Conjugate addition of lithiated (S)-4-isopropyl-3-[(methylthio)methyl]-5,5-diphenyloxazolidin-2-one to cinnamoyl derivatives: Preparation of enantiomerically pure 1,4-diols

Article abstract of DOI:10.1002/1522-2675(200203)85:3<772::AID-HLCA772>3.0.CO;2-I

The Li derivative of (S)-4-isopropyl-3-[(methylthlio)methyl]-5,5-diphenyloxazolidin-2-one (Li-2; synthetically equivalent to a chiral formyl anion) adds to enones and enoates in a 1,4-fashion. Best results are obtained with 1,3-diarylpropenones (chalcones

Full text of DOI:10.1002/1522-2675(200203)85:3<772::AID-HLCA772>3.0.CO;2-I

772
Helvetica Chimica Acta Vol. 85 (2002)
Conjugate Addition of Lithiated (S)-4-Isopropyl-3-
[(methylthio)methyl]-5,5-diphenyloxazolidin-2-one to Cinnamoyl
Derivatives: Preparation of Enantiomerically Pure 1,4-Diols
by Christoph Gaul1) and Dieter Seebach*
Laboratorium f¸r Organische Chemie der Eidgenˆssischen Technischen Hochschule, ETH-Hˆnggerberg,
CH-8093 Z¸rich
The Li derivative of (S)-4-isopropyl-3-[(methylthio)methyl]-5,5-diphenyloxazolidin-2-one (Li-2; syntheti-
cally equivalent to a chiral formyl anion) adds to enones and enoates in a 1,4-fashion. Best results are obtained
with 1,3-diarylpropenones (chalcones; Scheme 2), trityl enones, and 2,6-di(tert-butyl)-4-methoxyphenyl
cinnamates (Scheme 3), with yields up to 80% and diastereoselectivities up to and above 99 :1 of the products
(5a f and 8a,b,e) containing three stereogenic centers! X-Ray crystal-structure analysis reveals that the C,C-
bond formation occurs preferentially with relative topicity ul (Re/Si; Fig. 2). The MeS group of the 1,4-adducts
can be replaced by RO groups in Hg2‡-assisted substitutions, with subsequent removal and facile recovery of the
chiral auxiliary (Schemes 4 6). 4-Hydroxycarbonyl derivatives (−homoaldols×) and mono-, di-, and trisub-
stituted 1,4-diols are, thus, accessible in enantiomerically pure forms (cf. 15, 16, and 18 20).
1. Introduction. The 4-isopropyl-5,5-diphenyloxazolidin-2-one2) (1; developed in
our group3) and by others4)5) is a useful alternative to the widely employed amino-
acid- or ephedrine-derived Evans oxazolidinones [6]6). N-Acyl derivatives of 1 were
shown to be suitable substrates for diastereoselective alkylations, aldol additions, 1,4-
additions, cycloadditions, and numerous other reactions [3][4][9]. Recently, we have
also reported on the preparation of a new N-alkyl derivative of oxazolidinone 1, the 3-
[(methylthio)methyl]oxazolidin-2-one (2), the applicability of which as chiral reagent
(synthetically equivalent to a formyl anion) was demonstrated (Scheme 1) [10]. The
geminal Ph groups of oxazolidinone 2 protect the CˆO group from nucleophilic attack,
so that direct lithiation at the exocyclic CH2 group by BuLi is possible. Addition of an
aldehyde or unsymmetrical ketone to solutions of the lithium reagent Li-2 affords
adducts 3 (1,2-addition) in high yields and good-to-excellent diastereoselectivities.
Hg2‡-Promoted hydrolysis of the N,S-acetal moiety of 3 yields (protected) 2-hydroxy
1
)
)
Part of the Ph.D. thesis of C. G., Dissertation No. 14516, ETH Z¸rich, 2002.
2
Oxazolidinone 1 and its enantiomer are commercially available as (S)- and (R)-DIOZ (5,5-diphenyl-4-
isopropyl-1,3-oxazolidin-2-one): Shiratori Pharmaceutical Co., Ltd., Japan. DIOZ is also offered by Onyx
Scientific, Ltd., UK. Compound 1 has been mentioned in a patent [1]. An Organic Syntheses Procedure [2]
has been submitted, a copy of which will be provided by the correspondence author upon request.
The superior properties of auxiliary 1, as compared to the Evans auxiliaries, are discussed in [3].
For independent work with auxiliary 1 by other groups, see [4].
Oxazolidinone 1 has also been prepared by others, but not utilized as a chiral auxiliary [5].
For earlier work with analogous thiazolidinethiones, see Mukaiyama [7]. For a general discussion of
geminal-diarylmethanol derivatives, see Chapt. 11 in a recent review article [8a] and Scheme 17 in a book
chapter [8b].
3
4
5
6
)
)
)
)

Helvetica Chimica Acta Vol. 85 (2002)
773
aldehydes, which can be either reduced or trapped in situ with carbon nucleophiles to
give enantiomerically pure, selectively protected 1,2-diols, with recovery of the chiral
auxiliary 1 (Scheme 1).
Scheme 1. Overall Enantioselective Preparation of Specifically Protected 1,2-Diols with Formation of the Central
C,C-Bond (DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene)
O
O
2 steps
BuLi
O
N
SMe
O
NH
Boc-valine ester
MeSCH2Cl
Ph
Ph
Ph
Ph
1
2
O
SCH3
R1
R3
1) BuLi
1) Hg2+, H2O, then DBU
2) H– or Grignard reagent
O
N
2) R1COR2
R1
+
1
R2 OPG
HO
3) Protection
Ph
Ph
R2 OPG
3
PG = protecting group or H
R1, R2 = H, Alkyl or Aryl
selectively protected 1,2-diol
R1, R2, R3 = H, Alkyl or Aryl
We have now explored the scope and limitations of 1,4-additions of Li-2 to
conjugated enones and enoates. A survey of the literature reveals that there have been
only two reagents reported for the overall enantioselective nucleophilic formylation of
enones (Fig. 1). The synthetic use of the lithiated S,S-acetal S-oxide A of Scolastico and
co-workers is rather limited [11], but formaldehyde SAMP-hydrazone B of Lassaletta,
Enders, and their co-workers [12] undergoes conjugate addition to a wide range of a,b-
unsaturated carbonyl compounds7), leading, after release of the masked carbonyl
group, to 4-oxo aldehydes or derivatives thereof.
OMe
O
N
N
Tol
Tol
S
S
Li
H
H
A
B
Enders/Lassaletta
Scolastico
Fig. 1. Reagents that are synthetically equivalent to a chiral formyl anion and used in 1,4-additions to a,b-
unsaturated carbonyl compounds
In the present paper, we describe the diastereoselective conjugate addition of
[(methylthio)methyl]-oxazolidinone 2 to a series of chalcones, trityl (triphenylmethyl)-
7
)
For Michael additions of SAMP-hydrazone B to nitroalkenes, see [13].

774
Helvetica Chimica Acta Vol. 85 (2002)
enones, and a 2,6-di(tert-butyl)-4-methoxyphenyl (BHA) cinnamate, as well as further
elaborations of the adducts to enantiomerically pure 1,4-diols, a g-lactol ether, and a 4-
hydroxytrityl ketone.
2. Addition of [(Methylthio)methyl]-oxazolidinone 2 to Chalcones, Trityl Enones,
and an a,b-Unsaturated BHA Ester. The N,S-acetal 2 was obtained from oxazolidinone
1 by N-alkylation with (chloromethyl) methyl sulfide (Scheme 1). Sequential treatment
of compound 2 with BuLi at À788 and a chalcone8) 4 at À1008 gave the products of
conjugate addition 5 and 6 in good yields and excellent regio- and diastereoselectivities.
In Scheme 2, we have summarized the results obtained from this addition reaction. In
each case, only two of the four possibe diastereoisomers were formed. Major isomers 5
and minor isomers 6 have the same configuration at MeSÀC(1) and are epimeric9) at
Aryl1ÀC(2). After flash chromatography, 90 99% diastereoisomerically pure prod-
ucts 5 were obtained in 65 80% yield. The diastereoselectivity of the reaction is >90%
Scheme 2. Addition of Lithiated [(Methylthio)methyl]-oxazolidinone Li-2 to Chalcones
O
O
SMe
SMe
O
Aryl2
Aryl2
O
N
O
N
Aryl1
Aryl2
(4)
BuLi,
THF, –100°
+
2
Aryl1
O
Aryl1
O
Ph
Ph
Ph
Ph
5
6
___________________________________________________________________
Aryl1
Yield [%]b)
Products 5 and 6a)
Aryl2
dr (5/6)c)
Entry
___________________________________________________________________
Ph
1
2
3
4
5
6
a
Ph
79
72
71
71
65
70
98:2
>99:1
>99:1
96:4
Ph
CH=CHPh
1-naphthyl
5-methylfuran-2-yl
Ph
b
c
d
e
f
Ph
Ph
4-(MeO)C6H4
4-ClC6H4
91:9
Ph
96:4
___________________________________________________________________
a) Products derived from 1,2-addition can also be detected by 1H-NMR of the crude product in
some cases. Entry 1: 9%, Entry 5: 22%, Entry 6: 8%. b) Combined yield of both isomers 5 and
6 after FC. c) Determined by 1H-NMR (300 MHz) after FC.
8
9
)
References to the preparation of compounds 4c, 4d, 7a 7c, 7e, and a procedure for the preparation of
compound 7d are given in the Exper. Part.
)
The relative configuration of adducts 5c, 8b, of N,O-acetal 10, and of compounds 11 and 17 were
unambiguously assigned by single-crystal X-ray analysis. The X-ray structures and comparison of Rf values
of major and minor isomers led to configurational assignments of the other compounds by analogy (see
formulae in Schemes). Graphical illustrations and full experimental data associated with the X-ray crystal
structures of compounds 5c, 8b, 10, 11, 17, and of related compounds that are mentioned in [10] will be
published later in this journal.

Helvetica Chimica Acta Vol. 85 (2002)
775
in most cases, as determined by 1H-NMR spectroscopy of the crude products.
Formation of products derived from 1,2-addition takes place to only a small extent
(<10%, except for Entry 5).
We next turned our attention to the reaction of Li-2 with trityl enones 7a d and
BHA ester 7e. The Michael acceptors8) 7a e with −sterically protected but electroni-
cally effective carbonyl groups×10) are known to undergo −sterically enforced× 1,4-
additions with various carbon nucleophiles, even with the most reactive nucleophiles
such as BuLi or lithiumdithiane11). As is evident from the data in Scheme 3, Li-2 adds
particularly effectively to the b-monosubstituted trityl enones 7a (Entry 1) and 7b
(Entry 2). The adducts 8a and 8b were obtained as single diastereoisomers in 83% and
51% yield, respectively. The reaction of Li-2 with b,b-disubstituted trityl enones 7c
(Entry 3) and 7d (Entry 4), which would lead to the creation of quaternary stereogenic
centers, resulted in recovery of starting material or in isolation of a complex mixture of
products. We assume that proton abstraction, rather than nucleophilic addition, is the
predominant reaction of Li-2 with enone 7c. Conjugate addition of the lithiated N,S-
acetal 2 to BHA ester 7e is possible, although the yield of the reaction is low (Entry 5).
Scheme 3. Addition of Lithiated [(Methylthio)methyl]-oxazolidinone Li-2 to Trityl Enones and an a,b-
Unsaturated BHA Ester (BHA: 2,6-di(tert-butyl)-4-methoxyphenyl)
O
SMe
R2
R3
O
O
N
R1
R3
(7)
BuLi,
THF, –78°
R2
R1
2
O
Ph
Ph
8
___________________________________________________
R1
Yield of 8 [%]a)
Product 8
R2
R3
Entry
___________________________________________________
1
a
b
c
83
51
Ph
H
Ph3C
Ph3C
2
Me
H
3b)
–c)
–d)
30
Ph
Me
Ph
Ph3C
Ph3C
OBHA
d
e
4
5
CF3
Ph
H
___________________________________________________
a) Yield of a single diastereoisomer after FC. b) The C=C bond
geometry of this trityl enone is unknown. c) No reaction.
d) Complex mixture of products.
As reported previously [10], reactions of Li-2 with a,b-unsaturated aldehydes (e.g.,
methacrolein) and ketones (others than chalcones and trityl enones; e.g., cyclo-
hexenone) give exclusively 1,2-adducts. In the course of our investigations, several
attempts have been undertaken to achieve conjugate addition of Li-2 (or a derivative
10
)
)
For the use of this term, see, e.g., [14 16].
For Michael additions of carbon nucleophiles to trityl enones and to BHA esters, see, e.g., [15] and [16],
11
respectively.

776
Helvetica Chimica Acta Vol. 85 (2002)
thereof) to −standard× Michael acceptors by modifying reaction conditions and reagents.
For example, hexamethylphosphoramide (HMPA) [17a] and 3,4,5,6-tetrahydro-1,3-
dimethylpyrimidin-2(1H)-one (DMPU) [17b,c] are frequently used as additives to
cause reversal of regioselectivity (from 1,2- to 1,4-addition) in the reaction of
organolithium reagents to a,b-unsaturated carbonyl compounds12). In our case, the
presence of DMPU in the reaction of Li-2 with cyclohexenone did not yield the desired
1
effect; only the product of 1,2-addition could be detected by H-NMR spectroscopy.
Furthermore, it is known that lithiated S,S-acetals with additional anion-stabilizing
groups (such as the Me3Si group) and S,S-acetal S-oxides have an enhanced tendency
toward conjugate addition as compared to simple S,S-acetals13). Therefore, we
prepared the Me3Si-substituted derivative of N,S-acetal 2 (2, BuLi, Me3SiCl, THF)14
)
and the S-oxide derivative of N,S-acetal 2 (2, NalO4, H2O, MeOH)15). Unfortunately,
efforts to lithiate these derivatives with BuLi led to the formation of decomposition
products, which were not identified. Also, transmetallation of Li-2 to the corresponding
cuprate and subsequent addition of cyclohexenone did not give the desired product of
1,4-addition but, instead, resulted in decomposition of the educt, probably caused by
the high affinity of copper for sulfur in the reagent Li-2 (a-elimination).
Based on both the data obtained by X-ray crystallography and our structural studies
on Li-2 [10c], the steric course of the Michael addition leading to the major isomers 5
and 8 can be deduced. The Michael acceptor approaches the lithiated C-atom of Li-2
((4S,1'S)-configuration; Fig. 2, left) with its Re face, in an orientation that allows
transfer of the Li-atom from Li-2 to the enone O-atom (Fig. 2, right). The reaction
proceeds with relative topicity unlike.
R
O
O
R
Li
(S)
N SMe
O
Li
Aryl
O
Re
Si
H
H
H
(S)
Ph
N
SMe
SMe
Ph
Aryl
relative topicity ul (Si/Re) or (S/Re)
Li-2
Fig. 2. Proposed structure of Li-2 and a model for the stereochemical course of the conjugate addition of Li-2 to
chalcones, trityl enones, and a,b-unsaturated BHA esters
3. Conversion of the Adducts 5 and 8 to 1,4-Diols, a −g-Lactol Ether×, and a 3-
Hydroxypropyl Trityl Ketone. The synthetic value of chalcone adducts 5 for the
preparation of interesting chiral building blocks is demonstrated in Schemes 4 6.
12
)
)
For a recent study on the effects of HMPA and DMPU on the regioselectivity of addition of organolithium
reagents to enones and enals, see [17d] and references cited therein.
For examples of Michael additions of lithiated S,S-acetals with additional anion-stabilizing groups, lithiated
S,S-acetal S-oxides, and copper S,S-acetals to a,b-unsaturated carbonyl compounds, see Chapt. 3.5 in a
review article [18].
13
14
15
)
)
Obtained as a ca. 95 :5 mixture of diastereoisomers after trituration of the crude product in hexane.
Obtained as a ca. 2.5 :1 mixture of diastereoisomers (crude product).

Helvetica Chimica Acta Vol. 85 (2002)
777
Originally, we intended to hydrolyze the N,S-acetal moiety of 5 in order to obtain the
corresponding enantiomerically pure 4-oxo aldehydes (or derivatives thereof).
However, subjecting adduct 5a to the reaction conditions that were used for the
hydrolysis of 1,2-adducts 3 (Hg(O2CCF3)2, H2O, THF, then DBU; see Scheme 1 and
[10]) resulted in the formation of the cyclic enol ether 9 (Scheme 4). Obviously,
compound 9 is derived from an intramolecular attack of the intermediate acyliminium
ion by the carbonyl O-atom of the phenylcarbonyl moiety. Recrystallization of 9 in
MeOH gave the N,O-acetal 10 as a single diastereoisomer. Treatment of compounds 9
or 10 with aqueous or methanolic acid did not yield the desired 4-oxo aldehydes either,
but, instead, led to a complex mixture of products. Attempts to protect the
phenylcarbonyl group of 5a as an O,O-acetal prior to hydrolysis of the N,S-acetal, in
order to prevent the cyclization (5a ! 9), were also unsuccessful.
Scheme 4. An Unexpected Cyclization Reaction 5a ! 9
Ph
H
Ph
H
O
O
OMe
Ph
Ph
O
N
O
O
N
O
Hg2+, H2O, THF
MeOH
5a
Ph
Ph
Ph
Ph
10
9
(main product; sole product under
non-aqueous reaction conditions)
Subsequently, we decided to reduce the phenylcarbonyl moiety of 5a and then
cleave the N,S-acetal, with the hope to obtain −4-hydroxy aldehydes× ( ! −g-lactols×,
−homoaldol products×) or after an additional reduction step 1,4-diols. Treatment of
ketone 5a with NaBH4 provided the secondary alcohols 11 and 12 in excellent yield as a
1:1 mixture (Scheme 5). The reduction of 5a could also be conducted diastereose-
lectively, e.g., a 97:3 mixture 11/12 was obtained with i-PrOH and a chiral RuII
catalyst16). Addition of Hg(O2CCF3)2 to a solution of 11 in THF led to the cyclized
product17) 13. N,O-Acetal 13, isolated in 94% yield as a single diastereoisomer, is, in
contrast to the −unsaturated× analog 9, a stable compound, and, importantly, it can be
cleaved with H2SO4 in MeOH to the disubstituted −g-lactol ether× 15 and the auxiliary 1
in very high yield.
16
)
)
The Noyori catalyst (S,S)-i was used in the diastereoselective reduction of 5a (see Exper. Part). For the
preparation of catalyst i, see [19].
Ts
Ph
Ph
N
Ru
i
N
H
17
The diastereoisomeric alcohol 12 could also be cyclized to the corresponding N,O-acetal under the same
reaction conditions.

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Helvetica Chimica Acta Vol. 85 (2002)
Scheme 5. Conversions of the Chalcone Adduct 5a to a −g-Lactol Ether× and to Selectively Protected 1,4-Diols
(BOMCl: benzyl chloromethyl ether, DMAP: 4-(dimethylamino)pyridine)
5a
NaBH4
O
O
SMe
SMe
Ph
Ph
O
N
O
N
+
Ph
OH
Ph
OH
Ph
Ph
Ph
Ph
11
94%, 1:1 mixture
(97:3 mixture with i-PrOH/RuII catalyst)
12
BOMCl
i-Pr2NEt
Hg2+
THF
Ac2O
DMAP
Ph
O
O
O
O
SMe
SMe
H
Ph
OAc
Ph
OBOM
Ph
N
O
O
N
O
N
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
17 (71%)
14 (95%)
13 (94%)
1) Hg2+, H2O
H+, MeOH
1) Hg2+, H2O
1) Hg2+, H2O
2) MeMgCl
2) NaBH4, DBU
2) NaBH4, DBU
OMe
Ph
OAc
Ph
Ph
OBOM
Ph
O
HO
HO
HO
Ph
Ph
Ph
OBOM
Ph
15 (87%)a)
18 (89%)c)
19
16 (80%)b)
(83%, 3:1 mixture of
epimers)
a) Compound 15 was obtained as a 97:3 mixture with its C(3)-epimer. b) Compound 16 was obtained as a 97 :3
mixture with its C(3)-epimer. c) Compound 18 was obtained as a 96 :4 mixture with its C(2)-epimer.
Alternatively, the OH group of alcohol 11 was protected first, e.g., with Ac2O and 4-
(dimethylamino)pyridine (DMAP), to give in 95% yield the O-acetyl derivative 14,
which was then treated with aqueous Hg(O2CCF3)2 to provide the corresponding
N,OH-hemiacetal (MeS/OH displacement; OH protection prevents 14 from cyclizing).
Treatment of a THF/H2O solution of the hemiacetal with DBU generated the auxiliary

Helvetica Chimica Acta Vol. 85 (2002)
779
1 and the 4-OAc aldehyde, which was reduced in situ by NaBH4 to give the selectively
protected, disubstituted, enantiomerically pure 1,4-diol 16 of unlike-configuration
(80% yield from 14 to 16). Similarly, the diastereoisomeric alcohol 12 was BOM-
protected ( ! 17), and treated with Hg(O2CCF3)2 and NaBH4/DBU to furnish in 89%
yield the selectively protected, disubstituted, enantiomerically pure 1,4-diol 18 of like-
configuration. It is also possible to add a Grignard reagent to the N,OH-hemiacetals to
obtain trisubstituted 1,4-diols (in a C,C-bond-forming process and with generation of a
third stereogenic center): thus, the diol derivative 19 was prepared from 17 in 83% yield
as a 75 :25 mixture of diastereoisomers, according to this procedure. Fortunately, no (in
case of 19) or only marginal (in case of 15, 16, and 18) epimerization18) at C(3) and
C(2), respectively, had occurred during the preparation of the −g-lactol ether× 15 and of
the 1,4-diols 16, 18, and 19, although the intermediate 2-Ph-substituted aldehyde must
be highly susceptible to epimerization.
It is important to note that all processes described above involve the recycling of the
chiral auxiliary 1. Usually, oxazolidinone 1 precipitates in the course of these
transformations and is isolated in 75 85% yield, ready for the next use by simple
filtration, washing, and drying.
Experiments toward the elaboration of adduct 8a, derived from conjugate addition
of Li-2 to trityl enone 7a, were also carried out (Scheme 6). Hg2‡-Mediated hydrolysis
of the N,S-acetal moiety of 8a, followed by addition of NaBH4 and DBU gave the 3-
hydroxypropyl trityl ketone 20 in 70% yield, with recovery of the auxiliary 1. Clearly,
cyclization (cf. 5a ! 9) did not occur due to the steric bulk of the trityl group. It is
known that trityl ketones of type 20 can be reduced to the corresponding
monosubstituted 1,4-diols with LiBHEt3 (Super-Hydride) [15].
Scheme 6. Conversion of the Trityl Enone Adduct 8a to a 3-Hydroxypropyl Trityl Ketone
O
SMe
CPh3
1) Hg2+, H2O
2) NaBH4, DBU
CPh3
O
N
HO
Ph
O
Ph
Ph
O
Ph
8a
20 (70%)
4. Conclusions. In summary, an efficient and simple method for the enantiose-
lective preparation of selectively protected, di- and trisubstituted 1,4-diols, and
disubstituted −g-lactol ethers× from chalcones has been developed. The procedure
involves the high-yielding and diastereoselective conjugate addition of the lithiated
[(methylthio)methyl]-oxazolidinone Li-2 to chalcones (nucleophilic formylation). The
reaction of Li-2 with trityl enones also proceeds smoothly and gives access to 3-
hydroxypropyl trityl ketones, which may be used for the synthesis of enantiomerically
pure, monosubstituted 1,4-diols.
18
)
To suppress epimerization, it is essential to add first NaBH4, and then DBU to the solution of the N,OH-
hemiacetal in THF/H2O.

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Helvetica Chimica Acta Vol. 85 (2002)
We are grateful to B. Schweizer for determination of the X-ray crystal structures of compounds 5c, 8b, 10,
11, and 17. We thank B. Jaun for his help toward the elucidation of the relative configuration of compound 15 and
its diastereoisomers. We gratefully acknowledge Novartis Pharma AG, Basel, for donation of 4-isopropyl-5,5-
diphenyloxazolidin-2-one and for continuing financial support.
Experimental Part
General. Abbreviations: BOMCl: benzyl chloromethyl ether, DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene,
DMAP: 4-(dimethylamino)pyridine, FC: flash chromatography, dp: diastereoisomer purity, dr: diastereoisomer
ratio, h.v.: high vacuum (0.01 0.1 Torr). BuLi was used as a ca. 1.6m soln. (hexane), AlMe3 as a ca. 1.8m soln.
(heptane), and MeMgCl as a ca. 1.5m soln. (THF). THF was freshly distilled from K before use. Toluene was
freshly distilled from Na before use. CH2Cl2, DBU, i-Pr2NEt, and Et3N were distilled from CaH2 and stored over
4-ä molecular sieves. Solvents for FC and workup procedures were distilled from Sikkon (anh. CaSO4, Fluka)
or KOH/FeSO4 (Et2O). All other solvents and reagents were used as purchased from Fluka, Aldrich, J.T. Baker,
Scharlau, or Merck KGaA. Reactions involving air- or moisture-sensitive reagents or intermediates were
performed under Ar in glassware, which had been oven- or heat-gun dried under h.v. The chalcones 4c and 4d
were prepared from the corresponding aldehydes and methyl ketones with catalytic amounts of NaOH in
MeOH [20]. All other chalcones were purchased from Fluka or Lancester. The trityl enones 7a 7c were
prepared according to a literature procedure [15c], for the preparation of trityl enone 7d, see Exper. Part below.
The a,b-unsaturated BHA ester 7e was prepared from cinnamoyl chloride and lithium 2,6-di(tert-butyl)-4-
methoxyphenoxide in THF in 84% yield19). The chiral RuII catalyst i was prepared according to the procedure in
[19]. TLC: Merck silica gel 60 F254 plates; visualization by UV254 light and by dipping into phosphomolybdic acid
soln. (25 g of phosphomolybdic acid, 10g of Ce(SO 4)2 ¥ H2O, 60ml of conc. H 2SO4, 940ml of H 2O), followed by
heating with a heat-gun. FC: Fluka silica gel 60 (40 63 mm, at ca. 0.2 bar). M.p.: B¸chi-510 apparatus,
uncorrected. Optical rotations: Perkin-Elmer 241 polarimeter (10cm, 1-ml cell) at r.t. IR Spectra: Perkin-
Elmer 1600 FT-IR spectrophotometer; in cmÀ1. NMR Spectra: Bruker AMX-II-500 (1H: 500 MHz, 13C:
125 MHz), AMX-400 (1H: 400 MHz, 13C: 100 MHz), AMX-300 (1H: 300 MHz, 13C: 75 MHz), Varian Mercury
XL 300 (1H: 300 MHz, 19F: 282 MHz, 13C: 75 MHz); chemical shifts (d) in ppm downfield from internal TMS
(d ˆ 0.00 ppm); J values in Hz. MS: MALDI-MS (matrix-assisted laser-desorption ionization) and HR-
MALDI-MS: Ion Spec Ultima 4.7 FT Ion Cyclotron Resonance (ICR) mass spectrometer, 2,5-dihydroxybenzoic
acid matrix; FAB-MS (fast atom bombardment): VG ZAB-2-SEQ mass spectrometer, 3-nitrobenzyl alcohol
matrix; fragment ions in m/z with relative intensities (%) in parentheses. Elemental analyses were performed by
the Microanalytical Laboratory of the Laboratorium f¸r Organische Chemie, ETH-Z¸rich. Diastereoisomer
1
ratios were determined by H-NMR spectroscopy.
1. Addition of the N,S-Acetal 2 to Chalcones, Trityl Enones, and a BHA Ester. General Procedure 1 (GP 1).
To a soln. of N,S-acetal 2 (1 equiv.) in THF (0.2m) was added BuLi (1.1 1.2 equiv.) at À788. After stirring for
5 min, the mixture was cooled to À1008 (for the addition reaction to trityl enones, and the BHA ester, the temp.
was kept at À788), and a chalcone or trityl enone (1.2 1.3 equiv.) was added as a soln. in THF (ca. 1m). It was
allowed to warm to À788 within 10min, and then the reaction was stopped by quenching with sat. aq. NH 4Cl
soln. The mixture was diluted with Et2O, the org. layer was separated, and the aq. layer was extracted with
CH2Cl2 (2Â). The combined org. layers were dried (MgSO4) and concentrated under reduced pressure. The
crude product was purified by FC, trituration, and/or recrystallization.
2. Transformation of Some Adducts to 1,4-Diols and a 3-Hydroxypropyl Trityl Ketone with Hg(O2CCF3)2/
NaBH4/DBU. General Procedure 2 (GP 2). To a soln. (or suspension) of adduct (1 equiv.) in THF/MeCN/H2O
(2 :2 :1; 0.1m) was added Hg(O2CCF3)2 (1.1 equiv.) at r.t. After stirring for 5 min, H2O was added, and the
reaction mixture was diluted with Et2O. The org. layer was separated, and the aq. layer was extracted with Et2O
(2Â). The combined org. layers were dried (MgSO4) and concentrated under reduced pressure. The crude
product was dissolved in THF/H2O (4 :1; 0.15m), and NaBH4 (0.75 equiv.) and DBU (0.5 equiv.) were added
consecutively at 08. The auxiliary 1 precipitated in the course of the reaction. After stirring for 15 min, sat. aq.
NH4Cl soln. and Et2O were added, and the precipitate was filtered off. The precipitate was washed with sat. aq.
NH4Cl soln., H2O, and Et2O, and dried under h.v. to recover 1 as a white solid. The filtrate was diluted with Et2O,
19
)
Compound 7e was obtained in the manner previously described for the preparation of saturated BHA
esters [21]; BHA esters are readily cleaved by CAN (cerium ammonium nitrate) [16][21].

Helvetica Chimica Acta Vol. 85 (2002)
781
the org. layer was separated, and the aq. layer was extracted with Et2O (2Â). The combined org. layers were
dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by FC.
(S)-4-Isopropyl-3-[(1S,2R)-1-(methylsulfanyl)-4-oxo-2,4-diphenylbutyl]-5,5-diphenyloxazolidin-2-one20
)
(5a). Compound 2 (350 mg, 1.02 mmol) was treated with BuLi (0.79 ml, 1.23 mmol) and chalcone 4a (277 mg,
1.33 mmol) according to GP 1. Purification of the crude product by FC (CH2Cl2/pentane 3 :1 ! CH2Cl2 ‡ 1%
Et2O) yielded 5a (441 mg, 79%) as a 98 :2 mixture with its C(2)-epimer. For anal. purposes, a sample was
recrystallized (MeOH) to afford 5a (dr ꢀ99 :1). White solid. M.p. 224 2268. [a]rD:t: ˆ À99.8 (c ˆ 1, CHCl3). IR
(CHCl3): 3005m, 2954w, 1744s, 1682m, 1595w, 1487m, 1446m, 1405m, 1179m, 1092w. 1H-NMR (400 MHz,
CD2Cl2): 0.24 (d, J ˆ 6.9, Me); 0.83 (d, J ˆ 7.4, Me); 1.72 (s, MeS); 1.89 1.97 (m, Me2CH); 3.25 (dd, J ˆ 7.8, 17.1,
1 H, CH2); 3.86 (dd, J ˆ 4.8, 17.1, 1 H, CH2); 4.49 (d, J ˆ 1.7, NCH); 4.72 (d, J ˆ 10.9, CHSMe); 4.80( ddd, J ˆ
4.8, 7.8, 10.9, PhCH); 7.04 7.54 (m, 18 arom. H); 7.82 7.85 (m, 2 arom. H). 13C-NMR (100 MHz, CD2Cl2): 13.1,
15.6, 20.6 (Me); 30.0, 42.2 (CH); 45.4 (CH2); 68.9, 69.1 (CH); 87.8 (C); 125.5, 126.9, 127.7, 127.8, 128.2, 128.3,
128.7, 128.8, 128.86, 128.90, 133.2 (CH); 137.8, 139.6, 142.1, 145.0, 157.1, 197.6 (C). MALDI-MS: 572 (100, [M ‡
‡
‡
Na] ), 440(38, [ M À SMe À CO2 À H2O] ), 336 (32), 291 (50), 248 (56). Anal. calc. 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.
(S)-4-Isopropyl-3-[(1S,2R,E)-1-(methylsulfanyl)-4-oxo-2,6-diphenylhex-5-enyl]-5,5-diphenyloxazolidin-2-
one (5b). Compound 2 (350 mg, 1.02 mmol) was treated with BuLi (0.79 ml, 1.23 mmol) and 4b (312 mg,
1.33 mmol) according to GP 1. Purification of the crude product by FC (CH2Cl2/pentane 5 :1 ! CH2Cl2 ‡ 1%
Et2O) yielded 5b (421 mg, 72%) as a single diastereoisomer. White solid. M.p. 196 1988. [a]rD:t: ˆ À101.5 (c ˆ
1.1, CHCl3). IR (CHCl3): 3068w, 3008m, 1747s, 1610s, 1494m, 1450m, 1408m, 1324m, 1100w, 972w. 1H-NMR
(400 MHz, CDCl3): 0.32 (d, J ˆ 6.9, Me); 0.87 (d, J ˆ 7.3, Me); 1.83 (s, MeS); 1.93 2.02 (m, Me2CH); 2.94
(dd, J ˆ 8.1, 16.5, 1 H, CH2); 3.48 (dd, J ˆ 4.9, 16.5, 1 H, CH2); 4.47 (d, J ˆ 1.6, NCH); 4.64 (ddd, J ˆ 4.9, 8.1, 10.9,
PhCH); 4.82 (d, J ˆ 10.9, CHSMe); 6.62 (d, J ˆ 16.1, PhCHˆCH); 7.01 7.07 (m, 1 arom. H); 7.09 7.25
(m, 9 arom. H); 7.29 7.41 (m, 6 arom. H, 1 H, PhCHˆCH); 7.43 7.47 (m, 4 arom. H). 13C-NMR (100 MHz,
CDCl3): 13.1, 15.5, 20.3 (Me); 29.6, 42.1 (CH); 47.6 (CH2); 67.9, 68.7 (CH); 87.6 (C); 125.1, 126.3, 126.6, 127.35,
127.39, 127.7, 127.8, 128.1, 128.3, 128.4, 128.5, 128.9, 130.4 (CH); 134.5, 138.9, 141.2 (C); 142.2 (CH); 144.3, 157.1,
‡
‡
197.3 (C). MALDI-MS: 598 (42, [M ‡ Na] ), 484 (35, [M À SMe À CO2] ), 466 (38, [M À SMe À CO2 À
‡
H2O] ), 336 (62), 317 (43), 248 (200). Anal. calc. for C37H37NO3S (575.77): C 77.18, H 6.48, N 2.43, S 5.57;
found: C 77.06, H 6.33, N 2.48, S 5.56.
(S)-4-Isopropyl-3-[(1S,2R)-1-(methylsulfanyl)-4-(naphthalen-1-yl)-4-oxo-2-phenylbutyl]-5,5-diphenylox-
azolidin-2-one (5c). Compound 2 (380mg, 1.11 mmol) was treated with BuLi (0.86 ml, 1.34 mmol) and 4c
(373 mg, 1.44 mmol) according to GP 1. Purification of the crude product by FC (CH2Cl2/pentane 3 :1 !
CH2Cl2) yielded 5c (471 mg, 71%) as a single diastereoisomer. White solid. M.p. 188 1918. [a]rD:t: ˆ À97.9 (c ˆ 1,
CHCl3). IR (CHCl3): 3064w, 3008w, 2965w, 1748s, 1682m, 1494w, 1450m, 1409m, 1262m, 1101m, 1004m.
1H-NMR (400 MHz, CDCl3): 0.32 (d, J ˆ 6.9, Me); 0.87 (d, J ˆ 7.3, Me); 1.83 (s, SMe); 1.91 2.02 (m, Me2CH);
3.29 (dd, J ˆ 7.6, 16.6, 1 H, CH2); 3.92 (dd, J ˆ 4.7, 16.6, 1 H, CH2); 4.48 (d, J ˆ 1.6, NCH); 4.75 4.84
(m, CHSMe, PhCH); 7.03 7.27 (m, 9 arom. H); 7.29 7.33 (m, 4 arom. H); 7.39 7.48 (m, 5 arom. H); 7.63 7.65
(m, 1 arom. H); 7.79 7.82 (m, 1 arom. H); 7.89 7.91 (m, 1 arom. H); 8.10 8.12 ( m, 1 arom. H). 13C-NMR
(100 MHz, CDCl3): 13.2, 15.5, 20.3 (Me); 29.6, 42.4 (CH); 49.2 (CH2); 67.9, 68.7 (CH); 87.6 (C); 124.2, 125.1,
125.7, 126.3, 126.6, 126.7, 127.40, 127.42, 127.5, 127.7, 127.8, 128.2, 128.3, 128.47, 128.49 (CH); 130.0 (C); 131.1
‡
‡
(CH); 133.8, 136.7, 138.9, 141.0, 144.3, 157.0, 201.9 (C). MALDI-MS: 638 (6, [M ‡ K] ), 622 (100, [M ‡ Na] ),
‡
‡
‡
552 (9, [M À SMe] ), 508 (63, [M À SMe À CO2] ), 490(24, [ M À SMe À CO2 À H2O] ). Anal. calc. for
C39H37NO3S (599.79): C 78.10, H 6.22, N 2.34; found: C 77.94, H 6.25, N 2.32.
(S)-4-Isopropyl-3-[(1S,2R)-4-(5-methylfuran-2-yl)-1-(methylsulfanyl)-4-oxo-2-phenylbutyl]-5,5-diphenyl-
oxazolidin-2-one (5d). Compound 2 (355 mg, 1.04 mmol) was treated with BuLi (0.80 ml, 1.25 mmol) and 4d
(287 mg, 1.35 mmol) according to GP 1. Purification of the crude product by FC (CH2Cl2 ! CH2Cl2/Et2O 10 :1)
yielded 5d (407 mg, 71%) as a 96 :4 mixture with its C(2)-epimer. For anal. purposes, a sample was recrystallized
(MeOH) to afford 5d (dr ꢀ99 :1). White solid. M.p. 219 2228. [a]rD:t: ˆ À98.3 (c ˆ 1, CHCl3). IR (CHCl3):
3066w, 3008w, 1747s, 1665m, 1516s, 1494w, 1450w, 1409m, 1040w, 1004w, 926w. 1H-NMR (400 MHz, CDCl3): 0.33
(d, J ˆ 7.0, Me); 0.88 (d, J ˆ 7.3, Me); 1.86 (s, MeS); 1.92 2.01 (m, Me2CH); 2.32 2.33 (m, Me); 3.06 (dd, J ˆ
8.3, 16.3, 1 H, CH2); 3.59 (dd, J ˆ 4.9, 16.3, 1 H, CH2); 4.47 (d, J ˆ 1.6, NCH); 4.64 (ddd, J ˆ 4.9, 8.3, 10.9,
PhCH); 4.87 (d, J ˆ 10.9, CHSMe); 6.04 6.05 (m, 1 H of furan); 6.95 6.96 (m, 1 H of furan); 6.98 7.33
(m, 15 arom. H); 7.43 7.45 (m, 2 arom. ). 13C-NMR (100 MHz, CDCl3): 13.2, 14.0, 15.9, 20.3 (Me); 29.6, 41.9
20
)
The preparation and parts of the physical data of this compound have been reported before in [10b].

782
Helvetica Chimica Acta Vol. 85 (2002)
(CH); 44.6 (CH2); 67.8, 68.6 (CH); 87.6 (C); 108.8, 118.7, 125.1, 126.2, 127.3, 127.4, 127.68, 127.74, 128.1, 128.37,
‡
128.45 (CH); 139.0, 141.0, 144.3, 151.6, 157.1, 157.4, 185.9 (C). MALDI-MS: 592 (7, [M ‡ K] ), 576 (100, [M ‡
‡
‡
‡
‡
Na] ), 506 (29, [M À SMe] ), 462 (58, [M À SMe À CO2] ), 444 (17, [M À SMe À CO2 À H2O] ). Anal. calc. for
C34H35NO4S (553.72): C 73.75, H 6.37, N 2.53; found: C 73.56, H 6.20, N 2.66.
(S)-4-Isopropyl-3-[(1S,2R)-2-(4-methoxyphenyl)-1-(methylsulfanyl)-4-oxo-4-phenylbutyl]-5,5-diphenyloxaz-
olidin-2-one (5e). Compound 2 (349 mg, 1.02 mmol) was treated with BuLi (0.79 ml, 1.22 mmol) and 4e
(316 mg, 1.33 mmol) according to GP 1. Purification of the crude product by FC (CH2Cl2/pentane 7:1 !
CH2Cl2) yielded 5e (386 mg, 65%) as a 91:9 mixture with its C(2)-epimer. For anal. purposes, a sample was
recrystallized (MeOH) to afford 5e (drꢀ 99 :1). White solid. M.p. 189 1918. [a]rD:t: ˆ À106.3 (c ˆ 1, CHCl3). IR
(CHCl3): 3008w, 1744s, 1685m, 1611w, 1513s, 1036w, 1003w, 834w. 1H-NMR (400 MHz, CDCl3): 0.46 (d, J ˆ 6.4,
Me); 0.96 (d, J ˆ 7.3, Me); 1.97 (s, MeS); 2.00 2.09 (m, Me2CH); 3.18 (dd, J ˆ 8.0, 17.0, 1 H, CH2); 3.67
(s, MeO); 3.84 (dd, J ˆ 4.6, 17.0, 1 H, CH2); 4.43 (d, J ˆ 1.6, NCH); 4.47 4.53 (m, PhCH); 5.01 (d, J ˆ 11.3,
CHSMe); 6.55 6.57 (m, 2 arom. H); 7.13 7.21 (m, 8 arom. H); 7.31 7.40( m, 6 arom. H); 7.45 7.52 (m, 1 ar-
om. H); 7.81 7.83 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 14.1, 15.7, 20.3 (Me); 29.6, 41.4 (CH); 45.7
(CH2); 54.9 (Me); 67.6, 68.3 (CH); 87.5 (C); 113.8, 124.9, 126.7, 127.36, 127.41, 127.7, 127.9, 128.3, 128.4, 128.8,
‡
132.8 (CH); 132.9, 137.3, 139.0, 144.2, 157.2, 158.4, 197.7 (C). MALDI-MS: 602 (20, [M ‡ Na] ), 488 (31, [M À
‡
‡
SMe À CO2] ), 470(16, [ M À SMe À CO2 À H2O] ), 366 (37), 251 (100), 248 (82). Anal. calc. for C36H37NO4S
(579.76): C 74.58, H 6.43, N 2.42; found: C 74.64, H 6.58, N 2.44.
(S)-3-[(1S,2R)-2-(4-Chlorophenyl)-1-(methylsulfanyl)-4-oxo-4-phenylbutyl]-4-isopropyl-5,5-diphenylox-
azolidin-2-one (5f). Compound 2 (349 mg, 1.02 mmol) was treated with BuLi (0.79 ml, 1.22 mmol) and 4f
(323 mg, 1.33 mmol) according to GP 1. Purification of the crude product by FC (CH2Cl2/pentane 3 :1 !
CH2Cl2) yielded 5f (415 mg, 70%) as a 96 :4 mixture with its C(2)-epimer. For anal. purposes, a sample was
recrystallized (MeOH) to afford 5f (drꢀ 99 :1). White solid. M.p. 196 1988. [a]rD:t: ˆ À109.5 (c ˆ 1, CHCl3). IR
(CHCl3): 3060w, 3008w, 1745s, 1685m, 1598w, 1492m, 1449m, 1411m, 1093w, 1003w, 836w. 1H-NMR (400 MHz,
CDCl3): 0.46 (d, J ˆ 7.0, Me); 0.97 (d, J ˆ 7.3, Me); 1.97 (s, MeS); 2.01 2.11 (m, Me2CH); 3.18 (dd, J ˆ 8.0, 17.2,
1 H, CH2); 3.67 (s, MeO); 3.86 (dd, J ˆ 4.5, 17.2, 1 H, CH2); 4.41 (d, J ˆ 1.6, NCH); 4.53 4.59 (m, PhCH); 5.00
(d, J ˆ 11.4, CHSMe); 6.97 7.00 (m, 2 arom. H); 7.14 7.25 (m, 8 arom. H); 7.32 7.43 (m, 6 arom. H); 7.47
7.51 (m, 1 arom. H); 7.81 7.83 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 14.1, 15.7, 20.4 (Me); 29.6, 41.5
(CH); 45.4 (CH2); 67.1, 68.8 (CH); 87.6 (C); 124.7, 126.6, 127.4, 127.6, 127.7, 127.9, 128.4, 128.5, 128.6, 129.3 (CH);
‡
132.9 (C); 133.0 (CH); 137.0, 138.7, 139.5, 144.0, 157.1, 197.2 (C). MALDI-MS: 606 (15, [M ‡ Na] ), 492 (23,
‡
‡
[M À SMe À CO2] ), 474 (27, [M À SMe À CO2 À H2O] ), 370(35), 255 (47), 248 (1)0. Anal. calc. for
C35H34NO3SCl (584.18): C 71.96, H 5.87, N 2.40; found: C 71.92, H 5.90, N 2.47.
(E)-5,5,5-Trifluoro-1,1,1,4-tetraphenylpent-3-en-2-one (7d). 1,1,1-Triphenylpropan-2-one (3.30g,
11.5 mmol) was dissolved in toluene (45 ml) and treated with AlMe3 (8.30ml, 14.9 mmol) at r.t. After refluxing
for 4 h, the mixture was cooled to 08, and trifluoroacetophenone (3.10ml, 23.0mmol) was added. The mixture
was stirred for 1 h and was then poured into sat. aq. NH4Cl soln. After stirring for another 30min, the mixture
was filtered over Celite. The org. layer was separated, and the aq. layer was extracted with Et2O (3Â). The
combined org. layers were dried (MgSO4) and concentrated under reduced pressure to yield the crude aldol
product as a yellow oil. The crude aldol product was dissolved in CH2Cl2 (35 ml) and Et3N (7.00 ml, 50.0 mmol),
and a soln. of MeSO2Cl (1.00 ml, 12.9 mmol) in CH2Cl2 (8 ml) were added dropwise at 08. After the mesylation
was complete (usually instantaneously), DBU (3.80ml, 25.4 mmol) was added, and the mixture was stirred for
60h at r.t. Then, H 2O was added, the org. layer was separated, and the aq. layer was extracted with Et2O (3Â).
The combined org. layers were washed with 1m HCl (1Â), H2O (1Â), and sat. aq. NaCl soln. (1Â), dried
(MgSO4), and concentrated under reduced pressure. Recrystallization (hexane) of the crude product yielded 7d
(437 mg, 9%). Yellow solid. M.p. 128 1318. IR (CHCl3): 3063w, 3009w, 1712s, 1641w, 1600w, 1494m, 1448m,
1279s, 1177s, 1136s, 1034w, 882w. 1H-NMR (300 MHz, CDCl3): 6.92 (d, J ˆ 1.6, CHˆC); 7.05 7.38 (m, 20ar-
om. H). 13C-NMR (75 MHz, CDCl3): 72.3 (C); 127.3, 128.1, 128.4, 129.0, 129.96, 130.03, 130.5, 131.1 (CH, C);
140.0 (q, J(C,F) ˆ 30.5, CF3); 141.2, 195.2 (C). 19F-NMR (282 MHz, CDCl3): À67.65 (s, CF3). MALDI-MS: 465
‡
‡
(14, [M ‡ Na] ), 347 (18), 273 (61), 243 (100, [Ph3C] ). Anal. calc. for C29H21F3O (442.48): C 78.72, H 4.78;
found: C 78.57, H 5.02.
(S)-4-Isopropyl-3-[(1S,2R)-1-(methylsulfanyl)-4-oxo-2,5,5,5-tetraphenylpentyl]-5,5-diphenyloxazolidin-2-
one (8a). Compound 2 (900 mg, 2.64 mmol) was treated with BuLi (1.87 ml, 2.90 mmol) and 7a (1.19 g,
3.17 mmol) according to GP 1. Purification of the crude product by FC (pentane/Et2O 5 :1) yielded 8a (1.57 g,
83%) as a single diastereoisomer. White solid. M.p. 212 2148. [a]rD:t: ˆ À60.2 (c ˆ 1, CHCl3). IR (CHCl3): 3062w,
3006w, 2963w, 1745s, 1712s, 1601w, 1494m, 1450m, 1409m, 1364w, 1324w, 1093w, 1035w, 1004w, 913w. 1H-NMR
(400 MHz, CDCl3): 0.44 (d, J ˆ 7.0, Me); 0.84 (d, J ˆ 7.3, Me); 1.81 (s, MeS); 1.93 2.00 (m, Me2CH); 2.84

Helvetica Chimica Acta Vol. 85 (2002)
783
(dd, J ˆ 10.0, 18.3, 1 H, CH2); 3.28 (dd, J ˆ 2.4, 18.3, 1 H, CH2); 4.25 4.30( m, PhCH); 4.32 (d, J ˆ 1.6, NCH);
4.78 (d, J ˆ 11.3, CHSMe); 6.95 7.32 (m, 30arom. H). 13C-NMR (100 MHz, CDCl3): 14.4, 16.0, 20.1 (Me); 29.6,
42.5 (CH); 48.1 (CH2); 67.2, 68.4 (CH); 72.0, 87.4 (C); 124.8, 126.6, 126.7, 127.3, 127.38, 127.41, 127.7, 127.9, 128.41,
‡
128.44, 130.3 (CH); 139.0, 140.4, 142.4, 144.1, 157.0, 206.2 (C). MALDI-MS: 738 (100, [M ‡ Na] ), 624 (87,
‡
‡
[M À SMe À CO2] ), 460(27), 457 (83), 243 (16, [Ph 3C] ). Anal. calc. for C48H45NO3S (715.95): C 80.53, H 6.33,
N 1.96, S 4.48; found: C 80.48, H 6.50, N 1.98, S 4.48.
(S)-4-Isopropyl-3-[(1S,2S)-2-methyl-1-(methylsulfanyl)-4-oxo-5,5,5-triphenylpentyl]-5,5-diphenyloxazoli-
din-2-one (8b). Compound 2 (210 mg, 0.615 mmol) was treated with BuLi (0.48 ml, 0.783 mmol) and 7b
(250 mg, 0.800 mmol) according to GP 1. Purification of the crude product by FC (pentane/Et2O 5 :1) and
subsequent trituration (boiling hexane, 2 Â 5 ml) yielded 8b (204 mg, 51%) as a single diastereoisomer. White
solid. M.p. 207 2098. [a]rD:t: ˆ À105.0 (c ˆ 0.945, CHCl3). IR (CHCl3): 3060w, 3008w, 2970w, 1747s, 1709m,
1599w, 1493m, 1449m, 1410m, 1092w, 1038w, 1004w. 1H-NMR (400 MHz, CDCl3): 0.58 (d, J ˆ 6.6, Me); 0.69
(d, J ˆ 6.9, Me); 1.05 (d, J ˆ 7.3, Me); 1.62 (s, MeS); 2.09 2.20 (m, Me2CH); 2.53 (dd, J ˆ 8.0, 18.1, 1 H, CH2);
2.86 2.96 (m, MeCH); 3.13 (dd, J ˆ 3.1, 18.1, 1 H, CH2); 4.34 (d, J ˆ 10.6, CHSMe); 4.51 (d, J ˆ 1.8, NCH);
7.18 7.34 (m, 21 arom. H); 7.45 7.47 (m, 2 arom. H); 7.64 7.67 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3):
12.8, 16.2, 17.2, 20.8 (Me); 29.8, 32.0 (CH); 45.6 (CH2); 68.5, 68.9 (CH); 73.3, 87.7 (C); 125.3, 126.5, 126.7, 127.5,
‡
127.9, 128.0, 128.5, 130.5 (CH); 138.9, 142.5, 144.7, 156.8, 207.0 (C). MALDI-MS: 676 (14, [M ‡ Na] ), 562 (55,
‡
‡
[M À SMe À CO2] ), 396 (56), 243 (100, [Ph3C] ). Anal. calc. for C43H43NO3S (653.88): C 78.99, H 6.63, N 2.14,
S 4.90; found: C 78.97, H 6.74, N 2.19, S 4.95.
2,6-Di(tert-butyl)-4-methoxyphenyl (1S,2R)-4-[(S)-4-Isopropyl-2-oxo-5,5-diphenyloxazolidin-3-yl]-4-
(methylsulfanyl)-3-phenylbutanoate (8e). Compound 2 (207 mg, 0.606 mmol) was treated with BuLi (0.47 ml,
0.727 mmol) and 7e (289 mg, 0.788 mmol) according to GP 1. Purification of the crude product by FC (pentane/
Et2O 5 :1) yielded 8e (130mg, 30%) as a single diastereoisomer. White solid. M.p. 228 229 8. [a]rD:t: ˆ À78.0( c ˆ
1, CHCl3). IR (CHCl3): 3008w, 2964m, 1751s, 1589w, 1449w, 1416w, 1366w, 1301w, 1262w, 1135m, 1105w, 1062w,
1004w. 1H-NMR (400 MHz, CDCl3): 0.74 (d, J ˆ 6.9, Me); 0.90 (s, t-Bu); 1.24 (d, J ˆ 7.5, Me); 1.38 (s, t-Bu); 1.53
(s, MeS); 2.25 2.34 (m, Me2CH); 3.02 (dd, J ˆ 11.5, 17.4, 1 H, CH2); 3.55 (dd, J ˆ 2.2, 17.4, 1 H, CH2); 3.75
(s, MeO); 4.44 (d, J ˆ 11.5, CHSMe); 4.69 4.73 (m, PhCH); 4.77 (d, J ˆ 1.3, NCH); 6.72 (d, J ˆ 3.1, 1 arom. H);
6.82 (d, J ˆ 3.1, 1 arom. H); 7.18 7.39 (m, 11 arom. H); 7.42 7.44 (m, 2 arom. H); 7.64 7.66 (m, 2 arom. H).
13C-NMR (100 MHz, CDCl3): 11.1, 16.0, 22.4 (Me); 29.5 (CH); 30.8, 31.4 (Me); 35.0, 35.6 (C); 40.8 (CH2); 43.2,
55.2 (Me); 67.7, 68.2 (CH); 87.8 (C); 111.56, 111.60, 125.7, 126.4, 127.2, 127.7, 128.1, 128.3, 128.4, 128.5, 128.7
‡
(CH); 139.3, 141.3, 141.5, 143.4, 143.6, 143.7, 156.2, 157.1, 171.2 (C). MALDI-MS: 730(94, [ M ‡ Na] ), 616 (100,
‡
[M À SMe À CO2] ), 449 (39), 248 (35). Anal. calc. for C44H53NO5S (707.97): C 74.65, H 7.55, N 1.98, S 4.53;
found: C 74.58, H 7.64, N 2.02, S 4.53.
(S)-3-[(2S,3R)-2,3-Dihydro-3,5-diphenylfuran-2-yl]-4-isopropyl-5,5-diphenyloxazolidin-2-one20) (9). To a
soln. of 5a (400 mg, 0.728 mmol) in THF (5 ml) was added Hg(O2CCF3)2 (341 mg, 0.801 mmol) at r.t. After
stirring for 20min, H 2O was added, and the reaction mixture was diluted with Et2O. The org. layer was
separated, and the aq. layer was extracted with Et2O (2Â). The combined org. layers were dried (MgSO4) and
concentrated under reduced pressure. Purification of the crude product by FC (pentane/Et2O 4 :1, 1% Et3N)
and subsequent trituration (boiling hexane, 10ml) afforded 9 as a single diastereoisomer. Only small amounts of
product could be isolated due to the instability of the compound. White solid. M.p. 211 2138. [a]rD:t: ˆ ‡54.0
(c ˆ 1, CHCl3). IR (CHCl3): 3022w, 1754s, 1648w, 1602w, 1490m, 1445m, 1419m, 1374m, 1328w, 1252m, 1043m,
1010m, 1003m, 947m. 1H-NMR (400 MHz, CDCl3): 0.81 (d, J ˆ 6.7, Me); 0.91 (d, J ˆ 7.3, Me); 1.91 2.02
(m, Me2CH); 4.32 (dd, J ˆ 2.7, 7.3, PhCH); 4.68 (d, J ˆ 1.5, NCH); 5.47 (d, J ˆ 2.7, CCH); 5.98 (d, J ˆ 7.3,
NCHO); 6.76 6.78 (m, 2 arom. H); 7.10 7.16 ( m, 2 arom. H); 7.24 7.27 (m, 1 arom. H); 7.30 7.40 ( m, 10ar-
om. H); 7.53 7.55 (m, 3 arom. H); 7.67 7.69 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 15.6, 20.6 (Me);
29.5, 51.8, 68.6 (CH); 89.0(C); 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
‡
(CH); 129.9, 130.5, 141.3, 144.4, 155.2, 156.5 (C). MALDI-MS: 524 (100, [M ‡ Na] ), 458 (29), 248 (21). HR-
‡
MALDI-MS: 524.2196 (C34H31NO3, [M ‡ Na] ; calc. 524.2196).
4-Isopropyl-3-[(1S,2S,3R,5R)-5-methoxy-3,5-diphenyltetrahydrofuran-2-yl]-5,5-diphenyloxazolidin-2-
one20) (10). Compound 9 (30 mg, 0.060 mmol) was dissolved in MeOH (3 ml) at r.t. Colorless crystals were
formed upon standing for 3 days. The crystals were isolated and identified as compound 10 (single
diastereoisomer). White solid. M.p. 182 1848. [a]rD:t: ˆ À28.4 (c ˆ 0.5, CHCl3). IR (CHCl3): 3008w, 2963w,
1759s, 1602w, 1494w, 1449w, 1425w, 1381w, 1326w, 1129w, 1047w, 998m, 90 9w. 1H-NMR (400 MHz, CDCl3): 0.68
(d, J ˆ 6.7, Me); 0.82 (d, J ˆ 7.3, Me); 1.90 1.97 ( m, Me2CH); 2.56 (dd, J ˆ 6.3, 13.5, 1 H, CH2); 2.66 (dd, J ˆ
11.4, 13.5, 1 H, CH2); 3.11 (s, MeO); 4.03 4.08 (m, PhCH); 4.56 (d, J ˆ 1.6, NCH); 5.52 (d, J ˆ 8.3, CHO);
7.16 7.36 (m, 16 arom. H); 7.45 7.48 (m, 2 arom. H); 7.53 7.56 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3):

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Helvetica Chimica Acta Vol. 85 (2002)
14.9, 20.7 (Me); 29.7, 45.0 (CH); 47.4 (CH2); 49.4 (Me); 68.0 (CH); 88.5 (C); 92.4 (CH); 106.5 (C); 125.5, 126.0,
126.2, 126.9, 127.6, 127.9, 128.0, 128.12, 128.14, 128.4, 128.6 (CH); 138.9, 140.0, 140.2, 144.0, 156.6 (C). MALDI-
‡
‡
‡
MS: 556 (70, [M ‡ Na] ), 524 (47, [M ‡ Na À OMe] ), 458 (100, [M À OMe À CO2] ), 440(44, [ M À OMe À
‡
‡
CO2 À H2O] ), 248 (67). HR-MALDI-MS: 556.2438 (C35H35NO4, [M ‡ Na] ; calc. 556.2458).
(S)-3-[(1S,2R,4S)-4-Hydroxy-1-(methylsulfanyl)-2,4-diphenylbutyl]-4-isopropyl-5,5-diphenyloxazolidin-2-
one (11) and (S)-3-[(1S,2R,4R)-4-Hydroxy-1-(methylsulfanyl)-2,4-diphenylbutyl]-4-isopropyl-5,5-diphenylox-
azolidin-2-one (12). To a soln. of 5a (1.14 g, 2.07 mmol) in THF (20 ml) and H2O (5 ml), NaBH4 (78 mg,
2.07 mmol) was added at r.t. After stirring for 4 h, sat. aq. NH4Cl soln. was added, and the mixture was diluted
with Et2O. The org. layer was separated, and the aq. layer was extracted with Et2O (2Â). The combined org.
layers were dried (MgSO4) and concentrated under reduced pressure. Purification of the crude product by FC
(pentane/Et2O 3 :1 ! 2 :1) afforded 11 and 12 (1.07 g, 94%) as a 42 :58 mixture. The isolated product mixture
was purified again by FC (2 Â , pentane/Et2O 3 :1) to yield 11 (318 mg, 28%) as a single diastereoisomer and 12
(420mg, 37%) as a 94 :6 mixture with 11.
The reduction with the chiral RuII catalyst was carried out via the following procedure: To a soln. of 5a
(102 mg, 0.218 mmol) in CH2Cl2 (3 ml), i-PrOH (1.5 ml) and catalyst i (13 mg, 0.022 mmol) were added at r.t.
After stirring for 4 days, the mixture was concentrated and filtered through a silica plug (CH2Cl2) to afford 11
1
and 12 as a 97:3 mixture (at 40% conversion as determined by H-NMR).
Data of 11: White solid. M.p. 193 1948. [a]Dr:t: ˆ À77.5 (c ˆ 1, CHCl3). IR (CHCl3): 3612w, 3462w, 3065w,
1
3008m, 2966w, 1745s, 1602w, 1493m, 1450m, 1408m, 1034m, 1004m, 896w, 826w. H-NMR (400 MHz, CDCl3):
0.31 (d, J ˆ 7.0, Me); 0.84 (d, J ˆ 7.3, Me); 1.82 (ddd, J ˆ 2.2, 12.0, 14.1, 1 H, CH2); 1.85 (s, MeS); 1.90 2.05
(m, Me2CH, OH); 2.65 (ddd, J ˆ 3.1, 10.8, 14.1, 1 H, CH2); 4.19 4.29 (m, CHOH, PhCH); 4.54 (d, J ˆ 1.6,
NCH); 4.60( d, J ˆ 9.7, CHSMe); 7.12 7.37 (m, 18 arom. H); 7.51 7.54 (m, 2 arom. H). 13C-NMR (100 MHz,
CDCl3): 12.6, 15.7, 20.3 (Me); 29.5, 43.1 (CH); 44.6 (CH2); 68.5, 68.6, 71.2 (CH); 87.6 (C); 125.3, 125.5, 126.6,
127.3, 127.4, 127.8, 128.36, 128.42, 128.46, 128.54 (CH); 139.0, 141.3, 144.4, 145.2, 157.1 (C). MALDI-MS: 590 (6,
‡
‡
‡
[M ‡ K] ), 574 (70, [M ‡ Na] ), 442 (100, [M À SMe À CO2 À H2O] ). Anal. calc. for C35H37NO3S (551.75):
C 76.19, H 6.76, N 2.54; found: C 76.09, H 6.87, N 2.52.
Data of 12: White solid. 1H-NMR (400 MHz, CDCl3): 0.14 (d, J ˆ 6.9, Me); 0.72 (d, J ˆ 7.4, Me); 1.52
(s, MeS); 1.73 (d, J ˆ 3.1, OH); 1.78 1.88 (m, Me2CH); 2.19 (ddd, J ˆ 5.1, 11.0, 13.3, 1 H, CH2); 2.71 (ddd, J ˆ
3.3, 9.1, 13.3, 1 H, CH2); 3.73 (ddd, J ˆ 3.3, 11.0, 11.0, PhCH); 4.29 4.35 (m, CHOH); 4.38 (d, J ˆ 1.6, NCH);
4.49 (d, J ˆ 11.0, CHSMe); 7.10 7.38 ( m, 18 arom. H); 7.42 7.45 (m, 2 arom. H).
(S)-3-[(2S,3R,5S)-2,3,4,5-Tetrahydro-3,5-diphenylfuran-2-yl]-4-isopropyl-5,5-diphenyloxazolidin-2-one
(13). To a soln. of 11 (885 mg, 1.60mmol) in THF (10ml), Hg(O 2CCF3)2 (684 mg, 1.60mmol) was added at r.t.
After stirring for 5 min, H2O was added, and the mixture was diluted with CH2Cl2. The org. layer was separated,
and the aq. layer was extracted with CH2Cl2 (2Â). The combined org. layers were dried (MgSO4) and
concentrated under reduced pressure. Purification of the crude product by trituration (boiling hexane, 10ml)
and filtration through a silica plug (CH2Cl2) afforded 13 (757 mg, 94%) as a single diastereoisomer. White solid.
M.p. 214 2168. [a]rD:t: ˆ À107.5 (c ˆ 1, CHCl3). IR (CHCl3): 3064w, 3008w, 2965w, 1751s, 1603w, 1603w, 1494w,
1450m, 1381w, 1326w, 1028m, 1002m, 945w, 90 9w. 1H-NMR (400 MHz, CDCl3): 0.62 (d, J ˆ 6.7, Me); 0.87 (d, J ˆ
7.3, Me); 1.86 1.95 (m, Me2CH); 2.07 (ddd, J ˆ 10.5, 10.5, 12.7, 1 H, CH2); 2.82 (ddd, J ˆ 5.7, 7.2, 12.7, 1 H, CH2);
4.34 (ddd, J ˆ 7.2, 7.2, 10.5, PhCH); 4.55 (d, J ˆ 1.6, NCH); 5.16 (dd, J ˆ 5.7, 10.5, PhCHO); 5.64 (d, J ˆ 7.2,
NCHO); 7.11 7.37 (m, 16 arom. H); 7.42 7.45 (m, 2 arom. H); 7.50 7.53 ( m, 2 arom. H). 13C-NMR (100 MHz,
CDCl3): 15.3, 21.1 (Me); 29.8 (CH); 43.7 (CH2); 47.5, 68.3, 80.3 (CH); 88.4 (C); 92.7, 125.4, 125.7, 126.2, 126.9,
127.46, 127.49, 127.51, 127.9, 128.1, 128.39, 128.44, 128.7 (CH); 139.0, 140.1, 141.8, 143.9, 156.8 (C). MALDI-MS:
‡
‡
542 (6, [M ‡ K] ), 526 (100, [M ‡ Na] ), 442 (24). Anal. calc. for C34H33NO3 (503.64): C 81.08, H 6.60, N 2.78;
found: C 81.09, H 6.62, N 2.79.
The C(5)-epimer of 13 was prepared from 12 according to the same procedure. White solid. 1H-NMR
(300 MHz, CDCl3): 0.68 (d, J ˆ 6.8, Me); 0.92 (d, J ˆ 7.3, Me); 1.88 2.00 (m, Me2CH); 2.35 2.51 (m, CH2);
4.03 4.10 (m, PhCH); 4.56 (d, J ˆ 1.8, NCH); 5.16 5.21 (m, PhCHO); 5.51 (d, J ˆ 6.1, NCHO); 7.12 7.31
(m, 17 arom. H); 7.40 7.49 ( m, 3 arom. H).
(3R,5S)-2,3,4,5-Tetrahydro-2-methoxy-3,5-diphenylfuran (15). To a soln. of 13 (544 mg, 1.08 mmol) in
CHCl3 (10ml) and MeOH (10ml), conc. H 2SO4 (1.5 ml) was added slowly at r.t. The mixture was stirred for 14
days at r.t. Then, the white precipitate formed during the reaction was dissolved by adding CH2Cl2 to the
mixture, and the clear soln. was poured into 5m NaOH (16 ml). The org. layer was separated, and the aq. layer
was extracted with CH2Cl2 (2Â). The combined org. layers were dried (MgSO4) and concentrated under
reduced pressure. The crude product was suspended in Et2O (10ml), the insoluble white solid was filtered off,
washed with Et2O, and dried under h.v. to recover 1 (254 mg, 84%). The filtrate was concentrated under reduced

Helvetica Chimica Acta Vol. 85 (2002)
785
pressure, and the residual oil was purified by FC (pentane/Et2O 30:1) to afford 15 (239 mg, 87%) as a 78 :22
mixture (C(2)-epimers), also containing 3% of its C(3)-epimer. For anal. purposes, a sample was purified again
by FC (pentane/Et2O 30:1) to afford (2 S,3R,5S)-15 (dp 95%) as major product and (2R,3R,5S)-15, (dp ꢀ 98%)
as minor product.
Data of (2S,3R,5S)-15: Colorless oil. 1H-NMR (400 MHz, CDCl3): 1.96 (ddd, J ˆ 9.6, 10.5, 12.5, 1 H, CH2);
2.74 (dddd, J ˆ 0.5, 5.4, 8.2, 12.5, 1 H, CH2); 3.42 (s, MeO); 3.48 (ddd, J ˆ 3.2, 8.2, 9.6, PhCH); 5.13 (d, J ˆ 3.2,
CHOMe); 5.21 (dd, J ˆ 5.4, 10.5, PhCHO); 7.19 7.38 (m, 8 arom. H); 7.42 7.45 (m, 2 arom. H). 13C-NMR
(100 MHz, CDCl3): 43.2 (CH2); 52.7 (CH); 55.5 (Me); 80.0, 111.4, 126.1, 126.6, 127.3, 127.7, 128.4, 128.6 (CH);
140.9, 141.9 (C).
Data of (2R,3R,5S)-15: White solid. M.p. 65 688. [a]rD:t: ˆ À123.6 (c ˆ 1, CHCl3). IR (CHCl3): 3066w,
3008m, 2910w, 2835w, 1604w, 1497m, 1450w, 1368w, 1326w, 1169w, 1097w, 1121s, 1048s, 1024s, 980s, 90 4m, 856w.
1H-NMR (400 MHz, CDCl3): 2.43 (ddd, J ˆ 10.4, 11.9, 13.4, 1 H, CH2); 2.58 (ddd, J ˆ 6.1, 6.6, 11.9, 1 H, CH2);
3.38 (s, MeO); 3.54 (ddd, J ˆ 4.7, 6.6, 13.4, PhCH); 5.11 (d, J ˆ 4.7, CHOMe); 5.19 (dd, J ˆ 6.1, 10.4, PhCHO);
7.22 7.41 (m, 8 arom. H); 7.43 7.46 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 38.2 (CH2); 50.8 (CH); 55.1
‡
(Me); 82.0, 105.5, 126.6, 126.8, 127.5, 128.1, 128.4, 128.8 (CH); 137.3, 143.0 (C). FAB-MS: 254 (17, M ), 223 (100,
‡
‡
[M À OMe] ), 205 (47), 194 (61, [M À OCHOMe] ). Anal. calc. for C17H18O2 (254.33): C 80.28, H 7.13; found:
C 80.36, H 7.10.
(S)-3-[(1S,2R,4S)-4-Acetyl-1-(methylsulfanyl)-2,4-diphenylbutyl]-4-isopropyl-5,5-diphenyloxazolidin-2-
one (14). To a soln. of 11 (339 mg, 0.614 mmol) in CH2Cl2 (3 ml), Ac2O (70 ml, 0.737 mmol) and DMAP (98 mg,
0.798 mmol) were added consecutively at r.t. After stirring for 10 min, 0.1m HCl was added, and the mixture was
diluted with CH2Cl2. The org. layer was washed with 0.1m HCl (1Â) and sat. aq. NaHCO3 soln. (1Â), dried
(MgSO4), and concentrated under reduced pressure. Purification of the crude product by FC (pentane/Et2O
5 :2) afforded 14 (345 mg, 95%). White solid. M.p. 154 1558. [a]rD:t: ˆ À60.5 (c ˆ 1, CHCl3). IR (CHCl3): 3064w,
3008w, 2962w, 1744s, 1602w, 1494w, 1450w, 1409w, 1372w, 1248m, 1097w, 1027m, 1004m, 820w. 1H-NMR
(400 MHz, CDCl3): 0.08 (d, J ˆ 6.9, Me); 0.70 (d, J ˆ 7.4, Me); 1.67 (s, MeS); 1.75 1.87 (m, 2 H, Me2CH, CH2);
1.99 (s, Me); 2.85 (ddd, J ˆ 3.0, 10.9, 14.1, 1 H, CH2); 4.27 4.33 (m, PhCH); 4.40( d, J ˆ 11.1, CHSMe); 4.42
(d, J ˆ 1.5, NCH); 5.22 (dd, J ˆ 2.4, 10.9, CHOAc); 7.08 7.28 (m, 18 arom. H); 7.48 7.50( m, 2 arom. H).
13C-NMR (100 MHz, CDCl3): 11.3, 15.1, 20.4, 21.0 (Me); 29.4, 41.7 (CH); 42.3 (CH); 68.4, 68.7, 73.5 (CH); 87.4
(C); 125.3, 125.9, 126.4, 127.4, 127.5, 127.6, 127.76, 127.83, 128.3, 128.4, 128.5, 128.6 (CH); 138.9, 140.6, 141.1,
‡
‡
144.3, 157.0, 170.0 (C). MALDI-MS: 616 (1, [M ‡ Na] ), 556 (10), 442 (74, [M À SMe À CO2 À HOAc] ), 167
(100). Anal. calc. for C37H39NO4S (593.79): C 74.84, H 6.62, N 2.36; found: C 74.69, H 6.84, N 2.40.
(1S,3R)-4-Hydroxy-1,3-diphenylbutyl Acetate (16). Compound 14 (301 mg, 0.506 mmol) was treated with
Hg(O2CCF3)2 (238 mg, 0.557 mmol) and NaBH4 (14 mg, 0.380 mmol)/DBU (38 ml, 0.253 mmol) according to
GP 2. The auxiliary 1 was recovered by filtration (114 mg, 80%). Purification of the crude product by FC
(pentane/Et2O 3 :2) yielded 16 (115 mg, 80%) as a 97:3 mixture with its C(3)-epimer. For anal. purposes, a
sample was purified again by FC (pentane/Et2O 3 :2) to afford 16 (drꢀ 99 :1). Colorless oil. [a]rD:t: ˆ À34.2 (c ˆ
1, CHCl3). IR (CHCl3): 3595w, 3064w, 3008w, 2956w, 2875w, 1732s, 1603w, 1494m, 1454m, 1409w, 1373s, 1107m,
1020s, 946w, 821w. 1H-NMR (400 MHz, CDCl3): 1.51 (t, J ˆ 5.9, OH); 2.02 (s, Me); 2.03 (ddd, J ˆ 4.1, 10.0, 14.3,
1 H, CH2CHOAc); 2.33 (ddd, J ˆ 4.7, 9.5, 14.3, 1 H, CH2CHOAc); 2.90 2.97 ( m, PhCH); 3.73 3.77
(m, CH2OH); 5.53 (dd, J ˆ 4.1, 9.5, CHOAc); 7.15 7.18 (m, 2 arom. H); 7.22 7.35 (m, 8 arom. H). 13C-NMR
(100 MHz, CDCl3): 21.1 (Me); 39.2 (CH2); 45.1 (CH); 67.3 (CH2); 74.0, 126.2, 127.1, 127.8, 128.0, 128.4, 128.9
‡
(CH); 140.8, 141.2, 170.1 (C). MALDI-MS: 307 (100, [M ‡ Na] ), 247 (59), 207 (94). Anal. calc. for C18H20O3
(284.35): C 76.03, H 7.09; found: C 76.15, H 7.29.
(S)-3-{(1S,2R,4R)-4-[(Benzyloxy)methoxy]-1-(methylsulfanyl)-2,4-diphenylbutyl}-4-isopropyl-5,5-diphen-
yloxazolidin-2-one (17). To a soln. of 12 (1.55 g, 2.80mmol as a 90:10mixture with its C(4)-epimer) in CH2Cl2
(8 ml), EtN(i-Pr)2 (1.92 ml, 11.2 mmol) and BOMCl (1.56 ml, 11.2 mmol) were added consecutively at 08. After
stirring for 3 h at r.t., sat. aq. Na2CO3 soln. was added, and the mixture was stirred for 30min to hydrolyze excess
BOMCl. The org. layer was separated, and the aq. layer was extracted with CH2Cl2 (2Â). The combined org.
layers were dried (MgSO4) and concentrated under reduced pressure. Purification of the crude product by FC
(2 Â ; pentane/Et2O 6 :1) afforded 17 (1.33 g, 71%) as a 97:3 mixture with its C(4)-epimer. For anal. purposes, a
sample was purified again by FC (pentane/Et2O 6 :1) to afford 17 (drꢀ 99 :1). White solid. M.p. 135 1378.
[a]Dr:t: ˆ À14.5 (c ˆ 1, CHCl3). IR (CHCl3): 3008w, 2961w, 2884w, 1748s, 1494w, 1451w, 1408w, 1259w, 1161w,
1096w, 1038m, 90 9w. 1H-NMR (400 MHz, CDCl3): 0.09 (d, J ˆ 6.9, Me); 0.70 (d, J ˆ 7.3, Me); 1.48 (s, MeS);
1.75 1.87 (m, Me2CH); 2.21 2.28 (m, 1 H, CH2); 2.79 (ddd, J ˆ 3.2, 10.4, 13.4, 1 H, CH2); 3.65 3.71
(m, PhCH); 4.24 4.54 (m, CHSMe, NCH, CHOBOM, OCH2O, PhCH2O); 7.08 7.38 (m, 23 arom. H); 7.41
7.45 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 11.4, 15.2, 20.3 (Me); 29.4, 41.6 (CH); 42.4 (CH2); 68.4, 68.9

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Helvetica Chimica Acta Vol. 85 (2002)
(CH); 69.3 (CH2); 76.6 (CH); 87.4 (C); 91.9 (CH2); 125.3, 126.4, 127.30, 127.32, 127.6, 127.75, 127.83, 128.1, 128.2,
128.3, 128.4, 128.45, 128.47, 128.6 (CH); 137.7, 138.9, 140.5, 141.2, 144.4, 156.8 (C). MALDI-MS: 694 (95, [M ‡
‡
‡
Na] ), 442 (100, [M À SMe À CO2 À HOBOM] ), 413 (44). Anal. calc. for C43H45NO4S (671.90): C 76.87,
H 6.75, N 2.08; found: C 76.88, H 6.87, N 2.00.
(2R,4R)-4-[(Benzyloxy)methoxy]-2,4-diphenylbutan-1-ol (18). Compound 17 (460mg, 0.685 mmol) was
treated with Hg(O2CCF3)2 (322 mg, 0.754 mmol) and NaBH4 (20mg, 0.514 mmol)/DBU (51 ml, 0.343 mmol)
according to GP 2. The auxiliary 1 was recovered by filtration (152 mg, 79%). Purification of the crude product
by FC (pentane/Et2O 5 :2) yielded 18 (220mg, 89%) as a 96 :4 mixture with its C(2)-epimer. For anal. purposes,
a sample was purified again by FC (pentane/Et2O 5 :2) to afford 18 (drꢀ 99 :1). Colorless oil. [a]rD:t: ˆ ‡43.5
(c ˆ 1, CHCl3). IR (CHCl3): 3590w, 3064w, 3008m, 2946w, 2888w, 1602w, 1494m, 1454m, 1381w, 1160w, 1098m,
1
1037s. H-NMR (400 MHz, CDCl3): 1.54 (br. s, OH); 2.14 (ddd, J ˆ 5.7, 8.2, 13.7, 1 H, CH2); 2.26 (ddd, J ˆ 6.1,
9.2, 13.7, 1 H, CH2); 2.61 2.68 (m, PhCH); 3.60 3.71 ( m, CH2OH); 4.38 (d, J ˆ 11.5, 1 H, OCH2O or
PhCH2O); 4.50 4.62 ( m, 4 H, CHOBOM, OCH2O, PhCH2O); 7.13 7.34 (m, 15 arom. H). 13C-NMR
(100 MHz, CDCl3): 39.7 (CH2); 44.6 (CH); 67.4, 69.6 (CH2); 76.4 (CH); 92.2 (CH2); 126.9, 127.3, 127.7, 127.9,
‡
128.0, 128.1, 128.3, 128.4, 128.8 (CH); 137.7, 141.1, 141.8 (C). MALDI-MS: 385 (100, [M ‡ Na] ), 324 (2), 207
(6). Anal. calc. for C24H26O3 (362.47): C 79.53, H 7.23; found: C 79.47, H 7.36.
(3R,5R)-5-[(Benzyloxy)methoxy]-3,5-diphenylpentan-2-ol (19). Compound 17 (506 mg, 0.754 mmol) was
treated with Hg(O2CCF3)2 (354 mg, 0.829 mmol) according to GP 2. The crude hemiaminal was dissolved in
THF (5 ml), and MeMgCl (2.01 ml, 3.02 mmol) was added at À788. After stirring for 10min at À788, the
cooling bath was removed, and the mixture was stirred for another 10min. The auxiliary 1 precipitated in the
course of the reaction. Then, sat. aq. NH4Cl soln. and Et2O were added, and the precipitate was filtered off. The
precipitate was washed with sat. aq. NH4Cl soln., H2O, and Et2O, and dried under h.v. to recover 1 (163 mg, 77%)
as a white solid. The filtrate was diluted with Et2O, the org. layer was separated, and the aq. layer was extracted
with Et2O (2Â). The combined org. layers were dried (MgSO4) and concentrated under reduced pressure.
Purification of the crude product by FC (pentane/Et2O 5 :2) afforded 19 (235 mg, 83%) as a 75 :25 mixture
(C(2)-epimers). For anal. purposes, a sample was purified again by FC (pentane/Et2O 5 :2) to afford major-19
(drꢀ 99 :1). Colorless oil. [a]rD:t: ˆ ‡72.2 (c ˆ 1, CHCl3). IR (CHCl3): 3595w, 3066w, 3008m, 2953w, 1601w,
1494m, 1454m, 1381w, 1161w, 1095m, 1038s, 924w. 1H-NMR (400 MHz, CDCl3): 0.95 (d, J ˆ 6.3, Me); 1.61 (br. s,
OH); 2.29 2.40( m, CH2, PhCH); 3.78 3.88 (m, CHOH); 4.37 (d, J ˆ 11.5, 1 H, OCH2O or PhCH2O); 4.44
4.48 (m, CHOBOM); 4.49 (d, J ˆ 6.9, 1 H, OCH2O or PhCH2O); 4.57 (d, J ˆ 11.5, 1 H, OCH2O or PhCH2O);
4.61 (d, J ˆ 6.9, 1 H, OCH2O or PhCH2O); 7.07 7.11 (m, 2 arom. H); 7.15 7.21 (m, 4 arom. H); 7.23 7.35
(m, 9 arom. H). 13C-NMR (100 MHz, CDCl3): 21.1 (Me); 38.2 (CH2); 49.8 (CH); 69.6 (CH2); 71.6, 76.8 (CH);
92.2 (CH2); 126.8, 127.5, 127.7, 127.9, 128.0, 128.3, 128.4, 128.59, 128.60 (CH); 137.8, 141.0, 141.5 (C). MALDI-
‡
MS: 399 (100, [M ‡ Na] ), 221 (12). Anal. calc. for C25H28O3 (376.49): C 79.76, H 7.50; found: C 79.52, H 7.28.
(R)-5-Hydroxy-1,1,1,4-tetraphenylpentan-2-one (20). Compound 8a (821 mg, 1.15 mmol) was treated with
Hg(O2CCF3)2 (538 mg, 1.26 mmol) and NaBH4 (33 mg, 0.860 mmol)/DBU (86 ml, 0.573 mmol) according to
GP 2. The auxiliary 1 was recovered by filtration (232 mg, 72%). Purification of the crude product by FC
(pentane/Et2O 2 :1) yielded 20 (325 mg, 70%). White foam. [a]rD:t: ˆ À12.1 (c ˆ 1, CHCl3). IR (CHCl3): 3592w,
1
3434w, 3062m, 3008m, 2933w, 2878w, 1708s, 1599m, 1493s, 1448s, 1102m, 1063m, 1034m. H-NMR (300 MHz,
CDCl3): 1.82 (br. s, OH); 2.78 3.02 (m, CH2C(O), PhCH); 3.54 3.60( m, CH2OH); 7.03 7.06 (m, 2 arom. H);
7.18 7.34 (m, 18 arom. H). 13C-NMR (75 MHz, CDCl3): 44.4 (CH, CH2); 66.3 (CH2); 73.2 (C); 126.8, 127.8,
‡
128.0, 128.1, 128.5, 130.2, 130.3 (CH); 141.8, 142.0, 207.3 (C). MALDI-MS: 429 (100, [M ‡ Na] ), 389 (82, [M ‡
‡
H À H2O] ). Anal. calc. for C29H26O2 (406.52): C 85.68, H 6.45; found: C 85.70, H 6.59.
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Received September 7, 2001