1.8.3.3. Effect of Steric Hindrance on Mode of Cyclization

The synthetic potential of thermal enyne-allenes reactions was extended by Schmittel and co-workers. During the course of their study oon eneyne-allenes they found quite unexpected product which was different from Myers-Saito cyclised product when the the terminus of the enyne-allenes was attached of an aryl group or sterically bulky groups (e.g, ^tBu, SiMe3). The steric bulk of the terminus led to complete switch from the Myers-Saito C2 - C7 cyclization to a C2 - C6 cyclization, giving rise to a formal ene and Diels-Alder products. This C2 - C6 cyclization reaction is now popularly known as Schmittel cyclization (Scheme 43). Thus, simple replacement of the H atom at the acetylene end of ene-yne-allene with a phenyl group in switches the reaction (Scheme 43) from Myers-Saito to Schmittel cyclization.

Scheme 43. Myers-Saito vs. Schmittel cyclization.

In the following example, replacement of –Me group by a tolyl group in acetylenic arm lead to switch over from Myers-Saito to Schimittel cyclization. This is again attributed to the steric bulk of the tolyl group.

Scheme 43. Role of steric effect in switching the reaction from Myers-Saito to Schmittel cyclization.

It is well established that concerted Diels – Alder reactions are prevented by ortho-alkyl substituents because of steric hinderance, therefore the only option is a stepwise formal Diels-Alder cycloaddition. During the course of the synthesis of benzocarbazole, transformation of the –ph linked eneyne-allene to the Schmittel product gave strong evidence for the existence of the Schmittel biradical intermediate. However, Removal of the bulky phenyl on the acetylene terminus gave the C2 – C7 type cyclization product in 31% yield. The extra product formed (15% yield) is a product of addition of biradical intermediate to the hydrogen atom donor present (1,4-cyclohexadiene, 1,4-CHD) (Scheme 44).

Scheme 44. Role of steric effect in switching the reaction from Myers-Saito to Schmittel cyclization.

Initially it was thought that the switch in the mode of the reaction from Myers-Saito to Schimittel cyclization or vice versa is as a result of the stabilising effect of the aryl group on the vinyl radicals. However, further investigation clearly shows that replacement of the hydrogen at the acetylene unit by a phenyl group raises the barrier of the Myers cyclization significantly, presumably by steric hindrance and ground state stabilization of the acetylene moiety; therefore the reaction follows Schimittel cyclization pathway.