Mechanistic Studies of the Deslongchamps Annulation

Abstract

The CsCO-mediated annulations ("Deslongchamps annulations") of three spirocyclic benzoquinone monoketals 5b-d with an ester or acyl substituent at C-2 to two tert-butyl esters of γ,δ-unsaturated β-ketocarboxyl acids ("Nazarov reagents"; 2a,b) were monitored H NMR spectroscopically. This revealed that a primary product, by all likelihood the Michael adduct, forms fast and prior to the appearance of the Deslongchamps adduct. These primary products form reversibly. This was proved by two crossover and four scavenging experiments. Therein, components already incorporated in one of the mentioned primary products ended up in Deslongchamps adducts different from the one, which would have resulted if the respective primary product had reacted alone. However, these experiments leave open whether our primary products are intermediates en route to Deslongchamps products or whether they represent dead ends.

Quinazoline-2-Carboxamides as Selective PET Radiotracers for Matrix Metalloproteinase-13 Imaging in Atherosclerosis

“…We proposed to radiolabel 5j by 18 F-fluorination of the corresponding tosylate precursor (Scheme ). Initially, mono-tetrahydropyranyl (THP) protection of ethylene glycol was performed to afford 2-[(tetrahydro-2 H -pyran-2-yl)­oxy]­ethan-1-ol (compound 6 , 79%) . The THP protecting group was selected for its stability under strongly basic conditions, as in the following S N Ar reaction, mediated by sodium hydride.…”

“…HRMS (EI, m / z ): [M – H] + calculated C 7 H 14 O 3 as 145.0859, found as 145.0846. Spectrum in accordance with the literature …”

“…The crude mixture was purified by column chromatography (0−50% EtOAc/hexane) to obtain the title compound as a colorless oil (3.80 g, 26.0 mmol, 79%). 43…”

“…Initially, mono-tetrahydropyranyl (THP) protection of ethylene glycol was performed to afford 2-[(tetrahydro-2H-pyran-2-yl)oxy]ethan-1-ol (compound 6, 79%). 43 The THP protecting group was selected for its stability under strongly basic conditions, as in the following S N Ar reaction, mediated by sodium hydride. Coupling of 6 to intermediate 4d was conducted under identical conditions used for the formation of the 5-substituted derivatives 5a−j to obtain compound 7 (75%).…”