Sodium borohydride ketoesters

Reduction of the keto group in naphtho derivative 115 with sodium borohydride results in 69% of the alcohol 116 (Scheme 23, Section 2.1.3.3 (1999PHA645)). Further triethylsilane reduction gives 117 in 67% yield. Synthesis of a series of pyrrolo-benzazepine and pyrrolo-benzothiazepine acetic acids (Scheme 77, Section 5.1.1 (1994MI385)) includes reduction of ketoesters 380 into corresponding hydroxyl esters, subsequent deoxygenation with iodine/PPhs and hydrolysis. 

Esters may alternatively be reduced to primary alcohols either using hydrogen under pressure in the presence of a copper chromite catalyst,56 or with lithium aluminium hydride (Expt 5.38), but not with sodium borohydride which is insufficiently reactive. However it has been found recently that sodium borohydride in mixed solvents (methanol/tetrahydrofuran) reduces /1-ketoesters to 1,3-diols, and this method offers a convenient route to this type of compound.57... 

The lactone (46) was obtained in 65% yield via reduction of a ketoester with sodium borohydride in MeOH and subsequent acidic workup (Equation (21)) <90H(30)223>. 

A synthesis of 4-hydroxy-substituted TIQ has been developed in connection with plant isoquinolines (169,170), and the glycine ester route used for a similar purpose (171) is shown in Fig. 23. Reaction of the benzyl bromide 85 with N-methylglycine ester gave 86 the ketoester 87 was obtained on Dieckmann condensation. Alkaline hydrolysis of ester 87 followed by treatment with mineral acid gave ketone 88 alcohol 89 was obtained on reduction of 88 with sodium borohydride. 

The transformation of P-ketoester 20 into a,P-unsaturated ester 21 requires the reduction of the ketone chemoselectively in the presence of the ester. Sodium borohydride (NaBH4) is the standard reagent for this type of transformation. Subsequent reaction of the sterically hindered secondary alcohol with benzoyl triflate " provides a good leaving group in P-position to the ester moiety. Elimination under basic conditions provides the a,p-unsaturated ester 21 in 50 % yield over three steps. 

Deschenaux and Jacot-Guillarmod synthesised the Bartlett intermediate 124 with a chiral pool source and the Narasaka 1,3-diol synthesis for the C-6 to C-8 relationship (Scheme 16) (27). Methyl (-)-(3) )-3-hydroxybutanoate 115 (e.e. >99%) was converted to the p-ketoester 116. Reduction of the p-ketoalcohol using the Prasad version of the Narasaka method (23) with diethylmethoxyborane and sodium borohydride giving the diol 117. The acetonide 118 was homologated by way of the... 

Esterification of the ketoacid (39) with diazomethane afforded the ketoester (40). This, on treatment with sodium hydride and diethyl carbonate in 1,2-dimethoxyethane, furnished (41) whose NMR spectrum was rather complicated, probably due to contamination with a small amount of tautomer. Reduction of the free carbonyl group with sodium borohydride led to the formation of alcohol whose tosyl derivative on heating with lithium bromide and lithium carbonate in dimethylformamide gave the diester (42). Its spectroscopic properties were identical with those of the one reported [20]. As the diester (42) has already been converted to warburganal (12), the present route for the diester (42) constitutes a formal total synthesis of warburganal. 

It was found that 1,3-diethoxycarbonylallene 231 readily enters [4 -I- 2] cycloaddition with heterocyclic dienes. The adduct (232) obtained from 231 and furan was easily converted into ketoester 233. Treatment of the latter compound with lithium diisopropylamide and benzenediazonium fluoroborate resulted in the formation of the a-phenylazo compound 234, which in turn underwent sodium borohydride promoted scission of carbon-carbon bond affording the C-glycosylic compound 235 ... 

While the alkylation of compound 207 with diazoalkanes clearly indicates its enol character, some other reactions reveal that it can also behave as a typical (3-ketoester. For example, reduction with sodium borohydride in aqueous methanol yielded the saturated alcohol (208) which after chromatography was isolated as a crystalline substance in 30% yield. Acetylation with acetic anhydride in pyridine gave 3-acetox-ycepham (209) from which the acetic acid was eliminated upon treatment with triethylamine in methylene chloride, affording the 3-H cephalosporin (210). 

R. Kinishi, Y. Nakajima, J. Oda, and Y. Inouye. Asymmetric reduction of a-ketoesters with sodium borohydride by chiral phase transfer catalysts. Agric. Biol. Ghem., 1978,42,869. 

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