Asymmetric synthesis of cis -2-aminocyclopropanols by intramolecular mannich addition of silyloxy benzyl carbanions

Article abstract of DOI:10.1021/jo200585r

An efficient, highly diastereoselective method for the preparation of protected cis-2-aminocyclopropanols from N-tert-butanesulfinyl ketimines and various aryl acylsilanes is described. A tandem process for carbon-carbon bond formation via nucleophilic ad

Full text of DOI:10.1021/jo200585r

NOTE
pubs.acs.org/joc
Asymmetric Synthesis of cis-2-Aminocyclopropanols by
Intramolecular Mannich Addition of Silyloxy Benzyl Carbanions
Bo Liu and Chong-Dao Lu*
Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China
S Supporting Information
b
ABSTRACT: An efficient, highly diastereoselective method for the pre-
paration of protected cis-2-aminocyclopropanols from N-tert-butanesulfinyl
ketimines and various aryl acylsilanes is described. A tandem process for
carbonꢀcarbon bond formation via nucleophilic addition to acylsilanes,
Brook rearrangement, and intramolecular Mannich reaction has been
developed.
nantiomerically pure 1,2-aminoalcohols are key substruc-
tures in a number of bioactive compounds and can serve as
that LDA (entry 4) gave a better yield than LHMDS (entry 1).
Increasing the reaction temperature, which accelerates the 1,2-
Brook rearrangement, further improved the yield (entry 5 vs
entry 4). The best yield was obtained by using LDA as a base and
warming the reaction mixture gradually from ꢀ78 to ꢀ30 °C
over a period of 5 h [84% yield (Table 1, entry 5, and Table 2,
entry 1)]. We also observed that the bulkiness of the silyl groups
in the acylsilanes significantly influenced the reaction rate.
Compared to the example of 1a and PhCOTBS outlined above,
reactions involving acylsilanes with smaller silyl groups pro-
ceeded smoothly at lower temperatures with a shorter reaction
time. Warming the reaction mixture of 1a and acylsilane 2b
(PhCOTES) from ꢀ78 to ꢀ50 °C over a period of 3 h was
sufficient to consume 1a completely (Table 2, entry 2). In
addition, acyltrimethylsilane 2c reacted even faster than its
analogue with a slightly bulkier silyl group (2b, PhCOTES),
reaching completion when the reaction mixture was warmed
from ꢀ78 to ꢀ50 °C over 1.5 h. For further studies of the scope
of the reaction, acyltriethylsilanes (2b, 2d, 2e, and 2f) were
chosen instead of the acyltrimethylsilanes because TES ether
products exhibit better tolerance to silica gel chromatography.
We next examined the scope of the addition of N-sulfinyl
metalloenamines to acylsilanes. As illustrated in Table 2, the
reactions generally proceeded in moderate to good yields. N-
Sulfinyl aryl (or heteroaryl) methyl ketimines 1aꢀ1h served as
nucleophiles to attack aryl acylsilanes, and the addition-initiated
cascade reactions produced a diverse collection of enantioen-
riched cis-2-aminocyclopropanols with contiguous tertiary car-
bons bearing identical or different aryl groups. Both electron-rich
and electron-deficient aryl-substituted acylsilanes (2dꢀ2f)
proved to be suitable for this reaction.
E
useful precursors for several valuable ligands and auxiliaries in
asymmetric synthesis.1ꢀ3 Although 2-aminocyclopropanols make up
a unique subclass of 1,2-aminoalcohols, they have received little
attention, in part because few synthetic methods for their
efficient preparation are available. trans-2-Aminocyclopropanols
have been prepared by irradiation of β-aminoketones,4 whereas
[2þ1] cycloaddition reaction of bis(iodozincio)methane with
R-ketoimines yields the cis isomers.5 However, such methods
give racemic products that are of limited diversity.
Here, we report an efficient method for asymmetric synthesis
of cis-2-aminocyclopropanols possessing a silyl group on oxygen
and an N-tert-butanesulfinyl group on nitrogen. The synthesis
involves the reaction of N-tert-butanesulfinyl ketimines6ꢀ9 with
acylsilanes in the presence of lithium diisopropylamide via
nucleophilic addition of lithium enamines to acylsilanes, followed
by Brook rearrangement10 and trapping of the silyloxy benzyl
anion by intramolecular Mannich addition (Scheme 1).
A number of synthetically useful methodologies based on
Brook rearrangement have been developed by using organome-
tallic reagents as triggers, such as metallocyanide,11 metallophos-
phite,12 vinyl/propargyllic lithium,13 zinc acetylide,14 vinyl
Grignard reagents,15 and metalloenolates.16ꢀ18 The related in-
tramolecular transformations initiated by the addition of lithium
ketone enolates to acylsilanes and its applications in total
synthesis have been disclosed by the Takeda group in recent
years.19ꢀ21 However, the reactivity of metalloenamines derived
from N-tert-butanesulfinyl ketimines toward acylsilanes has not
been reported. This report serves as the first demonstration of
this reactivity.
The results from our preliminary experiments are presented in
Table 1. Lithiation of the (RS)-N-tert-butanesulfinyl imine of
acetophenone 1a with LHMDS at ꢀ78 °C followed by the
addition of acylsilane 2a resulted in cis-2-aminocyclopropanol 3a
in 66% isolated yield as a single diastereomer (entry 1). LHMDS
as a base is superior to NaHMDS and KHMDS for this reaction
(entries 2 and 3, respectively). Further experimentation revealed
The absolute configuration of the 2-aminocyclopropan-1-ol 3a
was determined to be (RS,1S,2R) by single-crystal X-ray diffraction
analysis, with 3bꢀ3p assigned by analogy.22 The relative configura-
tion between the tBS-amine group and the TBS-ether moiety
Received: March 17, 2011
Published: April 29, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo200585r J. Org. Chem. 2011, 76, 4205–4209
|

The Journal of Organic Chemistry
NOTE
Scheme 1. Reactions Involving 1,2-Brook Rearrangement and Intramolecular Mannich Addition
Table 1. Optimization of the Addition of N-Sulfinylketimine
Table 2. Addition of N-Sulfinyl Metalloenamines to
Acylsilanesa
1a to Acylsilane 2aa
entry
base (equiv)
temp (°C)
time (h)
yield (%)b
1
2
3
4
5
LHMDS (1.05)
NaHMDS (1.05)
KHMDS (1.05)
LDA (1.20)
ꢀ78
8
8
66
47
33
74
84
ꢀ78
ꢀ78
ꢀ78
ꢀ78 to ꢀ30
8
12
5
entry sulfinimine 1 (Ar) acylsilane 2b (Ar0, SiR3) product 3 yield (%)c
LDA (1.20)
a The reaction was performed on a 0.2 mmol scale using 1.5 equiv of 2a.
b Isolated yield after column chromatography on silica gel. 1H NMR of
the crude reaction mixture detected only one diastereomer.
1
1a (Ph)
2a (Ph, TBS)
3a
3b
3c
3d
3e
3f
84
84
74
69
47
63
84
94
77
75
74
80
65
62
69
67
2
1a (Ph)
2b (Ph, TES)
3
1a (Ph)
2c (Ph, TMS)
2d (p-MeOPh, TES)
2e (p-MePh, TES)
2f (p-ClPh, TES)
2a (Ph, TBS)
4
1a (Ph)
appeared to be cis. The reaction occurred with high diastereoselec-
tivity in all cases (Table 2, dr > 20:1). Although the origin of the high
degree of stereocontrol of this reaction is unclear, the observed
stereochemistry can be explained in the following way. On the basis
of the six- and four-membered bicyclic transition-state model ad-
vanced by Ellman in the reaction of metalloenamines and aldehydes
(Scheme 2),8 nucleophilic attack of the lithium enamine on the aryl
acylsilane should proceed preferentially from the opposite direction
of the tert-butyl group. However, according to Ellman and Liu’s
pioneering studies, this step does not proceed in a highly diaster-
eoselective manner without assistance from additives. In their studies,
reactions of lithium enamine derived from N-tert-butanesulfinyl imine
of acetophenone with phenacyl derivatives (PhCOR0), such as benz-
aldehyde (R0 = H) and phenyl trifluoromethyl ketone (R0 = CF3),
gave moderate to poor diastereoselectivity without assistance
from ZnBr2 (R0 = H, and dr = 73:27; R0 = CF3, and dr = 59:41).8,9
The facial selectivity from the aryl acylsilane (R0 = SiR3; re face or
si face) would be low in this case because the competing 1,
3-diaxial interactions in A and A0 are not overwhelmingly different.
It is likely that the silyloxy carbanions C (and C0), generated
from the stereospecific Brook rearrangement via B (and B0) with
retention of configuration, intramolecularly attack azomethine
with retention of configuration at the carbanion center for C and
with inversion for C0,23ꢀ26 leading to 3 as the sole product with
the requisite stereochemical features. The chair conformation of
C (and C0), together with the significant electron density on both
faces of the partially flattened R-oxybenzyl anion,27 permits the
diastereocontrol in the intramolecular Mannich trapping. Prior
to formation of the second CꢀC bond, partial epimerization
between carbanions C and C0 could also occur.
5
1a (Ph)
6
1a (Ph)
7
1b (p-MeOPh)
1b (p-MeOPh)
1b (p-MeOPh)
1b (p-MeOPh)
1c (o-MeOPh)
1d (p-ClPh)
1e (p-BrPh)
1f (2-pyridinyl)
1g (3-pyridinyl)
1h (2-furanyl)
3g
3h
3i
8
2b (Ph, TES)
9
2d (p-MeOPh, TES)
2f (p-ClPh, TES)
2b (Ph, TES)
10
11
12
13
14
15
16
3j
3k
3l
2b (Ph, TES)
2b (Ph, TES)
3m
3n
3o
3p
2b (Ph, TES)
2b (Ph, TES)
2b (Ph, TES)
a The reaction was performed on a 0.2 mmol scale using 1.5 equiv of 2.
b TBS indicates tert-butyldimethylsilyl, TES triethylsilyl, and TMS
trimethylsilyl. c Isolated yield after column chromatography on silica gel.
1H NMR of the crude reaction mixture indicated that only one
diastereomer was observed.
In summary, we have developed a diastereoselective synthesis of
protected cis-2-aminocyclopropanols by the reaction of N-tert-butyl-
sulfinyl ketimines with acylsilanes. A cascade transformation involving
the formation of two CꢀC bonds and an OꢀSi bond is a key feature
of this reaction. A mechanism rationalizing the observed diastereo-
control for the formation of cis-2-aminocyclopropanol is proposed.
’ EXPERIMENTAL SECTION
General Procedure for the Synthesis of cis-2-Aminocyclo-
propanol 3. THF (1.5 mL) and diisopropylamine (33.8μL, 0.24 mmol)
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dx.doi.org/10.1021/jo200585r |J. Org. Chem. 2011, 76, 4205–4209

The Journal of Organic Chemistry
NOTE
Scheme 2. Rationale for the Observed Stereochemistry
127.7, 127.7, 127.4, 126.6, 64.5, 55.8, 47.6, 22.6, 21.9, 6.9, 5.5; HRMS
(ESI) m/z calcd for C25H37NO2SSiNa [M þ Na]þ 466.2212, found
466.2200.
(RS)-N-[(1R,2S)-1,2-Diphenyl-2-(trimethylsilyloxy)cyclopr-
opyl]-2-methylpropane-2-sulfinamide (3c). The reaction
mixture was gradually warmed to ꢀ55 °C over a 1.5 h period, giving
complete conversion. Elution with a petroleum ether/EtOAc mixture
(15:1 to 10:1, v/v) gave 59.3 mg of product 3c (74% yield) as a white
solid: mp 88ꢀ90 °C; [R]25D = ꢀ24.0° (c 0.1, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ 7.15ꢀ6.91 (m, 10H), 4.89 (s, 1H), 2.36 (d, J = 7.7 Hz,
1H), 2.05 (d, J = 7.7 Hz, 1H), 1.20 (s, 9H), 0.06 (s, 9H); 13C NMR
(101 MHz, CDCl3) δ 138.9, 138.5, 129.1, 128.1, 127.8, 127.7, 127.3,
126.7, 64.6, 55.8, 47.2, 22.6, 22.1, 1.0; HRMS (ESI) m/z calcd for
C22H31NO2SSiNa [M þ Na]þ 424.1742, found 424.1737.
(RS)-N-[(1R,2S)-1-Phenyl-2-(4-methoxyphenyl)-2-(triethyl-
silyloxy)cyclopropyl]-2-methylpropane-2-sulfinamide (3d).
The reaction mixture was gradually warmed to rt over a 20 h period,
giving complete conversion. Elution with a petroleum ether/EtOAc
mixture (6:1 to 4:1, v/v) gave 65.3 mg of product 3d (69% yield) as a
slight yellow solid: mp 85ꢀ87 °C; [R]25D = 4.0° (c 0.1, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.10 (d, J = 7.8 Hz, 2H), 7.07ꢀ7.00 (m, 4H),
6.97 (t, J = 7.1 Hz, 1H), 6.58 (d, J = 8.8 Hz, 2H), 4.88 (s, 1H), 3.67
(s, 3H), 2.30 (d, J = 7.6 Hz, 1H), 1.98 (d, J = 7.6 Hz, 1H), 1.20 (s, 9H),
0.87 (t, J = 7.6 Hz, 9H), 0.59ꢀ0.43 (m, 6H); 13C NMR (101 MHz,
CDCl3) δ 158.5, 139.1, 130.6, 129.5, 128.7, 127.5, 126.3, 112.8, 64.1,
55.6, 55.0, 47.2, 22.4, 21.9, 6.7, 5.2; HRMS (ESI) m/z calcd for
C26H39NO3SSiNa [M þ Na]þ 496.2318, found 496.2312.
were added to a flame-dried flask equipped with a magnetic stirring bar
and purged with nitrogen. The solution was cooled to ꢀ10 °C, and
n-butyllithium (2.5 M in hexane, 96 μL, 0.24 mmol) was added by syringe.
The mixture was stirred at this temperature for 45 min and then cooled
to ꢀ78 °C. N-Sulfinyl imine 128,29 (0.2 mmol) in THF (1.5 mL) was
added to the reaction mixture at ꢀ78 °C, and the mixture was stirred for
an additional 45 min. A solution of acylsilane 230,31 (0.3 mmol) in THF
(0.5 mL) was added, and the mixture was gradually warmed to the
indicatedtemperature for the indicatedtime (see the details for eachofthe
examples), at which point the starting material had been completely
consumed, based on TLC detection. The reaction was quenched with
saturated aqueous ammonium chloride. After being warmed to ambient
temperature, the mixture was extracted with ethyl acetate. The combined
organic layer was washed with brine, dried over anhydrous sodium sulfate,
filtered, and concentrated byevaporation. The residue was analyzed by 1H
NMR (dr > 20:1) and purified by flash column chromatography on silica
gel to give the desired product.
(RS)-N-[(1R,2S)-1,2-Diphenyl-2-(tert-butyldimethylsilyloxy)-
cyclopropyl]-2-methylpropane-2-sulfinamide (3a). The reac-
tion mixture was gradually warmed to ꢀ30 °C over a 5 h period, giving
complete conversion. Elution with a petroleum ether/EtOAc mixture
(9:1 to 6:1, v/v) gave 74.1 mg of product 3a (84% yield) as a white solid:
mp 95ꢀ97 °C; [R]25D = ꢀ38.0° (c 0.1, CH2Cl2); 1H NMR (400 MHz,
CDCl3) δ 7.14ꢀ6.94 (m, 10H), 4.86 (s, 1H), 2.40 (d, J = 7.7 Hz, 1H),
2.02 (d, J = 7.7 Hz, 1H), 1.19 (s, 9H), 0.91 (s, 9H), 0.15 (s, 3H), ꢀ0.26
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 139.1, 138.5, 129.1, 128.5,
127.7, 127.6, 127.4, 126.6, 64.8, 55.8, 47.6, 26.0, 22.7, 21.5, 18.2, ꢀ3.7;
HRMS (ESI) m/z calcd for C25H37NO2SSiNa [M þ Na]þ 466.2212,
found 466.2206.
(RS)-N-[(1R,2S)-1-Phenyl-2-(4-methylphenyl)-2-(triethylsily-
loxy)cyclopropyl]-2-methylpropane-2-sulfinamide (3e). The
reaction mixture was gradually warmed to ꢀ50 °C over a 3 h period,
giving complete conversion. Elution with a petroleum ether/EtOAc
mixture (10:1 to 8:1, v/v) gave 43.3 mg of product 3e (47% yield) as a
white solid: mp 86ꢀ88 °C; [R]25D = ꢀ25.0° (c 0.1, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.10 (d, J = 7.2 Hz, 2H), 7.06ꢀ6.94 (m, 5H), 6.84
(d, J = 7.9 Hz, 2H), 4.89 (s, 1H), 2.32 (d, J = 7.6 Hz, 1H), 2.16 (s, 3H),
1.96 (d, J = 7.6 Hz, 1H), 1.18 (s, 9H), 0.87 (t, J = 7.9 Hz, 9H), 0.58ꢀ0.45
(m, 6H); 13C NMR (101 MHz, CDCl3) δ 139.0, 136.7, 135.3, 128.9,
128.2, 128.0, 127.4, 126.3, 64.2, 55.6, 47.3, 22.4, 21.8, 21.0, 6.7, 5.2;
HRMS (ESI) m/z calcd for C26H39NO2SSiNa [M þ Na]þ 480.2368,
found 480.2363.
(RS)-N-[(1R,2S)-1-Phenyl-2-(4-chlorophenyl)-2-(triethylsilylo-
xy)cyclopropyl]-2-methylpropane-2-sulfinamide (3f). The re-
action mixture was gradually warmed to rt over a 12 h period, giving
complete conversion. Elution with a petroleum ether/EtOAc mixture
(8:1 to 6:1, v/v) gave 60.4 mg of product 3f (63% yield) as a slight yellow
1
solid: mp 84ꢀ86 °C; [R]25 = ꢀ11.0° (c 0.1, CH2Cl2); H NMR
D
(400 MHz, CDCl3) δ 7.14ꢀ6.94 (m, 9H), 4.83 (s, 1H), 2.33 (d, J =
7.8 Hz, 1H), 2.01 (d, J = 7.7 Hz, 1H), 1.18 (s, 9H), 0.88 (t, J = 7.9 Hz,
9H), 0.62ꢀ0.45 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 138.5, 137.4,
132.9, 129.2, 128.9, 127.7, 127.7, 126.7, 63.7, 55.6, 47.6, 22.4, 21.7, 6.7,
5.3; HRMS (ESI) m/z calcd for C25H36ClNO2SSiNa [M þ Na]þ
500.1822, found 500.1817.
(RS)-N-[(1R,2S)-1-(4-Methoxyphenyl)-2-phenyl-2-(tert-but-
yldimethylsilyloxy)cyclopropyl]-2-methylpropane-2-sulfi-
namide (3g). The reaction mixture was gradually warmed to ꢀ15 °C
over a 3 h period, giving complete conversion. Elution with a petroleum
ether/EtOAc mixture (8:1 to 6:1, v/v) gave 79.0 mg of product 3g
(RS)-N-[(1R,2S)-1,2-Diphenyl-2-(triethylsilyloxy)cyclopro-
pyl]-2-methylpropane-2-sulfinamide (3b). The reaction mix-
ture was gradually warmed to ꢀ55 °C over a 3 h period, giving complete
conversion. Elution with a petroleum ether/EtOAc mixture (9:1 to 6:1,
(84% yield) as a colorless solid: mp 142ꢀ144 °C; [R]25 = ꢀ40.0°
D
v/v) gave 74.4 mg of product 3b (84% yield) as a white solid: mp
(c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.16ꢀ6.99 (m, 7H),
6.56 (d, J =8.7 Hz, 2H), 4.82 (s, 1H), 3.65 (s, 3H), 2.31 (d, J = 7.6 Hz, 1H),
1.96 (d, J = 7.6 Hz, 1H), 1.18 (s, 9H), 0.91 (s, 9H), 0.14 (s, 3H), ꢀ0.27
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 158.0, 138.5, 131.0, 130.1,
128.2, 127.5, 127.1, 112.8, 64.4, 55.5, 54.9, 47.0, 25.8, 22.5, 21.3, 18.0,
1
57ꢀ59 °C; [R]25 = ꢀ13.5° (c 0.1, CH2Cl2); H NMR (400 MHz,
D
CDCl3) δ 7.20ꢀ6.90 (m, 10H), 4.90 (s, 1H), 2.38 (d, J = 7.7 Hz, 1H),
2.01 (d, J = 7.7 Hz, 1H), 1.20 (s, 9H), 0.88 (t, J = 7.9 Hz, 9H), 0.63ꢀ0.44
(m, 6H); 13C NMR (101 MHz, CDCl3) δ 139.1, 138.7, 129.1, 128.3,
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NOTE
ꢀ3.9, ꢀ4.0; HRMS (ESI) m/z calcd for C26H39NO3SSiNa [M þ Na]þ
496.2318, found 496.2312.
(RS)-N-[(1R,2S)-1-(4-Bromophenyl)-2-phenyl-2-(triethylsi-
lyloxy)cyclopropyl]-2-methylpropane-2-sulfinamide (3m).
The reaction mixture was gradually warmed to ꢀ40 °C over a 4 h
period, giving complete conversion. Elution with a petroleum ether/
EtOAc mixture (10:1 to 8:1, v/v) gave 68.2 mg of product 3m (65%
(RS)-N-[(1R,2S)-1-(4-Methoxyphenyl)-2-phenyl-2-(triethyl-
silyloxy)cyclopropyl]-2-methylpropane-2-sulfinamide (3h).
The reaction mixture was gradually warmed to ꢀ40 °C over a 3 h
period, giving complete conversion. Elution with a petroleum ether/
EtOAc mixture (10:1 to 8:1, v/v) gave 89.3 mg of product 3h (94%
yield) as a colorless oil: [R]25D = 22.1° (c 0.1, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ 7.14ꢀ7.02 (m, 7H), 6.58 (d, J = 8.7 Hz, 2H), 4.86
(s, 1H), 3.67 (s, 3H), 2.30 (d, J = 7.6 Hz, 1H), 1.96 (d, J = 7.6 Hz, 1H),
1.19 (s, 9H), 0.89ꢀ0.81 (m, 9H), 0.63ꢀ0.45 (m, 6H); 13C NMR (101
MHz, CDCl3) δ 158.2, 139.0, 131.2, 130.4, 128.1, 127.7, 127.3, 113.0,
64.3, 55.7, 55.3, 47.4, 22.6, 22.0, 7.0, 5.5; HRMS (ESI) m/z calcd for
C26H39NO3SSiNa [M þ Na]þ 496.2318, found 496.2312.
yield) as a white solid: mp 102ꢀ104 °C; [R]25 = ꢀ19.0° (c 0.1,
D
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.17 (d, J = 7.7 Hz, 2H),
7.14ꢀ7.02 (m, 5H), 6.98 (d, J = 7.8 Hz, 2H), 4.88 (s, 1H), 2.33 (d, J = 7.7
Hz, 1H), 2.04 (d, J = 9.1 Hz, 1H), 1.20 (s, 9H), 0.90ꢀ0.85 (m, 9H),
0.63ꢀ0.43 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 138.2, 138.1,
130.6, 130.5 128.0, 127.7, 127.5, 120.3, 64.3, 55.7, 47.0, 22.4, 21.7, 6.7,
5.2; HRMS (ESI) m/z calcd for C25H36BrNO2SSiNa [M þ Na]þ
544.1317, found 544.1312.
(RS)-N-[(1R,2S)-1-(Pyridin-2-yl)-2-phenyl-2-(triethylsilylo-
xy)cyclopropyl]-2-methylpropane-2-sulfinamide (3n). The
reaction mixture was gradually warmed to ꢀ35 °C over a 3 h period,
giving complete conversion. Elution with a petroleum ether/EtOAc/
MeOH mixture (10:1:1, v/v) gave 55.0 mg of product 3n (62% yield) as
a slight yellowoil: [R]25D = ꢀ24.0° (c 0.1, CH2Cl2); 1H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 4.8 Hz, 1H), 7.48ꢀ7.36 (m, 2H), 7.16 (d, J =
6.6 Hz, 2H), 7.07ꢀ6.96 (m, 3H), 6.82ꢀ6.76 (m, 1H), 4.93 (s, 1H), 3.01
(d, J = 7.1 Hz, 1H), 2.13 (d, J = 7.1 Hz, 1H), 1.27 (s, 9H), 0.87 (t, J = 7.9
Hz, 9H), 0.53 (q, J = 15.2 Hz, 6H); 13C NMR (101 MHz, CDCl3)
δ 158.5, 148.1, 138.2, 135.5, 128.9, 127.5, 127.3, 123.7, 120.8, 65.8, 56.0,
48.7, 22.7, 22.2, 6.9, 5.4; HRMS (ESI) m/z calcd for C24H36N2O2SSiNa
[M þ Na]þ 467.2164, found 467.2159.
(RS)-N-[(1R,2S)-1,2-Bis(4-methoxyphenyl)-2-(triethylsilylo-
xy)cyclopropyl]-2-methylpropane-2-sulfinamide (3i). The re-
action mixture was gradually warmed to ꢀ20 °C over a 5 h period, giving
complete conversion. Elution with a petroleum ether/EtOAc mixture
(10:1 to 8:1, v/v) gave 77.2 mg of product 3i (77% yield) as a colorless
1
oil: [R]25 = ꢀ18.0° (c 0.1, CH2Cl2); H NMR (400 MHz, CDCl3)
D
δ 7.02 (dd, J = 8.6, 6.5 Hz, 4H), 6.58 (dd, J = 8.6, 6.9 Hz, 4H), 4.84 (s,
1H), 3.68 (s, 3H), 3.66 (s, 3H), 2.21 (d, J = 7.5 Hz, 1H), 1.90 (d, J = 7.5
Hz, 1H), 1.18 (s, 9H), 0.86 (t, J = 7.9 Hz, 9H), 0.59ꢀ0.43 (m, 6H); 13C
NMR (101 MHz, CDCl3) δ 158.5, 157.9, 131.2, 130.9, 130.0, 129.4,
112.9, 112.9, 63.8, 55.5, 55.0, 55.0, 46.9, 22.4, 21.9, 6.7, 5.2; HRMS (ESI)
m/z calcd for C27H41NO4SSiNa [M þ Na]þ 526.2423, found 526.2418.
(RS)-N-[(1R,2S)-1-(4-Methoxyphenyl)-2-(4-chlorophenyl)-
2-(triethylsilyloxy)cyclopropyl]-2-methylpropane-2-sulfina-
mide (3j). The reaction mixture was gradually warmed to ꢀ50 °C over
a 3 h period, giving complete conversion. Elution with a petroleum
ether/EtOAc mixture (10:1 to 8:1, v/v) gave 75.6 mg of product 3j (75%
yield) as a slight yellow solid: mp 88ꢀ89 °C; [R]25D = ꢀ31.0° (c 0.1,
CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.06 (s, 4H), 7.01 (d, J = 8.7
Hz, 2H), 6.60 (d, J = 8.7 Hz, 2H), 4.80 (s, 1H), 3.69 (s, 3H), 2.27 (d, J =
7.7 Hz, 1H), 1.96 (d, J = 7.7 Hz, 1H), 1.18 (s, 9H), 0.88 (t, J = 7.9 Hz,
9H), 0.61ꢀ0.48 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 158.1, 137.6,
132.8, 130.5, 130.2, 129.0, 127.8, 113.1, 63.5, 55.5, 55.0, 47.3, 22.5, 21.8,
6.7, 5.3; HRMS (ESI) m/z calcd for C26H38ClNO3SSiNa [M þ Na]þ
530.1928, found 530.1924.
(RS)-N-[(1R,2S)-1-(Pyridin-3-yl)-2-phenyl-2-(triethylsilyloxy)-
cyclopropyl]-2-methylpropane-2-sulfinamide (3o). The reac-
tion mixture was gradually warmed to ꢀ25 °C over a 4 h period, giving
complete conversion. Elution with a petroleum ether/EtOAc/MeOH
mixture (10:1:1, v/v) gave 61.2 mg of product 3o (69% yield) as a slight
1
yellow oil: [R]25 = ꢀ37.0° (c 0.1, CH2Cl2); H NMR (400 MHz,
D
CDCl3) δ 8.41 (d, J = 2.0 Hz, 1H), 8.19 (dd, J = 4.8, 1.5 Hz, 1H),
7.33ꢀ7.28 (m, 1H), 7.14ꢀ7.02 (m, 5H), 6.93 (dd, J = 7.9, 4.8 Hz, 1H),
4.90 (s, 1H), 2.38 (d, J = 7.9 Hz, 1H), 2.09 (d, J = 7.9 Hz, 1H), 1.21 (d, J =
7.2 Hz, 9H), 0.92ꢀ0.82 (m, 9H), 0.58ꢀ0.45 (m, 6H); 13C NMR (101
MHz, CDCl3) δ 150.5, 147.4, 137.7, 135.8, 134.9, 128.0, 127.9, 127.6,
122.3, 64.4, 55.8, 45.4, 22.4, 21.3, 6.6, 5.2; HRMS (ESI) m/z calcd for
C24H36N2O2SSiNa [M þ Na]þ 467.2164, found 467.2159.
(RS)-N-[(1R,2S)-1-(Furan-2-yl)-2-phenyl-2-(triethylsilyloxy)-
cyclopropyl]-2-methylpropane-2-sulfinamide (3p). The reac-
tion mixture was kept at ꢀ78 °C for 2.5 h, giving complete conversion.
Elution with a petroleum ether/EtOAc mixture (10:1 to 8:1, v/v) gave
58.3 mg of product 3p (67% yield) as a white solid: mp 82ꢀ84 °C;
[R]25D = ꢀ36.0° (c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.28
(dd, J = 7.3, 2.2 Hz, 3H), 7.20ꢀ7.13 (m, 3H), 7.01ꢀ6.96 (m, 1H), 6.04
(dd, J = 3.2, 1.8 Hz, 1H), 6.01ꢀ5.96 (m, 1H), 4.67 (s, 1H), 2.31 (d, J =
7.3 Hz, 1H), 2.07 (d, J = 7.3 Hz, 1H), 1.25 (s, 9H), 0.94ꢀ0.80 (m, 9H),
0.58ꢀ0.42 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 153.1, 141.6,
138.5, 128.6, 127.8, 127.8, 110.3, 108.3, 64.7, 56.0, 42.9, 23.30, 22.6,
6.9, 5.4; HRMS (ESI) m/z calcd for C23H35NO3SSiNa [M þ Na]þ
456.2005, found 456.1999.
(RS)-N-[(1R,2S)-1-(2-Methoxyphenyl)-2-phenyl-2-(triethyl-
silyloxy)cyclopropyl]-2-methylpropane-2-sulfinamide (3k).
The reaction mixture was kept at ꢀ78 °C for 4 h, giving complete
conversion. Elution with a petroleum ether/EtOAc mixture (10:1 to 8:1,
v/v) gave 70.3 mg of product 3k (74% yield) as a white solid: mp
1
62ꢀ63 °C; [R]25 = ꢀ35.0° (c 0.1, CH2Cl2); H NMR (400 MHz,
D
CDCl3) δ 7.19 (s, 1H), 7.09 (dd, J = 7.8, 1.7 Hz, 2H), 7.04ꢀ6.95
(m, 4H), 6.72 (d, J = 6.9 Hz, 1H), 6.41 (d, J = 6.5 Hz, 1H), 4.72 (s, 1H),
3.50 (s, 3H), 2.23 (s, 1H), 1.91 (d, J = 7.3 Hz, 1H), 1.06 (s, 9H), 0.90 (t,
J = 7.9 Hz, 9H), 0.67ꢀ0.52 (m, 6H); 13C NMR (101 MHz, CDCl3)
δ 157.9, 139.4, 130.4, 128.7, 127.2, 126.6, 126.5 (overlap), 126.5, 119.3,
109.8, 63.7, 55.3, 54.5, 46.6, 22.2, 6.8, 5.7, 5.4, 5.1; HRMS (ESI) m/z
calcd for C26H39NO3SSiNa [M þ Na]þ 496.2318, found 496.2312.
(RS)-N-[(1R,2S)-1-(4-Chlorophenyl)-2-phenyl-2-(triethyl-
silyloxy)cyclopropyl]-2-methylpropane-2-sulfinamide (3l).
The reaction mixture was gradually warmed to ꢀ25 °C over a 5 h
period, giving complete conversion. Elution with a petroleum ether/
EtOAc mixture (10:1 to 8:1, v/v) gave 76.0 mg of product 3l (80%
’ ASSOCIATED CONTENT
1
Supporting Information. Copies of H NMR and 13C
S
b
NMR spectra for all new compounds synthesized and X-ray
structure of compound 1a. This material is available free of charge
via the Internet at http://pubs.acs.org.
yield) as a white solid: mp 92ꢀ94 °C; [R]25 = ꢀ25.0° (c 0.1,
D
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.17ꢀ6.91 (m, 9H), 4.87
(s, 1H), 2.32 (d, J = 7.7 Hz, 1H), 2.03 (d, J = 7.8 Hz, 1H), 1.19 (s, 9H),
0.89ꢀ0.84 (m, 9H), 0.60ꢀ0.43 (m, 6H); 13C NMR (101 MHz,
CDCl3) δ 138.1, 137.7, 132.1, 130.1, 128.0, 127.7 (overlap), 127.4,
64.3, 55.7, 46.9, 22.4, 21.8, 6.7, 5.2; HRMS (ESI) m/z calcd for
C25H36ClNO2SSiNa [M þ Na]þ 500.1822, found 500.1817.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: clu@ms.xjb.ac.cn.
4208
dx.doi.org/10.1021/jo200585r |J. Org. Chem. 2011, 76, 4205–4209

The Journal of Organic Chemistry
NOTE
’ ACKNOWLEDGMENT
(28) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A.
J. Org. Chem. 1999, 64, 1278.
(29) Datta, G. K.; Ellman, J. A. J. Org. Chem. 2010, 75, 6283.
(30) Nicewicz, D. A.; Yates, C. M.; Johnson, J. S. Angew. Chem., Int.
Ed. 2004, 43, 2652.
We are indebted to Prof. Dr. Armen Zakarian at the University
of California (Santa Barbara, CA) for helpful comments. This
work was partially supported by the Chinese Academy of
Sciences, the National Natural Science Foundation of China
(Grant 20972182 to C.-D.L.), and the “Western Light” program
of the Chinese Academy of Sciences (to B.L.).
(31) Clayden, J.; Watson, D. W.; Chambers, M. Tetrahedron 2005,
61, 3195.
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