Rhodium-Catalyzed Rearrangement of α-Diazo Thiol Esters to Thio-Substituted Ketenes. Application in the Synthesis of Cyclobutanones, Cyclobutenones, and β-Lactams

Abstract

Exposure of alpha-diazo thiol esters (1) to the action of catalytic rhodium(II) acetate leads to a remarkably facile "thia-Wolff rearrangement", producing thio-substituted ketenes which combine with a variety of ketenophiles to provide access to alpha-thiocyclobutanones, cyclobutenones, and beta-lactams. Reductive desulfurization of these cycloadducts takes place under mild conditions and in excellent yield, and this sequence thus represents a useful new alternative to the existing dichloroketene-based methodology for the synthesis of four-membered carbocycles and heterocycles.

100 Years of the Wolff Rearrangement

“…Fortunately, α-diazothiolacetates can be rearranged by means of rhodium(II) acetate (273 Ǟ 274, Schemes 38 and 42). [238] There are other exceptions to the rule that Rh II does not promote rearrangement, see Scheme 15, [69] Scheme 44, [262,264] and Scheme 45. [273,275] Wolff rearrangement was found to be a major pathway in the Rh II -catalyzed decomposition of diazoacetylcycloalkanes.…”

“…[238] The thio-substituted ketenes 274 thus generated add to a variety of alkenes to afford cyclobutanones 275 which were desulfurized either directly or after α-alkylation. Useful oxidative transformations of 275 were also reported.…”

“…[252] Arylthioketenes 274, made by rhodium(II)-catalyzed rearrangement of 273, were added to a variety of alkynes to give cyclobutenones 312. [238] Cycloaddition of 274 with methoxypropyne proceeded more efficiently than with less-activated alkynes. The alkynylamine 313 was found to accept arylketenes which were generated by photolysis of aroyldiazomethanes.…”

[2+2] Cycloaddition of ketenes with ynamides. A general method for the synthesis of 3-aminocyclobutenone derivatives

“…15 Finally, addition of dimethylketene to ynamide 6 also proceeded in excellent yield when the ketene was prepared in situ via the triethylamine-promoted dehydrohalogenation of isobutyryl chloride. Best results were obtained using CH 2 Cl 2 as solvent; in Et 2 O the desired cyclobutenone was obtained in only 11% yield.…”

Metal‐Catalyzed One‐Step Synthesis: Towards Direct Alternatives to Multistep Heterocycle and Amino Acid Derivative Formation

“…While there have been a growing number of syntheses of b-lactams, including those utilizing catalysis, [37] a useful feature of this methodology is its simplicity, which employs commercially available or readily prepared building blocks, as well as a commercial metal catalyst, and in one step brings these together to directly generate a b-lactam. In addition, this reaction provides direct access to the peptidelike amide-substituted b-lactam core, which is the functional structure of a range of antibiotics (e.g., penicillin, nocardicins, etc.).…”