Applications of 2-Chloro-3,3,3-trifluoroprop-1-ene (HCFO-1233xf): A Rapid Entry to Various ß-Substituted-trifluoromethyl-ethenes.

An efficient base-promoted reaction of O-, N-, and S-nucleophiles with 2-chloro-3,3,3-trifluoprop-1-ene (HCFO-1233xf) is described providing access to various ß-substituted-trifluoromethyl-ethenes under mild reaction conditions. Mechanistic investigations shed some light on the regio-, chemo-, and stereoselectivities observed. The olefins prepared represent attractive intermediates in chemical discovery: some applications include their conversion to pyrrolidines via a [3 + 2] dipolar cycloaddition reaction. These weakly basic amines represent novel synthons that could be readily elaborated through a range of reactions.

First report on bio-catalytic N-formylation of amines using ethyl formate.

A bio-catalyzed N-formylation reaction of different amines has been developed using ethyl formate as a formylating agent. This protocol provides a facile and convenient strategy featuring mild reaction conditions, high efficacy, a broad substrate scope and recyclability of lipase. This method also works on a large scale in high yield.

A unified access to diverse heteroaromatic scaffolds using the radical chemistry of xanthates.

The degenerate transfer of xanthates allows generally difficult radical transformations, such as intermolecular additions to unactivated alkenes and cyclisations onto aromatic and heteroaromatic rings, to be accomplished under very practical experimental conditions. This translates into numerous approaches for the construction or modification of heteroaromatic structures. The present report aims to provide a brief overview of the various synthetic possibilities, with particular emphasis on medicinally interesting families of compounds.

An unprecedented radical ring closure on a pyridine nitrogen.

An unprecedented radical ring-closure onto the pyridine nitrogen was observed when certain types of substituents were present around the pyridine nucleus.

S-(3-Chloro-2-oxo-propyl)-O-ethyl xanthate: a linchpin radical coupling agent for the synthesis of heterocyclic and polycyclic compounds.

The preparation and use of S-(3-chloro-2-oxo-propyl)-O-ethyl xanthate to directly introduce an alpha-chloroketone motif is described, along with applications for the synthesis of heterocyclic and polycyclic structures.

An unusual radical Smiles rearrangement.

Radicals derived from N-(alpha-xanthyl)acetanilides or N-(alpha-xanthyl)acetylaminopyridines possessing a substituent next to the nitrogen undergo a hitherto undocumented Smiles rearrangement proceeding through a four-membered ring. It was also found that under certain conditions the amidyl radical produced by cleavage of the four-membered ring intermediate can undergo fragmentation to give an isocyanate. Such fragmentations are unprecedented at temperatures corresponding to refluxing benzene or chlorobenzene. [reaction: see text]

Tin-free radical cyclizations for the synthesis of 7-azaoxindoles, 7-azaindolines, tetrahydro[1,8]naphthyridines, and tetrahydro-5H-pyrido[2,3-b]azepin-8-ones.

[reaction: see text] Compounds containing a pyridine nucleus fused to a saturated nitrogen-containing ring, including 7-azaoxindoles, 7-azaindolines, tetrahydro[1,8]naphthyridines, and tetrahydro-5H-pyrido[2,3-b]azepin-8-ones, were prepared in good yield starting from various 2,6-dichloropyridines. The method hinges on a free-radical xanthate-mediated cyclization or intermolecular addition/cyclization sequence for the construction of the new fused rings.