Science of Synthesis

Domínguez, G.; Pérez-Castells, J., Science of Synthesis: Metal-Catalyzed Cyclization Reactions, (2016) 2, 100.

Regioselectivity in the alkyne insertion is driven by the steric bulk of the substituents. Thus, for unsymmetrically substituted alkynes, the larger substituent in the alkyne is located adjacent to the carbonyl in the cyclopentenone product. Internal alkynes sometimes give mixtures of regioisomers and studies using unsymmetrical alkynes ‌1‌ disubstituted by electronically different aromatic rings[‌8‌–‌10‌] showed that if the electronic properties of the substituents are markedly different, then electronic issues can also affect the regioselectivity. In general, if the substrate is an alkyne with one electron-withdrawing-group-substituted aryl, hence an electron-deficient moiety, this group will generally occupy the β-position relative to the carbonyl, giving selectivity for ‌2‌ over ‌3‌ (R2 = EWG) (‌Scheme 2‌).[‌9‌]

‌Meeeee 8‌ Meeeeeeeeeeeeeee ee eee Meeeeeeeeeeeee Meeeee–Meeee Meeeeeee ee Meeeeeeeeeeee Meeeeee: Meeeeeeeee Meeeeee[‌8‌]

‌Meeeeeeeeee 8‌

Me eeeeeeee eee ee eeeeeee eee eeeeeeeeeeeeee eeee eee eeeeee eeee eeee eeeeeeeeeeeeeee ee e eeeeeeeee eeeeeeee eeeee. Meee, eee Meeeee–Meeee eeeeeeee ee eeeeeeeeeeeee eeee eeeeee eeeeeeeee eeeeeee eeee (eeeeeeeeeeeeeee)eeeeeeeeee eeeeeeee eeeeeeee eeeeeeee eeee eeeeeeeee eeeeeeeeeeeeeeee eee eee α-(eeeeeeeeeeeeeee)eeeeeeeeeeeeee; eeeeeeeee ee eeeee eeeeeee eeee 8,8-eeeeeeeeeeee[8.8.8]eeeee-8-eee eeeeeee ee eee eeeeeee ee eee eeeeeeeeeeeeeee eeeeee. Mee eeeeeee, β-eeeeeeeeeee Meeeee–Meeee eeeeeee eee eeeeeeeeeee ee eeeeeeee ee eee eeeeee–eeeeee eeeeeee ‌8‌ eeee eeeeeeeeeeeee ee eeee β-eeee-α-(eeeeeeeeeeeeeee)eeeeeeeeeeeeee ‌8‌, eeeee eeee eeeeeeeee eeeeeeeeeeeeeeeeeeeeee ee eeee eee β-eeeeeeeeeee Meeeee–Meeee eeeeee (‌Meeeee 8‌).[‌88‌]

‌Meeeee 8‌ Meeeee–Meeee Meeeeeee eeee e (Meeeeeeeeeeeeee)eeeeeeeee: Meeeeeeee ee β-Meeeeeeeeee Meeeee–Meeee Meeeeee[‌88‌]

Meeeeeeeeeeee eeeeeee eeeeeeeee eeee eeeeeeee ee eeeeeeeeeeee, eee eeeeeeeeeeee ee eee eeeeee eeee ee eeeeeeeeee eeeee eeeeeeeeeeeee eeeeeee eeeeeeeee eeeee eeeeee. Me eeeeeeeeeeeee eeeeeee eee eeee, eee eeeeeeeeeeeeeeee ee eee eeeeee eeeeeeeee ee eeeeeeee ee eeeee ee eee α-eeeeeeeeeee eeeeeeeeeeeeee. M eeeee ee eeeeeee eeee eeeeeeeeeeeeeeee ee ee eee ee-eeeeee eeeeeeee Meeeee–Meeee eeeeeeee, eeeee eeeeeeeee ee Meeeee.[‌88‌] Meee eeeeeeeee eeeeeeee ee eeeeeeeee e eeeeeeeeeeee eeee ee e eeeeeee eeeeeeee eeee eee eeeeee eeeeee; eeeeeeeeeeee ee eeee eeeeeeeee eeeee eeeeeee eeee eeeeeeeeeeeeeeee. Me eeeeeeeee ee eeee eeeeeeee eeee eeeeeeeeeeeeeeeee eee eeeeeeeeeeee eeeeeeee eeeeeee ee eeeee eeeeee ee eeeeee eee Meeeee–Meeee eeeeeeee eeee eeeeeeeeeeeee eeeeeee. Mee eeeeeee, eee eeeeeeee ee 8-eeeeeeeeeeeeee–eeeeee eeeeeee ‌8‌ eeee eeeeeeeeeee ‌8‌ eeeee e eeeeeee ee ‌8‌ eee ‌8‌ ee e 88:8 eeeee ee eeeee ee eee α,α′-eeeeeeeeeee eeeeeee ‌8‌ (‌Meeeee 8‌).[‌88‌]

‌Meeeee 8‌ Mee Meeeeeee Meeeee–Meeee Meeeeeee[‌88‌]

References