Asymmetric conjugate addition of carbonyl compounds to nitroalkenes catalyzed by chiral bifunctional thioureas

Readily available chiral thioureas derived from cyclohexane-1,2-diamine were prepared and found to be highly effective organocatalysts for the conjugate addition of aldehydes and ketones to nitroalkenes. Excellent enantioselectivities and yields were obtained for a variety of aryl and heteroaryl nitroalkenes. The base additives are essential for good yields and excellent enantioselectivities in this transformation. Based on new experimental evidence, a modified catalytic mechanism was proposed to rationalize the important role of the base additives.     

Facile synthesis of 1H-pyrazolo[1,2-a]pyridazine-5,8-dione derivatives by a one-pot, three-component reactions

Protonation of the highly reactive 1:1 intermediate produced in the reaction between alkyl or aryl isocyanides and electron-deficient acetylenic esters with 3,6-dihydroxypyridazine, leads to a vinylisonitrilium cation, which undergoes an addition reaction with the conjugate base of the 3,6-dihydroxypyridazine to produce dialkyl 3-(alkyl or arylamino)-5,8-dioxo-5,8-dihydro-1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates in good yields at room temperature.     

Preparation of a novel diphosphine-palladium macrocyclic complex possessing a molecular recognition site. Oxidative addition studies

A disphosphine-palladium(0) complex capable of recognising barbiturates has been prepared. Oxidative addition studies with a barbitiurate:aryl iodide conjugate provided new Pd(ii) complexes where the positioning of the Pd-bound aryl group is controlled by the molecular recognition event.     

1,6-Asymmetric induction during the conjugate addition of arylcopper reagents to a chiral sulfinyl-substituted pyrrolyl alpha,beta-unsaturated amide.

The asymmetric conjugate addition of arylcopper reagents derived from aryl Grignard reagents and copper(I) iodide to a chiral 1-[2-(p-tolylsulfinyl)]pyrrolyl cinnamide proceeded smoothly to give (3R)-adducts with high diastereoselectivities (> or =92% de) in high yields. Conjugate additions either of the cinnamide with the alkyl Grignard reagent-copper(l) iodide combination or of the crotonamide derivative with aryl Grignard reagent-copper(l) iodide gave moderate to good diastereoselectivities. With these sulfinyl pyrrolyl alpha,beta-unsaturated amides, the chiral auxiliary was efficiently recovered without any loss of optical purity after asymmetric conjugate addition.     

Palladium-catalyzed desulfitative conjugate addition of aryl sulfinic acids and direct ESI-MS for mechanistic studies

A new and efficient method for palladium(II) catalytic desulfitative conjugate addition of arylsulfinic acids with α,β-unsaturated carbonyl compound has been developed. The key reacting intermediates including aryl Pd(II) sulfinic intermediate, aryl Pd(II), and C═O-Pd complexes were captured by ESI-MS/MS, which provide new experimental evidence for the understanding of addition mechanism.     

Heck-type coupling vs. conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyl compounds: a systematic investigation

The competition between Heck-type coupling and conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyls has been systematically investigated in a toluene-H(2)O biphasic system. Aside from the intrinsic nature of rhodium and the enolization of carbonyls, the phosphine supporting ligand on rhodium, the ratio of aryl boronic acid to alpha,beta-unsaturated carbonyl and the pH value of the aqueous phase were found to affect the competition significantly. Highly selective rhodium-based catalyst systems have therefore been developed for both Heck-type coupling and conjugate addition by synergistically tuning the supporting ligand, the boronic acid to olefin ratio and other reaction conditions. Conjugate addition with selectivity >99% and Heck-type coupling with selectivity of up to 100%, 98% and 84% for acrylates, acrylamides and methyl vinyl ketone, respectively, could be achieved in the rhodium-catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyls using the corresponding optimized rhodium-based catalyst systems.     

The palladium-catalyzed conjugate addition type reaction of aryl iodides with α,β-unsaturated aldehydes

α,β-Enals have been shown to react with aryl iodides in the presence of a palladium catalyst with selective formation of conjugate addition type products.     

Enantioselective rhodium-catalysed addition of boronic acids using C2-symmetric aryl diphosphite ligands

The enantioselective rhodium-catalysed conjugate addition of aryl boronic acids to dehydroalanine derivatives has been successfully carried out in the presence of C₂-symmetric aryl diphosphite ligand (R,R,R-4) to prepare unnatural amino acid esters. The products have been obtained in up to 72% ee and with good isolated yield.     

Reaction of the System Arene(Hetarene)thiol-Diselenide with Phenylacetylene

Liquid-phase thermal reactions of phenylacetylene with the system arene(hetarene)thioldiselenide at 110-180°C proceed through conjugate addition to the phenylacetylene triple bond of one alkylselanyl and one arene(hetarenesulfanyl groups to form 2-alkylselanyl-2-[aryl(hetaryl)sulfanyl]-1-phenylethenes and 1-alkylselanyl-2-[aryl(hetaryl)sulfanyl]-1-phenylethenes. Therewith, direct addition of thiols to phenylacetylene slows down.     

N-sulfinyl metalloenamine conjugate additions: asymmetric synthesis of piperidines

[reaction: see text] The first examples of conjugate additions of N-tert-butanesulfinyl metalloenamines are reported. Highly stereoselective conjugate additions (97:3 to 99:1 dr) were observed between metalloenamines derived from N-sulfinyl ketimines and alpha,beta-unsaturated ketones bearing either alkyl or aryl substituents. The conjugate addition products could rapidly be converted with high diastereoselectivity to 2,4,6-trisubstituted piperidines, which are difficult to access by other methods.     

Regio- and diastereoselective conjugate addition of Grignard reagents to aryl substituted α,β-unsaturated carbonyl compounds derived from Oppolzer's sultam

Asymmetric conjugate addition of Grignard reagents to aryl substituted α,β-unsaturated carbonyl compounds (1) has been achieved with great regioselectivity (>20:1) and good to excellent diastereoselectivity (de up to 98%). The nucleophilicity and stereospecific blockade of the Grignard reagents play a key role in controlling the regioselectivities and diastereoselectivities of the conjugate addition reaction.     

Traceless Rhodium‐Catalyzed Hydroacylation Using Alkyl Aldehydes: The Enantioselective Synthesis of β‐Aryl Ketones

A one‐pot three‐step sequence involving Rh‐catalyzed alkene hydroacylation, sulfide elimination and Rh‐catalyzed aryl boronic acid conjugate addition gave products of traceless chelation‐controlled hydroacylation employing alkyl aldehydes. The stereodefined β‐aryl ketones were obtained in good yields with excellent control of enantioselectivity. Good variation of all three reaction components is possible.     

Enantioselective 1,4-conjugate addition of diethylzinc to (E)-alkenyl aryl ketones catalysed by Cu/DiPPAM complex

We report here the use of the DiPPAM-L1 ligand for copper-catalysed asymmetric conjugate addition (ACA) of diethylzinc to various (E)-alkenyl aryl ketones where the aryl ring is either a phenyl group substituted by nitro, chloro or methoxy groups or not substituted, or a naphthyl group. When the conjugate addition was performed in the greener AcOEt solvent with 1 or 2 mol % of Cu(OTf)₂/DiPPAM complex, moderate to good yields (45–83%) and high enantioselectivities (up to 98%) were reached.     

Direct Palladium‐Catalyzed β‐Arylation of Lactams

A direct and catalytic method is reported here for β‐arylation of N‐protected lactams with simple aryl iodides. The transformation is enabled by merging soft enolization of lactams, palladium‐catalyzed desaturation, Ar?X bond activation, and aryl conjugate addition. The reaction is operated under mild reaction conditions, is scalable, and is chemoselective. Application of this method to concise syntheses of pharmaceutically relevant compounds is demonstrated.     

A new catalytic conjugate addition/aldol strategy that avoids preformed metalated nucleophiles

A new conjugate addition/aldol strategy has been developed. Unlike conventional procedures that require metalation of the nucleophilic species, the procedure allows the direct coupling of aryl iodides, aldehydes, and acrylates in a nickel-catalyzed, organozinc-promoted process.     

Chitosan-supported imine palladacycle complex and its catalytic performance for heck reaction

Summary A chitosan-supported imine palladacycle complex has been synthesized by salicyladehyde via grafting on chitosan to form chitosan-Schiff base, followed by reacting with Li₂PdCl₄ in methanol. The catalyst has high activity and stereoselectivity for arylation of conjugate alkenes with aryl halides. This chitosan-supported imine palladium catalyst can be recovered and reused.     

Organocatalytic asymmetric allylic carbon-carbon bond formation

Organocatalytic allylic C-C bond-forming addition of activated alkylidenes to alkyl and aryl nitroalkenes has been achieved with high diastereo- and enantioselectivity. Chiral tertiary amine catalysts are used to give allyl intermediates which exhibit gamma-selectivity in the C-C bond forming step. The reactions proceed with up to >99:1 syn:anti ratio for both the alkyl- and aryl nitroalkenes with up 96% and 98% ee, respectively. The products of this conjugate addition are transformed into a range of intermediates, such as optically active conjugated dienes and 1-substituted tetralones, which are difficult to access via alternative methods.     

Rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to nitroalkenes using olefin-sulfoxide ligands

An efficient rhodium/olefin-sulfoxide catalyzed asymmetric conjugate addition of organoboronic acids to a variety of nitroalkenes has been developed, where 2-methoxy-1-naphthyl sulfinyl functionalized olefin ligands have shown to be highly effective and are applicable to a broad scope of aryl, alkyl, and heteroaryl nitroalkenes.     

Organocatalyzed Asymmetric Conjugate Addition of Heteroaryl and Aryl Trifluoroborates: a Synthetic Strategy for Discoipyrrole D

Bis‐heteroaryl or bis‐aryl stereocenters were formed by an organocatalytic enantioselective conjugate addition using the respective trifluoroborate salts as nucleophiles. Control studies suggested that fluoride dissociation is necessary in the anhydrous conditions. This strategy is applicable to the synthesis of discoipyrrole D, an inhibitor of BR5 fibroblast migration.     

The synthesis of functionalized pyranophenalenones

Abstract  

Protonation of the highly reactive 1:1 intermediate produced in the reaction between alkyl or aryl isocyanides and electron-deficient acetylenic esters with 3-hydroxy-1H-phenalene-1-one leads to a vinylisonitrilium cation, which undergoes an addition reaction with the conjugate base of the 3-hydroxy-1H-phenalene-1-one to produce biologically interesting dialkyl 10-(alkyl or arylamino)-7-oxo-7H,8H-naphtho[1,8-gh]chromene-8,9-dicarboxylates in moderate to fairly good yields at room temperature.