Cyclizations lithium hexamethyldisilazide

DIAZO TRANSFER / -Tolucncsulfonyl azide. DICHLOROVINYLATION Trichloroethylene. DIECKMANN CYCLIZATION Lithium hexamethyldisilazide. 

An elegant cyclization-cleavage strategy has been devised for the removal of resin-bound 1,3-amino alcohol derivatives 392 as l,3-oxazin-2-ones 393 upon treatment with lithium hexamethyldisilazide (LiHMDS) (Equation 42) <20010L3177>. 

The /3-amino esters 387, obtained by hydrolysis of the corresponding /3-amino amides, have been cyclized in the presence of lithium hexamethyldisilazide (LHMDS)/THF to furnish the /ram-3,4-disubstituted azetidin-2-ones (Scheme 58) <2001JOC9030>. 

For the corresponding cyclization of acetylenic amides 418, Nagasaka etal.347,347a used a mixture of silver(i) triflate and lithium hexamethyldisilazide as the precatalyst. The process is probably initiated by the coordination of AgN(SiMe3)2 (generated in situ from AgOTf and LHMDS) to the triple bond, followed by nucleophilic attack of the lithium amide at the activated alkyne which affords (ZVy-alkylidene-y-butyrolactams 419 in high yields (Scheme 122). 

Spirocyclic oxindole 60 was synthesized by [3,3]-sigmatropic rearrangement of the Af-phenyl-O-acylhydroxamic acid 58 (equation 19). The potassium enolate formed by treatment of 58 with potassium hexamethyldisilazide at low temperature rearranged to 59, which easily cyclized to the spirocyclic oxindole 60. Spirooxindoles were previously synthesized by Wolff and Taddei. The spirooxindole 60 was formed in 51% yield from cyclohexanecarboxylic acid after heating the preformed lithium salts of phenyl hydrazide 61 to 205-210 °C. 

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)). 

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