SolutionsThe Negishi, Stille and Kumada couplings
Exercise 1
Which organometallic reagent would you use to attach a vinyl group to an aryl triflate bearing a ketone and an ester, if you wish to avoid both boron and magnesium compounds? Give the conditions.
Tributyl(vinyl)stannane (Stille coupling), which tolerates the ketone and the ester: Pd(PPh3)4, LiCl, THF or DMF at reflux. LiCl is needed with triflates: it replaces the triflate on palladium and facilitates transmetalation. An alternative is vinylzinc chloride or bromide (Negishi), although it is more sensitive.
Exercise 2
Rank Grignard reagents, organozinc reagents and organostannanes according to (a) their reactivity towards an aldehyde and (b) their toxicity. What are the consequences for the choice of coupling?
(a) RMgX > RZnX > RSnBu3: the more electropositive the metal, the more polar the C–metal bond and the more nucleophilic the carbon. Stannanes do not react with aldehydes without a catalyst. (b) Tin compounds are by far the most toxic. Kumada is the cheapest but least tolerant; Stille the most tolerant but the most problematic because of toxicity; Negishi lies in between.