Regioselective Reductive Opening of Benzylidene Acetals with Dichlorophenylborane/Triethylsilane: Previously Unreported Side Reactions and How to Prevent Them.

Arylidene acetals are widely used protecting groups, because of not only the high regioselectivity of their introduction but also the possibility of performing further regioselective reductive opening in the presence of a hydride donor and an acid catalyst. In this context, the EtSiH/PhBCl system presents several advantages: silanes are efficient, environmentally benign, and user-friendly hydride donors, while PhBCl opens the way to unique regioselectivity with regard to all other Brønsted or Lewis acids used with silanes. This system has been extensively used by several groups, and we have demonstrated its high regioselectivity in the reductive opening of 4,6- and 2,4---methoxybenzylidene moieties in protected disaccharides. Surprisingly, its use on 4,6--benzylidene-containing substrates and led to unreproducible yields due to the unexpected formation of several side products. Their characterizations allowed us to identify different pitfalls potentially affecting the outcome of reductive opening of arylidenes with the EtSiH/PhBCl reagent system: alkene hydroboration, azide reduction, and/or Lewis acid-promoted cleavage of the arylidene. With this knowledge, we optimized reproducible and high-yielding reaction conditions that secure and extend the scope of the EtSiH/PhBCl system as a reagent for the regioselective opening of arylidenes in complex and multifunctional molecules.