Application of β-hydroxysulfoximines in catalytic asymmetric phenyl transfer reactions for the synthesis of diarylmethanols

Article abstract of DOI:10.1021/jo7016718

(Chemical Equation Presented) Enantiomerically enriched diarylmethanols have been prepared by catalyzed asymmetric phenyl transfer reactions onto aromatic aldehydes with use of readily available β-hydroxysulfoximines as catalysts. As the aryl source, combinations of diethylzinc with either diphenylzinc or triphenylborane have been applied affording arylphenylmethanols with up to 93% ee in good yields. Various functionalized aldehydes and heterocyclic substrates are tolerated, yielding synthetically relevant products.

Full text of DOI:10.1021/jo7016718

Application of â-Hydroxysulfoximines in Catalytic Asymmetric
Phenyl Transfer Reactions for the Synthesis of Diarylmethanols
Jo¨rg Sedelmeier and Carsten Bolm*
Institute of Organic Chemistry, RWTH Aachen UniVersity, Landoltweg 1, D-52056 Aachen, Germany
carsten.bolm@oc.rwth-aachen.de
ReceiVed July 31, 2007
Enantiomerically enriched diarylmethanols have been prepared by catalyzed asymmetric phenyl transfer
reactions onto aromatic aldehydes with use of readily available â-hydroxysulfoximines as catalysts. As
the aryl source, combinations of diethylzinc with either diphenylzinc or triphenylborane have been applied
affording arylphenylmethanols with up to 93% ee in good yields. Various functionalized aldehydes and
heterocyclic substrates are tolerated, yielding synthetically relevant products.
Introduction
During the past decades, sulfoximines have attracted signifi-
cant attention due to their successful use as chiral auxiliaries in
asymmetric synthesis5 and ligands in enantioselective metal
catalysis.6 Their preparation is well-documented and several
synthetic routes have been established. On the basis of our
previous experience in addition reactions with dialkylzincs,7 we
decided to test the applicability of easily accessible â-hydroxy-
sulfoximines 2 in asymmetric phenyl transfer reactions. Sul-
Enantiopure diarylmethanols are important intermediates for
the synthesis of biologically active compounds, which show
physiologically interesting properties such as antihistaminic,
antiarrhythmic, diuretic, antidepressive, laxative, local-anes-
thetic, and anticholinergic effects.1 Previous approaches toward
enantiomerically enriched diarylmethanols involved asymmetric
reductions of prochiral ketones or aryl transfer reactions onto
aldehydes.2 Our group3 as well as several others4 have developed
various protocols for the latter transformation utilizing mixtures
of diethylzinc with either diphenylzinc, triphenylborane, or
boronic acids as aryl sources. Often, both yields and enantio-
selectivities are high. However, despite the immense progress
in this area, there is still a need for improvement. For example,
many catalysts are too complex to be applied on large scale
and furthermore, functionalized substrates often lead to only
moderate enantioselectivies.
(4) (a) Dosa, P. I.; Ruble, J. C.; Fu, G. C. J. Org. Chem. 1997, 62, 444.
(b) Huang, W.-S.; Pu, L. J. Org. Chem. 1999, 64, 4222. (c) Zhao, G.; Li,
X. G.; Wang, X. R. Tetrahedron: Asymmetry 2001, 12, 399. (d) Fontes,
M.; Verdaguer, X.; Sola, L.; Perica`s, M. A.; Riera, A. J. Org. Chem. 2004,
69, 2532. (e) Ko, D.-H.; Kim, K. H.; Ha, D.-C. Org. Lett. 2002, 4, 3759.
(f) Pizzuti, M. G.; Superchi, S. Tetrahedron: Asymmetry 2005, 16, 2263.
(g) Qin, Y.-C.; Pu, L. Angew. Chem., Int. Ed. 2006, 45, 273. (h) Ji, J.-X.;
Wu, J.; Au-Yeung, T. T.-L.; Yip, C.-W.; Haynes, R. K.; Chan, A. S. C. J.
Org. Chem. 2005, 70, 1093. (i) Hatano, M.; Miyamoto, T.; Ishihara, K.
AdV. Synth. Catal. 2005, 347, 1561. (j) Kim, J. G.; Walsh, P. J. Angew.
Chem., Int. Ed. 2006, 45, 4175.
(5) For reviews on sulfoximines and their use as chiral auxiliaries, see:
(a) Johnson, C. R. Acc. Chem. Res. 1973, 6, 341. (b) Pyne, S. Sulfur Rep.
1992, 12, 57. (c) Reggelin, M.; Zur, C. Synthesis 2000, 1.
(6) For reviews on sulfoximines and their use as chiral ligands in metal
catalysis, see: (a) Harmata, M. Chemtracts 2003, 16, 660. (b) Okamura,
H.; Bolm, C. Chem. Lett. 2004, 32, 482. (c) For a personel account, see:
Bolm, C. In Asymmetric Synthesis with Chemical and Biological Methods;
Enders, D., Ja¨ger, K.-E., Eds.; Wiley-VCH: Weinheim, Germany, 2007; p
149.
(1) (a) Harms, A. F.; Hespe, W.; Nauta, W. T.; Rekker, R. F. Drug Design
1976, 6, 1. (b) Rekker, R. F.; Timmerman, H.; Harms, A. F.; Nauta, W. T.
Arzneim. Forsch. 1971, 21, 688. (c) Bolshan, Y.; Chen, C. Y.; Chilenski,
J. R.; Gosselin, F.; Mathre, D. J.; O’ Shea, P. D.; Tillyer, A. R. Org. Lett.
2004, 6, 111. (d) Magnus, N. A.; Anzeveno, P. B.; Coffey, S. S.; Hay, D.
A.; Laurila, M. E.; Schkeryantz, J. M.; Shaw, B. W.; Staszak, M. A. Org.
Process Res. DeV. 2007, 11, 560. (e) Truppo, M. D.; Pollard, D.; Devine,
P. Org. Lett. 2007, 9, 335 and references cited therein.
(2) For a recent review, see: Schmidt, F.; Stemmler, R. T.; Rudolph, J.;
Bolm, C. Chem. Soc. ReV. 2006, 35, 454.
(7) (a) Bolm, C.; Mu¨ller, J.; Schlingloff, G.; Zehnder, M.; Neuburger,
M. J. Chem. Soc., Chem. Commun. 1993, 182. (b) Bolm, C.; Mu¨ller, J.
Tetrahedron 1994, 50, 4355. (c) See also: Bolm, C.; Felder, M.; Mu¨ller, J.
Synlett 1992, 439. For general overviews on catalyzed asymmetric reactions
with organozinc reagents, see: (d) Soai, K.; Niwa, S. Chem. ReV. 1992,
92, 833. (e) Soai, K.; Shibata, T. In ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, Germany,
1999; p 911. (f) Pu, L.; Yu, H.-B. Chem. ReV. 2001, 101, 757.
(3) For selected references from our laboratories, see: (a) Bolm, C.;
Hermanns, N.; Hildebrand, J. P.; Mun˜iz, K. Angew. Chem., Int. Ed. 2000,
39, 3465. (b) Rudolph, J.; Schmidt, F.; Bolm, C. AdV. Synth. Catal. 2004,
346, 867. (c) Rudolph, J.; Bolm, C. J. Am. Chem. Soc. 2002, 124, 14850.
(d) Schmidt, F.; Rudolph, J.; Bolm, C. AdV. Synth. Catal. 2007, 349, 703.
(e) Rudolph, J.; Hermanns, N.; Bolm, C. J. Org. Chem. 2004, 69, 3997.
10.1021/jo7016718 CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/11/2007
J. Org. Chem. 2007, 72, 8859-8862
8859

Sedelmeier and Bolm
SCHEME 1
SCHEME 2
foximines of this type can be prepared in a large variety
following the reaction sequence depicted in Scheme 1.8
TABLE 1. Catalyst Screening in the Conversion of 3a into
Arylphenylmethanol 4aa
Results and Discussion
The synthesis of â-hydroxysulfoximines 2 starts from the
readily accessible (and commercially available) enantiopure NH-
sulfoximine 1a,9 which can be silylated, alkylated, or arylated.10
Subsequent deprotonation of the N-substituted sulfoximines
1b-g by n-BuLi at -78 °C in ether and trapping of the resulting
carbanion by an aldehyde or a ketone affords â-hydroxysul-
foximines 2b-g in good yields. By variation of the carbonyl
compounds a broad range of products is accessible. For the
synthesis of NH-â-hydroxysulfoximines 2a silylated products
2b are deprotected with MeOH and aqueous NH4Cl. Generally,
the diastereomeric ratios depend on the carbonyl compounds
used in the trapping. In some cases single diastereomers are
formed. Most of the diastereomeric mixtures are separable
chromatographically or by fractional crystallization.
For the optimization of the aryl transfer reaction with respect
to solvent, temperature, catalyst loading, and catalyst structure,
â-hydroxysulfoximine 2ca, 4-chlorobenzaldehyde (3a), and a
combination of diphenylzinc and diethylzinc (in a 1:2 ratio) were
used. As a result, toluene proved superior to THF, Et2O, hexane,
and 1,4-dioxane as solvent in the formation of diarylmethanol
4a. Temperature variations indicated a maximal enantioselec-
tivity in reactions performed at 10 °C. Albeit the yield of 4a
remained about the same, lower enantiomeric excesses were
observed in reactions run at room temperature or below 0 °C.
With less than 10 mol % of â-hydroxysulfoximine 2ca the yield
and the ee of 4a were reduced. Scheme 2 summarizes the
optimal conditions.
conv of
ee
entry
2b
R′
R′′
R′′′
3a (%)c
(%)d
1
2
3
4
5
ab
ac
ca
cb
cc
cd
H
H
Ph
Ph
Me
(CH2)6
14
9
10
22
-80
32
-46
-86
-76
16
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
87
88
76
86
82
49
77
43
83
85
89
87
66
78
71
80
87
78
78
81
77
81
69
74
68
72
69
64
Ph
Ph
Me
i-Pr
Ph
Me
6
Ph
7
(dia)-cd
i-Pr
8e
9
ce
cf
cg
ch
H
4-Cl-Ph
t-Bu
Bn
1-Naph
2-Naph
Me
Me
Ph
Me
Me
2-Naph
(CH2)4
C6H4-C6H4
c-Hex
Ph
5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
-30
0
ci
-49
-78
-72
12
(dia)-ci
cj
ck
cl
f
Ph
-81
-68
-43
-33
-80
-80
-35
-80
-68
-32
2
(dia)-cl
cm
c-Hex
4-CF3-Ph
Ph
4-CF3-Ph
Me
cn
(dia)-cn
Ph
Me
dj
di
da
ej
ei
eh
fj
fi
(CH2)4
Et
Et
Me
2-Naph
(CH2)6
(CH2)4
2-Naph
1-Naph
(CH2)4
n-Pr
n-Pr
n-Pr
i-Bu
i-Bu
i-Bu
Ph
Me
Me
-70
-74
-74
10
Me
2-Naph
Ph
2-Naph
Me
Me
A variation of the phenyl source [use of Ph3B (1.0 equiv) in
combination with Et2Zn (1.3 equiv) instead of a Ph2Zn/Et2Zn
mixture] had no positive effect, and the results in the formation
(dia)-fi
gn
a Method: Ph2Zn (0.65 equiv), Et2Zn (1.30 equiv), sulfoximine 2 (10
mol %), and aldehyde 3a (1.0 equiv) were stirred in toluene at 10 °C for
12-16 h. b All sulfoximines have (S)-configuration at sulfur. c Conversion
(8) For previous syntheses and other applications of â-hydroxysulfox-
imines, see: (a) Johnson, C. R.; Shanklin, J. R.; Kirchhoff, R. A. J. Am.
Chem. Soc. 1973, 95, 6462. (b) Johnson, C. R.; Stark, C. J. Tetrahedron
Lett. 1979, 49, 4713. (c) Johnson, C. R.; Kirchhoff, R. A. J. Am. Chem.
Soc. 1979, 101, 3602. (d) Johnson, C. R.; Zeller, J. R. J. Am. Chem. Soc.
1982, 104, 4021. (e) Johnson, C. R.; Barbachyn, M. R. J. Am. Chem. Soc.
1982, 104, 4290. (f) Bolm, C.; Seger, A.; Felder, M. Tetrahedron Lett.
1993, 34, 8079. (g) Bolm, C.; Felder, M. Tetrahedron Lett. 1993, 34, 6041.
(9) (a) Fusco, R.; Tericoni, F. Chim. Ind. (Milan) 1965, 47, 61. (b)
Johnson, C. R.; Schroeck, C. W. J. Am. Chem. Soc. 1973, 95, 7418. For an
improved protocol, see: (c) Brandt, J.; Gais, H.-J. Tetrahedron: Asymmetry
1997, 6, 909.
(10) For selected transformations of NH-sulfoximine 1a, see: (a) Hwang,
K.-J.; Logusch, E. W.; Brannigan, L. H. J. Org. Chem. 1987, 52, 3435. (b)
Shiner, C. S.; Berks, A. H. J. Org. Chem. 1988, 53, 5542. (c) Johnson, C.
R.; Lavergne, O. M. J. Org. Chem. 1993, 58, 1922. (d) Bolm, C.;
Hildebrand, J. P. J. Org. Chem. 2000, 65, 169. (e) Bolm, C.; Cho, G. Y.;
Re´my, P.; Jansson, J.; Moessner, C. Org. Lett. 2004, 6, 3293. (f) Moessner,
C.; Bolm, C. Org. Lett. 2005, 7, 2667. (g) Sedelmeier, J.; Bolm, C. J. Org.
Chem. 2005, 70, 6904.
of aldehyde 3a to diarylmethanol 4a as determined by H NMR. d Enan-
1
tiomeric ratios were determind by HPLC analysis ,using a Chiracel OD or
Chiracel ODH column. Positive values refer to (S) and negative ones to
(R) enantiomers of 4a being formed in excess. e See ref 11. f Derived from
9-fluorenone according to Scheme 1.
of 4a starting from 3a were very similar to those obtained with
the original system.
Following on the optimization of the reaction conditions, the
dependence of the enantioselectivity on the catalyst structure
under conditions depicted in Scheme 2 was investigated. The
results are shown in Table 1.
From the results reported in Table 1, a number of conclusions
can be drawn. First, the N-substituent on the sulfoximine plays
an important role for both reactivity and enantioselectivity.
Whereas use of NH-sulfoximines 2ab and 2ac resulted in the
formation of only small product quantities (entries 1 and 2),
(11) Only one diastereomer of 2ce could be obtained in pure form, and
the relative stereochemistry of this â-hydroxysulfoximine remained unde-
termined.
8860 J. Org. Chem., Vol. 72, No. 23, 2007

Synthesis of Diarylmethanols
TABLE 2. Substrate Scope in the Catalyzed Aryl Transfer onto
Aldehydesa
N-arylated derivative 2gn led to a higher yield of 4a (entry 30).
The best results were obtained with N-alkylated catalysts (entries
3-29). This reactivity pattern was paralleled by the enantiose-
lectivities. Also here, N-alkylated â-hydroxysulfoximines led
to the best results. In the series of catalysts with R′ and R′′
equal to cyclopentyl (entries 14, 21, 24, and 27) all sulfoximines
led to the formation of (R)-4a (with 68-80% ee). Use of the
N-ethyl-substituted sulfoximine 2dj provided the product with
the highest ee (80%) in this series.
As second parameter the influence of the substitution pattern
at the â position of the â-hydroxysulfoximines was studied. For
that purpose the lithio anion derived from N-methyl sulfoximine
1c (Scheme 1) was trapped with various carbonyl compounds.
Application of 4-chlorobenzaldehyde-derived sulfoximine 2ce
(entry 8) having a hydrogen and a 4-chlorophenyl substituent
at the â carbon in the phenyl transfer reaction depicted in
Scheme 2 led to disappointing results in terms of both reactivity
and enantioselectivity (49% yield of 4a with 16% ee). However,
â-hydroxysulfoximines obtained from trappings with symmetric
(cyclic and acyclic) ketones such as 2ca, 2cb, 2cc, 2cj, and 2ck
provided 4a in good yields (up to 88%) and enantioselectivities
in the range of 12-80% ee (entries 3-5, 14, and 15). In this
series, the cycloheptanone-derived compound 2ca gave the best
results (87% yield, 80% ee).
entry
aldehyde
R
product
yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
5
4-Cl
4-Ph
4a
4b
4c
4d
4e
4f
4g
4h
6
82
95
90
99
88
89
84
86
96
45
86
93
86
80
84
85
91
90
87
33
4-CH3
2,4,6-(CH3)3
2-Cl
4-F
4-N(CH3)2
4-OCH3
10
7
8
a Use of 10 mol % of â-hydroxysulfoximine 2cd as catalyst under
conditions shown in Scheme 2.
When the lithio anion of N-methylsulfoximine 1c was reacted
with unsymmetrical ketones, diastereomeric mixtures of â-hy-
droxysulfoximines 2 resulted. Most of those were easily
separated by column chromatography. Table 1 contains the
results of the phenyl transfer reaction onto aldehyde 3a of five
diastereomer pairs (entries 5/6, 12/13, 16/17, 19/20, and 28/
29). In all cases, the yields of 4a obtained in catalyses with the
various diastereomers were similar (ranging from 69% to 89%).
Interestingly, the stereogenic center at sulfur determined the
absolute configuration of the product. Thus, sulfoximines with
S configuration at sulfur yielded predominately the R enantiomer
of 4a, independently of the relative configuration of the other
stereogenic center. With the exception of the reactions with
diastereomer pair 2fi and (dia)-2fi (entries 28 and 29) the
enantiomer ratios found for (S)- and (R)-4a in catalyses with
diastereomeric catalysts varied (∆ee up to 47%; entries 19 and
20). Overall, the best results were achieved with â-hydroxysul-
foximines having an isopropyl and a phenyl group at the
â-carbon. In this case, both diastereomers, 2cd and (dia)-2cd,
reacted well (86% and 82% yield) affording (R)-4a with 86%
and 76% ee, respectively (entries 6 and 7). NMR experiments
revealed that the more selective diastereomer [(S,R)-2cd] was
heterochiral at both stereogenic centers.12
FIGURE 1. Possible intermediates of the asymmetric phenyl transfer
reaction onto aromatic aldehydes.
phenyl transfer onto 4-phenylbenzaldehyde (3b), which afforded
the desired product 4b with 93% ee in 95% yield (entry 2).
To our surprise and in contrast to our previous findings with
other catalyst systems,3 both electronic and steric factors had
only a minor effect on the efficiency (in terms of yield and ee)
of the phenyl transfer onto aldehydes 3. Thus, regardless of the
electronic nature of the substituent R on the aldehyde, the yield
and the enantioselectivity was always in the same ee range. Even
the presence of ortho-substituents did not hamper the addition
reaction significantly (entries 4 and 5). Unfortunately, aliphatic
aldehyde 7 did not react well, affording the corresponding
product with only 33% ee in 45% yield. Although this result is
significant in itself, it is in accord with the common reactivity
pattern of catalyzed aryl transfer reactions.2 Alternatively, 8
could be prepared by alkyl transfer onto benzadehyde or
reduction of the corresponding carbonyl compounds, which both
are known to proceed with high enantioselectivities.7
Finally, the substrate scope in phenyl transfer reactions
catalyzed by â-hydroxysulfoximine (S,R)-2cd under conditions
shown in Scheme 2 was investigated. As illustrated by the data
presented in Table 2, various substitution patterns on the
aromatic aldehydes were tolerated. Even heterocyclic 2-fural-
dehyde (5) reacted well. Generally, the yields of the corre-
sponding diarylmethanols 4 and 6 were high (82-99%), and
in three (out of 9) cases the enantioselectivities even exceeded
90% (entries 2, 7, and 8). The best result was achieved in the
With respect to the mechanism the situation is complex.
Following the general reaction path elucidated by Noyori for
amino alcohol-catalyzed dialkyzinc addition reactions to
aldehydes,7d-f and taking into account our previous findings
on related zinc alkoxide formations,7a,b we assume that the
â-hydroxysulfoximines are deprotonated upon reaction with the
Et2Ph/Ph2Zn mixtures. The resulting chelates 9 would then be
the actual catalysts. (For clarity reasons, in the graphics zinc
alkoxides with the R-configuration at sulfur are shown in Figure
1.) In the absence of substrates, those chelates will be ag-
gregated. A complication arises from the fact that mixtures of
zinc reagents are applied. Theoretical studies have been
(12) This assignment is based on the assumption that the H-bond of the
hydroxyl group in â-hydroxysulfoximine 2cd bridges toward the sulfoximine
nitrogen. This scenario would be consistent with the bonding mode observed
in the majority of related â-hydroxysulfoximines as determined by NMR
spectroscopy and X-ray structure analysis. For details, see: (a) Reference
5. (b) Felder, M. Dissertation, University of Marburg, 1995.
J. Org. Chem, Vol. 72, No. 23, 2007 8861

Sedelmeier and Bolm
performed on amino alcohol-based systems,13 and they give
guidelines on the Et/Ph positional preferences in such zinc
alkoxides. However, they also reveal that various catalyst/
substrate aggregates are possible and that some of them are close
in energy. Consequently, we can only speculate on possible
intermediates. Two of those are shown in Figure 1.
By using heterochiral â-hydroxysulfoximine 2cd [here shown
as (R,S)-2cd] as the model, a cis arrangement as in cis-10
appears more likely than the corresponding trans aggregate,
trans-10, since it minimizes steric interactions between the bulky
phenyl substituent at the ligand and the R group at the
organozinc. Furthermore, the remote position of the N-alkyl
substituent of the sulfoximine would explain its low effect on
the observed enantioselectivity of the aryl transfer process.
Finally, following arrangement cis-10 the expected enantiomer
of the product would result.
In summary, we have synthesized various â-hydroxysulfox-
imines and proved their catalytic applicability in asymmetric
phenyl transfer reactions onto aldehydes. In contrast to many
other systems, the efficiency of the phenyl transfer shows only
a minor dependence on electronic and steric factors of the
substrate. The corresponding products have been obtained with
up to 93% ee in good yields. Albeit this enantioselectivity cannot
compete with the existing methodology,3,4 the straightforward
catalyst synthesis (with only two steps from a commercially
available and readily accessible intermediate) renders this
protocol synthetically interesting.
with a 75% yield as a white solid. Rf (pentane:EtOAc 1:1) 0.47;
1H NMR (CDCl3, 400 MHz) δ 4.09 (br s, 2H), 7.11 (m, 3H), 7.18-
7.34 (m, 7H), 7.46 (m, 3H), 7.59 (m, 2H, Ar); 13C NMR (CDCl3,
100 MHz) δ 64.9, 76.4, 125.9, 126.0, 127.2, 127.4, 127.9, 128.1,
128.2, 129.0, 132.8, 143.0, 143.8, 144.5; mp 158-161 °C; IR (KBr)
ν 3274, 1495, 1450, 1426, 1404, 1216, 1179, 760, 708, 681, 560,
489 cm-1; MS (EI, 70 eV) m/z 338 ([M + 1]+, 2%), 218 (43%),
217 (100%), 196 (21%), 169 (28%), 125 (45%), 105 (72%). Anal.
Calcd for C20H19NO2S: C, 71.19; H, 5.68; N, 4.15. Found: C,
71.00; H, 5.83; N, 4.08; [R]25 -45.2 (c 0.68, CHCl3).
D
General Procedure for the Phenyl Transfer onto Aldehydes.
In a glovebox a 10 mL vial was charged with diphenylzinc (35.5
mg, 0.16 mmol). The vial was sealed with a septum and removed
from the glovebox. Freshly distilled toluene was added (1.25 mL).
After the addition of ZnEt2 (1M in heptane, 0.33 mL, 0.33 mmol),
the mixture was stirred for 30 min at room temperature. Another
vial was charged with â-hydroxysulfoximine 2 (10 mol %, 0.025
mmol), sealed with a septum, and flushed with argon. Toluene (1.0
mL) was added to dissolve 2 and the solution was transferred via
syringe into the first vial. The resulting mixture was stirred for 0.5
h at room temperature, then cooled to 10 °C and stirred for an
additional 10 min at this temperature. A third vial was charged
with aldehyde 3 (0.25 mmol), closed with a septum, and flushed
with argon, then the substrate was dissolved in toluene (1.0 mL).
After cooling to 10 °C the solution was transferred via syringe into
the other reaction vial. The resulting mixture was stirred for 12-
16 h at 10 °C. Then the reaction was quenched with water and the
mixture extracted with dichloromethane. The organic layer was
washed with water, dried over MgSO4, and filtered, and the solvent
was removed under reduced pressure. The product was purified by
column chromatography to give the desired alcohol 4.
Experimental Section
(S)-4-(Chlorophenyl)phenylmethanol (4a).14 4a was obtained
from aldehyde (3a) (35 mg, 0.25 mmol) according to the general
General Procedure for the Synthesis of â-Hydroxysulfox-
imines 2. N-Substituted sulfoximines were prepared according to
literature procedures.10 One equivalent of n-butyllithium (1 M in
hexane) was added to a stirred solution of sulfoximine 1 in ether
at -78 °C, and the reaction mixture was allowed to warm to 0 °C.
The resulting suspension was stirred at this temperature for 0.5 h.
Then the carbonyl compound (1.10 equiv in ether) was added
slowly. The reaction mixture was stirred at ambient temperature
overnight and then quenched with water. After stirring for 0.5 h,
the phases were separated and the ether phase was extracted with
aqueous 3 N HCl. The organic phase was washed with brine, dried
over MgSO4, and concentrated in vacuo to yield the products, which
were purified by column chromatography (EtOAc-pentane). In
most cases a separation of the diastereomeric mixture was possible
either by fractional crystallization or chromatography on silica gel.
Synthesis of (S)-1,1-Diphenyl-2-(S-phenylsulfonimidoyl)etha-
nol (2ab). 2ab was prepared according to the general procedure
1
procedure in a yield of 45 mg (82%, 0.206 mmol, 86% ee). H
NMR (CDCl3, 300 MHz) δ 2.23 (br s, 1H), 5.78 (s, 1H), 7.23-
7.45 (m, 9H); 13C NMR (CDCl3, 75 MHz) δ 75.7, 126.6, 127.9,
128.7, 128.7, 133.3, 142.3, 143.5; HPLC (Chiralcel OB-H, 25 °C,
230 nm, 90:10 heptane/i-PrOH, 0.5 mL/min) tR ) 27.7 (R), 34.8
min (S).
Acknowledgment. This work was supported by the Fonds
der Chemischen Industrie and the Deutsche Forschungsgemein-
schaft (DFG) within the “Graduiertenkolleg” (GRK) 440
“Methods in Asymmetric Synthesis”. We also thank Dr. J.
Runsink, RWTH Aachen University, for extensive NMR studies.
Supporting Information Available: General synthetic proce-
1
dures, characterization data of all products, and copies of H and
13C NMR spectra of compounds 2 and 4. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO7016718
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