Cycloaddition of nitrile oxides to cyclic and acyclic α,β-unsaturated amides. Frontier orbital interactions and an unexpected steric drift determine regiochemistry

Strong deshielding in aromatic isoxazolines

“…1,3‐Dipolar cycloadditions of methyl 3‐(acridin‐4‐yl)propenoate ( 4 ) with 7a–c were performed at room temperature to ensure a kinetic control presumed for DCs of alkenes with NOs, until the dipolarophile had been consumed (TLC and NMR monitoring). To determine the conversion and regioselectivity precisely, parallel reactions of the dipolarophile (0.04 mmol) and dipole (0.12 mmol) in CDCl 3 (0.6 mL) were carried out in a sealed NMR tube at room temperature.…”

Directed 1,3-dipolar cycloadditions of ylidene piperazine-2,5-diones

“…10 In such cases, the stabilisation of the transition state that results from maximising the orbital overlap as predicted by FMO theory is insufficient to compensate for the steric repulsions. Thus to achieve the transition state leading to the 4,4-disubstituted regioisomer, a significant steric repulsion between the piperazinedione ring and the bulky mesityl system would be present as shown in Figure 2.…”

Synthesis of 5,6‐dihydro‐4H‐benzo[d]isoxazol‐7‐one and 5,6‐dihydro‐4H‐isoxazolo[5,4‐c]pyridin‐7‐one Derivatives as Potential Hsp90 Inhibitors

“…Literature reports (15) show that cycloaddition of arylnitriloxides to cyclohexenones affords 4acylisoxazolines. Similarly, cycloaddition to α, β-unsaturated lactams affords mainly 4-carboxamidoisoxazolines with high regioselectivity (16). Thus, in order to reverse the regiochemistry of the reaction, we planned to use lactams and ketones with a bromine atom in alfa position with respect to the carbonyl group.…”