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A highly tunable defluorophosphorylation of fluorinated peroxides for the preparation of C3,4-diphosphoryl furans and C4-monophosphoryl furans under conditions with no added transition metals is disclosed.

The direct cross-couplings of diaryl sulfoxides with aryl bromides via C-S bond cleavage could be readily accomplished using nickel(II) as the catalyst, 1,2-bis(diphenylphosphino)ethane (dppe) as the ligand, and magnesium turnings as the reducing metal in THF, leading to the corresponding biaryls in moderate to good yields. The reaction exhibited a broad substrate scope and could be applied to a gram-scale synthesis. The "one-pot" reaction, which avoids the utility of presynthesized and moisture-labile organometallic compounds, is operationally simple and step-economic.

An unprecedented four-component defluorinative reaction of allylic fluorides, amidines, and Cs2CO3 for the convenient synthesis of valuable pyrimidine-containing amidino carbamates under transition-metal-free conditions was developed.

A simple and practical Cs2CO3-promoted method for the synthesis of 6-nitroindole derivatives from enaminones and nitroaromatic compounds has been developed.

An efficient defluorinative net-[3 + 3]-cyclization strategy for the construction of perfluoroalkyl-substituted pyrimidine derivatives by using a series of perfluoroalkyl alkynes and amidines as starting materials was developed. The present reaction proceeded successfully under transition-metal-free conditions to form two new C–N bonds and a new heterocyclic ring through a sequence of hydroamination, defluorination, and annulation. The desired pyrimidines could be obtained with good functional group tolerance and moderate to good yields. Moreover, the distinctive fluorine effects of perfluoroalkyl substituents are vital for tuning the reactivity of alkynes for the anticipated defluorinative annulation. The pendant π system would lower associated bond dissociation energy significantly compared to that of a nonactivated C(sp3)–F bond.

An efficient transition-metal-free hydrodefluorination reaction of trifluoromethyl alkenes for accessing gem-difluoroalkenes is developed. It was surprising to find that the phosphoryl anion is able to mediate the defluorination.

A modular multicomponent reaction of readily available fluoroalkyl alkenes, amidines, ammonium carbonate, and water was developed for the facile construction of β-fluoroalkylated aminovinyl ketones, which provided chemists a novel access to value-added organofluorine compounds. The reaction proceeded regio-/stereoselectively under mild conditions and exhibited good functional group tolerance. Cheap, stable, and low-toxic inorganic salt (NH

A nickel-catalyzed direct reductive cross-coupling of disubstituted cycloalkyl iodides with aryl iodides was developed. The one-pot reaction, which is simple to operate, was capable of proceeding efficiently in a stereocontrolled manner to afford a variety of cross-coupled products with high diastereoselectivity and wide functional group tolerance.

An efficient Sonogashira coupling of a heterocyclic phosphonium salt with a terminal alkyne via C-P bond cleavage was developed. The reactions proceeded smoothly in the presence of palladium catalyst, copper(I) iodide, and

A Pd-catalyzed C–F bond alkynylation of polyfluoroalkyl ketones with terminal alkynes has been developed. The method gives access to a range of modular perfluoroalkyl- and alkynyl-substituted furan derivatives in moderate yields with high chemoselectivity and regioselectivity. The key to the success of the present cascade reaction mainly relies on the well-controlled sequence of functionalization and alkynylation of multiple C(sp3)–F bonds. Mechanistic studies showed that the reaction presumably proceeded through a chelation-assisted oxidative addition of Pd to the C–F bond.

An efficient nickel-catalyzed, iron-mediated hydrofluoroalkylation of alkynes with bromodifluoroacetate or perfluoroalkyl iodide was developed. The reactions proceeded efficiently via a radical reaction pathway to give fluoroalkylated (Z)-alkenes in moderate to good yields with good control of stereoselectivity (up to 99 : 1 Z/E), exhibiting both wide substrate scope and broad functional group tolerance. In addition, the method also entailed the easy functionalization of alkyne-tethered complex molecules derived from sugars and pharmaceuticals.

An efficient palladium-catalyzed direct reductive cross-coupling of aryltrimethylammonium salts with aryl bromides was developed. The reactions proceeded smoothly in the presence of a palladium catalyst, magnesium turnings, LiCl, and TMEDA in THF at room temperature, leading to the corresponding biaryl compounds in moderate to good yields with reasonable functional group tolerance. The one-pot reaction using cheap and readily available aryl bromide as a coupling partner is simple to handle, thereby avoiding the use of pre-prepared organometallic reagents.

Synthetic strategies by making use of one-pot multi-step cascade reactions are of special interest. Herein, an efficient three-component tandem reaction of polyfluoroalkyl peroxides with sulfinates for the facile construction of fluoroalkylated tetrasubstituted furan derivatives has been developed. The combination of DABCO and Cs2CO3 was found to be essential for the success of the reaction. This modular and regioselective approach proceeded via an unprecedented sequence of successive defluorination, dual sulfonylation, and annulation relay, along with four C(sp3)–F bonds cleaved and two new C–S bonds formed. In addition, this transition metal-free C–F bond functionalization which is amenable to gram-scale synthesis occurred under mild reaction conditions and has broad substrate scope and excellent functional group tolerance. Moreover, this defluorinative protocol also enabled the late-stage functionalization of complex compounds, which could potentially find synthetic utility in drug discovery.

Efficient synthesis of fluoroalkylated tri(hetero)arylphosphine oxides from perfluoroalkyl ketones and phosphine oxides or phosphonates has been achieved via successive C(sp3)–F bond activation under mild reaction conditions. This approach involving new C(sp2)–P/C(sp2)–O bond formation and fluoroalkylated heterocycle construction distinguishes itself by its broad substrate scope and synthetic simplicity. Moreover, tri(hetero)arylphosphines could also be prepared in high yields by further reductive transformation.

The direct cross-coupling of heterocyclic phosphonium salts with aryl bromides was successfully realized by performing the reactions in THF at ambient temperature with the aid of a nickel(II) catalyst, the 1,10-phenanthroline-5,6-dione ligand, magnesium turnings, and lithium chloride, providing an easy access to 4-arylated pyridine, quinoline, quinoxaline, and pyrazine.

An efficient method was developed for the conjugate addition of water to various α,β-unsaturated ketones by using bismuth(III) chloride as a catalyst. The reactions proceeded smoothly in the presence of a catalytic amount of BiCl3 (20 mol%) in aqueous media to furnish a variety of synthetically useful β-hydroxyl ketones in moderate to good yields. Apart from water molecule, various alcohols could also be employed as nucleophiles to react with α,β-unsaturated ketones, leading to β-alkoxyl ketones in modest to high yields. In addition, the mild reaction conditions also entailed the conjugate addition reactions to proceed with the tolerance to a range of functional groups.

An efficient water-based bismuth-mediated addition reaction of carbonyl compound with cyclic allylic halide was developed. The reactions proceeded smoothly in aqueous DMF in the presence of ammonium iodide to afford the corresponding syn -homoallylic alcohols in moderate to good yields with excellent diastereoselectivities (>99:1 syn : anti ). Reversal of product diastereoselectivity was observed when heteroaryl aldehyde possessing an adjacent chelating nitrogen atom was employed as substrate.

The direct cross-couplings of aryl sulfonium salts with aryl halides could be achieved by using nickel as a reaction catalyst. The reactions proceeded efficiently via C-S bond activation in the presence of magnesium turnings and lithium chloride in THF at ambient temperature to afford the corresponding biaryls in moderate to good yields, potentially serving as an attractive alternative to conventional cross-coupling reactions employing preprepared organometallic reagents.

Few methods are known for the synthesis of nitroindole derivatives. A simple and practical Cs

A titanium(IV)-mediated ring-opening/dehydroxylative cross-coupling of diaryl-substituted methanols with a cyclopropanol derivative was developed. The reactions proceeded efficiently to provide synthetically useful γ,γ-diaryl esters in moderate to good yields, which could be applied to the functionalization of complex molecules derived from bioactive fenofibrate and isoxepac and the synthesis of a precursor of Zoloft.

As the "chemical chameleon", sulfonyl-containing compounds and their variants have been merged with various types of reactions for the efficient construction of diverse molecular architectures by taking advantage of their incredible reactive flexibility. Currently, their involvement in radical transformations, in which the sulfonyl group typically acts as a leaving group via selective C-S, N-S, O-S, S-S, and Se-S bond cleavage/functionalization, has facilitated new bond formation strategies which are complementary to classical two-electron cross-couplings via organometallic or ionic intermediates. Considering the great influence and synthetic potential of these novel avenues, we summarize recent advances in this rapidly expanding area by discussing the reaction designs, substrate scopes, mechanistic studies, and their limitations, outlining the state-of-the-art processes involved in radical-mediated desulfonylation and related transformations. With a specific emphasis on their synthetic applications, we believe this review will be useful for medicinal and synthetic organic chemists who are interested in radical chemistry and radical-mediated desulfonylation in particular.

An efficient method for the synthesis of 4,5-diaryl-3,4-dihydropyrimidin-2(1H)-one by using 1,1′-(arylmethylene)diurea and 1-aryl-2-propanone as substrates was developed. The reactions proceeded efficiently in the presence of Cs2CO3 to give the desired products in moderate to good yields with wide substrate scope and good functional group tolerance, serving as an attractive alternative or complement to the previously reported methods for the facile assembly of biologically and pharmaceutically active 3,4-dihydropyrimidin-2(1H)-ones.

An efficient cobalt-catalyzed, indium-mediated difunctionalization of iodoalkyl-tethered unactivated alkenes via a cyclization/cross-coupling sequence was developed. The reactions proceeded effectively with wide functional group tolerance, leading to a wide variety of cyclic compounds, including cyclopentane, furan, pyrrolidine, octahydro-1H-indene, octahydro-benzofuran, hexahydro-4H-furo[2,3-b]pyran, and hexahydro-furo[2,3-b]furan, which are pivotal cores widely found in pharmaceutical and bioactive compounds.

Lead was found to efficiently mediate the allylation reactions of carbonyl compounds with cyclic allylic halides in the presence of stoichiometric amounts of lithium chloride and a catalytic amount of GaCl3 (20 mol %), leading to the desired homoallylic alcohols in modest to high yields with excellent diastereocontrol (>99:1 syn/anti) and good functional group tolerance. In contrast, the use of either 2-pyridinecarboxaldehyde as the carbonyl substrate or ( E)-cinnamyl bromide as the allylating agent produced the corresponding product with reversed diastereoselectivity (>99:1 anti/syn). Nanyang Technological University We gratefully acknowledge the financial support from Nanjing Tech University (Start-up grant nos. 39837118, 39837101, and 39837146), the SICAM Fellowship from Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Forestry University, and Nanyang Technological University.

A facile incorporation of a privileged sulfide, a naphthofuran framework, and a perfluoroalkyl moiety in one molecule was successfully accomplished through tandem defluorinative sulfenylation of α-perfluoroalkyl ketones with a sulfur source. The reaction presumably proceeds via a sequence involving defluorination, reductive sulfenylation, autoaromatization, and annulation, accompanied by the simultaneous cleavage of four C(sp3)-F bonds and the formation of new C-S and C-O bonds.

The copper(II)-mediated ring opening/alkynylation of cyclopropanol by employing inexpensive and commercially available terminal alkyne is developed. The reactions proceeded efficiently to afford synthetically useful alk-4-yn-1-ones in moderate to good yields with good functional group tolerance. Control experiments showed that the reaction presumably proceeds via the formation of intermediates of copper homoenolate and/or alkynylcopper species.

An efficient method for the synthesis of 4,5-diaryl-3,4-dihydropyrimidin-2(1

An efficient method for the synthesis of alkyl indium reagents by means of an indium(III) or lead(II) halidecatalyzed direct insertion of indium into alkyl iodides and their applications in palladium-catalyzed crosscoupling reactions with aryl halides is developed. NMR and ESI-MS analyses indicated that rather than the formation of the commonly recognized alkyl indium sesquihalide with the formulation of R3In2X3, the formed alkyl indium reagent in the present protocol should be a mixture of an alkyl indium dihalide (RInX2) and a dialkyl indium halide (R2InX) (both of them presumably exist as dimers). Nanyang Technological University We gratefully acknowledge the financial support from the Nanjing Tech University (Start-up Grant No. 39837118, 39837101, and 39837146), the SICAM Fellowship from the Jiangsu National Synergetic Innovation Center for Advanced Materials, and the Nanyang Technological University.

Oxidant-directed chemoselective sulfonylation and sulfonyloximation reactions for the divergent synthesis of valuable vinyl sulfones and α-sulfonylethanone oximes starting from simple alkenes and TosMIC by using tert-butyl hydroperoxide and tert-butyl nitrite, respectively, as terminal oxidants were developed. The success of this method could be attributed to the combination of a cobalt catalyst and a perfluoroalkyl halide additive. The feasibility of performing the reactions on a large scale potentially allows the further application of the method in industrial manufacture. Nanyang Technological University We gratefully acknowledge the financial support from the Natural Science Foundation of Jiangsu Province (BK20180690), the Nanjing Tech University (Start-up Grant No. 39837101, 39837118, and 39837146), the SICAM Fellowship from Jiangsu National Synergetic Innovation Center for Advanced Materials, and the Nanyang Technological University.

An efficient diastereoselective allylation of various carbonyl compounds with cyclic allylic halides by using commercially available bismuth powder in the presence of LiI was developed. Among all the metals screened, bismuth was found to be the best mediator for the transformation. The reactions involving various cyclic allylic halides proceeded smoothly at room temperature to produce the desired homoallylic alcohols in good to excellent yields with high diastereoselectivities (>99:1 dr). Reversed diastereoselectivity was obtained when carbonyl substrate (e. g., 2-pyridinecarboxaldehyde, glyoxylic acid) containing chelating substituent was used in the allylation reaction. In addition, the reactions involving acyclic (E)-cinnamyl bromide as substrate worked equally well with high diastereocontrol. (Figure presented.). Nanyang Technological University We gratefully acknowledge the financial support from Nanj-ing Tech University (Start-up Grant No. 39837118, 39837101,and 39837146), the SICAM Fellowship from Jiangsu NationalSynergetic Innovation Center for Advanced Materials, Post-graduate Research&Practice Innovation Program of JiangsuProvince (No. KYCX18_1075), and Nanyang Technological University.t

A convenient photoredox‐catalyzed defluorinative trifluoromethylation of α‐trifluoromethyl alkenes and gem‐difluoroalkenes is developed. The reactions proceeded efficiently via trifluoromethyl radical addition followed by β‐fluorine elimination process, providing a new entry to multifluorinated alkenes in moderate to good yields with excellent stereoselectivity. Ministry of Education (MOE)

The hydration of α,β-unsaturated ketones with water proceeded efficiently in the presence of In(OTf)3 (20 mol%) in aqueous media to afford synthetically versatile β-hydroxyketones in moderate to good yields with good functional group compatibility. The method also can be extended to the hydroalkoxylation of α,β-unsaturated ketones with various alcohols for the efficient synthesis of β-alkoxyketones as well as tetrahydrofuran derivatives.

An efficient method for the preparation of alkyl indium reagents by using unactivated and cheap alkyl chlorides as substrates in the presence of indium and LiI was developed. The thus-formed alkyl indium species effectively underwent palladium-catalyzed cross-coupling reactions with aryl halides with wide functional group tolerance.

In their recent report in Nature, Ritter and co-workers took advantage of a persistent sulfur-based radical cation to regioselectively install a thianthrene motif in simple or complex (hetero)arenes, and the resulting thianthrenium salts could undergo divergent late-stage transformations, offering chemists a powerful platform for introducing versatile functional groups and substituents in (hetero)arene rings.

An efficient copper-catalyzed three-component cyclization for the construction of highly functionalized pyrimidine derivatives from readily available amidines, styrenes and fluoroalkyl halides is developed. This protocol distinguishes itself by the formation of three new C-C/C-N bonds and a new six-membered ring through a radical addition/oxidation/cyclization sequence in a one-pot manner.

We present a Ag(i)/Co(ii) co-catalyzed tandem fragmentation and recombination reaction commencing from detachable nonaflates and amidines. This catalytic method offers a unique and expeditious access to various fluoroalkylated dihydrobenzo[h]quinazolines and benzo[h]quinazolines in the absence of external fluorine sources through a rationally designed radical desulfonylation, migration, defluorination, and polar condensation relay.

Chemoselective functionalizations of intrinsically less reactive C(sp3)–H bonds of alkyl nitriles are of particular interest to the chemical community because these strategies provide opportunities for the introduction of important cyanoalkyl groups onto target frameworks in a step-economical fashion. In recent years, the introduction of nitrile-containing alkyl radicals in tandem radical additions and oxidative couplings has inarguably brought chemists a new radical reaction platform for the diverse synthesis of natural products and pharmaceuticals. Compared with the wide applications of various C-centered radicals adjacent to a heteroatom, however, nitrile-containing alkyl radicals remain largely unexplored. New methods for C(sp3)–H bond oxidative functionalization of alkyl nitriles and new mechanistic manifolds would result in the development of a broad range of novel reactions. Therefore, this review will give an overview of various types of radical cyanoalkylation using the key alkyl nitrile reactants, which lie beyond traditional coupling chemistry.

An efficient, economical, and practical Reformatsky reaction of α-halo carbonyl compounds with aldehydes/ketones by using cheap and commercial iron(0) powder as reaction mediator is developed. The reactions proceeded effectively in the presence of a catalytic amount of iodine (20 mol %) to afford the synthetically useful β-hydroxyl carbonyl compounds in moderate to good yields.