Direct Catalytic Asymmetric Mannich-type Reaction of Hydroxyketone Using a Et₂Zn/Linked-BINOL Complex:  Synthesis of Eitheranti- orsyn-β-Amino Alcohols

Abstract

Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-beta-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-beta-amino alcohols in anti/syn = up to >98/2, up to >99% yield, and up to >99.5% ee, while Boc-imine 4 gave syn-beta-amino alcohols in anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05 mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described.

Highly Enantioselective Direct Michael Addition of 1H‐Benzotriazole to Chalcones Catalyzed by Sc(OTf)3/N,N′‐Dioxide Complex

“…Synthesis of chiral β-benzotriazolyl ester, β-benzotriazolyl alcohol, and β-benzotriazolyl amide. [12] Eur. …”

Diastereoselective Mannich Reaction of Chiral Enolates Formed by Enantioselective Conjugate Addition of Grignard Reagents

“…Dependence of the diastereoselection of the Mannich reaction on the nitrogen protecting group is interesting but not unprecedented. [22] Different stereoselectivity of the enolate addition to imine 2f in comparison to other imines led us to investigate possible transition states by computational methods. We assumed that the enolate reacts preferentially at its anti side with respect to the methyl group, and then we modeled two possible approaches of the imine.…”

Asymmetric Bifunctional Catalysis Using Heterobimetallic and Multimetallic Systems in Enantioselective Conjugate Additions

“…Inspired by the mechanism of type II aldolase enzymes, the Et 2 Zn/linked-BINOL complex 1 derived from BINOL ligand 2 and Et 2 Zn was developed as a catalyst for catalytic asymmetric C−C bond-forming reactions (Figure 4.2) [7,8].…”