Many classical and emerging methodologies in organic chemistry rely on CO2 extrusion to generate reactive intermediates for bond-forming events. Synthetic reactions that involve the microscopic reverse, the carboxylation of reactive intermediates, have conventionally been undertaken using very different conditions. We report that chemically stable C(sp3) carboxylates, such as arylacetic acids and malonate half-esters, undergo uncatalyzed reversible decarboxylation in dimethylformamide solution. Decarboxylation/carboxylation occurs with substrates resistant to protodecarboxylation by Brønsted acids under otherwise identical conditions. Isotopically labeled carboxylic acids can be prepared in high chemical and isotopic yield by simply supplying an atmosphere of 13CO2 to carboxylate salts in polar aprotic solvents. An understanding of carboxylate reactivity in solution enables conditions for the trapping of aldehydes, ketones, and α,β-unsaturated esters.

A regio- and stereoselective rhodium-catalyzed synthesis of trisubstituted allylic alcohols is described. The utility of these synthons is demonstrated in a convenient synthesis of indenes and quinolines.

An atom economical and catalytic route for the synthesis of aryl‐ and alkyl‐substituted secondary amines has been developed. Using a bis(amidate)bis(amido)titanium(IV) precatalyst, the hydroamination of terminal alkynes with a range of amines results in the selective formation of the anti‐Markovnikov product. The crude enamine/imine mixtures are effectively hydrogenated using palladium on carbon (Pd/C) and H2 to afford the corresponding secondary amine in excellent yields. Simple work‐up procedures allow for the isolation of pure compounds while avoiding purification via column chromatography.magnified image

An anti-Markovnikov selective hydroamination of alkynes with N-silylamines to afford N-silylenamines is reported. The reaction is catalyzed by a bis(amidate)bis(amido)Ti(IV) catalyst and is compatible with a variety of terminal and internal alkynes. Stoichiometric mechanistic studies were also performed. This method easily affords interesting N-silylenamine synthons in good to excellent yields and the easily removable silyl protecting group enables the catalytic synthesis of primary amines.

A modular and selective synthesis of mono-, di-, tri-, tetra-, and pentasubstituted pyridines is reported. Hydroamination of alkynes with N-silylamine using a bis(amidate)bis(amido)titanium(IV) precatalyst furnishes the regioselective formation of N-silylenamines. Addition of α,β-unsaturated carbonyls to the crude mixtures followed by oxidation affords 47 examples of pyridines in yields of up to 96%. This synthetic route allows for the synthesis of diverse pyridines containing variable substitution patterns, including pharmaceutically relevant 2,4,5-trisubstituted pyridines, using this one-pot protocol.