An efficient synthesis of Baylis-Hillman adducts of acrylamide: Pd-catalyzed hydration of Baylis-Hillman adducts of acrylonitrile

An efficient palladium-catalyzed two-step protocol for the synthesis of Baylis-Hillman adducts of acrylamide was developed. The method involved the preparation of Baylis-Hillman adducts of acrylonitrile and a Pd-catalyzed hydration of nitrile with acetaldoxime.     

Three-component coupling of alkynes, Baylis-Hillman adducts and sodium azide: a new synthesis of substituted triazoles

A three-component coupling was used to prepare a series of 1,4-disubstituted-1,2,3-triazoles from the corresponding acetylated Baylis-Hillman adducts, sodium azide and terminal alkynes. This one-pot reaction further increases the efficacy of ‘Click’ synthesis and diversifies the preparation of multi-functional 1,4-disubstituted-1,2,3-triazoles.     

Development of bis-thiourea-type organocatalyst for asymmetric Baylis-Hillman reaction

A new chiral bis-thiourea-type organocatalyst 2 developed for the Baylis-Hillman reaction provided a drastic rate enhancement. Allylic alcohols were obtained with up to 90% ee in the case of cyclohexanecarboxaldehyde (4i).     

Regioselective synthesis of poly-substituted thiophenes from Baylis-Hillman adducts

The reaction of Baylis-Hillman acetates and ethyl mercaptoacetate in the presence of DBU in DMF produced 2,3,4-trisubstituted tetrahydrothiophenes at room temperature as a diastereomeric mixture via the sequential S_N2′ and Michael addition. Aromatization of tetrahydrothiophenes by DDQ oxidation produced 2,3,4-trisubstituted thiophenes in good yields.     

Ring-closing metathesis toward the synthesis of 2,5-dihydrofuran and 2,5-dihydropyrrole skeletons from Baylis-Hillman adducts

We have developed an efficient method for the synthesis of 2,5-dihydrofuran and 2,5-dihydropyrrole skeletons from the simply modified Baylis-Hillman adducts via RCM reaction.     

First application of chiral ionic liquids in asymmetric Baylis-Hillman reaction

The first example of the use of chiral ionic liquids as reaction media in the asymmetric Baylis-Hillman reaction was described using N-alkyl-N-methylephedrinium salts. Good yields and significant enantiomeric excesses were obtained.     

An expedient synthesis of 2,4,5-trisubstituted 1,4-pentadienes from Baylis-Hillman adducts via the Pd-catalyzed decarboxylation-elimination protocol

We disclosed an efficient synthetic method of 2,4,5-trisubstituted 1,4-pentadienes from Baylis-Hillman adducts via the Pd-catalyzed decarboxylation-elimination protocol as the key step.     

Palladium-catalyzed carbonylative cyclization of Baylis-Hillman adducts. An efficient approach for the stereoselective synthesis of 3-alkenyl phthalides

A palladium-mediated carbonylative cyclization reaction of Baylis-Hillman adducts is disclosed. This simple, efficient and straightforward sequence leads to the formation of an array of 3-alkenylphthalides with different substitution patterns on the aromatic ring, with good chemical yields and selectivities.     

Pd-mediated synthesis of 2-arylquinolines and tetrahydropyridines from modified Baylis-Hillman adducts

We synthesized 2-arylquinolines and tetrahydropyridines via palladium-mediated Heck type reactions starting from the Baylis-Hillman adducts. 2-Arylquinolines were prepared via the Heck type cyclization followed by concomitant aerobic oxidation.     

A convenient synthesis of 1,5-diarylpyrazoles from Baylis-Hillman adducts using HY-zeolite

<正>A facile and convenient protocol was developed for the synthesis of 1,5-diarylpyrazoles using Baylis-Hillman adducts in the presence of HY-zeolite as an efficient recyclable heterogeneous catalyst in reasonable reaction times(1.5-2.5 h) and high yields (78-90%).     

Palladium-catalyzed addition of hydroxylamine derivatives to Baylis-Hillman acetate adducts

The first use of hydroxylamine derivatives as the aminoxy equivalent of nucleophiles in palladium catalyzed addition to Baylis-Hillman acetate adducts is described. The reaction proceeds smoothly to give the substituted allyloxy amines in good yield and selectivity.     

Synthesis of poly-substituted pyrroles starting from the Baylis-Hillman adducts

We synthesized poly-substituted pyrrole derivatives 4a-e, 7a-c and 10a-d from the reaction of phenacyl bromide and the aza-Baylis-Hillman adducts 1a-d or their rearranged derivatives 5a-e. The pyrroles were synthesized via the successive N-alkylation, Michael addition, elimination of p-toluenesulfinic acid and oxidative aromatization processes.     

Serendipitous synthesis of 2-amino-2,3-dihydrobenzofuran derivatives starting from Baylis-Hillman adducts

Serendipitous synthesis of 2-amino-2,3-dihydrobenzofuran derivatives 4a-g was achieved starting from the Baylis-Hillman adducts. In the reaction sequence, intramolecular oxygen atom transfer from nitrogen atom to arene moiety was observed.     

An approach to substituted dihydroisoquinolin-1(2H)-ones from Baylis-Hillman adducts

In this communication we describe an easy and straightforward alternative method for the preparation of 3,4-substituted isoquinolin-1(2H)-ones, using Baylis-Hillman adducts as starting material.     

Importance of Baylis-Hillman adducts in modern drug discovery

The Baylis-Hillman (BH) reaction plays a fascinating role in the field of synthetic and medicinal chemistry. BH adducts and their derivatives have been used as crucial synthons for the synthesis of various pharmaceutically useful natural products and compounds with carbocyclic or heterocyclic frameworks. This digest letter aims to discuss some key ideas for the synthesis of biologically active scaffolds using BH reaction and raise the awareness of this emerging research domain in modern drug discovery. In this review, we will present and discuss recent reports of various biologically active scaffolds derived from BH reaction, and their reported biological activities.     

An easy and stereoselective synthesis of N-Boc-dolaproine via the Baylis-Hillman reaction

In this communication we report a stereoselective total synthesis of N-Boc-dolaproine (Dap), an amino acid residue of the antineoplastic pentapeptide Dolastatin 10. Our strategy is based on a Baylis-Hillman reaction between N-Boc-prolinal and methyl acrylate, followed by a diastereoselective double bond hydrogenation and hydrolysis of the ester function.     

Regioselective synthesis of polysubstituted benzenes from Baylis-Hillman adducts via [4+2] annulation protocol

A new and regioselective [4+2] benzannulation protocol toward polysubstituted benzenes was developed. A nitroalkane derivative, which was prepared from Baylis-Hillman adduct, served as the four-carbon unit and a Michael acceptor as a two-carbon unit. Vinyltriphenylphosphonium salt could also be used as a Michael acceptor efficiently.     

An easy access to functionalized allyl dithiocarbamates from Baylis-Hillman adducts in water

A facile and direct highly stereoselective synthesis of [E]- and [Z]-allyl dithiocarbamates has been accomplished from acetates of Baylis-Hillman (BH) adducts in catalyst-free one-pot three-component coupling reactions of carbon disulfide and amine in water under a mild and green procedure with high yields. The reaction pathway involves the nucleophilic displacement (SN2′) of BH acetates by dithiocarbamate anions. The utility of these allyl dithiocarbamates has also been demonstrated in heterocyclic chemistry. © 2009 Elsevier Science. All rights reserved     

Synthesis of 3,5,6-trisubstituted α-pyrones from Baylis-Hillman adducts

3,5,6-Trisubstituted α-pyrones were synthesized starting from the Baylis-Hillman adducts. The synthesis was carried out via the sequential introduction of ketone at the primary position of Baylis-Hillman adduct, lactonization, and the following oxidation with PCC.     

Baylis-Hillman adducts between pyridine carboxaldehyde derivatives and cyclic enones

Baylis-Hillman (BH) adducts were synthesized using pyridinecarboxaldehyde derivatives and cyclic enones. The Baylis-Hillman reaction was examined by employing various organic tertiary bases and solvents. It was observed that DBU in MeOH as well as imidazole and N-methylimidazole in aqueous MeOH are very effective. These pyridinecarboxaldehydes were reactive and efficient towards the Baylis-Hillman reaction and the resulting adducts are highly stable. The crystal structure for one of the BH adducts was determined.