Hexamethylphosphoric Triamide enolate formation

On the other hand, the predominant formation of the diastereomeric aldols 3 b results from the titanium enolate 1 b of (S )-5,5-dimethyl-4-tert-butyldimethylsilyloxy-3-hexanone. For this purpose, the ketone is first deprotonated with A-(bromomagnesio)-2,2,6,6-tetramethylpiperidine and the magnesium enolate, presumably (E) configurated, formed is thereby treated with hexamethylphosphoric triamide and triisopropyloxytitanium chloride. After sonification, the aldehyde is added to give predominantly aldol adducts 3b the diastereomeric ratio of 3b/2b surpasses 95 5 and the chemical yields range from 85 to 88%53b. 

Formation of the enolate from 1-methyl-2-pyrrolidone (a y-lactam) is accomplished by treatment with lithium diethylamide in hexamethylphosphoric triamide/benzene at — 20 °C. Addition of bromomethane or (chloromethyl)benzene then results in good yield of the a-alkylation product15. 

The formation of ( )-enolates is favored in tetrahydrofuran alone, whereas addition of metalchelating solvents such as hexamethylphosphoric triamide, A,A, /V, Ar-tetranncthylcthylenedi-amine or l,4-dimethyltetrahydro-2(l//)-pyrimidinone reverses the enolate configuration to the (Z)-product. The best seleetivities were obtained with 45% l,3-dimethyltetrahydro-2(l//)-pyrimidinone. In comparison to lithium diisopropylamide in 23% hexamethylphosphoric triamide. slightly bulkier bases, i.e., lithium hexamethyldisilanazide, have proved to be more E selective256. 

Enolization of macrocyclic enediyne lactones 11 results surprisingly in the formation of (/ . )-silyl ketene acetals 12 or 13 [lithium hexamethyldisilazanide is usually a lithium diisopropyl-amide/hexamethylphosphoric triamide substitute giving rise to the formation of (Z)-silyl ketene acetals] whereas (Z)-12a,b are obtained in the presence of hexamethylphosphoric triamide. 

The reaction between cyclic ketone enolates and diethyl phosphorochloridite followed by aerial oxidation of the intermediate P(III) esters, yields mixtures of C - and (7-phosphorylated products. The formation of the (1 -oxoalkyl)phosphonic diesters was optimized using diethyl ether as solvent (although better yields were sometimes obtained for reactions in Et20/THF when hexamethylphosphoric triamide was added) when the... 

The use of hexamethylphosphoric triamide and triethylamine as ligands in place of the usual phosphines in the addition of ester enolates to 1 results in the formation of cyclopropanes via the unusual initial attack at the central carhon atom (eq 6). The process is very limited with respect to nucleophile, however, as only branched ester enolates produce a cyclopropane. N,NJ 1, N -tetramethylethylenediamine and carbon monoxide as hgands also promote central carbon attack by ester enolates. ... 

Due to its steric demand, LDA even leads to the less substituted enolate 18a from 2-phenylcyclohexanone, and the formation of the thermodynamically favored conjugated regioisomer is widely suppressed, as proven by oxidation with Vedejs reagent MoOj pyridine hexamethylphosphoric triamide (HMPA) leading diastereoselectively to hydroxyketone 19 [30]. To give a more recent example, the... 

Control of Regioselectivity and Stereoselectivity. The recognition by Ireland and co-workers that Hexamethylphosphoric Triamide has a profound effect on the stereochemistry of lithium enolates has led to the examination of the effects of other additives, as the ability to control enolate stereochemistry is of utmost importance for the stereochemical outcome of aldol reactions. Kinetic deprotonation of 3-pentanone with Lithium 2,2,6,6-Tetramethylpiperidide at 0 C in THF containing varying amounts of HMPA or TMEDA was found to give predominantly the (Z)-enolate at a base ketone additive ratio of ca. 1 1 1, whereas with a base.ketone.additive ratio 1 0.25 1, formation of the ( )-enolate was favored (Table I). This remarkable result contrasts with those cases where HMPA base ratios were varied towards larger amounts of HMPA, which favored formation of the (Z)-enolate. ... 

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