Domino Aldol Research Articles

One Pot Sequential Aldol condensation - Michael Addition – Sonogashira, and Heck Arylation toward Highly Functionalized Quinolines

A facile Pd/Cu-cocatalyzed one-pot domino aldol condensation/Michael addition/Sonogashira coupling has been developed. The reaction of 2-chloro-3-formylquinolines (CFQs), 1 acetophenones (APs), 2 and terminal acetylenes, 3 by employing triethylamine as a base, solvent as well as a ligand under mild conditions gave highly functionalized 1,5-diphenyl-3-(2-(2-phenylethynyl)quinolin-3-yl)pentane-1,5-diones, 4a-j, Additionally accomplished Heck arylation using CFQs in the presence of Pd catalyst. The present methodology gave the desired synthetic building blocks in acceptable yields.

Catalyst-free synthesis of novel 4H-indeno[1,2-b]furan-4-ones and furo[2,3-d]pyrimidines in water

ABSTRACTAn operationally simple, catalyst-free, and efficient protocol for the synthesis of novel 4H-indeno[1,2-b]furan-4-one and furo[2,3-d]pyrimidine derivatives by a one-pot reaction of 2-aminopyridines, 1,3-indandione, or barbituric acid and phenylglyoxal monohydrate in water at reflux, involving domino aldol condensation, Michael addition, and ring-closing reactions is described. This transformation has several advantages, including high yield, short reaction duration, simple workup, and simple purification.

Highly stereoselective metal-mediated domino aldol reactions of propiophenone enolates with heteroaromatic, aliphatic, and unsaturated aldehydes

The one-pot reaction of propiophenone with heteroaromatic, aliphatic, and unsaturated aldehydes in the presence of metal halides furnishes racemic tetrahydro-2H-pyran-2,4-diols in a highly diastereo-selective manner. The mechanism for the stereoselective product formation as well as the surprising formation of a side product was explained on the basis of DFT computations.

ChemInform Abstract: Scope and Mechanism of the Highly Stereoselective Metal‐Mediated Domino Aldol Reactions of Enolates with Aldehydes.

AbstractThe one‐pot transformation of ketones (I) and (IV) with aldehydes (II) in the presence of metal halide to furnish tetrahydro‐2H‐pyran‐2,4‐diols (III) and (V), resp., is investigated by experimental and computational studies.

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes.

A one-pot transformation, which involves the reaction of ketones with aldehydes in the presence of metal halides to furnish tetrahydro-2H-pyran-2,4-diols in a highly diastereoselective manner, is investigated thoroughly by experiments and computations. The reaction was also successfully implemented on a flow micro reactor system.

ChemInform Abstract: Regioselective and Enantioselective Domino Aldol—Oxa‐Michael Reactions to Construct Quaternary (Chroman) Stereocenters.

An asymmetric domino aldol–oxa-Michael reaction of salicylaldehydes and β,β-disubstituted α,β-unsaturated aldehydes has been developed by using dienamine-mediated catalysis. The developed strategy leading to the stereoselective and regioselective formation of novel chroman derivatives with quaternary (chroman) stereocenters is presented. Particularly, salicylaldehydes with variously substitution patterns dominate the efficient construction of the chroman derivatives with high molecular complexity and skeletal diversity in excellent diastereo- and enantioselectivities.

Regioselective and Enantioselective Domino Aldol–Oxa‐Michael Reactions to Construct Quaternary (Chroman) Stereocenters

AbstractAn asymmetric domino aldol–oxa‐Michael reaction of salicylaldehydes and β,β‐disubstituted α,β‐unsaturated aldehydes has been developed by using dienamine‐mediated catalysis. The developed strategy leading to the stereoselective and regioselective formation of novel chroman derivatives with quaternary (chroman) stereocenters is presented. Particularly, salicylaldehydes with variously substitution patterns dominate the efficient construction of the chroman derivatives with high molecular complexity and skeletal diversity in excellent diastereo‐ and enantioselectivities.

One-Pot Domino Aldol Reaction of Indium Enolates Affording 6-Deoxy-α-D,L-altropyranose Derivatives: Synthesis, Mechanism, and Computational Results.

The domino-aldol-aldol-hemiacetal-reaction cascade of indium and other group 13 metal enolates furnished 6-deoxy-α-D,L-altropyranose derivatives in up to 99% yield under thermodynamic control. At lower temperature and thus under kinetic control, the reaction proceeded in a much less diastereoselective manner. The changeover from kinetic to thermodynamic control operating in this multistep domino-aldol-aldol-hemiacetal protocol was used for probing the efficiency of DFT computations. Calculations at the B3LYP/6-31G(d)/LANL2DZ level provided a mechanistic picture in full agreement with the experimental outcome.

Efficient one pot multi-component domino Aldol condensation–Michael addition–Suzuki coupling reaction for the highly functionalized quinolines

A parallel and advantageous multi-component one pot reaction has been developed utilizing domino Aldol condensation–Michael addition–Suzuki coupling approach for a variety of 2,3-disubstituted highly functionalized quinolines. The domino reactions of 2-chloro-3-formylquinolines, 1 acetophenones, 2 and distinctive boronic acids, 3 were carried out utilizing PdCl2(PPh3)2/tripotassium phosphate/ethanol–water system. At 80°C they gave diversified functionalized quinolines in good yields.

ChemInform Abstract: Asymmetric Formal [3 + 2] Cycloaddition Reaction of Succinaldehyde via Diarylprolinol‐Mediated Domino Aldol—Acetalization Reaction for the Construction of Tetrahydrofuran.

AbstractTransformation of benzaldehyde and aliphatic aldehydes such as 3‐phenylpropanal hardly proceeds.

Asymmetric Formal [3 + 2] Cycloaddition Reaction of Succinaldehyde via Diarylprolinol-mediated Domino Aldol–Acetalization Reaction for the Construction of Tetrahydrofuran

Abstract Highly enantioselective synthesis of tetrahydrofurans was accomplished via a formal [3 + 2] cycloaddition reaction of succinaldehyde, which acts as a three-carbon unit. The reaction consists of the domino reaction of the diarylprolinol-mediated aldol reaction of succinaldehyde followed by an intramolecular acetalization reaction.

ChemInform Abstract: One‐Pot Synthesis of Substituted Tetrahydrocyclobuta[a]naphthalenes by Domino Aldol Condensation/Olefin Migration/Electrocyclization.

A facile one-pot synthetic route for preparing the novel benzofused tricyclic skeleton of 1,2,2a,8b-tetrahydrocyclobuta[a]naphthalenes 5 is developed. The route was realized by a NaH-mediated tandem aldol condensation/olefin migration/electrocyclization of o-allylbenzaldehydes 1 with cinnamyl sulfones 3 in good yields.

One-Pot Synthesis of Substituted Tetrahydrocyclobuta[a]naphthalenes by Domino Aldol Condensation/Olefin Migration/Electrocyclization

A facile one-pot synthetic route for preparing the novel benzofused tricyclic skeleton of 1,2,2a,8b-tetrahydrocyclobuta[a]naphthalenes 5 is developed. The route was realized by a NaH-mediated tandem aldol condensation/olefin migration/electrocyclization of o-allylbenzaldehydes 1 with cinnamyl sulfones 3 in good yields.

ChemInform Abstract: Synthesis of Tetrahydroanthracen‐9‐ones by the Domino Aldol Condensation/Diels—Alder Cycloaddition.

AbstractSequential NaOH‐mediated aldol condensation of allylacetophenones with cinnamaldehyde, intramolecular Diels—Alder reaction, and double bond migration allows the synthesis of the biologically interesting title compounds in a one‐pot manner.

Synthesis of tetrahydroanthracen-9-ones by the domino aldol condensation/Diels–Alder cycloaddition

A facile protocol toward several substituted 3-aryl-3,4,4a,10-tetrahydro-2H-anthracen-9-ones 1 starting with substituted 2-allylbenzaldehydes 2 was described. The overall synthetic process was carried out by the domino aldol condensation/Diels–Alder cycloaddition of skeleton 2 with substituted cinnamaldehydes 3 in an alkalic aqueous-methanolic solution followed by base-induced double migration of the resulting cycloadducts. Skeleton 2 was prepared from isovanillin (4) in moderate yield in five-steps via the known procedures with the synthetic sequence of O-allylation, Claisen rearrangement, O-methylation, Grignard methylation, and PCC-mediated oxidation.

Highly Chemoselective Baylis−Hillman and Aldol Reactions of 2H-Thiopyran-4(3H)-one Using Tertiary Amine Catalysts in Aqueous Media

For the first time, the Baylis-Hillman (BH) reaction of 2H-thiopyran-4(3H)-one is investigated, and surprisingly, the reaction of 2H-thiopyran-4(3H)-one with aldehydes in the presence of different tertiary amines shows excellent chemo- and regioselectivity in water. At room temperature, DBU affords BH adducts, but with DABCO, aldol products were obtained. In the case of DABCO, Et(3)N, or DMAP, domino aldol-rearrangement reactions occurred at 45-50 °C.

A Domino Aldol Addition/Hemiketal Formation/Hemiketal Formation/Epimerization Route to a Heteroadamantane. A Crystal-Structure, NMR, and Computational Study

It has been found by serendipity during the attempted synthesis of the potential tris-bidentate ligand 7 that this compound undergoes multiple ring-closure reactions to form the heterodamantane derivative 12. This reaction involves a domino aldol addition/hemiketal formation/hemiketal formation/epimerization sequence. Compound 12 was studied intensively by X-ray crystal-structure analysis, NMR, and AM1 computations. Complete assignment of all 1H- and 13C-NMR signals was achieved by a combination of HMQC, HMBC, DPFGSE-NOE, COSY, and long-range-COSY experiments. The NMR data agreed well with the crystallographic and computational results. Accordingly, 12 is present as the thermodynamically most-stable diastereoisomer with relative u-configuration at centers C(8) and C(9). In summary, five stereogenic centers were created starting from an achiral precursor in an efficient cascade reaction under thermodynamic control.

ChemInform Abstract: Aldolases as Leitmotiv — A Nonenzymatic Domino Aldol Reaction Triggered by Zinc Bisenolate and Polyenolate (ate) Complexes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Aldolases as Leitmotiv - A Nonenzymatic Domino Aldol Reaction Triggered by Zinc Bisenolate and Polyenolate (ate) Complexes

A new zinc(II) mediated sequential aldol reaction is described for the diastereoselective one-pot synthesis of tetrahydropyran-2,4-diols. The dependence of the yield on the ratio Zn2 +/enolate proposes that zinc(II) polyenolate and ate complexes may be involved.