Described herein is the enantioselective synthesis of multisubstituted biaryl derivatives by chiral phosphoric acid catalyzed asymmetric bromination. Two asymmetric reactions (desymmetrization and kinetic resolution) proceeded successively to afford chiral biaryls in excellent enantioselectivities (up to 99% ee). Both experimental and computational studies suggested that this excellent selectivity could be achieved via a highly organized hydrogen bond network among a substrate, a catalyst (chiral phosphoric acid), and a brominating reagent (N-bromophthalimide).

The oxidative kinetic resolution of 2-substituted indoline derivatives was achieved by hydrogen transfer to imines by means of a chiral phosphoric acid catalyst. The oxidative kinetic resolution was applicable to racemic alkyl- or aryl-substituted indolines, and the remaining indolines were obtained in good yields with excellent enantioselectivities.

Benzothiazoline is an efficient reducing agent for the chiral BINOL-phosphoric acid catalyzed enantioselective transfer hydrogenation of ketimines and α-imino esters to afford the corresponding amines with high enantioselectivities. DFT studies (M05-2X/6-31G*//ONIOM(B3LYP/6-31G*:HF/3-21G)) revealed the reaction mechanism and the origin of the high enantioselectivity in the present BINOL-phosphoric acid catalyzed transfer hydrogenation of ketimines and α-imino esters using benzothiazoline. The reaction mechanism is similar to that reported in the asymmetric transfer hydrogenation of ketimines using Hantzsch ester. Phosphoric acid simultaneously activates ketimine (α-imino ester) and benzothiazoline to form cyclic transition structures. The high enantioselectivity is attributed to the steric interaction between the substituents at the 3,3'-positions of BINOL-phosphoric acid and substrates. In contrast to the C2-symmetrical Hantzsch ester, the readily tunable 2-aryl substituent of unsymmetrical benzothiazoline plays a significant role in the steric interaction, influencing the asymmetric induction. This feature is responsible for the advantage of benzothiazoline over Hantzsch ester.

Guided by computational studies, the involvement of non-classical C–H⋯O hydrogen bonds and π–π stacking interactions were found to be crucial for high stereocontrol in a chiral phosphoric acid-catalyzed reaction.

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