Sequential Ring Opening/In Situ SO2-Capture/Alkynylation of Cyclopropanols with Alkynyl Triflones Initiated by Energy Transfer.

A visible-light-triggered ring opening/in situ SO2-capture/alkynylation sequence of cyclopropyl alcohols with alkynyl triflones using 4CzIPN as a triplet energy transfer photocatalyst is herein described. This metal-free protocol provides a straightforward and atom-economical approach to alkynyl-substituted γ-keto sulfones with a broad scope of substituents. In this transformation, alkynyl triflones could be used as both radical acceptors and SO2 donors. Preliminary experimental mechanistic studies and synthetic utility are also demonstrated.

Et2Zn-Mediated Radical (3 + 2) Cycloaddition of Vinyl Azides with Ethyl Iododifluoroacetate to Access 3,3-Difluoro-γ-lactams.

A diethylzinc-mediated radical (3 + 2) cycloaddition of vinyl azides with ethyl iododifluoroacetate is presented. The developed reaction features good functional group tolerance, broad substrate scope, and operational simplicity, enabling efficient assembly of a wide range of 3,3-difluoro-γ-lactam derivatives bearing an O-substituted quaternary carbon center in moderate to good yields. The utility of the method is showcased by a scaled-up reaction, conversion of the product, and late-stage structural modifications of a variety of pharmaceutical compounds.

Visible-Light-Initiated Sequential Trifluoromethylation/Remote C(sp3)-H Alkynylation of Vinyl Azides by Radical Relay.

A visible-light-initiated trifluoromethylation/remote aliphatic C-H alkynylation of α-alkyl-substituted vinyl azides using acetylenic triflones as both the trifluoromethyl and alkyne donors is described. The reaction occurred under environmentally benign and radical initiator-free reaction conditions, affording γ-alkynylated trifluoromethyl ketone derivatives with a broad scope of substituents. Mechanistic studies suggested that the reaction is initiated via a triplet-triplet energy transfer between the 4CzIPN catalyst and acetylenic triflone, followed by fragmentation to generate a trifluoromethyl radical and an alkynyl radical.

Organophotoredox and Hydrogen Atom Transfer Cocatalyzed C-H Alkylation of Quinoxalin-2(1H)-ones with Aldehydes, Amides, Alcohols, Ethers, or Cycloalkanes.

Described is a mild method that merges organophotoredox catalysis with hydrogen atom transfer to enable C-H alkylation of quinoxalin-2(1H)-ones with feedstock aldehydes, amides, alcohols, ethers, or cycloalkanes. This reaction occurred under environmentally benign and external oxidant-free reaction conditions, providing a general and sustainable access to various C3-alkylated quinoxalinone derivatives with broad substituent diversity and good functional group compatibility.

Radical borylation of vinyl azides with NHC-boranes: divergent synthesis of α-boryl ketones and borylated triazoles.

A divergent radical borylation of vinyl azides with N-heterocyclic carbene (NHC) boranes in the presence of tBuSH is described. The protocol enables the divergent synthesis of α-boryl ketones and borylated triazoles with excellent functional group tolerance and a broad substrate scope. Remarkably, this work shows that vinyl azides can serve as unprecedented five-atom synthons for the construction of 1,2,3-triazoles without N2 extrusion.

Radical Hydroboration and Hydrosilylation of gem-Difluoroalkenes: Synthesis of α-Difluorinated Alkylborons and Alkylsilanes.

A first example of radical hydroboration and hydrosilylation of gem-difluoroalkenes using ABIN as the radical initiator is described. This protocol features good functional group tolerance, operational simplicity, high atom economy, and easy scale-up, enabling efficient assembly of a wide range of α-difluorinated alkylborons and alkylsilanes in moderate to excellent yields. The synthetic utility of these products is demonstrated by further transformation of the C-B bond and C-Si bond into valuable CF2-containing molecules.

Silver-promoted decarboxylative radical addition/annulation of oxamic acids with gem-difluoroolefins: concise access to CF2-containing 3,4-dihydroquinolin-2-ones.

Described is a silver-promoted decarboxylative radical addition/annulation of oxamic acids with gem-difluoroalkenes. This reaction proceeded under mild reaction conditions with broad functional group compatibility, enabling the convenient synthesis of various structurally diverse CF2-containing 3,4-dihydroquinolin-2-ones that might find applications in medical chemistry.

Cobalt-catalyzed C2α-acyloxylation of 2-substituted indoles with tert-butyl peresters.

An efficient cobalt-catalyzed C2α selective C(sp3)-H acyloxylation of 2-substituted indoles with tert-butyl peresters to synthesize diverse 2α-acyloxylated indole derivatives is described. This newly developed method exhibits mild conditions, low-cost catalyst, and high functional group compatibility. In addition, the effectiveness of this chemistry is illuminated by a late-stage modification of methylated indomethacin.

Iodine-catalyzed oxidative annulation of 3-cyanoacetylindoles with benzylamines: facile access to 5-(3-indolyl)oxazoles.

An iodine-catalyzed oxidative annulation of 3-cyanoacetylindoles with benzylamines has been developed. This reaction enables the convenient synthesis of a variety of 5-(3-indolyl)oxazoles under mild conditions with broad functional group compatibility.

Iodine-Catalyzed C-H Amidation and Imination at the 2α-Position of 2,3-Disubstituted Indoles with Chloramine Salts.

A novel iodine-catalyzed amidation and imination at the 2α-position of 2,3-disubstituted indoles in the presence of chloramine salts with high regioselectivity has been achieved. The protocol is applicable to a wide range of substrates to deliver the corresponding 2α-nitrogen-containing indole derivatives. Furthermore, to demonstrate the synthetic value of this established transformation, a concise assembly of the bridged tetracyclic framework of akuammiline alkaloids from the 2α-amidated product has been accomplished in five steps.

AcOH-mediated dichloroimination of indoles using chloramine-B: a facile access to 2,3-functionalized indolines.

A new and mild method for the efficient synthesis of 3,3-dichloro-2-sulfonyliminoindolines via AcOH-mediated dichloroimination of indoles using chloramine-B is presented. Application of this method to the efficient construction of pyrrolidinoindoles and N-C3 linked pyrrolidinoindolines is demonstrated.

Total synthesis of (-)-teucvidin.

A concise enantioselective synthesis of (-)-teucvidin has been achieved. Our synthetic strategy involved the diastereoselective Michael/Conia-ene cascade cyclization reaction for rapid establishment of the cis-decalin skeleton with three new stereogenic centers in one pot (72%, single diastereomer), the epoxidation/dealkoxycarbonylation protocol for construction of the fused furanone moiety, and the O-allylation/Claisen rearrangement protocol for construction of the all-carbon quaternary center at C9 of the clerodane skeleton.

Amine-induced Michael/Conia-ene cascade reaction: application to a formal synthesis of (+/-)-Clavukerin A.

An efficient and versatile amine-induced Michael/Conia-ene cascade cyclization reaction has been developed for establishing 6,6- and 5,7-bicyclic fused carbocycles with simple acyclic beta-ketoesters as the substrates in one-pot condition and this new cyclization method has been successfully utilized in a formal synthesis of (+/-)-Clavukerin A.

Base-catalyzed Diels-Alder reactions of 2H-pyran-2,5-diones: a mild approach to basiliolide B.

A new class of base-catalyzed Diels-Alder reactions of 2H-pyran-2,5-diones has been developed using catalytic amount of dicyclohexylmethylamine in tert-butyl alcohol. This method has been successfully employed for construction of the tricyclic core of basiliolide B at room temperature with good yields and exclusive endo selectivity.