Electrophile promoted cyclization of ortho-aryl substituted ynamides: construction of 3-amino-4-halo- or 4 seleno-isocoumarin derivatives.

Isocoumarins are important building blocks in medicinal chemistry. They are widespread in the core structure of biologically active compounds. Here we report the development of an efficient and highly reactive electrophilic cyclization of ortho-ynamidyl benzoate esters providing access to 3-amino-4-halo- or 4-seleno-isocoumarins in a short time (<1 min) with good yields.

Photoinduced Aerobic Iodoarene-Catalyzed Spirocyclization of N-Oxy-amides to N-Fused Spirolactams*.

Iodoarene catalysis is a powerful methodology that usually requires an excess of oxidant, or of redox mediator if the terminal oxidant is dioxygen, to generate the key hypervalent iodine intermediate to proceed efficiently. We report that, using the spiro-cyclization of amides as a benchmark reaction, aerobic iodoarene catalysis can be enabled by relying on a pyrylium photocatalyst under blue light irradiation. This unprecedented dual organocatalytic system allows the use of low catalytic loading of both catalysts under very mild operating conditions.

Rapid synthesis of 3-amino-1H-isochromene from ortho-ynamidyl het(aryl) aldehyde derivatives.

A simple and original efficient synthesis of 3-amino-1H-isochromene bearing a bromine atom at the C-1 position via a 6-endo-cyclization approach from in situ generated ortho-ynamidyl het(aryl) aldehyde derivatives is achieved under mild reaction conditions and with good yields. Original ortho-ynamidyl benzaldehyde compounds were also successfully obtained.

Rapid synthesis of 3-amino isocoumarin derivatives from ynamides.

A novel and efficient fast synthesis of 3-amino isocoumarins in good to excellent yields is reported. These interesting scaffolds can be obtained either in a single step from readily available ynamides or in a two-step sequence from the corresponding alkynyl bromide after C-N cross-coupling. This protocol, which only requires a Brønsted or Lewis acid as a promoter, offers an alternative approach toward synthesizing 3-substituted isocoumarins under smooth and fast conditions.

Reaction of Ynamides with Iminoiodinane-Derived Nitrenes: Formation of Oxazolones and Polyfunctionalized Oxazolidinones.

This article describes the reaction of ynamides with metallanitrenes generated in the presence of an iodine(III) oxidant. N-(Boc)-Ynamides are converted to oxazolones via a cyclization reaction. The reaction is mediated by a catalytic dirhodium-bound nitrene species that first behaves as a Lewis acid. The oxazolones can be converted in a one pot manner to functionalized oxazolidinones following a regio- and stereoselective oxyamination reaction with the same nitrene reagent generated in stoichiometric amounts.

Cobalt-Catalyzed Carbozincation of Ynamides.

An original cobalt-catalyzed ynamide carbozincation leading mainly to diverse 3-aryl enamides with mild reaction conditions and good functional-group tolerance has been developed. This reaction displays an excellent regio- and total stereoselectivity and opens the way to appealing synthetic applications. Moreover, this approach allows the selective synthesis of biologically relevant 3,5-disubstituted oxazolone frameworks.