title: Highly diastereoselective Friedel-Crafts alkylation reactions via chiral alpha-functionalized benzylic carbocations.
abstract: A series of chiral 1-aryl-1-alkanols, which carry different functional groups (FGs) at the 2-position, were subjected to an acid (HBF4)-catalyzed reaction with various arenes. An S(N)1 substitution reaction was observed, in the course of which 1,1-diarylalkanes were formed. In most cases (40 out of 51 reactions), yields were very good to excellent (75-99 %). The diastereoselectivity of the reaction was heavily dependent on the FG at the 2-position. If the FG was methoxycarbonyl, nitro, hydroxy, cyano, trimethylsilylethynyl, or chloro, the corresponding anti products were favored and with a decreasing preference in this order. The methoxycarbonyl-substituted substrates gave the anti products with diastereomer ratios (d.r.) that exceeded 92:8 (16 examples). Nitro- and hydroxy-substituted products were obtained in most instances with d.r. > or = 90:10, whereas cyano-, trimethylsilylalkynyl-, or chloro-substituted substrates delivered only with certain arenes products with high selectivity (d.r. > or = 90:10). The sterically more demanding FGs ethylsulfonyl, ethoxysulfonyl, and diethoxyphosphonyl induced diastereofacial selectivity in favor of the corresponding syn products, with diethoxyphosphonyl being the most effective. The substrate with FG = PO(OEt)2 delivered, with eight different arenes, the corresponding syn substitution products (d.r. = 80:20 - >95:5). The relative configuration of the products was elucidated by spectroscopic and synthetic methods. On selected examples, the reactions were shown to proceed stereoconvergently, under kinetic control, and without racemization. Depending on the functional group, the onset of the reactions between 2-methylthiophene and some representative alcohols was found to occur at a temperature Theta between -78 and -40 degrees C. There was no correlation between the selectivity and theta. A model is suggested to explain the facial diastereoselectivity based on a preferred conformation of the putative intermediate carbocation.
authors.affiliation: Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stadler
authors.forename: Thorsten
authors.initials: T
authors.lastname: Bach