Mumm Rearrangement Research Articles

Electrochemical difunctionalization of isocyanides by a three-component reaction cascade Mumm rearrangement: Rapid access to sulfur-containing imides

An efficient and practical electrochemical method for the three-component reaction cascade Mumm rearrangement of imides has been developed using a simple undivided cell with carbon electrodes at room temperature, which provides a useful strategy for the rapid synthesis of sulfur-containing imides with broad substrate scope and high functional tolerance. It is a rare example of in situ generation of O-acyl isoamide precursor for Mumm rearrangement.

Electrochemical Decarboxylation/Mumm Rearrangement towards Imides

We report an electrochemically promoted decarboxylation of readily available carboxylic acid and subsequent Mumm rearrangement to synthesize the corresponding imides. The reaction features external oxidant‐free, transition metal‐free mild conditions, and good functional group tolerance, affording various imides in moderate to good yields. Mechanistic studies reveal that the selective oxidation of aliphatic carboxylic acids appears to be the key step in this transformation.

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters.

An efficient multicomponent reaction of newly designed β-trifluoromethyl β-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper-catalyzed conditions has been developed, which affords various unsymmetrical β-trifluoromethyl N,N-diacyl-β-amino esters in good to excellent yields. The reaction features mild conditions, a wide scope of β-amino esters and carboxylic acids, and also applicability to large-scale synthesis, thus providing an efficient way for the synthesis of β-trifluoromethyl β-diacylamino esters. Furthermore, this reaction represents the first example of a Mumm rearrangement of β-trifluoromethyl β-diazo esters.

Electrochemically-driven difunctionalization of the isocyanide and Mumm rearrangement cascade: expeditious synthesis of N-acyl-N-alkyl S-thiocarbamates.

We describe the novel electrochemical multicomponent reaction (e-MCR) of readily available isocyanides, thiols and carboxylic acids to form N-substituted S-thiocarbamate derivatives that are found in several biologically active compounds. The effectiveness of the μ-electro flow reactor (μ-EFR) was showcased through significant reduction in electrolyte volume during the reaction, achieving gram-scale production of 4a within a short 12 min residence time using a Pt/Pt flow cell.

Post-Biginelli Ugi reaction towards synthesis of novel bisamides of dihydropyrimidinones: Substrate scope, modification and mechanism

A Biginelli, hydrolysis and Ugi four component reaction sequence was developed for the synthesis of novel dihydropyrimidinone (DHPM) bisamides in which an unprecedented but moderate 1,6 asymmetric induction was observed for this compound class. A detailed study is carried out to understand effects of various substitutions on the diastereoselectivity. Steric congestion led to sluggish Mumm rearrangement in some examples allowing the trapping of imidate intermediate by methanol. This unprecedented trapping confirms that slow Mumm rearrangement can lead to side products formation in Ugi reaction.

Visible-Light-Induced Four-Component Ritter-Type Reaction: Access to β-Trifluoromethyl Imides.

A visible-light-induced four-component Ritter-type reaction was developed for the synthesis of β-trifluoromethyl imides from CF3Br, alkenes, carboxylic acids, and nitriles. This protocol features mild reaction conditions, a broad substrate scope, and excellent functional group compatibility. Furthermore, this method has been proven to be suitable for the late-stage diversification of drug molecules. A mechanism involving a Ritter-type reaction and Mumm rearrangement was proposed on the basis of the control experiments.

Boron Lewis acid-catalyzed formal insertion of isocyanides into a C–O bond of benzyl esters

A boron Lewis acid catalyzed cascade process consisting of a rare isocyanide insertion with benzyl esters and the Mumm rearrangement to afford valuable imides with 100% atom utilization.

Isocyanide-based MCRs: Diastereoselective cascade synthesis of perfluoroalkylated pyrano[3,4-c]pyrrole derivatives

The highly diastereoselective synthesis of perfluoroalkyl-containing pyrano[3,4-c]pyrroles has been accomplished via a cascade process involving Michael addition, Passerini-type reaction, Mumm rearrangement and an oxo-Diels–Alder reaction. This domino transformation of isocyanides, methyl perfluoroalk-2-ynoates and 3-aroyl (or heteroyl) acrylic acids proceeded smoothly at room temperature and led to the formation of the highly diastereoselective target compounds with high functional-group compatibility in good to excellent yields.

Computational Study on the Kinetics and Mechanisms of Unimolecular Reactions of (Z)-(Z)-N-(λ5-phosphanylidene) Formohydrazonic Formic Anhydride: Intramolecular aza-Wittig Reaction in Competition with Mumm Rearrangement

For (Z)-(Z)-N-(λ5-phosphanylidene) formohydrazonic formic anhydride, Aza-Wittig reaction and Mumm rearrangement are studied using both density functional and coupled cluster theories. For this purpose, two different products starting from one substrate are considered that are competing with each other. The obtained products, P1 and P2, are thermodynamically favorable. The product of the aza-Wittig reaction, P1, is more stable than the product of Mumm rearrangement (P2). For the mentioned products, just one reliable pathway is separately proposed based on unimolecular reaction. Therefore, the rate constants based on RRKM theory in 300-600 K temperature range are calculated. Results show that the P1 generation pathway is a suitable path due to low energy barriers than the path P2. The first path has three steps with three transition states, TS1, TS2, and TS3. The P2 production path is a single-step reaction. In CCSD level, the computed barrier energies are 14.55, 2.196, and 10.67 kcal/mol for Aza-Wittig reaction and 42.41 kcal/mol for Mumm rearrangement in comparison with the corresponding complexes or reactants. For final products, the results of the computational study are in a good agreement with experimental predictions.

Ag(I)-Catalyzed Addition of Cyclopropenones and Nitrones to Access Imides.

An unprecedented Ag-catalyzed addition reaction of cyclopropenones and nitrones to access imides was developed. Sequential C-C bond cleavage, N-O bond cleavage, and Mumm rearrangement were uncovered in this process. This protocol exhibited high efficiency, regioselectivity, good yields, and a broad tolerance of various functional groups.

A deeper computational look at Mumm rearrangement: Evaluation of substituent, solvent, and temperature effects

AbstractThe effect of substitution, solvent, and temperature on Mumm rearrangement has been investigated using density functional theory (DFT). A potential energy surface (PES) profiles of transition state (TS) is demonstrated to illustrate the alteration of ΔG‡ of Mumm rearrangements for various substitutions. The possible reasons have been studied for the impressive conditions needed for Mumm rearrangement.

Electrochemical Difunctionalization of Alkenes by a Four-Component Reaction Cascade Mumm Rearrangement: Rapid Access to Functionalized Imides.

An electrochemical four-component reaction cascade Mumm rearrangement was developed. It is a rare example of in situ generation of O-acyl isoamides for 1,3-(O→N) acyl transfer. Inexpensive, commercially available arylethylenes, aryl or heterocyclic acids, acetonitrile, and alcohols were used as substrates. A wide range of aryl acids and alcohols were tolerated and provided imides in satisfactory yields. Subsequent hydrolysis of imides could be utilized to synthesize valuable amides and β-amino alcohol derivatives.

Electrochemical Difunctionalization of Alkenes by a Four‐Component Reaction Cascade Mumm Rearrangement: Rapid Access to Functionalized Imides

AbstractAn electrochemical four‐component reaction cascade Mumm rearrangement was developed. It is a rare example of in situ generation of O‐acyl isoamides for 1,3‐(O→N) acyl transfer. Inexpensive, commercially available arylethylenes, aryl or heterocyclic acids, acetonitrile, and alcohols were used as substrates. A wide range of aryl acids and alcohols were tolerated and provided imides in satisfactory yields. Subsequent hydrolysis of imides could be utilized to synthesize valuable amides and β‐amino alcohol derivatives.

Visible‐Light‐Induced Passerini Multicomponent Polymerization

AbstractHerein, we introduce an additive‐free visible‐light‐induced Passerini multicomponent polymerization (MCP) for the generation of high molar mass chains. In place of classical aldehydes (or ketones), highly reactive, in situ photogenerated thioaldehydes are exploited along with isocyanides and carboxylic acids. Prone to side reactions, the thioaldehyde moieties create a complex reaction environment which can be tamed by optimizing the synthetic conditions utilizing stochastic reaction path analysis, highlighting the potential of semi‐batch procedures. Once the complex MCP environment is understood, step‐growth polymers can be synthesized under mild reaction conditions which—after a Mumm rearrangement—result in the incorporation of thioester moieties directly into the polymer backbone, leading to soft matter materials that can be degraded by straightforward aminolysis or chain expanded by thiirane insertion.

Coupling of Carboxylic Acids with Ynamides and Subsequent Rearrangement for the Synthesis of Imides/Amides.

A coupling of carboxylic acids with ynamides and subsequent rearrangement for the synthesis of imides and amides is reported. The carboxylic acids could couple with ynamides to form α-acyloxyenamide followed by sulfonyl group migration and Mumm rearrangement to furnish the amides. Additionally, the products could be subjected to further rearrangement to deliver β-keto amides. This metal-free process represents an interesting method for chemical bonds cleavage and regeneration. Furthermore, divergent transformation of products were conducted to deliver an array of compounds.

An Unprecedented Retro-Mumm Rearrangement Revealed by ESI-MS/MS, IRMPD Spectroscopy, and DFT Calculations.

Brønsted acids and protic solvents mediate acyl transfer, known as the Mumm rearrangement, from imidates to the corresponding acylamides. This represents a key step in several reactions, for example, the Ugi four-component reaction (U-4CR) and Passerini three-component reaction (P-3CR). Herein, an unprecedented break of the non-reversibility of the Mumm rearrangement is reported. A combination of electrospray tandem mass spectrometry (ESI-MS/MS), infrared multiphoton dissociation (IRMPD) ion spectroscopy and theoretical calculations demonstrates the occurrence of the retro-Mumm rearrangement of protonated isopeptides in the gas phase. In the gas phase, the extra proton acquired during ESI promotes the backward isomerisation reaction in a catalytic fashion.

DEAD‐Promoted Oxidative Ugi‐Type Reaction Including an Unprecedented Ugi Amidation Assisted by Dicarboxylic Acids

A mild and metal‐free DEAD‐promoted (DEAD = diethyl azodicarboxylate) oxidative Ugi‐type reaction of tertiary amines has been demonstrated. The reaction gives easy access to α‐amino amides and imides with diverse functional groups in good isolated yields. This Ugi‐type approach achieves an unprecedented synthesis of α‐amino amide analogues with the assistance of dicarboxylic acids, and not water, for the introduction of the carbonyl oxygen atom of the amide moiety. Mechanistic studies indicated that the dicarboxylic acids may readily undergo an intramolecular annulation, instead of the Mumm rearrangement, to give the desired amide with one molecule of anhydride released.

Nef–Perkow–Mumm Cascade towards Imido Phosphate Derivatives

A one-pot, four-component synthesis of imido phosphates has been achieved using a Nef–Perkow sequence followed by addition of carboxylic acid derivatives. The final imido moiety is formed via a Mumm rearrangement of an intermediate imidate.

Unexpected isocyanide-based three-component bicyclization for the stereoselective synthesis of densely functionalized pyrano[3,4-c]pyrroles.

A novel three-component bicyclization strategy for the efficient synthesis of densely functionalized pyrano[3,4-c]pyrroles has been established from readily accessible 3-aroylacrylic acids, dialkyl acetylenedicarboxylates and isocyanides. The reaction pathway involves Huisgen 1,3-dipole formation, Passerini-type reaction, Mumm rearrangement and an oxo-Diels-Alder reaction sequence, resulting in continuous multiple bond-forming events including C-N, C-O and C-H bonds to rapidly build up molecular complexity.

In situ generation of nitrilium from nitrile ylide and the subsequent Mumm rearrangement: copper-catalyzed synthesis of unsymmetrical diacylglycine esters.

A novel in situ generation of nitrilium from a nitrile ylide and the subsequent Mumm rearrangement of carboxylic acid, nitrile, and diazo compounds gave various unsymmetrical diacylglycine esters in moderate to high yields. This copper-catalyzed cascade reaction enables one-pot generation of two C-N bonds, one C[double bond, length as m-dash]O bond, and one C-H bond, with nitrogen as the only byproduct. The reaction has a broad functional-group tolerance, is rapid, easily scales up to the 100 mmol scale, and is insensitive to air and moisture.