Smith-Tietze Multicomponent Dithiane Linchpin Coupling

SMITH-TIETZE MULTICOMPONENT DITHIANE LINCHPIN COUPLING 

The key step of the mechanism is the solvent-controlled [1,4]-Brook-rearrangement, which proceeds through an intermediate having a pentacoordinate-silicon atom. This rearrangement does not take place until HMPA is added to the solvent. A similar solvent effect has been observed by K. Oshima, K. Utimoto and co-workers.The rearrangement was found to be completely intramolecular based on the results of a crossover experiment by A.B. Smith et.al.  

The stereocontrolled enantioselective synthesis of an advanced B-ring synthon of bryostatin 1 was achieved in the laboratory of K.J. Hale. The key step was a Smith-Tietze coupling of 2-lithio-2-TBS-1,3-dithiane with a homochiral epoxide in the presence of HMPA. The resulting dithiane alkoxide was trapped with TBSCI in situ followed by deprotection of the dithiane moiety to give a Crsymmetrical ketone. This ketone was then further elaborated into the target B-ring synthon. 

A one-pot five-component dithiane linchpin coupiing was applied as the key synthetic transformation in A.B. Smith s approach to Schreiber s C16-C28 trisacetonide subtarget for mycoticins A and B. To prevent a premature Brook rearrangement, ether was used instead of THF as a solvent for the initial deprotonation of 2-TBS-1,3-dithiane. The third component in the iinchpin coupiing was (S,S)-diepoxypentane that was added to the reaction mixture along with HMPA in THF. 

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SMITH-TIETZE MULTICOMPONENT DITHIANE LINCHPIN COUPLING... 

Smith-Tietze Multicomponent Dithiane Linchpin Coupling. 

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