Photoredox-Catalyzed Giese Reactions: Decarboxylative Additions to Cyclic Vinylogous Amides and Esters

An effective strategy has been developed for the photoredox-catalyzed decarboxylative addition of cyclic amino acids to both vinylogous amides and esters leading to uniquely substituted heterocycles. The additions take place exclusively trans to the substituent present on the dihydropyridone ring affording stereochemical control about the new carbon-carbon bond. These reactions are operationally simplistic and afford the desired products in good to excellent isolated yields.

The Synergetic and Multifaceted Nature of Carbon-Carbon Rotation Reveals the Origin of Stability for Bulky Alkane Dimers

Designing compounds with as long carbon-carbon bond distances as possible to challenge conventional chemical wisdom is of current interest in the literature. These compounds with exceedingly long bond lengths are commonly believed to be stabilized by dispersion interactions. In this work, we build nine dimeric models with varying sizes of alkyl groups, let the carbon-carbon bond flexibly rotate, and then analyze rotation barriers with energy decomposition and information-theoretic approaches in density functional theory. Our results show that these rotations lead to extraordinarily elongated carbon-carbon bond distances and rotation barriers are synergetic and multifaceted in nature. The dominant factor contributing to the stability of the dimers with bulky alkane groups is not the dispersion force but the electrostatic interaction with steric and exchange-correlation effects playing minor yet indispensable roles.

Electrochemical Radical C(sp3)-H Arylation of Xanthenes with Electron-Rich Arenes

C(sp3)-H arylation has recently emerged as a powerful straegy for complex organic molecules synthesis through a new carbon-carbon bond formation. We herein describe an efficient electrochemical C(sp3)-H arylation of xanthenes...

Organocatalytic Difluorobenzylation of 1,2-Diketones via Mild Cleavage of Carbon−Carbon Bonds

α-aryl-α,α-Difluoroacetophenones (DFAPs) are developed as a new type of difluorobenzylation reagents that can be facilely prepared from readily available and cheap starting materials. In-situ carbon-carbon bond cleavage of electron-deficient DFAPs...

A Mechanistic Study of Syngas to Light Olefins over OXZEO Bifunctional Catalysts: Insights into the Initial Carbon-Carbon Bond Formation on the Oxide

Direct conversion of syngas into light olefins (C2=-C4=) using bifunctional catalyst composed of oxide and zeolite (OXZEO) has attracted extensive attention in both academia and industry. However, the reaction intermediates...

Development of Chiral Potassium Strong Brønsted Base Catalysts for Enantioselective Carbon–Carbon Bond-Forming Reactions

Chiral alkaline metal Brønsted bases are traditional and reliable promoters in enantioselective catalysis. Here, new chiral potassium strong base catalysts were developed for enantioselective carbon–carbon bond-forming reactions of weakly acidic...

Mechanistic analysis of carbon–carbon bond formation by deoxypodophyllotoxin synthase

Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate–dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (±)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS’s catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel–Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs.

Decoding key transient inter-catalyst interactions in a metallaphotoredox-catalysed cross-electrophile coupling reaction

Metallaphotoredox chemistry has recently witnessed a renaissance through the use of abundant first-row transition metals combined with suitable photocatalysts. The intricate details arising from the combination of two (or more) catalytic components during the reaction and specially the inter-catalyst interactions remain poorly understood. As a representative example of a catalytic process featuring such intricacies, we here present a meticulous study of the mechanism of a cobalt-organophotoredox catalysed allylation of aldehydes. Importantly, the commonly proposed elementary steps in reductive metallaphotoredox chemistry are more complex than previously assumed. After initial reductive quenching, a transient charge-transfer complex forms that interacts with both the transition-metal catalyst, as well as the catalytic base. Surprisingly, the former interaction leads to deactivation due to induced charge recombination, while the latter promotes deprotonation of the electron donor, which is a crucial step in order to promote productive catalysis, but is often neglected. Due to the low efficiency of this process, the overall catalytic reaction is photon-limited and the cobalt catalyst remains in a dual resting state awaiting photoinduced reduction. These new insights are of general importance to the synthetic community, as photoredox chemistry has become a powerful tool used in the creation of elusive compounds through carbon-carbon bond formations. Understanding the underlying factors that determine the efficiency of such reactions provides a conceptually stronger reactivity paradigm to empower future approaches to synthetic challenges that rely on dual metallaphotoredox catalysis.

ASYMMETRIC ORGANOCATALYSIS

Dear Reader, Two basic reactions that were taught to us in the organic chemistry courses were the aldol condensation reaction and the Diels-Alder reaction. In aldol condensation, discovered by the French chemist Charles Wurtz in 1872, an enolate ion reacts with a carbonyl compound in the presence of an acid/ base catalyst to form a β-hydroxy aldehyde or a β-hydroxy ketone, usually followed by dehydration to give a conjugated enone. If the enolate ion and the carbonyl group are present in the same molecule, then the aldol reaction is intramolecular. It is an extremely useful carbon-carbon bond-forming reaction. The Diels-Alder reaction, discovered in 1928 by the German chemist Otto Diels and his student Kurt Alder, is the reaction between a conjugated diene and an alkene, a so-called dienophile, to form an unsaturated six-membered ring. It is called a cycloaddition reaction, since the reaction involves the formation of a cyclic product via a cyclic transition state. Uncatalysed Diels– Alder reactions usually require extended reaction times at elevated pressures and temperatures with the formation of by-products, hence various catalysts are employed. The Diels-Alder reaction also has great industrial relevance and the discoverers were crowned with the 1950 Nobel Prize in Chemistry. The aldol condensation reaction and the Diels-Alder reaction typically require catalysts, basically Brønsted acids, Brønsted bases, Lewis acids or Lewis bases. This triggered the minds of Dr. David MacMillan and Dr. Benjamin List for different reasons at different locations in USA around not so different times, more than twenty years ago, culminating in their being jointly awarded the Nobel Prize in Chemistry for this year.