KHMDS hexamethyldisilazane

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). 

The CDE rings of camptothecin were synthesized via an intramolecular Knoevenagel condensation of 124 (Equation 30) <2004TL7247>. The tricyclic dihydropyridone 125 was aromatized to the pyridone with NBS/ KHMDS (NBS - iV-bromosuccinimide, KHMDS - potassium hexamethyldisilazane). 

KHMDS LAH potassium hexamethyldisilazane lithium aluminium hydride... 

AD-mix-P 9-BBN Bn Boc Bz BOM CDI m-CPBA CSA Cy DBU DDQ DEAD DIAD DIBAL-H DIPT DME DMF DMAP DMSO EDC HMPA HOBT KHMDS LDA MEM MOM MoOPH NaHMDS NBS NMM NMO Piv PMB Reagent for Sharpless asymmetric dihydroxylation 9-Borabicyclo[3.3.1 ]nonyl Benzyl t-Butoxy carbonyl Benzoyl B enzyloxy methyl Carbonyldiimidazole m-Chloroperoxybenzoic acid Camphorsulfonic acid Cyclohexyl 1,8 -Diazabicy clo[5.4.0] undec-7-ene 2,3 -Dichloro-5,6-dicyano-p-benzoquinone Diethyl azodicarboxylate Diisopropyl azodicarboxylate Diisobutylaluminum hydride Diisopropyl tartrate Dimethoxyethane A,N-Dimethylformamide 4-Dimethylaminopyridine Dimethyl sulfoxide N-(3-Dimethylaminopropyl)-A -ethylcarbodiimide Hexamethylphosphoramide 1 -Hydroxybenzotriazole Potassium hexamethyldisilazane Lithium diisopropylamide Methoxyethoxymethyl Methoxymethyl Oxidodiperoxymolybdenum(pyridine)(hexamethylphophoramide) Sodium hexamethyldisilazane N - Bromosuccinimide A-Methylmorpholine A-Methylmorpholine A-oxide Pivaloyl /j-Methoxybenzyl... 

Ac, acetyl AIBN, azobis(isobutanonitrile) All, allyl AR, aryl Bn, benzyl f-BOC, ferf-butoxycarbonyl Bu, Butyl Bz, benzoyl CAN, ceric ammonium nitrate Cbz, benzyloxycarbonyl m-CPBA, m-chloroperoxybenzoic acid DAST, diethylaminosulfur trifluoride DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DCC, /V. /V - d i eye I oh e x y I c ar bo -diimide DCM, dichloromethyl DCMME, dichloromethyl methyl ether DDQ, 2,3-dichloro-5,6-dicyano-l,4-benzoquinone DEAD, diethyl azodicarboxylate l-(+)-DET, L-(+)-diethyl tartrate l-DIPT, L-diisopropyl tartrate d-DIPT, D-diisopropyl tartrate DMAP, 4-dimethylaminopyridine DME, 1,2-dimethoxyethane DMF, /V./V-dimethylformamide DMP, 2,2-dimethoxypropane Et, ethyl Im, imidazole KHMDS, potassium hexamethyldisilazane Me, methyl Me2SO, dimethyl sulfoxide MOM, methoxymethyl MOMC1, methoxymethyl chloride Ms, methylsulfonyl MS, molecular sieves NBS, N-bromosuccinimide NIS, /V-iodosuccinimide NMO, /V-methylmorpho-line N-oxide PCC, pyridinium chlorochromate Ph, phenyl PMB, / -methoxvbenzyl PPTs, pyridiniump-toluenesulfonate i-Pr, isopropyl Py, pyridine rt, room temperature TBAF, tetrabutylammonium fluoride TBS, ferf-butyl dimethylsilyl TBDMSC1, f-butylchlorodimethylsilane Tf, trifhioromethylsulfonyl Tf20, trifluoromethylsulfonic anhydride TFA, trifluoroacetic acid THF, tetrahydrofuran TMS, trimethylsilyl TPAP, tetra-n-propylammonium perruthenate / -TsOH. / -toluenesulfonic acid... 

KHMDS = potassium hexamethyldisilazane s-BuOK = potassium 1-methylpropoxide LICA = lithium isopropylcyclohexylamide. b Refers to the RjS ratio at the newly generated a-hydroxy chiral carbon atom. 

Typically, nonstabilized ylides are utilized for the synthesis of (Z)-alkenes. In 1986, Schlosser published a paper summarizing the factors that enhance (Z)-selectivity. Salt effects have historically been defined as the response to the presence of soluble lithium salts. Any soluble salt will compromise the (Z)-selectivity of the reaction, and typically this issue has been resolved by the use of sodium amide or sodium or potassium hexamethyldisilazane (NaHMDS or KHMDS) as the base. Solvent effects are also vital to the stereoselectivity. In general, ethereal solvents such as THF, diethyl ether, DME and t-butyl methyl ether are the solvents of choice." In cases where competitive enolate fomnation is problematic, toluene may be utilized. Protic solvents, such as alcohols, as well as DMSO, should be avoided in attempts to maximize (Z)-selectivity. Finally, the dropwise addition of the carbonyl to the ylide should be carried out at low temperature (-78 C). Recent applications of phosphonium ylides in natural product synthesis have been extensively reviewed by Maryanoff and Reitz. 

Abbreviations Ac acetyl Bn benzyl Cu(OTf)2 copper triflate Et ethyl HOTf trifluoromethanesulfonic acid KHMDS potassium hexamethyldisilazane Kim potassium imidazole / Hx / Hexyl Me methyl ... 

The treatment of 3-propionyl-3,4,5,6-tetrahydro-l,3,4-oxadiazin-2-one 194 with chlorotrimethylsilane in the presence of the non-nucleophilic base, potassium hexamethyldisilazane (KHMDS), in THF yields enol silane 195 (Equation 28) <2002OL3739>. Compound 195 is used as a starting material for subsequent aldol reactions. 

KHMDS potassium hexamethyldisilazane, potassium bis(trimethylsilyl)amide... 

Their stability at low temperature means that lithium enolates are usually preferred, but sodium and potassium enolates can also be formed by abstraction of a proton by strong bases. The increased separation of the metal cation from the enolate anion with the larger alkali metals leads to more reactive but less stable enolates. Typical very strong Na and K bases include the hydrides (NaH, KH) or amide anions derived from ammonia (NaNH2, KNH2) or hexamethyldisilazane (NaHMDS, KHMDS). The instability of the enolates means that they are usually made and reacted in a single step, so the base and electrophile need to be compatible. Here are two examples of cyclohexanone alkylation the high reactivity of the potassium enolate is demonstrated by the efficient tetramethylation with excess potassium hydride and methyl iodide. 

---