Sodium hexamethyldisilazides

To a solution of the silylated glycinate (50 mmol) in ether (50 ml), cooled to —10 to 0°C, was added a solution of sodium hexamethyldisilazide (55 mmol) in ether (100ml) with stirring. Stirring was continued at ambient temperature for a short time, and then the alkyl halide (50 mmol) was added dropwise. The mixture was heated under reflux for 10-15 h, cooled, filtered, and the product was distilled directly (52-70%). 

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. 

Finn and co-workers [87], who treated aromatic aldehydes with a mixed titanium-phosphorus ylide formed from iPrOTiCl3, (Me2N)3P=CH2 and an excess of sodium hexamethyldisilazide as base (Scheme 2.52). Symmetrical allenes 167 were thereby obtained with moderate to good yield. 

Tetrahydro-l,4-oxazin-2-ones can be deprotonated and then reacted with electrophiles. Thus, for example, the nonlabeled analog of compound 81 was deprotonated at the 3-position with sodium hexamethyldisilazide and ethylated using ethyl iodide. The reaction was performed in a 1 10 mixture of hexamethylphosphoramide (HMPA) and tetrahydrofuran <1998T10419>. If a dihalide is used and the oxazine has a free 4-nitrogen, cycloalkylation can be achieved as shown in the reaction of 219 to give 220 (Equation 17) <1993LA477>. 

Reaction of achiral biscyclopentadienyl zirconium-( /2-acyl-C,0) complexes, such as la and lb, with sodium hexamethyldisilazide generates the di-hapto enolates 2a and 2b91. Enolate 2b is believed to adopt a Z geomeLry, only one isomer was observable by H-NMR spectroscopy (d.r. >98 2). 

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)). 

The acid is converted with thionyl chloride into the corresponding acid chloride, which reacts in a second step with the anion of the Lvans oxazolidinone 3714 to give an /V-acyloxazolidinone. This is then deprotonated with sodium hexamethyldisilazide and subsequently alkylated selectively with methyl iodide to produce compound 8. 

Starling with the N-acyl derivative, sodium hexamethyldisilazide selectively forms the Z-enulate 38 (amides usually form Z-eno-lates). Chelate formation between sodium and the two oxygen atoms requires a conformation for 38 in which the isopropyl group shields the bottom of the molecule, so attack by the nucleophile oc curs from above. This method generally provides outstanding selectivity. The Fmns auxiliary has also been used successfully to achieve stereocontrol in aldol15 and Diels-Atder reactions.16... 

Sodium hexamethyldisilazide Silanamine, 1,1,1 -trimethyl-N-(trimethylsilyl)-, sodium salt (1070-89-9), 76, 37... 

The Step 2 product (1.0 mmol) dissolved in 5 ml THF at —40°C was treated with 1.1 ml 1M sodium hexamethyldisilazide (1.1 mmol) in THF and after 30 minutes the mixture was further treated with 2,5-dichlorobenzenesulfonyl chloride (1.1 mmol). The solution was stirred overnight at ambient temperature and then treated with saturated NH4C1 solution and concentrated. The residue was dissolved in EtOAc, then washed with brine, dried with Na2S04, concentrated, and an oil isolated. The residue was purified by MPLC using EtOAc/hexane, 2 1, and the product isolated as a colorless viscous oil. 

Macrocyclic ketones. A recent method for synthesis of macrocyclic ketones involves intramolecular alkylation of protected cyanohydrins. Sodium hexamethyldisilazide... 

Deprotonation of the benzo-l,3-dithiole dioxide 259 with -BuLi or sodium hexamethyldisilazide (NaHMDS) and subsequent reaction of the resulting carbanion with pivaldehyde gave a mixture of products 260 and 261 (Equation 21) <1995JO02174>. 

Sodium hexamethyldisilazide (NaHMDS) is a sterically demanding and strong but non-nucleophilic base. 

The Julia-Kocienski olefination of heterocyclic sulfones and aldehydes, which is an alternative to the modified Julia olefination, forms alkenes with good -selectivity. First, sulfone 54 is deprotonated in the a-position to the sulfur by sodium hexamethyldisilazide (NaHMDS) and the sulfur-stabilized anion 55 then adds to the alde-... 

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