C2-Alkenylation of N-heteroaromatic compounds:Via Brønsted acid catalysis

C2-alkenylated heteroaromatics can be accessed by simple Brønsted acid catalysed union of diverse heteroarene N-oxides with alkenes. The scope and limitations of the process are outlined.</p

Enantioselective Copper‐Catalyzed Borylative Cyclization for the Synthesis of Quinazolinones

From Wiley via Jisc Publications RouterHistory: received 2021-03-05, pub-electronic 2021-05-19Article version: VoRPublication status: PublishedFunder: Leverhulme Trust; Id: http://dx.doi.org/10.13039/501100000275; Grant(s): RPG-2016-360Funder: Horizon 2020 Framework Programme; Id: http://dx.doi.org/10.13039/100010661; Grant(s): 798846-CuCANAbstract: Quinazolinones are common substructures in molecules of medicinal importance. We report an enantioselective copper‐catalyzed borylative cyclization for the assembly of privileged pyrroloquinazolinone motifs. The reaction proceeds with high enantio‐ and diastereocontrol, and can deliver products containing quaternary stereocenters. The utility of the products is demonstrated through further manipulations

Chemistry glows green with photoredox catalysis

Can organic chemistry mimic nature in efficiency and sustainability? Not yet, but recent developments in photoredox catalysis animated the synthetic chemistry field, providing greener opportunities for industry and academia

Synthetic Methods Driven by the Photoactivity of Electron Donor− Acceptor Complexes

The association of an electron-rich substrate with an electron-accepting molecule can generate a new molecular aggregate in the ground state, called an electron donor−acceptor (EDA) complex. Even when the two precursors do not absorb visible light, the resulting EDA complex often does. In 1952, Mulliken proposed a quantum-mechanical theory to rationalize the formation of such colored EDA complexes. However, and besides a few pioneering studies in the 20th century, it is only in the past few years that the EDA complex photochemistry has been recognized as a powerful strategy for expanding the potential of visible- light-driven radical synthetic chemistry. Here, we explain why this photochemical synthetic approach was overlooked for so long. We critically discuss the historical context, scientific reasons, serendipitous observations, and landmark discoveries that were essential for progress in the field. We also outline future directions and identify the key advances that are needed to fully exploit the potential of the EDA complex photochemistry

Asymmetric Photocatalytic C−H Functionalization of Toluene and Derivatives

Reported herein is a visible-light-mediated organocatalytic direct C−H functionalization of toluene derivatives to afford enantioenriched β-benzylated alde- hydes from the corresponding enals. The process combines the oxidative power of a chiral excited-state iminium ion and the basic nature of its counteranion to trigger the generation of benzylic radicals by means of a sequential multisite proton-coupled electron transfer mechanism. This study shows that feedstock chemicals generally used as solvents, such as toluene and xylene derivatives, can be used as substrates for making chiral molecules with high enantioselectivity

Asymmetric Total Synthesis of (−)-Phaeocaulisin A

[Image: see text] The therapeutic properties of Curcuma (ginger and turmeric’s family) have long been known in traditional medicine. However, only recently have guaiane-type sesquiterpenes extracted from Curcuma phaeocaulis been submitted to biological testing, and their enhanced bioactivity was highlighted. Among these compounds, phaeocaulisin A has shown remarkable anti-inflammatory and anticancer activity, which appears to be tied to the unique bridged acetal moiety embedded in its tetracyclic framework. Prompted by the promising biological profile of phaeocaulisin A and by the absence of a synthetic route for its provision, we have implemented the first enantioselective total synthesis of phaeocaulisin A in 17 steps with 2% overall yield. Our route design builds on the identification of an enantioenriched lactone intermediate, tailored with both a ketone moiety and a conjugated alkene system. Taking advantage of the umpolung carbonyl-olefin coupling reactivity enabled by the archetypal single-electron transfer (SET) reductant samarium diiodide (SmI(2)), the lactone intermediate was submitted to two sequential SmI(2)-mediated cyclizations to stereoselectively construct the polycyclic core of the natural product. Crucially, by exploiting the innate inner-sphere nature of carbonyl reduction using SmI(2), we have used a steric blocking strategy to render sites SET-unreceptive and thus achieve chemoselective reduction in a complex substrate. Our asymmetric route enabled elucidation of the naturally occurring isomer of phaeocaulisin A and provides a synthetic platform to access other guaiane-type sesquiterpenes from C. phaeocaulis—as well as their synthetic derivatives—for medicinal chemistry and drug design