Rhodium-Catalyzed Regioselective [4 + 2] Cycloaddition of Ynamines and 2-(Cyanomethyl)phenylboronates.

A rhodium-catalyzed [4 + 2] cycloaddition of ynamines and 2-(cyanomethyl)phenylboronates has been developed, leading to efficient and excellent regioselective synthesis of valuable indole-linked aromatic compounds in a concise and flexible approach. Interestingly, this strategy was successful in the construction of C···N axially chiral indoles with high enantiocontrol by the introduction of a new phosphoramidite ligand (Xie-Phos).

Congested C(sp3)-rich architectures enabled by iron-catalysed conjunctive alkylation.

Catalytic cross-coupling by transition metals has revolutionized the formation of C-C bonds in organic synthesis. However, the challenge of forming multiple alkyl-alkyl bonds in crowded environments remains largely unresolved. Here, we report the regioselective functionalization of olefins with sp3-hybridized organohalides and organozinc reagents using a simple (terpyridine)iron catalyst. Aliphatic groups of various sizes are successfully installed on either olefinic carbon, furnishing a diverse array of products with congested cores featuring C- or heteroatom-substituted stereocenters. The method enables access to valuable but synthetically challenging C(sp3)-rich molecules, including alicyclic compounds bearing multiple contiguous stereocenters through annulation cascades. Mechanistic and theoretical studies suggest a stepwise iron-mediated radical carbometallation pathway followed by outer-sphere C-C bond formation, which potentially opens the door to a broader scope of transformations and new chemical space.

Ir/Zn-cocatalyzed chemo- and atroposelective [2+2+2] cycloaddition for construction of C─N axially chiral indoles and pyrroles.

Here, an Ir/Zn-cocatalyzed atroposelective [2+2+2] cycloaddition of 1,6-diynes and ynamines was developed, forging various functionalized C─N axially chiral indoles and pyrroles in generally good to excellent yields (up to 99%), excellent chemoselectivities, and high enantioselectivities (up to 98% enantiomeric excess) with wide substrate scope. This cocatalyzed strategy not only provided an alternative promising and reliable way for asymmetric alkyne [2+2+2] cyclotrimerization in an easy handle but also settled the issues of previous [Rh(COD)2]BF4-catalyzed system on the construction of C─N axial chirality such as complex operations, limited substrate scope, and low efficiency. In addition, control experiments and theoretical calculations disclosed that Zn(OTf)2 markedly reduced the barrier of migration insertion to significantly increase reaction efficiency, which was distinctly different from previous work on the Lewis acid for improving reaction yield through accelerating oxidative addition and reductive elimination.

Ruthenium-Catalyzed 1,6-Hydroalkylation of para-Quinone Methides with Ketones via the in Situ Activation of C(sp3)-H Bonds.

A simple and efficient method for the ruthenium-catalyzed 1,6-hydroalkylation of para-quinone methides (p-QMs) with ketones via the in situ activation of C(sp3)-H bonds has been disclosed. Without the need for preactivation of the substrates and oxidant, a broad range of p-QMs and ketones are well tolerated, producing the expected 1,6-hydroalkylation products with moderate to good yields. Step-by-step control experiments and DFT calculation were conducted systematically to gain insights for the plausible reaction mechanism. This finding may have potential application in the selective diarylmethylation of ketones at the α-C position in organic synthesis.

Copper-catalyzed atroposelective formal [4+1] annulation of 1,2-diketones with vinyl cations.

The enantioselective transformation of easily accessible 1,2-diketones represents a quick pathway towards enantioenriched molecules. Herein, we disclose a copper-catalyzed atroposelective formal [4+1] annulation of 1,2-diketones with vinyl cations, enabling the efficient and atom-economical construction of axially chiral arylpyrroles bearing 1,3-dioxole moieties with good to excellent enantioselectivities under mild reaction conditions. Importantly, this methodology constitutes the first enantioselective formal [4+1] annulation of 1,2-diketones.

Copper-catalyzed intermolecular formal (5 + 1) annulation of 1,5-diynes with 1,2,5-oxadiazoles.

One-carbon homologation reactions based on one-carbon insertion into the N-O bond of heterocycles have received tremendous interest over the past decades. However, these protocols have to rely on the use of hazardous and not easily accessible diazo compounds as precursors, and examples of the relevant asymmetric catalysis have not been reported. Here we show that a copper-catalyzed intermolecular formal (5 + 1) annulation of 1,5-diynes with 1,2,5-oxadiazoles involving one-carbon insertion into the heterocyclic N-O bond via non-diazo approach. This method enables practical and atom-economic synthesis of valuable pyrrole-substituted oxadiazines in generally moderate to good yields under mild reaction conditions. In addition, the possibility of such an asymmetric formal (5 + 1) annulation also emerges.

Copper-Catalyzed Aerobic Oxidative/Decarboxylative Phosphorylation of Aryl Acrylic Acids with P(III)-Nucleophiles.

A copper-catalyzed aerobic oxidative/decarboxylative phosphorylation of aryl acrylic acids with P(III)-nucleophiles via the Michaelis-Arbuzov rearrangement for the synthesis of ß-ketophosphine oxides, ß-ketophosphinates, and ß-ketophosphonates is reported. The present reaction could be conducted effectively without the use of a ligand and a base. Various kinds of aryl acrylic acids and P(III)-nucleophiles are tolerated in the transformation, generating the desired ß-keto-organophosphorus compounds as a valuable class of phosphorus-containing intermediates with good to excellent yields. In addition, the possible mechanism and kinetic studies for the reaction have been explored by step-by-step control experiments and competitive experiments, and the results proved that this transformation may follow second-order chemical kinetics as well as involve a radical process.

Copper-Catalyzed Tandem Cyclization/Direct C(sp2)-H Annulation of Azide-Ynamides via α-Imino Copper Carbenes: Access to Azepino[2,3-b:4,5-b']diindoles.

A novel copper-catalyzed tandem cyclization/direct C(sp2)-H annulation of phenyl azide-ynamides via α-imino copper carbenes has been developed, which provides a concise and flexible approach for the construction of a range of valuable azepino[2,3-b:4,5-b']diindoles in mostly good to excellent yields with high chemoselectivities. This tandem reaction also exhibits a broad substrate scope, excellent functional group tolerance, simple operation, and mild reaction conditions.

Brønsted acid-catalyzed asymmetric dearomatization for synthesis of chiral fused polycyclic enone and indoline scaffolds.

In the past two decades, substantial advances have been made on the asymmetric alkyne functionalization by the activation of inert alkynes. However, these asymmetric transformations have so far been mostly limited to transition metal catalysis, and chiral Brønsted acid-catalyzed examples are rarely explored. Here, we report a chiral Brønsted acid-catalyzed dearomatization reaction of phenol- and indole-tethered homopropargyl amines, allowing the practical and atom-economical synthesis of a diverse array of valuable fused polycyclic enones and indolines bearing a chiral quaternary carbon stereocenter and two contiguous stereogenic centers in moderate to good yields with excellent diastereoselectivities and generally excellent enantioselectivities (up to >99% enantiomeric excess). This protocol demonstrates Brønsted acid-catalyzed asymmetric dearomatizations via vinylidene-quinone methides.

I2 -Catalyzed Cycloisomerization of Ynamides: Chemoselective and Divergent Access to Indole Derivatives.

Herein, an I2 -catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom-economy. This protocol not only represents the first molecular-iodine-catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine-ynamides involving distinctively different C(sp3 )-C(sp3 ) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I2 . Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5-exo-dig cyclization/rearrangement process.

Highly Site-Selective Oxidative Cyclization of Ene-ynamides via Non-Noble-Metal Catalysis: Access to Functionalized Lactams.

Herein, an unprecedented non-noble-metal-catalyzed oxidation/cyclization of ene-ynamides is developed, allowing the synthesis of diversely functionalized lactams in moderate to good yields with excellent diastereoselectivities without the observation of typical cyclopropanation products. In combination with Ellman's tert-butylsulfinimine chemistry, chiral γ-lactams containing three contiguous stereocenters are obtained with high diastereo- and enantioselectivity. Moreover, density functional theory (DFT) calculations indicate that this protocol probably undergoes a carbon cation or proton transfer process.

Enantioselective Rh-Catalyzed Azide-Internal-Alkyne Cycloaddition for the Construction of Axially Chiral 1,2,3-Triazoles.

Significant advances have been achieved for the construction of chiral skeletons containing 1,2,3-triazoles via transition-metal-catalyzed asymmetric azide-alkyne cycloaddition; however, most of them have been limited to terminal alkynes in the synthesis of central chirality via desymmetrization and dynamic/dynamic kinetic resolution. Enantioselective transition-metal-catalyzed azide-internal-alkyne cycloaddition is extremely limited. Moreover, the construction of a challenging five-membered (hetero)biaryl axially chiral molecule via transition-metal-catalyzed asymmetric azide-internal-alkyne cycloaddition is still underexplored. Herein, we first report an atroposelective and atom-economical synthesis of axially chiral 1,4,5-trisubstituted 1,2,3-triazoles, directly acting as core chiral units of challenging five-membered atropisomers, via the enantioselective Rh-catalyzed azide-alkyne cycloaddition (E-RhAAC) of internal alkynes and azides. The reaction demonstrates excellent functional group tolerance, forging a variety of C-C axially chiral 1,2,3-triazoles under mild conditions with moderate to excellent yields (up to 99% yield) and generally high to excellent enantioselectivities (up to 99% ee) along with specific regiocontrol. The origin of regio- and enantioselectivity control is disclosed by density functional theory (DFT) calculations, providing new guidance for the facile construction of axially chiral compounds.

Radical Reactions of Ynamides.

Ynamides are electron-rich heteroatom-substituted alkynes with C-C triple bond directly tethered to the amide group. Over the past decades, ynamides have proven to be versatile reagents for organic synthesis and have received extensive attention. Compared with the well-established ionic reactions of ynamides, radical-based ynamide reactions have been exploited relatively seldom. Herein, radical reactions of ynamides, classified by radical attack at the α-position and ß-position of ynamides, are reviewed by highlighting the reaction selectivity, scope, mechanism, and applicability. The aim of this review is to provide a comprehensive summarization of these advances, casting light on the further development of ynamide chemistry.

Regio- and diastereoselective synthesis of trans-3,4-diaryldihydrocoumarins via metal-free [4+2] annulation of ynamides with o-hydroxybenzyl alcohols.

An efficient regio- and diastereoselective method for the construction of valuable trans-3,4-diaryldihydrocoumarins via metal-free [4+2] annulation of ynamides with o-hydroxybenzyl alcohols has been developed. Ynamides are first treated as 2-π partners to react with o-hydroxybenzyl alcohols via traceless sulfonamide directing groups, affording trans-3,4-diaryldihydrocoumarins in good yields with high regio- and diastereoselectivities. This metal-free methodology is also characterized by a wide substrate scope, good functional group tolerance, and efficiency on a gram scale.

Vinylene carbonate: beyond the ethyne surrogate in rhodium-catalyzed annulation with amidines toward 4-methylquinazolines.

In this paper, we developed a rhodium-catalyzed annulation of vinylene carbonate with amidines, leading to 4-methylquinazolines with moderate to excellent yields. This procedure proceeded by sequential ortho-acylation and annulation, where vinylene carbonate served as the acetylation reagent rather than the ethyne surrogate.

Solar-Driven Hydrogen Generation Catalyzed by g-C3N4 with Poly(platinaynes) as Efficient Electron Donor at Low Platinum Content.

A metal-complex-modified graphitic carbon nitride (g-C3N4) bulk heterostructure is presented here as a promising alternative to high-cost noble metals as artificial photocatalysts. Theoretical and experimental studies of the spectral and physicochemical properties of three structurally similar molecules Fo-D, Pt-D, and Pt-P confirm that the Pt(II) acetylide group effectively expands the electron delocalization and adjusts the molecular orbital levels to form a relatively narrow bandgap. Using these molecules, the donor-acceptor assemblies Fo-D@CN, Pt-D@CN, and Pt-P@CN are formed with g-C3N4. Among these assemblies, the Pt(II) acetylide-based composite materials Pt-D@CN and Pt-P@CN with bulk heterojunction morphologies and extremely low Pt weight ratios of 0.19% and 0.24%, respectively, exhibit the fastest charge transfer and best light-harvesting efficiencies. Among the tested assemblies, 10 mg Pt-P@CN without any Pt metal additives exhibits a significantly improved photocatalytic H2 generation rate of 1.38 µmol h-1 under simulated sunlight irradiation (AM1.5G, filter), which is sixfold higher than that of the pristine g-C3N4.

The intramolecular reaction of acetophenone N-tosylhydrazone and vinyl: Brønsted acid-promoted cationic cyclization toward polysubstituted indenes.

In the presence of TsNHNH2, a Brønsted acid-promoted intramolecular cyclization of o-(1-arylvinyl) acetophenone derivatives was developed, leading to polysubstituted indenes with complexity and diversity in moderate to excellent yields. In sharp contrast with either the radical or carbene involved cyclization of aldehydic N-tosylhydrazone with vinyl, a cationic cyclization pathway was involved, where N-tosylhydrazone served as an electrophile and alkylation reagent during this transformation.

Recent Progress in the Selective Functionalization of P(O)-OH Bonds.

As we all know, organic phosphorus compounds have high application values in chemical industries. Compared with traditional compounds with P-X (X = Cl, Br, I) and P-H bonds, phosphorylation reagents containing P(O)-OH bonds are stable, environmentally friendly, and inexpensive. However, in recent years, there have been few studies on the selective functionalization of P(O)-OH bonds for the fabrication of P-C and P-Z bonds. In general, four-coordinated P(O)-OH compounds have reached coordination saturation due to the phosphorus atom center, but cannot evolve the phosphorus coordination center through intra-molecular tautomerization; however, the weak coordination effects between the P=O bond and transition metals can be utilized to activate P(O)-OH bonds. This review highlights the most important recent contributions toward the selective functionalization of P(O)-OH bonds via cyclization/cross coupling/esterification reactions using transition metals or small organic molecules as the catalyst.

Nitrene Transfer and Carbene Transfer in Gold Catalysis.

Catalytic transformations involving metal carbenes are considered one of the most important aspects of homogeneous transition metal catalysis. Recently, gold-catalyzed generation of gold carbenes from readily available alkynes represents a significant advance in metal carbene chemistry. This Review summarizes the advances in the gold-catalyzed nitrene-transfer reactions of alkynes with nitrogen-transfer reagents, such as azides, nitrogen ylides, isoxazoles, and anthranils, and gold-catalyzed carbene-transfer reactions, involving oxygen atom-transfer reactions of alkynes with nitro compounds, nitrones, sulfoxides, and pyridine N-oxides, through the presumable α-imino gold carbene and α-oxo gold carbene intermediates, respectively. Gold-catalyzed processes are reviewed by highlighting their product diversity, selectivity, and applicability, and the mechanistic rationale is presented where possible.

Brønsted acid-mediated reactions of ynamides.

Over the past two decades, the development and application of ynamide chemistry have received more and more attention. Ynamides have proven to be versatile reagents for organic synthesis, and have been widely applied to the rapid assembly of a diverse range of structurally complex N-containing molecules, especially the valuable N-heterocycles. In comparison with the well-established transition metal-catalyzed reactions of ynamides, metal-free ynamide transformations have relatively seldom been exploited. Recently, Brønsted acid-mediated reactions of ynamides represent significant advances in ynamide chemistry. This review summarizes the latest trends and developments of Brønsted acid-mediated reactions of ynamides, including cycloaddition, cyclization, intramolecular alkoxylation-initiated rearrangement, oxygen atom transfer reactions and hydro-heteroatom addition reactions.