Spirocyclic cyclobutanone

Spirocyclic 2-alkylidenecyclobutanones can be prepared from vinylidenecycloalkane additions with dimethylketene (see Tabic 1). Alternatively, cycloaddition of cycloalkylidenemethanone to allenes permits synthesis of spirocyclic cyclobutanones. This latter route is more attractive because of the greater availability of simple allcnes as compared with the alkylidenecycloalka-nes. The in situ generation of cyclohexylidenemethanone in the presence of excess tetramethyl-allcnc produced the spirocyclic ketone 9 in reasonable yield.5... 

Various spirocyclic cyclobutanones 3 were obtained by this method in somewhat better yield. 

Ylide (1) adds selectively to the least hindered side of a spirocyclic cyclobutanone to afiord epoxide (10) as the sole product in 65% yield (Scheme 3). Where only steric factors are likely to be important, complementary stereochemical results are often possible by methylene addition to a carbonyl group or alternatively, by carrying out an epoxidation reaction on the derived alkene. In each case, the reagent approaches a double bond from the same stereochemical face. This point is nicely illustrated by the synthesis of epoxide (11). 

Fused and spirocyclic ring systems are present in many natural products and drug molecules. An approach to these systems was developed by [2 + 2] cycloaddition between 2,3-dihydrofurans and ketenes generated from ali-cyclic acid chlorides (14TL7240).This approach allows the construction of complex-fused, spirocyclic cyclobutanone frameworks in simple operations, even on a large scale (20 mol). 

Successive cleavage of C-C bonds occurred with spirocyclic cyclobutanone 75 (Scheme 3.43) [52]. First, rhodium(1) underwent insertion into the cyclobutanone C-C bond to generate a five-membered cyclic acylrhodium intermediate. 

Cyclobutanones.—The synthesis of spirocyclic carbon compounds by various rearrangement methods has recently been reviewed,and this Report covers the recent literature on the synthesis of cyclobutanones via oxaspiropentanes. 

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