Aryloxide‐Facilitated Catalyst Turnover in Enantioselective α,β‐Unsaturated Acyl Ammonium Catalysis

A new general concept for α,β‐unsaturated acyl ammonium catalysis is reported that uses p‐nitrophenoxide release from an α,β‐unsaturated p‐nitrophenyl ester substrate to facilitate catalyst turnover. This method was used for the enantioselective isothiourea‐catalyzed Michael addition of nitroalkanes to α,β‐unsaturated p‐nitrophenyl esters in generally good yield and with excellent enantioselectivity (27 examples, up to 79 % yield, 99:1 er). Mechanistic studies identified rapid and reversible catalyst acylation by the α,β‐unsaturated p‐nitrophenyl ester, and a recently reported variable‐time normalization kinetic analysis method was used to delineate the complex reaction kinetics.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

Catalytic Asymmetric Epoxidation of α,β‐Unsaturated Esters with Chiral Yttrium–Biaryldiol Complexes

The full details of the asymmetric epoxidation of α,β‐unsaturated esters catalyzed by yttrium complexes with biaryldiol ligands are described. An yttrium–biphenyldiol catalyst, generated from Y(OiPr)₃–biphenyldiol ligand–triphenylarsine oxide (1:1:1), is suitable for the epoxidation of various α,β‐unsaturated esters. With this catalyst, β‐aryl α,β‐unsaturated esters gave high enantioselectivities and good yields (≤99 % ee). The reactivity of this catalyst is good, and the catalyst loading could be decreased to as little as 0.5–2 mol % (the turnover number was up to 116), while high enantiomeric excesses were maintained. For β‐alkyl α,β‐unsaturated esters, an yttrium–binol catalyst, generated from Y(OiPr)₃–binol ligand–triphenylphosphine oxide (1:1:2), gave the best enantioselectivities (≤97 % ee). The utility of the epoxidation reaction was demonstrated in an efficient synthesis of (?)‐ragaglitazar, a potential antidiabetes agent.     

N‐Heterocyclic Carbene Catalyzed Cyclocondensation of α,β‐Unsaturated Carboxylic Acids: Enantioselective Synthesis of Pyrrolidinone and Dihydropyridinone Derivatives

The catalytic cyclocondensation of in situ activated α,β‐unsaturated carboxylic acids was developed. N‐heterocyclic carbenes efficiently catalyzed the generation of α,β‐unsaturated acyl azolium intermediates from α,β‐unsaturated carboxylic acids via in situ generated mixed anhydrides for the enantioselective [3+2] and [3+3] cyclocondensation with α‐amino ketones and alkyl(aryl)imines, respectively. The corresponding pyrrolidinones and dihydropyridinones were isolated in good yields with high to excellent enantioselectivities.     

Asymmetric Conjugate Addition of Malonate Esters to α,β‐Unsaturated N‐Sulfonyl Imines: An Expeditious Route to Chiral δ‐Aminoesters and Piperidones

The asymmetric conjugate addition of malonate esters to α,β‐unsaturated N‐sulfonyl imines is catalyzed by PyBOX/La(OTf)₃ complexes in the presence of 4 Å MS. The reaction gives the corresponding E enamines bearing a stereogenic center at the allylic position with good yields and enantiomeric ratios up to 97:3. This reaction provides a synthetic entry to chiral δ‐aminoesters and piperidones.     

A Mild Isomerization Reaction for β,γ‐Unsaturated Ketone to α,β‐Unsaturated Ketone

A series of β,γ‐unsaturated ketones were isomerized to their corresponding α,β‐unsaturated ketones by the introduction of DABCO in iPrOH at room temperature. The endo‐cyclic double bond (β,γ‐position) on ketone was rearranged to exo‐cyclic double bond (α,β‐position) under the reaction conditions.     

Palladium‐catalyzed decarboxylative coupling of α,β‐unsaturated carboxylic acids with aryl tosylates

We report a general method for selective cross‐coupling of α,β‐unsaturated carboxylic acids with aryl tosylates enabled by versatile Pd(II) complexes. This method features the general cross‐coupling of ubiquitous α,β‐unsaturated carboxylic acids by decarboxylation. The transformation is characterized by its operational simplicity, the use of inexpensive, air‐stable Pd(II) catalysts, scalability and wide substrate scope. The reaction proceeds with high trans selectivity to furnish valuable (E)‐1,2‐diarylethenes.     

Direct Conjugate Addition of Alkynes with α,β‐Unsaturated Carbonyl Compounds Catalyzed by NCN‐Pincer Ru Complexes

NCN‐pincer Ru‐complexes containing bis(oxazolinyl)phenyl ligands serve as suitable catalysts in the direct conjugate additions of α,β‐unsaturated carbonyl compounds, including ketones, esters, and amides, as well as vinylphosphonates, giving various β‐alkynyl carbonyl and phosphonate compounds. A bis(oxazolinyl)phenyl (phebox)–Ru complex also catalyzes the asymmetric conjugate addition of an alkyne with a β‐substituted, α,β‐unsaturated ketone to produce a chiral β‐alkynyl ketone.     

A Novel Method for the Synthesis of α,β‐Unsaturated Amides Mediated by Samarium Diiodide

Promoted by Samarium diiodide (SmI₂), α,β‐unsaturated amides were formed from nitrogen anions (formed in situ by the reduction of nitro compounds) and α,β‐unsaturated esters. This reaction contrasts with the conjugate addition between amines and α,β‐unsaturated esters promoted by samarium triiodide (SmI₃) and provides an alternative attractive way to obtain α,β‐unsaturated amides using SmI₂.     

Synthesis of β‐Haloketones by β‐Addition Reactions of α,β‐Unsaturated Ketones with BX3 (X = Br,Cl) as Halide Source

A series of β‐bromoketones and β‐chloroketones were synthesized by the addition reactions of α,β‐unsaturated ketones under BX₃ (X = Br, Cl) and ethylene glycol reaction system. The α,β‐unsaturated ester also was successfully converted to its corresponding β‐bromoester under the reaction condition.     

Chemoselective α,β‐Dehydrogenation of Saturated Amides

We report a method for the selective α,β‐dehydrogenation of amides in the presence of other carbonyl moieties under mild conditions. Our strategy relies on electrophilic activation coupled to in situ selective selenium‐mediated dehydrogenation. The α,β‐unsaturated products were obtained in moderate to excellent yields, and their synthetic versatility was demonstrated by a range of transformations. Mechanistic experiments suggest formation of an electrophilic Se^IV species.     

Facile Preparation of Homoallyl β′，γ′—Unsaturated Amines via 1,2—Addition of α，β—Unsaturated Imines with Allylsamarium Bromide

A series of homoallyl β′，γ′-unsaturated amines were synthe sized via 1,2-addition of α，β-unsaturated imines with allylsamarium bromide in excellent yields under mild and neutral conditions.     

Reactions of 3‐methylamino‐5‐phenylthiophene with α,β‐unsaturated esters and α,β‐unsaturated nitriles

Treatment of 3‐methylamino‐5‐phenylthiophene with α,β‐unsaturated esters, i.e., methyl acrylate, (E)‐methyl crotonate, diethyl fumarate, diethyl maleate and ethyl propiolate, in tetrahydrofuran for several days at reflux gave 1‐methyl‐3,4‐dihydrothieno[2,3‐e]pyridin‐2‐ones 4 and/or 1‐methylthieno[2,3‐e]pyridin‐2‐ones 5 , depending on the structure of the esters. On the other hand, the same reactions with α,β‐unsaturated nitriles such as acrylonitrile and tetracyanoethene, gave the corresponding thiophenes 7 and 10 bearing 2‐cyanoethyl and 1,2,2‐tricyanoethenyl groups at C‐2, respectively. The reaction with (Z)‐1,2‐dicyanoethene under the same conditions produced the corresponding thiophene 9 bearing the 1,2‐dicyanoethenyl group and 1,2‐dicyano‐5‐methylaminobiphenyl.     

Gold‐Catalyzed Heterogeneous Aerobic Dehydrogenative Amination of α,β‐Unsaturated Aldehydes to Enaminals

Although enaminals (β‐enaminals) are very important compounds and have been utilized as useful synthons for various important compounds, they have been synthesized through non‐green and/or limited procedures until now. Herein, we have successfully developed a green synthetic procedure using a heterogeneous catalyst. In the presence of gold nanoparticles supported on manganese‐oxide‐based octahedral molecular sieves OMS‐2 (Au/OMS‐2), dehydrogenative amination of α,β‐unsaturated aldehydes with amines proceeded efficiently, with the corresponding enaminals isolated in moderate to high yields (50–97 %). The catalysis was truly heterogeneous, and Au/OMS‐2 could be reused. Furthermore, the formal Wacker‐type oxidation of α,β‐unsaturated aldehydes to enaminones has been realized.     

Catalytic Asymmetric Formation of δ‐Lactones from Unsaturated Acyl Halides

Previously unexplored enantiopure zwitterionic ammonium dienolates have been utilized in this work as reactive intermediates that act as diene components in hetero‐Diels–Alder reactions (HDAs) with aldehydes to produce optically active δ‐lactones, subunits of numerous bioactive products. The dienolates were generated in situ from E/Z mixtures of α,β‐unsaturated acid chlorides by use of a nucleophilic quinidine derivative and Sn(OTf)₂ as co‐catalyst. The latter component was not directly involved in the cycloaddition step with aldehydes and simply facilitated the formation of the reactive dienolate species. The scope of the cycloaddition was considerably improved by use of a complex formed from Er(OTf)₃ and a simple commercially available norephedrine‐derived ligand that tolerated a broad range of aromatic and heteroaromatic aldehydes for a cooperative bifunctional Lewis‐acid‐/Lewis‐base‐catalyzed reaction, providing α,β‐unsaturated δ‐lactones with excellent enantioselectivities. Mechanistic studies confirmed the formation of the dienolate intermediates for both catalytic systems. The active Er^III complex is most likely a monomeric species. Interestingly, all lanthanides can catalyze the title reaction, but the efficiency in terms of yield and enantioselectivity depends directly on the radius of the Ln^III ion. Similarly, use of the pseudolanthanides Sc^III and Y^III also resulted in product formation, whereas the larger La^III and other transition metal salts, as well as main group metal salts, proved to be inefficient. In addition, various synthetic transformations of 6‐CCl₃‐ or 4‐silyl‐substituted α,β‐unsaturated δ‐lactones, giving access to a number of valuable δ‐lactone building blocks, were investigated.     

Diarylprolinol‐Mediated Asymmetric Direct Cross‐Aldol Reaction of α,β‐Unsaturated Aldehyde as an Electrophilic Aldehyde

The diarylprolinol‐mediated asymmetric direct cross‐aldol reaction of α,β‐unsaturated aldehyde as an electrophilic aldehyde was developed. The reaction becomes accelerated by an acid when a carbonyl group is introduced at the γ‐position of the α,β‐unsaturated aldehyde. Synthetically useful γ,δ‐unsaturated β‐hydroxy aldehydes were obtained with high anti‐selectivity and excellent enantioselectivity.     

PPh3⋅HBr‐DMSO Mediated Expedient Synthesis of γ‐Substituted β,γ‐Unsaturated α‐Ketomethylthioesters and α‐Bromo Enals: Application to the Synthesis of 2‐Methylsulfanyl‐3(2 H)‐furanones

An efficient chemoselective general procedure for the synthesis of γ‐substituted β,γ‐unsaturated α‐ketomethylthioesters from α,β‐unsaturated ketones has been achieved through an unprecedented PPh₃?HBr‐DMSO mediated oxidative bromination and Kornblum oxidation sequence. The newly developed reagent system serves admirably for the synthesis of α‐bromoenals from enals. Furthermore, AuCl₃‐catalyzed efficient access to 3(2H)‐furanones from the above intermediates under extremely mild conditions are described.     

Metal‐Free and Efficient Epoxidation of α,β‐Unsaturated Ketones with 1,1,2,2‐Tetrahydroperoxy‐1,2‐Diphenylethane as a Powerful Solid Oxidant

1,1,2,2‐Tetrahydroperoxy‐1,2‐diphenylethane was used for the efficient and metal‐free epoxidation of various α,β‐unsaturated ketones, carried out under mild alkaline conditions at room temperature.     

A Facile Synthesis of Bridged‐tricyclic Skeletons via Intramolecular Diels‐Alder Reaction of Cyclic 1,3‐Dienes Containing an α,β‐Unsaturated Ester

Intramolecular Diels‐Alder reaction (IMDA) precursors are easily available starting from addition of ester functionalized zinc‐copper reagents to cyclohexadienyl‐ and cycloheptadienylirontricarbonyl cation salts. The resulting cyclic 1,3‐dienes containing an α,β‐unsaturated ester functionality underwent smoothly IMDA reaction to afford bridged tricyclic compounds. Bridged heterotricyclic skeletons were also available via IMDA reaction of cyclic 1,3‐dienes bearing an imine or aldehyde functionality.     

A Versatile Methodology for the Synthesis of α,β‐Unsaturated 3‐Iminophosphines

Phorteen phine phosphines : Fourteen new α,β‐unsaturated β‐chloroimines were synthesized from inexpensive ketones by using the Vilsmeier–Haack reagent followed by Schiff‐base condensation. Each imine was subsequently converted to an α,β‐unsaturated 3‐iminophosphine through either late‐metal‐catalyzed phosphorus–carbon cross‐coupling or through an addition–elimination sequence (see scheme). This high‐yield protocol serves as a general means to produce α,β‐unsaturated 3‐iminophosphines.