Reactions of epoxy and aziridinyl enolsilanes with arenes

Abstract

Epoxy/aziridinyl enolsilanes that undergo (4+3) cycloaddition with traditional dienes, such as furan and cyclopentadiene, have now been demonstrated to undergo diastereoelective Friedel–Crafts alkylation, and (4+3) cycloaddition with arenes. Benzene substrates 2.10–2.16, 2.19, 2.24, 2.25–2.27 underwent Friedel–Crafts cyclizations with exclusive trans-diastereoselectivities in moderate to good yields, in which the best yields occur with electron-rich arenes. The alkylation products conserve the optical purity of the epoxide or aziridine. This method may be applied to the synthesis of optically enriched β-hydroxyl-α-arylketones and β-amino-α-arylketones.

By blocking the ortho-position and altering the tether length, epoxy/aziridinyl enolsilane tethered arene substrates have been induced to undergo dearomatizing (4+3) cycloadditions. This cycloaddition occurred for substrates 2.15, 2.18, 3.39–3.47, 3.52–3.56, and in some cases, with excellent yield and diastereoselectivity. The diastereoselectivity has been rationalized in terms of steric effects. This reaction transforms arenes, sourced from the petrochemical industry, to highly functionalized polycyclic scaffolds, and is among the most synthetically useful (4+3) cycloadditions of arenes reported to date.

The reaction scope of epoxy enolsilanes has been extended to some open dienes. Mechanistic studies with open diene substrates 4.58–4.63 revealed that intramolecular (4+3) cycloadditions with epoxy/aziridinyl enolsilanes probably proceed by a stepwise, formal cycloaddition mechanism. These open diene substrates reacted to form a variety of products, ranging from (4+3) cycloadducts, (3+2) cycloadducts, to alkylation products, and each can be rationalized to have been derived from a common carbocation intermediate from stepwise bond formation. This conclusion also finds support from computational studies. It was also demonstrated that conformationally flexible dienes are disfavoured for (4+3) cycloaddition, and that the diene being locked in an s-cis conformation is a prerequisite, accounting for the successful (4+3) cycloadditions of traditional dienes such as furan, cyclopentadiene, and bis-methylene cyclohexane . In their own right, open diene substrates undergo intramolecular (3+2) cycloadditions favourably to generate stereochemically defined hydrindane systems.