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

Abstract

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 Et3SiH/PhBCl2 system presents several advantages: silanes are efficient, environmentally benign, and user-friendly hydride donors, while PhBCl2 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-O-p-methoxybenzylidene moieties in protected disaccharides. Surprisingly, its use on 4,6-O-benzylidene-containing substrates 1 and 2 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 Et3SiH/PhBCl2 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 Et3SiH/PhBCl2 system as a reagent for the regioselective opening of arylidenes in complex and multifunctional molecules.

Adaptable synthesis of chondroitin sulfate disaccharide subtypes preprogrammed for regiospecific O-sulfation

“…To avoid this, use of only 1.1 equivalents of Et3SiH in CH2Cl2 at low temperatures has been reported. 31 Upon adopting these conditions for disaccharide 24 for 20 minutes all starting material was consumed and there was no notable side product formation by TLC analysis. Subsequent C6-O-benzoylation of the crude material delivered disaccharide 27 in 73% over two steps.…”

“…However, in CH2Cl2, when an excess of Et3SiH is used, the silane reduces PhBCl2 to PhBHCl, which can hydroborate alkenes, presenting a potential problem for our anomeric O-allyl moiety. To avoid this, use of only 1.1 equivalents of Et3SiH in CH2Cl2 at low temperatures has been reported 31. Upon adopting these conditions for disaccharide 24 for 20 minutes all starting material was consumed and there was no notable side product formation by TLC analysis.…”

Organoboron-Promoted Electrochemical Chlorosulfonylation of Alkenes with Sulfonyl Chlorides

“…Nevertheless, the chlorine-substituted borane 49 was detected by HRMS after electrolyzing for 45 min (Scheme A.c). We inferred that the chlorine radical might be quickly trapped by p -ethylphenylboronic acid as a reactive intermediate to avoid being consuming within the electrical double layer and then cross-coupled with carbon radical by forming dechlorinated boranes. ,− These observations indicated that the ATRA mechanism might be involved in the electrochemical process. No target product was observed under divided cell electrolysis, suggesting the importance of employing paired electrolysis in this process (Scheme A.d).…”

“…Based on the above experiments and literature precedents, ,− a plausible mechanism for electrochemical chlorosulfonylation is proposed in Scheme C. First, sulfonyl chloride is reduced to a sulfonyl radical, which is subsequently trapped by styrene to form P1 .…”