A three step synthesis of (S)-2(diphenylmethyl)pyrrolidine 4 is described which allows its preparation on a large scale. The C2 symmetric diamines 5 and 6 have been prepared from 4 and are attractive as potential ligands for asymmetric transformations. Pyrrolidine 4 has been assessed as a chiral solvating agent for the NMR analysis of chiral compounds. It emerges as a good CSA for carboxylic acids and some secondary alcohols. (~) 1997, Elsevier Science Ltd. All rights reserved.
(S)-2(Diphenylmethyl)pyrrolidine 4 was first reported as its hydrochloride salt in the patent literature in 19691 and has more recently been prepared from L-proline by Enders et al. 2. Despite the recent widespread interest focused on homochiral monoamines 3 and C2 symmetric diamines 4, in various aspects of asymmetric catalysis (deprotonations 3b,5, organo-zinc 6, magnesium 7, tin 8 and palladium 9 reactions, dihydroxylations 1Β°, epoxide ring opening 11, polymerisations 12, conjugate additions 13, amine oxides 14 etc.) to our knowledge 4 has never been evaluated in any of these arenas. We attribute this simply to its lack of availabilityl5 rather than to any undesirable structural features. On the contrary, the sterically large diphenylmethyl group renders the base potentially attractive for many applications. In the course of our interest in generating suitable pyrrolidines for the preparation of chiral fluorinating agents 16 we report a straightforward three step process to 4 from L-proline as outlined in Scheme 1.
Treatment of (S)-L-proline 1 with ethyl chloroformate and potassium carbonate in methanol furnished 2 in excellent yield 17. Compound 2 could be isolated and purified by chromatography, but for larger scale synthesis the crude product was subjected directly to a Grignard reaction with