A greener and efficient access to substituted four- and six-membered sulfur-bearing heterocycles?

Organic & Biomolecular Chemistry Pub Date: 2017-05-18 DOI: 10.1039/C7OB00846E

Abstract

The regioselective functionalization of four- and six-membered cyclic sulfones was investigated using a lithiation/electrophile trapping strategy. The protocol features an interesting eco-compatibility profile because of the use of 2-MeTHF as a solvent (more eco-friendly than other organic solvents) and n-hexyllithium as a lithiating agent safer than other alkyllithium compounds. Several derivatives were prepared with different stereochemistry and substitution patterns. A number of selected derivatives, spanning a range of 5 log?P units, were characterized for their lipophilicity through RP-HPLC. A good linear correlation, with a slope close to 1.0, was observed between the experimentally determined RP-HPLC lipophilicity parameters (log?k′w) and calculated log?P (clog?P) values, whereas a systematic difference in absolute values between the chromatographic parameters and in silico lipophilicity descriptors can be attributed mainly to silanophilic interactions between the H-bond acceptor SO2 group and free silanol groups on silica-based C18 columns, which results in increased retention times.

Graphical abstract: A greener and efficient access to substituted four- and six-membered sulfur-bearing heterocycles
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