Butyldiphenylsilyl TBPS

Lactaldehyde derivative 808 can be prepared in high yield by direct reduction of methyl ester 807 with diisobutylaluminum hydride at low temperature [129]. 

The anti stereochemistry is obtained, as predicted by the Felkin model, by addition of lithioacetylene derivatives to siloxyaldehyde 808. Trimethylsilylacetylene produces a 17 83 mixture of 809a and 810a, and 3,3-diethoxypropyne gives a 23 77 mixture of 809b and 810b. 

In both cases the TBPS group is removed with fluoride to afford the corresponding diols, R=TMS (90% overall yield) and R=CH(OEt)2 (70% overall yield) [225]. 

The requisite ketones 812 are prepared by reaction of the lithioacetylene reagent with N-methoxyW-methylamide (811). Reactions with this functional group are known to proceed without racemization. Thus, 812a is obtained in 46% yield, and 812b in 93% yield. 

Addition of lithio alkene 636, a formaldehyde-anion equivalent ( CHO), to 808 at low temperature gives adduct 813 with a diastereomeric excess of 92%. Lithium—bromine exchange, desilation, ketalization, and ozonolysis furnishes aldehyde 814 ( 98% de). The last stereocenter is introduced by aldol condensation with R-HYTRA, thus giving 815 as a 91 9 mixture of isomers. Lactonization to 816 followed by reduction with disiamylborane gives 817, which is separated from the accompanying minor isomer by column chromatography. 

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The addition, alteration, or removal of protecting groups will not be discussed here Ac = Acetyl, Ar = 2,4,6-triisopropylphenyl. Bn = benzyl, Bz = benzoyl, BOC = rerf-butoxycar-bonyl, BOM = benzyloxymethyl, TBPS = tert-butyldiphenylsilyl, TBS = fert-butyldime-thylsilyl, TES = triethylsilyl, TIPS = triisopro-pylsilyl, TMS = trimethylsilyl. Actual yields of the first published procedures are given, conversions and loss to formation of isomers were included in the calculations where necessary. For precursors the yields were taken from the references given by the authors and used to... 

Ethyl L-lactate can be protected with a TBPS group by reaction with rer -butyldiphenylsilyl chloride and imidazole in either tetrahydrofuran [134] or DMF [135]. Alternatively, using DBU as the base in methylene chloride furnishes 427 in 100% yield [140]. 

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