Novel synthons from mucochloric acid: the first use of alpha,beta-dichloro-gamma-butenolides and gamma-butyrolactams for direct vinylogous aldol addition

Novel 5-(1'-hydroxy)-gamma-butyrolactone and gamma-butyrolactam subunits were synthesized by direct vinylogous aldol addition of alpha,beta-dichloro gamma-butyrolactones and gamma-butyrolactams with aldehydes under basic conditions. Different bases and solvents were screened in the context of generating gamma-butyrolactones. Diastereoselectivity was observed and gamma-butenolides and gamma-butyrolactams showed opposite diastereoselectivity under the same reaction condition.     

An efficient, recoverable fluorous organocatalyst for direct reductive amination of aldehydes

A commercially available perfluorooctyl aniline and phenyl isothiocyanate were reacted under mild conditions to give 1-[4-(perfluorooctyl)phenyl]-3-phenylthiourea as an analogue of thiourea-based organocatalyst. This fluorous organocatalyst was successfully employed to direct reductive amination of aldehydes. It could be readily separated from reaction product by fluorous solid phase extraction for direct use.     

A simple method for preparing a diamino cellulose disk from a dialdehyde cellulose disk by reductive amination using 2-picoline-borane

Cellulose - A method for the preparation of dialdehyde cellulose disks (DACD) and subsequent diamino cellulose disks (DAmCD) was developed. DACD was prepared by oxidizing filter paper with sodium...     

Reinvestigation of mucohalic acids,versatile and useful building blocks for highly functionalized alpha,beta-unsaturated gamma-butyrolactones

[reaction: see text] Mucohalic acids (mucochloric acid (1, 3,4-dichloro-5-hydroxy-5H-furan-2-one) and mucobromic acid (2, 3,4-dibromo-5-hydroxy-5H-furan-2-one)) are inexpensive, commercially available starting materials with multiple functional groups. These compounds have been modified by way of reduction followed by Suzuki cross-coupling reactions involving arylboronic acids to afford highly functionalized alpha,beta-unsaturated gamma-butyrolactones in excellent yield. The synthetic utility of these building blocks was effectively demonstrated through preparation of the antiinflammatory drug Vioxx.     

A catalyst for efficient and highly enantioselective hydrogenation of aromatic, heteroaromatic, and alpha,beta-unsaturated ketones

PhanePhos-ruthenium-diamine complexes catalyze the asymmetric hydrogenation of a wide range of aromatic, heteroaromatic, and alpha, beta-unsaturated ketones with high activity and excellent enantioselectivity.     

Highly regioselective direct halogenation: a simple and efficient method for preparing 4-halomethyl-5-methyl-2-aryl-1,3-thiazoles

An unprecedented C4-methyl regioselective halogenation of 4,5-dimethyl-2-aryl-1,3-thiazoles (1) has been accomplished. The reaction of compound 1 with N-chlorosuccinimide and N-bromosuccinimide under mild conditions provides an efficient and operationally simple method for obtaining 4-chloromethyl-5-methyl-2-aryl-1,3-thiazoles (2) and 4-bromomethyl-5-methyl-2-aryl-1,3-thiazoles (3), respectively, in good yields without the formation of 4-methyl-5-halomethyl regioisomers.     

Functionalization of alpha,beta-unsaturated esters and ketones: a facile and highly stereoselective one-pot approach to N-protected alpha,beta-dehydroamino acid derivatives

A new, facile, and highly stereoselective protocol toward alpha,beta-dehydroamino acid derivatives has been developed. The one-pot synthesis was very convenient to perform by using the aminohalogenation reaction of alpha,beta-unsaturated esters and ketones followed by treatment with specific bases. Only two [2.2.2] bicyclic organic bases were found to be effective for this transformation. Good yields (58-68%) and excellent Z-selectivity were obtained for 12 examples. [reaction: see text]     

Sodium methoxide: a simple but highly efficient catalyst for the direct amidation of esters

A simple NaOMe catalyst provides superior accessibility to a wide variety of functionalized amides including peptides through direct amination of esters in an atom-economical and environmentally benign way.     

An efficient enantioselective method for asymmetric Michael addition of nitroalkanes to alpha,beta-unsaturated aldehydes

The addition of nitroalkanes to alpha,beta-unsaturated aldehydes under the catalysis of (S)-2-(diphenyl(trimethylsilyloxy)methyl)pyrrolidine and lithium acetate as additive afforded gamma-nitroaldehydes in good yield and up to 97% ee.     

First iron-catalyzed guanylation of amines: a simple and highly efficient protocol to guanidines

The first iron-catalyzed guanylation of amines is reported. Commercially available Fe(OAc)₂ acts as an excellent catalyst for the addition of amines to carbodiimides. The reaction is broadly applicable to a variety of primary, secondary, and heterocyclic amines, and tolerates a wide range of functionalities allowing the easy preparation of a large family of guanidines. The low price and low toxicity of the commercially available iron catalyst make this methodology highly attractive.     

Asymmetric Lewis acid-catalyzed Diels-Alder reactions of alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides

[reaction: see text] Conformational analysis, van der Waals attractions, and transition structure calculations are combined to design an asymmetric Lewis acid-catalyzed Diels-Alder reaction for simple acyclic alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides, giving up to 83 and 92% ee, respectively. The two-point-binding chiral recognition mechanism, Lewis acid-Lewis base coordination with boron and a van der Waals attraction with the naphthyl group, uses the inherent enone unit of simple alpha,beta-unsaturated carbonyl compounds, ending the need for auxiliary oxygen binding sites on the dienophile.     

A highly efficient phase transfer method for preparing alkylamine-stabilized Ru, Pt, and Au nanoparticles

A highly efficient phase-transfer method was developed to prepare alkylamine-stabilized nanoparticles of several noble metals. This method involved first mixing the metal hydrosols and an ethanol solution of dodecylamine and then extracting the dodecylamine-stabilized metal nanoparticles into toluene. The efficiency of this phase-transfer method was nearly 100%. Alkylamine-stabilized Ru, Pt, and Au nanoparticles 3.45, 4.33, and 7.89 nm in diameter, respectively, could be prepared this way. The self-assembly of dodecylamine-stabilized Pt and Au particles was also detected by transmission electron microscopy (TEM).     

A simple and efficient method of preparing α-bromo carboxylic acids

A new and convenient method for α-bromination of aliphatic carboxylic acids is reported. Heating carboxylic acids for 16 hours at 85 °C in trifluoroacetic acid with 1.5 equivalents of N-bromosuccinimide and a catalytic amount of concentrated H₂SO₄ leads to good yields of the respective α-bromocarboxylic acids.     

Phosphine-catalyzed domino reaction: an efficient method for the synthesis of highly functionalized spirooxazolines

A novel phosphine-catalyzed intermolecular [3 + 2] cycloaddition of ynones and N-substituted isatins was developed. In this reaction, substituted ynones, serving as a C(3) synthon, were successfully applied in intermolecular annulation reactions. A number of functionalized spirooxazolines were obtained in high yields and stereoselectivity.     

A simple and efficient approach to the synthesis of highly functionalized fused benzochromenes

Protonation of the reactive intermediates produced in the reaction between tert-butyl isocyanide and dimethyl acetylenedicarboxylate or dibenzoylacetylene, by 1-naphthol, 2-naphthol, 2,3-dihydroxynaphthalene, 2,7-dihydroxynaphthalene or 4-methyl-8-hydroxycoumarin leads to vinylnitrilium cations, which undergo carbon-centered Michael type addition with the conjugate base of the naphthols to produce highly functionalized benzochromenes.     

Organocatalytic and direct asymmetric vinylogous Michael addition of alpha,alpha-dicyanoolefins to alpha,beta-unsaturated aldehydes

The first highly regio-, chemo-, diastereo- and enantioselective direct vinylogous Michael addition of alpha,alpha-dicyanoolefins to alpha,beta-unsaturated aldehydes is described, employing readily available chiral alpha,alpha-diarylprolinol salts as iminium organocatalysts.     

Lewis base-catalyzed conjugate reduction and reductive aldol reaction of alpha,beta-unsaturated ketones using trichlorosilane

Lewis bases such as Ph3P=O and HMPA catalyze the 1,4-reduction of alpha,beta-unsaturated ketones with trichlorosilane, and because the 1,2-reduction of aldehydes scarcely proceeded under the conditions, one-pot reductive aldol reactions with aldehydes were successfully achieved; preliminary studies using a chiral Lewis base revealed a high potential for enantioselective catalysis.     

First example of direct reductive amination of aldehydes with primary and secondary amines catalyzed by water-soluble transition metal catalysts

An unprecedented efficient and highly selective direct reductive amination of aldehydes with primary and secondary amines in water using gaseous hydrogen and water-soluble catalysts is developed. The catalytic system formed in situ from Pd(PhCN)₂Cl₂ and 2,2′-biquinoline-4,4′-dicarboxylic acid dipotassium salt (BQC), allows full conversion of aldehydes and the formation of desired alkylated amines with excellent yields and selectivities. The catalytic system is stable and can be recycled and reused three times without loss of activity.     

A highly selective tandem cross-coupling of gem-dihaloolefins for a modular, efficient synthesis of highly functionalized indoles

A highly efficient method of indole synthesis using gem-dihalovinylaniline substrates and an organoboron reagent was developed via a Pd-catalyzed tandem intramolecular amination and an intermolecular Suzuki coupling. Aryl, alkenyl, and alkyl boron reagents are all successfully employed, making for a versatile modular approach. The reaction tolerates a variety of substitution patterns on the aniline leading to indoles with group at C2-C7. The orthogonal approach of the sequential copper- and palladium-mediated synthesis of 1,2-diarylindoles exploited the wide availability of diverse organoboron reagents.