Enantioselective Tandem Reactions Involvingα-Carbonyl Diazo Or Surrogates

Asymmetric metal/organo combined catalysis, as one of the hot topics in the area of asymmetric catalysis, conceptually adopts the superior features of both the catalysts, enabling numerous transformations that neither of the individual catalysts can realize alone. Combined catalysis generally includes:1) cooperative catalysis allows simultaneous and individual activations of substrates to drive a bond-forming process;2) relay catalysis basically means a cascade process involving two or more sequential reactions independently catalyzed by distinct catalysts;3) sequential catalysis describes a one-pot reaction containing two or more incompatible catalytic cycles. In most cases, combined catalytic reactions would reduce the solvent cost and waste*thus being relatively more environmentally benign.α-Carbonyl diazo compounds are an important class of synthetic building blocks in organic chemistry, which are often employed in various transition metal-catalyzed transformations as carbenoid precursors. For the first time, we designed a Rh(II)/quinine-derived chiral squaramide relay catalytic system to enable a cascade semi-pinacol rearrangement/asymmetric Michael addition reaction. This reaction provides a direct access to optically pure nitro compounds bearing multiple functionalities.Optically active3,3’-bisindole represents a unique structural element within a family of indole alkaloids, which own a wide spectrum of bioactivities and pose great interest for chemical synthesis. We developed an asymmetric three-component reaction of indoles,3-diazooxindoles and nitro alkenes by untilizing asymmetric Ru(II) or Rh(II)/chiral squaramide relay catalysis, affording a series of chiral3,3’-bisindole derivatives. The online reaction monitored by1H-NMR suggested a mechanism comprised of a metal-catalyzed C-H functionalization and asymmetric Michael addition process. Moreover, we accomplished a concise total synthesis of (-)-folicanthine on the basis of this protocol.Chiral phophine catalysis is an important part of asymmetric organocatalysis. Since chiral phosphines have rarely been used in combination with a transition metal (Jellerichs, B. G.;Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc.2003,125,7758), we successfully esablished the first metal/chiral phosphine sequential catalysis to allow cascade C-H functionalization/asymmetric addition reactions, providing an efficient entry to optically pure3,3’-indolyloxindoles with quanternary carbon stereogenic centers.Gold-catalyzed oxygen-atom transfer to alkynes steadily affords gold a-oxo carbenoid intermediates, avoiding the use of hazardous diazo compounds. While trying to develop a new cascade reaction based on the gold a-oxo carbenoids, however, we surprisingly found a metal free oxidative functionalization of unactivated alkynes. In this reaction, excess amounts of MsOH and pyridine N-oxide facilitated the transformation of2-ethynylanilines into2,3-dihydroquinolin-4(1H)-ones. Further deuterium-labeling and control experiments suggested that the reaction proceeded via a1,5-hydride transfer/cyclization/elimination process.