Palladium-Catalyzed Intramolecular Asymmetric Hydroamination of Alkynes

摘要

Nitrogen-containing heterocycles are the main components of many biologically important compounds. Their synthesis via the intramolecular hydroamination of C-C multiple bonds, an atom economical process, is a subject of great interest in synthetic organic chemistry. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminoallenes, aminodienes, and aminoalkynes has been abundantly documented. However, little progress has been made in the exploration of the enantioselective version of this process. To our knowledge, the only successful examples toward this goal involve the hydroamination/cyclization of aminoalkenes and aminodienes using lanthanide complexes. Although good enantioselectivities (ee up to 69%) were achieved, the susceptibility of these complexes to moisture and oxygen constitute a serious drawback. Recently, the intermolecular enantioselective hydroamination of olefins catalyzed by late transition metals has been an area of intense investigation. As part of an ongoing program directed to the development of new methodologies for the transition metal-catalyzed addition of pronucleophiles to C-C multiple bonds in our laboratory, we previously reported an efficient hydroamination of alkynes using catalytic amounts of Pd(PPh3)4.5d It was anticipated that the intramolecular reaction in the presence of a chiral palladium complex would lead to the synthesis of optically active cyclic amines. We now wish to report the first example of palladium-catalyzed intramolecular asymmetric hydroamination of alkynes. In this process, five- and six-membered nitrogen heterocycles are synthesized in high yields with high levels of enantioselectivity (eq 1).