Organocatalyzed regio- and enantioselective allylic trifluoromethylation of Morita-Baylis-Hillman adducts using Ruppert-Prakash reagent

The organocatalyzed regioselective allylic trifluoromethylation of Morita-Baylis-Hillman adducts using Ruppert-Prakash reagent was achieved in high to excellent yields via a successive S(N)2'/S(N)2' mode for the first time. The reaction was extended to the asymmetric allylic trifluoromethylation by the use of a bis-cinchona alkaloid catalyst with high enantioselectivities up to 94% ee.     

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.     

Asymmetric Morita-Baylis-Hillman reaction of arylaldehydes with 2-cyclohexen-1-one catalyzed by chiral bis(thio)urea and DABCO

Novel bis(thio)urea organocatalysts were synthesized from axially chiral (R)-(-)-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl-2,2'-diamine (H8-BINAM), and their catalytic abilities have been examined in the Morita-Baylis-Hillman reaction of 2-cyclohexen-1-one or 2-cyclopenten-1-one with a wide range of aromatic aldehydes in combination with DABCO. The best result was achieved in the reaction of 3-fluorobenzaldehyde with 2-cyclohexen-1-one to give the desired Morita-Baylis-Hillman product in 79% yield and 88% ee.     

Phosphine-catalyzed regiospecific allylic amination and dynamic kinetic resolution of Morita-Baylis-Hillman acetates

Exposure of Morita-Baylis-Hillman (MBH) acetates to tertiary phosphine catalysts in the presence of 4,5-dichlorophthalimide enables regiospecific allylic substitution through a tandem S(N)2'-S(N)2' mechanism. Through the use of the chiral phosphine catalyst (R)-Cl-MeO-BIPHEP, chiral racemic MBH acetate 4 is converted to the corresponding allylic amination product in 80% yield and 56% enantiomeric excess, thus establishing the feasibility of dynamic kinetic resolution. [reaction: see text]     

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.     

Room temperature asymmetric allylic trifluoromethylation of Morita-Baylis-Hillman carbonates

(DHQD)(2)PHAL-catalyzed asymmetric allylic trifluoromethylation of Morita-Baylis-Hillman adducts using a Rupert-Prakash reagent is reported. This transformation provided the S(N)2' trifluoromethylated products with good yields and excellent enantioselectivities at room temperature. It was also found that the reaction could be accelerated using acetonitrile as cosolvent.     

Traditional Morita-Baylis-Hillman reaction of aldehydes with methyl vinyl ketone co-catalyzed by triphenylphosphine and nitrophenol

In the Morita-Baylis-Hillman reaction of aldehydes with methyl vinyl ketone (MVK), we found that in the presence of a catalytic amount of phenol, the Lewis base triphenylphosphine can effectively promote the reaction to give the corresponding normal Morita-Baylis-Hillman adducts in good yields. The mechanism has been investigated by 31P NMR spectroscopy. The solvent and substituent effects were also examined.     

Organocatalytic asymmetric allylic alkylation of sulfonylimidates with Morita-Baylis-Hillman carbonates

The asymmetric allylic alkylation reaction of sulfonylimidates with various Morita-Baylis-Hillman (MBH) carbonates was accomplished by the catalysis of commercially available cinchona alkaloids catalyst (DHQD)2AQN.The corresponding allylic alkylation products were obtained in good yields with high stereoselectivities (up to 99% ee,89:11 dr).     

Asymmetric Morita-Baylis-Hillman reactions of 2-cyclohexen-1-one catalyzed by chiral biaryl-based bis(thiourea) organocatalysts

Newly-developed bis(thiourea) 1d was found to be an efficient organocatalyst for the Morita-Baylis-Hillman reaction. High enantioselectivities were obtained in the reaction of 2-cyclohexen-1-one with both aromatic aldehydes (up to 84% ee) and aliphatic aldehydes (up to 96% ee).     

1-Methylimidazole 3-N-oxide as a new promoter for the Morita-Baylis-Hillman reaction

The Morita-Baylis-Hillman reaction of aldehydes with α,β-unsaturated ketones can be affected by the Lewis bases. We have found that 1-methylimidazole 3-N-oxide promoted the Morita-Baylis-Hillman reaction of various activated aldehyde compounds in non-solvent system. This is a mild reaction condition and requires no special equipment to give the Morita-Baylis-Hillman adducts.     

Chiral phosphine-squaramides as enantioselective catalysts for the intramolecular Morita-Baylis-Hillman reaction

Novel squaramides containing tertiary phosphine were developed as chiral bifunctional organic catalysts to promote the asymmetric intramolecular Morita-Baylis-Hillman reaction of ω-formyl-enones. The adducts were obtained in high yields with good-to-excellent enantioselectivity (up to 93% ee).     

Diastereo- and enantioselective [3 + 2] cycloaddition reaction of Morita-Baylis-Hillman carbonates of isatins with N-phenylmaleimide catalyzed by Me-DuPhos

A Me-DuPhos-catalyzed efficient asymmetric [3 + 2] cycloaddition reaction between Morita-Baylis-Hillman carbonates of isatins and N-phenylmaleimide has been developed. This reaction constructs three chiral centers in one step to afford spirocyclopentaneoxindoles in good yields (up to 84%) with excellent diastereo- and enantioselectivies (up to 99% ee).     

Asymmetric Morita-Baylis-Hillman reactions catalyzed by chiral Brønsted acids

Chiral BINOL-derived Br?nsted acids catalyze the enantioselective asymmetric Morita-Baylis-Hillman (MBH) reaction of cyclohexenone with aldehydes. The asymmetric MBH reaction requires 2-20 mol % of the chiral Br?nsted acid 2e or 2f and triethylphosphine as the nucleophilic promoter. The reaction products are obtained in good yields (39-88%) and high enantioselectivities (67-96% ee). The Br?nsted-acid-catalyzed reaction is the first example of a highly enantioselective asymmetric MBH reaction of cyclohexenone with aldehydes.     

A highly E-stereoselective approach to beta-iodo Morita-Baylis-Hillman esters: synthesis of secokotomolide A

A geometric-selective synthesis of (E)-beta-iodo Morita-Baylis-Hillman esters has been developed through a three-component aldol-type reaction using BF3.Et2O and TMS-I. The synthetic utility of the (E)-beta-iodo Morita-Baylis-Hillman esters was demonstrated in the first reported short synthesis of secokotomolide A.     

Catalytic enone cycloallylation via concomitant activation of latent nucleophilic and electrophilic partners: merging organic and transition metal catalysis

Upon exposure of mono-enone mono-allylic carbonates to tributylphosphine and 1 mol % Pd(Ph3P)4, efficient conversion to the corresponding cycloallylated products is achieved. This transformation combines the nucleophilic features of the Morita-Baylis-Hillman reaction with the electrophilic features of the Trost-Tsuji reaction.     

Catalytic asymmetric synthesis of 3-hydroxyl-2-oxindoles via enantioselective Morita-Baylis-Hillman reaction of isatins

The enantioselective Morita-Baylis-Hillman reaction of acrylates to isatins was investigated for the first time, employing bifunctional phosphinothiourea organocatalysts based on chiral cyclohexane scaffold. The 3-hydroxyl-2-oxindole derivatives were obtained in excellent yields with moderate enantioselectivity (up to 69% ee) in the presence of 10 mol % catalyst 1b.     

A novel approach to Morita-Baylis-Hillman (MBH) lactones via the Lewis acid-promoted couplings of α,β-unsaturated lactone with aldehydes

The Morita-Baylis-Hillman (MBH)-type reaction of α,β unsaturated δ-lactone with various aldehydes has been achieved without the direct use of a Lewis base. The new MBH process can be conveniently carried out by the slow addition of the diethylaluminum iodide into the solution of lactone and aldehyde in dichloromethane at 0°C. Modest to good yields were obtained (50-65%) for eight examples.     

Synthesis of Indenes via Graphene Oxide Mediated Manipulation of Morita-Baylis-Hillman Alcohols

A new metal-free synthetic approach to functionalized indenes is documented. The use of commercially available graphene oxide (GO) allowed the direct access to indenyl cores (yield up to 80 %) via intramolecular Friedel-Crafts-type allylic alkylations with readily available Morita-Baylis-Hillman alcohols. Combined experimental and spectroscopic investigations contributed to shed light on the reaction mechanism dealing with a nanostructured carbon material-based C−C bond forming reaction.     

Highly efficient hydrazination of conjugated nitroalkenes via imidazole or DMAP mediated Morita-Baylis-Hillman reaction

Novel alpha-hydrazino-alpha,beta-unsaturated nitroalkenes, which exhibit dynamic phenomenon on the NMR time scale, were synthesized in excellent yields via imidazole or DMAP mediated Morita-Baylis-Hillman (MBH) type reaction of nitroalkenes with azodicarboxylates.     

Enantioselective Morita-Baylis-Hillman reaction promoted by L-threonine-derived phosphine-thiourea catalysts

A series of bifunctional phosphine-thiourea organic catalysts based on natural amino acid scaffolds were designed and prepared. L-threonine-derived bifunctional phosphine catalysts were found to be very efficient in promoting asymmetric Morita-Baylis-Hillman (MBH) reaction of acrylates with aromatic aldehydes, affording the desired MBH adducts with up to 90% ee. To gain mechanistic insights into the reaction, the effects of adding various additives on the MBH reaction were investigated. We propose that the hydrogen bonding interactions between the thiourea moiety of the catalyst and the enolate intermediate are crucial for the stereochemical outcome of the reaction. The method described in this report may provide a practical solution to the enantioselective MBH reaction of simple acrylates.