PRACTICAL SYNTHETIC PROCEDURES 2449
Highly Diastereoselective Michael Additions onto Dienyl Bis-Sulfoxides
Diastereoselective Michael Additions Franck Brebion, Jean Philippe Goddard, Louis Fensterbank,* Max Malacria*
Université Pierre et Marie Curie, UMR CNRS 7611, Institut de chimie moleculaire, FR 2769,
case 229, 4 place Jussieu, 75252 Paris cedex 05, France
E-mail: louis.fensterbank@upmc.fr; E-mail: max.malacria@upmc.fr
Received 14 March 2005; revised 27 May 2005
Dedicated to Professor Iwao Ojima for his outstanding achievement in asymmetric synthesis
and on the occasion of his 60th birthday.
SYNTHESIS 2005, No. 14, pp 2449–2452xx.xx.2005
Advanced online publication: 20.07.2005
DOI: 10.1055/s-2005-872089; Art ID: Z05905SS
© Georg Thieme Verlag Stuttgart · New York
Abstract: An optimized procedure for the preparation of (S
S
,S
S
)-bis(p-tolylsulfinyl)methane (4) is reported. Condensation of the lithium
salt of 4 onto cinnamaldehyde furnished bis-sulfoxide dienyl derivative 5, a remarkable 1,4-Michael acceptor that can lead in a highly dia-
stereoselective manner to vinylcyclopropyl adducts. In a chelating mode of reactivity using a methylcopper reagent, a complete reversal of
stereoselectivity is observed giving an enantiopure b,g-unsaturated methyl ester intermediate that is used in the synthesis of cryptophycin.
Key words: bis-sulfoxide, Michael addition, vinylcyclopropane, cryptophycin
Introduction
Alkylidene bis-p-tolylsulfoxides
1
of type 1
2
(Scheme 1)
are highly versatile partners for asymmetric synthesis that
we have used in the context of radical chemistry
3
and po-
lar Michael additions.
4
In comparison, dienyl derivatives
like 5 which have been first reported by Solladié et al.
have not been exploited.
5
While cycloaddition reactions
are likely an interesting field of applications for these sub-
strates,
6
we have initially examined Michael additions to
these compounds because of the interesting array of func-
tionalities of the putative adducts. Both 1,4- or 1,6-addi-
tions should be possible leaving an untouched double
bond, and a masked carbonyl group (Scheme 2).
Scope and Limitations
To probe this point, we focused on dienyl bis-sulfoxide 5
that was easily obtained from the condensation of cinna-
maldehyde on the lithium anion of (S
S
,S
S
)-bis(p-tolylsul-
foxide)methane (4),
2,5
itself originating from the addition
of the lithium anion of (R
S
)-3
7
on (S
S
)-2. We herein report
an optimized procedure for the isolation of 4 compared to
Kunieda’s original procedure.
8
This allows a net yield im-
Scheme 1
S
p-Tol
O
Me
S
p-Tol
O
S
O
p-Tol
1) LDA, THF
0 °C to r.t.
2) 2, 0 °C to r.t.
3) Precipitation
(R
s
)-3
(S
s
)-2
p-Tol
S
O
OMent
S
p-Tol
O
S
O
p-Tol
R
1
source of enantiopure
monooxidized sulfur:
(S
s
,S
s
)-4, 88%
S
p-Tol
O
S
O
p-Tol
Ph
1) BuLi, THF,
–40 °C
2) Cinnamaldehyde
–78 °C to –15 °C
(S
s
,S
s
)-5, 76%
Scheme 2
S
p-Tol
O
S
O
p-Tol
R
1. Nu
2. H
S
p-Tol
O
S
O
p-Tol
R
Nu
and/or
S
p-Tol
O
S
O
p-Tol
R Nu
1,4
1,6