Applications of high-potential quinones. Part I. The mechanism of dehydrogenation of steroidal ketones by 2,3-dichloro-5,6-dicyanobenzoquinone

Abstract

The reaction of 2,3-dichloro-5,6-dicyanobenzoquinone with steroidal 4-en-3-ones is catalysed by acids. 1,2-Dehydrogenation predominates in the presence of weak acids, as it does in the uncatalysed reaction, whereas strong acids promote exclusive formation of 6,7-dehydro-derivatives. These results are rationalised by a mechanism involving oxidation of the alternative enolic forms of the ketone. Thus, in the absence of acid or with weak acids, the kinetically determined 2,4-dien-3-ol undergoes C-1 hydride ion abstraction with dichlorodicyanobenzoquinone; strong acid accelerates the formation of the thermodynamically more stable 3,5-dien-3-ol, which readily suffers hydride abstraction from C-7 by the quinone. In the uncatalysed reaction the rate of 1,2-dehydrogenation depends upon both steroid and quinone concentration, whereas, in the presence of weak acids, the rate depends only on the concentration of ketone. Dehydrogenation of methylated and deuteriated 3-ketones reveals preferential elimination of the trans-diaxial 2β- and 1α-hydrogen atoms. Specific loss of the 1α-hydrogen is observed with 5α-3-ones, but the oxidation of 4-en-3-ones is less specific and involves some attack at the 1β-position.