JOSEPH V. CAREY
Key Organics Limited, Highfield Road Industrial Estate, Highfield Road, Camelford, Cornwall, PL32 9RA, United Kingdom

Abstract

The number of commercially available chiral bisphosphine ligands has grown substantially in the last decade, which has resulted in an increased range of applications in asymmetric chemocatalysis, together with improved enantioselectivity, higher S/C ratio’s and milder reaction conditions. However, the majority of new ligands introduced are variations of the C2 axially symmetrical BINAP or DIOP, which contain a chiral backbone. In comparison, the synthesis of new P-chiral bisphosphines, based on the pioneering DIPAMP ligand, is noteworthy because fewer new examples of this structural class have been introduced and utilised.

Key contributors agree that this is undoubtedly a consequence of the lack of general synthetic methodology. This paper reviews the approach introduced by Jugé, Kagan and Brown that is referred to herein as the “nucleophilic displacement route.” It involves the use of (l)-ephedrine as a chiral auxiliary in the formation of optically pure chloro-, alkyl- or aryl-oxazaphospholidine oxides or borane adducts, from which successive enantiospecific nucleophilic displacements can be made to afford a wide range of homochiral phosphines. The route offers substantial scope for new ligands with a more extensive range of substitution patterns at both phosphorus and the backbone.

INTRODUCTION

The success of homogeneous asymmetric catalysis has been attributed to the structure and stereochemistry of the coordinated ligand(s), which can be classified into three general structural types (Figure 1): (i) axial C2-symmetrical bisphosphines that contain a rigid chiral backbone linking two PPh₂ units such as BINAP and SEGPHOS, (ii) C2-symmetrical bisphosphines that contain a chiral backbone linking two PPh₂ or PR₂ units such as DIOP and DuPHOS, or (iii) P-chiral bisphosphines such DIPAMP and BisP* that contain two chiral phosphine units linked by an achiral backbone. However, despite the landmark discovery and success of DIPAMP, relatively little attention has been paid to this class of P-chiral phosphine ligands for more than 20 years, mainly because of the synthetic difficulty of their preparation and apprehension about possible stereomutation at the phosphorus atom(s)(1).

HISTORICAL PERSPECTIVE
DIPAMP (Figure 1) was conceived and developed by Knowles et al. at Monsanto Corporation in 1975, and subsequently stimulated the rapid development of asymmetric catalysi ...