Expedient synthesis of β,β-disubstituted α- methylenepropionates

Article abstract of DOI:10.1016/j.tet.2004.12.002

Baylis-Hillman alcohols are excellent sources of the allylic halides ArCHCH(CH₂X)(CO₂R) (X=Br, Cl; R¹=Me, Et, Bu^t). The Z double bond isomers are attained in high isomeric purity (>14:1, Z/E). The halides are ch

Full text of DOI:10.1016/j.tet.2004.12.002

Tetrahedron 61 (2005) 1433–1442
Expedient synthesis of b,b-disubstituted a-methylenepropionates
a
Kallolmay Biswas, Christoph Borner, Josepe Gimeno, Paul J. Goldsmith,
a
b
a
¨
Daniella Ramazzotti,c Angela L. K. Soa and Simon Woodwarda,
*
aSchool of Chemistry, Nottingham University, University Park, Nottingham NG7 2RD, UK
´ `
Departament de Quımica, Universitat Autonoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
b
c
`
Dipartimento di Chimica, Universita di Sassari, Via Vienna 2, 07100 Sassari, Italy
Received 30 September 2004; revised 9 November 2004; accepted 2 December 2004
Available online 21 December 2004
Abstract—Baylis–Hillman alcohols are excellent sources of the allylic halides ArCH]CH(CH2X)(CO2R) (XZBr, Cl; R1ZMe, Et, But).
The Z double bond isomers are attained in high isomeric purity (O14:1, Z/E). The halides are chemo- and regiospecifically transformed into
the acrylates (ArCHR2)C(]CH2)(CO2R1) on treatment with Zn(R2)2 (R2ZMe, Et, CH2TMS, CH2SiMe2OMe) or PrZnBr in the presence of
catalytic amounts of copper(I) salts (0.5–20 mol%) in high yield.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
racemates of 1 (especially in the cases where R1 is an aryl
group) and to identify conditions for the separation of their
enantiomers to support later mass asymmetric ligand
screening.
Acrylate fragments constitute exceptionally valuable build-
ing blocks in organic chemistry participating readily in
many asymmetric transformations including Diels–Alder1
and Michael addition2 reactions. While simple acrylate and
methylacrylate esters are commercially available surpris-
ingly few good (whether racemic or stereoselective) routes
exist to even the simplest disubstituted species 1. The two
limited literature approaches to 1 available are either to
access it through g-selective alkylations of organometallic
allyl species (route ‘A’, MZMgX, ZnX)3 or by a-selective
alkylations of organovinyl species (route ‘B’, MZZnX).4
Approach ‘A’ often suffers from competing a-alkylation,
leading to a mixture of regioisomers. The displacement of
the secondary halide in route ‘B’ is limited to highly
reactive allylic systems under palladium catalysis. We
thought that umpolung versions of this chemistry based on
organometallic additions of R2M to allylic halides might
offer a chemo- and regiospecific approach to 1. Such a route
could be attained conceptually through reliable conjugate
addition and Baylis–Hillman chemistry (approach ‘C’).
Preliminary studies by us had demonstrated the viability of a
catalytic approach and also indicated that route C offers
potential for asymmetric catalysis.5 However, the enantio-
selectivities attained in this early work were resistant to
optimisation. This led us to identify optimal routes to the
2. Results and discussion
2.1. Scope of the allylic halide ester
Due to the dearth of catalytic studies on Baylis–Hillman
derived allylic halides (and pseudohalides) we wished to
assure ourselves that the desired g-specific catalytic
addition was possible. As Ku¨ndig had demonstrated
g-specific addition of stoichiometric6 LiCuBu2$ZnCl2 to
related systems, we chose to concentrate on zinc and
copper-based catalytic systems. A range of suitable Baylis–
Hillman adducts 2 were prepared from ethyl acrylate and
suitable aromatic aldehydes in the presence of stoichio-
metric DABCO. The slower reacting electron rich alde-
hydes could be co-promoted with lanthanum triflate.7 In all
cases O60% conversion was attained in 7 days, the fastest
reacting aldehyde (4-NO2PhCHO) was essentially comple-
tely consumed within 8 h. Aromatic aldehydes were
selected for convenience as Baylis–Hillman reaction of
aliphatic aldehydes, while clean, is rather slow. Treatment
of 2 with concentrated HBr or HCl, in the presence of
H2SO4, leads cleanly to either the bromides 3 or chlorides 4
(Scheme 1). A yield range of 60–95% is observed with the
majority being over 90%. These eliminations proceed with
very high Z selectivity (O20:1 for compounds 3, w14:1 for
Keywords: Baylis–Hillman; SN20; Allylic substitution; Organozinc;
Copper.
* Corresponding author. Tel.: C44 115 951 3541; fax: C44 115 951 3541;
e-mail: simon.woodward@nottingham.ac.uk
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.12.002

1434
K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
the halide is required by the catalyst. Alternatively, the
enthalpy associated with formation of ZnCl2 may provide
the reason for the higher reactivity of 3/4. No SN2 products
(resulting from attack of ZnEt2 a to the leaving group) are
apparent in the crude reaction products within the limits of
1H NMR detection, behavior analogous to Ku¨ndig’s
stoichiometric system. One explanation for the reaction’s
regiospecificity may be that an addition–elimination
mechanism akin to conjugate addition operates via an
undetected enolate intermediate. Attempts to intercept such
potential intermediates through addition of PhCHO to the
reaction mixture were however unsuccessful.
The chlorides react much more slowly. For example, the
reaction of 4e is only 57% complete after 40 min at K20 8C.
Use of an alternative catalyst system employing CuCN
(20 mol%) and tetrabutylammonium bromide (TBAB)
(10 mol%), allowed rapid conversions of the chlorides
within 45 min at K20 8C. Several other quaternary
ammonium salts also provide strong rate acceleration in
these reactions. The reactions of 4 are completely clean -
only 5 is formed and simply isolated by column chroma-
tography. Additionally, it was found that use of P(OEt)3
(4 mol%) strongly retards the rate of reaction (w50%
conversion of 3a after 40 min at 0 8C). Similarly, Feringa’s
phosphoramidate9 with CuI catalyst provided less than 3%
conversion of 4 after 20 min at K20 8C), suggesting that
chiral phosphorus species may not be useful in asymmetric
variants of this reaction. Despite the wide difference in the
electronic factors in substrates 3, 4, and 9, all are effective
coupling partners within each series, allyl halides bearing
electron withdrawing substituents (–I, or –M) are the
quickest reacting. In all the cases investigated no evidence
was seen for attack at any of the aryl substituents in
compounds 3 or 4. For comparison of leaving group effects
the formate 6a was prepared by adaptation of known
procedures, and from this the reactive mesylate 7a also
prepared. The former was unreactive under [Cu(MeCN)4]-
BF4 (3 mol%) catalysis. The latter showed high reactivity,
Scheme 1.
4) originating from stereoelectronic controlled elimination
of the zwitterionic intermediates.8 In many cases the crude
halides 3–4 crystallise from Et2O or Et2O/pentane mixtures
as geometrically pure species (Scheme 2).
Table 1. Copper(I)-catalysed additions of ZnEt2 to allylic halides 3–4a
Halide
X
Ar
Yield 5/%b
3a
3b
3c
3d
3e
3f
3g
3h
4a
4b
4c
4d
4e
4f
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Ph
1-Nap
100 (80)
84
86
4-MePh
4-ClPh
4-NO2Ph
3-NO2Ph
2-NO2Ph
4-CF3Ph
Ph
Scheme 2. Reagents and conditions: (i) concd HX/H2SO4, 16–24 h, rt;
(ii) ZnEt2, THF, K20 8C, cat. [Cu(MeCN)4]BF4 (3 mol%) [for 3a–h, 6a,
7a] or, cat. CuCN (20 mol%) and NBu4Br (10 mol%) [for 4a–h]; (iii) NEt3/
HCO2H reflux; (iv) for 7a treatment of 6a with aq. HCl in methanol,
followed by mesylation (MeSO2Cl/NEt3) of the derived alcohol.
100 (63)
100 (63)
100 (80)
100 (50)
100 (95)
100 (88)
100 (95)
100 (93)
100 (97)
100 (97)
100 (95)
100 (98)
100 (98)
0
Complete conversion of the bromides 3 to acrylates 5 could
be achieved cleanly with 1.5 equiv of ZnEt2 in the presence
of [Cu(MeCN)4]BF4 (3 mol%). In general, the isolated
yields were in the range 60–80%. The reaction of the
bromides is very strongly promoted by [Cu(MeCN)4]BF4,
and at 0.5 mol% loading complete conversion is attained.
However, in the absence of copper(I) !15% conversions
are seen in control reactions under otherwise identical
conditions. The catalytic reactions of 3 are completely
chemo- and regiospecific. The product propionates 5,
although powerful Michael acceptors in their own right,
are not attacked under the reaction conditions We speculate
that bidentate coordination via both the ester function and
1-Nap
4-MePh
4-ClPh
4-NO2Ph
3-NO2Ph
2-NO2Ph
4-CF3Ph
Ph
4g
4h
6a
7a
C(]O)H
OMs
Ph
96
a Addition of ZnEt2 (1.5 equiv) to 3 or 4 (0.5–1.0 M in THF) at K20 8C in
the presence of [Cu(MeCN)4]BF4 (3 mol%), followed by 40 min at
K20 8C [for 3a–h, 6a, 7a] or, cat. CuCN (20 mol%) and NBu4Br
(10 mol%) [for 4a–h] (45 min, K20 8C).
b Yields based on NMR or GC versus internal standards. Isolated yields in
parentheses.

K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
1435
Table 2. Copper(I)-catalysed additions of ZnEt2 to allylic chlorides 9a
full conversion was attained even at K90 8C within 5 h.
These reactions are summarised in Table 1.
Chloride
R
Ar
Yield 10/%b
9a
9b
9c
9d
9e
9f
9g
9h
9i
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
But
Ph
95
98
94
91
97
90
95
94
85
97
83
We had selected the products 5 and 10 as we felt the
significant steric difference between the ethyl and phenyl
groups would favour rapid separation of their enantiomers
by automated chiral GC. In the end we could only identify a
suitable GC column for separation of (G)-5a. Separation of
(G)-5b–c and (G)-5e was achieved on a Daicel OD HPLC
column, but the enantiomers of compounds 5d and 5f–h
could not be resolved by chiral HPLC. Details of the assay
conditions are given in the experimental section (Table 4).
Unfortunately, even in the favourable cases these HPLC
assays are complicated in cases where less than a
quantitative conversion to 5 is attained. The starting halides,
3 and 4 commonly co-elute with one of the enantiomers of 5
in the HPLC invalidating the assay. This problem can,
however, be conveniently overcome by treatment of the
crude reaction products with DABCO and subsequent
washing with dilute acid leading to removal of 3, 4 and
excess DABCO as water soluble ammonium species. Other
esters were investigated to extend the scope of the reaction
and provide alternative systems for simpler enantiomeric
assay. The methyl and tert-butyl esters 9 were prepared
from 8 via use of oxalylchloride in the presence of a
catalytic amount of DMF (Scheme 3). These reactions were
entirely regiospecific under the conditions employed. The
mildness of this approach was vital to the preparation of
the tert-butyl ester 9i. Attempts to form 9i through the use
of HCl/H2SO4 mixtures on 8i led only to the derived free
acid via tert-Bu cleavage. Use of the alternative catalyst
system [CuCN (20 mol%) and TBAB (10 mol%)]
allowed all of the b,b-disubstituted a-methylenepropionates
10 to be isolated in good yield (Table 2). The enantiomers
of the following methyl and tert-butyl esters could be
separated by chiral GC: (G)-10a, 10i and 10k. Compounds
(G)-10b, 10d–f, 10h and 10j could be separated by chiral
HPLC.
1-Nap
2-Nap
4-MeOPh
4-MePh
2-BrPh
4-ClPh
4-FPh
4-CF3Ph
4-NO2Ph
Ph
9j
9k
a Addition of ZnEt2 (1.5 equiv) to 9 (0.5–1.0 M in THF) at K20 8C in the
presence of cat. CuCN (20 mol%) and NBu4Br (10 mol%) followed by
40 min. At K20 8C.
b Isolated yields.
2.2. Scope of the organometallic reagent
To increase the scope of the reaction beyond ZnEt2 other
organometallic reagents were investigated (Scheme 3). Both
ZnMe2 and ZnBu2 participated in the catalytic reaction
leading to good yields of isolated acrylates 11a–b (Table 3).
As the presumed by-products from reaction of ZnR2 with 3,
4 or 9 are RZnX (XZBr, Cl) we were encouraged to try the
reaction with a representative organozinc halide. Reward-
ingly n-PrZnBr participated in the reaction almost as well as
the diorganozincs. Attempts to extend this to use of
Grignard reagents were unsuccessful though—complex
Table 3. Copper(I)-catalysed additions of organozincs to allylic halides 3
and 9a
Product
R1
R2
Yield 11/%b
11a
11b
11c
11d
11e
Me
Me
Me
Et
Me
Bu
Pr
85
98
70
93
25
CH2SiMe2OMe
CH2SiMe3
Et
a Addition of Zn(R2)2 (1.5 equiv) (0.5–1.0 M in THF) at K20 8C in the
presence of cat. CuCN (20 mol%) and NBu4Br (10 mol%), followed by
40 min at K20 8C for 11a–c. Reaction K20 to K5 8C, Zn(R2)2
(1.5 equiv), THF; [CuMeCN)4]BF4 3 mol% for 11d–e.
b Isolated yields.
Scheme 4. Reagents and conditions: (i) K20 to K5 8C, THF;
[CuMeCN)4]BF4 3 mol% or, cat. CuCN (20 mol%) and NBu4Br
(10 mol%) (40 min K20 8C).
Scheme 3. Reagents and conditions: (i) (COCl)2 cat. DMF; (ii) ZnEt2, THF,
K20 8C, cat. CuCN (20 mol%) and NBu4Br (10 mol%).

1436
K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
mixtures resulted presumably through attack at the carbonyl
function of 11. Some additional screenings were carried
out using in situ prepared zinc reagents. Solutions of
Zn(CH2SiMe2OMe)2, prepared by transmetallation of
LiCH2SiMe2OMe10 with ZnCl2 As expected this material
demonstrated lower reactivity than the other organozinc
species used but could be added to more reactive 3a and
expected product 11d was isolated in acceptable yield
(Scheme 4) provided an acidic workup is excluded. If this
precaution is not undertaken 11d dimerises via Si–O–Si
bridges. The equivalent CH2TMS derivative 11e could
also be formed, albeit in lower yield, through use of
Zn(CH2TMS)2. For 11d–e all attempts to oxidatively cleave
the Si–C bonds and fashion the known molluscicide 12 have
been unsuccessful to date, either no reaction or complete
oxidative degradation are observed.
4.2. Representative preparation of the Baylis–Hillman
alcohols 2 and 8
Neat aldehyde (20.0 mmol) was added to a stirred solution
of ethyl acrylate (3.00 g, 30.0 mmol) and DABCO (2.23 g,
20.0 mmol) and left to stir overnight at room temperature.
Reaction was monitored by TLC analysis (1:1 light
petroleum/diethyl ether) until complete (1–30 days; elec-
tron-rich aromatic substrates react the slowest and were
often further promoted by addition of lanthanum triflate,
10 mol%). The reaction mixture was extracted with diethyl
ether (3!20 ml) and washed successively with HCl (2 M,
10 ml), NaOH (2 M, 10 ml) and brine (20 ml). The organic
layer was separated and dried (MgSO4) and the solvent
removed to yield the crude oil. Purification by column
chromatography (2:1 dichloromethane/light petroleum)
gave the alcohols as oils.
4.2.1. Ethyl 2-(1-hydroxy-1-(1-naphthyl)-methyl)-pro-
penoate 2b. Yield 75%; dH (400 MHz, CDCl3) 1.17 (3H,
t, JZ7.1 Hz, CH2Me), 3.05 (1H, d, JZ5.0 Hz, CH), 4.12–
4.17 (2H, m, CH2Me), 5.48 (1H, s, ]CH2a), 6.26 (1H, s,
]CH2b), 6.29 (1H, d, JZ5.0 Hz, OH), 7.37–7.42 (3H, m,
Ar), 7.56 (1H, d, JZ7.1 Hz, Ar), 7.73 (1H, d, JZ8.2 Hz,
Ar), 7.77–7.80 (1H, m, Ar), 7.91–7.95 (1H, m, Ar); dC
(100.6 MHz, CDCl3) 13.9, 60.4, 69.0, 123.7, 124.4, 125.7,
125.9, 126.1, 126.6, 128.4, 128.6, 130.8, 133.7, 136.6,
142.2, 166.9; nmax (CHCl3 solution)/cmK1 3426br, 3048m,
2935s, 2903s, 1714s, 1629m, 1598m, 1510s, 1444m,
1148m, 1080m, 863m; m/z (EI) 256 (MC, 98%), 210 (63),
183 (56), 165 (84), 129 (100). [Found (HRMS, EI): MC
256.1101. C16H16O3 requires M 256.1099].
3. Conclusions
We have identified a succinct route to b,b-disubstituted
a-methylenepropionates that proceeds from simple allylic
halide precursors attainable in multi-gram scales without the
need for chromatography. The reactions of these with either
diorganozincs or organozinc halides are chemo- and
regiospecific and afford high yields of the desired products.
The crude propionate products are of sufficient quality for
immediate further use. While our studies have concentrated
on allylic halides derived from aryl aldehydes this has been
for convenience rather than due to a limitation in the
synthetic method. It is worth noting that compound 5a is a
known intermediate in the synthesis of a potent ACE
inhibitor (see experimental section). Synthesis of all of the
aryl racemates 1 required for our further asymmetric
catalytic studies has been attained and conditions developed
for enantiomer assay on most of these species.
4.2.2. Ethyl 2-(1-hydroxy-1-(3-nitrophenyl)-methyl)-
propenoate 2f. Yield 92%; dH (400 MHz, CDCl3) 1.28
(3H, t, JZ7.1 Hz, CH2Me), 3.35 (1H, br, OH), 4.22 (2H, q,
JZ7.1 Hz, CH2Me), 5.64 (1H, s, br, unresolved long range
coupling to ]CH2, ArCH), 5.90 (1H, s, ]CH2), 6.43 (1H,
s, ]CH2), 7.54 (1H, t, JZ8.0 Hz, Ar5-H), 7.78 (1H, m,
Ar6-H), 8.18 (1H, m, Ar4-H), 8.28 (1H, apparent t, JZ
w0.8 Hz, Ar2-H); dC (67.8 MHz, CDCl3) 14.0, 61.3, 72.6,
121.5, 122.7, 127.0, 129.3, 132.6, 141.2, 143.7, 148.2,
165.9; nmax (CHCl3 solution)/cmK1 3600, 2983m, 2939m,
1715s, 1629m, 1464m, 1372m, 1352s, 1330m, 1147m,
1095m, 1047m, 967m; m/z (EI) 251 (MC, 3%), 105 (22),
233 (47), 188 (56), 234 (100). [Found (HRMS, EI): MC,
251.0803. C12H13NO5 requires M 251.0794].
4. Experimental
4.1. General
All addition reactions (both stoichiometric and catalytic)
involving air-sensitive reagents were performed in flame-
dried Schlenk tubes under argon. All other preparative
reactions were performed in a fumehood with appropriate
precautions. Proton NMR spectra were recorded on a Bruker
AM400 or AV400 (400 MHz) instruments; 13C NMR were
recorded on a Jeol EX270 or Bruker AV400 machines [all
coupling constants (J) are given in Hz]. Mass spectra were
recorded using electron ionisation (EI) and fast atom
bombardment (FAB) or chemical ionisation (CH4, CI)
techniques using Micromass 70E (EI) and Micromass
Autospec (FAB) machines. Infrared spectra were recorded
on a Perkin Elmer 1600 Series FTIR machine.
4.3. General preparation of the allylic halides 3–4
Either concentrated hydrobromic acid (4.2 ml of a 48% w/w
solution, 25.0 mmol; for 3) [or concentrated HCl (2.5 ml of
37% w/w solution, 25.0 mmol; for 4)] followed by
concentrated sulfuric acid (3.8 ml of a 98% w/w solution,
38 mmol; for 3) [or (2.3 ml of a 98% w/w solution,
23 mmol; for 4)] were added dropwise to stirred Baylis–
Hillman alcohol (25.0 mmol) using an ice bath for cooling.
The mixture was stirred overnight at room temperature and
extracted with diethyl ether (2!20 ml). The organic layers
were combined and washed successively with saturated
sodium hydrogen carbonate solution (10 ml), distilled water
(10 ml) and brine (10 ml), dried (Na2SO4) and the solvent
Various synthetic routes to the Baylis–Hillman adducts 2
and 8 are available.11 All of these are well detailed in the
literature except 2b and 2f. Some of the allylic bromides 312
and chlorides (4 and 9)13 and the precursors to 7 are also
known. All other compounds were commercial products or
employed procedures described by us previously.14

K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
1437
removed to give a yellow oils which were crystallised from
pentane or Kugelrohr distilled.
4.4. Representative addition of organometallics to the
allylic halides 3–4 and 9
A solution of ZnEt2 (1.5 ml of 1.0 M hexane solution,
1.5 mmol) was added to a cold (K20 8C) solution of 3
(1.00 mmol) and [Cu(MeCN)4]BF4 (9.4 mg, 0.03 mmol) in
THF (1.0 ml). The reaction was stirred (40 min) at K20 8C
and the reaction quenched with 2 M HClaq. The reaction
mixture was partitioned between dichloromethane and
water, the organic layer separated, dried (MgSO4), and the
solvent removed to give essentially pure 5. Similar reactions
were carried out using 4 and 9 (1.00 mmol) but with a
catalyst system comprised of CuCN (17.9 mg, 0.2 mmol)
and TBAB (32 mg, 0.1 mmol) in THF (1.0 ml). The reaction
was stirred for 25 min at K20 8C and the reaction was
quenched with 2 M HCl. Similar procedures were used for
the additions of other ZnR2 and n-PrZnBr reagents.
4.3.1. Ethyl (Z)-2-bromomethyl-3-(1-naphthyl)-propeno-
ate 3b. Yield 62%; low melting point solid; dH (400 MHz,
CDCl3) 1.45 (3H, t, JZ7.2 Hz, CH2Me), 4.34 (2H, s,
CH2Br), 4.43 (2H, q, JZ7.2 Hz, CH2Me), 7.54–7.61 (3H,
m, Ar), 7.79–7.94 (4H, m, Ar), 8.34 (1H, s, ]CH); dC
(67.8 MHz, CDCl3) 14.4, 27.0, 61.6, 124.2, 125.4, 126.2,
126.5, 126.8, 128.7, 129.8, 131.2, 131.6, 133.5, 141.0,
165.9; nmax (CHCl3 solution)/cmK1 2978m, 1715s, 1628m,
1366m, 1277s, 1256s, 1151m, 1089m, 1021m, 805s; m/z
(FAB) 318 (MC, 79Br, 10%), 240 (22), 239 (100). [Found
(HRMS, FAB): MC, 318.0265. C16H15BrO2 requires M
318.0255].
4.3.2. Ethyl (Z)-2-chloromethyl-3-(1-naphthyl)-propeno-
ate 4b. Yield 74%; low melting solid; dH (400 MHz,
CDCl3) 1.44 (3H, t, JZ7.1 Hz, CH2Me), 4.42 (4H, s
coincident with q, JZ7.1 Hz, CH2Cl and CH2Me), 7.54–
7.58 (3H, m, Ar), 7.73 (1H, d, JZ7.1 Hz, Ar), 7.89–7.93
(3H, m, Ar), 8.43 (1H, s, ]CH); dC (100.6 MHz, CDCl3)
14.8, 39.9, 61.9, 124.7, 125.4, 126.9, 127.1, 127.3, 129.0,
130.4, 131.8, 131.9, 133.9, 138.6, 143.9, 166.2; nmax (CHCl3
solution)/cmK1 2980m, 1715s, 1629m, 1369m, 1341m,
1255s, 1185s, 1098m, 805m, 778s; m/z (FAB) 274 (MC,
35Cl, 68%), 240 (19), 239 (68), 209, 195 (40), 167 (48), 166
(40), 165 (100). [Found (HRMS, FAB): MC, 274.0765.
C16H15ClO2 requires M 274.0761].
Alternative workup to facilitate removal of unreacted
starting halides 3–4. The crude oil (140 mg) was dissolved
in diethyl ether (10 ml) and DABCO (80 mg, 0.75 mmol)
was added. The solution was stirred overnight at room
temperature and then transferred to a separating funnel
where it was washed with HCl (1 M, 5 ml) and brine
(10 ml), dried (Na2SO4) and the solvent evaporated to give a
colourless oil. If analysis by 1H NMR spectroscopy showed
that there was still a residual amount of halide (especially
for 4) the oil was re-dissolved in diethyl ether (5 ml),
DABCO (60 mg, 0.54 mmol) was added and the solution
was stirred overnight at room temperature again. After
washing and drying as before the oil was found to be solely
SN20 product 5.
4.3.3. Ethyl (Z)-2-chloromethyl-3-(3-nitrophenyl)-pro-
penoate 4f. Yield 47%; mp 55 8C (pentane) (Found: C,
53.5; H, 4.4; N, 5.3%. Calcd for C12H12NO4Cl: C, 53.4; H,
4.5; N, 5.2%); dH (400 MHz, CDCl3) 1.41 (3, t, JZ7.1 Hz,
CH2Me), 4.38 (2H, q, JZ7.1 Hz, CH2Me), 4.43 (2H, s,
CH2Cl), 7.65 (1H, apparent t, JZ8.4 Hz, Ar), 7.86 (1H, s,
]CH), 7.89 (1H, ddd, JZ8.4, 1.3, 1.0 Hz, Ar), 8.21 (1H,
dd, JZ8.4, 1.3, 1.0 Hz, Ar), 8.40 (1H, dd, JZ1.3, 1.0 Hz,
Ar); dC (67.8 MHz, CDCl3) 14.1, 38.1, 61.7, 124.0, 124.2,
130.0, 131.1, 134.9, 135.7, 140.2, 148.4, 165.4; nmax (CHCl3
solution)/cmK1 2898m, 1716s, 1638m, 1359s, 1300s,
1093s, 1021m, 897w, 875m; m/z (EI) 269 (MC, 35Cl,
38%), 234 (36), 224 (39), 161 (22), 149 (20), 116 (22), 115
(100). [Found (HRMS, EI): MC, 269.0443. C12H12ClNO4
requires M 269.0455].
4.4.1. Ethyl 2-methylene-3-phenyl-pentanoate 5a. Yield
88%; dH (400 MHz, CDCl3) 0.86 (3H, t, JZ7.3 Hz,
CHCH2Me) 1.20 (3H, t, JZ7.1 Hz, OCH2Me), 1.77 (1H,
ddq, JZ13.4, 8.9, 7.3 Hz, CHCH2aMe), 1.89 (1H, ddq, JZ
13.4, 6.3, 7.3 Hz, CHCH2bMe), 3.73 (1H, dd, JZ8.9,
6.3 Hz, CH), 4.09 (2H, m, OCH2Me), 5.63 (2H, s, ]CH2a),
6.29 (1H, s, ]CH2b), 7.16–7.29 (5H, m, Ar); dC (67.8 MHz,
CDCl3) 12.4, 14.0, 27.4, 48.0, 60.6, 123.4, 126.2, 128.1,
128.2, 142.8, 144.1, 167.1; nmax (thin film)/cmK1 2964m,
1718s, 1627m, 1452m, 1368m, 1252s, 1149s; m/z (EI) 218
(MC, 100%). [Found (HRMS, EI): MC 218.1302.
C14H18O2 requires M 218.1307]. This compound has been
prepared once by an alternative route.15
4.4.2. Ethyl 2-methylene-3-(1-naphthyl)-pentanoate 5b.
Yield 95%; dH (400 MHz, CDCl3) 0.96 (3H, t, JZ7.3 Hz,
CHCH2Me), 1.14 (3H, t, JZ7.1 Hz, OCH2Me), 1.92–2.06
(2H, m, CHCH2Me), 4.09–4.17 (2H, m, OCH2Me), 4.71
(1H, dd, JZ7.4, 7.2 Hz, CH), 5.56 (1H, s, ]CH2a), 6.33
(1H, s, ]CH2b), 7.38 (1H, dd, JZ7.2, 1.1 Hz, Ar), 7.42–
7.55 (3H, m, Ar), 7.73 (1H, d, JZ8.1 Hz, Ar), 7.85 (1H, dd,
JZ8.0, 1.4 Hz, Ar), 8.19 (1H, d, JZ8.5 Hz, Ar); dC
(100.6 MHz, CDCl3) 12.8, 14.2, 28.2, 42.2, 48.3, 60.9,
123.9, 124.2, 124.5, 125.4, 125.5, 126.0, 128.9, 132.4,
134.2, 139.3, 144.6, 167.6; nmax (thin film)/cmK1 2960m,
2927m, 1713s, 1251m, 1145m, 797m; m/z (FAB) 268 (MC,
37%), 223 (69), 207 (51), 195 (37) 147 (100). [Found
(HRMS, FAB): MC, 268.1456. C18H20O2 requires M
268.1463].
4.3.4. Ethyl (Z)-2-chloromethyl-3-(4-trifluoromethyl-
phenyl)-propenoate 4h. Yield 86%; low melting solid.
(Found: C, 53.1; H, 4.0%. Calcd for C13H12ClF3O2: C,
53.35; H, 4.1%); dH (400 MHz, CDCl3) 1.40 (3H, t, JZ
7.1 Hz, CH2Me), 4.36 (2H, q, JZ7.1 Hz, CH2Me), 4.42
(2H, s, CH2Cl), 7.66 (2H, d, JZ8.3 Hz, Ar), 7.73 (2H, d, JZ
8.3 Hz, Ar), 7.87 (1H, s, ]CH); dC (100.6, MHz, CDCl3)
14.2, 38.5, 61.5, 123.9 (q, 1JCFZ272 Hz), 125.7 (q, 3JCF
Z
2
4 Hz), 129.7, 131.0, 131.2 (q, JCFZ33 Hz), 137.8, 141.6,
165.8; nmax (CHCl3 solution)/cmK1 2943w, 1713s, 1637m,
1373m, 1325s, 1301m, 1284m, 1168m, 1132s, 1115m,
1095m, 1068s, 1018m; m/z (EI) 292 (MC, 79%), 247 (54),
218 (19), 183 (100). [Found (HRMS, EI): MC 292.0477.
C13H12O2F3Cl requires M 292.0478].

1438
K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
4.4.3. Ethyl 2-methylene-3-(4-tolyl)-pentanoate 5c. Yield
93%; dH (400 MHz, CDCl3) 0.76 (3H, t, JZ7.3 Hz,
CHCH2Me), 1.11 (3H, t, JZ7.1 Hz, OCH2Me), 1.64 (1H,
ddq, JZ13.4, 8.6, 7.3 Hz, CHCH2aMe), 1.78 (1H, ddq, JZ
13.4, 6.5, 7.3 Hz, CHCH2bMe), 2.20 (3H, s, ArMe), 3.61
(1H, dd, JZ8.6, 6.5 Hz, CH), 4.00 (2H, m, OCH2Me), 5.51
(1H, s, ]CH2a), 6.17 (1H, s, ]CH2b), 6.97–7.01 (4H, m,
Ar); dC (67.8 MHz, CDCl3) 12.3, 14.0, 20.9, 27.4, 47.5,
60.5, 123.1, 127.9, 128.8, 129.1, 139.7, 144.3, 167.3; nmax
(thin film)/cmK1 2955m, 1717s, 1628m, 1512m, 1252m,
1149m, 814m; m/z (CI) 233 ([MCH]C, 100%). [Found
(HRMS, CI): [MCH]C, 233.1542. C15H21O2 requires [MC
H] 233.1542].
(1H, ddq, JZ14.7, 7.3, 6.4 Hz, CHCH2aMe), 1.89 (1H, ddq,
JZ14.5, 7.3, 6.6 Hz, CHCH2bMe), 3.96–4.02 (2H, m,
OCH2Me), 4.32 (1H, t, JZ7.3 Hz, CH), 5.66 (1H, s,
]CH2a), 6.34 (1H, s, ]CH2b), 7.22–7.27 (2H, m, Ar), 7.43
(1H, ddd, JZ8.7, 7.6, 1 Hz, Ar), 7.72 (1H, dd, JZ8.1 Hz,
Ar); dC (100.6 MHz, CDCl3) 12.2, 14.1, 27.4, 41.6, 61.1,
124.4, 124.9, 127.2, 129.0, 132.5, 137.8, 142.5, 150.6,
166.5; nmax (thin film)/cmK1 2935m, 1714s, 1630m, 1578m,
1527s, 1463m, 1356s; m/z (EI) 263 (MC, 1%), 255 (36), 218
(100). [Found (HRMS, EI): MC 263.1168. C14H17O4N
requires M 263.1157].
4.4.8. Ethyl-2-methylene-3-(4-trifluoromethylphenyl)-
pentanoate 5h. Yield 98%; dH (400 MHz, CDCl3) 0.86
(3H, t, JZ7.3 Hz, CHCH2Me), 1.21 (3H, t, JZ7.1 Hz,
OCH2Me), 1.76 (1H, ddq, JZ14.3, 8.9, 7.3 Hz, CHCH2a-
Me), 1.91 (1H, ddq, JZ14.3, 6.5, 7.3 Hz, CHCH2bMe), 3.80
(1H, dd, JZ8.9, 6.6 Hz, CH2), 4.02–4.19 (2H, m,
OCH2Me), 5.70 (1H, s, ]CH2a), 6.37 (1H, s, ]CH2b),
7.33 (2H, d, JZ8.2 Hz, Ar), 7.54 (2H, d, JZ8.2 Hz, Ar); dC
(100.6 MHz, CDCl3) 12.4, 14.3, 27.4, 48.1, 60.9, 124.3,
4.4.4. Ethyl 3-(4-chlorophenyl)-2-methylene-pentanoate
5d. Yield 97%; dH (400 MHz, CDCl3) 0.84 (3H, t, JZ
7.3 Hz, CHCH2Me), 1.19 (3H, t, JZ7.1 Hz, OCH2Me), 1.71
(1H, ddq, JZ13.5, 8.8, 7.3 Hz, CHCH2aMe), 1.87 (1H, ddq,
JZ13.5, 6.3, 7.3 Hz, CHCH2bMe), 3.89 (1H, dd, JZ8.8,
6.3 Hz, CH), 4.11 (2H, m, OCH2Me), 5.63 (1H, s, ]CH2a),
6.30 (1H, s, ]CH2b), 7.13 (2H, d, JZ8.4 Hz, Ar), 7.23 (2H,
d, JZ8.4 Hz, Ar); dC (67.8 MHz, CDCl3) 12.1, 13.9, 27.2,
47.3, 60.5, 123.5, 128.2, 129.4, 131.8, 141.3, 143.6, 166.6;
nmax (thin film)/cmK1 2965m, 1717s, 1627m, 1491m,
1252s, 1151s, 1092s, 1015m, 820m; m/z (FAB) 252 (MC,
35Cl, 12%), 219 (22), 207 (30), 176 (22), 155 (50), 154
(100). [Found (HRMS, FAB): MC, 252.0912. C14H17ClO2
requires M 252.0917].
1
3
124.5 (q, JCFZ272 Hz), 125.4 (q, JCFZ3 Hz), 128.6,
2
128.8 (q, JCFZ32 Hz), 143.5, 147.3, 166.9; nmax (CHCl3
solution)/cmK1 2933m, 1711s, 1618m, 1325s, 1125s,
1068s; m/z (EI) 286 (MC, 100%). [Found (HRMS, EI):
MC 286.1175. C15H17O2F3 requires M 286.1181].
4.5. Preparation of ethyl (Z)-2-methanesulfonylmethyl-
3-phenyl-propenoate 7
4.4.5. Ethyl-2-methylene-3-(4-nitrophenyl)-pentanoate
5e. Yield 97%; dH (400 MHz, CDCl3) 0.88 (3H, t, JZ
7.3 Hz, CHCH2Me), 1.21 (3H, t, JZ7.1 Hz, OCH2Me), 1.79
(1H, ddq, JZ13.4, 8.8, 7.3 Hz, CHCH2aMe), 1.78 (1H, ddq,
JZ13.4, 6.3, 7.3 Hz, CHCH2bMe), 3.84 (1H, dd, JZ8.8,
6.3 Hz, CH), 4.11 (2H, m, OCH2Me), 5.76 (1H, s, ]CH2a),
6.41 (1H, d, ]CH2b), 7.39 (2H, d, JZ8.7 Hz, Ar), 8.14 (2H,
d, JZ8.7 Hz, Ar); dC (67.8 MHz, CDCl3) 12.0, 13.8, 26.9,
47.8, 60.6, 123.3, 124.5, 128.8, 142.4, 146.3, 150.7, 166.2;
nmax (thin film)/cmK1 2967m, 1714s (C]O), 1520s,
1347m, 1254m, 1152m, 851m; m/z (FAB) 264 ([MCH]C,
13%), 221 (14), 207 (16), 147 (38), 77 (13), 73 (100).
[Found (HRMS, FAB): [MCH]C, 264.1244. C14H18NO4
requires [MCH] 264.1236].
The formate 6 was prepared by a literature method and
hydrolysed to the derived allylic alcohol.11f Both com-
pounds showed identical spectroscopic and physical proper-
ties to those published. Mesyl chloride (0.4 ml, 5.1 mmol)
was added to a stirred solution of allylic alcohol (0.7 g,
3.4 mmol) in dichloromethane (10 ml) at 0 8C, followed by
dropwise addition of NEt3 (0.96 ml, 6.9 mmol). The
reaction mixture was stirred at 0 8C for 30 min. The solution
was diluted with diethyl ether (10 ml), poured onto ice-
water and transferred to a separating funnel. The organic
layer was washed with chilled (0 8C) HCl (2 M, 5 ml) and
chilled (0 8C) brine (10 ml). The aqueous layer was re-
extracted with ether (10 ml) and washed as before. The
combined extracts were dried (Na2SO4) and the solvent
evaporated to give the crude oil which crystallised overnight
at K20 8C to give 7 (0.81 g, 84%) as a yellow solid. No
further purification was attempted due to the reactive nature
of 7a, however, the spectroscopic spectrum showed the
product to be essentially pure.
4.4.6. Ethyl-2-methylene-3-(3-nitrophenyl)-pentanoate
5f. Yield 95%; dH (400 MHz, CDCl3) 0.88 (3H, t, JZ
7.3 Hz, CHCH2Me), 1.22 (3H, t, JZ7.1 Hz, OCH2Me), 1.82
(1H, ddq, JZ13.8, 8.8, 7.3 Hz, CHCH2aMe), 1.94 (1H, ddq,
JZ13.7, 6.6, 7.3 Hz, CHCH2bMe), 3.86 (1H, dd, JZ7.3,
8.8 Hz, CH), 4.07–4.16 (2H, m, OCH2Me), 5.76 (1H, s,
]CH2a), 6.38 (1H, s, ]CH2b), 7.45 (1H, ddd, JZ7.5, 8.1,
1.5 Hz, Ar), 7.57 (1H, dt, JZ7.5, 1.0 Hz, Ar), 8.06–8.07
(1H, m, Ar); dC (67.8 MHz, CDCl3) 12.5, 14.3, 27.5, 48.1,
61.2, 121.9, 123.1, 125.0, 129.4, 134.9, 143.0, 145.6, 148.6,
166.7; nmax (CHCl3 solution)/cmK1 2995m, 1710s, 1629m,
1462m, 1353s, 1097m, 1025m, 954m, 900s, 648m; m/z (EI)
263 (MC, 32%), 246 (60), 218 (64), 172 (83), 143 (63), 115
(100). [Found (HRMS, EI): MC 263.1158. C14H17O4N
requires M 263.1157].
Mp dec. slowly at ambient temperature (t ⁄ w10 h); dH
1
2
(400 MHz, CDCl3) 1.38 (3H, t, JZ7.1 Hz, OCH2Me), 3.12
(3H, s, -SO2Me), 4.33 (2H, q, JZ7.1 Hz, OCH2Me), 5.07
(2H, s, CH2OMs), 7.43–7.48 (5H, m, Ar), 8.08 (1H, s,
]CH); dC (67.8 MHz, CDCl3) 14.3, 37.4, 61.5, 65.1, 124.4,
128.9 (2C), 129.5 (2C), 130.2, 133.5, 147.6, 166.3; nmax
(CHCl3 solution)/cmK1 3027m, 2980m, 2934m, 1709s,
1631s, 1448m, 1358s, 1347s, 1323m, 1241s, 1175s; m/z (EI)
284 (MC, 9%), 189 (13), 188 (13), 159 (64), 115 (100).
[Found (HRMS, EI): MC 284.0715. C13H16O5S requires M
284.0718].
4.4.7. Ethyl-2-methylene-3-(2-nitrophenyl)-pentanoate
5g. Yield 98%; dH (400 MHz, CDCl3) 0.90 (3H, t, JZ
7.3 Hz, CHCH2Me), 1.06 (3H, t, JZ7.1 Hz, OCH2Me), 1.83

K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
1439
4.6. Representative preparation of allylic chlorides 9
propenoate 9f. Yield 83%; dH (400 MHz, CDCl3) 3.88
(3H, s, OMe), 4.34 (2H, s, CH2Cl), 7.42–7.45 (2H, m, Ar),
7.48–7.51 (2H, m, Ar), 7.82 (1H, s, ]CH); dC (67.8 MHz,
CDCl3) 39.0, 52.8, 129.0, 129.4, 131.1, 132.7, 136.1, 142.6,
166.7; nmax (thin film)/cmK1 2951m, 1716s, 1491s, 1436s,
1089s, 1014m, 928m; m/z (EI) 244 (MC, 35Cl, 59%), 209
(80), 149 (100). [Found (HRMS, EI) MC 244.0061.
C11H11O2Cl2 requires M 244.0058].
Oxalyl chloride (0.5 ml, 5.7 mmol) was added dropwise
over 2 min to a stirred solution of allylic alcohol (4.0 mmol)
and N,N-dimethylformamide (0.1 ml; 33 mol%) in chloro-
form (10 ml) at room temperature under argon. After
stirring for a 3 h the reaction was quenched by cautious
addition of 2 M NaOH(aq.) (10 ml). After dilution with
EtOAc (50 ml) and H2O (50 ml) the organic layer was
separated, dried (MgSO4) and concentrated. Flash chroma-
tography (silica; EtOAc/Hexanes) gave the products as
colourless oils and solids.
4.6.6. Methyl (Z)-2-chloromethyl-3-(4-trifluoromethyl-
phenyl)-propenoate 9i. Yield 69%; dH (400 MHz,
CDCl3) 3.90 (3H, s, OMe), 4.42 (2H, s, CH2Cl), 7.65 (2H,
d, JZ8.4 Hz, Ar), 7.72 (2H, d, JZ8.4 Hz, Ar), 7.88 (1H, s,
]CH); dC (100.6 MHz, CDCl3) 38.6, 52.8, 125.3 (q, 1JCF
Z
4.6.1. Methyl (Z)-2-chloromethyl-3-(1-naphthyl)-pro-
penoate 9b. Yield 54%; mp 74–76 8C (Heptane). (Found:
C, 69.07; H, 5.04%. Calcd for C15H13ClO2: C, 69.10; H,
5.03%); dH (400 MHz, CDCl3) 3.95 (3H, s, OMe), 4.41 (2H,
s, CH2Cl), 7.53–7.57 (3H, m, Ar), 7.72 (1H, dt, JZ7.1,
1.0 Hz, Ar), 7.88–7.92 (3H, m, Ar), 8.43 (1H, s, ]CH); dC
(100.6 MHz, CDCl3) 39.6, 52.7, 124.4, 125.6, 126.6, 126.9,
127.0, 128.9, 130.1, 130.7, 131.5, 131.6, 133.6, 142.2,
166.6; nmax (CHCl3 solution)/cmK1 2954w, 1716s, 1634w,
1343m, 1289m, 1099m, 977w; m/z (EI) 260 (MC, 35Cl,
65%), 201 (22), 193 (20), 165 (100). [Found (HRMS, EI)
MC 260.0613. C15H13O2Cl requires M 260.0604].
272.2 Hz), 126.0 (q, 3JCFZ3.7 Hz), 129.8, 130.7, 131.5 (q,
2JCFZ33.0 Hz), 137.8, 142.0, 166.4; nmax (thin film)/cmK1
2955w, 1727s, 1635m, 1616m, 1437m, 1323s, 1281s,
1170s, 1127s, 1018m, 845m, 783m; m/z (EI) 278 (MC,
35Cl, 58%), 259 (11), 218 (18), 183 (100). [Found (HRMS,
EI) MC 278.0329. C12H10O2F3Cl requires M 278.0321].
4.6.7. Methyl (Z)-2-chloromethyl-3-(4-nitrophenyl)-pro-
penoate 9j. Yield 90%; mp 126–128 8C; dH (400 MHz,
CDCl3) 3.93 (3H, s, OMe), 4.42 (2H, s, CH2Cl), 7.71–7.74
(2H, m, Ar), 7.90 (1H, s, ]CH), 8.32–8.35 (2H, m, Ar); dC
(100.6 MHz, CDCl3) 38.3, 53.0, 124.3, 130.4, 131.8, 140.6,
140.9, 148.3, 166.1; nmax (CHCl3 solution)/cmK1 2954w,
1722s, 1598m, 1384s, 1092m, 981w; m/z (EI) 255 (MC,
35Cl, 69%), 224 (34), 174 (78), 144 (27), 115 (100). [Found
(HRMS, EI) MC 255.0925. C11H10NO4Cl requires M
255.0298].
4.6.2. Methyl (Z)-2-chloromethyl-3-(2-naphthyl)-pro-
penoate 9c. Yield 67%; mp 76–78 8C (Heptane); dH
(400 MHz, CDCl3) 3.91 (3H, s, OMe), 4.56 (2H, s,
CH2Cl), 7.51–7.58 (2H, m, Ar), 7.62 (1H, dd, JZ8.6,
1.8 Hz, Ar), 7.85–7.92 (3H, m, Ar), 8.04 (1H, s, ]CH), 8.08
(1H, d, JZ0.8 Hz, Ar); dC (100.6 MHz, CDCl3) 39.5, 52.7,
126.6, 126.9, 127.6, 127.9, 128.6, 128.8, 128.9, 130.2,
131.8, 133.3, 133.7, 144.1, 167.0; nmax (CHCl3 solution)/
cmK1 2953w, 1714s, 1624m, 1286m, 1092m, 861w; m/z
(EI) 260 (MC, 35Cl, 67%), 225 (26), 193 (11), 165 (100).
[Found (HRMS, EI) MC 260.0598. C15H13O2Cl requires M
260.0604].
4.6.8. tert-Butyl (Z)-2-chloromethyl-3-phenyl-propeno-
ate 9k. Yield 80%. (Found: C, 66.84; H, 6.72%. Calcd for
C14H17O2Cl: C, 66.53; H, 6.78%); dH (400 MHz, CDCl3)
1.57 (9H, s, tBu), 4.43 (2H, s, CH2Cl), 7.39–7.54 (5H, m,
Ar), 7.78 (1H, s, ]CH); dC (100.6 MHz, CDCl3) 28.3, 39.5,
81.8, 128.7, 129.0 (2C), 129.6, 129.7 (2C), 134.7, 142.7,
165.5; nmax (thin film)/cmK1 2934m, 1709s, 1632m, 1494m,
1451m, 1368s, 1155s, 1094m, 850m; m/z (EI) 252 (MC,
35Cl, 11%), 196 (86), 179 (50), 115 (72), 57 (100). [Found
(HRMS, EI) MC 252.0930. C14H17O2Cl requires M
252.0917].
4.6.3. Methyl (Z)-2-chloromethyl-3-(4-tolyl)-propenoate
9e. Yield 67%. (Found: C, 64.16; H, 5.80%. Calcd for
C12H13ClO2: C, 64.15; H, 5.83%); dH (400 MHz, CDCl3)
2.40 (3H, s, ArMe), 3.87 (3H, s, OMe), 4.50 (2H, s, CH2Cl),
7.26 (2H, d, JZ8.1 Hz, Ar), 7.47 (2H, d, JZ8.1 Hz, Ar),
7.85 (1H, s, ]CH); dC (67.8 MHz, CDCl3) 21.6, 39.5, 52.6,
127.5, 129.8, 130.0, 131.5, 140.4, 144.2, 167.1; nmax (thin
film)/cmK1 2951m, 1714s, 1436s, 1091s, 928m; m/z (EI)
224 (MC, 35Cl, 44%), 189 (66), 129 (100). [Found (HRMS,
EI) MC 224.0611. C12H13ClO2 requires M 224.0604].
4.7. General preparation of the b,b-disubstituted
a-methylenepropionates 10 and 11a–c
These compounds were prepared in an analogous manner to
compounds 5.
4.6.4. Methyl (Z)-2-chloromethyl-3-(2-bromophenyl)-
propenoate 9f. Yield 82%; mp 73–74 8C. (Found: C,
45.50; H, 3.34%. Calcd for C11H10O2BrCl: C, 45.63; H,
3.48%); dH (400 MHz, CDCl3) 3.91 (3H, s, OMe), 4.34 (2H,
s, CH2Cl), 7.25–7.29 (1H, m, Ar), 7.40–7.44 (1H, m, Ar),
7.62–7.66 (2H, m, Ar), 7.90 (1H, s, ]CH); dC (100.6 MHz,
CDCl3) 39.1, 52.8, 124.6, 127.8, 130.2, 130.3, 131.0, 133.2,
134.8, 142.7, 166.3; nmax (CHCl3 solution)/cmK1 2954w,
1716s, 1636m, 1364m, 1293m, 1094m; m/z (EI) 288 (MC,
35Cl/79Br, 2%), 257 (4), 209 (100). [Found (HRMS, EI) MC
287.9567. C11H10O2BrCl requires M 287.9553].
4.7.1. Methyl-2-methylene-3-phenyl-pentanoate 10a.
Yield 95%; colourless oil. (Found: C, 76.18; H, 7.85%.
Calcd for C13H16O2: C, 76.44; H, 7.90%); dH (500 MHz,
CDCl3) 0.86 (3H, t, JZ7.3 Hz, CH2Me), 1.72–1.93 (2H, m,
CH2Me), 3.67 (3H, s, OMe), 3.73 (1H, dd, JZ8.3, 7.0 Hz,
CH), 5.65 (1H, s, ]CH2a), 6.29 (1H, s, ]CH2b), 7.17–7.29
(5H, m, Ar); dC (125 MHz, CDCl3) 12.6, 27.7, 48.2, 52.0,
124.0, 126.5, 128.3 (2C), 128.4 (2C), 142.9, 144.0, 167.7;
nmax (thin film)/cmK1 2962m, 2875m, 1720s, 1623m,
1437m, 1255m, 1151m, 946m; m/z (EI) 204 (MC, 89%),
172 (53), 144 (48), 129 (31), 115 (100). [Found (HRMS, EI)
MC 204.1144. C13H16O2 requires M 205.1150].
4.6.5. Methyl (Z)-2-chloromethyl-3-(4-chlorophenyl)-

1440
K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
4.7.2. Methyl-2-methylene-3-(1-naphthyl)-pentanoate
10b. Yield 98%; dH (400 MHz, CDCl3) 0.94 (3H, t, JZ
7.3 Hz, CH2Me), 1.88–2.05 (2H, m, CH2Me), 3.67 (3H, s,
OMe), 4.69 (1H, br dd, JZ7.3 Hz, unresolved, CH), 5.53
(1H, s, ]CH2a), 6.30 (1H, s, ]CH2b), 7.35–7.53 (4H, m,
Ar), 7.71 (1H, d, JZ8.1 Hz, Ar), 7.83 (1H, dd, JZ8.0,
1.5 Hz, Ar), 8.15 (1H, d, JZ8.4 Hz, Ar); dC (100.6 MHz,
CDCl3) 12.9, 28.2, 42.3, 52.1, 123.8, 124.2, 124.9, 125.4,
125.6, 126.1, 127.2, 128.9, 132.3, 134.2, 139.1, 144.2,
168.0; nmax (thin film)/cmK1 2962m, 1721s, 1627m, 1427m,
1248s, 948m; m/z (EI) 254 (MC, 39%), 225 (44), 195 (39),
165 (100). [Found (HRMS, EI) MC 254.1306. C17H18O2
requires M 254.1307].
167.5; nmax (thin film)/cmK1 2964s, 2934m, 2875m, 1724s,
1628m, 1468s, 1252s, 1153s, 948m; m/z (CI) 283 ([MC
H]C, 79Br, 100%). [Found (HRMS, CI) [MCH]C
283.0317. C13H15O2Br requires MCH 283.0334].
4.7.7. Methyl-2-methylene-3-(4-chlorophenyl)-pentano-
ate 10g. Yield 95%. (Found: C, 65.43; H, 6.30%. Calcd
for C13H15O2Cl: C, 65.41; H, 6.33%); dH (400 MHz,
CDCl3) 0.85 (3H, t, JZ7.3 Hz, CH2Me), 1.67–1.93 (2H,
m, CH2Me), 3.67 (3H, s, OMe), 3.70 (1H, dd, JZ9.0,
6.9 Hz, CH), 5.65 (1H, s, ]CH2a), 6.30 (1H, s, ]CH2b),
7.12–7.15 (2H, m, Ar), 7.23–7.26 (2H, m, Ar); dC
(67.8 MHz, CDCl3) 12.5, 27.5, 47.6, 52.1, 124.2, 128.6,
129.6, 132.2, 141.4, 143.6, 167.5; nmax (thin film)/cmK1
2964m, 1721s, 1627m, 1437m, 1152s, 948m; m/z (EI) 238
(MC, 35Cl, 100%). [Found (HRMS, EI) MC 238.0765.
C13H15O2Cl requires M 238.0761].
4.7.3. Methyl-2-methylene-3-(2-naphthyl)-pentanoate
10c. Yield 94%; dH (400 MHz, CDCl3) 0.89 (3H, t, JZ
7.3 Hz, CH2Me), 1.82–2.02 (2H, m, CH2Me), 3.65 (3H, s,
OMe), 3.91 (1H, dd, JZ8.7, 6.4 Hz, CH), 5.72 (1H, s,
]CH2a), 6.34 (1H, s, ]CH2b), 7.34 (1H, dd, JZ8.4,
1.8 Hz, Ar), 7.39–7.46 (2H, m, Ar), 7.65 (1H, d, JZ1.2 Hz,
Ar), 7.75–7.80 (3H, m, Ar); dC (100.6 MHz, CDCl3) 12.7,
27.6, 48.3, 52.0, 124.1, 125.6, 126.0, 126.8 (2C), 127.7,
127.9, 128.0, 132.5, 133.7, 140.4, 144.0, 167.7; nmax (thin
film)/cmK1 2962m, 1721s, 1627m, 1436m, 1256s, 1151s,
947m; m/z (EI) 254 (MC, 70%), 194 (30), 165 (100). [Found
(HRMS, EI) MC 254.1298. C17H18O2 requires M
254.1307].
4.7.8. Methyl-2-methylene-3-(4-fluorophenyl)-pentano-
ate 10h. Yield 94%. (Found: C, 70.23; H, 6.75%. Calcd
for C13H15O2F: C, 70.25; H, 6.80%); dH (400 MHz, CDCl3)
0.85 (3H, t, JZ7.3 Hz, CH2Me), 1.67–1.93 (2H, m,
CH2Me), 3.67 (3H, s, OMe), 3.71 (1H, dd, JZ9.0, 6.3 Hz,
CH), 5.64 (1H, s, ]CH2a), 6.29 (1H, s, ]CH2b), 6.93–6.99
(2H, m, Ar), 7.13–7.18 (2H, m, Ar); dC (67.8 MHz, CDCl3)
2
12.5, 27.7, 47.5, 52.0, 115.2 (d, JCFZ21.2 Hz), 124.0,
3
4
129.7 (d, JCFZ7.8 Hz), 138.5 (d, JCFZ3.1 Hz), 143.9,
1
161.6 (d, JCFZ244.0 Hz), 167.6; nmax (thin film)/cmK1
2964m, 1723s, 1628m, 1603m, 1508s, 1151s, 948m; m/z
(EI) 222 (MC, 93%), 190 (55), 162 (32), 147 (23), 133
(100). [Found (HRMS, EI) MC 222.1060. C13H15O2F
requires M 222.1056].
4.7.4. Methyl-2-methylene-3-(4-methoxyphenyl)-pen-
tanoate 10d. Yield 91%. (Found: C, 71.81; H, 7.73%.
Calcd for C14H18O3: C, 71.77; H, 7.74%); dH (400 MHz,
CDCl3) 0.85 (3H, t, JZ7.3 Hz, CH2Me), 1.67–1.92 (2H, m,
CH2Me), 3.67 (3H, s, CO2Me), 3.78 (3H, s, ArOMe), 5.62
(1H, s, ]CH2a), 6.25 (1H, s, ]CH2b), 6.80–6.84 (2H, m,
Ar), 7.10–7.13 (2H, m, Ar); dC (67.8 MHz, CDCl3) 12.6,
27.7, 47.4, 52.0, 55.4, 113.8 (2C), 123.6, 129.2 (2C), 134.9,
144.3; nmax (thin film)/cmK1 2960m, 1722s, 1627m,1610m,
1253s, 1038m, 946m; m/z (EI) 234 (MC, 73%), 205 (100).
[Found (HRMS, EI) MC 234.1261. C14H18O3 requires M
234.1256].
4.7.9. Methyl-2-methylene-3-(4-trifluoromethylphenyl)-
pentanoate 10i. Yield 85%; dH (400 MHz, CDCl3) 0.87
(3H, t, JZ7.3 Hz, CH2Me), 1.73–1.95 (2H, m, CH2Me),
3.67 (3H, s, OMe), 3.79 (1H, dd, JZ8.4, 6.8 Hz, CH), 5.71
(1H, s, ]CH2a), 6.35 (1H, s, ]CH2b), 7.32 (2H, d, JZ
8.2 Hz, Ar), 7.53 (2H, d, JZ8.2 Hz, Ar); dC (100.6 MHz,
1
CDCl3) 12.4, 27.4, 48.1, 52.1, 124.5 (q, JCFZ272 Hz),
3
2
124.6, 125.4 (q, JCFZ3.8 Hz), 128.6, 128.8 (q, JCF
Z
32.2 Hz), 143.2, 147.2, 167.3; nmax (thin film)/cmK1 2937m,
2878m, 1725s, 1618s, 1439s, 1325s, 1255s, 1163s, 1123s,
1068s, 1019m, 834m; m/z (EI) 272 (MC, 100%). [Found
(HRMS, EI) MC 272.1013. C14H15O2F3 requires M
272.1024].
4.7.5. Methyl-2-methylene-3-(4-tolyl)-pentanoate 10e.
Yield 97%. (Found: C, 76.99; H, 8.27%. Calcd for
C14H18O2: C, 77.03; H, 8.31%); dH (400 MHz, CDCl3)
0.85 (3H, t, JZ7.3 Hz, CH2Me), 1.69–1.92 (2H, m,
CH2Me), 2.30 (3H, s, ArMe), 3.66 (3H, s, OMe), 3.70
(1H, dd, JZ8.9, 6.4 Hz, CH), 5.63 (1H, s, ]CH2a), 6.27
(1H, s, ]CH2b), 7.09 (4H, s, Ar); dC (67.8 MHz, CDCl3)
12.6, 21.2, 27.7, 47.8, 52.0, 123.8, 128.2, 129.2, 136.0,
139.9, 144.2, 167.8; nmax (thin film)/cmK1 2962m, 1721s,
1627m, 1437m, 1151s, 945m; m/z (EI) 218 (MC, 61%), 186
(38), 158 (40), 129 (100). [Found (HRMS, EI) MC
218.1305. C14H18O2 requires M 218.1307].
4.7.10. Methyl-2-methylene-3-(4-nitrophenyl)-pentano-
ate 10j. Yield 97%; dH (400 MHz, CDCl3) 0.87 (3H, t,
JZ7.3 Hz, CH2Me), 1.75–1.98 (2H, m, CH2Me), 3.67 (3H,
s, OMe), 3.84 (1H, br dd, JZ7.6 Hz, and unresolved, CH),
5.76 (1H, s, ]CH2a), 6.40 (1H, s, ]CH2b), 7.36–7.39 (2H,
m, Ar), 8.13–8.18 (2H, m, Ar); dC (100.6 MHz, CDCl3)
12.4, 27.3, 48.2, 52.2, 123.8, 125.2, 129.1 (2C), 142.6,
150.9, 167.1; nmax (thin film)/cmK1 2964m, 2876m, 1720s,
1628m, 1519s, 1347s, 1256s, 1153s, 953m, 842m, 714m;
m/z (EI) 249 (MC, 70%), 232 (100). [Found (HRMS, EI)
MC 249.0998. C13H15NO4 requires M 249.1001].
4.7.6. Methyl-2-methylene-3-(2-bromophenyl)-pentano-
ate 10f. Yield 90%; dH (400 MHz, CDCl3) 0.92 (3H, t, JZ
7.3 Hz, CH2Me), 1.71–1.90 (2H, m, CH2Me), 3.68 (3H, s,
OMe), 4.29 (1H, br dd, JZ7.4 Hz, and unresolved, CH),
5.59 (1H, s, ]CH2a), 6.37 (1H, s, ]CH2b), 7.05, (1H, ddd,
JZ8.0, 7.2, 1.8 Hz, Ar), 7.15 (1H, dd, JZ7.8, 1.8 Hz, Ar),
7.24 (1H, ddd, JZ7.8, 7.2, 1.3 Hz, Ar), 7.46 (1H, dd, JZ
8.0, 1.3 Hz, Ar); dC (100.6 MHz, CDCl3) 12.3, 27.6, 46.6,
52.1, 125.1, 126.1, 127.5, 128.0, 128.4, 133.2, 142.1, 142.9,
4.7.11. tert-Butyl-2-methylene-3-phenyl-pentanoate 10k.
Yield 83%; colourless oil; dH (400 MHz, CDCl3) 0.86 (3H,
t, JZ7.3 Hz, CH2Me), 1.35 (9H, s, CMe3), 1.67–1.93 (2H,
m, CH2Me), 3.65 (1H, dd, JZ8.9, 6.1 Hz, CH), 5.53 (1H, s,

K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
1441
]CH2a), 6.20 (1H, s, ]CH2b), 7.15–7.29 (5H, m, Ar); dC
(100.6 MHz, CDCl3): 12.6, 27.6, 28.1, 48.3, 80.8, 122.8,
126.3, 128.3 (2C), 128.4 (2C), 143.2, 145.8, 166.7; nmax
(thin film)/cmK1 2932s, 2875s, 1713s, 1628s, 1453s, 1392s,
1367s, 1254s, 1148s, 943m; m/z (EI) 246 (MC, 11%), 190
(100). [Found (HRMS, EI) MC 246.1632. C16H22O2
requires M 246.1620].
CHCH2), 3.67 (3H, s, OMe), 3.85 (1H, m, CH), 5.65 (1H, s,
]CH2a), 6.28 (1H, s, ]CH2b), 7.18–7.36 (5H, m, Ar); dC
(100.6 MHz, CDCl3) 14.2, 21.0, 36.9, 46.1, 52.0, 123.9,
126.5, 128.3, 128.4, 143.1, 144.2, 167.7; nmax (thin film)/
cmK1 2955s, 2871m, 1718s, 1627m, 1437m, 1244s, 1149s,
944m; m/z (EI) 218 (MC, 51%), 187 (55), 158 (19), 129
(34), 115 (100). [Found (HRMS, EI) MC 218.1308.
C14H18O2 requires M 218.1307].
4.7.12. Methyl-2-methylene-3-phenyl-butanoate 11a.
Yield 85%. (Found: C, 75.75; H, 7.37%. Calcd for
C12H14O2: C, 75.76; H, 7.42%); dH (400 MHz, CDCl3)
1.42 (3H, d, JZ7.2 Hz, CHMe), 3.67 (3H, s, OMe), 4.03
(1H, q, JZ7.2 Hz, CHMe), 5.61 (1H, s, ]CH2a), 6.28 (1H,
s, ]CH2b), 7.18–7.30 (5H, m, Ar); dC (100.6 MHz, CDCl3)
21.0, 40.7, 52.0, 124.0, 126.5, 127.6, 128.6, 144.5, 145.1,
167.6; nmax (thin film)/cmK1 2969m, 1721s, 1627m, 1437m,
1149s, 947m; m/z (EI) 190 (MC, 92%), 158 (42), 130 (100).
[Found (HRMS, EI) MC 190.0997. C12H14O2 requires M
190.0994].
4.7.15. Ethyl-4-(dimethylmethoxysilyl)-2-methylene-3-
phenyl-butanoate 11d. The reagent [Cu(MeCN)4]BF4
(8 mg, 0.015 mmol) was dissolved in dry THF (1.0 ml) at
K30 8C under an argon atmosphere and Zn(CH2SiMe2-
OMe)2 (2.0 ml of 0.25 M THF/pentane, 0.50 mmol) and
allyl bromide 3a (135 mg, 0.50 mmol, dissolved in dry
degassed THF (1.0 ml) were added at the same time via
syringe pump over 20 min. The reaction was allowed to
warm to K5 8C slowly over about 40 min, then quenched
with water. Standard workup with ether and purification by
flash chromatography (diethylether/light petroleum, 1:1)
gave the desired compound. Yield 93%, oil; dH (CDCl3,
400 MHz) K0.12, K0.05 (6H, 2!SiMe), 1.20 (3H, t, JZ
6.9 Hz, CH2Me), 1.24 (2H, m, CH2-Si), 3.31 (3H, s,
SiOMe), 4.10 (3H, m, CH2Me overlapped by CH), 5.70
(1H, s, ]CH2a), 6.25 (1H, ]CH2b), 7.14 - 7.28 (5H, m,
Ar); dC (CDCl3, 67.8 MHz) K2.3, K2.0, 14.0, 22.2, 41.4,
60.5, 123.0, 126.3, 128.1 (2C), 143.9, 146.2, 167.2; nmax
(thin film)/cmK1 2930s, 2874s, 1697s, 1628s, 1466m,
1430m, 1361m, 1254m, 1177m; m/z (EI) 261 ([MK
OMe]C, 18%) [Found (HRMS, EI): [MKOMe]C,
261.1318 C16H24O3Si requires [M -OMe] 261.1311].
4.7.13. Methyl-2-methylene-3-phenyl-heptanoate 11b.
Yield 98%; dH (400 MHz, CDCl3) 0.85 (3H, t, JZ7.2 Hz,
CH2Me), 1.11–132 (4H, m, CH2CH2Me), 1.69–1.88 (2H, m,
CHCH2), 3.67 (3H, s, OMe), 3.83 (1H, dd, JZ7.2, 6.9 Hz),
5.64 (1H, s, ]CH2a), 6.28 (1H, s, ]CH2b), 7.16–7.36 (5H,
m, Ar); dC (67.8 MHz, CDCl3) 14.2, 22.8, 30.1, 34.4, 46.3,
52.0, 124.0, 126.5, 128.3, 128.5, 143.1, 144.2, 167.7; nmax
(thin film)/cmK1 2954s, 2931s, 1723s, 1627m, 1437m,
1149s, 945m; m/z (EI) 232 (MC, 53%), 201 (62), 175 (31),
130 (47), 115 (100). [Found (HRMS, EI) MC 232.1471.
C15H20O2 requires M 232.1463].
The required organozinc was prepared from sodium
distilled MeOSiMe3 (2.76 ml, 20 mmol) in THF (7.5 ml)
and ButLi (12.1 ml of 1.65 M pentane solution, 20.0 mmol)
4.7.14. Methyl-2-methylene-3-phenyl-hexanoate 11c.
Yield 70%; dH (400 MHz, CDCl3) 0.89 (3H, t, JZ7.3 Hz,
CH2Me), 1.17–1.30 (2H, m, CH2Me), 1.69–1.85 (2H, m,
Table 4. Separation of enantiomers 5 and 10
Compound
Conditions
Retention times/min
5a (Ph)
GC: 2,6-Me-3-pe-g-CD; He carrier gas, 12 psia
11.0 (C)b
17.0 (K)
5b (1-Nap)
HPLC: Chiralcel OD; 99:1 hexane/isopropanol; flow rate of 0.5 ml minK1
HPLC: Chiralcel OD; 99:1 hexane/isopropanol; flow rate of 0.5 ml minK1
HPLC: Chiralcel OD; 99:1 hexane/isopropanol; flow rate of 0.5 ml minK1
GC: 2,6-Me-3-pe-d-CD; He carrier gas, 12 psi
13.5 (K)
36.1(C)
11.9 (C)
13.4 (K)
23.9 (C)
25.7 (K)
21.8
5c (4-MePh)
5e (4-NO2Ph)
10a (Ph)
22.8
9.5
17.4
15.7
20.4
14.1
24.8
11.1
23.0
17.0
23.0
51.8
52.9
22.6
24.7
31.9
10b (1-Nap)
10d (4-MeOPh)
10e (4-MePh)
10f (2-BrPh)
10h (4-FPh)
10i (4-CF3Ph)
10j (4-NO2Ph)
10k (Ph)
HPLC: Chiralcel OD-H; 90:10 hexane/isopropanol; flow rate of 0.5 ml minK1
HPLC: Chiralcel OD; 99.5:0.5 hexane/isopropanol; flow rate of 0.5 ml minK1
HPLC: Chiralcel OD; 99.8:0.2 hexane/isopropanol; flow rate of 0.5 ml minK1
HPLC: Chiralcel OD; 98:2 hexane/isopropanol; flow rate of 0.5 ml minK1
HPLC: Chiralcel OD; 99.9:0.1 hexane/isopropanol; flow rate of 0.5 ml minK1
GC: Cyclodextrin-B; He carrier gas, 12 psi
HPLC: Chiralcel OD; 99.5:0.5 hexane/isopropanol; flow rate of 0.5 ml minK1
GC: 2,6-Me-3-pe-g-CD; He carrier gas, 12 psi
33.6
a 2,6-Me-3-pe-d-CD is a 25 m octakis(2,6-di-O-methyl-3-0-pentyl)-g-cyclodextrin column.17
b Sign of optical rotation taken from preliminary studies.5

1442
K. Biswas et al. / Tetrahedron 61 (2005) 1433–1442
6. Xu, L.-H.; Ku¨ndig, E. P. Helv. Chim. Acta 1994, 77,
1480–1484.
lithiated at K78 8C followed by warming to ambient and
further reaction (2 h).10 A solution of fused ZnCl2 (1.36 g,
10.0 mmol) in THF (16 ml) was added slowly to the
LiCH2SiMe2OMe and the mixture was Schlenk filtered after
overnight stirring to afford a 0.25 M solution (Gilman
titration).
7. For reviews covering promotion of Baylis–Hillman procedures
see: (a) Basavaiah, D.; Rao, D.; Satyanarayana, T. Chem. Rev.
2003, 103, 811–891. (b) Basavaiah, D.; Rao, P. D.; Hyma,
R. S. Tetrahedron 1996, 52, 8001–8062. (c) Aggarwal, V. K.;
Emme, V. K.; Fulford, I. J. Org. Chem. 2003, 68, 692–700.
8. Buchholz, R.; Hoffmann, H. M. R. Helv. Chim. Acta 1991, 74,
1213–1220.
4.7.16. Ethyl 2-methylene-3-phenyl-4-trimethylsilyl-
butyrate 11e. Prepared in an identical manner to compound
8a. The required Zn(CH2TMS)2 was prepared by literature
routes.16 Yield 25%; dH (400 MHz, CDCl3) K0.15 (9H, s,
CH2SiMe3), 1.13–1.14 (2H, m, CH2SiMe3), 1.21 (3H, t, JZ
7.0 Hz, OCH2Me), 4.02 (1H, dd, JZ8.1, 7.8 Hz, CH), 4.06–
4.18 (2H, m, OCH2Me), 5.69 (1H, s, ]CH2a), 6.23 (1H, s,
]CH2b), 7.14–7.28 (5H, m, Ar); dC (67.8 MHz, CDCl3)
K1.24, 14.0, 22.8, 42.2, 60.5, 122.8, 126.2, 128.1 (2C),
144.1, 146.5, 167.0; nmax (thin film)/cmK1 2952m, 1718s,
1261m, 1248m, 1173m, 1150m; m/z (CI) 276 (MC, 29%),
263 (22), 262 (31), 261 (100). [Found (HRMS, CI): MC
276.1556. C16H24O2Si requires M 276.1546] (Table 4).
9. Feringa, B. L. Acc. Chem. Res. 2000, 33, 346–353.
10. Bates, T. F.; Dandekar, S. A.; Longlet, J. J.; Wood, K. A.;
Thomas, R. D. J. Organomet. Chem. 2000, 595, 87–92.
11. Most relevant review: (a) Drews, S. E.; Roos, G. H. P.
Tetrahedron 1988, 44, 4653–4670. For the specific synthesis
and spectroscopic data see: (b) Fort, Y.; Berthe, M. C.;
Caubere, P. Tetrahedron 1992, 48, 6371–6384 for 2a.
(c) Lawrence, N. J.; Crump, J. P.; McGown, A. T.; Hadfield,
J. A. Tetrahedron Lett. 2001, 42, 3939–3942 for 2c and 4c.
(d) Ciclosi, M.; Fava, C.; Galeazzi, R.; Orena, M.; Sepulveda-
Arques, J. Tetrahedron Lett. 2002, 43, 2199–2202 for 2d.
(e) Basavaiah, D.; Krishnamacharyulu, M.; Rao, J. Synth.
Commun. 2000, 30, 2061–2069. (f) Lee, K. Y.; Kim, J. M.;
Kim, J. N. Tetrahedron 2003, 59, 385–390 for 2g. (g) Amri,
Acknowledgements
´
´
¨
H.; Beltaıef, I.; Besbes, R.; Amri, H.; Villeras, M.; Villeras, J.
Synthesis 1998, 1765–1769 for 2h and precursor to 7.
(h) Coelho, F.; Almeida, W. P.; Veronese, D.; Mateus,
C. R.; Lopes, E. C. . . ; Rossi, R. C.; Silveria, G. P. C.;
Pavam, C. H. Tetrahedron 2002, 58, 7437–7448 for 8a, 8d,
8f–g, 8j. (i) Lawrence, R.; Perlmutter, P. Chem. Lett. 1992,
305–308 for 8b. (j) Nascimento, M. G.; Zanotto, S. P.;
Melegari, S. P.; Fernandes, L.; Sa, M. M. Tetrahedron:
Asymmetry 2003, 14, 3111–3116 for 8c. (k) Sammelson, R. E.;
Gurusinghe, C. D.; Kurth, J. M.; Olmstead, M. M.; Kurth, M. J.
J. Org. Chem. 2002, 67, 876–882 for 8e. (l) Yu, C.; Liu, B.;
Hu, L. J. Org. Chem. 2001, 66, 5413–5418. (m) Cai, J.; Zhou,
Z.; Zhao, G.; Tang, C. Org. Lett. 2002, 4, 4723–4726 for 8i.
(n) Hoffmann, H. M. R.; Gassner, A.; Eggert, U. Chem. Ber.
1991, 124, 2475–2480 for 8k.
The European Union is thanked for its support through
COST-D24 and the EPSRC for grant GR/S56054. We are
grateful to the Grundy Educational Trust and the University
of Nottingham for the support of a studentship (PJG). The
contribution of the EPSRC Mass Spectrometry Service is
also gratefully acknowledged.
References and notes
1. Recent overvies of Diels–Alder chemistry: (a) Hayashi, Y. In
Cycloaddition Reactions in Organic Synthesis; Kobayashi, S.,
Jorgensen, K. A., Eds.; Wiley-VCH: Germany, 2002; pp 5–55.
(b) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.;
Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41,
1668–1698. (c) Nicolaou, K. C.; Montagnon, T.; Snyder, S. A.
Chem. Commun. 2003, 551–564.
12. (a) Lambert, F.; Kirschleger, B.; Villieras, J. J. Organomet.
Chem. 1991, 406, 71–86 for 3a and 3d. (b) Du, Y.; Lu, X.;
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(c) Ameer, F.; Drewes, S. E.; Emslie, N. D.; Kaye, P. T.;
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2991–2998. (b) Ameer, F.; Drewes, S. E.; Hoole, R.; Kaye,
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