A new and one-pot synthesis of α,β-unsaturated ketones by dehydrogenation of various ketones with n-tert-butyl phenylsulfinimidoyl chloride

Article abstract of DOI:10.1246/cl.2000.1250

α,β-Unsaturated ketones were synthesized by one-pot procedure from various ketones in good to excellent yields on treatment of their lithium enolates with N-tert-butyl phenylsulfinimidoyl chloride (1) under mild conditions.

Full text of DOI:10.1246/cl.2000.1250

1250
Chemistry Letters 2000
α β
A New and One-Pot Synthesis of , -Unsaturated Ketones by Dehydrogenation of
Various Ketones with N-tert-Butyl Phenylsulfinimidoyl Chloride
Teruaki Mukaiyama,* Jun-ichi Matsuo, and Hideo Kitagawa
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received August 3, 2000; CL-000746)
α,β-Unsaturated ketones were synthesized by one-pot pro-
cedure from various ketones in good to excellent yields on
treatment of their lithium enolates with N-tert-butyl phenyl-
sulfinimidoyl chloride (1) under mild conditions.
the metals, lithium, sodium, and potassium enolates were tried.
Their in situ formed enolates were treated with a small excess
of 1 at –78 °C in THF. When the lithium enolate was generated
from 2 by the use of LDA, 3 was obtained in 93% yield while
other metal enolates such as sodium or potassium enolates gave
poor results. The above dehydrogenation reaction proceeded
efficiently also via the lithium enolate formed from the corre-
sponding trimethylsilyl enol ether by a reaction with methyl-
lithium8 (Scheme 1). This result suggested that diisopropyl-
amine formed after deprotonation with LDA did not work as a
base in a subsequent elimination step. Then, an intramolecular
proton abstraction by a sulfinimidoyl group is proposed which
is to be discussed later.
Transformation of saturated carbonyl compounds to α,β-
unsaturated ones by dehydrogenation1 is important since α,β-
unsaturated carbonyl compounds are versatile intermediates in
synthetic organic chemistry, especially in the synthesis to intro-
duce a desired substituent at their β-positions. For this transfor-
mation, some methods are known to be useful although the pro-
cedures are consisted of more than two steps. For example, car-
bonyl compounds are converted to α-halo compounds first and
then they are dehydrohalogenated with appropriate bases at
rather high temperatures in traditional halogenation–dehydro-
halogenation method.2 Methods such as sulfenylation–sulfox-
ide elimination3 and selenylation–selenoxide elimination4 are
also frequently being employed because of their versatility. In
those procedures, α-sulfur or selen compounds are usually pre-
pared from metal enolates and then they are oxidized to cause
elimination at suitable temperatures. Additionally, α,β-unsatu-
rated ketones or esters are synthesized by using catalytic
amounts of palladium(II) acetate from silyl enol ethers or silyl
ketene acetals which are prepared in advance from their parent
carbonyl compounds.5 On the other hand, there are several
methods reported for direct dehydrogenation of carbonyl com-
pounds,6 although their reaction conditions are severe and the
kind of carbonyl compounds is limited. Therefore, a mild and
direct dehydrogenation reaction of carbonyl compounds is
strongly desired especially for the case of complex molecules
having labile functional groups. Of many efforts to realize the
transformation under mild conditions, the elimination of
selenoxides is most advantageous because it takes place at
lower temperatures. On the other hand, selenium based
reagents have some disadvantageous properties such as toxicity,
unpleasant odors, etc. In this communication, we would like to
report a new and one-pot dehydrogenation reaction of various
ketones forming the corresponding α,β-unsaturated carbonyl
compounds by using N-tert-butyl phenylsulfinimidoyl chloride
(1)7 under very mild reaction conditions.
It was recently reported from our laboratory that a new and
efficient oxidation reaction of primary and secondary alcohols
by using 1 and DBU was performed to form the corresponding
carbonyl compounds.7 Then, it was considered that saturated
carbonyl compounds would be directly dehydrogenated to the
corresponding α,β-unsaturated ones by treating their enolates
with 1.
In the first place, dehydrogenation of cyclohexanone (2)
forming cyclohexenone (3) was examined under the reaction
conditions as listed in Table 1. In order to examine the effect of
The direct one-pot dehydrogenation of various ketones was
performed by using LDA and 1 (Table 2). The dehydrogenation
of both acyclic and cyclic ketones proceeded efficiently at –78
°C except for the reaction of 1-(p-bromophenyl)-1-hexanone
(entry 4), which is probably due to the incomplete introduction
of the sulfinimidoyl group. Concerning stereoselective forma-
tion of (E)- or (Z)-α,β-unsaturated ketones, only (E)-isomers
were detected in this procedure. In some cases, addition of 15-
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
1251
crown-5 slightly improved the yields of enones but normally,
the reaction worked well without adding it. Other additives
such as HMPA or TMEDA did not improve yields of enones.
Interestingly, the less substituted position was selectively dehy-
drogenated and 6-methyl-2-cyclohexen-1-one was obtained
exclusively when 2-methylcyclohexanone was dehydrogenated
by this procedure (entry 9).
The present reaction proceeds much easier to afford the
dehydrogenated products at –78 °C than the respective reac-
tions of using sulfoxides which generally require elevated tem-
peratures around 60 to 120 °C and selenoxides which cause
elimination at temperatures between 0 and 25 °C. It was then
assumed that a lithium enolate would react with 1 to give a sim-
ilar C-sulfinimidoylated intermediate (4) as in the cases of sul-
foxides and selenoxides.9 Thus formed 4 is immediately con-
verted to α,β-unsaturated ketones even at –78 °C by the
intramolecular elimination via a five-membered transition state
(see Scheme 2).10
References and Notes
1
2
3
4
D. R. Buckle and I. L. Pinto, “Comprehensive Organic
Synthesis,” ed. by B. M. Trost, Pergamon Press, Oxford
(1991), Vol. 7, p. 119.
a) E. W. Warnhoff, D. G. Martin, and W. S. Johnson, Org.
Synth., IV, 162 (1963). b) P. L. Stotter and K. A. Hill, J.
Org. Chem., 38, 2576 (1973).
a) B. M. Trost and T. N. Salzmann, J. Am. Chem. Soc., 95,
6840 (1973). b) B. M. Trost, T. N. Salzmann, and K.
Hiroi, J. Am. Chem. Soc., 98, 4887 (1976).
a) H. J. Reich, I. L. Reich, and J. M. Renga, J. Am. Chem.
Soc., 95, 5813 (1973). b) K. B. Sharpless, R. F. Lauer, and
A. Y. Teranishi, J. Am. Chem. Soc., 95, 6137 (1973). c) H.
J. Reich, J. M. Renga, and I. L. Reich, J. Am. Chem. Soc.,
97, 5434 (1975). d) D. L. J. Clive, J. Chem. Soc., Chem.
Commun., 1973, 695.
5
6
a) Y. Ito, T. Hirao, and T. Saegusa, J. Org. Chem., 43,
1011 (1978). b) J. Tsuji, I. Minami, and I. Shimizu,
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G. Stork and P. F. Hudrlik, J. Am. Chem. Soc., 90, 4464
(1968).
It was reported that β-keto arylsulfoxides were formed by
the reaction of ketones with NaH and methyl arylsulfinates
in ethereal solvents. a) R. M. Coates and H. D. Pigott,
Synthesis, 1975, 319. b) H. J. Monteiro and J. P. De
Souza, Tetrahedron Lett., 1975, 921.
Typical experimental procedure is as follows (Table 1,
entry 1). Under an argon atmosphere, to a mixture of diiso-
propylamine (151 mg, 1.49 mmol) in THF (1.5 mL) was added
n-BuLi (1.68 N in hexanes, 0.79 mL) at –78 °C and the result-
ing mixture was stirred for 10 min. Then, a solution of 2 (119
mg, 1.21 mmol) in THF (1.5 mL) was added and the mixture
was stirred for 10 min at –78 °C. Finally, a solution of 1 (345
mg, 1.46 mmol) in THF (1.0 mL) was added at –78 °C and the
resulting pale yellow solution was stirred for 30 min at the same
temperature. The reaction was quenched by adding 1%
hydrochloric acid (5 mL) and the mixture was extracted with
dichloromethane (20 mL × 3). The yield of 3 was determined
by GC analysis using an internal standard (93%).
7
8
9
10 K. Tsujihara, K. Harada, N. Furukawa, and S. Oae,
Tetrahedron, 27, 6101 (1971).