Heterocycles via Allene-Alkene Coupling

The metallacycle S6 (Equation 1.62) is also a a-bonded tautomer of a jr-allylruthe-nium complex. As such, it can be envisioned that it might be possible to capture this species with a nucleophile as illustrated in Equation 1.62, path b [58, 59]. Tethering a judiciously placed alcohol to the allene partner does indeed lead to such a product with excellent regioselectivity (Equation 1.69) [60], Both tetrahydrofurans and -pyrans form with equal efficiency. Interestingly, reduction followed by add treatment forms the spiroketal efficiently and reasonably atom economically (Equation 1.69). 

An even better nucleophile is nitrogen. The incompatibility of basic amines for almost every one of these reactions catalyzed by these coordinatively unsaturated Ru complexes led us to examine sulfonamides and carboxamides. However, no productive results ensued. A basic amino group was also examined to verify its incompatibility. In contrast to that expectation, cyclization proceeded without problems as summarized in Equation 1.70 [61]. A Lewis acid was required as a cocatalyst. For formation of pyrrolidines, titanium tetrachloride proved most efficacious whereas for formation of piperidines, methylaluminum dichloride proved best. In principle, any nucleophile, such as carbon, that satisfactorily reacts in ruthenium-catalyzed allylic alkylations should function here also. 

Efficiency in synthesis must include the efficiency with which the raw materials are utilized. In a resource-limited world, maximal use of starting materials and minimal 

I thank a great group of co-workers, all of whom are identified in the references, for making this chemistry possible. Financial support for the work in my laboratories from the National Science Foundation and, to a lesser extent, the National Institutes of Health is gratefully acknowledged. 

2 Shenvi, R.A., O Malley, D.P. and Baran, P.S. (2009) Chemoselectivity the mother of invention in total synthesis. Accounts of Chemical Research, 42, 530-541. 

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