Chiral furan-2-yl-substituted reagents based on (+)-α-methylbenzylamine

Abstract

The Schiff base obtained by condensation of furfural with (+)-α-methylbenzylamine was reduced with sodium tetrahydridoborate, and the resulting amine was alkylated with methyl iodide to obtain the corresponding chiral tertiary amine. Oxidation of the reduction product with m-chloroperoxybenzoic acid gave (1R)-N-(furan-2-ylmethylidene)-1-phenylethanamine N-oxide.Continuously increasing needs of medicinal chemistry in enantiomerically pure compounds stimulate development of new chiral reagents for asymmetric synthesis. For this purpose, relatively inexpensive and accessible (+)-and (-)-α-methylbenzylamines are widely used as source of chirality [1,2]. In the present communication we report on the synthesis of homochiral tertiary amine I and nitrone II from (+)-α-methylbenzylamine through secondary amine III [3]. chiral tertiary amines NR 3 [15], etc. The use of nitrones may be illustrated by two most important reactions, 1,3-dipolar cycloaddition to unsaturated compounds and addition of nucleophiles [16,17]. Examples of using sterically hindered nitrones as spin trap for hydroxy radicals were given in [18].By condensation of furfural with (+)-α-methylbenzylamine with simultaneous removal of liberated water we obtained Schiff base IV which was reduced (without additional purification) with sodium tetrahydridoborate (Scheme 1). After chromatographic purification on silica gel, the yield of amine III was more than 90%. An analytical sample of Schiff base IV can be obtained by purification of the crude product by column chromatography on silica gel. Me II O O I, R = Me; III, R = H. Chiral secondary amines have found diverse applications in asymmetric synthesis. In particular, they were used to develop methods for desymmetrization of cyclic meso-anhydrides [4], imides [5], and epoxides [6], asymmetric deprotonation of prochiral cyclic ketones [7], catalytic conjugate addition [8], stereoselective aldol reactions [9], etc. [10]. Chiral tertiary amines were also used: P,N-containing rhodium catalysts for asymmetric hydrogenation of olefins were described [11, 12]; condensations of organometallic compounds with aldehydes, catalyzed by chiral tertiary amines were reported [13]; Sharpless osmium complexes based on quinine and cinchonidine catalyzed asymmetric dihydroxylation of olefins [14]; BaylisHillman reaction was performed in the presence of Scheme 1. O CHO + H 2 N Ph Me PhMe, reflux N Ph Me O IV NaBH 4 MeOH, 0°C IIITertiary amine I was synthesized by metalation of compound III with butyllithium and subsequent alkylation with methyl iodide. The oxidation of III with m-chloroperoxybenzoic acid smoothly afforded nitrone II. The latter can also be prepared directly from Schiff base IV by oxidation with the same reagent, but