Zinc-mediated Preparation of Reactive Intermediates

The potential for introduction of chiral centres using a Diels-Alder approach makes this a particularly attractive route to benzo-fused cyclohexanes. However, the chemistry of orthoxylylenes is relatively unexplored as previous routes to this elusive intermediate involved the use of reagents such as disodium tetracarbonylferrate. This reagent is extremely intolerant of other functional groups, mainly as a result of its high basicity and the yields obtained are only a fraction of those available using the zinc/ultrasound route. 

Preparation of bicyclic systems via the reductive coupling of 1,3-dienes with a,a -dibromoketones to give bicyclic systems has been known for some time. Hoffmann discovered that moderate yields of coupled product were available using a zinc/copper couple. The reaction took between 12-80 h [158] however, yields could be significantly improved by use of a trimethyl-silylchloride mediator [159]. Complementary work by Noyori [160] had already shown that use of diiron-nonacarbonyl led to significant increases in yield despite the obvious disadvantages of its expense and toxicity. Hoffmann has recently examined the effects of ultrasound on his original reaction [161]. 

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