473

H 0.000019 -1.237191 -0.862512

C 2.403124 2.541879 -0.022331

H 2.994157 2.404243 0.885932

H 3.047958 2.320503 -0.875143

H 2.072365 3.580048 -0.081068

C -2.403130 2.541876 -0.022500

H -3.047865 2.320553 -0.875400

H -2.994272 2.404197 0.885686

H -2.072366 3.580048 -0.081141

C -2.544109 -0.489913 0.023204

O -3.640539 0.032918 0.083675

34

O -2.356316 -1.804280 -0.032940

C 2.544109 -0.489910 0.023288

O 3.640529 0.032908 0.084069

O 2.356327 -1.804262 -0.033234

C -3.546324 -2.613251 -0.021234

H -4.166448 -2.371549 -0.886463

H -3.195827 -3.641869 -0.074232

H -4.101883 -2.441141 0.902492

C 3.546335 -2.613234 -0.021600

H 3.195849 -3.641837 -0.074967

H 4.166582 -2.371266 -0.886666

H 4.101761 -2.441405 0.902258

TSα

E = -1320.739163 Hartree

G = -1320.368104 Hartree

C 4.999491 0.302824 1.040614

C 3.670474 0.133268 1.410592

C 2.666590 0.974348 0.886695

C 3.030576 1.983480 -0.031375

C 4.360097 2.153292 -0.389131

C 5.347060 1.317089 0.145793

H 5.763982 -0.350086 1.449886

H 3.390968 -0.650125 2.110680

H 2.274912 2.639974 -0.452098

H 4.634409 2.937214 -1.088202

H 6.385823 1.456556 -0.138493

C 1.310626 0.768714 1.329670

C 0.178085 1.399627 0.836454

H 1.162006 0.014697 2.101978

C -1.092507 1.244559 1.598826

O -1.291358 0.397853 2.450245

O -2.016238 2.108646 1.187043

C -3.289366 2.047022 1.856772

H -3.915538 2.786865 1.361797

H -3.718620 1.048727 1.755287

H -3.161048 2.295861 2.912251

H 0.243476 2.275244 0.194505

H -0.276465 0.463863 -0.220413

C -0.750958 -0.498365 -0.987083

35

C -2.164905 -0.571085 -0.683437

C 0.079751 -1.614146 -0.587458

H -0.479647 0.010663 -1.912474

C -2.648890 -1.584625 0.119284

C -3.053899 0.519757 -1.152125

C -0.431310 -2.585632 0.248400

C 1.499339 -1.645772 -1.007604

N -1.755221 -2.513012 0.565249

C -4.067857 -1.799445 0.538268

O -4.257747 0.571534 -0.974780

O -2.366144 1.470837 -1.782371

C 0.311041 -3.744357 0.830634

O 2.312450 -2.493074 -0.681654

O 1.796873 -0.621953 -1.808308

H -2.121649 -3.249522 1.165684

H -4.440438 -0.936941 1.094604

H -4.702518 -1.919941 -0.342795

H -4.148398 -2.690946 1.162806

C -3.119124 2.618773 -2.205942

H 0.716184 -4.371372 0.033036

H 1.153021 -3.387597 1.428451

H -0.350066 -4.343014 1.459289

C 3.149538 -0.577025 -2.292173

H -3.572148 3.105720 -1.339327

H -2.396706 3.279160 -2.681706

H -3.892002 2.318970 -2.916139

H 3.216894 0.334752 -2.882721

H 3.848184 -0.549538 -1.453133

H 3.346125 -1.452660 -2.914944

TSβ

E = -1320.732105 Hartree

G = -1320.361618 Hartree

C -3.683682 -1.140080 -1.481453

C -2.319514 -0.869690 -1.592166

C -1.381152 -1.653002 -0.906029

C -1.826187 -2.717529 -0.107424

C -3.185301 -2.990051 -0.006620

C -4.117385 -2.199919 -0.688193

H -4.402025 -0.523037 -2.013081

H -1.973758 -0.048355 -2.216154

H -1.116779 -3.325456 0.446217

36

H -3.523961 -3.814527 0.613778

H -5.178516 -2.412267 -0.595775

C 0.038990 -1.254959 -0.989302

C 1.123296 -2.051088 -0.622985

H 0.256748 -0.474981 -1.725047

H 1.023138 -2.963923 -0.046153

C 2.479510 -1.588189 -0.937233

O 2.740554 -0.541433 -1.515624

O 3.414524 -2.438315 -0.510422

C 4.774122 -2.090436 -0.821220

H 5.005261 -1.088181 -0.454112

H 5.387639 -2.836047 -0.318874

H 4.926681 -2.133511 -1.902106

H 0.068276 -0.302932 0.061017

C -0.023401 0.815480 0.813414

C -1.233332 1.458555 0.367088

C 1.232093 1.453446 0.498273

H -0.075173 0.256385 1.747308

C -1.156711 2.429956 -0.614875

C -2.543921 1.055204 0.935658

C 1.273468 2.427763 -0.474542

C 2.479078 0.941457 1.118524

N 0.083809 2.820979 -1.016467

C -2.304178 3.106143 -1.290668

O -3.592797 1.642589 0.741481

O -2.438221 -0.011095 1.724364

C 2.495633 3.097126 -1.010834

O 3.546259 1.524365 1.127566

O 2.285782 -0.253017 1.676512

H 0.127409 3.527300 -1.750055

H -3.047571 2.371039 -1.604881

H -2.792546 3.795049 -0.595766

H -1.954513 3.665900 -2.160129

C -3.637996 -0.418695 2.404875

H 2.898962 3.789655 -0.266661

H 3.267383 2.357311 -1.231448

H 2.254190 3.653179 -1.918222

C 3.409275 -0.829609 2.365388

H -4.438751 -0.599900 1.686512

H -3.375970 -1.336324 2.928819

H -3.936336 0.356530 3.114345

H 3.084011 -1.823668 2.666784

H 4.271866 -0.890459 1.700374

H 3.652649 -0.221695 3.239481

37

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40

Spectra

1H and 13C NMR for compound (1b)

41

1H and 13C NMR for compound (1c)

42

1H and 13C NMR for compound (1d)

43

1H, 13C and 19F NMR for compound (1e)

44

1H, 13C and 19F NMR for compound (1f)

46

1H, 13C and 19F NMR for compound (1g)

47

1H and 13C NMR for compound (1j)

48

1H and 13C NMR for compound (1k)

49

1H, 13C and 19F NMR for compound (1l)

51

1H and 13C NMR for compound (1m)

52

1H and 13C NMR for compound (1n)

53

1H and 13C NMR for compound (1o)

54

1H and 13C NMR for compound (1p)

55

1H and 13C NMR for compound (1q)

56

1H and 13C NMR for compound (1r)

57

1H and 13C NMR for compound (1t)

58

1H and 13C NMR for compound (1u)

59

1H and 13C NMR for compound (1v)

60

1H and 13C NMR for compound (1w)

61

1H and 13C NMR for compound (1z)

62

1H and 13C NMR for compound (2a)

63

1H and 13C NMR for compound (2b)

64

1H and 13C NMR for compound (2c)

65

1H and 13C NMR for compound (2d)

66

1H, 13C and 19F NMR for compound (2e)

67

1H, 13C and 19F NMR for compound (2f)

69

1H, 13C and 19F NMR for compound (2g)

70

1H and 13C NMR for compound (2i)

71

1H and 13C NMR for compound (2j)

72

1H and 13C NMR for compound (2k)

73

1H and 13C NMR for compound (2l)

75

1H and 13C NMR for compound (2m)

76

1H and 13C NMR for compound (2p)

77

1H and 13C NMR for compound (2q)

78

1H and 13C NMR for compound (2r)

79

1H and 13C NMR for compound (2t)

80

1H and 13C NMR for compound (2u)

81

1H and 13C NMR for compound (2y)

82

1H and 13C NMR for compound (2aa)

NMR purity = 81%; 16% of Hantzsch pyridine, 4% of starting material and 1% of Et2O.

83

1H and 13C NMR for compound (2ab)

84

1H NMR for compound (4,4’-d2-HE)

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efficient reduction of electron-deficient alkenes enabled

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