Pinene-derived iminodiacetic acid (PIDA): A powerful ligand for stereoselective synthesis and iterative cross-coupling of C(sp 3) boronate building blocks

Abstract

Efficient access to chiral C(sp 3) boronates in stereochemically pure form is critical for realizing the substantial potential of such building blocks in complex-molecule synthesis. We herein report that a pinene-derived iminodiacetic acid (PIDA) ligand enables the highly diastereoselective synthesis of a wide range of oxiranyl C(sp 3) boronates from the corresponding olefins. These oxiranyl PIDA boronates, in turn, can be readily transformed into unprecedented stable α-boryl aldehydes via a novel 1,2-migration of the boronate group that proceeds with complete maintenance of stereochemical purity. B-Protected haloboronic acids containing dual sp 3-hybridized C centers are readily accessible via this platform, and the herein demonstrated capacity for stereocontrolled iterative C(sp 3) cross-coupling with this novel type of bifunctional reagent to access a medicinally important chiral small-molecule target in highly enantioenriched form represents a substantial advance for the building-block-based approach to synthesis. © 2011 American Chemical Society.