A General Catalytic Hydroamidation of 1,3‐Dienes: Atom‐Efficient Synthesis of N‐Allyl Heterocycles,Amides, and Sulfonamides

Transition‐metal‐catalyzed hydroamination reactions are sustainable and atom‐economical C N bond‐forming processes. Although remarkable progress has been made in the inter‐ and intramolecular amination of olefins and 1,3‐dienes, related intermolecular reactions of amides are still much less known. Control of the regioselectivity without analogous telomerization is the particular challenge in the catalytic hydroamidation of alkenes and 1,3‐dienes. Herein, we report a general protocol for the hydroamidation of electron‐deficient N‐heterocyclic amides and sulfonamides with 1,3‐dienes and vinyl pyridines in the presence of a catalyst derived from [{Pd(π‐cinnamyl)Cl}₂] and ligand L7 or L10 . The reactions proceeded in good to excellent yield with high regioselectivity. The practical utility of our method is demonstrated by the hydroamidation of functionalized biologically active substrates. The high regioselectivity for linear amide products makes the procedure useful for the synthesis of a variety of allylic amides.     

A General and Highly Selective Palladium‐Catalyzed Hydroamidation of 1,3‐Diynes

A chemo‐, regio‐, and stereoselective mono‐hydroamidation of (un)symmetrical 1,3‐diynes is described. Key for the success of this novel transformation is the utilization of an advanced palladium catalyst system with the specific ligand Neolephos. The synthetic value of this general approach to synthetically useful α‐alkynyl‐α, β‐unsaturated amides is showcased by diversification of several structurally complex molecules and marketed drugs. Control experiments and density‐functional theory (M06L‐SMD) computations also suggest the crucial role of the substrate in controlling the regioselectivity of unsymmetrical 1,3‐diynes.     

A General and Efficient CuBr2‐Catalyzed N‐Arylation of Secondary Acyclic Amides

A general and efficient Cu(II)‐catalyzed cross‐coupling method is reported for the preparation of acyclic tertiary amides. Generally moderate to excellent yields and functional group tolerance were obtained with secondary acyclic amides and aryl halides as substrates in toluene.     

Palladium‐Catalyzed Aminocarbonylation of Aryl Iodides with Amides and N‐alkyl Anilines

A novel and efficient palladium‐catalyzed aminocarbonylation of aryl iodides with amides and N‐alkyl anilines has been developed. The reaction tolerates a wide range of functional groups and is a reliable method for the rapid synthesis of a variety of valuable imides and tertiary benzanilides under an atmospheric pressure of CO.     

Coumarin Sulfonamides and Amides Derivatives: Design,Synthesis, and Antitumor Activity In Vitro

Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound 9c was the most potent against MDA-MB-231 cells, with IC₅₀ value of 9.33 μM, comparable to 5-fluorouracil. Further investigation revealed that compound 9c had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound 9c promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound 9c could be promising lead compound for further antitumor drug research.     

Selenium‐Containing Heterocycles from Isoselenocyanates: Synthesis of 1,3‐Selenazinane and 1,3‐Selenazinanone Derivatives

The reaction of the intermediate ketene N,Se‐hemiacetal 3 , prepared from cyanomethylene derivatives 1 by treatment with Et₃N and aryl isoselenocyanates 2 , with bis‐electrophiles 6, 7, 9 , and 11 in DMF affords tetrahydro‐1H‐1,3‐selenazine (=1,3‐selenazinane) derivatives 8, 10 , and 12 in good yield (Scheme 2 and Tables 1–3). Chemical and spectroscopic evidence for the structures of the new compounds are described. The structures of 8d and 12e are established by X‐ray crystallography (Figs. 1 and 2).     

Ruthenium‐Catalyzed Multicomponent Reactions: Access to α‐Silyl‐β‐Hydroxy Vinylsilanes,Stereodefined 1,3‐Dienes,and Cyclohexenes

The synthesis of densly functionized α‐silyl‐β‐hydroxyl vinylsilanes via ruthenium‐catalyzed multicomponent reaction (MCR) is reported herein. Exceptionally high regio‐ and diastereoselectivity was achieved by employing an unprecedented hydrosilylation of bifunctional silyl‐propargyl boronates. The simple protocol, mild reaction conditions, and unique tolerability of this method make it a valuable tool for the synthesis of highly elaborated building blocks. The one‐pot synthesis of stereodefined olefins, the generation of a valuable cyclohexene building block through a four‐component MCR, and further functionalization in an abundance of diastereoselective reactions is disclosed herein.     

An Efficient Amide‐Aldehyde‐Alkene Condensation: Synthesis for the N‐Allyl Amides

The allylamine skeleton represents a significant class of biologically active nitrogen compounds that are found in various natural products and drugs with well‐recognized pharmacological properties. In this personal account, we will briefly discuss the synthesis of allylamine skeletons. We will focus on showing a general protocol for Lewis acid‐catalyzed N‐allylation of electron‐poor N‐heterocyclic amides and sulfonamide via an amide‐aldehyde‐alkene condensation reaction. The substrate scope with respect to N‐heterocyclic amides, aldehydes, and alkenes will be discussed. This method is also capable of preparing the Naftifine motif from N‐methyl‐1‐naphthamide or methyl (naphthalene‐1‐ylmethyl)carbamate, with paraformaldehyde and styrene in a one‐pot manner.     

Palladium‐Catalyzed Asymmetric Aminohydroxylation of 1,3‐Dienes

A Pd^II‐catalyzed asymmetric aminohydroxylation of 1,3‐dienes with N‐tosyl‐2‐aminophenols was developed by making use of a chiral pyridinebis(oxazoline) ligand. The highly regioselective reaction provides direct and efficient access to chiral 3,4‐dihydro‐2H‐1,4‐benzoxazines in high yield and enantioselectivity (up to 96:4 e.r.). The reaction employs readily available N‐tosyl‐2‐aminophenols as a unique aminohydroxylation reagent and is complementary to known asymmetric aminohydroxylation methods.     

A highly selective synthesis of 1‐substituted (E)‐buta‐1,3‐dienes with 4,4,5,5‐tetramethyl‐2‐vinyl‐1,3,2‐dioxaborolane as building block

Highly selective synthesis of 1‐substituted (E)‐buta‐1,3‐dienes via palladium‐catalyzed Suzuki–Miyaura cross‐coupling of (E)‐alkenyl iodides with 4,4,5,5‐tetramethyl‐2‐vinyl‐1,3,2‐dioxaborolane ( 1 ) is reported. The vinylboronate pinacol ester ( 1 ) acts as a vinyl building block to show high chemoselectivity for the Suzuki–Miyaura pathway versus Heck coupling in the presence of biphasic conditions (Pd(PPh₃)₄, aqueous K₂CO₃, toluene and ethanol). Copyright © 2014 John Wiley & Sons, Ltd.     

Palladium‐Catalyzed N‐Alkylation of Amides and Amines with Alcohols Employing the Aerobic Relay Race Methodology

Possibly because homogeneous palladium catalysts are not typical borrowing hydrogen catalysts and ligands are thus ineffective in catalyst activation under conventional anaerobic conditions, they had not been used in the N‐alkylation reactions of amines/amides with alcohols in the past. By employing the aerobic relay race methodology with Pd‐catalyzed aerobic alcohol oxidation being a more effective protocol for alcohol activation, ligand‐free homogeneous palladiums are successfully used as active catalysts in the dehydrative N‐alkylation reactions, giving high yields and selectivities of the alkylated amides and amines. Mechanistic studies implied that the reaction most probably proceeds via the novel relay race mechanism we recently discovered and proposed.