Abstract
The mechanism of the highly regioselective cycloisomerisation of dimethyl hept‐1,6‐dienyl‐4,4‐dicarboxylate (1) by a neutral pre‐catalyst, [(__t__BuCN)~2~PdCl~2~] (8), to generate dimethyl 3,4‐dimethylcyclopent‐2‐ene‐1,1‐dicarboxylate (3) has been investigated by isotopic labelling (reactions involving single and mixed samples of 1,1,2,6,7,7‐[^2^H~6~]‐1; 3,3,5,5‐[^2^H~4~]‐1; 1,7‐(Z,Z)‐[^2^H~2~]‐1; [1,3‐^13^C~1~,5,7‐^13^C~1~]‐1 and [1,3‐^13^C~1~,6‐^2^H~1~]‐1) and by study of the reactions of dimethyl 1‐aryl‐hept‐1,6‐dienyl‐4,4‐dicarboxylates (9 a–e, where aryl is p‐C~6~H~4~‐X; X=H, OMe, Me, Cl, CF~3~) and dimethyl hept‐1,5‐dienyl‐4,4‐dicarboxylate (14), a 1,5‐diene isomer of 1. The mechanism proposed involves the generation of a monochloro‐bearing palladium hydride which undergoes a simple hydropalladation, carbopalladation, Pd/H dyotropy, β‐H elimination sequence to generate 3. A key point that emerges is that chelation of the 1,6‐diene 1 at various stages in the mechanism plays an important role in determining the regioselectivity of the reaction. The selective generation of 3 with pre‐catalysts of the form L~2~PdCl~2~, as compared to the generation of dimethyl 3‐methylene‐4‐methyl‐cyclopentane‐1,1‐dicarboxylate (2) with pre‐catalysts of the form [(MeCN)~2~Pd(allyl)]OTf (5) is ascribed to the absence of chloride ion in the latter, which makes an additional coordination site available throughout turnover. Liberation of the product 3 when [(__t__BuCN)~2~PdCl~2~] (8) is employed as pre‐catalyst, is proposed to proceed via a mono‐ to bidentate switch in the π‐coordination of diene 1 (η^2^ to bis‐η^2^) displacing π‐coordinated 3 from Pd. When 1‐aryl‐1,6‐dienes 9 are employed as substrates, the electron‐donor property of the aryl group is found to influence the regioselectivity of cyclisation. Electron‐withdrawing groups favour dimethyl 3‐arylmethyl‐4‐methylcyclopent‐2‐ene‐1,1‐dicarboxylates (10), whilst electron‐donating aryl groups favour 3‐arylidene‐4‐methyl‐cyclopentane‐1,1‐dicarboxylates (11). The regioselectivity (10/11) correlates with the Hammett σ^+^ values (ρ^+^=1.3, r ^2^=0.975) indicative of a strong π‐resonance contribution from the aryl ring rather than a simple σ‐inductive effect. Intermolecular modulation of regioselectivity is observed and the net effect proposed to arise through the (π→d) donation ability of the vinyl arene in the diene displacing product (10/11) via a mono‐ to bidentate switch in coordination. The isomerisation process increasingly sequesters Pd as turnover proceeds leading to a powerful inhibition mechanism and ultimately a limitation in turnover number to about 80.