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

AbstractChiral 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 thermodynamic control. Stereochemical assignment of the cycloadducts was facilitated by conversion of the 1,3‐dicarbonyls with BF3 ⋅ OEt2 into BF2‐chelate complexes. Subsequent thermal Diels‐Alder reaction of BF2‐ 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 2,3‐dimethylbutadiene 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.