Synthesis and use of an asymmetric transfer hydrogenation catalyst based on iron(II) for the synthesis of enantioenriched alcohols and amines

• Published in: Nature protocols Vol. 10; no. 2; pp. 241 - 257
• Main Authors: Zuo, Weiwei, Morris, Robert H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2015; Nature Publishing Group
• Subjects: 639/638/263/406/77/883; 639/638/77/888; Alcohols; Alcohols - chemical synthesis; Alcohols - chemistry; Amines; Amines - chemical synthesis; Amines - chemistry; Analytical Chemistry; Biological Techniques; Catalysis; Catalysts; Chemistry Techniques, Synthetic; Computational Biology/Bioinformatics; Ferrous Compounds - chemistry; Hydrogenation; Iron; Ketones; Life Sciences; Methods; Microarrays; Molecular Structure; Organic Chemistry; Properties; protocol; Ruthenium; Stereoisomerism
• ISSN: 1754-2189; 1750-2799
• DOI: 10.1038/nprot.2015.012

Zuo and Morris describe an approach to catalytic hydrogenation of prochiral ketones and imines to produce enantioenriched alcohols and amines that uses a more environmentally friendly iron-based catalyst instead of conventional Ru-based catalysts. The catalytic hydrogenation of prochiral ketones and imines is an advantageous approach to the synthesis of enantioenriched alcohols and amines, respectively, which are two classes of compounds that are highly prized in pharmaceutical, fragrance and flavoring chemistry. This hydrogenation reaction is generally carried out using ruthenium-based catalysts. Our group has developed an alternative synthetic route that is based on the environmentally friendlier iron-based catalysis. This protocol describes the three-part synthesis of trans -[amine(imine)diphosphine]chlorocarbonyliron(II) tetrafluoroborate templated by iron salts and starting from commercially available chemicals, which provides the precatalyst for the efficient asymmetric transfer hydrogenation of ketones and imines. The use of the enantiopure ( S , S ) catalyst to reduce prochiral ketones to the ( R )-alcohol in good to excellent yields and enantioenrichment is also detailed, as well as the reduction to the amine in very high yield and enantiopurity of imines substituted at the nitrogen with the N -(diphenylphosphinoyl) group (-P(O)Ph 2 ). Although the best ruthenium catalysts provide alcohols in higher enantiomeric excess (ee) than the iron complex catalyst used in this protocol, they do so on much longer time scales or at higher catalyst loadings. This protocol can be completed in 2 weeks.