Unsymmetrical dendralene

Negishi or Kumada cross-couplings to incorporate one alkenyl substituent (9 or 12) twice, and also, in the former case, the related stepwise, stereoselective Stille couplings to form unsymmetrically substituted, chiral [3] dendralenes 16 (Scheme 1.2). An application of this stepwise approach en route to the natural product triptolide [14] highlighted that when using two different metalloalkene cross-coupling partners, complete control of the stereochemistry of the resulting alkene is sometimes unattainable. Thus, most successful applications of this method incorporate two identical alkenes, so no issues of stereochemistry arise. 

Isomerizations and rearrangements featured heavily in early approaches to [4]dendralene and derivatives [17, 149-155]. An interesting, recent case of unsymmetrical [4]dendralene formation was reported by Mukai and coworkers in... 

Scheme 1.32) [156]. Cu(II)-promoted intramolecular [2+2] cycloaddition of 1,4-diallenes 202 yielded bicyclooactadienes 204 however, under uncatalyzed thermal conditions, the authors noted that the formal [3,3]-sigmatropic rearrangement product, [4]dendralene 203, was formed m 50% yield. If optimized, this presents a nice method to form unsymmetrical [4]dendralenes, but relies on a lengthy synthesis of starting materials. 

Scheme 1.32 Thermal isomerization synthesis of an unsymmetrical [4]dendralene by Mukai and coworkers [156].

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