Nitrones natural product formation

Holmes et al. used another interesting pericyclic domino reaction in the synthesis of (-)-histrionico-toxine 116 (scheme 23).1631 In a not fully understood sequence 113 at 190 °C generates the cydoadduct 115 in 80% yidd with loss of styrene. It can be assumed that the process consists of a retro-13-dipolar and a 13-dipolar cydoaddition with the intermediary formation of the nitrone 114. Overall, three new stereogenic centers, necessary for the natural product, have been efficiently created. An... 

Perhydropyrrolo[l,2-fc]isoxazoles result from 1,3-dipolar cycloaddition of cyclic nitrones with alkenes. The high regio- and stereoselectivity of this cycloaddition has been used to control the stereochemistry in the synthesis of natural products. As one example, pyrroline N-oxide (70) and 3,4-dimethoxystyrene gave a diastereomeric mixture of pyrroloisoxazoles (71) and (72), in nearly quantitative yield with preferential formation of (71). 

A variety of elegant experiments serve to highlight the nature of the subtle factors which control dia-stereofaciad selectivity in dipolar cycloaddition reactions between optically active nitrones, of the type illustrated, and electron-rich dipolarophiles. In general, facial selectivity is found to be influenced by the nature of the substituent on nitrogen and by the presence of a second stereogenic center. As illustrated, selectivities ranging from zero to complete have been observed (Scheme 22). Notice also the preference for formation of the endo transition state derived product. 

Intramolecular cycloaddition of nitrones 996, derived from aldehydes 995, to the N-tethered olefin leads to the formation of two regioisomers, 997 and 998. The product distribution depends on the nature of the substituent (R) (Scheme 239) <2004TA3181>. 

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