Synthesis and Rh-catalyzed reductive cyclization of 1,6-enynes and 1,6-diynes containing alkynylboronate termini

Abstract

Ir-catalyzed dehydrogenative borylation of terminal alkynes (DHBTA) has been used to borylate the C(sp)-H bond in a series of 1,6-enynes and 1,6-diynes. Ir catalysts based on the diarylamido/bis(phosphine) PNP ligands proved to be capable of performing DHBTA on these substrates. The alkynylboronate products were then explored as substrates in reductive cyclization reactions designed to yield five-membered carbocycles and heterocycles with preservation of the carbon-boron bond. The reductive cyclization of enynes with H2 was carried out using cationic Rh catalysts (after the work of Krische et al.) supported by bidentate phosphine ligands, of which BINAP proved to be the generally best performing. Reductive cyclization of borylated enynes typically resulted in mixtures of isomeric products. Attempts to optimize the reductive cyclization of borylated 1,6-enynes to yield a single product were not successful; in addition, the distribution of products in these reactions was poorly reproducible. On the other hand, reductive cyclization of 1,6-diynes with the same Rh catalysts was better behaved, allowing for selectivity and reproducibility. In particular, alkynylboronate derivatives of bis(propargyl)amine underwent smooth reductive cyclization to 3,4-substituted pyrroles. The influence of substituents and conditions on the product distribution was explored and representative reactions utilizing new borylated heterocycles in Suzuki coupling reactions were carried out.