Formyl anion equivalent, lithiated

The foregoing examples do not represent useful chiral formyl anion equivalents in a direct sense since the stereoselectivity of the initial addition to aldehydes is poor, although as has been explained, the situation is salvaged by oxidation and re-reduction. On the other hand, by lithiation at the 2 position of the achiral oxazo-lidine 53 in the presence of (-)-sparteine followed by addition of benzaldehyde, useful levels of d.e. and e.e. are achieved directly (98TA3125). For example, by adding MgBr2 before the benzaldehyde, the major product obtained is 54 in 80% d.e. and 86% e.e. 

Dialkoxymethyllithiums 43 3649 and 434649 651, 2-lithio-l,3-dioxolane 435649 and 2-lithio-1,3-dioxane 436649 are formyl anion equivalents, which have been prepared either by reductive lithiation of 2-(phenylsulfanyl) substituted precursors at —95 °C649 or by trans-metallation of 2-(tri-n-butylstannyl) substituted compounds at —110649 or —78°C651. The starting acyclic phenylsulfanyl precursors can be prepared from the corresponding orthoformates by reaction with (phenylsulfanyl)trimethylsilane and trimethylsilyl triflate as catalyst (for compounds 433 and 434). The cyclic derivatives (435, 436) were prepared from l,2-bis(l,3-dioxolan-2-yloxy)ethane and propane, in the same way649. 

The preparation of protected 4-deoxy-L-threose 440 can be realized by addition of a formyl anion equivalent to the ester group of 427 followed by stereoselective reduction. The reagent of choice is lithiated bis-/7-tolylthiomethane, which gives ketone 436 in high yield (at a reaction temperature of —78 °C) without formation of any tertiary alcohol. Compare this to lithiated 1,3-dithiane, which must be added at —90 °C or below (see compound 416). 

Lithiated dithiane 35 is another example of a formyl anion equivalent. Acylation would provide 36 and thioacetal hydrolysis would provide 29. The thioacetal hydrolysis is the FGT that establishes the equivalency. Acylation of dimsyl anion 37 (from metallation of DMSO) would afford )8-ketosulfoxide 38. Once again an oxidation is needed to establish the desired equivalency. This can be accomplished using a Pummerer rearrangement wherein oxidation occurs at carbon with reduction at sulfur. Hydrolysis of the resulting S,0-acetal would complete the required FGT. 

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