Chiral Magnesium BINOL Phosphate-Catalyzed Phosphination of Imines: Access to Enantioenriched α-Amino Phosphine Oxides

Abstract

A new method to synthesize chiral α-amino phosphine oxides is reported. The reaction combines N-substituted imines and diphenylphosphine oxide, and is catalyzed by a chiral magnesium phosphate salt. A wide variety of aliphatic and aromatic aldimines substituted by electron neutral benzhydryl or dibenzocycloheptene groups were excellent substrates for the addition reaction. The dibenzocycloheptene protected imines afforded improved enantioselectivity in the resulting products. Substituted diphenylphosphine oxide nucleophiles also showed good reactivity.

Enantioselective magnesium-catalyzed transformations

“…For example, Antilla et al have reported a novel methodology to add diphenylphosphine oxide 166a to imines with generally moderate to quantitative yields (65-98%) and enantioselectivities of up to 99% ee. 90 The process was catalyzed with only 5 mol% of chiral phosphate magnesium complex 190 in acetonitrile at room temperature, as shown in Scheme 53. Two differently N-substituted imines were investigated under these conditions.…”

Copper-Catalyzed Electrophilic Amination of sp2 and sp3 C−H Bonds

“…177,[182][183][184] The biological importance of this class of compounds continues to drive efforts toward their efficient and rapid synthesis. [185][186][187][188][189][190][191][192][193][194] or an amide, 195 whereas, the Kabachnik-Fields reaction is a three-component reaction of an amine, an aldehyde, and a dialkyl phosphite. [196][197][198] Alternatively, α-amino phosphonic acids can be prepared through C−C bond formation, either through the addition of an anionic phosphonic analogue of glycine to an electrophilic carbon atom (Scheme 30, pathway c) or through the addition of a nucleophile to a cationic phosphoglycine equivalent (Scheme 30, pathway d).…”

Chiral Ca-, Sr-, and Ba-Catalyzed Asymmetric Direct-Type Aldol, Michael, Mannich, and Related Reactions

“…Antilla et al also investigated chiral calcium BINOL phosphate catalysts [94]; for reviews of asymmetric phospination reactions, see [95,96]. This type of calcium catalyst was applied to asymmetric phosphination reactions (Table 24).…”