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Unraveling the C−H Arylation of Benzo‐Fused Cycloalkanones: Combined Experimental and Computational Evidence
Author(s) -
Large Benjamin,
Prim Damien
Publication year - 2021
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.202001349
Subject(s) - chemistry , acetophenone , bicyclic molecule , ketone , ring (chemistry) , stereochemistry , reactivity (psychology) , molecule , structural isomer , combinatorial chemistry , computational chemistry , organic chemistry , catalysis , medicine , alternative medicine , pathology
The C−H functionalization of benzo‐fused cycloalkanones represents a synthetic challenge, since such scaffolds display different activation sites, at sp 2 and sp 3 carbons, a bicyclic structure, and various sizes of the cycloalkanone ring. Anticipating the outcome of C−H functionalization and the impact of the presence and size of the cycloalkanone ring would help to foresee synthetic routes to more complex molecular architectures. The mechanism of C−H arylation was studied using DFT calculations for tetralone, benzosuberone, and indanone and compared to acetophenone. Comparison of energetic profiles allowed identifying key steps of the process. Analysis of the topology of key intermediates allowed correlating the deformation of palladacycles to the potential reactivity of the benzo‐fused cycloalkanone family members. The experimental results were in full agreement with the trend provided by the theoretical study. A wide panel of diversely substituted benzo‐fused cycloalkanones has been successfully obtained using optimized conditions. Moreover, an approach towards polycyclic molecules has been illustrated featuring a C−H arylation and a second step taking advantage of the remaining ketone fragment and its ability to undergo diverse transformations leading to alternative pathways to more complex molecular architectures