A new and highly simple method for the synthesis of E-g-aryl-a-oxobutenoic esters is described. This unprecedented one-step procedure is based on an unexpected nucleophilic reactivity of alkyl pyruvates towards aromatic aldehydes in refluxing dichloromethane, when using catalytic amounts of Cu(OTf) 2 and in the presence of stoichiometric amounts of trimethyl orthoformate in the case of electron-rich aldehydes. Under these conditions, yields obtained are uniformly higher than those obtained by previous multistep procedures.In the past decade, a-oxo-b-unsaturated esters have emerged as novel useful synthons, 1 especially in DielsAlder reactions as heterodienes 2 or dienophiles. 3 Chiral E-g-C-substituted-a-oxo-b-unsaturated esters 4 have been employed in the asymmetric syntheses of biologically important subunits (e.g. b-unsaturated-and b-amino-a-hydroxy esters 5 ) and natural products (norlignans). 6 E-g-Aryl-a-oxo-b-unsaturated esters have been previously prepared by alkaline condensation of pyruvic acid (or ester) with aromatic aldehydes, acidification and final esterification. Sugimura's group introduced a more general three-steps procedure 7 involving O-silylation of the pyruvic acid ester, Mukayaima-aldol-type cross-condensation with an acetal (even in situ generated 8,5b ) at low temperature and subsequent b-elimination using silica gel (or florisil 2k ). In connection with our recent results concerning the solide-phase synthesis of dihydropyrans via cycloaddition of a solid-supported benzylidenepyruvic acid ester, 9 we needed a direct preparation method of title compounds 1 starting from the corresponding pyruvates, that would involve neither insoluble reagents for the elimination step nor alteration of the ester functionality.
We report the efficient synthesis of a series of new azlactone-based heterofunctional linkers bearing two orthogonal clickable groups that proceed with full atom economy. These new linkers comprise an azlactone (oxazolone) group that quickly reacts with amino groups in biologically relevant medium without byproduct elimination and a (bio)orthogonal handle which further undergoes facile and selective click reactions such as thiol-ene coupling, Diels-Alder or azide-alkyne cycloadditions. As an example, the application of this methodology to lysozyme PEGylation in aqueous medium is described.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.