Ring Expansions of 4-(2,6-Dithiacyclohexyl)- and 4-Oxiranylcyclobuten-1-ones

Abstract

Reported here are a number of unusual rearrangements of 4-alkyl-4-hydroxycyclobutenones in which the alkyl group bears a heteroatom at its 2-position, e.g., compound 1 in Scheme 1. Thermolysis of such compounds was envisaged to result in ring-expanded mediumsized heterocyclic compounds. That is, stereospecific electrocyclic ring opening of 1 to the cis-vinylketene 2 followed by intramolecular attack of the heteroatom on the ketene moiety would give 3, and this leads directly to the macrocycle 4.l In fact, some of the transformations reported herein involve this sequence but proceed further to ring-contracted products since the initially formed macrocycles are not stable under the reaction conditions.The most unusual examples were observed for the thermolyses of selected 4-(2,6-dithiacycloalkyl~cyclobutenones. Specifically, when a p-xylene solution containing 0.2 mmol of 5 was refluxed for 3 h a good to excellent yield (70-90%) of the spirobutenolide 11 was realized (Scheme 2). In reference to the mechanistic postulate presented above, this rearrangement is envisaged to involve formation of the thiolactone 8 via the ketene 6 and the zwitterion 7. The thiolactone then undergoes further intramolecular transannular ring closure leading to the zwitterion 9 which leads to 10 upon heterolytic cleavage and ultimately to the observed product 11.In an analogous fashion, the spirobutenolides 13a (70%) and 13b (50%) were obtained from the respective cyclobutenones 12a and 12b. The structures of 13a,b as well as 11 are based upon their spectral properties. They show carbonyl stretching at, respectively, 1756, 1760, and 1771 cm-' in their IR spectra, and an AB pattern for the methylene flanked by the quaternary carbon and the sulfur is apparent in their lH NMR spectra. Confirmation of their structures was unambiguously established by a complete X-ray analysis for 13b.Another mode of rearrangement was observed when p-xylene solutions of the related cyclobutenones 14a and 14b were refluxed for a prolonged period of time. Here, rather than ring expansion to the spirobutenolides, the cyclopentenediones 17a and 1% were realized in good yields (Scheme 3). That 16 is an intermediate in these reactions was established by its isolation when the thermolysis time was decreased. For example, 17b was isolated in 77% yield when 14b was thermolyzed for 3 h and 16b was obtained in 48% yield when the reaction time was reduced to 2 h. Similarly, 14c gave a 79% isolated yield of 16c.The formation of 16 and 17 is envisaged to be analogous to the formation of 11 in that the 10-membered thiolactone 15 is proposed as a key intermediate. How-(1) For recent reviews of the ring expansions of cyclobutenones see: a) Moore, H. W.; Yerxa, B. R.

Natural and Synthetic Spirobutenolides and Spirobutyrolactones

“…Similarly, thermolysis of 2‐vinyl‐3‐methoxy‐4‐hydroxy‐4‐(2,6‐dithocycloalkyl)cyclobutenones in p ‐xylene at 138 °C rearrange to afford functionalized spirobutenolide in 90% yield (Scheme ) …”

Mapping the Chemical Reactivity of Polyquinanes Produced by 2-fold Addition of Vinyl Anions to Squarate Esters. A Bicyclic Case Study

“…To our knowledge, this oxygenation pattern has not been described elsewhere. A close analogy is found in the dimethyl ether 4 , produced by treatment of gloiosiphone A ( 3 ) with diazomethane in order to facilitate its isolation 7a7b.…”

“…A close analogy is found in the dimethyl ether 4 , produced by treatment of gloiosiphone A ( 3 ) with diazomethane in order to facilitate its isolation 7a7b. As a consequence, a working knowledge of the chemical potential of this motif gains importance on its own merit.…”