Memory of chirality in the enantioselective synthesis of β-lactams derived from amino acids. Influence of the reaction conditions

Article abstract of DOI:10.1055/s-2003-39301

The asymmetric induction observed during cyclisation of N-benzyl-N-chloroacetyl-L-Phe derivatives to the corresponding S-enriched 2-azetidinones, ascribed to chirality memory, can be controlled by the appropriate choice of the base and solvent. Using the

Full text of DOI:10.1055/s-2003-39301

LETTER
1007
Memory of Chirality in the Enantioselective Synthesis of b-Lactams Derived
from Amino Acids. Influence of the Reaction Conditions
Memory of Chirality in
ª
the Synthesi
A
s of
b
-Lactams ngeles Bonache,a Guillermo Gerona-Navarro,a Mercedes Martín-Martínez,a Mª Teresa García-López,a
Pilar López,b Carlos Cativiela,b Rosario González-Muñiz*a
a
Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain
E-mail: iqmg313@iqm.csic.es
b
Departamento de Química Orgánica, ICMA, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
Received 26 February 2003
ing the diastereoisomeric ratio (RP-HPLC) of dipeptide
Abstract: The asymmetric induction observed during cyclisation
of N-benzyl-N-chloroacetyl-L-Phe derivatives to the corresponding
S-enriched 2-azetidinones, ascribed to chirality memory, can be
controlled by the appropriate choice of the base and solvent. Using
the organic base BTPP, the ee values obtained in different solvents
showed a good correlation with the AN solvent parameter, except
for NMP. It seems that a combination of the solvent properties, rath-
er than individual parameters, and the presence of enolate aggre-
gates are decisive for final enantiomer distribution.
derivatives (as in Scheme 1, compounds 3), we found that
the selectivity of the enolate-mediated cyclization is base
and solvent dependent.
To better understand the elements governing the phenom-
enon of the memory of chirality in the b-lactam ring for-
mation, we decided to initiate a detailed study on the
influence of several reaction variables (base, solvent, tem-
perature and concentration) on the selectivity of the in-
tramolecular cyclization. For such purpose, the L-Phe-O-
t-Bu derivative 1 has been selected as a model substrate,
following the synthetic protocol depicted in Scheme 1.
Now, to determine the enantioselectivity of the reaction,
additionally to the preparation of the diastereoisomeric
dipeptides 3, the HPLC separation of the enantiomeric
azetidinones 2a,b has been achieved by means of a non-
commercial chiral stationary phase, consisting of mixed
10-undecenoate/3,5-dimethylphenylcarbamate of cellu-
lose covalently bonded to allylsilica gel.6,7
Key words: amino acids, memory of chirality, b-lactams, enantio-
selectivity, AN solvent-depedency
Nowadays a new stereoinduction principle, known as
‘memory of chirality’, is emerging as an alternative to oth-
er more classical methods in stereoselective synthesis.
Memory of chirality describes a phenomenon in which the
reactive intermediate is imprinted with the stereochemical
memory of the starting substrate, even though the original
stereogenic center is destroyed.1 This means that the ste-
reochemical outcome of the reaction can be controlled
without using any external chiral source. Carbanions,2
carbenium cations,3 and different types of radicals4 can be
found among the reactive intermediates that are able to
preserve the information of chirality. In the chemistry of
amino acids, the memorized chirality has made an impor-
tant contribution to the stereochemical course of some a-
C-substitution reactions2 and different photocyclisation
processes.4 Thus, the asymmetric alkylation of N-methyl-
or N-Mom-N-Boc-L-amino acids and the intramolecular
stereoselective aldol cyclisation of 1-(3-oxobutyryl) de-
rivatives of Pro, and their 4-oxa and 4-thia analogues, are
assumed to proceed via chiral nonracemic enolate inter-
mediates.2b–g
From the data shown in Table 1, it can be observed that
the ratio of enantiomers 2a:2b, directly measured by
chiral HPLC, is very similar to the ratio of diastereoiso-
CO2t-Bu
Base
CO2t-Bu
CO2t-Bu
N
Cl
+
Solvent
N
N
O
O
O
1
OMe
2a
2b
OMe
OMe
1. TFA
2. H-L-Ala-OMe/BOP
In this context, we have recently reported that the base-
promoted cyclisation of N-benzyl-N-chloroacetyl deriva-
tives of L-Phe affords the corresponding 4-benzyl-4-
alkoxycarbonyl-2-azetidinones with modest selectivity
towards the preferential formation of the 4-(S) enantio-
mer.5 In this preliminary study, in which the ee of the
formed b-lactams were indirectly determined by measur-
O
O
N
H
CO2Me
N
CO2Me
+
H
N
N
O
O
Synlett 2003, No. 7, Print: 02 06 2003.
Art Id.1437-2096,E;2003,0,07,1007,1011,ftx,en;G05003ST.pdf.
OMe
OMe
© Georg Thieme Verlag Stuttgart · New York
3a
3b
Scheme 1

1008
Mª A. Bonache et al.
LETTER
mers 3a:3b (RP-HPLC), obtained after derivatization of they did not lead to the formation of the expected b-lac-
compounds 2. In general, the ratio of the major isomers tam.11,12 In contrast, the cyclization to the 2-azetidinone
was slightly higher in the dipeptide series (1–5%). The ring can be promoted by aqueous or solid hydroxides, un-
small differences in selectivity found between direct and der phase-transfer conditions, and by the soluble non-nu-
indirect methods could be attributed to the existence of cleophile phosphazene bases. Using toluene as solvent,
some kinetic resolution (2.5% on average) during dipep- low to moderate yields were obtained, due to the high de-
tide derivatives formation.
gree of O-alkylation.5 Under these conditions, the best se-
lectivity was found for the organic base BTPP, followed
by solid CsOH, while slightly lower ee were found for
aqueous NaOH and KOH (Table 1). Compared to previ-
ous results, the selectivity found for BTPP/toluene was
similar to that obtained with NaH/MeCN and lower than
that originated by Cs2CO3/MeCN.5 For ease of synthesis
and workup, BTPP was selected to gain further insight
into the significance of the solvent on the selectivity. Us-
ing this base, the reaction was readily accomplished in a
variety of solvents, including low dielectric media as well
as highly polarized solvents, with the best yield obtained
for the reaction in MeCN (Table 1). Concerning the selec-
tivity, it is interesting to note that quite different solvents,
such as dichloromethane (CH2Cl2) and MeCN gave rather
similar enantioselectivities.13 On the other hand, solvents
with very close dielectric constants as N-methyl-2-pyrro-
lidinone (NMP) and MeCN or DMF resulted in very dif-
ferent asymmetric inductions. A similar behaviour was
observed for the reactions carried out with BEMP as base
(compare entries 5, 8 and 9 with 11, 12 and 13, respective-
ly). Clearly, lower ee values were found for the reactions
carried out in NMP. Moreover, while a combination of
BEMP with NMP resulted in almost racemic compounds,
in the reaction with BTPP/NMP the sense of the asymmet-
ric induction was reversed. Considering not only the se-
lectivity, but also the rate of alkylation and the yield in the
b-lactam, CH2Cl2 and MeCN were the solvents of choice.
From these results it is clear that the properties intrinsic to
the solvent medium are decisive for affecting the enanti-
oselectivity, although a good correlation of the enantio-
meric excesses and individual solvent parameters (e, a,
p*)14 could not be found. However, setting NMP and bu-
tanone aside,15 the solvent-dependent selectivity correlat-
ed excellently with the Gutmann’s acceptor number
(AN),16 a solvent parameter that takes into account a com-
bination of solvent properties like polarity, polarizability,
and hydrogen bonding properties (Figure 1). The ratio-
nale for the particular behavior of NMP could be found in
the polar coordinating nature of this solvent that could
break up possible intermediate aggregates.17,18 To clarify
this point, we studied the influence of different alkaline
iodides on the selectivity of the cyclisation in NMP
(Table 2). It is known that alkaline halides can form
mixed enolate aggregates, and they are often employed
for increasing the degree of asymmetric induction in alky-
lation reactions.19 Under BTPP/NMP conditions, the use
of LiI as additive restored the preferential formation of the
S-enriched product, probably through coordination of the
Li-atom to the enolate intermediate (up to 40% increase in
the S-selectivity). The choice of the cation of the additive
also proved to be important. Thus, NaI gave similar selec-
tivity as LiI while KI and CsI were less effective. In the
To study the influence of the base on the selectivity,8 and
in addition to Cs2CO3 and NaH,5 different types of bases
were selected, namely a lithium amide (LHMDS), three
alkaline hydroxides (NaOH, KOH, CsOH) and three or-
ganic bases with different strength and nucleophilic char-
acter (DMAP, BTPP, BEMP).9,10 After a preliminary
exploration, DMAP and LHMDS were discarded since
Table 1 Influence of the Base and Solvent on the Selectivity of the
Cyclization of L-Phe-O-t-Bu Chloroacetyl Derivative 1
Entry Base
Solvent
25% NaOH Toluened
Toluened
CsOH·H2O Toluened
Yield
(%)a
2a:2bb
(ee)
3a:3bc
(de)
1
2
59
37
35
28
59
28
46
56
73
49
65
52
81
64:36
(28)
67:33
(34)
25% KOH
62:38
(24)
66:34
(32)
3
66:34
(32)
69:31
(38)
4
BTPP
BTPP
BTPP
BTPP
BTPP
BTPP
BTPP
BEMP
BEMP
BEMP
Toluene
DCM
68:32
(36)
73:27
(46)
5
74:26
(48)
74:26
(48)
6
THF
69:31
(38)
–
7
Butanone
NMP
68:32
(36)
72:28
(42)
8
43:57
(14)e
42:58
(16)e
9
MeCN
DMF
76:24
(52)
79:21
(58)
10
11
12
13
73:27
(46)
–
DCM
75:25
(50)
75:25
(50)
NMP
51:49
(2)
52:48
(4)
MeCN
76:24
(52)
79:21
(58)
a Isolated compounds.
b Measured by chiral HPLC.
c Measured by RP-HPLC after transformation into dipeptide
derivatives 3.
d Tetrabutylamoniun bromide (10%) was used as phase transfer
catalyst.
e Major isomer has R-configuration.
Synlett 2003, No. 7, 1007–1011 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
Memory of Chirality in the Synthesis of b-Lactams
1009
BEMP/NMP reaction, the addition of LiI led to a selectiv- While configurational stability of enolates generated from
ity degree analogous to that obtained in BEMP/MeCN N-methyl- or N-Mom-N-Boc-L-amino acids was shown to
(compare Table 1, entry 13, and Table 2, entry 7). In con- be markedly labile to temperature,2e the effect of this vari-
trast, addition of LiI to the BTPP/MeCN reaction lowered able was negligible in the cyclization to the b-lactam ring,
to some extent the selectivity, probably as a consequence indicating a different behavior between inter- and in-
of a change in the initial enolate structure. At the same tramolecular alkylation processes that occur with memory
time, in this latter case the addition of LiI had a detrimen- of chirality.
tal effect on the b-lactam yield.
Table 3 Influence of the Temperature and Concentration on the Se-
lectivity of the Cyclization of L-Phe-O-t-Bu Chloroacetyl Derivative
1 (BTPP, MeCN)
Entry
Temp
(°C)
Concentration Yield
2a:2bb
ee
(mM)
0.28
0.56
0.14
0.28
0.28
(%)a
1
2
3
4
5
25
25
25
0c
73
76:24
78:22
75:25
76:24
74:26
52
56
50
52
48
77
80
65
60
65
Figure 1 Plot of the stereoselectivity from the cyclisation of com-
pound 1 in different solvents versus the ‘solvent aceptor numbers’
(AN) taken from ref.16b
a Isolated compounds.
b Measured by chiral HPLC.
c Below this temperature the reaction did not appreciably proceed.
Table 2 Influence of Additives on the Selectivity of the Cyclization
of L-Phe-O-t-Bu Chloroacetyl Derivative 1
We have shown that the memory of chirality observed
during cyclization of N-chloroacetyl L-Phe derivatives to
2-azetidinones is highly dependent on the base and sol-
vent used, while temperature and concentration have neg-
ligible effects.20 The ee values were determined by two
alternative methods with seemingly minor deviations be-
tween them, a direct measure of enantiomer ratios using
chiral HPLC (non-commercial column) or in an indirect
manner, after derivatisation to the corresponding dipep-
tide analogues. The superior levels of reaction efficiency
and selectivity observed in BTPP(BEMP)/MeCN, BT-
PP(BEMP)/CH2Cl2 and BTPP/NMP/LiI prompted us to
select these reaction conditions, along with the previously
reported Cs2CO3/MeCN, for further exploration about the
importance of the amino acid substituents on the memory
of chirality phenomenon. Work in this direction is ongo-
ing in our laboratory.
Entry Base
Solvent Additive Yield
(%)a
2a:2bb
ee
1
2
3
4
5
6
7
8
9
BTPP
BTPP
BTPP
BTPP
BTPP
BEMP
BEMP
BTPP
BTPP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
MeCN
MeCN
–
56
70
31
31
37
52
52
73
18
43:57
63:37
62:38
57:43
53:47
51:49
75:25
76:24
73:27
14c
26
24
14
6
LiI
NaI
KI
CsI
–
2
LiI
–
50
52
46
LiI
a Isolated compounds.
b Measured by chiral HPLC.
c R-Enriched product.
Acknowledgment
This work was supported by CICYT (SAF 2000-0147). M.A.B. and
G.G.-N. are predoctoral fellows from the Ramón Areces Founda-
tion and Ministry of Science and Technology, respectively.
Taking into account that concentration is another variable
that could influence the aggregation stage, we next inves-
tigated the selectivity of the cyclization at different con-
centrations. As shown in Table 3, the slight increase and
decrease in the asymmetric induction observed for a dou-
ble and a half concentrated reactions, respectively, could
be attributed to high and low ordered transition-states.
Autocatalysis by the optically active starting material,
through formation of mixed aggregates with the enolate,
could be another possible rationale for these minor differ-
ences.
References
(1) Fuji, K.; Kawabata, T. Chem.–Eur. J. 1998, 4, 373.
(2) For examples of memory of chirality through enolate
intermediates see: (a) Kawabata, T.; Yahiro, K.; Fuji, K. J.
Am. Chem. Soc. 1991, 113, 9694. (b) Kawabata, T.; Wirth,
T.; Yahiro, K.; Suzuki, H.; Fuji, K. J. Am. Chem. Soc. 1994,
116, 10809. (c) Brewster, A. G.; Frampton, C. S.; Jayatissa,
J.; Mitchell, M. B.; Stoodley, R. J.; Vohra, S. Chem.
Commun. 1998, 299. (d) Betts, M. J.; Pritchard, R. G.;
Schofield, A.; Stoodley, R. J.; Vohra, S. J. Chem. Soc.,
Synlett 2003, No. 7, 1007–1011 ISSN 1234-567-89 © Thieme Stuttgart · New York

1010
Mª A. Bonache et al.
LETTER
Selected data for compound 4: HPLC: tR = 10.74 min
Perkin Trans. 1 1999, 1067. (e) Kawabata, T.; Suzuki, H.;
Nagae, Y.; Fuji, K. Angew. Chem. Int. Ed. 2000, 39, 2155.
(f) Kawabata, T.; Chen, J.; Suzuki, H.; Nagae, Y.; Kinoshita,
T.; Chancharunee, S.; Fuji, K. Org. Lett. 2000, 2, 3883.
(g) Brewster, A. G.; Jayatissa, J.; Mitchell, M. B.; Schofield,
A.; Stoodley, R. J. Tetrahedron Lett. 2002, 43, 3919.
[50:50, H2O/MeCN (0.05%TFA)]. 1H NMR (300 MHz,
CDCl3): major rotamer d = 8.09 (d, 2 H, J = 7.8 Hz,
pyridine), 7.32–7.12 (m, 10 H, Ph), 6.68 (d, 2 H, J = 7.8 Hz,
pyridine), 5.46 (d, 1 H, J = 16.8 Hz, CH2N+), 5.33 (d, 1 H,
J = 16.8 Hz, CH2N+), 4.72 (d, 1 H, J = 17.2 Hz, N-CH2),
4.39 (dd, 1 H, J = 8.8, 6.2 Hz, a-H), 4.25 (d, 1 H, J = 17.2
Hz, N-CH2), 3.25 (dd, 1 H, J = 14.9, 6.2 Hz, b-H), 3.17 (s, 6
H, NMe2), 3.07 (dd, 1 H, J = 14.9, 8.8 Hz, b-H), 1.31 (s, 9 H,
t-Bu). 13C NMR (75 MHz, CDCl3): major rotamer d =
168.29 (COO), 166.07 (CON), 156.34 (4-C, pyridine),
143.68 (2-C, 6-C, pyridine), 137.35, 135.32, 129.29, 128.91,
128.86, 127.91, 127.59, 126,79 (Ph), 107.14 (3-C, 4-C,
pyridine), 82.22 (C, t-Bu), 63.09 (a-C), 58.71 (CH2N+),
51.41 (N-CH2), 40.48 (CH3N), 35.53 (b-C), 27.92 (CH3, t-
Bu). MS (ES, positive mode): 475.6 (M+ + 1).
(3) On the chirality memory through carbenium ion chemistry:
(a) Matsumura, Y.; Shirakawa, Y.; Satoh, Y.; Umino, M.;
Tanaka, T.; Maki, T.; Onomura, O. Org. Lett. 2000, 2, 1689.
(b) Wanyoike, G. N.; Onomura, O.; Maki, T.; Matsumura,
Y. Org. Lett. 2002, 4, 1875.
(4) Radicals as reactive intermediates in memory of chirality
processes: (a) Sauer, S.; Schumacher, A.; Barbosa, F.;
Giese, B. Tetrahedron Lett. 1998, 39, 3685. (b) Giese, B.;
Wettstein, P.; Stähelin, C.; Barbosa, F.; Neuburger, M.;
Zehnder, M.; Wessig, P. Angew. Chem. Int. Ed. 1999, 38,
2586. (c) Buckmelter, A. J.; Kim, A. I.; Rychnovsky, S. D.
J. Am. Chem. Soc. 2000, 122, 9386. (d) Griesbeck, A. G.;
Kramer, W.; Lex, J. Angew. Chem. Int. Ed. 2001, 40, 577.
(e) Griesbeck, A. G.; Kramer, W.; Bartoschek, A.;
Schmickler, H. Org. Lett. 2001, 3, 537. (f) Griesbeck, A.
G.; Kramer, W.; Lex, J. Synthesis 2001, 1159.
(12) Reaction of chloroacetyl derivative 1 with LHMDS afforded
pyrrolidinone 5, which was characterized as its methoxy
derivative 6 after treatment with diazomethane. The
formation of compound 5 could be attributed to the initial
generation of the amide enolate and a Dieckmann-type
condensation of this enolate with the ester group, followed
by enolisation of the resulting ketone (Figure 3).
(5) Gerona-Navarro, G.; Bonache, M. A.; Herranz, R.; García-
López, M. T.; González-Muñiz, R. J. Org. Chem. 2001, 66,
3538.
RO
(6) Oliveros, L.; López, P.; Minguillón, C.; Franco, P. J. Liq.
Chromatogr. 1995, 18, 1521.
Cl
N
(7) Column OL-389. Eluent: hexane/acetone (96:4). Flow rate:
1.5 mL/min. UV detection at 220 nm. Isomer 2a: tR = 7.77
min. Isomer 2b: tR = 9.07 min.
O
5: R = H
6: R = Me
CH2N2
(8) A general procedure was as follows: Compound 1 (83 mg,
0.19 mmol) was dissolved in the corresponding solvent (0.7
mL) and treated, at r.t. and under Ar atmosphere, with the
appropriate base (0.28 mmol). The reaction was monitored
by TLC until complete disappearance of the starting
material. The solution was evaporated, redissolved in
EtOAc, washed with H2O, and dried over Na2SO4. After
evaporation, the resulting residue was purified on a silica gel
column using a gradient from 20 to 30% of EtOAc in
hexane. The obtained compound 2ab was directly evaluated
by chiral HPLC, or transformed into dipeptide derivatives 3a
and 3b as described (ref.5). For the phase transfer reactions,
3 equiv of NaOH and KOH, and 10 equiv of CsOH were
respectively used.
MeO
Figure 3
Selected data for compound 6: 1H NMR (300 MHz, CDCl3):
d = 7.26 (m, 3 H, Ph), 7.05 (m, 2 H, Ph), 7.00 (d, 2 H, J = 8.6
Hz, Pmb), 6.80 (d, 2 H, J = 8.6 Hz, Pmb), 5.18 (d, 1 H,
J = 15.1 Hz, 1-CH2), 4.16 (s, 3 H, OMe), 3.93 (dd, 1 H,
J = 5.4, 4.1 Hz, 5-H), 3.83 (d, 1 H, J = 15.1 Hz, 1-CH2), 3.78
(s, 3 H, OMe), 3.13 (dd, 1 H, J = 14.3, 4.1 Hz, 5-CH2), 2.89
(dd, 1 H, J = 14.3, 5.4 Hz, 5-CH2). 13C NMR (75 MHz,
CDCl3): d = 167.4 (2-C), 164.22 (4-C), 159.07, 134.95,
130.05, 129.45, 129.04, 128.74, 127.32, 114.03 (Ar), 97.91
(3-C), 59.05 (OMe), 58.65 (5-C), 55.21 (OMe), 43.88
(5-CH2), 35.47 (1-CH2). MS (ES, positive mode): 358.2
(M+ + 1).
(9) BTPP: tert-Butylimino-tri(pyrrolidino)phosphorane.
BEMP: 2-tert-Butylimino-2-diethylamino-1,3-
dimethylperhydro1,3,2-diazaphosphorine.
(13) These results are atypical with respect to other alkylation
reactions for which the use of polar solvents, like MeCN,
resulted in almost racemic products: Belokon, Y. N.;
Kochetkov, K. A.; Churkina, T. D.; Ikonnikov, N. S.;
Chesnokov, A. A.; Larionov, O. V.; Singh, I.; Parmar, V. S.;
Vyskocil, S.; Kagan, H. B. J. Org. Chem. 2000, 65, 7041.
(14) (a) Taft, R. W.; Kamlet, M. J. J. Am. Chem. Soc. 1976, 98,
2886. (b) Kamlet, M. J.; Abboud, J. L.; Taft, R. W. J. Am.
Chem. Soc. 1977, 99, 6027.
(10) (a) Schwesinger, R.; Willaredt, J.; Schlemper, H.; Keller,
M.; Schmitt, D.; Fritz, H. Chem. Ber. 1994, 127, 2435.
(b) O’Donnell, M. J.; Delgado, F.; Dominguez, E.; de Blas,
J.; Scott, W. L. Tetrahedron: Asymmetry 2001, 12, 821.
(11) Attempts to cyclize N-benzyl-N-chloroacetyl-L-Phe-O-t-Bu
with DMAP resulted in the nucleophilic attack of the
reactive to the chloroacetyl derivative (compound 4, 90%,
Figure 2), as previously found for the cyclization of Trp
analogues with DBU, see: Gerona-Navarro, G.; Bonache, M.
A.; Herranz, R.; García-López, M. T.; González-Muñiz, R.
Synlett 2000, 1249.
(15) NMP was not included because really poor correlations were
found. To the best of our knowledge, the AN value for 2-
butanone has not been described.
(16) (a) Taft, R. W.; Pienta, N. J.; Kamlet, M. J.; Arnett, E. M. J.
Org. Chem. 1981, 46, 661. (b) Malavolta, L.; Oliveira, E.;
Cilli, E. M.; Nakaie, C. R. Tetrahedron 2002, 58, 4383.
(17) Among all the solvents tested here, NMP has not only the
highest donor number (DN) but also the biggest difference
between AN and DN parameters. DN is a reasonably good
measure of the ability of the solvent to serve as an electron-
pair donor to solutes when oxygen bases are considered.
CO2t-Bu
N
N
+
4
O
-
N
Cl
Figure 2
Synlett 2003, No. 7, 1007–1011 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
Memory of Chirality in the Synthesis of b-Lactams
1011
(18) It has been described that the enantioselectivity of the
alkylation of Phe derivatives can be controlled by regulating
the aggregate structure of chiral enolate intermediates:
(a) Kawabata, T.; Kawakami, S.; Fuji, K. Tetrahedron Lett.
2002, 43, 1465. (b) Kawabata, T.; Kawakami, S.; Shimada,
S.; Fuji, K. Tetrahedron 2003, 59, 965.
(19) (a) Henderson, K. W.; Dorigo, A. E.; Liu, Q.-Y.; Williard, P.
G.; von Ragué Scheyer, P.; Bernstein, P. R. J. Am. Chem.
Soc. 1996, 118, 1339. (b) Asensio, G.; Alemán, P. A.;
Domingo, L. R.; Medio-Simón, M. Tetrahedron Lett 1998,
39, 3277.
(20) No memeory of chriality was observed in the
photochmically-induced cyclization of phenylglyoxylamide
to 3-hydroxy-b-lactams: Griesbeck, A. G.; Heckroth, H.
Synlett 2002, 131.
Synlett 2003, No. 7, 1007–1011 ISSN 1234-567-89 © Thieme Stuttgart · New York