A useful modification of the Evans auxiliary: 4-Isopropyl-5,5- diphenyloxazolidin-2-one

Article abstract of DOI:10.1002/(SICI)1522-2675(19981111)81:11<2093::AID-HLCA2093>3.0.CO;2-X

The 4-isopropyl-5,5-diphenyloxazolidinone (1) is readily prepared from (R)- or (S)-valine ester, PhMgBr, and ethyl chlorocarbonate. It has a melting point of ca. 250°, a low solubility in most organic solvents, and a C=O group which is sterically protected from nucleophilic attack. Thus, the soluble N-acyl-oxazolidinones (7-16) can be prepared from 1 with BuLi at temperatures around 0°instead of - 78°(Scheme 3), their Li enolates can be generated with BuLi, rather than with LDA, and deacylation in the final step of the procedure can be achieved with NaOH at ambient temperatures (Scheme 12), with facile recovery of the precipitating auxiliary 1 (filtering, washing, and drying). The following reactions of N-acyl-oxazolidinones from 1 have been investigated: alkylations (Scheme 4), aminomethylations and hydroxymethylations (Scheme 5), aldol additions (Schemes 6 and 7), Michael additions (Schemes 9 and 10), and a (4 + 2) cycloaddition (Scheme 11). The well-known features of reactions following the Evans methodology (yield, diastereoselectivity, dependence on conditions, counter ions, additives etc.) prevail in these transformations. Most products, however, have higher melting points and a much more pronounced crystallization tendency than those derived from conventional oxazolidinones, and can thus be purified by recrystallization, avoiding chromatography (Table 1). The disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is more than compensated by the ease of its application, especially on large scale. A number of crystal structures of oxazolidinones derived from 1 and a TiCl₄ complex of an oxazolidinone are described and discussed in view of the diastereoselective-reaction mechanisms.

Full text of DOI:10.1002/(SICI)1522-2675(19981111)81:11<2093::AID-HLCA2093>3.0.CO;2-X

Helvetica Chimica Acta ± Vol. 81 (1998)
2093
A Useful Modification of the Evans Auxiliary:
4-Isopropyl-5,5-diphenyloxazolidin-2-one
1
by Tobias Hintermann ) and Dieter Seebach*
Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH-Zentrum,
Universitätstrasse 16, CH-8092 Zürich
Dedicated to Professor Hans Bock on the occasion of his 70th birthday
The 4-isopropyl-5,5-diphenyloxazolidinone (1) is readily prepared from (R)- or (S)-valine ester, PhMgBr,
and ethyl chlorocarbonate. It has a melting point of ca. 2508, a low solubility in most organic solvents, and a
CˆO group which is sterically protected from nucleophilic attack. Thus, the soluble N-acyl-oxazolidinones (7 ±
16) can be prepared from 1 with BuLi at temperatures around 08 instead of 788 (Scheme 3), their Li enolates
can be generated with BuLi, rather than with LDA, and deacylation in the final step of the procedure can be
achieved with NaOH at ambient temperatures (Scheme 12), with facile recovery of the precipitating auxiliary 1
(filtering, washing, and drying). The following reactions of N-acyl-oxazolidinones from
1 have been
investigated: alkylations (Scheme 4), aminomethylations and hydroxymethylations (Scheme 5), aldol additions
(Schemes 6 and 7), Michael additions (Schemes 9 and 10), and a (4 ‡ 2) cycloaddition (Scheme 11). The well-
known features of reactions following the Evans methodology (yield, diastereoselectivity, dependence on
conditions, counter ions, additives etc.) prevail in these transformations. Most products, however, have higher
melting points and a much more pronounced crystallization tendency than those derived from conventional
oxazolidinones, and can thus be purified by recrystallization, avoiding chromatography (Table 1). The
disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is
more than compensated by the ease of its application, especially on large scale. A number of crystal structures of
oxazolidinones derived from 1 and a TiCl4 complex of an oxazolidinone are described and discussed in view of
the diastereoselective-reaction mechanisms.
1. Introduction. ± There are only three fundamentally different methods of
synthesizing enantiomerically pure compounds (EPC): resolution, enantioselective
transformations, and use of starting materials from the pool of chiral building blocks
[1]. Practical enantioselective transformations must be either catalytic, or the chiral
auxiliary must be efficiently recycled. Of the covalently bound chiral auxiliaries (for
review articles, see [2][3]), the ones which are attached to a carboxy C-atom are most
useful for organic syntheses, and the auxiliaries in current methodology are oxazolidin-
2-ones A (Scheme 1), introduced by Evans et al. in 1981 [4].
An ideal chiral auxiliary has to fulfil several criteria in the overall enantioselective
reaction cycle (B ! E; Scheme 1): i) It should be cheap, and both enantiomers should
be readily available. ii) Attachment of the substrate to the auxiliary (A ‡ B ! C)
should proceed in high yields by simple methods, applicable to a broad variety of
substrates. iii) There should be many different types of reactions to be carried out with
1
)
Part of the Ph. D. thesis of T.H.

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Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 1
derivatives C. iv) The auxiliary must be stable under the conditions of the
diastereoselective reaction (C ! D). v) There must be a high degree of diastereose-
lection. vi) The derivatives of the chiral auxiliary (C and D) should preferably be
crystalline, allowing easier purification, and removal of diastereoisomeric and other
impurities (especially from D) by simple crystallization. vii) The cleavage of the
auxiliary (D ! E ‡ A) must be possible with high yields under mild conditions, and the
procedures should be generally applicable. viii) The auxiliary should not be destroyed
under the conditions applied for cleavage, thus allowing for recycling of A (at least in
large-scale processes). ix) Isolation of the enantiomerically pure product E and
recovery of the auxiliary A should be possible by simple methods.
The oxazolidin-2-one auxiliaries F ± I (available from valine, phenylalanine,
phenylglycine, and norephedrine, resp.), all introduced by Evans et al. [4][5],
satisfactorily fulfil most of the criteria mentioned above. Thus, they are now widely
used in enantioselective syntheses. Several other oxazolidin-2-ones with partially better
properties have been proposed [3][6][7], but none of them has been generally
accepted by the ꢀsynthetic communityꢁ. Other heterocyclic carboxy derivatives have
also been applied with considerable succes (e.g., sultams K [8] or ureas L [9]).

Helvetica Chimica Acta ± Vol. 81 (1998)
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In the present paper, we report a general access to 5,5-diphenyloxazolidinones and
derivatives as well as several applications of the new2) chiral auxiliary 4-(1-
methylethyl)-5,5-diphenyloxazolidin-2-one (1). We will also underline the advantages
of our new chiral auxiliary 1 ± in every step of the reaction cycle shown in Scheme 1 ±
over the well-established oxazolidinones F ± I (see Conclusions).
2. Synthesis of the Chiral Oxazolidinone Auxiliaries 1, 5, and 6. ± The 5,5-diphenyl-
oxazolidin-2-ones 1, 5, and 6 were easily prepared in two steps starting from the
commercially available valine methyl ester, phenylalanine ethyl ester, and leucine
methyl ester (Scheme 2). Thus, treatment of the amino-acid esters with PhMgBr in
Et2O led to the 2-amino-1,1-diphenyl alcohols 2 ± 4. In contrast to a published
procedure [12], not the hydrochloride salt of the amino esters, but the free amines, and
only 3 equiv. of Grignard reagent (vs. 8 equiv.) had to be employed. Because of
difficulties associated with the purification of the amino alcohols, the yields were only
moderate (ca. 50% for 2 and 3). For a large-scale synthesis, it would, therefore, be more
reasonable to continue the process with the crude products3) (ca. 80% yield). This was
done in the case of tert-leucine-derived amino alcohol 4. For the cyclization to the
oxazolidin-2-ones, we followed a procedure published for the preparation of rac-5 [13].
The amino alcohols 2 ± 4 were first ethoxycarbonylated (ClCO2Et, Et3N) and then
cyclized by treatment with base (NaOH in MeOH). The yields of the cyclization were
excellent (91% for (S)-1, and 86% for (S)-5), and purification was possible by simple
filtration of the insoluble diphenyl-oxazolidinones from the reaction mixture and
washing with H2O, Et2O, and pentane. The oxazolidin-2-one (R)-6 was obtained in 66%
overall yield (from tert-leucine methyl ester). The compounds 1 and 5 were shown to be
>99.5% enantiomerically pure by HPLC on a chiral column (Chiralcel OD; see Exper.
Part for details).
Scheme 2
2
)
The oxazolidinone 1 has previously been prepared by others [10][11], but, to the best of our knowledge, it
has not been used as chiral auxiliary. 5,5-Disubstituted oxazolidin-2-ones with non-aryl-substituents at
C(5) have also been used as chiral auxiliaries [7]. After submission of the manuscript for the present full
paper, a communication, describing independent work on the use of 1, has appeared: C. L. Gibson,
K. Gillon, S. Cook, Tetrahedron Lett. 1998, 39, 6733 ± 6736 (issue 37 of September 10). Also, in that
communication, a related patent is referred to, which has escaped our notice: T. Isobe, K. Fukuda,
Japanese Patent JP09143173, 1995; Chem. Abstr. 1997, 127, 50635.
3
)
The crude product contains mainly biphenyl as an impurity.

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Helvetica Chimica Acta ± Vol. 81 (1998)
3. Acylation of the Oxazolidin-2-one Auxiliaries. ± By far the most popular method
of N-acylating an oxazolidin-2-one is the reaction of its Li salt (generated with BuLi at
788) with an acyl chloride [4][14]. Generally, this procedure leads to N-acyl-
oxazolidin-2-ones in excellent yields, but there are some limitations: i) acryloyl
derivatives tend to polymerize under these conditions [15]; ii) b,g-unsaturated
carboxylic-acid derivatives isomerize to the a,b-unsaturated compounds [16]; iii) the
method is not applicable to such carboxylic acids, which do not form stable acid halides;
iv) due to the basicity of the lithiated oxazolidinone group, substrates with relatively
acidic H-atoms or with a propensity for elimination cannot be employed; v) the use of
RLi at 788 is not desirable from an economic point of view (at least in large-scale
applications). To circumvent these limitations, a number of milder methods has been
proposed [15 ± 17].
For the N-acylation of the 5,5-diphenyloxazolidin-2-ones 1, 5, and 6, we used both,
the standard Evans procedure [4][14] (BuLi, acyl chloride), and a method introduced
by Ho and Mathre [15] (mixed anhydride, LiCl, Et3N). Thus, lithiation of the
oxazolidin-2-ones in THF with BuLi4) at 08 and subsequent treatment with various acyl
chlorides gave the N-acyl-oxazolidin-2-ones 7 ± 19, mostly purified by recrystalliza-
tion5), in good-to-excellent yields (80 ± 98%; Scheme 3)6). N-Acyl-oxazolidin-2-ones
containing either acidic H-atoms (20, 21, and 24), or readily eliminating substituents
(22), or highly nucleophilic groups (23), were prepared by acylation with the LiCl-
activated [18] pivaloyl mixed anhydride, using Et3N as base [15] (Scheme 3), with
somewhat lower yields of the products 20 ± 24 (which had to be purified chromato-
graphically). In summary, the N-acyl derivatives 7 ± 24 of 5,5-diphenyloxazolidin-2-
ones 1, 5, and 6, containing a variety of different functional groups, are readily available
in yields (of purified products!) ranging from 75 to 98%.
4. Diastereoselective Alkylations. ± A typical reaction for the exploration of the
potential of a chiral auxiliary is the alkylation of its propanoic-acid derivative. We,
therefore, first studied the alkylation of N-acyl-oxazolidin-2-ones 8 (from valine), 17
(from tert-leucine), and 18 (from phenylalanine) (see products 25 ± 30 in Scheme 4).
Benzylation of the lithium-diisopropylamide(LDA)-generated Li-enolate from 18
turned out to be very slow, even at 08, and the N-benzyl-oxazolidin-2-one7) was formed
as the main product. With the NHMDS-generated ( 788) Na-enolate, the allylation
product 28 was formed in good yield, however, with moderate diastereoselectivity (dr
4 : 1; Entry 1 in Scheme 4). Better results were obtained by using the Zn-enolate,
generated by transmetalation of the Li-enolate [19] (90% 28; dr 94 : 6; Entry 2). Under
the same conditions, the i-Pr-substituted derivative 8 led to the allylation product 25
4
)
The oxazolidin-2-ones 1, 5, and 6 are not soluble in THF; therefore, BuLi was added to a suspension in
THF, resulting in a clear solution. Although the reaction was performed at 08, rather than at 788, by-
products arising from nucleophilic attack at the heterocycle were not observed.
The yields were not optimized; mother liquors from recrystallization were discarded. Purification of the N-
acyl-oxazolidin-2-ones by flash chromatography resulted in yields of > 90%.
The acylation procedure worked equally well with 1, 5, and 6, as can be seen from the yields obtained with
propanoyl chloride ( ! 8, 17, and 18, 88 ± 98%).
5
6
7
)
)
)
Probably resulting from decomposition of the enolate to the ketene and the lithiated oxazolidinone which
is then benzylated.

Helvetica Chimica Acta ± Vol. 81 (1998)
2097
Scheme 3
7
8
9
10
11
12
13
R1 Me2CH
Me2CH
MeCH2
Me2CH
Me2CHCH2
Me2CH
Me2CH(CH2)2
MeCH2
Ph(CH2)2
Me2CH
MeCHˆCH(E)
Me2CH
PhCHˆCH(E)
R2
Me
14
15
16
17
18
19
R1
Me2CH
Me2CH
PhthN(CH2)2
Me2CH
(4-OBn)C6H4(CH2)2
t-Bu
Me2CH2
PhCH2
Me2CH2
PhCH2
PhthN(CH2)2
R2 MeOCO(CH2)3
20
21
22
23
Me2CH
24
R1
R2 BocNH(CH2)2
Me2CH
Me2CH
CbzNH(CH2)2
Me2CH
MeCH(OBn)CH2
PhCH2
BocNH(CH2)2
[(1-Cbz)indol-3-yl](CH2)2
Phth ˆ phthaloyl; Boc ˆ t-BuOCO; Cbz ˆ BnOCO
with even higher diastereoselectivity (dr 96 : 4; Entry 3), so we tested 8 for other
alkylations8). Indeed, reactions with BnBr and BrCH2CO2(t-Bu) afforded the
corresponding products in good yields with high selectivities (Entries 4 and 5). Using
the reactive electrophile BrCH2CO2(t-Bu), even the Li-enolates (generated with LDA,
BuLi, or t-BuLi; Entries 6 ± 10) could be alkylated at 788 (! succinic-acid derivatives
26, 29, and 30). It is remarkable that the Li-enolate of 8 could be generated with BuLi,
to give product 26 in essentially the same yield and selectivity as with LDA (cf. Entries 6
and 8)9). We were surprised to find that the diastereoselectivity observed with the t-Bu
substituted auxiliary was much poorer than with the i-Pr-substituted one (3 : 1 vs. 19 : 1;
Entries 8 and 10); normally, the tert-leucine-derived auxiliary is ꢀthe championꢁ10). N-
Acyl-oxazolidin-2-ones derived from other carboxylic acids can, of course, also be
alkylated; see the methylation (11 ! 31) shown on the bottom of Scheme 4.
The relative configuration at the newly formed stereogenic centers in compounds 29
and 30 was assigned by X-ray crystal-structure analysis (Chapt. 9). The configuration of
the other alkylation products was assigned by analogy11).
8
)
)
Additionally, it turned out that derivatives of 1 were generally ꢀmore crystallineꢁ than derivatives of 5. It
was thus possible to obtain diastereoisomerically pure products (dr >98 : 2) by simple recrystallization.
With the isopropyl-oxazolidinone 8, only ca. 5% by-products resulting from nucleophilic attack of BuLi on
the propanonyl group were detected, while, with benzyl-oxazolidinone 18, this reaction became a
dominant side reaction.
9
10
11
)
)
Cf. the discussion of X-ray crystal structures in Chapt. 9.
As expected for such systems, the electrophile is approaching the chelated enolate M from the face
opposite to the R group at C(4) of the heterocycle [20].

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Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 4
25
26
27
28
29
30
R
E
Me2CH
CH2 ˆ CHCH2
Me2CH
t-BuOCOCH2
Me2CH
PhCH2
PhCH2
CH2 ˆ CHCH2
PhCH2
t-BuOCOCH2
t-Bu
t-BuOCOCH2
Entry
R
Base
Electrophile
Product Temp. [8]
Yield [%]a) dr b)
1
2
3
4
5
6
7
8
9
PhCH2
PhCH2
Me2CH
Me2CH
Me2CH
Me2CH
Me2CH
Me2CH
NHMDS
CH2ˆCHCH2Br
28
28
25
27
78
75
4:1
94:6
96:4
> 98:2
92:8
95:5
LDA/ZnBr2 CH2ˆCHCH2Br
LDA/ZnBr2 CH2ˆCHCH2Br
LDA/ZnBr2 PhCH2Br
78 to 15 90
78 to 15 72 c)
78 to 15 81 c)
78 to 15 83
78
78
78
78
78
LDA/ZnBr2 BrCH2CO2(t-Bu) 26
LDA
t-BuLi
BuLi
BuLi
BuLi
BrCH2CO2(t-Bu) 26
BrCH2CO2(t-Bu) 26
BrCH2CO2(t-Bu) 26
BrCH2CO2(t-Bu) 29
BrCH2CO2(t-Bu) 30
80
56
82
55
49
95:5
95:5
d
PhCH2
)
n.d. e)
10
t-Bu d)
3:1
a) After FC. b) Diastereoisomer ratio, determined by 1H-NMR (300 MHz) of the crude product. c) After
recrystallization, dr > 98:2. d) The (R)-enantiomers of 17 and 18 were actually used in this experiment.
e) n.d. ˆ not determined (NHMDS ˆ hexamethyldisilazane).
5. Synthesis of b-Amino-Acid Derivatives. ± In the course of our investigation of b-
peptides (for a review, see [21]), we needed to have a general enantioselective route
to a-substituted b-amino acids (b2-amino acids). We chose the diastereoselective
aminomethylation of N-acyl-oxazolidin-2-one Ti-enolates, initially suggested by Evans
et al. [22], and later also used by Wyatt and co-workers [23]. Initially [24], we employed
N-(chloromethyl)benzamide as aminomethylating agent, to prepare N-benzoyl-pro-
tected b2-amino acids. Since the removal of the N-benzoyl group requires strongly
acidic conditions, under which partial racemization occurred, we switched to the N-
(methoxymethyl) N-[(benzyloxy)carbonyl] (Cbz) derivative also used by Evans and
co-workers [25]12), which leads to N-Cbz-protected b2-amino-acid derivatives, readily
deprotected under neutral conditions (H2, Pd/C).
12
)
Cf. the TiCl4-mediated reactions of methoxy derivatives obtained by electrolytic oxidative decarboxylation
of peptides [18][26].

Helvetica Chimica Acta ± Vol. 81 (1998)
2099
We found, that best results were obtained by generating a Ti-enolate at 208 (TiCl4/
tertiary amine), and performing the alkylation at 08 with the TiCl4-activated electro-
phile13). Thus, N-acyl-oxazolidin-2-ones 8 ± 11 (no functional groups in the acyl part!)
led to the b2-amino-acid derivatives 32 ± 35 in good yields and with high stereo-
selectivities (dr 12 : 1 ± 15 : 1; Scheme 5, Entries 1 ± 4)14). The method is, however, not
compatible with certain types of functional groups present in the acyl part: While an
ester (in 14) or phthalimido group (in 15) are tolerated (! 36, 37; Entries 5 and 6), the
(benzyloxy)phenyl group in 16 prevented a satisfactory yield of 38 (Entry 7), and with
the (R)-3-(benzyloxy)butanoyl and Cbz-indol-3-yl derivatives (22 and 23, resp.;
Entries 8 and 9), we did not even find products15).
Encouraged by the successful aminoalkylation of the 3-phthalimido-propanoyl-
oxazolidin-2-one 15 (! b,b'-diamino-acid derivative 37), we tried a hydroxymethyla-
tion of 15, to prepare a b2-serine: Reaction of the Ti-enolate of 15 with ClCH2OBn led
to a ca. 1 : 1 mixture of starting material and product 40 (difficult to separate), but
direct hydroxymethylation with trioxane [22] ( ! 92% 38) and subsequent benzylation
(87%) turned out to be a superior route to this compound (Scheme 5).
Since the use of Boc-protected b-amino acids has proven to be the method of choice
for the solution synthesis of b-peptides [21][24], a Cbz/Boc trans-protection by
hydrogenolysis of 32, 33, and 35 in the presence of Boc2O (2 h, 208) was performed
(! 41 ± 43, 81 ± 87%; Scheme 5). Interestingly, only traces of the by-product N resulting
from cleavage of the C(5) O bond in the auxiliary oxazolidinone ring were detected16).
6. Aldol Additions. ± Due to their central role in organic synthesis, stereoselective
aldol additions have been the subject of intensive studies. In particular, B- [4] and Ti-
enolates [17][28] of N-acyl-oxazolidin-2-ones are most useful reagents for the
preparation of 3-hydroxy carboxylic-acid derivatives of high enantiomeric purity.
Unfortunately, the simple N-acetyl-oxazolidin-2-ones generally undergo aldol addi-
tions with lower selectivities than their homologs [28][29]. We, therefore, chose
derivative 7 as a first substrate to test the auxiliary 1 in an aldol reaction17).
Addition of the Li-enolate of oxazolidin-2-one 7 to PhCHO at 788 afforded the
aldols 44 and 45 in high yield and with good selectivity 18) (dr 9 : 1; Scheme 6, Entry 1).
Use of the Ti-enolate, generated by transmetalation (3 equiv. (i-PrO)3TiCl) from the
Li-enolate [28], or of the B-enolate [14] gave poor selectivities (Entries 2 and 3). Direct
formation of a Ti-enolate [27] (1 equiv. TiCl4, EtN(i-Pr)2) led to a reversal of the
13
)
)
Activation of the electrophile with a second equiv. of TiCl4 is required to accelerate the reaction. At lower
temperatures, no alkylation was observed.
Besides the alkylation products, mainly starting material was recovered, probably resulting from proton
transfer from the electrophile to the enolate. To clearly identify the minor diastereoisomer in the 1H-NMR
spectra, authentic samples of the epimers of 32 ± 35 and 37 were prepared (acylation of (R)-1 with the Cbz-
protected amino acids from the reactions of (S)-1 and hydrolysis).
14
15
)
To assign the absolute configuration at the newly formed stereogenic center, 35 was transformed to the
known [24] free b2-amino acid (H2O2/LiOH; then H2, Pd/C).
16
17
)
)
Hydrogenolysis for 48 h under the same conditions led exclusively to N.
All aldol additions were carried out under conditions as reported in the literature for the corresponding
Evans oxazolidinones [14][27][28], in no case did we optimize for the 5,5-diphenyl derivatives.
The absolute configuration at the newly formed stereogenic center was derived by cleavage (H2O2/LiOH)
of 45, and comparison of the optical rotation of the free hydroxy acid [30].
18
)

2100
Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 5
Entry
Substrate
R
Product
Yield [%] a)
dr b)
1
2
3
4
5
6
7
8
9
8
9
Me
Me2CH
Me2CHCH2
PhCH2
MeOCO(CH2)2
PhthNCH2
(4-OBn)C6H4CH2
BnO(Me)CH
[(1-Cbz)indol-3-yl]CH2
32
33
34
35
36
37
69
70
64
78
42
65 c)
30d)
±
93:7
93:7
92:8
94:6
n.d.
95:5 c)
n.d.
±
10
11
14
15
16
22
23
38
± e)
± e)
±
±
a) After FC. b) Determined by 1H-NMR (300 MHz) of the crude product or after purification by FC.
c) Determined after recrystallization. d) Isolated as a 3:1 mixture of 38 and 16. e) No product was isolated.
diastereoselectivity of the reaction (dr 1 : 3; Entry 4), thus, aldol 45 was obtained as the
major product.
In aldol additions with propanoyl-oxazolidin-2-one 8, four diastereoisomeric
products, syn-1, syn-2, anti-1, and anti-2, can be formed (46 ± 51; see Scheme 7)19).
Addition of the Li-enolate to PhCHO at 788 gave syn-2 aldol 48 in very good
diastereoselectivity (dr 97: 3; Entry 1). A similar result was obtained when the Li-
Assignment of the configurations of aldols 46 ± 50 by cleavage (LiOH/H2O2) and comparison of 1H-NMR
19
)
and optical rotations of the resulting hydroxy acids with literature data [31].

Helvetica Chimica Acta ± Vol. 81 (1998)
2101
Scheme 6
Entry
Base
Solvent
Temp. [8]
Yield [%] a)
dr (44/45) b)
1
2
3
4
BuLi
THF
THF
CH2Cl2
CH2Cl2
78
88
89
74
82
90:10
56:44
67.33
25:75
BuLi, (i-PrO)3TiCl
EtN(i-Pr)2, Bu2BOTf
EtN(i-Pr)2, TiCl4
78 to 40
0
78 to 0
b
a) Combined yield of 44 and 45 after FC. ) Determined by H-NMR (300 MHz) of the crude product. Tf ˆ
1
CF3SO2.
enolate was transmetalated to the Ti-enolate (3 equiv. (iPrO)3TiCl) before addition to
the aldehyde (Entry 2). With the B-enolate, the aldol addition to PhCHO was almost
nonselective (syn-1 46/anti-1 50 3 : 2; Entry 3). Surprisingly, the result was quite
different when the nonaromatic isobutyraldehyde was employed: with the Li-enolate,
the selectivity was significantly lower, while a dramatic improvement was observed
with the B-enolate (dr 4 : 1 and 96 : 4; Entries 4 and 5); also lower yields were ob-
tained.
The stereochemical outcome of the aldol reactions can be discussed by using a
chair-like transition-state model [32]. Thus, R2B- and TiCl4-enolate derivatives
produce syn-1 aldols via intermediate O, and Li- or (i-PrO)3Ti-enolates are thought
to use an additional coordination site, to give syn-2 aldols via P (Scheme 8). Somewhat
strange are the results we obtained in the B-mediated aldol addition to PhCHO: In the
case of N-propionyl-oxazolidin-2-one 8 (Scheme 7, Entry 3), an unusually high amount
of anti-1 aldol 50 is formed20). This might be explained by an attractive interaction
between the Ph group of PhCHO and one of the Ph groups in the oxazolidinone ring
(see Q)21)22). In the aldol addition of N-acetyl-oxazolidin-2-one 7 B-enolate to
PhCHO, the selectivity is also better as compared to the analogous reaction of the
Evans oxazolidinone [4]. The stereochemical outcome of this reaction is not
compatible with the model used for the propionyl derivative, since addition to the
Re face (cf. syn-2 and anti-2) and not to the Si face of the aldehyde CˆO group occurs.
Also, the preferred formation of 44 would be in agreement with a favorable interaction
between the Ph groups of the aldehyde and the auxiliary, but with a boat-like transition
state (see R) which would only be favorable when R2 ˆ H. Further experiments would
20
)
)
)
As compared to the results with Evans oxazolidinones [4].
21
22
Resulting in a smaller difference of the transition-state energies between O and Q.
Since the results obtained with isobutyraldehyde are as expected, the anomalies in the case of PhCHO
probably result from an interaction between the Ph rings.

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Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 7
Entry
Base, Solvent
Aldehyde
Temp. [8]
Yield [%] a)
dr (s-1/s-2/a-1) b)
1
2
3
4
5
BuLi, THF
PhCHO
PhCHO
PhCHO
i-PrCHO
i-PrCHO
78
91
87
77
56
50
± c) : 97 : 3
6 : 93 : 1
60 : 2 : 37
6 : 80 : 14
96 :± c) : 4
BuLi, (i-PrO)3TiCl, THF
EtN(i-Pr)2, Bu2BOTf, CH2Cl2
BuLi, THF
78 to 40
0
78
0
EtN(i-Pr)2, Bu2BOTf, CH2Cl2
b
a) Combined yield of all isomers after FC. ) Determined by H-NMR (300 MHz) of the crude product; s ˆ
1
syn, a ˆ anti. c) A hyphen means that the corresponding isomer was not detected. Tf ˆ CF3SO2.
be necessary to arrive at a more definite interpretation of the unusual selectivities in the
aldol reactions of 7 and 8 with PhCHO23).
7. Michael and Diels-Alder Additions. ± As a consequence of the recent discovery,
that not only b-peptides [21], but also g-peptides [33] with short chain length, form
well-defined secondary structures in solution, there is now a need for efficient routes to
enantiomerically pure g-amino acids with various substitution patterns24).
To find out whether these would be accessible by Michael addition of the
derivatives of oxazolidinone (S)-1 to nitroolefins, we combined the Li-enolate of 8 with
1-nitro-2-phenylethene and RO-substituted nitrostyrenes (Scheme 9, Entries 1 ± 3) and
isolated the products 52 ± 54 in good yields and with high selectivities (ca. 10 :1); the
23
)
)
The aldol additions with PhCHO via P lead to significantly better selectivities than with the corresponding
Evans auxiliaries [28].
In the literature, we found only one example of a g-amino-acid derivative, having been prepared via
Michael addition of an N-acyl-oxazolidinone enolate to a nitroolefin and subsequent reduction of the NO2
to the NH2 group [34]. For our previous studies of diastereo- and enantioselective additions to nitroolefins,
see [35].
24

Helvetica Chimica Acta ± Vol. 81 (1998)
2103
Scheme 8
oxazolidinone 11 and nitrostyrene reacted with an even better selectivity (! 55; dr
32 : 1; Entry 4)25). These preliminary results show that the Michael addition of N-
acyloxazolidin-2-one enolates to nitroolefins may well be an ideal route to g-amino
acids26).
Scheme 9
Entry
Substrate
R
Ar
Product
Yield [%] a)
dr b)
1
2
3
4
8
8
8
11
Me
Me
Me
PhCH2
Ph
52
53
54
55
78 (58)
80
86
89:11
91:9
92:8
97:3
4-MeO ± C6H4
3,4-OCH2O-C6H3
Ph
92 (71)
b
a) After FC; numbers in brackets after recrystallization, dr > 98 : 2. ) Determined by 1H-NMR (300 MHz) of
the crude product.
In the reactions described so far, the enolate of an N-acyl-oxazolidin-2-one acted as
a donor to combine with an acceptor reactant. With a,b-unsaturated N-acyl-oxazolidin-
2-ones the relationship of reactants can be reversed [3]. As test reactions for the chiral
auxiliary 1 in this type of transformation, we chose the Diels-Alder reaction and the
Michael addition.
25
)
The relative configuration of the major diastereoisomer 55 was assigned by X-ray crystal-structure
analysis, that of products 52 ± 54 is assigned by analogy (the NMR spectra of the two series of epimers
show characteristic resemblances). The configuration of the minor diastereoisomer is unknown.
This reaction is the subject of a separate investigation (M. Brenner, ETH-Zürich).
26
)

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Helvetica Chimica Acta ± Vol. 81 (1998)
Thus, the addition of cuprates (prepared in situ from the corresponding Grignard
reagents [19]) to the Michael acceptors 12 and 13 was studied (Scheme 10). Phenyl
cuprate and N-crotonyl-oxazolidin-2-one 12 afforded a 2 :1 mixture of the epimers 56
and 57 (92%), and, in turn, treatment of N-cinnamoyl-oxazolidin-2-one 13 with methyl
cuprate led to a 1:2 mixture of these isomers, which could not be separated.
Scheme 10
Yield [%]
56/57
12 ‡ PhMgBr
13 ‡ MeMgBr
92
90
2 : 1
1 : 2
The Lewis-acid-promoted Diels-Alder reaction [36] of 12 with cyclopentadiene
gave endo-product 58 with excellent yield (87%) and with almost complete selectivity
(58(endo)/59(exo) 98 :2, dr in 58 >95 : 5; Scheme 11)27).
Scheme 11
8. Cleavage of the Chiral Auxiliary. ± Following a stereoselective reaction of an N-
acyl-oxazolidin-2-one, the chiral auxiliary has to be removed, separated from the
product, and preferably, recycled. There are numerous possibilities for this cleavage,
which lead to different derivatives: enantiomerically pure carboxylic acids, esters,
thioesters, amides, Weinreb amides, or alcohols are available from the same precursors
[3]. As model substrate for the cleavage reactions with our modified auxiliary 1, we
chose the alkylation product 27 (see Scheme 4).
27
)
The relative configuration of 58 was assigned by X-ray crystal-structure analysis. The diastereoselectivity
was determined by 1H-NMR of the crude product, the endo/exo ratio by 1H-NMR of the alcohols,
obtained by reductive removal (LiAlH4) of the auxiliary (cf. [37]).

Helvetica Chimica Acta ± Vol. 81 (1998)
2105
Hydrolysis to carboxylic acids is the by far most often used method for cleavage. To
prevent endocyclic cleavage (nucleophilic attack of the oxazolidinone CˆO group),
lithium hydroperoxide has often to be used instead of hydroxide [38]. In the case of 4-
isopropyl-5,5-diphenyloxazolidin-2-ones, endocyclic cleavage is efficiently prevented
by steric shielding from the Ph and i-Pr substituents. Thus, cleavage of 27 with NaOH
(208, 2.5 h) gave carboxylic acid 60 in essentially the same yield and enantiomeric purity
as cleavage with LiOH/H2O2 (08, 1.5 h; Scheme 12). Recycling of the auxiliary could be
achieved simply by filtrating and washing with H2O, Et2O, and pentane, which yielded
pure (S)-1 after drying. Alcoholytic cleavage to methyl ester 61 (MeOH, LiBr, DBU
[18][19]) or benzyl ester 62 (BnOLi [20]) proceeded with even better yields, and
recovery of (S)-1 was as easy as described above. Reductive cleavage (LiAlH4 [20]) to
the alcohol 63 was also possible, but recovery of the auxiliary turned out to be
problematic in this case, because of difficulties with the separation from Al salts.
In summary, we have shown that cleavage of the chiral oxazolidin-2-one 1 is feasible
under conditions commonly also used for other oxazolidinones, and recovery of the
Scheme 12

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Helvetica Chimica Acta ± Vol. 81 (1998)
auxiliary is very simple without the need for a purification step other than filtration and
washing. No partial racemization of the products 60 ± 63 or of the auxiliary was detected
(see enantiomeric purities, ep [%], given in Scheme 12)28).
9. X-Ray Crystal Structures. ± N-Acyl-oxazolidin-2-ones 11, 29, 30, 55, and 58 gave
crystals suitable for X-ray analysis. The asymmetric unit of the crystal of 55 contains
two crystallographically independent molecules which display almost the same
geometry. Thus, only one of the molecules is shown here. All other asymmetric units
contain only one molecule. Fig. 1 shows the ORTEP representations of crystal
structures that were used for the determination of the relative configurations of
reaction products.
Fig. 1. ORTEP Representations of the X-ray structures of 29 (a), 30 (b), 58 (c), and 55 (d). O-Atoms in red, N-
atoms in blue, C- and H-atoms in black; the thermal ellipsoids are drawn to the 50% probability level. The
structures were determined by Dr. B. Schweizer.
The overlay of the crystal structures of oxazolidin-2-ones 29 (derived from
phenylalanine), 30 (derived from tert-leucine), and 58 (derived from valine) shows that
the oxazolidinone ring, and also the diphenylmethylene unit, have the same
28
)
The enantiomeric purity of 1 was determined by HPLC on a chiral column (Chiralcel OD). Acid 60 was
converted to 61 (CH2N2). The enantiomeric purities of 61 and 63 were determined by HPLC (Chiralcel
OD), that of 62 by optical comparison [20] (see Exper. Part for details).

Helvetica Chimica Acta ± Vol. 81 (1998)
2107
conformation in all three compounds (Fig. 2,a). Small differences can be seen of the
pyramidalization of the oxazolidinone N-atom and of the orientation of the
substituents at C(4) of the oxazolidinone. The i-Pr group (e.g., in 58) is forced by the
neighboring Ph groups to shield the face towards the acyl group in all cases (see also
Fig. 2,b; superposition of 11, 55, and 58). In contrast, the PhCH2 group in the crystal
structure of 4-benzyl-oxazolidin-2-one 29 is directed towards the ring Ph group (aryl/
aryl interaction?); thus, the acyl group is not as efficiently shielded, which might be the
cause for the slightly lower stereoselectivity obtained in the alkylation of benzyl-
oxazolidinone vs. isopropyl-oxazolidinone (see Scheme 4). There is a hint for a possible
interpretation of the appreciably lower selectivity obtained in this reaction with 4-(tert-
butyl)-oxazolidin-2-one 17, in the superposition shown in Fig. 2,a: the bulky t-Bu group
induces a stronger pyramidalization of the N-atom, thus reducing the free space on the
face opposite to the inducing residue. If this effect would also be present in the enolate
of the corresponding N-acyl-oxazolidin-2-one, a lower diastereoselectivity should
indeed result!
To learn more about the N-acyl-oxazolidin-2-ones, we also tried to crystallize their
Lewis-acid complexes and enolates. Unfortunately, experiments with 5,5-diphenyl-
Fig. 2. Stereo representations of overlays of the oxazolidin-2-one X-ray structures. The structures were best fitted
on the oxazolidinone ring atoms. H-Atoms have been omitted for clarity; O-atoms in red, N-atoms in blue, C-
atoms in grey. The figure was generated by K. Gademann, using MolMol [42] and POV-Ray. a) Superposition of
the structures of oxazolidin-2-ones 11 (auxiliary derived from l-valine; the sense of chirality of the structures of
29 and 30 was actually inverted to allow for superposition), 29 (from d-phenylalanine), and 30 (from d-tert-
leucine). b) Superposition of the structures of the oxazolidin-2-ones 11, 55, and 58 (auxiliaries all derived from
l-valine). It is remarkable that the i-Pr group has exactly the same orientation in all three structures. Obviously,
the Ph substituent in cis-position forces the i-Pr group to present itself towards the acyl position like a t-Bu group!

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Helvetica Chimica Acta ± Vol. 81 (1998)
oxazolidin-2-one derivatives were not successful. However, we were able to determine
the crystal structure of the TiCl4/4-benzyl-N-propionyloxazolidin-2-one complex (64;
see Fig. 3,a). Fig. 3,b shows a hypothetical TiCl4-enolate of 5,5-diphenyl-oxazolidin-2-
one 8, constructed from the data of the crystal structures of the TiCl4-complex 64 and of
the oxazolidinone 11. It is obvious from the representation in Fig. 3,b, that one face of
the enolate is efficiently shielded by the i-Pr group, but also, that the Ph group trans to
the i-Pr group has probably no beneficial effect on the induction abilities of the
auxiliary.
Fig. 3. a) Stereo ORTEP representation of the X-ray crystal structure of the TiCl4-complex of (S)-4-benzyl-3-
propionyloxazolidin-2-one (64). One molecule of CH2Cl2 is present in the unit cell. O-Atoms in red, N-atoms in
blue, Cl-atoms in green, Ti-, C-, and H-atoms in black; the thermal ellipsoids are drawn to the 50% probability
level. The structure was determined by Dr. B. Schweizer. b) Hypothetical structure of the TiCl4-enolate of N-
propionyl-oxazolidin-2-one 8. The model was generated from the coordinates of 64 and of oxazolidinone 11. O-
Atoms in red, N-atom in blue, Ti-atom in black, Cl-atoms in green.

Helvetica Chimica Acta ± Vol. 81 (1998)
2109
10. Conclusions and Discussion. ± We have shown herein that the chiral auxiliary 1,
easily accessible from valine esters, is a useful alternative to the widely employed Evans
oxazolidinones F ± I. Thus, besides some minor drawbacks (higher molecular weight
and in some cases slightly lower stereoinduction), oxazolidinone 1 has a number of
advantages: i) N-Acyl-oxazolidin-2-ones of type C and D (Scheme 1) are generally
more prone to crystallize than the corresponding derivatives of F ± I (see Table 1). This
makes purification and separation from diastereoisomeric and other impurities easier.
ii) Because of the high insolubility of 1 in most organic solvents, recycling of the
auxiliary (see A in Scheme 1) after cleavage can be achieved by simply filtering and
washing (see Chapt. 8). iii) The stereoinduction of 1 in diastereoselective reactions
(C ! D) is generally comparable to that of Evans oxazolidinones [4][20][28][36].
However, in some cases there may be differences originating from aryl/aryl interactions
between auxiliary and reactants (see Chapt. 6), which can even render 1 a superior
auxiliary. iv) Acylation of the auxiliary 1 with BuLi may be performed at elevated
temperatures29) (08 as compared to 788 for Evans oxazolidinones), which is an
energetical and apparative advantage, especially in large-scale applications30). v) BuLi
can be used directly for the generation of Li-enolates29) (see Chapt. 4, 6, and 7), while,
for Evans oxazolidinones, the more expensive LDA is required. vi) The N-acyl-
oxazolidin-2-ones can be cleaved using NaOH without detectable nucleophilic attack
on the oxazolidinone ring29) (see Chapt. 8). For Evans oxazolidinones, the more costly
system LiOH/H2O2 must generally be used.
Finally, it is worth mentioning, in view of our work on b- and g-peptides [21][33],
that we have demonstrated the usefulness of oxazolidinone 1 for the preparation of
enantiomerically pure b- and g-amino-acid derivatives (Chapt. 5 and 7).
Dr. W. Pachinger of Novartis Pharma AG is gratefully acknowledged for the preparation and donation of a
large quantity of 1. We thank K. Gademann for his help in arranging the superpositions in Fig. 2. A. Häne and
M. Frei have carried out some of the experiments described herein, as a part of the requirements for the
advanced laboratory course in organic chemistry. We thank Dr. B. Schweizer for the determination of the X-ray
crystal structures. We thank Novartis Pharma AG, Basel, for continuing support.
Experimental Part
1. General. Abbreviations: BnOH: benzyl alcohol, Cbz: benzyloxycarbonyl, DBU: 1,8-diazabicy-
clo[5.4.0]undec-7-ene, h.v. (high vacuum, 0.01 ± 0.1 Torr), LDA: lithium diisopropylamide. BuLi was used as
a ca. 1.6m soln. (hexane), ClAlMe2 as 1m soln. (hexane), and Bu2BOTf as 1m soln. (CH2Cl2). THF was freshly
distilled over K under Ar before use. DIPA, Et3N, BnOH, and CH2Cl2 (for aldol reactions) were distilled over
CaH2 and stored over 4-Š molecular sieves. Aldehydes were freshly distilled. Solvents for FC and workup
procedures were distilled over Sikkon (anh. CaSO4; Fluka). LiBr, LiCl, and ZnBr2 were dried under h.v. at 1508
overnight. BnBr, allyl bromide, MeI, and tert-butyl bromoacetate were filtered through basic Al2O3 (activity I)
directly prior to use. 3-(Phthaloylamino)propanoyl chloride, (R)-3-(benzyloxy)butanoyl chloride, 4-methyl-
pentanoyl chloride, and 3-[4-(benzyloxy)phenyl]propanoyl chloride were prepared from the corresponding
carboxylic acids by treatment with oxalyl chloride [47]. (R)-3-(Benzyloxy)butanoic acid [47] and 3-[4-
(benzyloxy)phenyl]propanoic acid [48] were prepared according to, 3-[(1-Cbz)indol-3-yl]propanoic acid [23] in
29
)
It is tempting to compare the acyl derivatives of 1 with compounds containing what we have once called
sterically protected but electronically effective CˆO groups [43 ± 46]: the enolates of such compounds
have been shown to be generated with BuLi [44] and their enoyl moieties to undergo Michael additions
with RMgX and RLi reactants (without intervention of CuI additives) [45]; also, such compounds can be
used for the reactivity umpolung of C-atoms in a-positions with respest to N- and O-atoms [46].
Preparation of 1 in multi-kg scale has been achieved without encountering problems.
30
)

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Helvetica Chimica Acta ± Vol. 81 (1998)
Table 1. Comparison of the Melting Points of Derivatives of Evans Oxazolidinones F, G, I, and of the Geminally
Diphenyl-Substituted Auxiliary 1. As yet, there are no corresponding data available for 5,5-dimethyl-oxazolidin-
2-ones [7]. n.k. ˆ not known.
R
H
71 ± 72
[4]
liquid
[39]
56 ± 56.5
[36]
liquid
[20]
liquid
[20]
65 ± 66
[28]
94
[28]
87 ± 88.5
[5]
41
[40]
85 ± 86
[36]
92
[40]
n.k.
n.k.
n.k.
n.k.
n.k.
120 ± 121
[4]
99 ± 100
[41]
66 ± 66.5
[36]
liquid
[20]
69 ± 70
[20]
250 ± 252 111 ± 112
135 ± 136
131 ± 132
110 ± 111
146 ± 148
163 ± 164
analogy to known procedures. All other reagents were used as received from Fluka or Aldrich. TLC: Merck
silica gel 60 F254 plates; detection with UVor dipping into a soln. of KMnO4 (1.5 g in 333 ml 1m NaOH) or a soln.
of anisaldehyde (9.2 ml), AcOH (3.75 ml), conc. H2SO4 (12.5 ml), and EtOH (338 ml), followed by heating.
FC: Fluka silica gel 60 (40 ± 63 mm); at ca. 0.3 bar. Anal. HPLC: Knauer HPLC system (pump type 64,
EuroChrom 2000 integration package, degaser, UV detector (variable-wavelength monitor)); Chiralcel OD
(Daicel Chemical Industries, Ltd.; 4.6 Â 250 mm, 10 mm). M.p.: Büchi-510 apparatus; uncorrected. Optical
rotations: Perkin-Elmer 241 polarimeter (10 cm, 1 ml cell) at r.t. IR Spectra: Perkin-Elmer-782 spectropho-
tometer. NMR Spectra: Bruker AMX 500 (1H: 500 MHz, 13C: 125 MHz), AMX 400 (1H: 400 MHz, 13C:
100 MHz), Varian Gemini 300 (1H: 300 MHz, 13C: 75 MHz), or Gemini 200 (1H: 200 MHz, 13C: 50 MHz);
chemical shifts (d) in ppm downfield from Me4Si (ˆ 0 ppm); J values in Hz. MS: VG Tribrid (EI) or FG ZAB-2
SEQ (FAB; in a 3-nitrobenzyl-alcohol matrix) spectrometer; in m/z (% of basis peak). Elemental analyses were
performed by the Microanalytical Laboratory of the Laboratorium für Organische Chemie, ETH-Zürich.
2. Preparation of 2-Amino-1,1-diphenyl Alcohols. General Procedure 1 (GP 1). The appropriate amino-
acid ester salt (1 equiv.) was suspended in Et2O (5 ml/mmol) and extracted with 1m NaOH soln. (1.5 equiv.). The
aq. phase was separated and extracted with Et2O, the org. phases were dried (MgSO4) and evaporated. A soln.
of the resulting amino-acid ester in Et2O (2m) was added to a soln. of PhMgBr (3 ± 4 equiv.; freshly prepared
from Mg and PhBr) in Et2O (1.2m) over a period of 30 min. After addition to the Grignard reagent, the mixture
was refluxed for 7 ± 9 h. Excess PhMgBr and Mg salts were hydrolyzed by careful addition of ice and H2O.
Individual workup yielded the amino alcohols.
3. Preparation of 5,5-Diphenyl-oxazolidin-2-ones. General Procedure 2 (GP 2). To a soln. of the amino
alcohol (1 equiv.) and Et3N (1.1 equiv.) in CH2Cl2 (0.2m), ClCO2Et (1 equiv). was added at ca. 258 (dry ice/
acetone bath). The mixture was allowed to warm slowly to r.t., stirred overnight, diluted with CH2Cl2, and
washed with 1m HCl soln. The org. phase was evaporated, the residue suspended in 5 wt.-% NaOH in MeOH
(0.23m), refluxed for 9 h, diluted with H2O, and cooled to 48. The suspension was filtered, the residue washed
with H2O, Et2O (ca. 1 ml/mmol), and pentane. The resulting white powder was dried (h.v.) and used without
further purification.

Helvetica Chimica Acta ± Vol. 81 (1998)
2111
4. Acylation of the Auxiliary with Acyl Chlorides. General Procedure 3 (GP 3). To a suspension of the
auxiliary (1 equiv.) in THF (0.25m), BuLi (1.00 ± 1.05 equiv.) was slowly added at 08 (ice bath). To the resulting
clear soln., the acyl chloride (1.2 equiv.) was added in one portion. The mixture was allowed to warm slowly to
r.t. overnight, treated with sat. NH4Cl soln., and diluted with Et2O. The org. phase was washed with 1m HCl
(2Â), 1m NaOH (2Â) and sat. NaCl solns., dried (MgSO4), and evaporated. The resulting crude product was
purified by FC or recrystallization.
5. Acylation of the Auxiliary with Mixed Anhydrides [16]. General Procedure 4 (GP 4). To a soln. of the
appropriate acid (1.05 equiv.) in THF (0.2m), Et3N (2.6 equiv.) and pivaloyl chloride (1.05 equiv.) were added at
ca. 308. The resulting white suspension was stirred at this temp. for 1 ± 2 h, LiCl (1.15 equiv.) and the auxiliary
(1 equiv.) were added, and the mixture was allowed to warm slowly to r.t. overnight. The mixture was treated
with sat. NH4Cl soln. and diluted with Et2O. Workup according to GP 4.
6. Alkylation of N-Acyl-oxazolidin-2-ones Using LDA/ZnBr2 [19]. General Procedure 5 (GP 5). To a soln.
of N-acyl-oxazolidin-2-one (1 equiv.) in THF (0.2 ± 0.3m), a precooled soln. of LDA (1.25 equiv.) was added at
788 (LDA soln. was freshly prepared by treating a soln. of DIPA (1 equiv.) in THF (0.5m) with BuLi (1 equiv.)
at ca. 408 for 30 min). After stirring for 30 min at 788, a soln. of ZnBr2 (1.25 equiv.) in THF (0.5m) was
added. The resulting Zn-enolate was stirred for additional 30 min at 788 and then treated with the electrophile.
The mixture was allowed to warm to 158, stirred at this temp. for 24 h, treated with sat. NH4Cl soln., and
diluted with Et2O. Workup according to GP 4.
7. Alkylation of N-Acyl-oxazolidin-2-ones Using BuLi. General Procedure 6 (GP 6). To a soln. of N-acyl-
oxazolidin-2-one (1 equiv.) in THF (0.2m), BuLi (1.1 equiv.) was added at 788. After stirring for 30 min at
788, the clear soln. was treated with the electrophile. The mixture was stirred at 788 for 20 h, treated with sat.
NH4Cl soln., and diluted with Et2O. Workup according to GP 4.
8. Amidoalkylation of N-Acyl-oxazolidin-2-ones. General Procedure 7 (GP 7). To a soln. of the N-acyl-
oxazolidin-2-one (1 equiv.) in CH2Cl2 (0.2m), TiCl4 (1.00 ± 1.05 equiv.) was added at 208. To the yellow soln.,
Et3N or EtN(i-Pr)2 (1.00 ± 1.10 equiv.) was added and the resulting dark red soln. stirred at ca. 208 for 30 min
before addition of a soln. of the electrophile (1.1 equiv.) in CH2Cl2 (0.5m) and TiCl4 (1.1 equiv.). The mixture
was stirred at 08 (ice-bath) for 2 ± 3 h, treated with sat. NH4Cl soln., and diluted with CH2Cl2 or Et2O. The org.
phase was washed with 1m HCl (2Â), 1m NaOH, and sat. NaCl solns., dried (MgSO4), and evaporated. The
resulting crude product was purified by FC and, if required, recrystallization.
9. Aldol Reaction via Li-Enolate [28]. General Procedure 8 (GP 8). To a soln. of the N-acyl-oxazolidin-2-
one (1 equiv.) in THF (0.2m), BuLi (1.1 equiv.) was added at 788. The soln. was stirred for 30 min, the
aldehyde (1.1 equiv.) quickly added, and the reaction stopped after 30 s by treatment with sat NH4Cl soln.
Workup according to GP 7.
10. Aldol Reaction via B-Enolate [4]. General Procedure 9 (GP 9). To a soln. of the N-acyl-oxazolidin-2-one
(1 equiv.) in CH2Cl2 (0.4m), Bu2BOTf (1.2 equiv.) and EtN(i-Pr)2 (1.3 equiv.) was added at 08 (ice-bath). The
soln. was cooled to 788 and the aldehyde (1.1 equiv.) added. The mixture was stirred at 788 for 20 min, then
at 08 for 1 h, treated with phosphate buffer (pH 7, 1 ml/mmol), MeOH (3 ml/mmol), and H2O2/MeOH 1 : 2
(3 ml/mmol), and stirred at r.t. for 1 h. Et2O was added, the org. phase washed with 0.5m HCl, sat. NaHCO3, and
sat. NaCl solns., dried (MgSO4), and evaporated. The crude product was purified by FC.
11. Alkylation of N-Acyl-oxazolidin-2-ones with w-Nitrostyrenes. General Procedure 10 (GP 10). To a soln.
of the N-acyl-oxazolidin-2-one (1 equiv.) in THF (0.2m), BuLi (1.05 equiv.) was added at 788. The enolate was
stirred for 30 min at 788, a precooled soln. of the w-nitrostyrene (1.1 equiv.) in THF (0.5m) added, the mixture
stirred at 788 for further 2 h, then treated with sat. NH4Cl soln., and diluted with Et2O. The org. phase was
washed with 0.5m HCl, 1m NaOH, and sat. NaCl solns., dried (MgSO4), and evaporated. The crude product was
purified by FC.
12. Cbz-Deprotection/Boc-Protection of Amidoalkylation Products. General Procedure 11 (GP 11). To a
soln. of the Cbz-protected compound (1 equiv.) and Boc2O (1 equiv.) in THF (0.1 ± 0.2m), Pd/C (10 wt.-%) was
added. The apparatus was evacuated and flushed three times with H2 and the mixture stirred at r.t. for 2 h under
H2 (ballon). Filtration through Celite and concentration under reduced pressure yielded the crude Boc-
protected compound, which was purified by FC.
(S)-4-(1-Methylethyl)-5,5-diphenyloxazolidin-2-one ((S)-1). l-Valine methyl ester hydrochloride (16.8 g,
100 mmol) was treated with PhMgBr (300 mmol) according to GP 1. After hydrolysis, 1m HCl was added to the
mixture to generate a homogenous suspension. AcOEt (500 ml) was added, and the pH adjusted to 11 with conc.
aq. NH3 soln. The org. layer was separated and the aq. phase extracted with AcOEt. The combined org. phases
were dried (Na2SO4; ca. 20 ml of MeOH were added to prevent precipitation of the amino alcohol) and
evaporated. Recrystallization (EtOH) gave (S)-2-amino-3-methyl-1,1-diphenylbutanol ((S)-2; 7.8 g). From the

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mother liquor, further 2 (4.6 g) was obtained. Total yield: 12.3 g (48%). White needles. According to GP 2, (S)-2
(10.4 g, 41 mmol), Et3N (6.56 ml, 45 mmol), and ClCO2Et (4.10 ml, 43 mmol) were transformed to (S)-1 (10.5 g,
91%). The enantiomer ratio was determined by anal. HPLC (hexane/i-PrOH 90 :10; flow 1 ml/min, detection at
254 nm; (S)-1; tR 8 min, (R)-1: tR 24 min), to be >99 : 1. White powder. M.p. 250 ± 2528. [a]Dr:t:
ˆ
259.4 (c ˆ 0.32,
CHCl3). IR (CHCl3): 3458w, 2967w, 1757s, 1495w, 1450w, 1003w. 1H-NMR (300 MHz, CDCl3): 0.69 (d, J ˆ 6.3,
Me); 0.90 (d, J ˆ 6.9, Me); 1.80 ± 1.95 (m, Me2CH); 4.36 (d, J ˆ 3.6, NCH); 6.44 (s, NH); 7.22 ± 7.43
(m, 8 arom. H); 7.53 ± 7.56 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 15.6, 20.8 (Me); 29.6, 65.8 (CH);
‡
89.4 (C); 125.7, 126.3, 127.7, 128.1, 128.2, 128.5 (CH); 139.2, 143.9, 158.7 (C). EI-MS: 281 (6, M ), 238(4),
194(21), 183(100), 165(16).
(S)-4-Benzyl-5,5-diphenyloxazolidin-2-one ((S)-5). l-Phenylalanine ethyl ester hydrochloride (23.0 g,
100 mmol) was treated with PhMgBr (300 mmol) according to GP 1. After hydrolysis, 1m HCl was added to the
mixture to generate a homogenous suspension, and the pH adjusted to 11 with conc. aq. NH3 soln. Et2O (250 ml)
was added, the org. layer was separated and the aq. phase extracted with Et2O. The combined org. phases were
washed with H2O, dried (Na2SO4; ca. 20 ml of MeOH were added to prevent precipitation of the amino
alcohol), and evaporated. The resulting yellow solid was triturated (toluene, 50 ml) to yield (S)-2-amino-1,1,3-
triphenylpropan-1-ol ((S)-3; 11.4 g). From the residue of the mother liquor, further 3 (3.7 g) was obtained by
trituration. Total yield: 15.2 g (50%). White powder. According to GP 2, (S)-3 (12.1 g, 40 mmol), Et3N (6.40 ml,
44 mmol), and ClCO2Et (4.00 ml, 42 mmol) were transformed to yield after trituration (CHCl3, 40 ml) (S)-5
(11.4 g, 86%). The enantiomer ratio was determined by anal. HPLC (hexane/i-PrOH 93 :7; flow 1 ml/min,
detection at 254 nm; (S)-5: tR 18 min, (R)-5: tR 37 min) to be >99 : 1. White powder. M.p. 255 ± 2578. [a]Dr:t:
ˆ
281.5 (c ˆ 0.63, CHCl3). IR (CHCl3): 3442w, 3008w, 1763s, 1495w, 1449w, 1000w. 1H-NMR (300 MHz,
CDCl3): 2.19 (dd, J ˆ 13.7, 11.5, 1 H, PhCH2); 2.61 (dd, J ˆ 13.8, 3.0, 1 H, PhCH2); 4.68 (dd, J ˆ 11.4, 2.4, NCH);
4.93 (s, NH); 7.10 ± 7.16 (m, 2 arom. H); 7.20 ± 7.48 (m, 11 arom. H); 7.53 ± 7.60 (m, 2 arom. H). 13C-NMR
(75 MHz, CDCl3): 39.9 (CH2); 61.9 (CH); 89.1 (C); 126.4, 126.6, 127.5, 128.3, 128.6, 128.8, 128.9, 129.2, 129.4
‡
‡
(CH); 137.1, 139.5, 142.6, 157.5 (C). FAB-MS: 659 (49, [2M ‡ H] ), 330 (100, [M ‡ H] ).
(R)-4-(tert-Butyl)-5,5-diphenyloxazolidin-2-one ((R)-6). d-tert-Leucine methyl ester hydrochloride
(1.36 g, 7.5 mmol) was treated with PhMgBr (30 mmol) according to GP 1. After hydrolysis, 1m HCl was
added to the mixture to generate a homogenous suspension. AcOEt was added, and the pH adjusted to 11 with
conc. aq. NH3 soln. The org. layer was separated and the aq. phase extracted with AcOEt (2Â). The combined
org. phases were dried (MgSO4) and evaporated. The resulting crude (R)-2-amino-3,3-dimethyl-1,1-
diphenylbutan-1-ol ((R)-4; 2.04 g, 101%) was used without further purification. According to GP2, (R)-4
(1.34 g, 5 mmol), Et3N (8.80 ml, 5.5 mmol), and ClCO2Et (0.50 ml, 5 mmol) were transformed to (R)-6
(974 mg, 66%). White powder. M.p. 2908 (dec.). [a]rD:t: ˆ‡ 336.5 (c ˆ 0.36, CHCl3). IR (CHCl3): 3467w, 2968w,
1758s, 1450w, 1002w. 1H-NMR (300 MHz, CDCl3): 0.80 (s, t-Bu); 4.24 (s, NCH); 6.27 (s, NH); 7.22 ± 7.63
(m, arom. H). 13C-NMR (75 MHz, CDCl3): 26.8 (Me); 35.5 (C); 69.1 (CH); 90.1 (C); 126.9, 127.9, 128.1, 128.3,
‡
128.4, 128.7 (CH); 138.7, 145.1, 158.5 (C). EI-MS: 295 (3, M ), 251(2), 195(98), 183(100), 165(37).
(S)-3-Acetyl-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one ((S)-7). Compound (S)-1 (8.44 g, 30 mmol)
was treated with BuLi (19.8 ml, 31.5 mmol) and AcCl (2.56 ml, 36 mmol) according to GP 3. Recrystallization
(pentane/Et2O) yielded (S)-7 (5.74 g). From the mother liquor, further 7 (3.07 g) was obtained. Total yield:
8.81 g (91%). White needles. M.p. 121 ± 1228. [a]Dr:t:
ˆ
252.5 (c ˆ 1.33, CHCl3). IR (CHCl3): 2972m, 1779s,
1699s, 1494m, 1459m, 1369m, 1317m, 1177m, 1051m, 993m, 922m, 637m. 1H-NMR (400 MHz, CDCl3): 0.76
(d, J ˆ 6.8, Me); 0.88 (d, J ˆ 7.0, Me); 1.92 ± 2.03 (m, CH); 2.43 (s, C(O)Me); 5.37 (d, J ˆ 3.4, NCH); 7.26 ± 7.49
(m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 21.7, 23.5 (Me); 29.9, 64.4 (CH); 89.4 (C); 125.6, 126.0, 128.0,
‡
‡
128.4, 128.6, 128.9 (CH); 138.2, 142.3, 153.2, 170.1 (C). FAB-MS: 647 (6, [2M ‡ H] ), 324 (100, [M ‡ H] ),
280(58). Anal. calc. for C20H21NO3 (323.39): C 74.28, H 6.54, N 4.33; found: C 74.28, H 6.77, N 4.36.
(S)-4-(1-Methylethyl)-3-(1-oxopropyl)-5,5-diphenyloxazolidin-2-one ((S)-8). Compound (S)-1 (7.03 g,
25 mmol) was treated with BuLi (16.7 ml, 26 mmol) and propanoyl chloride (2.63ml, 30 mmol) according to
GP 3. Recrystallization (pentane/Et2O) yielded (S)-8 (6.27 g). From the mother liquor, further 8 (1.50 g) was
obtained. Total yield: 7.77 g (92%). White needles. M.p. 111 ± 1128. [a]Dr:t:
ˆ
239.7 (c ˆ 0.74, CHCl3). IR
(CHCl3): 2976w, 1781s, 1706m, 1450m, 1369m, 1319m, 1177m, 1050m. 1H-NMR (400 MHz, CDCl3): 0.74 (d, J ˆ
6.8, Me); 0.88 (d, J ˆ 7.0, Me); 1.08 (t, J ˆ 7.4, MeCH2); 1.92 ± 2.09 (m, CH); 2.68 ± 2.78 (m, 1 H, CH2); 2.88 ±
2.98 (m, 1 H, CH2); 5.38 (d, J ˆ 3.4, NCH); 7.25 ± 7.49 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 8.6, 16.4,
21.8 (Me); 28.9 (CH2); 29.9, 64.4 (CH); 89.4 (C); 125.6, 125.9, 127.9, 128.4, 128.6, 128.9 (CH); 138.3, 142.4,
‡
153.1, 174.0 (C). EI-MS: 338 (< 1, [M ‡ H] ), 294(11), 238(20), 220(30), 194(31), 183(100). Anal. calc. for
C21H23NO3 (337.42): C 74.75, H 6.87, N 4.15; found: C 74.70, H 6.87, N 4.13.

Helvetica Chimica Acta ± Vol. 81 (1998)
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(S)-4-(1-Methylethyl)-3-(3-methyl-1-oxobutyl)-5,5-diphenyloxazolidin-2-one ((S)-9). Compound (S)-1
(8.44 g, 30 mmol) was treated with BuLi (18.9 ml, 30 mmol) and 3-methylbutanoyl chloride (4.43 ml, 36 mmol)
according to GP 3. Recrystallization (AcOEt/hexane) yielded (S)-9 (8.53 g). From the mother liquor further 9
(0.99 g) was obtained. Total yield: 9.52 g (87%). White needles. M.p. 118 ± 1198. [a]Dr:t:
ˆ
205.5 (c ˆ 0.56,
1
CHCl3). IR (CHCl3): 2966m, 1781s, 1699m, 1450m, 1371m, 1318m, 1177m. H-NMR (400 MHz, CDCl3): 0.76
(d, J ˆ 6.8, Me); 0.81 (d, J ˆ 6.7, Me); 0.87 (d, J ˆ 6.8, Me); 0.88 (d, J ˆ 7.5, Me); 1.92 ± 2.09 (m, 2 Me2CH);
2.65 ± 2.75 (m, CH2); 5.37 (d, J ˆ 3.4, NCH); 7.25 ± 7.49 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 21.8,
22.2, 22.3 (Me); 25.4, 29.8 (CH); 43.6 (CH2); 64.6 (CH); 89.3 (C); 125.6, 125.9, 127.9, 128.4, 128.6, 128.9 (CH);
‡
‡
138.2, 142.4, 153.1, 172.5 (C). FAB-MS: 731 (4, [2M ‡ H] ), 366 (100, [M ‡ H] ), 322 (31). Anal. calc. for
C23H27NO3 (365.47): C 75.59, H 7.45, N 3.83; found: C 75.58, H 7.45, N 3.92.
(S)-4-(1-Methylethyl)-3-(4-methyl-1-oxopentyl)-5,5-diphenyloxazolidin-2-one ((S)-10). Compound (S)-1
(7.03 g, 25 mmol) was treated with BuLi (15.0 ml, 25 mmol) and 4-methylpentanoyl chloride (4.04 g, 30 mmol)
according to GP 3. FC (pentane/Et2O 9 :1) yielded (S)-10 (7.50 g, 79%). Colorless oil. [a]Dr:t:
ˆ
202.8 (c ˆ 1.60,
CHCl3). IR (CHCl3): 3011w, 2962m, 2873w, 1781s, 1699s, 1450m, 1366s, 1320m, 1177s, 1051m, 1001m. 1H-NMR
(400 MHz, CDCl3): 0.76 (d, J ˆ 6.8, Me); 0.82 (d, J ˆ 6.3, Me); 0.84 (d, J ˆ 6.4, Me); 0.88 (d, J ˆ 7.0, Me); 1.35 ±
1.50 (m, 3 H, Me2CHCH2); 1.91 ± 2.03 (m, Me2CH); 2.70 ± 2.78 (m, 1 H, C(O)CH2); 2.83 ± 2.92 (m, 1 H,
C(O)CH2); 5.37 (d, J ˆ 3.4, NCH); 7.25 ± 7.49 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 21.8, 22.2
(Me); 27.6, 29.9 (CH); 33.3, 33.4 (CH2); 64.5 (CH); 89.3 (C); 125.6, 125.9, 127.9, 128.4, 128.6, 128.9 (CH); 138.2,
‡
142.4, 153.1, 173.5 (C). FAB-MS: 380 (100, [M ‡ H] ), 336(39). Anal. calc. for C24H29NO3 (379.50): C 75.96,
H 7.70, N 3.69; found: C 75.92, H 7.73, N 3.70.
(S)-4-(1-Methylethyl)-5,5-diphenyl-3-(1-oxo-3-phenylpropyl)oxazolidin-2-one ((S)-11). Compound (S)-1
(14.1 g, 50 mmol) was treated with BuLi (33 ml, 52.5 mmol) and 3-phenylpropanoyl chloride (8.93 ml, 60 mmol)
according to GP 3. Recrystallization (pentane/Et2O) yielded (S)-11 (17.4 g, 92%). White needles. M.p. 97 ± 988.
[a]rD:t:
ˆ
179.0 (c ˆ 1.14, CHCl3). IR (CHCl3): 2969w, 1781s, 1701m, 1496w, 1450m, 1366m, 1320m, 1176m,
1052w, 991w. 1H-NMR (400 MHz, CDCl3): 0.73 (d, J ˆ 6.8, Me); 0.84 (d, J ˆ 7.0, Me); 1.90 ± 2.01 (m, Me2CH);
2.82 ± 2.97 (m, C(O)CH2); 3.02 ± 3.10 (m, 1 H, PhCH2); 3.20 ± 3.28 (m, 1 H, PhCH2); 5.37 (d, J ˆ 3.4, NCH);
7.12 ± 7.47 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 21.7 (Me); 29.9 (CH); 30.5, 36.7 (CH2); 64.5
(CH); 89.4 (C); 125.6, 125.9, 126.2, 128.0, 128.4, 128.4, 128.6, 128.9 (CH); 138.2, 140.3, 142.3, 153.0, 172.2 (C).
‡
‡
FAB-MS: 827 (8, [2M ‡ H] ), 414 (100, [M ‡ H] ), 370(34). Anal. calc. for C27H27NO3 (413.52): C 78.42,
H 6.58, N 3.39; found: C 78.56, H 6.73, N 3.38.
(S)-4-(1-Methylethyl)-3-[(E)-2-oxobut-2-enyl]-5,5-diphenyloxazolidin-2-one ((S)-12). Compound (S)-1
(5.63 g, 20 mmol) was treated with BuLi (12.6 ml, 20 mmol) and (E)-but-2-enoylchloride (2.32 ml, 24 mmol)
according to GP 3. Recrystallization (AcOEt/hexane) yielded (S)-12 (4.32 g). From the mother liquor, further
12 (1.35 g) was obtained. Total yield: 5.67 g (81%). White solid. M.p. 135 ± 1368. [a]Dr:t:
ˆ
239.4 (c ˆ 1.02,
CHCl3). IR (CHCl3): 2969m, 1777s, 1685m, 1638m, 1450m, 1343s, 1177s, 1036m, 970m, 920m. 1H-NMR
(400 MHz, CDCl3): 0.77 (d, J ˆ 6.8, Me); 0.89 (d, J ˆ 7.0, Me); 1.90 (dd, J ˆ 6.5, 1.2, Me); 1.95 ± 2.08
(m, Me2CH); 5.46 (d, J ˆ 3.4, NCH); 7.07 ± 7.51 (m, 10 arom. H, 2 CH ˆ ). 13C-NMR (100 MHz, CDCl3):
16.4, 18.4, 21.7 (Me); 30.1, 64.3 (CH); 89.2 (C); 121.6, 125.7, 126.0, 127.9, 128.3, 128.5, 128.8 (CH); 138.3, 142.3
‡
‡
(C); 147.0 (CH); 153.0, 164.8 (C). FAB-MS: 699 (2, [2M ‡ H] ), 350 (100, [M ‡ H] ), 306(31). Anal. calc. for
C22H23NO3 (349.43): C 75.62; H 6.63, N 4.01; found: C 75.33, H 6.84, N 4.03.
(S)-4-(1-Methylethyl)-3-[(E)-1-oxo-3-phenylprop-2-enyl]-5,5-diphenyloxazolidin-2-one ((S)-13). Com-
pound (S)-1 (7.03 g, 25 mmol) was treated with BuLi (16.5 ml, 26.3 mmol) and (E)-3-phenylprop-2-enoyl
chloride (5.00 g, 30 mmol) according to GP 3. FC (pentane/Et2O 6 :1) yielded (S)-13 (4.21 g, 41%). White solid.
M.p. 160.5 ± 161.58. [a]Dr:t:
ˆ
132.5 (c ˆ 1.44, CHCl3). IR (CHCl3): 3061w, 3032w, 2972w, 1775s, 1678s, 1617s,
1495m, 1450m, 1344s, 1177s, 1032m, 990m. 1H-NMR (400 MHz, CDCl3): 0.81 (d, J ˆ 6.8, Me); 0.93 (d, J ˆ 7.0,
Me); 1.97 ± 2.08 (m, Me2CH); 5.54 (d, J ˆ 3.4, NCH); 7.21 ± 7.60 (m, arom. H); nA ˆ 7.87, nB ˆ 7.80 (AB, J ˆ
15.7, 2 CH ˆ ). 13C-NMR (100 MHz, CDCl3): 16.4, 21.8 (Me); 30.2, 64.5 (CH); 89.4 (C); 116.8, 125.7, 126.0,
128.0, 128.4, 128.6, 128.6, 128.8, 128.9, 130.6 (CH); 134.6, 138.3, 142.3, 146.6, 153.1, 165.1 (C). FAB-MS: 412
‡
(100, [M ‡ H] ), 368(17). Anal. calc. for C27H25NO3 (411.50): C 78.81, H 6.12, N 3.40; found: C 78.70, H 6.35,
N 3.39.
(S)-3-[4-(Methoxycarbonyl)-1-oxobutyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one ((S)-14). Com-
pound (S)-1 (2.81 g, 10 mmol) was treated with BuLi (6.7 ml, 10.5 mmol) and monomethylglutaryl chloride
(1.98 g, 12 mmol) according to GP 3. FC (pentane/Et2O 3 :1 ! 2 : 1) yielded (S)-14 (3.47 g, 85%). Colorless oil.
[a]rD:t:
ˆ
195.9 (c ˆ 0.57, CHCl3). IR (CHCl3): 2966m, 1781s, 1732m, 1708m, 1450m, 1366m, 1319m, 1177m.
1H-NMR (400 MHz, CDCl3): 0.76 (d, J ˆ 6.8, Me); 0.87 (d, J ˆ 7.0, Me); 1.83 ± 2.03 (m, 3 H, Me2CH, CH2); 2.29
(t, J ˆ 7.5, C(O)CH2); 2.73 ± 2.82 (m, 1 H, C(O)CH2); 2.90 ± 3.00 (m, 1 H, C(O)CH2); 3.63 (s, MeO); 5.37

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Helvetica Chimica Acta ± Vol. 81 (1998)
(d, J ˆ 3.4, NCH); 7.25 ± 7.40 (m, 8 arom. H); 7.44 ± 7.48 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 16.4
(Me); 19.7 (CH2); 21.8 (Me); 29.9 (CH); 32.9, 34.3 (CH2); 51.5 (Me); 64.5 (CH); 89.5 (C); 125.6, 125.9, 128.0,
‡
128.4, 128.6, 128.9 (CH); 138.1, 142.3, 153.0, 172.3, 173.3 (C). FAB-MS: 410 (60, [M ‡ H] ), 366(15), 334(17),
238(100). Anal. calc. for C24H27NO5 (409.48): C 70.40, H 6.65, N 3.42; found: C 70.56, H 6.67, N 3.38.
(S)-4-(1-Methylethyl)-3-(1-oxo-3-phthalimidopropyl)-5,5-diphenyloxazolidin-2-one ((S)-15). Compound
(S)-1 (4.22 g, 15 mmol) was treated with BuLi (9.5ml, 15 mmol) and 3-(phthalimido)propanoyl chloride
(4.27 g, 18 mmol) according to GP 3. Recrystallization (AcOEt) yielded (S)-15 (3.76 g). From the mother
liquor, further 15 (2.67 g) was obtained. Total yield: 6.43 g (89%). White solid. M.p. 181 ± 1828. [a]Dr:t:
ˆ
132.6
(c ˆ 0.81, CHCl3). IR (CHCl3): 3011w, 1781s, 1717s, 1450m, 1381s, 1178m, 1114w, 1002m. 1H-NMR (400 MHz,
CDCl3): 0.76 (d, J ˆ 6.8, Me); 0.88 (d, J ˆ 7.0, Me); 1.92 ± 2.03 (m, Me2CH); 3.07 ± 3.17 (m, 1 H, C(O)CH2);
3.30 ± 3.42 (m, 1 H, C(O)CH2); 3.95 ± 4.06 (m, CH2N); 5.37 (d, J ˆ 3.2, NCH); 7.25 ± 7.42 (m, 8 arom. H); 7.44 ±
7.47 (m, 2 arom. H); 7.68 ± 7.73 (m, 2 arom. H); 7.80 ± 7.85 (m, 2arom. H). 13C-NMR (100 MHz, CDCl3): 16.3,
21.7 (Me); 30.0 (CH); 33.2, 33.9 (CH2); 64.6 (CH); 89.7 (C); 123.3, 125.5, 125.9, 128.0, 128.4, 128.7, 129.0 (CH);
‡
132.1 (C); 134.0 (CH); 138.1, 142.1, 152.9, 168.0, 170.2 (C). FAB-MS: 483 (70, [M ‡ H] ), 238(69), 202(96),
160(100). Anal. calc. for C29H26N2O5 (482.54): C 72.19, H 5.43, N 5.81; found: C 72.13, H 5.33, N 5.72.
(S)-3-{3-[4-(Benzyloxy)phenyl]-1-oxopropyl}-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one
((S)-16).
Compound (S)-1 (7.03 g, 25 mmol) was treated with BuLi (15.7 ml, 25 mmol) and 3-[4-(benzyloxy)phenyl]-
propanoyl chloride (4.43 ml, 30 mmol) according to GP 3. FC (pentane/Et2O 3 :1 ! 1 : 1) yielded (S)-16 (12.4 g,
96%). Colorless oil. [a]Dr:t:
ˆ
145.0 (c ˆ 0.73, CHCl3). IR (CHCl3): 3011w, 2973w, 1780s, 1702m, 1511s, 1450m,
1373m, 1319m, 1180s. 1H-NMR (400 MHz, CDCl3): 0.72 (d, J ˆ 6.8, Me); 0.84 (d, J ˆ 7.0, Me); 1.90 ± 2.01
(m, Me2CH); 2.76 ± 2.90 (m, PhCH2); 2.99 ± 3.07 (m, 1 H, C(O)CH2); 3.16 ± 3.24 (m, 1 H, C(O)CH2); 5.02
(s, CH2O); 5.36 (d, J ˆ 3.4, NCH); 6.82 ± 6.86 (m, 2 arom. H); 7.03 ± 7.08 (m, 2 arom. H); 7.25 ± 7.47 (m,
15 arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 21.7 (Me); 29.7 (CH2); 29.9 (CH); 37.0 (CH2); 64.5 (CH);
70.0 (CH2); 89.4 (C); 114.8, 125.6, 125.9, 127.4, 127.9, 128.0, 128.4, 128.5, 128.6, 128.9, 129.3 (CH); 132.7, 137.2,
‡
138.2, 142.3, 153.0, 157.2, 172.3 (C). FAB-MS: 520 (100, [M ‡ H] ). Anal. calc. for C34H33NO4 (519.64): C 78.59,
H 6.49, N 2.70; found: C 78.63, H 6.53, N 2.76.
(R)-4-(tert-Butyl)-3-(1-oxopropyl)-5,5-diphenyloxazolidin-2-one ((R)-17). Compound (R)-6 (886 mg,
3.0 mmol) was treated with BuLi (1.98 ml, 3.15 mmol) and propanoyl chloride (0.32 ml, 3.6 mmol) according
to GP 3. FC (pentane/Et2O 10 :1) yielded (R)-17 (923 mg, 88%). White solid. M.p. 103.5 ± 104.58. [a]Dr:t:
ˆ
‡ 259.6 (c ˆ 1.19, CHCl3). IR (CHCl3): 2969m, 1782s, 1706s, 1450m, 1370m, 1339s, 1327m, 1165m, 1052m,
986m. 1H-NMR (400 MHz, CDCl3): 0.81 (s, t-Bu); 0.98 (t, J ˆ 7.4, Me); 2.56 ± 2.66 (m, 1 H, CH2); 2.75 ± 2.85
(m, 1 H, CH2); 5.33 (s, NCH); 7.23 ± 7.55 (m, 10 arom. H). 13C-NMR (100 MHz, CDCl3): 8.7, 27.7 (Me); 28.7
(CH2); 37.0 (C); 67.0 (CH); 90.2 (C); 125.5, 127.9, 128.0, 128.4, 128.8 (CH); 137.8, 143.7, 153.6, 173.5 (C). FAB-
‡
‡
MS: 704 (5, [2M ‡ H] ), 352 (100, [M ‡ H] ), 252(18). Anal. calc. for C22H25NO3 (351.44): C 75.19, H 7.17,
N 3.99; found: C 75.15, H 7.18, N 4.01.
(S)-3-(1-Oxopropyl)-5,5-diphenyl-4-(phenylmethyl)oxazolidin-2-one ((S)-18). Compound (S)-5 (6.59 g,
20 mmol) was treated with BuLi (12.7 ml, 20 mmol) and propanoyl chloride (2.10 ml, 24 mmol) according to
GP 3. FC (pentane/Et2O 6 :1) yielded (S)-18 (7.53 g, 98%). Colorless glass. [a]Dr:t:
ˆ
277.4 (c ˆ 0.97, CHCl3).
IR (CHCl3): 3011w, 1782s, 1703m, 1496w, 1450m, 1372m. 1H-NMR (400 MHz, CDCl3): 1.03 (t, J ˆ 7.4, Me);
2.68 ± 2.78 (m, CH2); 2.81 ± 2.91 (m, CH2); 5.62 (dd, J ˆ 7.8, 5.0, NCH); 6.73 ± 6.76 (m, 2 arom. H); 7.07 ± 7.13
(m, 3 arom. H); 7.20 ± 7.36 (m, 8 arom. H); 7.42 ± 7.45 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 8.2 (Me);
29.1, 36.7 (CH2); 61.9 (CH); 88.5 (C); 126.0, 126.5, 128.2, 128.2, 128.8, 128.9, 129.0 (CH); 136.3, 137.6, 141.5,
‡
‡
‡
152.1, 173.3 (C). FAB-MS: 793 (1, [2M ‡ Na] ), 771 (2, [2M ‡ H] ), 386 (100, [M ‡ H] ), 342(43). Anal. calc.
for C25H23NO3 (385.46): C 77.90, H 6.01, N 3.63; found: C 77.62, H 6.22, N 3.63.
(S)-3-(1-Oxo-3-phthalimidopropyl)-5,5-diphenyl-4-(phenylmethyl)oxazolidin-2-one ((S)-19). Compound
(S)-5 (3.29 g, 10 mmol) was treated with BuLi (6.7 ml, 10.5 mmol) and 3-phthalimidopropanoyl chloride (2.85 g,
12 mmol) according to GP 3: Recrystallization (AcOEt/hexane) yielded (S)-19 (4.88 g, 92%). White powder.
M.p. 166 ± 1678. [a]Dr:t:
ˆ
197.9 (c ˆ 1.01, CHCl3). IR (CHCl3): 3032w, 1782s, 1716s, 1450w, 1381m, 1114w, 1002w.
1H-NMR (400 MHz, CDCl3): 2.72 (dd, J ˆ 14.1, 7.8, 1 H, PhCH2); 2.86 (dd, J ˆ 14.1, 5.3, 1 H, PhCH2); 3.05 ±
3.13 (m, 1 H, C(O)CH2); 3.25 ± 3.33 (m, 1 H, C(O)CH2); 3.87 ± 3.94 (m, CH2N); 5.61 (dd, J ˆ 7.8, 5.3, NCH);
6.73 ± 6.75 (m, 2 arom. H); 6.99 ± 7.03 (m, 1 arom. H); 7.06 ± 7.10 (m, 2 arom. H); 7.19 ± 7.28 (m, 5 arom. H);
7.29 ± 7.37 (m, 3 arom. H); 7.41 ± 7.44 (m, 2 arom. H); 7.67 ± 7.72 (m, 2 arom. H); 7.79 ± 7.84 (m, 2 arom. H).
13C-NMR (100 MHz, CDCl3): 33.0, 34.3, 36.6 (CH2); 61.8 (CH); 88.8 (C); 123.3, 126.0, 126.4, 126.5, 128.2, 128.2,
128.3, 128.9, 129.0, 129.0 (CH); 132.1 (C); 134.0 (CH); 136.2, 137.5, 141.1, 152.0, 167.9, 169.6 (C). FAB-MS: 531
‡
(100, [M ‡ H] ), 487(44), 286(25). Anal. calc. for C33H26N2O5 (530.58): C 74.70, H 4.94, N 5.28; found:
C 74.64, H 4.77, N 5.25.

Helvetica Chimica Acta ± Vol. 81 (1998)
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(S)-3-{3-[(tert-Butoxycarbonyl)amino]-1-oxopropyl}-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one ((S)-
20): Compound (S)-1 (8.44 g, 30 mmol) was treated with pivaloyl chloride (3.90 ml, 31.5 mmol), Boc-b-alanine
(5.96 g, 31.5 mmol), Et3N (10.8 ml, 78 mmol), and LiCl (1.46 g, 34.5 mmol) according to GP 4. FC (pentane/
Et2O 2 :1 ! 1 : 1) yielded (S)-20 (10.45 g, 77%). White solid. M.p. 113 ± 1148. [a]Dr:t:
ˆ
176.4 (c ˆ 0.96, CHCl3).
IR (CHCl3): 3452w, 2980m, 1783s, 1708s, 1505m, 1450m, 1368s, 1174s, 1051m. 1H-NMR (400 MHz, CDCl3): 0.75
(d, J ˆ 6.8, Me); 0.88 (d, J ˆ 7.0, Me); 1.41 (s, t-Bu); 1.92 ± 2.03 (m, Me2CH); 2.84 ± 2.92 (m, 1 H, C(O)CH2);
3.11 ± 3.19 (m, 1 H, C(O)CH2); 3.38 (br. m, CH2N); 4.86 (br. s, NH); 5.36 (d, J ˆ 3.4, NCH); 7.26 ± 7.48
(m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 21.8, 28.4 (Me); 29.9 (CH); 35.8, 36.0 (CH2); 64.6 (CH);
79.3, 89.6 (C); 125.5, 125.9, 128.0, 128.4, 128.7, 129.0 (CH); 138.0, 142.2, 152.9, 155.7, 171.9 (C). FAB-MS: 453
‡
(57, [M ‡ H] ), 397(100), 353(67), 238(60). Anal. calc. for C26H32N2O5 (452.55): C 69.01, H 7.13, N 6.19;
found: C 69.13, H 7.09, N 6.11.
(S)-3-{3-[(Benzyloxycarbonyl)amino]-1-oxopropyl}-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one ((S)-
21). Compound (S)-1 (5.63 g, 20 mmol) was treated with pivaloyl chloride (2.60 ml, 21 mmol), Cbz-b-alanine
(4.69 g, 21 mmol), Et3N (7.20 ml, 52 mmol), and LiCl (0.97 g, 23 mmol) according to GP 4. FC (pentane/Et2O
1:1) yielded (S)-21 (7.30 g, 75%). White solid. M.p. 131 ± 1338. [a]Dr:t:
ˆ
165.5 (c ˆ 1.10, CHCl3). IR (CHCl3):
3451w, 3011w, 2970w, 1783s, 1717s, 1511m, 1450m, 1373m, 1049m, 1002m. 1H-NMR (400 MHz, CDCl3): 0.74
(d, J ˆ 6.8, Me); 0.86 (d, J ˆ 7.0, Me); 1.91 ± 2.02 (m, Me2CH); 2.88 ± 2.95 (m, 1 H, C(O)CH2); 3.13 ± 3.20
(m, 1 H, C(O)CH2); 3.41 ± 3.51 (m, CH2N); 5.06 (s, CH2O); 5.14 (br. s, NH); 5.35 (d, J ˆ 3.4, NCH); 7.24 ± 7.39
(m, 13 arom. H); 7.43 ± 7.47 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 21.8 (Me); 29.9 (CH); 35.9,
36.2 (CH2); 64.6 (CH); 66.7 (CH2); 89.6 (C); 125.5, 125.9, 128.0, 128.1, 128.4, 128.5, 128.7, 129.0 (CH); 136.5,
‡
‡
138.0, 142.2, 152.9, 156.2, 171.8 (C). FAB-MS: 973 (10, [2M ‡ H] ), 487 (100, [M ‡ H] ), 443(18). Anal. calc.
for C29H30N2O5 (486.57): C 71.59, H 6.21, N 5.76; found: C 71.71, H 6.35, N 5.68.
(S)-3-[(R)-3-(Benzyloxy)-1-oxobutyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one ((S)-22). Com-
pound (S)-1 (4.64 g, 16.5mmol) was treated with pivaloyl chloride (2.15 ml, 17.3 mmol), (R)-3-(benzyloxy)-
butanoic acid (3.36 g, 17.3 mmol), Et3N (5.94 ml, 43 mmol), and LiCl (0.80 g, 19 mmol) according to GP 4. FC
(pentane/Et2O 6 :1 ! 4 : 1) yielded (S)-22 (5.78 g, 77%). Colorless oil. [a]Dr:t:
ˆ
175.3 (c ˆ 0.61, CHCl3). IR
(CHCl3): 2972w, 1781s, 1704m, 1450m, 1366m, 1320m, 1177m. 1H-NMR (400 MHz, CDCl3): 0.73 (d, J ˆ 6.8,
Me); 0.87 (d, J ˆ 7.0, Me); 1.15 (d, J ˆ 6.2, Me); 1.91 ± 2.02 (m, Me2CH); 2.82 (dd, J ˆ 15.8, 5.2, 1 H, C(O)CH2);
3.37 (dd, J ˆ 15.8, 7.4, 1 H, C(O)CH2); 3.96 ± 4.04 (m, CHO); nA ˆ 4.50, nB ˆ 4.35 (AB, J ˆ 11.4, CH2O); 5.41
(d, J ˆ 3.3, NCH); 7.22 ± 7.51 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 19.8, 21.7 (Me); 29.9 (CH);
42.4 (CH2); 64.5 (CH); 70.9 (CH2); 71.9 (CH); 89.3 (C); 125.6, 125.9, 127.4, 127.6, 128.0, 128.2, 128.4, 128.6,
‡
128.9 (CH); 138.7, 142.4, 153.0, 170.8 (C). FAB-MS: 458 (100, [M ‡ H] ), 350(29). Anal. calc. for C29H31NO4
(457.57): C 76.12, H 6.83, N 3.06; found: C 76.16, H 6.87, N 2.98.
(S)-3-{3-[1-(Benzyloxycarbonyl)indol-3-yl]-1-oxopropyl}-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one
((S)-23). Compound (S)-1 (3.38g, 12 mmol) was treated with pivaloyl chloride (1.57 mgl, 12.6 mmol), 3-[(1-
Cbz)indol-3-yl]propanoic acid (4.07 g, 12.6 mmol), Et3N (4.31 ml, 31.2 mmol), and LiCl (0.58 g, 13.8 mmol)
according to GP 4. FC (pentane/Et2O 3 :1 ! 1 : 1) yielded (S)-23 (5.90 g, 84%). White foam. [a]Dr:t:
ˆ
132.2
(c ˆ 0.80, CHCl3). IR (CHCl3): 3008w, 2968w, 1781s, 1729m, 1456m, 1400m, 1356m, 1087m. 1H-NMR (400 MHz,
CDCl3): 0.73 (d, J ˆ 6.8, Me); 0.84 (d, J ˆ 7.0, Me); 1.91 ± 2.02 (m, Me2CH); 2.88 ± 3.04 (m, CH2); 3.08 ± 3.16
(m, 1 H, C(O)CH2); 3.28 ± 3.36 (m, 1 H, C(O)CH2); 5.38 (d, J ˆ 3.4, NCH); 5.42 (s, CH2O); 7.21 ± 7.54
(m, 19 arom. H); 8.14 (br. s, arom. NCH). 13C-NMR (100 MHz, CDCl3): 16.4 (Me); 19.9 (CH2); 21.7 (Me);
29.8 (CH); 34.8 (CH2); 64.6 (CH); 68.5 (CH2); 89.5 (C); 115.2, 119.1 (CH); 120.3 (C); 122.3, 122.9, 124.7, 125.6,
125.9, 128.0, 128.4, 128.5, 128.6, 128.7, 128.8, 128.9 (CH); 130.3, 135.3, 135.6, 138.1, 142.2, 150.8, 153.1, 172.2 (C).
‡
FAB-MS: 586 (100, M ), 543(35). Anal. calc. for C37H34N2O5 (586.69): C 75.75, H 5.84, N 4.77; found: C 75.78,
H 5.73, N 4.79.
(S)-3-{3-[(tert-Butoxycarbonyl)amino]-1-oxopropyl}-4-phenylmethyl-5,5-diphenyloxazolidin-2-one ((S)-
24). Compound (S)-5 (3.29 g, 10 mmol) was treated with pivaloyl chloride (1.30 ml, 10.5 mmol), Boc-b-alanine
(1.99 g, 10.5 mmol), Et3N (3.60 ml, 26 mmol), and LiCl (0.49 g, 11.5 mmol) according to GP 4. FC (pentane/
Et2O 2 :1 ! 1 : 1) yielded (S)-24 (3.89 g, 78%). White solid. M.p. 146 ± 1478. [a]Dr:t:
ˆ
238.7 (c ˆ 1.19, CHCl3).
IR (CHCl3): 3454w, 3007w, 2980w, 1784s, 1707s, 1505m, 1450m, 1368s, 1168s, 997m. 1H-NMR (400 MHz,
CDCl3): 1.43 (s, t-Bu); 2.67 ± 2.87 (m, 3 H, PhCH2), C(O)CH2); 3.00 ± 3.07 (m, 1 H, C(O)CH2); 3.22 ± 3.39
(m, CH2N); 4.67 (br. s, NH); 5.61 (t, J ˆ 6.7, NCH); 6.79 ± 6.82 (m, 2 arom. H); 7.11 ± 7.16 (m, 3 arom. H);
7.24 ± 7.37 (m, 8 arom. H); 7.42 ± 7.45 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 28.4 (Me); 35.3, 36.4, 37.0
(CH2); 61.7 (CH); 79.2, 88.8 (C); 125.9, 126.3, 126.7, 128.2, 128.3, 128.4, 128.9, 129.0, 129.1 (CH); 136.2, 137.5,
‡
‡
141.1, 152.0, 155.6, 171.3 (C). FAB-MS: 1001 (16, [2M ‡ H] ), 501 (92, [M ‡ H] ), 445(75), 401(100). Anal.
calc. for C30H32N2O5 (500.60): C 71.98, H 6.44, N 5.60; found: C 71.75, H 6.49, N 5.54.

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Helvetica Chimica Acta ± Vol. 81 (1998)
(S)-4-(1-Methylethyl)-3-[(R)-2-methyl-1-oxopent-4-enoyl]-5,5-diphenyloxazolidin-2-one (25). The acyloxa-
zolidinone (S)-8 (814 mg, 2.4 mmol) was treated with LDA (3.1 mmol), ZnBr2 (708 mg, 3.1 mmol), and allyl
bromide (2.15 ml, 25 mmol) according to GP 5. Recrystallization (Et2O/pentane) yielded 25 (502 mg). From
the mother liquor, additional 25 (152 mg) was obtained. Total yield: 654 mg (72%). White needles. M.p. 110 ±
1118. [a]rD:t:
ˆ
203.4 (c ˆ 1.18, CHCl3). IR (CHCl3): 3011w, 2970w, 1784s, 1706s, 1494w, 1450m, 1375s, 1321s,
1
1288m, 1178m, 1043m, 984m, 648m. H-NMR (400 MHz, CDCl3): 0.76 (d, J ˆ 6.7, Me); 0.84 (d, J ˆ 6.8, Me);
0.87 (d, J ˆ 7.0, Me); 1.90 ± 2.01 (m, Me2CH); 2.12 ± 2.19 (m, 1 H, CH2); 2.50 ± 2.58 (m, 1 H, CH2); 3.74
(sext., J ˆ 6.9, C(O)CH); 5.01 ± 5.11 (m, CHˆCH2); 5.38 (d, J ˆ 3.3, NCH); 5.75 ± 5.86 (m, CHˆCH2); 7.24 ±
7.50 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 16.3, 21.7 (Me); 29.8, 37.0 (CH); 37.9 (CH2); 64.6 (CH);
89.3 (C); 117.0 (CH2); 125.7, 125.9, 127.9, 128.4, 128.6, 128.8, 135.5 (CH); 138.2, 142.4, 152.9, 176.3 (C).
‡
FAB-MS: 378 (100, [M ‡ H] ), 334(29). Anal. calc. for C24H27NO3 (377.48): C 76.36, H 7.21, N 3.71; found:
C 76.25, H 7.23, N 3.76.
(S)-3-[(R)-3-(tert-Butoxycarbonyl)-2-methyl-1-oxopropyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-
one (26). Compound (S)-8 (844 mg, 2.5 mmol) was treated with BuLi (1.73 ml, 2.75 mmol) and tert-butyl
bromoacetate (1.85 ml, 12.5 mmol) according to GP 6. FC (pentane/Et2O 12 :1) yielded 26 as a 96 :4 mixture
with its C(2)-epimer (924 mg, 82%), which was recrystallized (Et2O/pentane) to yield pure 26 for anal.
purposes. White solid. M.p. 111 ± 1138. [a]Dr:t:
ˆ
175.8 (c ˆ 0.99, CHCl3). IR (CHCl3): 2979m, 1782s, 1720m,
1699m, 1450m, 1393m, 1368m, 1318m, 1156s, 1052w, 994w, 845w. 1H-NMR (400 MHz, CDCl3): 0.73 (d, J ˆ 7.0,
Me); 0.83 (d, J ˆ 6.7, Me); 0.88 (d, J ˆ 7.0, Me); 1.42 (s, t-Bu); 1.91 ± 2.02 (m, Me2CH); 2.27 (dd, J ˆ 16.7, 5.0,
1 H, CH2); 2.76 (dd, J ˆ 16.7, 9.9, 1 H, CH2); 4.04 ± 4.13 (m, C(O)CH); 5.33 (d, J ˆ 3.3, NCH); 7.24 ± 7.47
(m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 16.6, 21.5, 28.1 (Me); 29.9, 34.2 (CH); 38.8 (CH2); 65.0
(CH); 80.5, 89.3 (C); 125.6, 125.9, 127.9, 128.4, 128.5, 128.8 (CH); 138.1, 142.5, 152.8, 171.0, 176.0 (C). FAB-MS:
‡
452 (27, [M ‡ H] ), 396(100), 334(37), 238(73). Anal. calc. for C27H33NO5 (451.56): C 71.82, H 7.37, N 3.10;
found: C 71.98, H 7.50, N 3.11.
(S)-4-(1-Methylethyl)-3-[(R)-2-methyl-1-oxo-3-phenylpropyl]-5,5-diphenyloxazolidin-2-one (27). Com-
pound (S)-8 (8.44g, 25 mmol) was treated with LDA (31 mmol), ZnBr2 (6.98 g, 31 mmol), and BnBr
(23.8 ml, 200 mmol) according to GP 5. Recrystallization (Et2O/pentane) yielded 27 (8.66 g, 81%). White solid.
M.p. 131 ± 1328. [a]Dr:t:
ˆ
201.3 (c ˆ 1.22, CHCl3). IR (CHCl3): 2972m, 1778s, 1699s, 1495m, 1459m, 1370s,
1320m, 1176s, 1051m, 992m. 1H-NMR (400 MHz, CDCl3): 0.59 (d, J ˆ 6.8, Me); 0.70 (d, J ˆ 7.0, Me); 0.84
(d, J ˆ 6.8, Me); 1.82 ± 1.94 (m, Me2CH); 2.60 (dd, J ˆ 13.4, 7.9, 1 H, PhCH2); 3.16 (dd, J ˆ 13.4, 7.2, 1 H,
PhCH2); 3.99 ± 4.08 (m, C(O)CH); 5.35 (d, J ˆ 3.3, NCH); 7.14 ± 7.49 (m, arom. H). 13C-NMR (100 MHz,
CDCl3): 16.1, 16.3, 21.5 (Me); 29.6, 39.2 (CH); 39.8 (CH2); 64.5 (CH); 89.3 (C); 125.7, 125.9, 126.3, 127.9, 128.3,
‡
128.4, 128.6, 128.8, 129.2 (CH); 138.1, 129.3, 142.3, 152.8, 176.2 (C). FAB-MS: 428 (100, [M ‡ H] ), 384(16).
Anal. calc. for C28H29NO3 (427.54): C 78.66, H 6.84, N 3.28; found: C 78.56, H 6.83, N 3.29.
(S)-4-Benzyl-3-[(R)-2-methyl-1-oxopent-4-enyl]-5,5-diphenyloxazolidin-2-one (28). Compound (S)-18
(964 mg, 2.5 mmol) was treated with LDA (3.1 mmol), ZnBr2 (708 mg, 3.1 mmol), and allyl bromide
(2.15 ml, 25 mmol) according to GP 5. FC (pentane/Et2O 6 :1) yielded 28 (959 mg, 90%). Colorless oil. [a]Dr:t:
ˆ
280.2 (c ˆ 0.52, CHCl3). IR (CHCl3): 3037w, 1780s, 1698m, 1496m, 1450m, 1350m, 1168m, 993m, 921m.
1H-NMR (400 MHz, CDCl3): 0.92 (d, J ˆ 6.8, Me); 2.03 ± 2.11 (m, 1 H, CH2); 2.38 ± 2.46 (m, 1 H, CH2); 2.74
(dd, J ˆ 14.2, 8.1, 1 H, PhCH2); 2.85 (dd, J ˆ 14.2, 4.7, 1 H, PhCH2); 3.68 (sext., J ˆ 6.8, C(O)CH); 4.98 ± 5.06
(m, CH2ˆCH); 5.61 ± 5.75 (m, 2 H, NCH, CH2ˆCH); 6.71 ± 6.78 (m, 2 arom. H); 7.05 ± 7.11 (m, 3 arom. H);
7.17 ± 7.45 (m, 10 arom. H). 13C-NMR (100 MHz, CDCl3): 16.3 (Me); 36.7 (CH2); 37.1 (CH); 37.5 (CH2); 62.2
(CH); 88.4 (C); 117.0 (CH2); 126.0, 126.4, 126.5, 128.1, 128.2, 128.2, 128.8, 129.0, 135.4 (CH); 136.3, 137.4, 141.4,
‡
151.9, 175.8 (C). FAB-MS: 426 (25, [M ‡ H] ), 382(35), 286(67), 268(56), 191(62), 167(100). Anal. calc. for
C28H27NO3 (425.53): C 79.03, H 6.40, N 3.29; found: C 79.00, H 6.35, N 3.46.
(R)-4-Benzyl-3-[(S)-3-(tert-butoxycarbonyl)-2-methyl-1-oxopropyl]-5,5-diphenyloxazolidin-2-one (29).
Compound (R)-18 (771 mg, 2.0 mmol) was treated with BuLi (1.65 ml, 2.6 mmol) and tert-butyl bromoacetate
(1.85 ml, 12.5 mmol) according to GP 6. FC (pentane/Et2O 12 :1 ! 6 : 1) yielded 29 (682 mg, ca. 55%) as a 4 : 1
mixture with 18, which was recrystallized (Et2O/pentane) to yield pure 29 for anal. purposes. White solid. M.p.
106 ± 1078. [a]Dr:t: ˆ‡ 211.5 (c ˆ 0.91, CHCl3). IR (CHCl3): 3011w, 2982w, 1782s, 1722m, 1450m, 1392m, 1355m,
1156s, 978m. 1H-NMR (400 MHz, CDCl3): 0.93 (d, J ˆ 7.0, Me); 1.40 (s, t-Bu); 2.28 (dd, J ˆ 16.7, 5.3, 1 H,
PhCH2); 2.75 (dd, J ˆ 16.7, 9.4, 1 H, PhCH2); 2.83 (dd, J ˆ 14.4, 8.9, 1 H, C(O)CH2); 3.00 (dd, J ˆ 14.3, 3.2, 1 H,
C(O)CH2); 4.04 ± 4.13 (m, C(O)CH); 5.56 (dd, J ˆ 8.9, 3.2, NCH); 6.64 ± 6.69 (m, 2 arom. H); 7.02 ± 7.45
(m, 13 arom. H). 13C-NMR (100 MHz, CDCl3): 16.9, 28.1 (Me); 34.4 (CH); 36.0, 38.7 (CH2); 62.8 (CH); 80.7,
88.3 (C); 126.0, 126.2, 126.7, 128.1, 128.1, 128.1, 128.8, 128.9 (CH); 136.7, 137.3, 141.5, 151.7, 171.0, 175.8 (C).

Helvetica Chimica Acta ± Vol. 81 (1998)
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‡
FAB-MS: 500 (52, [M ‡ H] ), 444(100), 400(30), 382(41), 286(76), 268(55). Anal. calc. for C31H33NO5
(499.61): C 74.53, H 6.66, N 2.80; found: C 74.62, H 6.51, N 2.83.
(R)-3-[(S)-3-(tert-Butoxycarbonyl)-2-methyl-1-oxopropyl]-4-(tert-butyl)-5,5-diphenyloxazolidin-2-one
(30). Compound (R)-17 (351 mg, 1.0 mmol) was treated with BuLi (0.69 ml, 1.1 mmol) and tert-butyl
bromoacetate (0.74 ml, 5.0 mmol) according to GP 6. FC (pentane/Et2O 12 :1 ! 8 : 1) yielded 30 as a 3 : 1
mixture with its C(2)-epimer (230 mg, 49%), which was recrystallized (Et2O/pentane) to yield pure 30 for anal.
purposes. White needles. M.p. 141 ± 1428. [a]Dr:t: ˆ‡ 186.7 (c ˆ 0.29, CHCl3). IR (CHCl3): 2972m, 1784s, 1698m,
1450m, 1354m, 1155s, 992m, 840m. 1H-NMR (400 MHz, CDCl3): 0.43 (d, J ˆ 7.0, Me); 0.82 (s, t-Bu); 1.40 (s, t-
BuO); 2.20 (dd, J ˆ 16.7, 5.0, 1 H, C(O)CH2); 2.69 (dd, J ˆ 16.7, 10.1, 1 H, C(O)CH2); 3.94 ± 4.02
(m, C(O)CH); 5.27 (s, NCH); 7.22 ± 7.51 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.1, 27.7, 28.0 (Me);
33.9 (CH); 37.0 (C); 38.8 (CH2); 67.7 (CH); 80.5, 90.2 (C); 125.4, 128.0, 128.4, 128.7 (CH); 137.6, 144.0, 153.4,
‡
171.1, 175.4 (C). FABMS: 466 (45, [M ‡ H] ), 410(100), 292(42), 240(43). Anal. calc. for C28H35NO5 (465.59):
C 72.23, H 7.58, N 3.01; found: C 72.33, H 7.73, N 2.93.
(S)-4-(1-Methylethyl)-3-[(S)-2-methyl-1-oxo-3-phenylpropyl]5,5-diphenyloxazolidin-2-one (31). Com-
pound (S)-11 (5.17 g, 12.5 mmol) was treated with LDA (15.5 mmol), ZnBr2 (3.49 g, 15.5 mmol), and MeI
(7.83 ml, 125 mmol) according to GP 5. FC (pentane/Et2O 15 :1 ! 10 : 1) yielded 31 (3.91 g, 73%). Colorless oil.
[a]rD:t:
ˆ
133.7 (c ˆ 0.46, CHCl3). IR (CHCl3): 2968m, 1778s, 1698s, 1495m, 1450m, 1372m, 1317m, 1177s, 991m.
1H-NMR (400 MHz, CDCl3): 0.77 (d, J ˆ 6.8, Me); 0.87 (d, J ˆ 7.0, Me); 1.23 (d, J ˆ 6.9, Me); 1.91 ± 2.02
(m,Me2CH); 2.45 (dd, J ˆ 13.8, 7.4, 1 H, PhCH2); 2.81 (dd, J ˆ 13.8, 7.1, 1 H, PhCH2); 3.92 ± 4.01 (m, C(O)CH);
5.36 (d, J ˆ 3.4, NCH); 6.96 ± 7.01 (m, 2 arom. H); 7.07 ± 7.14 (m, 3 arom. H); 7.22 ± 7.39 (m, 10 arom. H).
13C-NMR (100 MHz, CDCl3): 16.3, 17.6, 21.8 (Me); 29.9 (CH); 38.6 (CH2); 39.2, 64.4 (CH); 89.3 (C); 125.6,
125.9, 126.1, 127.9, 128.2, 128.4, 128.5, 128.8, 128.9 (CH); 138.2, 139.1, 142.1, 152.7, 176.2 (C). FAB-MS: 428
‡
(100, [M ‡ H] ), 384(25). Anal. calc. for C28H29NO3 (427.54): C 78.66, H 6.84, N 3.28; found: C 78.51, H 6.78,
N 3.29.
Benzyl N-(Methoxymethyl)carbamate (Cbz-NHCH2OMe). Some modifications to the literature procedure
[25] were necessary: To a suspension of N-benzylcarbamic acid (15.1 g, 100 mmol) in H2O (112.5 ml), K2CO3
(276 mg) and HCHO (36 wt.-% soln. in H2O, 8.5 ml, 105 mmol) were added. The mixture was stirred at 608 for
30 min, diluted with MeOH (45 ml), and cooled to 48. The resulting white crystals were dried and purified by FC
(pentane/Et2O 1:2 ! 0 : 1) to yield benzyl N-(hydroxymethyl)carbamate (8.02 g, 44%). To a soln. of benzyl N-
(hydroxymethyl)carbamate (3.62 g, 20 mmol) in Et2O (30 ml) and MeOH (6 ml), molecular sieves 4 Š (1.60 g)
and TsOH ´ H2O (60 mg) were added. The mixture was stirred at r.t. for 1 h, then filtered over SiO2 (Æ ˆ 3 cm,
h ˆ 1 cm), and the solvent removed under reduced pressure. Drying (h.v.) yielded benzyl N-(methoxyme-
thyl)carbamate (3.84 g, 98%) as colorless oil that solidifies when stored at 208. 1H-NMR: in agreement with
[25].
(S)-3-((R)-2-{[(Benzyloxycarbonyl)amino]methyl}-1-oxopropyl)-4-(1-methylethyl)-5,5-diphenyloxazoli-
din-2-one (32). Compound (S)-8 (675 mg, 2.0 mmol) was treated with TiCl4 (0.23 ml, 2.1 mmol), EtN(i-Pr)2
(0.38 ml, 2.2 mmol), Cbz-NHCH2OMe (430 mg, 2.2 mmol), and again TiCl4 (0.24 ml, 2.2 mmol) according to
GP 7. FC (pentane/Et2O 3 :1 ! 1 : 1) yielded 32 as a 93 : 7 mixture with its C(2)-epimer (691 mg, 69%). For anal.
purposes, a sample was recrystallized (Et2O/pentane). White solid. M.p. 110 ± 1118. [a]Dr:t:
ˆ
161.4 (c ˆ 0.83,
CHCl3). IR (CHCl3): 3448w, 2971w, 1782s, 1719s, 1514m, 1451m, 1365m, 1318m, 1051m, 1002m. 1H-NMR
(400 MHz, CDCl3): 0.73 (d, J ˆ 6.8, Me); 0.78 (d, J ˆ 6.9, Me); 0.84 (d, J ˆ 7.0, Me); 1.91 ± 2.02 (m, Me2CH);
3.34 ± 3.46 (m, CH2N); 3.81 ± 3.89 (m, C(O)CH); 5.08 (s, CH2O); 5.15 ± 5.23 (br. s, NH); 5.31 (d, J ˆ 3.5, NCH);
7.25 ± 7.47 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 14.4, 16.5, 21.7 (Me); 29.6, 38.2 (CH); 43.6 (CH2); 65.1
(CH); 66.7 (CH2); 89.7 (C); 125.5, 125.9, 128.1, 128.1, 128.5, 128.5, 128.7, 128.9 (CH); 136.6, 137.8, 142.2, 152.9,
‡
‡
156.3, 175.5 (C). FAB-MS: 1001 (7, [2M ‡ H] ), 501 (100, [M ‡ H] ), 457(25). Anal. calc. for C30H32N2O5
(500.60): C 71.98, H 6.44, N 5.60; found: C 71.75, H 6.39, N 5.37.
(S)-3-((R)-2-{[(Benzyloxycarbonyl)amino]methyl}-3-methyl-1-oxobutyl)-4-(1-methylethyl)-5,5-diphenyl-
oxazolidin-2-one (33). Compound (S)-9 (3.29 g, 9.0 mmol) was treated with TiCl4 (1.05 ml, 9.5 mmol), EtN(i-
Pr)2 (1.71 ml, 9.9 mmol), Cbz-NHCH2OMe (1.94 g, 9.9 mmol), and again TiCl4 (1.08 ml, 9.9 mmol) according to
GP 7. FC (pentane/Et2O 2 :1 ! 1 : 1) yielded 33 as a 93 : 7 mixture with its C(2)-epimer (3.33 g, 70%). White
foam. [a]rD:t:
ˆ
114.6 (c ˆ 1.03, CHCl3). IR (CHCl3): 3451w, 3011w, 2968m, 1780s, 1718s, 1513s, 1450m, 1363m,
1318m, 1178m, 1051m, 989w. 1H-NMR (400 MHz, CDCl3): 0.41 (d, J ˆ 6.7, Me); 0.68 (d, J ˆ 6.8, Me); 0.71
(d, J ˆ 6.7, Me); 0.83 (d, J ˆ 7.0, Me); 1.66 ± 1.76 (m, Me2CH); 1.94 ± 2.02 (m, Me2CH); 3.38 ± 3.43 (m, CH);
3.52 ± 3.59 (m, CH); 3.69 ± 3.74 (m, CH); 5.06 (s, CH2O); 5.14 (br. s, NH); 5.34 (d, J ˆ 3.5, NCH); 7.20 ± 7.52
(m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 19.0, 20.0, 21.7 (Me); 28.6, 29.6 (CH); 40.8 (CH2); 48.7, 65.7
(CH); 66.6 (CH2); 89.5 (C); 125.3, 125.7, 128.0, 128.1, 128.4, 128.5, 128.6, 128.9 (CH); 136.6, 137.7, 142.4, 153.3,

2118
Helvetica Chimica Acta ± Vol. 81 (1998)
‡
‡
156.2, 174.9 (C). FAB-MS: 1058 (18, [2M ‡ H] ), 529 (60, [M ‡ H] ), 485(100). Anal. calc. for C32H36N2O5
(528.65): C 72.70, H 6.86, N 5.30; found: C 72.80, H 6.79, N 5.27.
(S)-3-((R)-2-{[(Benzyloxycarbonyl)amino]methyl}-4-methyl-1-oxopentyl)-4-(1-methylethyl)-5,5-diphenyl-
oxazolidin-2-one (34). Compound (S)-10 (1.90 g, 5.0 mmol) was treated with TiCl4 (0.58 ml, 5.25 mmol), EtN-
(i-Pr)2 (0.95 ml, 5.5 mmol), Cbz-NHCH2OMe (1.08 g, 5.5 mol), and again TiCl4 (0.60 ml, 5.5 mmol) according
to GP 7. FC (pentane/Et2O 2 :1 ! 1 : 1) yielded 34 as a 92 : 8 mixture with its C(2)-epimer (1.73 g, 64%). For
anal. purposes, a sample was recrystallized (Et2O/pentane). White solid. M.p. 146 ± 1478. [a]Dr:t:
ˆ
119.4 (c ˆ
0.84, CHCl3). IR (CHCl3): 3444w, 3011w, 2962m, 1718s, 1515m, 1450m, 1365m, 1318m, 1051w. 1H-NMR
(400 MHz, CDCl3): 0.39 (d, J ˆ 6.2, Me); 0.62 (d, J ˆ 6.1, Me); 0.71 (d, J ˆ 6.7, Me); 0.84 (d, J ˆ 7.0, Me); 0.88 ±
1.01 (m, CH2); 1.32 ± 1.42 (m, Me2CH); 1.93 ± 2.01 (m, Me2CH); 3.30 ± 3.35 (m, 1 H, CH2N); 3.45 ± 3.56 (m, 1 H,
CH2N); 3.86 ± 3.91 (m, C(O)CH); 5.06 (s, CH2O); 5.26 (br. s, NH); 5.32 (d, J ˆ 3.4, NCH); 7.24 ± 7.50
(m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 21.7, 21.8, 22.6 (Me); 25.6, 29.6 (CH); 38.6 (CH2); 40.7
(CH); 43.6 (CH2); 65.7 (CH); 66.6 (CH2); 89.8 (C); 125.3, 125.7, 128.0, 128.2, 128.4, 128.5, 128.6, 128.9 (CH);
‡
‡
136.6, 137.7, 142.3, 153.4, 156.2, 175.1 (C). FAB-MS: 1086 (17, [2M ‡ H] ), 543 (100, [M ‡ H] ), 499(24).
Anal. calc. for C33H38N2O5 (542.67): C 73.04, H 7.06, N 5.16; found: C 73.21, H 7.23, N 5.15.
(S)-3-((R)-2-{[(Benzyloxycarbonyl)amino]methyl}-1-oxo-3-phenylpropyl)-4-(1-methylethyl)-5,5-diphenyl-
oxazolidin-2-one (35). Compound (S)-11 (4.41 g, 10.0 mmol) was treated with TiCl4 (1.16 ml, 10.5 mmol), Et3N
(1.54 ml, 11.0 mmol), Cbz-NHCH2OMe (2.15 g, 11.0 mmol), and again TiCl4 (1.22 ml, 11.0 mmol) according to
GP 7. FC (pentane/Et2O 2 :1 ! 1 : 1) yielded 35 (4.50 g, 78%). White solid. M.p. 126 ± 1288. [a]Dr:t:
ˆ
101.3 (c ˆ
1
1.11, CHCl3). IR (CHCl3): 3446w, 3008m, 2969m, 1779s, 1720s, 1514s, 1451m, 1364m, 1318m, 990m. H-NMR
(400 MHz, CDCl3): 0.71 (d, J ˆ 6.7, Me); 0.84 (d, J ˆ 7.0, Me); 1.92 ± 2.00 (m, Me2CH); 2.51 (dd, J ˆ 13.9, 7.2,
1 H, PhCH2); 2.71 (dd, J ˆ 14.0, 6.9, 1 H, PhCH2); 3.39 ± 3.53 (m, CH2N); 4.21 (br. m, C(O)CH); 5.06
(s, CH2O); 5.18 (br. s, NH); 5.33 (d, J ˆ 3.3, NCH); 6.89 ± 6.91 (m, 2 arom. H); 7.04 ± 7.08 (m, 3 arom. H);
7.18 ± 7.38 (m, 15 arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 21.7 (Me); 29.8 (CH); 35.2, 42.4 (CH2); 44.6,
65.1 (CH); 66.7 (CH2); 89.6 (C); 125.3, 125.8, 126.5, 128.0, 128.1, 128.1, 128.4, 128.4, 128.5, 128.7, 128.9 (CH);
‡
‡
136.5, 137.6, 137.9, 142.0, 153.0, 156.1, 173.9 (C). FAB-MS: 1153 (13, [2M ‡ H] ), 577 (100, [M ‡ H] ),
533(38), 412(11). Anal. calc. for C36H36N2O5 (576.69): C 74.98, H 6.29, N 4.86; found: C 74.85, H 6.11, N 5.05.
(S)-3-((R)-2-{[(Benzyloxycarbonyl)amino]methyl}-4-(methoxycarbonyl)-1-oxobutyl)-4-(1-methylethyl)-
5,5-diphenyloxazolidin-2-one (36). Compound (S)-14 (819 mg, 2.0 mmol) was treated with TiCl4 (0.22 ml,
2.0 mmol), Et3N (0.28 ml, 2.0 mmol), Cbz-NHCH2OMe (429 mg, 2.2 mmol), and again TiCl4 (0.24 ml,
2.2 mmol) according to GP 7. FC (pentane/Et2O 1:1) yielded 36 (4.82 mg, 42%). White solid. M.p. 93 ± 958.
[a]rD:t:
ˆ
110.4 (c ˆ 0.75, CHCl3). IR (CHCl3): 3448w, 3008m, 2972w, 1779s, 1725s, 1512m, 1450m, 1364m,
1318m, 1046m. 1H-NMR (500 MHz, CDCl3): 0.71 (d, J ˆ 6.7, Me); 0.83 (d, J ˆ 7.0, Me); 1.55 ± 1.65 (m, 1 H,
CH2); 1.65 ± 1.88 (m, 3 H, CH2); 1.93 ± 2.03 (m, Me2CH); 3.36 ± 3.40 (m, 1 H, CH2N); 3.49 ± 3.56 (m, 1 H,
CH2N); 3.52 (s, MeO); 3.84 ± 3.88 (br. m, 1 H, C(O)CH); 5.07 (d, J ˆ 3.0, CH2O); 5.23 (br. s, NH); 5.35 (d, J ˆ
3.5, NCH); 7.26 ± 7.48 (m, arom. H). 13C-NMR (125 MHz, CDCl3): 16.3, 21.6 (Me); 24.5 (CH2); 29.6 (CH);
30.7 (CH2); 42.2 (CH); 42.9 (CH2); 51.5 (Me); 65.3 (CH); 66.8 (CH2); 89.8 (C); 125.4, 125.8, 128.1, 128.1, 128.2,
128.5, 128.5, 128.7, 129.0 (CH); 136.5, 137.7, 142.1, 153.1, 156.2, 172.8, 174.0 (C). FAB-MS: 1146 (28, [2M ‡
‡
‡
H] ), 573 (100, [M ‡ H] ), 529(28). Anal. calc. for C33H36N2O7 (572.66): C 69.21, H 6.34, N 4.89; found:
C 68.93, H 6.58, N 5.03.
(S)-3-((S)-2-{[(Benzyloxycarbonyl)amino]methyl}-1-oxo-3-phthalimidopropyl)-4-(1-methylethyl)-5,5-di-
phenyloxazolidin-2-one (37). Compound (S)-15 (483 mg, 1.0 mmol) was treated with TiCl4 (0.12 ml,
1.05 mmol), Et3N (0.15 ml, 1.1 mmol), Cbz-NHCH2OMe (215 mg, 1.1 mmol), and again TiCl4 (0.12 ml,
1.1 mmol) according to GP 7. Recrystallization (AcOEt) yielded 37 (417 mg, 65%). White solid. M.p. 166 ± 1678.
[a]rD:t:
ˆ
116.6 (c ˆ 0.88, CHCl3). IR (CHCl3): 3435 (br.), 3011w, 2972w, 1777s, 1719s, 1516m, 1450m, 1365m,
1320m, 1052w, 990w. 1H-NMR (400 MHz, CDCl3): 0.72 (d, J ˆ 6.7, Me); 0.83 (d, J ˆ 7.0, Me); 1.90 ± 1.98
(m, Me2CH); 3.43 ± 3.50 (m, 1 H, CH2N); 3.72 ± 3.92 (m, 3 H, CH2N); 4.15 ± 4.18 (br. m, C(O)CH); 5.06
(s, CH2O); 5.38 (d, J ˆ 3.0, NCH); 5.60 (br. s, NH); 7.09 ± 7.13 (m, 1 arom. H); 7.19 ± 7.43 (m, 14 arom. H);
7.68 ± 7.77 (m, 4 Phth. H). 13C-NMR (100 MHz, CDCl3): 15.9, 21.6 (Me); 30.0 (CH); 36.1, 40.7 (CH2); 42.5, 64.9
(CH); 66.8 (CH2); 89.7 (C); 123.5, 125.5, 125.9, 128.0, 128.0, 128.1, 128.4, 128.5, 128.5, 128.8 (CH); 131.8 (C);
‡
134.0 (CH); 136.5, 138.1, 142.0, 152.8, 156.2, 168.0, 171.6 (C). FAB-MS: 1291 (6, [2M ‡ H] ), 646 (100, [M ‡
‡
H] ), 602(61), 512(8). Anal. calc. for C38H35N3O7 (645.71): C 70.68, H 5.46, N 6.51; found: C 70.53, H 5.50,
N 6.49.
(S)-3-((R)-2-{[(Benzyloxycarbonyl)amino]methyl}-3-[4-(benzyloxy)phenyl]-1-oxobutyl)-4-(1-methylethyl)-
5,5-diphenyloxazolidin-2-one (38). Compound (S)-16 (0.4 g, 20 mmol) was treated with TiCl4 (2.32 ml,
21 mmol), EtN(i-Pr)2 (3.80 ml, 22 mmol), Cbz-NHCH2OMe (4.30 g, 22 mmol), and again TiCl4 (2.40 ml,

Helvetica Chimica Acta ± Vol. 81 (1998)
2119
22 mmol) according to GP 7. FC (pentane/Et2O 2 :1 ! 1 : 1) yielded 38 (5.14 g, ca. 30%) as a 3 : 1 mixture with
16. For anal. purposes, a sample was recrystallized (Et2O/pentane) to yield pure 38. white solid. M.p. 114 ± 1198.
[a]rD:t:
ˆ
84.7 (c ˆ 1.04, CHCl3). IR (CHCl3): 3447w, 3008w, 2968w, 1779s, 1718s, 1610w, 1511s, 1451m, 1364m,
1318m, 1050w. 1H-NMR (400 MHz, CDCl3): 0.70 (d, J ˆ 6.7, Me); 0.84 (d, J ˆ 7.0, Me); 1.90 ± 2.01 (m, Me2CH);
2.45 (dd, J ˆ 14.0, 7.1, 1 H, PhCH2); 2.64 (dd, J ˆ 14.0, 6.8, 1 H, PhCH2); 3.34 ± 3.52 (m, CH2N); 4.12 ± 4.20
(m, C(O)CH); 4.98 (s, CH2O); 5.06 (s, CH2O); 5.19 (br. s, NH); 5.32 (d, J ˆ 3.3, NCH); 6.69 (d, J ˆ 8.5,
2 arom. H); 6.80 ± 6.82 (m, 2 arom. H); 7.19 ± 7.45 (m, 20 arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 21.7
(Me); 29.8 (CH); 34.3, 42.3 (CH2); 44.8, 65.0 (CH); 66.7, 69.9 (CH2); 89.5 (C); 114.7, 125.3, 125.8, 127.5, 127.9,
128.0, 128.1, 128.1, 128.4, 128.5, 128.6, 128.9, 129.7, 129.9 (CH); 136.5, 137.1, 137.9, 142.0, 153.0, 156.1, 157.3,
‡
‡
174.0 (C). FAB-MS: 1366 (6, [2M ‡ H] ), 683 (32, [M ‡ H] ), 639(100), 518(16). Anal. calc. for C43H42N2O6
(682.81): C 75.64, H 6.20, N 4.10; found: C 75.78, H 6.39, N 4.12.
(S)-3-[(R)-3-Hydroxy-1-oxo-2-(phthalimidomethyl)propyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-
one (39). To a soln. of (S)-15 (4.83 g, 10 mmol) in CH2Cl2 (50 ml), TiCl4 (1.16 ml, 10.5 mmol) and Et3N (1.54 ml,
11 mmol) were added at ca. 108. The resulting dark red soln. was stirred at this temp. for 30 min. 1,3,5-Trioxane
(0.99 g, 11 mmol) and TiCl4 (1.22 ml, 11 mmol) were added, and the mixture stirred at 08 for 1 h, treated with
sat. NH4Cl soln., and diluted with Et2O. The org. phase was washed with 1m HCl (2Â), 1m NaOH, and sat. NaCl
solns., dried (MgSO4), and evaporated. Recrystallization (AcOEt/hexane) of the resulting crude product
yielded 39 (3.66 g). FC (pentane/Et2O 1 : 2) of the mother liquor yielded further 39 (1.06 g). Total yield: 4.72 g
(92%). White solid. M.p. 169 ± 1728. [a]Dr:t:
ˆ
108.9 (c ˆ 0.90, CHCl3). IR (CHCl3): 3512 (br.), 3011w, 1773s,
1714s, 1366m, 1322m, 1178m, 1098w, 951w. 1H-NMR (400 MHz, CDCl3): 0.77 (d, J ˆ 6.7, Me); 0.94 (d, J ˆ 7.0,
Me); 1.92 ± 2.03 (m, Me2CH); 3.07 (dd, J ˆ 8.6, 6.4, OH); 3.76 ± 3.81 (m, CH); 3.88 ± 4.00 (m, CH2); 4.03 ± 4.15
(m, CH2); 5.51 (d, J ˆ 2.9, NCH); 7.21 ± 7.40 (m, 8 arom. H); 7.46 ± 7.49 (m, 2 arom. H); 7.70 ± 7.78
(m, 2 Phth. H); 7.79 ± 7.84 (m, 2 Phth. H). 13C-NMR (100 MHz, CDCl3): 15.9, 21.7 (Me); 30.3 (CH); 34.7
(CH2); 45.3 (CH); 61.2 (CH2); 64.2 (CH); 89.6 (C); 123.6, 125.6, 125.8, 127.9, 128.4, 128.7, 129.0 (CH); 131.8
‡
‡
(C); 134.2 (CH); 142.1, 152.8, 168.6, 171.8 (C). FAB-MS: 1025 (2, [2M ‡ H] ), 513 (100, [M ‡ H] ), 469(13),
214(13). Anal. calc. for C30H28N2O6 (512.56): C 70.30, H 5.51, N 5.47; found: C 70.26, H 5.31, N 5.40.
(S)-3-[(R)-3-(Benzyloxy)-1-oxo-2-(phthalimidomethyl)propyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-
2-one (40). To
a soln. of 39 (513 mg, 1.0 mmol) in CH2Cl2 (3.2 ml) and hexane (3.2 ml), benzyl
trichloroacetimidate (0.22 ml, 1.1 mmol) and CF3SO3H (4 drops) were added at 08. The mixture was stirred
for 10 min at 08, then at r.t. for 16 h, diluted with Et2O, washed with 1m HCl (2Â), 1m NaOH, and sat. NaCl
solns., dried (MgSO4), and evaporated. Purification by FC (pentane/Et2O 1 : 1) yielded 40 (521 mg, 87%). For
anal. purposes, a sample was recrystallized (pentane/Et2O). White crystals. M.p. 119 ± 1218. [a]Dr:t:
ˆ
114.8 (c ˆ
1.03, CHCl3). IR (CHCl3): 3011w, 2971w, 1776s, 1718s, 1450m, 1395m, 1366m, 1322m, 1178m, 1106m, 1050w,
992w. 1H-NMR (400 MHz, CDCl3): 0.65 (d, J ˆ 6.7, Me); 0.84 (d, J ˆ 7.0, Me); 1.86 ± 1.93 (m, Me2CH); 3.76
(dd, J ˆ 9.6, 5.5, 1 H, CH2N); 3.82 ± 4.04 (m, 3 H, CH2N, CH2O); 4.41 ± 4.48 (m, C(O)CH); nA ˆ 4.58, nB ˆ 4.45
(AB, J ˆ 11.7, PhCH2); 5.46 (d, J ˆ 2.9, NCH); 7.05 ± 7.42 (m, 15 arom. H); 7.64 ± 7.76 (m, 4 Phth. H).
13C-NMR (100 MHz, CDCl3): 15.8, 21.6 (Me); 30.1 (CH); 36.3 (CH2); 43.2, 64.2 (CH); 69.4, 73.3 (CH2);
89.3 (C); 123.3, 125.6, 125.9, 127.6, 127.9, 128.0, 128.3, 128.4, 128.7 (CH); 131.9 (C); 133.8 (CH); 137.7, 138.3,
‡
142.1, 152.5, 167.8, 171.6 (C). FAB-MS: 603 (100, [M ‡ H] ), 559(11), 495(17), 322(12). Anal. calc. for
C37H34N2O6 (602.69): C 73.74, H 5.69, N 4.65; found: C 73.57, H 5.60, N 4.53.
(S)-3-((R)-2-{[(tert-Butoxycarbonyl)amino]methyl}-1-oxopropyl)-4-(1-methylethyl)-5,5-diphenyloxazoli-
din-2-one (41). Compound 32 (250 mg, 0.50 mmol) was treated according to GP 11 to yield, after FC (pentane/
Et2O 3 :1), 41 (203 mg, 87%). White solid. M.p. 122 ± 1238. [a]Dr:t:
ˆ
174.9 (c ˆ 0.77, CHCl3). IR (CHCl3):
3456w, 2972m, 1781s, 1710s, 1506m, 1450m, 1367m, 1175s, 1050m, 1000m. 1H-NMR (400 MHz, CDCl3): 0.77
(d, J ˆ 6.8, Me); 0.80 (d, J ˆ 7.0, Me); 0.87 (d, J ˆ 7.0, Me); 1.41 (s, t-Bu); 1.94 ± 2.02 (m, Me2CH); 3.26 ± 3.39
(m, CH2N); 3.78 ± 3.88 (m, C(O)CH); 4.92 (br. s, NH); 5.34 (d, J ˆ 3.4, NCH); 7.26 ± 7.47 (m, arom. H).
13C-NMR (100 MHz, CDCl3): 14.3, 16.5, 21.8, 28.4 (Me); 29.7, 38.2 (CH); 43.3 (CH2); 64.9 (CH); 79.2, 89.6 (C);
‡
125.6, 125.9, 128.0, 128.4, 128.7, 128.9 (CH); 137.9, 142.2, 152.9, 155.8, 175.6 (C). FAB-MS: 934 (20, [2M ‡ H] ),
‡
467 (70, [M ‡ H] ), 411(92), 367(89), 238(100). Anal. calc. for C27H34N2O5 (466.58): C 69.51, H 7.34, N 6.00;
found: C 69.39, H 7.37, N 5.95.
(S)-3-((R)-2-{[(tert-Butoxycarbonyl)amino]methyl}-3-methyl-1-oxobutyl)-4-(1-methylethyl)-5,5-diphenyl-
oxazolidin-2-one (42). Compound 33 (2.22 g, 4.20 mmol) was treated according to GP 11 to yield, after FC
(pentane/Et2O 4 :1 ! 2 : 1), 42 (1.68 g, 81%). White foam. [a]Dr:t:
ˆ
124.1 (c ˆ 0.73, CHCl3). IR (CHCl3):
3460w, 2970m, 1779s, 1708s, 1507m, 1450m, 1391m, 1367m, 1318m, 1175s, 1052m. 1H-NMR (400 MHz, CDCl3):
0.39 (d, J ˆ 6.6, Me); 0.69 (d, J ˆ 6.7, Me); 0.79 (d, J ˆ 6.7, Me); 0.89 (d, J ˆ 7.0, Me); 1.40 (s, t-Bu); 1.65 ± 1.75
(m, Me2CH); 1.96 ± 2.05 (m, Me2CH); 3.32 ± 3.48 (m, CH2N); 3.67 ± 3.74 (m, C(O)CH); 4.88 (br. s, NH); 5.37

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Helvetica Chimica Acta ± Vol. 81 (1998)
(d, J ˆ 3.4, NCH); 7.23 ± 7.53 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.4, 19.1, 20.0, 21.8, 28.4 (Me); 28.7,
29.7 (CH); 40.5 (CH2); 48.7, 65.6 (CH); 79.2, 89.4 (C); 125.4, 125.7, 128.0, 128.5, 128.6, 128.9 (CH); 137.8, 142.4,
‡
‡
153.3, 155.6, 175.1 (C). FAB-MS: 990 (6, [2M ‡ H] ), 495 (8, [M ‡ H] ), 440(26), 395(100). Anal. calc. for
C29H38N2O5 (494.63): C 70.42, H 7.74, N 5.66; found: C 70.57, H 7.82, N 5.60.
(S)-3-((R)-2-{[(tert-Butoxycarbonyl)amino]methyl}-1-oxo-3-phenylpropyl)-4-(1-methylethyl)-5,5-diphenyl-
oxazolidin-2-one (43). Compound 35 (2.98 g, 5.20 mmol) was treated according to GP 11 to yield, after FC
(pentane/Et2O 3 :1 ! 2 : 1), 43 (2.46 g, 87%). White solid. M.p. 141 ± 1428. [a]Dr:t:
ˆ
104.5 (c ˆ 1.26, CHCl3). IR
(CHCl3): 3454 (br.), 3008m, 2978m, 1779s, 1710s, 1498m, 1450m, 1392m, 1367s, 1318m, 1175s, 1052m, 950w.
1H-NMR (400 MHz, CDCl3): 0.77 (d, J ˆ 6.8, Me); 0.88 (d, J ˆ 7.0, Me); 1.40 (s, t-Bu); 1.94 ± 2.02 (m, Me2CH);
2.52 ± 2.56 (m, 1 H, PhCH2); 2.71 ± 2.76 (m, 1 H, PhCH2); 3.30 ± 3.48 (m, CH2N); 4.21 (br. m, C(O)CH); 4.92
(br. s, NH); 5.35 (d, J ˆ 3.3, NCH); 6.92 (br. m, 2 arom. H); 7.07 (br. m, 3 arom. H); 7.24 ± 7.40 (m,
10 arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 21.8, 28.4 (Me); 29.9 (CH); 35.2, 42.2 (CH2); 44.6 (CH);
64.9 (CH2); 79.3, 89.5 (C); 125.4, 125.8, 126.4, 128.0, 128.4, 128.4, 128.6, 128.7, 128.9 (CH); 137.8, 138.0, 142.0,
‡
‡
153.0, 155.6, 174.0 (C). FAB-MS: 1085 (30, [2M ‡ H] ), 543 (62, [M ‡ H] ), 487(36), 443(100), 412(17),
238(23). Anal. calc. for C33H38N2O5 (542.68): C 73.04, H 7.06, N 5.16; found: C 72.88, H 7.19, N 5.13.
(S)-3-[(R)-3-Hydroxy-1-oxo-3-phenylpropyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (44). Com-
pound (S)-7 (1.62 g, 5 mmol) was transformed with PhCHO (0.55 ml, 5.5 mmol) according to GP 9. Purification
of the crude product by FC (pentane/Et2O 3 :1 ! 1 : 2) gave 44 as a 89 : 11 mixture with its epimer 45 (1.88 g,
88%). Recrystallization (pentane/Et2O) yielded pure 44 (0.64 g, 30%). White needles. M.p. 121 ± 1238. [a]Dr:t:
ˆ
129.7 (c ˆ 0.98, CHCl3). IR (CHCl3): 3544w, 3036w, 2966w, 1783s, 1692m, 1450m, 1371s, 1177m. 1H-NMR
(400 MHz, CDCl3): 0.79 (d, J ˆ 6.8, Me); 0.93 (d, J ˆ 7.0, Me); 1.96 ± 2.07 (m, Me2CH); 3.09 (d, J ˆ 3.1, OH);
3.15 (dd, J ˆ 16.9, 9.3, 1 H, C(O)CH2); 3.43 (dd, J ˆ 16.9, 3.1, 1 H, C(O)CH2); 5.21 (d, J ˆ 9.3, PhCH); 5.43
(d, J ˆ 3.3, NCH); 7.25 ± 7.52 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 21.8 (Me); 29.9 (CH); 44.1
(CH2); 64.6, 70.4 (CH); 89.7 (C); 125.5, 125.8, 125.9, 127.8, 128.0, 128.4, 128.5, 128.7, 129.0 (CH); 138.0, 142.1,
‡
‡
142.3, 152.9, 172.0 (C). FAB-MS: 859 (9, [2M ‡ H] ), 430 (11, [M ‡ H] ), 412(100). Anal. calc. for C27H27NO4
(429.51): C 75.50, H 6.34, N 3.26; found: C 75.39, H 6.46, N 3.29.
(S)-3-[(S)-3-Hydroxy-1-oxo-3-phenylpropyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (45). To a
soln. of (S)-7 (1.62 g, 5 mmol) in CH2Cl2 (25 ml), TiCl4 (0.63 ml, 5.5 mmol) and EtN(i-Pr)2 (1.03 ml, 6 mmol)
were added at 08. The resulting dark red soln. was stirred at 08 for 30 min, cooled to 788, and PhCHO (1.01 ml,
10 mmol) was added. The mixture was allowed to warm to 08 over a period of 6 h before addition of sat. NH4Cl
soln. The mixture was diluted with CH2Cl2, washed with 1m HCl (2Â), 1m NaOH, and sat. NaCl solns., dried
(MgSO4), and evaporated. Purification by FC (pentane/Et2O 3 : 1 ! 1 : 1) yielded 45 as a 87: 13 mixture with its
epimer 44 (1.77 g, 82%). Recrystallization (AcOEt/hexane) yielded 45 (1.22 g, 57%, dr 95 : 5). White crystals.
M.p. 146 ± 1488. [a]Dr:t:
ˆ
189.7 (c ˆ 0.94, CHCl3). IR (CHCl3): 3532w, 3008w, 2970w, 1783s, 1694m, 1450m,
1
1372s, 1176. H-NMR (400 MHz, CDCl3): 0.75 (d, J ˆ 6.8, Me); 0.87 (d, J ˆ 7.0, Me); 1.93 ± 2.03 (m, Me2CH);
3.10 (dd, J ˆ 17.1, 2.9, 1 H, C(O)CH2); 3.30 (d, J ˆ 4.6, OH); 3.44 (dd, J ˆ 17.1, 9.7, 1 H, C(O)CH2); 5.06
(ddd, J ˆ 9.6, 4.5, 2.9, PhCH); 5.41 (d, J ˆ 3.4, NCH); 7.22 ± 7.49 (m, arom. H). 13C-NMR (100 MHz, CDCl3):
16.3, 21.8 (Me); 30.0 (CH); 44.0 (CH2); 64.7, 70.1 (CH); 89.7 (C); 125.6, 125.7, 125.9, 127.7, 128.1, 128.4, 128.5,
‡
128.7, 129.0 (CH); 137.9, 142.2, 142.4, 153.0, 172.1 (C). FAB-MS: 430 (18, [M ‡ H] ), 412(100), 368(12). Anal.
calc. for C27H27NO4 (429.51): C 75.50, H 6.34, N 3.26; found: C 75.70, H 6.49, N 3.19.
(S)-3-[(2S,3S)-3-Hydroxy-2-methyl-1-oxo-3-phenylpropyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one
(46) and (S)-3-[(2R,3S)-3-Hydroxy-2-methyl-1-oxo-3-phenylpropyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-
2-one (50). Compound (S)-8 (1.69 g, 5 mmol) was treated with PhCHO (0.55 ml, 5.5 mmol) according to GP 9.
FC (pentane/Et2O 3 :1 ! 1 : 1) yielded 46 as a 3 : 2 mixture with its epimer 50 (1.71 g, 77%). For anal. purposes a
sample was further purified by FC and recrystallization to yield pure 46 and 50.
Data of 46: White foam. [a]Dr:t:
ˆ
142.5 (c ˆ 0.89, CHCl3). IR (CHCl3): 3600 ± 3300 (br.), 2970w, 1780s,
1684m, 1450m, 1365m, 1177m, 990m. 1H-NMR (400 MHz, CDCl3): 0.77 (d, J ˆ 6.8, Me); 0.88 (d, J ˆ 7.0, Me);
1.21 (d, J ˆ 7.1, Me); 1.90 ± 2.04 (m, Me2CH); 2.91 (d, J ˆ 2.6, OH); 3.94 (dq, J ˆ 7.1, 3.6, C(O)CH); 4.80 (t, J ˆ
3.1, PhCH); 5.40 (d, J ˆ 3.4, NCH); 7.16 ± 7.46 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 11.1, 16.3, 21.8
(Me); 30.0, 44.3, 64.3, 72.9 (CH); 89.5, (C); 125.6, 125.9, 126.0, 127.4, 128.1, 128.2, 128.4, 128.7, 129.0 (CH);
‡
138.0, 141.1, 142.1, 152.5, 176.8 (C). FAB-MS: 444 (38, [M ‡ H] ), 426(100). Anal. calc. for C28H29NO4
(443.54): C 75.82, H 6.59, N 3.16; found: C 75.81, H 6.72, N 3.05.
Data of 50: Colorless oil. [a]Dr:t:
ˆ
193.5 (c ˆ 0.82, CHCl3). IR (CHCl3): 3620w, 3600 ± 3300 (br.), 3008w,
2973w, 1781s, 1696m, 1450m, 1370m, 1177m, 1047m, 1000m. 1H-NMR (400 MHz, CDCl3): 0.66 (d, J ˆ 6.7, Me);
0.74 (d, J ˆ 7.0, Me); 0.76 (d, J ˆ 7.0, Me); 1.86 ± 1.97 (m, Me2CH); 3.24 (d, J ˆ 7.7, OH); 4.24 (dq, J ˆ 7.7, 7.0,
C(O)CH); 4.73 (t, J ˆ 7.7, PhCH); 5.34 (d, J ˆ 3.3, NCH); 7.20 ± 7.46 (m, arom. H). 13C-NMR (100 MHz,

Helvetica Chimica Acta ± Vol. 81 (1998)
2121
CDCl3): 15.0, 16.5, 21.9 (Me); 30.1, 44.2, 65.4, 77.4 (CH); 90.0 (C); 126.0, 126.3, 126.9, 128.2, 128.4, 128.8, 128.9,
‡
129.1, 129.3 (CH); 138.3, 142.6, 142.6, 153.7, 176.8 (C). FAB-MS: 444 (35, [M ‡ H] ), 426(100). Anal. calc. for
C28H29NO4 (443.54): C 75.82, H 6.59, N 3.16; found: C 75.86, H 6.81, N 3.08.
(S)-3-[(2S,3R)-3-Hydroxy-2,4-dimetyl-1-oxopentyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (47).
Compound (S)-8 (1.69 g, 5 mmol) was transformed with isobutyraldehyde (0.46 ml, 5.5 mmol) according to
GP 9 to yield, after FC (pentane/Et2O 3 :1 ! 1 : 1), 47 as a 96 : 4 mixture with its epimer 49 (1.02 g, 50%). For
anal. purposes, a sample was recrystallized (pentane/Et2O) to yield pure 47. White solid. M.p. 104 ± 1058.
[a]rD:t:
ˆ
181.9 (c ˆ 0.85, CHCl3). IR (CHCl3): 3522w, 2969m, 1780s, 1688m, 1450m, 1364m, 1316m, 1177m,
990m. 1H-NMR (400 MHz, CDCl3): 0.71 (d, J ˆ 6.6, Me); 0.75 (d, J ˆ 6.8, Me); 0.78 (d, J ˆ 6.8, Me); 0.87 (d, J ˆ
7.0, Me); 1.26 (d, J ˆ 7.0, Me); 1.38 ± 1.50 (m, Me2CH); 1.94 ± 2.06 (m, Me2CH); 2.36 (d, J ˆ 3.7, OH); 3.17
(ddd, J ˆ 7.6, 3.9, 3.7, CH(OH)); 3.78 (dq, J ˆ 7.0, 4.0, C(O)CH); 5.37 (d, J ˆ 3.5, NCH); 7.17 ± 7.52
(m, arom. H). 13C-NMR (100 MHz, CDCl3): 11.5, 16.4, 18.1, 19.0, 21.7 (Me); 29.8, 30.5, 39.9, 64.7, 76.6
(CH); 89.5 (C); 125.5, 125.8, 128.1, 128.5, 128.7, 128.9 (CH); 137.9, 142.4, 152.6, 177.3 (C). FAB-MS: 410 (100,
‡
[M ‡ H] ), 392(39). Anal. calc. for C25H31NO4 (409.52): C 73.32, H 7.63, N 3.42; found: C 73.28, H 7.90, N 3.43.
(S)-3-[(2R,3R)-3-Hydroxy-2-methyl-1-oxo-3-phenylpropyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-
one (48) [28]. To a soln. of (S)-8 (1.69 g, 5 mmol) in THF (25 ml), BuLi (3.46 ml, 5.5 mmol) was added at 788.
The clear soln. was stirred for 30 min at this temp. before addition of (i-PrO)3TiCl (1.79m soln. in hexane;
8.66 ml, 15.5 mmol). The resulting yellow soln. was allowed to warm to 408 over a period of 1 h, then cooled to
788, and PhCHO (0.56 ml, 5.5 mmol) was added. The mixture was allowed to warm to 408 over a period of
3 h, treated with sat. NH4Cl soln. and diluted with Et2O. The org. phase was washed with 1m HCl (2Â), 1m
NaOH (2Â), and sat. NaCl solns., dried (MgSO4), and evaporated. The resulting crude product was purified by
FC (pentane/Et2O 2 : 1 ! 1 : 2) to yield 48 as a 93 : 7 mixture with epimers (1.92 g. 87%). Recrystallization
(AcOEt/hexane) yielded pure 48 (1.46 g, 66%). M.p. 163 ± 1648. [a]Dr:t:
ˆ
158.8 (c ˆ 1.34, CHCl3). IR (CHCl3):
3608w, 3500w, 3008w, 2969w, 1780s, 1696m, 1450m, 1366s, 1176s, 1052m, 992m. 1H-NMR (400 MHz, CDCl3):
0.66 (d, J ˆ 6.7, Me); 0.77 (d, J ˆ 7.0, Me); 0.79 (d, J ˆ 6.9, Me); 1.87 ± 1.98 (m, Me2CH); 2.81 (d, J ˆ 3.1, OH);
4.04 ± 4.11 (m, C(O)CH); 5.18 (t, J ˆ 3.7, PhCH); 5.35 (d, J ˆ 3.3, NCH); 7.22 ± 7.46 (m, arom. H). 13C-NMR
(100 MHz, CDCl3): 10.5, 16.2, 21.5 (Me); 29.7, 44.0, 64.7, 74.0 (CH); 89.6 (C); 125.6, 125.9, 126.3, 127.6, 128.0,
‡
128.3, 128.4, 128.7, 128.9 (CH); 137.9, 141.4, 142.2, 152.9, 176.1 (C). FAB-MS: 444 (31, [M ‡ H] ), 426(100).
Anal. calc. for C28H29NO4 (443.54): C 75.82, H 6.59, N 3.16; found: C 75.76, H 6.49, N 3.12.
(S)-3-[(2R,3S)-3-Hydroxy-2,4-dimethyl-1-oxopentyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (49).
Compound (S)-8 (1.69 g, 5 mmol) was transformed with isobutyraldehyde (0.46 ml, 5.5 mmol) according to
GP 8 to yield, after FC (pentane/Et2O 4 :1 ! 1 : 1), 49 as a 4 : 1 mixture with epimers (1.15 g, 56%). For anal.
purposes, a sample was recrystallized (pentane/Et2O) to yield pure 49. M.p. 162 ± 1638. [a]Dr:t:
ˆ
172.0 (c ˆ 1.00,
CHCl3). IR (CHCl3): 3526w, 2967m, 1780s, 1685m, 1450m, 1364m, 1317m, 1177m, 990m. 1H-NMR (400 MHz,
CDCl3): 0.79 (d, J ˆ 6.8, Me); 0.81 (d, J ˆ 7.0, Me); 0.89 (d, J ˆ 7.0, Me); 0.92 (d, J ˆ 6.8, Me); 1.03 (d, J ˆ 6.6,
Me); 1.62 ± 1.74 (m, Me2CH); 1.93 ± 2.04 (m, Me2CH); 2.58 (d, J ˆ 4.0, OH); 3.60 ± 3.63 (m, CH(OH)); 3.92
(dq, J ˆ 7.0, 3.1, C(O)CH); 5.37 (d, J ˆ 3.4, NCH); 7.26 ± 7.48 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 9.5,
16.4, 18.9, 19.1, 21.7 (Me); 29.8, 31.1, 39.4, 64.6, 77.0 (CH); 89.5 (C); 125.6, 125.9, 128.0, 128.4, 128.7, 128.9 (CH);
‡
138.0, 142.2, 152.8, 177.3 (C). FAB-MS: 410 (100, [M ‡ H] ), 392(33), 348(19). Anal. calc. for C25H31NO4
(409.52): C 73.32, H 7.63, N 3.42; found: C 73.49, H 7.49, N 3.35.
(S)-3-[(2R,3S)-2-Methyl-4-nitro-1-oxo-3-phenylbutyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (52).
Compound (S)-8 (1.69 g, 5 mmol) was treated with (E)-b-nitrostyrene (0.82 g, 5.5 mmol) according to GP 10.
FC (pentane/Et2O 10 :1 ! 5 : 1) yielded 52 as a 9 : 1 mixture with an epimer (1.91 g, 78%). Recrystallization
(pentane/Et2O) yielded pure 52 (1.42 g, 58%). White needles. M.p. 151 ± 1528. [a]Dr:t:
ˆ
166.8 (c ˆ 0.90, CHCl3).
IR (CHCl3): 3011w, 2973w, 1781s, 1696m, 1557s, 1450m, 1374m, 1177m. 1H-NMR (400 MHz, CDCl3): 0.52
(d, J ˆ 6.9, Me); 0.79 (d, J ˆ 6.8, Me); 0.89 (d, J ˆ 7.0, Me); 1.96 ± 2.08 (m, Me2CH); 3.74 (dt, J ˆ 10.2, 4.2,
PhCH); 4.10 (dq, J ˆ 10.3, 6.9, C(O)CH); 4.65 (dd, J ˆ 12.3, 4.3, 1 H, CH2NO2); 4.81 (dd, J ˆ 12.3, 10.1, 1 H,
CH2NO2); 5.33 (d, J ˆ 3.6, NCH); 7.19 ± 7.46 (m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.6, 16.7, 21.8 (Me);
29.5, 39.9, 46.6, 65.6 (CH); 78.6 (CH2); 90.0 (C); 125.5, 125.8, 128.0, 128.2, 128.5, 128.7, 128.9, 129.0 (CH); 137.2,
‡
142.1, 153.0, 175.1 (C). FAB-MS: 487 (100, [M ‡ H] ), 440 (15). Anal. calc. for C29H30N2O5 (486.57): C 71.59,
H 6.21, N 5.76; found: C 71.64, H 6.08, N 5.77.
(S)-3-[(2R,3S)-3-(4-Methoxyphenyl)-2-methyl-4-nitro-1-oxobutyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-
2-one (53). Compound (S)-8 (1.69 g, 5 mmol) was treated with (E)-4-methoxy-b-nitrostyrene (0.99 g, 5.5 mmol)
according to GP 10. FC (pentane/Et2O 10 :1 ! 4 : 1) yielded 53 as a 92 : 8 mixture with an epimer (2.06 g, 80%).
White foam. [a]Dr:t:
ˆ
155.5 (c ˆ 1.17, CHCl3). IR (CHCl3): 2970w, 1780s, 1698m, 1556s, 1514m, 1450m, 1373m,
1035m. 1H-NMR (400 MHz, CDCl3): 0.52 (d, J ˆ 6.9, Me); 0.80 (d, J ˆ 6.8, Me); 0.90 (d, J ˆ 7.0, Me); 1.96 ± 2.08

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Helvetica Chimica Acta ± Vol. 81 (1998)
(m, Me2CH); 3.68 (dt, J ˆ 10.2, 4.3, PhCH); 3.76 (s, MeO); 4.05 (dq, J ˆ 10.3, 6.9, C(O)CH); 4.61 (dd, J ˆ 12.1,
4.3, 1 H, CH2NO2); 4.75 (dd, J ˆ 12.1, 10.2, 1 H, CH2NO2); 5.33 (d, J ˆ 3.6, NCH); 6.81 ± 6.85 (m, 2 arom. H);
7.10 ± 7.14 (m, 2 arom. H); 7.22 ± 7.46 (m, 10 arom. H). 13C-NMR (100 MHz, CDCl3): 16.6, 16.7, 21.8 (Me);
29.5, 40.0, 46.0 (CH); 55.2 (Me); 65.5 (CH); 78.8 (CH2); 90.0 (C); 114.4, 125.5, 125.8, 128.2, 128.5, 128.7, 128.9,
‡
129.0, 129.0 (CH); 137.6, 142.1, 153.1, 159.2, 175.2 (C). FAB-MS: 517 (100, [M ‡ H] ), 469(28), 424(17). Anal.
calc. for C30H32N2O6 (516.59): C 69.75, H 6.24, N 5.42; found: C 69.82, H 6.24, N 5.37.
(S)-4-(1-Methylethyl)-3-{(2R,3S)-3-[3,4-(methylenedioxy)phenyl]-2-methyl-4-nitro-1-oxobutyl}-5,5-diphe-
nyloxazolidin-2-one (54). Compound (S)-8 (1.69 g, 5 mmol) was treated with (E)-3,4-(methylenedioxy)-b-
nitrostyrene (1.06 g, 5.5 mmol) according to GP 10. FC (pentane/Et2O 10 :1 ! 4 : 1) yielded 54 as a 92 : 8
mixture with an epimer (2.28 g, 86%). Recrystallization (pentane/Et2O) yielded 54 (1.97 g, 74%); dr 96 : 4.
White powder. M.p. 143 ± 1478. [a]Dr:t:
ˆ
143.8 (c ˆ 1.35, CHCl3). IR (CHCl3): 3020w, 2990w, 1788s, 1705m,
1564s, 1512m, 1495m, 1457m, 1374m, 1050m, 945m. 1H-NMR (400 MHz, CDCl3): 0.53 (d, J ˆ 6.9, Me); 0.80
(d, J ˆ 6.8, Me); 0.90 (d, J ˆ 7.0, Me); 1.97 ± 2.08 (m, Me2CH); 3.65 (dt, J ˆ 10.3, 4.3, PhCH); 4.01 (dq, J ˆ 10.4,
6.9, C(O)CH); 4.59 (dd, J ˆ 12.2, 4.3, 1 H, CH2NO2); 4.72 (dd, J ˆ 12.2, 10.3, 1 H, CH2NO2); 5.33 (d, J ˆ 3.6,
NCH); nA ˆ 5.93, nB ˆ 5.92 (AB, J ˆ 1.5, CH2O); 6.64 ± 6.76 (m, 3 arom. H); 7.24 ± 7.46 (m, 10 arom. H).
13C-NMR (100 MHz, CDCl3): 16.6, 16.7, 21.8 (Me); 29.5, 40.1, 46.5, 65.6 (CH); 78.7 (CH2); 90.0 (C); 101.2
(CH2); 108.2, 108.6, 121.8, 125.5, 125.8, 128.2, 128.5, 128.8, 128.9 (CH); 130.7, 137.6, 142.1, 147.3, 148.1, 153.1,
‡
175.1 (C). FAB-MS: 531 (100, [M ‡ H] ), 483(25), 438(10). Anal. calc. for C30H30N2O7 (530.58): C 67.91,
H 5.70, N 5.28; found: C 67.91, H 5.68, N 5.51.
(S)-4-(1-Methylethyl)-3-[(2R,3S)-4-nitro-1-oxo-3-phenyl-2-(phenylmethyl)butyl]-5,5-diphenyloxazolidin-
2-one (55). Compound (S)-11 (2.07 g, 5 mmol) was treated with (E)-b-nitrostyrene (0.82 g, 5.5 mmol) according
to GP 10. FC (pentane/Et2O 10 :1 ! 5 : 1) yielded 55 as a 97: 3 mixture with an epimer (2.61 g, 92%).
Recrystallization (AcOEt/hexane) yielded pure 55 (2.01 g, 71%). White crystals. M.p. 184 ± 1878. [a]Dr:t:
ˆ
111.1 (c ˆ 0.81, CHCl3). IR (CHCl3): 3011w, 1777s, 1697m, 1556s, 1495m, 1451m, 1364m, 1318m, 1178m.
1H-NMR (400 MHz, CDCl3): 0.67 (d, J ˆ 6.8, Me); 0.91 (d, J ˆ 7.1, Me); 1.97 ± 2.04 (m, Me2CH); 2.44 (dd, J ˆ
14.2, 5.7, 1 H, PhCH2); 2.62 (dd, J ˆ 14.2, 7.7, 1 H, PhCH2); 3.66 ± 3.72 (m, PhCH); 4.64 ± 4.74 (m, CH2NO2);
5.08 (dd, J ˆ 12.4, 10.7, C(O)CH); 5.33 (d, J ˆ 2.8, NCH); 6.62 (d, J ˆ 6.8, 2 arom. H); 6.92 ± 7.02 (m, 3 ar-
om. H); 7.20 ± 7.40 (m, 15 arom. H). 13C-NMR (100 MHz, CDCl3): 16.3, 21.8 (Me); 30.0 (CH); 35.9 (CH2);
45.3, 46.9, 65.5 (CH); 77.9 (CH2); 89.3 (C); 125.0, 125.7, 126.7, 128.0, 128.1, 128.1, 128.3, 128.4, 128.5, 128.7,
‡
129.0, 129.1 (CH); 136.7, 137.3, 137.9, 142.0, 152.9, 173.4 (C). FAB-MS: 563 (100, [M ‡ H] ), 412(39). Anal.
calc. for C35H34N2O5 (562.66): C 74.71, H 6.09, N 4.98; found: C 74.61, H 6.15, N 4.98.
(S)-4-(1-Methylethyl)-3-[(R)/(S)-1-oxo-3-phenylbutyl]-5,5-diphenyloxazolidin-2-one (56/57) [49]. CuBr´
SMe2 (739 mg, 3.75 mmol) was suspended in THF (11 ml) and cooled to 308. PhMgBr (7.5 mmol in 10 ml
THF) was added, the mixture stirred for 5 min, and (S)-12 (8.74 mg, 2.5 mmol) in THF (6 ml) was added over a
period of 15 min. The mixture was allowed to warm to 158 in 1 h, treated with sat. NH4Cl soln., and diluted
with Et2O. The org. phase was washed with 1m HCl, 1m NaOH, and sat. NaCl solns., dried (MgSO4), and
evaporated. The resulting crude product was purified by FC (pentane/Et2O 12 : 1 ! 8 : 1) to yield a 2 : 1 mixture
56/57 (988 mg, 92%). Reaction of (S)-13 with MeMgBr under identical conditions yielded a 1 : 2 mixture 56/57
(90%). For anal. purposes, a sample was recrystallized twice to yield a 89 : 11 mixture of 56/57. White needles.
M.p. 107 ± 1098. [a]Dr:t:
ˆ
182.4 (c ˆ 0.77, CHCl3). IR (CHCl3): 3011w, 2969w, 1778s, 1702m, 1450m, 1367m,
1
1318m, 1176m. H-NMR (400 MHz, CDCl3): 0.62 (d, J ˆ 6.8, Me); 0.71 (d, J ˆ 7.0, Me); 1.19 (d, J ˆ 6.9, Me);
1.86 ± 1.96 (m, Me2CH); 2.99 ± 3.04 (m, PhCH); 3.26 ± 3.38 (m, C(O)CH2); 5.36 (d, J ˆ 3.3, NCH); 7.15 ± 7.52
(m, arom. H). 13C-NMR (100 MHz, CDCl3): 16.1, 21.5, 21.9 (Me); 29.7, 36.5 (CH); 42.7 (CH2); 64.5 (CH); 89.2
(C); 125.6, 125.9, 126.3, 127.0, 127.9, 128.4, 128.4, 128.6, 128.9 (CH); 138.1, 142.4, 145.5, 153.0, 171.7 (C). FAB-
‡
MS: 428 (100, [M ‡ H] ), 384(34). Anal. calc. for C28H29NO3 (427.54): C 78.66, H 6.84, N 3.28; found: C 78.58,
H 6.81, N 3.22.
(S)-3-[(1R,2R,3S,4S)-3-Methylbicyclo[2.2.1]hept-5-ene-2-carbonyl]-4-(1-methylethyl)-5,5-diphenyloxazo-
lidin-2-one (58). To a soln. of (S)-12 (874 mg, 2.5 mmol) in CH2Cl2 (5 ml), cyclopentadiene (5.15 ml,
62.5 mmol), and ClAlMe2 (3.5 ml, 3.5 mmol) were added at 958. The mixture stirred for 2 min at 958, 1m HCl
soln. was added, and the mixture extracted with CH2Cl2. The org. phase was dried (MgSO4) and the solvent
removed under reduced pressure. FC (pentane/Et2O) yielded 58 (900 mg, 87%). For anal. purposes, a sample
was recrystallyzed (AcOEt/hexane). White crystals. M.p. 134 ± 1358. [a]Dr:t:
ˆ
69.2 (c ˆ 1.09, CHCl3). IR
(CHCl3): 2970m, 2874w, 1777s, 1696s, 1450m, 1365m, 1325m, 1176s, 1051m, 912w. 1H-NMR (400 MHz, CDCl3):
0.78 (d, J ˆ 6.8, Me); 0.84 (d, J ˆ 7.0, Me); 0.93 (d, J ˆ 7.1, Me); 1.45 ± 1.48 (m, CH); 1.67 (d, J ˆ 8.6, CH); 1.87 ±
2.00 (m, Me2CH, CH); 2.47 (d, J ˆ 1.5, CH); 3.30 (dd, J ˆ 4.6, 3.3, CH); 3.43 (s, CH); 5.36 (d, J ˆ 3.1, NCH);
5.85 (dd, J ˆ 5.7, 2.8, CˆCH); 6.37 (dd, J ˆ 5.7, 3.2, CˆCH); 7.25 ± 7.50 (m, arom. H). 13C-NMR (100 MHz,