1353010-01-1Relevant academic research and scientific papers
Enantioselective synthesis of cis-1,2-disubstituted cyclopentanes and cyclohexanes by Suzuki-Miyaura cross-coupling and iridium-catalyzed asymmetric hydrogenation
Schumacher, Andreas,Schrems, Marcus G.,Pfaltz, Andreas
, p. 13502 - 13509 (2012/01/05)
A series of 1,2-disubstituted cyclohexene derivatives was prepared through Suzuki-Miyaura cross-coupling of 2-bromo-1-cyclohexenecarbaldehyde or 2-carbomethoxy-1-cyclohexen-1-yl triflate with arylboronates. These tetra-substituted cyclic alkenes were subjected to Ir-catalyzed asymmetric hydrogenation. In this way cis-1-methoxymethyl-2-arylcyclohexanes were obtained in high yield with excellent enantio- and diastereoselectivities (up to >99%ee, >99%cis) by using phosphinomethyloxazolines as ligands. Asymmetric hydrogenation of analogous cyclopentene derivatives, prepared by Suzuki-Miyaura cross-coupling, proved to be more difficult and proceeded with lower enantioselectivities of up to 88%ee. The synthetic potential of this cross-coupling/asymmetric-hydrogenation strategy was demonstrated by an enantioselective route to chiral hexahydrofluorenones. Alkene interest: Starting from arylboronates, a variety of cyclic, tetra-substituted olefins was prepared by Suzuki-Miyaura cross-coupling (see scheme). Subsequent Ir-catalyzed asymmetric hydrogenation with phosphanylmethyloxazoline ligand complexes led to cis-disubstituted cycloalkane derivatives in high yield and excellent enantio- and distereoselectivities. Copyright
