Pyrrolidine, ruthenium-catalyzed functionalization

Scheme 9.21 Ruthenium-catalyzed functionalization of a C(sp )—H bond in pyrrolidine 58.

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. 

The most recent example of pyrrolidine synthesis by C-H functionalization was illustrated in 2014, when Che and coworkers demonstrated the synthesis of pseu-doheliotridane, a simple pyrrolidine alkaloid, by employing a ruthenium-catalyzed C-H insertion reaction (Scheme 16.44) [89]. Although diazocarbonyl compounds are generally required as the precursor of the metal carbenoid intermediate, they utilized an alkyl diazomethane as the carbene source. To this end, tosylhydrazone 192 was reacted with [Ru(TTP)(CO)] (TTP tetra(p-tolyl)porphyrin) (1 mol%) and KjCOj, which generated ruthenium carbene 193 in situ, followed by C-H insertion to produce pseudohehotridane in 95% yield with high diastereoselectivity. 

In addition to copper and rhodium catalysts commonly used in the generation of metal carbene complexes, other transition metals have also been explored in the diazo decomposition and subsequent ylide generation.Che and co-workers have recently studied ruthenium porphyrin-catalyzed diazo decomposition and demonstrated a three-component coupling reaction of a-diazo ester with a series of iV-benzylidene imines and alkenes to form functionalized pyrrolidines in excellent diastereoselectivities (Scheme 20). ... 

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