Controllable one-pot synthesis for scaffold diversity via visible-light photoredox-catalyzed Giese reaction and further transformation.

This study presents a controllable one-pot synthesis for constructing valuable scaffolds (alcohols, 2,3-dihydrofurans, α-cyano-γ-butyrolactones, and γ-butyrolactones) via a visible-light photoredox-catalyzed Giese reaction and further transformation. This one-pot reaction can selectively synthesize the desired scaffold in excellent yields with good functional group tolerance. To further highlight the broad applicability of this controllable one-pot reaction, we have established flow reaction conditions with short reaction times for the scale-up of each scaffold and demonstrated the further transformation of 2,3-dihydrofurans and α-cyano-γ-butyrolactones to achieve scaffold diversity for applications in drug discovery.

Visible-Light Photoredox-Catalyzed Hydroalkoxymethylation of Activated Alkenes Using α-Silyl Ethers as Alkoxymethyl Radical Equivalents.

A new neutral silicon-based traceless activation group (TAG) for visible-light photoredox-catalyzed hydroalkoxymethylation of alkenes is presented. This reaction involves in-situ-generated alkoxymethyl radical via single electron oxidation (SET) of α-TMS-substituted ethers, followed by subsequent conjugate addition to activated alkenes. Various functional groups were tolerated both under mild metal and metal-free conditions to provide good to excellent yields.

Pd(II)/CuBr2 catalysed keto α-C(sp3)-H benzoxylation of N,N-dialkylamides directed by o-hydroxy groups.

A hydroxy group directed keto α-C(sp3)-H benzoxylation of amides, including N,N-dialkylamides and cyclic amides, has been accomplished involving ortho-hydroxy substrates possessing either an aldehydic or a keto methyl (-COCH3) group with a Pd(II)/CuBr2 catalytic combination. The carboxy group obtained via the in situ oxidation of -CHO or -COCH3 groups of ortho-hydroxy substrates then undergoes a cross-dehydrogenative coupling (CDC) with amides to furnish an α-benzoxylation product with concurrent aromatic ring bromination.

Palladium-Catalyzed Synthesis of 2-Aryl-2H-Benzotriazoles from Azoarenes and TMSN3.

Substrate-directed ortho C-H amination of azoarenes using TMSN3 as the source of nitrogen leading to the synthesis of 2-aryl-2H-benzotriazoles has been accomplished with the help of Pd/TBHP combinations. An intermolecular o-azidation (C-N bond formation) followed by an intramolecular N-N bond formation via nucleophilic attack of one of the azo nitrogen onto the o-azide nitrogen leads to cyclization with the expulsion of N2.

Oxidant controlled regioselective mono- and di-functionalization reactions of coumarins.

C-3 alkylation of coumarins has been accomplished using cycloalkanes or alkylbenzenes in the presence of di-tert-butylperoxide (DTBP) and Fe(III) catalyst. Under metal free conditions and just by switching the oxidant from DTBP to TBHP, an exclusive C-4 cycloalkylation-C-3 peroxidation reaction takes place. During C-3 alkylation, the C-C bond formation occurs at the expense of an existing C-C bond, while the C-4 alkylation is associated with the formation of new C-C and C-O bonds.

Generation of bis-acyl ketals from esters and benzyl amines under oxidative conditions.

Treatment of benzylamines with esters at an elevated temperature are expected to give amides. However, in the presence of TBAI/TBHP, esters possessing a methylene carbon α-to oxygen with benzylamines provide bis-esters rather than the expected amides. Benzylamines under oxidative conditions generate less nucleophilic carboxylates, which couples at the sp(3) C-H bonds of esters and cyclic ethers to give bis-acyl ketals and α-acyloxy ethers, respectively.

Copper(I)-promoted cycloalkylation-peroxidation of unactivated alkenes via sp(3) C-H functionalisation.

A copper(I)-promoted cycloalkylation-peroxidation strategy has been developed via a three-component reaction involving cycloalkanes, tert-butyl hydroperoxide (TBHP) and internal conjugated alkenes possessing electron-withdrawing groups (EWGs). This process installs C-O and C-C bonds via sp(3) C-H functionalisation with concomitant generation of two stereocentres. This regioselective radical addition of coumarin system is opposite to that of styrene.

Directing group assisted copper-catalyzed chemoselective O-aroylation of phenols and enols using alkylbenzenes.

By using alkylbenzenes as aroyl surrogates, copper(II) catalyzed chemoselective O-aroylations of 1,3-dicarbonyl compounds and phenolic -OH ortho to carbonyl (-CHO, -COR) groups have been achieved. A dual mechanism operating in tandem for these transformations has been supported by a crossover experiment.

Stable Cu(I) complexes with thioamidoguanidine possessing halide-bridge structure.

Treatment of an aryl-sec-alkyl unsymmetrical thiourea (Tu) with Cu(II)X(2) (X = I, Br) transform the thiourea (Tu) into a thioamidoguanidino (Tag) moiety with concomitant reduction of Cu(II) to Cu(I), which forms a [Cu(2)(I)(μ(2)-X)(2)Tag(2)] (X = I (for A) and X = Br (for B)) complex. Meanwhile, the treatment of same unsymmetrical thiourea (Tu) with Cu(I)X (X = Br) forms a stable cluster with a [Cu(I)(3)(μ(2)-S)(4)Tu(4)X(3)] core (C). Single crystal X-ray diffraction revealed that compounds A and B exhibit 1D chain with a Cu(2)(μ(2)-X)(2) core, whereas compound C is a Cu(I)(3)S(4)Br(3) cluster.

Tandem regioselective synthesis of tetrazoles and related heterocycles using iodine.

A one-pot, tandem process has been developed for the synthesis of a library of tetrazoles from aryl isothiocyanates. Condensation of aryl isothiocyanates with ammonia, and aryl amines (R-NH(2)) provided mono, 1,3-disubstituted symmetrical and unsymmetrical thioureas, which on desulfurization with molecular iodine (I(2)) led to formation of the corresponding heterocumulene (cyanamides or carbodiimides). The in situ generated heterocumulene on subsequent treatment with sodium azide at room temperature gave corresponding tetrazoles.