Lithiated 4-isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one: A chiral formyl anion equivalent for enantioselective preparations of 1,2-diols, 2-amino alcohols, 2-hydroxy esters, and 4-hydroxy-2-alkenoates

Article abstract of DOI:10.1021/jo0155254

The heterocyclic compound specified in the title (and readily prepared from commercial precursors) has a sterically protected C=O group, so that direct lithiation by BuLi at the exocyclic CH₂ group is possible (3 → Li-3). The lithiated N,S-acetal derivative (Li-3) adds diastereoselectively to aldehydes (Table 2), unsymmetrical ketones (Table 3), chalcone (1,4-addition, Scheme 2), and N-phosphinoyl-and N-sulfonylimines (Table 4). Protection of the newly formed OH groups (Scheme 3) and/or MeS/OH displacement by Hg(O₂CCF₃)₂ in aqueous THF/acetonitrile converts the N,S-acetals into hemiaminals (→ 20) which, in turn, are readily cleaved to aldehydes, with recovery of the chiral auxiliary (1, Scheme 4). The aldehydes (especially those lacking α-carbonyl hydrogens) may be isolated, or they are trapped in situ by reduction to (selectively protected) diols or amino alcohols, by addition of Grignard or Li reagents, which provides diols with two stereogenic centers, by oxidation to give 2-hydroxy esters, or by olefination to provide 4-hydroxy-2-alkenoates (Scheme 5). The scope and limitations of the new, overall enantioselective transformation are determined, and the readily recovered chiral auxiliary used is compared with oxazolidinones of other substitution patterns (Scheme 7). The configuration of a number of products has been assigned by single-crystal X-ray diffraction (cf. Figure 5). These structures and similarities of NMR data led to configurational assignment of the other products (see formulas in the schemes and tables) by analogy. A simple mechanistic model for the stereochemical course of the addition of Li-3 to aldehydes and ketones is presented (Figure 6).

Full text of DOI:10.1021/jo0155254

J . Org. Chem. 2001, 66, 3059-3073
3059
Lith ia ted
4-Isop r op yl-3-(m eth ylth iom eth yl)-5,5-d ip h en yloxa zolid in -2-on e: A
Ch ir a l F or m yl An ion Equ iva len t for En a n tioselective P r ep a r a tion s
of 1,2-Diols, 2-Am in o Alcoh ols, 2-Hyd r oxy Ester s, a n d
4-Hyd r oxy-2-a lk en oa tes
Christoph Gaul,1 Kaspar Scha¨rer,2 and Dieter Seebach*
Laboratorium fu¨r Organische Chemie, Eidgeno¨ssische Technische Hochschule Zu¨rich, ETH-Zentrum,
Universita¨tstrasse 16, CH-8092 Zu¨rich, Switzerland
seebach@org.chem.ethz.ch
Received J anuary 16, 2001
The heterocyclic compound specified in the title (and readily prepared from commercial precursors)
has a sterically protected CdO group, so that direct lithiation by BuLi at the exocyclic CH2 group
is possible (3 f Li-3). The lithiated N,S-acetal derivative (Li-3) adds diastereoselectively to aldehydes
(Table 2), unsymmetrical ketones (Table 3), chalcone (1,4-addition, Scheme 2), and N-phosphinoyl-
and N-sulfonylimines (Table 4). Protection of the newly formed OH groups (Scheme 3) and/or MeS/
OH displacement by Hg(O2CCF3)2 in aqueous THF/acetonitrile converts the N,S-acetals into
hemiaminals (f 20) which, in turn, are readily cleaved to aldehydes, with recovery of the chiral
auxiliary (1, Scheme 4). The aldehydes (especially those lacking R-carbonyl hydrogens) may be
isolated, or they are trapped in situ by reduction to (selectively protected) diols or amino alcohols,
by addition of Grignard or Li reagents, which provides diols with two stereogenic centers, by
oxidation to give 2-hydroxy esters, or by olefination to provide 4-hydroxy-2-alkenoates (Scheme 5).
The scope and limitations of the new, overall enantioselective transformation are determined, and
the readily recovered chiral auxiliary used is compared with oxazolidinones of other substitution
patterns (Scheme 7). The configuration of a number of products has been assigned by single-crystal
X-ray diffraction (cf. Figure 5). These structures and similarities of NMR data led to configurational
assignment of the other products (see formulas in the schemes and tables) by analogy. A simple
mechanistic model for the stereochemical course of the addition of Li-3 to aldehydes and ketones
is presented (Figure 6).
In tr od u ction
The N-Boc-protected lithiated oxazolidine and thiazo-
lidine are formed by what is sometimes referred to as
heteroatom-directed metalation.11 This methodology has
its origin in the early observations by Durst,12 Fraser,13
C,C-Bond-forming reactions leading to 1,2-difunction-
alized products, such as 1,2-diols, 2-amino alcohols,
2-hydroxy or 2-amino aldehydes, and esters (A-C in
Figure 1) require reagents with reactivity umpolung.3
The most common enantioselective version of this trans-
formation is the addition to a R1R2CdX trigonal center
of a reagent that is synthetically equivalent to a chiral
formyl anion (see retrosynthetic formalism4 in Figure 1).
The aldehydes thus accessible can be reduced to alco-
hols (A f B) or oxidized to carboxylic acid derivatives
(A f C).
In some of the more practical realizations of the desired
transformation the reagents presented in Figure 2 have
been used.5-10 As can be seen, four of the Li compounds
shown are actually acetal derivatives of formyllithium,
in one approach an aza-enamine is employed and in
another one a Br/Li carbenoid.
(6) (a) Aggarwal, V. K.; Davies, I. W.; Maddock, J .; Mahon, M. F.;
Molloy, K. C. Tetrahedron Lett. 1990, 31, 135. (b) Aggarwal, V. K.;
Franklin, R. J .; Rice, M. J . Tetrahedron Lett. 1991, 32, 7743. (c)
Aggarwal, V. K.; Thomas, A.; Franklin, R. J . J . Chem. Soc., Chem.
Commun. 1994, 1653. (d) Aggarwal, V. K.; Davies, I. W.; Franklin, R.;
Maddock, J .; Mahon, M. F.; Molloy, K. C. Chem. Soc., Perkin Trans. 1
1994, 2363. (e) Aggarwal, V. K.; Franklin, R. J .; Maddock, J .; Evans,
G. R.; Thomas, A.; Mahon, M. F.; Molloy, K. C.; Rice, M. J . J . Org.
Chem. 1995, 60, 2174. (f) Aggarwal, V. K.; Thomas, A.; Schade, S.
Tetrahedron 1997, 53, 16213. (g) Aggarwal, V. K.; Schade, S.; Adams,
H. J . Org. Chem. 1997, 62, 1139. (h) A reviewer has pointed out to us
that Li dithiane can be added to aldehydes enantioselectively in the
presence of a sparteine derivative: Kang, J .; Kim, J . I.; Lee, J . H. Bull.
Korean Chem. Soc. 1994, 15, 865.
(7) (a) Enders, D.; Syrig, R.; Raabe, G.; Fernandez, R.; Gasch, C.;
Lassaletta, J . M. Synthesis 1996, 48. (b) Lassaletta, J . M.; Fernandez,
R.; Martin-Zamora, E.; Diez, E. J . Am. Chem. Soc. 1996, 118, 7002.
(c) Lassaletta, J . M.; Fernandez, R.; Martin-Zamora, E.; Pareja, C.
Tetrahedron Lett. 1996, 37, 5787. (d) Diez, E.; Fernandez, R.; Gasch,
C.; Lassaletta, J . M.; Llera, J . M.; Martin-Zamora, E.; Vazquez, J . J .
Org. Chem. 1997, 62, 5144. (e) Enders, D.; Bolkenius, M.; Vazquez, J .;
Lassaletta, J . M.; Fernandez, R. J . Prakt. Chem. 1998, 340, 281. (f)
Pareja, C.; Martin-Zamora, E.; Fernandez, R.; Lassaletta, J . M. J . Org.
Chem. 1999, 64, 8846. (g) Enders, D.; Vazquez, J .; Raabe, G. Eur. J .
Org. Chem. 2000, 893.
(1) Part of the projected Ph.D. Thesis of C.G., ETH Zu¨rich.
(2) Part of the Master Thesis of K.S., ETH Zu¨rich 2000.
(3) Seebach, D. Angew. Chem., Int. Ed. Engl. 1979, 18, 239.
(4) Corey, E. J .; Cheng, X. M. In The Logic of Chemical Synthesis;
J ohn Wiley & Sons: New York, 1989.
(5) (a) Colombo, L.; Gennari, C.; Scolastico, C.; Guanti, G.; Narisano,
E. J . Chem. Soc., Chem. Commun. 1979, 591. (b) Colombo, L.; Gennari,
C.; Scolastico, C.; Guanti, G.; Narisano, E. J . Chem. Soc., Perkin Trans.
1 1981, 1278. (c) Colombo, L.; Gennari, C.; Resnati, G.; Scolastico, C.
J . Chem. Soc., Perkin Trans. 1 1981, 1284. (d) Colombo, L.; Gennari,
C.; Resnati, G.; Scolastico, C. Synthesis 1981, 74.
(8) (a) Braun, M.; Mahler, H. Tetrahedron Lett. 1987, 28, 5145. (b)
Mahler, H.; Braun, M. Chem. Ber. 1991, 124, 1379. (c) Braun, M.;
Obdenbusch, K. Angew. Chem., Int. Ed. Engl. 1991, 32, 578. (d) Braun,
M.; Obdenbusch, K. Liebigs Ann./ Recueil 1997, 141. (e) Braun, M.
Angew. Chem., Int. Ed. Engl. 1998, 37, 430.
10.1021/jo0155254 CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/12/2001

3060 J . Org. Chem., Vol. 66, No. 9, 2001
Gaul et al.
F igu r e 2. Some reagents that are synthetically equivalent
to a chiral formyl anion.
F igu r e 1. Retrosynthetic scheme for the enantioselective
preparation of 1,2-difunctionalized compounds with C,C-bond
formation.
Beak,14 Seebach,15 and their respective co-workers, who
found that carboxylic acid derivatives of appropriate
substitution pattern can be deprotonated “on the wrong
side”, i.e., next to the heteroatom rather than in the
R-carbonyl position; see selected examples and references
in Figure 3.15-24
At the time, this metalation was used to provide an
umpolung of alcohol, amine, or imine reactivity25,26 that
has also been realized through lithiated nitrosamines.25,27
One systematic way of generating such amido-alkyl-
lithium reagents was to use carboxylic or carbonic acid
(9) Gawley, R. E.; Zhang, Q.; McPhail, A. T. Tetrahedron: Asymmetry
2000, 11, 2093.
(10) Kise, N.; Urai, T.; Yoshida, J . Tetrahedron: Asymmetry 1998,
9, 3125.
(11) Beak, P.; Meyers, A. I. Acc. Chem. Res. 1986, 19, 356.
(12) Durst, T.; van den Elzen, R.; LeBelle, M. J . J . Am. Chem. Soc.
1972, 94, 9261.
(13) Fraser, R. R.; Boussard, G.; Portescu, D.; Whiting, J . J .;
Whitfield, Y. Y. Can. J . Chem. 1973, 51, 1109.
(14) (a) Beak, P.; Farney, R. J . Am. Chem. Soc. 1973, 95, 4771. (b)
Beak, P.; Brubaker, G. R.; Farney, R. J . Am. Chem. Soc. 1976, 98,
3621.
(15) (a) Seebach, D.; Lubosch, W. Angew. Chem., Int. Ed. Engl. 1976,
15, 313. (b) Seebach, D.; Lubosch, W. Helv. Chim. Acta 1980, 63, 102.
(16) Schlecker, R.; Seebach, D.; Lubosch, W. Helv. Chim. Acta 1978,
61, 512.
(17) Seebach, D.; Hassel, T. Angew. Chem., Int. Ed. Engl. 1978, 17,
274.
(18) (a) Hassel, T.; Seebach, D. Helv. Chim. Acta 1978, 61, 2237.
(b) Hassel, T.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1979, 18, 399.
(19) (a) Seebach, D.; Hansen, J .; Seiler, P.; Gromek, J . M. J .
Organomet. Chem. 1985, 285, 1. (b) Huber, I. M. P.; Seebach, D. Helv.
Chim. Acta 1987, 70, 1944.
(20) Schlecker, R.; Seebach, D. Helv. Chim. Acta 1977, 60, 1459.
(21) (a) Beak, P.; Reitz, D. B. Chem. Rev. 1978, 78, 275. (b) Beak,
P.; Zajdel, W. J .; Reitz, D. B. Chem. Rev. 1984, 84, 471.
(22) Beak, P.; Kerrick, S. T.; Wu, S.; Chu, J . J . Am. Chem. Soc. 1994,
116, 3231.
(23) Pfammatter, E.; Seebach, D. Liebigs Ann. Chem. 1991, 1323.
(24) (a) Hoppe, D.; Kra¨mer, T. Angew. Chem., Int. Ed. Engl. 1986,
25, 160. (b) Hoppe, D.; Zschage, O. Angew. Chem., Int. Ed. Engl. 1989,
28, 67. (c) For a review, see: Hoppe, D.; Hense, T. Angew. Chem., Int.
Ed. Engl. 1997, 36, 2283.
(25) Seebach, D.; Enders, D. Angew. Chem., Int. Ed. Engl. 1975,
14, 15.
F igu r e 3. Lithiated esters, amides, carbamates, ureas and
an imide for nucleophilic hydroxy- and amino alkylations or
as reagents that are synthetically equivalent to so-called
homoenolates (d3 synthons18,24).
derivatives with sterically protected CdO groups; see
Figure 3, top.
Considering the broad scope and applicability of amino
acid-derived chiral oxazolidinone auxiliaries (Evans aux-
iliaries28), it was highly desirable to also apply them to
the synthetic transformation discussed here. A directed
metalation on an exocyclic N-substituent of such an
oxazolidinone did not appear promising until recently:
the CdO group of these oxazolidinones is too reactive
toward strong nucleophiles/bases, such as BuLi. This is
why the Sn/Li exchange has been used (see D in Figure
4) for the generation of N-lithioalkyl oxazolidinones;29-31
a directed lithiation has only been reported for the
(28) For reviews, see: (a) Agar, D. J .; Prakash, I.; Schaad, D. R.
Chem. Rev. 1996, 96, 835. (b) Ager, D. J .; Prakash, I.; Schaad, D. R.
Aldrichim. Acta. 1997, 30, 3. (c) Regan, A. C. J . Chem. Soc., Perkin
Trans. 1 1998, 1151. (d) Regan, A. C. J . Chem. Soc., Perkin Trans. 1
1999, 357.
(26) (a) Gawley, R. E. In Advances in Asymmetric Synthesis;
Hassner, A., Ed.; J AI: Greenwich, CT, 1998; Vol. 3, p 77. (b) Gawley,
R. E. In Grignard Reagents: New Developments; Richey, H. G., Ed.;
J ohn Wiley & Sons: New York, 2000; p 139.
(27) Seebach, D.; Enders, D. Angew. Chem., Int. Ed. Engl. 1972,
11, 301. (b) Seebach, D.; Enders, D. Angew. Chem., Int. Ed. Engl. 1972,
11, 1101.
(29) (a) Pearson, W. H.; Lindbeck, A. C. J . Org. Chem. 1989, 54,
5651. (b) Pearson, W. H.; Lindbeck, A. C. J . Am. Chem. Soc. 1991,
113, 8546. (c) Pearson, W. H.; Lindbeck, A. C.; Kampf, J . W. J . Am.
Chem. Soc. 1993, 115, 2622.
(30) (a) Tomoyasu, T.; Tomooka, K.; Nakai, T. Synlett 1998, 1147.
(b) Tomoyasu, T.; Tomooka, K.; Nakai, T. Tetrahedron Lett. 2000, 41,
345.

4-Isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one
J . Org. Chem., Vol. 66, No. 9, 2001 3061
Sch em e 1
F igu r e 4. Chiral oxazolidinones metalated in the 1-position
and the modified Evans auxiliary 1 with superior properties.
oxazolidinone E with benzylic acidification of the NCH2
group.32 On the other hand, we have recently observed
that the 5,5-diphenyloxazolidinone 1 has a highly hin-
dered CdO group (no functional group selectivity problem
in N-acylated derivatives) and gives well-crystallizing
derivatives; see refs 33-38 and comments in Figure 4.
Thus, we have been able to lithiate N,S-acetals derived
from oxazolidinone 1 (F in Figure 4) and use them as
chiral nucleophilic formylation reagents. The results are
described in the present full paper.39
Ta ble 1. Ad d ition of Lith ia ted Aceta ls 2-5 to
Ben za ld eh yd e u n d er Va r yin g Rea ction Con d ition s
Resu lts a n d Discu ssion
products 7, 8
entry substrate
XR
conditionsa
yieldb (%)
dr (7/8)c
P r ep a r a tion of Ch ir a l N-(Meth oxym eth yl)-, N-
(Meth ylth iom eth yl)-, N-(P h en ylth iom eth yl)-, a n d
N-(ter t-Bu tylth iom eth yl)oxa zolid in on es. N,O-Acetal
2 and N,S-acetals 3-5 were prepared in order to examine
the effect of electronic and steric factors on the metalation
of these acetals and their subsequent addition to elec-
trophiles (Scheme 1). Compound 2 was obtained in 72%
yield from oxazolidinone 1 by N-alkylation with chloro-
methyl methyl ether (MOMCl).40 For the synthesis of
compounds 3-5, we chose to employ a procedure devel-
oped for the protection of OH groups as methylthiomethyl
ethers (MTM ethers).41 Thus, treatment of oxazolidinone
1 with BuLi, NaI, and the corresponding chloromethyl
sulfide42 in DME at 0 °C afforded the desired N,S-acetals
1
2
3
4
5
6
2
3
4
5
3
3
OMe
SMe
SPh
S-t-Bu
SMe
SMe
A
A
A
A
B
C
a
b
c
d
b
b
d
86
71e
f
92
90
90:10
95:5e (91:9)c
85:15
93:7
a
Key: (A) THF, -78 °C; (B) Et2O, -78 °C; (C) THF, -100 °C.
Combined yield of both isomers after FC. c Determined by 1H
b
NMR (300 MHz) of the crude product. No reaction. e Yield (95%
purity)/dr obtained/determined after trituration in hexane. f Com-
plex mixture of products.
d
3-5 in good yields (Scheme 1). Interestingly, “dimer” 6
was isolated as a side product only when chloromethyl
methyl sulfide (MTMCl) was used as alkylating reagent
(3 and 6 as a 4:1 mixture). Presumably, compound 6
results from the reaction of product 3 with Li-1, whereas
the sterically more demanding sulfur substituents of
products 4 and 5 prevent the attack by Li-1. The
undesired side reaction could be suppressed by using
DMSO/THF (5:1) as solvent; N,S-acetal 3 was formed in
86% yield as the exclusive product.
Lith ia tion a n d Ad d ition of Oxa zolid in on e Der iva -
tives 2-5 to Electr op h iles. Acetals 2-5 were treated
sequentially with BuLi and benzaldehyde in THF at -78
°C (Table 1, entries 1-4). In the case of N,O-acetal 2,
only starting material was recovered (cf. entry 1). Not
surprisingly, compound 2 could not be lithiated under
(31) J eanjean, F.; Fournet, G.; Le Bars, D.; Gore´, J . Eur. J . Org.
Chem. 2000, 1297.
(32) Gawley, R. E.; Rein, K.; Chemburkar, S. J . Org. Chem. 1989,
54, 3002. For direct lithiation of an imidazolidinone with allylic
acidification of the NCH2 group, see: Roder, H.; Helmchen, G.; Peters,
E. M.; Peters, K.; von Schnering, H. G. Angew. Chem., Int. Ed. Engl.
1984, 23, 898.
(33) Hintermann, T.; Seebach, D. Helv. Chim. Acta 1998, 81, 2093.
(34) Brenner, M.; Seebach, D. Helv. Chim. Acta 1999, 82, 2365.
(35) See also independent work with this oxazolidinone by other
groups: (a) Gibson, C. L.; Gillon, K.; Cook, S. Tetrahedron Lett. 1998,
39, 6733. (b) Bull, S. D.; Davies, S. G.; J ones, S.; Sanganee, H. J . J .
Chem. Soc., Perkin Trans. 1 1999, 387. (c) Fukuzawa, S.; Matsuzawa,
H.; Yoshimitsu, S. J . Org. Chem. 2000, 65, 1702.
(36) The oxazolidinone 1 and its enantiomer are commercially
available as (S)- and (R)-DIOZ: Shiratori Pharmaceutical Co., Ltd.,
J apan. Isobe, T.; Fukuda, K. J apanese Patent J P 09143173, 1995;
Chem. Abstr. 1997, 127, 50635.
(37) Use of 1 for the preparation of diphenylmethylamines: O’Hagan,
D.; Tavasli, M. Tetrahedron: Asymmetry 1999, 10, 1189.
(38) Bull, S. D.; Davies S. G.; Key, M. S.; Nicholson, R. L.; Savory,
E. D. J . Chem. Soc., Chem. Commun. 2000, 1721.
(42) Chloromethyl methyl sulfide is commercially available. Chlo-
romethyl phenyl sulfide and chloromethyl tert-butyl sulfide were
prepared according to general procedures: (a) Turchaninova, L. P.;
Voronkov, M. G.; Shipov, A. G.; Korchevin, N. G.; Baukov, Y. I.;
Deryagina, E. N. Zh. Obshch. Khim. 1989, 59, 722. (b) Beight, D. W.;
Mehdi, S.; Koehl, J . K.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1996, 6,
2053.
(39) Preliminary communication: Gaul, C.; Seebach, D. Org. Lett.
2000, 2, 1501.
(40) The preparation of 1 has been described previously.33,35b
(41) Corey, E. J .; Bock, M. C. Tetrahedron Lett. 1975, 16, 3269.

3062 J . Org. Chem., Vol. 66, No. 9, 2001
Gaul et al.
Ta ble 3. Ad d ition of Lith ia ted Meth ylth iom eth yl
Ta ble 2. Ad d ition of Lith ia ted Metylth iom eth yl
Oxa olid in on e 3 to Ald eh yd es
Oxa zolid in on e 3 to Keton es
products 9, 10
entry
R
yielda (%)
dr (9/10)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
2-naphthyl
4-(MeO)C6H4
3-(TBSO)C6H4
4-(NC)C6H4
furfuryl
2-thiophenyl
1-methyl-2-pyrrolyl
3-pyridinyl
phenylpropargyl
(E)-PhCHdCH
CH2dCMe
a
b
c
d
e
f
g
h
i
j
k
l
m
n
87
92
91:9
91:9
91:9
85:15
90:10
92:8
91
77c
90
92
81d
72d
80e
91
91:9d (83:17)b
96:4d (84:16)b
93:7
86:14
85:15
86:14
71:29
88
84
1-cyclopentenyl
i-Pr
Pr
84 (61)e
83
70:30
a
b
Combined yield of both isomers after FC. Determined by 1H
NMR (300 MHz) of the crude product. c Only 88% conversion.
d
Yield/dr obtained/determined after recrystallization from MeOH.
e Yield of the major isomer (dr 99:1) after FC.
these reaction conditions.43 With N,S-acetals 3 and 4,
however, the reaction proceeded efficiently to afford
adducts 7b and 7c in high yields and very good stereo-
selectivities (cf. entries 2 and 3). In each case, only two
of the four possible diastereoisomers were formed. Major
isomers 7 and minor isomers 8 have the same configu-
ration at C(1)-SR and are epimeric at C(2)-OH.44 At-
tempted lithiation and addition of N,S-acetal 5 to benz-
aldehyde resulted in a complex mixture of products (cf.
entry 4). As illustrated by the data in Table 1, the optimal
protocol involves lithiation of N,S-acetal 3 with BuLi in
THF at -78 °C and subsequent addition of benzaldehyde
at -100 °C (cf. entry 6); adduct 7b was isolated in 90%
yield as a 93:7 mixture with its C(2)-OH epimer 8b.
In Table 2, we have summarized the results of our
studies on the addition reaction of the lithiated methyl-
thiomethyl oxazolidinone 3 to various aldehydes. While
the yield of the reaction is very high for all aldehydess
products 9/10 were isolated in 72-92% combined yields
the stereoselectivity is dependent on the type of alde-
hyde.44 Thus, Li-3 adds smoothly to aromatic, hetero-
aromatic, and propargylic aldehydes (cf. entries 1-9)
with diastereoselectivities greater than 90%, while the
adducts with R,â-unsaturated aldehydes are usually
formed somewhat less selectively (cf. entries 10-12)
(products resulting from 1,4-addition were not detected).
The addition to aliphatic aldehydes is also high yielding,
but the selectivities are lower (cf. entries 13 and 14).
Fortunately, competing enolization of the aliphatic alde-
a
b
Yield of the major isomer (dr g 98:2). Determined by 1H
NMR (300 MHz) of the crude product. c Yield of a 77:23 mixture.
Yield of a 97:3 mixture. e Moderate yield due to difficult purifica-
d
tion. f Not determined. Yield of a 83:17 mixture.
g
hydes by Li-3 was not observed. The diastereoisomeric
products 9 and 10 from aliphatic, R,â-unsaturated, and
propargylic aldehydes can usually be separated by flash
chromatography, with the major isomer eluting first. In
the case of aromatic aldehydes, diastereoisomeric prod-
ucts 9 and 10 were separated by recrystallization from
MeOH. Furthermore, simple trituration of the crude
products in hexane afforded cleanly mixtures of 9 and
10 with enhanced diastereoisomer ratios.
We next turned our attention to the reaction of Li-3
with unsymmetrical ketones R1COR2. Adducts to ketones
with their newly created tertiary stereocenters would be
synthetically especially valuable intermediates. As is
evident from the data in Table 3, Li-3 adds particulary
effectively to (hetero)aryl/alkyl ketones (cf. entries 1-7).44
The major isomers 11 were isolated in 55-76% yield
(dr g 98:2) after recrystallization from MeOH or tritu-
ration in MeOH. The diastereoselectivities are excellent,
(43) Gilman, H.; Webb, F. J . J . Am. Chem. Soc. 1949, 71, 4092.
(44) The relative configuration of adducts 9d ,e, 10m , 11a ,e,i-k ,
15d , of acyloxazolidinones 30, 31, and of N,O-acetal 37 was unambigu-
ously assigned by single-crystal X-ray diffraction. Additionally, the
configuration at C(2)-OH of adducts 7b, 9m , 11a and the configuration
at C(1)-NH of adduct 14c were confirmed by optical comparison of
compounds 21, 23, 24, and 25 with the data reported in the literature.
The X-ray structures, similarities of NMR data, and comparison of Rf
values of major and minor products led to configurational assignment
of the other compounds by analogy (see formulas in the schemes and
tables).

4-Isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one
J . Org. Chem., Vol. 66, No. 9, 2001 3063
Sch em e 2
Ta ble 4. Ad d ition of Lith ia ted Meth ylth iom eth yl
Oxa zolid in on e 3 to Im in e Der iva tives
products 14, 15
entry
PG
R
yielda (%)
dr (14/15)a
1
2
3
4
-P(O)Ph2
-SO2Tol
-SO2Mes
-SO2Mes
Ph
Ph
Ph
i-Pr
a
b
c
d
44
67
62
43b
97:3
75:25
95:5
3:97
a
Yield/dr obtained/determined after FC or trituration in MeOH.
95% purity after FC.
b
even surpassing the selectivities found with aldehydes
in some cases (cf. entries 5 and 6). Only highly reactive
ketones (cf. entry 2) or ketones with sterically similar R1
and R2 groups (cf. entry 3) reacted with diminished
selectivities. The addition to alkenyl/alkyl ketones and
alkyl/alkyl ketones proceeded in lower conversion/yield
and selectivity (cf. entries 9-11). The incomplete conver-
sion is due to competing enolization of these ketones by
Li-3. Note that the conversion with (hetero)aryl/alkyl
ketones is considerably higher, although their R-carbonyl
hydrogens are more acidic. This surprising result might
be due to a favorable interaction of the phenyl rings of 3
with the aryl group of the ketones.45
F igu r e 5. X-ray crystal structures of products 9d , 11e, and
15d . N: blue. O: red. S: yellow.
crude product in MeOH. Unexpectedly, the diastereo-
selectivity of the reaction was reversed in the addition
of Li-3 to the N-mesitylsulfonylimine derived from isobu-
tyraldehyde (cf. entry 4), furnishing adduct 15d in 43%
yield.44
Furthermore, Li-3 displayed a remarkable reactivity
toward benzalacetophenone. Product 13 of conjugate
addition was obtained in 79% yield as a 98:2 mixture with
its C(2)-Ph epimer after flash chromatography (Scheme
1
2).44 1,2-Adducts were formed in only 9% yield (by H
We were able to obtain single crystals of a number of
products of type 7-15 suitable for structure determina-
tion by X-ray crystallography.44 The X-ray crystal struc-
tures of major adducts 9d , 11e, and 15d are depicted in
Figure 5 as selected examples. Referring to the two newly
created stereocenters, 9d and 11e have (S,S)- or l-
configuration. Hence, the new C,C-bond is formed with
the relative topicity ul. X-ray crystal structure analysis
of several other aldehyde and ketone adducts revealed
the same stereochemical course of formation of the major
isomer.
Based on the data obtained by X-ray crystallography,
a simple model for the stereochemical course of the
reaction may be suggested (Figure 6).48 The intermediate
organolithium species Li-3 may have a defined five-
membered ring chelate structure,49 with the i-Pr and the
MeS substituent being on opposite sides of a bicyclic
system. In the formation of the major product, the
NMR spectroscopy of the crude product). This result is
in sharp contrast to the outcome of the reaction of Li-3
with 2-benzylidene-1-tetralone, in which only the 1,2-
adduct 11h was isolated (cf. Table 3, entry 8).
We then investigated the behavior of several imine
derivatives in the addition reaction (Table 4). N-Diphen-
ylphosphinoylimines and N-tolyl- and N-mesitylsulfo-
nylimines are known to be particulary suitable for
enantio- and diastereoselective reactions with nucleo-
philes.46 Therefore, we prepared the benzaldehyde-
derived phosphinoyl- and sulfonylimines47 and tested
them in the reaction with Li-3 (cf. entries 1-3).44 Best
results were achieved with the N-mesitylsulfonylimine:
Major isomer 14c was obtained in 62% yield as a 95:5
mixture with its C(1)-NH epimer after trituration of the
(45) A similar effect of these phenyl groups had been observed
previously.33
(46) (a) Soai, K.; Hatanaka, T.; Miyazawa, T. J . Chem. Soc., Chem.
Commun. 1992, 1097. (b) Reference 8c,d.
(47) The phosphinoylimine was prepared according to: J ennings,
W. B.; Lovely, C. J . Tetrahedron 1991, 47, 5561. The sulfonylimines
were prepared according to: Chemla, F.; Hebbe, V.; Normant, J . F.
Synthesis 2000, 75.
(48) This model is consistent with observations made by Pearson29
and Nakai.30
(49) The structure of Li-3 is drawn arbitrarily; the configuration of
the lithiated carbon is unknown. Cf. the X-ray crystal structure of a
1-bromomagnesio-2-pivaloyltetrahydroisoquinoline.19a

3064 J . Org. Chem., Vol. 66, No. 9, 2001
Gaul et al.
Sch em e 4
treated with tert-butyldimethylsilyl triflate (TBSOTf) in
CH2Cl2 to afford 18 in 53% overall yield (dr g 99:1) from
oxazolidinone 3. The in situ OH protection of the ketone
adducts has never been attempted by us; it probably
requires highly reactive protecting reagents, since the
tertiary alcohols (alkoxides) are sterically severely crowded.
F igu r e 6. Proposed model for the stereochemical course of
the addition of Li-3 to aldehydes and ketones.
Sch em e 3a
Con ver sion of Ad d u cts 19 to Syn th etica lly Va lu -
a ble Ch ir a l Bu ild in g Block s. At this point, the hy-
drolysis of the N,S-acetal moiety in the products 19,
which is crucial to the usefulness of the diastereoselective
addition of Li-3 to electrophiles, was envisaged. We
intended to convert adducts 19 to protected 2-hydroxy
and 2-amino aldehydes with recycling of the chiral
auxiliary 1 (Scheme 4). Several desulfurization reagents
such as HgCl2, AgNO3, CuCl2, NBS, or MeI were tested,
but all of them led to either complex product mixtures
or to no reaction at all. In first successful experiments,
treatment of N,S-acetals 19 with bis(trifluoroacetoxy)-
iodobenzene51 in MeOH cleanly furnished the analogous
N,OMe-acetals. To our disappointment, we were unable
to hydrolyze them. Similarly, Hg(OAc)2-assisted hydroly-
sis of N,S-acetals 19 in THF/MeCN (1:1) yielded the
corresponding N,OAc-acetals, which also resisted our
attempts of cleavage to the desired aldehydes and
auxiliary 1.52
To our delight, treatment of protected and unpro-
tected adducts 19 with Hg(O2CCF3)2 in MeCN/THF/H2O
(2:2:1) at room temperature gave the corresponding
hemiaminals 20 within 5 min (cf. a in Scheme 5). Since
these hemiaminals were rather sensitive to decomposi-
tion, they were used for further transformations without
purification.53 NMR experiments in CDCl3 provided
evidence that hemiaminals 20 collapse instantaneously
to the corresponding aldehydes and oxazolidinone 1 upon
addition of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
Interestingly, compounds 20 were stable in the presence
of Et3N or Hu¨nig’s base. As chiral enolizable 2-hydroxy
and 2-amino aldehydes are fairly susceptible to racemi-
zation, dimerization (reversible) and air oxidation, it is
desirable to convert them in situ into chemically stable
a
Key: * yield/dr obtained/determined after purification.
aldehyde or ketone would then approach the C,Li-bond
with its Re face to avoid steric repulsion between the R1
and the MeS group. The proposed model is consistent
with the stereochemical course of the addition reaction
of Li-3 to aldehydes and ketones, but cannot be applied
to the preferred mode of reaction with imine derivatives
(cf. Table 4, entries 3 and 4, and Figure 5, 15d ). In this
case, an appropriate model is expected to be more
complex, since it is very likely that the phosphinoyl and
sulfonyl groups also coordinate to lithium via their
oxygen atoms.
To further extend the scope of the reaction, the in situ
OH protection of the aldehyde adducts was examined
(Scheme 3). Consecutive addition of benzaldehyde and
MOMCl to a solution of Li-3 afforded the MOM-protected
benzaldehyde adduct 16. Similarly, the initially formed
methacrolein adduct reacted in situ with BnBr to give
17. However, the use of N,N′-dimethylpropyleneurea
(DMPU) as a cosolvent was necessary for an efficient
introduction of the benzyl protecting group. Presumably,
DMPU enhances the reactivity of the in situ generated
Li-alkoxide by coordinating to lithium.50 In the case of
isobutyraldehyde, we were unable to perform the addition
reaction and the protecting step (with MOMCl, BnBr as
well as AcCl) in a one-pot procedure. Therefore, the major
isobutyraldehyde adduct 9m was first isolated and then
(50) For nucleophilicity enhancement in the presence of DMPU,
see: (a) Beck, A. K.; Seebach, D. In Encyclopaedia of Reagents in
Organic Chemistry; Paquette, L. A., Ed.; J ohn Wiley & Sons: New
York, 1995; Vol. 3, p 2123. (b) Mukhopadhyay, T.; Seebach, D. Helv.
Chim. Acta 1982, 65, 385. (c) Seebach, D.; Maestro, M. A.; Sefkow,
M.; Neidlein, A.; Sternfeld, F.; Adam, G.; Sommerfeld, T. Helv. Chim.
Acta 1991, 74, 2112. (d) Seebach, D.; Maestro, M. A.; Sefkow, M.; Adam,
G.; Hintermann, S.; Neidlein, A. Liebigs Ann. Chem. 1994, 701. (e)
Lipshutz, B. H.; Moretti, R.; Crow, R. Tetrahedron Lett. 1989, 30, 15.
(51) Stork, G.; Zaho, K. Tetrahedron Lett. 1989, 30, 287.
(52) For similar observations, see: Sarma, D. N.; Barua, N. C.;
Sharma, R. P. Chem. Ind. (London) 1984, 223.
(53) For oxazolidinone-derived hemiaminals, see: (a) Bach, J .; Bull,
S. D.; Davies, S. G.; Nicholson, R. L.; Sanganee, H. J .; Smith, A. D.
Tetrahedron Lett. 1999, 40, 6677. (b) Bull, S. D.; Davies, S. G.;
Nicholson, R. L.; Sanganee, H. J .; Smith, A. D. Tetrahedron: Asymmetry
2000, 11, 3475.

4-Isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one
Sch em e 5
J . Org. Chem., Vol. 66, No. 9, 2001 3065
products such as (selectively protected) 1,2-diols, 2-amino
alcohols, 2-hydroxy esters or 4-hydroxy-2-alkenoates (cf.
b-e in Scheme 5). After extensive experimentation, a
variety of p r oced u r es were developed that do not
require the isolation of these sensitive aldehydes but
make use of the synthetically valuable intermediate
aldehyde functionality.
and DBU at 0 °C, yielding (selectively protected) 1,2-diols
or 2-amino alcohols (cf. b in Scheme 5). Following this
procedure, compounds 21-27 were obtained in 61-90%
yield (from 19). The enantiopurities of 21, 23, and 25
were determined by GC, indicating that no detectable
racemization had occurred during the reduction. It is
reasonable to assume that the diol and amino alcohol
derivatives 22, 24, 26, and 27 are also enantiopure, since
they were obtained under the same reaction conditions.
P r oced u r e 1. Hemiaminals of type 20 are dissolved
in THF/H2O (4:1) and treated consecutively with NaBH4

3066 J . Org. Chem., Vol. 66, No. 9, 2001
Gaul et al.
Sch em e 6
P r oced u r e 2. Slow addition of organolithium or Grig-
nard reagents to a solution of hemiaminals 20 in THF
at -78 °C furnishessin a C,C-bond-forming process and
with the generation of a new stereocenters1,2-diols (cf.
c in Scheme 5). The selectively protected diols 28 and 29
were thus prepared in 76% and 79% yield (from 19) as
ca. 4:1 mixtures with their C(2)-OH epimers. The enan-
tiopurities of 28 and 29 were determined by GC to be
g99:1. The relative configuration of the major isomers
was established using NOE difference analysis carried
out on the corresponding dioxolane derivatives. Each of
the major isomers was formed by a nonchelating addition
reaction of the C-nucleophile to the in situ generated
2-siloxy aldehyde. Perhaps, significantly higher and
“opposite” diastereoselectivities can be accomplished
when chelating OH-protecting groups such as Bn or
MOM ethers are employed.54
P r oced u r e 3. It is also possible to oxidize the crude
hemiaminals 20 by PCC in CH2Cl2, yielding the corre-
sponding acyloxazolidinones, which then can be cleaved
to protected 2-hydroxy esters or other 2-hydroxy or
2-amino carboxylic acid derivatives by numerous meth-
ods55 (cf. d in Scheme 5). Thus, PCC oxidation, followed
by methanolysis (LiBr, DBU, MeOH) of the acyloxazoli-
dinones 30 and 31 (derived from 16 and 17, respectively),
provided 2-alkoxy methylesters 32 and 33 in 61% and
63% yield and in enantiomerically pure form (determined
for compound 32 by HPLC.
P r oced u r e 4. Consecutive addition of DBU and a
stabilized phosphorus ylide to a solution of hemiaminals
20 in CH2Cl2 at room temperature produces 4-hydroxy-
2-alkenoates and/or butenolides via a Wittig reaction (cf.
e in Scheme 5). This procedure was applied to obtain the
4-hydroxy-2-alkenoate 34 and the butenolide 35, which
were isolated as single enantiomers (racemization of the
tertiary stereocenters is not possible!) and in excellent
yield. In particular, the enantioselective synthesis of
butenolides is of great interest, since they are part of
numerous natural products. Treatment of hemiaminals
20 with the Ando or Still reagent56 (highly Z-selective
Horner-Emmons reagents) should directly afford a
variety of substituted butenolides in enantiopure form.
Importantly, all processes described above involve
recycling of the chiral auxiliary 1. Usually, oxazolidinone
1 precipitates in the course of these transformations and
is recovered in 70-90% yield, ready for the next use by
simple filtration, washing, and drying.
Experiments aimed at extending this strategy to the
elaboration of 1,4-adduct 13 have not been fruitful thus
far. When compound 13 was treated with Hg(O2CCF3)2
in MeCN/THF/H2O (2:2:1), a ca. 1:1 mixture of the
desired hemiaminal and enolether 36 was isolated. If the
same reaction was carried out under nonaqueous condi-
tions, compound 36 was obtained as the sole product as
a single diastereoisomer (Scheme 6). Obviously, enol
ether 36 is derived from an intramolecular attack of the
intermediate acyliminium ion by the carbonyl oxygen of
the phenyl ketone moiety. Recrystallization of 36 from
MeOH yielded single crystals of N,O-acetal 37. X-ray
crystal structure analysis of 37 revealed the configuration
of the three newly created stereocenters as shown in
Scheme 6.
We have also tested the scope of the method presented
here and compared our reagent 3 with analogs of differ-
ent substitution on the oxazolidinone ring (Scheme 7).
Thus, the branched precursor 38, obtained as a 83:17
mixture of diastereoisomers by methylation of Li-3, and
the tert-leucine-, phenylglycin-, and leucine-derived meth-
ylthiomethyl derivatives 39, 40, and 41, all prepared
analogously to compound 3, were submitted to the
standard reaction conditions (BuLi, PhCHO, THF, -78
°C). The results are summarized in Scheme 7 and show
(i) that branching at the acetal carbon (38) is “allowed”,
but leads to a nonstereoselective reaction (products 42
and 43), (ii) that the tert-butyl substituent of 39 does not
improve diastereoselectivity (product 44), (iii) that the
triphenyl derivative 40 adds with poorer diastereoselec-
tivity (product 45), and (iv) that the “trans”-phenyl group
in reagent 3 does not have a negative impact on the
diastereoselectivity in the addition reaction, since the use
of the cis-oxazolidinone 41 is not advantageous compared
to oxazolidinone 3 (product 46).
Con clu sion s
We have developed a novel chiral oxazolidinone-derived
reagent Li-3 for the enantioselective nucleophilic for-
mylation of carbonyl compounds. Treatment of meth-
ylthiomethyl oxazolidinone 3 with BuLi in THF and
subsequent addition of an aldehyde, ketone, or imine
derivative affords adducts 19 in high yields and good to
excellent stereoselectivities. Hydrolysis of adducts 19
under mild conditions yields enantiomerically pure (se-
lectively protected) 2-hydroxy and 2-amino aldehydes
that are reduced, oxidized, or treated with C-nucleophiles
in situ to give (protected) 1,2-diols, 2-amino alcohols,
2-hydroxy esters, or 4-hydroxy-2-alkenoates. This se-
quence represents a new and more practical alternative
to existing methodologies for the enantioselective nu-
cleophilic formylation of carbonyl compounds. Experi-
ments to elucidate the solution structure of Li-3 and to
extend the presented methodology to conjugate addition
of Li-3 to enones are currently underway in our labora-
tories.
(54) For a review, see: Reetz, M. T. Angew. Chem., Int. Ed. Engl.
1984, 23, 556.
(55) For examples, see: (a) Evans, D. A.; Britton, T. C.; Ellman, J .
A. Tetrahedron Lett. 1987, 28, 6141. (b) Damon, R. E.; Coppola, G. M.
Tetrahedron Lett. 1990, 31, 2849. (c) Reference 33.
(56) (a) Ando, K.; Oishi, T.; Hirama, M.; Ohno, H.; Ibuka, T. J . Org.
Chem. 2000, 65, 4745. (b) Ando, K. J . Org. Chem. 1998, 63, 8411. (c)
Ando, K. J . Org. Chem. 1997, 62, 1934. (d) Still, W. C.; Gennari, C.
Tetrahedron Lett. 1983, 24, 4405.
Exp er im en ta l Section
Gen er a l In for m a tion . All reactions involving air- or
moisture-sensitive reagents or intermediates were carried out
in heat-gun dried glassware under an argon atmosphere.

4-Isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one
Sch em e 7
J . Org. Chem., Vol. 66, No. 9, 2001 3067
Tetrahydrofuran (THF) was freshly distilled from potassium
under argon. Diethyl ether (Et2O) was freshly distilled from
sodium under argon. Dichloromethane (CH2Cl2) and dimethyl
sulfoxide (DMSO) were distilled from calcium hydride (CaH2)
and stored under argon over activated 4 Å molecular sieves.
DME was stored over potassium hydroxide (KOH) pellets.
Diisopropylethylamine ((i-Pr)2NEt), N,N′-dimethylpropyl-
eneurea (DMPU), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
were distilled from CaH2 and stored under argon. All liquid
aldehydes and ketones were distilled. Lithium bromide (LiBr)
was dried in a Kugelrohr apparatus at 150 °C under high
vacuum. All other reagents were used as received from Aldrich
or Fluka. Flash column chromatography (FC) was performed
using Fluka silica gel (40-63 µm). Melting points (mp) are
uncorrected. Coupling constants are reported in Hz. Elemental
analyses were performed by the Microanalytical Laboratory
of the Laboratorium fu¨r Organische Chemie, ETH Zu¨rich.
solved in THF/H2O (4:1, 0.15 M), and NaBH4 (0.75 equiv) and
DBU (0.5 equiv) were added consecutively at 0 °C. The
auxiliary 1 precipitated in the course of the reaction. After the
mixture was stirred for 15 min, saturated aqueous NH4Cl
solution and Et2O were added, and the precipitate was filtered
off. The precipitate was washed with saturated aqueous NH4-
Cl solution, H2O, and Et2O and dried under high vacuum to
recover 1 as a white solid. The filtrate was diluted with Et2O,
the organic layer was separated, and the aqueous layer was
extracted with Et2O (2×). The combined organic layers were
dried (MgSO4) and concentrated under reduced pressure. The
crude product was purified by FC.
Gen er a l P r oced u r e 4 (GP 4) for th e Tr a n sfor m a tion
of Ad d ition P r od u cts to 1,2-Diols Usin g Hg(O2CCF 3)2/RLi
or RMgCl. A solution (or suspension) of addition product (1
equiv) in THF/MeCN/H2O (2:2:1; 0.1 M) was treated with Hg-
(O2CCF3)2 (1.1 equiv) according to GP 3. The crude product
was dissolved in THF (0.25 M), and RLi (4 equiv) or RMgCl (4
equiv) was added at -78 °C. After the mixture was stirred for
10 min at -78 °C, the cooling bath was removed, and the
mixture was stirred for another 10 min. The auxiliary 1
precipitated in the course of the reaction. Then, saturated
aqueous NH4Cl solution and Et2O were added and the pre-
cipitate was filtered off. The precipitate was washed with
saturated aqueous NH4Cl solution, H2O, and Et2O and dried
under high vacuum to recover 1 as a white solid. The filtrate
was diluted with Et2O, the organic layer was separated, and
the aqueous layer was extracted with Et2O (2×). The combined
organic layers were dried (MgSO4) and concentrated under
reduced pressure. The crude product was purified by FC.
Gen er a l P r oced u r e 5 (GP 5) for th e Tr a n sfor m a tion
of Ad d ition P r od u cts to N-Acyloxa zolid in on es. A solution
(or suspension) of addition product (1 equiv) in THF/MeCN/
H2O (2:2:1; 0.1 M) was treated with Hg(O2CCF3)2 (1.1 equiv)
according to GP 3. The crude product was dissolved in CH2-
Cl2 (0.15 M) and treated with PCC (2.1 equiv) and powdered
4 Å molecular sieves (1 weight equiv to PCC) at room
temperature. After being stirred for 2.5 h, the reaction mixture
was diluted with Et2O and filtered through a silica plug eluting
with pentane/Et2O (1:1). The crude product was purified by
FC or recrystallization.
1
Diastereoisomeric ratios were determined by H NMR.
Gen er a l P r oced u r e 1 (GP 1) for th e Meth ylth iom eth -
yla tion of Oxa zolid in on es. To a solution (or suspension) of
oxazolidinone (1 equiv) in THF (1 M) was added BuLi (1.05
equiv) at 0 °C. After the solution was stirred for 10 min, DMSO
(5-fold excess compared to the amount of THF) and chloro-
methyl methyl sulfide (MTMCl) (1.2 equiv) were added con-
secutively to the reaction mixture. After being stirred for 4 h
at room temperature, the reaction mixture was quenched with
saturated aqueous NH4Cl solution and diluted with Et2O. The
organic layer was separated, and the aqueous layer was
extracted with Et2O (2×). The combined organic layers were
washed with H2O (1×), dried (MgSO4), and concentrated under
reduced pressure. The crude product was purified by FC.
Gen er a l P r oced u r e 2 (GP 2) for th e Ad d ition of N,S-
Aceta ls to Ald eh yd es, Keton es, a n d Im in e Der iva tives.
To a solution of N,S-acetal (1 equiv) in THF (0.2 M) or Et2O
(0.2 M) was added BuLi (1.2 equiv) at -78 °C. After being
stirred for 5 min, the reaction mixture was cooled to -100 °C
(or kept at -78 °C), and an aldehyde, ketone, or imine
derivative (1.3 equiv) was added dropwise neat or as a solution
in THF (ca. 1 M) or Et2O (ca. 1 M). It was allowed to warm to
-78 °C within 20 min, and then the reaction was stopped by
quenching with saturated aqueous NH4Cl solution. The reac-
tion mixture was diluted with Et2O, the organic layer was
separated, and the aqueous layer was extracted with CH2Cl2
(2×). The combined organic layers were dried (MgSO4) and
concentrated under reduced pressure. The crude product was
purified by trituration, FC, or recrystallization.
Gen er a l P r oced u r e 6 (GP 6) for th e Meth a n olysis of
N-Acyloxa zolid in on es to 2-Hyd r oxy Meth ylester s. To a
solution of N-acyloxazolidinone (1 equiv) in MeOH/THF (2:1,
0.15 M) were added DBU (2 equiv) and LiBr (5 equiv)
consecutively at 0 °C. The auxiliary 1 precipitated in the course
of the reaction. After the mixture was stirred for 45 min,
saturated aqueous NH4Cl solution and Et2O were added and
the precipitate was filtered off. The precipitate was washed
with saturated aqueous NH4Cl solution, H2O, and Et2O and
dried under high vacuum to recover 1 as a white solid. The
filtrate was diluted with Et2O, the organic layer was separated,
and the aqueous layer was extracted with Et2O (2×). The
combined organic layers were dried (MgSO4) and concentrated
under reduced pressure. The crude product was purified by
FC.
Gen er a l P r oced u r e 3 (GP 3) for th e Tr a n sfor m a tion
of Ad d ition P r od u cts to 1,2-Diols Usin g Hg(O2CCF 3)2/
Na BH4/DBU. To a solution (or suspension) of addition product
(1 equiv) in THF/MeCN/H2O (2:2:1; 0.1 M) was added Hg(O2-
CCF3)2 (1.1 equiv) at room temperature. After the mixture was
stirred for 5 min, H2O was added, and then the reaction
mixture was diluted with Et2O. The organic layer was sepa-
rated, and the aqueous layer was extracted with Et2O (2×).
The combined organic layers were dried (MgSO4) and concen-
trated under reduced pressure. The crude product was dis-

3068 J . Org. Chem., Vol. 66, No. 9, 2001
Gaul et al.
Gen er a l P r oced u r e 7 (GP 7) for th e Tr a n sfor m a tion
of Ad d it ion P r od u ct s t o 4-H yd r oxy-2-a lk en oa t es a n d
Bu ten olid es. A solution (or suspension) of addition product
(1 equiv) in THF/MeCN/H2O (2:2:1; 0.1 M) was treated with
Hg(O2CCF3)2 (1.1 equiv) according to GP 3. The crude product
was dissolved in CH2Cl2 (0.15 M), and DBU (0.5 equiv) and
(methoxycarbonylmethylen)triphenylphosphorane (2 equiv)
were added consecutively at room temperature. After the
mixture was stirred for 12 h at room temperature, saturated
aqueous NH4Cl solution was added. The organic layer was
separated, and the aqueous layer was extracted with CH2Cl2
(2×). The combined organic layers were dried (MgSO4) and
concentrated under reduced pressure. The crude product was
triturated in Et2O for 30 min, and the insoluble material was
filtered off, washed with 1 N HCl and H2O, triturated with
hexane and CH2Cl2, and dried under high vacuum to recover
1 as a white solid. The filtrate was concentrated under reduced
pressure and purified by FC.
J ) 6.9, 6 H); 0.89 (d, J ) 7.5, 6 H); 1.82-1.97 (m, 2 H); 4.27
(d, J ) 1.9, 2 H); 5.07 (s, 2 H); 7.10-7.30 (m, 16 H); 7.33-7.37
(m, 4 H). 13C NMR (75 MHz, CDCl3): 15.6, 21.4, 29.1, 53.0,
66.9, 88.2, 125.5, 126.3, 127.6, 128.0, 128.2, 128.3, 139.0, 143.1,
157.4. FAB-MS: 575 (23, [M + H]+), 530 (14, [M - CO2]+),
250 (100, [M - CO2 - C18H18NO2). Anal. Calcd for C37H38N2O4
(574.72): C, 77.33; H, 6.66; N, 4.87. Found: C, 77.33; H, 6.71;
N, 4.94.
(S)-4-Isop r op yl-5,5-d ip h en yl-3-(p h en ylsu lfa n ylm et h -
yl)oxa zolid in -2-on e (4). To a suspension of 1 (1.07 g, 3.80
mmol) in DME (8 mL) was added BuLi (2.89 mL, 4.18 mmol)
at 0 °C. After the mixture was stirred for 10 min, NaI (627
mg, 4.18 mmol) and chloromethyl phenyl sulfide (542 µL, 4.18
mmol) were added consecutively to the reaction mixture. After
being stirred for 12 h at room temperature, the reaction
mixture was quenched with saturated aqueous NH4Cl solution
and diluted with Et2O. The organic layer was separated, and
the aqueous layer was extracted with Et2O (2×). The combined
organic layers were washed with H2O (1×), dried (MgSO4), and
concentrated under reduced pressure. The crude product was
purified by FC (pentane/AcOEt 10:1) to afford 4 (807 mg, 53%)
as a white solid. Mp: 137-141 °C. [R]rtD ) +9.3 (c ) 1, CHCl3).
IR (CHCl3): 3008, 1749, 1417, 1040, 1002 cm-1. 1H NMR (400
MHz, CDCl3): δ 0.69 (d, J ) 6.8, 3 H); 1.07 (d, J ) 7.4, 3 H);
1.88-1.98 (m, 1 H); 4.38 (d, J ) 14.5, 1 H); 4.80 (d, J ) 1.6, 1
H); 5.41 (d, J ) 14.5, 1 H); 6.92-6.95 (m, 2 H); 7.00-7.07 (m,
3 H); 7.16-7.30 (m, 6 H); 7.39-7.42 (m, 2 H); 7.46-7.50 (m, 2
H). 13C NMR (100 MHz, CDCl3): δ 15.5, 22.6, 29.7, 49.3, 65.6,
88.1, 125.4, 126.1, 127.0, 127.6, 128.0, 128.1, 128.4, 128.9,
130.4, 132.7, 138.9, 143.8, 156.2. FAB-MS: 294 (5, [M -
(S)-4-Isop r op yl-3-(m eth oxym eth yl)-5,5-d ip h en yloxa zo-
lid in -2-on e (2). To a suspension of 1 (2.00 g, 7.10 mmol) in
THF (30 mL) was added BuLi (5.44 mL, 8.16 mmol) at 0 °C.
After the mixture was stirred for 10 min, chloromethyl methyl
ether (MOMCl) (650 µL, 8.51 mmol) was added, and the
reaction mixture was stirred for 5 h at room temperature. Then
the mixture was quenched with saturated aqueous NH4Cl
solution and diluted with Et2O. The organic layer was sepa-
rated, and the aqueous layer was extracted with Et2O (2×).
The combined organic layers were dried (MgSO4) and concen-
trated under reduced pressure. The crude product was recrys-
tallized (AcOEt/hexane) to yield 2 (1.66 g, 72%) as a white
solid. Mp: 115-117 °C. [R]rt ) -183.8 (c ) 1, CHCl3). IR
SPh]+), 250 (100, [M - SPh - CO2]+). Anal. Calcd for C25H25
-
NO2S (403.54): C, 74.41; H, 6.24; N, 3.47; S, 7.95. Found: C,
74.24; H, 6.36; N, 3.52; S, 8.04.
D
(CHCl3): 2966, 1751, 1600, 1450 cm-1
.
1H NMR (300 MHz,
CDCl3): δ 0.70 (d, J ) 6.5, 3 H); 1.05 (d, J ) 7.2, 3 H); 1.88-
2.01 (m, 1 H); 2.86 (s, 3 H); 4.54 (d, J ) 1.9, 1 H); 4.72 (d, J )
11.2, 1 H); 4.83 (d, J ) 11.2, 1 H); 7.21-7.38 (m, 6 H); 7.43-
7.46 (m, 2 H); 7.61-7.64 (m, 2 H). 13C NMR (75 MHz, CDCl3):
15.4, 21.9, 29.6, 55.8, 66.5, 76.3, 88.4, 125.3, 126.0, 127.6, 128.1,
128.6, 138.8, 144.1, 157.4. FAB-MS: 282 (7, [M + H - CO2]+),
250 (100, [M - OMe - CO2]+). Anal. Calcd for C20H23NO3
(325.41): C, 73.82; H, 7.12; N, 4.30. Found: C, 73.54; H, 7.33;
N, 4.39.
(S)-3-[(1S,2S)-2-Hyd r oxy-1-(m eth ylsu lfa n yl)-2-p h en yl-
eth yl]-4-isopr opyl-5,5-diph en yloxazolidin -2-on e (7b). Com-
pound 3 (430 mg, 1.26 mmol) was treated with BuLi (0.97 mL,
1.51 mmol) and benzaldehyde (166 µL, 1.64 mmol) according
to GP 2. Purification of the crude product by FC (pentane/
AcOEt 8:1) yielded 7b (505 mg, 90%) as a 93:7 mixture with
its C(2)-OH epimer. For analytical purposes, a sample was
recrystallized twice (MeOH) to afford 7b (dr 97:3) as a white
solid. Mp: 200-201 °C. [R]rt ) -72.2 (c ) 1, CHCl3). IR
(S)-4-Isop r op yl-3-(m eth ylsu lfa n ylm eth yl)-5,5-d ip h en -
yloxa zolid in -2-on e (3) a n d (S)-4-Isop r op yl-3-[[(S)-4-iso-
p r op yl-2-oxo-5,5-d ip h en yloxa zolin -3-yl]m et h yl]-5,5-d i-
p h en yloxa zolid in -2-on e (6). (a) To a suspension of 1 (5.15
g, 18.3 mmol) in DME (40 mL) was added BuLi (14.4 mL, 20.1
mmol) at 0 °C. After the mixture was stirred for 10 min, NaI
(2.74 g, 18.3 mmol) and MTMCl (1.89 mL, 18.3 mmol) were
added consecutively to the reaction mixture. After being stirred
for 12 h at room temperature, the reaction mixture was
quenched with saturated aqueous NH4Cl solution and diluted
with Et2O. The organic layer was separated, and the aqueous
layer was extracted with Et2O (2×). The combined organic
layers were washed with H2O (1×), dried (MgSO4), and
concentrated under reduced pressure. Compounds 3 and 6
were obtained as a 4:1 mixture, determined by 1H NMR of the
crude product. Compounds 3 and 6 were separated by FC
(pentane/AcOEt 10:1) to afford 3 (3.28 g, 53%) and 6 (yield
not determined). (b) Compound 1 (15.7 g, 55.8 mmol) was
treated with BuLi (38.8 mL, 58.6 mmol) and MTMCl (5.60 mL,
67.0 mmol) according to GP 1. The crude product was purified
by FC (pentane/Et2O 5:1) to afford 3 (16.4 g, 86%) as a white
D
(CHCl3): 3512, 3008, 1729, 1450, 1422, 1046 cm-1. H NMR
1
(300 MHz, CDCl3): δ 0.81 (d, J ) 6.5, 3 H); 1.08 (d, J ) 7.5,
3 H); 1.36 (s, 3 H); 2.00-2.07 (m, 1 H); 4.40 (d, J ) 9.3, 1 H);
4.46 (d, J ) 5.6, 1 H); 4.70 (d, J ) 2.2, 1 H); 5.47 (dd, J ) 5.6,
9.3, 1 H); 7.22-7.45 (m, 13 H); 7.72-7.75 (m, 2 H). 13C NMR
(75 MHz, CDCl3): δ 10.5, 15.5, 21.9, 29.9, 68.4, 68.7, 74.0, 89.0,
125.2, 125.9, 127.0, 127.5, 128.1, 128.18, 128.21, 128.5, 138.4,
140.9, 143.8, 157.5. FAB-MS: 446 (2, [M - H]+), 400 (47,
[M - SMe]+), 356 (100, [M - SMe - CO2]+). Anal. Calcd for
C
27H29NO3S (447.60): C, 72.45; H, 6.53; N, 3.13. Found: C,
72.15; H, 6.57; N, 3.32.
(S)-3-[(1S,2S)-2-Hyd r oxy-2-p h en yl-1-(p h en ylsu lfa n yl)-
eth yl]-4-isopr opyl-5,5-diph en yloxazolidin -2-on e (7c). Com-
pound 3 (403 mg, 0.999 mmol) was treated with BuLi (0.82
mL, 1.20 mmol) and benzaldehyde (131 µL, 1.30 mmol)
according to GP 2. Trituration of the crude product (boiling
hexane, 2 × 10 mL) yielded 7c (360 mg, 71%) as a 95:5 mixture
with its C(2)-OH epimer and 5 mol % of inseparable unidenti-
fied side products. White solid. Mp: 200-203 °C. [R]rt
)
D
-191.5 (c ) 1, CHCl3). IR (CHCl3): 3335, 3008, 1734, 1451,
1
solid. Mp: 124-125 °C. [R]rt ) -89.6 (c ) 1, CHCl3). IR
1423, 1091 cm-1. H NMR (400 MHz, CDCl3): δ 0.55 (d, J )
D
(CHCl3): 2954, 1744, 1451, 1421, 1041 cm-1
.
1H NMR (300
6.8, 3 H); 0.89 (d, J ) 7.3, 3 H); 1.96-2.08 (m, 1 H); 4.37 (d,
J ) 6.0, 1 H); 4.51 (d, J ) 1.9, 1 H); 4.81 (d, J ) 8.7, 1 H); 5.36
(dd, J ) 6.0, 8.7, 1 H); 6.78-6.81 (m, 2 H); 7.06-7.42 (m, 16
H); 7.53-7.59 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ 15.2,
21.6, 29.8, 69.8, 74.0, 75.1, 88.8, 125.4, 126.3, 127.65, 127.71,
127.8, 128.0, 128.2, 128.4, 128.7, 128.9, 132.8, 133.8, 138.7,
140.5, 144.0, 157.3. FAB-MS: 492 (5, [M + H - H2O]+), 400
(52, [M - SPh]+), 356 (100, [M - SPh - CO2]+).
(S)-3-[(1S,2S)-2-Hyd r oxy-3-m eth yl-1-(m eth ylsu lfa n yl)-
bu t-3-en yl]-4-isopr opyl-5,5-diph en yloxazolidin -2-on e (9k).
Compound 3 (355 mg, 1.04 mmol) was treated with BuLi (0.83
mL, 1.25 mmol) and methacrolein (111 µL, 1.35 mmol) accord-
MHz, CDCl3): δ 0.72 (d, J ) 6.5, 3 H); 1.04 (d, J ) 7.2, 3 H);
1.37 (s, 3 H); 1.88-2.03 (m, 1 H); 4.06 (d, J ) 14.3, 1 H); 4.76
(d, J ) 1.9, 1 H); 4.95 (d, J ) 14.3, 1 H); 7.20-7.38 (m, 6 H);
7.43-7.49 (m, 2 H); 7.66-7.72 (m, 2 H). 13C NMR (75 MHz,
CDCl3): δ 12.9, 15.6, 22.4, 29.7, 48.7, 64.9, 88.3, 125.3, 125.9,
127.5, 128.2, 128.6, 138.7, 144.2, 156.9. FAB-MS: 342 (2,
[M + H]+), 294 (12, [M - SMe]+), 250 (100, [M - SMe - CO2]+).
Anal. Calcd for C20H23NO2S (341.47): C, 70.35; H, 6.79; N,
4.10. Found: C, 70.25; H, 7.08; N, 4.09. 6. White solid. Mp:
190-192 °C. [R]rtD ) -152.9 (c ) 1, CHCl3). IR (CHCl3): 2966,
1
1750, 1493, 1450, 1037. H NMR (300 MHz, CDCl3): 0.59 (d,

4-Isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one
J . Org. Chem., Vol. 66, No. 9, 2001 3069
ing to GP 2. Purification of the crude product by FC (pentane/
AcOEt 9:1) yielded 9k (375 mg, 88%) as a 85:15 mixture with
its C(2)-OH epimer. For analytical purposes, a sample was
purified by FC (pentane/AcOEt 9:1) to afford 9k (dr 98.5:1.5)
with BuLi (1.10 mL, 1.68 mmol) and phenyl trifluoromethyl
ketone (265 µL, 1.95 mmol) according to GP 2. The crude
product was recrystallized (MeOH) to give 11b (372 mg, 55%)
as a single diastereoisomer. White solid. Mp: >240 °C.
as a white solid. Mp: 181-182 °C. [R]rt ) -99.6 (c ) 1,
[R]rt ) -99.7 (c ) 1, CHCl3). IR (CHCl3): 3007, 1746, 1685,
D
D
CHCl3). IR (CHCl3): 3508, 2967, 1730, 1450, 1423, 1003 cm-1
.
1494, 1410, 1034 cm-1. 1H NMR (400 MHz, CDCl3): δ 0.77 (d,
J ) 7.0, 3 H); 1.19 (d, J ) 7.4, 3 H); 1.46 (s, 3 H); 2.19-2.26
(m, 1 H); 4.67 (s, 1 H); 4.81 (d, J ) 1.8, 1 H); 7.25-7.43 (m, 12
H); 7.62-7.64 (m, 2 H); 8.24 (s, 1 H). 13C NMR (100 MHz,
CDCl3): δ 14.3, 15.5, 20.7, 29.5, 68.5, 71.1, 80.8 (q, J C,F ) 27.7),
90.2, 125.5, 126.6, 128.0, 128.1, 128.3, 128.5, 128.62, 128.64,
137.4, 138.2, 143.7, 160.2. 19F NMR (282 MHz, CDCl3): -73.82
(s, 3 F). MALDI-MS: 538 (100, [M + Na]+), 424 (60, [M -
SMe - CO2]+), 249 (89). Anal. Calcd for C28H28F3NO3S
(515.60): C, 65.23; H, 5.47; N, 2.72; S, 6.22. Found: C, 65.15;
H, 5.54; N, 2.67; S, 6.21.
1H NMR (300 MHz, CDCl3): δ 0.85 (d, J ) 6.9, 3 H); 1.10 (d,
J ) 7.2, 3 H); 1.38 (s, 3 H); 1.77 (s, 3 H); 2.00-2.14 (m, 1 H);
3.70 (d, J ) 4.7, 1 H); 4.34 (d, J ) 10.0, 1 H); 4.73 (d, J ) 2.2,
1 H); 4.93-4.98 (m, 2 H); 5.06-5.08 (m, 1 H); 7.21-7.40 (m, 6
H); 7.45-7.49 (m, 2 H); 7.71-7.75 (m, 2 H). 13C NMR (125
MHz, CDCl3): δ 9.8, 15.9, 17.0, 22.0, 30.1, 65.2, 68.5, 74.2,
88.8, 115.3, 125.4, 126.0, 127.7, 128.2, 128.3, 128.6, 138.6,
143.5, 144.1, 157.3. FAB-MS: 412 (7, [M + H]+), 364 (76,
[M - SMe]+), 320 (100, [M - SMe - CO2]+). Anal. Calcd for
C
24H29NO3S (411.56): C, 70.04; H, 7.10; N, 3.40. Found: C,
70.03; H, 6.97; N, 3.37.
(S)-4-Isop r op yl-3-[(1S,2R)-2-m eth yl-1-(m eth ylsu lfa n yl)-
4-oxo-2,4-d ip h en ylb u t yl]-5,5-d ip h en yloxa zolid in -2-on e
(13). Compound 3 (350 mg, 1.02 mmol) was treated with BuLi
(0.79 mL, 1.23 mmol) and benzalacetophenone (277 mg, 1.33
mmol) according to GP 2. Purification of the crude product by
FC (CH2Cl2/pentane 3:1 to CH2Cl2 + 1% Et2O) yielded 13 (441
mg, 79%) as a 98:2 mixture with its C(2)-Ph epimer. For
analytical purposes, a sample was recrystallized (MeOH) to
afford 13 (dr g 99:1) as a white solid. Mp: 224-226 °C.
(S)-3-[(1S,2S)-2-Hyd r oxy-3-m eth yl-1-(m eth ylsu lfa n yl)-
bu tyl]-4-isopr opyl-5,5-diph en yloxazolidin -2-on e (9m ) an d
(S)-3-[(1S,2R)-2-Hyd r oxy-3-m eth yl-1-(m eth ylsu lfa n yl)bu -
tyl]-4-isopr opyl-5,5-diph en yloxazolidin -2-on e (10m ). Com-
pound 3 (1.11 g, 3.25 mmol) was treated with BuLi (2.55 mL,
3.90 mmol) and isobutyraldehyde (384 µL, 4.23 mmol) accord-
ing to GP 2. Trituration of the crude product (boiling hexane,
2 × 6 mL) yielded 9m (1.13 g, 84%) as a 71:29 mixture with
its C(2)-OH epimer 10m . Alternatively, purification of the
crude product by FC (pentane/Et2O 10:1) yielded 9m (61%)
and 10m (21%) as single diastereoisomers. 9m . White solid.
[R]rt ) -99.8 (c ) 1, CHCl3). IR (CHCl3): 3005, 1744, 1682,
D
1487, 1179, 1092 cm-1
.
1H NMR (400 MHz, CD2Cl2): δ 0.24
(d, J ) 6.9, 3 H); 0.83 (d, J ) 7.4, 3 H); 1.72 (s, 3 H); 1.89-
1.97 (m, 1 H); 3.25 (dd, J ) 7.8, 17.1, 1 H); 3.86 (dd, J ) 4.8,
17.1, 1 H); 4.49 (d, J ) 1.7, 1 H); 4.72 (d, J ) 10.9, 1 H); 4.80
(ddd, J ) 4.8, 7.8, 10.9, 1 H); 7.04-7.54 (m, 18 H); 7.82-7.85
(m, 2 H). 13C NMR (100 MHz, CD2Cl2): δ 13.1, 15.6, 20.6, 30.0,
42.2, 45.4, 68.9, 69.1, 87.8, 125.5, 126.9, 127.7, 127.8, 128.2,
128.3, 128.7, 128.8, 128.86, 128.90, 133.2, 137.8, 139.6, 142.1,
145.0, 157.1, 197.6. MALDI-MS: 572 (100, [M + Na]+), 440
(38, [M - SMe - CO2 - H2O]+). Anal. Calcd for C35H35NO3S
(549.73): C, 76.47; H, 6.42; N, 2.56; S, 5.83. Found: C, 76.35;
H, 6.47; N, 2.49; S, 5.85.
Mp 217-218 °C. [R]rt ) -108.3 (c ) 1, CHCl3). IR (CHCl3):
D
3520, 2964, 1730, 1450, 1002 cm-1
.
1H NMR (300 MHz,
CDCl3): δ 0.83 (d, J ) 6.9, 6 H); 1.01 (d, J ) 6.9, 3 H); 1.07 (d,
J ) 7.5, 3 H); 1.35 (s, 3 H); 2.00-2.21 (m, 2 H); 3.48 (s, 1 H);
4.23-4.31 (m, 2 H); 4.74 (d, J ) 2.2, 1 H); 7.20-7.38 (m, 6 H);
7.47-7.49 (m, 2 H); 7.74-7.76 (m, 2 H). 13C NMR (75 MHz,
CDCl3): δ 9.6, 14.1, 15.9, 20.7, 21.8, 29.1, 30.0, 65.4, 68.5, 73.2,
88.7, 125.3, 126.0, 127.5, 128.1, 128.5, 138.6, 144.1, 157.4. FAB-
MS: 366 (7, [M - SMe]+), 322 (100, [M - SMe-CO2]+). Anal.
Calcd for C24H31NO3S (413.58): C, 69.70; H, 7.55; N, 3.39.
Found: C, 69.77; H, 7.57; N, 3.43. 10m . White solid. Mp: 204-
205 °C. [R]rtD ) -163.8 (c ) 1, CHCl3). IR (CHCl3): 3388, 3007,
N-[(1S,2S)-2-((S)-4-Isop r op yl-2-oxo-5,5-d ip h en yloxa zo-
lidin -3-yl)-2-m eth ylsu lfan yl-1-ph en yleth yl]diph en ylph os-
p h in a m id e (14a ). Compound 3 (257 mg, 0.753 mmol) was
treated with BuLi (0.60 mL, 0.903 mmol) and a solution of
N-diphenylphosphinoylimine (derived from benzaldehyde)47
(299 mg, 0.978 mmol) in THF (1 mL) according to GP 2.
Trituration of the crude product (boiling MeOH, 2 × 5 mL)
yielded 14a (214 mg, 44%) as a 97:3 mixture with its C(1)-NH
epimer. For analytical purposes, a sample was recrystallized
(MeOH) to afford 14a (dr g 99:1) as a white solid. Mp: >240
°C. [R]rtD ) -86.5 (c ) 1, CHCl3). IR (CHCl3): 3319, 2986, 1736,
1451, 1438, 1124 cm-1. 1H NMR (400 MHz, CDCl3): δ 0.33 (d,
J ) 6.9, 3 H); 0.87 (d, J ) 7.3, 3 H); 1.67 (s, 3 H); 1.90-2.01
(m, 1 H); 4.61 (d, J ) 8.0, 1 H); 4.79-4.87 (m, 2 H) (H,P-
coupling); 5.33 (br s, 1 H); 7.08-7.48 (m, 19 H); 7.57-7.68 (m,
4 H); 7.75-7.85 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ 14.6,
15.4, 20.6, 29.5, 58.8, 69.2 (d, J C,P ) 6.9), 69.4, 88.7, 125.4,
126.4, 127.6, 127.7, 127.89, 127.93, 128.0, 128.1, 128.25,
128.31, 128.4, 128.5, 131.18, 131.20, 131.56, 131.59, 131.8,
131.9, 132.0, 132.1, 132.3, 133.2, 133.6, 138.8, 140.2, 143.9,
157.8 (C,P-coupling). 31P NMR (162 MHz, CDCl3): 21.66.
MALDI-MS: 669 (42, [M + Na]+), 599 (39, [M - SMe]+), 581
(12, [M - SMe-H2O]+), 555 (65, [M - SMe - CO2]+), 338 (100).
Anal. Calcd for C39H39N2O3PS (646.79): C, 72.42; H, 6.08; N,
4.33; S, 4.96. Found: C, 72.45; H, 6.22; N, 4.27; S, 5.14.
N-[(1S,2S)-2-((S)-4-Isop r op yl-2-oxo-5,5-d ip h en yloxa zo-
lid in -3-yl)-2-m eth ylsu lfa n yl-1-p h en yleth yl]-2,4,6-tr im eth -
ylben zen esu lfon a m id e (14c). Compound 3 (341 mg, 0.999
mmol) was treated with BuLi (0.80 mL, 1.20 mmol) and a
solution of N-mesitylsulfonylimine (derived from benzalde-
hyde)47 (374 mg, 1.30 mmol) in THF (1 mL) according to GP
2. Trituration of the crude product (boiling MeOH, 2 × 6 mL)
yielded 14c (390 mg, 62%) as a 95:5 mixture with its C(1)-NH
epimer. For analytical purposes, a sample was recrystallized
(MeOH) to afford 14c (dr g 99:1) as a white solid. Mp: >240
°C. [R]rtD ) -69.4 (c ) 1, CHCl3). IR (CHCl3): 3270, 1736, 1451,
1728, 1450, 1425, 908 cm-1 1H NMR (300 MHz, CDCl3): δ
.
0.76 (d, J ) 6.9, 3 H); 0.89 (d, J ) 6.9, 3 H); 1.00 (d, J ) 6.5,
3 H); 1.08 (d, J ) 7.2, 3 H); 1.58 (s, 3 H); 1.81-1.95 (m, 1 H);
2.05-2.18 (m, 1 H); 3.78-3.86 (m, 1 H); 4.40 (d, J ) 2.5, 1 H);
4.60 (d, J ) 1.9, 1 H); 4.72 (d, J ) 2.5, 1 H); 7.22-7.39 (m, 6
H); 7.48-7.51 (m, 2 H); 7.69-7.72 (m, 2 H). 13C NMR (75 MHz,
CDCl3): δ 13.1, 16.0, 18.4, 20.0, 21.6, 29.8, 31.3, 67.7, 71.2,
78.8, 89.0, 125.1, 126.0, 127.7, 128.2, 128.3, 128.7, 138.4, 144.2,
157.6. FAB-MS: 414 (8, [M + H]+), 366 (67, [M - SMe]+), 322
(100, [M - SMe - CO2]+). Anal. Calcd for C24H31NO3S
(413.58): C, 69.70; H, 7.55; N, 3.39. Found: C, 69.66; H, 7.55;
N, 3.46.
(S)-3-[(1S,2S)-2-Hyd r oxy-1-(m eth ylsu lfa n yl)-2-p h en yl-
p r op yl]-4-isop r op yl-5,5-d ip h en yloxa zolid in -2-on e (11a ).
Compound 3 (605 mg, 1.77 mmol) was treated with BuLi (1.45
mL, 2.13 mmol) and a solution of acetophenone (269 µL, 2.30
mmol) in THF (1 mL) according to GP 2. The crude product
was triturated (boiling hexane, 2 × 7 mL) and recrystallized
(MeOH) to give 11a (456 mg, 56%) as a single diastereoisomer.
White solid. Mp: 204-206 °C. [R]rt ) -118.6 (c ) 1, CHCl3).
D
IR (CHCl3): 3692, 3314, 2936, 1721, 1450, 1036 cm-1. 1H NMR
(400 MHz, CDCl3): δ 0.23 (d, J ) 7.1, 3 H); 0.51 (d, J ) 7.3,
3 H); 1.67 (s, 3 H); 1.73 (d, J ) 0.9, 3 H); 1.80-1.92 (m, 1 H);
4.45 (s, 1 H); 4.61 (d, J ) 1.9, 1 H); 6.55 (br s, 1 H); 7.13-7.34
(m, 11 H); 7.45-7.48 (m, 2 H); 7.58-7.61 (m, 2 H). 13C NMR
(100 MHz, CDCl3): δ 13.0, 16.4, 18.3, 29.5, 31.2, 69.5, 71.6,
79.3, 89.1, 125.19, 125.22, 126.6, 127.2, 127.6, 127.8, 128.1,
128.2, 128.6, 138.1, 144.1, 145.5, 158.3. FAB-MS: 462 (14,
[M + H]+), 444 (19, [M + H - H2O]+), 414 (100, [M - SMe]+),
370 (65, [M - SMe - CO2]+). Anal. Calcd for C28H31NO3S
(461.62): C, 72.85; H, 6.77; N, 3.03. Found: C, 72.78; H, 6.86;
N, 3.16.
(S)-4-Isop r op yl-5,5-d ip h en yl-3-((1S,2R)-3,3,3-tr iflu or o-
2-h yd r oxy-1-m eth ylsu lfa n yl-2-p h en ylp r op yl)oxa zolid in -
2-on e (11b). Compound 3 (443 mg, 1.30 mmol) was treated
1
1328, 1157 cm-1. H NMR (400 MHz, CDCl3): δ 0.21 (d, J )

3070 J . Org. Chem., Vol. 66, No. 9, 2001
Gaul et al.
6.9, 3 H); 0.73 (d, J ) 7.3, 3 H); 1.69 (s, 3 H); 1.80-1.89 (m, 1
H); 2.14 (s, 3 H); 2.43 (s, 6 H); 4.52 (d, J ) 7.5, 1 H); 4.67 (d,
J ) 1.6, 1 H); 5.03 (dd, J ) 7.5, 8.5, 1 H); 6.62 (d, J ) 0.5, 2
H); 6.95-7.06 (m, 5 H); 7.16-7.31 (m, 5 H); 7.35-7.41 (m, 4
H); 7.65-7.68 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ 14.4,
15.0, 20.4, 22.8, 29.5, 61.8, 67.3, 69.4, 89.0, 125.3, 126.2, 127.4,
127.6, 127.7, 127.9, 128.0, 128.3, 128.8, 131.4, 135.4, 136.9,
138.0, 138.5, 141.3, 143.7, 157.7. MALDI-MS: 651 (100, [M +
Na]+), 537 (6, [M - SMe - CO2]+). Anal. Calcd for C36H40N2O4S2
(628.86): C, 68.76; H, 6.41; N, 4.45; S, 10.20. Found: C, 68.83;
H, 6.32; N, 4.48; S, 10.19.
ature, the reaction was stopped by quenching with saturated
aqueous NH4Cl solution. The organic layer was separated, and
the aqueous layer was extracted with CH2Cl2 (2×). The
combined organic layers were dried (MgSO4) and concentrated
under reduced pressure. The crude product was filtered
through a silica plug (pentane/Et2O 5:1) and triturated (boiling
hexane, 3 × 10 mL) to give 17 (1.27 g, 55%) as a single
diastereoisomer. White solid. Mp: 193-195 °C. [R]rtD ) -104.1
(c ) 1, CHCl3). IR (CHCl3): 3067, 1748, 1450, 1047, 912 cm-1
.
1H NMR (400 MHz, CDCl3): δ 0.62 (d, J ) 6.8, 3 H); 1.03 (d,
J ) 7.3, 3 H); 1.59 (s, 3 H); 1.68 (d, J ) 0.5, 3 H); 2.01-2.13
(m, 1 H); 4.39-4.49 (m, 3 H); 4.56 (d, J ) 1.9, 1 H); 5.05-5.06
(m, 1 H); 5.10 (d, J ) 10.0, 1 H); 5.13 (s, 1 H); 7.17-7.33 (m,
11 H); 7.43-7.46 (m, 2 H); 7.67-7.70 (m, 2 H). 13C NMR (100
MHz, CDCl3): δ 11.4, 15.2, 16.2, 21.2, 30.0, 63.4, 69.1, 71.2,
81.9, 87.7, 117.1, 125.4, 126.3, 127.2, 127.4, 127.95, 127.98,
128.1, 128.4, 138.5, 139.1, 141.3, 144.7, 156.5. FAB-MS: 502
(13, [M + H]+), 454 (100, [M - SMe]+), 410 (51, [M - SMe -
CO2]+). Anal. Calcd for C31H35NO3S (501.69): C, 74.22; H, 7.03;
N, 2.79. Found: C, 74.20; H, 7.16; N, 2.87.
N-{(1R,2S)-2-[(S)-4-Isop r op yl-2-oxo-5,5-d ip h en yloxa zo-
lid in -3-yl]-2-m et h ylsu lfa n yl-1-isop r op ylet h yl}-2,4,6-t r i-
m eth ylben zen esu lfon a m id e (15d ). Compound 3 (335 mg,
0.981 mmol) was treated with BuLi (0.79 mL, 1.18 mmol) and
a solution of N-mesitylsulfonylimine (derived from isobutyral-
dehyde)47 (323 mg, 1.28 mmol) in THF (1 mL) according to
GP 2. Purification of the crude product by FC (pentane/Et2O
3:1) yielded 15d (251 mg, 43%) as a 97:3 mixture with its C(1)-
NH epimer and 5 mol % of inseparable unidentified side
products. For analytical purposes, a sample was recrystallized
(MeOH) to afford 15d (dr g 99:1) as a white solid. Mp:196-
198 °C. [R]rtD ) -120.2 (c ) 1, CHCl3). IR (CHCl3): 3370, 3009,
(S)-3-[(1S,2S)-2-(ter t-Bu tyld im eth ylsila n yloxy)-3-m eth -
yl-1-(m eth ylsu lfa n yl)bu tyl]-4-isop r op yl-5,5-d ip h en ylox-
a zolid in -2-on e (18). To a solution of compound 9m (503 mg,
1.22 mmol) in CH2Cl2 (3 mL) were added i-Pr2NEt (563 µL,
3.29 mmol) and 3-(tert-butyldimethylsilanyloxy)triflate (560
µL, 2.44 mmol) at 0 °C. After being stirred for 10 min at 0 °C,
the reaction mixture was quenched with MeOH (2 mL) and
concentrated under reduced pressure. The crude product was
purified by FC (pentane/Et2O 15:1 to 10:1) to yield 18 (560
1745, 1408, 1336, 1158, 657 cm-1 1H NMR (400 MHz,
.
CDCl3): δ 0.29 (d, J ) 6.9, 3 H); 0.48 (d, J ) 6.9, 3 H); 0.78 (d,
J ) 7.0, 3 H); 1.12-1.21 (m, 1 H); 1.19 (d, J ) 7.3, 3 H); 2.17
(s, 3 H); 2.29 (s, 3 H); 2.29-2.36 (m, 1 H); 2.68 (s, 6 H); 3.55-
3.62 (m, 1 H); 4.85 (d, J ) 4.5, 1 H); 4.92 (d, J ) 1.8, 1 H);
4.96 (d, J ) 9.9, 1 H); 6.94 (d, J ) 0.5, 2 H); 7.20-7.38 (m, 6
H); 7.52-7.56 (m, 2 H); 7.75-7.78 (m, 2 H). 13C NMR (100
MHz, CDCl3): δ 15.2, 16.9, 17.1, 17.7, 19.7, 20.9, 23.1, 29.7
30.9, 60.3, 64.3, 67.7, 89.2, 125.1, 126.4, 127.6, 128.06, 128.08,
128.7, 132.0, 136.5, 137.8, 138.3, 141.9, 144.8, 157.3. MALDI-
MS: 617 (100, [M + Na]+), 503 (46, [M - SMe - CO2]+). Anal.
Calcd for C33H42N2O4S2 (594.84): C, 66.63; H, 7.12; N, 4.71;
S, 10.78. Found: C, 66.76; H, 7.11; N, 4.82; S, 10.74.
mg, 87%) as a white foam. [R]rt ) -163.0 (c ) 1, CHCl3). IR
D
(CHCl3): 2964, 1741, 1408, 834 cm-1. 1H NMR (300 MHz, C6D6,
50 °C): δ 0.16 (s, 3 H); 0.40 (s, 3 H); 0.61 (d, J ) 6.5, 3 H);
0.72 (d, J ) 6.5, 3 H); 0.81 (d, J ) 7.5, 3 H); 1.02-1.08 (m, 1
H); 1.03 (d, J ) 6.9, 3 H); 1.09 (s, 9 H); 2.12 (s, 3 H); 2.91-
3.03 (m, 1 H); 3.92-3.99 (m, 1 H); 5.05 (d, J ) 3.7, 1 H); 5.20
(d, J ) 3.1, 1 H); 6.90-7.02 (m, 4 H); 7.06-7.11 (m, 2 H); 7.60-
7.63 (m, 2 H); 7.75-7.78 (m, 2 H). 13C NMR (100 MHz,
CDCl3): δ -4.8, -2.3, 15.8, 16.7, 18.8, 19.3, 19.4, 19.8, 26.8,
29.4, 31.0, 64.3, 70.2, 83.4, 87.7, 125.3, 127.48, 127.52, 127.6,
127.9, 128.2, 138.1, 145.1, 157.5. FAB-MS: 528 (13, [M + H]+),
480 (100, [M - SMe]+), 436 (80, [M - SMe - CO2]+). Anal.
Calcd for C30H45NO3SiS (527.84): C, 68.26; H, 8.59; N, 2.65.
Found: C, 68.31; H, 8.50; N, 2.67.
(S)-4-Isopr opyl-3-[(1S,2S)-2-(m eth oxym eth oxy)-1-(m eth -
ylsu lfa n yl)-2-p h en yl-eth yl]-5,5-d ip h en yloxa zolid in -2-on e
(16). To a solution of compound 3 (500 mg, 1.46 mmol) in THF
(8 mL) was added BuLi (1.20 mL, 1.76 mmol) at -78 °C. After
being stirred for 15 min, the reaction mixture was cooled to
-100 °C and benzaldehyde (192 µL, 1.90 mmol) was added
dropwise. It was allowed to warm to -78 °C within 20 min,
and then MOMCl (189 µL, 2.49 mmol) was added. After the
mixture was stirred for 4 h at room temperature, the white
precipitate that developed in the course of the reaction was
dissolved in CH2Cl2 and the reaction was stopped by quenching
with saturated aqueous NH4Cl solution. The organic layer was
separated, and the aqueous layer was extracted with CH2Cl2
(2×). The combined organic layers were dried (MgSO4) and
concentrated under reduced pressure. The crude product was
triturated (boiling hexane, 2 × 5 mL) and recrystallized
(MeOH/CH2Cl2) to give 16 (557 mg, 77%) as a 98.5:1.5 mixture
with its C(2)-OH epimer. White solid. Mp: 201-203 °C.
(S)-2-(Meth oxym eth oxy)-2-p h en yleth a n ol (21). Com-
pound 16 (450 mg, 0.915 mmol) was treated with Hg(O2CCF3)2
(430 mg, 1.01 mmol) and NaBH4 (26 mg, 0.686 mmol)/DBU
(69 µL, 0.458 mmol) according to GP 3. The chiral auxiliary 1
was recoverd by filtration (184 mg, 71%). Purification of the
crude product by FC (pentane/AcOEt 4:1) yielded 21 (151 mg,
90%). The enantiomeric purity of 21 was determined by GC
to be g99:1. Colorless oil. 1H NMR (300 MHz, CDCl3): 2.84
(dd, J ) 4.4, 8.7, 1 H); 3.40 (s, 3 H); 3.63-3.79 (m, 2 H); 4.64
(d, J ) 6.7, 1 H); 4.66 (d, J ) 6.7, 1 H); 4.71 (dd, J ) 3.9, 7.9,
1 H); 7.27-7.38 (m, 5 H). The physical data are in agreement
with the values reported in the literature.57
[R]rt ) -60.6 (c ) 1, CHCl3). IR (CHCl3): 3008, 1750, 1419,
D
1101, 1022 cm-1. H NMR (300 MHz, CDCl3): δ 0.87 (d, J )
1
(S)-2-Ben zyloxy-3-m eth ylbu t-3-en -1-ol (22). Compound
17 (616 mg, 1.23 mmol) was treated with Hg(O2CCF3)2 (576
mg, 1.35 mmol) and NaBH4 (35 mg, 0.921 mmol)/DBU (92 µL,
0.614 mmol) according to GP 3. The chiral auxiliary 1 was
recoverd by filtration (287 mg, 83%). Purification of the crude
product by FC (pentane/AcOEt 6:1) yielded 22 (194 mg, 82%)
6.9, 3 H); 1.25 (d, J ) 7.2, 3 H); 1.44 (s, 3 H); 2.13-2.23 (m, 1
H); 3.21 (s, 3 H); 4.43 (d, J ) 10.6, 1 H); 4.48 (d, J ) 6.4, 1 H);
4.63 (d, J ) 1.9, 1 H); 4.70 (d, J ) 6.4, 1 H); 5.60 (d, J ) 10.6,
1 H); 7.21-7.36 (m, 11 H); 7.49-7.52 (m, 2 H); 7.69-7.72 (m,
2 H). 13C NMR (75 MHz, CDCl3): δ 12.9, 15.1, 21.6, 30.1, 56.1,
67.9, 69.4, 78.1, 88.0, 95.6, 125.4, 126.2, 127.4, 127.9, 127.96,
127.99, 128.2, 128.3, 128.4, 139.2, 139.8, 144.6, 156.4. FAB-
MS: 492 (7, [M + H]+), 444 (100, [M - SMe]+), 400 (36, [M -
SMe - CO2]+). Anal. Calcd for C29H33NO4S (491.65): C, 70.85;
H, 6.77; N, 2.85. Found: C, 70.63; H, 6.81; N, 2.85.
as a colorless oil. [R]rt ) +71.3 (c ) 1, CHCl3). IR (CHCl3):
D
3587, 3008, 1454, 1394, 1102, 912 cm-1. H NMR (400 MHz,
1
CDCl3): δ 1.71-1.72 (m, 3 H); 2.31 (br s, 1 H); 3.52-3.58 (m,
1 H); 3.60-3.65 (m, 1 H); 3.91 (dd, J ) 4.2, 7.8, 1 H); 4.21 (d,
J ) 11.6, 1 H); 4.58 (d, J ) 11.6, 1 H); 5.05-5.06 (m, 2 H);
7.23-7.36 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ 18.0, 64.4,
70.5, 83.7, 114.8, 127.7, 127.9, 128.4, 138.1, 141.8. EI-MS: 161
(9, [M - CH2OH]+), 91 (100, Bn+). Anal. Calcd for C12H16O2
(192.26): C, 74.97; H, 8.39. Found: C, 74.87; H, 8.27.
(S)-3-[(1S,2S)-2-Ben zyloxy-3-m et h yl-1-(m et h ylsu lfa n -
yl)bu t-3-en yl]-4-isop r op yl-5,5-d ip h en yloxa zolid in -2-on e
(17). To a solution of compound 3 (1.58 g, 4.62 mmol) in THF
(20 mL) was added BuLi (3.77 mL, 5.55 mmol) at -78 °C. After
being stirred for 15 min, the reaction mixture was cooled to
-100 °C and methacrolein (493 µL, 6.01 mmol) was added
dropwise. It was allowed to warm to -78 °C within 20 min,
and then BnBr (933 µL, 7.85 mmol) and DMPU (2 mL) were
added. After the mixture was stirred for 5 h at room temper-
(S)-2-(ter t-Bu tyld im eth ylsila n yloxy)-3-m eth ylbu ta n -1-
ol (23). Compound 18 (326 mg, 0.618 mmol) was treated with
(57) Ko, K. Y.; Eliel, E. L. J . Org. Chem. 1986, 51, 5353.

4-Isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one
J . Org. Chem., Vol. 66, No. 9, 2001 3071
Hg(O2CCF3)2 (290 mg, 0.680 mmol) and NaBH4 (18 mg, 0.464
mmol)/DBU (46 µL, 0.309 mmol) according to GP 3. The chiral
auxiliary 1 was recoverd by filtration (137 mg, 79%). Purifica-
tion of the crude product by FC (pentane/AcOEt 13:1) yielded
23 (112 mg, 83%). The enantiomeric purity of 23 was deter-
mined by GC to be g99:1. Colorless oil. 1H NMR (300 MHz,
CDCl3): 0.05 (s, 6 H); 0.85-0.89 (m, 15 H); 1.74-1.87 (m, 2
H); 3.42-3.52 (m, 2 H). The physical data are in agreement
with the values reported in the literature.58
N-((S)-2-H yd r oxy-1-p h en ylet h yl)-2,4,6-t r im et h ylb en -
zen esu lfon a m id e (24). Compound 14c (292 mg, 0.464 mmol)
was treated with Hg(O2CCF3)2 (218 mg, 0.511 mmol) and
NaBH4 (13 mg, 0.348 mmol)/DBU (35 µL, 0.232 mmol) accord-
ing to GP 3. The chiral auxiliary 1 was recoverd by filtration
(92 mg, 70%). Purification of the crude product by FC (CH2-
Cl2, 0.5% MeOH) yielded 24 (101 mg, 68%) as a white solid.
[R]rtD ) +68.4 (c ) 1, CHCl3). 1H NMR (300 MHz, CDCl3): 2.04
(t, J ) 6.1, 1 H); 2.26 (s, 3 H); 2.51 (s, 6 H); 3.71-3.76 (m, 2
H); 4.31 (dd, J ) 5.8, 11.5, 1 H); 5.36 (d, J ) 5.8, 1 H); 6.84 (s,
2 H); 7.03-7.09 (m, 2 H); 7.15-7.23 (m, 3 H). The physical
data are in agreement with the values reported in the
literature.59
17.0, 18.3, 21.1, 26.0, 29.3, 76.7, 80.1, 126.7, 127.4, 128.2, 141.4.
EI-MS: 277 (14, [M + H - H2O]+), 187 (100, [M - PhCHOH]+).
Anal. Calcd for C17H30O2Si (294.51): C, 69.33; H, 10.27.
Found: C, 69.22; H, 10.34. The enantiomeric purity of 29
minor was determined by GC to be g99:1. 29 minor. Colorless
1
oil. [R]rt ) +49.6 (c ) 1, CHCl3). H NMR (300 MHz, CDCl3):
D
δ -0.27 (s, 3 H); 0.00 (s, 3 H); 0.90 (s, 9 H); 0.95 (d, J ) 6.9,
3 H); 1.00 (d, J ) 6.9, 3 H); 1.74-1.83 (m, 1 H); 2.96 (d, J )
6.2, 1 H); 3.63 (t, J ) 4.0, 1 H); 4.67 (dd, J ) 4.0, 6.2, 1 H);
7.24-7.37 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ -4.9, -4.3,
17.7, 18.3, 19.1, 26.0, 31.8, 73.0, 81.6, 126.2, 127.1, 128.1, 143.3.
(S)-4-Isop r op yl-3-((S)-m eth oxym eth oxyp h en yla cetyl)-
5,5-d ip h en yloxa zolid in -2-on e (30). Compound 16 (557 mg,
1.13 mmol) was treated with Hg(O2CCF3)2 (532 mg, 1.25 mmol)
and PCC (512 mg, 2.37 mmol) according to GP 5. Purification
of the crude product by FC (pentane/AcOEt 7:1) yielded 30
(382 mg, 73%) as a white solid. Mp: 130-134 °C. [R]rtD ) -52.5
(c ) 1, CHCl3). IR (CHCl3): 3008, 1782, 1710, 1371, 1151, 1043
cm-1 1H NMR (300 MHz, CDCl3): δ 0.83 (d, J ) 6.9, 3 H);
.
0.95 (d, J ) 6.8, 3 H); 1.95-2.06 (m, 1 H); 3.38 (s, 3 H); 4.72
(d, J ) 6.9, 1 H); 4.75 (d, J ) 6.9, 1 H); 5.25 (d, J ) 3.7, 1 H);
6.33 (s, 1 H); 6.98-7.37 (m, 15 H). 13C NMR (75 MHz, CDCl3):
δ 16.5, 21.6, 29.6, 56.0, 65.7, 76.1, 89.8, 95.9, 125.0, 125.7,
127.8, 127.9, 128.2, 128.3, 128.4, 128.6, 134.8, 137.7, 141.9,
152.6, 170.5. FAB-MS: 460 (13, [M + H]+), 444 (37), 398 (100,
[M - OCH2OCH3]+). Anal. Calcd for C28H29NO5 (459.54): C,
73.18; H, 6.36; N, 3.05. Found: C, 73.14; H, 6.36; N, 3.11.
(S)-2-P h en ylp r op a n e-1,2-d iol (25). Compound 11a (370
mg, 0.802 mmol) was treated with Hg(O2CCF3)2 (376 mg, 0.882
mmol) and NaBH4 (23 mg, 0.601 mmol)/DBU (60 µL, 0.401
mmol) according to GP 3. The chiral auxiliary 1 was recoverd
by filtration (192 mg, 85%). Purification of the crude product
by FC (pentane/AcOEt 2:1) yielded 25 (101 mg, 82%). The
enantiomeric purity of 25 was determined by GC to be g99:1.
(S)-3-((S)-2-Ben zyloxy-3-m eth ylbu t-3-en oyl)-4-isop r o-
p yl-5,5-d ip h en yloxa zolid in -2-on e (31). Compound 17 (512
mg, 1.02 mmol) was treated with Hg(O2CCF3)2 (479 mg, 1.12
mmol) and PCC (462 mg, 2.14 mmol) according to GP 5.
Purification of the crude product by FC (pentane/AcOEt 13:1)
yielded 31 (362 mg, 76%) with 13 mol % of a inseparable
compound (later identified as compound (S)-3-formyl-4-isopro-
pyl-5,5-diphenyloxazolidin-2-one). This mixture was used for
further transformations. For analytical purposes, a sample was
recrystallized three times (CH2Cl2/hexane) to afford pure 31
1
Colorless oil. H NMR (300 MHz, CDCl3): 1.52 (s, 3 H); 2.21
(br s, 1 H); 2.83 (br s, 1 H); 3.60 (d, J ) 11.1, 1 H); 3.77 (d,
J ) 11.1, 1 H), 7.24-7.46 (m, 5 H). The physical data are in
agreement with the values reported in the literature.60
(2R,3S)-3-(ter t-Bu tyld im eth ylsila n yloxy)-4-m eth ylp en -
ta n -2-ol (28). Compound 18 (615 mg, 1.17 mmol) was treated
with Hg(O2CCF3)2 (547 mg, 1.28 mmol) and MeMgCl (4.66 mL,
4.66 mmol) according to GP 4. The chiral auxiliary 1 was
recoverd by filtration (300 mg, 91%). Purification of the crude
product by FC (pentane/Et2O 15:1) yielded 28 (207 mg, 76%)
as a 83:17 mixture with its C(2)-OH epimer. For analytical
purposes, a sample was purified by FC (pentane/Et2O 15:1) to
afford 28 as a single diastereoisomer. The enantiomeric purity
of 28 and its C(2)-OH epimer were both determined by GC to
as a white solid. Mp: 107-108 °C. [R]rt ) -83.7 (c ) 1,
D
CHCl3). IR (CHCl3): 3063, 1783, 1710, 1450, 1178, 1094 cm-1
.
1H NMR (400 MHz, CDCl3): δ 0.78 (d, J ) 6.8, 3 H); 0.91 (d,
J ) 7.0, 3 H); 1.47 (dd, J ) 0.9, 1.3, 3 H); 1.98-2.07 (m, 1 H);
4.45-4.46 (m, 1 H); 4.49 (d, J ) 11.5, 1 H); 4.54-4.55 (m, 1
H); 4.56 (d, J ) 11.5, 1 H); 5.31 (d, J ) 3.6, 1 H); 5.50 (d, J )
0.4, 1 H); 7.24-7.38 (m, 11 H); 7.40-7.42 (m, 2 H); 7.46-7.49
(m, 2 H). 13C NMR (100 MHz, CDCl3): δ 16.5, 18.7, 21.8, 29.7,
65.9, 71.6, 80.3, 89.8, 116.3, 125.3, 125.7, 127.8, 128.0, 128.1,
128.4, 128.46, 128.52, 128.8, 137.6, 137.8, 139.7, 142.6, 152.8,
170.1. FAB-MS: 470 (100, [M + H]+), 426 (14, [M + H -
CO2]+), 362 (52, [M - OBn]+). Anal. Calcd for C30H31NO4
(469.58): C, 76.73; H, 6.65; N, 2.98. Found: C, 76.67; H, 6.65;
N, 3.01.
be g99:1. Colorless oil. [R]rt ) -11.6 (c ) 1, CHCl3). IR
D
(CHCl3): 3599, 2958, 1472, 1113, 1049, 858 cm-1.1H NMR (400
MHz, CDCl3): δ 0.09 (s, 3 H); 0.10 (s, 3 H); 0.89 (d, J ) 6.9, 3
H); 0.93 (s, 9 H); 0.94 (d, J ) 6.9, 3 H); 1.15 (d, J ) 6.4, 3 H);
1.74-1.83 (m, 1 H); 1.86 (d, J ) 5.1, 1 H); 3.38 (dd, J ) 3.7,
5.0, 1 H); 3.79-3.87 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ
-4.3, -3.9, 17.7, 18.3, 18.4, 20.4, 26.1, 30.1, 69.8, 80.5. EI-
MS: 187 (44, [M - MeCHOH]+), 159 (100). Anal. Calcd for
C
12H28O2Si (232.44): C, 62.01; H, 12.14. Found: C, 62.11; H,
11.95.
(1R,2S)-2-(ter t-Bu t yld im et h ylsila n yloxy)-3-m et h yl-1-
(S)-Meth oxym eth oxyp h en yla cetic Acid Meth yl Ester
(32). Compound 30 (358 mg, 0.779 mmol) was treated with
DBU (233 µL, 1.56 mmol) and LiBr (338 mg, 3.90 mmol)
according to GP 6. The chiral auxiliary 1 was recoverd by
filtration (186 mg, 85%). Purification of the crude product by
FC (pentane/AcOEt 7:1) yielded 32 (135 mg, 83%). The
enantiomeric purity of 32 was determined by HPLC to be g99:
p h en ylbu ta n -1-ol (29) a n d (1S,2S)-2-(ter t-Bu tyld im eth -
ylsila n yloxy)-3-m eth yl-1-p h en ylbu ta n -1-ol (29 m in or ).
Compound 18 (555 mg, 1.05 mmol) was treated with Hg(O2-
CCF3)2 (493 mg, 1.16 mmol) and PhLi (2.63 mL, 4.20 mmol)
according to GP 4. The chiral auxiliary 1 was recoverd by
filtration (258 mg, 87%). Purification of the crude product by
FC (pentane/Et2O 30:1 to 25:1) yielded 29 (194 mg, 63%) and
29 minor (50 mg, 16%) as single diastereoisomers. The
enantiomeric purity of 29 was determined by GC to be g99:1.
1
1. Colorless oil. H NMR (300 MHz, CDCl3): δ 3.37 (s, 3 H);
3.69 (s, 3 H); 4.67 (d, J ) 6.9, 1 H); 4.74 (d, J ) 6.9, 1 H); 5.17
(s, 1 H); 7.32-7.38 (m, 3 H); 7.42-7.46 (m, 2 H). The physical
data are in agreement with the values reported in the
literature.61
29. Colorless oil. [R]rt ) -21.6 (c ) 1, CHCl3). IR (CHCl3):
D
(S)-2-Ben zyloxy-3-m eth ylbu t-3-en oic Acid Meth yl Es-
ter (33). Compound 31 (362 mg, 0.770 mmol, 13 mol % of (S)-
3-formyl-4-isopropyl-5,5-diphenyloxazolidin-2-one) was treated
with DBU (230 µL, 1.54 mmol) and LiBr (334 mg, 3.85 mmol)
according to GP 6. The chiral auxiliary 1 was recoverd by
filtration (203 mg, 71% overall yield from 17). Purification of
the crude product by FC (pentane/AcOEt 16:1) yielded 33 (141
3606, 2958, 2930, 1472, 1043, 836 cm-1.1H NMR (400 MHz,
CDCl3): δ -0.11 (s, 3 H); 0.08 (s, 3 H); 0.80 (d, J ) 6.8, 3 H);
0.91 (s, 9 H); 0.94 (d, J ) 6.8, 3 H); 1.66-1.74 (m, 1 H); 2.43
(br s, 1 H); 3.72 (dd, J ) 3.1, 5.2, 1 H); 4.75 (d, J ) 5.2, 1 H);
7.23-7.39 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ -4.6, -4.4,
(58) Nubbemeyer, U.; O¨ hrlein, R.; Gonda, J .; Ernst, B.; Bellus, D.
Angew. Chem. 1991, 103, 1533.
mg, 63% overall yield from 17). Colorless oil. [R]rt ) +55.0
D
(59) Hoppe, I.; Hoffman, H.; Ga¨rtner, I.; Krettek, T.; Hoppe, D.
Synthesis 1991, 1157.
(60) Agami, C.; Couty, F.; Lequesne, C. Tetrahedron 1995, 51, 4043.
(61) Barrett, A. G. M.; Rys, D. J . J . Chem. Soc., Perkin Trans. 1
1995, 1009.

3072 J . Org. Chem., Vol. 66, No. 9, 2001
Gaul et al.
(c ) 1, CHCl3). IR (CHCl3): 3008, 1746, 1454, 1177, 1096, 913
(S)-4-Isop r op yl-3-(1-m eth ylsu lfa n yleth yl)-5,5-d ip h en -
yloxa zolid in -2-on e (38). To a solution of compound 3 (210
mg, 0.615 mmol) in THF (3 mL) was added BuLi (0.48 mL) at
-78 °C. After the solution was stirred for 10 min, MeI (50 µL,
0.800 mmol) was added dropwise. After being stirred for 15
min, the reaction was stopped by quenching with saturated
aqueous NH4Cl solution. The reaction mixture was diluted
with Et2O, the organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 (2×). The combined organic
layers were dried (MgSO4) and concentrated under reduced
pressure. Trituration of the crude product (boiling hexane, 4
mL) yielded 38 (192 mg, 88%) as a 83:17 mixture with its C(1)-
SMe epimer. For analytical purposes, a sample was recrystal-
lized twice (Et2O) to afford 38 (dr 95:5) as a white solid. Mp:
1
cm-1. H NMR (300 MHz, CDCl3): δ 1.78-1.79 (m, 3 H); 3.75
(s, 3 H); 4.38 (s, 1 H); 4.52 (d, J ) 12.0, 1 H); 4.58 (d, J ) 12.0,
1 H); 5.11-5.14 (m, 2 H); 7.26-7.37 (m, 5 H). 13C NMR (75
MHz, CDCl3): δ 17.9, 52.1, 70.6, 81.4, 116.4, 127.8, 127.9,
128.3, 137.1, 139.9, 170.8. EI-MS: 181 (4), 161 (32, [M - CO2-
Me]+), 114 (33, [M + H - OBn]+), 91 (100, Bn+). Anal. Calcd
for C13H16O3 (220.27): C, 70.89; H, 7.32. Found: C, 70.84; H,
7.46.
(E)-(R)-4-Hyd r oxy-4-p h en ylp en t-2-en oic Acid Meth yl
Ester (34) an d (R)-5-Meth yl-5-ph en yl-5H-fu r an -2-on e (35).
Compound 11a (750 mg, 1.63 mmol) was treated with Hg(O2-
CCF3)2 (762 mg, 1.79 mmol) and DBU (122 µL, 0.812 mmol)/
ylide (1.09 g, 3.25 mmol) according to GP 7. The chiral
auxiliary 1 was recoverd (365 mg, 80%). Purification of the
crude product by FC (CH2Cl2/pentane 3:1) yielded 34 (208 mg,
62%) and 35 (75 mg, 27%) as single stereoisomers. 34.
166-167 °C. [R]rt ) -138.2 (c ) 1, CHCl3, dr 83:17). IR
D
(CHCl3): 3008, 1739, 1493, 1450, 1178, 1002 cm-1. H NMR
1
(400 MHz, CDCl3): δ 0.71 (d, J ) 7.0, 3 H); 1.03 (d, J ) 7.3,
3 H); 1.32 (s, 3 H); 1.52 (d, J ) 7.3, 3 H); 1.97-2.08 (m, 1 H);
4.74 (d, J ) 1.9, 1 H); 4.94 (q, J ) 7.3, 1 H); 7.21-7.37 (m, 6
H); 7.50-7.53 (m, 2 H); 7.69-7.72 (m, 2 H). 13C NMR (100
MHz, CDCl3): δ 14.0, 16.6, 19.4, 22.4, 30.0, 59.0, 67.2, 89.1,
125.3, 126.5, 127.6, 128.1, 128.2, 128.6, 138.7, 144.8, 157.0.
MALDI-MS: 378 (6, [M + Na]+), 264 (54, [M - SMe - CO2]+),
167 (100). Anal. Calcd for C21H25NO2S (355.50): C, 70.95; H,
7.09; N, 3.94. Found: C, 70.99; H, 7.25; N, 3.95.
Colorless oil. [R]rt ) +20.3 (c ) 1, CHCl3). IR (CHCl3): 3595,
D
3009, 1718, 1436, 1281, 1174 cm-1.1H NMR (300 MHz,
CDCl3): δ 1.71 (s, 3 H); 2.23 (s, 1 H); 3.73 (s, 1 H); 6.12 (d,
J ) 15.8, 1 H); 7.17 (d, J ) 15.8, 1 H); 7.24-7.38 (m, 3 H);
7.42-7.48 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ 28.9, 51.7,
74.2, 118.0, 125.1, 127.6, 128.5, 144.6, 153.4, 167.2. EI-MS:
205 (1, [M - H]+), 188 (21, [M - H2O]+), 131 (100). Anal. Calcd
for C12H14O3 (206.24): C, 69.89; H, 6.84. Found: C, 69.62; H,
6.91. 35. Colorless oil. [R]rtD ) +275.6 (c ) 1, CHCl3). 1H NMR
(300 MHz, CDCl3): 1.82 (s, 3 H); 6.04 (d, J ) 5.6, 1 H); 7.28-
7.40 (m, 5 H); 7.64 (d, J ) 5.6, 1 H).13C NMR (75 MHz,
CDCl3): 26.2, 88.8, 119.2, 124.7, 128.3, 128.8, 139.2, 160.4,
172.3.
(S)-4-ter t-Bu tyl-3-(m eth ylsu lfa n ylm eth yl)-5,5-d ip h en -
yloxa zolid in -2-on e (39). (S)-4-tert-Butyl-5,5-diphenyloxazo-
lidin-2-one62 (1.52 g, 5.15 mmol) was treated with BuLi (3.65
mL, 5.66 mmol) and MTMCl (520 µL, 6.18 mmol) according to
GP 1. Purification of the crude product by filtering through a
silica plug (CH2Cl2) and subsequent trituration (boiling hex-
ane, 10 mL) yielded 39 (1.03 g, 56%) as a white solid. Mp:
(S)-3-((2S,3R)-3,5-Dip h en yl-2,3-d ih yd r ofu r a n -2-yl)-4-
isop r op yl-5,5-d ip h en yloxa zolid in -2-on e (36). To a solution
of ketone 13 (400 mg, 0.728 mmol) in THF (5 mL) was added
Hg(O2CCF3)2 (341 mg, 0.801 mmol) at room temperature. After
the mixture was stirred for 20 min, H2O was added, and the
reaction mixture was diluted with Et2O. The organic layer was
separated, and the aqueous layer was extracted with Et2O
(2×). The combined organic layers were dried (MgSO4) and
concentrated under reduced pressure. Purification of the crude
product by FC (pentane/Et2O 4:1, 1% Et3N) and trituration
(boiling hexane, 10 mL) afforded 36 as a single diastereoiso-
mer. Due to purification problems only small amounts of
product could be isolated. White solid. Mp: 211-213 °C.
196-197 °C. [R]rt ) -134.3 (c ) 1.03, CHCl3). IR (CHCl3):
D
3007, 2964, 1744, 1450, 1405, 1086, 882 cm-1. H NMR (400
1
MHz, CDCl3): δ 0.86 (s, 9 H); 1.08 (s, 3 H); 4.21 (d, J ) 14.7,
1 H); 4.55 (s, 1 H); 4.94 (d, J ) 14.7, 1 H); 7.18-7.30 (m, 4 H);
7.34-7.39 (m, 2 H); 7.54 (br s, 2 H); 7.74-7.77 (m, 2 H). 13C
NMR (100 MHz, CDCl3): δ 13.0, 28.1, 37.3, 50.9, 69.1, 89.6,
125.5, 127.6, 127.7, 128.2, 128.6, 138.1, 145.1, 157.7. MALDI-
MS: 378 (8, [M + Na]+), 264 (2, [M - SMe - CO2]+), 208 (100,
[M - SMe - CO2 - isobutene]+). Anal. Calcd for C21H25NO2S
(355.50): C, 70.95; H, 7.09; N, 3.94, S: 9.02. Found: C, 70.82;
H, 7.15; N, 3.93, S: 8.94.
(R)-3-(Meth ylsu lfan ylm eth yl)-4,5,5-tr iph en yloxazolidin -
2-on e (40). (R)-4-Phenyl-5,5-diphenyloxazolidin-2-one35b (1.81
g, 5.74 mmol) was treated with BuLi (4.07 mL, 6.31 mmol)
and MTMCl (580 µL, 6.89 mmol) according to GP 1. Purifica-
tion of the crude product by FC (pentane/Et2O 4:1) and
subsequent trituration (boiling hexane, 10 mL) yielded 40 (1.62
[R]rt ) +54.0 (c ) 1, CHCl3). IR (CHCl3): 3022, 1754, 1490,
D
1374, 1010, 947 cm-1 1H NMR (400 MHz, CDCl3): 0.81 (d,
.
J ) 6.7, 3 H); 0.91 (d, J ) 7.3, 3 H); 1.91-2.02 (m, 1 H); 4.32
(dd, J ) 2.7, 7.3, 1 H); 4.68 (d, J ) 1.5, 1 H); 5.47 (d, J ) 2.7,
1 H); 5.98 (d, J ) 7.3, 1 H); 6.76-6.78 (m, 2 H); 7.10-7.16 (m,
2 H); 7.24-7.27 (m, 1 H); 7.30-7.40 (m, 10 H); 7.53-7.55 (m,
3 H); 7.67-7.69 (m, 2 H). 13C NMR (100 MHz, CDCl3): 15.6,
20.6, 29.5, 51.8, 68.6, 89.0, 94.1, 98.3, 125.2, 125.3, 126.0, 127.2,
127.4, 127.7, 128.2, 128.3, 128.7, 128.86, 128.88, 129.9, 130.5,
141.3, 144.4, 155.2, 156.5. MALDI-MS: 524 (100, [M + Na]+),
458 (29), 248 (21). MALDI-HRMS: m/z 524.2196 [C34H31NO3
(M + Na)+ requires 524.2196].
g, 75%) as a white solid. Mp: 129-131 °C. [R]rt ) +39.8
D
(c ) 1, CHCl3). IR (CHCl3): 3008, 1749, 1450, 1410, 1080, 882
cm-1. 1H NMR (400 MHz, CDCl3): δ 1.79 (s, 3 H); 3.60 (d, J )
14.2, 1 H); 4.91 (d, J ) 14.2, 1 H); 5.79 (s, 1 H); 6.97-7.07 (m,
7 H); 7.12-7.15 (m, 3 H); 7.32-7.37 (m, 1 H); 7.40-7.45 (m, 2
H); 7.73-7.76 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ 13.7,
46.7, 66.6, 88.4, 126.1, 126.5, 127.3, 127.6, 128.48, 128.51,
128.6, 128.7, 134.4, 138.9, 142.1, 156.8. MALDI-MS: 398 (3,
[M + Na]+), 284 (100, [M - SMe - CO2]+), 206 (22). Anal.
Calcd for C23H21NO2S (355.50): C, 73.57; H, 5.64; N, 3.73, S:
8.54. Found: C, 73.40; H, 5.76; N, 3.78, S: 8.48.
Isop r op yl-3-((1S,2S,3R,5R)-5-m eth oxy-3,5-d ip h en yltet-
r a h yd r ofu r a n -2-yl)-5,5-d ip h en yloxa zolid in -2-on e (37).
Compound 36 (30 mg, 0.060 mmol) was dissolved in MeOH (3
mL) at room temperature. Colorless crystals were formed upon
standing for 3 days. The crystals were isolated and identified
as compound 37 (single diastereoisomer). White solid. Mp:
182-184 °C. [R]rtD ) -28.4 (c ) 0.5, CHCl3). IR (CHCl3): 3008,
(4S,5R)-4-Isop r op yl-3-(m eth ylsu lfa n ylm eth yl)-5-p h en -
yloxa zolid in -2-on e (41). (4S,5R)-4-Isopropyl-5-phenyloxazo-
lidin-2-one63 (798 mg, 3.89 mmol) was treated with BuLi (3.17
mL, 4.67 mmol) and MTMCl (424 µL, 5.06 mmol) according to
GP 1. Purification of the crude product by FC (pentane/AcOEt
8:1) yielded 41 (915 mg, 89%) as a white solid. Mp: 91-93
°C. [R]rtD ) +27.9 (c ) 1, CHCl3). IR (CHCl3): 3008, 2924, 1748,
1759, 1449, 1129, 998 cm-1 1H NMR (400 MHz, CDCl3): δ
.
0.68 (d, J ) 6.7, 3 H); 0.82 (d, J ) 7.3, 3 H); 1.90-1.97 (m, 1
H); 2.56 (dd, J ) 6.3, 13.5, 1 H); 2.66 (dd, J ) 11.4, 13.5, 1 H);
3.11 (s, 3 H); 4.03-4.08 (m, 1 H); 4.56 (d, J ) 1.6, 1 H); 5.52
(d, J ) 8.3, 1 H); 7.16-7.36 (m, 16 H); 7.45-7.48 (m, 2 H);
7.53-7.56 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ 14.9, 20.7,
29.7, 45.0, 47.4, 49.4, 68.0, 88.5, 92.4, 106.5, 125.5, 126.0, 126.2,
126.9, 127.6, 127.9, 128.0, 128.12, 128.14, 128.4, 128.6, 138.9,
140.0, 140.2, 144.0, 156.6. MALDI-MS: 556 (70, [M + Na]+),
524 (47, [M + Na - OMe]+), 458 (100, [M - OMe - CO2]+).
MALDI-HRMS: m/z 556.2438 [C35H35NO4 (M + Na)+ requires
556.2458].
1
1454, 1418, 997 cm-1. H NMR (300 MHz, CDCl3): δ 0.70 (d,
J ) 6.9, 3 H); 0.84 (d, J ) 7.2, 3 H); 1.61-1.78 (m, 1 H); 2.20
(62) We are grateful to Novartis Pharma AG for donation of 4-tert-
butyl-5,5-diphenyloxazolidin-2-one (preparation in analogy to ref 35b).
(63) Preparation in analogy to: (a) Fujita, M.; Hiyama, T. J . Org
Chem. 1988, 53, 5415. (b) Kano, S.; Yokomatsu, T.; Iwasawa, H.;
Shibuya, S. Chem. Pharm. Bull. 1988, 36, 3341.

4-Isopropyl-3-(methylthiomethyl)-5,5-diphenyloxazolidin-2-one
J . Org. Chem., Vol. 66, No. 9, 2001 3073
(s, 3 H); 4.10 (d, J ) 14.2, 1 H); 4.21 (dd, J ) 2.6, 8.1, 1 H);
5.06 (d, J ) 14.2, 1 H); 5.66 (d, J ) 8.1, 1 H); 7.31-7.42 (m, 5
H). 13C NMR (75 MHz, CDCl3): δ 14.4, 16.4, 21.0, 28.2, 48.5,
61.6, 79.9, 126.1, 128.3, 128.4, 134.6, 158.2. FAB-MS: 531 (50,
[2M + H]+), 266 (13, [M + H]+), 218 (100, [M - SMe]+), 174
(84, [M - SMe - CO2]+). Anal. Calcd for C14H19NO2S
(265.38): C, 63.36; H, 7.22; N, 5.28. Found: C, 63.41; H, 7.36;
N, 5.25.
(461.62): C, 72.85; H, 6.77; N, 3.03. Found: C, 72.92; H, 6.95;
N, 3.16.
(R)-3-[(1R,2R)-2-Hyd r oxy-1-(m eth ylsu lfa n yl)-2-p h en yl-
eth yl]-4,5,5-tr ip h en yloxa zolid in -2-on e (45). Compound 40
(218 mg, 0.580 mmol) was treated with BuLi (0.45 mL, 0.697
mmol) and benzaldehyde (76 µL, 0.754 mmol) according to GP
2. Trituration of the crude product (boiling hexane, 2 × 5 mL)
yielded 45 (253 mg, 91%) as a 79:21 mixture with its C(2)-OH
epimer. For analytical purposes, a sample was recrystallized
(MeOH) to afford 45 (dr 90:10) as a white solid. Mp: 207-213
°C. [R]rtD ) +12.3 (c ) 1, CHCl3). IR (CHCl3): 3378, 3008, 1732,
(S)-3-[2-Hyd r oxy-1-m eth yl-1-(m eth ylsu lfa n yl)-2-p h en -
yleth yl]-4-isopr opyl-5,5-diph en yloxazolidin -2-on e (42) an d
3-[(S)-1-(H yd r oxyd ip h en ylm et h yl)-2-m et h ylp r op yl]-4-
m eth yl-4-(m eth ylsu lfan yl)-5-ph en yl-oxazolidin -2-on e (43).
Compound 38 (368 mg, 1.04 mmol, dr 83:17) was treated with
BuLi (0.82 mL, 1.24 mmol) and benzaldehyde (136 µL, 1.35
mmol) according to GP 2. Compounds 42 and 43 were obtained
as a 60:40 mixture, determined by 1H NMR of the crude
product. Purification of the crude product by FC (pentane/Et2O
6:1 to 3:1) yielded 42 (201 mg, 42%) as a 61:17:14:8 mixture
of diastereoisomers and 43 (yield not determined) as a 55:45
mixture of diastereoisomers. For analytical purposes, a sample
of 42 was recrystallized twice (MeOH) to afford 42 as a single
1450, 1403, 1003, 866 cm-1 1H NMR (400 MHz, CDCl3): δ
.
1.83 (s, 3 H); 4.10 (d, J ) 7.3, 1 H); 4.70 (d, J ) 7.0, 1 H); 5.25
(dd, J ) 7.0, 7.3, 1 H); 5.83 (s, 1 H); 6.87-6.93 (m, 2 H); 6.97-
7.05 (m, 5 H); 7.12-7.27 (m, 7 H); 7.32-7.44 (m, 4 H); 7.65-
7.68 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ 13.7, 66.9, 69.9,
75.1, 89.0, 125.9, 126.55, 126.61, 127.4, 127.5, 127.9, 128.2,
128.5, 128.69, 128.71, 133.8, 138.6, 140.5, 142.7, 157.8. MALDI-
MS: 504 (22, [M + Na]+), 390 (88, [M - SMe-CO2]+), 372 (100,
[M - H2O - SMe - CO2]+). Anal. Calcd for C30H27NO3S
(481.61): C, 74.82; H, 5.65; N, 2.91. Found: C, 74.78; H, 5.53;
N, 3.01.
diastereoisomer. 42. White solid. Mp: 182-183 °C. [R]rt
)
D
-83.6 (c ) 1, CHCl3). IR (CHCl3): 3063, 3008, 1721, 1451,
(4S,5R)-3-[(1S,2S)-2-Hydr oxy-1-(m eth ylsu lfan yl)-2-ph en -
yleth yl]-4-isop r op yl-5-p h en yloxa zolid in -2-on e (46). Com-
pound 41 (260 mg, 0.980 mmol) was treated with BuLi (0.80
mL, 1.18 mmol) and benzaldehyde (129 µL, 1.27 mmol)
according to GP 2. Purification of the crude product by FC
(pentane/AcOEt 5:1) yielded 46 (313 mg, 86%) as a 88:12
mixture with its C(2)-OH epimer. For analytical purposes, a
sample was recrystallized (MeOH) to afford 46 (dr 98.5:1.5)
1
1387, 1023 cm-1. H NMR (300 MHz, CDCl3): δ 0.71 (d, J )
7.5, 3 H); 0.82 (d, J ) 7.2, 3 H); 1.25 (s, 3 H); 1.51 (s, 3 H);
1.89-2.03 (m, 1 H); 4.63 (d, J ) 2.2, 1 H); 4.68 (d, J ) 6.5, 1
H); 5.54 (d, J ) 6.5, 1 H); 7.18-7.39 (m, 9 H); 7.42-7.53 (m,
4 H); 7.71-7.76 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ 11.0,
17.5, 18.9, 22.1, 31.7, 68.1, 72.7, 75.7, 88.7, 125.5, 126.6, 127.4,
127.6, 127.7, 127.9, 128.2, 128.5, 128.6, 138.6, 139.2, 144.5,
157.5. MALDI-MS: 370 (100, [M - SMe - CO2]+), 352 (19,
as a white solid. Mp: 160-163 °C. [R]rt ) +19.6 (c ) 1,
D
[M - H2O - SMe - CO2]+), 310 (54). Anal. Calcd for C28H31
-
CHCl3). IR (CHCl3): 3365, 3008, 1735, 1454, 1413, 1041 cm-1
.
NO3S (461.62): C, 72.85; H, 6.77; N, 3.03. Found: C, 72.96;
H, 6.65; N, 3.10. 43 major. White solid. 1H NMR (400 MHz,
CDCl3): δ 0.91 (d, J ) 7.3, 3 H); 1.07 (d, J ) 7.1, 3 H); 1.19 (s,
3 H); 1.54 (s, 3 H); 2.48-258 (m, 1 H); 4.54 (d, J ) 1.6, 1 H);
5.15 (s, 1 H); 7.08-7.40 (m, 11 H); 7.74-7.76 (m, 2 H); 7.79-
7.81 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ 11.7, 19.7, 24.6,
24.8, 30.0, 65.9, 75.1, 82.3, 85.3, 125.9, 126.3, 126.6, 126.7,
127.2, 127.6, 128.1, 128.5, 129.1, 134.1, 144.9, 146.1, 158.8.
MALDI-TOF-MS: 484 (100, [M + Na]+), 400 (25).
1H NMR (400 MHz, CDCl3): δ 0.69 (d, J ) 7.0, 3 H); 0.83 (d,
J ) 7.2, 3 H); 1.78-1.89 (m, 1 H); 2.12 (s, 3 H); 4.06 (d, J )
5.7, 1 H); 4.17 (dd, J ) 2.7, 7.7, 1 H); 4.75 (d, J ) 8.2, 1 H);
5.35 (dd, J ) 5.7, 8.2, 1 H); 5.53 (d, J ) 7.7, 1 H); 7.29-7.41
(m, 8 H); 7.48-7.50 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ
14.6, 16.9, 19.7, 28.8, 64.8, 69.0, 74.7, 81.1, 126.2, 126.9, 128.3,
128.5, 128.6, 134.3, 140.7, 159.0. FAB-MS: 372 (5, [M + H]+),
354 (15, [M + H - H2O]+), 324 (100, [M - SMe]+), 280 (65,
[M - SMe - CO2]+). Anal. Calcd for C21H25NO3S (371.50): C,
67.90; H, 6.78; N, 3.77. Found: C, 67.96; H, 6.68; N, 3.85.
(S)-4-ter t-Bu tyl-3-[(1S,2S)-2-h ydr oxy-1-(m eth ylsu lfan yl)-
2-p h en yleth yl]-5,5-d ip h en yloxa zolid in -2-on e (44). Com-
pound 39 (235 mg, 0.661 mmol) was treated with BuLi (0.52
mL, 0.793 mmol) and benzaldehyde (87 µL, 0.859 mmol)
according to GP 2. Trituration of the crude product (boiling
hexane, 2 × 5 mL) yielded 44 (279 mg, 91%) as a 90:10 mixture
with its C(2)-OH epimer. For analytical purposes, a sample
was recrystallized (MeOH) to afford 44 (dr 91:9) as a white
Ack n ow led gm en t. We thank B. Schweizer and P.
Seiler for determination of the X-ray crystal structures
of compounds 9d , 11e, and 15d . We are also grateful to
Novartis Pharma AG for donation of 4-isopropyl-5,5-
diphenyloxazolidin-2-one and 4-tert-butyl-5,5-diphenyl-
oxazolidin-2-one as well as for continuing financial
support.
solid. Mp: 239-247 °C. [R]rt ) -142.8 (c ) 1.33, CHCl3). IR
D
(CHCl3): 3512, 3008, 1729, 1450, 1416, 1048 cm-1. H NMR
1
(400 MHz, CDCl3): δ 0.98 (s, 9 H); 1.15 (s, 3 H); 4.26 (d, J )
5.0, 1 H); 4.39 (s, 1 H); 4.46 (d, J ) 9.9, 1 H); 5.52 (dd, J ) 5.0,
9.9, 1 H); 7.20-7.38 (m, 11 H); 7.53 (br s, 2 H); 7.75-7.78 (m,
2 H). 13C NMR (100 MHz, CDCl3): δ 9.4, 28.2, 37.6, 69.6, 72.5,
73.6, 90.1, 125.8, 127.3, 127.7, 127.8, 128.1, 128.26, 128.31,
128.4, 138.2, 141.1, 144.8, 158.3. MALDI-MS: 484 (13, [M +
Na]+), 370 (6, [M - SMe - CO2]+), 314 (42, [M - SMe -
CO2 - isobutene]+), 296 (100). Anal. Calcd for C28H31NO3S
Su p p or tin g In for m a tion Ava ila ble: Full experimental
data of compounds 5, 9a -j,l,n , 11c-k , 14b, 26, and 27 and
detailed 1H and 13C NMR spectra with signal assignments;
further IR, MS, HPLC, GC, and optical rotation data of all
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O0155254