Ring size effects in the C²–C⁶ biradical cyclisation of enyne–allenes and the relevance for neocarzinostatin

The regioselectivity of the thermal cyclisations of enyne–allenes 1 can be toggled as a function of the ring size of the cycloalkene. With a cyclopentene as the ene moiety the Myers–Saito (C²–C⁷) cycloaromatisation product is formed, whereas with six- and seven-membered cycloalkenes the novel C²–C⁶ cyclisation is observed. DFT calculations are used to rationalise these changes. The implications of these findings for alternative thermal biradical cyclisations of neocarzinostatin are discussed.