Ni-Catalyzed Stereoconvergent Reductive Dimerization of Bromocyclobutenes.

A nickel-catalyzed reductive dimerization of bromocyclobutenes to produce unusual and unprecedented cyclobutene dimers was developed. In a stereoconvergent procedure, various bromocyclobutenes were readily dimerized in good yields, with good diastereoselectivities and broad functional group tolerance. Notably, the presence of a carbonyl group in the starting material appears to dictate diastereoselectivity.

Cobalt-electrocatalytic HAT for functionalization of unsaturated C-C bonds.

The study and application of transition metal hydrides (TMHs) has been an active area of chemical research since the early 1960s, for energy storage, through the reduction of protons to generate hydrogen, and for organic synthesis, for the functionalization of unsaturated C-C, C-O and C-N bonds. In the former instance, electrochemical means for driving such reactivity has been common place since the 1950s but the use of stoichiometric exogenous organic- and metal-based reductants to harness the power of TMHs in synthetic chemistry remains the norm. In particular, cobalt-based TMHs have found widespread use for the derivatization of olefins and alkynes in complex molecule construction, often by a net hydrogen atom transfer (HAT).

Recent discoveries on the structure of iodine(iii) reagents and their use in cross-nucleophile coupling.

This perspective article discusses structural features of iodine(iii) compounds as a prelude to presenting their use as umpolung reagents, in particular as pertains to their ability to promote the selective coupling of two nucleophilic species 2e oxidation.

Formal Enone α-Arylation via I(III)-Mediated Aryl Migration/Elimination.

A formal enone α-arylation is described. This metal-free transformation relies on the I(III)-mediated skeletal reorganization of silyl enol ethers and features mild conditions, good yields, and high stereoselectivities for β-substituted enones.

A Novel Class of 7-Membered Heterocyclic Compounds.

The work presented herein describes the synthesis of a formerly inaccessible class of heterocyclic compounds. The reaction relies on α-phthalimido-amides, which are readily prepared from amino acids in 2 simple reactions steps. Under amide activation conditions in which classical keteniminium ions are not formed, the nitrile solvent is incorporated into the new fused 7-membered ring system.

An α-Cyclopropanation of Carbonyl Derivatives by Oxidative Umpolung.

The reactivity of iodine(III) reagents towards nucleophiles is often associated with umpolung and cationic mechanisms. Herein, we report a general process converting a range of ketone derivatives into α-cyclopropanated ketones by oxidative umpolung. Mechanistic investigation and careful characterization of side products revealed that the reaction follows an unexpected pathway and suggests the intermediacy of non-classical carbocations.

Chemoselective formal β-functionalization of substituted aliphatic amides enabled by a facile stereoselective oxidation event.

Aliphatic C-H functionalization is a topic of current intense interest in organic synthesis. Herein, we report that a facile and stereoselective dehydrogenation event enables the functionalization of aliphatic amides at different positions in a one-pot fashion. Derivatives of relevant pharmaceuticals were formally functionalized in the β-position in late-stage manner.

A Mild Synthesis of Bicyclic Alkoxyoxazolium Salts from Proline and Pipecolic Acid Derivatives.

A regio- and chemoselective preparation of bicyclic alkoxyoxazolium salts from amide derivatives of proline and pipecolic acid by electrophilic amide activation is reported. Mechanistic NMR experiments suggest an unusual role for the base and highlight the effect of substitution pattern of the substrates.

α-Arylation of Carbonyl Compounds through Oxidative C-C Bond Activation.

A synthetically useful approach for the direct α-arylation of carbonyl compounds through a novel oxidative C-C bond activation is reported. This mechanistically unusual process relies on a 1,2-aryl shift and results in all-carbon quaternary centers. The transformation displays broad functional-group tolerance and can in principle also be applied as an asymmetric variant.

A Catalytic Cross-Olefination of Diazo Compounds with Sulfoxonium Ylides.

A ruthenium-catalysed cross-olefination of diazo compounds and sulfoxonium ylides is presented. Our reaction design exploits the intrinsic difference in reactivity of diazo compounds and sulfoxonium ylides as both carbene precursors and nucleophiles, which results in a highly selective reaction.

Amide activation: an emerging tool for chemoselective synthesis.

It is textbook knowledge that carboxamides benefit from increased stabilisation of the electrophilic carbonyl carbon when compared to other carbonyl and carboxyl derivatives. This results in a considerably reduced reactivity towards nucleophiles. Accordingly, a perception has been developed of amides as significantly less useful functional handles than their ester and acid chloride counterparts.

A Stereoselective Reductive Hosomi-Sakurai Reaction.

A novel reductive variant of the classical Hosomi-Sakurai reaction is reported. This transformation hinges on a redox-neutral, stereoselective internal reduction event under mild conditions. This operationally simple reaction relies on readily available starting materials and leads to useful products in diastereoselectivities of up to 7:1.

Kinetic Resolution of 2-Substituted Indolines by N-Sulfonylation using an Atropisomeric 4-DMAP-N-oxide Organocatalyst.

The first catalytic kinetic resolution by N-sulfonylation is described. 2-Substituted indolines are resolved (s=2.6-19) using an atropisomeric 4-dimethylaminopyridine-N-oxide (4-DMAP-N-oxide) organocatalyst.

Modern tools for the chemical ligation and synthesis of modified peptides and proteins.

The ability to improve nature's capacity by introducing modification of biological interest in proteins and peptides (P&P) is one of the modern challenges in synthetic chemistry. Due to the unfavorable pharmacokinetic properties, many native P&P are of little use as therapeutic agents. Today, few methods for the preparation of modified proteins are available.