Michael addition reactions between chiral Ni(II) complex of glycine and 3-(trans-enoyl)oxazolidin-2-ones. A case of electron donor - Acceptor attractive interaction-controlled face diastereoselectivity

Article abstract of DOI:10.1021/jo0014865

This study has demonstrated that the readily available and inexpensive 3-(trans-3′-alkyl/arylpropenoyl)oxazolidin-2-ones, featuring high electrophilicity and conformational homogeneity, are synthetically superior Michael acceptors over the conventionally used alkyl enoylates, allowing for a remarkable improvement in reactivity and, in most cases, diastereoselectivity of the addition reactions with a Ni(II) complex of the chiral Schiff base of glycine with (S)-o-[N-(N-benzylprolyl)-amino]benzophenone. Kinetically controlled diastereoselectivity in the corresponding Michael addition reactions between the Ni(II) complex of glycine and the oxazolidin-2-ones was systematically studied as a function of steric, electronic, and position effects of the substituents on the starting Michael acceptor. In both aliphatic and aromatic series the simple diastereoselectivity was found to be virtually complete, affording the products via the corresponding TSs with the approach geometry like. The face diastereoselectivity of the reactions between the Ni(II) complex of glycine and the 3-(trans-3′-alkylpropenoyl)oxazolidin-2-ones was found to depend exclusively on the steric bulk of the alkyl group on the starting Michael acceptor. In contrast, the face diastereoselectivity in the reactions of aromatic oxazolidin-2-ones with the Ni(II) complex of glycine was shown to be controlled predominantly by the electronic properties of the aryl ring. In particular, the additions of the Ni(II) complex of glycine with 3-(trans-3′-arylpropenoyl)oxazolidin-2-ones, bearing electron-withdrawing substituents on the phenyl ring, afforded the (2S,3R)-configured products with synthetically useful diastereoselectivity and in quantitative chemical yields, thus allowing for an efficient access to the sterically constrained β-aryl-substituted pyroglutamic and glutamic acids.

Full text of DOI:10.1021/jo0014865

J . Org. Chem. 2001, 66, 1339-1350
1339
Mich a el Ad d ition Rea ction s betw een Ch ir a l Ni(II) Com p lex of
Glycin e a n d 3-(tr a n s-En oyl)oxa zolid in -2-on es. A Ca se of Electr on
Don or -Accep tor Attr a ctive In ter a ction -Con tr olled F a ce
Dia ster eoselectivity1
Chaozhong Cai, Vadim A. Soloshonok,* and Victor J . Hruby*
Department of Chemistry, University of Arizona, Tucson, Arizona 85721
hruby@u.arizona.edu
Received October 17, 2000
This study has demonstrated that the readily available and inexpensive 3-(trans-3′-alkyl/
arylpropenoyl)oxazolidin-2-ones, featuring high electrophilicity and conformational homogeneity,
are synthetically superior Michael acceptors over the conventionally used alkyl enoylates, allowing
for a remarkable improvement in reactivity and, in most cases, diastereoselectivity of the addition
reactions with a Ni(II) complex of the chiral Schiff base of glycine with (S)-o-[N-(N-benzylprolyl)-
amino]benzophenone. Kinetically controlled diastereoselectivity in the corresponding Michael
addition reactions between the Ni(II) complex of glycine and the oxazolidin-2-ones was systematically
studied as a function of steric, electronic, and position effects of the substituents on the starting
Michael acceptor. In both aliphatic and aromatic series the simple diastereoselectivity was found
to be virtually complete, affording the products via the corresponding TSs with the approach
geometry like. The face diastereoselectivity of the reactions between the Ni(II) complex of glycine
and the 3-(trans-3′-alkylpropenoyl)oxazolidin-2-ones was found to depend exclusively on the steric
bulk of the alkyl group on the starting Michael acceptor. In contrast, the face diastereoselectivity
in the reactions of aromatic oxazolidin-2-ones with the Ni(II) complex of glycine was shown to be
controlled predominantly by the electronic properties of the aryl ring. In particular, the additions
of the Ni(II) complex of glycine with 3-(trans-3′-arylpropenoyl)oxazolidin-2-ones, bearing electron-
withdrawing substituents on the phenyl ring, afforded the (2S,3R)-configured products with
synthetically useful diastereoselectivity and in quantitative chemical yields, thus allowing for an
efficient access to the sterically constrained â-aryl-substituted pyroglutamic and glutamic acids.
In tr od u ction
interested in generalizing of this method to afford the
corresponding â-alkyl- and â-aryl-substituted derivatives,
which are extraordinary useful compounds in the de novo
design of peptides with rationally modified three-
dimensional structures and biological functions.5 How-
ever, our attempts to involve â-alkyl- or â-arylacrylic
esters in the reaction with complex 1 encountered
unexpected problems of low reactivity of these substrates
and poor stereochemical outcome. Apparently, the suc-
cessful results of the additions between 1 and trifluoro-
methyl containing acrylates are due to the enhanced
electrophilicity and steric demands of these derivatives
provided by the trifluoromethyl group.6 To overcome the
problems associated with â-alkyl/arylacrylic esters, we
searched for other derivatives of R,â-unsaturated car-
boxylic acids which would feature higher electrophilicity
(issue of reactivity) and conformational homogeneity
(issue of diastereoselectivity). Recently, we have found
that readily available and inexpensive 3-(trans-enoyl)-
oxazolidin-2-ones (2) perfectly meet the required char-
Recently, we reported asymmetric Michael addition
reactions between a Ni(II) complex of the chiral Schiff
base of glycine with (S)-o-[N-(N-benzylprolyl)amino]-
benzophenone (1) and a series of the â-trifluoromethyl-
substituted alkyl acrylates leading to the corresponding
sterically constrained and trifluoromethyl-containing py-
roglutamic acids in enantiomerically pure form.1a,b Since
pyroglutamic acids could serve as key compounds to a
whole variety of five-carbon atom amino acids,2-4 we were
(1) Stereochemically Defined C-Substituted Glutamic Acids and
Their Derivatives. 9. For previous papers in this series, see: (a)
Soloshonok, V. A.; Cai, C.; Hruby, V. J .; Meervelt, L. V.; Mischenko,
N. Tetrahedron 1999, 55, 12031. (b) Soloshonok, V. A.; Cai, C.; Hruby,
V. J .; Meervelt, L. V. Tetrahedron 1999, 55, 12045. (c) Soloshonok, V.
A.; Cai, C.; Hruby, V. J . Tetrahedron: Asymmetry 1999, 10, 4265. (d)
Soloshonok, V. A.; Cai, C.; Hruby, V. J . Tetrahedron Lett. 2000, 41,
135. (e) Soloshonok, V. A.; Cai, C.; Hruby, V. J . Angew. Chem., Int.
Ed. 2000, 39, 2172. (f) Soloshonok, V. A.; Cai, C.; Hruby, V. J . Org.
Lett. 2000, 2, 747. (g) Soloshonok, V. A.; Cai, C.; Hruby, V. J .; Meervelt,
L. V.; Yamazaki, T. J . Org Chem. 2000, 29, 6688. (h) Soloshonok, V.
A.; Cai, C.; Hruby, V. J . Tetrahedron Lett. 2000, 41, 9645.
(2) For reviews on asymmetric synthesis of R-amino acids in general
and the target amino acids in particular, see: (a) Duthaler, R. O.
Tetrahedron 1994, 50, 1539. (b) Williams, R. M. Synthesis of Optically
Active R-Amino Acids; Pergamon Press: Oxford, 1989.
(5) For reviews see: (a) Goodman, M.; Ro, S. In Burger’s Medicinal
Chemistry and Drug Discovery, 5th ed.; Wolff, M. E., Ed.; J ohn Wiley
and Sons: New York, 1995; Vol. 1, pp 803-861. (b) Gante, J . Angew.
Chem., Int. Ed. Engl. 1994, 33, 1699. (c) Giannis, A.; Kolter, T. Angew.
Chem., Int. Ed. Engl. 1993, 32, 1244. (d) Hruby, V. J .; Al-Obeidi, F.;
Kazmierski, W. Biochem. J . 1990, 268, 249. (e) Hruby, V. J . Med. Res.
Rev. 1989, 9, 343.
(3) For papers, see: (a) Kanemasa, S.; Tatsukawa, A.; Wada, E.; J .
Org. Chem. 1991, 56, 2875. (b) Scho¨llkopf, U.; Pettig, D.; Busse, U.
Synthesis 1986, 737.
(4) For recent review on various synthetic transformations of
pyroglutamic acid and its derivatives, see: Najera, C.; Yus, M.
Tetrahedron: Asymmetry 1999, 10, 2245.
(6) Enantiocontrolled Synthesis of Fluoro-Organic Compounds: Ster-
eochemical Challenges and Biomedicinal Targets; Soloshonok, V. A.,
Ed.; Wiley: Chichester, 1999.
10.1021/jo0014865 CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/31/2001

1340 J . Org. Chem., Vol. 66, No. 4, 2001
Cai et al.
Ta ble 1. Ad d ition Rea ction s of Ni(II) Com p lex (S)-1 w ith
N-((E)-En oyl)-3-oxa zolid in -2-on es 2a -va
Sch em e 1
products 3a -v, 4a -v
entry
2a -v
time
yield,b %
ratio 3/4c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
15 min
20 min
35 min
45 min
>98
96
94
2.4/1
3.1/1
3.1/1
5.2/1
91
no reaction
94
15 min
20 min
20 min
2.5 h
25 min
40 min
20 min
2 min
2 min
1 h
<2 min
5 min
5 min
2 min
2 min
2 min
2 min
4.0/1
3.5/1
5.3/1
2.7/1
4.2/1
4.5/1
8.5/1
5.4/1
8.4/1
4.5/1
>26/1
2.6/1
3.6/1
7.2/1
2.6/1
9.7/1
7.6/1
93
98
98
96
99
95
95
98
94
>98
95
>98
98
96
98
>98
Sch em e 2a
s
t
u
v
a
All reactions were run in DMF in the presence of 15 mol % of
b
DBU at ambient temperature. Ratio 1/2 1/1.05-1.1. Isolated
acteristics of the ideal Michael acceptors allowing the
corresponding additions with achiral Ni(II) complex of
glycine Schiff base with o-(N-R-picolylamino)acetophe-
none (Scheme 1) to proceed with virtually complete simple
diastereoselectivity (>98% de) at room temperature in the
presence of nonchelating organic base.1d,g In this paper,
we describe in full detail1c the asymmetric version of the
reaction using a Ni(II) complex 1 as a chiral equivalent
of nucleophilic glycine in the additions with various
3-(trans-enoyl)oxazolidin-2-ones (2) to demonstrate the
scope and limitations of this method for preparing the
target ø-constrained amino acids.7
yield of crude product. c Determined by NMR (500 MHz) analysis
of the crude reaction mixtures.
oxazolidin-2-ones 2b,c. However, the major products
(2S,3S)-3b,c were obtained with higher selectivity (en-
tries 2 and 3). Sterically bulky isopropyl-containing
oxazolidin-2-one 2d readily reacted with complex 1 to give
quantitatively a mixture of (2S,3R)-3d and (2R,3S)-
diastereomers 4d 9 with a synthetically useful excess of
the major product (entry 4). It is interesting to note that
attempts to conduct addition between complex 1 and
ethyl 4-methylpentenoylate failed,11 undoubtedly, due to
the sterically congested nature of the ester. On the other
hand, these results could serve as a clear example of the
synthetic superiority of the oxazolidin-2-one derivatives
2, as Michael acceptors, over the corresponding esters.
However, application of oxazolidin-2-one derivatives 2 in
Michael additions with complex 1 was found to have some
limitations. Thus, the reaction between 1 and tert-butyl-
containing derivative 2e did not occur at all under the
standard conditions. Application of equimolar amounts
of the base or elevated temperatures resulted in forma-
tion of decomposition products.
Resu lts a n d Discu ssion
Mich a el Ad d ition Rea ction s of Glycin e Ni(II)
Com p lex 18 w ith 3-(tr a n s-3′-Alk ylp r op en oyl)oxa zo-
lid in -2-on es (2a-d ). Previously, we have shown that the
Michael addition reaction between complex 1 and ethyl
crotonate, conducted in DMF in the presence of DBU (50
mol %) for 1 h, gave rise to a mixture of the corresponding
(2R,3R)-, (2S,3S)-, and (2S,3R)-diastereomers in a ratio
of 19.0/76.2/4.8, respectively, and in 78% chemical yield.1a
In contrast, we have found that reaction of N-trans-
crotonyl-derived oxazolidin-2-one 2a with complex 1 in
the presence of catalytic amounts of DBU (10-15 mol
%) proceeds at a substantially higher reaction rate (15
min), affording quantitatively a mixture of (2S,3S)- and
(2R,3R)-configured products in a ratio of 2.4/1 (3a and
4a , respectively) (Scheme 2, Table 1, entry 1). Due to the
quantitative chemical yield, this outcome is synthetically
superior to the previously reported procedure,1a as the
diastereomerically pure major product (2S,3S)-3a could
be isolated in 67% yield simply by crystallizing the
resultant mixture from benzene/hexanes. Increasing the
steric bulk of the alkyl group on the starting oxazolidin-
2-one resulted in a reduced reaction rate of the additions
of complex 1 with the ethyl- and n-propyl-containing
Considering the kinetically controlled (vide infra) ster-
eochemical outcome of these reactions, we can conclude
that oxazolidin-2-ones 2a -d feature much higher reac-
(8) For recent papers on asymmetric synthesis of R-amino acids
using Ni(II) complex 1, see: (a) Soloshonok, V. A.; Avilov, D. V.;
Kukhar′, V. P. Tetrahedron: Asymmetry 1996, 7, 1547. (b) Soloshonok,
V. A.; Avilov, D. V.; Kukhar′, V. P. Tetrahedron 1996, 52, 12433. (c)
Soloshonok, V. A.; Avilov, D. V.; Kukhar′, V. P.; Meervelt, L. V.;
Mischenko, N. Tetrahedron Lett. 1997, 38, 4671. (d) Soloshonok, V.
A.; Avilov, D. V.; Kukhar′, V. P.; Meervelt, L. V.; Mischenko, N.
Tetrahedron Lett. 1997, 38, 4903. (e) Qiu, W.; Soloshonok, V. A.; Cai,
C.; Tang, X.; Hruby, V. J ., Tetrahedron 2000, 56, 2577. (f) Tang, X.;
Soloshonok, V. A.; Hruby, V. J . Tetrahedron: Asymmetry 2000, 11,
2917.
(9) (2S,3R) or (2R,3S) absolute stereochemistry for the isopropyl-
or aryl-containing (R ) i-Pr, Ph) derivatives is a consequence of the
Cahn-Ingold-Prelog priority (see ref 10) and is stereochemically
equivalent to the (2S,3S) or (2R,3R) configuration, respectively, in the
aliphatic (R ) Me, Et, n-Pr) series of compounds.
(10) Cahn, R. S.; Ingold, C.; Prelog, V. Angew. Chem., Int. Ed. Engl.
1966, 5, 385.
(11) Soloshonok, V. A.; Cai, C.; Hruby, V. J . Unpublished data.
(7) For recent reviews on ø-constrained amino acids, see: (a) Hruby,
V. J .; Li, G.; Haskell-Luevano, C.; Shenderovich, M. Biopolymers
(Peptide Sci.) 1997, 43, 219. (b) Gibson, S. E.; Guillo, N.; Tozer, M. J .
Tetrahedron 1999, 55, 585.

Reactions between Glycine Complexes and Oxazolidin-2-ones
J . Org. Chem., Vol. 66, No. 4, 2001 1341
tivity than the corresponding alkyl esters and provide
better diastereoselectivity in the addition reaction with
complex 1. The absolute configuration (vide infra) of the
diastereomeric products suggests that the reactions occur
with virtually complete simple diastereoselectivity, while
the complex 1 derived enolate (2S)/(2R)-face selectivity
is relatively poor.
9-11) series, we can conclude that ortho substitution on
the aromatic ring in the starting Michael acceptors is
unfavorable for both the reaction rate and diastereo-
selectivity of the corresponding addition reactions. In
agreement with this conclusion, the reaction of o-tri-
fluoromethylphenyl-substituted 2l with complex 1 oc-
curred with the slowest rate (entry 12), as compared with
the almost instant additions of the meta- and para-
substituted derivatives 2m ,n , respectively (entries 13 and
14). However, the diastereoselectivity of the reaction
between 2l and 1 was the highest in a series of trifluoro-
methylphenyl-containing Michael acceptors 2l-n . This
unexpected result could be rationalized assuming that
in the corresponding transition state (TS) (vide infra) the
o-trifluoromethyl group is situated in close proximity with
the positively charged Ni(II) cation of the glycine complex
1, allowing for corresponding electrostatic attractive
interactions, which would contribute to the thermody-
namic stability of the TS.13 In general, high reaction
rates, even in the case of ortho-substituted 2l (20 min),
observed in the series of trifluoromethylphenyl-contain-
ing Michael acceptors, was a pleasant result suggesting
that the present method would be of particular use for
preparing the target amino acids containing electron-
withdrawing substituents.
Next, we studied the reactions of complex (S)-1 with
Michael acceptors containing indolyl- (2o) and penta-
fluorophenyl-containing derivatives 2p, representing elec-
tron-excessive and electron-deficient aromatic rings,
respectively. As expected, considering the reduced elec-
trophilicity of the C,C double bond in 2o due to the
electron-releasing effect of the indolyl group, the reaction
with complex (S)-1 occurred at relatively low rate, but
with slightly enhanced diastereoselectivity (ca. 82%) as
compared with the addition of 2f (entry 15 vs 6). In
contrast, the exothermic reaction (<2 min) of the penta-
fluorophenyl derivative 2p afforded the major product
(2S,3R)-3p with at least 96% diastereoselectivity (entry
16). While the reaction rates of these reactions could be
readily accounted for by electronic effects, such dramatic
differences in the diastereoselectivity were unexpected.
We assumed first that the reason behind the phenom-
enon observed is the fact that pentafluorophenyl ring and
C,C double bond in 2p cannot adopt a coplanar geometry
due to the steric demands of the two o-fluorine atoms, a
property that makes 2p different from all previously
studied Michael acceptors. Therefore, we conducted the
addition reactions between complex 1 and a series of bis-
and monofluoro-substituted derivatives 2q-s. The reac-
tion of 2,6-difluorophenyl derivative 2q occurred at high
rate, but with disappointedly low diastereoselectivity
(entry 17). The addition of mono-2-fluorophenyl-substi-
tuted 2r proceeded at the same rate and with higher
diastereoselectivity (entry 18). Surprisingly, the dia-
stereoselectivity of the reaction of 3,4-difluorophenyl
derivative 2s (entry 19) featured the level observed in
the series of trifluoromethylphenyl-containing Michael
acceptors (entries 12-14). These results allowed us to
conclude that the origin of the diastereoselectivity ob-
served in the reaction between complex 1 and penta-
fluorophenyl-containing 2p is not the steric or geometric
Mich a el Ad d ition Rea ction s of Glycin e Ni(II)
Com p lex 1 w ith 3-(tr a n s-3′-Ar ylp r op en oyl)oxa zoli-
d in -2-on es (2f-w ). As in the aliphatic series, all reac-
tions between complex 1 and aryl-containing Michael
acceptors 2f-w were conducted under the same, stand-
ard reaction conditions: DMF as a solvent, 15 mol %
DBU as a base, ambient temperature. The addition of
phenyl-containing oxazolidin-2-one 2f with complex 1
occurred with the same rate and quantitative yield as
the reaction of methyl derivative 2a , but with more
appreciable diastereoselectivity (entry 6). The main
product (2S,3R)-3f 3 was isolated in 76% chemical yield
simply by crystallizing the resulting mixture of diaster-
eomers. The reaction of more sterically bulky12 R- and
â-naphthyl-containing oxazolidin-2-ones 2g,h , respec-
tively, proceeded at a slightly lower rate and with
noticeably different diastereoselectivities (entries 7 and
8). Thus, the stereochemical outcome in the reaction of
the R-naphthyl derivative 2g with complex 1 was poorer,
as compared with the addition of phenyl-containing 2f
(entry 7 vs 6). In contrast, the diastereoselectivity of the
reaction between â-naphthyl-containing oxazolidin-2-one
2h and complex 1 was found to be higher than that of
phenyl derivative 2f (entry 8 vs 6). These data suggested
that in the addition of complex 1 with aryl-containing
oxazolidin-2-ones 2 not only the total steric bulk of the
substituent, as observed in the aliphatic series (entries
1-4), but also the pattern of substitution on the aromatic
ring might play an important role in determining the
stereochemical outcome. Therefore, to investigate sys-
tematically electronic and position effects of substituents
on the phenyl ring of the starting oxazolidin-2-ones on
the stereochemical outcome of the reactions, we prepared
a series of o-, m-, and p-methoxy- (2i-k ) and o-, m-, and
p-trifluoromethylphenyl derivatives 2l-n . The reaction
of o-methoxy-substituted 2i with complex 1 occurred at
low reaction rate and with noticeably lower diastereo-
selectivity as compared with the outcome of unsubsti-
tuted phenyl derivative 2f reaction (entry 9 vs 6).
Surprisingly, m-methoxyphenyl-containing 2j reacted
with complex 1 at a high rate, furnishing the correspond-
ing diastereomeric products (2S,3R)-3j and (2R,3S)-4j in
a ratio comparable with the result obtained in the
reaction of 2f with 1 (entry 10 vs 9, 6). The addition of
the p-methoxyphenyl derivative 2k occurred at a rela-
tively low rate but with the highest diastereoselectivity
in the series (entry 11 vs 9, 10). Considering the electron-
releasing effect of methoxy group decreasing electrophi-
licity of the C,C double bond in the corresponding
derivatives 2i-k , the lowering in the reaction rates of
the additions between complex 1 and 2i-k was quite
anticipated. However, such a noticeable influence of the
position of the methoxy group on the reaction rate (entry
9 vs 10) and the diastereoselectivity (entry 9 vs 11) was
rather intriguing. Considering the results obtained for
the naphthyl (entries 7, 8) and methoxyphenyl (entries
(13) Electrostatic attractive interactions between the nickel(II) ion
and fluorine atoms, were shown to be a paramount factor controlling
virtually complete diastereoselectivity in the aldol addition reaction
between trifluoromethyl alkyl/aryl ketones and complex (S)-1; see refs
8a,b and 14.
(12) Attempts to conduct the reactions of complex 1 with the ethyl
esters of trans-3-(R- or â-naphthyl)propenoic acids failed.

1342 J . Org. Chem., Vol. 66, No. 4, 2001
Cai et al.
Sch em e 3a
acceptor attractive interactions that render the (2S,3R)-
configured diastereomers 3 substantially favored over
(2R,3S)-4. Accordingly, the stereochemical outcome of the
addition reactions under study is governed by the com-
bined effect of steric and electronic/electrostatic15 interac-
tions which are a function of the substitution pattern on
the aromatic ring and the nature of the substituent.
In general, as shown in the aliphatic series, the
addition reactions between complex (S)-1 and aromatic
Michael acceptors 2f-v proceeded with excellent simple
and variable face diastereoselectivity giving rise to a
mixture of (2S,3R)-3f-v and (2R,3S)-4f-v diastereomers.
On the other hand, the face diastereoselectivity was
found to vary from poor to excellent depending, in
contrast to the aliphatic series, on the combined effect of
steric and electronic factors, allowing for the efficient
asymmetric synthesis of the target â-aryl-substituted
glutamic/pyroglutamic acids containing electron-with-
drawing substituents on the aryl group (vide versa).
Deter m in a tion of th e Absolu te Con figu r a tion of
th e P r od u cts. Decom p osition of th e Dia ster eom er i-
ca lly P u r e Com p lexes 3 a n d 4: Isola tion of P yr o-
glu ta m ic Acid s 8 a n d Recover y of th e Ch ir a l Liga n d
(S)-10. The R-absolute configuration of the glutamic acid
residue in the diastereomeric products 3, 4 and 6, 7 could
be easily determined on the basis of their chiroptical
properties and NMR data.16 The absolute configuration
of the â-stereogenic carbon in 3, 4 and 6, 7 also could be
reliably assigned using proton NMR data.17 Nevertheless,
taking advantage of the fact that physicochemical and
chiroptical data for â-methyl- and â-phenyl-substituted
pyroglutamic acids were available in the literature,1a,19,20
we decomposed, under the standard conditions,1a,b dia-
properties of the latter but the extreme electron-deficient
nature of the pentafluorophenyl ring. To have a final and
straightforward proof to this conclusion, we synthesized
p-methoxytetrafluorophenyl derivative 2t, which, pos-
sessing the steric and geometric profile of 2p , lacks its
extreme electron-deficient nature,6 due to the presence
of the electron-releasing methoxy group. The result was
quite convincing; the addition of 2t with complex 1
occurred at a high reaction rate and with the same, low
diastereoselectivity that was obtained in the reaction of
2,6-difluorophenyl-containing 2q (entry 20 vs 17). To
demonstrate the generality of this electron-deficient
aromatic ring-induced diastereoselectivity, and being
aware of the unique stereocontrolling ability of fluorine
atoms,6 we investigated the reactions of the Michael
acceptors 2u ,v bearing electron-withdrawing substitu-
ents other than fluorine. To our satisfaction, the exo-
thermic and quantitative additions of complex 1 with 3,4-
dichlorophenyl 2u and 4-nitrophenyl derivatives 2v
featured high diastereoselectivity (entries 21, 22), sug-
gesting that the electron-deficiency of the phenyl ring,
rather than the presence of fluorine atoms, is the cause
of the results obtained.
(14) Soloshonok, V. A.; Kukhar′, V. P.; Galushko, S. V.; Svistunova,
N. Y.; Avilov, D. V.; Kuzmina, N. A.; Raevski, N. I.; Struchkov, Y. T.;
Pisarevsky, A. P.; Belokon, Y. N. J . Chem. Soc., Perkin Trans. 1 1993,
3143.
(15) (a) Coates, G. W.; Dunn, A. R.; Henling, L. M.; Dougherty, D.
A.; Grubbs, R. H. Angew. Chem., Int. Ed. Engl. 1997, 36, 248. (b)
Coates, G. W.; Dunn, A. R.; Henling, L. M.; Ziller, J . W.; Lobkovsky,
E. B.; Grubbs, R. H. J . Am. Chem. Soc. 1998, 120, 3641. (c) Weck, M.;
Dunn, A. R.; Matsumoto, K.; Coates, G. W.; Lobkovsky, E. B.; Grubbs,
R. H. Angew. Chem., Int. Ed. 1999, 38, 2741.
With these results in hand, we next examined the
origin of this electron-deficient aromatic ring-induced
high diastereoselectivity. Considering the structure of
glycine complex (S)-1, one can identify at least four
potential sites for nonbonded interactions with the
electron-deficient aromatic ring on the starting Michael
acceptors: the three aromatic rings of (S)-1 can be
involved in the corresponding attractive interactions and
the Ni(II) ion in repulsive interactions. Taking into
account that the electron-deficient aromatic ring on the
starting Michael acceptors favors a (2S,3R) absolute
configuration of the major diastereomeric product, we
assumed that the ketimine phenyl of complex (S)-1 might
be involved in the corresponding electron donor-acceptor
attractive interactions. To prove this, we prepared glycine
complex (S)-5 (Scheme 3) in which the ketimine phenyl
is substituted by the methyl. Since the methyl group in
complex (S)-5 cannot be involved in the interactions
under study, we expected that the reaction between
complex (S)-5 and pentafluorophenyl-containing 2p would
feature lower diastereoselectivity, as compared with the
outcome of the addition of complex (S)-1 with 2p (entry
16). Indeed, the reaction between complex (S)-5 and 2p
proceeded at a high rate, giving rise to (2S,3R)-6p and
(2R,3S)-diastereomeric products 7p in a ratio of 3/1,
respectively. Most interestingly, the addition between
complex (S)-5 and unsubstituted phenyl-containing 2f
gave the diastereomers (2S,3R)-6f and (2R,3S)-7f in
exactly the same ratio of 3/1, respectively. These data
clearly demonstrate that the ketimine phenyl of complex
(S)-1 and the electron-deficient aromatic ring of the
Michael acceptor are involved in the electron donor-
(16) As has been demonstrated (see refs 1 and 8), the CD and ORD
spectra of Ni(II) complexes of this type in neutral solutions exhibit
two maxima in the region of metal d-d transition (Cotton effects at
450 and 550 nm). In the ORD spectra, the sign of Cotton effects in
this region strictly depends on a conformation of the polycyclic system
of chelate rings. Thus, in the case of complexes containing R-mono-
substituted R-amino acid, the pseudoaxial orientation of the amino acid
side chain, corresponding to an R-(L) configuration of R-amino acid,
causes a Cotton effect with a positive sign at the 500-700 nm region
and negative sign at 400-450 nm. On the other hand, a pseudoequa-
torial orientation of the amino acid side chain brings about opposite
signs of the Cotton effects at 400-450 (positive) and at the 500-700
nm (negative) region. As was established in numerous studies, this
general trend is not influenced by the structure and nature of the
R-amino acid side chain, and the configuration of stereogenic centers
within it. 1H NMR spectra of the complexes containing R-L- and R-D-
amino acids also are very characteristic, featuring substantial differ-
ences in chemical shifts of aromatic and methylene protons of the (N-
benzyl)proline moiety.
(17) Due to the sterically congested nature and structural sophis-
tication of Ni(II)-complexes 3, 4 and 6, 7 free rotation of the glutamic
acid residues in the complexes is substantially restricted. As a result
of this, the corresponding diastereomeric products differing for the
absolute configuration in the â-position have characteristic patterns
in their proton NMR spectra. For a discussion of the NMR data
characteristic for the diastereomeric Ni(II) complexes containing
â-alkyl- and â-aryl-substituted glutamic acid residues, see refs 1a,b
and 18, respectively.
(18) Belokon′, Y. N.; Bulychev, A. G.; Ryzhov, M. G.; Vitt, S. V.;
Batsanov, A. S.; Struchkov, Y. T.; Bakchmutov, V. I.; Belikov, V. M. J .
Chem. Soc., Perkin Trans. 1 1986, 1865.
(19) Ezquerra, J .; Pedregal, C.; Merino, I.; Flo´rez, J .; Barluenga, J .;
Garc´ıa-Granda, S.; Llorca, M.-A. J . Org. Chem. 1999, 64, 6554.

Reactions between Glycine Complexes and Oxazolidin-2-ones
J . Org. Chem., Vol. 66, No. 4, 2001 1343
Sch em e 4
F igu r e 1. Possible TSs in the addition between 1 and 2
tivity in the addition between complex (S)-1 and o-
trifluoromethyl-containing 2l (Table 1, entry 12) also
could be easily accounted for considering TS A′ in which
the fluorine atoms are located in close proximity with the
Ni(II) and could interact13 with the latter, adding to the
stability of TS A′.
stereomerically pure complexes 3a ,f and 4a ,f to afford
the corresponding pyroglutamic acids 8a ,f and 9a ,f,
respectively, along with recovery of the chiral ligand (S)-
10 and the oxazolidin-2-one (Scheme 4). Comparison of
the proton NMR and chiroptical data of 8a ,f and 9a ,f,
with those of the literature revealed (2S,3S) and (2R,3R)
absolute configurations for 8a and 9a , respectively, and
(2S,3R) and (2R,3S)9 stereochemistry for 8f and 9f,
respectively. The absolute configurations of the rest of
diastereomeric products 3b-d ,g-v and 4b-d ,g-v were
assigned on the basis of a close similarity of their
chiroptical and proton NMR data to those of 8a ,f and
9a ,f.
To demonstrate the synthetic aspects of the method,
we performed preparative (3-5 g) synthesis of (2S,3R)-
8f,s,u (Scheme 4). Major products (2S,3R)-3f,s,u were
isolated in diastereomerically pure form by recrystalli-
zation of the resulting reaction mixture, and decomposed
to afford the target pyroglutamic acids (2S,3R)-8f,s,u
along with quantitative recovery of ligand (S)-10. Fur-
thermore, phenyl-containing (2S,3R)-8f was hydrolyzed
to the corresponding glutamic acid (2S,3R)-12f in high
chemical yield.
Mech a n istic Con sid er a tion s. First, we investigated
the reversibility of the reactions under study to determine
whether the stereochemical outcome is kinetically or
thermodynamically controlled. Resubmission of the dia-
stereomerically pure products 3a ,f and 4a ,f to the
original reaction conditions did not give any of the
starting compounds in detectable amounts (1H NMR, 500
MHz). These results suggested that the reactions are
rather irreversible, and thus, the stereochemical outcome
of the addition reactions is most likely kinetically con-
trolled. That is in good agreement with previous results
obtained on the DBU-catalyzed Michael addition reac-
tions of Ni(II) complexes with R,â-unsaturated carboxylic
acid derivatives.1a,b,h According to the absolute configura-
tions of diastereomeric products 3 and 4, the relative
topicity20 of coupling is like. Taking into account the
mechanistic rationale for the addition reactions between
the achiral Ni(II) complex of glycine Schiff base with o-(N-
R-picolylamino)acetophenone and Michael acceptors 2
(Scheme 1),1h we can suggest that the formation of the
major diastereomeric products 3 in the reaction under
study proceeds through TS A (Figure 1). As one can see,
in TS A the aromatic ring of the Michael acceptor and
the ketimine phenyl of the Ni(II) complex are in close
proximity to each other, and that would allow for non-
bonding electron donor-acceptor attractive interactions
adding to the stability of TS A. The high diastereoselec-
In conclusion, we have demonstrated that the readily
available and inexpensive 3-(trans-3′-alkyl/arylpropen-
oyl)oxazolidin-2-ones (2a -d ,f-v), featuring high electro-
philicity and conformational homogeneity, are syntheti-
cally more superior Michael acceptors than the corre-
sponding alkyl enoylates, allowing for a remarkable
improvement in reactivity and, in most cases, diastereo-
selectivity of the addition reactions with a Ni(II) complex
of the chiral Schiff base of glycine (S)-1. The kinetically
controlled diastereoselectivity in the Michael addition
reactions between (S)-1 and 2a -v was systematically
studied as a function of steric, electronic and position
effects of the substituents on the starting Michael ac-
ceptor. In both the aliphatic and aromatic series, simple
diastereoselectivity was found to be virtually complete,
affording the products via the corresponding TSs with
the approach geometry like. The face diastereoselectivity
of the reactions between complex (S)-1 and 3-(trans-3′-
alkylpropenoyl)oxazolidin-2-ones (2a -d ) was found to
depend exclusively on the steric bulk of the alkyl group
on the starting Michael acceptor. In contrast, the face
diastereoselectivity of aromatic oxazolidin-2-ones 2f-v
was shown to be controlled predominantly by the elec-
tronic properties of the aryl ring. In particular, the
additions of complex (S)-1 with 3-(trans-3′-arylpropenoyl)-
oxazolidin-2-ones bearing electron-withdrawing substit-
uents on the phenyl ring afforded the (2S,3R)-configured
products with synthetically useful diastereoselectivities
and in quantitative chemical yields, thus allowing for an
efficient access to sterically constrained â-aryl-substitut-
ed pyroglutamic and glutamic acids.
Exp er im en ta l Section
Gen er a l Meth od s. 1H, 13C, and 19F NMR (299.94 MHz)
were recorded using TMS, CDCl3, and CCl3F as internal
standards. High-resolution mass spectra (HRMS) and optical
rotations were recorded at facilities available at the Depart-
ment of Chemistry, University of Arizona. Melting points (mp)
are uncorrected and were obtained in open capillaries. All
reagents and solvents, unless otherwise stated, are com-
mercially available and were used as received. Unless other-
wise stated, yields refer to isolated yields of products of greater
than 95% purity as estimated by 1H, 13C, and 19F NMR
spectrometry. All new compounds were characterized by 1H,
13C, and 19F NMR and HRMS.
For an updated, improved large-scale preparation of chiral
ligand (S)-o-[N-(N-benzylprolyl)amino]benzophenone (BPB)
(10) and the corresponding Ni(II) complex, see ref 21. Michael
acceptors 2a -v were prepared according to the general
methods A and B described previously.1h For properties,
(20) Seebach, D.; Prelog, V. Angew. Chem., Int. Ed. Engl. 1982, 21,
654.

1344 J . Org. Chem., Vol. 66, No. 4, 2001
Cai et al.
constants, and NMR data of derivatives 2a ,c,d ,f-h ,k ,n -p , see
ref 1h. The new Michael acceptors used in this study are listed
below.
7.38 (1H, m), 7.41-7.48 (1H, m), 7.75, 7.84 (2H, AB, J ) 15.9
Hz); 19F NMR (CDCl3) δ -137.7 (1F, m), -134.6 (1F, m); 13C
NMR (CDCl3) δ 42.7, 62.1, 116.8 (m), 117.7 (m), 125.3 (m),
131.7 (m), 143.7, 148.8 (m), 150.0 (m), 152.2 (m), 153.4 (m),
164.9; HRMS(FAB) [M + H]+ calcd for C12H10F2NO3 254.0629,
found 254.0636.
3-(tr a n s-2′-P en t en oyl)oxa zolid in -2-on e (2b ) (method
A): yield 52%; oil; 1H NMR (CDCl3) δ 1.11 (3H, t, J ) 7.5 Hz),
2.27-2.36 (2H, m), 4.07-4.43 (4H, AB, J ) 8.0 Hz), 7.16-
7.28 (2H, m); 13C NMR (CDCl3) δ 12.2, 25.8, 42.7, 60.0, 119.1,
3-(tr a n s-4′-Met h oxy-2′,3′,5′,6′-t et r a flu or ocin n a m oyl)-
oxa zolid in -2-on e (2t) (method B): yield 86%; mp 83.0-83.5
153.0, 153.5, 165.4; HRMS(FAB) [M + H]+ calcd for C8H12
NO3 170.0817, found 170.0817.
-
1
°C; H NMR (CDCl3) δ 4.15 (3H, s), 4.16, 4.48 (4H, AB, J )
8.0 Hz), 7.81, 8.11 (2H, AB, J ) 16.3 Hz); 19F NMR (CDCl3) δ
-159.5 (2F, m), -141.6 (2F, m); 13C NMR (CDCl3) δ 42.7, 62.0,
62.1 (t, J ) 5.0 Hz), 107.8 (t, J ) 13.6 Hz), 122.7 (t, J ) 8.6
Hz), 129.9, 139.0 (m), 139.5 (m), 142.2 (m), 144.3 (m), 147.7
(m), 153.3, 164.8; HRMS(FAB) [M + H]+ calcd for C13H10F4-
NO4 320.0546, found 320.0561.
3-(4′,4′-Dim et h yl-tr a n s-2-p en t en oyl)oxa zolid in -2-on e
(2e) (method B): yield 79%; mp 73.0-73.5 °C; 1H NMR
(CDCl3) δ 1.12 (9H, s), 4.08, 4.43 (4H, AB, J ) 8.1 Hz), 7.71
(2H, s); 13C NMR (CDCl3) δ 28.5, 34.2, 42.7, 61.9, 115.4, 153.4,
161.1, 165.8; HRMS(FAB) [M + H]+ calcd for C10H16NO3
198.1130, found 198.1130.
3-(tr a n s-3′,4′-Dich lor ocin n a m oyl)oxa zolid in -2-on e (2u )
(method B): yield 84%; mp 182.0-183.0 °C; 1H NMR (CDCl3)
δ 4.14, 4.48 (4H, AB, J ) 8.1 Hz), 7.45-7.49 (2H, m), 7.68-
7.69 (1H, m), 7.73, 7.88 (2H, AB, J ) 15.6 Hz); 13C NMR
(CDCl3) δ 42.8, 62.2, 118.3, 127.5, 128.6, 130.1, 130.9, 133.2,
134.5, 143.4, 153.5, 164.8; HRMS(FAB) [M + H]+ calcd for
3-(tr a n s-2′-Met h oxycin n a m oyl)oxa zolid in -2-on e (2i)
(method A): yield 56%; mp 169.0-170.0 °C; 1H NMR (CDCl3)
δ 3.91 (3H, s), 4.14, 4.45 (4H, AB, J ) 8.0 Hz), 6.91-7.00 (2H,
m), 7.34-7.40 (1H, m), 7.64 (1H, dd, J ) 1.7, 7.8 Hz), 7.97,
8.21 (2H, AB, J ) 15.9 Hz); 13C NMR (CDCl3) δ 42.9, 55.5,
62.0, 111.1, 116.9, 120.7, 123.5, 129.3, 131.9, 141.6, 158.7,
165.9; HRMS(FAB) [M + H]+ calcd for C13H14NO4 248.0923,
found 248.0926.
3-(tr a n s-3′-Met h oxycin n a m oyl)oxa zolid in -2-on e (2j)
(method B): yield 84%; mp 134.0-135.0 °C; 1H NMR (CDCl3)
δ 3.84 (3H, s), 4.14, 4.46 (4H, AB, J ) 8.0 Hz), 6.94-6.97 (1H,
m), 7.12-7.13 (1H, m), 7.29 (2H, m), 7.82, 7.90 (2H, AB, J )
15.7 Hz); 13C NMR (CDCl3) δ 42.8, 55.3, 62.1, 113.4, 116.6,
116.8, 121.3, 129.9, 135.8, 146.2, 153.6, 159.8, 165.3;
HRMS(FAB) [M + H]+ calcd for C13H14NO4 248.0923, found
248.0927.
3-(tr a n s-2′-Tr iflu or om et h ylcin n a m oyl)oxa zolid in -2-
on e (2l) (method B): yield 85%; mp 128.0-129.0 °C; 1H NMR
(CDCl3) δ 4.16, 4.49 (4H, AB, J ) 8.0 Hz), 7.47-7.52 (1H, m),
7.57-7.62 (1H, m), 7.70-7.73 (1H, m), 7.84-7.86 (1H, m), 7.89,
8.23 (2H, ABX, J ) 2.1, 5.6 Hz); 19F NMR (CDCl3) δ -59.9
(3F, s); 13C NMR (CDCl3) δ 42.8, 62.2, 120.7, 123.9 (q, J ) 274.0
Hz), 126.1 (q, J ) 6.0 Hz), 128.3, 129.1 (q, J ) 32.3 Hz), 129.9,
132.1, 133.3, 141.4 (q, J ) 2.0 Hz), 153.6, 164.5; HRMS(FAB)
[M + H]+ calcd for C13H11F3NO3 286.0691, found 286.0681.
3-(tr a n s-3′-Tr iflu or om et h ylcin n a m oyl)oxa zolid in -2-
on e (2m ) (method B): yield 79%; mp 141.5-142.0 °C; 1H NMR
(CDCl3) δ 4.16, 4.49 (4H, AB, J ) 8.0 Hz), 7.51-7.56 (1H, m),
7.64-7.67 (1H, m), 7.80-7.82 (2H, m), 7.86, 7.97 (2H, AB, J
) 15.6 Hz); 19F NMR (CDCl3) δ -64.0 (3F, s); 13C NMR (CDCl3)
δ 42.8, 62.2, 118.4, 123.7 (q, J ) 274.0 Hz), 125.3 (q, J ) 4.0
Hz), 127.0 (q, J ) 3.0 Hz), 129.4, 131.3, 131.4 (q, J ) 32.3
Hz), 135.2, 144.3, 153.6, 164.9; HRMS(FAB) [M + H]+ calcd
for C13H11F3NO3 286.0691, found 286.0704.
3-(tr a n s-2′,6′-Diflu or ocin n a m oyl)oxa zolid in -2-on e (2q)
(method B): yield 73%; mp 164.0-165.0 °C; 1H NMR (CDCl3)
δ 4.15, 4.46 (4H, AB, J ) 8.0 Hz), 6.91-6.99 (2H, m), 7.27-
7.37 (1H, m), 7.94, 8.14 (2H, AB, J ) 15.9 Hz); 19F NMR
(CDCl3) δ -110.6 (2F, s); 13C NMR (CDCl3) δ 38.6, 57.9, 107.7
(m), 108.4, 118.2 (t, J ) 9.1 Hz), 127.2 (t, J ) 11.1 Hz), 127.6,
149.1, 155.9 (d, J ) 7.0 Hz), 159.3 (d, J ) 7.0 Hz), 161.2;
HRMS(FAB) [M + H]+ calcd for C12H10F2NO3 254.0629, found
254.0621.
C
12H10Cl2NO3 286.0038, found 286.0031.
3-(tr a n s-4′-Nitr ocin n am oyl)oxazolidin -2-on e (2v) (meth-
od B): yield 75%; mp 235.0-236.0 °C; 1H NMR (CDCl3) δ 4.16,
4.51 (4H, AB, J ) 8.0 Hz), 7.76, 8.26 (2H, AB, J ) 8.8 Hz),
7.86, 8.04 (2H, AB, J ) 15.9 Hz); 13C NMR (CDCl3) δ 42.8,
62.2, 120.7, 124.2, 129.1, 140.5, 142.9, 148.6, 153.5, 164.5;
HRMS(FAB) [M + H]+ calcd for C12H11N2O5 263.0668, found
263.0669.
Gen er a l P r oced u r e for th e Rea ction s of Glycin e Ni(II)
Com p lex (S)-1 w ith Mich a el Accep tor s 2a -v. To a suspen-
sion of Ni(II) complex (S)-1 (0.500 mmol) in DMF (2.0 mL) was
added the corresponding Michael acceptor 2 (0.525 mmol).
After the mixture was stirred for 10 min at ambient temper-
ature, DBU (0.01 mL, 0.07 mmol) was added. The reaction was
monitored by TLC (each sample was quenched with 5%
aqueous acetic acid and the products were extracted with
chloroform before being applied to the plate). Upon disappear-
ance of the starting (S)-1, the reaction mixture was poured
into icy 5% aqueous acetic acid (80 mL) and stirred with a
glass bar to initiate crystallization of the product. The crystal-
line product was filtered off, thoroughly washed with water,
and dried in vacuo to afford addition products 3 and 4. The
major diastereomeric products 3 were obtained in diastereo-
merically pure form by recrystallization of the reaction mixture
from benzene/hexanes or by column chromatography on SiO2
(eluent: acetone/chloroform 1/4). Minor reaction products 4
were obtained only by column chromatography on SiO2.
Diastereomers 4 always emerged first from the column. Yields
and ratios of the diastereomeric products 3 and 4 are given in
Table 1; physicochemical and NMR data are listed below.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3S)-3-m eth yl-5-[3′-(2′-oxa zolid in on yl)]glu ta m ic a cid
1
(3a ): mp 241.0-242.0 °C; [R]25 +2665 (c 0.011, CHCl3); H
D
NMR (CDCl3) δ 1.97 (3H, d, J ) 6.6 Hz), 2.02-2.12 (2H, m),
2.41-2.59 (2H, m), 2.78-2.88 (3H, m), 3.34-3.54 (3H, m), 3.60
(1H, part of AB, J ) 12.7 Hz), 3.80-3.87 (2H, m), 4.10 (1H, d,
J ) 5.1 Hz), 4.27-4.34 (2H, m), 4.44 (1H, part of AB, J ) 12.7
Hz), 6.59-6.68 (2H, m), 6.98 (1H, d, J ) 7.3 Hz), 7.11-7.18
(2H, m), 7.27-7.35 (3H, m), 7.43-7.57 (3H, m), 8.04 (2H, d, J
) 7.3 Hz), 8.23 (1H, d, J ) 8.5 Hz); 13C NMR (CDCl3) δ 16.6,
23.1, 30.7, 33.7, 38.4, 42.4, 56.7, 61.8, 63.2, 70.4, 72.7, 120.6,
123.2, 126.3, 127.2, 128.1, 128.7, 129.1, 129.5, 131.5, 132.3,
133.2, 133.6, 134.0, 142.4, 153.1, 171.0, 171.3, 177.4, 180.3;
HRMS(FAB) [M + H]+ calcd for C34H35N4NiO6 653.1910, found
653.1900.
3-(tr a n s-2′-Flu or ocin n am oyl)oxazolidin -2-on e (2r ) (meth-
od B): yield 88%; mp 133.0-134.0 °C; 1H NMR (CDCl3) δ 4.15,
4.47 (4H, AB, J ) 8.0 Hz), 7.08-7.21 (2H, m), 7.35-7.40 (1H,
m), 7.66-7.71 (1H, m), 7.96, 8.05 (2H, AB, J ) 15.9 Hz); 19F
NMR (CDCl3) δ -115.5 (1F, m); 13C NMR (CDCl3) δ 42.8, 62.1,
116.2 (d, J ) 22.1 Hz), 118.7 (d, J ) 5.1 Hz), 122.6 (d, J )
12.4 Hz), 124.4 (d, J ) 4.0 Hz), 129.0 (d, J ) 2.0 Hz), 132.1 (d,
J ) 9.1 Hz), 138.4 (d, J ) 4.1 Hz), 153.5, 159.8, 163.2, 165.2;
HRMS(FAB) [M + H]+ calcd for C12H11FNO3 236.0723, found
236.0722.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3R)-3-m eth yl-5-[3′-(2′-oxa zolid in on yl)]glu ta m ic a cid
(4a ): mp 206.0-207.0 °C; [R]25 -1277 (c 0.021, CHCl3); 1H
D
3-(tr a n s-3′,4′-Diflu or ocin n a m oyl)oxa zolid in -2-on e (2s)
(method B): yield 72%; mp 156.5-157.0 °C; 1H NMR (CDCl3)
δ 4.14, 4.48 (4H, AB, J ) 8.0 Hz), 7.15-7.24 (1H, m), 7.33-
NMR (CDCl3) δ 1.68-1.94 (2H, m), 1.82 (3H, d, J ) 6.8 Hz),
2.10-2.20 (1H, m), 2.44-2.64 (3H, m), 2,77, 2.87 (2H, ABX, J
) 6.7, 7.3, 17.1 Hz), 3.63-3.67 (1H, m), 3.83-4.09 (5H, m),
4.30-4.35 (2H, m), 4.88 (1H, part of AB, J ) 13.4 Hz), 6.71-
6.81 (2H, m), 7.12 (1H, d, J ) 6.6 Hz), 7.23-7.31 (2H, m),
7.39-7.51 (6H, m), 7.64-7.67 (2H, m), 8.53 (1H, d, J ) 8.5
(21) Belokon′, Y. N.; Tararov, V. I.; Maleev, V. I.; Savel’eva, T. F.;
Ryzhov, M. G. Tetrahedron: Asymmetry 1998, 9, 4249.

Reactions between Glycine Complexes and Oxazolidin-2-ones
J . Org. Chem., Vol. 66, No. 4, 2001 1345
Hz); 13C NMR (CDCl3) δ 16.4, 23.5, 30.9, 34.5, 38.6, 42.4, 56.4,
61.1, 61.9, 68.4, 73.1, 120.7, 123.6, 126.0, 127.0, 128.4, 128.6,
128.9, 129.0, 129.2, 129.5, 131.9, 132.0, 132.5, 133.9, 134.3,
142.9, 153.1, 171.0, 172.1, 177.8, 182.2; HRMS(FAB) [M + H]+
calcd for C34H35N4NiO6 653.1910, found 653.1907.
(CDCl3) δ 15.9, 21.9, 23.5, 27.1, 30.4, 30.7, 42.5, 45.4, 57.6,
62.3, 63.5, 70.7, 71.7, 120.5, 122.1, 125.4, 127.7, 128.4, 128.7,
129.1, 129.3, 129.7, 131.2, 132.5, 133.8, 134.1, 142.4, 153.4,
172.0, 172.4, 178.6, 180.3; HRMS(FAB) [M + H]+ calcd for
C36H39N4NiO6 681.2223, found 681.2242.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3S)-3-eth yl-5-[3′-(2′-oxazolidin on yl)]glu tam ic acid (3b):
(2R,3R)-3-isopr opyl-5-[3′-(2′-oxazolidin on yl)]glu tam ic acid
1
1
mp 194.0-195.0 °C; [R]25 +2052 (c 0.032, CHCl3); H NMR
(4d ): mp 134.0-135.0 °C; [R]25 -2189 (c 0.015, CHCl3); H
D
D
(CDCl3) δ 1.05 (3H, t, J ) 7.5 Hz), 1.84-1.94 (1H, m), 2.01-
2.18 (2H, m), 2.31-2.42 (1H, m), 2.46-2.60 (1H, m), 2.77-
3.01 (3H, m), 3.38-3.59 (4H, m), 3.56, 4.42 (2H, AB, J ) 12.7
Hz), 3.73-3.87 (2H, m), 4.15-4.33 (3H, m), 6.58-6.68 (2H,
m), 6.97-7.01 (1H, m), 7.10-7.17 (2H, m), 7.27-7.34 (3H, m),
7.44-7.58 (3H, m), 8.04 (2H, d, J ) 7.1 Hz), 8.22 (1H, d, J )
8.8 Hz); 13C NMR (CDCl3) δ 11.8, 22.9, 23.3, 30.4, 34.5, 39.8,
42.2, 56.7, 61.8, 63.1, 70.3, 71.5, 120.4, 122.9, 126.2, 127.1,
128.0, 128.5, 128.6, 128.9, 129.2, 131.2, 132.0, 133.2, 133.4,
133.7, 142.1, 153.1, 171.1, 177.5, 180.1; HRMS(FAB) [M + H]+
calcd for C35H37N4NiO6 667.2067, found 667.2065.
NMR (CDCl3) δ 0.38 (3H, d, J ) 6.8 Hz), 0.96 (3H, d, J ) 6.8
Hz), 1.44-1.61 (2H, m), 1.91-1.97 (1H, m), 2.18-2.28 (1H,
m), 2.55-2.77 (3H, m), 3.10 (1H, part of ABX, J ) 10.0, 18.3
Hz), 3.40-3.46 (1H, m), 3.76-4.06 (6H, m), 4.16 (1H, part of
AB, J ) 13.7 Hz), 4.22-4.27 (1H, m), 5.47 (1H, part of AB, J
) 13.7 Hz), 6.73-6.89 (2H, m), 7.21-7.51 (11H, m), 8.62 (1H,
d, J ) 8.5 Hz); 13C NMR (CDCl3) δ 16.0, 21.9, 23.7, 27.2, 31.0,
31.1, 42.7, 45.3, 55.5, 60.3, 62.4, 68.7, 71.9, 120.8, 122.7, 125.6,
127.8, 128.7, 128.8, 129.1, 129.3, 129.4, 129.7, 132.0, 132.2,
132.7, 134.0, 134.4, 142.9, 153.5, 171.9, 172.9, 178.8, 182.1;
HRMS(FAB) [M + H]+ calcd for C36H39N4NiO6 681.2223, found
681.2220.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3R)-3-eth yl-5-[3′-(2′-oxazolidin on yl)]glu tam ic acid (4b):
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-p h en yl-5-[3′-(2′-oxa zolid in on yl)]glu ta m ic a cid
1
mp 152.0-153.0 °C; [R]25 -1446 (c 0.023, CHCl3); H NMR
D
(CDCl3) δ 1.01 (3H, t, J ) 7.3 Hz), 1.66-1.91 (3H, m), 2.05-
2.08 (1H, m), 2.36-2.67 (3H, m), 2.87, 3.00 (2H, ABX, J ) 4.9,
8.8, 17.3 Hz), 3.10-3.22 (1H, m), 3.69 (1H, part of ABX, J )
3.7, 9.5 Hz), 3.76-3.91 (2H, m), 3.96-4.36 (4H, m), 4.02, 4.90
(2H, AB, J ) 13.4 Hz), 6.70-6.80 (2H, m), 7.10-7.31 (3H, m),
7.42-7.66 (8H, m), 8.55 (1H, d, J ) 8.5 Hz); 13C NMR (CDCl3)
δ 12.1, 23.3, 23.5, 30.8, 35.0, 40.5, 42.7, 56.5, 60.8, 61.9, 68.5,
71.9, 120.7, 123.4, 126.0, 127.2, 128.5, 128.8, 129.0, 129.2,
129.4, 132.0, 132.5, 134.0, 134.2, 142.9, 153.4, 171.5, 171.9,
178.1, 182.2; HRMS(FAB) [M + H]+ calcd for C35H37N4NiO6
667.2067, found 667.2074.
(3f): mp 158.0-159.0 °C; [R]25 +2303 (c 0.011, CHCl3); 1H
D
NMR (CDCl3) δ 1.47-1.57 (1H, m), 1.94-2.04 (2H, m), 2.14-
2.24 (2H, m), 2.89-2.97 (2H, m), 3,25 (1H, t, J ) 8.6 Hz), 3.42
(1H, part of AB, J ) 12.7 Hz), 3.46-3.52 (1H, m), 3.64-3.81
(3H, m), 4.22-4.31 (4H, m), 6.67 (2H, d, J ) 3.9 Hz), 7.11-
7.21 (3H, m), 7.25-7.38 (5H, m), 7.45-7.62 (6H, m), 7.98 (2H,
d, J ) 7.3 Hz), 8.27 (1H, d, J ) 8.5 Hz); 13C NMR (CDCl3) δ
23.1, 30.7, 37.3, 42.3, 44.9, 57.3, 61.8, 63.6, 70.4, 73.5, 120.5,
123.0, 125.9, 127.2, 127.9, 128.3, 128.7, 128.9, 129.0, 129.3,
129.6, 131.5, 132.5, 133.2, 133.7, 134.3, 138.8, 143.0, 153.0,
170.5, 171.7, 177.1, 180.3; HRMS(FAB) [M + H]+ calcd for
Ni(II) com p lex of Sch iff ba se of (S)-BP B a n d (2S,3S)-
C
39H37N4NiO6 715.2067, found 715.2079.
3-n -p r op yl-5-[3′-(2′-oxa zolid in on yl)]glu ta m ic a cid (3c):
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
1
mp 255.0-256.0 °C; [R]25 +2809 (c 0.017, CHCl3); H NMR
(2R,3S)-3-p h en yl-5-[3′-(2′-oxa zolid in on yl)]glu ta m ic a cid
D
(CDCl3) δ 1.08 (3H, t, J ) 7.2 Hz), 1.21-1.42 (1H, m), 1.53-
1.63 (1H, m), 1.83-2.14 (3H, m), 2.25-2.38 (1H, m), 2.48-
2.61 (1H, m), 2.80-2.92 (1H, m), 2.85, 2.96 (2H, ABX, J ) 4.4,
9.3, 17.3 Hz), 3.43-3.67 (4H, m), 3.59, 4.44 (2H, AB, J ) 12.7
Hz), 3.71-3.86 (2H, m), 4.19-4.34 (3H, m), 6.58 (1H, part of
ABX, J ) 1.8, 8.3 Hz), 6.63-6.68 (1H, m), 6.95-6.98 (1H, m),
7.10-7.17 (2H, m), 7.27-7.34 (3H, m), 7.43-7.58 (3H, m), 8.03
(2H, d, J ) 7.3 Hz), 8.23 (1H, d, J ) 8.1 Hz); 13C NMR (CDCl3)
δ 14.2, 20.6, 22.9, 30.5, 32.8, 35.0, 38.0, 42.3, 56.6, 61.8, 63.2,
70.4, 71.6, 120.5, 123.0, 126.3, 127.2, 128.0, 128.5, 128.6, 128.9,
129.3, 131.3, 132.1, 133.1, 133.5, 133.9, 142.2, 153.2, 171.1,
171.2, 177.6, 180.1; HRMS(FAB) [M + H]+ calcd for C36H39N4-
NiO6 681.2223, found 681.2239.
(4f): mp 164.0-165.5 °C; [R]25 -2102 (c 0.010, CHCl3); 1H
D
NMR (CDCl3) δ 1.11-1.40 (2H, m), 1.79-1.86 (1H, m), 2.00-
2.13 (1H, m), 2.46-2.55 (1H, m), 3.10 (1H, part of ABX, J )
6.6, 17.6 Hz), 3.33 (1H, part of ABX, J ) 3.2, 9.5 Hz), 3.43
(1H, part of AB, J ) 13.9 Hz), 3.48-3.54 (1H, m), 3.62 (1H,
part of AB, J ) 14.2 Hz), 3.66-3.84 (4H, m), 4.28 (2H, t, J )
8.3 Hz), 4.34 (1H, d, J ) 3.9 Hz), 6.73-6.83 (2H, m), 7.15-
7.17 (2H, m), 7.24-7.36 (6H, m), 7.50-7.61 (8H, m), 8.44 (1H,
d, J ) 8.5 Hz); 13C NMR (CDCl3) δ 23.6, 31.3, 36.7, 42.3, 45.2,
55.1, 59.5, 61.8, 68.6, 73.7, 120.7, 123.5, 126.3, 127.2, 128.1,
128.3, 128.7, 128.8, 129.1, 129.3, 129.7, 130.3, 131.7, 131.9,
132.7, 133.9, 134.2, 139.0, 143.2, 153.0, 170.4, 171.6, 176.8,
181.6; HRMS(FAB) [M + H]+ calcd for C39H37N4NiO6 715.2067,
found 715.2070.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3R)-3-n -pr opyl-5-[3′-(2′-oxazolidin on yl)]glu tam ic acid
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-r-n a p h t h yl-5-[3′-(2′-oxa zolid in on yl)]glu t a m ic
a cid (3g): mp 185.0-186.0 °C; [R]25D +1768 (c 0.014, CHCl3);
1H NMR (CDCl3) δ 1.19-1.33 (2H, m), 1.47-1.59 (1H, m),
1.75-1.94 (2H, m), 2.58 (1H, part of ABX, J ) 5.8, 11.4 Hz),
2.65 (1H, part of ABX, J ) 4.4, 17.3 Hz), 3.03 (1H, part of
ABX, J ) 7.8, 9.3 Hz), 3.30, 4.11 (2H, AB, J ) 12.7 Hz), 3.54-
3.71 (2H, m), 4.16-4.34 (3H, m), 4.37 (1H, d, J ) 2.9 Hz),
4.47-4.53 (1H, m), 6.67-6.80 (2H, m), 7.08-7.34 (8H, m),
7.44-7.63 (6H, m), 7.86-7.96 (4H, m), 8.32 (1H, d, J ) 8.1
Hz); 13C NMR (CDCl3) δ 22.7, 30.0, 38.6, 39.4, 42.0, 56.9, 61.6,
63.0, 70.0, 75.1, 120.0, 122.7, 123.2, 125.2, 125.7, 126.0, 126.9,
127.3, 127.8, 128.3, 128.5, 128.8, 129.1, 129.4, 131.1, 132.3,
133.0, 133.2, 133.4, 133.8, 133.9, 135.2, 142.8, 152.8, 170.0,
171.5, 176.7, 179.6; HRMS(FAB) [M + H]+ calcd for C43H39N4-
NiO6 765.2223, found 765.2236.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3S)-3-r-n a p h t h yl-5-[3′-(2′-oxa zolid in on yl)]glu t a m ic
a cid (4g): mp 255.0-256.0 °C; [R]25D -1171 (c 0.033, CHCl3);
1H NMR (CDCl3) δ 1.04-1.30 (2H, m), 1.62-1.78 (1H, m),
1.98-2.32 (2H, m), 2.75-3.06 (4H, m), 3.50-3.76 (3H, m),
4.22-4.57 (5H, m), 6.76-7.01 (4H, m), 7.24-7.62 (13H, m),
7.78 (1H, d, J ) 8.1 Hz), 7.95-8.01 (2H, m), 8.49 (1H, d, J )
8.8 Hz); 13C NMR (CDCl3) δ 23.4, 31.0, 38.2, 40.3, 42.3, 54.3,
58.7, 61.9, 67.9, 75.9, 120.5, 123.6, 123.9, 125.5, 125.8, 126.1,
1
(4c): mp 129.0-130.0 °C; [R]25 -1190 (c 0.032, CHCl3); H
D
NMR (CDCl3) δ 1.03 (3H, t, J ) 7.2 Hz), 1.30-1.96 (5H, m),
2.05-2.18 (1H, m), 2.43-2.68 (3H, m), 2.87, 3.02 (2H, ABX, J
) 4.6, 8.8, 17.3 Hz), 3.20-3.31 (1H, m), 3.68 (1H, part of ABX,
J ) 3.8, 9.6 Hz), 3.75-4.01 (3H, m), 4.08, 4.97 (2H, AB, J )
13.3 Hz), 4.22-4.35 (3H, m), 6.70-6.79 (2H, m), 7.10-7.12
(1H, m), 7.20-7.31 (2H, m), 7.39-7.63 (8H, m), 8.53 (1H, d, J
) 8.5 Hz); 13C NMR (CDCl3) δ 14.3, 20.5, 23.5, 29.2, 30.9, 32.7,
35.5, 42.4, 56.1, 60.9, 61.9, 68.3, 72.0, 120.7, 123.4, 126.1, 127.1,
128.4, 128.6, 128.8, 129.0, 129.2, 129.4, 131.8, 132.1, 132.5,
133.9, 134.2, 142.8, 153.3, 171.4, 171.9, 178.2, 182.1;
HRMS(FAB) [M + H]+ calcd for C36H39N4NiO6 681.2223, found
681.2228.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3S)-3-i-p r op yl-5-[3′-(2′-oxa zolid in on yl)]glu ta m ic a cid
1
(3d ): mp 155.0-156.0 °C; [R]25 +2699 (c 0.029, CHCl3); H
D
NMR (CDCl3) δ 0.40 (3H, d, J ) 6.8 Hz), 0.95 (3H, d, J ) 6.8
Hz), 2.06-2.18 (2H, m), 2.43-2.70 (3H, m), 2.87-2.96 (1H,
m), 2.92 (1H, part of ABX, J ) 9.8, 18.1 Hz), 3.28-3.34 (1H,
m), 3.40 (1H, part of AB, J ) 12.5 Hz), 3.47 (1H, dd, J ) 6.0,
11.2 Hz), 3.55-2.60 (1H, m), 3.70-3.92 (5H, m), 4.13-4.18
(1H, m), 4.39 (1H, part of AB, J ) 12.7 Hz), 6.63-6.75 (2H,
m), 7.00-7.11 (2H, m), 7.22-7.28 (4H, m), 7.48-7.58 (3H, m),
8.09 (2H, d, J ) 7.3 Hz), 8.33 (1H, d, J ) 8.5 Hz); 13C NMR

1346 J . Org. Chem., Vol. 66, No. 4, 2001
Cai et al.
126.3, 126.5, 127.2, 127.7, 128.1, 128.5, 128.6, 128.9, 129.3,
129.6, 131.4, 131.8, 132.8, 133.6, 133.9, 134.1, 134.2, 135.4,
143.4, 153.1, 170.3, 171.7, 176.9, 181.1; HRMS(FAB) [M + H]+
calcd for C43H39N4NiO6 765.2223, found 765.2231.
m), 7.11-7.20 (3H, m), 7.25-7.40 (4H, m), 7.52-7.60 (3H, m),
7.99 (2H, d, J ) 7.1 Hz), 8.29 (1H, d, J ) 8.5 Hz); 13C NMR
(CDCl3) δ 23.1, 30.7, 37.1, 42.3, 45.1, 55.1, 57.3, 61.8, 63.5,
70.4, 73.4, 114.0, 114.2, 120.4, 122.1, 123.0, 125.8, 127.2, 128.3,
128.6, 128.9, 129.2, 129.6, 129.8, 131.5, 132.4, 133.2, 133.7,
134.2, 140.2, 143.0, 153.0, 159.9, 170.4, 171.6, 177.1, 180.2;
HRMS(FAB) [M + H]+ calcd for C40H39N4NiO7 745.2172, found
745.2161.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3S)-3-(3′-m et h oxyp h en yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (4j): mp 267.0-268.0 °C; [R]25D -2005 (c 0.021,
CHCl3); 1H NMR (CDCl3) δ 1.17-1.43 (2H, m), 1.82-1.89 (1H,
m), 2.09-2.18 (1H, m), 2.43-2.52 (1H, m), 3.01 (1H, part of
ABX, J ) 6.3, 17.6 Hz), 3.36 (1H, dd, J ) 3.4, 9.5 Hz), 3.46-
3.51 (1H, m), 3.54 (1H, part of AB, J ) 14.2 Hz), 3.63 (3H, s),
3.71-3.90 (5H, m), 4.25-4.32 (3H, m), 6.73-6.84 (2H, m),
7.00-7.08 (3H, m), 7.18-7.56 (12H, m), 8.49 (1H, d, J ) 8.5
Hz); 13C NMR (CDCl3) δ 23.6, 31.2, 36.6, 42.2, 45.3, 54.9, 55.0,
59.5, 61.8, 68.4, 73.7, 114.1, 114.8, 120.6, 122.5, 123.5, 126.1,
127.2, 128.3, 128.7, 129.3, 129.7, 129.8, 131.6, 131.9, 132.7,
133.9, 134.1, 140.4, 143.2, 153.0, 160.1, 170.4, 171.5, 176.8,
181.6; HRMS(FAB) [M + H]+ calcd for C40H39N4NiO7 745.2172,
found 745.2174.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-â-n a p h t h yl-5-[3′-(2′-oxa zolid in on yl)]glu t a m ic
a cid (3h ): mp 159.0-160.0 °C; [R]25D +1344 (c 0.018, CHCl3);
1H NMR (CDCl3) δ 0.76-1.00 (2H, m), 1.31-1.47 (1H, m),
1.73-1.84 (2H, m), 2.53-2.64 (1H, m), 2.98, 3.94 (2H, ABX, J
) 5.9, 9.0, 17.3 Hz), 3.07 (1H, t, J ) 8.6 Hz), 3.25, 4.13 (2H,
AB, J ) 12.5 Hz), 3.58-3.78 (3H, m), 4.18-4.30 (2H, m), 4.36
(1H, d, J ) 3.9 Hz), 6.65-6.73 (2H, m), 7.08-7.17 (2H, m),
7.22-7.36 (4H, m), 7.43-7.64 (6H, m), 7.89-7.92 (4H, m), 7.96
(2H, d, J ) 7.8 Hz), 8.23 (1H, d, J ) 8.5 Hz); 13C NMR (CDCl3)
δ 22.3, 30.1, 37.1, 42.1, 44.8, 57.4, 61.7, 63.5, 70.1, 73.5, 120.2,
122.9, 125.7, 126.0, 126.2, 127.0, 127.4, 127.9, 128.1, 128.4,
128.5, 128.8, 129.1, 129.5, 131.3, 132.3, 133.1, 133.2, 133.5,
133.8, 134.1, 136.2, 142.9, 152.9, 170.2, 171.4, 176.9, 180.1;
HRMS(FAB) [M + H]+ calcd for C43H39N4NiO6 765.2223, found
765.2234.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3S)-3-â-n a p h t h yl-5-[3′-(2′-oxa zolid in on yl)]glu t a m ic
a cid (4h ): mp 162.0-163.0 °C; [R]25D -1208 (c 0.051, CHCl3);
1H NMR (CDCl3) δ 0.88-1.02 (1H, m), 1.12-1.26 (1H, m),
1.63-1.73 (1H, m), 1.84-2.00 (1H, m), 2.35-2.44 (1H, m), 2.63
(1H, part of AB, J ) 14.1 Hz), 2.77-2.85 (1H, m), 3.06 (1H,
part of AB, J ) 14.1 Hz), 3.14 (1H, part of ABX, J ) 6.1, 17.8
Hz), 3.64-3.79 (4H, m), 3.97 (1H, part of ABX, J ) 8.4, 17.7
Hz), 4.21-4.33 (2H, m), 4.38 (1H, d, J ) 3.7 Hz), 6.52 (2H, d,
J ) 7.3 Hz), 6.75-6.86 (2H, m), 7.12-7.57 (12H, m), 7.87-
7.93 (2H, m), 8.02 (1H, d, J ) 8.3 Hz), 8.10 (1H, s), 8.44 (1H,
d, J ) 8.5 Hz); 13C NMR (CDCl3) δ 23.5, 31.2, 36.6, 42.2, 45.4,
54.8, 59.4, 61.8, 68.6, 73.9, 120.6, 123.5, 126.2, 126.6, 127.2,
127.7, 128.1, 128.2, 128.4, 128.9, 129.3, 129.7, 131.2, 131.6,
132.7, 133.3, 133.9, 134.1, 136.4, 143.3, 153.0, 170.3, 171.5,
176.7, 181.4; HRMS(FAB) [M + H]+ calcd for C43H39N4NiO6
765.2223, found 765.2237.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-(2′-m et h oxyp h en yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (3i): mp 179.0-180.0 °C; [R]25D +2329 (c 0.018,
CHCl3); 1H NMR (CDCl3) δ 1.40-1.54 (1H, m), 1.76-1.92 (1H,
m), 1.97-2.24 (3H, m), 2.87-2.98 (1H, m), 2.98 (1H, part of
ABX, J ) 6.6, 17.6 Hz), 3.23-3.32 (1H, m), 3.30 (3H, s), 3.44
(1H, part of AB, J ) 12.5 Hz), 3.64-3.80 (3H, m), 4.20-4.29
(5H, m), 6.64-6.71 (2H, m), 7.04-7.15 (4H, m), 7.24-7.30 (3H,
m), 7.37-7.47 (3H, m), 7.51-7.61 (3H, m), 7.99 (2H, d, J )
7.1 Hz), 8.30 (1H, d, J ) 8.5 Hz); 13C NMR (CDCl3) δ 23.0,
30.6, 30.8, 36.5, 42.2, 54.8, 57.2, 61.7, 63.6, 70.1, 73.4, 110.4,
120.1, 121.3, 122.7, 125.9, 127.1, 127.6, 128.5, 128.6, 128.7,
128.9, 129.4, 131.4, 132.0, 133.2, 133.4, 134.4, 142.6, 152.9,
158.0, 170.5, 171.8, 177.3, 180.2; HRMS(FAB) [M + H]+ calcd
for C40H39N4NiO7 745.2172, found 745.2180.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-(4′-m et h oxyp h en yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (3k ): mp 155.0-156.0 °C; [R]25 +2294 (c
D
1
0.013, CHCl3); H NMR (CDCl3) δ 1.49-1.60 (1H, m), 1.97-
2.24 (4H, m), 2.87 (1H, part of ABX, J ) 5.9, 17.3 Hz), 3.00
(1H, part of ABX, J ) 5.3, 10.2 Hz), 3.24-3.46 (3H, m), 3.64-
3.80 (3H, m), 3.83 (3H, s), 4.23-4.28 (4H, m), 6.66 (2H, d, J )
3.9 Hz), 7.02 (2H, d, J ) 8.1 Hz), 7.10-7.32 (8H, m), 7.52-
7.59 (3H, m), 8.00 (2H, d, J ) 7.3 Hz), 8.25 (1H, d, J ) 9.0
Hz); 13C NMR (CDCl3) δ 22.9, 30.6, 37.2, 42.2, 44.2, 55.2, 57.4,
61.8, 63.6, 70.4, 73.6, 114.2, 120.4, 122.9, 125.9, 127.2, 128.2,
128.6, 128.8, 129.2, 129.6, 130.6, 131.5, 132.3, 133.2, 133.6,
134.2, 142.9, 153.0, 159.3, 170.4, 171.4, 177.1, 180.2;
HRMS(FAB) [M + H]+ calcd for C40H39N4NiO7 745.2172, found
745.2179.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3S)-3-(4′-m et h oxyp h en yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (4k ): mp 154.0-155.0 °C; [R]25 -2047 (c
D
1
0.018, CHCl3); H NMR (CDCl3) δ 1.14-1.45 (2H, m), 1.79-
2.13 (2H, m), 2.48-2.57 (1H, m), 3.04 (1H, part of ABX, J )
6.6, 17.6 Hz), 3.35 (1H, dd, J ) 3.2, 9.5 Hz), 3.43-3.50 (1H,
m), 3.48 (1H, party of AB, J ) 13.9 Hz), 3.65 (3H, s), 3.71-
3.84 (5H, m), 4.25-4.31 (3H, m), 6.73-6.82 (2H, m), 7.09 (2H,
part of AB, J ) 8.5 Hz), 7.17-7.36 (8H, m), 7.44 (2H, part of
AB, J ) 8.8 Hz), 7.54-7.56 (3H, m), 8.44 (1H, d, J ) 8.5 Hz);
13C NMR (CDCl3) δ 23.6, 31.3, 36.7, 42.2, 44.4, 54.9, 55.0, 59.6,
61.8, 68.5, 73.8, 114.2, 120.6, 123.4, 126.3, 127.2, 128.2, 128.6,
128.7, 128.8, 129.2, 129.7, 130.7, 131.2, 131.6, 131.9, 132.6,
133.9, 134.1, 143.2, 153.0, 159.5, 170.4, 171.4, 176.8, 181.6;
HRMS(FAB) [M + H]+ calcd for C40H39N4NiO7 745.2172, found
745.2181.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3S)-3-(2′-m et h oxyp h en yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (4i): mp 169.0-170.0 °C; [R]25D -1889 (c 0.015,
CHCl3); 1H NMR (CDCl3) δ 1.09-1.41 (2H, m), 1.78-1.85 (1H,
m), 2.02-2.15 (1H, m), 2.45-2.54 (1H, m), 3.16 (1H, part of
ABX, J ) 7.1, 18.3 Hz), 3.30 (1H, part of ABX, J ) 3.2, 9.5
Hz), 3.38 (3H, s), 3.48 (1H, part of AB, J ) 14.2 Hz), 3.60-
3.86 (5H, m), 4.23-4.31 (4H, m), 6.72-6.83 (2H, m), 7.08-
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-(2′-t r iflu or om et h ylp h en yl)-5-[3′-(2′-oxa zolid i-
n on yl)]glu ta m ic a cid (3l): mp 166.0-167.0 °C; [R]25D +1989
(c 0.019, CHCl3); 1H NMR (CDCl3) δ 1.64-1.80 (1H, m), 1.96-
2.05 (1H, m), 2.26-2.52 (2H, m), 2.60-2.76 (1H, m), 3.10-
3.18 (1H, m), 3.11 (1H, part of ABX, J ) 6.4, 16.4 Hz), 3.34
(1H, dd, J ) 7.0, 9.9 Hz), 3.40 (1H, part of AB, J ) 12.7 Hz),
3.47 (1H, part of ABX, J ) 7.6, 17.1 Hz), 3.67-3.72 (2H, m),
4.06 (1H, dd, J ) 8.4, 16.8 Hz), 4.16-4.42 (4H, m), 6.63-6.72
(2H, m), 7.07-7.17 (3H, m), 7.24-7.34 (4H, m), 7.43-7.56 (5H,
m), 7.79 (1H, d, J ) 7.6 Hz), 8.01 (2H, d, J ) 7.1 Hz), 8.37
(1H, d, J ) 8.5 Hz); 19F NMR (CDCl3) δ -58.2 (3F, s); 13C NMR
(CDCl3) δ 23.0, 30.5, 38.7, 40.6, 42.1, 57.1, 61.8, 63.2, 70.5,
74.4, 120.1, 122.4, 125.3, 126.1 (q, J ) 6.0 Hz), 127.1, 127.4,
128.1, 128.3, 128.4, 129.0, 129.1, 129.5, 129.7, 131.1, 132.2,
132.3, 133.3, 133.7, 133.8, 138.2, 142.7, 152.9, 169.3, 172.5,
176.6, 179.9; HRMS(FAB) [M + H]+ calcd for C40H36F3N4NiO6
783.1940, found 783.1934.
7.36 (9H, m), 7.43-7.58 (6H, m), 8.41 (1H, d, J ) 8.5 Hz); 13
C
NMR (CDCl3) δ 23.6, 30.9, 31.2, 35.7, 36.3, 42.2, 54.8, 59.2,
61.7, 68.5, 74.1, 110.3, 120.3, 121.4, 123.2, 126.4, 127.1, 127.9,
128.5, 128.6, 128.7, 128.8, 128.9, 129.4, 129.5, 131.8, 132.1,
133.6, 134.3, 142.9, 153.0, 158.4, 170.5, 171.9, 177.0, 181.5;
HRMS(FAB) [M + H]+ calcd for C40H39N4NiO7 745.2172, found
745.2185.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-(3′-m et h oxyp h en yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (3j): mp 271.0-272.0 °C; [R]25D +2309 (c 0.016,
CHCl3); 1H NMR (CDCl3) δ 1.51-1.63 (1H, m), 1.98-2.27 (4H,
m), 2.87 (1H, part of ABX, J ) 6.0, 17.2 Hz), 2.99 (1H, part of
ABX, J ) 5.8, 10.9 Hz), 3.24-3.29 (1H, m), 3.43 (1H, part of
AB, J ) 12.5 Hz), 3.43-3.49 (1H, m), 3.64-3.85 (3H, m), 3.75
(3H, s), 4.24-4.29 (4H, m), 6.66-6.68 (2H, m), 6.90-7.01 (3H,
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3S)-3-(2′-t r iflu or om et h ylp h en yl)-5-[3′-(2′-oxa zolid i-
n on yl)]glu ta m ic a cid (4l): mp 160.0-161.5 °C; [R]25D -1401

Reactions between Glycine Complexes and Oxazolidin-2-ones
J . Org. Chem., Vol. 66, No. 4, 2001 1347
(c 0.025, CHCl3); 1H NMR (CDCl3) δ 1.28-1.42 (2H, m), 1.62-
1.78 (1H, m), 1.87-1.96 (1H, m), 2.10-2.22 (1H, m), 2.38-
2.64 (1H, m), 3.29 (1H, dd, J ) 5.6, 7.8 Hz), 3.53-3.55 (1H,
m), 3.63 (1H, part of AB, J ) 13.9 Hz), 3.73-3.78 (3H, m),
3.90-4.06 (1H, m), 4.19-4.37 (4H, m), 6.71-6.83 (2H, m),
6.91-7.09 (1H, m), 7.37-7.53 (13H, m), 7.84 (1H, d, J ) 7.6
Hz), 8.57 (1H, d, J ) 8.5 Hz); 19F NMR (CDCl3) δ -58.1 (3F,
s); 13C NMR (CDCl3) δ 23.7, 31.4, 38.7, 41.0, 42.3, 55.0, 60.1,
62.0, 68.5, 74.7, 120.6, 123.3, 126.0, 126.6 (q, J ) 6.6 Hz),
127.3, 127.7, 128.4, 128.7, 128.9, 129.2, 129.7, 130.4, 131.6,
132.0, 132.5, 132.9, 134.0, 134.1, 138.2, 143.2, 153.2, 169.7,
173.3, 177.2, 181.8; HRMS(FAB) [M + H]+ calcd for C40H36F3N4-
NiO6 783.1940, found 783.1942.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2S,
3R)-3-[3′-(1′-m esitylen esu lfon yl)]in d olyl-5-[3′-(2′-oxa zoli-
d in on yl)]glu ta m ic a cid (3o): mp 185.0-186.0 °C; [R]25
D
+1815 (c 0.025, CHCl3); 1H NMR (CDCl3) δ 1.12-1.46 (2H,
m), 1.52-1.96 (3H, m), 2.26 (3H, s), 2.55 (6H, s), 2.65-2.86
(2H, m), 3.10-3.15 (1H, m), 3.32 (1H, part of AB, J ) 12.7
Hz), 3.66-3.91 (4H, m), 4.21-4.34 (4H, m), 6.66-6.77 (2H,
m), 6.93 (2H, s), 7.05-7.44 (10H, m), 7.54-7.64 (4H, m), 7.96
(2H, d, J ) 7.1 Hz), 8.33 (1H, d, J ) 8.8 Hz); 13C NMR (CDCl3)
δ 20.9, 22.6, 22.7, 30.1, 37.4, 37.6, 42.3, 57.5, 61.9, 63.2, 70.0,
73.8, 112.3, 117.5, 120.3, 120.7, 122.9, 123.2, 124.6, 125.4,
125.5, 127.1, 128.1, 128.5, 129.0, 129.4, 129.6, 131.3, 132.3,
132.5, 132.7, 133.3, 133.6, 134.2, 134.8, 140.2, 143.1, 143.9,
153.0, 170.0, 171.8, 177.2, 180.3; HRMS(FAB) [M + H]+ calcd
for C50H48N5NiO8S 936.2577, found 936.2597.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-(3′-t r iflu or om et h ylp h en yl)-5-[3′-(2′-oxa zolid i-
n on yl)]glu ta m ic a cid (3m ): mp 164.0-165.0 °C; [R]25
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2R,
3S)-3-[3′-(1′-m esitylen esu lfon yl)]in d olyl-5-[3′-(2′-oxa zoli-
D
+1902 (c 0.022, CHCl3); 1H NMR (CDCl3) δ 1.54-1.66 (2H,
m), 1.92-2.32 (3H, m), 2.92-3.01 (2H, m), 3.28 (1H, part of
ABX, J ) 6.8, 9.5 Hz), 3.41 (1H, part of AB, J ) 12.7 Hz),
3.59-3.82 (4H, m), 4.23-4.30 (4H, m), 6.65-6.72 (2H, m),
7.11-7.22 (3H, m), 7.26-7.37 (3H, m), 7.48-7.72 (7H, m), 7.98
(2H, d, J ) 7.1 Hz), 8.32 (1H, d, J ) 8.5 Hz); 19F NMR (CDCl3)
δ -63.4 (3F, s); 13C NMR (CDCl3) δ 22.9, 30.3, 37.2, 42.1, 44.9,
57.2, 61.8, 63.3, 70.1, 73.2, 120.3, 122.8, 124.6 (q, J ) 4.1 Hz),
125.4, 127.0, 128.1, 128.5, 128.8, 129.0, 129.2, 129.6, 131.2,
132.5, 133.2, 133.4, 133.6, 133.9, 140.1, 152.9, 169.8, 172.0,
176.5, 180.2; HRMS(FAB) [M + H]+ calcd for C40H36F3N4NiO6
783.1940, found 783.1959.
d in on yl)]glu ta m ic a cid (4o): mp 174.0-175.0 °C; [R]25
D
-1541 (c 0.031, CHCl3); 1H NMR (CDCl3) δ 1.05-1.38 (2H,
m), 1.61-1.88 (2H, m), 2.13 (3H, s), 2.27-2.40 (1H, m), 2.49
(6H, s), 2.57-2.70 (1H, m), 2.86-3.07 (3H, m), 3.74-4.09 (5H,
m), 4.29-4.34 (3H, m), 6.76-6.91 (6H, m), 7.22-7.35 (9H, m),
7.55-7.61 (4H, m), 7.75 (1H, d, J ) 6.1 Hz), 8.55 (1H, d, J )
8.5 Hz); 13C NMR (CDCl3) δ 21.1, 22.6, 23.4, 31.1, 37.1, 38.8,
42.4, 54.5, 58.8, 61.9, 68.2, 74.4, 112.5, 117.6, 120.8, 122.0,
123.0, 124.0, 124.6, 125.5, 125.8, 127.1, 128.2, 128.5, 129.0,
129.5, 129.7, 131.1, 131.9, 132.2, 132.3, 132.9, 133.9, 134.3,
135.3, 140.2, 143.3, 144.0, 153.0, 170.2, 172.1, 177.3, 181.7;
HRMS(FAB) [M + H]+ calcd for C50H48N5NiO8S 936.2577,
found 936.2569.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3S)-3-(3′-t r iflu or om et h ylp h en yl)-5-[3′-(2′-oxa zolid i-
n on yl)]glu ta m ic a cid (4m ): mp 166.0-167.0 °C; [R]25
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2S,
3R)-3-pen taflu or oph en yl-5-[3′-(2′-oxazolidin on yl)]glu tam -
D
1
-957.2 (c 0.021, CHCl3); H NMR (CDCl3) δ 1.33-1.47 (2H,
m), 1.87-1.94 (1H, m), 2.23-2.42 (2H, m), 3.00 (1H, part of
ABX, J ) 5.6, 17.6 Hz), 3.32 (1H, part of ABX, J ) 4.2, 9.8
Hz), 3.46 (1H, part of AB, J ) 13.7 Hz), 3.59-3.90 (6H, m),
4.28-4.33 (3H, m), 6.75-6.88 (2H, m), 7.13-7.17 (2H, m),
7.29-7.37 (6H, m), 7.56-7.71 (7H, m), 8.58 (1H, d, J ) 8.5
Hz); 19F NMR (CDCl3) δ -63.4 (3F, s); 13C NMR (CDCl3) δ 23.6,
31.3, 36.7, 42.3, 45.6, 54.7, 59.3, 61.9, 67.9, 73.8, 120.8, 123.6,
124.8, 125.6, 126.6 (q, J ) 4.0 Hz), 127.1, 128.4, 128.7, 128.9,
129.4, 130.8, 131.1, 131.5, 132.0, 133.0, 133.2, 133.9, 134.2,
140.2, 143.4, 153.0, 170.0, 172.4, 176.6, 182.0; HRMS(FAB)
[M + H]+ calcd for C40H36F3N4NiO6 783.1940, found 783.1939.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2S,3R)-3-(4′-t r iflu or om et h ylp h en yl)-5-[3′-(2′-oxa zolid i-
n on yl)]glu ta m ic a cid (3n ): mp 179.0-180.5 °C; [R]25D +2152
(c 0.028, CHCl3); 1H NMR (CDCl3) δ 1.50-1.62 (1H, m), 1.86-
1.95 (2H, m), 2.08-2.30 (2H, m), 2.83 (1H, part of ABX, J )
5.5, 17.7 Hz), 2.89-2.94 (1H, m), 3.25 (1H, dd, J ) 7.4, 9.6
Hz), 3.43 (1H, part of AB, J ) 12.7 Hz), 3.51-3.58 (1H, m),
3.65-3.84 (3H, m), 4.20-4.30 (4H, m), 6.68(2H, d, J ) 3.9 Hz),
7.10-7.34 (6H, m), 7.47 (2H, part of AB, J ) 8.1 Hz), 7.54-
7.64 (3H, m), 7.75 (2H, part of AB, J ) 8.1 Hz), 7.97 (2H, d, J
) 7.1 Hz), 8.31 (1H, d, J ) 8.8 Hz); 19F NMR (CDCl3) δ -63.5
(3F, s); 13C NMR (CDCl3) δ 22.7, 30.5, 37.1, 42.1, 44.7, 57.0,
61.8, 63.4, 70.2, 73.1, 120.4, 122.9, 125.6, 125.7 (q, J ) 4.0
Hz), 127.0, 128.1, 128.6, 128.8, 129.3, 129.7, 129.8, 131.3,
132.6, 133.2, 133.6, 134.1, 142.9, 143.0, 152.9, 169.8, 172.0,
176.6, 180.2; HRMS(FAB) [M + H]+ calcd for C40H36F3N4NiO6
783.1940, found 783.1973.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d
(2R,3S)-3-(4′-t r iflu or om et h ylp h en yl)-5-[3′-(2′-oxa zolid i-
n on yl)]glu ta m ic a cid (4n ): mp 170.0-171.0 °C; [R]25D -1690
(c 0.014, CHCl3); 1H NMR (CDCl3) δ 1.32-1.49 (2H, m), 1.82-
1.92 (1H, m), 2.14-2.26 (1H, m), 2.38-2.47 (1H, m), 3.02 (1H,
part of ABX, J ) 5.9, 17.8 Hz), 3.34 (1H, dd, J ) 3.7, 9.5 Hz),
3.50 (1H, part of AB, J ) 13.7 Hz), 3.58-3.90 (6H, m), 4.28-
4.33 (3H, m), 6.75-6.86 (2H, m), 7.14-7.17 (2H, m), 7.24-
7.36 (6H, m), 7.56-7.59 (5H, m), 7.79 (2H, d, J ) 8.1 Hz), 8.54
(1H, d, J ) 8.5 Hz); 19F NMR (CDCl3) δ -63.2 (3F, s); 13C NMR
(CDCl3) δ 23.7, 31.4, 36.8, 42.3, 45.3, 54.7, 59.6, 61.9, 68.3,
73.6, 120.8, 123.4, 125.7 (q, J ) 4.1 Hz), 127.2, 128.3, 128.7,
128.9, 129.5, 129.9, 130.3, 130.8, 131.9, 133.0, 134.0, 134.2,
143.2, 143.4, 153.0, 170.0, 172.2, 176.7, 182.0; HRMS(FAB)
[M + H]+ calcd for C40H36F3N4NiO6 783.1940, found 783.1952.
ic a cid (3p ): mp 165.0-166.0 °C; [R]25 +2008 (c 0.042,
D
CHCl3);1H NMR (CDCl3) δ 2.10-2.36 (2H, m), 2.49-2.63 (1H,
m), 2.76-2.88 (1H, m), 3.02, 3.23 (2H, ABX, J ) 4.2, 10.5, 18.6
Hz), 3.42, 4.33 (2H, AB, J ) 12.7 Hz), 3.48-3.54 (2H, m), 3.72-
4.00 (3H, m), 4.09 (1H, d, J ) 10.7 Hz), 4.26-4.38 (2H, m),
5.52 (1H, ddd, J ) 4.2 Hz), 6.68-6.73 (1H, m), 6.79 (1H, part
of ABX, J ) 1.7, 8.3 Hz), 7.08-7.18 (2H, m), 7.22-7.34 (4H,
m), 7.51-76.0(3H, m), 8.10 (2H, d, J ) 7.1 Hz), 8.21 (1H, d, J
) 8.5 Hz); 19F NMR (CDCl3) δ -162.9 (m), -162.4 (m), -155.9
(m), -142.2 (m), -141.3 (m); 13C NMR (CDCl3) δ 23.5, 30.6,
35.7, 38.0, 42.1, 57.5, 62.2, 63.1, 70.6, 71.1, 112.6 (m), 120.6,
122.6, 125.5, 127.4, 128.5, 128.6, 128.8, 129.0, 129.4, 130.1,
131.0, 132.7, 132.9, 133.5, 134.1, 135.5 (m), 138.6 (m), 141.9
(m), 142.7, 143.2 (m), 147.0 (m), 153.0, 169.8, 172.6, 175.6,
180.1; HRMS(FAB) [M + H]+ calcd for C39H32F5N4NiO6
805.1595, found 805.1603.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2R,
3S)-3-pen taflu or oph en yl-5-[3′-(2′-oxazolidin on yl)]glu tam -
ic a cid (4p ): mp 161.5-162.0 °C; [R]25 -1651 (c 0.021,
D
CHCl3); 1H NMR (CDCl3) δ 1.60-1.79 (2H, m), 1.97-2.09 (1H,
m), 2.15-2.30 (1H, m), 2.75-2.84 (1H, m), 3.21, 3.36 (2H, ABX,
J ) 4.6, 10.0, 18.3 Hz), 3.72-4.13 (4H, m), 3.78, 4.80 (2H, AB,
J ) 13.2 Hz), 4.17 (1H, d, J ) 10.0 Hz), 4,31-4.43 (2H, m),
5.16 (1H, td, J ) 4.6, 10.0 Hz), 6.75-6.80 (1H, m), 6.93 (1H,
d, J ) 8.1 Hz), 7.22-7.34 (3H, m), 7.40-7.73 (8H, m), 8.60
(1H, d, J ) 8.8 Hz); 19F NMR (CDCl3) δ -163.0 (m), -162.4
(m), -156.0 (m), -141.7 (m), -140.6 (m); 13C NMR (CDCl3) δ
23.3, 30.7, 36.0, 37.2, 42.4, 56.6, 60.0, 62.4, 68.3, 71.4, 130.0
(m), 120.9, 122.9, 125.4, 127.5, 128.4, 128.5, 129.1, 129.2, 129.7,
130.2, 131.8, 131.9, 132.0, 132.1, 133.4, 133.5, 134.8, 135.6 (m),
138.9 (m), 140.1 (m), 143.4, 144.8 (m), 147.2 (m), 153.4, 170.0,
173.8, 176.4, 181.9; HRMS(FAB) [M + H]+ calcd for C39H32F5N4-
NiO6 805.1595, found 805.1609.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2S,
3R )-3-(2′,6′-d iflu or op h e n yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (3q): mp 168.5-170.0 °C; [R]25 +2323 (c
D
1
0.031, CHCl3); H NMR (CDCl3) δ 2.00-2.17 (2H, m), 2.38-
2.68 (2H, m), 3.17 (1H, part of ABX, J ) 5.4, 18.3 Hz), 3.30-
3.47 (5H, m), 3.76-3.92 (2H, m), 4.19-4.36 (4H, m), 5.10-
5.18 (1H, m), 6.65-6.98 (4H, m), 7.08-7.31 (7H, m), 7.50-
7.57 (3H, m), 8.06 (2H, d, J ) 7.3 Hz), 8.25 (1H, d, J ) 8.8
Hz); 19F NMR (CDCl3) δ -113.4 (1F, s), -110.7 (1F, s); 13C
NMR (CDCl3) δ 23.2, 30.6, 35.6, 36.9, 42.1, 57.2, 62.0, 63.1,

1348 J . Org. Chem., Vol. 66, No. 4, 2001
Cai et al.
70.5, 71.5, 111.2 (d, J ) 23.2 Hz), 111.9 (d, J ) 20.1 Hz), 114.8
(t, J ) 17.7 Hz), 120.3, 122.5, 125.6, 127.4, 128.4, 128.5, 128.7,
128.8, 129.0, 129.1, 129.3, 129.7, 131.1, 132.3, 133.3, 133.8,
142.6, 153.0, 159.9 (d, J ) 8.1 Hz), 163.2 (d, J ) 8.0 Hz), 170.2,
172.1, 176.2, 180.0; HRMS(FAB) [M + H]+ calcd for C39H35F2N4-
NiO6 751.1878, found 751.1884.
1.94 (1H, m), 2.09-2.24 (1H, m), 2.52-2.64 (1H, m), 2.94-
3.02 (1H, m), 3.45 (1H, part of ABX, J ) 3.4, 9.5 Hz), 3.51-
3.57 (1H, m), 3.63 (1H, part of AB, J ) 13.9 Hz), 3.70-3.89
(3H, m), 3.94 (1H, part of AB, J ) 13.7 Hz), 4.27-4.34 (3H,
m), 6.74-6.84 (2H, m), 7.12-7.40 (11H, m), 7.46-7.62 (3H,
m), 8.47 (1H, d, J ) 8.5 Hz); 19F NMR (CDCl3) δ -139.7 (1F,
m), -137.4 (1F, m); 13C NMR (CDCl3) δ 23.5, 31.2, 36.9, 42.2,
44.6, 55.3, 60.1, 61.9, 68.4, 73.4, 117.4 (d, J ) 17.1 Hz), 118.3
(d, J ) 17.1 Hz), 120.7, 123.5, 125.8, 126.2, 127.0, 128.2, 128.4,
128.7, 128.9, 129.4, 129.8, 129.9, 131.2, 131.7, 132.9, 133.9 (m),
136.1 (m), 143.1, 144.2 (m), 146.0 (m), 153.0, 169.9, 172.1,
176.6, 181.5; HRMS(FAB) [M + H]+ calcd for C39H35F2N4NiO6
751.1878, found 751.1876.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2R,
3S )-3-(2′,6′-d iflu or op h e n yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (4q): mp 174.0-175.0 °C; [R]25 -1587 (c
D
1
0.052, CHCl3); H NMR (CDCl3) δ 1.29-1.51 (2H, m), 1.85-
1.93 (1H, m), 2.06-2.21 (1H, m), 2.60-2.70 (1H, m), 3.39-
3.49 (2H, m), 3.59 (1H, part of ABX, J ) 7.6, 18.3 Hz), 3.75-
4.01 (4H, m), 4.23-4.34 (4H, m), 4.41-4.51 (1H, m), 6.72-
6.84 (2H, m), 6.94-7.16 (2H, m), 7.25-7.46 (9H, m), 7.53-
7.56 (3H, m), 8.48 (1H, d, J ) 8.8 Hz); 19F NMR (CDCl3) δ
-111.8 (1F, s), -107.9 (1F, s); 13C NMR (CDCl3) δ 23.4, 31.1,
35.3, 36.0, 42.2, 55.4, 59.7, 62.0, 68.5, 71.7, 111.8 (m), 112.5
(m), 115.3 (t, J ) 17.1 Hz), 120.5, 122.9, 125.9, 127.2, 128.7,
128.8, 129.0, 129.2, 129.3, 129.7, 131.7, 132.6, 133.7, 134.0,
143.1, 153.0, 160.9 (m), 164.0 (m), 170.3, 172.7, 176.6, 181.3;
HRMS(FAB) [M + H]+ calcd for C39H35F2N4NiO6 751.1878,
found 751.1896.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2S,
3R)-3-(4′-m et h oxy-2′,3′,5′,6′-t et r a flu or op h en yl)-5-[3′-(2′-
oxa zolid in on yl)]glu ta m ic a cid (3t): mp 161.0-162.0 °C;
1
[R]25 +1873 (c 0.034, CHCl3); H NMR (CDCl3) δ 2.10-2.31
D
(2H, m), 2,47-2.61 (1H, m), 2.74-2.83 (1H, m), 3.04, 3.25 (2H,
ABX, J ) 4.4, 10.3, 18.6 Hz), 3.44 (1H, part of AB, J ) 12.7
Hz), 3.48-3.54 (2H, m), 3.67-3.99 (3H, m), 4.02 (3H, s), 4.11
(1H, d, J ) 10.3 Hz), 4.25-4.35 (2H, m), 4.34 (1H, part of AB,
J ) 12.5 Hz), 5.43 (1H, dt, J ) 4.2, 10.3 Hz), 6.67-6.99 (2H,
m), 7.09-7.18 (2H, m), 7.23-7.32 (4H, m), 7.46-7.61 (3H, m),
8.09 (2H, d, J ) 7.3 Hz), 8.22 (1H, d, J ) 8.5 Hz); 19F NMR
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2S,
3R)-3-(2′-flu or op h en yl)-5-[3′-(2′-oxa zolid in on yl)]glu ta m -
ic a cid (3r ): mp 272.0-273.0 °C; [R]25 +2490 (c 0.016,
(CDCl3) δ -159.0 (2F, m), -158.3 (1F, m), -143.4 (1F, m); 13
C
D
CHCl3); 1H NMR (CDCl3) δ 1.49-1.72 (1H, m), 1.93-2.28 (4H,
m), 2.95-3.05 (2H, m), 3.26 (1H, m), 3.47 (1H, part of AB, J )
12.5 Hz), 3.62-3.82 (3H, m), 3.99-4.06 (1H, m), 4.24-4.34
(4H, m), 6.66 (2H, d, J ) 3.9 Hz), 7.11-7.31 (8H, m), 7.40-
7.60 (5H, m), 7.96 (2H, d, J ) 7.1 Hz), 8.32 (1H, d, J ) 8.5
Hz); 19F NMR (CDCl3) δ -166.7 (1F, s); 13C NMR (CDCl3) δ
22.8, 30.5, 35.7, 36.5, 42.1, 56.9, 61.7, 63.3, 70.2, 72.5, 115.3,
115.6, 120.1, 122.6, 124.8 (d, J ) 3.1 Hz), 125.8, 126.1, 126.9,
128.4, 128.7, 128.8, 129.0, 129.1, 129.3 (d, J ) 3.0 Hz), 131.3,
132.2, 133.0, 133.5, 134.0, 142.8, 152.9, 159.8, 163.1, 169.6,
NMR (CDCl3) δ 23.5, 30.7, 35.8, 37.9, 42.2, 57.5, 61.8, 62.2,
63.2, 70.6, 71.4, 110.5 (t, J ) 16.1 Hz), 120.6, 122.6, 125.6,
127.5, 128.3, 128.6, 128.7, 128.9, 129.0, 129.4, 129.9, 130.1,
131.1, 131.7, 132.7, 133.1, 133.4, 134.2, 137.5 (m), 139.0 (m),
142.3 (m), 142.7, 143.8 (m), 146.9 (m), 153.1, 170.0, 172.4,
175.9, 180.2; HRMS(FAB) [M + H]+ calcd for C40H35F4N4NiO7
817.1795, found 817.1800.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2R,
3S)-3-(4′-m et h oxy-2′,3′,5′,6′-t et r a flu or op h en yl)-5-[3′-(2′-
oxa zolid in on yl)]glu ta m ic a cid (4t): mp 163.0-164.0 °C;
172.4, 176.9, 180.8; HRMS(FAB) [M + H]+ calcd for C39H36
-
[R]25 -909.8 (c 0.022, CHCl3); H NMR (CDCl3) δ 1.54-1.69
1
D
FN4NiO6 733.1972, found 733.1987.
(2H, m), 1.97-2.05 (1H, m), 2.14-2.28 (1H, m), 2.71-2.80 (1H,
m), 3.26, 3.41 (2H, ABX, J ) 5.1, 9.3, 18.3 Hz), 3.49 (1H, d, J
) 4.4 Hz), 3.69 (1H, dd, J ) 3.5, 9.1 Hz), 3.83 (1H, part of AB,
J ) 13.4 Hz), 3.88-4.11 (2H, m), 4.00 (3H, s), 4.20 (1H, d, J )
8.8 Hz), 4.33-4.39 (2H, m), 4.72 (1H, part of AB, J ) 13.4
Hz), 4.96 (1H, ddd, J ) 5.6, 8.8, 9.3 Hz), 6.74-6.92 (2H, m),
7.24-7.61 (11H, m), 8.57 (1H, d, J ) 8.5 Hz); 19F NMR (CDCl3)
δ -159.0 (2F, m), -158.3 (1F, m), -142.2 (1F, m); 13C NMR
(CDCl3) δ 23.2, 30.7, 35.7, 36.8, 42.2, 56.1, 59.9, 61.8, 62.1,
68.2, 71.4, 110.7 (t, J ) 16.1 Hz), 120.7, 122.8, 125.4, 127.2,
128.6, 128.9, 129.0, 129.2, 129.9, 131.7, 133.0, 133.5, 134.4,
137.5 (m), 138.9 (m), 142.1 (m), 143.2, 144.2 (m), 147.5 (m),
153.2, 169.9, 173.3, 176.4, 181.5; HRMS(FAB) [M + H]+ calcd
for C40H35F4N4NiO7 817.1795, found 817.1894.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2R,
3S)-3-(2′-flu or op h en yl)-5-[3′-(2′-oxa zolid in on yl)]glu ta m -
ic a cid (4q): mp 279.0-280.0 °C; [R]25 -1887 (c 0.025,
D
CHCl3); 1H NMR (CDCl3) δ 1.16-1.42 (2H, m), 1.83-1.90 (1H,
m), 2.01-2.23 (1H, m), 2.43-2.53 (1H, m), 3.18 (1H, part of
ABX, J ) 6.8, 17.8 Hz), 3.31 (1H, part of ABX, J ) 3.4, 9.5
Hz), 3.51 (1H, part of AB, J ) 13.9 Hz), 3.63-3.84 (5H, m),
4.01-4.07 (1H, m), 4.27-4.33 (2H, m), 4.37 (1H, d, J ) 4.4
Hz), 6.71-6.81 (2H, m), 7.15-7.18 (2H, m), 7.25-7.61 (13H,
m), 8.45 (1H, d, J ) 8.5 Hz); 19F NMR (CDCl3) δ -116.1 (1F,
s); 13C NMR (CDCl3) δ 23.5, 31.2, 36.0, 36.1, 42.2, 54.9, 59.5,
61.8, 68.4, 72.9, 115.6, 115.9, 120.5, 123.2, 125.1 (d, J ) 3.0
Hz), 126.3, 126.6, 126.8, 127.0, 128.6, 128.7, 128.8, 129.0,
129.2, 129.3, 129.6, 129.9 (d, J ) 3.0 Hz), 131.5, 131.8, 132.5,
133.8, 134.1, 143.1, 153.0, 160.4, 163.6, 170.0, 172.6, 176.8,
181.3; HRMS(FAB) [M + H]+ calcd for C39H36FN4NiO6 733.1972,
found 733.1977.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2S,
3R)-3-(3′,4′-d ich lor op h e n yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (3u ): mp 166.0-167.0 °C; [R]25 +1942 (c
D
0.031, CHCl3); 1H NMR (CDCl3) δ 2.01-2.35 (5H, m), 2.83 (1H,
part of ABX, J ) 5.5, 17.7 Hz), 2.99-3.06 (1H, m), 3.30 (1H,
dd, J ) 7.5, 9.2 Hz), 3.40-3.47 (2H, m), 3.65-3.83 (3H, m),
4.22-4.33 (4H, m), 6.68 (2H, d, J ) 3.9 Hz), 7.11-7.18 (4H,
m), 7.26-7.32 (4H, m), 7.47 (1H, d, J ) 2.0 Hz), 7.53-7.63
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2S,
3R )-3-(3′,4′-d iflu or op h e n yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (3s): mp 146.0-147.0 °C; [R]25 +2581 (c
D
1
0.023, CHCl3); H NMR (CDCl3) δ 1.68-1.78 (1H, m), 1.99-
2.08 (1H, m), 2.21-2.39 (3H, m), 2.81 (1H, part of ABX, J )
5.4, 17.6 Hz), 3.02-3.11 (1H, m), 3.29-3.34 (1H, m), 3.45 (1H,
part of AB, J ) 12.7 Hz), 3.50-3.55 (1H, m), 3.62-3.84 (3H,
m), 4.23-4.32 (4H, m), 6.68 (2H, d, J ) 4.4 Hz), 6.95-7.06
(1H, m), 7.12-7.32 (8H, m), 7.51-7.63 (3H, m), 7.99 (2H, d, J
) 7.3 Hz), 8.29 (1H, d, J ) 8.8 Hz); 19F NMR (CDCl3) δ -140.1
(1F, m), -137.4 (1F, m); 13C NMR (CDCl3) δ 22.9, 30.8, 37.5,
42.2, 44.4, 57.3, 61.9, 63.6, 70.4, 73.2, 117.4 (d, J ) 16.1 Hz),
118.0 (d, J ) 17.1 Hz), 120.6, 123.1, 125.7, 125.9 (m), 127.1,
128.2, 128.7, 128.9, 129.4, 129.8, 131.4, 132.7, 133.2, 133.7,
134.1, 136.0 (m), 143.0, 148.8 (m), 152.1 (m), 153.0, 170.0,
172.0, 176.7, 180.3; HRMS(FAB) [M + H]+ calcd for C39H35F2N4-
NiO6 751.1878, found 751.1856.
(3H, m), 8.00 (2H, d, J ) 8.3 Hz), 8.30 (1H, d, J ) 8.8 Hz); 13
C
NMR (CDCl3) δ 22.9, 30.8, 37.2, 42.2, 44.3, 57.6, 61.9, 63.7,
70.4, 73.2, 120.5, 123.1, 125.6, 127.1, 128.1, 128.7, 128.9, 129.3,
129.4, 129.8, 130.7, 131.0, 131.4, 132.3, 132.7, 133.2, 133.3,
133.7, 134.1, 139.3, 143.1, 153.0, 169.9, 172.0, 176.6, 180.3;
HRMS(FAB) [M + H]+ calcd for C39H35Cl2N4NiO6 785.1261,
found 785.1281.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2R,
3S )-3-(3′,4′-d ich lor op h e n yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (4u ): mp 174.0-175.0 °C; [R]25 -1271 (c
D
1
0.023, CHCl3); H NMR (CDCl3) δ 1.26-1.44 (2H, m), 1.84-
1.91 (1H, m), 2.11-2.20 (1H, m), 2.49-2.58 (1H, m), 2.95 (1H,
part of AB, J ) 5.8, 18.0 Hz), 3.42-3.52 (2H, m), 3.59 (1H,
part of AB, J ) 13.7 Hz), 3.71-3.86 (5H, m), 4.26-4.75 (3H,
m), 6.74-6.84 (2H, m), 7.24-7.38 (9H, m), 7.56-7.65 (5H, m),
8.53 (1H, d, J ) 8.5 Hz); 13C NMR (CDCl3) δ 23.6, 31.3, 36.5,
42.2, 44.6, 54.9, 59.9, 61.9, 68.5, 73.4, 120.7, 123.5, 125.7, 127.0,
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2R,
3S )-3-(3′,4′-d iflu or op h e n yl)-5-[3′-(2′-oxa zolid in on yl)]-
glu ta m ic a cid (4s): mp 151.0-152.0 °C; [R]25 -1618 (c
D
1
0.020, CHCl3); H NMR (CDCl3) δ 1.29-1.49 (3H, m), 1.87-

Reactions between Glycine Complexes and Oxazolidin-2-ones
J . Org. Chem., Vol. 66, No. 4, 2001 1349
128.1, 128.6, 128.8, 129.2, 129.4, 129.8, 130.6, 131.0, 131.5,
132.0, 132.2, 132.9, 133.2, 133.9, 139.3, 143.3, 153.0, 169.8,
60.9, 62.1, 68.6, 72.1, 121.3, 124.7, 127.1, 128.1, 128.6, 128.7,
128.9, 129.4, 130.0, 131.7, 131.9, 132.0, 138.9, 141.4, 153.2,
170.8, 172.5, 177.7, 180.8; HRMS(FAB) [M + H]+ calcd for
172.1, 176.4, 181.7; HRMS(FAB) [M + H]+ calcd for C39H35
-
Cl2N4NiO6 785.1261, found 785.1260.
C
34H35N4NiO6 653.1910, found 653.1915.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2S,
3R)-3-(4′-n it r op h en yl)-5-[3′-(2′-oxa zolid in on yl)]glu t a m -
Ni(II) com p lex of th e Sch iff ba se of (S)-BP A a n d (2S,
3R)-3-pen taflu or oph en yl-5-[3′-(2′-oxazolidin on yl)]glu tam -
ic a cid (3v): mp 175.0-176.0 °C; [R]25 +2906 (c 0.024,
ic a cid (6p ): yield 73%; mp 168.0-169.0 °C; [R]25 +1862 (c
D
D
CHCl3); 1H NMR (CDCl3) δ 1.55-1.68 (1H, m), 1.91-2.31 (4H,
m), 2.84 (1H, dd, J ) 3.4, 16.1 Hz), 2.94-2.99 (1H, m), 3.29
(1H, dd, J ) 7.2, 9.6 Hz), 3.42 (1H, part of AB, J ) 12.5 Hz),
3.67-3.82 (4H, m), 4.22-4.32 (4H, m), 6.69-6.70 (2H, m),
7.11-7.34 (6H, m), 7.50 (2H, part of AB, J ) 8.8 Hz), 7.53-
7.64 (3H, m), 7.98 (2H, d, J ) 7.8 Hz), 8.29 (1H, d, J ) 9.3
Hz), 8.32 (2H, part of AB, J ) 8.8 Hz); 13C NMR (CDCl3) δ
22.8, 30.6, 37.2, 42.1, 45.1, 57.2, 61.9, 63.5, 70.2, 73.1, 120.5,
122.9, 123.8, 125.4, 127.0, 128.0, 128.6, 128.9, 129.4, 129.8,
130.3, 131.2, 132.7, 133.1, 133.7, 133.9, 142.9, 146.7, 147.6,
152.9, 169.7, 172.2, 176.3, 180.1; HRMS(FAB) [M + H]+ calcd
for C39H36N5NiO8 760.1917, found 760.1921.
0.036, CHCl3); H NMR (CDCl3) δ 2.06-2.28 (2H, m), 2.47-
1
2.55 (1H, m), 2.58 (3H, s), 2.69-2.80 (1H, m), 3.22 (1H, part
of ABX, J ) 6.8, 18.6 Hz), 3.33 (1H, part of AB, J ) 12.5 Hz),
3.45 (1H, part of ABX, J ) 5.9, 11.0 Hz), 3.50-3.54 (1H, m),
3.61 (1H, part of ABX, J ) 6.7, 18.5 Hz), 3.71-3.94 (4H, m),
4.18-4.26 (1H, m), 4.27 (1H, part of AB, J ) 12.7 Hz), 4.44
(1H, d, J ) 10.7 Hz), 5.54 (1H, ddd, J ) 6.8, 6.8, 10.7 Hz),
6.88-6.93 (1H, m), 7.07-7.16 (2H, m), 7.23-7.28 (2H, m), 7.61
(1H, dd, J ) 1.5, 8.3 Hz), 7.98 (1H, dd, J ) 1.0, 8.5 Hz), 8.09
(2H, d, J ) 6.8 Hz); 19F NMR (CDCl3) δ -162.5 (1F, m), -161.9
(1F, m), -155.3 (1F, m), -141.5 (2F, m); 13C NMR (CDCl3) δ
18.9, 23.7, 30.5, 35.2, 37.1, 42,1, 58.0, 62.2, 63.6, 70.7, 71.0,
113.1 (m), 121.2, 123.5, 125.0, 128.6, 128.7, 129.7, 131.1, 132.1,
133.6, 135.9 (m), 139.0 (m), 141.5, 142.4 (m), 143.7 (m), 147.1
(m), 153.2, 169.4, 170.1, 176.0, 180.0; HRMS(FAB) [M + H]+
calcd for C34H30F5N4NiO6 743.1439, found 743.1437.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP B a n d (2R,
3S)-3-(4′-n it r op h en yl)-5-[3′-(2′-oxa zolid in on yl)]glu t a m -
ic a cid (4v): mp 179.0-180.0 °C; [R]25 -2739 (c 0.021,
D
CHCl3); 1H NMR (CDCl3) δ 1.34-1.46 (2H, m), 1.86-1.93
(1H,m), 2.17-2.26 (1H, m), 2.43-2.52 (1H, m), 2.97 (1H, dd,
J ) 5.0, 17.7 Hz), 3.34 (1H, dd, J ) 3.7, 9.3 Hz), 5.49 (1H,
part of AB, J ) 13.7 Hz), 3.69-3.91 (6H, m), 4.27-4.34 (3H,
m), 6.75-6.87 (2H, m), 7.15-7.36 (8H, m), 7.58-7.63 (5H, m),
8.34 (2H, d, J ) 8.8 Hz), 8.51 (1H, d, J ) 8.8 Hz); 13C NMR
(CDCl3) δ 23.6, 31.2, 37.1, 42.2, 45.6, 55.2, 59.9, 62.0, 68.1,
73.6, 120.9, 123.5, 123.9, 125.7, 127.2, 128.3, 128.9, 129.1,
129.6, 130.0, 130.8, 131.6, 133.2, 134.0, 143.4, 146.9, 147.9,
153.1, 169.9, 172.6, 176.4, 181.9; HRMS(FAB) [M + H]+ calcd
for C39H36N5NiO8 760.1917, found 760.1933.
Ni(II) com p lex of Sch iff ba se of (S)-BP A a n d (2R,3S)-
3-p en t a flu or op h en yl-5-[3′-(2′-oxa zolid in on yl)]glu t a m ic
a cid (7p ): yield 23%; mp 144.0-145.0 °C; [R]25 +181.9 (c
D
1
0.029, CHCl3); H NMR (CDCl3) δ 1.74-1.85 (1H, m), 1.91-
2.04 (1H, m), 2.11-2.25 (1H, m), 2.30-2.39 (1H, m), 2.56-
2.64 (1H, m), 2.75 (3H, s), 3.31 (1H, part of ABX, J ) 5.9, 18.8
Hz), 3.42 (1H, dd, J ) 4.6, 10.0 Hz), 3.67 (1H, part of AB, J )
13.2 Hz), 3.78-3.86 (1H, m), 3.91-4.00 (3H, m), 4.26-4.42
(2H, m), 4.55 (1H, part of AB, J ) 12.9 Hz), 4.56-4.62 (1H,
m), 4.71 (1H, d, J ) 8.1 Hz), 6.96-7.01 (1H, m), 7.25-7.31
(1H, m), 7.37-7.39 (3H, m), 7.67 (1H, dd, J ) 1.2, 8.5 Hz),
7.73-7.76 (2H, m), 8.08 (1H, d, J ) 8.5 Hz); 19F NMR (CDCl3)
δ -162.2 (2F, m), -154.9 (1F, m), -141.0 (1F, m), -137.8 (1F,
m); 13C NMR (CDCl3) δ 19.9, 23.4, 29.2, 30.5, 35.5, 42.3, 57.1,
61.9, 62.2, 68.7, 69.8, 112.8 (m), 121.6, 124.8, 126.9, 128.8,
129.2, 129.7, 131.7, 132.1, 132.3, 136.0 (m), 139.0 (m), 141.3,
142.4 (m), 144.1 (m), 146.7 (m), 153.3, 170.8, 173.0, 177.1,
181.2; HRMS(FAB) [M + H]+ calcd for C34H30F5N4NiO6
743.1439, found 743.1442.
Ni(II) Com p lex of th e Ch ir a l Sch iff Ba se of Glycin e
w ith (S)-o-[N-(N-Ben zylp r olyl)a m in o]a cetop h en on e (5).
Chiral ligand (S)-o-[N-(N-benzylprolyl)amino]-acetophenone
(BPA) and the corresponding Ni(II)-complex (S)-5 were syn-
thesized following the standard procedure (ref 21) for prepar-
ing BPB-(S)-10 and (S)-1 with the difference that instead of
o-aminobenzophenone the o-aminoacetophenone was used.
Mich a el Ad d ition Rea ction s betw een Com p lex (S)-5
a n d 2f,p . For the reactions of the acetophenone-derived
complex (S)-5 with phenyl- (2f) and pentafluorophenyl-
containing derivatives 2p , the general procedure described for
the reactions of complex (S)-1 with Michael acceptors was
followed. Yields and physicochemical and NMR data of the
diastereomeric products 6f,p and 7f,p are listed below.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP A a n d
(2S,3R)-3-p h en yl-5-[3′-(2′-oxa zolid in on yl)]glu ta m ic a cid
Decom p osition of Dia ster eom er ica lly P u r e Com p lexes
3 a n d 4. Isola tion of P yr oglu ta m ic Acid s 8 a n d 9 a n d
Recover y of Ch ir a l Liga n d BP B (S)-10 a n d Oxa zolid in -
2-on e (11). Diastereomerically pure complex 3 or 4 (2.3 mmol)
was dissolved in methanol (20 mL) and added to a 1/1 mixture
(40 mL) of 3 N HCl and water at 70 °C. After the decomposition
of the complex was completed (disappearance of the orange
color), the mixture was evaporated in vacuo, treated with
concentrated ammonia, and extracted with CHCl3 to remove
ligand BPB (S)-10 (95-99% yield). The aqueous phase was
evaporated in vacuo, and the solid residue was washed with
acetone to remove 2-oxazolidinone (11) (90-97% yield). The
resultant product was dissolved in water and loaded on a
Dowex ion-exchange resin column, which was washed with
H2O/EtOH (2/1). The acidic fraction which emerged from the
column was collected and evaporated to afford pyroglutamic
acid 8 or 9, which was recrystallized from THF/hexanes to give
an analytically pure sample. Yields and physicochemical and
NMR data of the amino acids are listed below.
(6f): yield 71%; mp 273.0-274.0 °C; [R]25 +1875 (c 0.033,
D
CHCl3); 1H NMR (CDCl3) δ 1.43-1.54 (1H, m), 1.81-2.21 (4H,
m), 2.82 (3H, s), 2.85-2.93 (1H, m), 3.18 (1H, t, J ) 8.7 Hz),
3.29 (1H, part of AB, J ) 12.7 Hz), 3.42 (1H, part of ABX, J )
3.91, 18.6 Hz), 3.60 (1H, td, J ) 4.3, 10.3 Hz), 3.95-4.03 (2H,
m), 4.14 (1H, part of AB, J ) 12.5 Hz), 4.38-4.47 (3H, m),
4.61 (1H, d, J ) 4.4 Hz), 6.88-6.93 (1H, m), 7.08-7.34 (6H,
m), 7.49-7.53 (3H, m), 7.71 (1H, d, J ) 8.3 Hz), 8.00 (2H, d,
J ) 7.1 Hz), 8.11 (1H, d, J ) 8.5 Hz); 13C NMR (CDCl3) δ 18.6,
23.0, 30.0, 37.1, 42.3, 44.2, 57.5, 62.0, 63.6, 70.2, 72.3, 120.6,
123.3, 125.1, 127.9, 128.4, 128.9, 129.4, 129.9, 131.3, 131.6,
133.1, 138.9, 141.8, 153.1, 169.2, 172.3, 177.3, 179.8;
HRMS(FAB) [M + H]+ calcd for C34H35N4NiO6 653.1910, found
653.1917.
(2S,3S)-3-Meth ylp yr oglu ta m ic a cid (8a ): yield 96%; mp
110.0-111.5 °C; [R]25D +41.2 (c 1.18, CH3OH) [lit.1e [R]25D +41.0
(c 1.16, CH3OH)]; 1H NMR (CD3OD) δ 1.27 (3H, d, J ) 6.4
Hz), 1.99, 2.54 (2H, ABX, J ) 8.5, 9.3, 20.0 Hz), 2.50-2.59
(1H, m), 3.82 (1H, d, J ) 4.9 Hz); 13C NMR (CD3OD) δ 20.1,
34.8, 38.4, 63.1, 174.0, 178.3; HRMS(FAB) [M + H]+ calcd for
C6H10NO3 144.0661, found 144.0660.
Ni(II) com p lex of th e Sch iff ba se of (S)-BP A a n d
(2R,3S)-3-p h en yl-5-[3′-(2′-oxa zolid in on yl)]glu ta m ic a cid
(7f): yield 23%; mp 181.0-182.0 °C; [R]25 -259.5 (c 0.044,
D
CHCl3); 1H NMR (CDCl3) δ 1.51-1.60 (2H, m), 1.96-2.05 (1H,
m), 2.19-2.26 (1H m), 2.36-2.46 (1H, m), 2.83 (3H, s), 3.24
(1H, dd, J ) 4.6, 9.8 Hz), 3.34 (1H, part of AB, J ) 13.4 Hz),
3.42 (1H, part of ABX, J ) 3.9, 18.8 Hz), 3.57 (1H, td, J ) 4.2,
6.1 Hz), 3.62-3.69 (1H, m), 3.83 (1H, part of AB, J ) 13.4
Hz), 3.95-4.09 (2H, m), 4.38-4.49 (3H, m), 4.77 (1H, d, J )
4.4 Hz), 6.93-7.02 (1H, m), 7.24-7.28 (8H, m), 7.47-7.52 (3H,
m), 7.71 (1H, dd, J ) 1.2, 8.3 Hz), 8.06 (1H, dd, J ) 1.0, 8.5
Hz); 13C NMR (CDCl3) δ 19.4, 23.5, 30.8, 36.9, 42.2, 44.6, 55.8,
(2R,3R)-3-Meth ylp yr oglu ta m ic a cid (9a ): yield 97%; mp
1
110.5-112.0 °C; [R]25 -40.7 (c 1.02, CH3OH); H NMR and
D
13C NMR (CD3OD) spectra are identical to those of (2S,3S)-
8a .
(2S,3R)-3-P h en ylp yr oglu ta m ic a cid (8f): yield 95%; mp
139.0-140.0 °C; [R]25D +82.5 (c 1.11, CH3OH) [lit.1e [R]25D +82.8
(c 1.10, CH3OH)]; 1H NMR (CD3OD) δ 2.34, 2.75 (2H, ABX, J

1350 J . Org. Chem., Vol. 66, No. 4, 2001
Cai et al.
) 16.8, 9.3, 6.3 Hz), 3.72 (1H, ddd, J ) 9.3, 6.3, 5.1 Hz), 4.25
(1H, d, J ) 5.1 Hz), 7.25-7.41 (5H, m); 13C NMR (CD3OD) δ
38.7, 44.9, 63.1, 127.8, 127.9, 129.6, 143.9, 173.5, 176.4;
HRMS(FAB) [M + H]+ calcd for C11H12NO3 206.0817, found
206.0809.
pyroglutamic acid 8f (0.205 g, 1.00 mmol) was refluxed with
6 N HCl (10 mL) overnight. After the solvent was evaporated,
the residue was dissolved in ethanol (2 mL). The resulting
solution was then refluxed with propylene oxide (3 mL) for 30
min and cooled to room temperature. The white precipitate
was filtered out, washed with ethanol, and dried in vacuo to
(2R,3S)-3-P h en ylp yr oglu ta m ic a cid (9f): yield 93%; mp
1
139.5-140.5 °C; [R]25 -82.3 (c 1.10, CH3OH); H NMR and
give (2S,3R)-3-phenylglutamic acid 12f (0.220 g): yield 99%;
D
13C NMR (CD3OD) spectra are identical to those of (2S,3R)-
mp 158.0-158.5 °C; [R]25 +16.7 (c 1.36, 6 N HCl); H NMR
1
D
8f.
(D2O) δ 2.86, 2.96 (2H, ABX, J ) 5.6, 10.0, 16.4 Hz), 3.52-
(2S,3R)-3-(3′,4′-Diflu or op h en yl)p yr oglu ta m ic a cid (8s):
3.59 (1H, m), 3.90 (1H, d, J ) 4.9 Hz), 7.62-7.31 (5H, m); 13
C
yield 85%; mp 185.0-186.0 °C; [R]25 +57.8 (c 0.81, CH3OH);
NMR (D2O) δ 31.5, 37.8, 54.1, 123.8, 124.0, 124.8, 132.2, 167.7,
171.6; HRMS(FAB) [M + H]+ calcd for C11H14NO4 224.0923,
found 224.0923.
D
1H NMR (CD3OD) δ 2.32, 2.71 (2H, ABX, J ) 6.8, 9.3, 17.1
Hz), 3.60 (1H, ddd, J ) 5.8, 6.6, 9.3 Hz), 4.11 (1H, d, J ) 5.6
Hz), 7.01-7.22 (3H, m); 19F NMR (CD3OD) δ -143.9 (1F, m),
-141.0 (1F, m); 13C NMR (CD3OD) δ 39.3, 44.8, 64.2, 117.2
(d, J ) 18.2 Hz), 118.4 (d, J ) 17.1 Hz), 124.6 (dd, J ) 3.5, 6.5
Hz), 141.1 (m), 149.5 (dd, J ) 12.6, 60.4 Hz), 152.8 (dd, J )
13.1, 61.5 Hz), 174.4, 179.0; HRMS(FAB) [M + H]+ calcd for
Ack n ow led gm en t. This work was supported by a
U.S. Public Health Service Grant and the National
Institute of Drug Abuse (DA 06284, DA 13449, and DK
17420). The views expressed are those of the authors
and not necessarily of the USPHS. We thank Dr.
Dominic McGrath of the University of Arizona and his
group for the use of their polarimeter.
C
11H10F2NO3 242.0629, found 242.0620.
(2S,3R)-3-(3′,4′-Dich lor oph en yl)pyr oglu tam ic acid (8u ):
yield 84%; mp 216.0-217.0 °C; [R]25 +60.7 (c 0.22, CH3OH);
D
1H NMR (CD3OD) δ 2.32, 2.71 (2H, ABX, J ) 6.8, 9.3, 17.3
Hz), 3.60 (1H, ddd, J ) 5.4, 6.8, 9.3 Hz), 4.12 (1H, d, J ) 5.4
Hz), 7.18 (1H, dd, J ) 2.2, 8.3 Hz), 7.39 (1H, d, J ) 8.3 Hz),
7.42 (1H, d, J ) 2.2 Hz); 13C NMR (CD3OD) δ 39.1, 44.8, 64.0,
128.0, 130.5, 132.0, 132.2, 144.4, 174.3, 178.9; HRMS(FAB)
[M + H]+ calcd for C11H10Cl2NO3 274.0038, found 274.0033.
Hyd r olysis of (2S,3R)-3-P h en ylp yr oglu ta m ic Acid (8f)
to (2S,3R)-3-P h en ylglu ta m ic Acid (12f). (2S,3R)-3-Phenyl-
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
spectra of compounds 3a-d,f-v, 4a-d,f-v, 6f,p, 7f,p, 8a,f,s,u ,
and 12f. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O0014865