Studies On The Friedel-Crafts Alkylation Of α-Hydroxyketene-S, S-acetals With Arenes And Applications

α-Oxo ketenedithioacetals are a kind of versatile intermediates in organic synthesis. It can be used in aromatization, cyclization, reduction, condensation reactions and it can construct many compounds with special structures for their special stereoelectronic effect from the alkylthio functionalities. So it has been applied in organic synthesis and the composition of natural products.The carbon-carbon bond-forming reaction is one of the most fundamental reactions for the construction of the molecular framework in organic chemistry. From the standpoint of atom efficiency, the direct substitution of a hydroxy group in an alcohol (ROH) by a carbon nucleophile (R'H) via a formal dehydration process is an attractive salt-free method because there is no requirement for the transformation of nucleophiles and alcohols to the corresponding reactive organometallic compounds (R`M) and halides or a related species (RX) (Scheme1). Therefore, continuous efforts have been devoted to the direct C-C bond forming reactions between ROH and R`H in recent years. Among those reported, the C-C coupling reactions between allylic or benzylic alcohols and active methylenes, or arenes have proven successful.A simple and efficient AlCl₃-mediated C-C coupling reaction between readily availableα-hydroxyketene-S,S-acetals and various arenes via direct substitution of the hydroxy group in alcohols has been developed. On the basis of this C-C coupling reaction, a series of bio- and pharmacologically important 3,4-disubstituted dihydrocoumarins, difficult to obtain by other methods, were prepared in high yields by a sequential Friedel-Crafts alkylation and intramolecular annulation reaction ofα-hydroxyketene acyclic-S,S-acetals with phenols under mild conditions.