Enantioselective organocatalytic rearrangement of α-acyloxy- β-keto sulfides to α-acyloxy thioesters

Article abstract of DOI:10.1002/adsc.201000376

The first highly enantioselective organocatalytic rearrangement of α-acyloxy-β-keto sulfides to α-acyloxy thioesters has been developed which provides a number of important synthetic building blocks in high yield and with excellent enantioselectivities (e

Full text of DOI:10.1002/adsc.201000376

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DOI: 10.1002/adsc.201000376
Enantioselective Organocatalytic Rearrangement of a-Acyloxy-
b-keto Sulfides to a-Acyloxy Thioesters
Francesca Capitta,a Angelo Frongia,a,* Pier Paolo Piras,a Patrizia Pitzanti,a
and Francesco Seccia
a
Dipartimento di Scienze Chimiche, Universitꢀ degli studi di Cagliari, Complesso Universitario di Monserrato, S.S. 554,
Bivio per Sestu, I-09042 Monserrato (Cagliari), Italy
Fax : (+39)-070-675-4388; phone: (+39)-070-675-4405; e-mail: angelo.frongia@gmail.com
Received: May 14, 2010; Revised: September 15, 2010; Published online: November 17, 2010
Dedicated to Professor Saverio Florio on the occasion of his 70th birthday.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000376.
Abstract: The first highly enantioselective organo-
catalytic rearrangement of a-acyloxy-b-keto sulfides
to a-acyloxy thioesters has been developed which
provides a number of important synthetic building
blocks in high yield and with excellent enantioselec-
tivities (ee: up to 92%).
b-Keto sulfoxides can be prepared by several meth-
ods like: (i) oxidation of b-hydroxy sulfoxides which
are obtained by reaction of a-sulfinylcarbanions with
aldehydes;[3] (ii) reaction of methylsulfinylcarbanion
with esters;[3a] (iii) reaction of phenylsulfinylacetone
dianion with alkyl halides, aldehydes, ketones, a,b-un-
saturated esters, or oxiranes.[4] This method provides
therefore a direct and efficient route for the synthesis
of versatile building blocks from easily available ma-
terials (Scheme 1).
Keywords: Cinchona alkaloids; domino reaction;
enantioselectivity; organocatalysis; protonation;
Pummerer reaction
Although this pathway is frequently used for the
synthesis of relevant molecules,[2d,e] no catalytic asym-
metric version has been reported to date. Realising
the potential of such reaction products for the synthe-
Asymmetric organocatalysis has emerged as a very sis of a-hydroxy acids and their derivatives,[5] it would
powerful methodological approach for the enantiose- be interesting to develop an organocatalysed asym-
lective preparation of chiral compounds, and currently metric variant of this important reaction.
it constitutes a very interesting alternative to the stan-
dard metal-catalysed reactions.[1] Anyhow, despite the
important advances in asymmetric organocatalysis,
several issues still remain unsolved. In particular, the
application of organocatalytic reactions to carry out
key transformations in the context of the synthesis of
complex molecules or natural products still remains
rather unexplored.
For this reason, we consider that the development
of organocatalytic synthetic procedures for the prepa-
ration of basic organic skeletons in a simple and mod-
ular way is an area of particular interest which would
also contribute to the progress in the field.
Within this context, the Pummerer reaction of b-
keto sulfoxides, followed by acyl migration, is a well-
documented strategy[2] for a simple route to a-acyloxy
thioesters, which can be easily transformed into
sulfur-free products such as a-hydroxy acids, amides,
Scheme 1. Pummerer reaction of b-keto sulfoxides, followed
esters and ketones without racemisation.
by acyl migration.
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Table 1. Initial screening studies: catalyst, solvent and reac-
Herein we report the first highly enantioselective
organocatalytic rearrangement of an a-acyloxy-b-keto
sulfide to an a-acyloxy thioester which involves the
generation of a transient enolate through a proton ab-
straction from terminal carbon by a chiral base (Cin-
chona alkaloids), followed by an in situ enantioselec-
tive protonation.
tion temperatures.[a]
Recent research witnesses an increasing application
of organocatalysis in enantioselective protonation re-
actions.[6] These methods are based on the use of an
enol or enolate prepared in situ from a suitable pre-
cursor in the absence of metal components
(Scheme 2).[7]
Entry
Catalyst
[x mol%]
Solvent
T
[8C]
Yield[b]
[%]
ee[c]
[%]
G
1
2
3
4
5
6
7
8
I [20]
I [20]
I [20]
I [20]
I [20]
I [20]
I [10]
I [5]
II [20]
III [20]
IV [20]
I [20]
CH2Cl2
CH2Cl2
DMF
r.t.
0
92
33
98
96
54
96
80
50
90
34
36
50
73
75
14
rac
38
84
88
84
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
DMSO
n-hexane
toluene
toluene
toluene
toluene
toluene
toluene
toluene
Scheme 2. Organocatalysed enantioselective protonation of
transient enolates, formed in situ from enolate precursors.
9
À80
In this connection, Cinchona alkaloids have
emerged as a class of powerful and versatile asymmet-
ric catalysts[8] that may act as an acid-base bifunction-
al catalyst by first deprotonating the substrate to gen-
erate the enolate and then, as an acid (chiral proton
source), by reprotonating the carbanion.
Inspired by the proven ability of Cinchona alkaloids
to behave as effective bifunctional organic catalysts,
we began our investigation by examining the ability
of quinidine I (20 mol%) to promote the organocata-
lytic asymmetric rearrangement of the a-acyloxy b-
keto sulfide 1a to the a-acyloxy thioester 2a. To our
10
11
12[d]
80
À54
56
[a]
Reaction conditions: 1a (0.135 mmol), catalyst (x mol%)
in solvent (0.5 mL), 24 h.
Isolated yield after chromatography.
Determined by HPLC analysis using a chiral stationary
column.
[b]
[c]
[d]
The reaction of 1b in the presence of I was examined.
delight, by performing the reaction in CH2Cl2 we less effective for the selectivity but gave excellent
were able to isolate the desired adduct 2a in 92% chemical yields (Table 1, entries 3 and 4). Changing
yield and 73% ee (Table 1, entry 1). At lower temper- the solvent to n-hexane led to decreases in both enan-
ature (entry 2), the reaction rate is considerably re- tioselectivity and yield of the product (Table 1,
duced, but a slightly improved enantioselectivity was entry 5), while a considerable improvement of the
observed (75% ee). In order to improve the enantio- enantioselectivity with values of 84% ee was obtained
selectivity, we screened different solvents and also the in toluene (Table 1, entry 6).
catalysts II–IV (the results are summarised in
Table 1).
Next we examined the catalyst loading. It should be
noted that the catalyst loading could be reduced to 10
For what concerns the reaction medium it appeared and 5 mol% without any detrimental effect on the se-
that the polarity of the solvent had a pronounced lectivity (ee values ranging from 84 to 88%), although
effect on the yield and/or enantioselectivity. More with concomitant decreasing chemical yield (Table 1,
polar solvents such as DMF and DMSO proved to be entries 7 and 8).
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Enantioselective Organocatalytic Rearrangement of a-Acyloxy-b-keto Sulfides to a-Acyloxy Thioesters
Access to ent-2a could be achieved by changing the not react at room temperature, but after 65 h at 708C
catalyst employed. Indeed, the opposite configuration the adduct was obtained in good yield (60%) and
of 2a (90% yield and À80% ee) was obtained using good enantioselectivity (70% ee).
quinine II (pseudo-enantiomer of I) as catalyst
When an aromatic a-acyloxy b-keto sulfide (R’’=
(Table 1, entry 9). On the other hand cinchonine III C6H5, entries 6 and 7, Table 2), was subjected to the
(Table 1, entry 10) gave a satisfying ee (80%) albeit same reaction conditions, the rearrangement proceed-
with moderate conversion (34% yield), whereas (À)- ed with almost no selectivity even at 08C (0% ee and
N-methylephedrine IV (Table 1, entry 11) displayed 16% ee, respectively). In this case, the stereocenter
poor reactivity (36% yield) and enantioselectivity formed in the reaction should be prone to be racem-
(À54% ee) giving, as expected, the desired product ised due to the phenyl group attached to it (here de-
with the opposite configuration.[9]
protonation at the a-carbon is facilitated by the en-
Only moderate ee (56%) was achieved with the less hanced acidity provided by phenyl substitution).
reactive O-benzoyl substituted substrate 1b (Table 1, However, as shown in Table 2, introduction of a me-
entry 12). As the best results were obtained using qui- thoxy group in the para position of the aromatic ring
nidine I in toluene, we decided to pursue this study gave significant improvement of the ee (entry 8, 40%
using these reaction conditions for examining the sub- ee at 08C) although the reaction rate was considerably
strate scope and the results are reported in Table 2.
reduced.
The use of different substituents in the phenylthio
Linear and branched 3-alkyl-substituted a-acyloxy
b-keto sulfides 1c–e were both effective in the reac- group does not affect the outcome of the reaction.
tion (Table 2, entries 2–4), leading to increased ee Indeed, the presence of an electron-withdrawing
values (88 to 92%) in comparison with the results ob- group such as bromine in 1i (Table 2, entry 9) or of a
tained with 1a, b. On the other hand the more steri- methyl electron-donating group in 1k (Table 2,
cally congested tert-butyl derivative 1f (entry 5) did entry 10) does not have any influence on the enantio-
selectivity of the reaction. When R’ was an aliphatic
group, a relatively slow reaction was observed in the
case of 1l, bearing an ethyl substituent on sulfur (R’=
Table 2. Preliminary scope of the organocatalytic asymmet-
Et), that gave 2l in 62% yield with 62% ee (Table 2,
entry 11). Replacing the ethyl with a benzyl group, as
in a-acyloxy b-keto sulfide 1m, the reaction failed to
afford the desired product 2m (Table 2, entry 12).[10]
The mechanism of this stereoselective rearrange-
ment still remains to be determined. We currently
speculate that the quinidine deprotonates the more
acidic methine position of 1 furnishing the enolate
species A (Scheme 3).
An acyl migration may reasonably be expected to
furnish a transient enolate B followed by an in situ
enantioselective protonation. Proton transfer from
the protonated quinidine catalyst to species B pro-
vides the product and releases the catalyst back into
the cycle. The protonation can occur within the cata-
lyst-enolate ion pair.
ric rearrangement of a-acyl
ACHTUNGTRENNUNG
ACHTUNGTNERoNUNG xy b-keto sulfides 1 to a-acyl-
Entry
R’
R’’
Prod-
uct
Yield
[%][b]
ee[c]
[%]
1
2
Ph
Ph
Me
Et
2a
2c
2d
2e
2f
2g
2g
2h
2i
96
85
98
93
60
96
90
70
95
90
62
0
84
90
88
92
70
rac
16
40
84
90
62
–
3
Ph
Ph
Ph
Ph
Ph
Ph
p-BrC6H4
p-MeC6H4
Et
CH2CH2Ph
i-Pr
t-Bu
Ph
Ph
p-MeOC6H4
Me
i-Pr
CH2CH2Ph
Me
4
5[d]
6
The absolute stereochemistries of compounds 2a–l
were assigned by analogy with that assigned to 2d
after its conversion (via an established and racemisa-
tion-free hydrolysis) to the (À)-2-hydroxy-4-phenyl-
butanoic acid 3 that is an important building block for
the production of a large variety of angiotensin con-
verting enzyme (ACE) inhibitors. Previously pub-
lished characterisation of a-hydroxy acid 3[11] indicates
that the absolute stereochemistry at the 2 position is
R, with [a]2D0: À8.5 (c 1.0, EtOH), matching our exper-
7[e]
8[e]
9
10
11[f]
12
2k
2l
2m
Bn
[a]
Reaction conditions:
1
(0.135 mmol),
quinidine
(20 mol%) in toluene (0.5 mL) at room temperature,
30 h.
[b]
[c]
Isolated yield after chromatography.
Determined by HPLC analysis using a chiral stationary
column.
At 708C, 65 h.
At 08C, 96 h.
imental data for intermediate
Scheme 4.
3
prepared via
[d]
[e]
[f]
Using the method described in Scheme 4, we were
able also to prepare 4-[(R)-2-hydroxypropionyl]mor-
pholine 4. The intermediate 4 can be easily modified
At room temperature, 48 h.
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Scheme 3. Proposed catalytic cycle.
and expanded substrate scope, are under investigation
in our laboratory.
Experimental Section
General Procedure for the Synthesis of Optically
Active a-Acyloxy Thioesters
To a solution of 1a–m (0.135 mmol) in toluene (0.5 mL) was
added quinidine (8.5 mg, 0.027 mmol), and the mixture was
stirred for 30–48 h at room temperature. The crude reaction
mixture was directly loaded on silica gel column without
aqueous work-up and pure products were obtained by flash
column chromatography (silica gel, mixture of hexane/
ether).
Scheme 4. Synthesis of the a-hydroxy acid 3 and morpholino
amide 4.
to prepare optically active antifungal azoles[12] and tri-
cyclic NMDA-glycine antagonists indole-2-carboxylic
acids.[13] Moreover, this formal synthesis allowed us to
confirm the absolute stereochemistry of our a-acyloxy
thioester.
In summary, the methodology reported in this
study adds to the repertoires of organocatalysed enan-
tioselective protonation of transient enolates, formed
in situ from enolate precursors and catalysed by Cin-
1-[(Phenylthio)carbonyl]ethyl acetate (2a): Colourless oil;
yield: 96%. IR (neat): n=1753, 1710 cmÀ1; [a]D22: +60 (c
1
2.88, CHCl3); H NMR (300 MHz, CDCl3): d=1.53 (d, 3H,
J=6.9 Hz), 2.2 (s, 3H), 5.3 (q, 1H, J=6.9), 7.40 (m, 5H);
13C NMR (75 MHz, CDCl3): d=17.7, 20.7, 74.8, 126.2, 129.2,
129.5, 134.7, 169.8, 197.6; MS: m/z=137 (M+À87, 3%), 115
(100%), 87 (65%), 65 (17%), 51 (4%). The ee was deter-
mined to be 84% ee by HPLC (Chiralcel OJ column,
hexane/i-PrOH=90:10, flow rate 1.0 mLminÀ1, l =254 nm):
tRACHTNUTRGENNUG(major)=21.27 min, tRACHUTGNTREN(NUGN minor)=17.27 min; anal. calcd. for
chona alkaloid derivatives. To the best of our knowl- C11H12O3S: C 58.91, H 5.39, S 14.30; found: C 58.97, H 5.43,
S14.25.
1-[(Phenylthio)carbonyl]ethyl benzoate (2b): Colourless
edge this is the first example of an enantioselective
protonation-terminated base-catalysed intramolecular
oxidation-reduction, with concomitant acetyl transfer,
tandem reaction.
Applying this newly developed organocatalytic re-
action we prepared important synthetic building
blocks in high yield and with excellent enantioselec-
tivities (ee: up to 92%).
oil; yield: 50%. IR (neat): n=1729 cmÀ1; [a]D22: À14 (c 1.13,
CHCl3); 1H NMR (300 MHz, CDCl3): d=1.64 (d, 3H, J=
6.9 Hz), 6.56 (q, 1H, J=6.9 Hz), 7.39–7.6 (m, 8H), 8.13–8.17
(m, 2H); 13C NMR (75 MHz, CDCl3): d=17.9, 75.2, 126.1,
128.4, 129.1, 129.4, 129.8, 133.4, 134.6, 165.1, 197.7; MS:
m/z=177 (M+À109, 30%), 105 (100%), 77 (28%), 51 (7%).
The ee was determined to be 56% ee by HPLC (Chiralcel
OJ column, hexane/i-PrOH=90:10, flow rate 1.0 mLminÀ1,
Further extension of this method toward the prepa-
ration of chiral a-amino acids, a detailed mechanism l=254 nm):
tRACTHNGUTRENNU(G major)=22.83 min, tRACHTUNGTREN(NUNG minor)=19.11 min;
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Enantioselective Organocatalytic Rearrangement of a-Acyloxy-b-keto Sulfides to a-Acyloxy Thioesters
anal. calcd. for C16H14O3S: C 67.11, H 4.93, S 11.20; found:
C 67.06, H 4.85, S 11.09.
tRACHTNGUTERNNU(G major)=46.07 min, tRACTHGNUTREN(NUGN minor)=32.63 min; anal. calcd. for
C16H14O3S: C 67.11, H 4.93, S 11.20; found: C 67.20, H 4.98,
S 11.31.
1-[(Phenylthio)carbonyl]propyl acetate (2c): Colourless
oil; yield: 85%. IR (neat): n=1756, 1708 cmÀ1; [a]D19: +87.5
(c 2.08, CHCl3); 1H NMR (300 MHz, CDCl3): d=0.99 (t,
3H), 1.88–1.95 (m, 2H), 2.19 (s, 3H), 5.23–5.27 (m, 1H),
7.35–7.40 (m, 5H); 13C NMR (75 MHz, CDCl3): d=7.3, 20.6,
25.3, 79.1, 126.2, 129.1, 129.4, 134.6, 169.9, 197.0; MS: m/z=
129 (M+À109, 93%), 110 (100%), 101 (93%), 65 (22%). The
ee was determined to be 90% ee by HPLC (Chiralcel OJ
column, hexane/i-PrOH=90:10, flow rate 1.0 mLminÀ1, l=
[(Phenylthio)carbonyl](4-methoxyphenyl)methyl acetate
(2h): Reaction performed over 96 h at 08C; colourless oil;
yield: 70%. IR (neat): n=1750, 1707 cmÀ1. [a]D19: À25 (c
1
0.71, CHCl3); H NMR (300 MHz, CDCl3): d=2.22 (s, 3H),
3.81 (s, 3H), 6.19 (s, 1H), 6.92 (d, 2H), 7.36–7.42 (m, 7H);
13C NMR (75 MHz, CDCl3): d=20.8, 55.3, 79.6, 114.3, 125.8,
129.1, 129.2, 129.3, 129.5, 134.7, 160.4, 169.7, 195.1; MS:
m/z=229 (M+À87, 3%), 179 (31%), 137 (100%), 109
(14%), 77 (7%). The ee was determined to be 40% ee by
HPLC (Chiralcel OJ column, hexane/i-PrOH=70:30, flow
254 nm): tRACHTUNGTRENNUNG(major)=26.05 min, tRACHTUGNTREN(NUGN minor)=21.76 min; anal.
calcd. for C12H14O3S: C 60.48, H 5.92, S 13.46; found: C
60.57, H 5.83, S 13.51.
rate 1.0 mLminÀ1, l=254 nm):
RA
t CHTUNGTREN(NUGN major)=56.59 min,
t HCTUGNTREN(NUGN minor)=47.95 min; anal. calcd. for C17H16O4S: C 64.54, H
RA
1-[(Phenylthio)carbonyl]-3-phenylpropyl acetate (2d):
Colourless oil; yield: 98%. IR (neat): n=1750, 1708 cmÀ1
;
5.10, S 10.14; found: C 64.61, H 4.99, S 9.97.
1
[a]1D9: +63 (c 2.08, CHCl3); H NMR (300 MHz, CDCl3): d=
2.20–2.28 (m, 2H), 2.22 (s, 3H), 2.74–2.80 (m, 2H), 5.33–
5.37 (m, 1H), 7.18–7.47 (m, 10H); 13C NMR (75 MHz,
CDCl3): d=20.7, 31.1, 33.5, 77.7, 126.1, 126.2, 128.3, 128.5,
129.2, 129.6, 134.7, 140.2, 169.9, 197.0; MS: m/z=205
(M+À109, 37%), 163 (22%), 117 (100%), 91 (24%),
77 (6%). The ee was determined to be 88% ee by HPLC
(Chiralcel OJ column, hexane/i-PrOH=90:10, flow
1-[(4-Bromophenylthio)carbonyl]ethyl acetate (2i): Col-
ourless oil; yield: 95%. IR (neat): n=1753, 1711 cmÀ1; [a]D22:
1
+67 (c 1.57, CHCl3); H NMR (300 MHz, CDCl3): d=1.49
(d, 3H, J=6.9 Hz), 2.17 (s, 3H), 5.35 (q, 1H, J=6.9 Hz),
7.22 (d, 2H, J=6.9 Hz), 7.51 (d, 2H, J=6.6 Hz); 13C NMR
(75 MHz, CDCl3): d=17.6, 20.6, 74.6, 124.2, 125.2, 132.3,
136.0, 169.6, 196.9; MS: m/z=188 (M+À116, 25%), 115
(100%), 87 (97%), 69 (10%). The ee was determined to be
84% ee by HPLC (Chiralcel OJ column, hexane/i-PrOH=
rate 1.0 mLminÀ1, l=254 nm):
RA(minor)=29.02 min; anal. calcd. for C18H18O3S: C 68.76, H
tRACTHNGUTERN(UNG major)=36.20 min,
90:10, flow rate 1.0 mLminÀ1, l=254 nm):
14.32 min, RA(minor)=12.89 min; anal.
t CHTUNGTRENNUNG
calcd.
RA
t CHTUNGTRENNUNG
t CHTUNGTRENNUNG
5.77, S 10.20; found: C 68.69, H 5.81, S 10.13.
C11H11BrO3S: C 43.58, H 3.66, S 10.58; found: C 43.47, H
3.58, S 10.49.
1-[(p-Tolylthio)carbonyl]-2-methylpropyl acetate (2k):
1-[(Phenylthio)carbonyl]-2-methylpropyl acetate (2e):
Colourless oil; yield: 93%. IR (neat): n=1756, 1704 cmÀ1
;
[a]3D0: +119 (c 1.24, CHCl3); 1H NMR (300 MHz, CDCl3):
d=1.01 (d, 3H, J=1.5 Hz), 1.03 (d, 3H, J=1.5 Hz), 2.23 (s,
3H), 2.27–2.36 (m, 1H), 5.21 (d, 1H, J=4.5 Hz), 7.34–7.45
(m, 5H); 13C NMR (75 MHz, CDCl3): d=16.7, 18.7, 20.7,
31.0, 82.2, 126.5, 129.2, 129.5, 134.7, 170.2, 197.0; MS: m/z=
143 (M+À109, 77%), 115 (100%), 110 (95%), 65 (15%). The
ee was determined to be 92% ee by HPLC (Chiralcel OJ
column, hexane/i-PrOH=95:5, flow rate 1.0 mLminÀ1, l=
Colourless oil; yield: 90%. IR (neat): n=1756, 1704 cmÀ1
;
[a]1D9: +106.8 (c 1.03, CHCl3); H NMR (300 MHz, CDCl3):
d=1.00 (d, 3H, J=1.5 Hz), 1.02 (d, 3H, J=1.5 Hz), 2.22 (s,
3H), 2.36 (s, 3H), 5.20 (d, 1H, J=4.5 Hz), 7.19–7.27 (m,
4H); 13C NMR (75 MHz, CDCl3): d=16.7, 18.7, 20.7, 21.3,
30.9, 82.2, 122.9, 130.0, 134.6, 139.8, 170.1, 197.4; MS: m/z=
143 (M+À123, 61%), 124 (100%), 91 (25%), 77 (10%). The
ee was determined to be 90% ee by HPLC (Chiralcel OJ
column, hexane/i-PrOH=95:5, flow rate 1.0 mLminÀ1, l=
1
254 nm): tRACHTUNGTRENNUNG(major)=29.95 min, tRACHTUGNTREN(NUGN minor)=42.35 min; anal.
calcd. for C13H16O3S: C 61.88, H 6.39, S 12.71; found: C
61.76, H 6.43, S 12.80.
254 nm): tRACTHNUGTRENNGU(major)=17.37 min, tRACHTUTGNREN(NUGN minor)=15.00 min; anal.
calcd. for C14H18O3S: C 63.13, H 6.81, S 12.04; found: C
63.20, H 6.90, S 12.13.
1-[(Phenylthio)carbonyl]-2,2-dimethylpropyl acetate (2f):
Reaction performed over 65 h at 708C; colourless oil; yield:
60%. IR (neat): n=1756, 1707 cmÀ1. [a]D22: +81.3 (c 2.09,
1-[(Ethylthio)carbonyl]-3-phenylpropyl acetate (2l): Col-
ourless oil; yield: 62%. IR (neat): n=1753, 1689 cmÀ1; [a]D20:
1
CHCl3); H NMR (300 MHz, CDCl3): d=1.04 (s, 9H), 2.22
1
+33.6 (c 1.19, CHCl3); H NMR (300 MHz, CDCl3): d=1.25
(s, 3H), 5.02 (s, 1H), 7.34–7.39 (m, 5H); 13C NMR (75 MHz,
CDCl3): d=20.7, 26.0, 34.5, 84.4, 126.8, 129.0, 129.3, 134.6,
170.0, 196.4; MS: m/z=157 (M+À109, 55%), 129 (63%), 110
(96%), 87 (100%). The ee was determined to be 70% ee by
HPLC (Chiralcel OJ column, hexane/i-PrOH=95:5, flow
(t, 3H), 2.11–2.22 (m, 2H), 2.17 (s, 3H), 2.68–2.74 (m, 2H),
2.85–2.92 (m, 2H), 5.20–5.24 (m, 1H), 7.16–7.31 (m, 5H);
13C NMR (75 MHz, CDCl3): d=14.4, 20.7, 22.7, 31.1, 33.6,
77.7, 126.1, 128.3, 128.4, 140.3, 170.0, 198.9; MS: m/z=206
(M+À60, 51%), 145 (20%), 117 (100%), 91 (53%), 77 (8%).
The ee was determined to be 62% ee by HPLC (Chiralcel
OJ column, hexane/i-PrOH=95:5, flow rate 1.0 mLminÀ1,
rate 1.0 mLminÀ1, l=254 nm):
RA
6.81, S 12.04; found: C 63.05, H 6.70, S 11.92.
[(Phenylthio)carbonyl](phenyl)methyl acetate (2g): Reac-
t CHTUNGTREN(NUGN major)=11.28 min,
RA
t CHTUNGTRENNUNG(minor)=13.86 min; anal. calcd. for C14H18O3S: C 63.13, H
l=254 nm):
t
G
tRACTHNGUTERN(UNG minor)=13.07 min;
AHCTUNGTRENNUNG
anal. calcd. for C14H18O3S: C 63.13, H 6.81, S 12.04; found:
C 63.05, H 6.73, S 11.97.
tion performed over 96 h at 08C; colourless oil; yield: 90%.
IR (neat): n=1753, 1710 cmÀ1; [a]D24: +1.4 (c 1.4, CHCl3);
1H NMR (300 MHz, CDCl3): d=2.23 (s, 3H), 6.24 (s,1H),
7.32–7.51 (m, 10H); 13C NMR (75 MHz, CDCl3): d=20.8,
79.9, 126.2, 127.7, 128.8, 129.2, 129.3, 129.6, 133.8, 134.7,
169.6, 195.0; MS: m/z=199 (M+À87, 4%), 177 (39%), 149 Acknowledgements
(66%), 107 (100%), 77 (21%), 65 (11%). The ee was deter-
mined to be 16% ee by HPLC (Chiralcel OJ column,
hexane/i-PrOH=90:10, flow rate 1.0 mLminÀ1, l=254 nm):
Financial support from the MIUR, Rome, and by the Univer-
sity of Cagliari (National Project “Stereoselezione in Sintesi
Adv. Synth. Catal. 2010, 352, 2955 – 2960
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2959

Francesca Capitta et al.
COMMUNICATIONS
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is gratefully acknowledged.
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2960
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ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2955 – 2960