A Straightforward Approach Towards Phosphadecalones by Microwave-Assisted Diels–Alder Reaction

A stereoselective and scalable strategy for the synthesis of phosphorus-containing bicyclic and tricyclic compounds from 1-phenylphosphin-2-en-4-one 1-oxide is presented. This activated dienophile, available in both racemic and enantiopure forms, undergoes smooth [4+2] cycloadditions with acyclic and cyclic dienes, affording products with excellent yields and controlled stereochemistry. Notably, the <i>cis</i>/<i>trans</i>-fusion of the cycloadducts (phosphadecalones and phosphahexahydrochrysene) can be selectively controlled by fine-tuning the conditions of microwave-assisted cycloaddition reaction. The influence of temperature, time, and steric effects on <i>cis</i>/<i>trans</i> and <i>endo</i>/<i>exo</i> selectivity was examined in detail. The molecular structure, including the absolute configuration, of eight products has been determined by X-ray crystallography. These analyses further established the <i>endo</i>-selective nature of the cycloaddition, favoring the P=O face of the dienophile. Post-cycloaddition transformations of selected <i>P</i>-stereogenic phosphadecalone, such as isomerization, reduction and deoxygenation, demonstrate the synthetic versatility of the resulting products.