AN IMPROVED METHOD FOR REDUCTIVE ALKYLATION OF AMINES USING TITANIUM(IV) ISOPROPOXIDE AND SODIUM CYANOBOROHYDRIDE

The reductive alkylation of amines is one of the fundamental reactions of synthetic organic chemistry. The Borch reductive alkylation method4 works well provided the intermediate iminium adduct forms readily. For this reason the Borch procedure usually requires an excess of amine to favor the formation of the iminium intermediates. When both the ketone and amine starting materials are valuable or the iminium intermediate is difficult to form, the Borch method can be less than satisfactory. Titanium (IV) chloride has been used as a Lewis acid catalyst in cases when the formation of enamines has proven to be difficult;5 however, an excess of amine is still needed6 and the presence of acid-sensitive functionality is limited. Titanium(IV) isopropoxide has been used as a trans-esterification catalyst compatible with a variety of functional groups, such as lactam, acetonide, and tert-butyldimethylsilyl ether.7 We now report that titanium(IV) isopropoxide is a mild and effective Lewis acid catalyst for the reductive alkylation of amines with ketones and aldehydes in the presence of acid-sensitive functional groups. © 1990, American Chemical Society. All rights reserved.