Nonenzymatic kinetic resolution of 3-hydroxyalkanamides with chiral copper catalyst

Article abstract of DOI:10.1055/s-2008-1032057

Kinetic resolution of 3-hydroxyalkanamides with good to high selectivities was achieved by benzoylation using copper(II) triflate and (R,R)-PhBox [2,2′-isopropylidenebis(4-phenyl-2-oxazoline)] as catalyst, which also mediated enantioselective tosylation o

Full text of DOI:10.1055/s-2008-1032057

LETTER
433
Nonenzymatic Kinetic Resolution of 3-Hydroxyalkanamides with Chiral
Copper Catalyst
Nonenzymatic
K
in
o
etic Resoluti
s
on of 3-H
u
ydroxyalkan
k
amides e Demizu, Yuki Kubo, Yoshihiro Matsumura, Osamu Onomura*
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
Fax +81(95)8192476; E-mail: onomura@nagasaki-u.ac.jp
Received 29 October 2007
H
Abstract: Kinetic resolution of 3-hydroxyalkanamides with good
R
R
R
OH
OH
O
+
to high selectivities was achieved by benzoylation using copper(II)
triflate and (R,R)-PhBox [2,2¢-isopropylidenebis(4-phenyl-2-ox-
azoline)] as catalyst, which also mediated enantioselective tosyla-
tion of 2,2-bis(hydroxymethyl)alkanamides with high efficiency.
BzCl
Cu2
+
Cu2 L*
base
L*
O
H
R
– HCl
1
2
Key words, kinetic resolution, 3-hydroxyalkanamides, acylations,
chiral copper complex, molecular recognition
Bz
O
O
R
O
*
Cu+2 L*
Optically active 3-hydroxyalkanoic acid derivatives are
important precursors for the preparations of various bio-
logically active compounds.1 A variety of enzymatic ki-
netic resolution methods has been developed for the
preparation of optically pure 3-hydroxyalkanoic acid de-
rivatives.2 To the best of our knowledge, nonenzymatic
method has been little known to date.3 Recently, we have
reported an efficient method for kinetic resolution of 1,2-
diols 1. The method is based on the recognition of 1 by
copper ion associated with chiral ligand (R,R)-PhBox4 to
afford the activated intermediates 2 followed by benzoy-
lation (Scheme 1).5–9
+
N
N
*
R
O
H
Ph
Ph
L* (R,R)-PhBox
3
Scheme 1 Asymmetric benzoylation of 1,2-diols 1 based on the re-
cognition by Cu(II)–(R,R)-PhBox
BzCl (0.5 equiv)
OH
O
OBz
O
K2CO3 (1.0 equiv)
OEt
OEt
EtOAc, r.t., 12 h
4
5
no catalyst
Cu(OTf)2 (0.1 equiv)
<1% based on 4
19% based on 4
We report herein nonenzymatic kinetic resolution of 3-hy-
droxyalkanamides by benzoylation with Cu(II)–(R,R)-Ph-
(R,R)-PhBox (0.1 equiv)
Box
catalyst
affording
optically
active
3-
hydroxyalkanamide derivatives in good to high yields and
enantioselectivities.
OH
O
BzCl (0.5 equiv)
K2CO3 (1.0 equiv)
OBz O
Ph
Ph
We began our investigation by trying the benzoylation of
ethyl DL-3-hydroxybutanoate (4) as a model compound to
see whether it could be recognized by chiral copper(II)
complex or not. We found out the following: in the ab-
sence of copper(II) triflate and (R,R)-PhBox the reaction
of 4 with BzCl barely took place, while in the presence of
the catalysts, benzoylated product 5 was obtained in 19%
yield based on 4. In contrast, DL-3-hydroxy-N-phenylbu-
tanamide (6a) was benzoylated more efficiently in the
presence of Cu(II)–(R,R)-PhBox to afford the benzoylated
product 7a in 41% yield (Scheme 2). These results imply
that 6a was efficiently recognized by the Cu(II)–(R,R)-Ph-
Box complex.
N
N
EtOAc, r.t., 2 h
H
H
6a
no catalyst
7a
no reaction
41% based on 6a
Cu(OTf)2 (0.1 equiv)
(R,R)-PhBox (0.1 equiv)
Scheme 2 Benzoylation of ester 4 and amide 6a in the absence or
presence of Cu(OTf)2 and (R,R)-PhBox
sively formed, whereas in the absence of Cu(II)–(R,R)-
PhBox only the monobenzoylated diol 9 (syn/anti ≈
63:37) was generated. From these results, we deduced that
6a was preferentially recognized over 8 by the copper cat-
alyst.10,11 Acceleration of benzoylation of 6a was also ob-
served in the presence of Cu(OTf)2 without (R,R)- or rac-
PhBox.
Next, we tried the competitive reaction between 6a and
2,4-pentanediol (8) (syn/anti ≈ 50:50) with or without
Cu(II)–(R,R)-PhBox (Scheme 3). In the presence of
Cu(II)–(R,R)-PhBox or Cu(II)–rac-PhBox, 7a was exclu-
In our quest to get excellent reaction conditions for kinetic
resolution of DL-6a, we investigated the effect of bases
and solvents on benzoylation.12 These results are summa-
rized in Table 1. They show a dependence of yield and
SYNLETT 2008, No. 3, pp 0433–0437
x
x.
x
x.
2
0
0
8
Advanced online publication: 16.01.2008
DOI: 10.1055/s-2008-1032057; Art ID: U10507ST
© Georg Thieme Verlag Stuttgart · New York

434
Y. Demizu et al.
LETTER
BzCl (0.05 mmol)
K2CO3 (0.25 mmol)
OH OH
OBz OH
OBz
O
OH
O
+
Ph
Ph
+
EtOAc
r.t., 2 h
N
N
H
H
6a (0.25 mmol)
8 (0.25 mmol)
7a
9
~
~
(syn/anti
50:50)
no catalyst
ratio
0
:
100
~
(syn/anti
63:37)
63:37)
~
:
:
Cu(OTf)2 (0.025 mmol)
ratio
ratio
ratio
75
100
100
25
~
~
0
0
(syn/anti
Cu(OTf)2 (0.025 mmol) + (R,R)-PhBox (0.025 mmol)
Cu(OTf)2 (0.025 mmol) + rac-PhBox (0.025 mmol)
:
Scheme 3 Competitive reaction between 6a and 8 by benzoylation in the absence or presence of Cu(OTf)2 and (R,R)- or rac-PhBox
%ee of the product 7a as well as the reaction time on the and (R,R)-PhBox led to a slightly inferior result compared
solvents and bases used. Use of EtOAc as a solvent and to that using 0.1 equivalent of chiral Cu(II) catalyst (entry
K2CO3 as a base gave (S)-7a13,14 in 41% yield and a high 12).
enantioselectivity (85% ee) with a selectivity s value15 of
Utilizing the conditions optimized in Table 1, we
27 for two hours (entry 1). THF and 1,4-dioxane gave
screened the effect of amide N-substituents shown in
comparable results to EtOAc (entries 2 and 3), while
Table 2. The s value of N-4-chlorophenyl amide 6b was
slightly lower than that of 6a (entry 1), while N-4-meth-
ylphenyl amide 6c gave high s value of 34 (entry 2). Ben-
CH2Cl2 and Et2O were less efficient (entries 4 and 5).
Moreover, use of alcohols such as i-PrOH or EtOH gave
(S)-7a in high enantioselectivity (entries 6 and 7). K2CO3
zoylation of N-3,5-dimethylphenyl amide 6d and the
was the most effective base (entry 1) among the tested
corresponding hexafluorinated amide 6e required longer
reaction times, and the s values were moderate for 6d and
bases (entries 8–11). Use of 0.05 equivalent of Cu(OTf)2
Table 1 Kinetic Resolution of DL-3-Hydroxy-N-phenylbutanamide (DL-6a)a
(R,R)-PhBox
Cu(OTf)2
OH
O
OBz
O
OH
O
Ph
Ph
Ph
+
N
N
N
H
BzCl (0.5 equiv)
base (1.0 equiv)
solvent, r.t.
H
H
(S)-7a
(R)-6a
DL-6a
Entry
Solvent
Base
Time (h)
Product (S)-7a
Recovered (R)-6a
Selectivity
s
Yield (%)
41
eeb (%)
85
Yield (%)
eeb (%)
1
EtOAc
THF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Li2CO3
Na2CO3
NaHCO3
DIPEA
K2CO3
2
52
55
56
62
60
63
82
74
46
52
70
63
74
64
52
45
48
47
27
28
80
64
36
56
27
21
21
10
11
13
20
7
2
2
45
83
3
1,4-dioxane
CH2Cl2
Et2O
12
12
2
44
85
4
38
74
5
40
75
6
i-PrOH
EtOH
12
24
24
24
24
24
2
37
78
7
18
88
8
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
26
68
9
45
82
25
11
9
10
11
12c
48
70
30
73
37
85
22
a Reaction conditions: DL-6a (0.5 mmol), Cu(OTf)2 (0.05 mmol), (R,R)-PhBox (0.05 mmol), BzCl (0.25 mmol), base (0.5 mmol) in a solvent
(2.0 mL) at r.t.
b Determined by HPLC.
c Reaction conditions: DL-6a (0.5 mmol), Cu(OTf)2 (0.025 mmol), (R,R)-PhBox (0.025 mmol), BzCl (0.25 mmol), K2CO3 (0.5 mmol) in EtOAc
(2.0 mL) at r.t.
Synlett 2008, No. 3, 433–437 © Thieme Stuttgart · New York

LETTER
Nonenzymatic Kinetic Resolution of 3-Hydroxyalkanamides
435
Table 2 Kinetic Resolution of DL-3-Hydroxybutanamide Derivatives DL-6b–ja
(R,R)-PhBox (0.1 equiv)
Cu(OTf)2 (0.1 equiv)
OH
O
OBz
O
OH
O
+
R1
R1
R1
N
R2
N
R2
N
BzCl (0.5 equiv)
K2CO3 (1.0 equiv), EtOAc, r.t.
R2
DL-6b–j
(S)-7b–j
(R)-6b–j
Entry Substrate
R1
R2
Time (h) Product (S)-7b–jb
Recovered (R)-6b–j
Selectivity
s
Yield (%)
eec (%)
79
Yield (%) eec (%)
1
2
3
4
5
6
7
8
9
6b
6c
6d
6e
6f
4-ClC6H4
4-MeC6H4
3,5-diMeC6H3
3,5-diCF3C6H3
2-MeC6H4
Bn
H
2
7b
7c
7d
7e
7f
46
44
47
30
37
48
37
46
39
54
56
53
70
63
47
53
7
66
73
65
27
56
65
60
31
57
17
34
16
5
H
3
88
H
24
24
1.5
3
78
H
57
H
89
30
16
21
10
18
6g
6h
6i
H
7g
7h
7i
78
Ph
Me
Me
12
3
84
Me
76
6j
–(CH2)2O(CH2)2–
24
7j
82
23
a Reaction conditions: DL-6b–j (0.5 mmol), Cu(OTf)2 (0.05 mmol), (R,R)-PhBox (0.05 mmol), BzCl (0.25 mmol), K2CO3 (0.5 mmol)
in EtOAc (2.0 mL) at r.t.
b Absolute stereoconfigurations of 7b–j were deduced on the basis of that of (S)-7a.
c Determined by HPLC.
Table 3 Kinetic Resolution of Various DL-3-Hydroxyalkanamides DL-6ap–awa
(R,R)-PhBox (0.1 equiv)
Cu(OTf)2 (0.1 equiv)
OH
O
OBz
O
OH
O
Ph
Ph
Ph
+
R3
DL-6ap–aw
N
R3
N
R3
recovered 6ap–aw
N
BzCl (0.5 equiv)
K2CO3 (1.0 equiv), EtOAc, r.t.
H
H
H
7ap–aw
Entry
Substrate
R3
Time (h) Product 7ap–aw
Recovered 6ap–aw
Selectivity
s
Yield (%)
38
eeb (%)
67
Yield (%)
eeb (%)
41
1
2
3
4
5
6
6ap
6aq
6ar
6as
6at
Et
12
24
24
24
24
24
(S)-7ap
(S)-7aq
(R)-7ar
(S)-7as
7at
(R)-6ap
(R)-6aq
(S)-6ar
(R)-6as
6at
62
64
80
52
100
82
8
8
6
5
–
8
n-Pr
i-Pr
34
20
23
0
68
45
64
24
i-Bu
cyclohexyl
Ph
58
37
–
0
6au
(R)-7au
18
74
(S)-6au
20
7
8
6av
2
(S)-7av
(S)-7aw
40
40
80
82
(R)-6av
(R)-6aw
60
50
58
55
16
18
Br
4
Boc
N
6aw
12
3
H
a Reaction conditions: 6ap–aw (0.5 mmol), Cu(OTf)2 (0.05 mmol), (R,R)-PhBox (0.05 mmol), BzCl (0.25 mmol), K2CO3 (0.5 mmol) in EtOAc
(2 mL) at r.t.
b Determined by HPLC.
Synlett 2008, No. 3, 433–437 © Thieme Stuttgart · New York

436
Y. Demizu et al.
LETTER
poor for 6e (entries 3 and 4). N-2-Methylphenyl amide 6f
was smoothly asymmetrically benzoylated to afford 7f
with 89% ee. N-Benzyl amide 6g was inferior to N-phenyl
amide 6a (entry 6). N,N-Disubstituted amides 6h, 6i and
6j also gave slightly lower s values compared to that of 6a
(entries 7–9).
Table 4 Asymmetric Benzoylation and Tosylation of Prochiral
10a–ca
OH OR5
*
R5Cl
OH OH
H
(R,R)-PhBox
H
N
N
R4
Ph
Cu(OTf)2
K2CO3
EtOAc
r.t.
R4
Ph
O
O
Table 3 summarizes kinetic resolution of various 3-hy-
droxyalkanamides 6ap–aw by benzoylation under the op-
timized reaction condition. Compounds 6ap substituted
with Et and 6aq with n-Pr group were asymmetrically
benzoylated to afford the corresponding optically active
(S)-7ap16 and (S)-7aq,16 respectively, in good yield and
moderate enantioselectivity, (entries 1 and 2). Although
compounds 6ar and 6as substituted with i-Pr and i-Bu, re-
spectively, were kinetically resolved with moderate enan-
tioselectivity, the yield was low (entries 3 and 4).
Benzoylation of cyclohexylated compound 6at did not
proceed (entry 5), while phenylated 6au was benzoylated
to afford (R)-7au17 in moderate yield and good enantiose-
lectivity (entry 6). Straight-chained carbon compounds
6av terminally functionalized with Br atom and 6aw with
N-Boc-protected amino group gave good s value of 16 and
18, respectively (entries 7 and 8).
11a–c R5 = Bz
12a–c R5 = Ts
10a–c
Entry Substrate R4
R5
Product
Yield eeb (%)
(%)
73
95
76
89
99
85
1
2
3
4
5
6
10a
10b
10c
10a
10b
10c
H
Bz
Bz
Bz
Ts
Ts
Ts
11a
11b
11c
12a
12b
12c
75
77
71
85
90
85
Me
Et
H
Me
Et
a Reaction conditions: 10a–c (0.5 mmol), Cu(OTf)2 (0.05 mmol),
(R,R)-PhBox (0.05 mmol), R5Cl (0.5 mmol), K2CO3 (0.75 mmol) in
EtOAc (2 mL) at r.t. for 4 h (benzoylation) or 12 h (tosylation).
b Determined by HPLC.
To increase the scope of our reaction, we tried enantiose-
lective benzoylation and tosylation18 of 2,2-bis(hy-
droxymethyl)alkanamides 10a–c. The results are shown
in Table 4. Asymmetric benzoylation and tosylation of
10a–c smoothly proceeded to give the corresponding
monobenzoylated compounds 11a–c19 and monotosylated
compounds 12a–c19 with good to high yields and enan-
tioselectivities (entries 1–6). It is noteworthy that 12a–c
were obtained in higher enantiomeric purity than 11a–c
(entries 4–6), partially due to an intramolecular acyl
transfer20 which caused racemization of optically pure
benzoylated compound 11c, but did not happen in the case
of tosylation. This is illustrated in Scheme 4.
Acknowledgment
O.O. and Y.D. are grateful for a Grant-in-Aid for Scientific Rese-
arch (C) (19550109) from the Japan Society for the Promotion of
Science and a Grant-in-Aid for Young Scientists (B) (19790017)
from the Ministry of Education, Science, Sports and Culture, Japan,
respectively.
References and Notes
(1) (a) Berks, A. H. Tetrahedron 1996, 52, 331. (b) Pàmies, O.;
Bäckvall, J.-E. Adv. Synth. Catal. 2002, 344, 947.
(c) Genet, J.-P. Acc. Chem. Res. 2003, 36, 908.
(d) Mlynarski, J. Eur. J. Org. Chem. 2006, 4779.
(2) For recent literature on kinetic resolution of 3-
hydroxyalkanoic acid derivatives by enzymatic methods,
see: (a) Xu, C.; Yuan, C. Tetrahedron 2005, 61, 2169.
(b) Turcu, M. C.; Kiljunen, E.; Kanerva, L. T. Tetrahedron:
Asymmetry 2007, 18, 1682.
(3) Ishihara, K.; Kosugi, Y.; Akakura, M. J. Am. Chem. Soc.
2004, 126, 12212.
(4) For a recent review of chiral bis(oxazoline) ligands, see:
Desimoni, G.; Faita, G.; Jørgensen, K. A. Chem. Rev. 2006,
106, 3561.
(5) For monobenzoylation, see: Matsumura, Y.; Maki, T.;
Murakami, S.; Onomura, O. J. Am. Chem. Soc. 2003, 125,
2052.
(6) For monocarbamoylation, see: Matsumoto, K.; Mitsuda, M.;
Ushijima, N.; Demizu, Y.; Onomura, O.; Matsumura, Y.
Tetrahedron Lett. 2006, 47, 8453.
OH OR5
(R,R)-PhBox (0.1 equiv)
11c (5% ee)
Cu(OTf)2 (0.1 equiv)
H
*
or
N
K2CO3 (1.5 equiv)
EtOAc, r.t., 12 h
12c (85% ee)
Et
Ph
O
11c R5 = Bz (71% ee)
12c R5 = Ts (85% ee)
Scheme 4 Racemization of 11c and 12c
In summary, we have accomplished the nonenzymatic ki-
netic resolution of 3-hydroxyalkanamides by benzoyla-
tion
and
desymmetrization
of
2,2-
bis(hydroxymethyl)alkanamides by tosylation utilizing
chiral copper catalyst. The mechanistic study of these re-
actions and their synthetic applications21 are underway.
(7) For monooxidation of 1,2-diols, see: Onomura, O.; Arimoto,
H.; Matsumura, Y.; Demizu, Y. Tetrahedron Lett. 2007, 48,
8668.
Synlett 2008, No. 3, 433–437 © Thieme Stuttgart · New York

LETTER
Nonenzymatic Kinetic Resolution of 3-Hydroxyalkanamides
437
(8) For benzoylation of vic-aminoalcohols, see: Mitsuda, M.;
Tanaka, T.; Tanaka, T.; Demizu, Y.; Onomura, O.;
Matsumura, Y. Tetrahedron Lett. 2006, 47, 8073.
(9) For a review, see: Matsumura, Y.; Onomura, O.; Demizu, Y.
Yuki Gosei Kagaku Kyokaishi 2007, 65, 216.
(13) The absolute stereoconfiguration of recovered (R)-6a was
determined by comparing with the specific rotation of an
authentic sample. Compound (R)-6a (74% ee): [a]D22 –28.6
(c = 1.1, CHCl3) [lit.14 (R)-6a [a]D20 –37 (c = 1.0, CHCl3)].
(14) Gendre, P. L.; Offenvecher, M.; Bruneau, C.; Dixneuf, P. H.
Tetrahedron: Asymmetry 1998, 9, 2279.
(15) The selectivity factor s was determined using the equation
s = krel(fast/slow) = ln[(1 – C)(1 – eeA)]/ln[(1 – C)(1 + eeA)],
where C = eeA/(eeA + eeB), eeA = ee of recovered starting
material, eeB = ee of product: Kagan H. B., Fiaud J. C.;
Topics in Stereochemistry; Vol. 18. Eliel E. L.; Wiley &
Sons: New York, 1988; 249–330.
(10) For representative literature on nonenzymatic asymmetric
desymmetrization of 1,3-diols, see:
(a) Monocarbamoylation: Otera, J.; Sakamoto, K.;
Tsukamoto, T.; Orita, A. Tetrahedron Lett. 1998, 39, 3201.
For monobenzoylation, see: (b) Oriyama, T.; Taguchi, H.;
Terakado, D.; Sano, T. Chem. Lett. 2002, 31, 26. (c) Trost,
B. M.; Mino, T. J. Am. Chem. Soc. 2003, 125, 2410.
(d) Mizuta, S.; Tsuzuki, T.; Fujimoto, T.; Yamamoto, Y.
Org. Lett. 2005, 7, 3633.
(16) Absolute stereoconfigurations of 7ap–at,av,aw shown in
Table 3 were deduced on the basis of those of (S)-7a and (R)-
7au.
(11) For monoacetylation of 2-amino-1,3-diols, see: Honjo, T.;
Nakano, M.; Sano, S.; Shiro, M.; Yamaguchi, K.; Sei, Y.;
Nagao, Y. Org. Lett. 2007, 9, 509.
(17) The absolute stereoconfiguration of (R)-7au was determined
by comparing with that of authentic (S)-7au, which was
prepared from commercially available (S)-(–)-3-hydroxy-3-
phenylpropionitrile: Dicel Chiralcel OD-H column (f: 4.6
mm, l: 250 mm), n-hexane–isopropanol (10:1), wavelength:
l = 220 nm, flow rate: 1.0 mL/min, tR = 36 min [(R)-7au],
tR = 42 min [(S)-7au]. (R)-7au (74% ee): [a]D25 –13.8 (c =
1.0, CHCl3).
(12) Typical Procedure for Kinetic Resolution: To a solution of
Cu(OTf)2 (0.05 mmol, 18.1 mg) and (R,R)-PhBox (0.05
mmol, 16.7 mg) in EtOAc (2 mL) were added DL-6a (0.5
mmol, 89.6 mg), K2CO3 (0.5 mmol, 69.1 mg) and benzoyl
chloride (0.25 mmol, 0.029 mL). After stirring for 2 h at r.t.,
to the reaction mixture H2O (10 mL) was added. The organic
portion was extracted with EtOAc (3 × 20 mL). The
combined organic layer was dried over MgSO4 and the
solvent was removed in vacuo. The residue was
(18) Kinetic resolution of DL-6a with p-TsCl gave S-configured
tosylated product with somewhat lower yield (36%) and
enantioselectivity (67% ee) than those of benzoylation.
(19) Specific rotations. 11a: [a]D28 –16.4 (c = 1.0, CHCl3). 11b:
[a]D28 +6.9 (c = 1.0, CHCl3). 11c: [a]D28 +0.6 (c = 1.0,
chromatographed on SiO2 (n-hexane–EtOAc, 3:1) to afford
(S)-7a (58.1 mg, 41% yield, 85% ee) as a white solid; mp
98–99 °C; [a]D23 +55.4 (c = 1.0, CHCl3). 1H NMR (300
MHz, CDCl3): d = 8.03 (d, J = 7.2 Hz, 1 H), 7.78 (br s, 1 H),
7.56 (t, J = 9.0 Hz, 1 H), 7.38–7.51 (m, 4 H), 7.29 (t, J = 9.0
Hz, 3 H), 7.09 (t, J = 9.0 Hz, 1 H), 5.50–5.63 (m, 1 H), 2.85
(dd, J = 6.3, 14.4 Hz, 1 H), 2.68 (dd, J = 6.3, 14.4 Hz, 1 H),
1.51 (d, J = 6.3 Hz, 3 H). Optical purity of product (S)-7a
was determined by chiral HPLC: Dicel Chiralcel OD-H
column (f: 4.6 mm, l: 250 mm), n-hexane–isopropanol
(10:1), wavelength: l = 220 nm, flow rate: 1.0 mL/min, tR =
20.0 min [(R)-7a], tR = 22.5 min [(S)-7a].
24
CHCl3). 12a: [a]D24 +15.2 (c = 0.95, CHCl3). 12b: [a]D
–21.8 (c = 1.0, CHCl3). 12c: [a]D26 –43.2 (c = 1.0, CHCl3).
(20) Edin, M.; Martín-Matute, B.; Bäckvall, J.-E. Tetrahedron:
Asymmetry 2006, 17, 708.
(21) Mesylation of (R)-6a followed by cyclization under basic
conditions gave the corresponding optically active b-lactam
with complete stereoinversion.16
(22) Sakaki, J.; Kobayashi, S.; Sato, M.; Kaneko, C. Chem.
Pharm. Bull. 1989, 37, 2952.
Synlett 2008, No. 3, 433–437 © Thieme Stuttgart · New York

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