Access to P-stereogenic compounds via desymmetrizing enantioselective bromination

Abstract

A novel and efficient desymmetrizing asymmetric ortho-selective mono-bromination of bisphenol phosphine oxides under chiral squaramide catalysis was reported. Using this asymmetric ortho-bromination strategy, a wide range of chiral bisphenol phosphine oxides and bisphenol phosphinates were obtained with good to excellent yields (up to 92%) and enantioselectivities (up to 98.5 : 1.5 e.r.). The reaction could be scaled up, and the synthetic utility of the desired P-stereogenic compounds was proved by transformations and application in an asymmetric reaction.

Fig. 1. (a) Examples of natural products containing P-stereogenic centers. (b) P-Stereogenic compound type ligand and catalyst. (c) Typical P-stereogenic compounds' synthetic strategies.

Scheme 1. (a) Constructing axially chiral compounds by asymmetric bromination. (b) Known synthesis of central chiral compounds via asymmetric bromination. (c) This work: access to P-stereogenic compounds via desymmetrizing enantioselective bromination.

Scheme 2. (a) Large-scale reaction. (b) Synthetic transformations. (c) Application of the transformed product.

Scheme 3. Kinetic resolution process.

Scheme 4. Control experiments: (a) mono-methyl protected phosphine oxide substrate was evaluated; (b) dimethyl protected phosphine oxide substrate was examined; (c) thiophosphine oxide substrate was investigated.