A novel method for generation of carbenoid from α-chloro sulfoxides: A new and versatile procedure for one-carbon homologation of carbonyl compounds to carbonyl compounds having an α-alkyl substituent

Article abstract of DOI:10.1016/S0040-4039(00)60819-5

Addition of the carbanion of 1-chloroalkyl p-tolyl sulfoxides to carbonyl compound gave the adducts, which were treated with a base followed by t-butyllithium to afford one-carbon homologated carbonyl compounds having an alkyl group at the α-position, via the β-oxido carbenoids, in moderate to good yields.

Full text of DOI:10.1016/S0040-4039(00)60819-5

+
Vol. 33. No. 49.
in Great Britain
A NOVEL METHOD FOR GENERATION OF CARBENOID FROM a-CHLORO
SULFOXIDES: NEW AND VERSATILE PROCEDURE FOR ONE-CARBON
A
HOMOLOGATION OF CARBONYL COMPOUNDS TO CARBONYL
COMPOUNDS HAVING AN a-ALKYL SUBSTITUENT
Tsuyoshi
Norifumi
Gengyo, and
Yamakawa*
Faculty of
Sciences,
University of
Shiijuku-ku, Tokyo
Japan
exchange reaction;
homologatioa of
compound; ring
Key
Abstract: Addition
which were treated with a base
having an group at the a -p osition , via
of 1
sulfoxides to carbonyl
gave the
by t-butyllithium to
one-carbon homologated carbonyl compounds
in moderate to good yields.
Homologation of carbonyl compounds from lower carbonyl compounds by carbon-carbon
coupling is one of the most useful and reliable methods for obtaining desired carbonyl
compounds.
One-carbon ring-expansion of cyclic ketones via an oxido carbenoid is one example
of the homologation. and a few methods have been reported.2
We recently reported some new methods for homologation of carbonyl compounds using
alkyl
sulfoxides as the homologating agents.3
sulfoxides in organic synthesis,
In continuation of our studies on the use of
haloalkyl
we report herein a new and versatile method for
one-carbon homologation of carbonyl compounds 1 to carbonyl compounds having an alkyl
group at the a-position 7 via carbenoid (Scheme 1).
In previous papers, we and others reported the desulfinylation reaction of sulfoxides with alkyl
metals and
via the ligand exchange of
Especially, we found that the

desulfinylation of a-halo a-sulfinyl ketones and a-halo
sulfoxides gave
As an extension of these reactions, we assumed that
the dcsulfinylation of a-halo sulfoxidcs having no good leaving group on the g-carbon from the
and
respectively, in high yields.
haloalkencs.7
group (such
3) gave
(such as 5); as
this reaction did take place.
p-tolyl sulfoxidcs (2, and
3f was
was slowly
Quite fast reaction took place and after 5
The procedure is reported
mono-ethylene
as a typical experiment (Scheme 2).
The
First, 5 equiv. of
synthesized from I-chloroethyl p-tolyl sulfoxide in 90% yield.
added to a solution of 3f in
at -60
(Method A).
the reaction was quenched to give
(4%) and a fair
of the alcohol g.
Obviously,
8
these ring-expanded products were produced via
was thought to be from
material 3 in the reaction mixture.
carbenoid (Scheme 1, 5). The
which was derived from the enolatc 6 and the starting
Next,
was
treated with 1.2 equiv. of lithium diisopropylamide (LDA) at -70
to give
This reaction gave a relatively
lithium alcoholate; then, 4 cquiv. of
was added (Method
clean reaction mixture, and 7f was obtained in 69% yield without any alcohol 8.
Some representative results for one-carbon expansion of cyclic ketones giving a-alkyl ketones
As shown in the Table, this method is applicable from small- to
In the case of
group (entry a and b). method A gave better results than method
of the gave different results in this reaction.
however, these results imply that the
are summarized in Table 1.
ring ketones giving one-carbon ring-expanded ketones in moderate to good yields.
the alcohol 3 having a long
Entry g shows that the
B.
The
reason for this difference has not yet been clarified;
reaction proceeds stereospecifically in its intermediate.
Table 2 shows the representative results for the treatment of the
sulfoxide and with (Method A). In the reaction of the
Generally, rearrangement of hydrogen is
of
9, both the
hydrogen and the alkyl group (R) may rearrange.
faster than the alkyl (or aryl) group in the rearrangement of alkyl
results shown in Table 2 again show some specificity especially when R =
can be explained that the reaction takes place via a carbcnoid 5.9
Further studies of these rearrangements and the mechanistic
reported in due course.
However, the
This specificity
of the reaction will be
which is gratefully acknowledged.
Science Foundation,
This study was supported by

Table 1. One-Carbon Ring Expansion of Cyclic Ketones
to Cyclic Ketones Having an a-Alkyl Substituent
Ketone
R
a
0
A
A
b
0
0
B
0
d
B
B
B
0
0
(L)
B
B
h
B
B
i
a) See text.
The yield from ‘the chloro alcohol 3. Isolated yield.
c) Two diastereomers of the
were separated and they were
( less polar
and more polar
(P) )
separately with

7546
Table 2. Synthesis of Ketones and Aldehydes from Aldehydes
0
Cl OH
1 0
RCHO
Ar
+
9
11
9
Product
Ar
Ph
R
10 11
1
2
3
4
5
89
89
71
82
76
Ph
21
6
80
a) the
carbon
two
of the
chlorine atom is controlled by the chiiity of
and in the though 9 has
of 2
the stereochemistry of
sulfur.
centers?
are only
References and Notes
1. For reviews: 0. William Lever, Jr., Tetrahedron, 32, 1943 (1976); S. F. Martin, Synthesis, 1 9 7 9 ,
633; J. C. Stowell. Chem. Rev., 84, 409 (1984).
2.
T. Hiyama and H. Nozaki, Syn. Org.
35. 979 (1977); G. R. Krow. Tetrahedron. 43, 1
(1987); W. D. Abraham, M. Bhupathy, and T. Cohen, Tetrahedron Lett., 28, 2203 (1987); M.
1991; H. D. Ward, D. S. Teager, and R.
“Ring Enlargement in Organic Chemistry” VCH. Weinheim,
K. Murray, Jr., Org. Chem., 57, 1926 (1992).
3. T.
Chemistry” S.
1 1 1 , 205 (1991); T.
Ed., 6, 218 MYU, Tokyo (1992); T.
and K. Yamakawa. “Reviews on Heteroatom
and K. Yamakawa. Synlett., 1 9 9 2 , 455.
27, 2379 (1986); N. Furukawa, T.
4.
T.
Y. Kaneko, and K. Yamakawa, Tetrahedron
Shibutani, K. Matsumura. H. Fujihara. and S. Oae, Tetrahedron Lett.. 27, 3899 (1986); T.
Y.
Jpn.. 59, 2463 (1986); N. Furukawa, T. Shibutani. and
H. Fujihara, Tetrahedron Left., 28, 2727 (1987); T. T. Oohara, Y. Ueda, and K. Yamakawa,
Tetrahedron Lett.. 29. 313 (1988); T. T. Oohara. and K. Yamakawa. Tetrahedron Lett.. 29,
2851 (1988); T. T. Oohara, and K. Yamakawa, Tetrahedron Lett., 29, 4093 (1988); T.
Oohara. Y. Ueda, and K. Yamakawa, Org. Chem. 54. 3130 (1989); T.
Kaneko. and K. Yamakawa,
T.
T. Sato, T. Oohara, and
K. Yamakawa,
741 (1990); S. Ogawa and N. Furukawa. Org.
Matsumura, and H. Fujihara, Org. Chem., 56, 6341 (1991); H. Uno, K. Sakamoto, F. Semba, and H.
Chem., 54, 3973 (1989); P. G.
and W. H. Okamura. Org. Chem.,
56. 5723 (1991); N. Furukawa. S. Ogawa. K.
Suzuki, Bull. Chem.
Jpn., 65. 218 (1992).
65, 210 (1992); H. Uno, K. Sakamoto, and H. Suzuki, Bull. Chem.
5. S. Oae, “Reviews on Heteroatom Chemistry” S. Oae, Ed.. MYU, Tokyo, 4, 195 (1991).
T.
T.
K. Onda, N.
N.
and K. Yamakawa, Tetrahedron Lett., 32, 5599 (1991).
6.
7.
8.
K. Onda, Y.
and K. Yamakawa. Tetrahedron
33, 1483 (1992).
L. Friedman and H. Shechter,
Am.
83. 3159 (1961); H.
and J. Keating.
Tetrahedron Lett., 1 9 6 1 , 5 2 3 ; J. H.
H. Taguchi, H.
and H. Shechter, Am.
89, 7112 (1967).
and H. Nozaki, Bull. Chem.
50, 1592 (1977).
9.
(Received in Japan 10 August 1992; accepted 14 September 1992)