cu-catalyzed electrophilic amination of internal alkynes ... · pdf file1 cu-catalyzed...
TRANSCRIPT
1
Cu-Catalyzed Electrophilic Amination of Internal Alkynes via
Hydroalumination
Hongju Yoon, Yuna Kim and Yunmi Lee*
Department of Chemistry, Kwangwoon University, Seoul 01897, Republic Korea
Supporting Information
General. 1H NMR spectra were recorded on a 400 MHz spectrometer. Chemical shifts are reported in
ppm from tetramethylsilane, with the solvent resonance as the internal standard (CDCl3: δ 7.27 ppm).
Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet,
m = multiplet), coupling constants (Hz), and integration. 13C NMR spectra were recorded on a 100 MHz
spectrometer with complete proton decoupling. Chemical shifts are reported in ppm from
tetramethylsilane with the solvent resonance as the internal standard (CDCl3: δ 77.00 ppm). High-
resolution mass spectra (HRMS) were obtained using an electrospray ionization (ESI) time-of-flight
mass spectrometer. Melting points were determined using a melting point apparatus and are uncorrected.
Unless otherwise noted, all reactions were carried out with distilled solvents under an atmosphere of dry
N2 in oven-dried (130 oC) glassware. Tetrahydrofuran was purified by distillation from sodium
benzophenone ketyl immediately prior to use unless otherwise specified. All work-up and purification
procedures were carried out with reagent grade solvents in air. A variety of N,N-dialkyl-O-benzoyl
hydroxylamines1 and internal alkynes
2 were prepared according to reported experimental procedures.
(1) (a) T. J. Barker, E. R. Jarvo, J. Am. Chem. Soc. 2009, 131, 15598. (b) A. M. Berman, J. S. Johnson, J. Org.
Chem. 2006, 71, 219. (c) A. M. Berman, J. S. Johnson, J. Org. Chem. 2005, 70, 364. (d) A. M. Berman, A. M.; J.
S. Johnson, Synlett 2005, 1799. (e) A. M. Berman, J. S. Johnson, J. Am. Chem. Soc. 2004, 126, 5680.
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2016
2
� Experimental procedure for Cu-catalyzed electrophilic amination of vinylaluminum 2a via
direct hydroalumination of diphenylacetylene (1a):
Ph Phhexanes, 60 oC Ph Ph
Al(i-Bu)2
used in situ
THF, 22 oC, 1 h
BzO-N(Bn)2 3a Ph Ph
N(Bn)2
12 h
75% conv
1 mol % CuCl
>98% conv, 53% yield
H Al(i-Bu)2
no CuCl: 45% conv, <2% yield
1a
H
2a 4aa
To a solution of diphenylacetylene (1a) (178 mg, 1.00 mmol) in hexanes (1.25 mL) was added
diisobutylaluminum hydride (178 μL, 1.00 mmol) slowly under N2 gas. The solution was allowed to
heat to 60 °C and stir for 12 h. After that time, the resulting vinylaluminum reagent 2a (~0.7 M, >98%
E-vinylAl) 3
was directly used for the amination without further filtration and purification.
O-Benzoyl-N,N-dibenzylhydroxylamine (3a) (47.6 mg, 0.150 mmol), CuCl (0.200 mg, 1.50x10-3
mmol)
and THF (0.5 mL) were added to a 8 mL vial under N2 gas and then vinylaluminum reagent 2a (~0.7 M
in hexanes, 0.320 mL, 0.225 mmol) was added slowly. The reaction mixture was allowed to stir at room
temperature for 1 h. After that time, reaction was quenched with an aqueous solution of 1 M NaOH (1
mL) and a saturated aqueous solution of Rochelle`s salt (1 mL). The resulting solution was allowed to
stir vigorously for 10 min and washed with EtOAc (3 x 2 mL). The combined organic layers were dried
over MgSO4, filtered and concentrated. The stereoselectivity of E-enamine was determined by analysis
of 1H NMR spectra of the unpurified reaction mixtures through comparison of the previously reported
data.4 (E)-N,N-Dibenzyl-1,2-diphenylethenamine (4aa) was dominatly observed (>98:<2 E:Z-enamine).
The crude enamine product was dissolved in CH2Cl2 (1.5 mL) and then NaB(OAc)3H (127 mg, 0.60
mmol) and AcOH (34.3 μL, 0.60 mmol) were added. The reaction mixture was allowed to stir at 22 °C
for 12 h. After that time, The resulting solution was quenched with an aqueous solution of 1 M NaOH (1
(2) (a) T. Torigoe, T. Ohmura, M. Suginome, Chem. Eur. J. 2016, 22, 10415. (b) K. Park, G. Bae, J. Moon, J.
Choe, K. H. Song, S. Lee, J. Org. Chem. 2010, 75, 6244.
(3) The vinylaluminum reagents reagent 2a was quenched with H2O and conversion and stereoselectivity were
determined by analysis of 1H NMR spectrum. The (Z)-1,2-diphenylethene was observed in >98:<2 Z:E selectivity.
The spectra data of the obtained (Z)-1,2-diphenylethene match those reported previously. For spectra data of (Z)-
1,2-diphenylethene, see: (a) Y. S. Wagh, N. Asao, J. Org. Chem. 2015, 80, 847. For spectra data of (E)-1,2-
diphenylethene, see: (b) F. Zhao, J. Luo, Q. Tan, Y. Liao, S. Peng, G.-J. Deng, Adv. Synth. Catal. 2012, 354, 1914.
(4) J. S. Bandar, M. T. Pirnot, S. L. Buchwald, J. Am. Chem. Soc. 2015, 137, 14812.
3
mL) and washed with CH2Cl2 (3 x 1mL). The combined organic layers were dried over MgSO4, filtered
and concentrated. The desired product was quantified by analysis of 1H NMR spectra using 1,3,5-
trimethoxybenzene as an internal standard (53% NMR yield).
� Representative experimental procedures for Cu-catalyzed electrophilic amination of
vinylaluminum 2 via Ni-catalyzed hydroalumination of internal aryl acetylene 1:
General procedure A: 1,2-Bis(4-(trifluoromethyl)phenyl)ethyne (1b) (141 mg, 0.450 mmol),
Ni(PPh3)2Cl2 (2.90 mg, 0.00450 mmol) and THF (0.28 mL) were added to a 8 mL vial and then
diisobutylaluminum hydride (80.0 μL, 0.450 mmol) was added slowly under N2 gas. The solution was
allowed to stir at 22 °C for 3 h. After that time, to a solution of O-benzoyl-N,N-dibenzylhydroxylamine
(3a) (95.2 mg, 0.300 mmol) and CuCl (0.300 mg, 0.00300 mmol) in THF (1 mL) was added slowly the
resulting vinylaluminum reagent 2b. The reaction mixture was allowed to stir at room temperature for
0.5 h. And then the resulting solution was quenched with an aqueous solution of 1 M NaOH (1 mL) and
a saturated aqueous solution of Rochelle`s salt (1 mL). The solution was allowed to stir vigorously for
10 min and washed with EtOAc (3 x 2 mL). The combined organic layers were dried over MgSO4,
filtered and concentrated. The crude product was purified by neutral alumina (100% hexanes with 1% of
Et3N → EtOAc:hexanes=1:20) to afford the desired (E)-N,N-dibenzyl-1,2-bis(4-(trifluoromethyl)
phenyl)ethenamine (4ba) (132 mg, 0.258 mmol, 86%) as a yellow sticky oil.
General procedure B: Diphenylacetylene (1a) (80.2 mg, 0.450 mmol), Ni(PPh3)2Cl2 (2.90 mg, 0.00450
mmol) and THF (0.28 mL) were added to a 8 mL vial and then diisobutylaluminum hydride (80.0 μL,
0.450 mmol) was added slowly under N2 gas. The solution was allowed to stir at 22 °C for 3 h. After
that time, to a solution of O-benzoyl-N,N-dibenzylhydroxylamine (3a) (95.2 mg, 0.300 mmol) and CuCl
(0.300 mg, 0.00300 mmol) in THF (1 mL) was added slowly the resulting vinylaluminum reagent 2b.
The reaction mixture was allowed to stir at room temperature for 0.5 h. And then the resulting solution
was quenched with an aqueous solution of 1 M NaOH (1 mL) and a saturated aqueous solution of
Rochelle`s salt (1 mL). The solution was allowed to stir vigorously for 10 min and washed with EtOAc
(3 x 2 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The crude
enamine product was dissolved in CH2Cl2 (3 mL). And then NaB(OAc)3H (254 mg, 1.20 mmol) and
AcOH (68.7 μL, 1.20 mmol) were added to the mixture, which was allowed to stir at 22 °C for 12 h.
After that time, the resulting solution was quenched with an aqueous solution of 1 M NaOH (2 mL) and
washed with CH2Cl2 (3 x 2 mL). The combined organic layers were dried over MgSO4, filtered and
4
concentrated. The crude product was purified by silica gel column chromatography (100% hexanes with
1% of Et3N → EtOAc:hexanes=1:20) to afford the desired N,N-dibenzyl-1,2-diphenylethanamine (4aa’)
(102 mg, 0.270 mmol, 90%) as a colorless oil.
(E)-N,N-Dibenzyl-1,2-bis(4-(trifluoromethyl)phenyl)ethenamine (4ba). Compound 4ba was
synthesized according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300
mmol) to obtain as a yellow solid in 86% yield (132 mg, 0.258 mmol). The compound exists as a 98:2
mixture of E:Z isomers after alumina purification. 1H NMR (CDCl3, 400 MHz): δ 7.64 (d, J = 7.9 Hz,
2H), 7.60 (d, J = 7.9 Hz, 2H), 7.36 (dd, J = 7.2, 7.2 Hz, 4H), 7.30 (d, J = 6.8 Hz, 2H), 7.24 (d, J = 7 Hz,
6H), 6.74 (d, J = 8.1 Hz, 2H), 5.70 (s, 1H), 4.15 (s, 4H); 13
C NMR (CDCl3, 100 MHz): δ 149.8, 142.2,
140.6, 137.6, 131.0, 130.3 (q, J = 20 Hz), 129.9 (q, J = 20 Hz), 128.6, 128.0, 128.0, 127.4, 125.9 (q, J =
4.0 Hz), 124.7 (q, J = 4.0 Hz), 124.4 (q, J = 270 Hz), 124.0 (q, J = 271 Hz), 106.6, 52.8; HRMS (ESI)
m/z: [M+H]+ Calcd for C30H24F6N 512.1813, Found 512.1807.
(E)-N,N-Dibenzyl-1,2-bis(3-(trifluoromethyl)phenyl)ethenamine (4ca). Compound 4ca was
synthesized according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300
mmol) to obtain as slightly yellow sticky oil in 71% yield (108 mg, 0.220 mmol). The compound exists
as a 96:4 mixture of E:Z isomers after alumina purification. 1H NMR (CDCl3, 400 MHz): δ 7.71 (s, 1H),
7.65 (dd, J = 5.7, 5.7 Hz, 2H), 7.50 (dd, J = 7.6, 7.6 Hz, 1H), 7.40-7.37 (m, 4H), 7.32 (d, J = 6.8 Hz,
2H), 7.29-7.20 (m, 4H), 7.16 (d, J = 7.0 Hz, 1H), 7.10 (dd, J = 7.6, 7.6 Hz, 1H), 6.87 (s, 1H), 6.84 (d, J
= 7.4 Hz, 1H), 5.73 (s, 1H), 4.19 (s, 4H); 13
C NMR (CDCl3, 100 MHz): δ 149.5, 139.1, 137.7, 134.0,
131.5 (q, J = 33 Hz), 130.1 (q, J = 32 Hz), 129.5, 128.9, 128.7, 128.6, 128.1, 128.0, 127.4 (q, J = 4.0
Hz), 127.4, 125.5 (q, J = 4.0 Hz), 124.7 (q, J = 4.0 Hz), 124.1 (q, J = 272 Hz), 123.9 (q, J = 272 Hz),
120.7 (q, J = 4.0 Hz), 106.4, 52.9; HRMS (ESI) m/z: [M+H]+ Calcd for C30H24F6N 512.1813, Found
512.1810.
(E)-N,N-Dibenzyl-1,2-bis(3-methoxyphenyl)ethenamine (4da). Compound 4da was synthesized
according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to
obtain as slightly yellow sticky oil in 91% yield (119 mg, 0.273 mmol). The compound exists as a 93:7
mixture of E:Z isomers after alumina purification. 1H NMR (CDCl3, 400 MHz): δ 7.36-7.31 (m, 5H),
7.30-7.26 (m, 6H), 7.13 (d, J = 7.8 Hz, 1H), 7.06 (s, 1H), 6.99-6.89 (m, 2H), 6.49 (dd, J = 8.2, 2.1 Hz,
1H), 6.41 (d, J = 7.6 Hz, 1H), 6.28 (s, 1H), 5.62 (s, 1H), 4.17 (s, 4H), 3.76 (s, 3H), 3.53 (s, 3H); 13C
NMR (CDCl3, 100 MHz): δ 160.1, 159.1, 149.5, 140.4, 138.9, 138.4, 129.8, 129.2, 128.5, 128.4, 128.1,
5
127.3, 127.0, 123.2, 121.0, 116.0, 114.2, 112.5, 110.4, 106.4, 55.2, 54.7, 52.7; HRMS (ESI) m/z:
[M+H]+
Calcd for C30H30NO2 436.2277, Found 436.2265.
(E)-N,N-Dibenzyl-1,2-bis(4-chlorophenyl)ethenamine (4ea). Compound 4ea was synthesized
according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to
obtain as yellow-green sticky oil in 85% yield (114 mg, 0.256 mmol). The compound exists as a >98:<2
mixture of E:Z isomers after alumina purification. 1H NMR (CDCl3, 400 MHz): δ 7.40 (d, J = 8.3 Hz,
2H), 7.36-7.32 (m, 6H), 7.29-7.26 (m, 2H), 7.24-7.22 (m, 4H), 6.98 (d, J = 8.6 Hz, 2H), 6.64 (d, J = 8.5
Hz, 2H), 5.58 (s, 1H), 4.11 (s, 4H); 13C NMR (CDCl3, 100 MHz): δ 148.8, 138.0 137.2, 135.5, 134.5,
132.0, 129.6, 129.4, 129.2, 129.1, 129.0, 128.6, 128.6, 128.5, 128.1, 127.9, 127.2, 106.6, 52.7; HRMS
(ESI) m/z: [M+H]+
Calcd for C28H24Cl2N 444.1286, Found 444.1290.
N,N-Dibenzyl-1,2-bis(4-fluorophenyl)ethanamine (4fa’). Compound 4fa’ was synthesized according
to general procedure B using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to obtain as a
white solid in 95% yield (118 mg, 0.285 mmol). mp 107-108 °C; 1H NMR (CDCl3, 400 MHz): δ 7.30-
7.27 (m, 5H), 7.25-7.20 (m, 7H), 7.08 (dd, J = 8.6, 8.6 Hz, 2H), 7.02 (dd, J = 8.6, 5.4 Hz, 2H), 6.94 (dd,
J = 8.6, 8.6 Hz, 2H), 4.00 (t, J = 7.7 Hz, 1H), 3.87 (d, J = 13.9 Hz, 2H), 3.35 (dd, J = 13.9, 8.2 Hz, 1H),
3.18 (d, J = 13.9 Hz, 2H), 3.00 (dd, J = 13.9, 7.3 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 162.0 (d, J
= 245 Hz), 161.5 (d, J = 243 Hz), 139.7, 135.3 (d, J = 3.0 Hz), 134.0 (d, J = 3.0 Hz), 130.8 (d, J = 8.0
Hz), 130.4 (d, J = 8.0 Hz), 128.6, 128.3, 126.9, 115.0 (d, J = 5.8 Hz), 114.7 (d, J = 5.8 Hz), 62.7, 53.5,
36.9; HRMS (ESI) m/z: [M+H]+ Calcd for C28H26F2N 414.2033, Found 414.2032.
6
N,N-Dibenzyl-1,2-bis(4-methoxyphenyl)ethanamine (4ga’). Compound 4ga’ was synthesized
according to general procedure B using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to
obtain as a white solid in 87% yield (114 mg, 0.261 mmol). mp 75-76 °C; 1H NMR (CDCl3, 400 MHz):
δ 7.26-7.20 (m, 10H), 7.18 (d, J = 8.5 Hz, 2H), 6.98 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 8.3 Hz, 2H), 6.78
(d, J = 8.5 Hz, 2H), 3.96 (t, J = 7.7 Hz, 1H), 3.86 (d, J = 14.4 Hz, 2H), 3.83 (s, 3H), 3.81 (s, 3H), 3.30
(dd, J = 13.9, 8.0 Hz, 1H), 3.19 (d, J = 14.1 Hz, 2H), 3.00 (dd, J = 14.0, 7.2 Hz, 1H); 13
C NMR (CDCl3,
100 MHz): δ 158.6, 157.9, 140.2, 132.9, 132.1, 130.4, 130.1, 128.6, 128.2, 126.7, 113.4, 113.2, 62.6,
55.2, 55.1, 53.4, 36.8; HRMS (ESI) m/z: [M+H]+
Calcd for C30H32NO2 438.2433, Found 438.2436.
N,N-Dibenzyl-1,2-di-p-tolylethanamine (4ha’). Compound 4ha’ was synthesized according to general
procedure B using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to obtain as colorless
sticky oil in 93% yield (113 mg, 0.279 mmol). mp 66-67 °C; 1H NMR (CDCl3, 400 MHz): δ 7.26-7.18
(m, 10H), 7.16 (dd, J = 7.1, 7.1 Hz, 4H), 7.04 (d, J = 7.8 Hz, 2H), 6.97 (d, J = 7.8 Hz, 2H), 4.00 (t, J =
7.6 Hz, 1H), 3.86 (d, J = 13.9 Hz, 2H), 3.33 (dd, J = 13.9, 8.0 Hz, 1H), 3.19 (d, J = 13.9 Hz, 2H), 3.05
(dd, J = 14.1, 7.2 Hz, 1H), 2.37 (s, 3H), 2.34 (s, 3H); 13
C NMR (CDCl3, 100 MHz): δ 140.2, 136.9,
136.6, 135.4, 135.2, 129.4, 129.0, 128.7, 128.7, 128.2, 126.7, 62.8, 53.5, 37.1, 21.0, 21.0; HRMS (ESI)
m/z: [M+H]+
Calcd for C30H32N 406.2535, Found 406.2534.
(E)-N,N-Dibenzyl-1,2-bis(2-fluorophenyl)ethenamine (4ia). Compound 4ia was synthesized
according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to
obtain as pale yellow sticky oil in 62% yield (76.1 mg, 0.185 mmol). 1H NMR (CDCl3, 400 MHz): δ
7.41-7.24 (m, 12H), 7.12-7.05 (m, 2H), 6.88 (dd, J = 6.0, 6.0 Hz, 2H), 6.66-6.62 (m, 1H), 6.46 (dd, J =
7.8, 7.8 Hz, 1H), 5.77 (s, 1H), 4.22 (s, 4H); 13
C NMR (CDCl3, 100 MHz): δ 160.9 (d, J = 248 Hz),
159.9 (d, J = 244 Hz), 144.5, 138.2, 132.6 (d, J = 4.0 Hz), 130.5 (d, J = 4.0 Hz), 128.8 (d, J = 3.0 Hz),
128.4, 128.0, 127.0, 126.7, 125.5 (d, J = 8.0 Hz), 124.9, 124.5 (d, J = 4.0 Hz), 123.1 (d, J = 4.0 Hz),
116.1 (d, J = 22.4 Hz), 114.7 (d, J = 22.4 Hz), 98.7, 52.8; HRMS (ESI) m/z: [M+H]+
Calcd for
C28H24F2N 412.1877, Found 412.1880.
(E)-N,N-Dibenzyl-1,2-di-o-tolylethenamine (4ja). Compound 4ja was synthesized according to
7
general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to obtain as
yellowish sticky oil in 30% yield (36.5 mg, 0.090 mmol). 1H NMR (CDCl3, 400 MHz): δ 7.36-7.29 (m,
10H), 7.20 (dd, J = 6.7, 6.7 Hz, 2H), 7.12 (dd, J = 6.3, 6.3 Hz, 2H), 7.01 (d, 7.4 Hz, 1H), 6.82 (dd, J =
7.3, 7.3 Hz, 1H), 6.66 (dd, J = 7.5, 7.5 Hz, 1H), 6.36 (d, J = 7.9 Hz, 1H), 5.67 (s, 1H), 4.30 (d, J = 15.4
Hz, 2H), 4.14 (d, J = 15.3 Hz, 2H), 2.21 (s, 6H); 13
C NMR (CDCl3, 100 MHz): δ 148.2, 139.6, 138.9,
137.8, 136.6, 135.2, 131.1, 130.3, 129.4, 129.1, 128.4, 128.0, 126.9, 126.6, 125.8, 125.0, 124.1, 103.5,
52.7, 20.3, 19.7; HRMS (ESI) m/z: [M+H]+ Calcd for C30H30N 404.2378, Found 404.2376.
(E)-N,N-Dibenzyl-1,2-di(thiophen-2-yl)ethenamine (4ka). Compound 4ka was synthesized according
to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to obtain as
yellow sticky oil in 76% yield (88.7 mg, 0.229 mmol). 1H NMR (CDCl3, 400 MHz): δ 7.54 (dd, J = 5.0,
1.0 Hz, 1H), 7.38-7.31 (m, 5H), 7.30-7.23 (m, 6H), 7.11 (dd, J = 5.1, 3.7 Hz, 1H), 6.84 (dd, 5.3, 0.9 Hz,
1H), 6.78 (dd, J = 5.1, 3.7 Hz, 1H), 6.54 (d, J = 3.7 Hz, 1H), 5.94 (s, 1H), 4.20 (s, 4H); 13
C NMR
(CDCl3, 100 MHz): δ 142.5, 140.5, 138.1, 137.7, 130.4, 128.5, 128.2, 127.9, 127.5, 127.1, 126.1, 124.0,
122.0, 102.6, 52.7; HRMS (ESI) m/z: [M+H]+ Calcd for C24H22NS2 388.1194, Found 388.1179.
N,N-Dibenzyl-1,4-diphenylbutan-2-amine (4la’).
Compound 4la’ was synthesized according to
general procedure B using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to obtain as
colorless oil in 72% yield (88.0 mg, 0.217 mmol). 1H NMR (CDCl3, 400 MHz): δ 7.36-7.10 (m, 16H),
7.02 (dd, J = 5.6, 5.6 Hz, 4H), 3.83 (d, J = 13.6 Hz, 2H), 3.59 (d, J = 13.9 Hz, 2H), 3.13 (dd, J = 13.2,
4.6 Hz, 1H), 2.96-2.82 (m, 2H), 2.49 (dd, J = 13.2, 8.8 Hz, 1H), 2.35-2.26 (m, 1H), 1.94-1.82 (m, 1H),
1.66-1.56 (m, 1H); 13
C NMR (CDCl3, 100 MHz): δ 140.7, 140.3, 139.7, 130.4, 130.0, 129.4, 128.9,
128.5, 128.4, 128.3, 126.9, 126.0, 57.9, 53.4, 35.2, 33.4, 32.3; HRMS (ESI) m/z: [M+H]+ Calcd for
C30H32N 406.2535, Found 406.2535.
N,N-Dibenzyl-1,2-diphenylethanamine (4aa’). Compound 4aa’ was synthesized according to general
procedure B using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to obtain as a white solid
in 90% yield (102 mg, 0.270 mmol). This compound has been previously reported and spectra data
8
match described.5 1H NMR (CDCl3, 400 MHz): δ 7.44-7.40 (m, 2H), 7.36-7.23 (m, 16H), 7.14-7.12 (m,
2H), 4.10 (dd, J = 7.4, 7.4 Hz, 1H), 3.93 (d, J = 14.2 Hz, 2H), 3.43 (dd, J = 14.0, 8.5 Hz, 1H), 3.24 (d, J
= 13.9 Hz, 2H), 3.12 (dd, J = 13.9, 7.1 Hz, 1H); 13
C NMR (CDCl3, 100 MHz): δ 140.0, 139.9, 138.5,
129.6, 129.1, 128.7, 128.2, 128.1, 128.0, 127.2, 126.7, 126.0, 63.1, 53.5, 37.6.
N-(1,2-Diphenylethyl)-N-isopropylpropan-2-amine (4ab). Compound 4ab was synthesized according
to general procedure B using O-benzoyl-N,N-diisopropylhydroxylamine (3b, 0.300 mmol). The
resulting reaction product was purified by acid/base workup. The crude product was diluted with Et2O
(1 mL) and acidified with 1 N HCl (3 x 1 mL). The aqueous layers were combined, basified with 1 N
NaOH (3 mL) and washed with Et2O (3 x 3 mL). Then the organic layers were combined, dried over
MgSO4 and concentrated to afford as a colorless oil in 66% yield (56.1 mg, 0.199 mmol). This
compound has been previously reported and spectra data match described.6 1H NMR (CDCl3, 400
MHz): δ 7.33 (d, J = 7.3 Hz, 2H), 7.24-7.13 (m, 5H), 7.13-7.07 (m, 3H), 4.22 (dd, J = 8.8, 5.9 Hz, 1H),
3.30 (sept, J = 6.7 Hz, 2H), 3.21-3.10 (m, 2H), 1.06 (d, J = 6.6 Hz, 6H), 0.91 (d, J = 6.8 Hz, 6H); 13C
NMR (CDCl3, 100 MHz): δ 144.1, 140.6, 129.3, 128.8, 128.0, 127.8, 126.2, 125.6, 60.5, 45.6, 41.0,
23.0, 22.4.
N-Allyl-N-(1,2-Diphenylethyl)prop-2-en-1-amine (4ac). Compound 4ac was synthesized according to
general procedure B using N,N-diallyl-O-benzoylhydroxylamine (3c, 0.300 mmol) to obtain as colorless
oil in 61% yield (51.1 mg, 0.184 mmol). 1H NMR (CDCl3, 400 MHz): δ 7.30-7.27 (m, 2H), 7.24-7.17
(m, 5H), 7.13 (d, J = 7.1 Hz, 1H), 7.05 (d, J = 7.1 Hz, 2H), 5.82-5.72 (m, 2H), 5.16-5.09 (m, 4H), 4.03
(t, J = 7.5 Hz, 1H), 3.36-3.27 (m, 3H), 2.97 (dd, J = 13.5, 8.3 Hz, 1H), 2.86 (dd, J = 14.4, 7.3 Hz, 2H);
13C NMR (CDCl3, 100 MHz): δ 140.1, 139.9, 136.9, 129.4, 128.9, 127.9, 127.9, 127.0, 125.8, 116.8,
65.1, 52.7, 38.5; HRMS (ESI) m/z: [M+H]+ Calcd for C20H24N 278.1909, Found 278.1897.
N-Benzyl-N-methyl-1,2-diphenylethanamine (4ad). Compound 4ad was synthesized according to
general procedure B using O-benzoyl-N-benzyl-N-methylhydroxylamine (3d, 0.300 mmol) to obtain as
colorless oil in 75% yield (68.0 mg, 0.226 mmol). 1H NMR (CDCl3, 400 MHz): δ 7.44-7.26 (m, 13H),
7.16 (d, J = 7.3 Hz, 2H), 3.95 (t, J = 7.5 Hz, 1H), 3.76 (d, J = 13.2 Hz, 1H), 3.49 (dd, J = 13.7, 6.6 Hz,
1H), 3.43 (d, J = 13.4 Hz, 1H), 3.14 (dd, J = 13.6, 8.4 Hz, 1H), 2.31 (s, 3H); 13
C NMR (CDCl3, 100
MHz): δ 140.0, 140.0, 139.5, 129.5, 128.9, 128.7, 128.2, 128.0, 127.9, 127.0, 126.8, 125.8, 69.5, 58.8,
38.8, 38.0; HRMS (ESI) m/z: [M+H]+ Calcd for C22H24N 302.1909, Found 302.1910.
(5) S. Zhu, N. Niljianskul, S. L. Buchwald, J. Am. Chem. Soc. 2013, 135, 15746
(6) H. Takahashi, T. Tsubuki, K. Higashiyama, Synthesis 1988, 3, 238.
9
1-(1,2-Diphenylethyl)piperidine (4ae). Compound 4ae was synthesized according to general procedure
B using piperidin-1-yl benzoate (3e, 0.300 mmol) to obtain as colorless oil in 80% yield (63.5 mg, 0.239
mmol). This compound has been previously reported and spectra data match described.7 1H NMR
(CDCl3, 400 MHz): δ 7.33-7.25 (m, 3H), 7.22-7.14 (m, 5H), 7.08 (d, J = 7.0 Hz, 2H), 3.67 (dd, J = 9.2,
5.1 Hz, 1H), 3.39 (dd, J = 13.3, 5.0 Hz, 1H), 3.07 (dd, J = 13.0, 9.6 Hz, 1H), 2.56-2.51 (m, 4H), 1.71-
1.58 (m, 4H), 1.45 (q, J = 5.6 Hz, 2H); 13
C NMR (CDCl3, 100 MHz): δ 140.0, 139.5, 129.4, 129.0,
127.9, 127.7, 126.7, 125.7, 72.3, 51.3, 39.1, 26.3, 24.6.
4-(1,2-Diphenylethyl)thiomorpholine (4af). Compound 4af was synthesized according to general
procedure B using thiomorpholino benzoate (3f, 0.300 mmol) to obtain as a white solid in 85% yield
(72.6 mg, 0.256 mmol). This compound has been previously reported and spectra data match described.7
1H NMR (CDCl3, 400 MHz): δ 7.30-7.21 (m, 3H), 7.20-7.09 (m, 5H), 7.06 (d, J = 7.1 Hz, 2H), 3.73 (t,
J = 7.3 Hz, 1H), 3.27 (dd, J = 13.7, 6.3 Hz, 1H), 3.02 (dd, J = 13.7, 8.5 Hz, 1H), 2.87-2.82 (m, 2H),
2.74-2.67 (m, 2H), 2.65-2.59 (m, 4H); 13C NMR (CDCl3, 100 MHz): δ 139.8, 139.0, 129.3, 128.7,
128.1, 128.0, 127.2, 125.9, 72.0, 52.2, 29.6, 28.2.
4-(1,2-Diphenylethyl)morpholine (4ag). Compound 4ag was synthesized according to general
procedure B using morpholino benzoate (3g, 0.300 mmol) to obtain as colorless oil in 79% yield (63.3
mg, 0.237 mmol). This compound has been previously reported and spectra data match described.7
1H
NMR (CDCl3, 400 MHz): δ 7.25-7.19 (m, 3H), 7.17-7.08 (m, 5H), 6.94 (d, J = 6.9 Hz, 2H), 3.71 (t, J =
4.7 Hz, 4H), 3.49 (dd, J = 9.4, 5.3 Hz, 1H), 3.34 (dd, J = 13.2, 5.2 Hz, 1H), 2.89 (dd, J = 12.9, 9.5 Hz,
1H), 2.56-2.45 (m, 4H); 13C NMR (CDCl3, 100 MHz): δ 139.8, 139.3, 129.4, 128.8, 127.9, 127.1, 125.8,
72.5, 67.2, 51.2, 39.2.
tert-Butyl 4-(1,2-diphenylethyl)piperazine-1-carboxylate (4ah). Compound 4ah was synthesized
according to general procedure B using tert-butyl 4-(benzoyloxy)piperazine-1-carboxylate (3h, 0.300
mmol) to obtain as colorless oil in 83% yield (91.3 mg, 0.249 mmol). This compound has been
previously reported and spectra data match described.7
1H NMR (CDCl3, 400 MHz): δ 7.25-7.20 (m,
3H), 7.17-7.10 (m, 5H), 6.98 (d, J = 6.8 Hz, 2H), 3.59 (dd, J = 9.1, 5.7 Hz, 1H), 3.40 (brs, 4H), 3.32 (dd,
J = 13.3, 5.7 Hz, 1H), 2.96 (dd J = 13.3, 9.2 Hz, 1H), 2.44 (brs, 4H), 1.43 (s, 9H); 13
C NMR (CDCl3,
100 MHz): δ 154.7, 139.4, 139.4, 129.4, 128.7, 128.0, 127.2, 125.8, 79.4, 71.8, 50.1, 44.2, 39.1, 28.3.
(7) K. D. Hesp, M. Stradiotto, M. J. Am. Chem. Soc. 2010, 132, 18026.
10
tert-Butyl 4-(1,2-diphenylethyl)-1,4-diazepane-1-carboxylate (4ai). Compound 4ai was synthesized
according to general procedure B using tert-butyl 4-(benzoyloxy)-1,4-diazepane-1-carboxylate (3i,
0.300 mmol) to obtain as colorless sticky oil in 69% yield (78.4 mg, 0.206 mmol). The compound exists
as a 1:1 mixture of ratamers. 1H NMR (CDCl3, 400 MHz): δ 7.26-7.09 (m, 8H), 7.05 (dd, J = 7.5, 7.5
Hz, 2H), 3.90 (dd, J = 12.7, 5.9 Hz, 1H), 3.52-3.30 (m, 4H), 3.30-3.20 (m, 1H), 3.04-2.92 (m, 1H),
2.86-2.70 (m, 2H), 2.70-2.62 (m, 1H), 2.62-2.52 (m, 1H), 1.79-1.72 (m, 1H), 1.72-1.65 (m, 1H), 1.44 (d,
J = 3.9 Hz, 9H); 13
C NMR (CDCl3, 100 MHz): δ 155.6, 140.6, 139.9, 129.3, 128.4, 128.0, 127.9, 127.0,
125.8, 79.1, 70.4, 52.9, 51.9, 47.6, 45.9, 39.2, 28.4; HRMS (ESI) m/z: [M+H]+ Calcd for C24H33N2O2
381.2542, Found 381.2549.
N-(1,2-Diphenylethyl)-2-methylpropan-2-amine (4aj). Compound 4aj was synthesized according to
general procedure B using O-benzoyl-N-(tert-butyl)hydroxylamine (3j, 0.300 mmol). The resulting
reaction product was purified by acid/base workup. The crude product was diluted with Et2O (1 mL)
and acidified with 1 N HCl (3 x 1 mL). The aqueous layers were combined, basified with 1 N NaOH (3
mL) and washed with Et2O (3 x 3 mL). Then the organic layers were combined, dried over MgSO4 and
concentrated to afford as colorless oil in 36% yield (27.0 mg, 0.107 mmol). This compound has been
previously reported and spectra data match described.8 1H NMR (CDCl3, 400 MHz): δ 7.38 (d, J = 7.5
Hz, 2H), 7.26 (dd, J = 13.7, 7.1 Hz, 3H), 7.18 (dd, J = 7.1, 7.1 Hz, 3H), 7.13 (d, J = 7.6 Hz, 2H), 3.98
(dd, J = 8.8, 5.7 Hz, 1H), 2.91 (dd, J = 13.5, 5.4 Hz, 1H), 2.70 (dd, J = 13.5, 9.1 Hz, 1H), 0.82 (s, 9H);
13C NMR (CDCl3, 100 MHz): δ 147.6, 139.3, 129.4, 128.3, 128.1, 127.2, 126.5, 126.4, 59.2, 51.1, 47.1,
29.8.
� Ni-catalyzed hydroalumination of internal aryl acetylene 5a:
OMe
5a
1 mol % Ni(PPh3)2Cl2
DIBAL-H, THF, 22 °C, 3 h
OMe
Al(i-Bu)2
OMe
(i-Bu)2Al
+
7a6a
OMe
D
OMe
D
+
D2O
6a' 7a'
(8) M. Esteruelas, A. M. López, A. C. Mateo, E. Oñate, Organometallics 2005, 24, 5084.
11
1-Methoxy-2-(phenylethynyl)benzene (5a) (41.7 mg, 0.200 mmol), Ni(PPh3)2Cl2 (1.30 mg, 0.00200
mmol) and THF (0.2 mL) were added to a 8 mL vial and then diisobutylaluminum hydride (35.6 μL,
0.200 mmol) was added slowly under N2 gas. The solution was allowed to stir at 22 °C for 3 h. After
that time, the solution was quenched with D2O (or H2O) and the stereo- and site selectivity were
determined by analysis of 1H NMR spectra. The (Z)-1-methoxy-2-styrylbenzene was observed in
>98:<2 Z:E selectivity. The (Z)-1-methoxy-2-styrylbenzene has been previously reported and spectra
data match described.9 (Z)-1-methoxy-2-styrylbenzene:
1H NMR (CDCl3, 400 MHz): δ 7.27-7.16 (m,
6H), 6.90 (d, J = 8.3 Hz , 1H), 6.76 (t, J = 7.4 Hz, 1H), 6.70 (d, J = 12.2 Hz, 1H), 6.64 (d, J = 12.2 Hz,
1H), 3.86 (s, 3H); (Z)-1-(1-deutrio-2-phenylvinyl)-2-methoxybenzene (6a’): 1H NMR (CDCl3, 400
MHz): δ 7.27-7.16 (m, 6H), 6.90 (d, J = 8.3 Hz , 1H), 6.76 (t, J = 7.4 Hz, 1H), 6.64 (s, 1H), 3.86 (s, 3H).
Site selectivity (91:9) was determined by analysis of 1H NMR spectra of the unpurified reaction
mixtures through comparison of the protonated sample (below left) with deuterated sample (below
right).
(E)-N,N-Dibenzyl-1-(2-methoxyphenyl)-2-phenylethenamine (8aa). Compound 8aa was synthesized
according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300 mmol) to
obtain as slightly yellow oil in 89% yield (108 mg, 0.267 mmol). 1H NMR (CDCl3, 400 MHz): δ 7.38-
7.32 (m, 10H), 7.29-7.22 (m, 2H), 6.99-6.94 (m, 4H), 6.85 (dd, J = 7.2, 7.2 Hz, 1H), 6.65 (d, J = 7.6 Hz,
2H), 5.64 (s, 1H), 4.32 (d, J = 15.9 Hz, 2H), 4.23 (d, J = 15.9 Hz, 2H), 3.78 (s, 3H); 13
C NMR (CDCl3,
100 MHz): δ 158.1, 145.7, 139.5, 138.9, 132.0, 129.9, 128.3, 127.8, 127.6, 127.1, 128.7, 126.3, 123.3,
121.3, 111.3, 103.6, 55.4, 52.4; HRMS (ESI) m/z: [M+H]+ Calcd for C29H28NO 406.2171, Found
406.2148.
(9) J. Li, R. Hua, T. Liu, J. Org. Chem. 2010, 75, 2966.
12
(E)-N,N-Dibenzyl-2-(3-chlorophenyl)-1-(2-methoxyphenyl)ethenamine (8ba). Compound 8ba was
synthesized according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300
mmol) to obtain as slightly yellow sticky oil in 84% yield (111 mg, 0.252 mmol). 1H NMR (CDCl3, 400
MHz): δ 7.40-7.24 (m, 12H), 6.98 (dd, J = 7.3, 7.3 Hz, 2H), 6.85 (dd, 7.7, 7.7 Hz, 1H), 6.80 (d, J = 7.8
Hz, 1H), 6.58 (s, 1H), 6.46 (d, J = 7.8 Hz, 1H), 5.53 (s, 1H), 4.35 (d, J = 15.8 Hz, 2H), 4.25 (d, J = 15.8
Hz, 2H), 3.80 (s, 3H); 13
C NMR (CDCl3, 100 MHz): δ 157.9, 147.0, 141.6, 138.6, 133.4, 131.7, 130.3,
128.6, 128.4, 127.6, 126.8, 126.8, 125.7, 124.9, 122.9, 121.5, 111.3, 101.3, 55.4, 52.4; HRMS (ESI)
m/z: [M+H]+ Calcd for C29H27ClNO 440.1781, Found 440.1787.
(E)-N,N-Dibenzyl-1-(2-methoxyphenyl)-2-(3-(trifluoromethyl)phenyl)ethenamine (8ca). Compound
8ca was synthesized according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine
(3a, 0.300 mmol) to obtain as yellow sticky oil in 80% yield (114 mg, 0.241 mmol). 1H NMR (CDCl3,
400 MHz): δ 7.39-7.24 (m, 12H), 7.03-7.01 (m, 2H), 6.96 (dd, J =7.3, 4.4 Hz, 2H), 6.80 (s, 1H), 6.75 (d,
J = 6.8 Hz, 1H), 5.58 (s, 1H), 4.34 (d, J = 15.8 Hz, 2H), 4.24 (d, J = 15.8 Hz, 2H), 3.76 (s, 3H); 13C
NMR (CDCl3, 100 MHz): δ 157.9, 147.4, 140.4, 138.5, 131.7, 130.4, 129.8 (q, J = 32 Hz), 128.4, 128.4
(q, J = 17 Hz), 127.6, 127.7 (q, J = 16 Hz), 126.9, 125.5, 124.4 (q, J = 272 Hz), 123.5 (q, J = 4 Hz),
121.5, 111.2, 101.2, 55.5, 52.4; HRMS (ESI) m/z: [M+H]+ Calcd for C30H27F3NO 474.2045, Found
474.2048.
(E)-N,N-Dibenzyl-2-(4-fluorophenyl)-1-(2-methoxyphenyl)ethenamine (8da). Compound 8da was
synthesized according to general procedure A using O-benzoyl-N,N-dibenzylhydroxylamine (3a, 0.300
mmol) to obtain as colorless sticky oil in 87% yield (111 mg, 0.262 mmol). 1H NMR (CDCl3, 400
MHz): δ 7.58-7.50 (m, 1H), 7.38-7.23 (m, 10H), 6.98-6.93 (m, 3H), 6.66 (dd, J = 12.2, 8.8 Hz, 2H),
6.59 (dt, J = 6.0, 2.7 Hz, 2H), 5.58 (s, 1H), 4.28 (d, J = 15.6 Hz, 2H), 4.21 (d, J = 15.6 Hz, 2H), 3.77 (s,
3H); 13
C NMR (CDCl3, 100 MHz): δ 159.7 (d, J = 242 Hz), 158.0, 145.5, 138.9, 135.6 (d, J = 3.0 Hz),
133.6 (d, J = 3.0 Hz), 132.1, 130.0, 129.9, 128.3 (d, J = 6.0 Hz), 127.8, 126.8, 126.1, 121.2, 120.6,
114.2 (d, J = 12 Hz), 111.2, 102.5, 55.3, 52.5; HRMS (ESI) m/z: [M+H]+ Calcd for C29H27FNO
424.2077, Found 424.2063.
13
���� Cu-catalyzed electrophilic amination of 1-phenyl-1-propyne:10
���� Cu-catalyzed electrophilic amination of phenylacetylene:11
1 mol % Ni(dppp)Cl2
Al(i-Bu)2(i-Bu)2Al
+
>98:<2, S8:S9
S8 S9
5 mol % CuCl
THF, 22 C, 1 h
N
S10 (55% yield)
BzO N 3e
S7
>98% conv+
H Al(i-Bu)2
THF, 22 C, 3 h
(10) (a) Reaction was performed according to general procedure A. Yields were determined by 1H NMR
spectrum analysis using 1,3,5-trimethoxybenzene as an internal standard. (b) The hydroalumination of 1-phenyl-
1-propyne (S1) in the presence of 1 mol % of Ni(dppp)Cl2 was also not regioselective, delivering a 55:45 mixture
of S2 and S3 vinylaluminums.
(11) Reactions were performed according to general procedure A. Yields were determined by 1H NMR spectrum
analysis using 1,3,5-trimethoxybenzene as an internal standard. Hydroalumination of phenylacetylene (S7) with 1
mol % Ni(dppp)Cl2 provided the internal vinylaluminum S8 in >98% yield. Cu-catalyzed electrophilic amination
of S8 with 3e was less efficient than that of 1,2-diaryl-substituted vinylaluminums, affording the desired enamine
product S10 in 55% yield with unidentified byproducts. In the presence of 1 mol % Ni(PPh3)2Cl2,
hydroalumination of S7 resulted in a 23:77 mixture of S8 and S9 vinylaluminums (a 12:88 mixture of S8 and S9
under the conditions developed by the Hoveyda group (F. Gao, A. H. Hoveyda, J. Am. Chem. Soc. 2010, 132,
10961.)). When the following amination with a mixture of regioisomers was carried out, vinylaluminum S8 was
aminated in 18% yield of the desired enamine S10. However, amination of terminal vinylaluminum S9 did not
proceed efficiently to give the enamine product S11 (<5% yield) under the optimized conditions for internal aryl
acetylenes.
14
���� 2D-NOSEY proton NMR specta of enamines 4ca and 8ba and 1H NOESY correlations
6.0 5.5 5.0 4.5 4.0
F2 Chemical Shift (ppm)
4.5
5.0
5.5
6.0
F1
Ch
em
ica
l S
hift
(pp
m)
5.5 5.0 4.5 4.0
F2 Chemical Shift (ppm)
4.5
5.0
5.5 F1
Ch
em
ica
l S
hift
(pp
m)
15
■ 1H NMR and
13C NMR spectra for all products:
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)
0
0.5
1.0
No
rma
lize
d I
nte
nsity
0.144.161.000.022.146.632.034.724.46
4.1
5
5.7
0
6.7
36.7
57.2
37.2
57.2
97.3
17.3
47.3
67.3
87.6
17.6
3
NPh
Ph
CF3F3C
E
Z
Figure S1.
1H NMR spectrum of the compound 4ba (98:2 mixture of E:Z isomers)
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
Chemical Shift (ppm)
0.5
1.0
Norm
aliz
ed Inte
nsity
52
.83
76
.68
77
.00
77
.32
10
6.5
9
12
5.2
01
25
.92
12
7.3
71
27
.97
12
8.0
31
28
.59
12
9.0
31
29
.06
12
9.6
11
31
.01
13
7.6
0
14
2.1
9
14
9.8
5
Figure S2. 13
C NMR spectrum of the compound 4ba
16
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)
0
0.5
1.0
No
rma
lize
d I
nte
nsity
0.214.301.000.042.121.121.174.862.424.631.312.241.09
1.5
7
4.1
9
5.7
3
6.8
56
.87
7.1
07
.15
7.2
67
.27
7.3
17
.33
7.3
77
.38
7.4
07
.64
7.6
57
.72
NPh
Ph
CF3F3C
E
Z
Figure S3. 1H NMR spectrum of the compound 4ca (96:4 mixture of E:Z isomers)
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0.5
1.0
No
rma
lize
d I
nte
nsity
14
9.4
71
39
.15
13
7.6
71
33
.99
13
1.2
31
29
.47
12
8.9
61
28
.73
12
8.5
91
28
.11
12
8.0
01
27
.35
12
5.4
81
24
.80
12
0.7
3
10
6.3
7
77
.31
77
.00
76
.68
52
.89
Figure S4. 13
C NMR spectrum of the compound 4ca
17
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
3.333.174.311.000.071.011.151.142.311.181.366.735.823
.53
3.7
5
4.1
7
5.6
2
6.2
86
.40
6.4
26
.48
6.4
86
.89
6.9
36
.95
7.0
67
.11
7.1
37
.27
7.2
97
.32
7.3
47
.36
7.3
7
E
Z
N
Ph
Ph
OMeMeO
Figure S5. 1H NMR spectrum of the compound 4da (93:7 mixture of E:Z isomers)
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
Chemical Shift (ppm)
0.5
1.0
No
rma
lize
d I
nte
nsity
16
0.0
71
59
.08
14
9.4
9
14
0.3
71
38
.91
13
8.4
41
29
.80
12
9.2
01
28
.52
12
8.3
91
28
.05
12
7.3
31
27
.00
12
3.1
71
20
.95
11
5.9
71
14
.15
11
2.5
21
10
.44
10
6.4
1
77
.31
77
.00
76
.68
55
.24
54
.70
52
.65
Figure S6. 13
C NMR spectrum of the compound 4da
18
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
4.461.000.012.072.074.641.586.842.34
4.1
1
5.5
8
6.6
36
.65
6.9
76
.99
7.2
27
.24
7.2
47
.27
7.2
97
.33
7.3
57
.39
7.4
1N
Ph
Ph
ClCl
Figure S7. 1H NMR spectrum of the compound 4ea (>98:<2 mixture of E:Z isomers)
160 140 120 100 80 60 40 20
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
14
8.8
1
13
7.9
81
35
.49
13
2.0
21
29
.39
12
9.1
51
28
.64
12
8.6
31
28
.47
12
8.0
81
27
.90
12
7.1
9
10
6.5
8
77
.31
77
.00
76
.68
52
.72
Figure S8. 13
C NMR spectrum of the compound 4ea
19
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
1.092.091.012.061.012.302.302.257.335.29
2.9
72
.99
3.0
13
.03
3.1
63
.19
3.3
23
.34
3.3
63
.38
3.8
63
.89
3.9
84
.00
4.0
2
6.9
46
.97
7.0
17
.08
7.2
07
.22
7.2
37
.25
7.2
77
.28
7.3
0
N
Ph
Ph
FF
Figure S9. 1H NMR spectrum of the compound 4fa’
180 160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
16
3.2
71
62
.70
16
0.8
21
60
.27
13
9.7
11
35
.26
13
4.0
21
30
.76
13
0.4
51
30
.37
12
8.6
41
28
.59
12
8.3
11
26
.93
11
4.9
81
14
.93
11
4.7
7
77
.32
77
.00
76
.68
62
.68
53
.50
36
.90
Figure S10. 13
C NMR spectrum of the compound 4fa’
20
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
1.052.031.023.125.881.000.881.982.431.972.229.64
2.9
93
.01
3.0
33
.17
3.2
03
.27
3.2
93
.31
3.3
33
.81
3.8
33
.87
3.9
43
.96
3.9
84
.12
4.1
4
6.7
96
.90
6.9
26
.97
7.1
67
.19
7.2
17
.23
7.2
47
.26
7.2
7N
Ph
Ph
OMeMeO
Figure S11. 1H NMR spectrum of the compound 4ga’
160 140 120 100 80 60 40 20
Chemical Shift (ppm)
0
0.5
1.0
1.5
No
rma
lize
d I
nte
nsity
15
8.6
11
57
.87
14
0.1
71
32
.91
13
2.0
81
30
.61
13
0.3
91
30
.08
12
8.6
41
28
.17
12
6.6
9
11
3.9
71
13
.40
11
3.2
3
77
.31
77
.00
76
.68
62
.57
55
.20
55
.11
53
.44
36
.77
Figure S12. 13
C NMR spectrum of the compound 4ga’
21
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
No
rma
lize
d I
nte
nsity
5.971.002.031.011.941.002.192.234.0511.24
7.2
57
.25
7.2
37
.22
7.2
17
.20
7.1
77
.15
7.0
36
.98
4.0
24
.00
3.9
83
.88
3.8
4
3.3
53
.33
3.3
23
.30
3.2
13
.17
3.0
73
.05
3.0
4
2.3
72
.34
N
Ph
Ph
MeMe
Figure S13. 1H NMR spectrum of the compound 4ha’
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
14
0.2
01
36
.88
13
6.6
01
35
.43
13
5.2
21
29
.42
12
9.0
11
28
.77
12
8.6
81
28
.15
12
6.6
7
77
.32
77
.00
76
.68
62
.79
53
.49
37
.10
20
.97
Figure S14. 13
C NMR spectrum of the compound 4ha’
22
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)
0
0.5
1.0
1.5
No
rma
lize
d I
nte
nsity
4.111.001.051.082.262.611.9410.14
4.2
2
5.7
7
6.4
46
.46
6.4
86
.64
6.8
76
.89
6.9
07
.10
7.2
67
.27
7.2
97
.32
7.3
37
.34
7.3
57
.36
N
Ph
Ph
FF
Figure S15. 1H NMR spectrum of the compound 4ia
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
16
2.1
11
61
.09
15
9.6
31
58
.65
14
4.4
91
38
.17
13
2.5
31
30
.42
12
8.7
61
28
.73
12
8.4
21
27
.95
12
7.0
41
25
.54
12
5.4
61
24
.47
12
3.0
91
16
.18
11
5.9
61
14
.77
11
4.5
5
98
.71
77
.32
77
.00
76
.68
52
.82
Figure S16. 13
C NMR spectrum of the compound 4ia
23
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d In
ten
sity
6.632.272.211.011.051.021.511.3312.898.64
2.2
02.2
1
4.1
14.1
5
4.2
74.3
1
5.6
7
6.3
56.3
7
6.6
56.6
76.8
16.9
97.1
27.1
77.1
97.1
97.2
47.2
67.3
07.3
27.3
37.3
4
N
Ph
Ph
MeMe
Figure S17. 1H NMR spectrum of the compound 4ja
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d In
ten
sity
148.2
0139.6
4138.8
7137.6
5131.1
3130.3
3129.3
5129.1
2128.3
6128.0
3127.9
8126.9
1125.8
2124.9
8
103.5
3
77.3
177.0
076.6
8
52.7
0
20.3
319.6
9
Figure S18. 13
C NMR spectrum of the compound 4ja
24
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
4.141.000.991.021.031.106.794.981.07
4.2
0
5.9
4
6.5
36
.54
6.7
76
.78
6.8
37
.10
7.2
47
.25
7.2
57
.26
7.2
77
.28
7.3
27
.34
7.5
27
.54
N
Ph
Ph
SS
Figure S19. 1H NMR spectrum of the compound 4ka
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
Chemical Shift (ppm)
0.5
1.0
1.5
No
rma
lize
d I
nte
nsity
14
2.4
71
40
.47
13
8.1
1
13
0.3
71
29
.32
12
8.4
91
28
.40
12
8.2
01
27
.87
12
7.5
11
27
.10
12
6.0
71
23
.96
12
1.9
8
10
2.5
9
77
.32
77
.00
76
.68
52
.71
Figure S20. 13
C NMR spectrum of the compound 4ka
25
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
0.950.991.020.991.891.202.421.983.828.668.78
1.5
91
.60
1.6
11
.62
1.6
4
1.8
92
.30
2.3
22
.46
2.4
82
.49
2.5
22
.85
2.8
62
.87
2.8
92
.92
3.1
03
.12
3.1
43
.15
3.5
73
.60
3.8
13
.85
7.0
27
.03
7.2
07
.21
7.2
37
.25
7.3
07
.32
7.3
37
.35
N
Ph
Ph
Figure S21. 1H NMR spectrum of the compound 4la’
160 140 120 100 80 60 40 20
Chemical Shift (ppm)
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
14
0.7
21
40
.30
12
9.3
81
28
.90
12
8.7
81
28
.54
12
8.4
01
28
.39
12
8.2
61
26
.84
12
6.0
3
77
.32
77
.00
76
.68
57
.88
53
.43
35
.24
33
.36
32
.30
Figure S22. 13
C NMR spectrum of the compound 4la’
26
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
1.001.911.021.871.001.8615.511.97
3.1
13
.13
3.1
53
.22
3.2
53
.40
3.4
33
.44
3.4
6
3.9
13
.94
4.0
84
.10
4.1
2
7.1
47
.23
7.2
47
.25
7.2
77
.29
7.3
07
.31
7.3
17
.42
N Ph
Ph
Figure S23. 1H NMR spectrum of the compound 4aa’
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0.5
1.0
No
rma
lize
d I
nte
nsity
14
0.0
4
13
8.5
01
29
.61
12
9.0
91
28
.68
12
8.2
01
28
.05
12
7.1
71
26
.74
12
5.9
6
77
.32
77
.00
76
.69
63
.14
53
.51
37
.55
Figure S24. 13
C NMR spectrum of the compound 4aa’
27
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
6.416.382.112.131.003.145.122.11
0.9
20
.94
1.0
81
.10
3.1
83
.19
3.2
03
.30
3.3
13
.33
3.3
5
4.2
04
.22
4.2
4
7.0
87
.10
7.1
17
.15
7.1
67
.18
7.2
07
.22
7.3
57
.36
N
Figure S25. 1H NMR spectrum of the compound 4ab
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
Chemical Shift (ppm)
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
14
4.0
5
14
0.5
8
12
9.3
01
28
.83
12
7.9
71
27
.75
12
6.1
91
25
.62
77
.31
77
.00
76
.68
60
.47
45
.63
40
.98
22
.95
22
.35
Figure S26. 13
C NMR spectrum of the compound 4ab
28
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
2.101.043.121.004.162.001.970.925.202.42
1.5
8
2.8
32
.85
2.8
72
.89
2.9
83
.01
3.2
83
.30
3.3
23
.32
3.3
53
.36
4.0
14
.03
4.0
5
5.0
95
.12
5.1
6
5.7
45
.74
5.7
55
.76
5.7
85
.79
5.7
95
.80
7.0
57
.06
7.1
77
.18
7.1
97
.20
7.2
17
.24
7.2
77
.28
N
Figure S27. 1H NMR spectrum of the compound 4ac
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
Chemical Shift (ppm)
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
14
0.0
71
39
.90
13
6.9
4
12
9.4
31
28
.85
12
7.9
41
26
.95
12
5.7
6
11
6.8
2
77
.32
77
.00
76
.69
65
.09
52
.72
38
.52
Figure S28. 13
C NMR spectrum of the compound 4ac
29
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
3.141.021.070.971.231.002.0313.70
2.3
1
3.1
23
.14
3.1
53
.17
3.4
13
.45
3.4
73
.48
3.5
23
.74
3.7
73
.93
3.9
53
.97
7.1
77
.19
7.2
97
.31
7.3
37
.35
7.3
67
.38
7.4
07
.42
N Ph
CH3
Figure S29. 1H NMR spectrum of the compound 4ad
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
13
9.9
91
39
.50
12
9.4
51
28
.89
12
8.7
41
28
.18
12
7.9
91
27
.04
12
5.8
2
77
.32
77
.21
77
.00
76
.68
69
.54
58
.80
38
.83
37
.97
Figure S30. 13
C NMR spectrum of the compound 4ad
30
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
No
rma
lize
d I
nte
nsity
2.214.224.041.041.041.042.005.043.04
1.4
31
.44
1.4
61
.47
1.6
11
.62
1.6
41
.65
1.6
61
.68
2.5
12
.52
2.5
43
.05
3.0
73
.08
3.1
13
.37
3.3
83
.40
3.4
13
.65
3.6
63
.67
3.6
9
7.0
97
.19
7.2
07
.20
7.2
17
.21
7.2
27
.22
7.3
07
.33
N
Figure S31. 1H NMR spectrum of the compound 4ae
180 160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
No
rma
lize
d I
nte
nsity
14
0.0
31
39
.44
12
9.4
11
28
.97
12
7.8
91
27
.70
12
6.8
61
25
.66
77
.32
77
.00
76
.69
72
.28
51
.35
39
.11
26
.27
24
.56
Figure S32. 13
C NMR spectrum of the compound 4ae
31
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
3.882.202.031.011.001.001.975.083.33
1.5
7
2.6
22
.63
2.6
42
.64
2.6
52
.71
2.7
22
.84
2.8
53
.02
3.0
43
.26
3.2
93
.73
3.7
33
.75
3.7
8
7.0
57
.07
7.1
57
.17
7.1
87
.26
7.2
67
.27
7.2
77
.29
N
S
Figure S33. 1H NMR spectrum of the compound 4af
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
No
rma
lize
d I
nte
nsity
13
9.8
01
38
.96
12
9.3
31
28
.70
12
8.0
41
27
.97
12
7.1
81
25
.88
77
.31
77
.00
76
.68
72
.01
52
.15
29
.63
28
.22
Figure S34. 13
C NMR spectrum of the compound 4af
32
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
3.910.950.981.003.921.984.982.97
2.4
62
.48
2.4
92
.50
2.5
3
2.8
82
.89
2.9
23
.32
3.3
33
.37
3.4
63
.48
3.4
93
.70
3.7
13
.72
6.9
36
.95
7.1
17
.12
7.1
37
.14
7.1
97
.21
7.2
27
.25
N
O
Figure S35. 1H NMR spectrum of the compound 4ag
160 140 120 100 80 60 40 20
Chemical Shift (ppm)
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
13
9.7
61
39
.26
12
9.4
11
28
.76
12
7.9
11
27
.11
12
5.7
9
77
.31
77
.00
76
.68
72
.45
67
.18
51
.21
39
.19
Figure S36. 13
C NMR spectrum of the compound 4ag
33
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
9.133.920.951.053.971.001.925.042.88
1.4
3
2.4
42
.93
2.9
52
.96
2.9
83
.29
3.3
13
.33
3.3
43
.40
3.5
73
.58
3.5
93
.61
6.9
76
.99
7.1
07
.11
7.1
37
.15
7.1
77
.22
7.2
37
.25
N
NBoc
Figure S37. 1H NMR spectrum of the compound 4ah
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0.5
1.0
No
rma
lize
d I
nte
nsity
15
4.7
4
13
9.4
31
39
.35
12
9.3
71
28
.74
12
7.9
61
27
.17
12
5.8
4
79
.41
77
.32
77
.00
76
.69
71
.77
50
.12
44
.23
39
.13
28
.32
Figure S38. 13
C NMR spectrum of the compound 4ah
34
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
9.622.342.112.111.031.174.161.022.018.67
1.4
4
1.6
91
.75
2.5
82
.64
2.7
82
.96
2.9
93
.01
3.2
43
.27
3.2
73
.36
3.4
1
3.9
0
7.0
47
.11
7.1
27
.13
7.1
57
.18
7.2
07
.24
7.2
6N
NBoc
Figure S39. 1H NMR spectrum of the compound 4ai
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
No
rma
lize
d I
nte
nsity
15
5.6
21
55
.51
14
0.5
61
39
.90
13
9.8
2
12
9.2
91
28
.44
12
7.9
81
27
.92
12
6.9
81
26
.96
79
.09
79
.04
77
.31
77
.00
76
.68
70
.43
70
.29
52
.89
52
.53
51
.92
51
.56
47
.63
47
.23
45
.86
45
.05
39
.18
28
.41
Figure S40. 13
C NMR spectrum of the compound 4ai
35
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
No
rma
lize
d I
nte
nsity
10.011.011.011.002.152.704.732.21
0.8
2
2.6
72
.69
2.7
02
.72
2.8
82
.90
2.9
22
.93
3.9
53
.97
3.9
73
.99
7.1
17
.13
7.1
87
.20
7.2
37
.25
7.2
77
.29
7.3
77
.38
NH
Figure S41. 1H NMR spectrum of the compound 4ai
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0.5
1.0
No
rma
lize
d I
nte
nsity
14
7.6
2
13
9.3
4
12
9.3
51
28
.34
12
8.1
21
27
.15
12
6.4
81
26
.35
77
.31
77
.00
76
.68
59
.19
51
.07
47
.13
29
.80
Figure S42. 13
C NMR spectrum of the compound 4ai
36
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
3.322.202.161.002.061.084.102.4610.38
3.7
7
4.2
04
.24
4.3
04
.34
5.6
4
6.6
46
.66
6.9
46
.95
6.9
66
.97
6.9
86
.99
7.2
67
.27
7.3
27
.33
7.3
6
N Ph
Ph
OMe
Figure S43. 1H NMR spectrum of the compound 8aa
160 140 120 100 80 60 40 20 0
Chemical Shift (ppm)
0.5
1.0
No
rma
lize
d I
nte
nsity
15
8.0
6
14
5.7
21
39
.50
13
8.9
21
32
.02
12
9.8
81
28
.26
12
7.7
71
27
.60
12
7.0
81
26
.72
12
6.3
41
23
.27
12
1.2
9
11
1.2
7
10
3.5
6
77
.32
77
.00
76
.69
55
.38
52
.44
Figure S44. 13
C NMR spectrum of the compound 8aa
37
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
3.642.322.141.061.041.121.091.132.3715.37
3.8
0
4.2
34
.27
4.3
34
.37
5.5
3
6.4
56
.47
6.5
86
.81
6.8
56
.97
6.9
87
.26
7.2
67
.29
7.3
17
.32
7.3
47
.36
7.4
0N Ph
Ph
OMe
Cl
Figure S45. 1H NMR spectrum of the compound 8ba
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30
Chemical Shift (ppm)
0
0.5
1.0
No
rma
lize
d I
nte
nsity
15
7.8
5
14
6.9
8
14
1.5
9
13
8.5
81
33
.36
13
1.7
41
30
.26
12
8.6
41
28
.36
12
7.6
11
26
.84
12
6.7
9
12
4.9
41
22
.89
12
1.4
5
11
1.2
5
10
1.3
1
77
.32
77
.00
76
.68
55
.39
52
.40
Figure S46. 13
C NMR spectrum of the compound 8ba
38
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.5
1.0
1.5
2.0
No
rma
lize
d I
nte
nsity
3.262.121.951.001.161.022.192.0213.47
3.7
7
4.2
24
.26
4.3
24
.36
5.5
8
6.7
46
.80
6.9
46
.95
6.9
67
.03
7.2
47
.26
7.2
77
.29
7.3
07
.32
7.3
4N Ph
Ph
OMe
F3C
Figure S47. 1H NMR spectrum of the compound 8ca
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
Chemical Shift (ppm)
0
0.5
1.0
1.5
No
rma
lize
d I
nte
nsity
15
7.8
7
14
7.3
7
14
0.4
21
38
.54
13
1.6
71
30
.35
12
9.9
41
28
.53
12
8.3
91
27
.79
12
7.7
11
27
.62
12
6.8
81
25
.51
12
1.4
11
19
.45
11
1.1
8
10
1.2
1
77
.32
77
.00
76
.68
55
.45
52
.41
Figure S48. 13
C NMR spectrum of the compound 8ca
39
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
No
rma
lize
d I
nte
nsity
3.534.501.022.152.243.0613.491.00
7.5
77
.56
7.3
57
.33
7.3
17
.29
7.2
97
.27
7.2
67
.25
6.9
66
.95
6.6
66
.64
6.5
96
.58
5.5
8
4.3
04
.26
4.2
34
.19
3.7
7
1.5
6
N Ph
Ph
OMeF
Figure S49. 1H NMR spectrum of the compound 8da
180 160 140 120 100 80 60 40 20
Chemical Shift (ppm)
0.5
1.0
No
rma
lize
d I
nte
nsity
16
0.9
51
58
.53
15
8.0
4
14
5.4
91
38
.89
13
5.6
01
33
.62
13
2.0
51
29
.96
12
9.8
81
28
.29
12
7.7
81
26
.76
12
6.1
11
21
.27
12
0.5
61
15
.65
11
5.4
41
14
.36
11
4.1
51
11
.24
10
2.5
4
77
.32
77
.00
76
.68
55
.33
52
.52
Figure S50. 13
C NMR spectrum of the compound 8da