Oxidations hexamethyldisilazide

Silyl enol ethers, 23, 77, 99-117,128 Silyl enolates, 77 Silyl peroxides, 57 Silyl triflate, 94 Silyl vinyl lithium, 11 (E)-l -Silylalk-1 -enes, 8 Silylalumimum, 8 Silylation, 94 reductive, 26 a-C-Silylation, 113 O-Silylation.99,100 / -SilyIketone, 54 non-cydic, 55 Silylmagnesium, 8 Silyloxydienes, 112 Sodium hexamethyldisilazide, 89 Sodium thiosulphate pentahydrate, 59 Stannylation, see Hydrostannylation Stannylethene, 11 (Z)-Stilbene, 70 (E)-Stilbene oxide, 70 /3-Styryltrimethylsilane, 141 Swern oxidation. 84,88... 

In the reaction of 1,3-dithiane oxide anions with iV-acylimidazoles the optimum procedure involved a sodium hexamethyldisilazide/butyllithium mixture as base [101]... 

When one of the reacting partners in the Wittig-Horner reaction, either the phosphine oxide or the carbonyl compound, has a double bond, the product is a diene. The Wittig-Horner reaction was utilized by Smith and coworkers in the total synthesis of milbemycin (equation 98)170. They found that when sodium hexamethyldisilazide was employed as a base, the desired E-diene selectivity is high (85%). Some examples from the literature where the Wittig-Horner reaction has been utilized for the construction of E-double bonds present in dienes and polyenes are given in Table 19171. 

Page et al. (see [298] and references therein) have shown that generally excellent stereocontrol in organic reactions can be obtained by using DITOX (1,3-dithiane-l-oxide) derivatives as chiral auxiliaries. The one-pot stereo-controlled cycloalkanone synthesis given here outlines some aspects of the chemistry worked out for efficient acylation-alkylations steps. Of note are the use of N-acyl imidazoles under mixed base (sodium hexamethyldisilazide/n-butyllithium) conditions to yield the lithium enolates of 2-acyl-l,3-dithiane-l-oxides) and the sequential alkylation-cyclization of the latter (steps (iv) and (v)). 

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). 

For the case of tri(o-tolyl)phosphine-ligated catalysts, the upper pathway appears to predominate. Oxidative addition occurs first via loss of a ligand from the bisphosphine precursor to form the oxidative adduct, which exists as a dimer bridged through the halogen atoms (equation 33). This dimer is broken up by amine, the coordination of which to palladium renders its proton acidic. Subsequent deprotonation by base leads to the amido complex, which can then reductively eliminate to form the product. When tert-butoxide is used as the base, the rate is limited by formation of and reductive elimination from the amido complex, while for the stronger hexamethyldisilazide, the rate-determining step appears to be oxidative addition. ... 

Treatment of a,/ -unsaturated lactam 252 with lithium hexamethyldisilazide (LiHMDS) followed by oxidation of the resulted dienolate with A -sulfonyloxaziridine 33 gave rise to the a-hydroxylated product 253 in 38% yield <2001TL7879>. The y-hydroxy product 354 was also isolated in 35% yield. 

NMR speetroseopie studies of Li- N labeled lithium hexamethyldisilazide in solvents ineluding THF, 2-methyltetrahydrofuran (2-MeTHF), 2,2-dimethyltetrahydrofuran (2,2-Me2THF), diethyl ether (Et20), t-butyl methyl ether (Bu OMe), n-butyl methyl ether (Bu OMe), tetra-hydropyran (THP), methyl i-propyl ether (Pr OMe), and trimethylene oxide (oxetane) have been used to eharaeterize the nature of the solvated speeies. Mono-, di-, and mixed-solvated dimers ean be identified in the limit of slow solvent exehange, but ligand exehange is too fast to observe... 

Recently, the Homer coupling was utilized by Smith and coworkers in the total synthesis of milbe-mycin (equation 59). In an excellent example of the sensitivity of the alkene stereochemistry to the base utilized, when the phosphine oxide anion (253) was generated with NaH as the base the ( ) (Z) ratio was 7 1, but epimerization occurred at the aldehyde methine (252) and the yield was only 15%. Switching to KHMDS, the yield improved to 74% but virtually a 1 1 ratio of alkenes formed. Use of sodium hexamethyldisilazide solved these difficulties, forming the desired ( )-diene (254) in a 7 1 ratio with the (Z)- in 85-95% yield. Additional examples of the use of phosphine oxides in the synthesis of milbemy-cins and FK-506 are presented in Section 3.1.11.4. 

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. 

Mitsunobu reaction with alcohols and subsequent oxidation with MCPBA. Deprotonation of such a sulfone with sodium or potassium hexamethyldisilazide in DME followed by reaction with an aldehyde results in an ( )-alkene. 

Potassium dichromate, 3 24 Potassium diisopropylamide, 324 Potassium ethanethiolate, 325 Potassium fluoride, 279, 325-326 Potassium formate, 329 Potassium-Graphite, 326 Potassium hexamethyldisilazide, 326-327 Potassium hydride, 327-328 Potassium hydrogen persulfate, 328 Potassium hydroxide-Alumina, 328 Potassium iodide-Boron(ill) iodide, 329 Potassium iodide-Zinc-Phosphorus(V) oxide, 329... 

Exposure of 877 to lithium hexamethyldisilazide ( — 78° 0 °C) results in intramolecular alkylation of the ester enolate to afford 878. Reduction of the ester to an alcohol and oxidation of sulfur followed by elimination of the resulting sulfoxide introduces the unsaturation leading to 869. This is then converted to ( H- )-heliotridine (850) by reduction of the carbonyl group. 

Chiral N-sulfonyloxaziridines are useful reagents for the asymmetric synthesis of sulfoxides, selenoxides, and other substrates. Davis and co-workers <97JOC3625> have reported the first example of an e.vtt-camphorylsulfonyloxaziridine 175. prepared by the MCPBA oxidation of camphor inline 174 in the presence of potassium hexamethyldisilazide. This compound was then studied in various asymmetric oxidation applications. 

---