Catalytic Reductive Cross Coupling and Enantioselective Protonation of Olefins to Construct Remote Stereocenters for Azaarenes.

Abstract: Radical hydroalkylation of olefins enabled by hydrogen atom transfer (HAT) catalysis represents a straightforward means to access C(sp3)-rich molecules from abundant feedstock chemicals without the need for prefunctionalization. While Giese-type hydroalkylation of activated olefins initiated by HAT of hydridic carbon-hydrogen bonds is well-precedented, hydroalkylation of unactivated olefins in a similar fashion remains elusive, primarily owing to a lack of general methods to overcome the inherent polarity-mismatch in this scenario. Here, we report the use of visible-light-driven dual HAT catalysis to achieve this goal, where catalytic amounts of an amine-borane and an in situ generated thiol were utilized as the hydrogen atom abstractor and donor, respectively. The reaction is completely atom-economical and exhibits a broad scope. Experimental and computational studies support the proposed mechanism and suggest that hydrogen-bonding between the amine-borane and substrates is beneficial to improving the reaction efficiency.

Abstract: A modular strategy to access the remote fluoroalkylated azaarene derivatives and the α-deuterated analogues, which are the isosteres of many pharmaceutically important compounds, is reported. Transformations under the sustainable photoredox catalysis platform could efficiently experience cascade radical addition, 1,n-hydrogen atom transfer (HAT), and single-electron reduction to offer the crucial anions α to azaarenes. Through reacting with H2O or the inexpensive D2O, two series of valuable products were obtained in high yields with substantial deuterium incorporation. The work demonstrates that the HAT of the α-sp3 C-H of the electron-withdrawing azaarenes with alkyl radicals is viable.

Abstract: An efficient radical conjugate addition/enantioselective protonation process was developed for N-aryl glycines and alkenyl oxazolines enabled by the cooperative photoredox catalysis and chiral phosphoric acid catalysis, which generated a series of chiral oxazolines bearing an α-stereocenter with high enantioselectivities. The facile transformations of the chiral oxazoline products into enantioenriched lactams and γ-amino esters bearing α-stereocenters demonstrate the value of this method.

Abstract: The first enantioselective Beckwith-Enholm cyclization reaction is reported herein. Under cooperative photoredox and chiral hydrogen-bonding catalysis mediated by visible light, cyclization of carbonyls with azaarene-based olefins as a new reaction system offers a general and divergent synthetic pathway to furnish a variety of highly valuable enantioenriched azaarene-functionalized carbocyclic and heterocyclic alcohols, which bear adjacent 1,2- or nonadjacent 1,3-stereocentres on distinct cyclic frameworks, in high yields and enantio- and diastereoselectivities. The good compatibility of various azaarenes and carbonyls as well as the diversity of cyclic structures of the products underscores the generality of the catalysis platform. In addition to the ability to precisely introduce deuterium into molecules in an enantioselective manner, the considerable synthetic value of this method includes the excellent antioxidant stress potential of the products. In particular, molecule 29 was determined to be a promising lead compound for antioxidant stress drug design.

Abstract: A fundamental aim in the field of catalysis is the development of new modes of small molecule activation. One approach toward the catalytic activation of organic molecules that has received much attention recently is visible light photoredox catalysis. In a general sense, this approach relies on the ability of metal complexes and organic dyes to engage in single-electron-transfer (SET) processes with organic substrates upon photoexcitation with visible light. Many of the most commonly employed visible light photocatalysts are polypyridyl complexes of ruthenium and iridium, and are typified by the complex tris(2,2′-bipyridine) ruthenium(II), or Ru(bpy)32+ (Figure 1). These complexes absorb light in the visible region of the electromagnetic spectrum to give stable, long-lived photoexcited states.1,2 The lifetime of the excited species is sufficiently long (1100 ns for Ru(bpy)32+) that it may engage in bimolecular electron-transfer reactions in competition with deactivation pathways.3 Although these species are poor single-electron oxidants and reductants in the ground state, excitation of an electron affords excited states that are very potent single-electron-transfer reagents. Importantly, the conversion of these bench stable, benign catalysts to redox-active species upon irradiation with simple household lightbulbs represents a remarkably chemoselective trigger to induce unique and valuable catalytic processes. Open in a separate window Figure 1 Ruthenium polypyridyl complexes: versatile visible light photocatalysts.

Abstract: In recent years, photoredox catalysis has come to the forefront in organic chemistry as a powerful strategy for the activation of small molecules. In a general sense, these approaches rely on the ability of metal complexes and organic dyes to convert visible light into chemical energy by engaging in single-electron transfer with organic substrates, thereby generating reactive intermediates. In this Perspective, we highlight the unique ability of photoredox catalysis to expedite the development of completely new reaction mechanisms, with particular emphasis placed on multicatalytic strategies that enable the construction of challenging carbon–carbon and carbon–heteroatom bonds.

Abstract: 2. The Incubation Period 2904 3. Alkylation with Activated Alkenes 2905 3.1. Copper Complexes 2905 3.2. Other Metal Complexes 2907 3.3. Organocatalysis 2907 4. Alkylation with Carbonyl Compounds 2908 4.1. Copper Complexes 2908 4.2. Other Metal Complexes 2909 4.3. Organocatalysis 2910 5. Alkylation with Imines 2911 5.1. Copper Complexes 2911 5.2. Organocatalysis 2912 6. Miscellaneous 2913 7. Conclusion and Perspectives 2914 8. Acknowledgments 2914 9. Note Added in Proof 2914 10. References 2914

Abstract: The asymmetric Friedel–Crafts reaction is one of the most powerful methods to synthesize optically active aromatic compounds. Particularly, the Friedel–Crafts alkylation of arenes with unsaturated compounds activated by chiral Bronsted acids provides direct access to enantiopure aromatic derivatives with perfect atom economy. In this tutorial review, recent progress in the development of chiral Bronsted acid-catalyzed asymmetric Friedel–Crafts reactions is presented.

Abstract: The nature of the excited state renders the development of chiral catalysts for enantioselective photochemical reactions a considerable challenge. The absorption of a 400 nm photon corresponds to an energy uptake of approximately 300 kJ mol(-1) . Given the large distance to the ground state, innovative concepts are required to open reaction pathways that selectively lead to a single enantiomer of the desired product. This Review outlines the two major concepts of homogenously catalyzed enantioselective processes. The first part deals with chiral photocatalysts, which intervene in the photochemical key step and induce an asymmetric induction in this step. In the second part, reactions are presented in which the photochemical excitation is mediated by an achiral photocatalyst and the transfer of chirality is ensured by a second chiral catalyst (dual catalysis).