Malonate Anion Induced Favorskii Type Rearrangement. 21. Reaction of Acyclic α-Halo Ketones with Carbanions Leading to Cyclopropanols2

Article abstract of DOI:10.1021/jo00327a017

The reaction of 3-bromo-3-methyl-2-butanone (6a) with ethyl sodiomalonate (2) in refluxing THF gave 1--2,2-dimethylcyclopropanol (9a), the Favorskii-type intermediate, in 51percent yield.Similar reactions of acyclic halo ketones such as 2-bromo-2-methyl-3-pentanone (6b), 1-acetyl-1-bromocyclohexane (6c), and 1-acetyl-1-bromocyclopentane (6d) with 2 also gave the corresponding cyclopropanols 9b-d in 42-56percent yields.On the contrary, the α-halo ketones (6f-l) possessing a primary or secondary carbon atom at the α position afforded the S_N2 products10f-l.The behavior of 3-chloro-3-methyl-2-butanone (6e) was quite different from that of its bromo homologue 6a, giving a mixture (16:45:39) of 9a, 1,1-bis-2,2-dimethylcyclopropane (14), and 1--2,2-dimethyl-1-<(ethoxycarbonyl)methyl>cyclopropane (15) in 75percent total yield.Hydrolysis of 9a with 0.2 N NaOH at room temperature gave the acid ester 18, which afforded a mixture of 3-carboxy-4,5,5-trimethyl-2(5H)-furanone (22a, 27percent yield) and its ethyl ester (22b, 39percent yield) on heating.When the hydrolysis was carried out in 2 N NaOH at 10 deg C, 9a gave 1-(dicarboxymethyl)-2,2-dimethylcyclopropanol (23, 60percent yield) together with 22a (27percent yield).Similar hydrolysis of 9a at 30 deg C afforded 4,4-dimethyl-3-oxopentanoic acid (24, 38percent yield) and 3,3-dimethyl-2-butanone (25, 18percent yield).The bromination of 9a with Br2 caused the ring opening to give ethyl 5-bromo-4,4-dimethyl-2-(ethoxycarbonyl)-3-oxopentanoate (30) in 76percent yield.The ester 30 was cyclized to the oxetane 31 in 77percent yield.