Bases Potassium hexamethyldisilazide

Recently, the ability of N-heterocyclic carbenes to promote the Staudinger reaction has been investigated using ionic liquids, in the presence of suitable base as pre-catalysts. According to the procedure suggested by Smith et al., a solution of base (potassium hexamethyldisilazide KHMDS, toluene as solvent) was added to the suspension of ionic liquid (triazolium salt) in Et O and stirred under N. Subsequently, the mixture was added of diphenylketene and of imine and stirred at room temperature before concentration in vacuo (Scheme 16.6). The order of addition of reactants is critical for the success of the synthesis [95]. 

Some interesting modifications with respect to the base-induced isomerization have recently been developed. For example, conversion of 4-hydroxy-l-thiophenyl-2-alkynes 299 into the corresponding 4-hydroxy-substituted thiophenylallenes 300 was achieved by treatment with potassium hexamethyldisilazide at low temperature (Scheme 8.79) [165], If the hydroxyl group is protected as the THP ether an elimination reaction occurred, resulting in the formation of an enyne instead of allene 300. 

KHMDS (potassium hexamethyldisilazide) is a strong non-nucleophilic base. 

The most widely used method for the preparation of free NHCs is the deprotonation of an azohum salt with NaH or KOBuf [10,14,37]. In the case of N,N -methylene-bridgcd bisimidazolium salts, the preparation of the free dicarbenes is only possible by the use of potassium hexamethyldisilazide (KHMDS) in toluene [14,41]. Other strong bases deprotonate the methylene bridge breaking the bisazol unit [42],... 

This asymmetric induction is strongly affected by the base. Asymmetric methylation of 32 occurred with retention of configuration when lithium 2,2,6,6-tetramethylpiperidide (LTMP) or LDA was used, while inversion of configuration was observed with potassium hexamethyldisilazide (KHMDS)... 

Z)-OL, -Unsaturated esters,l Wittig-Homer reactions generally show a preference for formation of (E)-alkenes. Thus (E)-a,p-unsaturated esters are obtained preferentially on reaction of aldehydes with trimethyl phosphonoacetate under usual conditions (potassium f-butoxide). Use of a highly dissociated base can favor (Z)-selectivity. The most effective base for this purpose is potassium hexamethyldisilazide, KN[Si(CH3)3]2, in combination with 18-crown-6, although even potassium carbonate with the crown ether is fairly effective. The (Z)-selectivity can be further enhanced by use of 1 as the phos-phonoester. Under these conditions, (Z)-unsaturated esters can be prepared from aliphatic and aromatic aldehydes with Z/E ratios as high as 50 1. The method is also useful for transformation of unsaturated aldehydes to (E,Z)-dienoates and (E,E,Z)-trienoates. 

Enolate hydroxylation (cf. 11, 108).2 Enolates of ketones or esters are oxidized by this oxaziridine to a-hydroxy carbonyl compounds. Yields are highly dependent on the base they are highest with potassium hexamethyldisilazide. Yields are generally higher than those obtained with the Vedejs reagent (MoOPH, 8, 207). 

The (Z)-selectivity is presumed to occur because of rapid elimination of the 3-hydroxyphosphonate before equilibration can take place. Several base and solvent combinations were explored, including triton B, K2CO3 and KOBu, but potassium hexamethyldisilazide with 18-crown-6 in THF gave the most... 

E)-Styrenes. The phosphoranium salts are prepared by alkylation of the phosphine immediately after its generation from the corresponding phosphine oxide. The stereoselectivity of the Wittig reaction with ArCHO is very sensitive to the base used. Potassium hexamethyldisilazide is the preferred base for obtaining ( )-styrenes. 

Potassium hexamethyldisilazide, KHMDS, has been used successfully in the past for a-deprotonation of sulfoxides. Aiming to probe the nature of the transition state in the reaction of a-metalated (i )-methyl //-tolyl sulfoxide with A -(benzylidene) aniline under kinetic conditions, the effect of the choice of the bases for the a-deprotonation on the reactivity and diastereoselectivity was studied, using LDA, LHMDS, NaHMDS, and KHMDS. Best yields anddiastereoselectivities (90%, 84 16) were achieved with LDA, whereas LHMDS showed diminished reactivity (50%) without a loss of diastereoselectivity (87 13). Improved yields and lower diastereoselectivities were recorded in reactions mediated by NaHMDS and KHMDS, providing the amine in 60% (dr 81 19) and 77% (dr 69 31) yields and diastereoselectivities, respectively (eq 64). 

The Julia reaction is remarkably versatile but it does need three steps to make the alkene addition, acylation, and reduction. A more recent version of the reaction cuts this down to one by using not a phenylsulfone but instead a sulfone carrying an electron-deficient heterocycle, for example a tetrazole. The anion of the sulfone is made with a strong base (here potassium hexamethyldisilazide, KHMDS—see p. 635) and is added to an aldehyde to give an alkene directly. 

The first DKR of a-aminoaldehydes was reported by Reiser s group who treated aldehydes 1-3 (Scheme 1.42) with chiral phosphonates in the presence of a slight excess of base such as potassium hexamethyldisilazide (KHMDS). According to the nature of the phosphonate, the E- or the Z-product was selectively obtained (Scheme 1.42, Table 1.1)." ... 

Some catalysts such as potassium hexamethyldisilazide (K[NSiMc3]2) lead to high molar mass PTMC or TMC-based block copolymers with high efficiency and desired end groups. The polymerisation can be carried out in solution at room temperature (Lemmouchi et al., 2008). The resulting polymers contain no traces of metal... 

The most general protocol (eq 10) has therefore been based on potassium hexamethyldisilazide (KHMDS) as the base addition of trisyl azide at —78 °C and then acetic acid at the same temperature. Excellent levels of diastereoselectivity are ohsCTved with most substrates and the method has been used widely in the enantioselective synthesis of a-amino acids from chiral iniides. Chemoselective azidation of an imide enolate in the presence of an ester function has been demonstrated (eq 11). The product distribution is nevertheless finely balanced, as discovered with the respective dimethyl and dihenzyl ethers of the 3,5-substituted phenylacetyl imide (3) (eq 12). ... 

Base for a-Deprotonation of Carbonyl Compounds. Potassium hexamethyldisilazide, KN(TMS)2 (KHMDS) has been... 

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