Applications of the chiral auxiliaries DIOZ and TRIOZ for conjugate additions and comparison with other auxiliaries

Article abstract of DOI:10.1002/hlca.200900385

A number of N-acryloyl-, N-crotonoyl-, N-(3,3,3-trifluorocrotonoyl)-, N-cinnamoyl-, and N-(3-nitroacryloyl)-4-isopropyl- or -4-phenyl-oxazolidin-2- ones with geminal diphenyl substitution, i.e., 7-15, have been prepared and used for conjugate additions of organocuprate reagents (Me, ⁱPr, Ph, 4-MeOPh) in the β-carbonyl (Table 2) and in the α-carbonyl position (NO₂-derivative 11 in Scheme 3). The yields and diastereoselectivities are compared with previously tested enoyl-oxazolidinones (Table 2). Highest diastereoselectivities (>90%) are always observed with the 4-Ph derivatives (Hruby effect). Nitroacryloyl-oxazolidinones and a corresponding phenylmenthol ester undergo less diastereoselective additions (Scheme 3). A 3-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (DIOZ)-derived Li₂-enolatenitronate was also tested for α-carbonyl alkylation (Scheme 4). The X-ray crystal structures of three acryloyl-oxazolidinones and of four adducts are described (Tables 1 and 3), and they serve for configurational assignments and description of the stereochemical courses of the additions and alkylation. Possible applications of the nitro compounds for the preparation of β²-amino acids are discussed (Scheme 2).

Full text of DOI:10.1002/hlca.200900385

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Helvetica Chimica Acta – Vol. 93 (2010)
Applications of the Chiral Auxiliaries DIOZ and TRIOZ for Conjugate
Additions and Comparison with Other Auxiliaries
by Hanspeter Sprecher1), Stefan Pletscher1), Manuel Mçri1), and Roger Marti*2)
Zꢀrcher Hochschule fꢀr Angewandte Wissenschaften ZHAW, Institut fꢀr Chemie und Biologische
Chemie, CH-8400 Winterthur
and
Christoph Gaul3), Krystyna Patora-Komisarska4), Ekatarina Otchertianova5), Albert K. Beck, and
Dieter Seebach*
Laboratorium fꢀr Organische Chemie, Departement fꢀr Chemie und Angewandte Biowissenschaften,
ETH-Zꢀrich, Hçnggerberg, Wolfgang-Pauli-Strasse 10, CH-8093 Zꢀrich
(phone: þ 41-44-632-2990; fax: þ 41-44-632-1144; e-mail: seebach@org.chem.ethz.ch)
A number of N-acryloyl-, N-crotonoyl-, N-(3,3,3-trifluorocrotonoyl)-, N-cinnamoyl-, and N-(3-
nitroacryloyl)-4-isopropyl- or -4-phenyl-oxazolidin-2-ones with geminal diphenyl substitution, i.e., 7 – 15,
have been prepared and used for conjugate additions of organocuprate reagents (Me, iPr, Ph, 4-MeOPh)
in the b-carbonyl (Table 2) and in the a-carbonyl position (NO2-derivative 11 in Scheme 3). The yields
and diastereoselectivities are compared with previously tested enoyl-oxazolidinones (Table 2). Highest
diastereoselectivities (> 90%) are always observed with the 4-Ph derivatives (Hruby effect). Nitro-
acryloyl-oxazolidinones and a corresponding phenylmenthol ester undergo less diastereoselective
additions (Scheme 3). A 3-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (DIOZ)-derived Li2-enolate-
nitronate was also tested for a-carbonyl alkylation (Scheme 4). The X-ray crystal structures of three
acryloyl-oxazolidinones and of four adducts are described (Tables 1 and 3), and they serve for
configurational assignments and description of the stereochemical courses of the additions and
alkylation. Possible applications of the nitro compounds for the preparation of b2-amino acids are
discussed (Scheme 2).
1. Introduction. – Overall enantioselective Michael additions using a chiral auxiliary
group (now rivaled by organocatalytic methods [1]) have been achieved by acylating
chiral heterocycles with an a,b-unsaturated carboxylic acid derivative, performing a
diastereoselective conjugate addition and cleaving off the auxiliary (preferably with
1
)
Bachelor Theses of H. S. (2006), S. P. (2007), and M. M. (2008), Zꢀrcher Hochschule fꢀr
Angewandte Wissenschaften (ZHAW); the experimental work was carried out in the Laboratorium
fꢀr Organische Chemie of ETH-Zꢀrich in all three cases.
2
´
´
)
New address: Ecole dꢂIngenieurs et dꢂArchitectes de Fribourg, Departement des Technologies
`
´
Industrielles, Filiere de Chimie, Bd de Perolles 80, CH-1705 Fribourg (phone: þ 41-26-4296703;
fax: þ 41-26-4296600; e-mail: roger.marti@hefr.ch).
3
4
)
)
Part of the Ph.D. Thesis of C. G., ETH-Zꢀrich Dissertation No. 14516, 2002.
Postdoctoral co-worker at ETH-Zꢀrich (2008/09), financed by Swiss National Science Foundation
(SNF-Project No. 200020-117586). We thank Novartis AG for continuing financial support.
Postdoctoral co-worker at ETH-Zꢀrich (2002), we thank Novartis AG for financial support.
5
)
ꢁ 2010 Verlag Helvetica Chimica Acta AG, Zꢀrich

Helvetica Chimica Acta – Vol. 93 (2010)
91
recovery!) (Scheme 1). The most commonly used auxiliaries are the oxazolidinones
popularized by D. Evans [2]. It turned out that, as compared to the simple valine- or
phenylalanine-derived oxazolidinones 1, the geminally disubstituted derivatives 2 [3]
and 3 [4]6) have certain general advantages (amply discussed in the literature [3 – 5]).
In the Michael addition outlined in Scheme 1, it turned out that the phenylglycine-
derived auxiliaries 1 and 2, R ¼ Ph, give highest diastereoselectivities (RNuMgBr/CuBr
as nucleophiles) [3a][6]7); the 4,5,5-triphenyloxazolidin-2-one (4; TRIOZ) had, so far,
not been used for this purpose.
Scheme 1. Principle of Enantioselective Michael Additions Using a Chiral Auxiliary Group
2. Preparation of the Starting Materials. – We have now prepared a number of
oxazolidinone derivatives 5 – 15 and the phenylmenthol derivative 16 of a,b-unsatu-
rated carboxylic acids, to test and compare the reactivities and diastereoselectivities in
Michael additions to their enoylic (i.e., 5, 7 – 10, and 12 – 15) or nitroolefinic (i.e., 6 and
11) C¼C bonds.
The substrates 5 – 16 for conjugate additions were prepared according to known
procedures: the classical Evans-type acryloyl-oxazolidinone 5 [2b][7] was nitrated
6
)
Besides our group [4], the groups of Gibson et al. [5b], and Davies and wo-workers [3b] have also
tested auxiliary 3. In two papers and in a patent, the preparation of 3 has been described previously
[3g][5]. The term DIOZ (¼3-(1-methylethyl)-5,5-diphenyloxazolidin-2-one) for compound 3 was
first used in an advertisement of the Shiratori Pharmaceutical Company, which offered both
enantiomers for sale.
A SciFinder search for N-enoyl-4-phenyloxazolidinone 1 (R ¼ Ph) produced 200 references, 28
alone by Hruby and co-workers, who had first reported the superiority of this auxiliary for Michael
additions [6].
7
)

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Helvetica Chimica Acta – Vol. 93 (2010)
(!6) by addition of NO2Cl to the C¼C bond, followed by HCl elimination with
AcONa as base [8]. With a similar procedure8) acryloyl-DIOZ 7 gave nitro com-
pound 11 (for crystal structure, see Table 1). The enoyl-oxazolidinones 7 – 10 and 12 –
15 were prepared9) from the corresponding parent heterocycles 3 (DIOZ) or 4
(TRIOZ), and enoyl-chlorides or anhydrides, as described in the literature [4a] and in
the Exper. Part. The phenylmenthol-derived10) nitro-acrylate 16 was obtained
according to a published procedure [9]. X-Ray crystal structures of the acryloyl-
oxazolidinones 5, 11, and 12, are shown in Table 1. As in numerous published structures
of other 3-acyl-oxazolidinones and as in the product structures, also listed in Table 1, the
exocyclic NꢀCO bond has s-trans configuration, with OC(2)ꢀNꢀC(1’)¼O torsion
angles close to 1808.
3. Conjugate Additions to the Cinnamoyl- and Crotonoyl-Oxazolidinones 8 – 10,
13 – 15. – All reactions were carried out with excess organocuprates as nucleophiles,
generated from Grignard reagents MeMgBr, PhMgBr, or 4-MeOPhMgBr and CuBr·
SMe2 (ratio 2 :1)11). In Table 2, the yields and diastereoselectivities are listed, together
with values reported in the literature for analogous additions to enoyl-oxazolidinones
(Entries 1 – 7) other than DIOZ and TRIOZ derivatives (Entries 8 – 17). With the
8
)
)
We did not succeed in preparing the corresponding nitro-acryloyl-TRIOZ from acryloyl-TRIOZ 12.
Compound 7 was first prepared (59% yield) by Meinrad Brenner (ETH-Zꢀrich Dissertation No.
14409, 2001), using the anhydride method. Most acrylations were carried out by first treating DIOZ
or TRIOZ, with BuLi or MeMgBr, and then with the corresponding acid chloride.
Phenylmenthol was introduced as a chiral auxiliary by Corey and Ensley [9a].
The copper trick for directing Grignard reagents from the 1,2- to the 1,4-mode of addition to a,b-
unsaturated carbonyl compounds was introduced by Kharash and Tawney [10a]. For leading
references to the use of CuBr· SMe2, see [10b].
9
10
11
)
)

Helvetica Chimica Acta – Vol. 93 (2010)
93
Table 1. X-Ray Crystal Structures of Starting Materials 5, 11, and 12 of the Dichloro Derivative 17, and of
the Products 19, 24a, 24c, and 25c. For crystal data, see Table 3 in the Exper. Part.

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Helvetica Chimica Acta – Vol. 93 (2010)
Table 1 (cont.)

Helvetica Chimica Acta – Vol. 93 (2010)
95
Table 2. Examples of Diastereoselective Conjugate Additions of Grignard Reagents/CuBr · SMe2 to 3-
Enoyl-4-benzyl-, -4-isopropyl-, and -4-phenyl-Substituted Oxazolidinones from the Literature (Entries 3 –
9) and from the Present Investigation (Entries 1, 2, and 10 – 17). Some of the data (Entries 1, 2, and 11) are
taken from [11], with no experimental details given herein. In all cases, the solution of the Michael
acceptor was added to the organometallic reagent at low temperatures (ꢀ 308 in THF). For the X-ray
crystal structure of epi-19, see Table 1. All diastereoisomer ratios A/epi-A and B/epi-B were determined
by NMR peak integrations with the crude products. The yields are total yields of major and minor
products of type A or B. In most cases, recrystallization led to diastereoisomerically pure samples of the
major isomer (see Exper. Part).
Entry
Starting material
Product
Major
No.
Yield [%]
Ratio
A/epi-A
B/epi-B
Ref.
[11]
1
65 : 35
66 : 34
55 : 45
2
3
[11]
[6]
85

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Helvetica Chimica Acta – Vol. 93 (2010)
Table 2 (cont.)
Entry Starting material Product
Major
No.
Yield [%] Ratio
A/epi-A
Ref.
[6]
B/epi-B
4
5
6
7
90
90
67
87
99 : 1
74 : 26
97: 3
96 : 4
[6]
[3a]
[3a]
8
(S)-8
(S)-9
(S)-9
(S)-10
(R)-13
86
92
67: 33
70 : 30
[4a]
[11]
9
90
88
67: 33
85 : 15
82 : 18
[4a]
10
11
12
18
this work
this work
epi-18 78
19
53
71
98 : 2
96 : 4
[11]
this work

Helvetica Chimica Acta – Vol. 93 (2010)
97
Table 2 (cont.)
Entry
Starting material
Product
Major
No.
Yield [%]
74
Ratio
A/epi-A
B/epi-B
Ref.
13
(R)-13
(S)-14
(S)-14
(R)-15
(S)-15
20
91 : 9
this work
this work
this work
14
21
55
60
61 : 39
69 : 31
15
22
16
epi-19
23
71
68
93 : 7
96 : 4
[11]
this work
17
64
97: 3
this work
exception of the CF3-substituted acceptors (Entries 14 and 15), the diastereoselectiv-
ities of addition to 3-enoyl-4-phenyl-oxazolidinones are above 90%; with iPr groups in
the 4-position, the selectivities tend to be near 2 :1 (Entries 8 and 9) or 4 :1 (Entries 10
and 11); the yields are moderate to excellent; the configurations of the major products
as shown in A and B (Table 2) are assigned by analogy with literature assignments,
and in one case (epi-19, Entry 16 of Table 2) by X-ray-structure analysis (see
Table 1)12).
12
)
This is compatible with the assumption that a metal complex of the enoyl-oxazolidinone of s-cis-
configuration around the exocyclic NꢀCO bond [2] is approached by the nucleophile from the face
of the trigonal b-carbonyl C-atom that is remote from the R group at C(4) of the heterocycle, as
shown here for an (S)-oxazolidinone derivative (see i).

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Helvetica Chimica Acta – Vol. 93 (2010)
In view of the fact that the TRIOZ derivatives (Entries 12 – 17 of Table 2) do not
seem to perform better than simpler 3-enoyl-4-phenyl-oxazolidinones (Entries 4 – 7),
the advantage of using TRIOZ as an auxiliary for overall enantioselective conjugate
additions (Scheme 1) remains to be the high crystallization tendency of its derivatives
and the facile removal of this auxiliary group (similar to that of DIOZ [4a,e]).
4. Experiments with the NO2 Derivatives 11, 16, and 26. – In our pursuit of new
routes to b2-amino acids [4h], we have now employed N-(nitropropenyl)- and N-
(nitropropanoyl)-oxazolidinones in two processes, which are related by umpolung [12]
(Scheme 2): with respect to the C¼O group, conjugate addition of a nucleophile to a 3-
nitroacrylate system, where C¼CꢀNO2 is a much stronger Michael acceptor than
C¼CꢀCOR, constitutes an umpolung (nucleophilic attack occurs in the a-carbonyl,
rather than in the b-carbonyl position; see Route a in Scheme 2). On the other hand, a
doubly deprotonated nitropropanoate system is attacked by electrophiles in b-position
to the N-atom (an enolate is more reactive than a nitronate; see Route b in Scheme 2)
[13].
Scheme 2. Two Possible Routes with Chiral Auxiliaries to b2-Amino Acids. a) Michael addition in a-
carbonyl position of a nitroacryloyl derivative. b) Alkylation of a doubly deprotonated 3-nitropropanoyl
derivative. Both processes lead to a-substituted b-nitropropanoic acid derivatives, hydrogenation of
which will produce b2-amino acids.
Removal of the auxiliary from the ꢃcommonꢂ product and hydrogenation of the NO2
group will lead to b2-amino acid derivatives of the same general type, but with the R
group stemming from a nucleophilic reagent (R-metal) in the first case (Route a) and
from an electrophlic reagent (RꢀX) in the second case (Route b). Thus, the two
transformations a and b are an umpolung of each other.
The results of addition of organomagnesium and organozinc reagents (in the
presence of CuI salts) to nitroacryloyl derivatives 11 and 16 are shown in Scheme 3. The
yields are generally modest, and so are the diastereoselectivities. In most cases, pure
samples were prepared by flash chromatography and/or recrystallization. The config-
urations of two adducts, i.e., 24a and 24c, to the nitroacryloyl-oxazolidinone 11 and of
one of the adducts, 25c, to the nitroacrylate ester 16 were determined by X-ray crystal-

Helvetica Chimica Acta – Vol. 93 (2010)
99
Scheme 3. Conjugate Addition of Mg/Cu and Zn/Cu Reagents to N-3-(Nitroacryloyl)-DIOZ 11 and to
the 3-Nitroacrylate Ester 16 of Phenylmenthol. All reactions were carried out in THF at dry-ice
temperature, by adding a soln. of the nitro compound to the organometallic reagent. The yields of 24a –
24c and 25c refer to materials obtained after recrystallization. The yields of 25a and 25b are those
obtained after flash chromatography. The dr values were determined by NMR spectroscopy of the crude
products. For X-ray-crystal structures of 24c and 25c, see Table 1.
structure analysis (Table 1); the configurations of the three major products 24b, and 25a
)
and 25b are assigned by analogy13 14).
13
)
As in the case of ꢃnormalꢂ conjugate additions to 3-enoyl-oxazolidinones (Table 2 and Footnote 12),
the stereochemical course of reaction is compatible with the assumption that the R group of the
organometallic reagent is preferentially transferred from the face opposite to the iPr group at C(4)
of a metal complex with s-cis-configuration around the exocyclic NꢀCO bond (see ii). The reversal
observed with the Zn reagent (!mainly epi-24b) may be taken as an indication that there is no
metal chelation in this case, i.e., the acylated oxazolidinone reacts in its preferred ꢃdipol-minimizedꢂ
s-trans configuration [2] with an anti-arrangement of the 2 C¼O groups (cf. the crystal structures in
Table 1 and the discussion in Sect. 2, above).
14
)
The stereochemical course of reactions of phenylmenthol derivatives is commonly explained by
assuming steric hindrance of a p-face by the neighboring Ph group (ꢃp-stackingꢂ; see textbooks of
stereochemistry, e.g., [14]). This is in agreement with the assigned configuration of our major
diastereoisomers 25a – c (see iii).

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Helvetica Chimica Acta – Vol. 93 (2010)
Scheme 4. Methylation of the Li2-Enolate/Nitronate of N-(3-Nitropropanoyl)-DIOZ 26 with MeI
Finally, we have prepared the N-(nitropropanoyl)-DIOZ 26, which was methylated
through a dilithio derivative to give product 24a (Scheme 4), identical with the sample
obtained by methylcuprate addition to the nitroacryloyl-DIOZ 11 (cf. Scheme 3)15).
Other, less reactive alkylating reagents, such as BnBr, gave only traces of desired
product. This may not be surprising, in view of the previously observed [3b][4a] rather
poor yields of Li-enolate alkylations using 5,5-diphenyl-substituted oxazolidinone
derivatives16). Further experiments with other auxiliaries are in progress, in the hope
that this attractive general approach to b2-amino acid17) precursors may eventually
become general and practical.
5. Conclusions. – The triphenyl-oxazolidinone auxiliary TRIOZ has turned out to
give higher diastereoselectivities in conjugate additions, and the nitroacryloyl-DIOZ
may be used for diastereoselective preparations of b2-amino acid precursors. The yields
and selectivities observed with the DIOZ and TRIOZ derivatives are not better than
those reported for analogous auxiliaries, including phenylmenthol, so that the main
15
)
)
As indicated by the drawing of the intermediate dilithio-derivative in Scheme 4, the configuration of
the product 24a (safely assigned by X-ray analysis; see Table 1) is, again (cf. Footnotes 12 – 14),
compatible with a metal-chelated structure; the stereochemical course of the reaction follows the
general rules for reactions of Evans Li-enolates with electrophiles [2].
This is caused by the instability of the Li-enolates of this type with respect to Li-oxazolidinone
elimination iv ! v (recovery and N-alkylation of DIOZ!), a process, which does not occur with the
corresponding Ti-enolates [4] (and which is less pronounced, with the analogous 5,5-dimethyl-
substituted oxazolidinone derivatives [3b]).
16
17
)
In a preliminary experiment, reduction of 24a with Raney-Ni in the presence of Boc2O gave the
DIOZ-derivative vi of b2hAla in 75% yield. The analytical data were in agreement with those
reported in [4a].

Helvetica Chimica Acta – Vol. 93 (2010)
101
advantage is the high crystallinity of all products, combined with the milder removal of
the auxiliary groups, which has previously been demonstrated in other DIOZ
applications [4]. In the preliminary experiment with a DIOZ Li2-enolate-nitronate,
another new route to b2-amino acid precursors has been outlined, for which, however, a
better auxiliary will have to be identified. With a single exception (Zn/Cu reagent !
epi-24b), the stereochemical courses of all reactions are compatible with metal-
chelated oxazolidinone derivatives as reactive intermediates.
The contribution to this work by P. Kꢀlin and M. Schneider (Elementary Analyses unit of
Laboratorium fꢀr Organische Chemie), R. Hꢀfliger, L. Bertschi, and O. Greter (MS Service), and Dr.
W. B. Schweizer and M. Solar (X-Ray Service unit of Laboratorium fꢀr Organische Chemie) are
gratefully acknowledged.
Experimental Part
1. General. All reactions were performed under Ar in dried glassware using anh. solvents except
when using aq. reagents. All chemicals were of reagent grade and used as supplied, unless stated
otherwise. Solvents for extractions and chromatography were of technical grade and were distilled prior
to use. Sat. hydrocarbon solvents were kept over Na wire. Extracts were dried over MgSO4. Anal. TLC:
pre-coated Merck silica gel 60 F 254 plates (0.25 mm). Flash column chromatography (FC): Fluka silica
gel 60 (230 – 400 mesh). Melting points (M.p.): Bꢁchi 510 melting point apparatus; uncorrected. Optical
rotations ([a]2D0 ): Jasco P-2000 Polarimeter. IR Spectra: neat solid/oil on a Perkin-Elmer precisely
1
Universal ATR Sampling Accessory; in cmꢀ1. H-, 13C-, and 19F-NMR spectra: Bruker AVANCE (1H:
300 MHz, 13C: 75 MHz), DRX (1H: 400 MHz, 13C: 101 MHz), and AV (1H: 400 MHz, 13C: 101 MHz)
spectrometer, or Varian Gemini-300 XL (1H: 300 MHz, 19F: 282 MHz, 13C: 75 MHz) spectrometer;
chemical shifts (d) in ppm relative to Me4Si (0.00 ppm). MS: VG Tribrid (EI), IonSpecUltima 4.7-T-FT
Ion Cyclotron Resonance (ICR; HR-MALDI; in 2,5-dihydroxybenzoic acid matrix) mass spectrometer.
Elemental analyses were performed by the Microanalytical Laboratorium at the Laboratory for Organic
Chemistry, ETH Zꢀrich.
2. Preparation of the Starting Materials. (S)-3-[(E)-3-Nitroprop-2-enoyl]-4-(phenylmethyl)oxazoli-
din-2-one ((S)-6). Compound (S)-5 [2b] (1.15 g, 5.0 mmol) was suspended in Et2O (25 ml) and cooled to
08. In a separate flask, to ice-cooled 100% HNO3 (1.26 ml, 30 mmol) was added during 10 min ClSO3H
(1.0 ml, 15 mmol, 3 equiv.), immediately NO2Cl was formed, which was transferred by a slow stream of
N2 into the reaction mixture. After 1 h, additional ClSO3H (1.0 ml, 15 mmol, 3 equiv.) was added to the
HNO3, and the NO2Cl was transferred into the reaction mixture. The resulting yellow soln. was stirred for
an additional 1 h at r.t., and then the reaction was quenched by the addition of H2O (20 ml). The mixture
was extracted with Et2O. The org. layer was washed with H2O and brine, dried (MgSO4), and
concentrated under reduced pressure. The crude product (1.54 g) was dissolved in Et2O (35 ml) and
treated with AcONa (410 mg, 5 mmol) and a trace hydrochinone. The mixture was heated for 5 h under
reflux. After cooling to r.t., the mixture was filtered and then concentrated under reduced pressure. The
residual oil was dissolved in AcOEt (5 ml) and treated with hexane (13 ml), and the precipitated (S)-6
was filtered off (130 mg). The mother liquid was concentrated under reduced pressure, and by FC
(toluene) additional product was isolated to give overall (S)-6 (260 mg, 20%). Yellow crystals. M.p. 144 –
1508. [a]2D0 ¼ þ77.2 (c ¼ 0.88, CHCl3). IR (CHCl3): 3008w, 3011w, 1788s, 1692s, 1542s, 1385s, 1351s, 1113m,
1
1050m, 1001m, 950m. H-NMR (400 MHz, CDCl3): 2.85 (dd, J ¼ 13.5, 9.5, 1 H, PhCH2); 3.35 (dd, J ¼
13.5, 3.4, 1 H, PhCH2); 4.26 – 4.35 (m, CH2O); 4.74 – 4.80 (m, CHN); 7.2 – 7.38 (m, 10 arom. H); 7.77
(d, J ¼ 13.3, ¼CH); 8.47 (d, J ¼ 13.2, ¼CH). 13C-NMR (100 MHz, CDCl3): 37.5 (CH2); 55.4 (CH); 66.8
(CH2); 126.9, 127.7, 129.2, 129.4 (CH); 134.4 (C); 149.1 (CH); 152.8, 161.2 (C). MS (EI): 276 (1, Mþ), 230
(13), 158 (5), 100 (9), 91 (100). Anal. calc. for C13H12N2O5 (276.25): C 56.52, H 4.38, N 10.14; found: C
56.43, H 4.53, N 9.97.
(S)-4-(1-Methylethyl)-5,5-diphenyl-3-[(E)-prop-2-enoyl]oxazolidin-2-one ((S)-7). To an ice-cold
suspension of (S)-3 (2.81 g; 10.0 mmol) in THF (40 ml) was added a soln. of MeMgBr (3.5 ml, 10.5 mmol,

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Helvetica Chimica Acta – Vol. 93 (2010)
3m in Et2O) during 10 min. At the end of the addition, the deprotonated DIOZ precipitated. The
resulting white suspension was stirred for an additional 30 min at 08 and then cooled to ꢀ 708. Within
5 min, acroyl chloride (1 ml, 10.5 mmol) was added, and the mixture was allowed to warm to r.t.
overnight. The reaction was quenched with sat. aq. NH4Cl soln. (10 ml), and the mixture was extracted
with Et2O. The org. layer was washed with sat. aq. NH4Cl soln., dried (MgSO4), and concentrated under
reduced pressure. The residue was triturated with hexane (30 ml) to yield (S)-7 (3.24 g, 90%). Colorless
solid. Rf (hexane/AcOEt 2 :1) 0.7. M.p. 1468. [a]2D0 ¼ ꢀ232 (c ¼ 1.00, CH2Cl2). IR (CHCl3): 3011w, 2969w,
1779s, 1689m, 1619w, 1494w, 1450w, 1408m, 1364m, 1322m, 1151w, 1120w, 1050w, 1002m, 984w, 958w.
1H-NMR (400 MHz, CDCl3): 0.78 (d, J ¼ 6.8, Me); 0.90 (d, J ¼ 7.0, Me); 1.96 – 2.04 (m, MeCH); 5.46 (d,
J ¼ 3.4, CHN); 5.85 (dd, J ¼ 10.5, 1.8, 1 H, CH2); 6.50 (dd, J ¼ 17.0, 1.8, 1 H, CH2); 7.25 – 7.49 (m, 10 arom.
H). 13C-NMR (100 MHz, CDCl3): 16.4, 21.8 (Me); 30.1, 65.5 (CH); 89.5 (C); 125.7, 126.0, 127.1, 128.0,
128.4, 128.6, 128.9 (CH); 131.9 (CH2); 138.2, 142.2, 152.9, 164.8 (C). MS (EI): 335 (2, Mþ), 292 (13), 291
(9), 237 (11), 220 (10), 195 (36), 194 (26), 184 (12), 183 (8), 167 (19), 166 (12), 165 (26), 109 (19), 105
(22), 77 (13), 55 (100), 41 (9). Anal. calc. for C21H21NO3 (335.40): C 75.20, H 6.31, N 4.18; found: C 75.28,
H 6.41, N 4.20.
(S)-4-(1-Methylethyl)-3-[(E)-1-oxobut-2-enyl]-5,5-diphenyloxazolidin-2-one ((S)-8a). Starting
from (S)-3, (S)-8a was prepared as described in [4a]. Yield and anal. data were in agreement with
those reported in [4a].
(S)-4-(1-Methylethyl)-3-(2-methylprop-2-enoyl)-5,5-diphenyloxazolidin-2-one ((S)-8b). To an ice-
cold suspension of (S)-3 (0.4 g, 1.42 mmol) in THF (5 ml) was added a soln. of MeMgBr (0.5 ml,
1.5 mmol, 3m in Et2O) during 10 min. At the end of the addition, the deprotonated DIOZ precipitated.
The resulting white suspension was stirred for an additional 30 min at 08 and then cooled to ꢀ 708. Within
5 min, methacroyl chloride (0.34 ml, 3.55 mmol) was added, and the reaction mixture was allowed to
warm to r.t. overnight. The reaction was quenched with sat. aq. NH4Cl soln. (10 ml), and the mixture was
extracted with Et2O. The org. layer was washed with sat. aq. NH4Cl soln., dried (MgSO4), and
concentrated under reduced pressure. FC (pentane/Et2O 9 :1) yielded (S)-8b (0.42 g, 85%). Colorless
solid. Rf (pentane/Et2O 2 :1) 0.8. M.p. 111 – 1138. [a]2D0 ¼ ꢀ181.1 (c ¼ 0.5, CHCl3). IR (CHCl3): 2968w,
1789s, 1686m, 1494w, 1450m, 1365w, 1324m, 1176m, 1001w, 918w. 1H-NMR (300 MHz, CDCl3): 0.80 (d,
J ¼ 6.5, Me); 0.92 (d, J ¼ 6.85, Me); 1.92 (s, Me); 2.00 – 2.04 (m, Me2CH); 5.07 (s, 1 H, CH2); 5.28 (d, J ¼
1.2, 1 H, CH2); 5.38 (d, J ¼ 3.4, CHN); 7.24 – 7.37 (m, 6 arom. H); 7.40 – 7.44 (m, 2 arom. H); 7.50 – 7.53 (m,
2 arom. H). 13C-NMR (75 MHz, CDCl3): 16.4; 19.4; 21.8; 30.1; 64.9; 89.5; 119.7; 125.6; 125.8; 127.9; 128.3;
128.5; 128.8; 138.0; 139.3; 142.3; 152.1; 170.6. MS (EI): 721 ([2 M þ Na]þ), 388 ([M þ K]þ), 372 ([M þ
Na]þ), 350 ([M þ 1]þ). Anal. calc. for C22H23NO3 (349.43): C 75.62, H 6.63, N 4.01; found: C 75.66, H
6.75, N 4.02.
(S)-4-(1-Methylethyl)-3-[(E)-3-phenylprop-2-enoyl]-5,5-diphenyloxazolidin-2-one ((S)-9). Starting
from (S)-3, (S)-9 was prepared as described in [4a]. Yield and anal. data were in agreement with those
reported in [4a].
(S)-3-[(E)-3-(3-Methoxyphenyl)prop-2-enoyl]-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one
((S)-10). To an ice-cold suspension of (S)-3 (602 mg, 2.14 mmol) in THF (10 ml) was added a soln. of
BuLi (1.45 ml, 2.35 mmol, 1.6m in hexane) during 5 min. After stirring for 5 min, (E)-3-(4-methoxy-
phenyl)prop-2-enoyl chloride (505 mg, 2.57 mmol) in THF (2 ml) was added, and the mixture was
allowed to warm to r.t. overnight. The reaction was quenched with sat. aq. NH4Cl soln. (10 ml), and the
mixture was extracted with Et2O. The org. layer was washed with 1m HCl, 1m NaOH, and brine, dried
(MgSO4), and concentrated under reduced pressure. FC (pentane/AcOEt 15 :1) yielded (S)-10 (674 mg,
71%). Colorless solid. M.p. 159 – 1618. [a]D20 ¼ ꢀ89.2 (c ¼ 1, CHCl3). IR (CHCl3): 3008w, 2968w, 1775s,
1676m, 1599s, 1574w, 1512s, 1450w, 1348m, 1257m, 1172s, 1030m, 987w, 829m. 1H-NMR (300 MHz,
CDCl3): 0.81 (d, J ¼ 6.9, Me); 0.93 (d, J ¼ 6.9, Me); 1.97 – 2.09 (m, Me2CH); 3.82 (s, MeO); 5.54 (d, J ¼
3.4, CHN); 6.86 – 6.92 (m, 2 arom. H); 7.23 – 7.45 (m, 8 arom. H); 7.50 – 7.56 (m, 4 arom. H); 7.72 (d, J ¼
15.7, ArylCH¼CH); 7.80 (d, J ¼ 15.7, ArylCH¼CH). 13C-NMR (75 MHz, CDCl3): 17.0, 21.0 (Me); 28.8
(CH); 55.4 (Me); 64.4 (CH); 89.3 (C); 114.2, 114.3, 125.7, 126.0, 127.4, 127.9, 128.4, 128.9, 130.4 (CH);
138.4, 142.4 (C); 146.4 (CH); 153.1, 161.7, 165.3 (C). MS (MALDI): 480 (10, [M þ K]þ), 464 (100, [M þ
Na]þ), 442 (6, [M þ H]þ). Anal. calc. for C28H27NO4 (441.53): C 76.17, H 6.16, N 3.17; found: C 76.14, H
6.23, N 3.14.

Helvetica Chimica Acta – Vol. 93 (2010)
103
(S)-4-(1-Methylethyl)-3-[(E)-3-nitroprop-2-enoyl]-5,5-diphenyloxazolidin-2-one ((S)-11) and (S)-3-
(2,3-Dichloropropanoyl)-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (17). Compound (S)-7 (5.03 g,
13.95 mmol) was suspended in Et2O (110 ml) and cooled to 08. In a separate flask, to ice-cooled 100%
HNO3 (3.47 ml, 83.7 mmol) was added during 10 min ClSO3H (2.8 ml, 41.9 mmol), immediately NO2Cl
was formed, which was transferred by a slow stream of N2 into the reaction mixture. After 1 h, additional
ClSO3H (2.8 ml, 41.9 mmol) was added to the HNO3, and the NO2Cl was transferred into the reaction
mixture. The resulting yellow soln. was stirred for an additional 1 h at r.t., and then the reaction was
quenched by the addition of H2O (90 ml). The mixture was extracted with Et2O. The org. layer was
washed with H2O and brine, dried (MgSO4), and concentrated under reduced pressure. FC (pentane/
AcOEt 9 :1) yielded (S)-11 (1.42 g, 22%) as yellow solid and 17 (1.31 g, 23%) as colorless solid.
1
Data of (S)-11. Rf (hexane/AcOEt 4 :1) 0.53. M.p. 1128. [a]2D0 ¼ ꢀ185 (c ¼ 1.05, CH2Cl2). H-NMR
(400 MHz, CDCl3): 0.80 (d, J ¼ 6.8, Me); 0.92 (d, J ¼ 7, Me); 2.02 – 2.09 (m, Me2CH); 5.46 (d, J ¼ 3.4,
CHN); 7.26 – 7.49 (m, 10 arom. H); 7.68 (d, J ¼ 13.2, ¼CH); 8.38 (d, J ¼ 13.2, ¼CH). 13C-NMR (100 MHz,
CDCl3): 16.3; 21.8; 30.1; 65.2; 90.4; 125.4; 125.8; 126.8; 128.3; 128.6; 129.0; 129.2; 137.5; 141.6; 149.2;
152.3; 161.1. Anal. calc. for C21H20N2O5 (380.39): C 66.31, H 5.30, N 7.36; found: C 66.23, H 5.46, N 7.02.
Data of 17. Rf (hexane/AcOEt 4 :1) 0.63. 1H-NMR (400 MHz, CDCl3): 0.80 (d, J ¼ 6.7, Me); 0.93 (d,
J ¼ 7, Me); 1.97 – 2.05 (m, Me2CH); 3.80 (dd, J ¼ 10.7, 4.5, 1 H, CH2); 4.12 (dd, J ¼ 10.7, 9.7, 1 H, CH2);
5.41 (d, J ¼ 3.3, CHN); 5.78 (dd, J ¼ 9.7, 4.5, CH); 7.26 – 7.45 (m, 10 arom. H). 13C-NMR (100 MHz,
CDCl3): 16.2; 21.7; 29.8; 42.8; 51.3; 90.2; 125.6; 125.9; 128.2; 128.5; 128.8; 128.9; 137.6; 152.3; 166.3. Anal.
calc. for C21H21N1O3Cl2 (406.30): C 62.07, H 5.21, N 3.45, Cl 17.45; found: C 62.44, H 5.29, N 3.50, Cl 16.89.
(S)-4,5,5-Triphenyl-3-[(E)-prop-2-enoyl]oxazolidin-2-one ((S)-12). To an ice-cold suspension of
(S)-4 (3.15 g, 10.0 mmol) in THF (40 ml) was added a soln. of MeMgBr (3.5 ml, 10.5 mmol, 3m in Et2O)
during 10 min. At the end of the addition, the deprotonated TRIOZ precipitated. The resulting white
suspension was stirred for an additional 30 min at 08 and then cooled to ꢀ 708. Within 5 min, acryloyl
chloride (1.0 ml, 10.5 mmol) was added, and the mixture was allowed to warm to r.t. overnight. The
reaction was quenched with sat. aq. NH4Cl soln. (10 ml), and the mixture was extracted with Et2O. The
org. layer was washed with sat. aq. NH4Cl soln., dried (MgSO4), and concentrated under reduced
pressure. FC (hexane/AcOEt 8 :1) yielded (S)-12 (1.58 g, 40%). Colorless solid. Rf (hexane/AcOEt 1:1)
0.8. M.p. 136 – 1378. [a]2D0 ¼ ꢀ236 (c ¼ 1.00, CH2Cl2). 1H-NMR (400 MHz, CDCl3): 5.81 (dd, J ¼ 10.3, 1.6,
1 H, ¼CH2); 6.20 (s, CHN); 6.42 (dd, J ¼ 17.1, 1.6, 1 H, ¼CH2); 6.92 – 7.61 (m, 16 arom. H, CH¼CH2).
13C-NMR (100 MHz, CDCl3): 66.1; 89.2; 126.0; 126.2; 127.2; 127.5; 127.6; 127.7; 128.2; 128.3; 128.9; 129.0;
132.3; 137.9; 141.7; 152.6; 164.0. Anal. calc. for C24H19NO3 (369.41): C 78.03, H 5.18, N 3.79; found: C
77.85, H 5.37, N 3.77.
(S)- or (R)-3-[(E)-But-2-enoyl]-4,5,5-triphenyloxazolidin-2-one ((S)- or (R)-13). To an ice-cold
suspension of (S)- or (R)-4 (3.70 g, 11.7 mmol) in THF (50 ml) was added BuLi (8.6 ml, 13.8 mmol, 1.6m
in hexane) over a period of 25 min. During addition, the TRIOZ dissolved, and, after an additional
35 min at 08, a clear yellow soln. was obtained. Within 15 min, crotonoyl chloride (1.73 ml, 16.2 mmol)
was added, and the mixture was allowed to warm to r.t. overnight. The reaction was quenched with sat.
aq. NH4Cl soln. (25 ml), and the mixture was extracted with Et2O. The org. layer was washed with 1m
HCl, 1m NaOH, and brine, dried (MgSO4), and concentrated under reduced pressure. FC (hexane/
AcOEt 8 :1) yielded (S)- or (R)-13 (ca. 3.6 g, ca. 80%). M.p. 150 – 1528. (S)-13: [a]2D0 ¼ ꢀ232.3 (c ¼ 1,
CHCl3). (R)-13: [a]2D0 ¼ þ240.8 (c ¼ 1, CHCl3). IR (CHCl3): 3007w, 1778s, 1687m, 1638m, 1495w, 1449m,
1341s, 1179m, 1059m. 1H-NMR (400 MHz, CDCl3): 1.91 (d, J ¼ 8.5, Me); 6.27 (s, CHN); 7.02 – 7.44 (m, 13
arom. H, CH¼CH); 7.63 – 7.65 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 18.5 (Me); 66.1 (CH); 89.0
(C); 121.7, 126.3, 128.9 (CH); 135.9, 138.1, 141.8 (C); 147.5 (CH); 152.8, 164.1 (C). Anal. calc. for
C25H21NO3 (383.44): C 78.31, H 5.52, N 3.65; found: C 78.23, H 5.48, N 3.68.
(S)-3-[(E)-4,4,4-Trifluorobut-2-enoyl]-4,5,5-triphenyloxazolidin-2-one ((S)-14). To an ice-cold
suspension of (S)-4 (2.31 g, 7.3 mmol) in THF (50 ml) was added BuLi (4.85 ml, 7.8 mmol, 1.6m in
hexane) over a period of 10 min. During addition, the TRIOZ dissolved, and, after an additional 35 min
at 08, a clear yellow soln. was obtained. Within 15 min, a soln. of 4,4,4-trifluorocrotonoyl chloride18
)
(1.28 g, 8.1 mmol) in THF (10 ml) was added, and the mixture was allowed to warm to r.t. overnight. The
18
)
Prepared according to a literature procedure [15].

104
Helvetica Chimica Acta – Vol. 93 (2010)
reaction was quenched with sat. aq. NH4Cl soln. (10 ml), and the mixture was extracted with AcOEt. The
org. layer was washed with 1m HCl, 1m NaOH, and brine, dried (MgSO4), and concentrated under
reduced pressure to yield (S)-14 (2.77 g, 63%). M.p. 153 – 1548. [a]2D0 ¼ ꢀ188.1 (c ¼ 1, CHCl3). IR
(CHCl3): 3032w, 1774s, 1698m, 1496w, 1450w, 1349s, 1305s, 1276m, 1150s, 1033w, 1016w, 1000w, 973w,
639w. 1H-NMR (300 MHz, CDCl3): 6.27 (s, CH); 7.78 (dq, J ¼ 15.3, 6.3, CH¼CHCF3); 7.02 – 7.14 (m, 10
arom. H); 7.39 – 7.48 (m, 3 arom. H); 7.62 – 7.66 (m, 2 arom. H); 7.91 (dq, J ¼ 15.3, 1.8, CH¼CHCF3).
13C-NMR (75 MHz, CDCl3): 66.2 (CH); 89.7 (C); 122.0 (q, J ¼ 269.0, CF3); 125.8, 126.1, 127.3, 127.4,
127.6, 127.8, 128.4, 128.5, 129.1 (CH); 132.2 (q, J ¼ 35.8, CH); 134.9, 137.5, 141.3 (C); 152.3, 161.6 (C). 19F-
NMR (282 MHz, CDCl3): ꢀ 65.20 (dd, J ¼ 6.5, 1.7, CF3). Anal. calc. for C25H18F3NO3 (437.42): C 68.65, H
4.15, N 3.20; found: C 68.42, H 4.41, N 3.15.
(S)- or (R)-4,5,5-Triphenyl-3-[(E)-3-phenylprop-2-enoyl]oxazolidin-2-one ((S)- or (R)-15). To an
ice-cold suspension of (S)- or (R)-4 (3.60 g, 11.4 mmol) in THF (50 ml) was added BuLi (8.55 ml,
13.6 mmol, 1.6m in hexane) over a period of 10 min. During addition, the TRIOZ dissolved, and, after an
additional 35 min at 08, a clear yellow soln. was obtained. Within 15 min, a soln. of cinnamoyl chloride
(2.47 g, 14.8 mmol) in THF (8 ml) was added, and the reaction mixture was allowed to warm to r.t.
overnight. The reaction was quenched with sat. aq. NH4Cl soln. (25 ml), and the mixture was extracted
with AcOEt. The org. layer was washed with 1m HCl, 1m NaOH, and brine, dried (MgSO4), and
concentrated under reduced pressure. The residue was triturated twice with hot hexane (30 ml) to yield
(S)- or (R)-15 (ca. 5.0 g, ca. 90%). Colorless solid. M.p. > 2408. (S)-15: [a]2D0 ¼ ꢀ234.6 (c ¼ 1, CHCl3).
(R)-15: [a]2D0 ¼ þ242.8 (c ¼ 1, CHCl3). IR (CDCl3): 3008w, 1777s, 1681m, 1617m, 1496w, 1450m, 1344s,
1170m. 1H-NMR (400 MHz, CDCl3): 6.34 (s, CHN); 7.06 – 7.25 (m, 10 arom. H); 7.37 – 7.39 (m, 4 arom.
H); 7.41 – 7.46 (m, 2 arom. H); 7.55 – 7.58 (m, 2 arom. H); 7.66 – 7.68 (m, 2 arom. H); 7.76 (d, J ¼ 15.7,
PhCH¼CH); 7.92 (d, J ¼ 15.7, PhCH¼CH). 13C-NMR (100 MHz, CDCl3): 66.2 (CH); 89.1 (C); 116.8,
126.9, 128.9 (CH); 134.4, 138.0, 141.8 (C); 146.9 (CH); 152.8, 164.4 (C). Anal. calc. for C30H28NO3
(445.51): C 80.88, H 5.20, N 3.14; found: C 80.72, H 5.50, N 3.16.
3. Conjugate Additions to the Cinnamoyl- and Crotonoyl-oxazolidinones. General Procedure 1 (GP
1). To a CuIBr-DMS (1.5 equiv.) suspension in THF (2.5 ml/mmol) was added at ꢀ 408 the appropriate
Grignard reagent (3 equiv., as 1m soln. in THF). After 10 min, the temp. was adjusted to ꢀ 40 or ꢀ 708,
and the acyl-TRIOZ derivative (1 equiv.) as a soln. in THF (5 ml/mmol) was added dropwise. After
stirring for 30 min at ꢀ 35 or ꢀ 708, the mixture was allowed to warm to r.t. (1 – 2 h), and the reaction was
quenched with sat. aq. NH4Cl soln., and the mixture was extracted with AcOEt. The org. layer was
washed with 1m HCl, 1m NaOH, and brine, dried (MgSO4), and concentrated under reduced pressure to
yield the crude products which were analyzed by NMR for determination of the dr. FC and crystallization
yielded the 1,4-addition products.
(S)-3-[(S)- or (R)-3-(4-Methoxyphenyl)-3-phenylpropanoyl]-4-(1-methylethyl)-5,5-diphenyloxazo-
lidin-2-one (18 or epi-18). Compound (S)-9 (113 mg, 0.275 mmol) was treated with a soln. of (4-
MeOPh)MgBr (0.825 ml, 0.825 mmol, 1m in THF), or (S)-10 (121 mg, 0.275 mmol) with a soln. of
PhMgBr (0.825 ml, 0.825 mmol, 1m in THF) at ꢀ 308, according to GP 1. Purification of the crude
product by FC (pentane/AcOEt 15 :1) yielded 18 (110 mg, 88%, dr 85 :15) or epi-18 (78%, dr 82 :18).
Colorless solid. For anal. purposes, a sample was re-crystallized from hexane to afford diastereomerically
pure 18 (drꢁ 99 :1). M.p. 138 – 1408. [a]2D0 ¼ þ156.9 (c ¼ 1, CHCl3). IR (CHCl3): 3008w, 2966w, 2837w,
1779s, 1703m, 1610w, 1511s, 1450m, 1372m, 1319w, 1176s, 1034w, 831w. 1H-NMR (400 MHz, CDCl3): 0.61
(d, J ¼ 6.7, Me); 0.65 (d, J ¼ 7.0, Me); 1.82 – 1.92 (m, Me2CH); 3.44 (dd, J ¼ 16.5, 7.9, 1 H, CH2); 3.74 (s,
MeO); 3.74 (dd, J ¼ 16.5, 7.9, 1 H, CH2); 4.56 (dd, J ¼ 7.9, 7.9, PhCH); 5.28 (d, J ¼ 3.2, CHN); 6.75 – 6.79
(m, 2 arom. H); 7.08 – 7.20 (m, 7 arom. H); 7.24 – 7.41 (m, 10 arom. H). 13C-NMR (100 MHz, CDCl3): 16.1,
21.4 (Me); 29.8 (CH); 40.8 (CH2); 45.8 (CH); 55.2 (Me); 64.4 (CH); 89.4 (C); 113.9, 125.6, 125.9, 126.3,
127.5, 127.9, 128.3, 128.5, 128.5, 128.9, 128.9 (CH); 135.6, 138.1, 142.2, 143.5, 153.1, 158.1, 171.1 (C). MS
(MALDI): 558 (11, [M þ K]þ), 542 (100, [M þ Na]þ), 498 (32). Anal. calc. for C34H33NO4 (519.64): C
78.59, H 6.40, N 2.70; found: C 78.52, H 6.46, N 2.64.
(R)-4,5,5-Triphenyl-[(S)-3-phenylbutyanoyl]oxazolidion-2-one (19). Compound (R)-13 (667 mg,
1.74 mmol) was treated at ꢀ 408 with a soln. of PhMgBr (5.22 ml, 5.22 mmol, 1m in THF) according to
GP 1 to yield the crude product (dr 96 :4). FC (pentane/AcOEt 9 :1) and crystallization from hexane/
AcOEt yielded 19 (568 mg, 71%; pure diastereoisomer). Colorless solid. Rf (hexane/AcOEt 4 :1) 0.48.

Helvetica Chimica Acta – Vol. 93 (2010)
105
M.p. 112 – 1148. [a]2D0 ¼ þ232.7 (c ¼ 1, CHCl3). IR (CHCl3): 3032w, 1781s, 1705m, 1495w, 1450m, 1365m,
1
1333m, 1172m, 1081w, 1033w, 998w. H-NMR (300 MHz, CDCl3): 1.18 (d, J ¼ 6.6, Me); 3.08 – 3.33 (m,
CH2, CH); 6.16 (s, CH); 6.91 – 7.22 (m, 15 arom. H); 7.43 – 7.46 (m, 3 arom. H); 7.63 – 7.67 (m, 2 arom. H).
13C-NMR (75 MHz, CDCl3): 21.5 (Me); 36.1 (CH2); 43.3 (CH); 65.9 (CH); 88.9 (C); 125.9, 126.1, 126.2,
126.8, 127.2, 127.4, 127.6, 127.9, 128.1, 128.3, 128.8, 128.9 (CH); 135.4, 137.8, 141.7, 145.2, 171.0 (C). Anal.
calc. for C31H27NO3 (461.55): C 80.67, H 5.90, N 3.03; found: C 80.51, H 5.98, N 3.01.
(R)-4,5,5-Triphenyl-[(R)-3-phenylbutanoyl]oxazolidion-2-one (epi-19). Compound (R)-15
(537 mg, 2.61 mmol) was treated at ꢀ 408 with a soln. of MeMgBr (3.75 ml, 5.25 mmol, 1.4m in THF/
toluene) according to GP 1 to yield the crude product (dr 96 :4). FC (hexane/AcOEt 4 :1) and
crystallization from hexane/AcOEt yielded epi-19 (547 mg, 68%; pure diastereoisomer). Colorless solid.
M.p. 153 – 1558. [a]2D0 ¼ þ156.3 (c ¼ 1, CHCl3). IR (CHCl3): 3008w, 2990w, 1780s, 1706m, 1464w, 1450m,
1
1367m, 1332m, 1170m, 1064w, 1034w, 999w, 629w. H-NMR (300 MHz, CDCl3): 1.20 (d, J ¼ 6.9, Me);
3.11 – 3.371 (m, CH2, CH); 6.12 (s, CH); 7.01 – 7.19 (m, 15 arom. H); 7.35 – 7.38 (m, 3 arom. H); 7.50 – 7.53
(m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 22.2 (Me); 35.9 (CH2); 43.2 (CH); 66.0 (CH); 125.9, 126.2,
126.7, 127.4, 127.6, 128.1, 128.2, 128.3, 128.8, 128.9 (CH); 135.7, 137.9, 141.5, 145.6, 170.9 (C). Anal. calc. for
C31H27NO3 (461.55): C 80.67, H 5.90, N 3.03; found: C 80.52, H 6.08, N 2.99.
(R)-3-[(S)-3-(4-Methoxyphenyl)butanoyl]-4,5,5-triphenyloxazolidin-2-one (20). Compound (R)-13
(667 mg, 1.74 mmol) was treated at ꢀ 408 with a soln. of 4-MeOPhMgBr (5.22 ml, 5.22 mmol, 1.4m in
THF) according to GP 1 to yield the crude product (dr 91:9). FC (pentane/AcOEt 15 :1) yielded 20
(631 mg, 74%; mixture of diastereoisomers). Colorless solid. M.p. 120.5 – 1228. [a]2D0 ¼ þ206.8 (c ¼ 1,
CHCl3). IR (CHCl3): 3032w, 2663w, 1780s, 1705m, 1611w, 1514m, 1450w, 1365m, 1332m, 1248m (br.),
1035w, 999w, 831w. 1H-NMR (300 MHz, CDCl3): 1.18 (d, J ¼ 6.3, Me); 3.06 – 3.35 (m, CH, CH2); 3.78 (s,
MeO); 6.17 (s, CH); 6.75 – 6.79 (m, 2 arom. H); 6.90 – 7.10 (m, 12 arom. H); 7.41 – 7.50 (m, 3 arom. H);
7.65 – 7.68 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 22.0 (Me); 35.7 (CH2); 43.7 (CH); 55.3 (Me);
66.1 (CH); 88.9 (C); 113.7, 126.0, 127.2, 127.4, 127.6, 127.7, 128.0, 128.1, 128.8, 128.9 (CH); 135.5, 137.3,
137.8, 141.7, 152.6, 157.9, 171.0 (C). Anal. calc. for C32H29NO4 (491.57): C 78.19, H 5.95, N 2.85; found: C
78.24, H 6.08, N 2.83.
(S)-4,5,5-Triphenyl-3-[(S)-4,4,4-trifluoro-3-methylbutanoyl]oxazolidin-2-one (21). Compound (S)-
14 (437 mg, 1.0 mmol) was treated at ꢀ 408 with a soln. of MeMgBr (2.2 ml, 3.0 mmol, 1.4m in THF/
toluene) according to GP 1 to yield the crude product (dr 61:39). FC (pentane/AcOEt 9 :1) yielded 21
(248 mg, 55%; mixture of diastereoisomers). Colorless solid. M.p. 52 – 538. [a]2D0 ¼ ꢀ184.2 (c ¼ 1, CHCl3).
IR (CHCl3): 3032w, 1783s, 1709m, 1496w, 1450w, 1332m, 1271m, 1174m, 1132m, 1087w, 1034w, 998w,
909w, 636w. 1H-NMR (300 MHz, CDCl3): 1.05 (t, J ¼ 6.6, Me); 2.77 – 2.88 (m, CH); 2.93 – 3.35 (m, CH2);
6.25 (s, CH, minor diastereoisomer); 6.26 (s, CH, major diastereoisomer); 7.02 – 7.15 (m, 10 arom. H);
7.40 – 7.48 (m, 3 arom. H); 7.63 – 7.68 (m, 2 arom. H). 19F-NMR (282 MHz; CDCl3): ꢀ 73.27 (d, J ¼ 8.7,
CF3, major diastereoisomer); ꢀ 73.28 (d, J ¼ 8.7, CF3, minor diastereoisomer). Anal. calc. for
C26H22F3NO3 (453.45): C 68.87, H 4.89, N 3.09; found: C 66.20, H 4.85, N 2.91.
(S)-4,5,5-Triphenyl-3-[(R)-4,4,4-trifluoro-3-phenylbutanoyl]oxazolidin-2-one (22). Compound (S)-
14 (437 mg, 1.00 mmol) was treated at ꢀ 408 with a soln. of PhMgBr (3.0 ml, 3.0 mmol, 1m in THF)
according to GP 1 to yield the crude product (dr 69 :31). FC (pentane/AcOEt 9 :1) yielded 22 (311 mg,
60%; mixture of diastereoisomers). Colorless solid. M.p. 103 – 1068. [a]2D0 ¼ ꢀ157.3 (c ¼ 1, CHCl3). IR
(CHCl3): 3032w, 1782s, 1710m, 1496w, 1450w, 1390w, 1363w, 1332m, 1250m, 1166m, 1034w, 1115m, 1033w,
999w. 1H-NMR (300 MHz, CDCl3): 3.39 – 3.54 (m, CH); 3.75 – 4.03 (m, CH2); 6.04 (s, CH, minor
diastereoisomer); 6.12 (s, CH2, major diastereoisomer); 6.71 – 7.10 (m, 10 arom. H); 7.23 – 7.62 (m, 10
arom. H). 19F-NMR (282 MHz, CDCl3): ꢀ 69.95 (d, J ¼ 8.7, CF3, major diastereoisomer); ꢀ 69.83 (d,
J ¼ 8.7, CF3, minor diastereoisomer). Anal. calc. for C31H24F3NO3 (515.52): C 72.22, H 4.69, N 2.72;
found: C 72.01, H 4.97, N 2.55.
(S)-3-[(S)-3-(4-Methoxyphenyl)-3-phenylpropanoyl]-4,5,5-triphenyloxazolidin-2-one (23). Com-
pound (S)-15 (775 mg, 1.74 mmol) was treated at ꢀ 408 with a soln. of 4-MeOPhMgBr (5.22 ml,
5.22 mmol, 1.4m in THF) according to GP 1 to yield the crude product (dr 97:3). FC (pentane/AcOEt
9 :1) yielded 23 (614 mg, 64%; pure diastereoisomer). Colorless solid. M.p. 165 – 1688. [a]2D0 ¼ ꢀ170.6
(c ¼ 1, CHCl3). IR (CHCl3): 3008w, 1779s, 1707m, 1610w, 1512m, 1496w, 1450w, 1373m, 1332m, 1248m,
1
1034w, 1000w, 831w. H-NMR (300 MHz, CDCl3): 3.68, 3.72 (d, J ¼ 7.8, CH2); 3.75 (s, MeO); 4.50 (d,

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Helvetica Chimica Acta – Vol. 93 (2010)
J ¼ 7.8, CH); 6.09 (s, CH); 6.72 – 6.75 (m, 2 arom. H); 6.87 – 7.19 (m, 17 arom. H); 7.39 – 7.41 (m, 3 arom.
H); 7.52 – 7.55 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 41.0 (CH2); 45.7 (CH); 55.1 (CH3); 65.8
(CH); 89.0 (C); 113.8, 126.0, 126.2, 127.2, 127.4, 127.6, 127.9, 128.1, 128.4, 128.7, 128.8, 128.9 (CH); 135.2,
135.3, 137.7, 141.5, 143.5, 152.7, 158.0, 170.5 (C). Anal. calc. for C37H31NO4 (553.65): C 80.27, H 5.64, N
2.53; found: C 80.29, H 5.68, N 2.51.
(S)-4-(1-Methylethyl)-3-(2-methyl-3-nitropropanoyl)-5,5-diphenyloxazolidin-2-one (24a). a) Com-
pound (S)-11 (380 mg, 0.83 mmol) was treated at ꢀ 708 with a soln. of MeMgBr (1.0 ml, 3.0 mmol, 3m in
Et2O) according to GP 1 to yield the crude product (dr 65 :35). Crystallization from hexane yielded 24a
(150 mg, 40%). The same compound was obtained by methylation of the nitropropanoyl derivative 26 as
described in the following procedure.
b) A soln. of iPr2NH (0.79 ml, 4.54 mmol) in DMPU/THF (1:5; 20 ml) was cooled to ꢀ 358. To this
cold soln., BuLi (2.84 ml, 4.54 mmol, 1.6m in hexane) was added, and the mixture was stirred for 10 min at
ca. ꢀ 358 and then for 20 min at ꢀ 768. A soln. of 26 (0.764 g, 2.0 mmol) in DMPU/THF (1:5, 5 ml) was
then added at once, and stirring was continued for 60 min. To the soln. of this double deprotonated nitro-
DIOZ derivative MeI (0.158 ml, 2.54 mmol) was added at ꢀ 768, and the mixture was allowed to warm to
ꢀ 258 over 4 h. AcOH (0.114 ml, 2.0 mmol) was added, followed after 5 min by H2O (10 ml), and the
hydrolyzed mixture was allowed to warm to r.t., H2O and Et2O were added, the org. layer was separated,
and the aq. layer was extracted twice with Et2O. The combined org. layers were washed successively with
H2O, sat. aq. NaHCO3 soln., and brine, dried (MgSO4), and concentrated under reduced pressure.
Purification by FC (hexane/AcOEt 4 :1) and crystallization from hexane/AcOEt yielded diastereomeri-
cally pure 24a (456 mg, 58%). Colorless powder. Rf (hexane/AcOEt 4 :1) 0.44. M.p. 171 – 1738. [a]D20
¼
ꢀ183.4 (c ¼ 1.0, CHCl3). IR (CHCl3): 2970w, 1781s, 1700m, 1555s, 1495w, 1451m, 1395s, 1378s, 1317w,
1259w, 1212m, 1178m, 1053m, 993w, 761m, 703m, 666w, 638w. 1H-NMR (400 MHz, CDCl3): 0.70 (d, J ¼
6.8, Me); 0.79 (d, J ¼ 6.8, Me); 1.28 (d, J ¼ 7.2, Me); 1.88 – 1.94 (m, Me2CH); 4.18 (dd, J ¼ 14.8, 4.4, 1 H,
CH2); 4.21 – 4.28 (m, MeCH); 4.76 (dd, J ¼ 14.8, 10.0, 1 H, CH2); 5.34 (d, J ¼ 3.2, CHN); 7.21 – 7.35 (m,
10 arom. H). 13C-NMR (100 MHz, CDCl3): 14.9, 16.3, 21.8 (Me); 29.9, 36.2, 64.3 (CH); 75.1 (CH2); 90.1
(C); 125.8, 126.0, 128.1, 128.4, 128.9, 129.0 (CH); 138.0, 141.5, 152.5, 173.2 (C). EI-MS: 396.17 (2, Mþ),
353.11, 238.08, 220.12, 195.08, 183.08, 165.07. Anal. calc. for: C22H24N2O5 (396.44): C 66.65, H 6.10, N 7.07;
found: C 66.67, H 5.93, N 7.03.
(S)-4-(1-Methylethyl)-3-[(S)-2-(1-methylethyl)-3-nitropropanoyl]-5,5-diphenyloxazolidin-2-one
i
(24b). Compound (S)-11 (380 mg, 0.83 mmol) was treated at ꢀ 708 with a soln. of PrMgBr (1.5 ml,
3.0 mmol, 2m in Et2O) according to GP 1 to yield the crude product (dr 80 :20) (24b/epi-24b).
Crystallization from hexane/Et2O yielded 24b (150 mg, 40%; mixture of diastereoisomers). Colorless
solid. 1H-NMR (300 MHz, CDCl3; main diastereoisomer): 0.77 (d, J ¼ 6.9, Me); 0.91 (d, J ¼ 7.6, Me); 0.93
(d, J ¼ 6.9, Me); 1.13 (d, J ¼ 6.9, Me); 1.9 – 2.1 (m, Me2CH); 2.25 – 2.4 (m, Me2CH); 4.15 – 4.23 (m, CH);
4.26 (dd, J ¼ 2.9, 14.5, 1 H, CH2); 4.86 (dd, J ¼ 11.2, 14.7, 1 H, CH2); 5.45 (d, J ¼ 3, CHN); 7.29 – 7.42 (m, 10
arom. H).
(S)-4-(1-Methylethyl)-3-[(R)-2-(1-methylethyl)-3-nitropropanoyl]-5,5-diphenyloxazolidin-2-one
(epi-24b). A soln. of (S)-11 (380 mg (0.83 mmol) in Et2O (10 ml) was treated at r.t. with CuII-triflate
(15 mg, 0.04 mmol). The yellow soln. was cooled to ꢀ 458, and a soln. of (iPr2)Zn (1.1 ml, 1.1 mmol, 1m in
Et2O) was added during 20 min. The resulting red soln. was stirred for an additional 40 min at ꢀ 408 and
then warmed to 08 during 45 min, and then the reaction was quenched with sat. aq. NH4Cl soln., and the
mixture was extracted with Et2O. The org. layer was washed with sat. aq. NH4Cl soln., dried (MgSO4),
and concentrated under reduced pressure to yield the crude product with a dr 75 :25 (epi-24b/24b).
Crystallization from hexane yielded epi-24b (150 mg, 40%; mixture of diastereoisomers). Colorless solid.
1H-NMR (400 MHz, CDCl3): 0.56 (d, J ¼ 6.9, Me); 0.63 (d, J ¼ 6.9, Me); 0.84 (d, J ¼ 6.8, Me); 0.91 (d, J ¼
7, Me); 1.48 – 1.55 (m, Me2CH); 1.97 – 2.05 (m, Me2CH); 4.43 (dd, J ¼ 14.8, 3.0, 1 H, CH2); 4.51 – 4.56 (m,
CH); 4.94 (dd, J ¼ 14.8, 11.2, 1 H, CH2); 5.39 (d, J ¼ 3.1, CHN); 7.24 – 7.54 (m, 10 arom. H). 13C-NMR
(100 MHz, CDCl3): 16.0; 18.0; 19.8; 21.5; 28.7; 29.9; 45.7; 65.7; 73.2; 125.4; 125.6; 128.0; 128.5; 128.6;
128.8; 128.9; 137.6; 152.8; 172.3. MALDI-MS: 446.04 ([M þ Na]þ). Anal. calc. for C24H28N2O5 (424.49): C
67.91, H 6.65, N 6.60; found: C 67.96, H 6.71, N 6.50.
(S)-4-(1-Methylethyl)-3-[(S)-3-nitro-2-phenylpropanoyl]-5,5-diphenyloxazolidin-2-one (24c). Com-
pound (S)-11 (380 mg, 0.83 mmol) was treated at ꢀ 708 with a soln. of PhMgBr (3.0 ml, 3.0 mmol, 1m in

Helvetica Chimica Acta – Vol. 93 (2010)
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THF) according to GP 1 to yield the crude product (dr 95 :5). Crystallization from hexane yielded
diastereomerically pure 24c (200 mg, 55%). Colorless solid. Rf (hexane/AcOEt 4 :1) 0.9. M.p. 1688.
[a]2D0 ¼ ꢀ226 (c ¼ 1, CH2Cl2). 1H-NMR (400 MHz, CDCl3): 0.39 (d, J ¼ 6.7, Me); 0.72 (d, J ¼ 7, Me ) ;
1.80 – 1.88 (m, Me2CH); 4.46 (dd, J ¼ 15.1, 4.16, 1 H, CH2); 5.24 (dd, J ¼ 15.1, 11.0, 1 H, CH2); 5.45 (d, J ¼
3.1, CHN); 5.66 (dd, J ¼ 11.0, 4.2, PhCH); 7.25 – 7.46 (m, 15 arom. H). 13C-NMR (100 MHz, CDCl3): 15.6;
21.6; 30.1; 46.2; 64.3; 75.1; 89.8; 125.9; 125.9; 128.0; 128.3; 128.7; 128.8; 128.9; 129.0; 129.1; 132.4; 137.9;
141.5; 152.2; 170.5. Anal. calc. for C27H26N2O5 (458.51): C 70.73, H 5.72, N 6.11; found: C 70.45, H 5.64, N
6.12.
(1R,2S,5R)-5-Methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 2-Methyl-3-nitropropanoate (25a). Com-
pound 16 (1.0 g, 3.0 mmol) was treated at ꢀ 708 with a soln. of MeMgBr (3.7 ml, 10.9 mmol, 3m in THF)
according to GP 1 to yield the crude product (dr 78 :22). FC (hexane/AcOEt 10 :1) yielded 25a (380 mg,
36%; mixture of diasterioisomers). Oily residue. IR (CHCl3): 2955w, 2922w, 2870w, 1725s, 1601w, 1556s,
1549s, 1495w, 1473w, 1455w, 1413w, 1375m, 1345w, 1240m, 1241s, 1228m, 1199m, 1174s, 1095m, 1094m,
977m, 961m, 908w, 845w, 774w, 764m, 742m, 699s, 627m. 1H-NMR (600 MHz, CDCl3): 0.87, 8.8 (2d, J ¼
6.6, Me); 0.94, 1.05 (2d, MeCH); 0.85 – 0.97 (m, CH2); 1.18, 1.19, 1.29, 1.31 (4s, MeCPh); 1.10 – 1.20 (m,
1 H, CH2); 1.43 – 1.52 (m, MeCH); 1.66 – 1.71 (m, 1 H, CH2); 2.08 – 2.12 (m, CH); 2.34 – 2.40, 2.56 – 2.62
(2m, MeCH); 3.91 (dd, J ¼ 14, 6.2, 1 H, CH2NO2, minor diastereoisomer); 3.96 (dd, J ¼ 14, 5.5, 1 H,
CH2NO2, minor diastereoisomer); 4.00 (dd, J ¼ 14, 6.2, 1 H, CH2NO2, major diastereoisomer); 4.21 (dd,
J ¼ 14, 7.7, 1 H, CH2NO2, major diastereoisomer); 4.81 (dt, J ¼ 10.7, 4.4, CHꢀO, major diastereoisomer);
4.84 (dt, J ¼ 10.7, 4.4, CHꢀO, minor diastereoisomer); 7.11 – 7.33 (m, 5 arom. H). 13C-NMR (150 MHz,
CDCl3): 13.4; 14.1; 21.7; 23.3; 23.6; 26.3; 26.4; 29.1; 29.4; 31.2; 34.5; 37.3; 37.4; 39.4; 39.5; 49.2; 49.9; 50.0;
75.6; 75.65; 75.7; 76.4; 125.1; 125.2; 125.25; 125.3; 128.0; 128.1; 151.9; 151.2; 170.9; 171.5. Anal. calc. for
C20H29NO4 (347.45): C 69.14, H 8.41, N 4.03; found: C 69.16, H 8.41, N 4.00.
(1R,2S,5R)-5-Methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 3-Methyl-2-(nitromethyl)butanoate
(25b). Compound 16 (1.0 g, 3.0 mmol) was treated at ꢀ 708 with a soln. of iPrMgBr (5.5 ml, 10.9 mmol,
2m in THF) according to GP 1 to yield the crude product (dr 51:49). FC (hexane/AcOEt 10 :1) yielded
25b (830 mg, 73%; mixture of diastereoisomers). Oily residue. IR (CHCl3): 2956w, 2922w, 2871w, 1726s,
1601w, 1556s, 1549s, 1495w, 1473w, 1456w, 1413w, 1375m, 1346w, 1242m, 1228m, 1199m, 1175s, 1095m,
978m, 961m, 909w, 845w, 845w, 774w, 764m, 742m, 699s, 627m. 1H-NMR (600 MHz, CDCl3; ca. 1:1
mixture of epimers): 0.74, 0.82 (2d, Me); 0.86 – 1.00 (m, CH2, 2 Me); 1.06 – 1.16 (m, CH); 1.17, 1.20, 1.30,
1.31 (4s, 2 Me); 1.43 – 1.52 (m, CH); 1.63 – 1.78, 1.83 – 1.88, 1.90 – 1.95 (3m, 2 CH2); 2.07 – 2.16 (m, CH);
2.42 – 2.45, 2.55 – 2.58 (2m, CHCOO); 3.91, 4.53 (2dd, 1 H, CH2NO2); 4.08, 4.17 (2dd, 1 H, CH2NO2);
4.72, 4.85 (2dt, CHꢀO); 7.11 – 7.33 (m, 5 arom. H). 13C-NMR (150 MHz, CDCl3; ca. 1:1 mixture of
epimers): 18.8; 19.4; 19.5; 20.1; 21.7; 21.8; 23.9; 24.7; 26.5; 26.7; 27.8; 28.3; 28.5; 28.6; 31.2; 31.3; 34.5; 34.6;
39.5; 39.6; 41.3; 41.4; 48.0; 48.8; 49.6; 50.3; 72.7; 72.8; 76.0; 76.1; 125.0; 125.1; 125.3; 125.4; 127.9; 128.1;
151.7; 151.9; 170.5; 170.9. Anal. calc. for C22H33NO4 (375.50): C 70.37, H 8.86, N 3.73; found: C 70.51, H
8.73, N 3.72.
(1R,2S,5R)-5-Methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 3-Nitro-2-phenylpropanoate (25c).
Compound 16 (1.0 g, 3.0 mmol) was treated at ꢀ 708 with a soln. of PhMgBr (10.9 ml, 10.9 mmol, 1m
in THF) according to GP 1 to yield the crude product (85%, dr 80 :20). Crystallization from AcOEt/
hexane yielded diastereomerically pure 25c (520 mg, 42%). Colorless solid. M.p. 1158. [a]2D0 ¼ ꢀ87.9 (c ¼
0.5, CHCl3). IR (CHCl3): 2955w, 2922w, 2870w, 1725s, 1601w, 1556s, 1473w, 1455w, 1413w, 1375m, 1345w,
1240m, 1228m, 1199m, 1173s, 1094m, 1032w, 977m, 960m, 908w, 845w, 773w, 764m, 741m, 699s, 627m.
1H-NMR (600 MHz, CDCl3): 0.57 (dd, J ¼ 23, 11, Me); 0.77 (d, J ¼ 6.5, MeCH); 0.80 (ddd, J ¼ 25.0, 13.0,
3.6, 1 H, CH2CHMe); 1.08 (dq, J ¼ 13.2, 3.4, 1 H, CH2CHCPh); 1.20 (s, MeCPh): 1.34 (s, MeCPh); 1.38 –
1.44 (m, MeCH); 1.61 – 1.66 (m, 1 H each, CH2CHMe, CH2CHO); 1.75 – 1.80 (m, 1 H, CH2CHCPh);
1.99 – 2.03 (m, CHCPh); 3.49 (dd, J ¼ 8.9, 6.1, CHCOO); 4.35 (dd, J ¼ 14.3, 6.1, 1 H, CH2NO2); 4.73 (dt,
J ¼ 10.7, 4.2, CHꢀO); 4.81 (dd, J ¼ 14.3, 8.9, 1 H, CH2NO2); 6.92 – 7.37 (m, 10 arom. H). 13C-NMR
(150 MHz, CDCl3): 21.6, 23.4 (Me); 26.3 (CH2); 29.1 (Me); 31.1 (CH); 34.5 (CH2); 39.5 (C); 40.3 (CH2);
48.2, 50.02 (CH); 75.5 (CH2); 76.0 (CH); 125.2, 125.5, 127.7, 128.0, 128.2, 129.0 (CH); 133.8, 152.0, 169.73
(C). Anal. calc. for C25H31NO4 (409.52): C 73.32, H 7.63, N 3.42; found: C 73.11, H 7.48, N 3.41.
(S)-4-(1-Methylethyl)-3-(3-nitropropanoyl)-5,5-diphenyloxazolidin-2-one (26). a) BuLi (33.1 ml,
52.9 mmol, 1.6m in hexane) was added slowly to a suspension of (S)-3 (14.2 g, 50.4 mmol) in THF

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(200 ml) at ꢀ 408. The mixture was allowed to warm up to ꢀ 108 over 15 min. and then cooled down to
ꢀ 708, followed by dropwise addition of a soln. of 3-nitropropanoyl chloride19) (6.93 g, 50.4 mmol) in
THF (10 ml) so that the temp. did not exceed ꢀ 508. After addition, the mixture was stirred for 1 h at
ꢀ 658, followed by slow warm-up to r.t. The reaction was then quenched with half-sat. NH4Cl (50 ml),
and the mixture was extracted with AcOEt. The org. layers were washed with sat. aq. NaHCO3, H2O, and
brine, dried (MgSO4), and concentrated under reduced pressure. Purification by FC (hexane/AcOEt
4 :1) afforded besides 7 (product of HNO2 elimination; 2.98 g, 17%) and (S)-3 (1.87 g, 13%), 26 (4.94 g,
26%) as a colorless powder. For anal. purposes, a sample was recrystallized from hexane/AcOEt.
b) To a mixture of (S)-7 (1.0 g, 3 mmol) and NaNO2 (1.5 g, 22.5 mmol) in THF (10 ml) at 508 was
added AcOH (1.25 ml, 22.5 mmol) during 2 h. The reaction was quenched with sat. aq. NaHCO3 soln.,
and the mixture was extracted with Et2O. The org. layer was washed with sat. aq. NH4Cl soln. and brine,
dried (MgSO4), and concentrated under reduced pressure. FC (pentane/Et2O 9 :1) yielded beside
unreacted (S)-7 (0.32 g, 32%), 26 (0.43 g, 55%). Colorless solid. Rf (pentane/Et2O 2 :1) 0.5. M.p. 93 – 968.
[a]2D0 ¼ ꢀ212.2 (c ¼ 1.0, CHCl3). IR (CHCl3): 2970w, 1779s, 1705m, 1556s, 1495w, 1450m, 1386s, 1372s,
1319m, 1265m, 1245w, 1211m, 1178m, 1052m, 1002m, 988m, 948w, 909w, 869w, 843w, 761m, 733m, 704m,
666w, 638w. 1H-NMR (300 MHz, CDCl3): 0.78 (d, J ¼ 6.9, Me); 0.87 (d, J ¼ 6.9, Me); 1.98 (m, CH); 3.29
(ddd, J ¼ 19.2, 6.9, 4.2, 1 H, CH2); 3.69 (ddd, J ¼ 18.9, 8.1, 4.2, 1 H, CH2); 4.58 – 4.75 (m, CH2NO2); 5.38
(d, J ¼ 3.3, CH); 7.28 – 7.46 (m, 10 arom. H). 13C-NMR (100 MHz, CDCl3): 16.29, 21.73 (Me); 29.9 (CH);
32.3 (CH2); 64.8 (CH); 68.9 (CH2); 90.1 (C); 125.6, 125.9, 128.1, 128.5, 128.8, 129.0 (CH); 137.8, 141.9,
153.0, 168.9 (C). EI-MS: 382.15 (2, Mþ), 339.09, 220.12, 195.08, 183.08, 165.07. Anal. calc. for: C21H22N2O5
(382.41): C 65.96, H 5.80, N 7.33; found: C 66.05, H 5.94, N 7.31.
4. Determination of the X-Ray Structures (Table 3). All structures were determined by the X-ray
service unit of the Laboratorium fꢀr Organische Chemie, ETH-Zꢀrich. Suitable single crystals were
measured on a Bruker– Nonius Kappa CCD diffractometer with MoKa radiation (l ¼ 0.71073 ꢄ,
graphite monochromator). Structures were solved by direct methods (SIR97) [17] and refined by full-
matrix least-squares on F2 (SHELXL97) [18]. If possible, H-atoms were located from a difference
electron-density map or constrained at ideal positions and included in the refinement. The absolute
configurations are derived from the known senses of chirality of the chiral auxiliaries.
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Received November 3, 2009