Search

In contrast to the wealth of asymmetric transformations for generating central chirality from alkyl radicals, the enantiocontrol over the allenyl radicals for forging axial chirality represents an uncharted domain. The challenge arises from the unique elongated linear configuration of the allenyl radicals that necessitates the stereo‐differentiation of remote motifs away from the radical reaction site. We herein describe a copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes via the coupling of allenyl radicals with terminal alkynes, providing diverse synthetically challenging tetrasubstituted chiral allenes. A chiral N,N,P‐ligand is crucial for both the reaction initiation and the enantiocontrol over the highly reactive allenyl radicals. The reaction features a broad substrate scope, covering a variety of (hetero)aryl and alkyl alkynes and 1,3‐enynes as well as radical precursors with excellent functional group tolerance. [ABSTRACT FROM AUTHOR]

We describe a photoinduced copper‐catalyzed asymmetric radical decarboxylative alkynylation of bench‐stable N‐hydroxyphthalimide(NHP)‐type esters of racemic alkyl carboxylic acids with terminal alkynes, which provides a flexible platform for the construction of chiral C(sp3)−C(sp) bonds. Critical to the success of this process are not only the use of the copper catalyst as a dual photo‐ and cross‐coupling catalyst but also tuning of the NHP‐type esters to inhibit the facile homodimerization of the alkyl radical and terminal alkyne, respectively. Owing to the use of stable and easily available NHP‐type esters, the reaction features a broader substrate scope compared with reactions using the alkyl halide counterparts, covering (hetero)benzyl‐, allyl‐, and aminocarbonyl‐substituted carboxylic acid derivatives, and (hetero)aryl and alkyl as well as silyl alkynes, thus providing a vital complementary approach to the previously reported method. [ABSTRACT FROM AUTHOR]

The radical-involved 1,2-difunctionalization of alkenes has developed into a robust tool for preparation of complex organic molecules. Despite significant advances in this area, the catalytic asymmetric version still remains a challenging task mainly due to the difficulty in the stereocontrol of the highly reactive radical intermediates. Recently, owing to the good single-electron transfer ability and coordination with chiral ligands of copper catalysts, remarkable achievements in radical-involved asymmetric alkene difunctionalization have been made via synergistic combination of copper and chiral ligands. This tutorial review highlights the recent progress in copper-catalysed radical-involved asymmetric 1,2-difunctionalization of alkenes and the mechanistic scenarios governing the stereocontrol, with an emphasis on utilization of chiral ligands. [ABSTRACT FROM AUTHOR]

Transition metal-catalyzed enantioselective Sonogashira-type oxidative C(sp3)—C(sp) coupling of unactivated C(sp3)−H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C(sp3)—H bond functionalization and the inhibition of readily occurring Glaser homocoupling of terminal alkynes. Here, we report a copper/chiral cinchona alkaloid-based N,N,P-ligand catalyst for asymmetric oxidative cross-coupling of unactivated C(sp3)—H bonds with terminal alkynes in a highly regio-, chemo-, and enantioselective manner. The use of N-fluoroamide as a mild oxidant is essential to site-selectively generate alkyl radical species while efficiently avoiding Glaser homocoupling. This reaction accommodates a range of (hetero)aryl and alkyl alkynes; (hetero)benzylic and propargylic C(sp3)−H bonds are all applicable. This process allows expedient access to chiral alkynyl amides/aldehydes. More importantly, it also provides a versatile tool for the construction of chiral C(sp3)—C(sp), C(sp3)—C(sp2), and C(sp3)—C(sp3) bonds when allied with follow-up transformations. Enantioselective oxidative cross-coupling of unactivated C(sp3)−H bonds and terminal alkynes is challenging. Here, the authors developed a copper/cinchona alkaloid catalyst for the asymmetric Sonogashira-type alkynylation of C(sp3)-H bonds via radical intermediates. [ABSTRACT FROM AUTHOR]

Abstract: A copper‐catalyzed asymmetric radical oxytrifluoromethylation of alkenyl oxime and Togni's reagent has been successfully developed, thereby providing straightforward access to CF3‐containing isoxazolines bearing α‐tertiary stereocenters with excellent yield and enantioselectivity. The key to success is the rational design of cinchona‐alkaloid‐based sulfonamides as neutral/anionic hybrid ligands to effectively control the stereochemistry in copper‐catalyzed reactions involving free alkyl radical species. The utility of this method is illustrated by efficient transformation of the products into useful chiral CF3‐containing 1,3‐aminoalcohols. [ABSTRACT FROM AUTHOR]

Abstract A mild and efficient copper-catalyzed radical oxytrifluoromethylation reaction of alkenyl oximes was successfully developed. The method provides a straightforward access to a wide range of CF 3 -containing isoxazolines in good to excellent yields. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Trifluoromethylation of alkenes has long been the interest of synthetic chemists. It is not only because of the great importance of F-containing compounds, but also on account of the pleasure of cracking the challenges in methodology development in this field. In particular, amino- and azidotrifluoromethylation of alkenes have recently been developing in a fast speed. This digest mainly deals with this advancement in racemic copper- and photocatalyzed amino- and azidotrifluoromethylation of alkenes while giving special highlight on our recent breakthrough on the copper-catalyzed asymmetric aminotrifluoromethylation reaction. [ABSTRACT FROM AUTHOR]

A general copper-catalyzed C(sp 3)−C(sp 2) cross-coupling of (hetero)benzyl bromides with the air- and moisture-stable aryl nucleophiles has been developed, providing a facile access to pharmaceutically useful 1,1-di(hetero)arylalkane and 1-aryl-1-heteroarylalkane scaffolds. Critical to the success is the utilization of a proline-based N,N,P-ligand to enhance the reducing capability of copper, thus easily converting benzyl bromides to the corresponding radical species via a single-electron transfer process under ambient conditions. The reaction features a broad substrate scope, covering (hetero)arylboronate esters, oxadiazoles, and benzo[ d ]oxazoles, as well as primary and secondary (hetero)benzyl bromides with excellent functional group tolerance. [Display omitted] [ABSTRACT FROM AUTHOR]