Diastereoselective Domino Reactions of Chiral 2-Substituted 1-(2′,2′,3′,3′-Tetramethylcyclopropyl)-alkan-1-ols under Friedel−Crafts Conditions

Abstract

The 2-substituted 1-(2',2',3',3'-tetramethylcyclopropyl)-alkan-1-ols 3-7 were prepared by carbonyl addition of tetramethylcyclopropyl lithium to the respective aldehydes or by addition of the respective substituted carbanions to tetramethylcyclopropyl carbaldehyde 16. Under Brønsted acidic conditions (HBF(4).OEt(2)), the alcohols served as substrates in Friedel-Crafts alkylation reactions with 2-methylthiophene (8) and N-tosylpyrrole (9). The alkanols 3-6 carrying the groups (t)Bu, Ph, CN, PO(OEt)(2) in 2-position delivered the rearranged substitution products 17-20 in very good chemical yields (9 examples, 81-97%). The products were formed presumably via ring-opening of the tetramethylcyclopropyl-substituted cation, which rearrange by a Wagner-Meerwein shift to allylic cations I. The latter cations are eventually attacked by the arene nucleophile. The diastereoselectivity of this process is good (anti-preference for Ph, CN, PO(OEt)(2)) to excellent (syn-preference for (t)Bu). The esters 7, carrying a methoxycarbonyl group in 2-position, yielded under the same reaction conditions products 25 and 26, which are formed by an intermolecular Friedel-Crafts reaction followed by a subsequent intramolecular Friedel-Crafts alkylation (3 examples, 80-93%).