RESUMO
The iodine-catalyzed Prins cyclization of homoallylic alcohols and aldehydes was investigated under metal-free conditions and without additives. Anhydrous conditions and inert atmosphere are not required. The reaction of 2-(3,4-dihydronaphthalen-1-yl)propan-1-ol and 21 aldehydes (aliphatic and aromatic) in CH2Cl2 in the presence of 5 mol % of iodine gave 1,4,5,6-tetrahydro-2H-benzo[f]isochromenes in 54%-86% yield. Under similar conditions, the Prins cyclization of six alcohols containing an endocyclic double bond (primary, secondary, or tertiary) led to dihydropyrans in 52%-91% yield. The acyclic homoallylic alcohols gave 4-iodo-tetrahydropyran in 29%-41% yield in the presence of 50 mol % of iodine. This type of substrate is the main limitation of the methodology. The relative configuration of the products was assigned by NMR and X-ray analysis. The mechanism and the ratio of the products are discussed, based on DFT calculations.
Assuntos
Iodo/química , Piranos/síntese química , Álcoois/química , Aldeídos/química , Catálise , Cristalografia por Raios X , Ciclização , Modelos Químicos , Modelos Moleculares , Conformação Molecular , Teoria Quântica , EstereoisomerismoRESUMO
An efficient and concise synthesis of nine populene D analogues was performed using an iodine-catalyzed Prins cyclization as the key transformation. The antiproliferative activity of these new pyrans against several cancer cell lines was then investigated. Among them, an isochromene with moderate activity (mean logGI(50) = 0.91) was found. Additionally, compounds with selectivity toward the tumor cell lines NCI-ADR/RES, OVCAR-3, and HT29 were discovered.