A new system for catalytic enantioselective reduction of achiral ketones to chiral alcohols. Synthesis of chiral α-hydroxy acids

Ligand Design for Catalytic Asymmetric Reduction

“…Migration of the borane hydride to the carbonyl carbon gives 28D, which is converted to 28A directly or 28B through a borane adduct 28E with releasing of the R alkoxide product. For this reaction, borane-THF complex is most commonly used, whereas catecholborane gives better results for reaction of a,b-unsaturated ketones 123,124 and alkynyl ketones. 124 The skeletally fixed prolinol ring gives the best performance for enantioface selection of substrates in 28C.…”

Effective Stereoselective Total Synthesis of 16,16-Dimethyl Prostaglandin E2

“…However the use of two equivalents of KN(TMS) 2 , in the presence of 18-crown-6, at -70 °C followed by quenching at the same temperature with ammonium chloride, produced cleanly (R)-4,4-dimethyl-1-iodo-1(E)-octen-3-ol 9 . 1 H NMR and 19 Mild desilylation to the methyl ester 10 followed by enzymatic hydrolysis (pH 7, PPL Sigma) produced 16,16-dimethyl prostaglandin E 2 1 in 78% overall yield, identical in all aspects with an authentic sample ( 1 H NMR, 13 C NMR, FT-IR, HPLC).…”

“…Sato et al applied the Sharpless kinetic resolution to γ-iodo allylic alcohols, as well as γ-chloro, bromo, trimethylsilyl, and tributylstannyl allylic alcohols, obtaining products of 99% ee, but again the drawback is that 50% of the product is lost and that generally chromatographic purification is required [11][12] . Earlier, Corey et al described the reduction of 1-iodo-1(E)-octen-3-one, by means of chiral oxazaborolidines, and obtained products with high ee values [13][14] . Unfortunately, in the synthesis of 16,16-dimethyl PGEs, the reduction of the hindered ketone resulted in low yields and poor ee values.…”

Practical and Efficient Procedure for the In Situ Preparation of B-Alkoxyoxazaborolidines. Enantioselective Reduction of Prochiral Ketones

“…In spite of the advantages of this new type of catalysts, the various methods described for their obtention, many times discourage their use, being time consuming [4] or requiring extensive separation steps prior to their use [5].…”

“…Numerous OAB synthesized from different aminoalcohols have been reported [3], however the most used OAB is that derived from α,α-diphenylpyrrolidinemethanol (8) developed by Corey. In spite of the advantages of this new type of catalysts, the various methods described for their obtention, many times discourage their use, being time consuming [4] or requiring extensive separation steps prior to their use [5].…”