Steric effects in the thermal C-C diradical cyclization of enyne-allenes

The thermal reaction of enyne-allenes 1 carrying bulky substituents (tert-butyl, trimethylsilyl, triisopropylsilyl) at the acetylene terminus uniquely leads to C-C cyclization products in high yields independent of other structural motifs at the enyne-allene (e.g. benzannulation, substituents at allene). The thermal cyclization can also be set up in a continous process, the latter protocol explored with a Cellular Process Chemistry (CPC) reactor. Bulky groups (e.g. tBu, TMS, TIPS) at the alkyne terminus stabilize the enyne-allene against cyclization, while the exchange of a hydrogen by a methyl group at the inner locus of the allene unit destabilizes the enyne-allene. DFT calculations at B3LYP/6-311G** level suggest that the observed acceleration is mostly brought about by increasing the equilibrium amount of the reactive s-cis conformer.