1 research outputs found
Intramolecular Heteroatom and Styryl Diels–Alder Reactions, Asymmetric Cycloadditions of Chiral 3‑Phenylallyl Maleic Esters
Polycyclic aryl naphthalene and tetralin dihydro arylnaphthalene
lactone lignans possess anticancer and antibiotic activity. Related
furo[3,4-c]pyranones, typified by the sequester-terpenoid
isobolivianine, show similar antiproliferative bioactivity. Efficient
syntheses of compounds featuring these polycyclic cores have proven
challenging due to low yields and poor stereoselectivity. We report
the synthesis of chiral cinnamyl but-2-enanoates and 3,3-diphenylallyl-but-2-enoates
1 as new Diels–Alder substrates. These compounds undergo [4
+ 2]-cycloadditions to give furo[3,4-c]pyranones
2 in good yield (70%) and diastereoselectivity (7:1), together with
naphthyl 3 and dihydronaphthyl tetralins 4 as minor products. Molecular
structures and stereochemistries of the major products were verified
using X-ray diffraction. Density functional theory calculations revealed
that the cycloaddition process involves a bispericyclic/ambimodal
process where there is a single transition state that leads to both
intramolecular styryl Diels–Alder (ISDA) 3, 4 and intramolecular
hetero Diels–Alder (IHDA) cycloadducts 2. With the elevated
temperature conditions after cycloaddition, the resulting ISDA cycloadduct
either undergoes [3,3]-sigmatropic rearrangement to the more stable
major IHDA product or aromatization leading to the phenyltetralin