Hydroxy esters, borane reduction

Segment Cl was synthesized from (tf)-malic acid as a starting material in the following three steps (Scheme 27) (I) diesterification with acetyl chloride in methanol, (II) selective reduction of a-hydroxy ester with boran dimethylsulfide complex and sodium borohydride in THF, and (III) acid catalyzed lactonization of 145 (90). 

The use of alpine-borane (3) has also been extended to include the reduction of acyl cyanides (14) to optically active p-amino alcohols (15),10 as well as the reduction of a-keto esters (16) into the corresponding a-hydroxy esters (17). ... 

Regioselective reduction of the a-hydroxy ester group in 822 to the highly labile dihydroxy azido ester 829 is accomplished with borane-dimethylsulfide complex and a catalytic amount of sodium borohydride. Immediate treatment of 829 with dimethoxypropane affords the isolable ethyl 2-azido-3,4-(9-isopropylidene-3,4-dihydroxybutanoate (830) in 59% yield for the two steps. Subsequent catalytic reduction of the azido group followed by either N-Boc or N-Cbz protection provides either 831 or 832 in excellent yield. These are equivalent to e /iro- -hydroxymethyl-L-serine. The enantiomeric 833 and 834 are readily available from diethyl D-tartrate through a similar series of transformations [239] (Scheme 182). 

One of the most potent frameworks for the synthesis of two contiguous stereochemically defined asymmetric centers is the chiral epoxy functionality. Prepared in molar-scale quantity from dimethyl L-tartrate (la), bromohydrin 860 is a shelf-storable solid that undergoes selective reduction at the a-hydroxy ester function with borane-dimethylsulfide complex in the presence of catalytic sodium borohydride to provide a 4 1 mixture of methyl (2S,3S)-2-bromo-3,4-dihydroxybutanoate (861) and methyl (2i, 3i )-3-bromo-2,4-dihydroxybutanoate (862). Without purification this mixture is treated with ert-butyldimethylsilylchloride and then exposed to sodium methoxide, which results in conversion to the single epoxide methyl (2i, 3iS)-4-( err-butyldimethylsilyloxy)-2,3-epoxybutanoate (863) in 95% yield and with 99% optical purity (Scheme 188). 

Hydroxy-esters. - Once again, most contributions to this area involve the synthesis of chiral hydroxy-esters. Almost complete enantioselectivity is achieved in the reduction of a-keto-esters to a-hydroxy-esters using Alpine-Borane (B-(3-pinanyl)-9-BBN) derived from either (+)- or (-)-a-pinene when the reactions are carried out at relatively high concentrations (>2M). Many other types of prochiral ketones are also reduced with excellent asymmetric inductions although 3-keto-esters may not be particularly suitable substrates as ethyl acetoacetate is reduced to ethyl 3-hydroxybutanoate with an enantiomeric excess of only... 

Reduction of aldehydes and ketones is possible with borane. Stereoselective reduction of ketones is possible when a heteroatom is located a- or p- to the carbonyl group. Treatment of a (3-hydroxy-ketone with catecholborane results in the selective formation of the syn 1,3-diol product (7.94). The borane reacts preferentially with the alcohol to release hydrogen gas and to form the boronic ester 107. A second equivalent of the borane then effects the reduction to give the syn diastereomer. For the preparation of the anti diastereomer, triacetoxyborohydride can be used (see Scheme 7.86). 

Borane-trimethylamine has been found to be a superior reagent to BHa-py (3,297) for the reduction of a-oximino-esters to the corresponding AT-hydroxy-a-amino-acid esters. ... 

Selective reduction. A soln. of borane in tetrahydrofuran added dropwise at -18 during 19 min. to a mixture of adipic acid monoethyl ester and tetrahydrofuran, stirred and allowed to warm to room temp, during 16 hrs. -> ethyl 6-hydroxy-hexanoate. Y 75-88%. - Other functional groups such as cyano, halogeno, keto, or nitro, are likewise retained during this highly convenient reduction. F. e., also reduction of sterically hindered acids, s. N. M. Yoon, H. C. Brown et al., J. Org. Chem. 38, 2786 (1973) 2-aminoalcohols from a-aminocarboxylic acids s. M. L. Anhoury et al., Soc. Perkin 11974,191 via reduction with aq. NaBH of enolesters obtained from the acids and N-ethyl-5-phenylisoxazolium 3 -sulfonate (s. Synth. Meth. 16, 448) s. P. L. Hall and R. B. Perfetti, J. Org. Chem. 39, 111 (1974). 

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