Khmds

Potassium Amides. The strong, extremely soluble, stable, and nonnucleophilic potassium amide base (42), potassium hexamethyldisilazane [40949-94-8] (KHMDS), KN [Si(CH2]2, pX = 28, has been developed and commercialized. KHMDS, ideal for regio/stereospecific deprotonation and enolization reactions for less acidic compounds, is available in both THF and toluene solutions. It has demonstrated benefits for reactions involving kinetic enolates (43), alkylation and acylation (44), Wittig reaction (45), epoxidation (46), Ireland-Claison rearrangement (47,48), isomerization (49,50), Darzen reaction (51), Dieckmann condensation (52), cyclization (53), chain and ring expansion (54,55), and elimination (56). 

Structural effects on the rates of deprotonation of ketones have also been studied using veiy strong bases under conditions where complete conversion to the enolate occurs. In solvents such as THF or DME, bases such as lithium di-/-propylamide (LDA) and potassium hexamethyldisilylamide (KHMDS) give solutions of the enolates in relative proportions that reflect the relative rates of removal of the different protons in the carbonyl compound (kinetic control). The least hindered proton is removed most rapidly under these... 

They are cleaved by refluxing in ethanol," methanolic sodium carbonate, TFA, or ammonium chloride. The aminoborane was found to be stable to LDA and KHMDS."... 

For the TBDMS group, KHMDS, THF, TBDMSOTf, -78°, 98% yield. The TDS group behaves similarly, except that it is slightly more hindered. 

In a separate report, the Darzens reaction was recently used by Barluenga, Concellon, and coworkers for the preparation of enantiopure a"-amino a,P-epoxy ketones. Accordingly, the Z enolate of a"-amino a-bromo ketone 41 was generated with KHMDS at -100°C. Benzaldehyde was added, and trans epoxyketone 42 was isolated in 87% yield and >95% de. ... 

BINAP 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl KHMDS potassium bis(trimefhylsilyl)amide... 

A range of amide bases can be employed. Typically LDA is used, but in certain complex cases, LiNEt2 was found to be more effective. One exceptional case involves the ostensibly simple alkylation of a cyanohydrin acetonide with allyl chloride (Eq. 12). Here, use of LDA gave essentially none of the desired product 39, whereas KHMDS or LHMDS gave excellent yields [5]. 

The difference in reactivity between the anions generated from LDA and LHMDS is difficult to rationalize, but nonetheless reproducible. The same effect has been observed with substituted allyl halides and propargyl halides. Instability of the product under the reaction conditions may account for this phenomenon. Thus, for alkylation of allylic and propargylic halides, LHMDS and KHMDS are the bases of choice. 

The conditions can be modified to favor the Z-isomer. Use of KHMDS with 18-crown-6 favors the Z-product.255 This method was used, for example, to control the... 

V-Sulfonyloxaziridines are useful reagents for oxidation of enolates to a-hydroxyketones.251 The best results are frequently achieved by using KHMDS to form the enolate. The hydroxylation occurs preferentially from the less hindered enolate face. 

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