Application of an Enyne Metathesis/Diels–Alder Cycloaddition Sequence: A New Versatile Approach to the Syntheses of C‐Aryl Glycosides and Spiro‐C‐Aryl Glycosides

An efficient approach for the synthesis of a variety of C‐aryl and spiro‐C‐aryl glycosides is described. This diversity‐oriented strategy employed here relies on a sequential enyne metathesis to generate the 1,3‐diene moiety and Diels–Alder reaction with different dienophiles followed by aromatisation. Whereas cross‐enyne metathesis with ethylene gas is used to install the 1,3‐diene moiety at the anomeric centre for the synthesis of C‐aryl glycosides, an intramolecular enyne metathesis on the sugar enyne is performed to generate the 1,3‐diene moiety for the synthesis of spiro‐C‐aryl glycosides. Efforts to extend this strategy to the synthesis of the core structure of natural C‐aryl glycoside gilvocarcin are also described. A combination of both C‐aryl and spiro‐C‐aryl glycosides in the same moiety to combine the features thereof has also been accomplished. A tandem enyne metathesis/Diels–Alder reaction/aromatisation has also been attempted to directly access the C‐aryl glycosides in one pot albeit in low yield.     

Palladium‐Catalyzed CH Activation of N‐Allyl Imines: Regioselective Allylic Alkylations to Deliver Substituted Aza‐1,3‐Dienes

A new mode of activation of an imine via a rare aza‐substituted π‐allyl complex is described. Palladium‐catalyzed C(sp³)? H activation of the N‐allyl imine and the subsequent nucleophilic attack by the α‐alkyl cyanoester produced the 1‐aza‐1,3‐diene as the sole regioisomer. In contrast, nucleophilic attack by the α‐aryl cyanoester exclusively delivered the 2‐aza‐1,3‐diene, which was employed in an inverse‐electron‐demand Diels–Alder reaction for heterobiaryl synthesis.     

Preparation of a Porous polymer by a catalyst‐free diels‐alder reaction and its structural modification by post‐reaction

A microporous polymer is prepared by a catalyst‐free Diels–Alder reaction. A cyclopentadiene with both a diene and a dienophile functionality and a dienophilic maleimide are used for the Diels–Alder reaction. 1,3,5‐Tris(bromomethyl)‐2,4,6‐trimethylbenzene is reacted with sodium cyclopentadienide to produce the multicyclopentadiene‐functionalized monomer. A crosslinked polymer ( CDAP ) is obtained by the reaction of the cyclopentadiene monomer with N,N′‐1,4‐phenylenedimaleimide. The thermal dissociation of the cyclopentadiene dimeric unit and the subsequent Diels–Alder reaction with the maleimide group are investigated by the model reaction. We are able to restructure the crosslinked polymer network by taking advantage of the thermal reversibility of the Diels–Alder linkage. After the post thermal treatment, the BET surface area of the polymer ( CDAP‐T ) is greatly increased from 317 to 1038 m² g^?1. CDAP‐T is functionalized with pyrene by bromination with N‐bromosuccinimide and the subsequent substitution reaction with aminopyrene. The adsorption property of the pyrene‐functionalized polymer for an aromatic dye is investigated using malachite green. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3646–3653     

Efficient Synthesis of 1,3‐Dithiol‐2‐one Derivatives via 4,5‐Bis(dibromomethyl)‐1,3‐dithiol‐2‐one

A series of 1,3‐dithiol‐2‐one derivatives via [4 + 2] Diels–Alder cycloaddition reaction of 4,5‐bis(dibromomethyl)‐1,3‐dithiol‐2‐one with vinyl‐substituted compounds have been synthesized. Structures of all the newly synthesized compounds are well supported by spectral data such as ¹H‐NMR, MS, and elemental analysis. The structures of IVf and IVg have been analyzed by X‐ray crystallography.     

An Unexpected Double Diels–Alder Reaction of (E)‐2‐Bromo‐4‐aryl‐1,3‐pentadiene Involving [1,5]‐Hydrogen Migration and HBr Elimination: Synthesis of Bicyclo[2.2.2]octene Derivatives

An unexpected double Diels–Alder (DDA) reaction of (E)‐2‐bromo‐4‐aryl‐1,3‐pentadiene was developed and resulted in a series of “butterfly‐like” bicyclo[2.2.2]octene derivatives in moderate to good yields without the need for a metal catalyst. The proposed mechanism involves a [1,5]‐sigmatropic hydrogen migration and HBr elimination. Through this decisive [1,5]‐hydrogen shift step, the electronic properties and steric hindrance of the conjugated diene substrate are completely altered and the DDA reaction of this potential diene synthon is successfully achieved.     

Hydrogen‐Bonding Catalysis of Tetraalkylammonium Salts in an Aza‐Diels–Alder Reaction

A piperidine‐derived tetraalkylammonium salt with a non‐coordinating counteranion worked as an effective hydrogen‐bonding catalyst in an aza‐Diels–Alder reaction of imines and a Danishefsky diene. The hydrogen‐bonding interaction between the ammonium salt and an imine was observed as part of a ¹H NMR titration study.     

Enantioselective Biomimetic Total Syntheses of Kuwanons I and J and Brosimones A and B

The first enantioselective total syntheses of prenylflavonoid Diels–Alder natural products (?)‐kuwanon I, (+)‐kuwanon J, (?)‐brosimone A, and (?)‐brosimone B have been accomplished from a common intermediate based on a concise synthetic strategy. Key elements of the synthesis include a biosynthesis‐inspired asymmetric Diels–Alder cycloaddition mediated by a chiral ligand/boron Lewis acid, as well as a process involving regioselective Schenck ene reaction, reduction, and dehydration to realize a biomimetic dehydrogenation for generation of the required diene precursor. Furthermore, a remarkable tandem inter‐/intramolecular asymmetric Diels–Alder cycloaddition process was applied for the synthesis of (?)‐brosimone A.     

Theoretical Investigations on the Mechanism of Hetero‐Diels–Alder Reactions of Brassard’s Diene and 1, 3‐Butadiene Catalyzed by a Tridentate Schiff Base Titanium(IV) Complex

The mechanism of the hetero‐Diels–Alder reactions of Brassard’s diene and 1,3‐butadiene catalyzed by a titanium(IV) complex of a tridentate Schiff base was investigated by DFT and ONIOM methods. The calculations indicate that the mechanism of the reaction is closely related to the nucleophilicity–electrophilicity between diene and carbonyl substrates. A stepwise pathway is adopted for Brassard’s diene, and the step corresponding to the formation of the C? C bond is predicted to be the rate‐determining step with a free‐energy barrier of 8.4 kcal mol^?1. For 1,3‐butadiene, the reaction takes place along a one‐step, two‐stage pathway with a free‐energy barrier of 14.9 kcal mol^?1. For Brassard’s diene as substrate, the OCH₃ and OSi(CH₃)₃ substituents may play a key role in the formation of the transition state and zwitterionic intermediate by participating in charge transfer from Brassard’s diene to formaldehyde. The combination of the phenyl groups at the amino alcohol moiety and the ortho‐tert‐butyl group of the salicylaldehyde moiety in the chiral tridentate Schiff base ligand plays an important role in the control of the stereoselectivity, which is in agreement with experimental observations.     

Copper‐Catalyzed Aminothiolation of 1,3‐Dienes via a Dihydrothiazine Intermediate

Heteroatom‐containing organic molecules are of particular interest to medicinal chemists and materials scientists. A strategy to reach these architectures via direct difunctionalization of abundant 1,3‐dienes is especially attractive. Herein, we describe the development of a regio‐ and diastereoselective 1,4‐aminothiolation of 1,3‐dienes with a sulfur diimide reagent, a copper catalyst, and alkyl Grignard reagents. This unique protocol provides remote nitrogen and sulfur functionalities with high levels of stereocontrol. The reaction proceeds via a tandem hetero‐Diels–Alder cycloaddition of N,N′‐bis(benzenesulfonyl)sulfur diimide with 1,3‐diene followed by copper‐catalyzed Grignard substitution. Mechanistic studies support a copper catalyzed formation of an unprecedented [10‐S‐4] sulfurane that reductively eliminates to afford a 3,6‐dihydrothiazine, which is selectively converted to 1,4‐aminothiols.     

Radical copolymerization of N‐phenylmaleimide and diene monomers in competition with diels–alder reaction

Radical copolymerization of N‐phenylmaleimide (PhMI) is carried out with various diene monomers including naturally occurring compounds and the copolymers are efficiently produced by the suppression of Diels–Alder reaction as the competitive side reaction. Diene monomers with an exomethylene moiety and a fixed s‐trans diene structure, such as 3‐methylenecyclopentene and 4‐isopropyl‐1‐methyl‐3‐methylenecyclohexene, exhibit high copolymerization reactivity to produce a high‐molecular‐weight copolymer in a high yield. The copolymerization of sterically hindered noncyclic diene monomers, such as 2,4‐dimethyl‐1,3‐pentadiene and 2,4‐hexadiene, also results in the formation of a high‐molecular‐weight copolymer in a moderate yield. The NMR spectroscopy reveals that the obtained copolymers consist of predominant 1,4‐repeating structures for the corresponding diene unit. The copolymers have excellent thermal stability, that is, an onset temperature of decomposition over 330 °C and a glass transition temperature over 130 °C. The copolymerization reactivity of these diene monomers is discussed based on the results of the DFT calculations. The efficient copolymer formation in competition with Diels–Alder addition is investigated under various conditions of the temperature, solvents, and initiators used for the copolymerization. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3616–3625.     

Crystallographic characterization of a stable 7‐phosphanorbornadiene‐7‐oxide: 2,3‐benzo‐1,4,5,6,7‐pentaphenyl‐7‐phosphabicyclo[2.2.1] hepta‐2,5‐diene‐7‐oxide

The stable 7‐phosphanorbornadiene derivative, 2,3‐benzo‐1,4,5,6,7‐pentaphenyl‐7‐phosphabicyclo[2.2.1]hepta‐2,5‐diene‐7‐oxide ( 1 ) was synthesized in 45% yield via the Diels‐Alder reaction of pentaphenylphosphole oxide and benzyne. The reaction occurs specifically to give a single isomer, which was characterized by use of X‐ray crystallography and ³¹P NMR spectroscopy. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:182–186, 2000     

Total Synthesis of (+)‐Neomarinone

The first total synthesis of (+)‐neomarinone has been achieved by following a concise and convergent route using methyl (R)‐lactate and (R)‐3‐methylcyclohexanone as chiral building blocks. Key steps of the synthesis are the stereocontrolled formation of the two quaternary stereocenters by diastereoselective 1,4‐conjugate addition and enolate alkylation reactions, and the construction of the furanonaphthoquinone skeleton by regioselective Diels–Alder reaction between a 1,3‐bis(trimethylsilyloxy)‐1,3‐diene and a bromoquinone. The synthesis proves the relative and absolute stereochemistry of natural neomarinone.     

Cationic palladium complex‐catalyzed carbonylation of 2,3‐dien‐1‐ols to 1,3‐diene‐2‐carboxylic acids and esters under mild conditions

A cationic palladium complex, [Pd(PPh₃)₂(MeCN)₂](BF₄)₂, catalyzed the carbonylation of 2,3‐dien‐1‐ols under mild conditions. The dienols bearing two or more alkyl substituents on the diene part afforded 1,3‐diene‐2‐carboxylic acids successfully in tetrahydrofuran (THF), while those possessing one or no alkyl substituent gave polymers of the products exclusively. The former afforded the corresponding methyl esters in good yields when the reactions were carried out in methanol, while the latter afforded mainly the Diels–Alder reaction products of the resulting esters. An alkylidene group‐substituted π‐allylpalladium species has been presumed to be an intermediate. Copyright © 2000 John Wiley & Sons, Ltd.     

Asymmetric Hetero‐Diels–Alder Reaction of Danishefsky’s Diene with α‐Ketoesters and Isatins Catalyzed by a Chiral N,N′‐Dioxide/Magnesium(II) Complex

A highly enantioselective hetero‐Diels–Alder reaction of Danishefsky’s diene with α‐ketoesters and isatins has been realized by using a chiral N,N′‐dioxide/Mg^II complex. In the presence of only 0.1–0.5 mol % catalyst, a series of substrates were transformed into the corresponding tetrasubstituted 2,3‐dihydropyran‐4‐ones in up to 99 % yield and more than 99 % ee in two hours.     

Palladium‐Catalyzed C?H Activation of N‐Allyl Imines: Regioselective Allylic Alkylations to Deliver Substituted Aza‐1,3‐Dienes

A new mode of activation of an imine via a rare aza‐substituted π‐allyl complex is described. Palladium‐catalyzed C(sp³) H activation of the N‐allyl imine and the subsequent nucleophilic attack by the α‐alkyl cyanoester produced the 1‐aza‐1,3‐diene as the sole regioisomer. In contrast, nucleophilic attack by the α‐aryl cyanoester exclusively delivered the 2‐aza‐1,3‐diene, which was employed in an inverse‐electron‐demand Diels–Alder reaction for heterobiaryl synthesis.     

Gas‐Phase Synthesis of 1‐Silacyclopenta‐2,4‐diene

Silole (1‐silacyclopenta‐2,4‐diene) was synthesized for the first time by the bimolecular reaction of the simplest silicon‐bearing radical, silylidyne (SiH), with 1,3‐butadiene (C₄H₆) in the gas phase under single‐collision conditions. The absence of consecutive collisions of the primary reaction product prevents successive reactions of the silole by Diels–Alder dimerization, thus enabling the clean gas‐phase synthesis of this hitherto elusive cyclic species from acyclic precursors in a single‐collision event. Our method opens up a versatile and unconventional path to access a previously rather obscure class of organosilicon molecules (substituted siloles), which have been difficult to access through classical synthetic methods.     

Evolution of a Multicomponent System: Computational and Mechanistic Studies on the Chemo‐ and Stereoselectivity of a Divergent Process

The evolution of a ternary molecular system (imine, diene and nitrile) is analyzed to disclose the pathways leading to a divergent synthetic outcome. The Lewis acid catalyzed reaction between cyclohexadiene, 2‐phenyl‐indol‐3‐one and acetonitrile yields the imino‐Diels–Alder adduct as the major product together with minor amounts of the Mannich–Ritter‐amidine product. The experimental and computational data show that the relative orientation of the initial reactants dictates the synthetic outcome. The exo approach between imine and diene leads to the Diels–Alder adduct in a concerted process, whereas the endo mode leads to a polarized intermediate, which is trapped by acetonitrile to yield the multicomponent adduct.     

Gold‐Catalyzed 1,2‐/1,2‐Bis‐acetoxy Migration of 1,4‐Bis‐propargyl Acetates: A Mechanistic Study

The late transition metal catalyzed rearrangement of propargyl acetates offers an interesting platform for the development of synthetically useful transformations. We have recently shown that gold complexes can catalyze a highly selective tandem 1,2‐/1,2‐bis‐acetoxy migration in 1,4‐bis‐propargyl acetates to form 2,3‐bis‐acetoxy‐1,3‐dienes. In this way, (1Z,3Z)‐ or (1Z,3E)‐ and (1E,3Z)‐1,3‐dienes could be obtained in a stereocontrolled manner depending on the electronic and steric features of the ancillary ligand bound to gold and the substituents at the propargylic positions. In this work, we report an experimental study on the scope of this transformation, plus a detailed theoretical examination of the reaction mechanism, which has revealed the key features responsible for the reaction stereoselectivity. Synthetic applications towards the one‐pot synthesis of quinoxaline heterocycles and tandem Diels–Alder processes have also been devised.     

A theoretical study for the regioselective Diels–Alder reaction of 5,6‐fulleroid with strained anti‐Bredt olefins

Regioselectivity of Diels–Alder reaction of the anti‐Bredt olefin of fulleroid, the 5,6‐methylene‐bridged fullerene derivative, is theoretically clarified by DFT calculations. In transition state calculations, the addition of a noncyclic diene 2,3‐dimethyl‐1,3‐butadiene (DMBD) at the anti‐Bredt olefin has considerably lower activation energy than those at the other sixteen olefins, while the reaction of a rigid cyclic diene cyclohexadiene (CHD) has similar activation energy at both anti‐Bredt and another nontwisted olefin. The changes in strain and interaction of the reactants are estimated along its reaction coordinate by activation strain model. Noncyclic diene shows asynchronous C? C bond formation with a significant gain of interaction energy, while the rigid cyclic diene shows a large growth of strain energy canceling out the interaction energy between diene and fulleroid.     

The Molecular Structure of gauche‐1,3‐Butadiene: Experimental Establishment of Non‐planarity

The planarity of the second stable conformer of 1,3‐butadiene, the archetypal diene for the Diels–Alder reaction in which a planar conjugated diene and a dienophile combine to form a ring, is not established. The most recent high level calculations predicted the species to adopt a twisted, gauche structure owing to steric interactions between the inner terminal hydrogens rather than a planar, cis structure favored by the conjugation of the double bonds. The structure cis‐1,3‐butadiene is unambiguously confirmed experimentally to indeed be gauche with a substantial dihedral angle of 34°, in excellent agreement with theory. Observation of two tunneling components indicates that the molecule undergoes facile interconversion between two equivalent enantiomeric forms. Comparison of experimentally determined structures for gauche‐ and trans‐butadiene provides an opportunity to examine the effects of conjugation and steric interactions.