Synthesis of optically active deuterated primary amines via reduction of N - Tert -butanesulfinyl aldimines

Article abstract of DOI:10.1021/jo500767k

Optically active deuterated primary amines have been obtained with 78-98% ee's from chiral N-tert-butanesulfinyl aldimines via reduction with N-Selectride and subsequent alcoholysis.

Full text of DOI:10.1021/jo500767k

Note
pubs.acs.org/joc
Synthesis of Optically Active Deuterated Primary Amines via
Reduction of N-tert-Butanesulfinyl Aldimines
Mao Liu,† Ying Xie,† Jing Li,† Hongjie Pan,† Hua Tian,† and Yian Shi*,†,‡,§
†Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of
Chemistry, Chinese Academy of Sciences, Beijing 100190, China
‡State Key Laboratory of Coordination Chemistry, Center for Multimolecular Organic Chemistry, School of Chemistry and Chemical
Engineering, Nanjing University, Nanjing 210093, China
§Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States
S
* Supporting Information
ABSTRACT: Optically active deuterated primary amines have been obtained with
78−98% ee’s from chiral N-tert-butanesulfinyl aldimines via reduction with N-
Selectride and subsequent alcoholysis.
ecently, we have reported an efficient biomimetic
transamination of α-keto esters to optically active α-
Scheme 2
R
amino esters with high ee’s with a quinine-derived chiral base as
catalyst and o-ClPhCH2NH2 as nitrogen source (Scheme 1).1
Scheme 1
a
Table 1. Studies on Reaction Conditions
b
c
entry
hydride
DIBAL
solvent
yield (%)
de (%)
1
2
3
4
5
6
7
8
THF
88
87
93
94
98
90
92
94
40 (RS, R)
44 (RS, R)
90 (RS, S)
95 (RS, S)
98 (RS, S)
63 (RS, S)
95 (RS, S)
86 (RS, S)
In this transamination process, the enantioselectivity is
determined by the [1,3]-proton shift from ketimine 4 and/or
5 to aldimine 6. To further understand the influencing factors
for the enantioselectivity, optically active deuterated primary
amine o-ClPhCHDNH2 would provide a useful probe for the
study. During such efforts, we have found that o-ClPhCH-
DNH2 can be efficiently synthesized from the corresponding
chiral N-tert-butanesulfinyl aldimines2 via reduction with N-
Selectride and subsequent alcoholysis (Scheme 2).3 Consider-
ing the potential usefulness of deuterated chiral primary amines
for the study of other reaction mechanisms,4−9 we further
investigated the reaction scope of this process. Herein, we wish
to report our studies on this subject.
NaBH4
THF
LiAlH4
THF
LiBEt3H
THF
N-Selectride
N-Selectride
N-Selectride
N-Selectride
THF
CH2Cl2
Et2O
toluene
a
The reactions were carried out with 7a (0.50 mmol) and hydride
b
(0.75 mmol) in solvent (5 mL) at −90 °C under N2 for 3 h. Isolated
yield based on 7a. The de’s were determined by H NMR.
c
1
and up to 98% de was obtained with N-Selectride in THF at
−90 °C (Table 1, entry 5). As shown in Table 2, the reaction
N-tert-Butanesulfinyl aldimine 7a, prepared from deuterated
2-chlorobenzaldehyde and (R)-(+)-tert-butanesulfinamide,10
was used as a test substrate for initial studies (Table 1).
Among various hydrides examined, LiAlH4, LiBEt3H, and N-
Selectride were found to be highly effective for the reduction,
Received: April 4, 2014
© XXXX American Chemical Society
A
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The Journal of Organic Chemistry
Note
Table 2. Reduction of Deuterated N-tert-Butanesulfinyl
Aldimines
Table 2. continued
a b
,
d
e
1
The de’s were determined by H NMR. The ee’s were determined
by 1H NMR after the primary amines were converted to the
corresponding (R)-MαNP amides unless otherwise stated. For entry
1
13, the ee was determined by H NMR after the primary amine was
f
converted to the corresponding (S)-Mosher amide. For entry 4, the
absolute configuration (S) of 9d was determined by comparing the 1H
NMR of the corresponding (R)-MαNP amide and (S)-Mosher amide
with the reported ones (refs 9b and 4o,) as well as supported by
comparing its optical rotation with the reported one (ref 4d). The
absolute configurations of remaining amines were tentatively proposed
by analogy.
can be applied to a variety of deuterated N-tert-butanesulfinyl
aromatic aldimines 7 to give the corresponding tert-
butanesulfinamides (8) in 90−97% yields and 94−98% de’s
(Table 2, entries 1−9). The substituents on the phenyl group
appear to have little effect on diastereoselectivity in the cases
examined. An alkynyl aldimine was also an effective substrate,
giving the reduction product in 93% yield and 93% de (Table 2,
entry 10). Slightly lower diastereoselectivities (78−86% de’s)
were obtained with aliphatic aldimines (Table 2, entries 11−
13). The tert-butanesulfinamides can be readily converted to
the corresponding chiral deuterated primary amines in 65−89%
yields and 78−98% ee’s with HCl/EtOH at rt. No racemization
was observed during the alcoholysis. The ee was determined by
1
the H NMR analysis of the corresponding (R)-2-methoxy-2-
(1-naphthyl)propionic amides [(R)-MαNP amides]9b,11 or (S)-
Mosher amide.12 The (R)-deuterated primary amine (12) was
obtained with 98% ee from (S)-(−)-tert-butanesulfinamide
(Scheme 3).
Scheme 3
In conclusion, we have developed an efficient method for the
synthesis of deuterated primary amines with high ee’s via
reduction of deuterated N-tert-butanesulfinyl aldimines with N-
Selectride and subsequent alcoholysis. The current process
provides ready access to various optically active deuterated
primary amines, which could be useful for studies of reaction
mechanisms in the future.
EXPERIMENTAL SECTION
■
General Methods. All commercially available reagents were used
without further purification unless otherwise noted. All solvents were
freshly distilled under nitrogen from appropriate drying agents before
use. Tetrahydrofuran, toluene, and ethyl ether were distilled from
sodium-benzophenone. Dichloromethane was distilled from CaH2.
Column chromatography was performed on silica gel (200−300
mesh). 1H NMR spectra were recorded on a 400 MHz NMR
spectrometer, and 13C NMR spectra were recorded on a 100 MHz
NMR spectrometer. High-resolution mass spectra (HRMS) were
obtained using an ESI-FTICR or ESI-LTQ-Orbitrap mass spectrom-
eter. IR spectra were recorded on an FT-IR spectrometer. Melting
points were uncorrected. Deuterated aldehydes were prepared from
a
All reductions were carried out with 7 (1.50 mmol) and N-Selectride
(2.25 mmol) in THF (15 mL) at −90 °C under N2 for 3 h unless
otherwise stated. For entry 7, the reaction was carried out with N-
Selectride (4.50 mmol) for 48 h. For entries 8 and 9, the reactions
b
were carried out with N-Selectride (4.50 mmol) for 24 h. The
alcoholysis was carried out with tert-butanesulfinamides (8) (1.25
mmol) and 33% HCl/EtOH (3 mL) in EtOH (6 mL) at rt for 3 h.
c
13
Isolated yield of 8 based on 7, and isolated yield of 9 based on 8.
the corresponding esters by reduction with LiAlD4 and subsequent
B
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Note
oxidation with PCC.14 N-tert-Butanesulfinyl aldimines were prepared
from the deuterated aldehydes according to the reported procedure.10
Representative Procedure for Diastereoselective Reduction
of N-tert-Butanesulfinyl Aldimines (Table 2, Entry 1). To a
stirred solution of 7a (0.367 g, 1.50 mmol) in THF (15 mL) at −90
°C was added N-Selectride (1.0 M in THF) (2.25 mL, 2.25 mmol)
dropwise under N2.3c The reaction mixture was stirred at −90 °C for 3
h, quenched with saturated aqueous NH4Cl, extracted with EtOAc (3
× 30 mL), washed with brine, dried over MgSO4, filtered,
concentrated, and purified by flash chromatography (silica gel,
petroleum ether/ethyl acetate = 4/3) to give tert-butanesulfinamide
8a as a white solid (0.358 g, 97% yield, 98% de).
Representative Procedure for Alcoholysis (Table 2, Entry 1).
To a solution of tert-butanesulfinamide 8a (0.308 g, 1.25 mmol) in
EtOH (6 mL) was added HCl (33% in EtOH) (3 mL) at rt.3d Upon
stirring at rt for 3 h, the reaction mixture was diluted with water (30
mL), concentrated to remove EtOH, washed with Et2O (4 × 15 mL),
brought to pH > 13 with 4 N NaOH, extracted with Et2O (3 × 30
mL), washed with brine, dried over MgSO4, filtered, and concentrated
to give deuterated amine 9a as a light yellow oil (0.152 g, 85% yield,
98% ee).
Hz, 1H), 1.51 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ 142.5,
133.0, 129.3, 128.7, 127.9, 123.7, 46.9 (t, JC‑D = 21.0 Hz); HRMS
Calcd for C7H8BrDN (M + H): 186.9976; Found: 186.9970.
(R)-2-Methyl-N-[(S)-o-tolylmethyl-d]propane-2-sulfinamide
(8c). White solid (0.321 g, 94% yield, 95% de); mp. 75−76 °C; IR
1
(film) 3217, 1483, 1456, 1056 cm−1; H NMR (400 MHz, CDCl3) δ
7.34−7.28 (m, 1H), 7.25−7.15 (m, 3H), 4.21 (d, J = 8.8 Hz, 1H), 3.31
(d, J = 8.8 Hz, 1H), 2.36 (s, 3H), 1.24 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 136.9, 136.2, 130.6, 129.0, 128.0, 126.2, 55.9, 47.1 (t, JC‑D
=
22.0 Hz), 22.8, 19.1; HRMS Calcd for C12H19DNOS (M + H):
227.1323; Found: 227.1323.
(S)-o-Tolylmethan-d-amine (9c). Yellow oil (0.127 g, 83% yield,
95% ee); IR (film) 3371, 3299, 1605, 1460 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.31 (d, J = 6.8 Hz, 1H), 7.24−7.13 (m, 3H), 3.85 (t, J = 2.0
Hz, 1H), 2.35 (s, 3H), 1.36 (br s, 2H); 13C NMR (100 MHz, CDCl3)
δ 141.3, 135.6, 130.4, 127.2, 127.0, 126.3, 44.0 (t, JC‑D = 21.0 Hz),
19.0; HRMS Calcd for C8H11DN (M + H): 123.1027; Found:
123.1025.
(R)-2-Methyl-N-[(S)-phenylmethyl-d]propane-2-sulfinamide
(8d). White solid (0.300 g, 94% yield, 96% de); mp. 66−68 °C; IR
1
(film) 3184, 1494, 1451, 1046 cm−1; H NMR (400 MHz, CDCl3) δ
7.38−7.32 (m, 4H), 7.32−7.26 (m, 1H), 4.24 (d, J = 8.0 Hz, 1H), 3.51
(d, J = 7.6 Hz, 1H), 1.24 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
138.5, 128.4, 127.9, 127.4, 55.7, 48.8 (t, JC‑D = 21.0 Hz), 22.6; HRMS
Calcd for C11H17DNOS (M + H): 213.1166; Found: 213.1164.
(S)-Phenylmethan-d-amine (9d).9b Yellow oil (0.110 g, 81%
yield, 96% ee); IR (film) 3362, 3286, 1604, 1450 cm−1; 1H NMR (400
MHz, CDCl3) δ 7.37−7.28 (m, 4H), 7.28−7.21 (m, 1H), 3.85 (t, J =
2.0 Hz, 1H), 1.44 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ 143.4,
128.6, 127.2, 126.9, 46.3 (t, JC‑D = 21.0 Hz).
(R)-2-Methyl-N-[(S)-m-tolylmethyl-d]propane-2-sulfinamide
(8e). White solid (0.319 g, 94% yield, 94% de); mp. 74−75 °C; IR
(film) 3181, 1608, 1040 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.24 (t,
J = 8.0 Hz, 1H), 7.17−7.08 (m, 3H), 4.20 (d, J = 8.0 Hz, 1H), 3.43 (d,
J = 8.0 Hz, 1H), 2.35 (s, 3H), 1.25 (s, 9H); 13C NMR (100 MHz,
Representative Procedure for the Determination of the
Optical Purity of Chiral Amines. To a solution of DCC (0.031 g,
0.15 mmol) and (R)-(−)-2-methoxy-2-(1-naphthyl)propionic acid
(0.035 g, 0.15 mmol) in CH2Cl2 (5 mL) at rt was added amine 9a
(0.014 g, 0.10 mmol).9b The reaction mixture was stirred at rt for 3 h
and filtrated. The filtrate was concentrated and purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate = 4/1) to
give the corresponding (R)-MαNP amide 13a as a colorless oil (0.025
g, 71%). The enantiomeric excess was determined by 1H NMR
analysis of the resulting (R)-MαNP amide.
(R)-N-[(S)-(2-Chlorophenyl)methyl-d]-2-methylpropane-2-
sulfinamide (8a). White solid (0.358 g, 97% yield, 98% de); mp.
1
107−108 °C; IR (film) 3205, 1464, 1439, 1057 cm−1; H NMR (400
MHz, CDCl3) δ 7.45−7.34 (m, 2H), 7.30−7.21 (m, 2H), 4.33 (d, J =
8.0 Hz, 1H), 3.57 (d, J = 7.6 Hz, 1H), 1.23 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 136.3, 134.0, 130.2, 129.8, 129.2, 127.2, 56.2, 47.3 (t,
JC‑D = 21.0 Hz), 22.8; HRMS Calcd for C11H16ClDNOS (M + H):
247.0777; Found: 247.0775.
CDCl3) δ 138.5, 138.4, 129.0, 128.6, 128.5, 125.3, 56.0, 49.2 (t, JC‑D
=
21.0 Hz), 22.8, 21.5; HRMS Calcd for C12H19DNOS (M + H):
227.1323; Found: 227.1324.
(S)-m-Tolylmethan-d-amine (9e). Yellow oil (0.124 g, 81% yield,
94% ee); IR (film) 3371, 3287, 1608, 1488 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.23 (t, J = 7.6 Hz, 1H), 7.18−7.03 (m, 3H), 3.82 (br s,
1H), 2.36 (s, 3H), 1.44 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ
143.5, 138.4, 128.6, 128.0, 127.7, 124.3, 46.4 (t, JC‑D = 20.0 Hz), 21.6;
HRMS Calcd for C8H11DN (M + H): 123.1027; Found: 123.1026.
(R)-N-[(S)-(4-Chlorophenyl)methyl-d]-2-methylpropane-2-
sulfinamide (8f). White solid (0.342 g, 92% yield, 95% de); mp.
(S)-(2-Chlorophenyl)methan-d-amine (9a). Yellow oil (0.152 g,
85% yield, 98% ee); IR (film) 3368, 3312, 1620, 1471 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.43−7.30 (m, 2H), 7.29−7.15 (m, 2H), 3.91 (t,
J = 2.0 Hz, 1H), 1.51 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ
140.8, 133.5, 129.6, 129.1, 128.3, 127.2, 44.4 (t, JC‑D = 21.0 Hz);
HRMS Calcd for C7H8ClDN (M + H): 143.0481; Found: 143.0479.
(S)-N-[(R)-(2-Chlorophenyl)methyl-d]-2-methylpropane-2-
sulfinamide (11). White solid (0.355 g, 96% yield, 98% de); mp.
1
106−107 °C; IR (film) 3172, 1491, 1471, 1039 cm−1; H NMR (400
1
108−109 °C; IR (film) 3211, 1466, 1440, 1047 cm−1; H NMR (400
MHz, CDCl3) δ 7.35−7.25 (m, 4H), 4.22 (d, J = 7.6 Hz, 1H), 3.45 (d,
J = 7.6 Hz, 1H), 1.24 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 137.1,
133.6, 129.6, 128.9, 56.1, 48.6 (t, JC‑D = 22.0 Hz), 22.8; HRMS Calcd
for C11H16ClDNOS (M + H): 247.0777; Found: 247.0777.
MHz, CDCl3) δ 7.43−7.34 (m, 2H), 7.28−7.21 (m, 2H), 4.33 (d, J =
7.6 Hz, 1H), 3.57 (d, J = 7.2 Hz, 1H), 1.23 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 136.3, 133.7, 130.1, 129.7, 129.1, 127.1, 56.1, 47.1 (t,
JC‑D = 22.0 Hz), 22.7.
(S)-(4-Chlorophenyl)methan-d-amine (9f).9b Yellow oil (0.150
1
(R)-(2-Chlorophenyl)methan-d-amine (12). Yellow oil (0.149 g,
84% yield, 98% ee); IR (film) 3373, 3297, 1593, 1471 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.42−7.30 (m, 2H), 7.29−7.13 (m, 2H), 3.90
(br s, 1H), 1.57 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ 140.8,
133.5, 129.7, 129.1, 128.4, 127.2, 44.5 (t, JC‑D = 22.0 Hz).
(R)-N-[(S)-(2-Bromophenyl)methyl-d]-2-methylpropane-2-
sulfinamide (8b). White solid (0.407 g, 93% yield, 97% de); mp.
g, 84% yield, 95% ee); IR (film) 3372, 3298, 1595, 1491 cm−1; H
NMR (400 MHz, CDCl3) δ 7.34−7.21 (m, 4H), 3.83 (t, J = 2.0 Hz,
1H), 1.43 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ 141.8, 132.6,
128.8, 128.6, 45.6 (t, JC‑D = 21.0 Hz).
(R)-N-[(S)-(4-Methoxyphenyl)methyl-d]-2-methylpropane-2-
sulfinamide (8g). White solid (0.341 g, 94% yield, 94% de); mp. 62−
1
64 °C; IR (film) 3206, 1612, 1514, 1055 cm−1; H NMR (400 MHz,
1
114−115 °C; IR (film) 3213, 1470, 1459, 1058 cm−1; H NMR (400
CDCl3) δ 7.29−7.23 (m, 2H), 6.90−6.85 (m, 2H), 4.17 (d, J = 8.0 Hz,
1H), 3.81 (s, 3H), 3.38 (d, J = 8.0 Hz, 1H), 1.24 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 159.4, 130.7, 129.6, 114.2, 56.0, 55.5, 48.8 (t,
JC‑D = 21.0 Hz), 22.9; HRMS Calcd for C12H19DNO2S (M + H):
243.1272; Found: 243.1276.
MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz, 1H), 7.41 (dd, J = 7.6, 1.2 Hz,
1H), 7.30 (t, J = 7.6 Hz, 1H), 7.16 (td, J = 8.0, 1.6 Hz, 1H), 4.31 (d, J
= 7.6 Hz, 1H), 3.61 (d, J = 7.6 Hz, 1H), 1.23 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 137.8, 132.7, 130.0, 129.1, 127.5, 123.6, 55.9, 49.2 (t,
JC‑D = 21.0 Hz), 22.6; HRMS Calcd for C11H16BrDNOS (M + H):
291.0272; Found: 291.0275.
(S)-(4-Methoxyphenyl)methan-d-amine (9g).9b Yellow oil
(0.139 g, 81% yield, 94% ee); IR (film) 3366, 3281, 1611, 1514
1
(S)-(2-Bromophenyl)methan-d-amine (9b). Yellow oil (0.208 g,
89% yield, 97% ee); IR (film) 3372, 3287, 1590, 1466, 1437 cm−1; 1H
NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 7.6
Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.16−7.05 (m, 1H), 3.89 (t, J = 2.0
cm−1; H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.4 Hz, 2H), 6.87
(d, J = 8.4 Hz, 2H), 3.79 (s, 3H), 3.78 (t, J = 2.0 Hz, 1H), 1.39 (br s,
2H); 13C NMR (100 MHz, CDCl3) δ 158.6, 135.8, 128.4, 114.1, 55.4,
45.7 (t, JC‑D = 21.0 Hz).
C
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Note
(R)-N-[(S)-Furan-2-ylmethyl-d]-2-methylpropane-2-sulfina-
mide (8h). Colorless oil (0.283 g, 93% yield, 94% de); IR (film) 3209,
1475, 1364, 1057 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.40−7.36 (m,
1H), 6.33 (dd, J = 3.2, 2.0 Hz, 1H), 6.27 (d, J = 3.2 Hz, 1H), 4.26−
4.18 (m, 1H), 3.44 (d, J = 6.8 Hz, 1H), 1.22 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 152.0, 142.6, 110.5, 108.0, 56.2, 42.1 (t, JC‑D = 21.0
Hz), 22.7; HRMS Calcd for C9H15DNO2S (M + H): 203.0959;
Found: 203.0959.
2H), 1.35 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ 142.3, 128.51,
128.48, 125.9, 41.5 (t, JC‑D = 21.0 Hz), 35.4, 33.4; HRMS Calcd for
C9H13DN (M + H): 137.1184; Found: 137.1181.
(R)-N-[(S)-Cyclohexylmethyl-d]-2-methylpropane-2-sulfina-
mide (8m). White solid (0.302 g, 92% yield, 78% de); mp. 85−86 °C;
IR (film) 3208, 1470, 1444, 1052 cm−1; 1H NMR (400 MHz, CDCl3)
δ 3.13 (d, J = 7.2 Hz, 1H), 2.85 (t, J = 7.6 Hz, 1H), 1.83−1.61 (m,
5H), 1.51−1.39 (m, 1H), 1.29−1.11 (m, 12H), 0.98−0.84 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 55.7, 51.8 (t, JC‑D = 21.0 Hz), 39.0,
(S)-Furan-2-ylmethan-d-amine (9h). Yellow oil (0.080 g, 65%
1
yield, 94% ee); IR (film) 3361, 3291, 1660, 1505, 1147 cm−1; H
30.9, 30.8, 26.5, 25.90, 25.88, 22.7; HRMS Calcd for C11H23DNOS (M
+ H): 219.1636; Found: 219.1634.
NMR (400 MHz, CDCl3) δ 7.33 (d, J = 1.2 Hz, 1H), 6.29 (dd, J = 3.2,
2.0 Hz, 1H), 6.12 (d, J = 3.2 Hz, 1H), 3.79 (t, J = 2.4 Hz, 1H), 1.49 (br
s, 2H); 13C NMR (100 MHz, CDCl3) δ 156.9, 141.7, 110.3, 105.2,
39.2 (t, JC‑D = 21.0 Hz); HRMS Calcd for C5H7DNO (M + H):
99.0663; Found: 99.0666.
(S)-Cyclohexylmethan-d-amine (9m). Yellow oil (0.115 g, 81%
yield, 78% ee); IR (film) 3360, 3289, 1574, 1448 cm−1; 1H NMR (400
MHz, CDCl3) δ 2.47 (d, J = 5.2 Hz, 1H), 1.79−1.60 (m, 5H), 1.47 (br
s, 2H), 1.31−1.09 (m, 4H), 0.95−0.79 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 48.6 (t, JC‑D = 20.0 Hz), 41.3, 30.9, 26.8, 26.2; HRMS Calcd
for C7H15DN (M + H): 115.1340; Found: 115.1339.
(R)-2-Methyl-N-[(S)-thiophen-2-ylmethyl-d]propane-2-sulfi-
namide (8i). White solid (0.294 g, 90% yield, 94% de); mp. 79−81
1
°C; IR (film) 3171, 1473, 1459, 1048 cm−1; H NMR (400 MHz,
CDCl3) δ 7.25 (d, J = 4.8 Hz, 1H), 7.00 (d, J = 3.6 Hz, 1H), 6.96 (dd,
J = 4.8, 3.6 Hz, 1H), 4.41 (d, J = 7.6 Hz, 1H), 3.57 (d, J = 7.2 Hz, 1H),
1.25 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 142.0, 126.9, 125.9,
125.5, 56.1, 44.1 (t, JC‑D = 22.0 Hz), 22.7; HRMS Calcd for
C9H15DNOS2 (M + H): 219.0731; Found: 219.0730.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR and 13C NMR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
(S)-Thiophen-2-ylmethan-d-amine (9i). Yellow oil (0.111 g,
78% yield, 94% ee); IR (film) 3364, 3295, 1592, 1439 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.20 (d, J = 5.2 Hz, 1H), 6.95 (dd, J = 5.2, 3.2
Hz, 1H), 6.92 (d, J = 3.2 Hz, 1H), 4.04 (t, J = 2.0 Hz, 1H), 1.63 (br s,
2H); 13C NMR (100 MHz, CDCl3) δ 147.5, 126.9, 124.1, 123.8, 41.2
(t, JC‑D = 21.0 Hz); HRMS Calcd for C5H7DNS (M + H): 115.0435;
Found: 115.0436.
AUTHOR INFORMATION
Corresponding Author
*E-mail: yian@lamar.colostate.edu.
Notes
■
The authors declare no competing financial interest.
(R)-2-Methyl-N-[(S)-non-2-yn-1-yl-1-d]propane-2-sulfina-
mide (8j). Yellow oil (0.341 g, 93% yield, 93% de); IR (film) 3204,
2242, 1057 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.81 (dt, J = 6.8, 2.0
Hz, 1H), 3.25 (d, J = 6.4 Hz, 1H), 2.18 (td, J = 6.8, 2.0 Hz, 2H), 1.54−
1.43 (m, 2H), 1.42−1.24 (m, 6H), 1.23 (s, 9H), 0.88 (t, J = 6.8 Hz,
ACKNOWLEDGMENTS
■
We gratefully acknowledge the National Basic Research
Program of China (973 program, 2010CB833300) and the
Chinese Academy of Sciences for the financial support.
3H); 13C NMR (100 MHz, CDCl3) δ 85.5, 76.2, 56.1, 35.0 (t, JC‑D
=
22.0 Hz), 31.5, 28.69, 28.67, 22.7, 18.9, 14.2; HRMS Calcd for
C13H25DNOS (M + H): 245.1792; Found: 245.1795.
REFERENCES
■
(1) (a) Xiao, X.; Xie, Y.; Su, C.; Liu, M.; Shi, Y. J. Am. Chem. Soc.
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(S)-Non-2-yn-1-d-1-amine (9j). Yellow oil (0.146 g, 83% yield,
93% ee); IR (film) 3373, 3284, 2221, 1602 cm−1; 1H NMR (400 MHz,
CDCl3) δ 3.38 (br s, 1H), 2.16 (t, J = 6.4 Hz, 2H), 1.55−1.43 (m,
2H), 1.42−1.18 (m, 8H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 82.8, 81.0, 31.6 (t, JC‑D = 21.0 Hz), 31.5, 29.0, 28.7,
22.7, 18.8, 14.2; HRMS Calcd for C9H17DN (M + H): 141.1497;
Found: 141.1495.
(R)-2-Methyl-N-[(S)-nonyl-1-d]propane-2-sulfinamide (8k).
Colorless oil (0.351 g, 94% yield, 85% de); IR (film) 3203, 1053
cm−1; 1H NMR (400 MHz, MeOD) δ 3.02 (t, J = 7.2 Hz, 1H), 1.61−
1.51 (m, 2H), 1.42−1.26 (m, 12H), 1.22 (s, 9H), 0.90 (t, J = 6.8 Hz,
3H); 13C NMR (100 MHz, MeOD) δ 56.8, 46.5 (t, JC‑D = 21.0 Hz),
33.0, 32.1, 30.7, 30.4, 27.8, 23.7, 23.1, 14.4; HRMS Calcd for
C13H29DNOS (M + H): 249.2105; Found: 249.2109.
(S)-Nonan-1-d-1-amine (9k). Yellow oil (0.155 g, 86% yield, 85%
1
ee); IR (film) 3330, 1467 cm−1; H NMR (400 MHz, CDCl3) δ 2.65
(t, J = 6.8 Hz, 1H), 1.46−1.37 (m, 2H), 1.36−1.14 (m, 14H), 0.87 (t, J
= 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 42.1 (t, JC‑D = 20.0
Hz), 34.0, 32.1, 29.8, 29.7, 29.5, 27.1, 22.9, 14.3; HRMS Calcd for
C9H21DN (M + H): 145.1810; Found: 145.1808.
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(i) Nicewonger, R.; Rammelsberg, A.; Costello, C. A.; Begley, T. P.
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1
1603, 1455, 1051 cm−1; H NMR (400 MHz, MeOD) δ 7.30−7.22
(m, 2H), 7.22−7.12 (m, 3H), 3.04 (t, J = 7.2 Hz, 1H), 2.75−2.60 (m,
2H), 1.94−1.82 (m, 2H), 1.23 (s, 9H); 13C NMR (100 MHz, CDCl3)
δ 141.6, 128.7, 128.6, 126.2, 55.7, 45.0 (t, JC‑D = 21.0 Hz), 33.2, 32.7,
22.8; HRMS Calcd for C13H21DNOS (M + H): 241.1479; Found:
241.1476.
(S)-3-Phenylpropan-1-d-1-amine (9l). Colorless oil (0.148 g,
87% yield, 86% ee); IR (film) 3364, 3296, 1602, 1496, 1454 cm−1; 1H
NMR (400 MHz, CDCl3) δ 7.32−7.24 (m, 2H), 7.22−7.15 (m, 3H),
2.71 (t, J = 7.2 Hz, 1H), 2.65 (t, J = 7.6 Hz, 2H), 1.77 (q, J = 7.2 Hz,
D
dx.doi.org/10.1021/jo500767k | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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E
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