C–H Functionalization of Amines via Alkene-Derived Nucleophiles through Cooperative Action of Chiral and Achiral Lewis Acid Catalysts: Applications in Enantioselective Synthesis

Abstract

Catalytic transformations of α-amino C-H bonds to afford valuable enantiomerically enriched α-substituted amines, entities that are prevalent in pharmaceuticals and bioactive natural products, have been developed. Typically, such processes are carried out under oxidative conditions and require precious metal-based catalysts. Here, we disclose a strategy for an enantioselective union of N-alkylamines and α,β-unsaturated compounds, performed under redox-neutral conditions, and promoted through concerted action of seemingly competitive Lewis acids, B(CF), and a chiral Mg-PyBOX complex. Thus, a wide variety of β-amino carbonyl compounds may be synthesized, with complete atom economy, through stereoselective reaction of an in situ-generated enantiomerically enriched Mg-enolate and an appropriate electrophile.

Delayed catalyst function enables direct enantioselective conversion of nitriles to NH 2 -amines

“…We therefore needed to conceive of a strategy that would favor Cu–B(pin) addition to the allene even in the presence of the Cu–H species. Despite many examples of multi-catalytic transformations (29), those involving catalysts that possess competing functions are relatively uncommon (30, 31), especially when the one that is formed more slowly and is less reactive must nonetheless participate first.…”

B(C6F5)3-catalyzed dehydrogenative cyclization of N-tosylhydrazones and anilines via a Lewis adduct: a combined experimental and computational investigation

“…Tris(pentauorophenyl)borane has recently emerged as a powerful Lewis acid catalyst. [1][2][3] The strong Lewis acidity 2,3 at the boron center allows us to establish a wide range of organic transformations via C-B, [4][5][6] C-C, [7][8][9][10] C-N, 11,12 C-O 13,14 and C-Si [15][16][17][18] bond formations. Pioneered by Stephan and Erker, B(C 6 F 5 ) 3 has gained popularity in frustrated Lewis pair (FLP) chemistry which encompasses widespread applications in organic reactions.…”

Toward Rational Understandings of α-C–H Functionalization: Energetic Studies of Representative Tertiary Amines

“…Under this circumstance, only an equilibrium may be realized. Recently, such reversible H À T between tertiary amines and B(C 6 F 5 ) 3 was indeed observed in a double-acid catalyzed amine a-C-H functionalization (Shang et al, 2018).…”