Preparation and Cyclization of Some N-(2,2-Dimethylpropargyl) Homo- and Heteroaromatic Amines and the Synthesis of Some Pyrido[2,3-d]pyrimidines

Abstract

The Cu(i) catalyzed cyclization of o-substituted N-(2,2-dimethylpropargyl)anilines yields 8-substituted 2,2-dimethyl-1,2-dihydroquinolines, while m-substituted analogues provide a mixture of 5- and 7-substituted dihydroquinoline systems. This reaction can be extended to 2-amino-N-(2,2-dimethylpropargyl)anthracene, yielding a dihydronaphtho[2,3-f]quinoline product, and to aminoquinoline derivatives, which yield substituted phenanthroline products. Pyridine analogues did not cyclize, apparently because of complexation with the copper reagent.

An alternative synthetic approach to these cyclized products, when complexation may be a problem, is illustrated by the following example. 2-Chloro-4-N-(2,2-dimethylpropargyl)pyrimidine was reduced using a Lindlar catalyst to the corresponding alkene which did not undergo an amino-Claisen rearrangement. However, the 5-bromopyrimidine alkene analogue underwent addition with phenylselanyl bromide to give a product that cyclized, using butyllithium, to a pyrido[2,3-d]pyrimidine selenium-containing product from which the selenium moiety could be removed to yield either a dihydro- or a tetrahydro-pyrido[2,3-d]pyrimidine system. A Heck reaction on the 5-bromopyrimidine alkene gave a 5-methylene-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine.