Theoretical elucidation of the regioselectivity in a tandem 1,4-hydride addition/acylation of diethylphosphonocoumarin

Influence of BH3 and alkaline cation released from the reduction agent on a tandem reduction/acylation reaction—A computational study

“…These observations have been explained by our recent computational investigations [3]. The high C-acylation selectivity was connected with the higher stability of C-acylation isomer in solution compared to the O-acylated isomer, by 56 kJ/mol.…”

“…The obtained results (Table I, Fig. 1) are compared to those reported earlier [3] for Na ϩ cation and for the interaction of BH 3 with DMAP and solvent molecules.…”

“…First we modeled the complex of anionic adduct, H-ad, with Li ϩ and K ϩ as counter cations starting from the optimized structure of H-ad/Na complex [3]. The optimized structures of the complexes Had/Li and H-ad/K are very similar to that of H-ad/ Na.…”

“…This is particularly important when a multistep reaction is performed as a tandem onepot reaction. Here, we report a theoretical study on the stability of possible complexes of both Lewis acids, BH 3 and alkaline cations, with intermediates, solvent molecules, and basic additives in a tandem hydride reduction/acylation reaction of 3-diethylphosphonocoumarin (DPC). This reaction is interesting since the acylation could occur both at C3 carbon (see the numbering in Scheme 1) and carbonyl oxygen O9.…”

“…However, the experiments [2] resulted only in C-acylated product, while the Oacylated is not observed. We explained this selectivity on the basis of the higher stability of C-acylated product in the solvent (pyridine) [3]. Here, we consider also the stabilization of both possible acylated products by formation of coordination complexes with alkaline cations and their counter anion in the reaction mixture CH 3 COO Ϫ (Scheme 1).…”