Skeletal Editing of Isatins for Heterocycle Molecular Diversity.

Isatins have been widely used in the preparation of a variety of heterocyclic compounds, where the skeletal editing of isatins has shown significant advantages for the construction of diverse heterocycles. This review highlights the progress made in the last decade (2013-2023) in the skeletal editing of the isatin scaffold. A series of ring expansion reactions for the construction of quinoline skeleton, quinolone skeleton, polycyclic quinazoline skeleton, medium-sized ring skeleton, as well as a series of ring opening reactions for the generation of 2-(azoly)aniline skeleton by the cleavage of C-C bond and C-N bond are highlighted. It is hoped that this review will provide some understanding of the chemical transformations of isatins and contribute to the further realization of its molecular diversity.

Advancements in Desilylation Reactions for the Synthesis of Valuable Organic Molecules.

Silicon, due to its abundance, non-toxicity, and cost-effectiveness, is a critical element in the earth's crust with significant industrial applications. In organic chemistry, main group elements, and in particular silicon, are extensively utilized as versatile synthetic intermediates. Despite the current challenges associated with harsh reaction conditions and unsustainable practices in synthesizing crucial organic structural molecules, desilylation reactions have emerged as a facilitative method, offering milder conditions and operational simplicity. This review provides a comprehensive analysis of recent advancements in the synthesis of valuable organic molecules through two distinct desilylation reactions. It systematically presents the synthesis of a variety of derivatives, such as furan, alcohol, N-heterocyclic, and ketone, highlighting the broad substrate tolerance of these reactions. This broad functional group compatibility suggests a promising future for the synthesis of a wide range of bioactive molecules, underscoring the significant potential of desilylation in contemporary organic synthesis.

Precision Propargylic Substitution Reaction: Pd-Catalyzed Suzuki-Miyaura Coupling of Nonactivated Propargylamines with Boronic Acids.

Palladium-catalyzed Suzuki-Miyaura cross-coupling is an efficient approach for C-C bond construction. Here we report a deaminative Suzuki-Miyaura reaction to achieve chemo- and regioselectivity in the cross-coupling of nonactivated propargylamines with boronic acids, in which methyl propiolate is introduced to promote the cleavage of the C-N bond to form the C-C bond. This method features a wide range of substrates, good functional group tolerance, and ease of operation, providing an alternative approach to accessing valuable propargylated aromatic compounds.

Application of Metal-Free Dearomatization Reaction as a Sustainable Strategy to Direct Access Complex Cyclic Compounds.

The highly efficient construction of complicated heterocyclic frameworks in an atom- and step-economic manner is still one of the cores of synthetic chemistry. Dearomatization reactions show the unique advantage for the construction of functionalized heterocycles and have attracted widespread attention over the past two decades. The metal-free approach has proved to be a green and sustainable paradigm for the synthesis of spirocyclic, polycyclic and heterocyclic scaffolds, which are widely present in natural products and bioactive molecules. In this review, the advances in the recent six years (2017-2023) in metal-free dearomatization reactions are highlighted. Emphasis is placed on developments in the field of organo-catalyzed dearomatization reactions, oxidative dearomatization reactions, Brønsted acid- or base-promoted dearomatization reactions, photoredox-catalyzed dearomatization reactions, and electrochemical oxidation dearomatization reactions.

Selectivity Controlled Hydroamination of Alkynes to Sulfonyl Fluoride Hubs: Development and Application.

A hydroamination of unactivated alkynes and lithium bis(fluorosulfonyl)imide (LiN(SO2F)2) is described under mild conditions, affording a single regioisomer of the sulfonyl fluorides. This method features broad functional group compatibility and delivers the target vinyl fluorosulfonimides in good to excellent yields. Moreover, gram-scale hydroamination of terminal and internal alkynes is achieved. Further transformations exploiting the reactivity of the vinyl fluorosulfonimide are subsequently developed for the synthesis of fluorosulfates and diphenyl sulfate.

Microwave-assisted decarboxylative reactions: advanced strategies for sustainable organic synthesis.

The decarboxylation or decarboxylative coupling reactions of carboxylic acids and their derivatives are some of the most powerful tools for the construction of platform molecules and valuable chemicals in organic synthetic chemistry. Additionally, microwave-assisted technology, which is strongly endorsed by industry in addition to academia, has been recognized as an alternative synthetic chemist's toolbox. Many decarboxylative reactions using microwave-assisted technology have been developed as an advanced strategy for sustainable organic synthesis for decades. This review highlights the recent developments in microwave-assisted decarboxylative reactions, including transition-metal-catalyzed and metal-free approaches.

Microwave-Assisted Cu(I)-Catalyzed Synthesis of Unsymmetrical 1,4-Diamino-2-butynes via Cross-A3-Coupling/Decarboxylative A3-Coupling.

1,4-Diamino-2-butynes display both chemical and physiological properties. Here a highly efficient synthesis avenue to generate unsymmetric 1,4-diamino-2-butynes has been developed by microwave-assisted Cu(I)-catalyzed cross-A3-coupling/decarboxylative coupling of two different amines, formaldehyde, and propiolic acid through a domino process. This multicomponent reaction provides a series of target products in moderate to good yields with high chemoselectivity.

Chemodivergent Synthesis of Oxazolidin-2-ones via Cu-Catalyzed Carboxyl Transfer Annulation of Propiolic Acids with Amines.

Carboxylic acids are widely found in natural products and bioactive molecules and have served as raw material compounds in industry. We now report the first example of copper(I)-catalyzed carboxyl transfer annulation of propiolic acids with amines, thereby chemodivergently constructing the oxazolidine-2-ones. In this reaction, two kinds of key propargyamine intermediates were formed through sequential CuI/NBS-catalyzed oxidative deamination/decarboxylative alkynylation or CuI-catalyzed decarboxylative hydroamination/alkynylation. The advantages of this decarboxylative coupling/carboxylative cyclization are showcased in the atom economy, chemical specificity, and functional group tolerance.

CF3SO3H-enabled cascade ring-opening/dearomatization of indole derivatives to polycyclic heterocycles.

A novel dearomatization process to produce fused polycyclic indolines via a CF3SO3H-mediated cascade ring-opening of a ß-lactam and hydroaminative cyclization is demonstrated. It provides a new strategy for the synthesis of important polycyclic indoline-2-amine derivatives in moderate to excellent yields, as well as with good functional group tolerance. Moreover, transformation of the product was performed to deliver the corresponding acid, alcohol and amide smoothly.

Chemo- and Diastereoselective Synthesis of N-Propargyl Oxazolidines through a Copper-Catalyzed Domino A3 Reaction.

Herein we describe a highly chemoselective A3-coupling/annulation of amino alcohols, formaldehyde, two kinds of aldehydes and alkynes, catalyzed by copper(II). This cascade reaction, employing readily available materials, provides a new and highly effective access to chiral N-propargyl oxazolidines with good diastereoselectivity (up to >20:1). In the case of ortho-substituted aromatic aldehydes, an intriguing steric effect is observed: a bulky group exhibits a remarkably adverse effect on the diastereoselectivity for the formation of the title molecule.

Carboxyl Transfer of α-Keto Acids toward Oxazolidinones via Decarboxylation/Fixation of Liberated CO2.

A novel strategy for the direct carboxyl transfer involving a decarboxylative A3 reaction of α-keto acids, primary amines, and alkynes has been developed under a Cu(I)/Cu(II) binary catalysis system. This multicomponent reaction provides a facile and efficient approach for the production of a diverse range of 2-oxazolidinones in moderate to excellent yields through a one-pot CO2 elimination-fixation procedure. The conciseness of the "CO2 recycling" process makes this ideal synthesis superior over classical CO2 utilization.

Synthetic Access to Secondary Propargylamines via a Copper-Catalyzed Oxidative Deamination/Alkynylation Cascade.

A novel and selective cascade reaction of primary amines and alkynes for the synthesis of the corresponding secondary propargylamines is described. This protocol proceeds with a CuBr2/TBHP system through a process of oxidative deamination of primary amines to imine and alkynylation, featuring a wide scope of substrates with good functional-group tolerance and operational simplicity. Additionally, the use of two different primary amines could also work smoothly using this protocol.

Direct Amidation of Carboxylic Acids through an Active α-Acyl Enol Ester Intermediate.

The development of a highly efficient and simple protocol for the direct amidation of carboxylic acids is described employing ynoates as novel coupling reagents. The transformation proceeds in good to excellent yields via in situ α-acyl enol ester intermediates formation under mild reaction conditions. This useful method has been demonstrated for a range of substrates to provide a succinct access to structurally diverse amides, including key intermediates of glibenclamide, tiapride hydrochloride, and nateglinide, and can be conducted on a mole scale.

Multicomponent domino reactions of hydrazinecarbodithioates: concise access to 3-substituted 5-thiol-1,3,4-thiadiazolines.

Two classes of addition/cycloaddition cascade reactions of hydrazinecarbodithioate (1) have been developed under mild reaction conditions. Reaction of hydrazinecarbodithioate (1) with formaldehyde solution (2) and propiolic acid (3) gives 3-propargyl-5-thiol-2,3-dihydro-1,3,4-thiadiazoles (5) via a decarboxylative coupling/cycloaddition domino sequence. When propiolic acid (3) is switched to phenyl boronic acid (4), a petasis/cycloaddition domino reaction is instead observed, in which 3-benzyl-5-thiol-2,3-dihydro-1,3,4-thiadiazoles (6) are obtained. Both these reactions show a wide range of functional-group compatibility for propiolic acids and aryl boronic acids, and give the corresponding products in moderate to good yields.

Mild and catalyst-free petasis/decarboxylative domino reaction: chemoselective synthesis of N-benzyl propargylamines.

Multicomponent domino reactions are attractive for assembling functionalized compounds. To this end, a one-pot catalyst-free chemoselective synthesis of N-benzyl propargylamines is reported with good functional group compatibility. This mild process involves in situ formation of an active amine through Petasis reaction of primary amines, formaldehyde solution, and boronic acids, which reacts with propiolic acids to give product in up to 94% yield via decarboxylative coupling reaction.

Organocatalytic Deoxygenative [3+2] Cycloaddition of N-Hydroxyamides with Alkynes to Access Isoxazoles.

Although the transition-metal-catalyzed [3+2] cycloadditions to access isoxazoles have been described well, organocatalytic methods remain underdeveloped. Herein, we report the use of an organophosphine catalyst for the preparation of a series of isoxazoles with exceptional regioselectivity via the [3+2] cycloaddition of N-hydroxyamides and alkynes. The scope of this organocatalytic transformation is broad, tolerating numerous functional groups and proceeding uniformly in an environmentally friendly, simple, and efficient manner.

Palladium-Catalyzed Regioselective Monofluoroallylation of Indoles with gem-Difluorocyclopropanes.

We present a palladium-catalyzed ring-opening reaction that induces indoles to cross-couple with gem-difluorocyclopropanes. The reaction proceeds through a domino process of C-C bond activation and C-F bond elimination, followed by C-C(sp2) coupling to produce various 2-fluoroallylindoles. This method is characterized by its high functional group tolerance, good yields and high regioselectivity, under base-free conditions. The synthetic utility of the products is illustrated by the functionalization of the NH and C2 positions of the indole scaffold.

Synthesis of symmetric 1,4-diamino-2-butynes via a Cu(I)-catalyzed one-pot A3-coupling/decarboxylative coupling of a propiolic acid, an aldehyde, and an amine.

A novel microwave-assisted approach for the one-pot Cu(I)-catalyzed A(3)-coupling/decarboxylative coupling (PA(2)-coupling) of a propiolic acid, an aldehyde, and an amine, resulting in the formation of diversely substituted 1,4-diamino-2-butynes,is described. It is noteworthy that this new multicomponent coupling provides an efficient access to introduce alkyl and aryl group at the 1,4-position of the 1,4-diamino-2-butynes.

Regio- and Chemoselective Copper-Catalyzed Formal [2+2+2] Cycloaddition of Primary Amines with Arylacetylenes to 2,4,5-Trisubstituted Pyridines.

Disclosed herein is an efficient strategy for the synthesis of 2,4,5-trisubstituted pyridines via CuI/NBS-catalyzed formal intermolecular [2+2+2] cycloaddition of easily available primary amines and nonactivated terminal alkynes. Moreover, this given reaction features a new mode of cycloaddition with high regio- and chemoselectivity, good atom- and step-economy, broad substrate scope, and wide functional group compatibility. Further mechanism studies indicate that this transformation starts with oxidative alkynylation of the amine to form a propargylamine intermediate, followed by radical addition to the alkyne and intramolecular cycloaddition, delivering the pharmacologically interesting multisubstituted pyridines.

Pd-Catalyzed Ring Restructuring of Oxazolidines with Alkenes Leading to Fused Polycyclic Indolizines.

A palladium-catalyzed reaction of N-propargyl oxazolidines with alkenes for the synthesis of indolizidines has been developed. Through a sequential 6-exo-dig cyclization/proton transfer/[3+2] cycloaddition/cycloreversion/aromatization process, a series of fused polycyclic indolizines are obtained in moderate to good yields with high functional group tolerance. Experimental and theoretical studies suggest that the [3+2] cycloaddition/cycloreversion of the oxazolidine ring probably involves C-C and C-O bond cleavage, providing a new ring restructuring approach for the synthesis of heterocycles.