Iodoarene-directed photoredox ß-C(sp3)-H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer and hydrogen atom transfer.

Site selective functionalization of inert remote C(sp3)-H bonds to increase molecular complexity offers vital potential for chemical synthesis and new drug development, thus it has been attracting ongoing research interest. In particular, typical ß-C(sp3)-H arylation methods using chelation-assisted metal catalysis or metal-catalyzed oxidative/photochemical in situ generated allyl C(sp3)-H bond processes have been well developed. However, radical-mediated direct ß-C(sp3)-H arylation of carbonyls remains elusive. Herein, we describe an iodoarene-directed photoredox ß-C(sp3)-H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). The method involves diethylaminoethyl radical-mediated generation of an aryl radical intermediate via XAT, then directed 1,5-HAT to form the remote alkyl radical intermediate and radical-radical coupling with cyanoarenes, and is applicable to a broad scope of unactivated remote C(sp3)-H bonds like ß-C(sp3)-H bonds of o-iodoaryl-substituted alkanones and α-C(sp3)-H bonds of o-iodoarylamides. Experimental findings are supported by computational studies (DFT calculations), revealing that this method operates via a radical-relay stepwise mechanism involving multiple SET, XAT, 1,5-HAT and radical-radical coupling processes.

Electroreductive Remote Benzylic C(sp3)-H Arylation of Aliphatic Ethers Using Cyanoarenes for the Synthesis of α-(Hetero)aryl Ethers.

An iodoarene-driven electroreductive remote C(sp3)-H arylation of unsymmetrical 1-(o-iodoaryl)alkyl ethers with cyanoarenes for the site selective synthesis of α-(hetero)aryl ethers is developed. With the introduction of cyanoarenes as both aryl sources and electron transfer mediators, this method includes an iodoarene-driven strategy to enable the regiocontrollable formation of two new bonds, one C(sp2)-H bond, and one C(sp2)-C(sp3) bond, in a single reaction step through the sequence of halogen atom transfer (XAT), hydrogen atom transfer (HAT), radical-radical coupling, and decyanation.

Nickel-Catalyzed C-S Reductive Cross-Coupling of Alkyl Halides with Arylthiosilanes toward Alkyl Aryl Thioethers.

A nickel-catalyzed C-S reductive cross-coupling of alkyl halides with arylthiosilanes for producing alkyl aryl thioethers is developed. This reaction is initiated by umpolung transformations of arylthiosilanes followed by C-S reductive cross-coupling with alkyl halides to manage an electrophilic alkyl group onto the electrophilic sulfur atom and then construct a C(sp3)-S bond, and features exquisite chemoselectivity, excellent tolerance of diverse functional groups, and wide applications for late-stage modification of biologically relevant molecules.

Rhodium-Catalyzed Reductive trans-Alkylacylation of Internal Alkynes via a Formal Carborhodation/C-H Carbonylation Cascade.

A rhodium-catalyzed reductive annulation cascade reaction that consists of a formal anti-carborhodation of a C≡C bond and an aromatic C-H carbonylation cascade for producing cyclopenta[de]quinoline-2,5(1H,3H)-diones is described. This method uses the Mn reductant to reductively regenerate the active rhodium species, hence obviating the need for prefunctionalization, and represents a new route to the carbonylation of aromatic C-H bonds with alkynes leading to aryl vinyl ketone frameworks.

Electrochemical dehydrogenative cross-coupling of two anilines: facile synthesis of unsymmetrical biaryls.

A new, general ortho/para-selective anodic dehydrogenative cross-coupling of two aryl amines, naphthalen-2-amine derivatives and anilines, is described. This electrochemical protocol assembles a wide range of unsymmetrical biaryls in good to excellent yields under mild, additional-metal-catalyst-free, oxidant-free conditions with excellent selectivity, broad substrate scope, and wide functional group tolerance. This electrochemical technology is highlighted with facile incorporation of important pharmacophores into the resulting biaryls, and is applicable to the homocoupling of anilines for producing symmetrical biaryls.

Decarboxylative [4+2] annulation of arylglyoxylic acids with internal alkynes using the anodic ruthenium catalysis.

A new electrochemical decarboxylative [4+2] annulation of arylglyoxylic acids with internal alkynes involving C-H functionalization by means of a cooperative anode and ruthenium catalysis is presented. This reaction represents a mechanistically novel strategy as an ideal supplement to the decarboxylative [4+2] annulation methodology by employing an electrooxidative process to avoid the use of an additional external oxidizing reagent and utilizing H2O as the carboxyl oxygen atom source to be engaged in the synthesis of 1H-isochromen-1-ones.

Ruthenium(ii)-catalyzed electrooxidative [4+2] annulation of benzylic alcohols with internal alkynes: entry to isocoumarins.

A new ruthenium(ii)-catalyzed electrooxidative [4+2] annulation of primary benzylic alcohols with internal alkynes is described, which enables benzylic alcohols as weakly directing group precursors to access isocoumarins via multiple C-H functionalization. The reaction works well with a broad substrate scope, tolerates a wide range of functional groups, and incorporates practically the isocoumarin unit into diverse bioactive molecules. Mechanistic studies indicate that activation of aryl C(sp2)-H bonds is achieved through the generation of the active benzoyloxy-Ru(ii) intermediates via oxidation of benzylic alcohols using an electrooxidative Ru(ii) catalyst.

Copper-Catalyzed Annulation Cascades of Alkyne-Tethered α-Bromocarbonyls with Alkynes: An Access to Heteropolycycles.

We here describe a new Cu-catalyzed annulation cascade of alkyne-tethered α-bromocarbonyls with common alkynes for the synthesis of various heteropolycycle frameworks, including 1 H-benzo[ de]quinolin-2(3 H)-ones, 4 H-dibenzo[ de,g]quinolin-5(6 H)-one, and benzo[ de]chromen-2(3 H)-one, which were constructed with high selectivity. This was achieved by two-component annulation cascades, rather than atom-transfer radical cyclization (ATRC), with alkyne-tethered α-bromocarbonyls for one-step accessing heteropolycycles via C-Br bond split, intramolecular cyclization, intermolecular [4 + 2] annulation, and aryl C(sp2)-H functionalization cascades.

An access to 1,3-azasiline-fused quinolinones via oxidative heteroannulation involving silyl C(sp3)-H functionalization.

A Mn-promoted intermolecular oxidative radical heteroannulation of N-(2-cyanoaryl)-acrylamides and tertiary silanes has been described, which provides an efficient route to produce silicon/nitrogen heterocycles, sila-analogues of the known carbon-based structural motifs prevalent in bioactive natural products, pharmaceuticals and materials. The reaction enables Si-incorporation by controlling accurately several chemical bond cleavage and formation processes. Moreover, this reaction represents a new one-step construction of 1,3-azasiline-fused quinolinones that was achieved via silyl C(sp3)-H functionalization using an oxidative radical strategy.

Oxidative radical divergent Si-incorporation: facile access to Si-containing heterocycles.

A copper-catalyzed oxidative radical strategy to avoid the use of the highly expensive noble metal/ligand catalytic systems is described, which allows selective activation of dual chemical bonds around the Si-atom center relying on the nature of alkylsilanes. While for tertiary silanes selective functionalization of Si-H/silyl C(sp3)-H bonds in intermolecular oxidative annulation cascades with N-(2-(ethynyl)aryl)acrylamides toward silino[3,4-c]quinolin-5(3H)-ones, when using secondary silanes and HSi(TMS)3, dual Si-H bonds or Si-H/Si-Si bonds are selectively cleaved leading to 4H-silolo[3,4-c]quinolin-4-ones.

[Linear scanning analysis of prehistoric human bones in Xigongqiao Site, Tengzhou, Shandong Province by use of SEM-EDS].

Ancient human bones in Xigongqiao Site, Tengzhou, Shandong Province, were analyzed by use of SEM-EDS. SEM indicated that the microstructure of Haversian system was destroyed under the impact of bone diagenesis. The apparent difference in elemental distribution in the bone cross section showed that the enrichment or loss of elements can occur not only in the inner and outer surface, but also in the middle. This study will have great influence on how to deal with the ancient human bones before any palaeodietary research in the future.