Lithium borohydride hydroxy esters

Asymmetric reduction of -arylcarbonyl esters.1 Reduction of these esters with lithium borohydride and (R,R )-1 and t-butyl alcohol affords the corresponding 3-hydroxy esters in 80-92% ee (equation I). 

Lithium tri-sec-butylborohydride, 21 B-3-Pinanyl-9-borabicyclo[3.3.1]-nonane, 249 Sodium borohydride, 21 (3-Hydroxy esters and lactones By aldol-type reactions (R)-( + )-f-Butyl p-tolylsulfinylace-tate, 59 Cadmium, 60... 

Lithium borohydride, 92 y-Hydroxy esters and lactones Zinc chloride, 349... 

Lithium borohydride decomposed by /V-benzoylcysteine (61) or /V/v -dibenzoylcystine (62), a sulfur-containing modifier, is a highly efficient chiral reducing agent. A complex prepared from (61), t-butyl alcohol and LiBH4 affords carbinols in maximum 92% ee by the reduction of aryl alkyl ketones in THF at -78 °C (Scheme 13). A LiBH4 complex with (62) and t-butyl alcohol is useful for the reduction of -keto esters to give (R)-P-hydroxy esters in up to 91 % ee. In both cases the use of r-butyl alcohol is essential in order to achieve efficient enantiofacial differentiation. ... 

The cyclic anhydride was converted into the amide acid which on Hofmann rearrangement followed by lithium borohydride reduction on the ester gave a derivative of ip-amino-2a, 3a-dihydroxy-43-hydroxy-methylcyclopentane. Condensation of the amino-triol with 5-amino-4,6-dichloropyrimidine followed by ring closure with triethyl orthoformate gave the 6-chloropurine derivative which on treatment with ammonia gave 11. ... 

In contrast to the usual reaction of aromatic aldehydes with cyclic ketones o-nitrobenzaldehyde condenses with 17-ketones to produce good yields of seco-acids, a reaction which has been applied to the preparation of 16-oxa-steroids. Thus, 3 -hydroxy-5a-androstan-17-one or its acetate affords the seco-steroid (153), which can be oxidised either as the free acid by ozone and alkaline hydrogen peroxide to the diacid (155) or, as its methyl ester (154), with chromium trioxide to the monomethyl ester (156). Diborane reduction of the diacid (155) or lithium aluminium hydride reduction of the dimethyl ester (157) gave the trans-diol (158), cyclised with toluene-p-sulphonic acid to 16-oxa-androstan-3)5-ol (159) or, by oxidation with Jones reagent to the lactone (152) (as 3-ketone) in quantitative yield. This lactone could also be obtained by lithium borohydride reduction of the monomethyl ester (156), whilst diborane reduction of (156) and cyclisation of the resulting (151) afforded the isomeric lactone (150). The diacid (155) reacted with acetic anhydride to afford exclusively the cis-anhydride (161) which was reduced directly with lithium aluminium hydride to the cis-lactone (160) or, as its derived dimethyl ester (162) to the cis-diol (163) which cyclised to 16-oxa-14)5-androstan-3) -ol (164). 

Further work on the preparation of cryt/iro-2-alkyl-3-hydroxy-esters (140) by various condensations between propionic acid derivatives and aldehydes has been reported " the use of zirconium enolates seems to be particularly efficacious. Rules for predicting the stereochemical outcome of condensations between lithium enolates of esters and ketones and a-alkoxy-aldehydes have also been delineated. Pure erythro-isomer (140) can also be obtained in some cases by reduction of the corresponding jS-keto-ester with zinc borohydride. In related work it has been found that sodium borohydride in isopropanol reduces t-butyl a-alkoxy-j8-keto-esters to the corresponding -hydroxy compounds with erythro-threo ratios of between 2 1 and 20 1 in favour of the eryt/iro-isomer. In an extension of his previous work, Frdter has reported that dianions derived from cyclohexanol (141) can be alkylated with 95% stereoselectivity, to give (142). When the starting alcohol (141) is optically pure, a sequence of alkylation and oxidation leads to 2-ethoxycarbonylcyclohexanones with 76% enantiomeric enrichments. 

Hydroxy-containing fluorovinyl ether monomers (5,6) were prepared in excellent yields (80-90%) in a single step from the corresponding esters (1,3)12"14 with sodium borohydride in absolute ethanol. Protection of the sensitive vinyl ether groups was not required during the reduction. In contrast, the use of a more powerful reducing agent, such as lithium aluminum hydride, resulted in the reduction of the double bond ... 

A modestly enantioselective pyrrole carbinol formation has been investigated <05SL2420>. Treatment of lithium pyrrolate with a ketoaldehyde in the presence of a chiral ligand preferentially led to the formation of pyrrole carbinol 49 (50% ee). A hydroxy-directed reduction of the ketone in the side chain by the addition of zinc borohydride provided 50 (88% de). Pyrrole carbinols serve as convenient precursors to aldehydes. A subsequent deprotective Horner-Wadsworth-Emmons reaction involving 50 and phosphonate ester 51 gave unsaturated ester 52. 

Reduction. An early report2 stated that aldehydes and a-hydroxy ketones are reduced by this reagent but that ketones, nitro compounds, carboxylic acids, and esters are not reduced. Borch and Durst,3 however, found that some ketones are reduced, but more slowly than with sodium borohydride. One advantage over the latter reagent is that lithium cyanohydridoborate is stable in acid up to pH 3 and hence can be used for reduction of groups sensitive to high pH (e.g., thiamine). 

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