The asymmetric hydroformylation in the synthesis of pharmaceuticals

Abstract

The asymmetric hydroformylation reaction represents a potential powerful synthetic tool for the preparation of large number of different chiral products to be used as precursors of several organic compounds endowed with therapeutic activity. Essential and nonessential amino acids, 2-arylpropanoic acids, aryloxypropyl- and beta-phenylpropylamines, modified beta-phenylethylamines, pheniramines, and other classes of pharmaceuticals are available through enantioselective oxo-reaction of appropriate functionalized olefins; this process is catalyzed by rhodium or platinum complexes with chiral ligands, mainly chelating phosphines, and sometimes affords very high enantiomeric excesses. Furthermore, the application of many simple optically active aldehydes arising from asymmetric hydroformylation as chiral building blocks for the synthesis of complex pharmacologically active molecules such as antibiotics, peptides, antitumor macrocycle compounds, and prostaglandins is conveniently emphasized. The possibility of a future application of this asymmetric process for the production of many synthons to obtain other valuable pharmaceuticals is widely discussed too.

Enantiomerically Pure Bis(phosphanyl)carbaborane(12) Compounds

“…[25] Aldehyde groups are one of the most versatile functional groups in organic synthesis and can be transformed into alcohols, amines, imines and acids. [26] A useful hydroformylation reaction needs to produce aldehydes with high productivity, and simultaneously be chemo-, regio-and stereoselective and is thus an ongoing challenge in academic and industrial research.…”

Computational aspects of hydroformylation

“…For leading reviews of asymmetric hydroformylation, see ref. [16][17][18][19]. The hydroformylation utilising alternative metals is reviewed recently by Beller and coworkers.…”

Easily Accessible TADDOL‐Derived Bisphosphonite Ligands: Synthesis and Application in the Asymmetric Hydroformylation of Vinylarenes

“…[1] Performing this atom economic reaction in an asymmetric fashion opens up the possibility of converting inexpensive starting materials into enantiopure chiral aldehydes, which are highly valuable building blocks for the synthesis of a plethora of fine chemicals and pharmaceutical products. [2] Although the utility of this method is well documented, [3] the asymmetric hydroformylation (AHF) of olefins remains a challenge in organic chemistry today. The reason for this lies in the difficult task of controlling chemo-, regio-and enantioselectivity simultaneously while keeping high reaction rates.…”