Auto-tandem Catalysis Research Articles

Asymmetric Auto-Tandem Catalysis with Chiral Organosuperbases: Intramolecular Cyclization/Enantioselective Direct Mannich-Type Addition Sequence.

An enantioselective addition reaction of alkynyl esters with imines was developed under asymmetric autotandem catalysis with a chiral Brønsted base. A chiral bis(guanidino)iminophosphorane organosuperbase, which has much higher basicity than that of conventional chiral organic bases, efficiently promoted both the intramolecular cyclization for the construction of a benzofuran ring or a benzothiophene ring and the sequential enantioselective direct Mannich-type reaction of diarylmethane derivatives, affording enantio-enriched diarylalkane derivatives that are otherwise difficult to access.

Auto tandem triple cascade organocatalysis: access to bis-lactone and butenolide derivatives.

The synthesis of bis-lactone and butenolide derivatives was described using alkylidene Meldrum's acid as nucleophiles. The process operates in a triple cascade through an auto tandem catalysis promoted by DBU.

One-Pot Synthesis of Pentasubstituted Pyridines following the Gold(I)-Catalyzed Aza–Enyne Metathesis/6π-Electrocyclization–Aromatization Sequence

The one-pot de novo synthesis of pentasubstituted pyridines was realized following the process of Au(I)-autotandem catalysis and subsequent aromatization. The process involves aza-enyne metathesis with aryl propiolates to yield 1-azabutadienes and their addition/6π-electrocyclization sequence with the other propiolate units. The resultant 1,4-dihydropyridines were aromatized to furnish the pyridines in the presence of atmospheric oxygen. The aryl propiolates were regioselectively incorporated into the ring system to afford 2-arylpyridines as the sole product.

Oxidative Cleavage and Ammoxidation of Unsaturated Hydrocarbons via Heterogeneous Auto-Tandem Catalysis.

The oxidative cleavage and functionalization of unsaturated C-C bonds are important processes for synthesis of carbonyl compounds from hydrocarbon feedstocks, yet there has been no report of direct amidation of unsaturated hydrocarbons via an oxidative cleavage of unsaturated C-C bonds with molecular oxygen as an environmentally benign oxidant. Herein, for the first time, we describe a manganese oxide-catalyzed auto-tandem catalysis strategy that enables direct synthesis of amides from unsaturated hydrocarbons by coupling oxidative cleavage with amidation. With oxygen as an oxidant and ammonia as a nitrogen source, a wide range of structurally diverse mono- and multisubstituted activated and unactivated alkenes or alkynes can smoothly undergo unsaturated C-C bond cleavage to deliver one- or multiple-carbon shorter amides. Moreover, a slight modification of the reaction conditions also allows for the direct synthesis of sterically hindered nitriles from alkenes or alkynes. This protocol features excellent functional group tolerance, a broad substrate scope, flexible late-stage functionalization, facile scalability, and a cost-effective and recyclable catalyst. Detailed characterizations reveal that the high activity and selectivity of the manganese oxides are attributed to the large specific surface area, abundant oxygen vacancies, better reducibility, and moderate acid sites. Mechanistic studies and density functional theory calculations indicate that the reaction proceeds through divergent pathways depending on the structure of substrates.

Keggin heteropolyacid in auto-tandem catalysis: confinement effects over ordered mesoporous silica in the synthesis of 2-pyridones

The inherent duality of active sites in Keggin acid (H3PW12O40) is explored under its confinement over ordered mesoporous silicas such as SBA-15 and MCF in the multicatalytic synthesis of 2-pyridones through auto-tandem catalysis.

Corrigendum: Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition/Kinetic Resolution Sequence for the Enantioselective Synthesis of Spiro‐Dihydropyranone from Benzylidene Meldrum's Acid

Corrigendum: Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition/Kinetic Resolution Sequence for the Enantioselective Synthesis of Spiro‐Dihydropyranone from Benzylidene Meldrum's Acid

Asymmetric Auto-Tandem Palladium Catalysis for 2,4-Dienyl Carbonates: Ligand-Controlled Divergent Synthesis.

Developing new asymmetric auto-tandem catalysis processes, especially in a divergent manner, is highly attractive but extremely challenging. Presented herein is a palladium-catalyzed auto-tandem reaction between 2,4-dienyl carbonates and o-TsNH arylimines or trifluoroacetophenones that proceeds through a consecutive N-allylation, vinylogous addition, π-σ-π isomerization, and another N-allylation sequence. Importantly, switchable diastereodivergent synthesis could be achieved by tuning the chiral bisphosphine ligands, which led to the construction of a broad spectrum of fused tetrahydroquinoline architectures with moderate to excellent enantioselectivity. Ligand control even enabled effective access to regiodivergent azetidine or chemodivergent β-H elimination with fair enantioselectivity, further showing the versatility of the current auto-tandem catalysis.

One-step synthesis of sequence-controlled multiblock polymers with up to 11 segments from monomer mixture

Switchable polymerization holds considerable potential for the synthesis of highly sequence-controlled multiblock. To date, this method has been limited to three-component systems, which enables the straightforward synthesis of multiblock polymers with less than five blocks. Herein, we report a self-switchable polymerization enabled by simple alkali metal carboxylate catalysts that directly polymerize six-component mixtures into multiblock polymers consisting of up to 11 blocks. Without an external trigger, the catalyst polymerization spontaneously connects five catalytic cycles in an orderly manner, involving four anhydride/epoxide ring-opening copolymerizations and one L-lactide ring-opening polymerization, creating a one-step synthetic pathway. Following this autotandem catalysis, reasonable combinations of different catalytic cycles allow the direct preparation of diverse, sequence-controlled, multiblock copolymers even containing various hyperbranched architectures. This method shows considerable promise in the synthesis of sequentially and architecturally complex polymers, with high monomer sequence control that provides the potential for designing materials.

Formal nucleophilic pyrrolylmethylationviapalladium-based auto-tandem catalysis: switchable regiodivergent synthesis and remote chirality transfer

Although nucleophilic benzylation-type reaction to introduce various aromatic systems into molecules has been widely explored, the related pyrrolylmethylation version remains to be disclosed. Reported herein is a palladium-catalysed multiple auto-tandem reaction between N-Ts propargylamines, allyl carbonates and aldimines in the presence of an acid, proceeding through sequential allylic amination, cycloisomerisation, vinylogous addition and aromatisation steps. A diversity of formal pyrrolylmethylated amine products were finally furnished efficiently. In addition, switchable regiodivergent 3-pyrrolylmethylation and 4-pyrrolylmethylation were realised by tuning catalytic conditions. Moreover, remote chirality transfer with readily available enantioenriched starting materials was well achieved with an achiral ligand, relying on diastereoselective generation of η2-Pd(0) complexes between Pd(0) and chiral 1,3-diene intermediates in the key vinylogous addition step. A few control experiments were conducted to elucidate the palladium-involved tandem reaction and regiodivergent synthesis.

Autotandem Catalysis: Inexpensive and Green Access to Functionalized Ketones by Intermolecular Iron-Catalyzed Amidoalkynylation/Hydration Cascade Reaction via N-Acyliminium Ion Chemistry.

Iron-based catalysts were applied in cascade-type reactions for the synthesis of different carbonyl compounds. The reactions proceeded by a new iron-catalyzed cascade of alkynylation/hydration by using both the σ- and π-Lewis acid properties of iron salts. The alkynylation reactions of several endo and exocyclic acetoxylactams were achieved with three different catalysts including FeCl3 ⋅ 6H2 O, FeCl3 , and Fe(OTf)3 showing the efficiency of σ-Lewis acidity of iron (III) salts in catalyzing the alkynylation reaction. We also demonstrated that the reaction sequence could be shortened by the direct use of hydroxylactams, leading to an environmentally friendly protocol, avoiding the need to perform unnecessary lengthy steps. A combination of the hard/soft iron Lewis acid properties was then used to implement an unprecedented tandem intermolecular alkynylation/intramolecular hydration sequence allowing expedient access to a new carbonyl structures from trivial materials.

Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition/Kinetic Resolution Sequence for the Enantioselective Synthesis of Spiro‐Dihydropyranone from Benzylidene Meldrum's Acid

AbstractA catalytic enantioselective vinylogous domino reaction has been achieved from ketone‐derived benzylidene Meldrum's acid and α‐ketolactones to provide spirolactone dihydropyranones with more than 99% ee. An Auto Tandem Catalysis (ATC) process resulting from dual and complementary role of (DHQ)2PHAL organocatalyst resulted in a sequence involving an asymmetric vinylogous formal (4+2) cycloaddition of benzylidene and the subsequent kinetic resolution operating through a 1,3‐prototropic shift leading to good yields (>50%) and the high selectivity.magnified image

Au(I) Catalyzed Synthesis of Densely Substituted Pyrazolines and Dihydropyridines via Sequential Aza-Enyne Metathesis/6π-Electrocyclization.

A gold(I) autotandem catalysis protocol is reported for the de novo synthesis of densely substituted pyrazolines and dihydropyridines from the corresponding imine derivatives in a highly regioselective fashion via a one-pot aza-enyne metathesis/6π-electrocyclization sequence. The substituents on the nitrogen atom of the imine perfectly control the reaction pathways from the pivotal 1-azabutadiene intermediate; thus, carbazates were converted into pyrazolines via 6π-electrocyclization of α,β-unsaturated hydrazones, while aryl imines provided dihydropyridines via 6π-electrocyclization of 3-azahexatrienes.

Aluminum Porphyrin Complex Mediated Auto-Tandem Catalysis for One-Pot Synthesis of Block Copolymers

Auto-tandem catalysis that uses a single catalyst to bridge and discriminate different catalytic cycles in a one-pot process is highly desirable for obtaining a high degree of structural complexity...

Benzoic acid resin (BAR): a heterogeneous redox organocatalyst for continuous flow synthesis of benzoquinones from β-O-4 lignin models

Benzoic acid resin (BAR), a redox organocatalyst for both Baeyer–Villiger and phenol oxidation, is described. BAR enabled the continuous-flow synthesis of benzoquinones from β-O-4 lignin models in a one-pot protocol via auto-tandem catalysis.

Access to 1,3-Dinitriles by Enantioselective Auto-tandem Catalysis: Merging Allylic Cyanation with Asymmetric Hydrocyanation.

Enantioselective auto-tandem catalysis represents a challenging yet highlight attractive topic in the field of asymmetric catalysis. In this context, we describe a dual catalytic cycle that merges allylic cyanation and asymmetric hydrocyanation. The one-pot conversion of a broad array of allylic alcohols into their corresponding 1,3-dinitriles proceeds in good yield with high enantioselectivity. The products are densely functionalized and can be easily transformed to chiral diamines, dinitriles, diesters, and piperidines. Mechanistic studies clearly support a novel sequential cyanation/hydrocyanation pathway.

Integrated-Trifunctional Single Catalyst with Fine Spatial Distribution via Stepwise Anchored Strategy for Multistep Autotandem Catalysis

Tandem catalysis that facilitates a series of consecutive catalytic reactions to perform in a concurrent behavior is regarded as one of the most important future directions for enabling sustainable...

Synthesis of diarylalkanes through an intramolecular/intermolecular addition sequence by auto-tandem catalysis with strong Brønsted base.

An auto-tandem catalysis with a strong Brønsted base enabled the synthesis of diarylalkanes containing a benzofuran moiety. Potassium tert-butoxide efficiently catalyzed both the intramolecular cyclization of less acidic ortho-alkynylaryl benzyl ethers and the following intermolecular addition of diarylmethanes to styrenes, demonstrating the high potential of the catalysis in organic synthesis.

A step-economic and one-pot access to chiral Cα-tetrasubstituted α-amino acid derivatives via a bicyclic imidazole-catalyzed direct enantioselective C-acylation.

Cα-Tetrasubstituted α-amino acids are ubiquitous and unique structural units in bioactive natural products and pharmaceutical compounds. The asymmetric synthesis of these molecules has attracted a lot of attention, but a more efficient method is still greatly desired. Here we describe the first sequential four-step acylation reaction for the efficient synthesis of chiral Cα-tetrasubstituted α-amino acid derivatives from simple N-acylated amino acids via an auto-tandem catalysis using a single nucleophilic catalyst. The synthetic efficiency is improved via a direct enantioselective C-acylation; the methodology affords the corresponding Cα-tetrasubstituted α-amino acid derivatives with excellent enantioselectivities (up to 99% ee). This step-economic, one-pot, and auto-tandem strategy provides facile access to important chiral building blocks, such as peptides, serines, and oxazolines, which are often used in medicinal and synthetic chemistry.

Auto‐Tandem Cooperative Catalysis Using Phosphine/Palladium: Reaction of Morita–Baylis–Hillman Carbonates and Allylic Alcohols

Auto-tandem catalysis (ATC), in which a single catalyst promotes two or more mechanistically different reactions in a cascade pattern, provides a powerful strategy to prepare complex products from simple starting materials. Reported here is an unprecedented auto-tandem cooperative catalysis (ATCC) for Morita-Baylis-Hillman carbonates from isatins and allylic carbonates using a simple Pd(PPh3 )4 precursor. Dissociated phosphine generates phosphorus ylides and the Pd leads to π-allylpalladium complexes, and they undergo a γ-regioselective allylic-allylic alkylation reaction. Importantly, a cascade intramolecular Heck-type coupling proceeds to finally furnish spirooxindoles incorporating a 4-methylene-2-cyclopentene motif. Experimental results indicate that both Pd and phosphine play crucial roles in the catalytic Heck reaction. In addition, the asymmetric versions with either a chiral phosphine or chiral auxiliary are explored, and moderate results are obtained.

Lewis Acid-Catalyzed Synthesis of Benzofurans and 4,5,6,7-Tetrahydrobenzofurans from Acrolein Dimer and 1,3-Dicarbonyl Compounds.

2,3-Disubstituted benzofurans were synthesized from acrolein dimer and 1,3-dicarbonyl compounds by using N-bromosuccinimide as an oxidizing agent. The method was used to synthesize two commercial drug molecules, benzbromarone and amiodarone. The proposed mechanism of the reaction involves a N-bromosuccinimide (NBS)-assisted autotandem catalysis with Lewis acid catalyst. To proof the proposed mechanism, an intermediate was isolated successfully, which can be converted to 4,5,6,7-tetrahydrobenzofurans.