Regio-, Enantio-, and Diastereo-selective Reduction Reactions

Regio-, Enantio-, and Diastereo-selective Reduction Reactions 

An integration of readily available computational methods and visualization techniques has rendered a simple method to predict nucleophilic asymmetric induction of prochiral electrophiles.303 Taking the examples of ketone and aldehyde reductions, electrostatic potential has been mapped on to the frontier orbital involved. A distinct difference in 

In a probe for the presence of stereoelectronic effects in nucleophilic addition to 12 sterically unbiased ketones, calculations have identified subtle bond length differences in the C-Nu bond of the diastereomeric alcohol products, where Nu- = H-or Me-.304 The calculated differences are weak ( 1%) but consistent the bond is longer in the major product, acting as a fossil record of the TS. Using microscopic reversibility, the easier bond to cleave (the longer one) is the easier to form. The effect bears comparison with the kinetic anomeric effect in sugars, where such bond length differences in calculation are borne out in X-ray crystal structures. 

Asymmetric hydrogenation of ketones is one of the more common reduction methods, with ruthenium complexes often used as catalysts, a topic which has been reviewed.305 

Perfluoroalkyl ketones have been reduced in high ee using a simple alkoxide lithium (S)-l-phenylethoxide, for example, reduces 2,2,2-trifluoroacetophenone to its (5 carbinol in 80% ee and 61% yield at 0°C, with acetophenone produced as by-  

The reagent L-TarB-N02 (78), prepared from tartaric and /w-nitrophenylboronic acids, asymmetrically reduces ketones in the presence of sodium borohydride.301 Evidence for a monoacyloxyborohydride intermediate (79) is presented. 

The diastereoselectivities of the reduction of tricyclo[5.2.1.02 6]decan-10-one (80) (g) and its 3,4-ene and 3-one derivatives have been measured, using NaBH4 in methanol 

While chiral catalysts containing N-P=0 moieties have been increasingly studied in borane-mediated asymmetric reduction of ketones, a study of a range of such species (e.g. 81) indicates that the configuration at phosphorus plays little or no role in determining enantioselectivity, and indeed the stereochemistry at the phosphorus centre may be scrambled under the reaction conditions.304 

Me2S reduction of aryl alkyl ketones can be carried out with ees up to 98% using 3 mol% of a chiral oxazaborolidine derived from (-)-/l-pinenc.3 5 

Chiral ruthenabicyclic complexes, where a BINAP and a diamine provide chelation to produce the rings, provide excellent catalysis of hydrogenation of ketones, giving 99% ee and turnover frequency of 35000min for acetophenone. Spectroscopic and deuteration experiments suggest that the ruthenabicyclic structure is retained throughout.  

A ruthenium(II) complex, an achiral diphosphane, and (15, l 5 )-l,l -biisoindoline (141, a new rigid axially chiral diamine), catalyse highly enantioselective hydrogenation of aromatic ketones.  

Economical copper(II) acetate catalyses hydrogenation of ketones in the presence of chiral BE JOL-derived phosphine ligands, giving ees up to 89%.  

A range of azolium salts (143, X/Y = S/CH, NR/N, and NR/CH) have been prepared from f5j-pyroglutamic acid. They act as NHCs in the rhodium-promoted transfer 

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