Heterobimetallic Transition Metal/Rare Earth Metal Bifunctional Catalysis: A Cu/Sm/Schiff Base Complex for Syn-Selective Catalytic Asymmetric Nitro-Mannich Reaction

摘要

The full details of a catalytic asymmetric syn-selective nitro-Mannich reaction promoted by heterobimetallic Cu/Sm/dinucleating Schiff base complexes are described, demonstrating the effectiveness of the heterobimetallic transition metal/rare earth metal bifunctional catalysis. The first-generation system prepared from Cu(OAc)_2/Sm(O-iPr)_3/Schiff base 1a = 1:1:1 with an achiral phenol additive was partially successful for achieving the syn-selective catalytic asymmetric nitro-Mannich reaction. The substrate scope and limitations of the first-generation system remained problematic. After mechanistic studies on the catalyst prepared from Sm(O-iPr)_3, we reoptimized the catalyst preparation method, and a catalyst derived from Sm_5O(O-iPr)_(13) showed broader substrate generality as well as higher reactivity and stereoselectivity compared to Sm(O-iPr)_3. The optimal system with Sm_5O(O-iPr)_(13) was applicable to various aromatic, heteroaromatic, and isomerizable aliphatic N-Boc imines, giving products in 66-99% ee and syn/anti = >20:1 -13:1. Catalytic asymmetric synthesis of nemonapride is also demonstrated using the catalyst derived from Sm_5O(O-iPr)_(13).