Potassium hexamethyldisilazides

Azatriquinadiene (2,3-dihydroazatriquinacene) 39 has been efficiently synthesized from enamine 389. Enamine 389 on treatment with bromine followed by aqueous work-up afforded the tetrabromohemiaminal 390. Dehydrohalogenation of 390 with potassium hexamethyldisilazide (KHMDS) and compound 391 on reduction with lithium aluminium hydride yielded the target molecule azatriquinadiene 39 in good overall yield (Scheme 85) <2000JOC7253>. 

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. 

Spirocyclic oxindole 60 was synthesized by [3,3]-sigmatropic rearrangement of the Af-phenyl-O-acylhydroxamic acid 58 (equation 19). The potassium enolate formed by treatment of 58 with potassium hexamethyldisilazide at low temperature rearranged to 59, which easily cyclized to the spirocyclic oxindole 60. Spirooxindoles were previously synthesized by Wolff and Taddei. The spirooxindole 60 was formed in 51% yield from cyclohexanecarboxylic acid after heating the preformed lithium salts of phenyl hydrazide 61 to 205-210 °C. 

Almost complete retention of chirality was achieved in the alkylations of l-propionyl-l,4-dihydro-2//-3,1-benz-oxazines 242 bearing a stereogenic center in the substituent at position 2 (TBDPS = /< rt-butyldiphenylsilyl, KHMDS = potassium hexamethyldisilazide). The alkylations took place with high de s (70-92%) in favor of isomers 243, isolated after chromatographic separation. The allyl-substituted compound 243 (R = allyl) was reduced with LAH to yield the enantiopure (R)-3-methylpent-4-en-l-ol 244 and the N-unsubstituted 3,1-benzoxazine 245 as a 5 1 diastereomeric mixture (Scheme 45) <2000JOC6540>. 

The phosphorylated bromobenzamide derivative 180 cyclizes to produce the phosphorylated isoindolinone on exposure to an excess of potassium hexamethyldisilazide (KHMDS) (Equation 116) <2000T1491>. 

Iminomethyldithiolane 7 can be deprotonated with potassium hexamethyldisilazide in THF at — 78 °C and alkylated to give 8 in good yield and with high diastereoselectivity. From 8, a-aminoalkylphosphonic acids 5 are easily obtained by mild acidic hydrolysis. 

The racemic C2-symmetric l,3-diacyl-1,3-imidazolidinones 1 and 2 can be obtained from either rra/t.v-l,2-diaminocyclohexane or nwM-l,2-diphenyl-l,2-ethanediamineu 13. On deprotona-tion with potassium hexamethyldisilazide in THF at —78 C these furnish dianions which are alkylated by activated halides or iodomethane (R2X) to give mixtures of diastereomeric dialky-lated products 3-5 and 6-812,13. 

Butylsodium-Tetramethylethylene-diamine, 59 Lithium hydride, 165 Potassium /-butoxide, 252 Potassium diisopropylamide, 255 Potassium hexamethyldisilazide, 257 Potassium hydride, 257 Methoxylation... 

Enol carbonates Di-f-butyl dicarbonate, 94 Potassium hexamethyldisilazide, 257 Enol esters Enol acetates Acetic anhydride, 93 Bis(7i5-cyclooctadienyl)ruthenium(II), 35... 

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

To a suspension of methyltriphenylphosphonium bromide (0.196 g, 0.55 mmol) in 1 mL of benzene under argon at room temperature was added a 0.5 M solution of potassium hexamethyldisilazide in toluene (1.2 mL, 0.6 mmol), and the yellow solution was stirred for 5 min. A solution of keto-ester (1) (0.1 g, 0.274 mmol) in 1.5 mL of benzene was added and the orange solution was stirred for 3 h at room temperature. The reaction mixture was filtered through a plug of silica gel with 40% ethyl acetate/hexane. The filtrate was concentrated to afford a solid. Flash chromatography (30% 40% dichloromethane/hexane) yielded the desired product (3) as a white solid (0.077 g, 78%) m.p. 167°-168°C Rf 0.4 (50% dichloromethane/hexane). The structure of the product was also confirmed using IR, iH NMR and mass spectroscopy. 

Fig. 6. Nicolaou s total synthesis construction of the maleic anhydride moiety. KHMDS = potassium hexamethyldisilazide, DIBAL = diisobutyl-aluminium hydride, acac = acetylacetonate, Ms = methanesulfonyl.

Hydrogenation of olefin 4, followed by 0-desilylation and 0-tosylation next procured tosylate 3, which cyclised readily when exposed to excess potassium hexamethyldisilazide. Elaboration of the ketophosphonate side chain of 20 was accomplished by condensing ester 2 with the lithiated anion of dimethyl methylphosphonate. After concurrent removal of the 1,3-dioxolane acetal and the MOM ether from 20, the resulting secondary alcohol was oxidised with pyridinium chlorochromate (PCC) to produce methyl ketone 1. 

Y—F = fluorinating agent, e.g. Y-fluoro sultams KHMDS = potassium hexamethyldisilazide... 

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],... 

Potassium Hexamethyldisilazide Linear combination of atomic orbitals Lithium diisopropylamide Lithium hexamethyldisilazide Lithium isopropylcyclohexylamide Lithium 2,2,6,6-tetrame thy) p iper i d i de Lowest unoccupied molecular orbital weta-Chloroperoxybenzoic acid Methyl... 

Danopoulos and co-workers reported on the preparation of NHC ligands with pendant indenyl and fluorenyl groups.19 Deprotonation of the alkyl -indene or -fluorene imidazolium salts with one equivalent of potassium hexamethyldisilazide leads to NHCs functionalised with neutral indene or fluorene moieties (IndH-NHC and F1H-NHC). Further deprotonation with... 

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)... 

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