Chasing Polycyclic Natural Products: 5/6/5‐ or 5/6/6‐Carbotricyclic Scaffold Construction via Stereodivergent Diels‐Alder Reaction of Chiral Hydrindanes and Their Boron Complexes

Abstract

Chiral trans-hydrindanes (bicyclo[4.3.0]nonanes) are important building blocks of polycyclic natural products. In order to access 5/6/5-and 5/6/6-carbotricyclic scaffolds scope and limitation of [4 + 2] cycloadditions of tetrahydroindanones with various dienes were studied. Cyclopentadiene gave a tetracylic endo-(R,R)-diastereomer under acid-catalysis, whereas thermal conditions provided the endo-(S,S)-diastereomer with the opposite diastereofacial selectivity. The stereodivergent outcome was rationalized by high-level quantum-chemical computations which revealed the acid-catalysis to be a kinetically controlled reaction and the thermal cycloaddition to be under thermody-namic control. Stereochemical assignment of the cycloadducts was facilitated by conversion of the 1,3-dicarbonyls with BF 3 • OEt 2 into BF 2 -chelate complexes. Subsequent thermal Diels-Alder reaction of BF 2 -or BBN-chelates (from 9-BBN-OTf) gave endo/exo-mixtures of the (R,R)-and (S,S)-diastereomers, while more elevated temperatures yielded primarily the endo/exo-(S,S)-diastereomers. Thermal [4 + 2] cycloadditions with 2,3dimethylbutadiene proceeded with lower diastereoselectivity as the reaction was kinetically controlled according to calculations. Attempted Diels-Alder-reactions with furan gave furyl-substituted indanones rather than cycloadducts.