LiHMDS

The Darzens condensation reaction has been used with a wide variety of enolate equivalents that have been covered elsewhere. A recent application of this important reaction was appljed toward the asymmetric synthesis of aziridine phosphonates by Davis and coworkers.In this application, a THF solution of sulfinimine 34 (0.37 mmol, >98% ee) and iodophosphonate 35 (0.74 mmol) was treated with LiHMDS (0.74 mmol) at -78 °C to give aziridine 36 in 75% yield. Treatment of 36 with MeMgBr removed the sulfinyl group to provide aziridine 37 in 72% yield. 

Williams and McClymont have observed that acylation reactions of the dianion of 2-(5-oxazolyl)-l,3-dithiane (15) lead to formation of 4,5-disubstituted oxazole products through a Comforth rearrangement pathway under base-induced, low-temperature conditions. For example, deprotonation of 15 with LiHMDS (3.0 equivalents) at -78°C, followed by addition of benzoyl chloride or p-chlorobenzoyl chloride and warming to 0°C, provided 16 in 74% and 47% yield, respectively. 

HYPHAT Bis(tetrachlorobenzenediolato)mono(l,2-diarylethanediolato)phosphate(v) LiHMDS Lithium l,l,l,3>3,3-hexamethyl-disilazane... 

Evans Jr. and coworkers reported a similar olefination reaction employing spirooxyphosphoranes of type 66. Upon treatment with a strong base (LiHMDS) and subsequent addition of benzaldehyde, the reaction proceeded to form anionic P(VI) intermediates (67,6 -106 to -116 ppm) that decomposed at room temperature to form the corresponding olefins and spiropentaoxyphosphoranes [ 105]. The stereoselectivity (E Z ratio) of the double bond-forming reaction depended upon the conditions evidence indicated the possibility of kinetic or thermodynamic control (Scheme 21). 

Scheme 1.1 shows data for the regioselectivity of enolate formation for several ketones under various reaction conditions. A consistent relationship is found in these and related data. Conditions of kinetic control usually favor formation of the less-substituted enolate, especially for methyl ketones. The main reason for this result is that removal of a less hindered hydrogen is faster, for steric reasons, than removal of a more hindered hydrogen. Steric factors in ketone deprotonation are accentuated by using bulky bases. The most widely used bases are LDA, LiHMDS, and NaHMDS. Still more hindered disilylamides such as hexaethyldisilylamide9 and bis-(dimethylphenylsilyl)amide10 may be useful for specific cases. 

In contrast to LDA, LiHMDS favors the Z-enolate.14 Certain other bases show a preference for formation of the Z-enolate. For example, lithium 2,4,6-trichloroanilide, lithium diphenylamide, and lithium trimethylsilylanilide show nearly complete Z-selectivity with 2-methyl-3-pentanone.15... 

Very significant acceleration in the rate of deprotonation of 2-methylcyclohexanone was observed when triethylamine was included in enolate-forming reactions in toluene. The rate enhancement is attributed to a TS containing LiHMDS dimer and triethylamine. Steric effects in the amine are crucial in selective stabilization of the TS and the extent of acceleration that is observed.18... 

Chelation affects the stereochemistry of enolate formation. For example, the formation of the enolates from a-siloxyesters is Z for LiHMDS, but E for LiTMP.19... 

It has been suggested that this stereoselectivity might arise from a chelated TS in the case of the less basic LiHMDS. 

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