Threo-selective reduction

THREO-SELECTIVE REDUCTION OF (J-KETO AMIDES WITH PhMe2SiH/F- REAGENT a... 

The configuration at a-C in 8 (R-C6H5) was assigned by its conversion to (-)-norephedrine (11, R = C6H5). After hydrolysis of crude 8 (R = C6H5) evaporation of the aqueous phase, erythro-selective reduction of the /J-keto-Ar-hydroxylamine hydrochloride 9 with sodium boro-hydride in methanol to 10 followed by reductive cleavage of the N-O bond afforded (-)-norephedrine (11, R = C6H5) in 68% overall yield (erythro/threo 95 5 ee 96%). 

Unlike the Peterson alkenation, which is in principle similar, the phosphine oxide anion addition can be controlled to produce predominantly the erthyro isomer (206). The threo isomer can be obtained by selective reduction of the a-ketophosphine oxide (210), allowing highly stereoselective alkene fonna-tion. Since a two-step sequence is employed, this reaction does not require a stabilizing functionality to be conjugated to the phosphine oxide in order to produce the alkene. In fact, unlike the phosphonate HWE reagents, the reaction of a ketophosphine oxide (211) with a carbonyl derivative does not occur to produce the unsaturated carbonyl (213 Scheme 30). ° The addition step is presumably too rapidly reversible and the elimination of phosphine oxide too slow. 

Warren has also studied dibenzophosphole oxides. The ketophosphine oxide (230) substrate can be formed and selective reduction to either the erythro (233) or the threo (231) adducts carried out. The normal NaBH4 conditions were used for reduction to the threo isomer and CeCb was added to obtain the erythro adduct. This methodology was applied to the synthesis of ( )- and (Z)-isosafroles (232) and... 

Unlike the elimination of erythro adducts, the elimination of the threo intermediate is stereospecifle for aromatic and aliphatic substituents. A study of various methods of reduction found that NaBH4 in EtOH gave the best combination of threo selectivity and yield. ... 

Dimethyl(phenyl)silane reduces aldehyde and ketone carbonyls with the aid of fluoride ion or acid. a-Acylpropionamides, 1-aminoethyl ketones, and 1-alkoxyethyl ketones are readily converted into the corresponding -hydroxy amides, o -amino alcohols, and a-alkoxy alcohols, respectively. The stereoselectivity is complementary and generally high erythro (or syn) isomers are obtained with trifluoroacetic acid (TFA), whereas threo (or anti) isomers are obtained with fluoride ion activator (eq 1). The erythro selectivity in the acid-promoted carbonyl reduction is ascribed to a proton-bridged Cram s cyclic transition state. On the other hand, the threo selectivity in the fluoride-mediated reduction is explained in terms of the Felkin-Anh t) e model, wherein a penta-or hexacoordinated fluorosilicate is involved. No epimerization at the chiral center is observed during the reaction. 

Amino-Alditols.- Anti-selective reduction of acyclic or-alkoxy and of, -dialkoxy ketone oximes occurs with aluminium hydride reagents, L-threo-ketotetrose derivatives (24) giving L-xylitol... 

The diastereoselectivity of the reduction of a-substiluted ketones has been the subject of much investigation. The reagent combination of trifluoroacetic acid and dimethylphenylsilane is an effective method for the synthesis of erythro isomers of 2-amino alcohols, 1,2-diols, and 3-hydroxyalkanoic acid derivatives.86,87,276,375 Quite often the selectivity for formation of the erythro isomer over the threo isomer of a given pair is >99 1. Examples where high erythro preference is found in the products are shown below (Eqs. 218-220).276 Similar but complementary results are obtained with R3SiH/TBAF, where the threo isomer product... 

C=X bonds The stereochemistry of the reduction of carbonyl compounds has been intensely studied with regard to synthetic and mechanistic aspects. The reduction of 1,2-diphenyl-l-propanone at a Hg cathode in aqueous EtOH and pH 8 affords the erythro alcohol as the major diastereomer (erythro threo = 5 to 1.4 1) [332]. This selectivity is in accord with a protonation of the intermediate anion, formed in an ECE sequence, from the least hindered side (Fig. 61). 

The selectivity of the reduction of methyl a-DL-ald-2-enopyranosid-4-ulose 326 and, consequently, the low availability of the 2,3-unsatu-rated pyranosides of the a-threo (329) configuration, required the inversion of the configuration of C-4 (C-5 in the glyeulopyranosides) for completion of several syntheses. The benzoic acid-diethyl azodicar-boxylate-triphenylphosphine reagent was reported to effect the esterification specifically, with inversion of the configuration the yields were significantly higher than those obtained in the two-step, sulfonic-ester, displacement procedure.229... 

Stoichiometric Reactions. In 1974, Touboul reported amazing selectivity in the controlled potential electrochemical reduction of the enone (Scheme 36) (63). While the dimerization of the enantiomerically pure enone gives solely the cis,threo,cis diol, the racemic compound behaves similarly to produce the racemic dimer with the same relative configuration and no other possible diastereomers. A radical anion intermediate... 

An alternative route to the erythro.threo diastereoisomeric mixture of alcohols results from the acylation of the alkyldiphenylphosphine oxide with an ester or lactone to yield the /J-ketophosphine oxide, followed by reduction with sodium borohydride. This reduction shows f/ireo-selectivity, so that, following separation of the diastereoisomers, a preparatively useful route to ( )-alkenes is achieved. 

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