Synthesis of alpha-ketoester- and alpha-hydroxyester-substituted isoindazoles via the thermodynamic coarctate cyclization of ester-terminated azo-ene-yne systems.
The synthesis of isoindazoles bearing alpha-ketoester and alpha-hydroxyester groups via the coarctate cyclization of ester-terminated azo-ene-yne precursors is described. Whereas previous studies on isoindazole formation have shown the reaction to proceed through a kinetic coarctate pathway, functionalization of the terminal acetylene with a methyl ester sufficiently stabilizes the carbene intermediate to make the coarctate cyclization the thermodynamic pathway. Density functional theory (DFT) computations reveal ca. 8-9 kcal mol(-1) lower energy transition states for the coarctate pathway compared to the parent system.
McClintock
Sean P
SP
Department of Chemistry, University of Oregon, Eugene, Oregon 97403-1253, USA.
Forster
Nathan
N
Herges
Rainer
R
Haley
Michael M
MM
D000114:Acetylene / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D004952:Esters / Q000737:chemistry; D007191:Indazoles / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D012984:Software; D013816:Thermodynamics; D014227:Triazines / Q000737:chemistry
D004952:Esters; D007191:Indazoles; D014227:Triazines; D000114:Acetylene