All-Carbon Quaternary Centers in Natural Products and Medicinal Chemistry: Recent Advances (2023)

Here we report on Ag⁺/S₂Europa₈²⁻Induction measurements of functionalized succinamides with all-carbon quaternary centers via a radical carbamylation/aryl migration/desulfonylation cascade. An improved process was developed by radical Smiles rearrangement using readily available and inexpensive oxalic acid monoamides as carbamoyl radical precursors. Furthermore, oxygen and water tolerance, ease of operation, convenient reagents, and scalability increase the practical value of the proposed synthetic strategy.

All-carbon quaternary centers are ubiquitous structural motifs in natural products, bioactive molecules, and drugs. The formation of these crowded carbon centers is notoriously challenging, and methods to access them remain in high demand. Transition metal-based strategies have emerged as efficient approaches for quaternary carbons, mainly relying on cross-coupling reactions and alkene arylation processes. Presented here is a simple method for generating benzylic all-carbon quaternary centers usinggem- difluoropropadiene. Features of the method include C–H functionalization at room temperature, intercalationgem-difluoroalene, and productsgem- Difluoroalkene products with wide application in synthesis and pharmaceutical sciences. Mechanistic studies support rhodium-catalyzed C–H cleavage-limiting transformations, possibly via a coordinated metalation-deprotonation pathway. selective region insertiongem-Difluoropropadiene is controlled by electronic effects.

The novel indium-mediated difluoroalkylation of iododifluoromethyl ketones with α,β-unsaturated ketones provides an apparently important route to 1,2-addition products with excellent regioselectivity. The method has a wide range of substrates, high efficiency and mild reaction conditions. In addition, this method has also been applied to the synthesis of difluoro derivatives of bioactive molecules containing unsaturated ketone structures, which can serve as potentially valuable fluorinated intermediates in drug discovery.

Tetrahedra: Asymmetry, Volume 28, Number 11, 2017, Pages 1633-1643

Practical synthesis of new phosphoramidite, phosphite and diaminophosphiteP,Yes- Ligands derived from (R,R)-tartaric acid. Studies of these chiral inductors have shown that they provide up to 93%AndIn the asymmetric allylation catalyzed by Pd (Other)-Allyl 1,3-diphenylacetate yield 84%AndIn the asymmetric alkylation of cinnamyl acetate with ethyl 2-oxocyclohexane-1-carboxylate catalyzed by Pd, up to 63%AndIn Pd-catalyzed desymmetryYes,Yes'-Xylenesulfonyl-middle view-cyclopent-4-ene-1,3-diol biscarbamate. The effects of structural modules, such as the nature of the phosphorus-containing ring or exocyclic substituents and the nature of the palladium source, on the catalytic activity and enantioselectivity were investigated.

Tetrahedron, Vol. 73, Number 29, 2017, p. 4023-4038

Pericyclic reactions can be challenging processes that exhibit asymmetry due to the coordinated and nonpolar nature of the transition state. Several examples have been reported where suitable catalysts bind heteroatom-containing substituents in substrates and accelerate the reaction rate. The requirement for coordination of functionalized substrates limits the generalizability of such asymmetric transformations. Multifunctional Brønsted acids are promising catalysts that represent a new paradigm for asymmetric pericyclic reactions. These chiral catalysts, which rely on multiple noncovalent interactions in the transition state for asymmetric induction, have been used to activate more general classes of substrates. In this review, we present recent advances in acid-catalyzed Brønsted pericyclic reactions and discuss the impact of catalyst design on expanding the substrate range for highly enantioselective processes.

Key Chiral Assisted Applications, 2014., str. 173-261

Integrative Organometallic Chemistry IV, Volume 13, 2022, Pages 132-193

Transition metal-catalyzed difunctionalization of unsaturated organics is a powerful bonding strategy in organic chemistry. Incorporation of combinations of amino, oxo, carbon and halogen groups on double or triple carbon-carbon bonds enables rapid construction of molecular complexity in a highly selective and efficient manner. This chapter focuses on a general type of reaction in which a transition metal mediates the addition of a coupling partner via a double or triple bond. Reactions in which transition metals play an auxiliary role (without addition or binding of unsaturated species) are not included. Given the broad scope of the topic, the material in this chapter is not intended to be exhaustive; this chapter is written to provide an overview of the topics covered in it. Representative examples have been selected to highlight the latest advances and draw attention to outstanding challenges and limitations of current approaches.

Tetrahedron Letters, Volume 60, Number 42, 2019, Number 151148

reported the one-pot reaction of zinc bicyclic enolate catalyzed with different electrophiles. Zinc enolate as a key intermediate can be efficiently released from the nickel-catalyzed reductive cyclization of alkynylcyclohexadienone. Multifunctionalization of this new class of one-pot reactions using aldehydes, imines, nitroalkenes, and α,β-unsaturated carbonyl compounds as electrophilescis-hydrobenzofurans and octahydro-4,7-ethanobenzofuran-9-one derivatives in moderate yields.

Cell Reports Physical Science, Volume 2, Issue 5, 2021, Article 100406

The development of catalyzed allyl-metal complexes via allylic C–H cleavage of alkenes without prefunctionalization followed by site- and stereoselective carbon-carbon bond formation is important in organic synthesis, providing a direct and economical step-by-step method for the introduction of multifunctional allyl groups into organic molecules. Despite significant progress in the enantioselective transformation of electrophilic allylic metal complexes and allylic radicals, the enantioselectivity of nucleophilic allylic metal intermediates obtained by the allylic C–H cleavage reaction remains undeveloped. Here we identify a multifunctional chiral catalyst derived from commercially available phosphine ligands and cobalt salts that enables precise control of the chemoselective formation of allyl-cobalt complexes and the location and position of carbonyl groups. Stereoselective addition to provide high yields and stereoselectivity over a wide range of homoallylic alcohols. This work may establish a platform for the development of enantioselective transformations of nucleophilic organometallic complexes resulting from catalytic C–H functionalization.