Transannular spirocyclization

The naturaiiy occurring potent antitumor antibiotic (+)-duocarmycin A, its epimer, and unnatural enantiomers were prepared by D.L. Boger et al." The last step of the synthesis was the elaboration of the reactive cyclopropane moiety, which was carried out via a transannular spirocyclization using Mitsunobu conditions. This is a special case when the Mitsunobu reaction is utilized to create new carbon-carbon bonds. 

Catalyst 70 is very effective for the reaction of terminal alkenes, however 1,1-disubstituted olefins provide hydrosilylation products presumably, this is due to steric hindrance [45]. When a catalyst with an open geometry (78 or 79) is employed, 1,1-disubstituted alkenes are inserted into C-Y bonds to give quaternary carbon centers with high diastereoselectivities (Scheme 18). As before, initial insertion into the less hindered alkene is followed by cyclic insertion into the more hindered alkene (entry 1) [45]. Catalyst 79 is more active than is 78, operating with shorter reaction times (entries 2 and 3) and reduced temperatures. Transannular cyclization was possible in moderate yield (entry 4), as was formation of spirocyclic or propellane products... 

The same research group also explored a transannular nitrone-olefin [3 + 2] dipolar cycloaddition approach to the spirocyclic core of pinnaic acid, an inhibitor of phospholipase A2 (CPLA2) that was isolated from the Okinawan bivalve Pinna muricata The nitrone 34 was prepared by acidic hydrolysis of the ethylene ketal and the oxaziridine of 32 to generate transiently the keto... 

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