organocatalytic asymmetric remote aziridination of 2,4-dienals · 3.1 organocatalytic asymmetric...

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Organocatalytic Asymmetric Remote Aziridination of 2,4-Dienals

Kim Søholm Halskov, Tricia Naicker, Magnus E. Jensen and Karl Anker Jørgensen*

[*] Center for Catalysis

Department of Chemistry, Aarhus University

DK-8000 Aarhus C, Denmark

Fax (45) 8715 5956, e-mail: [email protected]

Contents

1. General methods S2

2. Synthesis of starting materials S3

3. General procedure for the organocatalytic reactions S5

3.1 Organocatalytic asymmetric remote aziridinaton

of 2,4-dienals S5

3.2 NHC-Catalyzed allylic aziridine ring-opening S8

3.3 Oxazolidinone formation S8

3.4 Organocatalytic asymmetric 1,6-addition of thiols S9

4. Assignment of absolute configuration by NMR analysis S11

5. NMR spectra of novel compounds S17

6. UPC2 traces S39

Electronic Supplementary Material (ESI) for Chemical CommunicationsThis journal is © The Royal Society of Chemistry 2013

mailto:[email protected]

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1. General methods

NMR spectra were acquired on a Bruker AVANCE III HD spectrometer running at 400 MHz for 1H

and 100 MHz for 13C. 2D homonuclear COSY experiments and heteronuclear HSQC and HMBC

experiments were recorded according to the standard Bruker library with 8 and 512, 8 and 256

and 16 and 512 scans, respectively. Chemical shifts () are reported in ppm relative to residual

solvent signals (CHCl3, 7.26 ppm for 1H NMR, CDCl3, 77.0 ppm for

13C NMR). The following

abbreviations are used to indicate the multiplicity in NMR spectra: s, singlet; d, doublet; t, triplet;

q, quartet; m, multiplet; bs, broad signal. 13C NMR spectra were acquired in broad band decoupled

mode. Mass spectra were recorded on a Bruker MicroTOF-Q High Performance LC-MS system.

Analytical thin layer chromatography (TLC) was performed using pre-coated aluminium-backed

plates (Merck Kieselgel 60 F254) and visualized by ultraviolet radiation, KMnO4 or p-anisaldehyde

stains. For flash chromatography (FC) silica gel (Silica gel 60, 230-400 mesh, Fluka) was used.

Optical rotations were measured on a Bellingham+Stanley ADP440+ polarimeter, α values are

given in deg·cm3·g-1·dm-1; concentration c in g·(100 ml)-1. The enantiomeric excess (ee) of the

products was determined by chiral stationary phase Waters ACQUITY UPC2 (Daicel Chiralpak).

Unless otherwise noted, gradient runs were performed with 100% supercritical CO2 for 30 s, then

going from 99% CO2 to 60:40 CO2/solvent over 4 min. Racemic samples were prepared using

equimolar amounts of product obtained from reactions with 3 and ent-3. Unless otherwise noted,

analytical grade solvents and commercially available reagents were used without further

purification.


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2. Synthesis of starting materials

The dienals were synthesized starting from their corresponding cyclohexenones using a Horner-

Wadsworth-Emmons and DIBAL-H reduction sequence according to the procedures previously

reported.1 The synthesis and characterizational data of dienals 1a and 1c are described in the

literature.2 The cyclohexenone precursors of compounds 1f, 1h and 1i were purchased from

commercial sources. The cyclohexenone precursor of dienal 1b was synthesized from 2-

ethylcyclohexanone by an α-bromination and the elimination sequence carried out in similar

fashion as the procedure previously reported for 2-methylcyclohexanone.3 The cyclohexenone

precursors of compounds 1d and 1g were synthesized from their cyclohexenone and

cycloheptenone, respectively, via an α-iodation, benzylation sequence carried out according to

procedures previously reported.4 The cyclohexenone precursor of compound 1e was formed by a

Morita-Baylis-Hillman reaction followed by silyl-ether protection carried out according to

procedures previously reported.5 Aziridination reagent 2 was synthesized according to procedures

previously reported.6 Catalysts 3 and 5 were purchased from commercial sources.

Pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 10.14 (d, J = 8.0 Hz, 1H), 6.18–6.14 (m, 1H), 5.99–

5.94 (m, 1H), 2.89 (ddd, J = 8.1, 4.7, 1.7 Hz, 2H), 2.30–2.18 (m, 4H), 1.82–1.73 (m, 2H), 1.05 (t, J = 7.4

Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 191.8, 156.78, 138.7, 136.2, 122.3, 26.5, 26.2, 25.6, 22.5,

13.3. HRMS (ESI+) m/z calcd. for C10H14O3 [M+H]+: 151.1123; found: 151.1141.

Pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 10.11 (d, J = 8.1 Hz, 1H), 7.20 (t, J = 7.9 Hz, 1H),

6.78-6.72 (m, 2H), 6.72-6.69 (m, 1H), 6.13 (t, J = 4.3 Hz, 1H), 5.96 (d, J = 8.1 Hz, 1H), 3.79 (s, 3H),

3.54 (s, 2H), 2.94 (dt, J = 6.5; 1.6 Hz, 2H), 2.34 (d, J = 6.0 Hz, 2H), 1.88-1.80 (m, 2H). 13C NMR

(100 MHz, CDCl3): δ 191.4, 159.7, 156.0, 140.8, 139.8, 135.9, 129.4, 123.2, 121.0, 114.6, 111.3,

55.1, 39.2, 26.5, 26.1, 22.2. HRMS (ESI+) m/z calcd. for C16H18O2 [M+H]+: 243.1380; found:

243.1382.

1 H. Jiang, K. S. Halskov, T. K. Johansen, K. A. Jørgensen, Chem. Eur. J. 2011, 17, 3842.

2 K. S. Halskov, T. K. Johansen, R. L. Davis, M. Steurer, F. Jensen, K. A. Jørgensen, J. Am. Chem. Soc. 2012, 134, 12943.

3 L. Baker, T. Minehan, J. Org. Chem. 2004, 69, 3957.

4 a) M. E. Krafft, J. W. Cran, Synlett. 2005, 1263; b) E. Negishi, Z. Tan, S.-Y. Liou, B. Liao, Tetrahedron, 2000, 56, 10197.

5 a) K. P. Guerra, C. A. M. Alonso, Eur. J. Org. Chem. 2011, 2372; b) K. C. M. Kurtz, R. P. Hsung, Y. Zhang, Org. Lett. 2006,

8, 231. 6 H. Lebel, K. Huard, S. Lectard, J. Am. Chem. Soc. 2005, 127, 14198.


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Pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 10.13 (d, J = 8.1 Hz, 1H), 6.49 (t, J = 4.5 Hz,

1H), 5.84 (d, J = 8.1 Hz, 1H), 4.29 (q, J = 2.0 Hz, 2H), 2.91 (dt, J = 6.5 Hz; 1.7 Hz, 2H), 2.36-

2.29 (m, 2H), 1.84-1.76 (m, 2H), 0.90 (s, 9H), 0.07 (s, 6H). 13C NMR (100 MHz, CDCl3): δ

191.4, 154.9, 136.6, 135.6, 121.7, 62.7, 26.1, 25.9 (3C), 25.8, 22.2, 18.4, -5.4 (2C). HRMS (ESI+)

m/z calcd. for C15H26O2Si [M-TBS+H+Na]+: 175.0730; found: 175.0729.

Pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 9.93–9.85 (m, 1H), 6.40 (dt, J = 3.0, 1.5 Hz, 1H), 5.90

(dt, J = 8.2; 2.4 Hz, 1H), 3.08 (dt, J = 7.3, 2.3 Hz, 2H), 2.58 (dp, J = 7.1; 2.2 Hz, 2H), 2.16 (ddt, J = 9.7;

5.5; 1.8 Hz, 2H), 1.55–1.44 (m, 2H), 1.30 (m, 4H), 0.88 (dt, J = 6.1; 2.6 Hz, 3H). 13C NMR (100 MHz,

CDCl3): δ 191.8, 171.5, 146.1, 144.8, 117.0, 31.8, 31.5, 28.6, 27.5, 26.8, 22.6, 14.1. HRMS (ESI+)

m/z calcd. for C12H18O [M+H]+: 179.1430; found: 179.1417.

Pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 9.71 (d, J = 8.5 Hz, 1H), 7.33–6.88 (m, 5H), 5.82 (d, J =

8.5 Hz, 1H), 5.76 (t, 1H), 3.55–3.31 (s, 2H), 2.11–2.00 (m, 3H), 2.01–1.87 (m, 2H), 1.83–1.62 (m, 2H),

1.57–1.34 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 192.1, 170.0, 141.7, 138.2, 129.3, 129.1, 128.4,

127.3, 126.5, 47.2, 37.8, 31.8, 27.8, 25.4. HRMS (ESI+) m/z calcd. for C16H19O [M+H]+: 227.1430;

found: 227.1413.

Pale yellow oil. [ ] = +15.9 (c 3.99, CHCl3, 1i).

1H NMR (400 MHz, CDCl3): δ

10.16 (d, J = 8.0 Hz, 1H), 6.25–6.12 (m, 1H), 5.95 (dd, J = 8.1, 2.0 Hz, 1H), 4.87–4.70 (m,

2H), 3.47–3.29 (m, 1H), 2.49–2.14 (m, 4H), 1.92–1.72 (m, 6H). 13C NMR (100 MHz,

CDCl3): δ 191.4, 191.4, 157.2, 157.1, 147.7, 137.4, 137.3, 132.8, 123.0, 110.3, 41.3,

31.8, 30.8, 20.5, 19.4. HRMS (ESI+) m/z calcd. for C12H16O [M+H]+: 177.1274;

found: 177.1256.


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3. General procedure for the organocatalytic reactions

3.1 Organocatalytic asymmetric remote aziridinaton of 2,4-dienals

A glass vial equipped with a magnetic stirring bar was charged with dienal 1 (0.1 mmol, 1.0 eq.),

aziridination reagent 2 (0.2 mmol, 2 eq.), catalyst 3 (0.01 mmol, 0.1 eq.), NaOAc (0.4 mmol, 4.0 eq.) and

CH2Cl2 (0.3 mL). The mixture was stirred for 20 h at ambient temperature. The mixture was subsequently

subjected directly to FC on silica gel with a thin layer of neutral Al2O3 to yield product type 4.

Table S1 Optimization of the Organocatalytic Asymmetric Remote Aziridination of the 2,4-dienal 1a.a

Entry 1 3 (mol%) Conv. (%)b Solvent eec

1 10 72 CH2Cl2 92

2 10 40 Toluene 98 3 15 75 CH2Cl2 92

4d 10 68 CH2Cl2 92

5e 10 >95 (77) CH2Cl2 95 6e 10 62 Toluene 98

a Reactions were performed on a 0.1 mmol scale. b Determined by 1H NMR analysis of the crude mixture of 4a after 20 h. Isolated yield by FC is

given in parenthesis. c Determined by chiral stationary phase UPC2. d The reaction was performed at 40 ˚C. e 2.0 eq. of 2 and 4 eq. NaOAc were used.

Pale yellow oil. [ ] = +24.1 (c 0.4, CHCl3).

1H NMR (400 MHz, CDCl3): δ 10.07 (d, J = 7.8

Hz, 1H), 6.16 (d, J = 7.8 Hz, 1H), 2.86 (ddd, J = 14.9 Hz; 8.2 Hz; 3.8 Hz, 1H), 2.75 (dd, J = 4.1

Hz; 1.4 Hz, 1H), 2.59-2.50 (m, 1H), 2.12-2.02 (m, 1H), 1.95-1.85 (m, 1H), 1.78-1.66 (m, 1H),

1.58-1.48 (m, 1H), 1.46 (s, 9H), 1.43 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 190.4, 162.0,

160.2, 127.5, 81.6, 45.3, 43.6, 28.0 (3C), 24.6, 23.1, 20.0, 18.6. HRMS (ESI+) m/z calcd. for

C14H21NO3 [M+H2O+Na]+: 292.1519; found: 292.1541. UPC2: IC, CO2/i-PrOH gradient, 3.0 mL·min

–1; tmajor =

2.61 min; tminor = 2.67 min.


1H NMR (400 MHz, CDCl3): δ 10.30 (d, J = 7.8

Hz, 1H), 6.41 (d, J = 7.8 Hz, 1H), 3.35 (dt, J = 15.3 Hz; 4.1 Hz, 1H), 2.86 (dd, J = 3.5 Hz; 1.7 Hz,

1H), 2.66-1.89 (m, 4H), 1.64 (s, 11 H), 1.44 (d, J = 6.6 Hz, 1H), 1.24-0.99 (m, 3H). 13C NMR

(100 MHz, CDCl3): δ 190.3, 160.1, 159.6, 128.4, 81.4, 47.4, 42.8, 28.0 (3C), 26.7, 26.1, 23.7,

18.3, 10.7. HRMS (ESI+) m/z calcd. for C15H23NO3 [M+H2O+Na]+: 306.1676; found: 306.1673.

UPC2: IC, CO2/i-PrOH gradient, 3.0 mL·min–1; tmajor = 2.95 min; tminor = 3.00 min.


1H NMR (400 MHz, CDCl3): δ 9.99 (d, J = 7.8 Hz,

1H), 7.31-7.18 (m, 3H), 7.15 (d, J = 7.2 Hz, 2H), 6.31 (d, J = 7.8 Hz, 1H), 3.63 (d, J = 14.5 Hz,


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1H), 3.12-3.04 (m, 1H), 3.02-2.98 (m, 1H), 2.31 (d, J = 14.5 Hz, 1H), 2.27-2.19 (m, 1H), 1.93-1.82 (m, 1H),

1.75-1.65 (m, 1H), 1.63-1.54 (m, 1H), 1.51 (s, 9H), 1.31-1.26 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 190.1,

159.9, 159.3, 136.3, 129.5, 128.8 (2C), 128.7 (2C), 127.0, 81.8, 46.0, 43.4, 39.7, 28.1 (3C), 26.2, 23.4, 17.9.

HRMS (ESI+) m/z calcd. for C20H25NO3 [M+H2O+Na]+: 368.1832; found: 368.1835. UPC2: IA, CO2/i-PrOH

gradient, 3.0 mL·min–1; tmajor = 2.20 min; tminor = 2.37 min.


1H NMR (400 MHz, CDCl3): δ 10.0 (d, J = 7.8

Hz, 1H), 7.19 (t, J= 7.9 Hz, 1H), 6.78-6.72 (m, 2H), 6.69 (s, 1H), 6.30 (dd, J = 7.8; 1.6 Hz,

1H), 3.77 (s, 3H), 3.60 (d, J = 14.7 Hz, 1H), 3.09 (dt, J = 15.1; 3.6 Hz, 1H), 2.29 (d, J= 14.7

Hz, 1H), 2.24 (dt, J = 15.1; 4.6 Hz, 1H), 1.95-1.84 (m, 1H), 1.83-1.72 (m, 1H), 1.64-1.53 (m,

1H), 1.51. (s, 9H), 1.32-1.23 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 190.1, 159.9, 159.8,

159.2, 137.9, 129.7, 129.5, 121.1, 114.8, 112.1, 81.8, 55.2, 45.9, 43.7, 39.7, 28.1 (3C),

26.2, 23.4, 18.0. HRMS (ESI+) m/z calcd. for C21H27NO4 [M+H2O+Na]+: 398.1938; found: 398.1837. UPC2: IC,

CO2/i-PrOH gradient, 3.0 mL·min–1; tmajor = 3.26 min; tminor = 3.36 min.

Pale yellow oil. [ ] = -2.5 (c 0.8, CHCl3).

1H NMR (400 MHz, CDCl3): δ 10.08 (d, J = 7.6

Hz, 1H), 6.12 (d, J = 7.6 Hz, 1H), 4.07 (d, J = 11.2 Hz, 1H), 3.81 (d, J = 11.2 Hz, 1H), 3.11-

3.03 (m, 1H), 3.03-2.99 (m, 1H), 2.28-2.11 (m, 2H), 1.87-1.75 (m, 1H), 1.44 (s, 9H), 1.32-

1.22 (m, 2H), 0.87 (s, 9H), 0.05 (s, 3H), 0.04 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 190.2,

159.3, 159.1, 128.2, 81.2, 61.3, 45.8, 39.6, 29.7, 28.1 (3C), 25.9 (3C), 25.5, 23.1, 18.8, -5.3,

-5.4. HRMS (ESI+) m/z calcd. for C20H35NO4Si [M+H2O+Na]+: 422.2333; found: 422.2338. UPC2: ID, CO2/i-

PrOH 95:5, 3.0 mL·min–1; tmajor = 1.72 min; tminor = 1.49 min.



1H), 6.14 (dt, J = 7.4 Hz; 2.2 Hz, 1H), 3.26-3.16 (m, 1H), 3.13 (d, J = 3.1 Hz, 1H), 2.43-2.33 (m,

1H), 2.18-2.06 (m, 1H), 2.05-1.91 (m, 2H), 1.73 (ddd, J = 14.6, 9.9, 6.1 Hz, 1H), 1.41 (s, 9H),

1.32-1.23 (m, 3H), 0.93-0.84 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 190.9, 165.1, 158.4,

125.5, 81.3, 55.4, 49.7, 31.8, 28.5, 28.0 (3C), 25.9, 25.2, 23.9, 22.5, 14.0. HRMS (ESI+) m/z

calcd. for C17H27NO3 [M+H2O+Na]+: 334.1989; found: 334.1994. UPC2: IC, CO2/i-PrOH gradient, 3.0 mL·min

–1;

tmajor = 3.11 min; tminor = 3.02 min.


1H NMR (400 MHz, CDCl3): δ 9.93 (d, J = 8.0

Hz, 1H), 7.42–6.92 (m, 5H), 6.35 (d, J = 8.0 Hz, 1H), 3.24 (d, J = 14.0 Hz, 1H), 3.02–2.45 (m,

3H), 2.19 (ddd, J = 14.2, 8.8, 4.9 Hz, 1H), 1.88–0.94 (m, 15H). 13C NMR (100 MHz, CDCl3): δ

190.7, 164.5, 160.0, 136.1, 130.7, 129.7, 129.7, 128.7, 127.1, 81.5, 77.2, 54.4, 44.8, 41.9,

30.3, 29.5, 29.3, 28.1 (3C), 27.4, 22.7. HRMS (ESI+) m/z calcd. for C21H27NO3 [M+H]+:

342.2065; found: 342.2064. UPC2: IA, CO2/CH2Cl2 gradient, 3.0 mL·min–1; tmajor = 3.42 min; tminor = 3.66 min.


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1H NMR (400 MHz, CDCl3): δ 10.09 (d, J = 7.7

Hz, 1H), 6.22 (d, J = 7.7 Hz, 1H), 4.80 (s, 1H), 4.73 (s, 1H), 3.15 (d, J = 15.4 Hz, 1H), 2.81-2.78

(m, 1H), 2.46-2.37 (m, 1H), 2.31-2.21 (m, 2H), 1.72 (s, 3H), 1.55 (s, 3H), 1.48 (s, 9H), 1.47-

1.41 (m, 1H). 13C NMR (100 MHz, CDCl3): 190.2, 160.2, 160.1, 147.2, 128.8, 110.5, 81.7,

45.0, 43.0, 36.0, 30.4, 28.9, 28.1 (3C), 20.7, 18.8. HRMS (ESI+) m/z calcd. for C17H25NO3

[M+H2O+Na]+: 332.1832; found: 3321833.



1H), 6.12 (d, J = 7.8 Hz, 1H), 4.78-4.72 (m, 2H), 3.12-3.04 (m, 1H), 2.86-2.81 (m, 1H), 2.47-

2.32 (m, 1H), 2.27-2.04 (m, 2H), 1.72 (s, 3H), 1.55 (s, 3H), 1.46 (s, 9H), 1.36-1.21 (m, 1H). 13C

NMR (100 MHz, CDCl3): δ 190.2, 163.0, 160.1, 147.2, 126.7, 110.6, 81.8, 47.0, 44.7, 44.2,

28.5, 28.4, 28.0 (3C), 19.8, 17.6. HRMS (ESI+) m/z calcd. for C17H25NO3 [M+H2O+Na]+:

332.1832; found: 332.1836.


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3.2 NHC-Catalyzed allylic aziridine ring-opening

Aziridine enal 4 (0.1 mmol, 1.0 eq.) was dissolved in a 1:1 mixture of CH2Cl2 and MeOH (0.3 mL) in a glass

vial equipped with a magnetic stirring bar. NHC catalyst 6 (0.005 mmol, 0.05 eq.) was added along with

NaOAc (0.01 mmol, 0.1 eq). The mixture was stirred for 20 h at ambient temperature. The mixture was

subsequently subjected directly to FC on silica gel to yield product type 6.

Colourless oil. [ ] = +56.9 (c 1.3, CHCl3).

1H NMR (400 MHz, CDCl3): δ 7-30-7.22 (m,

2H), 7.20-7.09 (m, 3H), 4.57-4.47 (d, J = 8.9 Hz, 1H), 4.13-4.04 (m, 1H), 3.65 (s, 3H), 3.55

(d, J = 15.8 Hz, 1H), 3.37 (d, J = 15.8 Hz, 1H), 3.22 (d, J = 15.6 Hz, 1H), 3.01 (d, J = 15.6 Hz,

1H), 2.20-2.02 (m, 2H), 1.81-1.52 (m, 4H), 1.40 (s, 9H). 13C NMR (100 MHz, CDCl3): δ

171.8, 155.1, 139.5, 133.3, 130.5, 128.4 (2C), 128.2 (2C), 126.0, 79.0, 51.8, 47.8, 38.9,

36.0, 30.2, 29.7, 28.4 (3C), 18.4. HRMS (ESI+) m/z calcd. for C21H29NO4 [M+Na]+:

382.1989; found: 382.1991. UPC2: IC, CO2/i-PrOH gradient, 3.0 mL·min–1; tmajor = 2.80 min; tminor = 3.09 min.


1H NMR (400 MHz, CDCl3): δ 4.75 (s, 1H), 4.72

(s, 1H), 4.62 (d, J = 8.8 Hz, 1H), 4.15-4.07 (m, 1H), 3.68 (s, 3H), 3.11 (d, J = 15.4, 1H), 2.97

(d, J = 15.4 Hz, 1H), 2.23-2.06 (m, 2H), 1.97-1.85 (m, 1H), 1.73 (s, 3H), 1.72 (s, 3H), 1.62-

1.51 (m, 1H), 1.43 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 171.8, 155.4, 148.6, 129.9, 127.9,

109.3, 79.3, 51.8, 50.5, 38.7, 36.6, 35.7, 34.3, 28.4 (3C), 20.8, 16.8. HRMS (ESI+) m/z

calcd. for C18H29NO4 [M+Na]+: 346.1989; found: 346.1993.

3.3 Oxazolidinone formation

To a solution of aziridine enal 4 (0.30mmol, 1 eq.) in MeOH (3 mL) was added NaBH4 (0.45 mmol, 1.5 eq.) at

0 0C. After stirring for 15 min the reaction was allowed to reach rt and stirred for further 10 min. Water (5.0

mL) was then added and the resulting solution was extracted three times with EtOAc. The combined

organic layers were dried over Na2SO4 and concentrated in vacuo. To the crude alcohol intermediate, HCl in

dioxane (1M, 1.5 mL) was added and stirred at rt for 1 h. The mixture was then neutralized with saturated

NaHCO solution and extracted three times with EtOAc. The combined organic layers were dried over

Na2SO4 and concentrated in vacuo and directly subjected to FC on silica gel (100% EtOAc).

Colourless oil. [ ] = -14.7 (c 0.4, CHCl3).

1H NMR (400 MHz, CDCl3): δ 5.83 (ddt, J = 6.4,

4.7, 2.4 Hz, 1H), 5.61 (s, 1H), 4.22 (d, J = 6.5 Hz, 2H), 4.04 (d, J = 5.2 Hz, 1H), 2.75–2.24 (m,

2H), 2.10–1.53 (m, 4H), 1.47–1.12 (m, 6H), 1.04–0.70 (m, 3H). 13C NMR (100 MHz, CDCl3): δ

158.8, 144.0, 91.7, 60.5, 35.9, 31.8, 30.9, 26.2, 23.2, 22.4. HRMS (ESI+) m/z calcd. for

C13H21NO3 [M+Na]+: 262.1414; found: 262.1393. UPC2: IC, CO2/i-PrOH gradient, 3.0

mL·min–1; tmajor = 5.74 min; tminor = 5.49 min.


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1H NMR (400 MHz, CDCl3): δ 6.14–5.95 (m,

1H), 4.88–4.58 (m, 2H), 4.33–4.15 (m, 2H), 3.88 (t, J = 3.2 Hz, 1H), 3.81–3.71 (m, 1H),

3.69–3.54 (m, 1H), 2.83–2.59 (m, 1H), 2.42–2.27 (m, 1H), 1.75 (t, J = 1.1 Hz, 2H), 1.63–

1.50 (m, 6H) 13C NMR (100 MHz, CDCl3): δ 147.4, 140.3, 110.0, 83.2, 72.2, 71.1, 58.6,

58.5, 31.8, 30.6, 28.9, 26.9. HRMS (ESI+) m/z calcd. for C13H19NO3 [M+H]+: 238.1438;

found: 238.1430.

3.4 Organocatalytic asymmetric 1,6-addition of thiols

A glass vial equipped with a magnetic stirring bar was charged with dienal 1 (0.1 mmol, 1.0 eq.), catalyst 3

(0.02 mmol, 0.2 eq.) and toluene (0.3 mL). Thiol 8 was then added to the mixture, which was then stirred

for 48 h at ambient temperature. The mixture was subsequently subjected directly to FC on silica gel to

yield product type 9.

Yellow oil. [ ] = +78.4 (c 4.7, CHCl3).

1H NMR (400 MHz, CDCl3): δ 9.50 (t, J = 2.5 Hz, 1H),

7.36-7.28 (m, 4H), 7.26-7.21 (m, 1H), 3.73 (s, 2H), 3.11-2.99 (m, 4H), 2.01-1.86 (m, 4H), 1.80-

1.69 (m, 1H), 1.65 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 199.0, 138.7, 131.5, 128.9 (2C), 128.4

(2C), 126.9, 125.7, 49.1, 46.9, 36.6, 31.0, 28.8, 18.6, 18.3. HRMS (ESI+) m/z calcd. for

C16H20OS [M+Na]+: 283.1127; found: 283.1128. UPC2: IB, CO2/i-PrOH gradient, 3.0 mL·min

–1;

tmajor = 2.97 min; tminor = 3.05 min.

Yellow oil. [ ] = +3.81 (c 0.18, CHCl3).

1H NMR (400 MHz, CDCl3): δ 9.52 (s, 1H), 7.39–7.17

(m, 5H), 3.72 (s, 2H), 3.05 (d, J = 2.5 Hz, 2H), 2.05 (d, J = 7.6 Hz, 2H), 1.99–1.90 (m, 3H), 1.75–

1.62 (m, 3H), 1.55 (s, 1H), 0.76 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 199.7, 138.7,

137.6, 128.9 (2C), 128.5 (2C), 126.9, 125.4, 48.7, 43.6, 36.8, 30.8, 28.8, 24.8, 18.4, 13.6.

HRMS (ESI+) m/z calcd. for C17H22OS [M+H]+: 275.1464; found: 275.1464. UPC2: IB,

CO2/CH2Cl2 gradient, 3.0 mL·min–1; tmajor = 3.07 min; tminor = 3.14 min.


S10

Yellow oil. [ ] = +3.07 (c 3.02, CHCl3).

1H NMR (400 MHz, CDCl3): δ 9.50 (t, J = 2.2 Hz, 1H),

7.36-7.08 (m, 8H), 6.89 (d, J = 7.4 Hz, 2H), 3.66 (d, J = 3.6 Hz, 2H), 3.55 (d, J = 15.5 Hz, 1H),

3.44 (d, J = 15.5 Hz, 1H), 3.24 (dd, J = 15.8 Hz; 2.2 Hz, 1H), 3.15-3.07 (m, 2H), 2.16-1.53 (m,

6H). 13C NMR (100 MHz, CDCl3): δ 199.2, 139.7, 138.7, 134.6, 128.9 (2C), 128.5 (2C), 128.4

(2C), 128.3 (2C), 127.8, 126.9, 126.0, 49.0, 44.0, 36.8, 36.6, 30.9, 28.5, 18.2. HRMS (ESI+) m/z

calcd. for C22H24OS [M+Na]+: 359.1440; found: 359.1446. UPC2: IB, CO2/i-PrOH gradient, 3.0 mL·min

–1; tmajor =

2.67 min; tminor = 2.91 min.


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4. Assignment of absolute configuration by NMR analysis

8a 2a

4b


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HSQC SPECTRUM 4h

HMBC SPECTRUM 4h


S13

COSY SPECTRUM 4h

NOESY SPECTRUM 4h


S14

3 6 8a 2a 4b 5

7a


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HSQC SPECTRUM 4i

HMBC SPECTRUM 4i


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COSY SPECTRUM 4i

NOESY SPECTRUM 4i


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5. NMR spectra of novel compounds


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S19


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S21


S22


S23


S24


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S27


S28


S29


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6. UPC2 traces

Default109

Project Name: Kim HReported by User: Group 109 (group)

Report Method: Default109 Date Printed:

1106 5/29/2013Report Method ID: 1106

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3.0

30

3.1

30

AU

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

Minutes

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

1

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Retention Time

(min)% Area

3.030

3.130

82.75

17.25Default109



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3.0

71

3.1

65

AU

-0.05

0.00

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0.15

0.20

0.25

0.30

0.35

0.40

Minutes

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

1

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Retention Time

(min)% Area

3.071

3.165

2.29

97.71


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2.9

51

2.9

93

AU

0.00

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0.30

0.40

0.50

0.60

Minutes

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

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Retention Time

(min)% Area

2.951

2.993

16.73

83.27

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2.9

54

2.9

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AU

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Retention Time

(min)% Area

2.954

2.997

97.74

2.26


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2.2

12 2

.38

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0.10

0.12

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0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

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Retention Time

(min)% Area

2.212

2.386

43.10

56.90

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2.2

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2.3

74

AU

-0.02

0.00

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0.04

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Minutes

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2.201

2.374

97.06

2.94


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65

3.4

46

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0.00

0.02

0.04

0.06

Minutes

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

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Retention Time

(min)% Area

3.365

3.446

50.30

49.70

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3.3

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Retention Time

(min)% Area

3.262

3.355

93.78

6.22


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0.040

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Retention Time

(min)% Area

1.484

1.705

40.42

59.58

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61

1.5

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AU

0.000

0.010

0.020

0.030

0.040

0.050

0.060

0.070

Minutes

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

1

2

Retention Time

(min)% Area

1.361

1.559

2.55

97.45


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2.8

70

2.9

78

AU

-0.02

0.00

0.02

0.04

0.06

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0.10

0.12

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0.16

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0.20

0.22

Minutes

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

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(min)% Area

2.870

2.978

17.43

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0.20

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Minutes

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Retention Time

(min)% Area

3.021

3.113

4.76

95.24


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3.4

21

3.6

21

AU

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0.80

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0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00

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Retention Time

(min)% Area

3.421

3.621

45.03

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Retention Time

(min)% Area

3.453

3.655

70.41

29.59


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AU

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1.00

1.50

2.00

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Minutes

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

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2

Retention Time

(min)% Area

2.771

3.050

52.28

47.72

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3.0

92

AU

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0.02

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0.06

0.08

Minutes

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00

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Retention Time

(min)% Area

2.800

3.092

98.18

1.82


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5.7

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AU

0.000

0.010

0.020

0.030

0.040

0.050

0.060

0.070

Minutes

0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00

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Retention Time

(min)% Area

5.469

5.733

75.11

24.89

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89

5.7

41

AU

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

0.16

Minutes

0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00

1

2

Retention Time

(min)% Area

5.489

5.741

2.97

97.03


organocatalytic asymmetric remote aziridination of 2,4-dienals · 3.1 organocatalytic asymmetric...

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