Radicals in Cascade Chemistry

Many chemists will recollect or have seen acid-induced reaction of polyenes to construct steroidal skeletons in a manner analogous to their biosynthetic origins.  Also, many chemists may remember a resurgence of radical chemistry in the late 1980’s, much of it using tributyltin hydride to generate the radical by reduction of a halide.  Naturally, the toxicity of organotin reagents resulted in this synthetic strategy remaining largely an academic pursuit, but controlled radical formation and utilisation remains a potentially powerful synthetic tool.  

MacMillan et al recently published an interesting chiral polyene cascade synthesis of polycyclic skeletons using an organocatalytic approach as outlined below.  It is notable that the reaction combines the relatively modern theme of organocatalysis with the more mature themes of polyene cascade and radical chemistry.  It seems to me that this may yet result in chemistry that is amenable to larger scale industrial application to make 5 or 6 membered carbocyclic rings with good regio- and stereocontrol.

The procedure involves preparing a solution of the polyenal starter with 0.3 molar equivalents of the amine catalyst as its TFA salt in 1:2 i-PrCN : DME as solvent and slowly adding a solution of copper triflate (2.5 molar equiv) as oxidant with sodium trifluoroacetate (2 molar equiv) and TFA (2 molar equiv) in i-PrCN at room temperature over a period of about 7h followed by a period of 17h at room temperature.