Siloxyallenes revisited. A useful functional intermediate for the synthesis of (Z)-β-branched Morita-Baylis-Hillman type adducts and (Z)-chalcones

Siloxyallenes proved to be a useful functional intermediate in the preparation of (Z)-β-branched Morita-Baylis-Hillman type adducts by the reaction of aldehydes with silylacetylenes or siloxypropynes. Various (Z)-chalcones were stereoselectively synthesized from siloxypropynes via siloxyallenes.     

One-pot synthesis of aza-Morita-Baylis-Hillman adducts from α-oxo ketene-S,S-acetals, arylaldehydes and nitriles

Promoted by TiCl₄, a series of α-(1,3-dithiolan-2-ylidene)-β-amino carbonyl derivatives--the aza-Morita-Baylis-Hillman adducts, have been synthesized from α-oxo cyclic ketene-S,S-acetals, arylaldehydes, and nitriles in good to excellent yields. A mechanism involving sequential Morita-Baylis-Hillman and Ritter reactions for this novel one-pot, three-component reaction is described.     

3,5-Disubstituted 6H-pyrrolo[1,2-c][1,2,3]triazoles from Morita-Baylis-Hillman adducts of propargyl aldehydes

A simple method for synthesizing several 6H-pyrrolo[1,2-c][1,2,3]triazole derivatives having a methoxycarbonyl or an acetyl group at C-5 position and 7,8-dihydro-4H-[1,2,3]triazolo[1,5-a]indol-5(6H)-ones via an intramolecular 1,3-dipolar cycloaddition reaction of azido enynes, which were readily obtained from the Morita-Baylis-Hillman acetates of propargyl aldehydes with sodium azide, has been developed.     

Highly Z/E stereoselective approach to β-iodo aza Morita-Baylis-Hillman adducts

A multicomponent reaction between sulfonyl-protected imines, magnesium iodide, and acetylenic esters or ketones is described. The resulting β-iodo aza Morita-Baylis-Hillman adducts were obtained in good yields and excellent Z/E stereoselectivities. The reaction showed good tolerance for sulfonyl protecting groups, as well as for acetylenic ketones and esters. This work presents the first synthetic approach to β-iodo aza Morita-Baylis-Hillman adducts.     

Morita-Baylis-Hillman route to 4H-pyrrolo[1,2-a][1]benzazepine derivatives

A simple method for synthesizing substituted 4H-pyrrolo[1,2-a][1]benzazepines using acid-assisted cyclization of the Morita-Baylis-Hillman adducts of 2-(1H-pyrrol-1-yl)benzaldehydes with methyl acrylate or methyl vinyl ketone as a key step has been developed.     

First construction of 12H-thiochromeno[2,3-b]quinolines and 5H-benzo[7,8]thiocino-[2,3-b]quinolines via intramolecular Friedel-Crafts reaction of Morita-Baylis-Hillman adducts

An acid-promoted intramolecular Friedel-Crafts reaction of the Morita-Baylis-Hillman adducts 3 derived from 2-arylthioquinolin-3-carbaldehydes 2 was investigated. Interestingly, promoted by sulfuric acid, the substrates with electron-donating groups on the aromatic ring gave six-membered fused-ring 12H-thiochromeno[2,3-b]quinolines 4 with good yields, while those with electron-withdrawing groups afforded eight-membered fused-ring 5H-benzo[7,8]thiocino[2,3-b]quinolines 5 in moderate yields. Using triflic acid instead of sulfuric acid, only products 4 could be obtained under the similar condition.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

Enzyme promiscuity: first protein-catalyzed Morita-Baylis-Hillman reaction

The Morita-Baylis-Hillman reaction of cyclohexenone and p-nitro benzaldehyde is catalyzed by carrier proteins such as serum albumins or enzymes such as certain lipases, conversion of up to 35% and enantioselectivities of up to 19% being observed.     

An efficient and simple Morita-Baylis-Hillman reaction based on the N-methylpyrrolidine-Ba(OH)2 catalytic system

By using of precise catalytic amount of N-methylpyrrolidine (5 mol %) and Ba(OH)₂ (1.5 mol %) in H₂O/CH₃OH 5/1 or CH₃OH/CH₂Cl₂ 3/1 solvent mixtures at T=0 °C a Morita-Baylis-Hillman derivatives could be obtained in good to excellent yield from 2-cyclopenten-1-one, 2-cyclohexen-1-one and formaldehyde and diverse aryl aldehydes after suitable reaction time.     

Alkaloids-catalyzed regio- and enantioselective allylic nucleophilic substitution of tert-butyl carbonate of the Morita-Baylis-Hillman products

The alkaloids-catalyzed regio- and enantioselective allylic nucleophilic substitution reactions of tert-butyl carbonate of the Morita-Baylis-Hillman products with pronucleophiles are reported. A number of pronucleophiles, such as nitrogen, oxygen, and active carbon pronucleophiles have been used in this facile reaction. In general, the reaction proceeded efficiently to give the substitution product in good yields with high regioselectivity and medium enantioselectivity.     

Morita-Baylis-Hillman reaction of indole-2-carboxaldehyde: new vistas for indole-annulated systems

DABCO-mediated Morita-Baylis-Hillman reactions of several 1-substituted-indole-2-carboxaldehydes are disclosed. It was discovered that carboethoxy or tert-butoxycarbonyl groups installed at N-1 undergo cleavage under the reaction conditions to afford 2-substituted indoles. Utility of the N-substituted adducts for preparing a variety of annulated indoles has been exemplified.     

ortho-Acidic aromatic thiols as efficient catalysts of intramolecular Morita-Baylis-Hillman and Rauhut-Currier reactions

ortho-Mercaptobenzoic acid and ortho-mercaptophenols were discovered as efficient thiol catalysts of both the intramolecular Morita-Baylis-Hillman (MBH) and Rauhut-Currier (RC) reaction. High reaction rates were achieved under mildly basic, aqueous conditions. The unprecedented catalytic activity of these protic nucleophiles could originate from a Brønsted acid induced destabilization of intermediate thioethers and thus represent a unique mechanism of multifunctional Lewis base catalysis.     

Stereoselective synthesis of 3-spiro-α-methylene-γ-butyrolactone oxindoles from Morita-Baylis-Hillman adducts of isatin

A concise stereoselective synthesis of 3-spiro-α-methylene-γ-butyrolactone oxindoles from Morita-Baylis-Hillman adducts of isatin in excellent yield has been achieved following a three-step reaction sequences viz. (1) Isomerisation of the Morita-Baylis-Hillman adducts of isatin with trimethyl orthoformate and montmorillonite K10 clay catalyst, (2) a second Morita-Baylis-Hillman reaction with formaldehyde, and (3) an acid catalysed lactonization. The structure and stereochemistry of the products were assigned by X-ray crystallographic and NMR spectroscopic studies. Formation and mechanism of the minor product spirofuran oxindoles and a one-pot base promoted second Morita-Baylis-Hillman adduct formation-lactonization reaction have also been achieved.     

A highly active ionic liquid catalyst for Morita-Baylis-Hillman reaction

The Morita-Baylis-Hillman reaction is an efficient carbon-carbon bond forming reaction for the preparation of α-methylene-β-hydroxycarbonyl compounds. A new and highly active di-naphthalene imidazolium salt has been synthesized. We have found that 1,3-bis[2-(naphthalene-2-yloxy)propyl]imidazolium bromid promoted the Morita-Baylis-Hillman reaction of various aryl aldehyde compounds in the absence of solvents. Our studies show that the Morita-Baylis-Hillman reaction by the influence of ionic liquid to give a high yield and short reaction time.     

Enantioselective Morita-Baylis-Hillman (MBH) reaction promoted by a heterobimetallic complex with a Lewis base

A new double-activation catalysis is presented for the Morita-Baylis-Hillman (MBH) reaction of an α,β-unsaturated ketone and an aldehyde by the combined use of a heterobimetallic asymmetric complex and tributylphosphine ((n-Bu)₃P) to afford the α-methylene-β-hydroxy ketone with up to 99% ee.     

ZrCl4-catalyzed X-C/C-C bond formation for the geometric selective synthesis of (E)-β-iodo aza Morita-Baylis-Hillman (MBH) adducts

A geometric selective synthesis of (E)-β-iodo and β-alkyl vinyl ketones (MBH amino adducts) has been developed through a three-component Mannich-type reaction. The reaction was conveniently conducted by generating 3-iodo allenolate intermediates via the α,β-unsaturated addition of TMS-I to 3-butyn-2-one followed by a carbonyl addition onto N-aryl imines in the presence of ZrCl₄ catalyst. The resulting β-iodo allylic amines can be readily converted into β-alkyl Morita-Baylis-Hillman adducts by performing Suzuki and Kumada cross-couplings.     

Enzymatic kinetic resolution of Morita-Baylis-Hillman acetates

Racemic Morita-Baylis-Hillman adducts derived from the reaction of acrylonitrile with benzaldehyde, cinnamaldehyde and hydrocinnamaldehyde have been successfully resolved by means of enzymatic kinetic resolution. The (+)-alcohol products were isolated with 94–97% ee after lipase-mediated enantioselective hydrolysis of the corresponding acetates. Mosher’s double derivatisation protocol was applied to these isolated products and the absolute configuration of the alcohols was found to be (S) for all three substrates.     

Ozonolysis of Morita-Baylis-Hillman adducts originated from aromatic aldehydes: an expeditious diastereoselective approach for the preparation of α,β-dihydroxy-esters

We disclose herein ozonolysis of Morita-Baylis-Hillman adducts originated from aromatic aldehydes. This efficient reaction provides α-ketoesters with different substitution patterns on the aromatic ring. Diastereoselective reduction of the corresponding α-ketoester obtained in the oxidative cleavage step provides α,β-dihydroxy-esters with excellent degree of anti diastereoselection. The method is simple and easy to execute and is therefore a valuable alternative to prepare either α-ketoesters or α,β-dihydroxy-esters.     

The Morita-Baylis-Hillman reaction in aqueous-organic solvent system

We have found that water and organic solvents mixed at different proportions can give good to excellent yields and short reaction times for the Morita-Baylis-Hillman reaction. The present Letter details our findings in the Morita-Baylis-Hillman reaction between several aromatic aldehydes and methyl acrylate or acrylonitrile. The selection of the catalyst was also evaluated and DABCO affored the best results when compared to DBU, DMAP, HMT, Imidazole and Triethylamine.     

Mechanism and synthesis of pharmacologically active quinolones from Morita-Baylis-Hillman adducts

The synthesis of quinolones from Morita-Baylis-Hillman (MBH) adducts is reported. The quinolone skeleton is formed via a TFA-mediated cyclization of the MBH adduct, and a mechanism study using ESI(+)-MS(/MS) has indicated the role played by TFA in this key reaction step. The total syntheses of Norfloxacin and a benzyl quinolone carboxylic acid (BQCA) derivative are described. Norfloxacin is a fluoroquinolonic antibacterial drug whereas BQCA is M₁ receptor positive allosteric modulator and seem to provide access to new potential drugs for Alzheimer disease, pain, and sleep disorders. The syntheses of these two important quinolones exemplify the versatility and potentiality of the approach.