Protection hexamethyldisilazide

Parts A and B of the procedure correspond to preparation of lithium tetramethylpiperidide, and its use in the in situ preparation and addition of dibromomethyllithium to the ester 1 producing tetrahedral intermediate 2. In Part C a mixture of lithium hexamethyldisilazide and lithium ethoxide is prepared for addition in Part D to the solution of 2. The silazide base serves to deprotonate the mono and dibromo ketones that are formed on initial warming of the reaction to -20°C, thus protecting them as the enolate anions 4 and 3. Addition of the sec-butyllithium in Part... 

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. 

An alternate approach, which utilizes lithium amides such as lithium hexamethyldisilazide or lithium amide, was also efficient in converting 2-chloropyridine into 2-aminopyridine (7.73.), In these reactions 2-(dicyclohexylphosphino)biphenyl was used as catalyst and the silyl protecting group was removed by TBAF.94... 

Lactams may be alkylated at the a-position by reaction with a strong base, such as LDA or hexamethyldisilazide, followed by treatment with an alkyl halide. Baldwin and coworkers have used this methodology in their synthesis of unnatural amino acids from protected pyroglutamates (equation 81)563. The same reaction has been used for alkylating 5- to 9-membered lactams564. It is noteworthy that a-alkylated 7- to 9-membered lactams are... 

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

NPf) protected amine. The final ring formation was carried out by deprotonation of the benzylic methyl with potassium hexamethyldisilazide (KHMDS) which then added to the methyl ester to provide ketone 316. This compound was then carried on through a series of transformations to provide a common intermediate for every member of the FR900482 family. 

This reaction can sometimes be useful in synthesis. In the Honda et al. formal synthesis of securinine,2h N-benzylamino-ketone (97) was treated with lithium hexamethyldisilazide and then sorbic anhydride. This gave dienyl ester 98 by O-alkylation of the initially formed enolate anion. When the nitrogen protecting group was... 

The myo-inositol acceptor l-0-allyl-2,3,4,5-tetra-0-benzyl-D-myo-inositol was synthesized from meso-2,5-di-0-benzoyl-myo-inositol for use in the total synthesis of a heptaose mimetic, a GPI anchor compound of T. brucei (see Vol. 32, p.71. ref. 156). The inositol was desymmetrized using the bis(spiroketal) protected intermediate 175 to enable the stepwise glycosylation at 0-6 and attachment of a phosphoglyceride moiety at 0-1. Cleavage of the dispoke was effected by oxidizing the thiophenyl substituents with mCPBA and then treating the product disulfone with lithium hexamethyldisilazide in THF. In a similar synthesis... 

A new and convenient synthesis of small-ring ketones is based on the anion derived from a protected cyanohydrin. The cyclization step (14) - (15) proceeds in 62% yield by employing sodium hexamethyldisilazide in refluxing benzene (Scheme 1). 

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