Cooperative Cu/azodiformate system-catalyzed allylic C-H amination of unactivated internal alkenes directed by aminoquinoline.

Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp3)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp3)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.

Electrochemical collective synthesis of labeled pyrroloindoline alkaloids with Freon-type methanes as functional C1 synthons.

Utilization of Freon-type methanes as functional one-carbon synthons in the synthesis of various deuterated indoline alkaloids was demonstrated here. A series of halomethyl radicals were generated from electro-reductive C-X cleavage of Freon-type methanes and captured efficiently by acrylamides to provide various halogenated oxindoles via radical cyclization. This reaction features good functional group tolerance, and deuterium and fluorine atoms could be introduced facilely from Freon-type methanes. Further transformation of halogenated oxindoles enabled the synthesis of many (labeled) bioactive drug molecules and skeletons, such as deuterated (±)-physostigmine, deuterated (±)-esermethole and deuterated (±)-lansai B.

Bioinspired Palladium-Catalyzed Intramolecular C(sp3 )-H Activation for the Collective Synthesis of Proline Natural Products.

Bioinspired palladium-catalyzed intramolecular cyclization of amino acid derivatives containing a vinyl iodide moiety by C-H activation enabled rapid access to a wide range of functionalized proline derivatives with an exocyclic olefin. To demonstrate the practicality of this methodology, the functionalized prolines were used as intermediates for the synthesis of several natural products: lucentamycin A, oxotomaymycin, oxoprothracarcin, and barmumycin.

Base-Promoted Cobalt-Catalyzed Regio- and Enantioselective para-Friedel-Crafts Alkylation of Aniline Derivatives.

Herein we disclose a highly efficient enantioselective para-C-H alkylation of aniline derivatives promoted by a base/Co/indeno-pybox ligand system. This methodology leads to the efficient construction of a series of enantioenriched aniline derivatives bearing all-carbon quaternary stereocenters. In addition, several special biologically or medicinally active indoles are facilely synthesized by our Co-catalyzed asymmetry synthesis method. Density functional theory calculations and experiment results suggest that the (acac)- anion of Co(acac)2 plays a very important role in chiral control during the nucleophilic reaction.

Paired Electrolysis Enabled Ni-Catalyzed Unconventional Cascade Reductive Thiolation Using Sulfinates.

Herein, we have reported a nickel-catalyzed cascade reductive thiolation of aryl halides with sulfinates driven by paired electrolysis. This protocol uses sulfinates as the sulfur source, and various thioethers could be synthesized under mild conditions. By mechanism exploration, we find that a cascade chemical step is allowed on the electrode interface and could alter the reaction pathway in paired electrolysis, whose findings could help the discovery of novel cascade reactions with unique reactivity.

Remote C6-Enantioselective C-H Functionalization of 2,3-Disubstituted Indoles through the Dual H-Bonds and π-π Interaction Strategy Enabled by CPAs.

A versatile dual H-bonds and π-π interaction strategy that enables enantioselective remote C6-selective C-H functionalization of 2,3-disubstituted indoles was first reported. The N-H bond of indole was pivotal to achieve the C6 functionalization with excellent yield and enantioselectivity. Furthermore, this methodology leads to the efficient construction of numerous enantioenriched C6-functionalized indole products under mild reaction conditions employing different electrophiles. Preliminary cell proliferation investigations revealed that the synthesized chiral C6-substituted indole derivatives had potential anticancer activities.

Electrochemical Semipinacol Rearrangements of Allylic Alcohols: Construction of All-Carbon Quaternary Stereocenters.

The first examples of electrochemical trifluoromethylation and sulfonylation/semipinacol rearrangements of allylic alcohols were developed using cheap and stable RSO2Na (R = CF3, Ph) as reagents. Various ß-trifluoromethyl and sulfonated ketones were obtained in moderate to excellent yields. This strategy provides a facile, direct, and complementary approach to construct all-carbon quaternary stereocenters. In addition, the reaction has the advantages of being chemical oxidant-free and metal-free and has safe and mild reaction conditions.

Copper-Catalyzed Selective ortho-C-H/N-H Annulation of Benzamides with Arynes: Synthesis of Phenanthridinone Alkaloids.

An efficient and convenient copper-catalyzed method has been developed to achieve direct ortho-C-H/N-H annulation to synthesize phenanthridinones with arynes. This method highlights an emerging strategy to transform inert C-H bonds into versatile functional groups in organic synthesis and provides a new way to synthesize phenanthridinone alkaloids efficiently.