Electrochemical Oxidative C−H/N−H Coupling between γ‐Lactams and Anilines

A mild method for the direct C?H/N?H coupling between γ‐lactams and anilines through electrochemical oxidation has been developed. The protocol proceeded smoothly without metal catalysts at room temperature to afford γ‐substituted γ‐lactams in good yields. It has been revealed that the quasi‐divided cell which provided high current density on the anode was crucial for this reaction.     

Catalytic Asymmetric 1,2‐Addition of α‐Isothiocyanato Phosphonates: Synthesis of Chiral β‐Hydroxy‐ or β‐Amino‐Substituted α‐Amino Phosphonic Acid Derivatives

α‐Amino phosphonic acid derivatives are considered to be the most important structural analogues of α‐amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2‐addition reactions of α‐isothiocyanato phosphonate were developed. Through these processes, derivatives of β‐hydroxy‐α‐amino phosphonic acid and α,β‐diamino phosphonic acid, as well as highly functionalized phosphonate‐substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α‐phosphonic acid derivatives.     

Synthesis of β‐Boryl‐α‐Aminosilanes by Copper‐Catalyzed Aminoboration of Vinylsilanes

A copper‐catalyzed regioselective and stereospecific aminoboration of vinylsilanes with bis(pinacolato)diboron (pinB‐Bpin) and hydroxylamines has been developed. In the presence of a CuCl/MeO‐dppbz catalyst, the boryl group and amino group are incorporated at the β position and α position, respectively, and the corresponding β‐boryl‐α‐aminosilanes are obtained with good diastereoselectivity. The boryl group is a good latent functional group, and subsequent manipulations provide a variety of β‐functionalized α‐aminosilanes of great potential in medicinal chemistry. Additionally, preliminary application to asymmetric catalysis is also described.     

Radical‐initiated polymerization of β‐methyl‐α‐methylene‐γ‐butyrolactone

β‐Methyl‐α‐methylene‐γ‐butyrolactone (MMBL) was synthesized and then was polymerized in an N,N‐dimethylformamide (DMF) solution with 2,2‐azobisisobutyronitrile (AIBN) initiation. The homopolymer of MMBL was soluble in DMF and acetonitrile. MMBL was homopolymerized without competing depolymerization from 50 to 70 °C. The rate of polymerization (R_p) for MMBL followed the kinetic expression R_p = [AIBN]^0.54[MMBL]^1.04. The overall activation energy was calculated to be 86.9 kJ/mol, k_p/k_t^1/2 was equal to 0.050 (where k_p is the rate constant for propagation and k_t is the rate constant for termination), and the rate of initiation was 2.17 × 10^?8 mol L^?1 s^?1. The free energy of activation, the activation enthalpy, and the activation entropy were 106.0, 84.1, and 0.0658 kJ mol^?1, respectively, for homopolymerization. The initiation efficiency was approximately 1. Styrene and MMBL were copolymerized in DMF solutions at 60 °C with AIBN as the initiator. The reactivity ratios (r₁ = 0.22 and r₂ = 0.73) for this copolymerization were calculated with the Kelen–Tudos method. The general reactivity parameter Q and the polarity parameter e for MMBL were calculated to be 1.54 and 0.55, respectively. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1759–1777, 2003     

Oxidative β‐Csp3−H Functionalization of tBuOH: A Selective Radical/Radical Cross‐Coupling Access to β‐Hydroxy Thioethers

An oxidative β‐Csp³?H functionalization of tert‐butanol (tBuOH) for the construction of C?S bonds through an iodine‐catalyzed Csp³?H/S?H coupling was successfully achieved. Different kinds of mercaptans were shown to be good coupling partners, affording the desired products in good yields. This protocol not only offers a novel method for the synthesis of β‐hydroxy thioethers, but also provides an effective strategy for selective radical/radical cross‐coupling.     

Visible Light Promoted β‐C—H Alkylation of β‐Ketocarbonyls via a β‐Enaminyl Radical Intermediate

A 5πe carbonyl activation mode is reported on the basis of photo‐induced single‐electron‐transfer (SET) oxidation of a secondary enamine. The resultant β‐enaminyl radical intermediate was trapped by a wide range of Michael acceptors, producing β‐alkylation products of β‐ketocarbonyls in a highly efficient manner.     

Iridium(I)‐catalyzed C−H Borylation of α,β‐Unsaturated Esters with Bis(pinacolato)diboron

A new process has been developed for the iridium(I)‐catalyzed vinylic C?H borylation of α,β‐unsaturated esters with bis(pinacolato)diboron (B₂pin₂). These reactions proceeded in octane at temperatures in the range of 80–120 °C to afford the corresponding alkenylboronic compounds in high yields with excellent regio‐ and stereoselectivities. The presence of an aryl ester led to significant improvements in the yields of the acyclic alkenylboronates. Crossover experiments involving deuterated substrates as well as a mixture of stereoisomers confirmed that this reaction proceeds via a 1,4‐addition/β‐hydride elimination mechanism. Notably, this reaction was also used to develop a one‐pot borylation/Suzuki–Miyaura cross‐coupling procedure.     

Ligand‐Enabled Arylation of γ‐C−H Bonds

Pd^II‐catalyzed arylation of γ‐C(sp³)?H bonds of aliphatic acid‐derived amides was developed by using quinoline‐based ligands. Various γ‐aryl‐α‐amino acids were prepared from natural amino acids using this method. The influence of ligand structure on reactivity was also systematically investigated.     

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.     

Heterocycles from α‐Aminonitriles

Owing to their various modes of reactivity, α‐aminonitriles represent versatile building blocks for the construction of a wide range of nitrogen heterocycles. The present Concept article focuses on synthetic methodologies using their bifunctional nature which is the basis of their reactivity as α‐amino carbanions and as iminium ions. Reactions exclusively taking place on either the amine or on the nitrile moiety will not be considered.     

Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

Reductive C−C Coupling from α,β‐Unsaturated Nitriles by Intercepting Keteniminates

We present an atom‐economic strategy to catalytically generate and intercept nitrile anion equivalents using hydrogen transfer catalysis. Addition of α,β‐unsaturated nitriles to a pincer‐based Ru?H complex affords structurally characterized κ‐N‐coordinated keteniminates by selective 1,4‐hydride transfer. When generated in situ under catalytic hydrogenation conditions, electrophilic addition to the keteniminate was achieved using anhydrides to provide α‐cyanoacetates in high yields. This work represents a new application of hydrogen transfer catalysis using α,β‐unsaturated nitriles for reductive C?C coupling reactions.     

Synthesis of new optically active α,α′,β‐trisubstituted‐β‐lactones as monomers for stereoregular biopolyesters

Various optically active (4R)‐alkyloxycarbonyl‐3,3‐dialkyl‐2‐oxetanones as monomers were synthesized from L‐(S)‐malic acid in six steps to prepare a new family of stereopolyesters for biomedical applications. The synthesis began with an esterification followed of a dialkylation in the aim to introduce hydrophobic groups as methyl or reactive group as allyl. Then, a saponification has permitted to obtain the corresponding diacids that reacted with appropriate alcohols to furnish different monoesters. The last and most important step was activation of hydroxyl group of monoesters with the asymmetric carbon configuration inversion according to the Mitsunobu reaction. Thus, this reaction has provided lactones from monoesters with 100% enantiomeric excess which was confirmed by ¹H NMR and by the synthesis of corresponding isotactic and semicrystalline homopolyesters. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2586–2597     

Oxidative acylation of α,α‐diarylallylic alcohols: Synthesis of 1,2,4‐triarylbutane‐1,4‐diones

A metal‐free mediated oxidative acylation of α,α‐diarylallylic alcohols with simple aromatic aldehydes for the synthesis of 1,2,4‐triphenylbutane‐1,4‐diones is presented. In the presence of TBPB (tert‐butyl peroxybenzoate), desired products were obtained in good to excellent yields for 28 examples. This protocol features high regioselectivity, wide functional group tolerance and atom economy.     

A Model Study of Intramolecular Asymmetric Radical Cyclizations of α-Ester and α-Amide Radicals

Starting from malonate, a practical route was developed for the synthesis of α-phenylthio acid 3. Several chiral compounds including (-)-menthol, (-)-8-pbenylmenthol and a camphor based oxazolidinone 8 reacted with 3 to give α-phenylthio esters or amide. These sulfides cyclized efficiently when reacted with tributyltin hydride. Among the chiral auxiliaries used, 8-phenylmenthyl group displayed moderate asymmetric induction (64% ee for cis-product and 40% ee for trans-product). Based on this results, a transition state model was proposed to explain the observed stereoselectivity. In this model, due to π,π-orbital overlap of the phenyl ring and the carbonyl, the si-face of the most stable conformer of the radical was shielded. This controlled the carbon-carbon bond formation to occur from the re-face.     

Organocatalytic Enantioselective Synthesis of Tetrasubstituted α‐Amino Allenoates by Dearomative γ‐Addition of 2,3‐Disubstituted Indoles to β,γ‐Alkynyl‐α‐imino Esters

The first asymmetric synthesis of tetrasubstituted α‐amino allenoates by a chiral phosphoric acid catalyzed dearomative γ‐addition reaction of 2,3‐disubstituted indoles to β,γ‐alkynyl‐α‐imino esters is reported. This method provides access to a series of highly functionalized tetrasubstituted allenes featuring quaternary stereocenters in high yields, and with excellent regio‐, diastereo‐, and enantioselectivities under mild conditions without by‐product formation. Representative large‐scale reactions and diverse transformations of the products into various scaffolds with potential biological activities render are also disclosed. The mechanism of the reaction was elucidated by control reactions and DFT calculations.     

Merging Aerobic Oxidation and Enamine Catalysis in the Asymmetric α‐Amination of β‐Ketocarbonyls Using N‐Hydroxycarbamates as Nitrogen Sources

We describe herein an unprecedented asymmetric α‐amination of β‐ketocarbonyls under aerobic conditions. The process is enabled by a simple chiral primary amine through the coupling of a catalytic enamine ester intermediate and a nitrosocarbonyl (generated in situ) derived from N‐hydroxycarbamate. The reaction features high chemoselectivity and excellent enantioselectivity for a broad range of substrates.     

The Renaissance of α‐Methylene‐γ‐butyrolactones: New Synthetic Approaches

The amount of research activity concerning α‐methylene‐γ‐butyrolactones and α‐alkylidene‐γ‐butyrolactones has increased dramatically in recent years. This Review summarizes the structural types, biological activities, and biosynthesis of these compounds, concentrating on publications from the past 10 years. Traditional approaches to α‐methylene‐γ‐butyrolactones and α‐alkylidene‐γ‐butyrolactones are then reviewed together with novel approaches, including those from our own research group, reported more recently.