Sodium borohydride/diethylmethoxyborane

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... 

After TBS protection, methanolysis of the dioxolenone liberates the heptanoic acid ester 950. Stereocontrolled reduction of the -keto function furnishes either syn or anti diols depending on the hydride reagent employed. Diethylmethoxyborane-sodium borohydride gives syn-d o 952 as a single isomer in 86% yield, whereas tetramethylammonium triacetoxyborohydride produces a mixture of anti and yw-diols 953 and 952 (ratio anti syn = 10 1) in 85% yield [173] (Scheme 129). 

Diethylmethoxyborane—sodium borohydride gives tbe syn product 121 in 96% yield and 30 1 diastereoselectivity, whereas tetrametbylammonium triacetoxyborobydride fumisbes tbe anti product 122 in 90% yield and 1 12 diastereoselectivity. Metbylation of tbe trianion of either 121 or 122 using 5 equivalents of LDA and 10 equivalents of methyl iodide gives 2,3-anti 123 (63% yield, 6 1 diastereoselectivity) or 2,3-anti 124 (61% yield, 13 1 diastereoselectivity) respectively. 

An enantioselective synthesis of ( —)-(2i ,3i ,6S,8i )-epi-nonactic acid (124) is shown in Scheme 89. The reduction of (122) with diethylmethoxyborane/sodium borohydride yields a iyn-diol (not isolated), which cyclizes spontaneously to the lactol (123). Pyridinium -toluenesulfonate-catalyzed dehydration, desulfurization with Raney nickel, Rh/Al203-catalyzed hydrogenation, and hydrolysis of the ester group affords (124) <94JOC3898>. 

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