A [3,3]-sigmatropic process catalysed by acetate. The decarboxylative Claisen rearrangement

Article abstract of DOI:10.1016/j.tet.2005.09.073

Allylic tosylacetates and tosylmalonates undergo acetate-catalysed decarboxylative Claisen rearrangement in the presence of N,O-bis(trimethylsilyl) acetamide. The homoallylic sulfones formed in these transformations correspond to the products of regiospecific allylation of sulfone-stabilised carbanions. A mechanistic rationale is proposed.

Full text of DOI:10.1016/j.tet.2005.09.073

Tetrahedron 62 (2006) 483–495
A [3,3]-sigmatropic process catalysed by acetate.
The decarboxylative Claisen rearrangement
*
Damien Bourgeois, Donald Craig, Fabienne Grellepois, David M. Mountford
and Alan J. W. Stewart
Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Received 15 June 2005; revised 30 August 2005; accepted 16 September 2005
Available online 14 October 2005
Abstract—Allylic tosylacetates and tosylmalonates undergo acetate-catalysed decarboxylative Claisen rearrangement in the presence of
N,O-bis(trimethylsilyl)acetamide. The homoallylic sulfones formed in these transformations correspond to the products of regiospecific
allylation of sulfone-stabilised carbanions. A mechanistic rationale is proposed.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
characterised by the mildness of the conditions used for the
rearrangement step, which often takes place at ambient or
sub-ambient temperature, and by the ready availability of
the substrates from allylic alcohol and carboxylic acid
starting materials.
The Claisen rearrangement enjoys widespread use as a key
strategy-level transformation in organic synthesis.1 The
power of the process stems from (i) its ability to deliver new
carbon–carbon bonds with regiospecific allylic transposition
from simple derivatives of alcohol precursors; (ii) ease of
substrate synthesis; (iii) high levels of stereoslectivity,
which may be predicted largely on the basis of well-
established trends; and (iv) compatibility with a wide range
of functionality, which makes it amenable to application in
total synthesis. Following the discovery of the Claisen
rearrangement in 1912, several variations have been
devised, which augment the original process in terms of
reaction conditions and product functionality. Arguably the
most versatile of these is the Ireland–Claisen rearrangement,
in which silyl ketene acetals derived from allylic carboxylic
esters provide rearranged carboxylic acids on hydrolysis of
the initial silyl ester products (Scheme 1).2 This variant is
In 1991 Davidson and co-workers reported the Ireland–
Claisen rearrangement of a highly substituted allylic
a-phenylsulfonylacetate ester-derived substrate.3 They
generated the requisite sulfonyl-substituted silyl ketene
acetal using the standard lithium diisopropylamide-TMSCl
conditions, and carried out decarboxylation post-rearrange-
ment by heating the product acid under weakly basic
conditions. Following repeated failures in our own
laboratory to repeat the standard rearrangement step on
structurally different tosylacetate substrates, we uncovered
alternative conditions using silylating agent and catalytic,
weak base, which effect rearrangement and decarboxylation
to give homoallylic sulfones 2 in a single step directly
from the allylic a-tolylsulfonylacetate esters 1 (Scheme 2).
We term this process a decarboxylative Claisen rearrange-
ment4 (dCr) reaction; this paper describes our results
in full.5
Scheme 1. The Ireland–Claisen rearrangement.
Keywords: Acetate-catalysed; Claisen rearrangement; Decarboxylation;
Regiospecific allylation.
*
Corresponding author. Fax: C44 20 7594 5868;
e-mail: d.craig@imperial.ac.uk
Scheme 2.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.073

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D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
2. Results and discussion
acyclic substrate possessing a heteroatom-bearing stereo-
centre adjacent to but outside the pericyclic array reacted
with high selectivity (entry 16), though the major
diastereoisomer has yet to be assigned. Yields for the two
silyl ether-containing substrates (entries 13 and 16) were
significantly lower than those for all other substrates, and
this may reflect competing acetate-induced desilylation
taking place under the thermal conditions of the
rearrangement.
2.1. Acetate-catalysed dCr reactions of simple allylic
tosylacetates
Most of the tosylacetate ester substrates 1 required for our
study were easily prepared by combining allylic alcohols
and commercially available6 tosylacetic acid in the presence
of DCC and DMAP.7 Substrates 1m and 1n were made
from 2-hydroxymethyl-2-cyclohexenone 38 according to the
sequence depicted in Scheme 3. Thus, tosylacetylation of 3
followed by enantioselective reduction using (C)-(R)-5,5-
diphenyl-2-methyl-3,4-propano-1,3,2-oxazaborolidine 5 in
conjunction with BH3$THF9 gave secondary alcohol 4 in
high yield and 82% ee as evidenced by 1H NMR analysis of
the derived Mosher esters. Attempted triisopropylsilyl
(TIPS) protection of the alcohol in 4 led to tosylacetyl
migration and silylation of the primary alcohol, providing
substrate 1m in 59% yield. Compound 4 was more
straightforwardly alkylated to give the 4-methoxybenzyl
(PMB) derivative 1n in 66% yield using 4-methoxybenzyl
trichloroacetimidate in conjunction with BF3$OEt2.10
Subsequent to the initial phase of our investigation it
occurred to us that the acetate-catalysed rearrangement
process might equally be viable in the presence of sub-
stoichiometric quantities of BSA as well as of potassium
acetate. This idea was based on the notion that acetate ions
might catalyse trimethylsilyl transfer from the presumed
initial silyl ester rearrangement product to 1, generating
further silyl ketene acetal substrate and rendering the
reaction catalytic in silylating agent. Therefore, we
subsequently investigated a modification of the dCr reaction
using 10 mol% each of BSA and KOAc. In all cases studied
the yields of 2 were comparable with those obtained in the
stoichiometric reactions (Table 2).
2.2. Mechanistic considerations
As alluded to above, we propose a catalytic cycle for the dCr
reactions of 1 in which acetate functions as a silyl transfer
reagent. The cycle is initiated through the generation of 6,
the silyl ketene acetal derivative of 1. This could in principle
take place through the reversible combination of BSA and
KOAc, giving the conjugate base of N-trimethylsilyl-
acetamide and TMSOAc; the former species effects
deprotonation of 1, and the resulting enolate is silylated
by TMSOAc. Alternatively, 1 undergoes direct proton-silyl
exchange with BSA, giving N-trimethylsilylacetamide and
the ketene acetal. Support for the involvement of the latter
pathway comes from the observation that heating of 1a with
BSA alone gave in 49% yield the carboxylic acid 8, the
product of rearrangement but not decarboxylation. Once
formed, silyl ketene acetal 6 undergoes [3,3]-sigmatropic
rearrangement to the silyl ester 7, which is intercepted by
acetate to give the derived carboxylate anion and
regenerated TMSOAc. Decarboxylation gives the conjugate
base of product 2, which can then abstract a proton either
directly from 1, or from N-trimethylsilylacetamide, in which
case the conjugate base of N-trimethylsilylacetamide effects
deprotonation of 1 prior to silylation by TMSOAc in the
next cycle. The proposed mechanisms are depicted in
Scheme 4.
Scheme 3.
Following work by Poli11 and by Trost12 on palladium(0)-
catalysed allylation reactions involving arylsulfonylacetate
esters we examined the use of N,O-bis(trimethylsilyl)-
acetamide (BSA) in conjunction with potassium acetate. We
established that heating of 1 with one equivalent of BSA and
10 mol% KOAc in toluene at 110 8C overnight (conditions
A) gave homoallylic sulfone products 2 in good to excellent
yields. Little or no diminution in yield was observed when
the dCr reactions were carried out using microwave
irradiation in the presence (conditions B) or absence
(conditions C) of solvent (Table 1).
Evidence to support the mechanistic proposals depicted in
Scheme 4 was obtained from the following observations.
Heating of toluene solutions of 1a in the presence of
potassium acetate alone (0.1, 0.5, 1.0 equiv) resulted in
quantitative recovery of starting material. Replacing BSA
with Me3SiOAc, Me3SiOSiMe3 or (Me3Si)2NH likewise
resulted in complete recovery of starting material, and the
same outcome was observed when N-trimethylsilyl-
acetamide was used instead of BSA. In contrast, substitution
of KOAc with Et3N, DBU or pyrrolidine resulted in
formation of acid 8 in yields of 70, 56 and 63%,
respectively. As stated above, treatment of 1a with BSA
The data in Table 1 demonstrate the dCr reaction to be
compatible with a wide range of substrate structure and
functionality. Notably, the transformation worked well
irrespective of allylic geometry (compare entries 1 and 2)
and level of substitution (entries 5 and 6), and delivered
homoallylic sulfones possessing quaternary centres in high
yields (entries 7, 8, 11). Reactions of cyclic, chiral
substrates (entries 9, 10, 12, 13) were usually completely
diastereoselective (but see entry 14), and in one instance an

D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
485
Table 1. Acetate-catalysed decarboxylative Claisen rearrangement reactions of 1: stoichiometric BSA
Entry
Substrate
Product
Yield (%)
Conditions Aa Conditions Bb Conditions Cc
1
2
80
92
81
—
92
59
1a
1b
2a
2a
3
90
81
—
2c
1c
4
5
77
74
—
—
58
—
2d
2e
1d
1e
6
7
88
88
—
—
72
—
1f
2f
2g
2h
1g
8
83
89
81
89
67
—
83
80
80
1hd
9
1i
2i
10
1j
2j
2k
2l
11
12
86
87
—
—
74
—
1ke
1lf
13
55h
—
—
1mg
2m

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D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
Table 1 (continued)
Entry
Substrate
Product
Yield (%)
Conditions Aa Conditions Bb Conditions Cc
14
15
64
86
—
—
—
—
2ni
1ng
2o
1o
16
17
18
62
74
63
—
18
—
—
67
—
1pe
2pj
1q
2qk
1re
2rl
a Conditions A: BSA (1 equiv), KOAc (0.1 equiv), PhMe, reflux, 16 h.
b Conditions B: BSA (1 equiv), KOAc (0.1 equiv), PhMe, microwave irradiation (150 8C [250 W]), 3 min.
c Conditions C: BSA (1 equiv), KOAc (0.1 equiv), no solvent, microwave irradiation (150 8C [250 W]), 3 min.
d See Ref. 13.
e Racemic substrate.
f
Substrate had 84% ee by Mosher ester analysis of precursor alcohol.
g Substrate had 82% ee by Mosher ester analysis of precursor alcohol 4.
h Yield based on 29% recovered 1m.
Product was formed as a 3:1 mixture of anti and syn diastereoisomers (major isomer shown).
i
j
Product was formed as a 7:1 mixture of diastereoisomers (not assigned).
k Product was formed as a 1:1 mixture of diastereoisomers.
l
Product was formed as a 3:2 mixture of diastereoisomers (not assigned).
alone (1.1 equiv) in toluene under reflux gave 8 in 49%
yield; evidently silyl ketene acetal formation and rearrange-
ment, but not decarboxylation take place under these
conditions, pointing to the key, catalytic role of acetate
ion in the silyl transfer step. Use of Me3SiOTf or
t-BuMe2SiOTf together with DBU gave 2a in respective
yields of 15 and 28%, whilst combinations of Me3SiCl and
DBU again gave 8. Lastly, exposure of 1a to a mixture
containing N-trimethylsilylacetamide, t-BuLi and Me3-
SiOAc gave 2a in 67% yield; replacing t-BuLi with KH in
this modified reaction gave the same product in a yield of
51%. These results strongly suggest that whilst the catalytic
cycle requires acetate, the manner of its generation is less
important.
Table 2. Acetate-catalysed decarboxylative Claisen rearrangement
reactions of 1: sub-stoichiometric BSA
Entry
Substrate
Product
Yield (%)
Whilst this work was in progress a report14 appeared from
the laboratory of Posner of a related transformation of
allylic tosylacetate 9, in which exposure to strong base
under thermal conditions effected [3,3]-sigmatropic
rearrangement and decarboxylation in situ. This reaction
was described as a Carroll-type process,15 in which the
substrate was rendered reactive by formation of its
conjugate base. That our acetate-catalysed dCr reaction is
distinct mechanistically from the Carroll reaction is
evidenced by the failure of 1a to react in the presence of
acetate alone, demonstrating that both nucleophile/base and
silylating agent are necessary for the catalytic cycle to be
viable. In our hands, substrate 1s did undergo rearrangement
Conditions Conditions
Aa
Bb
1
2
3
4
1a
1e
1h
1j
2a
2e
2h
2j
88
92
75
98
94
85
87
93
5
91
87
2s
1s
a Conditions A: BSA (0.1 equiv), KOAc (0.1 equiv), PhMe, reflux, 15 h.
b Conditions B: BSA (0.1 equiv), KOAc (0.1 equiv), PhMe, microwave
irradiation (150 8C [250 W]), 3 min.

D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
487
followed by tosylation using t-BuOK–TsF in DMSO. Four
equivalents of the anion of 10 with respect to TsF were
required for acceptable levels of conversion; unconsumed
malonate was usually recoverable in good yield.17,18
Treatment of 11 with one equiv BSA and 0.1 equiv KOAc
in CH2Cl2 at rt during reaction times ranging from 4 to 16 h
resulted in generally high-yielding dCr reactions, providing
the products 12 of formal regiospecific allylation of methyl
tosylacetate. The reactions of all substrates other than 11a
and 11e gave rise to mixtures of diastereoisomers on
account of the additional a-stereocentre in the products.19
The dCr reactions of chiral substrates showed the
diastereoselectivities for new C–C bond formation expected
on the basis of simple steric considerations. The synthesis
and dCr reactions of 11 are depicted in Scheme 6 and the
results summarised in Table 3.
Scheme 4.
and decarboxylation to give 2s in good yield when
exposed to NaH in toluene under reflux over a 4-day period
(Scheme 5).
Scheme 6.
The reduction in minimum temperature required for the
acetate-catalysed dCr reactions of these modified substrates
to occur is striking. Also noteworthy was the observation
that these room-temperature transformations took place
with similar efficiencies but significantly more rapidly when
the BSA–OAc reagent system was substituted with
DBU–TBDMSOTf.5b In the dCr reactions of tosylacetates
1 DBU–TBDMSOTf was markedly inferior to BSA–OAc,
and combinations of BSA and Et3N gave rearrangement but
no decarboxylation.5a We have interpreted5b these findings
in terms of an alternative dCr reaction mechanism for
malonate substrates 11, in which the ketene acetals formed
in the [3,3]-sigmatropic rearrangement step undergo
decarboxylation by a mechanism not requiring acetate,
involving silatropic rearrangement23 in a formal retro-ene
reaction. Formation of the silyl ketene acetal derivatives of
the isolated products 12 in this way would consume BSA,
consistent with the finding that the use of sub-stoichiometric
quantities of BSA resulted in incomplete conversion of 11.
Scheme 5.
2.3. dCr Reactions of allylic methyl tosylmalonates
With the efficiency and scope of the dCr reaction of simple
allylic tosylacetates established, our attention was turned to
the development of modified substrates. It was anticipated
that addition of an electron-withdrawing group at the ester
a-position would enhance reactivity, such that ambient-
temperature reactions would be attainable. This was an
attractive goal in view of our longer-term plan to realise
high levels of selectivity in the reactions of acyclic, chiral
substrates related to 1p, 1q, and 1r. Methoxycarbonyl was
chosen as the electron-withdrawing auxiliary group.
Substrates 11 were readily prepared from methyl malonate16
in generally good yields by DCC–MAP-mediated esterifica-
tion with allylic alcohols to give mixed malonates 10,5b
3. Conclusions
In summary, we have uncovered an acetate-catalysed
variant of the Claisen rearrangement reaction, which allows
regiospecific allylation of sulfone-substituted carbon
moieties.24 To our knowledge, this is the first example of
a ketene acetal formation-Claisen rearrangement sequence,
which utilises sub-stoichiometric amounts of base and

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D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
Table 3. Synthesis and dCr reactions of allylic methyl tosylmalonates 11
Entry
10
11
12
OR
Substrate
Structure
Yielda
Structure
Yield
1
2
10a
11a
11b
67 (79)
12ab
12b
62
10b
60 (65)
74
3
4
5
6
10c
10d
10e
10f
11c
11d
11e
11f
70 (74)
56 (99)
90 (91)
79 (83)
12cc
12d
12e
12f
81
59
80
88
7
8
10g
10h
11g
11h
78 (99)
12g
12h
72
45
81 (100)
9
10i
11i
74 (66)
12i
19
a See Ref. 20.
b See Ref. 21.
c See Ref. 22.
silylating agent. Addition of an electron-withdrawing group
to the sulfone-substituted carbon atom results in significant
acceleration of the acetate-catalysed tandem process such
that the reactions proceed at rt. We are presently applying
this chemistry in the synthesis of pyridines, phenols, and
alkaloid natural products, and have investigated dia-
stereoselective dCr reactions of the sulfoximine analogues
of 1.25 The results of these studies will be the subject of
future reports from this laboratory.
apparatus and are uncorrected. Chromatography refers to
flash chromatography on BDH (40–63 mM) silica gel.
Analytical thin-layer chromatography was performed
using pre-coated aluminium-backed plates (Merck
Kieselgel 60 F254) and visualised with ultraviolet light
and/or acidic ammonium molybdate(IV), acidic vanillin,
ethanolic potassium permanganate or acidic 3,5-dinitro-
phenylhydrazine solutions. Standard solvents were distilled
under nitrogen; Et2O and THF from sodium-benzophenone
ketyl, CH2Cl2 and MeCN from calcium hydride and PhMe
from sodium. Petrol refers to petroleum ether bp 40–60 8C.
Other solvents and reagents were used as received or
purified before use according to standard procedures.26 All
reactions were performed under an atmosphere of nitrogen
unless stated otherwise.
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded in CDCl3 (unless
otherwise stated) on either Jeol GX-270a, DRX 300, DRX
400 or Aspect 500 spectrometers, using residual isotopic
solvents as internal reference. Infra-red spectra were
measured on a Mattson 5000 FTIR spectrometer. Mass
spectra were recorded using VG 707E or VG Autospec Q
instruments. Accurate masses were determined using the
Autospec Q instrument at Imperial College. Elemental
combustion analyses were performed in the Imperial
College microanalytical laboratory. Melting points were
measured on a Stuart Scientific SMP1 melting point
4.1.1. Preparation of (S)-6-hydroxycyclohexen-1-
ylmethyl tosylacetate (4). To a stirred solution of
2-hydroxymethyl-2-cyclohexenone 38 (494 mg, 3.9 mmol)
in CH2Cl2 (53 mL) was added a solution of DCC (892 mg,
4.33 mmol, 1.1 equiv) in CH2Cl2 (11 mL) and tosylacetic
acid (927 mg, 4.33 mmol), the solution stirred for 5 min and
DMAP (48 mg, 0.39 mmol) added. The cloudy reaction
mixture was stirred at rt for 24 h, filtered through Celite, the
pad washed with EtOAc (10 mL) and the organic layers
washed with 1 M KHSO4 (50 mL), saturated NaHCO3

D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
489
(50 mL) and brine (50 mL). The organic layers were dried
(MgSO4), concentrated under reduced pressure and purified
by chromatography (60% EtOAc/petrol) to give 6-oxo-
cyclohexen-1-ylmethyl tosylacetate (1.01 g, 80%) as a
colourless solid; mp 134–136 8C; Rf 0.27 (60% EtOAc/
petrol); nmax (CH2Cl2) 2936, 2888, 1742, 1672, 1453, 1327,
1272, 1150, 1118, 815, 646 cmK1; dH (270 MHz) 7.67 (2H,
d, JZ8.0 Hz, ortho-ArH), 7.24 (2H, d, JZ8.0 Hz, meta-
ArH), 6.58 (1H, t, JZ4.0 Hz, C]CH), 4.76 (2H, d, JZ
1.0 Hz, CH2O), 4.10 (2H, s, CH2SO2), 2.46–2.39 (4H, m,
ring CH2), 2.41 (3H, s, CH3), 2.00–1.92 (2H, m, ring CH2);
dC (67.5 MHz) 197.6 (C]C–C]O), 162.2 (OC]O), 149.4
(C]CH), 145.4 (C]CH), 135.8 (para-Ar), 133.2 (ipso-
Ar), 129.9 (meta-Ar), 128.4 (ortho-Ar), 62.8 (CH2O), 60.9
(CH2SO2), 37.9 (CH2CH2C]O), 25.7 (ring CH2), 22.5
(ring CH2), 21.7 (CH3); m/z (CI) 340 [MCNH4]C (found:
[MCNH4]C, 340.1219. C16H18O5S requires [MCNH4]C,
340.1219) (found: C, 59.69; H, 5.84. C16H18O5S requires C,
59.61; H, 5.84%). To a stirred solution of (R)-5,5-diphenyl-
2-methyl-3,4-propano-1,3,2-oxazaborolidine (1 M in
PhMe; 31 ml, 0.03 mmol) in THF (0.2 mL) at 0 8C was
added BH3$THF (1 M in THF; 200 ml, 0.20 mmol) and the
solution stirred for 5 min before dropwise addition of a
solution of 6-oxocyclohexen-1-ylmethyl tosylacetate
(100 mg, 0.31 mmol) in CH2Cl2 (0.8 mL) at 0 8C. The
reaction was stirred at 0 8C for 10 min, H2O (0.5 mL) added
and reaction mixture partitioned between brine (5 mL) and
CH2Cl2 (10 mL). The organic layers were separated, the
aqueous phase further extracted with CH2Cl2 (10 mL), the
combined organic layers dried (MgSO4) and concentrated
under reduced pressure. Chromatography (60% EtOAc/
petrol) gave the ester 4 (87 mg, 87%) as a colourless oil; Rf
0.28 (60% EtOAc/petrol); [a]2D5K28.5 (c 2.5, CHCl3); nmax
(film) 3528, 3456, 2934, 2867, 1732, 596, 1441, 1323, 1304,
1150, 1085, 812, 729, 644 cmK1; dH (270 MHz) 7.77 (2H,
d, JZ8.0 Hz, ortho-ArH), 7.33 (2H, d, JZ8.0 Hz, meta-
ArH), 5.85 (1H, t, JZ3.5 Hz, C]CH), 4.79 (1H, d, JZ
12.0 Hz, CH2O), 4.47 (1H, d, JZ12.0 Hz, CH2O), 4.11 (1H,
m, CHOH), 4.09 (2H, s, CH2SO2), 2.44 (3H, s, CH3), 2.29
(1H, br s, OH), 2.15–1.82 (2H, m, ring CH2), 1.80–1.49 (4H,
m, ring CH2); dC (67.5 MHz) 162.5 (C]O), 145.6
(C]CH), 135.7 (para-Ar), 134.0 (ipso-Ar), 132.2
(C]CH), 130.0 (meta-Ar), 128.5 (ortho-Ar), 68.6
(CH2O), 64.9 (CHOH), 61.2 (CH2SO2), 31.6 (CH2CHOH),
25.4 (ring CH2), 21.8 (CH3), 18.1 (ring CH2); m/z (CI) 342
[MCNH4]C (found: [MCNH4]C, 342.1378. C16H20O5S
requires [MCNH4]C, 342.1375) (found: C, 58.95; H, 6.03.
C16H20O5S requires C, 59.24; H, 6.21%).
a colourless oil; Rf 0.27 (20% EtOAc/petrol); [a]2D5K40.0 (c
0.1, CHCl3); nmax (film) 3563, 3523, 3386, 3060, 2989,
2923, 1469, 1452, 1284, 1242, 1227, 1161, 1030 cmK1; dH
(270 MHz) 5.52 (1H, br s, C]CH), 3.97 (1H, br s, CHOH),
3.17 (1H, q, JZ7.5 Hz, OH), 2.10–1.83 (2H, m, ring CH2),
1.81–1.32 (4H, m, ring CH2), 1.77 (3H, s, Me); dC
(125.8 MHz) 135.2 (C]CH), 125.4 (C]CH), 68.4
(CHOH), 32.2 (CH2CHOH), 25.4 (CH3), 20.6 (ring CH2),
18.1 (ring CH2); m/z (CI) 130 [MCNH4]C (found: [MC
NH4]C, 130.1227. C7H12O requires [MCNH4]C,
130.1231).
4.2. Standard procedure for preparation of 1 by
tosylacetylation of allylic alcohols
To a solution of allylic alcohol (2.00 mmol, 1.0 equiv) in
dichloromethane (10 mL) was added 4-(dimethylamino)-
pyridine (24.3 mg, 0.20 mmol, 0.1 equiv) followed by a
solution of 1,3-dicyclohexylcarbodiimide (453 mg,
2.20 mmol, 1.1 equiv) in dichloromethane (2 mL). After
5 min tosylacetic acid (471 mg, 2.20 mmol, 1.1 equiv) was
added and the reaction stirred at rt for 15 h. The crude
mixture was filtered, and the precipitate washed with EtOAc
(10 mL). The solution was then washed with aqueous
KHSO4 (1 M; 10 mL), saturated aqueous NaHCO3 (10 mL),
brine (10 mL) and dried (MgSO4). Concentration under
reduced pressure and chromatography (EtOAc/petrol)
yielded tosylacetates 1.
4.2.1. Spectroscopic data for 1a. Yield 94%; Rf 0.16 (20%
EtOAc/petrol); nmax (film) 2960, 2932, 2874, 1740 (C]O),
1598, 1455, 1399, 1379, 1326 (SO2), 1304, 1154 (SO2),
1086, 971, 725, 646 cmK1; dH (270 MHz, CDCl3) 7.64 (2H,
d, JZ8.0 Hz, ortho SO2–Ar-CH3), 7.17 (2H, d, JZ8.0 Hz,
meta SO2–Ar-CH3), 5.61–5.44 (1H, m, H-3), 5.31–5.16 (1H,
m, H-2), 4.31 (2H, dd, JZ6.5, 1.0 Hz, CH2-1), 3.98 (2H, s,
CH2–SO2–Ar-CH3), 2.25 (3H, s, SO2–Ar-CH3), 1.88–1.73
(2H, m, CH2-4), 1.29–1.11 (2H, m, CH2-5), 0.71 (3H, t, JZ
7.5 Hz, CH3-6); dC (67.5 MHz, CDCl3) 162.3 (C]O),
145.2 (para SO2–Ar-CH3), 137.1 (ipso SO2–Ar-CH3), 136.0
(C-3), 129.5 (meta SO2–Ar-CH3), 128.5 (ortho SO2–Ar-
CH3), 123.8 (C-2), 66.6 (C-1), 60.9 (CH2–SO2–Ar-CH3),
34.1 (C-4), 21.8 (C-5), 21.5 (SO2–Ar-CH3), 13.5 (C-6); m/z
(CI) 314 [MCNH4]C, 232, 174, 160, 82 (found: [MC
NH4]C, 314.1431. C15H20O4S requires [MCNH4]C,
314.1426) (found: C, 60.83; H, 6.85. C15H20O4S requires
C, 60.79; H, 6.80%).
4.2.2. Spectroscopic data for 1b. Yield 85%; Rf 0.22 (25%
EtOAc/petrol); nmax (film) 3006, 2959, 2933, 2872, 1735
(C]O), 1599, 1455, 1359, 1328 (SO2), 1284, 1153 (SO2),
1085, 972, 813, 731, 647 cmK1; dH (270 MHz, CDCl3) 7.76
(2H, d, JZ8.5 Hz, ortho SO2–Ar-CH3), 7.30 (2H, d, JZ
8.5 Hz, meta SO2–Ar-CH3), 5.66–5.50 (1H, m, H-3),
5.42–5.28 (1H, m, H-2), 4.57 (2H, d, JZ7.0 Hz, CH2-1),
4.06 (2H, s, CH2–SO2–Ar-CH3), 2.39 (3H, s, SO2–Ar-CH3),
2.04–1.91 (2H, m, CH2-4), 1.41–1.23 (2H, m, CH2-5), 0.83
(3H, t, JZ7.5 Hz, CH3-6); dC (67.5 MHz, CDCl3) 162.5
(C]O), 145.4 (para SO2–Ar-CH3), 136.2 (C-3), 135.8 (ipso
SO2–Ar-CH3), 129.9 (meta SO2–Ar-CH3), 128.6 (ortho
SO2–Ar-CH3), 122.3 (C-2), 61.9 (C-1), 61.1 (CH2–SO2–Ar-
CH3), 29.5 (C-4), 22.5 (C-5), 21.7 (SO2–Ar-CH3), 13.7
(C-6); m/z (CI) 610 [2MCNH4]C, 314 [MCNH4]C, 288,
4.1.2. (S)-2-methyl-2-cyclohexenol. To a stirred solution of
(R)-5,5-diphenyl-2-methyl-3,4-propano-1,3,2-oxazaboro-
lidine (1 M in PhMe; 1.38 mL, 1.38 mmol) in THF (9 mL)
at 0 8C was added borane–THF complex (1 M in THF;
9.04 mL, 9.04 mmol) and the solution stirred for 5 min before
addition of a solution of 2-methyl-2-cyclohexenone (1.53 g,
13.89 mmol)inTHF(37 mL)at0 8Cviacannula. Thereaction
was stirred at 0 8C for 2 min, H2O (20 mL) slowly added and
the reaction mixture partitioned between brine (100 mL) and
CH2Cl2 (200 mL). The organic layers were separated, the
aqueous phase further extracted with CH2Cl2 (200 mL), the
combined organic layers dried (MgSO4) and concentrated
under reduced pressure. Chromatography (20% EtOAc/
petrol) gave (S)-2-methyl-2-cyclohexenol (1.22 g, 79%) as

490
D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
248, 82 (found: [MCNH4]C, 314.1425. C15H20O4S
requires [MCNH4]C, 314.1426).
(270 MHz, CDCl3) 7.79 (2H, d, JZ8.5 Hz, ortho SO2–Ar-
CH3), 7.37–7.14 (7H, m, meta SO2–Ar-CH3, Ph), 6.42 (1H,
s, H-3), 4.60 (2H, s, CH2-1), 4.15 (2H, s, CH2–SO2–Ar-
CH3), 2.32 (3H, s, SO2–Ar-CH3), 1.77 (3H, d, JZ1.0 Hz,
CH3-30); dC (67.5 MHz, CDCl3) 162.4 (C]O), 145.5 (para
SO2–Ar-CH3), 136.8 (C-2), 135.9 (ipso SO2–Ar-CH3),
131.6 (ipso Ph), 130.0 (meta SO2–Ar-CH3), 129.5 (meta
Ph), 129.0 (para Ph), 128.6 (ortho SO2–Ar-CH3), 128.3
(ortho Ph), 127.1 (C-3), 71.9 (C-1), 61.1 (CH2–SO2–Ar-
CH3), 21.7 (SO2–Ar-CH3), 15.5 (C-30); m/z (CI) 362 [MC
NH4]C, 188, 116, 108 (found: [MCNH4]C, 362.1430.
C19H20SO4 requires [MCNH4]C, 362.1426) (found: C,
66.38; H, 5.70. C19H20SO4 requires C, 66.26; H, 5.85%).
4.2.3. Spectroscopic data for 1c. Yield 83%; Rf 0.14 (20%
EtOAc/petrol); nmax (film) 3009, 2944, 2882, 1741 (C]O),
1661, 1597, 1328 (SO2), 1276, 1151 (SO2), 1085, 992, 814,
727, 647, 609 cmK1; dH (270 MHz, CDCl3) 7.73 (2H, d, JZ
8.5 Hz, ortho SO2–Ar-CH3), 7.27 (2H, d, JZ8.5 Hz, meta
SO2–Ar-CH3), 6.17–6.03 (1H, m, H-3), 5.99–5.84 (1H, m,
H-4), 5.74–5.57 (1H, m, H-2), 5.46–5.31 (1H, m, H-5), 4.48
(2H, d, JZ6.5 Hz, CH2-1), 4.04 (2H, s, CH2–SO2–Ar-CH3),
2.36 (3H, s, SO2–Ar-CH3), 1.69 (3H, d, JZ6.5 Hz, CH3-6);
dC (67.5 MHz, CDCl3) 162.3 (C]O), 145.4 (para SO2–Ar-
CH3), 136.0 (ipso SO2–Ar-CH3), 131.9 (C-2), 130.3 (C-4),
129.9 (meta SO2–Ar-CH3), 128.6 (C-3, ortho SO2–Ar-CH3),
122.3 (C-5), 66.6 (C-1), 61.1 (CH2–SO2–Ar-CH3), 21.7
(SO2–Ar-CH3), 18.2 (C-6); m/z (CI) 312 [MCNH4]C, 188,
98, 821 (found: [MCNH4]C, 312.1278. C15H18O4S
requires [MCNH4]C, 312.1270) (found: C, 61.31; H,
6.07. C15H18O4S requires C, 61.20; H, 6.16%).
4.2.7. Spectroscopic data for 1g. Yield 85%; nmax (film)
3028, 2973, 2938, 1732 (C]O), 1597, 1387, 1326 (SO2),
1151 (SO2), 1085, 959, 814, 726 cmK1; dH (270 MHz,
CDCl3) 7.78 (2H, d, JZ8.0 Hz, ortho SO2–Ar-CH3), 7.25
(2H, d, JZ8.0 Hz, meta SO2–Ar-CH3), 5.14 (1H, tsept, JZ
7.0, 1.0 Hz, H-2), 4.50 (2H, d, JZ7.5 Hz, CH2-1), 4.03 (2H,
s, CH2–SO2–Ar-CH3), 2.36 (3H, s, SO2–Ar-CH3), 1.68 (3H,
s, CH3-4), 1.59 (3H, s, CH3-40); dC (67.5 MHz, CDCl3)
162.5 (C]O), 145.3 (para SO2–Ar-CH3), 140.6 (C-3),
135.7 (ipso SO2–Ar-CH3), 129.8 (meta SO2–Ar-CH3), 128.6
(ortho SO2–Ar-CH3), 117.4 (C-2), 63.0 (C-1), 61.0
(CH2–SO2–Ar-CH3), 25.7 (C-4), 21.7 (SO2–Ar-CH3), 18.0
(C-40); m/z (CI) 300 [MNH4]C, 232, 188, 139, 108, 86
(found: [MNH4]C, 300.1269. C14H18O4S requires
[MNH4]C, 300.1262).
4.2.4. Spectroscopic data for 1d. Yield 96%; Rf 0.09 (20%
EtOAc/petrol); nmax (film) 3030, 2931, 2860, 1741 (C]O),
1597, 1495, 1454, 1398, 1327 (SO2), 1282, 1149 (SO2),
1086, 1018, 968, 814, 735, 700, 646, 607 cmK1; dH
(270 MHz, CDCl3) 7.77 (2H, d, JZ8.5 Hz, ortho SO2–Ar-
CH3), 7.36–7.19 (7H, m, meta SO2–Ar-CH3, Ph), 5.84–5.72
(1H, m, H-3), 5.59–5.47 (1H, m, H-2), 4.61 (2H, d, JZ
7.0 Hz, CH2-1), 4.45 (2H, s, CH2-Ph), 4.07 (2H, s, CH2–
SO2–Ar-CH3), 4.04 (2H, dd, JZ6.5, 1.0 Hz, CH2-4), 2.38
(3H, s, SO2–Ar-CH3); dC (67.5 MHz, CDCl3) 162.4 (C]O),
145.5 (para SO2–Ar-CH3), 138.0 (ipso Ph), 135.8 (ipso
SO2–Ar-CH3), 131.9 (C-3), 129.9 (meta SO2–Ar-CH3),
128.6 (meta Ph), 128.5 (ortho Ph), 127.8 (para Ph), 127.7
(ortho SO2–Ar-CH3), 125.4 (C-2), 72.5 (CH2-Ph), 65.7
(C-4), 62.0 (C-1), 61.0 (CH2–SO2–Ar-CH3), 21.8 (SO2–Ar-
CH3); m/z (CI) 392 [MCNH4]C, 375 [MCH]C, 322, 238,
161, 108, 91 (found: [MCNH4]C, 392.1531. C20H22SO5
requires [MCNH4]C, 392.1532) (found: C, 64.28; H, 5.77.
C20H22O5S requires C, 64.15; H, 5.92%).
4.2.8. Spectroscopic data for 1h. Yield 85%; Rf 0.23 (20%
EtOAc/petrol); nmax (film) 2966, 2925, 2858, 1739 (C]O),
1668, 1597, 1448, 1379, 1329 (SO2), 1280, 1151 (SO2),
1086, 960, 814, 727, 648 cmK1; dH (270 MHz, CDCl3) 7.78
(2H, d, JZ8.0 Hz, ortho SO2–Ar-CH3), 7.32 (2H, d, JZ
8.0 Hz, meta SO2–Ar-CH3), 5.19 (1H, dt, JZ7.0, 1.0 Hz,
H-2), 5.07–4.97 (1H, m, H-6), 4.56 (2H, d, JZ7.0 Hz, CH2-
1), 4.06 (2H, s, CH2–SO2–Ar-CH3), 2.42 (3H, s, SO2–Ar-
CH3), 2.09–1.93 (4H, m, CH2-4, CH2-5), 1.64 (3H, d, JZ
0.5 Hz, CH3-8), 1.63 (3H, d, JZ1.0 Hz, CH3-8), 1.56 (3H, s,
CH3-40); dC (67.5 MHz, CDCl3) 162.5 (C]O), 145.4 (para
SO2–Ar-CH3), 143.7 (ipso SO2–Ar-CH3), 135.9 (C-3),
132.0 (C-7), 129.8 (meta SO2–Ar-CH3), 128.7 (ortho
SO2–Ar-CH3), 123.6 (C-6), 117.1 (C-2), 63.1 (C-1), 61.1
(CH2–SO2–Ar-CH3), 39.6 (C-4), 26.3 (C-8), 25.7 (C-5),
21.8 (SO2–Ar-CH3), 17.8 (C-8), 16.5 (C-40); m/z (CI) 368
[MCNH4]C, 232, 188, 154, 137 (found: [MCNH4]C,
368.1886. C19H26SO4 requires [MCNH4]C, 368.1896)
(found: C, 65.28; H, 7.56. C19H26SO4 requires C, 65.11;
H, 7.48%); in agreement with published data.13
4.2.5. Spectroscopic data for 1e. Yield 94%; Rf 0.11 (20%
EtOAc/petrol); mp 55–56 8C; nmax (film) 3058, 3028, 2945,
1741 (C]O), 1597, 1448, 1327 (SO2), 1275, 1149 (SO2),
1084, 966, 814, 744, 692, 646 cmK1; dH (270 MHz, CDCl3)
7.79 (2H, d, JZ8.0 Hz, ortho SO2–Ar-CH3), 7.41–7.23 (7H,
m, meta SO2–Ar-CH3, Ph), 6.59 (1H, d, JZ16.0 Hz, H-3),
6.12 (1H, dt, JZ16.0, 6.5 Hz, H-2), 4.72 (2H, dd, JZ6.5,
1.0 Hz, CH2-1), 4.12 (2H, s, CH2–SO2–Ar-CH3), 2.37 (3H,
s, SO2–Ar-CH3); dC (67.5 MHz, CDCl3) 171.0 (C]O),
145.2 (para SO2–Ar-CH3), 135.5 (ipso SO2–Ar-CH3, ipso
Ph), 129.9 (meta SO2–Ar-CH3, meta Ph), 128.7 (ortho SO2–
Ar-CH3, ortho Ph), 128.4 (C-3), 126.7 (para Ph), 121.7
(C-2), 66.7 (C-1), 61.2 (CH2–SO2–Ar-CH3), 21.7 (SO2–Ar-
CH3); m/z (CI) 348 [MCNH4]C, 194, 174, 134, 117 (found:
[MCNH4]C, 348.1272. C18H18SO4 requires [MCNH4]C,
348.1270) (found: C, 65.50; H, 5.55. C18H18SO4 requires C,
65.43; H, 5.49%).
4.2.9. Spectroscopic data for 1i. Yield 95%; Rf 0.19 (20%
EtOAc/petrol); [a]2D3K36.5 (c 1.07, CHCl3); nmax (film)
2924, 2839, 1739 (C]O), 1644, 1598, 1452, 1436, 1327
(SO2), 1276, 1151 (SO2), 1085, 968, 888, 813, 728,
641 cmK1; dH (270 MHz, CDCl3) 7.80 (2H, d, JZ8.0 Hz,
ortho SO2–Ar-CH3), 7.35 (2H, d, JZ8.0 Hz, meta SO2–Ar-
CH3), 5.71 (1H, d, JZ4.0 Hz, H-2), 4.77–4.65 (2H, m,
H-60), 4.45 (2H, s, CH2-20), 4.09 (2H, s, CH2–SO2–Ar-
CH3), 2.44 (3H, s, SO2–Ar-CH3), 2.21–1.38 (7H, m, H-4,
CH2-3, CH2-5, CH2-6), 1.72 (3H, m, CH3-600); dC
(67.5 MHz, CDCl3) 162.5 (C]O), 156.8 (C-50), 149.4
(C-1), 145.3 (para SO2–Ar-CH3), 131.6 (ipso SO2–Ar-CH3),
4.2.6. Spectroscopic data for 1f. Yield 88%; Rf 0.14 (20%
EtOAc/petrol); nmax (film) 3024, 2979, 2943, 1741 (C]O),
1598, 1492, 1446, 1398, 1327 (SO2), 1279, 1151 (SO2),
1086, 1026, 985, 814, 750, 727, 700, 642, 607 cmK1; dH

D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
491
129.9 (meta SO2–Ar-CH3), 128.7 (ortho SO2–Ar-CH3),
127.4 (C-2), 109.0 (C-60), 70.4 (C-20), 61.1 (CH2–SO2–Ar-
CH3), 40.7 (C-4), 30.5 (C-5), 27.3 (C-3), 26.3 (C-6), 21.8
(SO2–Ar-CH3), 20.8 (C-600); m/z (CI) 366 [MCNH4]C, 232,
188, 135, 108 (found: [MCNH4]C, 366.1727. C19H24O4S
requires [MCNH4]C, 366.1739) (found: C, 65.69; H, 7.06.
C19H24SO4 requires C, 65.49; H, 6.94%).
4.2.13. Preparation of (S)-2-(triisopropylsilyloxy-
methyl)cyclohex-2-enyl tosylacetate (1m). To a stirred
solution of alcohol 4 (130 mg, 0.40 mmol) in CH2Cl2
(1.4 mL) was added TIPSOTf (128 ml, 0.48 mmol) and
imidazole (55 mg, 0.80 mmol) and the reaction mixture
stirred at rt for 16 h. DMAP (10 mg, 0.08 mmol) was added,
the reaction mixture stirred for 40 h and further TIPSOTf
(128 ml, 0.48 mmol) added. The reaction mixture was stirred
for a further 2 h, partitioned between CH2Cl2 (20 mL) and
1 M HCl (10 mL), the organic layers separated and then
washed with brine (10 mL), dried (MgSO4) and concen-
trated under reduced pressure. Chromatography (20% Et2O/
petrol) gave the title ester 1m (190 mg, 59%) as a colourless
oil; q0.14 (20% Et2O/petrol); [a]2D5K33.2 (c 4.8, CHCl3);
nmax (film) 2942, 2908, 2865, 1735, 1462, 1331, 1303, 1273,
1159, 1085, 812, 684 cmK1; dH (270 MHz) 7.79 (2H, d, JZ
8.0 Hz, ortho-ArH), 7.32 (2H, d, JZ8.0 Hz, meta-ArH),
6.00 (1H, m, C]CH), 5.33 (1H, t, JZ3.5 Hz, CHOCO),
4.08 (2H, d, JZ1.5 Hz, CH2OSi), 4.05 (2H, s, CH2SO2),
2.46 (3H, s, ArCH3), 2.12–1.42 (6H, m, ring CH2),
1.06–0.93 (21H, m, TIPS); dC (67.5 MHz) 162.2 (C]O),
145.3 (C]CH), 136.0 (para-Ar), 134.2 (ipso-Ar), 129.9
(Ar), 128.6 (Ar), 128.4 (C]CH), 69.5 (CHOCO), 64.3
(CH2OSi), 61.3 (CH2SO2), 28.3 (ring CH2), 24.7 (ring
CH2), 21.7 (ArCH3), 18.1 (CH(CH3)2), 17.8 (ring CH2),
12.0 (CH(CH3)2); m/z (CI) 481 [MCH]C (found: [MC
H]C, 481.2435. C25H40O5SSi requires [MCH]C,
481.2444) (found: C, 62.69; H, 8.05. C25H40O5SSi requires
C, 62.46; H, 8.39%).
4.2.10. Spectroscopic data for 1j. Yield 80%; Rf 0.28 (20%
EtOAc/petrol); [a]2D0K10.7 (c 1.5, CHCl3); nmax (film)
3020, 2976, 2933, 1739 (C]O), 1522, 1427, 1330 (SO2),
1279, 1216, 1151 (SO2), 1086, 1045, 930, 771, 669 cmK1
;
dH (270 MHz, CDCl3) 7.82 (2H, d, JZ8.0 Hz, ortho SO2–
Ar-CH3), 7.33 (2H, d, JZ8.0 Hz, meta SO2–Ar-CH3),
5.49–5.46 (1H, m, H-3), 4.41 (2H, d, JZ1.5 Hz, CH2-1),
4.07 (2H, s, CH2–SO2–Ar-CH3), 2.42 (3H, s, SO2–Ar-CH3),
2.39–1.94 (5H, m, H-4eq, H-5, H-7, CH2-8), 1.23 (3H, s,
CH3-70), 1.08 (1H, d, JZ8.5 Hz, H-4ax), 0.73 (3H, s, CH3-
700); dC (67.5 MHz, CDCl3) 162.5 (C]O), 145.4 (para
SO2–Ar-CH3), 141.9 (C-2), 135.9 (ipso SO2–Ar-CH3),
129.9 (meta SO2–Ar-CH3), 128.6 (ortho SO2–Ar-CH3),
122.8 (C-3), 68.9 (C-1), 61.1 (CH2–SO2–Ar-CH3), 43.5
(C-5), 40.6 (C-7), 38.0 (C-6), 31.5 (C-4), 31.3 (C-8), 26.1
(C-70), 21.8 (SO2–Ar-CH3), 21.0 (C-700); m/z (CI) 366 [MC
NH4]C, 212, 135 (found: [MCNH4]C, 366.1746.
C19H24SO4 requires [MCNH4]C, 366.1739) (found: C,
65.30; H, 6.73. C19H24O4S requires C, 65.49; H, 6.94%).
4.2.11. Spectroscopic data for 1k. Yield 61%; Rf 0.32
(20% EtOAc/petrol); nmax (film) 2937, 2868, 1732 (C]O),
1672, 1597, 1448, 1398, 1381, 1327 (SO2), 1277, 1151
(SO2), 1117, 1086, 920, 893, 813, 719, 646 cmK1; dH
(270 MHz, CDCl3) 7.69 (2H, d, JZ8.0 Hz, ortho SO2–Ar-
CH3), 7.24 (2H, d, JZ8.0 Hz, meta SO2–Ar-CH3),
5.27–5.18 (1H, m, H-2), 5.10–5.02 (1H, m, H-1), 3.98
(2H, s, CH2–SO2–Ar-CH3), 2.32 (3H, s, SO2–Ar-CH3),
1.79–1.37 (6H, m, CH2-4, CH2-5, CH2-6), 0.90 (3H, m,
CH3-40); dC (67.5 MHz, CDCl3) 162.2 (C]O), 145.2 (para
SO2–Ar-CH3), 142.1 (C-3), 135.9 (ipso SO2–Ar-CH3),
129.8 (meta SO2–Ar-CH3), 128.6 (ortho SO2–Ar-CH3),
118.8 (C-2), 71.0 (C-1), 61.2 (CH2–SO2–Ar-CH3), 29.8
(C-6), 27.5 (C-4), 23.7 (C-5), 21.6 (SO2–Ar-CH3), 18.5
(C-40); m/z (CI) 326 [MCNH4]C, 188, 172, 145, 128, 112,
95 (found: [MCNH4]C, 326.1429. C16H20SO4 requires
[MCNH4]C, 326.1426).
4.2.14. Preparation of (S)-6-(4-methoxybenzyloxy)cyclo-
hexen-1-ylmethyl tosylacetate (1n). To a stirred suspen-
sion of NaH (60% w/w in mineral oil; 150 mg, 3.8 mmol) in
Et2O (40 mL) was added a solution of p-methoxybenzyl
alcohol (5.2 g, 37.6 mmol) in Et2O (35 mL), the resultant
cloudy orange mixture stirred for 30 min at rt, cooled to 0 8C
and trichloroacetonitrile (3.8 mL, 37.6 mmol) added. The
reaction mixture was allowed to warm to rt over 4 h,
concentrated under reduced pressure and petrol (50 mL) and
MeOH (0.16 mL, 4.0 mmol) added. The suspension was
filtered through Celite and concentrated under reduced
pressure to give the crude imidate (10.5 g, 100%) as a
yellow oil. To a stirred solution of the crude imidate (65 mg,
0.23 mmol) in hexane (0.37 mL) was added a solution of
alcohol 4 (50 mg, 0.15 mmol) in CH2Cl2 (0.19 mL), the
solution cooled to 0 8C and BF3$OEt2 (0.6 ml) added. The
reaction mixture was allowed to warm to rt over 16 h,
filtered through a pad of Celite and the pad washed with 1:2
CH2Cl2/hexane (10 mL). The organic layers were washed
with saturated NaHCO3 (5 mL), dried (MgSO4), concen-
trated under reduced pressure and purified by chromato-
graphy (20% EtOAc/petrol) to give the title ether 1n
(45 mg, 66%) as a colourless oil; Rf 0.40 (40% EtOAc/
petrol); [a]2D5K4.3 (c 4.6, CHCl3); nmax (film) 2935, 2864,
4.2.12. Spectroscopic data for 1l. Yield 95%; Rf 0.23 (20%
EtOAc/petrol); [a]2D5K68.9 (c 4.7, CHCl3); nmax (film)
2937, 2866, 1734, 1664, 1597, 1454, 1329, 1275, 1155,
1086, 987, 814, 719 cmK1; dH (270 MHz) 7.76 (2H, d, JZ
8.0 Hz, meta-Ar), 7.31 (2H, d, JZ8.0 Hz, ortho-Ar), 5.64
(1H, br s, C]CH), 5.14 (1H, t, JZ4.0 Hz, CHOCO), 4.05
(2H, s, CH2SO2), 2.43 (3H, s, ArCH3), 2.06–1.85 (2H, m,
ring CH2), 1.68–1.62 (2H, m, ring CH2), 1.55 (3H, d, JZ
1.5 Hz, CH]CCH3), 1.49–1.34 (2H, m, ring CH2); dC
(67.5 MHz) 162.4 (C]O), 145.4 (C]CH), 136.0 (para-
Ar), 130.6 (ipso-Ar), 129.9 (C]CH), 129.8 (meta-Ar),
128.6 (ortho-Ar), 73.1 (CHOCO), 61.3 (CH2SO2), 28.6
(ring CH2), 25.1 (ring CH2), 21.7 (CH3), 20.5 (C]CCH3),
17.9 (ring CH2); m/z (CI) 326 [MCNH4]C (found: [MC
NH4]C, 326.1432. C16H20O4S requires [MCNH4]C,
326.1426); (found: C, 62.45; H, 6.34. C16H20O4S requires
C, 62.31; H, 6.54%).
1738, 1612, 1599, 1514, 1326, 1247, 1153, 1083, 816 cmK1
;
dH (270 MHz) 7.76 (2H, d, JZ8.5 Hz, ortho-ArSO2), 7.34
(2H, d, JZ8.0 Hz, meta-ArSO2), 7.23 (2H, d, JZ8.0 Hz,
meta-ArOCH3), 6.84 (2H, d, JZ8.0 Hz, ortho-ArOCH3),
5.87 (1H, t, JZ3.5 Hz, C]CH), 4.70 (1H, d, JZ10.5 Hz,
CH2OCO), 4.54 (1H, d, JZ11.0 Hz, CH2Ar), 4.43 (1H, d,
JZ12.0 Hz, CH2OCO), 4.33 (1H, d, JZ11.0 Hz, CH2Ar),
4.00 (1H, d, JZ14.0 Hz, CH2SO2), 3.95 (1H, d, JZ14.0 Hz,
CH2SO2), 3.86 (1H, br s, CHOCH2Ar), 3.78 (3H, s, OCH3),

492
D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
2.43 (3H, s, ArCH3), 2.13–1.86 (3H, m, ring CH2),
1.78–1.49 (3H, m, ring CH2); dC (125.8 MHz) 162.2
(C]O), 159.1 (ipso-ArOCH3), 145.2 (C]CH), 135.8
(para-ArSO2), 132.4 (C]CH), 132.3 and 130.7 (ipso-
ArSO2 and para-ArOCH3), 129.8 (ArH), 129.6 (Ar), 128.5
(Ar), 113.7 (ortho-ArOCH3), 70.8 (CH2Ar), 70.7
(CHOCH2Ar), 67.7 (CH2OCO), 60.9 (CH2SO2), 55.2
(OCH3), 26.9 (ring CH2), 25.2 (ring CH2), 21.6 (ArCH3),
17.7 (ring CH2); m/z (CI) 462 [MCNH4]C (found: [MC
NH4]C, 462.1936. C24H28O6S requires [MCNH4]C,
462.1950) (found: C, 65.11; H, 6.16. C24H28O6S requires
C, 64.84; H, 6.39%).
0.75 (3H, s, CH3-70); dC (67.5 MHz, CDCl3) 162.2 (C]O
ester), 155.8 (C]O Boc), 145.3 (para SO2–Ar-CH3), 139.7
(ipso Ph, ipso SO2–Ar-CH3), 135.9 (C-3), 129.8 (meta SO2–
Ar-CH3), 128.6 (meta Ph), 128.3 (ortho Ph), 127.4 (ortho
SO2–Ar-CH3), 126.8 (para Ph), 124.2 (C-2), 80.0 (O–C–
CH3), 66.1 (C-1), 60.9 (CH2–SO2–Ar-CH3), 55.8 (C-4),
47.7 (CH2-Ph), 41.3 (C-5), 28.4 (3!O––CH3), 24.6 (C-6),
22.6 (C-7), 22.5 (C-70), 21.7 (SO2–Ar-CH3); m/z (CI)
547 [MCNH4]C, 530 [MCH]C, 491, 430, 337, 276,
216, 174, 139, 109 (found: [MCH]C, 530.2576.
C29H39NO6S requires [MCH]C, 530.2576) (found: C,
65.67; H, 7.30; N, 2.55. C29H39NO6S requires C, 65.76;
H, 7.42; N, 2.64%).
4.2.15. Spectroscopic data for 1o. Yield 65%; Rf 0.28
(40% EtOAc/petrol); nmax (film) 2929, 2852, 1741, 1328,
1288, 1153, 1084, 912, 733 cmK1; dH (270 MHz) 7.81 (2H,
d, JZ8.0 Hz, ortho-Ar), 7.34 (2H, d, JZ8.0 Hz, meta-Ar),
5.97 (1H, tt, JZ4.0, 1.0 Hz, C]CH), 4.61 (2H, d, JZ
1.0 Hz, CH2OC]O), 4.09 (2H, s, CH2SO2), 3.94 (4H, s,
OCH2CH2O), 2.44 (3H, s, CH3), 2.08–2.01 (2H, m, ring
CH2), 1.77–1.70 (4H, m, ring CH2); dC (125.8 MHz) 162.5
(C]O), 145.2 (C]CH), 135.9 (para-Ar), 134.9 (C]CH),
131.9 (ipso-Ar), 129.8 (meta-Ar), 128.6 (ortho-Ar), 105.2
(OCO), 65.1 (OCH2CH2O), 64.5 (CH2OCO), 61.0
(CH2SO2), 33.4 (ring CH2), 25.3 (ring CH2), 21.6 (CH3),
20.2 (ring CH2); m/z (CI) 384 [MCNH4]C, 367 [MCH]C
(found: [MCH]C, 367.1215. C18H22O6S requires [MC
H]C, 367.1216) (found: C, 58.94; H, 5.99. C18H22O6S
requires C, 59.00; H, 6.05%).
4.2.18. Spectroscopic data for 1r. Yield 79%; nmax (film)
3083, 3060, 3003, 2875, 1740 (C]O), 1598, 1494, 1453,
1396, 1382, 1328 (SO2), 1305, 1150 (SO2), 1085, 815,
649 cmK1; dH (270 MHz, CDCl3) 7.79 (2H, d, JZ8.5 Hz,
ortho SO2–Ar-CH3), 7.38–7.13 (7H, m, meta SO2–Ar-CH3,
Ph), 5.92 (1H, ddt, JZ15.5, 6.5, 1.0 Hz, H-3), 5.49 (1H, dtd,
JZ15.5, 6.5, 1.5 Hz, H-2), 4.53 (2H, d, JZ6.5 Hz, CH2-1),
4.07 (2H, s, CH2–SO2–Ar-CH3), 3.47 (1H, quin, JZ6.5 Hz,
H-4), 2.40 (3H, s, SO2–Ar-CH3), 1.34 (3H, d, JZ6.5 Hz,
CH3-5); dC (67.5 MHz, CDCl3) 162.3 (C]O), 145.5 (para
SO2–Ar-CH3), 144.8 (ipso Ph), 141.7 (ipso SO2–Ar-CH3),
129.8 (meta SO2–Ar-CH3), 128.7 (meta Ph), 128.6 (ortho
SO2–Ar-CH3, ortho Ph), 127.2 (para Ph), 126.4 (C-2), 121.5
(C-3), 66.8 (C-1), 61.1 (CH2–SO2–Ar-CH3), 42.0 (C-4),
21.8 (SO2–Ar-CH3), 20.9 (C-5); m/z (CI) 376 [MNH4]C,
350, 232, 188, 145, 118 (found: [MNH4]C, 376.1580.
C20H22SO4 requires [MNH4]C, 376.1583).
4.2.16. Spectroscopic data for 1p. Yield 78%; nmax (film)
2967, 2856, 1744 (C]O), 1664, 1331 (SO2), 1154 (SO2),
1085, 1000, 903, 836 cmK1; dH (270 MHz, CDCl3) 7.81
(2H, d, JZ8.0 Hz, ortho SO2–Ar-CH3), 7.34 (2H, d, JZ
8.0 Hz, meta SO2–Ar-CH3), 5.72 (1H, ddt, JZ15.0, 7.0,
1.0 Hz, H-3), 5.57 (1H, dtd, JZ15.0, 6.0, 1.0 Hz, H-2), 4.54
(2H, d, JZ6.0 Hz, CH2-1), 4.13 (1H, q, JZ7.0 Hz, H-4),
4.09 (2H, s, CH2–SO2–Ar-CH3), 2.43 (3H, s, SO2–Ar-CH3),
1.66 (1H, apparent septet, JZ7.0 Hz, H-6), 1.40 (1H, dt, JZ
13.5, 7.0 Hz, H-5), 1.25–1.15 (1H, m, H-5), 0.88 (3H, d, JZ
7.0 Hz, CH3-7), 0.87 (3H, d, JZ7.0 Hz, CH3-70), 0.86 (9H,
s, Si–tBu), 0.01 (3H, s, Si–Me), K0.02 (3H, s, Si–Me); dC
(67.5 MHz, CDCl3) 162.3 (C]O), 145.4 (para SO2–Ar-
CH3), 140.0 (C-3), 135.5 (ipso SO2–Ar-CH3), 129.9 (meta
SO2–Ar-CH3), 128.6 (ortho SO2–Ar-CH3), 121.6 (C-2),
70.8 (C-1), 66.3 (C-4), 61.0 (CH2–SO2–Ar-CH3), 47.3
(C-5), 25.9 (Si–C–CH3), 24.1 (C-6), 23.2 (C-7), 22.5 (C-7),
21.7 (SO2–Ar-CH3), 18.2 (Si–C–CH3), K4.1 (Si–CH3),
K4.7 (Si–CH3); m/z (CI) 472 [MNH4]C, 318, 241, 188, 109
(found: [MNH4]C, 472.2552. C23H38O5SSi requires
[MNH4]C, 472.2553).
4.2.19. Spectroscopic data for 1s. Yield 73%; Rf 0.22 (20%
EtOAc/petrol); mp 79–82 8C; [a]2D6K14.4 (c 0.97, CHCl3);
nmax (film) 2970, 2935, 2870, 1736 (C]O), 1597, 1331
(SO2), 1273, 1153 (SO2), 1086, 975, 813, 714, 640 cmK1
;
dH (270 MHz, CDCl3) 7.71 (2H, d, JZ8.0 Hz, ortho SO2–
Ar-CH3), 7.25 (2H, d, JZ8.0 Hz, meta SO2–Ar-CH3), 5.42
(1H, d, JZ7.5 Hz, H-30), 4.91 (1H, s, H-30), 4.77 (1H, s,
H-1), 4.03 (2H, s, CH2–SO2–Ar-CH3), 2.35 (1H, s, H-3),
2.34 (3H, s, SO2–Ar-CH3), 2.27–2.10 (2H, m, CH2-4), 1.084–
1.75 (1H, m, H-60eq), 1.57 (1H, dd, JZ15.5, 4.0 Hz, H-6 ax),
1.22 (1H, d, JZ10.0 Hz, H-5), 1.16 (3H, s, CH3-7), 0.54
(3H, s, CH3-7); dC (67.5 MHz, CDCl3) 161.9 (C]O), 148.9
(C-2), 145.3 (para SO2–Ar-CH3), 135.9 (ipso SO2–Ar-
CH3), 129.8 (meta SO2–Ar-CH3), 128.6 (ortho SO2–Ar-
CH3), 115.3 (C-30), 70.8 (C-1), 61.4 (CH2–SO2–Ar-CH3),
50.5 (C-3), 40.5 (C-6), 39.3 (C-5), 32.6 (C-60), 27.4 (C-4),
25.8 (C-7), 21.9 (C-7), 21.7 (SO2–Ar-CH3); m/z (CI) 366
[MCNH4]C, 317, 303, 188, 152, 135, 108 (found: [MC
NH4]C, 366.1726. C19H24SO4 requires [MCNH4]C,
366.1739) (found: C, 65.45; H, 7.08. C19H24SO4 requires
C, 65.49; H, 6.94).
4.2.17. Spectroscopic data for 1q. Yield 85%; Rf 0.38
(30% EtOAc/petrol); [a]2D8K18.5 (c 1.08, CHCl3); nmax
(film) 2959, 2934, 2871, 1744 (C]O ester), 1688 (C]O
Boc), 1453, 1329 (SO2), 1159 (SO2), 1086, 973, 814, 734,
702, 646 cmK1; dH (270 MHz, CDCl3) 7.80 (2H, d, JZ
8.0 Hz, ortho SO2–Ar-CH3), 7.35 (2H, d, JZ8.0 Hz, meta
SO2–Ar-CH3), 7.25–7.11 (5H, m, Ph), 5.68–5.60 (1H, m,
H-3), 5.59–5.35 (1H, m, H-2), 4.78–4.56 (1H, m, H-4), 4.47
(2H, d, JZ6.0 Hz, CH2-1), 4.31 (2H, s, CH2-Ph), 4.07 (2H,
s, CH2–SO2–Ar-CH3), 2.44 (3H, s, SO2–Ar-CH3), 1.64–
1.26 (12H, m, CH2-5, H-6, 3!C–H3), 0.86 (3H, s, CH3-7),
4.3. Standard procedure for dCr reaction of 1
Conventional thermal conditions: BSA (16.6 mL,
0.07 mmol, 0.1 equiv) and KOAc (6.6 mg, 0.07 mmol,
0.1 equiv) were added to a solution of ester 1 (0.7 mmol,
1 equiv) in dry toluene (5 mL; ca. 0.14 M), and the resulting
mixture was heated at 110 8C for 15 h. Concentration under
reduced pressure and chromatography (EtOAc/petrol) gave
sulfone 2.

D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
493
Microwave conditions: KOAc (0.1 equiv) was added to a
microwave vial followed by tosylacetate 1 (1 equiv), BSA
(0.1 or 1 equiv) and toluene (1 mL; ca. 0.3 M). The mixture
was heated at 150 8C (250 W) for 3 min. Concentration
under reduced pressure and chromatography (EtOAc/petrol)
gave sulfone 2.
(1H, d, JZ11.5 Hz, CH2Ar), 3.87 (1H, m, CHOCH2), 3.80
(3H, s, OCH3), 3.42 (1H, dd, JZ14.0, 4.5 Hz, CH2SO2),
3.08 (1H, dd, JZ14.0, 8.0 Hz, CH2SO2), 2.96 (1H, m,
CHCH2SO2) 2.41 (3H, s, ArCH3), 2.18–2.11 (2H, m, ring
CH2), 1.95–1.45 (4H, m, ring CH2); dC (125.8 MHz) 159.0
(ipso-ArOCH3), 148.9 (C]CH2), 144.5 (para-ArSO2),
137.0 (ipso-ArSO2), 130.7 (para-ArOCH3), 129.9 (Ar),
129.1 (Ar), 127.9 (Ar), 113.7 (Ar), 108.9 (C]CH2), 79.0
(CHOCH2Ar), 69.1 (OCH2Ar), 58.6 (CH2SO2), 55.2
(OCH3), 36.7 (CHCH2SO2), 34.2 (ring CH2), 33.6 (ring
CH2), 21.6 (ArCH3), 20.6 (ring CH2).
4.4. Spectroscopic data for dCr reaction products 2
Spectroscopic data for the dCr reaction products 2a, 2c–2k,
2p–2r may be found in the Supporting information in
Ref. 5a: http://www.wiley-vch.de/contents/jc_2002/2005/
z462023_s.pdf.
Minor, syn-diastereoisomer. dH (270 MHz) 7.74 (2H, d, JZ
8.0 Hz, ortho-ArSO2), 7.32 (2H, d, JZ8.0 Hz, meta-
ArSO2), 7.19 (2H, d, JZ8.5 Hz, meta-ArOCH3), 6.82
(2H, d, JZ8.5 Hz, ortho-ArOCH3), 4.97 (1H, s, C]CH),
4.78 (1H, s, C]CH2), 4.46 (1H, d, JZ12.5 Hz, CH2OAr),
4.28 (1H, d, JZ11.5 Hz, CH2OAr), 3.79 (3H, s, OCH3),
3.73 (1H, m, CHOCH2), 3.41 (1H, dd, JZ14.0, 4.5 Hz,
CH2SO2), 3.29 (1H, dd, JZ14.0, 8.0 Hz, CH2SO2), 2.86
(1H, m, CHCH2SO2), 2.44 (3H, s, ArCH3), 1.95–1.42 (6H,
m, ring CH2); dC (125.8 MHz) 158.9 (ipso-ArOCH3), 147.6
(C]CH2), 144.4 (para-ArSO2), 137.4 (ipso-ArSO2), 130.6
(para-ArOCH3), 129.8 (Ar), 128.9 (Ar), 127.8 (Ar), 113.7
(Ar), 109.6 (C]CH2), 79.0 (CHOCH2Ar), 69.8 (OCH2Ar),
59.1 (CH2SO2), 55.2 (OCH3), 36.7 (CHCH2SO2), 33.9 (ring
CH2), 32.8 (ring CH2), 21.6 (ArCH3), 19.4 (ring CH2).
4.4.1. Spectroscopic data for 2l. Rf 0.36 (20% EtOAc/
petrol); mp 62–64 8C; [a]2D5C54.1 (c 3.4, CHCl3); nmax
(film) 3035, 2929, 2863, 2837, 1597, 1448, 1311, 1300,
1147, 1088, 817, 752 cmK1; dH (500 MHz) 7.80 (2H, dt, JZ
8.5, 2.0 Hz, ortho-Ar), 7.34 (2H, dd, JZ8.5, 0.5 Hz, meta-
Ar), 5.46–5.44 (1H, m, C]CH), 3.11 (1H, ddd, JZ14.5,
2.0, 0.5 Hz, CH2SO2), 3.04 (1H, dd, JZ14.5, 9.5 Hz,
CH2SO2), 2.51–2.46 (1H, m, CHCH2SO2), 2.44 (3H, s,
ArCH3), 1.94–1.90 (2H, m, ring CH2), 1.88–1.83 (1H, m,
ring CH2), 1.71–1.66 (1H, m, ring CH2), 1.57–1.53 (1H, m,
ring CH2), 1.49–1.48 (3H, m, CH]CCH3), 1.46–1.42 (1H,
m, ring CH2); dC (125.8 MHz) 144.5 (C]CH), 136.9 (para-
Ar), 132.9 (ipso-Ar), 129.8 (meta-Ar), 127.9 (ortho-Ar),
125.1 (C]CH), 58.4 (CH2SO2), 33.6 (CHCH2SO2), 27.2
(ring CH2), 24.9 (ring CH2), 21.6 (CH3), 21.5 (CH3), 17.7
(ring CH2); m/z (CI) 282 [MCNH4]C (found: [MCNH4]C,
282.1532 C15H20O2S requires [MCNH4]C, 282.1528); 265
[MCH]C (found: [MCH]C, 265.1270. C15H20O2S
requires [MCH]C, 265.1262) (found: C, 67.94; H, 7.48.
C15H20O2S requires C, 68.14; H, 7.62%).
4.4.4. Spectroscopic data for 2o. Rf 0.15 (20% EtOAc/
petrol); nmax (film) 2937, 2889, 1302, 1288, 1192, 1147,
1089, 1049, 1020, 922, 895, 818, 756 cmK1; dH (270 MHz)
7.76 (2H, d, JZ8.5 Hz, ortho-Ar), 7.34 (2H, d, JZ8.0 Hz,
meta-Ar), 5.11 (1H, s, C]CH2), 4.70 (1H, s, C]CH2),
3.93–3.75 (4H, m, OCH2CH2O), 3.39 (1H, dd, JZ14.0,
5.0 Hz, CH2SO2), 3.18 (1H, dd, JZ14.0, 8.0 Hz, CH2SO2),
3.04 (1H, m, CHCH2SO2), 2.43 (3H, s, CH3), 1.96–1.36
(6H, m, ring CH2); dC (125.8 MHz) 147.2 (C]CH2), 144.4
(para-Ar), 137.3 (ipso-Ar), 129.8 (meta-Ar), 127.9 (ortho-
Ar), 108.4 (C]CH2), 108.0 (OCO), 64.3 (OCH2CH2O),
58.9 (CH2SO2), 37.3 (CHCH2SO2), 36.8 (ring CH2), 32.5
(ring CH2), 21.6 (CH3), 21.2 (ring CH2); m/z (CI) 340 [MC
NH4]C, 323 [MCH]C (found: [MCH]C, 323.1317.
C17H22O4S requires [MCH]C, 323.1313).
4.4.2. Spectroscopic data for 2m. Rf 0.42 (40% Et2O/
petrol); [a]2D5C12.0 (c 1.0, CHCl3); nmax (film) 2940, 2891,
1733, 1598, 1461, 1312, 1150, 1086, 882, 759, 686 cmK1
;
dH (500 MHz) 7.79 (2H, d, JZ8.0 Hz, ortho-ArH), 7.34
(2H, d, JZ8.0 Hz, meta-ArH), 5.74 (1H, br s, C]CH), 3.92
(2H, s, CH2OSi), 3.39 (1H, dd, JZ14.5, 2.0 Hz, CH2SO2),
3.10 (1H, dd, JZ14.5, 10.0 Hz, CH2SO2), 2.69 (1H, m,
CHCH2SO2), 2.44 (3H, s, ArCH3), 2.01–1.98 (3H, m, ring
CH2), 1.62–1.55 (3H, m, ring CH2), 1.10–0.94 (21H, m,
TIPS); dC (125.8 MHz) 144.4 (para-Ar), 137.2 (ipso-Ar),
136.7 (C]CH), 129.8 (meta-ArH), 127.9 (ortho-ArH),
125.6 (C]CH), 66.1 (CH2OSi), 58.5 (CH2SO2), 30.4
(CHCH2SO2), 26.7 (ring CH2), 24.6 (ring CH2), 21.6
(ArCH3), 18.0 (CH(CH3)2 and ring CH2), 12.0 (CH(CH3)2);
m/z (CI) 437 [MCH]C (found: [MCH]C, 437.2547.
C24H40O3SSi requires [MCH]C, 437.2545).
4.4.5. Spectroscopic data for 2s. Rf 0.33 (20% EtOAc/
petrol); mp 54–55 8C; [a]2D4C24.7 (c 1.03, CHCl3); nmax
(film) 2983, 2918, 2833, 1599, 1444, 1315 (SO2), 1302,
1272, 1226, 1149 (SO2), 1088, 912, 814, 733, 653 cmK1; dH
(270 MHz, CDCl3) 7.72 (2H, d, JZ8.0 Hz, ortho SO2–Ar-
CH3), 7.30 (2H, d, JZ8.0 Hz, meta SO2–Ar-CH3),
5.18–5.11 (1H, m, H-3), 3.08–2.97 (2H, m, CH2-40), 2.38
(3H, s, SO2–Ar-CH3), 2.33–2.22 (3H, m, H-1, CH2-30),
2.16–2.07 (1H, m, H-60), 2.03–1.94 (1H, m, H-60), 1.90–
1.81 (1H, m, H-5), 1.23–1.12 (1H, m, H-4eq), 1.18 (3H, s,
CH3-7), 1.00 (1H, d, JZ8.5 Hz, H-4ax), 0.70 (3H, s, CH3-7);
dC (67.5 MHz, CDCl3) 144.8 (para SO2–Ar-CH3), 144.0
(C-2), 136.2 (ipso SO2–Ar-CH3), 130.0 (meta SO2–Ar-
CH3), 128.2 (ortho SO2–Ar-CH3), 118.5 (C-3), 54.6 (C-40),
45.6 (C-10), 40.7 (C-5), 38.1 (C-6), 31.6 (C-4), 31.3 (C-60),
29.8 (C-3 ), 26.2 (C-7), 21.7 (SO2–Ar-CH3), 21.2 (C-7); m/z
(CI) 322 [MCNH4]C, 305 [MCH]C, 149, 105 (found:
[MCNH4]C, 322.1838. C18H24SO2 requires [MCNH4]C,
4.4.3. Spectroscopic data for 2n. Rf 0.22 (20% EtOAc/
petrol); nmax (film) 2924, 2850, 1612, 1512, 1456, 1301,
1248, 1147, 1086, 1034, 818 cmK1; m/z (CI) 418 [MC
NH4]C (found: [MCNH4]C, 418.2049. C23H28O4S
requires [MCNH4]C, 418.2052).
Major, anti-diastereoisomer. dH (270 MHz) 7.78 (2H, d,
JZ8.0 Hz, ortho-ArSO2), 7.30 (2H, d, JZ8.0 Hz, meta-
ArSO2), 7.16 (2H, d, JZ8.5 Hz, meta-ArOCH3), 6.85 (2H,
d, JZ8.5 Hz, ortho-ArOCH3), 4.90 (1H, s, C]CH2), 4.70
(1H, s, C]CH2), 4.26 (1H, d, JZ11.5 Hz, CH2Ar), 4.09

494
D. Bourgeois et al. / Tetrahedron 62 (2006) 483–495
(b) For recent examples of regio- and enantioselective metal-
catalysed decarboxylative allylation reactions, see: Burger,
E. C.; Tunge, J. A. Org. Lett. 2004, 6, 2603. (c) Burger, E. C.;
Tunge, J. A. Org. Lett. 2004, 6, 4113. (d) Burger, E. C.; Tunge,
J. A. Chem. Commun. 2005, 2835. (e) For a review
of transition metal-catalysed decarboxylative additions of
enolates, see: Tunge, J. A.; Burger, E. C. Eur. J. Org. Chem.
2005, 1715.
322.1841) (found: C, 71.04; H, 8.20. C18H24SO2 requires C,
71.01; H, 7.95).
4.5. Standard procedure for tosylation of 10
To a solution (R2 M) of allylic methyl malonates 10a–i
(4.5 equiv) in DMSO was added very slowly, at rt and
under N2, potassium tert-butoxide (4 equiv of a 1 M
solution in THF). The reaction was then stirred for
15 min before the addition of tosyl fluoride (1 equiv).
After 20 h of stirring at rt, the mixture was poured into
aqueous HCl (10%), extracted twice with ether and the
combined organic layers were washed with brine, dried
(MgSO4) and concentrated under reduced pressure.
Chromatography on silica gel (25–50% EtOAc/petrol) of
the residual mixture gave recovered excess allylic methyl
malonates 10a–i, followed by the desired allylic methyl
tosylmalonates 11a–i.
5. Parts of this work have been communicated in preliminary
form: (a) Bourgeois, D.; Craig, D.; King, N. P.; Mountford,
D. M. Angew. Chem., Int. Ed. 2005, 44, 618. Angew. Chem.,
Int. Ed. 2005, 117, 524. (b) Craig, D.; Grellepois, F. Org. Lett.
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6. Purchased from Aldrich Chemical Co.
7. Kazmaier, U.; Schneider, C. Synthesis 1998, 1321.
8. Rezgui, F.; El Gaied, M. M. Tetrahedron Lett. 1998, 39, 5965.
9. Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987,
109, 5551.
10. Nakajima, N.; Horita, K.; Abe, R.; Yonemitsu, O. Tetrahedron
Lett. 1988, 29, 4139.
4.6. Standard procedure for dCr reaction of 11
11. Giambastiani, G.; Pacini, B.; Porcelloni, M.; Poli, G. J. Org.
Chem. 1998, 63, 804.
To solutions of tosylmalonates 11a–11i in CH2Cl2 were
added, at rt and under N2, BSA (1 equiv) and KOAc
(0.1 equiv). After stirring for 4–16 h, the reaction mixtures
were concentrated under reduced pressure. Chromatography
on silica gel afforded the decarboxylated rearranged
products 12a–i.
12. Trost, B. M.; Murphy, D. J. Organometallics 1985, 4, 1143.
13. Compound 1h has been described previously: Sato, K.; Inoue,
S.; Sakamoto, T. Synthesis 1981, 796.
14. Hatcher, M. A.; Posner, G. H. Tetrahedron Lett. 2002, 43,
5009.
15. (a) Carroll, M. F. J. Chem. Soc. 1940, 704. (b) For recent
applications of the Carroll rearrangement in synthesis, see:
Defosseux, M.; Blanchard, N.; Meyer, C.; Cossy, J. Org. Lett.
2003, 5, 4037. (c) Jung, M. E.; Duclos, B. A. Tetrahedron Lett.
2004, 45, 107. (d) For a review, including an account of
asymmetric Carroll rearrangements, see: Job, A.; Janeck,
C. F.; Bettray, W.; Peters, R.; Enders, D. Tetrahedron 2002,
58, 2253.
4.7. Spectroscopic data for dCr reaction products 12
Spectroscopic data for the dCr reaction products 12a–12i
may be found in the Supporting information in Ref. 5b:
http://pubs.acs.org/subscribe/journals/orlef7/suppinfo/
ol047577w/ol047577wsi20041220_092954.pdf.
16. Brooks, D. W.; Castro de Lee, N.; Peevey, R. Tetrahedron
Lett. 1984, 25, 4623.
Acknowledgements
17. (a) Hirsh, E.; Hu¨nig, S.; Reissig, H.-U. Chem. Ber. 1982, 115,
399. (b) Kende, A. S.; Mendoza, J. S. J. Org. Chem. 1990, 55,
1125. (c) Sandanayaka, V. P.; Zask, A.; Venkatesan, A. M.;
Baker, J. Tetrahedron Lett. 2001, 42, 4605.
We thank EPSRC (postdoctoral research associateship to D.
B. [grant GR/N31412]; DTA Studentship to D. M. M.; quota
Studentship to A. J. W. S.), GlaxoSmithKline (additional
funding of Studentship to D. M. M.) and the European
Community Human Potential program (Marie Curie
Individual Fellowship to F. G. [contract number HPMT-
CT-2002-02015]) for support.
18. We have found subsequently that two equivalents of the mixed
malonate conjugate base are generally sufficient for efficient
tosylation with TsF: Paina, F., unpublished results.
19. Compounds 12d and 12h were formed as 70:30 mixtures of
diastereoisomers; compound 12i was formed as a 61:39
mixture of diastereoisomers. Major isomers have not been
assigned in these cases.
20. Yields cited for 11 are based on tosyl fluoride; yields in
parentheses are for recovered 10 and are calculated from
the total recoverable amount based on the yield of 11
and the amount of 10 used (4.5 equiv with respect to
TsF). For example, a 70% yield of 11 means the total
recoverable amount of 10 is (4.5K0.7)Z3.8 equiv; 74%
recovery means that (0.74!3.8Z2.81 equiv) of 10 was
recovered.
References and notes
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