Kinetic resolution of the racemic 2-hydroxyalkanoates using the enantioselective mixed-anhydride method with pivalic anhydride and a chiral acyl-transfer catalyst

Article abstract of DOI:10.1002/chem.200902257

A variety of optically active 2-hydroxyalkanoates and the corresponding 2-acyloxyalkanoates are produced by the kinetic resolution of racemic 2-hydroxyalkanoates by using achiral 2,2-diarylacetic acid with hindered carboxylic anhydrides as the coupling reagents. The combined use of diphenylacetic acid, pivalic anhydride, and (+)-(R)-benzotetramisole ((R)-BTM) effectively produces (S)-2-hydroxyalkanoates and (R)-2-acyloxyalkanoates from the racemic 2-hydroxyalkanoates (s-values = 47-202). This protocol directly provides the desired chiral 2-hydroxyalkanoate derivatives from achiral diarylacetic acid and racemic secondary alcohols that do not include the sec-phenethyl alcohol moiety by using the transacylation process to generate the mixed anhydrides from the acid components with bulky carboxylic anhydrides under the influence of the chiral acyl-transfer catalyst. The transition state that provides the desired (R)-2-acyloxyalkanoate from (R)-2-hydroxyalkanoate included in the racemic mixture is disclosed by DFT calculations, and the structural features of the transition form are also discussed.

Full text of DOI:10.1002/chem.200902257

FULL PAPER
DOI: 10.1002/chem.200902257
Kinetic Resolution of the Racemic 2-Hydroxyalkanoates Using the
Enantioselective Mixed-Anhydride Method with Pivalic Anhydride and a
Chiral Acyl-Transfer Catalyst
Isamu Shiina,* Kenya Nakata, Keisuke Ono, Masuhiro Sugimoto, and
Akihiro Sekiguchi[a]
Abstract: A variety of optically active
2-hydroxyalkanoates and the corre-
sponding 2-acyloxyalkanoates are pro-
duced by the kinetic resolution of race-
mic 2-hydroxyalkanoates by using achi-
ral 2,2-diarylacetic acid with hindered
carboxylic anhydrides as the coupling
reagents. The combined use of diphe-
nylacetic acid, pivalic anhydride, and
(+)-(R)-benzotetramisole ((R)-BTM)
effectively produces (S)-2-hydroxyalka-
noates and (R)-2-acyloxyalkanoates
from the racemic 2-hydroxyalkanoates
(s-values=47–202). This protocol di-
rectly provides the desired chiral 2-hy-
droxyalkanoate derivatives from achi-
ral diarylacetic acid and racemic secon-
dary alcohols that do not include the
sec-phenethyl alcohol moiety by using
the transacylation process to generate
the mixed anhydrides from the acid
components with bulky carboxylic an-
hydrides under the influence of the
chiral acyl-transfer catalyst. The transi-
tion state that provides the desired
(R)-2-acyloxyalkanoate from (R)-2-hy-
droxyalkanoate included in the racemic
mixture is disclosed by DFT calcula-
tions, and the structural features of the
transition form are also discussed.
Keywords: anhydrides · chirality ·
density functional calculations
·
enantioselectivity · kinetic resolu-
tion
Introduction
ble materials through the resolution of the racemic sub-
strates.
Optically active 2-hydroxy- and 2-acyloxyalkanoates[1] are
frequently utilized as fundamental synthons for the produc-
tion of chiral molecules, such as medicines, biologically
active chemicals, and advanced functionalized polymers. Re-
cently, several effective methods for the kinetic resolution of
racemic sec-phenethyl alcohol derivatives were developed
that afforded the corresponding chiral secondary alcohols
with high enantiomeric excesses [Eq. (1)]:[2] however, to the
best of our knowledge a general artificial method for the ki-
netic resolution of 2-hydroxyalkanoates [Eq. (2)] has not yet
appeared until now. Because of the extensive synthetic utili-
ty of the chiral 2-hydroxyalkanoate derivatives, it is strongly
desired to establish a facile protocol to prepare these valua-
[a] Prof. Dr. I. Shiina, Dr. K. Nakata, K. Ono, M. Sugimoto,
A. Sekiguchi
We have recently reported the first asymmetric esterifica-
tion of achiral carboxylic acids with racemic benzylic alco-
hols[3] through the formation of mixed anhydrides in situ by
using aromatic or pivalic anhydrides with chiral acyl-transfer
catalysts, such as (À)-(S)-tetramisole and (+)-(R)-benzote-
tramisole ((R)-BTM), which were introduced by Birman
et al.[4] The asymmetric esterification also directly provides
Department of Applied Chemistry, Faculty of Science
Tokyo University of Science, Kagurazaka, Shinjuku-ku
Tokyo 162-8601 (Japan)
Fax : (+81)3-3260-5609
E-mail: shiina@rs.kagu.tus.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902257.
Chem. Eur. J. 2010, 16, 167 – 172
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
167

the chiral 2-arylpropionic acid derivatives from the corre-
sponding racemic 2-arylpropionic acids by using kinetic res-
olution with achiral secondary alcohols through the forma-
tion of the mixed anhydrides derived from the acid compo-
nents and aromatic anhydrides under the influence of (R)-
BTM or (S)-b-Np-BTM.[5] Because these protocols utilized
rapid transacylation to form the suitable mixed anhydrides
from free carboxylic acids in situ, we expected that the pres-
ent asymmetric esterification could be applicable for not
only preparation of chiral sec-phenethyl alcohol derivatives,
but also for the production of optically active 2-hydroxyal-
kanoates. Herein, we report the novel and useful kinetic res-
olution of racemic 2-hydroxyalkanoates that do not contain
an aryl alkyl carbinol moiety, by using the present mixed-an-
hydride technology with free achiral carboxylic acids and
hindered carboxylic anhydrides.
termediary mixed anhydrides by introducing several sub-
stituents to the 2-positions of the electrophiles. The results
are shown in entries 3–7 of Table 1. Fortunately, we discov-
ered that diphenylacetic acid is a very effective electrophile
and it afforded the desired chiral benzyl 2-(diphenylacetox-
y)propanoate ((R)-2e) and benzyl lactate ((S)-1) in good en-
antiomeric excesses (95 and 62% ee, respectively) with high
chemical conversion (35% yield of (R)-2e and 48% recov-
ery of (S)-1) as depicted in entry 5 in Table 1. Because an
excellent s-value (s=70) and medium chemoselectivity (2e/
2’=80/20) were attained in this case in which the kinetic res-
olution was carried out in the presence of PMBA as shown
above, we further attempted to improve the chemoselectivi-
ty of the desired ester 2e over the undesired byproduct 2’
for practical use of this reaction.
Several carboxylic anhydrides including two aromatic an-
hydrides and four other kinds of aliphatic anhydrides were
next examined as coupling reagents for the kinetic resolu-
tion of (Æ)-1 with diphenylacetic acid (3) in order to pre-
vent the formation of 2’ (Table 2). Surprisingly, all of the re-
Results and Discussion
First, the reactions of racemic benzyl lactate ((Æ)-1) with
several achiral carboxylic acids were chosen as model cases
for optimization of electrophile structure (Table 1). In the
Table 2. Kinetic resolution of racemic benzyl lactate ((Æ)-1) with diphe-
nylacetic acid (3).
Table 1. Kinetic resolution of racemic benzyl lactate ((Æ)-1) by using the
mixed-anhydride method.
Entry R1
Yield
of 2
2/2’[b]
ee (2) Yield ee (1)
s
[%]
of 1
[%]
[%][a]
[%][a]
1
2
3
4
Ph
46
35
44
27
37
11
44
87/13
80/20
98/ 2
92
95
94
95
96
97
97
43
48
55
43
44
75
55
84
62
68
75
62
12
82
64
70
62
92
87
Entry R1
Yield
of 2
2/2’[b]
ee (2) Yield ee (1)
s
[PMBA]
4-MeOC6H4
tBu
PhMe2C
Ph2MeC
Ph3C
[%]
of 1
[%]
[%][a]
[%][a]
98/ 2
1
2
3
4
5
6
7
Ph
(CH2)2 (a)
33
35
50
38
35
8
86/14
86/14
95/ 5
87/13
80/20
84/16
89/11
1
80
85
85
88
95
94
95
54
42
47
34
48
86
52
42
46
78
56
62
6
14
20
29
27
70
35
63
5
>99/<1
>99/<1
98/ 2
pTolCH2 (b)
iPr (c)
cHex (d)
Ph2CH (e)
6
72
146
7[c]
tBu
[a] Isolated yield. [b] Determined by 1H NMR spectroscopy. [c] Diethyl
ether was used as a solvent instead of dichloromethane.
ACHTUNGTRENNUNG
G
31
51
[a] Isolated yield. [b] Determined by H NMR spectroscopy.
actions afforded very good enantioselectivities, and the cor-
responding carboxylic ester (R)-2e and the resulting alcohol
(S)-1 were obtained in high enantiomeric excesses (s=>62).
It was found that the use of bulky anhydrides, such as pivalic
anhydride, provided the optically active ester 2e with almost
no formation of the undesirable ester 2’ as shown in en-
tries 3–6 in Table 2.[3b] The solvent effect was further exam-
ined in the above reaction and we found that diethyl ether
functions as a suitable medium for the kinetic resolution of
(Æ)-1 to produce the desired ester (R)-2e in good yield
(44%) with an excellent enantiomeric excess (97% ee), so
that the s-value dramatically increased to 146 (Table 2,
entry 7).
presence of 4-methoxybenzoic anhydride (PMBA) as a cou-
pling reagent, (R)-BTM was used for chiral induction ac-
cording to the standard reaction conditions established in
our preceding papers.[3] As shown in entries 1 and 2 in
Table 1, the esterification provides the chiral lactate ((S)-1)
and the corresponding 2-acyloxypropanoates ((R)-2a and
(R)-2b) with medium selectivities (s=14 and 20).[6] We next
increased the bulkiness around the carbonyl group of the in-
168
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 167 – 172

Kinetic Resolution of the Racemic 2-Hydroxyalkanoates
FULL PAPER
Table 4. Kinetic resolution of racemic benzyl 2-hydroxy-3-methylbuta-
noate ((Æ)-4d) with diphenylacetic acid (3).
Eventually, esterification of a variety of racemic 2-hydrox-
yalkanoates ((Æ)-4a–j) with diphenylacetic acid (3) by pro-
motion with pivalic anhydride and (R)-BTM was demon-
strated in order to assess the generality of this novel method
(Table 3). All the reactions with 2-hydroxyalkanoates that
Table 3. Kinetic resolution of racemic benzyl 2-hydroxyalkanoates ((Æ)-
4a–j) by the mixed-anhydride method.
Entry Solvent
Yield 5d/5d’[b] ee (5d) [%] Yield ee (4d)
s
of 5d
of 4d
[%]
[%][a]
[%][a]
1
2
3
4
5
6
7
8
CH2Cl2
toluene
Et2O
32
26
46
44
40
36
38
10
>99/<1
>99/<1
>99/<1
>99/<1
>99/<1
>99/<1
>99/<1
>99/<1
84
84
92
92
93
93
90
92
47
58
50
54
54
58
61
82
49
65
73
77
69
53
57
22
19
22
53
57
52
50
33
28
iPr2O
MTBE[c]
CPME[d]
THF[e]
DMF[f]
Entry
R
Yield
of 5
5/5’[b]
ee (5) Yield ee (4)
s
[%]
of 4
[%]
[%][a]
[%][a]
1
2
3
4
5
6
7
8
9
Me (a)
Et (b)
44
46
50
46
47
45
43
48
47
45
98/2
97
95
95
92
96
94
91
96
93
96
55
43
48
50
51
55
53
47
50
52
82[c] 146
[a] Isolated yield. [b] Determined by 1H NMR spectroscopy. [c] Methyl
tert-butyl ether. [d] Cyclopentyl methyl ether. [e] Tetrahydrofuran.
[f] N,N-Dimethylformamide.
>99/<1
>99/<1
>99/<1
>99/<1
>99/<1
>99/<1
99/1
94
97
73
88
97
75
95
87
87
126
171
53
128
140
47
202
80
146
nPr (c)
iPr (d)
nBu (e)
iBu (f)
cHex (g)
Ph
TBSOCH2 (i)
(CH2)2 (j)
coupling between alcohol (R)-4d and carboxylic acid 3 in
the presence of (R)-BTM. Other solvents such as dichloro-
methane and toluene were rather less effective (Table 4, en-
tries 1 and 2; s=19 and 22) compared with dialkyl ethers
(Table 4, entries 3–6; s=>50),[7] and N,N-dimethylforma-
mide (DMF) was ineffective for this reaction because only
10% of the desired ester 5d was obtained although the
enantioselectivity factor was acceptable (Table 4, entry 8;
s=28).
The estimated reaction pathway is illustrated in Scheme 1.
First, a mixed anhydride (B) forms as a key intermediate in
situ from pivalic anhydride (A) with diphenylacetic acid (3)
after generation of the zwitterion (Int-I) during steps i and ii
by the promotion of the nucleophilic catalyst ((R)-BTM).
Actually, when pivalic anhydride (A) was treated with 3 in
the presence of triethylamine with (R)-BTM, the facile for-
mation of the mixed anhydride (B) was observed on the
(CH2)2 (h)
>99/<1
>99/<1
10 TBSO
U
[a] Isolated yield. [b] Determined by 1H NMR spectroscopy. [c] 5a=2e,
4a=1.
have linear alkyl substituents R next to the carbonyl group
produced the corresponding esters (R)-5a–c, 5e, 5 f, and 5h
in good enantiomeric excesses (Table 3, entries 1–3, 5, 6, and
8; R=Me, Et, nPr, nBu, iBu, and PhACTHNUGTRNEG(UN CH2)2; 94–97% ee)
with excellent s-values (s=126–202). It is noteworthy that
this protocol was successfully applied for the preparation of
chiral dihydroxy ester equivalents (R)-5i (93% ee) and (S)-
4i (87% ee) in the same manner by the asymmetric coupling
reaction starting from the racemic benzyl 3-(tert-butyldime-
thylsiloxy)-2-hydroxypropanoate ((Æ)-4i) with the achiral
electrophile 3, as shown in entry 9 in Table 3 (R=
TBSOCH2, s=80). Furthermore, the kinetic resolution of
racemic benzyl 4-(tert-butyldimethylsiloxy)-2-hydroxybuta-
noate ((Æ)-4j) with 3 also effectively produced the optically
active malic acid derivatives (R)-5j (96% ee) and (S)-4j
(87% ee) in 45% and 52% yields, respectively (Table 3,
1
basis of a H NMR experiment. Next, the mixed anhydride
(B) is activated again by (R)-BTM to form the correspond-
ing zwitterionic species (Int-II), which then selectively reacts
with benzyl (R)-2-hydroxyalkanoates ((R)-4a–j) included in
the racemic mixture (Æ)-4a–j to afford the desired carbox-
ylic esters (R)-5a–j with high enantiomeric excesses through
steps iii and iv. Furthermore, the remaining half of the nu-
cleophiles can be recovered as the unreacted optically active
alcohols (S)-4a–j with high enantiopurities.
Determination of the transition state forming the optically
active diester from methyl (R)-lactate ((R)-8) with the elec-
trophile (Int-II) was carried out by using density functional
theory (DFT) calculations at the B3LYP/6-31G*//B3LYP/6-
31G* level according to the method reported by Houk and
Birman et al.[8] We obtained several transition states, and
the most stable structure that produces (S)- or (R)-diester
((S)- or (R)-9) is depicted in Scheme 2.[9,10] It was found that
entry 10; R=TBSOACHTUNGTRENNUNG(CH2)2, s=146).
Several kinds of solvents were next examined in order to
reveal the difference of those effects on the reaction of race-
mic benzyl 2-hydroxy-3-methylbutanoate ((Æ)-4d) with 3
(Table 4). The reactivity of substrate improved when dialkyl
ether was used as a reaction medium (Table 4, entries 3–
7).[4i] These results showed that not only diethyl ether func-
tions as a good medium, but also other ethers such as diiso-
propyl ether, methyl tert-butyl ether (MTBE), and cyclopen-
tyl methyl ether (CPME) facilitated the desirable selective
Chem. Eur. J. 2010, 16, 167 – 172
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169

I. Shiina et al.
the coordination of oxygens in
the pivalate anion onto hydro-
gen in hydroxy (1.132 ꢁ) and
hydrogen at C-2 of the imidazo-
lium salt (2.103 ꢁ). On the
other hand, complexation of
the imidazolium salt (Int-II)
with methyl (S)-lactate ((S)-8),
an enantiomer of methyl (R)-
lactate ((R)-8), produced an un-
stable structure, (S)-8-ts,[11] that
has a higher energy derived
from steric repulsion between
the alkyl substituent at the 2-
position of (S)-8 and one of the
phenyl groups of diphenylacetic
acid moiety of the imidazolium
salt to afford the corresponding
ester (S)-9. Therefore, the de-
sired (R)-diester was selectively
obtained by the rapid transfor-
mation of (R)-8 into (R)-9
through the transition state (R)-
8-ts.
Based on the above theoreti-
cal studies of the reaction
mechanism, it was revealed that
the aromatic part of the benzyl
ester group in 2-hydroxyalka-
noates 4a–j is not required to
achieve high selectivity. Actual-
ly, the use of the racemic ethyl
2-hydroxypentanoate ((Æ)-6) as
an acyl-donor instead of benzyl
2-hydroxyalkanoates for the
present kinetic resolution under
the standard reaction conditions
also afforded the optically
active diester (R)-7 with a high
Scheme 1. Reaction pathway to form the optically active 2-acyloxyalkanoates ((R)-5a–j) and 2-hydroxyalka-
noates ((S)-4a–j).
the high selectivity attained in the present kinetic resolution
can be explained by the rapid transformation of (R)-8 into
(R)-9 through the stabilized transition state (R)-8-ts, which
consists of (R)-8 and the imidazolium salt (Int-II) derived
from the mixed anhydride (B) and (R)-BTM. The distance
enantiomeric excess (97% ee), whereas the unreacted ethyl
2-hydroxypentanoate ((S)-6) was additionally recovered
with a high optical purity (89% ee); this gave excellent se-
lectivity (s=217) as shown in Scheme 3. According to the
above theoretical predictions, the reaction of racemic
methyl lactate ((Æ)-8) with diphenylacetic acid (3) success-
fully proceeded to provide the desired optically active 2-acy-
loxyester (R)-9 and the recovered 2-hydroxyester (S)-8 with
a high selectivity factor (s=119).
À
of the forming C O bond (between carbonyl carbon of the
acid component and oxygen of hydroxy) is 2.172 ꢁ, and the
À
distance of the cleaved O H bond (between oxygen and hy-
drogen in hydroxy) is 1.313 ꢁ. A frequency analysis of (R)-
8-ts revealed that the nucleophilic attack of the alcohol to
carbonyl group and the deprotonation of the hydroxyl group
with the pivalate anion proceeded under the concerted reac-
Conclusions
À
tion mechanism because the C O bond-forming step and
À
the O H bond-cleaving process occurred simultaneously.
In summary, we have developed the first practical method
to provide the optically active 2-hydroxy- and 2-acyloxyalka-
noates by the nonenzymatic kinetic resolution of the race-
mic 2-hydroxyalkanoates by using diphenylacetic acid (3),
pivalic anhydride, and the chiral acyl-transfer catalyst. This
The lactate moiety has a rigid structure in which the confor-
mation is restricted by the attractive interaction between
oxygen in the ester carbonyl group and the positive elec-
tronic charge on the face of the imidazolium salt as well as
170
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 167 – 172

Kinetic Resolution of the Racemic 2-Hydroxyalkanoates
FULL PAPER
2-hydroxyalkanoates, free acid
3, and pivalic anhydride at
room temperature affords both
optically active 2-acyloxyalka-
noates and 2-hydroxyalkanoates
in good yields with high enan-
tiopurities. The utility of the
present protocol will be demon-
strated by the applications of
this reaction system to the syn-
theses of useful and complex
natural molecules in the future.
Experimental Section
General methods, detailed experimen-
tal procedures, spectroscopic data of
all compounds, and Cartesian coordi-
nates and absolute energies for all cal-
culated structures have been provided
in the Supporting Information.
Typical procedure for the synthesis of
the optically active 2-acyloxyalka-
noates from the racemic 2-hydroxyal-
kanoates with diphenylacetic acid (3)
by using pivalic anhydride and (R)-
BTM:
(46.4 mL,
Diisopropylethylamine
0.266 mmol), (R)-BTM
(2.8 mg, 0.0111 mmol) and a solution
of racemic benzyl 4-(tert-butyldime-
thylsiloxy)-2-hydroxybutanoate ((Æ)-
4j; 72.1 mg, 0.222 mmol) in diethyl
ether (0.5 mL) were successively
added to a solution of pivalic anhy-
dride (27.0 mL, 0.133 mmol) and diphe-
nylacetic acid (3; 23.6 mg, 0.111 mmol)
in diethyl ether (0.6 mL) at room tem-
perature. The mixture was stirred for
12 h at room temperature and then
quenched with saturated aqueous
NaHCO3. The organic layer was sepa-
rated and the aqueous layer was ex-
tracted with diethyl ether. The com-
bined organic layers were dried over
Na2SO4. After filtration of the mixture
and evaporation of the solvent, the
crude product was purified by prepa-
rative thin layer chromatography on
silica (hexane/ethyl acetate 5:1) to
afford the corresponding diester (R)-
5j (51.7 mg, 45%, 96% ee) and the re-
covered optically active hydroxyester
(S)-4j (37.2 mg, 52%, 87% ee) as col-
orless oils [Table 3, entry 10, s=146].
Scheme 2. Calculated transition states to form methyl 2-(diphenylacetoxy)propanoate (9) from methyl lactate
(8).
Scheme 3. Kinetic resolution of racemic ethyl 2-hydroxypentanoate ((Æ)-6) and methyl lactate ((Æ)-8) by the
enantioselective mixed-anhydride method.
protocol affords optically active compounds directly from
racemic 2-hydroxyalkanoates that do not contain the sec-
phenethyl alcohol moiety, through transacylation of the
mixed anhydrides generated from 3 with bulky carboxylic
anhydrides under the influence of (R)-BTM. One of the fea-
tures of the present protocol is that it provides a very simple
procedure for producing the desired chiral ester derivatives.
That is, the addition of promoters to the mixture of racemic
Acknowledgements
This study was partially supported by a Research Grant from the Toray
Science Foundation, and a Research Grant from the Center for Green
Photo-Science and Technology.
Chem. Eur. J. 2010, 16, 167 – 172
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171

I. Shiina et al.
sion CHPLC used in the above equation was calculated as CHPLC
=
[1] Enzymatic resolution of (R)- and (S)-hydroxylesters, see: a) T.
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948.
eeA/A(eeE+eeA), in which eeE is the enantiomeric excess of 2-acylox-
CTHUNGTRENNUNG
yalkanoate and eeA is the enantiomeric excess of the unreacted 2-hy-
droxyalkanoate. The conversion values thus obtained were generally
within 1–2% of the values obtained by 1H NMR integration of the
crude reaction mixture.
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[7] A similar solvent effect was observed in the present study for the re-
action of racemic benzyl lactate ((Æ)-1) with propionic anhydride as
shown below.
[8] X. Li, P. Liu, K. N. Houk, V. B. Birman, J. Am. Chem. Soc. 2008,
130, 13836.
[9] All calculations were performed with the program package Spartan
ꢂ08 1.1.1 of Wavefunction Inc. (http://www.wavefun.com).
[10] Cartesian coordinates and absolute energies for all reported struc-
tures are included in the Supporting Information.
[3] a) I. Shiina, K. Nakata, Tetrahedron Lett. 2007, 48, 8314; b) I. Shiina,
K. Nakata, M. Sugimoto, Y. Onda, T. Iizumi, K. Ono, Heterocycles
2009, 77, 801.
[4] a) V. B. Birman, X. Li, Org. Lett. 2006, 8, 1351; b) V. B. Birman, L.
Guo, Org. Lett. 2006, 8, 4859. See also: c) V. B. Birman, E. W.
Uffman, H. Jiang, X. Li, C. J. Kibane, J. Am. Chem. Soc. 2004, 126,
12226; d) V. B. Birman, H. Jiang, Org. Lett. 2005, 7, 3445; e) V. B.
Birman, H. Jiang, X. Li, L. Guo, E. W. Uffman, J. Am. Chem. Soc.
2006, 128, 6536; f) V. B. Birman, X. Li, H. Jiang, E. W. Uffman, Tet-
rahedron 2006, 62, 285; g) V. B. Birman, X. Li, Z. Han, Org. Lett.
2007, 9, 37; h) H. Zhou, Q. Xu, P. Chen, Tetrahedron 2008, 64, 6494;
i) Q. Xu, H. Zhou, X. Geng, P. Chen, Tetrahedron 2009, 65, 2232.
[5] I. Shiina, K. Nakata, Y. Onda, Eur. J. Org. Chem. 2008, 5887.
[6] The s values were determined according to the literature meth-
[11] Another transition state (S)-8-ts-2 to afford (S)-9 was determined.
This structure has earlier transition form compared with (S)-8-ts and
the energy is higher than that of (S)-8-ts (Erel((S)-8-ts) =2.75 kcalmolÀ1
,
E
rel((S)-8-ts-2) =7.66 kcalmolÀ1). Cartesian coordinates of the second
stable transition state (S)-8-ts-2 to afford (S)-9 are described in the
Supporting Information.
Received: August 31, 2009
Published online: November 10, 2009
od:[2b,4c] s=ln
[(1ÀCHPLC
)
E
[(1ÀCHPLC
)
N
172
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