Garst et al.
yield (%)
TABLE 1. Summary of Diene Synthesis and Diels-Alder Reactions
ketone/aldehyde
diene
yield (%)/method
dienophile
product
2-methylcyclohexanone
3-methyl-2-butanone
2-butanone
isobutyraldehyde
2-methylcycloheptanone
1a
3
5
11
1b
A
methyl acrylate
methyl acrylate
2a
4
49
36
ca. 40/A
26/A
7.5/B
42/A
maleic anhydride
2b
30
SCHEME 1
We have made a preliminary study of the scope of this
reaction by using various ketones and aldehydes with three
sulfones.
Results and Discussion
Reaction of Ketones with Dimethyl Sulfone. A study of
reaction conditions was carried out for the synthesis of diene
1a. First, a variety of solvents were explored. N-methylpyrroli-
done, DMSO, DMAC, DMF, glyme, and diglyme gave similar
results. However, a poor yield (<10%) was obtained in refluxing
THF: this is most likely due to the lower reaction temperature.
To test this hypothesis, two identical reactions in DMAC were
run at 100 and 90 °C giving the diene 1a in yields of 60% and
40%, respectively. DMAC was chosen as the solvent simply
because it is easily removed by aqueous extraction.
Treatment of 2-butanone under identical conditions gave
isoprene (5) in 26% yield after distillation (eq 2).
The scope of this reaction was explored by studying variations
in ring size and substituents for cyclic ketones. The reaction
was further examined with several aromatic and acyclic ketones.
The reaction of cyclohexanone and dimethyl sulfone with
potassium t-butoxide in DMAC was expected to give 3-meth-
ylenecyclohexene. The reaction gave a mixture of four com-
pounds by GC analysis. Analysis of the mixture by UV, NMR,
and GC/MS showed all four of the compounds to be isomers
of the molecular formula C7H10.3 It appears that the expected
product is formed and suffers double-bond isomerization under
the strongly basic reaction conditions. Unfortunately, no reaction
occurred when potassium carbonate was used as the base.
However, the diene products obtained from dimethyl sulfone
and cyclohexanone are markedly different from the product
obtained with dimethyl sulfoxide and cyclohexanone which was
identified as 2-methylenecyclohexyl methanesulfenate.1b This
result shows that the products obtained with dimethyl sulfoxide
are not derived from contaminating dimethyl sulfone. The
reaction of 2,6-dimethylcyclohexanone with dimethyl sulfone
and potassium t-butoxide in DMAC gave a mixture of seven
unidentified compounds. Similarly, the reaction of 2-methyl-
cyclopentanone gave no useful products. However, under the
same conditions, 2-methylcycloheptanone gave 1,2-dimethyl-
enecycloheptane1e,g (1b), isolated as the Diels-Alder adduct
of maleic anhydride (5-oxatricyclo[7.5.0.0 3,7 ]tetradec-1(9)-
ene-4,6-dione, 2b) in 30% overall yield (Table 1). These
conditions, when applied to 3-methyl-2-butanone, gave 2,3-
dimethyl-1,3-butadiene (3, Scheme 1). To get an estimate of
the yield, a portion of the crude product was treated with methyl
acrylate to give 3,4-dimethylcyclohex-3-ene carboxylate (4)4 in
36% yield. This reaction is thus quite convenient for producing
a solution of 2,3-dimethyl-1,3-butadiene (3) to use in Diels-
Alder condensations if an alternative to the pinacol procedure
is needed.5
When a solution of R-tetralone and dimethyl sulfone in
DMAC was treated with potassium t-butoxide, a 9:1 mixture
of 1-methylnaphthalene (6) and naphthalene (7) was obtained
in 85% combined yield (eq 3). The origin of the naphthalene
was explored in connection with the study of the condensation
of R-tetralone with diethyl sulfone, a reaction which gives
naphthalene (7) exclusively (vide infra).
However, when â-tetralone was used instead of R-tetralone,
no reaction took place. It appears that â-tetralone is converted
to the enolate under the reaction conditions, and there is not a
high enough concentration of dimethyl sulfone anions and free
â-tetralone to give a reaction.
Surprisingly, when propiophenone was treated with dimethyl
sulfone and potassium t-butoxide in DMAC, 2′-methyl-p-
terphenyl (8)6 was formed in 61% yield (eq 4). That 8 is indeed
the product was confirmed by X-ray crystallography. Formation
of 8 requires two molecules of propiophenone and one carbon
from dimethyl sulfone as well as a two-electron oxidation.
(3) Spangler, C. W.; Hartford, T. W. J. Chem. Soc., Perkin Trans. I 1976,
16, 1792.
(4) Inukai, T.; Kasai, M. J. Org. Chem. 1965, 30, 3567.
(5) Allen, C. F. H.; Bell, A. Org. Synth. Coll. Vol III, 312.
(6) Sidorova, N. G.; Nikonovich, S. D. Zh. Obshch. Khim. 1960, 30,
921; Chem. Abstr. 1960, 55, 6451f.
554 J. Org. Chem., Vol. 71, No. 2, 2006