Radical Chain Monoalkylation of Pyridines

<p>The monoalkylation of N-methoxypyridinium salts with alkyl radicals generated from alkenes (via hydroboration with catecholborane), alkyl iodides (via iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and does not require the use of an external oxidant. A rate constant for the addition of a primary radical to N-methoxylepidinium >107 M–1 s–1 was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radical to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction could be extended to a three component carbopyridinylation of electron rich alkenes including enol esters, enol ethers and enamides.</p>

Enantioselective access to chiral aliphatic amines and alcohols via Ni-catalyzed hydroalkylations

Chiral aliphatic amine and alcohol derivatives are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic acyl amines and esters in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral secondary alkyl-substituted amine and secondary alkyl-substituted alcohol derivatives from simple starting materials with great functional group tolerance.

Organoboron Mediated Homolytic Aromatic Substitution of N-Methoxypyridinium Salts

<p>The monoalkylation of N-methoxypyridinium salts with alkyl radicals generated from alkenes (via hydroboration with catecholborane), alkyl iodides (via iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and does not require the use of an external oxidant. A rate constant for the addition of a primary radical to N-methoxylepidinium >107 M–1 s–1 was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radical to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction could be extended to a three component carbopyridinylation of electron rich alkenes including enol esters, enol ethers and enamides.</p>

Organoboron Mediated Homolytic Aromatic Substitution of N-Methoxypyridinium Salts

<p>The monoalkylation of N-methoxypyridinium salts with alkyl radicals generated from alkenes (via hydroboration with catecholborane), alkyl iodides (via iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and does not require the use of an external oxidant. A rate constant for the addition of a primary radical to N-methoxylepidinium >107 M–1 s–1 was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radical to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction could be extended to a three component carbopyridinylation of electron rich alkenes including enol esters, enol ethers and enamides.</p>

Recent Advances in the Transition Metal Catalyzed Addition of Carboxylic Acids to Alkynes

: Recent advances in the metal-catalyzed hydrofunctionalization of alkynes with carboxylic acids are comprehensively reviewed. Both inter- and intramolecular processes, leading respectively to enol esters and lactones, are discussed, as well as the involvement of these transformations in the synthesis of natural products and biologically active molecules, and the assembly of elaborated heterocyclic compounds though cascade processes. Literature published since 2011 is covered.

Enantioselective Access to Dialkyl Amines and Alcohols via Ni-Catalyzed Reductive Hydroalkylations

Chiral dialkyl amines and alcohols are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective reductive hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic amines and alcohols in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral dialkyl amine and alcohol derivatives from simple starting materials with great functional group tolerance.

Metal-free catalytic hydrocarboxylation of hexafluorobut-2-yne

An efficient method for stereoselective synthesis of trifluorinated enol esters catalyzed by base was introduced.

A Giese Reaction for Electron-Rich Alkenes

A general method for the hydroalkylation of electron-rich terminal and non-terminal alkenes such as enol esters, alkenyl sulfides, enol ethers, silyl enol ethers, enamides and enecarbamates has been developed. The reactions are carried out at room temperature under air initiation in the presence of triethylborane acting as a chain transfer reagent and 4-<i>tert</i>-butylcatechol (TBC) as a source of hydrogen atom. The efficacy of the reaction is best explained by very favorable polar effects supporting the chain process and minimizing undesired polar reactions. The stereoselective hydroalkylation of chiral <i>N</i>-(alk-1-en-1-yl)oxazolidin-2-ones takes place with good to excellent diastereocontrol.

A Giese Reaction for Electron-Rich Alkenes

A general method for the hydroalkylation of electron-rich terminal and non-terminal alkenes such as enol esters, alkenyl sulfides, enol ethers, silyl enol ethers, enamides and enecarbamates has been developed. The reactions are carried out at room temperature under air initiation in the presence of triethylborane acting as a chain transfer reagent and 4-<i>tert</i>-butylcatechol (TBC) as a source of hydrogen atom. The efficacy of the reaction is best explained by very favorable polar effects supporting the chain process and minimizing undesired polar reactions. The stereoselective hydroalkylation of chiral <i>N</i>-(alk-1-en-1-yl)oxazolidin-2-ones takes place with good to excellent diastereocontrol.