Remote Stereocenter through Amide-Directed, Rhodium-Catalyzed Enantioselective Hydroboration of Unactivated Internal Alkenes

Abstract

Despite the frequent occurrence of γ-branched amines in bioactive molecules, the direct catalytic asymmetric synthesis of this structural motif containing a remote stereocenter remains an important synthetic challenge. Here, we report an amide-directed, rhodium-catalyzed highly diastereo-and enantioselective hydroboration of unactivated internal alkenes. This method provided facile access to enantioenriched amines containing β,γ-vicinal stereocenters. The application of this strategy to the synthesis of bioactive molecules was demonstrated. Computational studies indicated that migratory insertion of the alkene into rhodium hydride controls the enantioselectivity.

Coordination Assistance: A Powerful Strategy for Metal-Catalyzed Regio- and Enantioselective Hydroalkynylation of Internal Alkenes

“…This strategy is also applicable to other types of hydrofunctionalization. For example, we have developed a series of enantioselective hydroborations and hydrosilylations of alkenes bearing a polar functional group. These enantioselective carbon–carbon and carbon–heteroatom bond formation reactions provided expedited access to diverse useful building blocks with complete atom economy and minimal waste generation.…”

Directing Group Repositioning Strategy Enabled Site- and Enantioselective Addition of Heteroaromatic C–H Bonds to Acyclic Internal Alkenes

“…In asymmetric hydrogenation, the two-point binding of the π bond and a polar group to the metal center greatly facilitates the enantioselective hydrogenation of diverse alkene substrates . Recently, we have taken advantage of this coordination assistance to achieve a number of enantioselective alkenes’ hydrofunctionalizations, where relatively reactive alkynyl C–H and B–H bonds were cleaved. To exploit the power of the coordination-assisted hydrofunctionalizations further, here, we report an iridium-catalyzed site-selective and enantioselective addition of inert C–H bonds in furans and thiophenes to internal alkenes (Scheme d).…”

Catalytic Asymmetric Hydrosilylation of β,β-Disubstituted Enamides

“…烯烃不对称氢硅化反应最早于 1991 年由日本化学家 Hayashi 报道, 此前的研究主要集 中在芳基乙烯、共轭二烯、共轭烯炔、联烯以及环丙烯 等, 对氨基烯烃底物的高效不对称氢硅化反应依然是一 个挑战性的问题 [5][6][7] . [8][9] . 近期, 他们通过相同的 策略解决氨基烯烃不对称氢硅化反应中的 C-Si 键选择 性构建问题, 实现手性 α-氨基硅烷的高效合成(Scheme 2) [10] .…”