4-Lithio-l,3-dioxanes

Lithio-l,3-dioxanes are prepared by reductive lithiation of 4-(phenylthio)-l,3-dioxanes and by transmetallation of the corresponding 4-(tributylstannyl)-l,3-dioxanes. This section describes the use of 4-lithio-l,3-dioxanes in the synthesis ofsyn- and anfz-l,3-diols. 

Our group has exploited 4-phenylthio-l,3-dioxanes as convenient precursors to 4-lithio-l,3-dioxanes [45,65-69]. 4-Phenylthio-l,3-dioxanes 184 were originally prepared from -silyloxy aldehydes 183 [65] (Eq. 28). Lewis acid-promoted addition of phenylthiotrimethylsilane gave an unstable thioacetal intermediate, which could be converted in situ to the corresponding 1,3-dioxane. Yields for this process are variable, as the product is unstable under the conditions of its formation. The reaction slowly evolves to a mixture of the desired product, the phenylthio acetal of 183, the phenylthio acetal of acetone, and a variety of other unidentified products. 

Fig. 7. Conformations of substituted 4-lithio-l,3-dioxanes calculated at B3LYP/6-31-i-G(d)// HF/3-21G. Only the lowest energy 4,6-czs and 4,6-trans conformations are listed, along with the relative energy for each pair. The (4,6-czs)-5-axial conformation is 1.81 kcal/mol higher in energy than the (4,6-ds)-5-equatorial conformation...

Displacement of a phenylthio group by lithium using LiDBB at —78°C was found to be effective for the preparation of a /ra r-4-lithio-l,3-dioxane configurationally stable at that temperature. Reaction with alkyl halides with retention of the configuration afforded the /ra r-dioxanes with 99 1 selectivity. Equilibration of the trans-configurated 4-lithio-l,3-dioxane to the thermodynamically more stable r-derivative was achieved upon warming the solution to —20 °C. The transjcis-ratio was approximately 1 5. This ratio was also found after alkylation with alkyl halides (Scheme 60) <1999JOC6849>. 

In contrast, with cuprates derived from 2-lithiotetrahydropyrans and 4-lithio-l,3-dioxanes, bearing at least one further stereogenic center, the stereochemical integrity is maintained. 

Rychnovsky SD, Buckmelter AJ, Dahanukar VH, Skalitzky DJ. Synthesis, equilibration, and coupling of 4-lithio-l,3-dioxanes synthons for syn- and anti-l,3-diols. J. Org. Chem. 1999 64 6849-6860. 

Alkylations of 4-cyano-l,3-dioxanes (cyanohydrin acetonides) represent a highly practical approach to syn-l,3-diol synthesis. Herein we present a comprehensive summary of cyanohydrin acetonide chemistry, with particular emphasis on practical aspects of couplings, as well as their utility in natural product synthesis. Both 4-acetoxy-l,3-dioxanes and 4-lithio-1,3-dioxanes have emerged as interesting anri-l,3-diol synthons. The preparation and utility of these two synthons are described. 

As already demonstrated in the previous natural product synthesis, the alkylation of 2,2-dimethyl-l,3-dioxan-5-one SAMP/RAMP hydrazones is a reliable tool with which to synthesize chiral 4-substituted 2,2-dimethyl-l,3-dioxan-5-ones in gram quantities and with high enantiomeric excesses [68]. Thus, after metalla-tion of the RAMP hydrazone (R) -96 the corresponding lithio azaenolate was alkyl-... 

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