Titanium Enolates in Aldol Additions

The problem of diastereoselective aldol addition has been largely solved48,108). Under kinetic control Z enolates favor erythro adducts and E enolates the threo diastereomers, although exceptions are known. This has been explained on the basis of a six-membered chair transition state in which the faces of the reaction partners are oriented so as to minimize 1,3 axial steric interactions 481108). This means that there is no simple way to prepare erythro aldols from cyclic ketones, since the enolates are geometrically fixed in the E geometry. 

We have prepared a number of titanium enolates by quenching the lithium analogs withchlorotitanium triisopropoxide 3, chloro- or bromotitanium tris(diethylamide) 15 or chlorotitanium tris(dimethylamide) 103 25). In mqst cases the solutions can be freed from the ether or THF and the stable liquid titanium enolates studied by NMR if so desired. In case of the amino derivative 186 flash distillation is possible. The H-NMR spectra of the distilled and non-distilled compound are identical and 

A number of other acyclic Z and E lithium enolates were quenched similarly. In all cases the stereochemistry at the enol double bond was retained, as shown by subsequent conversion into the corresponding silyl enol ether. Upon reacting the titanium enolates with aldehydes, very clean aldol addition occured ( 90% conversion at —78 °C). Generally, erythro-selectivity was observed irrespective of the geometry of the enolate. Equations 64 and 65 are typical25). 

In isolated cases diastereoselectivity is reversed 2S . Either acyclic transition states are transversed, or the usual pericycles are involved, having chair or boat conformations depending upon the enolate geometry, the substituents and the nature of the aldehyde 25 . These possibilities have also been discussed in irregularities reported for other enolates 48 109-m). For example, dicyclopentadienylchlorozirconium-109 , triphenyltin u0 and tris(dialkylamino)-sulfoniumnl (TAS) enolates also favor 

Variation of the ligands at titanium can lead to improvements. For example, enolates 197a b react with benzaldehyde to afford 92 8 and 97 3 mixtures of 195 a and 196a, respectively 25). Enolates 199-202, derived from ketones, lactones and lactams, add erythro-selectively to benzaldehyde to yield the corresponding aldols (erythro threo as 85 15, 91 9, 92 8, 58 42 and 88 12, respectively) 25,77). 

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