2-Pyridylsulfinamides as effective catalysts in the asymmetric alkylation of aldehydes with diethylzinc Dedicated to Dr. N.N. Joshi, National Chemical Laboratory, Pune, India

Article abstract of DOI:10.1016/j.tet.2013.07.061

Chiral 2-pyridylsulfinamides were shown to be effective catalysts in the alkylation of aryl and alkyl aldehydes with diethylzinc providing the corresponding alcohols in excellent enantioselectivity. Sulfinamide catalysts possessing solitary chirality at the sulfur center produced the product phenethyl alcohol in good enantioselectivity. Diastereomeric sulfinamides possessing chirality at the carbon-bearing nitrogen and at the sulfur of the sulfinamide increased the enantioselectivity of the product alcohols up to >99%. However, there is no effect of the match-mismatch pair of sulfinamide diastereomers on the outcome of the chiral induction of the product phenethyl alcohols. It was conclusively proved that chirality at the sulfur center is mandatory for obtaining good enantioselectivity in the reaction.

Full text of DOI:10.1016/j.tet.2013.07.061

Tetrahedron 69 (2013) 8422e8428
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
2-Pyridylsulfinamides as effective catalysts in the asymmetric
alkylation of aldehydes with diethylzinc
*
Kavirayani R. Prasad , Omkar Revu
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 May 2013
Received in revised form 13 July 2013
Accepted 16 July 2013
Available online 24 July 2013
Chiral 2-pyridylsulfinamides were shown to be effective catalysts in the alkylation of aryl and alkyl al-
dehydes with diethylzinc providing the corresponding alcohols in excellent enantioselectivity. Sulfina-
mide catalysts possessing solitary chirality at the sulfur center produced the product phenethyl alcohol in
good enantioselectivity. Diastereomeric sulfinamides possessing chirality at the carbon-bearing nitrogen
and at the sulfur of the sulfinamide increased the enantioselectivity of the product alcohols up to >99%.
However, there is no effect of the match-mismatch pair of sulfinamide diastereomers on the outcome of
the chiral induction of the product phenethyl alcohols. It was conclusively proved that chirality at the
sulfur center is mandatory for obtaining good enantioselectivity in the reaction.
Dedicated to Dr. N.N. Joshi, National Chem-
ical Laboratory, Pune, India
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Chiral sulfinamides
Chiral pyridyl ligands
Asymmetric catalysis
Asymmetric alkylation
1. Introduction
enantioselective addition of diethylzinc to aryl aldehydes8 has also
surfaced in the literature.
The advent of chiral sulfinamides such as the Davis’ p-toluene
sulfinamide and Ellman’s tert-butanesulfinamide has given a new
direction for synthesis of chiral amines and in general for asym-
metric synthesis of nitrogen containing compounds.1 Application of
these sulfinamides (including the industrial application) in the
synthesis of a variety of amine containing compounds of thera-
peutic significance is evident by a plethora of publications. How-
ever, in spite of these advances, application of the sulfinamides as
ligands or catalysts in asymmetric transformations is limited. Ell-
mann’s group reported the use of tert-butanesulfinamide derived
ligands in enantioselective DielseAlder reaction,2 while a urea
derivative derived from tert-butanesulfinamide was utilized as an
organocatalyst for aza-Henry reaction3 and in the conjugate addi-
tion of Meldrum’s acid derivatives to nitrostyrenes.4 Enantiose-
lective hydrosilylation of imines5 and enantioselective protonation
of enol silanes6 using sulfinamide-based catalysts were also dis-
closed recently. Sulfinamides in combination with rhodium cata-
lysts were proven to be excellent catalysts for asymmetric
conjugate addition of aryl boronic acids to unsaturated ketones.7 A
solitary publication on the use of sulfinamides as ligands in the
Pyridine containing ligands in particular chiral pyridyl alcohols
have attracted attention in asymmetric catalysis.9 2-Pyridylmethyl
amines were also explored as ligands in asymmetric reactions.10
Study of metal complexes of 2-pyridylmethylamines with metals
such as copper, cobalt, and zinc has been a subject of interest for
a long time in structural inorganic chemistry.11 However, to the best
of our knowledge, use of chiral pyridylsulfinamides was never
studied for their efficiency as catalysts in organic reactions. We
envisaged that the zinc amides derived from chiral 2-pyridyl
sulfinamides can exert the dual nature of a Lewis acid and Lewis
base. As a proof of this concept, we undertook examination of the
enantioselective alkylation of aryl aldehydes with diethylzinc,
a bench mark reaction for the efficiency of a catalyst.12 We antici-
pated that the Lewis acidic metal center (zinc of the amide) would
activate the carbonyl group while oxygen of the sulfinamide would
act as a Lewis base to facilitate the alkyl transfer from diethylzinc
and also would provide the chiral environment required for the
reaction (Fig. 1).
2. Results and discussion
With the above hypothesis, a series of pyridine sulfinamides
2aef were prepared by addition of Grignard reagents to the sulfi-
nimine 1 as described in literature.13 Accordingly, addition of
* Corresponding author. Tel.: þ91 80 2293 2524; fax: þ91 80 2360 0529; e-mail
addresses: kavirayaniprasad@yahoo.com, prasad@orgchem.iisc.ernet.in (K.R. Prasad).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.061

K.R. Prasad, O. Revu / Tetrahedron 69 (2013) 8422e8428
8423
identical enantioselectivities (89e91% ee). All these results are
summarized in Table 2.
Table 2
Addition of diethylzinc to benzaldehyde catalyzed by 2-pyridylsulfinamidesa
Yieldb (%)
erc (S:R)
Fig. 1. Proposed TS for the addition of Et2Zn to aldehydes with zinc amide derived
from pyridylsulfinamide as catalyst.
S. no.
1
Catalyst
Time (h)
6
72
88.8:11.2
PhMgBr to the sulfinimine 1 furnished the product sulfinamide 2a
as the major product in >95:5 diastereomeric ratio. As expected for
the pyridylsulfinamides, addition of the Grignard reagent took
place from a face opposite to that of the sulfinyl oxygen and with
chelation to the pyridyl nitrogen. Stereochemistry of the newly
formed stereogenic center of the major diastereomer 2a was un-
ambiguously confirmed by X-ray crystal structure analysis.14 Sim-
ilarly, addition of 2-naphthyl and 1-naphthylmagnesium bromides
proceeded smoothly and the corresponding sulfinamides 2b and 2c
were obtained in >95:5 ratio. However, addition of iso-
propylmagnesium chloride, tert-butylmagnesium chloride, as well
as methylmagnesium iodide furnished an inseparable mixture of
product sulfinamides in 91:9, 95:5, and 95:5 ratios, respectively. All
these results are summarized in Table 1.
2
3
20
16
86
87
92.9:7.1
87.3:12.7
4
5
6
4
10
9
70
71
80
88
90.4:9.6
95.1:4.9
94.9: 5.1
94.6:5.4
Table 1
Addition of Grignard reagents to 2-pyridylsulfinimine 1
Solvent/temp Diastereomeric ratio 2/3a Yield %
7
4
S. no. Product [R]
1
2
3
4
Ph (2a)
THF/ꢀ78 ꢁC
>95:5
>95:5
>95:5
91:9c
95:5c
95:5c
d
82b
80b
95b
68
73
89
2-Naphthyl (2b) THF/ꢀ78 ꢁC
1-Naphthyl (2c) THF/ꢀ78 ꢁC
Isopropyl (2d)
tert-Butyl (2e)
Methyl (2f)
H (2g)
THF/ꢀ78 ꢁC
THF/ꢀ78 ꢁC
THF/ꢀ78 ꢁC
MeOH/0 ꢁC
a
All reactions were performed with 20 mol % of the catalyst with 1.5 equiv of
5
Et2Zn.
6
b
c
Yield refers to isolated yield after column chromatography.
Enantiomeric ratio (er) was estimated by HPLC analysis on a chiral column.
7d
81
a
Diastereomeric ratio (dr) was estimated by 1H NMR.
Yield refers to isolated yield of the pure diastereomer after column
b
chromatography.
c
Non-separable mixture of diastereomers.
Reaction was performed with NaBH4.
It was intriguing to investigate whether chirality at the sulfur
d
center in 2a is necessary for the enantioselectivity realized in the
alkylation reaction. Accordingly, sulfinamide 2a was oxidized to the
sulfonamide 5 (which lacks chirality at the sulfur center) with m-
CPBA, and was employed as the catalyst in alkylation of benzal-
dehyde. It was surprising to find that the product alcohol 4 was
formed in 30% ee, comprehensively suggesting that the chirality
present at the sulfinyl oxygen plays an important role in the re-
action outcome. We then examined the role of match and mismatch
pair of diastereomeric sulfinamides. Thus sulfinamides 2f and 615
possessing same chirality at sulfur center but epimeric at the chi-
ral center bearing the methyl groups were employed as catalysts in
the alkylation reaction. However, the corresponding alcohol was
produced with the same configuration in almost identical enan-
tiopurities, with both sulfinamides as catalysts, suggesting that
With the sulfinamides in hand, we examined, at the outset, the
sulfinamide 2g prepared by simple reduction of sulfinimine 1 as the
catalyst in the addition of Et2Zn to benzaldehyde. Thus, reaction of
benzaldehyde with 1.5 equiv of diethylzinc in presence of 20 mol %
of 2g afforded the product phenethyl alcohol 4 in 72% yield and
with 78% ee. It is important to note that the chiral element in this
catalyst resided only at the sulfur center bearing sulfinamide.
Employing the sulfinamide 2f possessing chirality at the sulfur
center and also at the amine bearing carbon as catalyst afforded the
product phenethyl alcohol in 86% yield and in 86% ee. Sulfinamides
2aec bearing aryl substitution such as phenyl, 2-naphthyl, and 1-
naphthyl a- to the amine afforded the product alcohol in almost

8424
K.R. Prasad, O. Revu / Tetrahedron 69 (2013) 8422e8428
chirality at the carbon-bearing nitrogen does not play a role in the
outcome of the reaction. This clearly suggested that the reaction
does proceed through the TS proposed (Fig. 1). To substantiate the
hypothesis that chirality at the carbon-bearing nitrogen is of no
consequence, sulfinamide 7 possessing the gem dimethyl sub-
stitution at the carbon-bearing nitrogen was employed as the cat-
alyst. We were pleased to find that the reaction proceeded
smoothly and the product phenethyl alcohol was obtained in 90%
ee. We then examined the proximity of the heteroatom by
employing the 3-pyridylsulfinamide 8 as a catalyst. As expected the
sulfinamide 8 produced the product alcohol 4 in 35% ee suggesting
that the proximity of the heteroatom was necessary for better in-
duction. The nature of heteroatom present in the sulfinamide was
then examined for its efficiency as a catalyst in the alkylation re-
action. Thus, employing the sulfinamides 9 and 10 containing furan
and thiophene moieties, respectively, afforded the product alcohols
with diminished enantioselectivities suggesting that the pyridine
presence is pivotal for the catalysis. Also, a point of interest was that
substitution on the pyridine ring also influenced the outcome of the
reaction. Thus, employing sulfinamide 11, possessing phenyl sub-
stitution at the sixth position of the pyridine ring furnished the
product alcohol with diminished enantioselectivity (w63% ee). All
these results are summarized in Table 3.
After optimizing the reaction conditions, we generalized the
alkylation reaction of a series of aldehydes with diethylzinc with 2a
as the catalyst. Alkylation of the aryl aldehydes proceeded with
excellent enantioselectivity, the highest being >99% for 4a from the
ethylation of 3-chlorobenzaldehyde. Presence of dimethylamino
substitution in the aryl aldehyde, capable of strong chelation to
Et2Zn rendered the corresponding phenethyl alcohol 4l in low
enantiomeric purity. It was also noteworthy that the alkylation of
cyclohexane carbaxaldehyde also furnished the corresponding al-
cohol 4m with 91% ee. Very few catalysts are effective for this
transformation with cyclohexane carbaxaldehyde. However, alkyl-
ation of unsaturated aldehyde such as cinammaladehyde resulted
in the corresponding alcohol 4k with poor (40%) enantioselectivity.
All these results are summarized in Table 4.
Table 4
Addition of diethylzinc to aldehydes catalyzed by sulfinamide 2aa
Aldehyde (R)
Product
Time (h)
Yieldb (%)
erc (S:R)
3-Chlorophenyl
4-Chlorophenyl
4-Fluorophenyl
3-Bromophenyl
4-Bromophenyl
4-Methoxyphenyl
3-Phenoxyphenyl
3,4,5-Trimethoxyphenyl
1-Naphthyl
4-Nitrophenyl
Cinnamyl
4-Dimethylamino phenyl
Cyclohexyl
4a
4b
4c
4d
4e
4f
4g
4h
4i
11
13
12
18
5
80
60
84
89
83
81
80
35
95
50
70
33
77
99.8:0.2
95.3:4.7
94.7:5.3
94.4:5.6
93.2:6.8
91.9:8.1
95:5
89:11
94:6
92.3:7.7
70.4:29.6
69.4:30.6
95.7:4.3
Table 3
Addition of diethylzinc to benzaldehyde catalyzed by various sulfinamidesa
S. no.
1
Catalyst
Time (h)
Yieldb (%)
erc (S:R)
7
16
16
2
12
18
17
15
6
67
65.2:34.8
4j
4k
4l
2
3
4
86
86
91:9
4m
a
All reactions were performed with 20 mol % of the catalyst with 1.5 equiv of
Et2Zn.
b
c
Yield refers to isolated yield after column chromatography purification.
Enantiomeric ratio (er) was estimated by HPLC analysis on a chiral column.
16
92.9:7.1
As for the mechanism, we believe that the reaction is proceeding
through the TS (Fig. 1) proposed. Lewis acidic metal center (zinc of
the amide) activates the carbonyl group, and oxygen of the sulfi-
namide facilitates the alkyl transfer reaction. It was essential to
have the chirality at the sulfur center in the sulfinamide catalyst for
an exclusive chelation and transfer of diethylzinc from Si face of the
aldehyde, rendering S-phenethyl alcohol.
4
18
72
95.3:4.7
5
6
4
75
60
67.4:32.6
60.8:39.2
3. Conclusion
In conclusion, a series of 2-pyridylsulfinamides were prepared
by the addition of Grignard reagents to the sulfinimine. It was
found that these sulfinamides were effective catalysts in the al-
kylation of aromatic aldehydes. It was also found that the chirality
at the sulfur center in the catalyst is essential for higher enantio-
selectivity of the product alcohols. Other heteroatom substituted
sulfinamides were found to be ineffective catalysts in the alkylation
reaction. Further applications of these catalysts in other asym-
metric transformations are underway.
18
7
4
59
75
62.8:37.2
81.4:18.6
8
17
4. Experimental section
4.1. General
a
All reactions were performed with 20 mol % of the catalyst with 1.5 equiv of
Et2Zn.
b
c
Column chromatography was performed on silica gel, Acme
grade 100e200 mesh and neutral alumina, SD-Fine grade. TLC
Yield refer to isolated yield after column chromatography.
Enantiomeric ratio (er) was estimated by HPLC analysis on a chiral column.

K.R. Prasad, O. Revu / Tetrahedron 69 (2013) 8422e8428
8425
plates were visualized either with UV, in an iodine chamber, or with
phosphomolybdic acid spray. All reagents were purchased from
commercial sources and were used without additional purification.
THF was freshly distilled over Na-benzophenone ketyl. Melting
points were uncorrected. 1H NMR and 13C NMR spectra were
recorded on a 400 MHz machine in CDCl3 or (CD3)2SO as solvent
with TMS as reference unless otherwise indicated. Unless stated
otherwise, all reactions were performed under inert atmosphere.
All specific rotations were determined at 24 ꢁC. HRMS was obtained
using a micromass-QTOF spectrometer using electrospray ioniza-
tion (ESI).
4.1.3. Preparation of (S)-2-methyl-N-((S)-naphthalen-1-yl(pyridin-2-
yl)methyl)propane-2-sulfinamide (2c).
4.1.1. Representative procedure for the addition of Grignard reagents
to sulfinimine: preparation of (S)-2-methyl-N-((S)-phenyl (pyridin-2-
yl)methyl) propane-2-sulfinamide (2a).
Following the general procedure mentioned above, addition of
1-naphthylmagnesium bromide to sulfinimine 1 afforded 2c as
a white solid in 95% yield. Rf 0.60 (100% EtOAc); mp: 128e129.7 ꢁC;
24
[a
]
þ232.0 (c 0.86, CHCl3); IR (KBr) 2957, 2924, 1591, 1435,
D
1066 cmꢀ1; 1H NMR (400 MHz, CDCl3) dH 8.61 (d, J¼4.8 Hz,1H), 7.98
(d, J¼8.5 Hz, 1H), 7.84 (d, J¼8.1 Hz, 2H), 7.60 (d, J¼6.9 Hz, 1H),
7.56e7.37 (m, 3H), 7.34 (t, J¼7.5 Hz, 1H), 7.21e7.10 (m, 1H), 6.89 (d,
J¼7.9 Hz, 1H), 6.21 (s, 1H), 6.12 (s, 1H), 1.19 (s, 9H); 13C NMR
(100 MHz, CDCl3) dC 159.7, 148.6, 137.0, 136.5, 134.7, 131.3, 129.4,
129.0, 128.8, 126.1, 125.9, 125.5, 125.4, 122.5 (2C), 60.9, 55.9, 22.9
(3C); HRMS: [MþNa] found 361.1351. C20H22N2OSþNa requires
361.1351.
In a two-necked 50 mL round-bottomed flask equipped with
a magnetic stirbar, rubber septum, and argon inlet was placed
pyridylsulfinimine 1 (0.10 g, 0.48 mmol). This was dissolved in dry
THF (3 mL) and the solution was cooled to ꢀ78 ꢁC. A THF solution of
phenylmagnesium bromide (1 mL of 0.7 M solution in THF,
0.71 mmol) was added dropwise at the same temperature. Progress
of the reaction was monitored by TLC and after the reaction was
complete (w1.0 h), it was cautiously quenched by the addition of
satd NH4Cl solution (10 mL) and extracted with EtOAc (3ꢂ10 mL).
The combined organic extracts were washed with brine (15 mL)
and dried over anhydrous Na2SO4. Evaporation of the solvent fol-
lowed by silica gel column chromatography of the residue with
petroleum ether/EtOAC (2:8) as eluent afforded 2a as a white solid
4.1.4. Preparation of (S)-2-methyl-N-((S)-2-methyl-1-(pyridin-2-yl)
propyl)propane-2-sulfinamide (2d).
in 82% yield. Rf 0.50 (100% EtOAc); mp: 109e111 ꢁC; [
a
]
D
24 þ194.2 (c
Following the general procedure mentioned above, addition of
isopropylmagnesium chloride to sulfinimine 1 afforded 2d as a col-
orless oil in 68% yield with 88:12 dr. Rf 0.50 (80% EtOAc/petroleum
1.0, CHCl3); IR (KBr) 3218, 2976, 2964, 2952, 2860, 1589, 1430, 1066,
1042 cmꢀ1; 1H NMR (400 MHz, CDCl3) dH 8.56 (d, J¼4.6 Hz,1H), 7.57
(t, J¼7.7 Hz, 1H), 7.41e7.21 (m, 5H), 7.22e7.09 (m, 1H), 7.04 (d,
ether); [
a
]
24 þ82.7 (c 1.0, CHCl3); IR (neat) 3443, 3253, 2963, 2930,
D
J¼7.9 Hz, 1H), 5.78 (br s, 1H), 5.65 (d, J¼2.7 Hz, 1H), 1.26 (s, 9H); 13
C
2873, 1593, 1471, 1053 cmꢀ1; 1H NMR (400 MHz, CDCl3) dH 8.54 (d,
J¼4.6 Hz, 1H), 7.62 (td, J¼7.6, 1.1 Hz, 1H), 7.25e7.08 (m, 2H), 5.06 (d,
J¼7.3 Hz, 1H), 4.14 (t, J¼6.6 Hz, 1H), 2.05 (sextet, J¼6.6 Hz, 1H), 1.29
(s, 9H), 0.87 (dd, J¼5.3, 5.8 Hz, 6H); 13C NMR (100 MHz, CDCl3)
dC 160.5, 148.8, 136.3, 122.4, 122.2, 65.8, 56.2, 35.3, 22.9 (3C), 19.8,
17.8; HRMS: [MþNa] found 277.1350. C13H22N2OSþNa requires
277.1351.
NMR (100 MHz, CDCl3) dC 159.8, 148.5, 141.7, 136.6, 128.6 (2C), 128.3
(2C), 127.8, 122.4, 122.3, 61.9, 55.8, 22.7 (3C); HRMS: [MþNa] found
311.1194. C16H20N2OSþNa requires 311.1194.
4.1.2. Preparation of (S)-2-methyl-N-((S)-naphthalen-2-yl (pyridin-
2-yl)methyl) propane-2-sulfinamide (2b).
4.1.5. Preparation of (S)-N-((S)-2,2-dimethyl-1-(pyridin-2-yl)pro-
pyl)-2-methylpropane-2-sulfinamide (2e).
Following the general procedure mentioned above, addition of
2-naphthylmagnesium bromide to sulfinimine 1 afforded 2b as
a white solid in 80% yield. Rf 0.60 (100% EtOAc); mp: 122e125 ꢁC;
Following the general procedure mentioned above, addition of
24
[
a]
þ218.7 (c 1.0, CHCl3); IR (KBr) 3435, 3195, 2974, 2959, 1591,
tert-butylmagnesiumchlorideafforded2easawhitesolidin73%yield
D
1568, 1470, 1088, 1063 cmꢀ1; 1H NMR (400 MHz, CDCl3) dH 8.59 (d,
J¼4.8 Hz, 1H), 7.94e7.74 (m, 4H), 7.60e7.33 (m, 4H), 7.23e7.10 (m,
1H), 7.05 (d, J¼7.9 Hz, 1H), 5.93 (s, 1H), 5.81 (d, J¼2.0 Hz, 1H), 1.27 (s,
9H); 13C NMR (100 MHz, CDCl3) dC 159.5, 148.5, 138.9, 136.7, 133.2,
133.0, 128.7, 128.0,127.8, 127.7, 126.3,126.2,125.8,122.6,122.4, 62.0,
55.8, 22.8 (3C); HRMS: [MþH] found 339.1534. C20H22N2OSþH
requires 339.1531.
with 92:8 dr. Rf 0.50 (80% EtOAc/petroleum ether); mp: 132e135 ꢁC;
24
[a]
þ105.1 (c 0.5, CHCl3); IR (KBr) 3255, 2956, 2358, 1470, 1393,
D
1064 cmꢀ1; 1HNMR (400 MHz, CDCl3) dH 8.53(d, J¼4.4 Hz,1H), 7.57 (t,
J¼7.6 Hz, 1H), 7.22e7.06 (m, 2H), 5.29 (d, J¼7.6 Hz, 1H), 4.03 (d,
J¼7.8 Hz, 1H), 1.28 (s, 9H), 0.90 (s, 9H); 13C NMR (100 MHz, CDCl3) dC
159.3, 148.5, 135.5, 123.8, 122.2, 68.6, 56.2, 36.5, 26.6 (3C), 23.0 (3C);
HRMS: [MþNa] found 291.1507. C14H24N2OSþNa requires 291.1507.

8426
K.R. Prasad, O. Revu / Tetrahedron 69 (2013) 8422e8428
Following the general procedure described for the addition of
4.1.6. Preparation of (S)-2-methyl-N-((S)-1-(pyridin-2-yl)ethyl)pro-
Grignard reagents to sulfinimines, addition of methylmagnesium
pane-2-sulfinamide (2f).
iodide to ketimine afforded 7 as a colorless oil in 87% yield. Rf
24
0.50 (100% EtOAc); [
a
]
þ91.9 (c 0.9, CHCl3); IR (neat) 3484,
D
2979, 2927, 1592, 1366, 1052 cmꢀ1 1H NMR (400 MHz, CDCl3) dH
;
8.54 (d, J¼4.6 Hz, 1H), 7.67 (td, J¼7.96, 0.96 Hz, 1H), 7.42 (d,
J¼8.0 Hz, 1H), 7.16 (dd, J¼7.08, 5.12 Hz, 1H), 5.02 (s, 1H), 1.72 (s,
3H), 1.64 (s, 3H), 1.22 (s, 9H); 13C NMR (100 MHz, CDCl3) dC 164.9,
148.4, 136.7, 121.9, 119.0, 58.5, 55.6, 30.3, 29.4, 22.7 (2C), 22.1;
Following a similar procedure mentioned above, addition of
methylmagnesium iodide to sulfinimine 1 afforded 2f (0.095 g,
HRMS: [MþNa] found 263.1196.
C
12H20N2OSþNa requires
24
89%) as a colorless oil with 95:5 dr. Rf 0.40 (100% EtOAc); [a]
D
263.1194.
þ80.7 (c 0.14, CHCl3); IR (neat) 3162, 2978, 2959, 1594, 1481, 1437,
1128, 1063 cmꢀ1
;
1H NMR (400 MHz, CDCl3) dH 8.53 (d, J¼4.7 Hz,
4.1.10. Procedure for the reduction of sulfinimine. The following for
the preparation of (S)-2-methyl-N-(pyridin-2-ylmethyl) propane-
2-sulfinamide (2g) is representative. To a stirred solution of pyr-
idylsulfinimine 1 (0.1 g, 0.47 mmol) in MeOH (3 mL) was added
NaBH4 (0.027 g, 0.714 mmol) portion wise at 0 ꢁC and stirred at
the same temperature (w30 min). After the reaction was complete
(TLC), most of the solvent was removed under reduced pressure,
water (10 mL) was added to the reaction mixture and extracted
with EtOAc (2ꢂ20 mL). The combined organic layers were washed
with brine (10 mL), dried over anhydrous Na2SO4. Evaporation of
solvent followed by silica gel column chromatography of the crude
residue with petroleum ether/EtOAc (1:9) as eluent afforded pyr-
1H), 7.64 (td, J¼7.7, 0.93 Hz, 1H), 7.27 (d, J¼8.4 Hz, 1H), 7.16 (dd,
J¼7.4, 4.9 Hz, 1H), 4.82 (d, J¼4.7 Hz, 1H), 4.58 (qd, J¼12.8, 6.5 Hz,
1H), 1.49 (d, J¼6.74 Hz, 3H), 1.24 (s, 9H); 13C NMR (100 MHz, CDCl3)
dC 161.8, 148.9, 136.8, 122.3, 121.0, 55.6, 55.2, 23.2, 22.6 (3C); HRMS:
[MþNa] found 249.1040. C11H18N2OSþNa requires 249.1038.
4.1.7. Preparation of (S)-2-methyl-N-(phenyl(pyridin-2-yl)methyl)
propane-2-sulfonamide (5). To a stirred solution of 2a (0.10 g,
0.35 mmol) in CH2Cl2 (3 mL) was added 3-chloroperbenzoic acid
(0.12 g, 0.7 mmol) at room temperature. The reaction mixture was
stirred at rt for 40 min. After the reaction was complete (TLC), it was
washed with a mixture of a solution of satd NaHSO3 (10 mL) and
NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc
(2ꢂ10 mL). The combined organic layers were washed with brine
(10 mL), dried over anhydrous Na2SO4. Evaporation of solvent fol-
lowed by silica gel column chromatography of the crude residue with
petroleum ether/EtOAc (2:3) as eluent afforded pyridylsulfonamide
idylsulfinamide 2g (0.082 g, 81%) as colorless oil. Rf 0.40 (100%
24
EtOAc); [
a
]
þ60.0 (c 1.65, CHCl3); IR (neat) 3469, 2980, 2960,
D
1599, 1440, 1048 cmꢀ1 1H NMR (400 MHz, CDCl3) dH 8.51 (d,
;
J¼4.8, 1H), 7.65 (t, J¼7.7 Hz, 1H), 7.32 (d, J¼7.8 Hz, 1H), 7.17 (t,
J¼6.1 Hz, 1H), 4.51e4.30 (m, 3H), 1.21 (s, 9H); 13C NMR (100 MHz,
CDCl3) dC 157.7, 148.8, 137.2, 122.6, 122.4, 56.3, 49.9, 22.7
(3C); HRMS: [MþNa] found 235.0882. C10H16N2OSþNa requires
235.0881.
5 (0.095 g, 91%) as a white solid. Rf 0.60 (40% EtOAc/petroleum
24
ether); mp: 139e141 ꢁC; [
a]
D
þ94.4 (c 0.8, CHCl3); IR (KBr) 3311,
3292, 1698, 1437, 1422, 1303, 1129 cmꢀ1; 1H NMR (400 MHz, CDCl3)
dH 8.57 (d, J¼4.7 Hz, 1H), 7.64 (t, J¼7.6 Hz, 1H), 7.46e7.24 (m, 7H),
6.64 (d, J¼7.0 Hz, 1H), 5.80 (d, J¼6.9 Hz, 1H), 1.28 (s, 9H); 13C NMR
(100 MHz, CDCl3) dC 159.3, 149.0, 142.2, 137.5, 129.0 (2C), 128.0, 127.7
(2C), 122.9, 122.8, 61.7, 60.1, 24.4 (3C); HRMS: [MþNa] found
327.1143. C16H20N2SO2þNa requires 327.1143.
4.1.11. Preparation of (S)-2-methyl-N-(pyridin-3-ylmethyl)propane-
2-sulfinamide (8). Following
a similar procedure mentioned
above, reduction of the corresponding sulfinimine with NaBH4
afforded 8 as a colorless oil in 80% yield. Rf 0.40 (100% EtOAc);
24
[
a
]
þ44.6 (c 1.7, CHCl3); IR (neat) 3469, 3208, 1599, 1440,
D
1048 cmꢀ1; 1H NMR (400 MHz, CDCl3) dH 8.58e8.41 (m, 2H), 7.66
(d, J¼7.7 Hz, 1H), 7.26 (br s, 1H), 4.32 (dd, J¼14.3, 5.1 Hz, 1H), 4.24
(dd, J¼14.3, 7.1 Hz, 1H), 3.80 (s, 1H), 1.96 (s, 9H); 13C NMR
(100 MHz, CDCl3) dC 149.4, 149.0, 135.8, 134.0, 123.5, 56.0, 46.8,
22.5 (3C); HRMS: [MþNa] found 235.0883. C10H16N2OSþNa re-
quires 235.0881.
4.1.8. Preparation of (S)-2-methyl-N-((R)-1-(pyridin-2-yl)ethyl) pro-
pane-2-sulfinamide (6). To a stirred solution of the ketimine (0.10 g,
0.446 mmol) in THF (3 mL) was added K-Selectride (0.6 mL of 1 M
solution in THF, 0.58 mmol) dropwise at ꢀ78 ꢁC under argon at-
mosphere. The reaction mixture was stirred at ꢀ78 ꢁC for 5 h. After
completion of the reaction, it was quenched with dropwise addi-
tion of water (10 mL), and extracted with EtOAc (3ꢂ10 mL). The
combined organic layer was washed with brine (10 mL), and dried
over Na2SO4. Evaporation of the solvent followed by silica gel col-
umn chromatography of the resulting residue with petroleum
ether/EtOAc (9:1) as eluent afforded 6 (0.071 g, 71%) as white solid.
4.1.12. Preparation of (S)-N-(furan-2-ylmethyl-2-methyl)propane-2-
sulfinamide (9). Following a similar procedure mentioned above,
reduction of the corresponding sulfinimine with NaBH4 afforded 9
as a colorless oil in 90% yield. Rf 0.50 (80% EtOAc/petroleum ether);
24
[a
]
þ41.8 (c 1.0, CHCl3); IR (neat) 3208, 2959, 2926, 2869, 1149,
D
Rf 0.40 (100% EtOAc); mp: 101e103 ꢁC; [
a]
24 þ88.0 (c 0.06, CHCl3);
D
1057, 1013 cmꢀ1; 1H NMR (400 MHz, CDCl3) dH 7.35 (s, 1H), 6.29 (d,
J¼1.0 Hz, 1H), 6.29e6.28 (m, 1H), 4.30 (dd, J¼14.8, 5.2 Hz, 1H), 4.20
(dd, J¼14.8, 6.8 Hz, 1H), 3.56 (br s, 1H), 1.19 (s, 9H); 13C
NMR (100 MHz, CDCl3) dC 152.2, 142.7, 110.6, 108.1, 56.3, 42.5, 22.8
(3C); HRMS: [MþNa] found 224.0725. C9H15NO2SþNa requires
224.0721.
IR (KBr) 3352, 2930, 2867, 1466, 1026 cmꢀ1
;
1H NMR (400 MHz,
CDCl3) dH 8.53 (d, J¼4.6 Hz, 1H), 7.64 (t, J¼7.5 Hz, 1H), 7.64 (d,
J¼7.8 Hz, 1H), 7.16 (dd, J¼7.3, 5.0 Hz, 1H), 6.60 (q, J¼6.6 Hz, 1H), 3.95
(d, J¼6.0 Hz, 1H), 1.58 (d, J¼6.7 Hz, 3H), 1.17 (s, 9H); 13C NMR
(100 MHz, CDCl3) dC 162.2, 149.2, 136.7, 122.3, 121.0, 56.6, 55.9, 24.1,
22.5 (3C); HRMS: [MþNa] found 249.1040. C11H18N2SOþNa re-
quires 249.1038.
4.1.13. Preparation of (S)-2-methyl-N-(thiophen-2-ylmethyl)pro-
pane-2-sulfinamide (10). Following a similar procedure mentioned
above, reduction of the corresponding sulfinimine with NaBH4
4.1.9. Preparation of (S)-2-methyl-N-(2-(pyridin-2-yl)propan-2-yl)
propane-2-sulfinamide (7).
afforded 10 as a white solid in 95% yield. Rf 0.60 (80% EtOAc/pe-
24
troleum ether); mp: 73.6e74.3 ꢁC; [
a]
þ26.4 (c 1.1, CHCl3); IR
D
(KBr) 3468, 3207, 2980, 2959, 2868, 1455, 1366, 1057 cmꢀ1; 1H NMR
(400 MHz, CDCl3) dH 7.24 (d, J¼5.0 Hz, 1H), 7.03e6.88 (m, 2H), 4.55
(dd, J¼14.5, 4.6 Hz, 1H), 4.41 (dd, J¼14.4, 7.5 Hz, 1H), 3.64 (br s, 1H),
1.23 (s, 9H); 13C NMR (100 MHz, CDCl3) dC 142.2, 127.1, 126.1, 125.7,

K.R. Prasad, O. Revu / Tetrahedron 69 (2013) 8422e8428
8427
56.3, 44.6, 22.9 (3C); HRMS: [MþNa] found 240.0493. C9H15
NS2OþNa requires 240.0493.
analysis (CHIRAL PAK AD-H, 1% IPA in hexane, 0.5 mL/min, 254 nm
24
UV detector). tR¼40.18 min for (R) and tR¼43.26 min for (S). [
a]
D
ꢀ25.7 (c 1.78, CHCl3); 1H NMR (400 MHz, CDCl3) dH 7.49 (s, 1H), 7.39
(d, J¼6.6 Hz, 1H), 7.31e7.13 (m, 2H), 4.54 (td, J¼12.5, 6.2 Hz, 1H),
2.36 (br s, 1H), 1.86e1.65 (m, 2H), 0.90 (td, J¼7.3, 2.0 Hz, 3H); 13C
NMR (100 MHz, CDCl3) dC 146.9, 130.5, 129.9, 129.0, 124.6, 122.5,
75.2, 31.9, 10.0.
4.1.14. Preparation of (S)-2-methyl-N-((6-phenylpyridin-2-yl)methyl)
propane-2-sulfinamide (11). Following a similar procedure men-
tioned above, reduction of the corresponding sulfinimine with
NaBH4 afforded 11 as a white solid in 99% yield. Rf 0.60 (100% EtOAc);
mp: 110e111 ꢁC; [
a]
D
24 þ68.0 (c 1.1, CHCl3); IR (KBr) 3154, 2919, 2317,
1807, 1449, 1364, 1047 cmꢀ1
;
1H NMR (400 MHz, CDCl3) dH 8.51 (d,
4.1.21. (S)-1-(4-Bromophenyl)propan-1-ol (4e). Yield 83%, er (S:R):
J¼7.2 Hz, 2H), 8.24 (t, J¼7.6 Hz, 1H), 8.14 (d, J¼7.7 Hz, 1H), 8.05e7.86
(m, 3H), 7.77 (d, J¼7.6 Hz, 1H), 5.14 (br s, 1H), 5.11e4.99 (m, 2H), 1.80
(s, 9H); 13C NMR (100 MHz, CDCl3) dC 157.3, 156.6, 139.0, 137.4, 129.0,
128.7 (2C), 126.8 (2C), 120.2, 119.0, 56.1, 49.3, 22.7 (3C); HRMS:
[MþNa] found 311.1195. C16H20N2OSþNa requires 311.1194.
93.2:6.8. Enantiomeric ratio was determined by chiral HPLC anal-
ysis (CHIRAL CEL OD-H, 2.5% IPA in hexane, 0.5 mL/min, 254 nm UV
24
detector). tR¼16.49 min for (R) and tR¼18.19 min for (S). [
a]
D
ꢀ15.94 (c 1.6, C6H6); 1H NMR (400 MHz, CDCl3) dH 7.47 (d, J¼8.3 Hz,
2H), 7.20 (d, J¼8.3 Hz, 2H), 4.55 (t, J¼6.5 Hz, 1H), 2.1 (br s, 1H),
1.86e1.61 (m, 2H), 0.89 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
dC 143.5, 131.5 (2C), 127.7 (2C), 121.2, 75.3, 31.9, 10.0.
4.1.15. Representative procedure for the addition of Et2Zn to aldehy-
de. To a stirred solution of pyridylsulfinamide ligand 2a (0.057 g,
0.2 mmol) in dry toluene (2 mL) was added diethylzinc (1.1 M so-
lution in toluene,1.4 mL,1.51 mmol) at 0 ꢁC dropwise and stirred for
15 min at 0 ꢁC. Aldehyde (0.12 mL, 1.0 mmol) was added into the
reaction mixture at 0 ꢁC and reaction mixture was warmed slowly
to rt and stirred at rt until the completion of the reaction. After
completion of the reaction, it was quenched by the addition of satd
NH4Cl solution (10 mL) and the mixture was extracted with EtoAc
(15 mLꢂ2). The combined organic layers were washed with brine
(20 mL), dried over Na2SO4, and concentrated in vacuo. The residue
was purified by silica gel column chromatography using EtoAc/
hexane mixture as eluent to give the product alcohols.
4.1.22. (S)-1-(4-Methoxyphenyl)propan-1-ol (4f). Yield 81%, er
(S:R): 92:8. Enantiomeric ratio was determined by chiral HPLC
analysis (CHIRAL CEL OD-H, 2% IPA in hexane, 0.8 mL/min, 254 nm
24
UV detector). tR¼16.39 min for (R) and tR¼18.02 min for (S). [
a]
D
ꢀ21.3 (c 0.52, C6H6); 1H NMR (400 MHz, CDCl3) dH 7.26 (d, J¼8.8 Hz,
2H), 6.88 (d, J¼8.8 Hz, 2H), 4.53 (t, J¼6.6 Hz, 1H), 3.80 (s, 3H), 2.0 (br
s, 1H), 1.90e1.62 (m, 2H), 0.89 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) dC 158.9, 136.7, 127.1 (2C), 113.7 (2C), 75.6, 55.2, 31.7, 10.1.
4.1.23. (S)-1-(3-Phenoxyphenyl)propan-1-ol (4g). Yield 80%, er
(S:R): 95:5. Enantiomeric ratio was determined by chiral HPLC
analysis (CHIRAL CEL OD-H, 3% IPA in hexane,1 mL/min, 254 nm UV
4.1.16. (S)-1-Phenylpropan-1-ol (4). Yield 88%, er (S:R) 94.6:5.4. En-
antiomeric ratio was determined by chiral HPLC analysis (CHIRALCEL
OD-H, 2.5% IPA in hexane, 0.5 mL/min, 254 nm UV detector).
detector). tR¼14.73 min for (S) and tR¼18.29 min for (R). [
a
]
24 ꢀ18.6
D
(c 0.88, CHCl3); 1H NMR (400 MHz, CDCl3) dH 7.40e7.20 (m, 3H),
7.16e7.01 (m, 2H), 7.51e6.94 (m, 3H), 6.90 (dq, J¼2.4, 0.8 Hz, 1H),
4.57 (t, J¼6.4 Hz, 1H), 2.0 (br s, 1H), 1.85e1.65 (m, 2H), 0.91 (t,
J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) dC 157.3, 157.1, 146.7, 129.7
(2C), 129.6, 123.2, 120.7, 118.8 (2C), 117.7, 116.4, 75.6, 31.8, 10.0.
tR¼15.19minfor(R)andtR¼17.13 min for (S).[
a
]
24 ꢀ39.8(c1.0, CHCl3);
D
1H NMR (400 MHz, CDCl3) dH 7.42e7.27 (m, 5H), 4.58 (t, J¼6.4 Hz,1H),
2.11 (br s, 1H), 1.91e1.66 (m, 2H), 0.92 (t, J¼7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) dC 144.5,128.3 (2C),127.4,125.9 (2C), 75.9, 31.8,10.1.
4.1.24. (S)-1-(3,4,5-Trimethoxyphenyl)propan-1-ol (4h). Yield 35%,
er (S:R): 89:11. Enantiomeric ratio was determined by chiral HPLC
analysis (CHIRAL CEL OD-H, 3% IPA in hexane,1 mL/min, 254 nm UV
4.1.17. (S)-1-(3-Chlorophenyl)propan-1-ol (4a). Yield 80%, er (S:R):
99.8:0.2. Enantiomeric ratio was determined by chiral HPLC anal-
ysis (CHIRAL CEL OD-H, 1% IPA in hexane, 0.5 mL/min, 254 nm UV
detector). tR¼27.85 min for (R) and tR¼39.08 min for (S). [
a
]
24 ꢀ15.1
D
detector). tR¼47.60 min for (R) and tR¼53.49 min for (S). [
a
]
24 ꢀ34.1
(c 0.88, CHCl3); 1H NMR (400 MHz, CDCl3) dH 6.57 (s, 2H), 4.52 (t,
J¼6.4 Hz, 1H), 3.86 (s, 6H), 3.83 (s, 3H), 2.10 (br s, 1H), 1.88e1.64 (m,
2H), 0.94 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) dC 153.1 (2C),
140.5, 137.0, 102.7 (2C), 76.1, 60.8, 56.0 (2C), 31.9, 10.2.
D
(c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) dH 7.32 (s, 1H), 7.33e7.18
(m, 2H), 7.18 (d, J¼6.78 Hz, 1H), 4.54 (t, J¼6.5 Hz, 1H), 2.35 (br s, 1H),
1.85e1.62 (m, 2H), 0.90 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
dC 146.7, 134.3, 129.7, 127.5, 126.2, 124.2, 75.3, 31.9, 10.0.
4.1.25. (S)-1-(Naphthalen-2-yl)propan-1-ol (4i). Yield 95%, er (S:R):
94:6. Enantiomeric ratio was determined by chiral HPLC analysis
(CHIRAL CEL OD-H, 5% IPA in hexane, 1 mL/min, 254 nm UV de-
4.1.18. (S)-1-(4-Chlorophenyl)propan-1-ol (4b). Yield 60%, er (S:R)
95:5. Enantiomeric ratio was determined by chiral HPLC analysis
(CHIRAL CEL OD-H, 1% IPA in hexane, 1 mL/min, 254 nm UV de-
tector). tR¼11.09 min for (S) and tR¼24.25 min for (R). [
a
]
24 ꢀ49.8 (c
D
tector). tR¼13.97 min for (S) and tR¼15.75 min for (R). [
a
]
24 ꢀ40.9 (c
1.25, CHCl3); 1H NMR (400 MHz, CDCl3) dH 8.12 (d, J¼8.4 Hz, 1H),
7.94e7.82 (m, 1H), 7.79 (d, J¼8.2 Hz, 1H), 7.64 (d, J¼7.1 Hz, 1H),
7.57e7.40 (m, 3H), 5.40 (br s, 1H), 2.13e1.94 (m, 3H), 1.04 (t,
J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) dC 141.6, 135.2, 131.9,
130.3, 129.3, 127.3, 126.9, 126.8, 124.7, 124.3, 74.0, 32.5, 12.0.
D
1.7, CHCl3); 1H NMR (400 MHz, CDCl3) dH 7.30 (d, J¼8.4 Hz, 2H), 7.25
(d, J¼8.2 Hz, 2H), 4.55 (t, J¼4.2 Hz, 1H), 2.14 (br s, 1H), 1.86e1.60 (m,
2H), 0.89 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) dC 143.0,
133.1, 128.5 (2C), 127.4 (2C), 75.3, 31.9, 10.0.
4.1.19. (S)-1-(4-Fluorophenyl)propan-1-ol (4c). Yield 84%, er (S:R):
94.7:5.3. Enantiomeric ratio was determined by chiral HPLC anal-
ysis (CHIRAL CEL OJ-H, 1% IPA in hexane, 1 mL/min, 254 nm UV
4.1.26. (S)-1-(4-Nitrophenyl)propan-1-ol (4j). Yield 50%, er (S:R):
92:8. Enantiomeric ratio was determined by chiral HPLC analysis
(CHIRAL PAK AD-H, 5% IPA in hexane, 0.5 mL/min, 254 nm UV de-
detector). tR¼22.88 min for (R) and tR¼24.86 min for (S). [
a
]
D
24 ꢀ40.6
tector). tR¼20.94 min for (R) and tR¼22.48 min for (S). [
a
]
D
24 ꢀ27.6 (c
(c 0.76, CHCl3); 1H NMR (400 MHz, CDCl3) dH 7.30 (dd, J¼8.3, 5.6 Hz,
2H), 7.02 (t, J¼8.6 Hz, 2H), 4.57 (t, J¼5.9 Hz, 1H), 2.0 (br s, 1H),
2.06e1.62 (m, 2H), 0.89 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
dC 160.9, 140.3, 127.6, 127.5, 115.2, 115.0, 75.3, 31.9, 10.0.
0.3, CHCl3); 1H NMR (400 MHz, CDCl3) dH 8.16 (d, J¼8.5 Hz, 2H), 7.49
(d, J¼8.5 Hz, 2H), 4.73 (t, J¼6.4 Hz, 1H), 2.41 (br s, 1H), 1.85e1.66 (m,
2H), 0.92 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) dC 152.1, 147.1,
126.7 (2C), 123.6 (2C), 74.8, 32.1, 9.8.
4.1.20. (S)-1-(3-Bromophenyl)propan-1-ol (4d). Yield 89%, er (S:R):
4.1.27. (S,E)-1-Phenylpent-1-en-3-ol (4k). Yield 70%, er (S:R): 70:30.
94.4:5.6. Enantiomeric ratio was determined by chiral HPLC
Enantiomeric ratio was determined by chiral HPLC analysis (CHIRAL

8428
K.R. Prasad, O. Revu / Tetrahedron 69 (2013) 8422e8428
CEL OD-H, 5% IPA in hexane, 1 mL/min, 254 nm UV detector).
References and notes
tR¼7.82 min for (R)andtR¼12.71 min for (S). [
a
]
24 ꢀ4.15 (c3.25, CHCl3);
D
1H NMR (400 MHz, CDCl3)dH 7.45e7.18 (m, 5H), 6.58 (d, J¼15.9 Hz, 1H),
6.22 (dd, J¼15.9, 6.7 Hz,1H), 4.21 (td, J¼12.9, 6.4 Hz,1H),1.78e1.56 (m,
3H), 0.98 (t, J¼7.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) dC 136.8, 132.3,
130.4, 128.6 (2C), 127.6, 126.5 (2C), 74.4, 30.2, 9.8.
1. For a review on Davis’ p-toluenesulfinamide as auxiliary in the synthesis of
chiral nitrogen containing compounds, see: (a) Davis, F. A. J. Org. Chem. 2006, 71,
8993; (b) Zhou, P.; Chen, B.-C.; Davis, F. A. Tetrahedron 2004, 60, 8003 For
a review on the use of Ellman’s tert-butylsulfinamide as auxiliary in the syn-
thesis of chiral nitrogen containing compounds, see: Robak, M. T.; Herbage, M.
A.; Ellman, J. A. Chem. Rev. 2010, 110, 3600.
2. (a) Owens, T. D.; Souers, A. J.; Ellman, J. A. J. Org. Chem. 2003, 68, 3; (b) Owens,
T. D.; Hollander, F. J.; Allen, G.; Oliver, A. G.; Ellman, J. A. J. Am. Chem. Soc. 2001,
123, 1539.
3. (a) Kimmel, K. L.; Robak, M. T.; Ellman, J. A. J. Am. Chem. Soc. 2009, 131, 8754; (b)
Robak, M. T.; Trincado, M.; Ellman, J. A. J. Am. Chem. Soc. 2007, 129, 15110.
4. Kimmel, K. L.; Weaver, J. D.; Ellman, J. A. Chem. Sci. 2012, 3, 121.
5. Nielsen, L.; Skrydstrup, T. J. Am. Chem. Soc. 2008, 130, 13145.
6. Beck, E. M.; Hyde, A. M.; Jacobson, E. N. Org. Lett. 2011, 13, 4260.
7. For a recent review on Rh-catalyzed asymmetric arylation with boronic acids
see: Tian, P.; Dong, H. Q.; Lin, G. Q. ACS Catal. 2012, 2, 95.
4.1.28. (S)-1-(4-(Dimethylamino)phenyl)propan-1-ol (4l). Yield 33%,
er (S:R): 69.5:30.5. Enantiomeric ratio was determined by chiral
HPLC analysis (CHIRAL CEL OD-H, 5% IPA in hexane, 1 mL/min,
254 nm UV detector). tR¼8.11 min for (R) and tR¼9.52 min for (S).
24
[a]
ꢀ2.83 (c 0.6, CHCl3); 1H NMR (400 MHz, CDCl3) dH 7.22 (d,
D
J¼8.5 Hz, 2H), 6.73 (d, J¼8.5 Hz, 2H), 4.50 (t, J¼6.7 Hz, 1H), 2.95 (s,
6H), 1.91e1.64 (m, 3H), 0.90 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) dC 150.2,132.5,127.0 (2C),112.5 (2C), 75.9, 40.7 (2C), 31.5,10.4.
8. Huang, Z.; Lai, H.; Qin, Y. J. Org. Chem. 2007, 72, 1373.
9. (a) Eidamshaus, C.; Reissig, H. U. Tetrahedron: Asymmetry 2011, 22, 1644; (b)
Chang, T. C.; Chen, C. J. Chin. Chem. Soc. 2008, 55, 606; (c) Kwong, H. L.; Yeung,
H. L.; Yeung, C. T.; Lee, W. S.; Lee, C. S.; Wong, W. L. Coord. Chem. Rev. 2007, 251,
2188; (d) Bolm, C.; Zehnder, M.; Bur, D. Angew. Chem., Int. Ed. Engl. 1990, 29,
205; (e) Bolm, C.; Schlingloff, G.; Harms, K. Chem. Ber. 1992, 125, 1191.
10. (a) Banerjee, S.; Groeper, J. A.; Standard, J. M.; Hitchcock, S. R. Tetrahedron:
Asymmetry 2009, 20, 2154; (b) Chelucci, G.; Baldino, S.; Chessa, S. Tetrahedron
2006, 62, 619; (c) Baratta, W.; Chelucci, G.; Gladiali, S.; Siega, K.; Toniutti, M.;
Zanette, M.; Zangrando, E.; Rigo, P. Angew. Chem., Int. Ed. 2005, 44, 6214; (d)
Chelucci, G.; Conti, S.; Falorni, M.; Giacomelli, G. Tetrahedron 1991, 47, 8251.
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Hampel, F.; Monkowius, U.; Hirtenlehner, C.; Knor, G.; Schindler, G. Dalton Trans.
2011, 40, 5090; (b) Mikata, Y.; Fujimoto, T.; Fujiwara, T.; Kondo, S. Inorg. Chim.
Acta 2011, 370, 420; (c) Sharma, A. K.; Mukherjee, R. Inorg. Chim. Acta 2008, 361,
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2003, 42, 8087.
4.1.29. (S)-1-Cyclohexylpropan-1-ol (4m). Yield 77%, er (S:R): 95.7:
4.3. Enantiomeric ratio was determined by chiral HPLC analysis for
benzoate derivative (CHIRAL PAK AD-H,1% IPA in hexane, 0.3 mL/min,
254 nm UV detector). tR¼10.33 min for (R) and tR¼12.47 min for (S).
[a]
24 ꢀ4.67 (c 0.45, CHCl3); 1H NMR (400 MHz, CDCl3) dH 3.28e3.26
D
(m,1H),1.82e1.01 (m, 14H), 0.95 (t, J¼7.5 Hz, 3H); 13C NMR (100 MHz,
CDCl3) dC 77.6, 43.1, 29.3, 27.7, 26.8, 26.5, 26.3, 26.2, 10.2.
Acknowledgements
K.R.P. thanks the Department of Science and Technology (DST),
New Delhi for funding of this project. K.R.P. is Swarnajayanthi fel-
low of DST. O.R. thanks the council of scientific and industrial re-
search (CSIR), New Delhi for a research fellowship.
12. (a) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833; (b) Pu, L.; Yu, H.-B. Chem. Rev.
2001, 101, 757.
13. Kuduk, S. D.; DiPardo, R. M.; Chang, R. K.; Ng, C.; Bock, M. G. Tetrahedron Lett.
2004, 45, 6641.
14. Crystal structure was deposited with Cambridge crystallographic data center
(CCDC No. 918917). The data can be collected free of charge from CCDC www.
ccdc.cam.ac.uk/data_request/cif.
Supplementary data
15. Sulfinamide 6 was prepared according to the literature procedure by reduction
of the ketimine derived from 2-acetylpyridine Chelucci, G.; Baldino, S.; Chessa,
S.; Pinna, G. A.; Soccolini, F. Tetrahedron: Asymmetry 2006, 17, 3163.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.07.061.