Prof. David Procter’s group from the University of Manchester has done a lot of work with fluorous tags, particularly in sulfur chemistry. F-Blog has highlighted several of his publications in the past. (see here, here, and here) Their latest paper in Organic & Biomolecular Chemistry describes how they form nitrogen containing heterocycles using a connective Pummerer-type cyclization.
In a classical Pummer reaction a sulfoxide is acylated, usually with something like acetic anhydride. A thionium ion is then formed by elimination of a carboxylic acid. This same thionium ion can be accessed through by reacting a thiol with an aldehyde to form a hemithioacetal. Acylation of the hydroxyl group and ionization provides the thionium ion, hence the name connective Pummerer.
Within the paper a variety of thiols are used while the the aldehyde is in the form of various glyoxamides. This leads to a numer of different heterocycles, but primarily substituted oxindoles as shown below.
Prof. Procter then goes old-school by finishing a methodology paper with a total synthesis. In this instance the synthesis of neocryptolepine, an inhibitor of topoismerase II isloated from the roots of the West African Cryptolepis sanguinolenta. As shown below, the thiol used in this case is a fluorous thiol. After attaching the fluorous thiol, fluorous solid phase extraction (FSPE) rapidly purifies synthetic intermediates A and B without the need for chromatography. Removal of the fluorous group by reduction with samarium iodide then reductive cyclization through the nitro group provides the neocryptolepine skeleton. The total synthesis is then completed by removal of the phenylsulfonylethyl (PSE) protecting group.
