One-pot Domino Process Research Articles

Scalable Total Syntheses of Some Natural and Unnatural Lamellarins: Application of a One-Pot Domino Process for Regioselective Access to the Central 1,2,4-Trisubstituted Pyrrole Core.

Short and scalable total syntheses of lamellarin G trimethyl ether, lamellarin D trimethyl ether, lamellarin H, lamellarin η, dihydrolamellarin η, and lamellarin U have been realized in four to six linear steps with an overall yield of ≤22%. Highlights of the synthesis include single-step access to the central 1,2,4-trisubstituted pyrrole core in a highly regioselective manner via a one-pot [3+2] cycloaddition/elimination/aromatization sequence-based domino process. Subsequent, palladium-mediated double C-H oxidative coupling in a single-pot operation provides access to the pentacyclic coumarin-fused pyrrolo-dihydroisoquinoline core present in lamellarins.

One-pot sequential synthesis of 3-carbonyl-4-arylbenzo[f]indole and 3-carbonyl-4-arylnaphthofuran fluorophores

A robust synthetic method for the construction of valuable fluorophores, 3-carbonyl-4-arylbenzo[f]indoles and 3-carbonyl-4-arylnaphthofurans, has been developed. The strategy involved a one-pot domino process to achieve the products in moderate to excellent yields.

Metal-Free Triple Annulation of Ene-Yne-Ketones with Isocyanides: Domino Access to Furan-Fused Heterocycles via Furoketenimine.

A new furoketenimine intermediate from the coupling of ene-yne-ketones and o-alkenyl arylisocyanides, which enables the efficient synthesis of a wide range of tetracyclic and pentacyclic furan-fused heterocycles in a one-pot domino process under catalyst-free conditions, is disclosed. Based on the control experiments, a cascade of 1,6-addition, cyclization, intramolecular Diels-Alder reaction, and oxidative aromatization was proposed for the mechanism.

Syntheses of 1-Aryl-5-nitro-1H-indazoles and a General One-Pot Route to 1-Aryl-1H-indazoles.

An efficient route to substituted 1-aryl-1H-indazoles has been developed and optimized. The method involved the preparation of arylhydrazones from acetophenone or benzaldehyde substituted by fluorine at C2 and nitro at C5, followed by deprotonation and nucleophilic aromatic substitution (SNAr) ring closure in 45–90%. Modification of this procedure to a one-pot domino process was successful in the acetophenone series (73–96%), while the benzaldehyde series (63–73%) required a step-wise addition of reagents. A general one-pot protocol for 1-aryl-1H-indazole formation without the limiting substitution patterns required for the SNAr cyclization has also been achieved in 62–78% yields. A selection of 1-aryl-1H-indazoles was prepared in high yield by a procedure that requires only a single laboratory operation.

Synthesis and Structural Evaluation of 5-Methyl-6-acetyl Substituted Indole and Gramine.

The synthesis and crystal structures of 1-(5-methyl-1H-indol-6-yl)ethan-1-one (7), C11H11NO, and 1-3-[(dimethylamino) methyl]-5-methyl-1H-indol-6-ylethan-1-one (8), C14H18N2O, are reported. The synthesis is based on the Diels-Alder cycloaddition of a substituted 2H-pyran-2-one derivative, followed by an acid-catalyzed cyclization and concomitant deprotection (the last two steps were carried out as a one-pot domino process) yielding substituted indole 7, which was further derivatized via Mannich reaction to the gramine derivative 8. Both structures 7 and 8 were determined on the basis of IR, 1H NMR and mass spectroscopy, as well as by the elemental analysis and melting point determination. According to the single-crystal X-Ray diffraction analysis, the structure 7 has a single unique molecule in the asymmetric unit whereas the structure 8 contains four unique molecules in the asymmetric unit. Molecules 7 are linked via N-H···O hydrogen bonds between the secondary amine group and carbonyl moiety of the acetyl group of adjacent molecules, whereas molecules 8 are linked via N-H···N hydrogen bonds between the secondary and tertiary amine groups of adjacent molecules. Both structures are further stabilized by weak C-H···O, C-H···π and π···π interactions.

ChemInform Abstract: Enantioselective Synthesis of 1,2,5,6‐Tetrahydropyridines (THPs) via Proline‐Catalyzed Direct Mannich‐Cyclization/Domino Oxidation—Reduction Sequence: Application for Medicinally Important N‐Heterocycles.

An enantioselective multi-component synthesis of 1,2,5,6-tetrahydropyridines (THPs) has been developed through a one-pot domino-process. This transformation proceeds through proline-catalyzed direct Mannich reaction-cyclization of glutaraldehyde with in situ generated imines, followed by site-selective oxidation–reduction sequence under mild conditions. Chiral 1,2,5,6-THPs are obtained in good to high yields (up to 80%) and with the excellent enantioselectivity (up to 98 : 2 er). The usefulness of this operationally simple method is also shown to synthesize other medicinally important nitrogen-heterocycles.

Original Mitsunobu-Triggered Sequence Involved in a One-Pot Domino Process toward Tetracyclic Systems Bearing a Bis-N,O-acetal Junction.

Herein is reported an efficient, one-pot domino process through a 1,6-aza-Michael addition-triggered sequence and an original Mitsunobu-type concerted sequence for the synthesis of tetracyclic systems containing a bis-N,O-acetal junction. This methodology led to the construction of four new bonds, the cleavage of three C-O bonds, and the generation of an asymmetric center. Mitsunobu activation afforded final ring closure involving the creation of two bonds, which remains unprecedented among reported Mitsunobu-type sequences. The latter occurred in a regioselective fashion at the challenging C6-position of 2-pyridone intermediates. In the case of adequately substituted enantiopure amino alcohols, up to 95:5 of diastereoisomeric excess was achieved. Computational studies allowed the discrimination of a favored pathway for Mitsunobu sequence and supported the regioselectivity as well as the diastereoselectivity observed for this step.

Enantioselective synthesis of 1,2,5,6-tetrahydropyridines (THPs) via proline-catalyzed direct Mannich-cyclization/domino oxidation–reduction sequence: application for medicinally important N-heterocycles

An enantioselective multi-component synthesis of 1,2,5,6-tetrahydropyridines (THPs) has been developed through a one-pot domino-process.

Pd-catalyzed cross-coupling reactions of arenediazonium salts with arylsilanes and aryltrifluoroborates in water

Pd-catalyzed cross-coupling reactions of various arenediazonium salts with ArSi(OR)3 and KArBF3 have been achieved in good to excellent yields under simple aerobic conditions in water at room temperature. The functional group tolerance makes these transformations as attractive alternatives to the traditional cross-coupling approaches. Furthermore, the sequence can also be performed in a one-pot domino process, omitting the isolation of the intermediate arenediazonium salt.

ChemInform Abstract: Nano‐Cu2O‐Catalyzed Formation of C—C and C—O Bonds: One‐Pot Domino Process for Regioselective Synthesis of α‐Carbonyl Furans from Electron‐Deficient Alkynes and 2‐Yn‐1‐ols.

The formation of carbon–carbon and carbon–oxygen bonds continues to be an active and challenging field of chemical research. Nanoparticle catalysis has attracted considerable attention owing to its environmentally benign and high activity toward the reactions. Herein, we described a novel and effective nano-Cu2O-catalyzed one-pot domino process for the regioselective synthesis of α-carbonyl furans. Various electron-deficient alkynes with 2-yn-1-ols underwent this process smoothly in moderate to good yields in the presence of air at atmospheric pressure. It is especially noteworthy that a novel 2,4,5-trisubstituted 3-ynylfuran was formed in an extremely direct manner without tedious stepwise synthesis. Additionally, as all of the starting materials are readily available, this method may allow the synthesis of more complex α-carbonyl furans. An experiment to elucidate the mechanism suggested that the process involved a carbene intermediate.

Nano‐Cu2O‐Catalyzed Formation of CC and CO Bonds: One‐Pot Domino Process for Regioselective Synthesis of α‐Carbonyl Furans from Electron‐Deficient Alkynes and 2‐Yn‐1‐ols

The formation of carbon-carbon and carbon-oxygen bonds continues to be an active and challenging field of chemical research. Nanoparticle catalysis has attracted considerable attention owing to its environmentally benign and high activity toward the reactions. Herein, we described a novel and effective nano-Cu(2)O-catalyzed one-pot domino process for the regioselective synthesis of α-carbonyl furans. Various electron-deficient alkynes with 2-yn-1-ols underwent this process smoothly in moderate to good yields in the presence of air at atmospheric pressure. It is especially noteworthy that a novel 2,4,5-trisubstituted 3-ynylfuran was formed in an extremely direct manner without tedious stepwise synthesis. Additionally, as all of the starting materials are readily available, this method may allow the synthesis of more complex α-carbonyl furans. An experiment to elucidate the mechanism suggested that the process involved a carbene intermediate.

Domino Reaction of α-Acetyl-α-carbamoyl Ketene Dithioacetals with Vilsmeier Reagents: A Novel and Efficient Synthesis of 4-Halogenated 2(1H)-Pyridinones

A novel and efficient route to 4-halogenated N-substituted 2(1H)-pyridinones has been developed via a one-pot domino process of readily available alpha-acetyl-alpha-carbamoyl ketene dithioacetals with Vilsmeier reagents. These 4-halogenated-2(1H)-pyridinones constitute useful intermediates due to the easy elaboration on either the pyridinone core (by the displacement of the halogen atom) or functionality transformation (dithiocarbonyl functionality) and have proven to be a useful synthetic scaffold in the synthesis of the bio- and pharmacologically important fused-ring diazepine core.

Domino 6π‐Electrocyclization/Diels–Alder Reactions on 1,6‐Disubstituted (E,Z,E)‐1,3,5‐Hexatrienes: Versatile Access to Highly Substituted Tri‐ and Tetracyclic Systems

The (E,Z,E)-1,3,5-hexatrienes 1a, 2a,b and 3b undergo 6pi-electrocyclization within 15-30 min upon heating to 200-215 degrees C. While the cyclohexene-annelated products 8a,b were stable, the analogous cyclopentene- and cycloheptene-annelated derivatives 7a and 9b easily underwent dehydrogenation to the corresponding aromatic compounds 10a and 12b during the work-up. The cyclohexadiene derivatives 8a,b were employed in thermal Diels-Alder reactions with 4-phenyl-3H-1,2,4-triazoline-3,5-dione (PTAD) and tetracyanoethylene (TCNE) to give the expected [4+2] cycloadducts 13a and 14a in good yields (60 and 78%). The initially formed cycloadduct of 8a and dimethyl acetylenedicarboxylate (DMAD) underwent a subsequent retro-Diels-Alder reaction to give the tetrahydronaphthalene 11b (47%). Under high pressure (10 kbar), the cycloadduct 15a was formed at room temperature and could be isolated in 44% yield. TCNE and N-phenylmaleimide with 8a under high pressure also led to the [4+2] cycloadducts 14a and 16a in good yields (60 and 77%). The 6pi-electrocyclization and subsequent Diels-Alder reaction, when performed as a one-pot domino process, provided direct access to Diels-Alder products of intermediately formed 6pi-electrocyclization products, for example from the 1,3,5-hexatrienes 1a,b, 2a,b, 3b and TCNE to the corresponding tricyclic products 17a,b, 14a,b, 18b in moderate to good yields (27-80%) depending on the nature of the alkoxycarbonyl group. Such sequential reactions with N-phenylmaleimide, maleic anhydride, dimethyl maleate and fumarodinitrile, the latter two under high pressure (10 kbar), worked as well to yield 16b (70%), 19a,b (19, 32%) and 20b (39%) and 21b (76%), respectively. With PTAD, however, the hexatrienes 2a,b reacted at ambient temperature without 6pi-electrocyclization to give the formal [4+2] cycloadducts 27a,b (48 and 46%), most probably via zwitterionic intermediates 23a,b and 25a,b.

A Domino Copper‐Catalyzed C—O Coupling—Claisen Rearrangement Process.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A domino copper-catalyzed C-O coupling-Claisen rearrangement process.

A practical method for the diastereoselective generation of two adjacent quarternary stereocenters by combining a copper-catalyzed C-O coupling reaction with a subsequent Claisen rearrangement in a one-pot domino process is described. Furthermore, an experimentally simple method for the stereoselective synthesis of a variety of different types of vinyl ethers is delineated using the same catalyst system.