1.8.3.2. Decarboxylation as a Trigger for Myers-Saito Cyclization

Decarboxylation of A under basic conditions triggers formation of the allene B. In protic solvent such as methanol, an ionic pathway prevails (Case 1). The reaction path switches from radical chemistry likely because of the ability of a protic solvent to stabilize ionic species like C; methanol then traps the zwitterion to yield F. In benzene, the radical pathway dominates the reaction as evidenced by the formation of G and H, with no evidence of F (Case 2). Under these conditions, decarboxylation to afford B followed by Myers-Saito cylization gives D and 1,4-cyclohexadiene traps the biradical, providing G directly. Use of an ortho methoxy methyl substituent adds an element of complexity to the reaction pathway, because the biradical D may undergo intramolecular 1,5 hydrogen abstraction to form the oxygen stabilized radical E leading to H. Interestingly, when DMF is employed as solvent, the radical pathway proceeds even without 1,4-cyclohexadiene; however, even 10% methanol directs the reaction along the ionic pathway (Case 4). The authors suggest that the ionic pathway renders the abstraction of hydrogen atoms from DNA less likely, thus highlighting the importance of reaction environment on the Myers-Saito cyclization (Scheme 42).

Scheme 42. Myers-Saito cyclization triggered by decarboxylation.