Reports: B448578-B4: Fundamental Studies on the Nature of Diradical Intermediates in [1,3] Carbon Migrations of Bicyclic and Tricyclic Vinylcyclobutanes

Phyllis A. Leber , Franklin and Marshall College

Bicyclo[3.2.0]hept-2-ene undergoes thermal isomerization to norbornene. 1  This conversion has received considerable attention as an exemplar of a [1,3] sigmatropic vinylcyclobutane-to-cyclohexene rearrangement.2,3  Competitive isomerization and fragmentation processes at temperatures in excess of 300 ºC convert bicyclo[3.2.0]hept-2-ene either to its norbornene or to fragments cyclopentadiene and ethylene, which can form directly or indirectly via Diels-Alder cycloreversion of norbornene.

The cyclopropyl carbinyl- homoallylic radical rearrangement, also known as a “radical clock” reaction, has been used to monitor kinetics and to elucidate mechanisms, and to detect free radicals, in biochemical4 and chemical5 reactions.  We have thus conceived of spiro[bicyclo[3.2.0]hept-5-ene-2,1¢-cyclopropane] as a potential 1,4-diradical probe due to the inclusion of a cyclopropyl substituent attached to C6 via a spiro linkage. 

The novel synthetic strategy we employed for the preparation of both spiro[bicyclo[3.2.0]hept-5-ene-2,1¢-cyclopropane] and its isomeric spironorbornene [1,3] rearrangement product was to attempt a selective kinetic cyclopropanation of the exocyclic olefins in diolefins 6-methylenebicyclo[3.2.0]hept-2-ene and 5-methylenebicyclo[2.2.1]hept-2-ene. To avoid the use of diazomethane as a means of delivering methylene, we envisioned the Furukawa modification6 of the Simmons-Smith Reaction as a viable methodology for sequential addition of reagents, including the homogenous catalyst diethylzinc, at reduced temperatures.

Thermal reactions of spiro[bicyclo[3.2.0]hept-5-ene-2,1¢-cyclopropane] were monitored at 275 ºC. An experimental concentration versus time kinetic plot for disappearance of starting material, when subjected to a best curve fit using the Solver function in Microsoft ExcelÒ, gave a first-order rate constant for decomposition (kd) at 275 ºC of 4.75 ´ 10-5 s-1.   The starting material is ten times more reactive than bicyclo[3.2.0]hept-2-ene based on the rate constant measured directly at 275 ºC.5 This constitutes direct experimental evidence for an electronic rate effect afforded by the cyclopropyl substituent on C6, an observation best explained by electronic stabilization of the 1º radical center at C7. The presence of minor amounts of other rearrangement products in the thermal reaction mixture constitutes direct evidence of a CPC rearrangement and thus strong confirmation for a 1,4-diradical intermediate. Of the series of four minor rearrangement products, two have been characterized definitively as CPC rearrangement products by independent synthesis.  The identification of the other two rearrangement products is pending.This study strongly supports more inferential experimental evidence that the vinylcyclobutane-to-cyclohexene rearrangement is a stepwise diradical-mediated process.3

Impact of the Research

The present study is an attempt to utilize a potential CPC rearrangement as a probe of a single diradical intermediate generated under thermal conditions.  The results provide conclusive evidence for a diradical-mediated process in [1,3] carbon shifts. Publication of the results of several ongoing studies incorporating CPC probes will provide greater visibility to our undergraduate research program because these thermal data offer the first definitive evidence of a singlet 1,4-diradical.

A total of eight undergraduate students will have worked on variants of the CPC rearrangement project by the expiration of this PRF grant in August 2012.  Of these students three are currently attending graduate school.  Of those students who have not yet graduated, four intend to apply to medical school or dental school; the fifth aspires to a Ph.D. in chemistry.



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