A Lewis acid promoted asymmetric umpolung reaction with chiral N-sulfinyl imines as the electrophiles

Article abstract of DOI:10.1002/ejoc.200400775

An new asymmetric umpolung reaction has been developed by reacting N-sulfinyl imines with 2-lithio-2-phenyl-1,3-dithiane. The reaction was conducted at between -20 and -25°C in THF in the presence of Et ₂AlCl as the Lewis acid promoter. Excelle

Full text of DOI:10.1002/ejoc.200400775

FULL PAPER
A Lewis Acid Promoted Asymmetric Umpolung Reaction with Chiral
N-Sulfinyl Imines as the Electrophiles
Xin Xu,[a] Jun-ying Liu,[a] Dian-jun Chen,[a] Cody Timmons,[a] and Guigen Li*[a]
Keywords: Amino ketones / Asymmetric synthesis / 1,3-Dithianes / N-Sulfinyl imines / Umpolung
An new asymmetric umpolung reaction has been developed
by reacting N-sulfinyl imines with 2-lithio-2-phenyl-1,3-di-
thiane. The reaction was conducted at between –20 and
–25 °C in THF in the presence of Et2AlCl as the Lewis acid
promoter. Excellent diastereoselectivities (up to Ͼ95% de)
and chemical yields (64–95%) have been achieved for nine
substrates with all individual isomers separated and charac-
terized. The absolute structure of the chiral products has
been unambiguously determined by synthetic conversions to
a known sample. 2-Lithio-2-phenyl-1,3-dithiane was found
to be much less reactive than its 2-methyl counterpart, which
was reported very recently. All individual isomers have been
readily separated by column chromatography. The absolute
structure of the chiral products has been unambiguously de-
termined by conversion into a known compound. This
method provides an easy access to enantiomerically pure α-
amino ketones.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
for organic synthesis. We later envisioned that N-sulfinyl
imines could be utilized as the electrophilic component in
a reaction with dithiane anions to give the corresponding
N-sulfinyl-α-amino-1,3-dithianes, which are the direct pre-
cursors to α-amino ketones.[10] In this paper, we report our
preliminary results on this asymmetric reaction, which is
exemplified in Scheme 1.[11]
Introduction
The umpolung reaction is a very useful synthetic tool in
organic chemistry and has been widely applied for numer-
ous transformations by temporarily reversing the character-
istic reactivity of carbonyl groups.[1–4] This reaction is often
conducted by allowing dithiane anions derived from alde-
hydes to react with various electrophiles.[2] Although the
racemic umpolung reaction has become classic and well-
known, there has been little work on the asymmetric umpo-
lung reaction documented so far.[1b,4]
Results and Discussion
A few years ago, we reported several asymmetric carbon–
carbon bond formations with N-sulfinyl imines[6,7] as the
At the beginning, the reaction of N-sulfinyl imine with
electrophiles and lithium (α-carbalkoxyvinyl)cuprates.[8] 2-lithio-2-phenyl-1,3-dithiane (entry 1 of Table 1) was per-
These reactions resulted in β-branched Morita–Baylis–Hill- formed at –78 °C in THF, but only a very small amount of
man ester adducts[9] functionalized with an array of multi- the product was observed after the reaction was performed
functional groups that can serve as versatile building blocks for more than 10 hours. The reaction temperature was then
Scheme 1.
increased to between –20 and –25 °C; no obvious improve-
[a] Department of Chemistry and Biochemistry, Texas Tech Uni- ment was observed. Since Et2AlCl has been successfully uti-
versity,
lized to promote our previous N-sulfinyl imine-based asym-
Lubbock, TX 79409-1061, USA
metric C–C bond formations,[8] it was thus examined for
E-mail: guigen.li@ttu.edu
Eur. J. Org. Chem. 2005, 1805–1809
DOI: 10.1002/ejoc.200400775
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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X. Xu, J. Liu, D. Chen, C. Timmons, G. Li
FULL PAPER
Table 1. The results of asymmetric umpolung reaction promoted
by Et2AlCl.[a]
The N-sulfinyl imine starting materials employed in this
reaction were prepared according to a literature procedure
in which the Andersen reagent was treated with LiHMDS,
followed by treatment with aldehydes.[6] Meanwhile, 2-
phenyl-1,3-dithiane was synthesized by reacting benzalde-
hyde with 1,3-dithiol in the presence of hydrogen chloride in
CHCl3,[2] followed by deprotonation with nBuLi at –20 °C.
The 2-lithio-2-phenyl-1,3-dithiane used in our reaction
showed much lower reactivity toward N-sulfinyl imines
than 2-lithio-2-methyl-1,3-dithiane as reported by Davis.[12]
The former did not give any of the desired product at
–78 °C, whereas the latter reacted with N-sulfinyl imines at
this temperature completely within 20 minutes. We believe
that the stabilization effect of the phenyl ring on the anion
is responsible for the lower reactivity of 2-lithio-2-phenyl-
1,3-dithiane.
The absolute structure was determined by converting an
authentic sample, synthesized by a Sharpless asymmetric
aminohydroxylation (AA) reaction,[13] into product 1 in
Table 1 (Scheme 2). In this procedure, the AA-derived N-
tosyl-1,2-amino alcohol was first oxidized to the corre-
sponding N-tosyl-α-amino ketone.[14] This ketone was then
protected to give the α-amino dithioketal. Chiral HPLC
analysis proved that the resulting α-amino dithioketal is
identical to the minor isomer of product 1 after oxidation
of the sulfinyl group to a sulfonyl group [chiralcel-OD-H,
iPrOH/hexane (1:19), 1.0 mL/min, 22.05 min, (SS,R)-(–)-
isomer]. It should be mentioned that this determination
procedure itself can serve as an effective approach to α-
amino ketones, although it sacrifices one chiral center and
requires an additional step should carbonyl protection be
required for further transformations.
Scheme 2.
As shown in Table 1, 2-lithio-2-phenyl-1,3-dithiane re-
acted very well with all aldehydes examined under the new
conditions. The first four substrates (entries 1–4 of Table 1)
gave good to excellent diastereoselectivity and high yields.
For all aldehydes, chemical yields are very good, although
diastereoselectivity is low for the rest of the substrates. The
low diastereoselectivities could potentially be the result of
the high reactivity associated the use of such a strong Lewis
acid promoter. However, both isomers of the product can
be cleanly separated by column chromatography. The op-
tical rotations of all major and minor isomers were mea-
sured and found to be positive; this indicates that the op-
[a] All experiments were performed during 19 hours. [b] Yield after
column chromatography. [c] Optical rotation and melting point
data for minor isomers are given in parentheses. CH2Cl2 was used
as the solvent for the measurements of optical rotations.
the present reaction. It was found that N-sulfinyl imine was tical rotation is determined by the N-sulfinyl group instead
consumed with 19 hours and the reaction provided a good of the newly created chiral center of each product. Davis
yield (64%) with excellent diastereoselectivity (Ͼ95%).
and coworkers have also noted similar positive optical rota-
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 1805–1809

A Lewis Acid-Promoted Asymmetric Umpolung Reaction
FULL PAPER
tion data,[12] although none of their products are the same
as ours.
reaction mixture was stirred for 1 h at this temperature. A solution
of N-sulfinyl phenylimine in THF (47.4 mg, 0.195 mmol, 1.0 mL)
was then added, followed by dropwise addition of Et2AlCl
(0.15 mL, 0.15 mmol, 1.0 m in hexane). After the addition was com-
plete, stirring was continued for 19 h at the same temperature. The
reaction was quenched with 3 mL of saturated NH4Cl. The mixture
was extracted with EtOAc (3×5 mL). The organic extracts were
washed with brine and dried with Na2SO4. After removal of the
solvents, the crude product was purified by column chromatog-
raphy (hexane/EtOAc, 4:1) to give (SS,S)-N-[phenyl(2-phenyl-1,3-
To understand the asymmetric induction pattern of this
reaction, a straightforward hypothesis of a chair-like transi-
tion state is proposed in Figure 1, which is similar to that
suggested by Davis (Figure 1).[12] 2-Lithio-2-phenyl-1,3-di-
thiane approaches the electrophilic carbon center of the sul-
fonyl imine from the less-hindered side of the stereogenic
sulfur center, which is the side that contains the lone pair
of electrons. In this model, the two lone-pairs of electrons dithian-2-yl)methyl]-p-toluenesulfinamide (1) (55 mg, 64%, only
one isomer) as a white solid. M.p. 75–77 °C. [α]2D5 = +95.0 (c =
are both coordinated by Lewis acidic centers (Li and Al,
respectively). The phenyl group of 2-lithio-2-phenyl-1,3-di-
thiane and that of N-sulfinyl imine are arranged in gauche
positions.
0.06, CH2Cl2). IR (deposit from CH2Cl2 solution on a NaCl plate):
1
ν = 3258, 3056, 2923, 1093 cm–1. H NMR (CDCl , 300 MHz): δ
˜
3
= 7.58–7.55 (m, 2 H), 7.39–7.35 (m, 2 H), 7.19–7.15 (m, 3 H), 6.97–
6.91 (m, 3 H), 6.86–6.81 (m, 2 H), 6.46–6.43 (m, 2 H), 5.15 (d, J
= 6.9 Hz, 1 H), 4.69 (d, J = 6.9 Hz, 1 H), 2.67–2.49 (m, 4 H), 2.19
(s, 3 H), 1.84–1.81 (m, 2 H) ppm. 13C NMR (CDCl3, 125 MHz): δ
= 140.9, 140.8, 137.4, 137.0, 130.6, 129.0, 128.8, 128.2, 127.5, 127.2,
126.7, 125.8, 65.3, 65.1, 27.4, 27.2, 24.6, 21.2 ppm. HRMS [M +
H+]: m/z = 440.1165; calcd. for C24H26NOS3 440.1171.
(SS,S)-N-[3-Bromophenyl(2-phenyl-1,3-dithian-2-yl)methyl]-p-tolu-
enesulfinamide (2): White solid, 74 mg (95%, only one isomer).
Figure 1. Model of asymmetric induction.
M.p. 110–112 °C. [α]2D5 = +15.6 (c = 4.4, CH2Cl2). IR (deposit from
CH Cl solution on a NaCl plate): ν = 3293, 3055, 2906, 1092 cm–1.
Even though this model can be reasonably used to ex-
plain the resulting stereochemistry of this reaction, a pos-
sible open-chain model cannot be excluded.[15]
˜
2
2
1H NMR (CDCl3, 300 MHz): δ = 7.62–7.59 (m, 2 H), 7.35–7.32
(m, 2 H), 7.27–7.22 (m, 3 H), 7.10–7.06 (m, 1 H), 6.95–6.92 (m, 2
H), 6.72–6.67 (m, 1 H), 6.49–6.48 (m, 1 H), 6.40 (m, 1 H), 5.47 (d,
J = 5.4 Hz, 1 H), 4.64 (d, J = 5.4 Hz, 1 H), 2.71–2.63 (m, 4 H),
2.22 (s, 3 H), 1.90 (m, 2 H) ppm. 13C NMR (CDCl3, 125 MHz): δ
= 141.0, 139.8, 139.3, 137.3, 132.2, 130.2, 129.8, 128.7, 128.4, 127.9,
127.8, 127.7, 125.6, 120.6, 64.9, 62.4, 27.5, 27.1, 24.5, 21.1 ppm.
Conclusion
In summary, an asymmetric umpolung reaction has been
developed by reacting N-sulfinyl imines with 2-lithio-2-
phenyl-1,3-dithiane in the presence of Et2AlCl as the pro-
(SS,S)-N-[4-Fluorophenyl(2-phenyl-1,3-dithian-2-yl)methyl]-p-tolu-
enesulfinamide (3): Yield: 95%. M.p. 134–136 °C. [α]2D5 = +62.7 (c
moter. 2-Lithio-2-phenyl-1,3-dithiane was found to be = 1.6, CH2Cl2). IR (deposit from CH2Cl2 solution on a NaCl
plate): ν = 3295, 3054, 2907, 1093 cm–1 1H NMR (CDCl3,
.
˜
much less reactive than its 2-methyl counterpart. All indi-
vidual isomers have been readily separated by column
chromatography. The absolute structure of the chiral prod-
ucts has been unambiguously determined by conversion
into a known compound. This method provides an easy
access to enantiomerically pure α-amino ketones.
300 MHz): δ = 7.63–7.60 (m, 2 H), 7.40–7.38 (m, 2 H), 7.27–7.21
(m, 3 H), 7.00–6.97 (m, 2 H), 6.60–6.54 (m, 2 H), 6.48–6.43 (m, 2
H), 5.35 (d, J = 6.2 Hz, 1 H), 4.72 (d, J = 6.2 Hz, 1 H), 2.72–2.58
(m, 4 H), 2.24 (s, 3 H), 1.92–1.88 (m, 2 H) ppm. 13C NMR (CDCl3,
125 MHz): δ = 162.9, 160.9, 140.9, 140.4, 137.4, 132.9, 132.8, 130.6,
130.6, 130.4, 128.8, 128.3, 127.6, 125.7, 113.5, 113.3, 65.2, 63.5,
27.5, 27.1, 24.5, 21.1 ppm.
(SS,S)-N-[(2-Phenyl-1,3-dithian-2-yl)(3,4,6-trimethylphenyl)methyl]-
p-toluenesulfinamide (4): Yield: 90%. Major isomer, white solid,
60 mg, m.p. 73–75 °C. [α]2D5 = +61.5 (c = 1.0, CH2Cl2). IR (deposit
Experimental Section
General Information: All reactions were conducted under nitrogen
atmosphere in oven-dried glassware with magnetic stirring. THF
was dried by freshly distilling from sodium and benzophenone un-
der nitrogen protection. nBuLi (in hexane) and Et2AlCl (in hexane)
were purchased from commercial sources and were used without
purification. Their stoichiometries were calculated based on the re-
ported purities from the manufacturers. Flash chromatography was
performed on E. Merck silica gel 60 (230–400 mesh). NMR spectra
were recorded at 300 MHz for 1H NMR and 125 MHz for 13C
NMR spectroscopy. CDCl3 was the only solvent used for the NMR
analysis, with TMS as the internal standard. High-resolution mass
spectral analysis was conducted by the Scripps Research Institute.
from CH2Cl2 solution on a NaCl plate): ν = 3308, 3053, 2919,
˜
1
1094 cm–1. H NMR (CDCl3, 500 MHz): δ = 7.77–7.73 (m, 2 H),
7.53–7.48 (m, 2 H), 7.30–7.24 (m, 3 H), 7.09–7.05 (m, 2 H), 6.58
(s, 1 H), 6.15 (s, 1 H), 5.10 (d, J = 7.2 Hz, 1 H), 4.78 (d, J = 7.2 Hz,
1 H), 2.71–2.52 (m, 4 H), 2.31 (s, 3 H), 2.08 (s, 3 H), 1.95 (s, 3 H),
1.95–1.87 (m, 2 H), 1.85 (s, 3 H) ppm. 13C NMR (CDCl3,
125 MHz): δ = 141.3, 140.8, 136.9, 135.6, 134.1, 133.1, 132.4, 131.4,
130.8, 130.2, 128.8, 128.0, 127.5, 125.7, 65.9, 60.6, 31.5, 27.3, 27.2,
24.7, 21.2, 19.3, 19.1 ppm. HRMS [MH+]: m/z = 482.1646; calcd.
for C27H32NOS3 482.164.
(SS,R)-Isomer: Minor isomer, white solid, 5 mg, m.p. 173–175 °C
(dec.). [α]2D5 = +101.0 (c = 0.3, CH2Cl2). IR (deposit from CH2Cl2
Typical Procedure for the Asymmetric Umpolung Reaction Repre-
sented by Entry 1 of Table 1: Under an N2 atmosphere, a dry flask
was loaded with 2-phenyl-1,3-dithiane (60 mg, 0.3 mmol) and dry
THF (1.5 mL). The solution was cooled to between –20 and –25 °C
and nBuLi (0.19 mL, 0.31 mmol in hexane) was then added. The
solution on a NaCl plate): ν = 3257, 3050, 2920, 1093 cm–1. 1H
˜
NMR (CDCl3, 500 MHz): δ = 7.71–7.68 (m, 2 H), 7.56–7.52 (m, 2
H), 7.31–7.25 (m, 5 H), 6.90 (s, 1 H), 6.75 (s, 1 H), 5.11 (d, J =
3.5 Hz, 1 H), 5.02 (d, J = 3.5 Hz, 1 H), 2.76–2.48 (m, 4 H), 2.42
Eur. J. Org. Chem. 2005, 1805–1809
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X. Xu, J. Liu, D. Chen, C. Timmons, G. Li
FULL PAPER
(s, 3 H), 2.18 (s, 3 H), 2.15 (s, 3 H), 1.90 (s, 3 H), 1.90–1.78 (m, 2
H) ppm. 13C NMR (CDCl3, 125 MHz): δ = 142.5, 141.1, 137.3,
136.4, 135.6, 132.7, 131.2, 131.2, 131.1, 131.0, 129.5, 128.1, 127.5,
(SS,R)-Isomer: Minor isomer, white solid, 17 mg; m.p. 90–92 °C.
[α]2D5 = +34.3 (c = 1.5, CH2Cl2). IR (deposit from CH2Cl2 solution
on a NaCl plate): ν = 3257, 3055, 2907, 1094 cm–1 1H NMR
.
˜
125.7, 65.5, 61.4, 27.7, 27.0, 24.5, 21.4, 19.5, 19.4, 19.1 ppm. (CDCl3, 300 MHz): δ = 7.71–7.67 (m, 2 H), 7.54–7.51 (m, 2 H),
HRMS [MH+]: m/z = 482.1638; calcd. for C27H32NOS3 482.164.
7.31–7.24 (m, 6 H), 6.25 (dd, J = 1.8, 3.3 Hz, 1 H), 6.05 (dd, J =
0.5, 3.3 Hz, 1 H), 5.00 (d, J = 5.3 Hz, 1 H), 4.75 (d, J = 5.3 Hz, 1
H), 2.66–2.60 (m, 4 H), 2.40 (s, 3 H), 1.85–1.82 (m, 2 H) ppm. 13C
NMR (CDCl3, 125 MHz): δ = 149.4, 142.2, 141.5, 141.4, 137.9,
129.9, 129.6, 128.4, 127.7, 125.9, 110.7, 110.2, 63.8, 60.7, 27.6, 27.3,
24.4, 21.4 ppm.
(SS,S)-N-[Biphenyl(2-phenyl-1,3-dithian-2-yl)methyl]-p-toluenesulfin-
amide (5): Yield: 82%. Major isomer, white solid, 55 mg; m.p. 129–
131 °C. [α]2D5 = +40.3 (c = 0.33, CH2Cl2). IR (deposit from CH2Cl2
solution on a NaCl plate): ν = 3299, 3054, 2906, 1093 cm–1. 1H
˜
NMR (CDCl3, 500 MHz): δ = 7.69–7.66 (m, 2 H), 7.49–7.23 (m,
10 H), 7.14 (d, J = 8.1 Hz, 2 H), 7.00 (d, J = 8.1 Hz, 2 H), 6.58 (d,
J = 8.1 Hz, 2 H), 5.26 (d, J = 6.8 Hz, 1 H), 4.82 (d, J = 6.8 Hz, 1
H), 2.78–2.58 (m, 4 H), 2.22 (s, 3 H), 1.95–1.87 (m, 2 H) ppm. 13C
NMR (CDCl3, 125 MHz): δ = 140.9, 140.8, 140.7, 140.0, 137.4,
136.1, 130.6, 129.5, 128.9, 128.6, 128.3, 127.6, 127.1, 126.9, 125.8,
125.4, 65.2, 64.6, 27.5, 27.3, 24.6, 21.2 ppm.
(SS,S)-N-[2-Methyl-1-(2-phenyl-1,3-dithian-2-yl)propyl]-p-toluene-
sulfinamide (8): Yield 76%. Major isomer, white solid, 35 mg; m.p.
131–132 °C. [α]2D5 = +64.4 (c = 0.86, CH2Cl2). IR (deposit from
CH2Cl2 solution on a NaCl plate): ν = 3344, 3055, 2959, 2906,
˜
1
1092 cm–1. H NMR (CDCl3, 300 MHz): δ = 7.96–7.90 (m, 4 H),
7.39–7.26 (m, 5 H), 3.98 (d, J = 10.8 Hz, 1 H), 3.78 (dd, J = 1.0,
10.8 Hz, 1 H), 2.75–2.61 (m, 4 H), 2.44 (s, 3 H), 2.28–2.19 (m, 1
H), 1.95 (m, 2 H), 1.08 (d, J = 6.9 Hz, 3 H), 0.25 (d, J = 6.9 Hz, 3
H) ppm. 13C NMR (CDCl3, 125 MHz): δ = 143.6, 141.3, 138.1,
130.0, 129.4, 128.7, 127.5, 126.1, 71.5, 66.2, 27.5, 27.3, 27.2, 25.0,
22.8, 21.4, 17.3 ppm.
(SS,R)-Isomer: Minor isomer white solid, 8.0 mg; m.p. 89–91 °C.
[α]2D5 = +11.4 (c = 0.14, CH2Cl2). IR (deposit from CH2Cl2 solution
on a NaCl plate): ν = 3257, 3050, 2920, 1093 cm–1 1H NMR
.
˜
(CDCl3, 500 MHz): δ = 7.64–7.61 (m, 4 H), 7.58–7.55 (m, 2 H),
7.43–7.38 (m, 4 H), 7.35–7.32 (m, 3 H), 7.27–7.24 (m, 3 H), 7.01
(d, J = 8.5 Hz, 2 H), 5.35 (d, J = 2.5 Hz, 1 H), 4.86 (d, J = 2.5 Hz,
1 H), 2.76–2.60 (m, 4 H), 2.44 (s, 3 H), 1.90–1.85 (m, 2 H) ppm.
13C NMR (CDCl3, 125 MHz): δ = 142.3, 141.4, 140.9, 140.6, 137.7,
134.6, 130.3, 130.2, 129.6, 128.7, 128.3, 127.7, 127.3, 127.0, 125.8,
125.6, 66.6, 64.7, 27.7, 27.0, 24.4, 21.4 ppm.
(SS,R)-Isomer: Minor isomer, white solid, 11 mg; m.p. 142–144 °C.
[α]2D5 = +72.2 (c = 0.36, CH2Cl2). IR (deposit from CH2Cl2 solution
on a NaCl plate): ν = 3356, 2958, 2925, 1092 cm–1 1H NMR
.
˜
(CDCl3, 500 MHz): δ = 7.95–7.93 (m, 2 H), 7.69–7.66 (m, 2 H),
7.41–7.37 (m, 2 H), 7.31–7.28 (m, 3 H), 4.67 (d, J = 7.5 Hz, 1 H),
3.57 (dd, J = 1.5, 7.5 Hz, 1 H), 2.75–2.61 (m, 3 H), 2.58–2.52 (m,
1 H), 2.43 (s, 3 H), 2.00–1.94 (m, 1 H), 1.87–1.81 (m, 2 H), 0.88
(d, J = 7.5 Hz, 3 H), 0.68 (d, J = 7.5 Hz, 3 H) ppm. 13C NMR
(CDCl3, 125 MHz): δ = 142.5, 141.1, 139.3, 129.9, 129.5, 128.8,
127.4, 125.8, 68.9, 65.0, 28.7, 27.5, 27.4, 24.4, 23.4, 21.4, 17.9 ppm.
(SS,S)-N-[2-Naphthyl(2-phenyl-1,3-dithian-2-yl)methyl]-p-toluene-
sulfinamide (6): Yield: 68%. Major isomer, white solid, 33 mg; m.p.
82–84 °C. [α]2D5 = +29.5 (c = 1.1, CH2Cl2). IR (deposit from CH2Cl2
solution on a NaCl plate): ν = 3297, 3054, 2919, 1094 cm–1. 1H
˜
NMR (CDCl3, 300 MHz): δ = 7.66–7.63 (m, 3 H), 7.46–7.43 (m, 1
H), 7.40–7.34 (m, 5 H), 7.22–7.20 (m, 3 H), 6.88–6.80 (m, 3 H),
6.67–6.64 (m, 1 H), 5.35 (d, J = 6.5 Hz, 1 H), 4.93 (d, J = 6.5 Hz,
1 H), 2.71–2.66 (m, 4 H), 2.00 (s, 3 H), 1.91 (m, 2 H) ppm. 13C
NMR (CDCl3, 125 MHz): δ141.0, 140.5, 137.4, 134.5, 132.5, 132.1,
130.6, 128.8, 128.7, 128.3, 127.9, 127.6, 127.3, 126.6, 126.1, 125.7,
125.6, 125.5, 65.2, 64.6, 27.5, 27.3, 24.7, 20.9 ppm. HRMS [MH+]:
m/z = 490.1326; calcd. for C28H28NOS3 490.1327.
(SS,S)-N-[3,4-Dimethylphenyl(2-phenyl-1,3-dithian-2-yl)methyl]-p-
toluenesulfinamide (9): Yield: 86 %. Major isomer, white solid,
41 mg; m.p. 103–105 °C. [α]2D5 = +95.7 (c = 0.23, CH2Cl2). IR (de-
posit from CH Cl solution on a NaCl plate): ν = 3320, 3053, 2919,
˜
2
2
1
1094 cm–1. H NMR (CDCl3, 500 MHz): δ = 7.71–7.67 (m, 2 H),
7.56–7.53 (m, 2 H), 7.28–7.25 (m, 3 H), 7.12–7.09 (m, 2 H), 6.78
(d, J = 7.9 Hz, 1 H), 6.36 (dd, J = 1.8, 7.9 Hz, 1 H), 6.26–6.22 (m,
1 H), 4.88–4.80 (m, 2 H), 2.71–2.52 (m, 4 H), 2.32 (s, 3 H), 2.12 (s,
3 H), 2.00 (s, 3 H), 1.97–1.86 (m, 2 H) ppm. 13C NMR (CDCl3,
125 MHz): δ = 141.6, 140.9, 137.1, 135.8, 134.9, 134.3, 130.9, 130.3,
128.9, 128.3, 128.1, 127.5, 126.3, 125.7, 66.4, 65.1, 27.4, 27.3, 24.7,
21.2, 19.5, 19.4 ppm.
(SS,R)-Isomer: Minor isomer, white solid, 17 mg; m.p. 96–98 °C.
[α]2D5 = +21.3 (c = 0.54, CH2Cl2). IR (deposit from CH2Cl2 solution
on a NaCl plate): ν = 3259, 3054, 2908, 1093 cm–1 1H NMR
.
˜
(CDCl3, 300 MHz): δ = 7.79–7.75 (m, 2 H), 7.67–7.60 (m, 4 H),
7.45–7.22 (m, 9 H), 7.09–7.05 (m, 1 H), 5.36 (d, J = 2.7 Hz, 1 H),
4.99 (d, J = 2.7 Hz, 1 H), 2.73–2.61 (m, 4 H), 2.44 (s, 3 H), 1.88
(m, 2 H) ppm. 13C NMR (CDCl3, 125 MHz): δ = 142.3, 141.4,
137.7, 133.2, 133.0, 132.4, 130.3, 129.9, 129.2, 128.3, 128.2, 127.7,
127.5, 127.2, 126.5, 126.1, 125.8, 125.5, 67.0, 64.8, 27.7, 27.0, 24.5,
21.4 ppm. HRMS [MH+]: m/z = 490.1332; calcd. for C28H28NOS3
490.1327.
(SS,R)-Isomer: Minor isomer, white solid, 15 mg; m.p. 164–166 °C.
[α]2D5 = +38.1 (c = 0.16, CH2Cl2). IR (deposit from CH2Cl2 solution
on a NaCl plate): ν = 3260, 3054, 2921, 1093 cm–1 1H NMR
.
˜
(CDCl3, 500 MHz): δ = 7.64–7.57 (m, 4 H), 7.33–7.25 (m, 6 H),
6.95 (d, J = 7.8 Hz, 1 H), 6.77–6.74 (m, 1 H), 5.17 (d, J = 2.7 Hz,
1 H), 4.77 (d, J = 2.7 Hz, 1 H), 2.78–2.55 (m, 4 H), 2.43 (s, 3 H),
2.20 (s, 3 H), 2.10 (s, 3 H), 1.94–1.80 (m, 2 H) ppm. 13C NMR
(CDCl3, 125 MHz): δ = 142.5, 141.2, 137.8, 136.6, 135.2, 132.6,
131.4, 130.4, 129.6, 128.5, 128.1, 127.6, 127.2, 125.6, 66.6, 64.6,
27.6, 27.1, 24.5, 21.4, 19.7, 19.6 ppm.
(SS,S)-N-[2-Furyl-(2-phenyl-1,3-dithian-2-yl)methyl]-p-toluenesulfin-
amide (7): Yield: 76%. Major isomer, white solid, 32 mg; m.p. 50–
52 °C. [α]2D5 = +76.1 (c = 0.44, CH2Cl2). IR (deposit from CH2Cl2
solution on a NaCl plate): ν = 3307, 3054, 2907, 1095 cm–1. 1H
˜
NMR (CDCl3, 300 MHz): δ = 7.72–7.69 (m, 2 H), 7.59–7.54 (m, 2
H), 7.26–7.16 (m, 5 H), 7.08 (dd, J = 0.8, 1.8 Hz, 1 H), 6.08 (dd,
J = 1.8, 3.4 Hz, 1 H), 5.79 (dd, J = 0.8, 3.4 Hz, 1 H), 4.92 (d, J =
8.4 Hz, 1 H), 4.86 (d, J = 8.4 Hz, 1 H), 2.70–2.64 (m, 4 H), 2.33
Acknowledgments
We gratefully acknowledge financial support from NIH (CA,
(s, 3 H), 1.94–1.83 (m, 2 H) ppm. 13C NMR (CDCl3, 125 MHz): δ 99995-1) and the Robert A. Welch Foundation (grant no. D-1361).
= 149.8, 141.7, 141.6, 141.1, 137.6, 130.1, 129.2, 128.3, 127.6, 125.7,
The contents of this article are solely the responsibility of the au-
110.0, 109.6, 64.7, 60.8, 27.5, 27.5, 24.6, 21.3 ppm. HRMS [MH+]: thors and do not necessarily represent the official views of the
m/z = 430.0961; calcd. for C22H24NO2S3 430.0964.
1808
National Cancer Institute.
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1805–1809

A Lewis Acid-Promoted Asymmetric Umpolung Reaction
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Received: October 28, 2004
Eur. J. Org. Chem. 2005, 1805–1809
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1809