Chiral 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. 

Two final examples of cross-coupling to furnish [3]dendralenes via C2-C3 bond formation are part of very short and efficient total syntheses, and highlight the versatility and attractiveness ofthe approach. As an extension of their work on 1,1-divinylallene (153) (Scheme 1.22), Sherburnel /. [123] synthesized allenic [3]den-dralene 188 via Kumada cross-coupUng of a metallated alkene 187 and a chiral, propargyl mesylate. A subsequent Diels-Alder reaction produced cyclic [3]den-dralene 190 en route to a pseudopterosin aglycone 191 (Scheme 1.29). Allenic [3]dendralenes are prone to decomposition [136], so the subsequent DA reaction was carried out in situ. 

Scheme 1.29 Chiral [3]dendralene synthesis via sp -sp cross-coupling as part of a total synthesis by Sherburn and coworkers [123].

Elimination reactions to reveal masked dendralenes featured prominently in early attempts to synthesize cross-conjugated compounds [1]. Cheletropic extrusion of sulfur dioxide was used to convert lower dendralenes to [5], [6], and [8] dendralene [10], and to make substituted chiral [4] dendralenes [12]. 

Both of the previous examples describe the use of achiral dendralenes to synthesize racemic products. In 2007, the Sherburn group illustrated that chiral 3-substituted [3]dendralene 34 allowed for the preparation of enantiomerically pure cycloadducts (Scheme 12.6) [7]. DA addition of maleic anhydride, followed by in situ lactonization, yielded carboxylic acid 36. This was esterified with diazomethane to improve solubility, and then subjected to a high-pressure double DA sequence using 2,6-dimethyl-/ -benzoquinone, forming the C2 symmetric heptacycle 38 in 85% yield. 

Scheme 12.6 A DTDA sequence of chiral [3]substituted [3]dendralene 34 by the Sherburn...

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