Asymmetric Diels–Alder Reaction of α‐Substituted and β,β‐Disubstituted α,β‐Enals via Diarylprolinol Silyl Ether for the Construction of All‐Carbon Quaternary Stereocenters

The asymmetric Diels–Alder reaction of α‐substituted acrolein proceeds in the presence of the trifluoroacetic acid salt of trifluoromethyl‐substituted diarylprolinol silyl ether to afford the exo‐isomer with both excellent diastereoselectivity and high enantioselectivity. In the Diels–Alder reaction of a β,β‐disubstituted α,β‐unsaturated aldehyde, good exo‐selectivity and excellent enantioselectivity was obtained when the perchloric acid salt of the bulky triisopropyl silyl ether of trifluoromethyl substituted diarylprolinol was employed as an organocatalyst in the presence of water. In both cases, all‐carbon quaternary stereocenters are constructed enantioselectively.     

Bifunctional Hydrogen Bond Donor-Catalyzed Diels–Alder Reactions: Origin of Stereoselectivity and Rate Enhancement

The selectivity and rate enhancement of bifunctional hydrogen bond donor-catalyzed Diels–Alder reactions between cyclopentadiene and acrolein were quantum chemically studied using density functional theory in combination with coupled-cluster theory. (Thio)ureas render the studied Diels–Alder cycloaddition reactions exo selective and induce a significant acceleration of this process by lowering the reaction barrier by up to 7 kcal mol⁻¹. Our activation strain and Kohn–Sham molecular orbital analyses uncover that these organocatalysts enhance the Diels–Alder reactivity by reducing the Pauli repulsion between the closed-shell filled π-orbitals of the diene and dienophile, by polarizing the π-orbitals away from the reactive center and not by making the orbital interactions between the reactants stronger. In addition, we establish that the unprecedented exo selectivity of the hydrogen bond donor-catalyzed Diels–Alder reactions is directly related to the larger degree of asynchronicity along this reaction pathway, which is manifested in a relief of destabilizing activation strain and Pauli repulsion.     

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     

How Oriented External Electric Fields Modulate Reactivity

A judiciously oriented external electric field (OEEF) can catalyze a wide range of reactions and can even induce endo/exo stereoselectivity of cycloaddition reactions. The Diels–Alder reaction between cyclopentadiene and maleic anhydride is studied by using quantitative activation strain and Kohn–Sham molecular orbital theory to pinpoint the origin of these catalytic and stereoselective effects. Our quantitative model reveals that an OEEF along the reaction axis induces an enhanced electrostatic and orbital interaction between the reactants, which in turn lowers the reaction barrier. The stronger electrostatic interaction originates from an increased electron density difference between the reactants at the reactive center, and the enhanced orbital interaction arises from the promoted normal electron demand donor–acceptor interaction driven by the OEEF. An OEEF perpendicular to the plane of the reaction axis solely stabilizes the exo pathway of this reaction, whereas the endo pathway remains unaltered and efficiently steers the endo/exo stereoselectivity. The influence of the OEEF on the inverse electron demand Diels–Alder reaction is also investigated; unexpectedly, it inhibits the reaction, as the electric field now suppresses the critical inverse electron demand donor–acceptor interaction.     

Liquid‐Crystalline Ionic Liquids as Ordered Reaction Media for the Diels–Alder Reaction

Liquid‐crystalline ionic liquids (LCILs) are ordered materials that have untapped potential to be used as reaction media for synthetic chemistry. This paper investigates the potential for the ordered structures of LCILs to influence the stereochemical outcome of the Diels–Alder reaction between cyclopentadiene and methyl acrylate. The ratio of endo‐ to exo‐product from this reaction was monitored for a range of ionic liquids (ILs) and LCILs. Comparison of the endo:exo ratios in these reactions as a function of cation, anion and liquid crystallinity of the reaction media, allowed for the effects of liquid crystallinity to be distinguished from anion effects or cation alkyl chain length effects. These data strongly suggest that the proportion of exo‐product increases as the reaction media is changed from an isotropic IL to a LCIL. A detailed molecular dynamics (MD) study suggests that this effect is related to different hydrogen bonding interactions between the reaction media and the exo‐ and endo‐transition states in solvents with layered, smectic ordering compared to those that are isotropic.     

Regio‐ and Enantioselective Aza‐Diels–Alder Reactions of 3‐Vinylindoles: A Concise Synthesis of the Antimalarial Spiroindolone NITD609

An asymmetric aza‐Diels–Alder reaction of 3‐vinylindoles with isatin‐derived ketimines has been developed. A series of spiroindolone derivatives were thus obtained in good to excellent yields with excellent enantioselectivity (up to 96 % yield and 99 % ee). Furthermore, the antimalarial compound NITD609 could be obtained in three steps with an overall yield of 40.6 %. Control experiments and operando IR experiments imply a concerted reaction pathway. The regioselectivity and exo selectivity result from π–π interactions between the two indoline rings of the two reactants.     

Enantioselective Organocatalytic Diels–Alder Trapping of Photochemically Generated Hydroxy‐o‐Quinodimethanes

The photoenolization/Diels–Alder strategy offers straightforward access to synthetically valuable benzannulated carbocyclic products. This historical light‐triggered process has never before succumbed to efforts to develop an enantioselective catalytic approach. Herein, we demonstrate how asymmetric organocatalysis provides simple yet effective catalytic tools to intercept photochemically generated hydroxy‐o‐quinodimethanes with high stereoselectivity. We used a chiral organic catalyst, derived from natural cinchona alkaloids, to activate maleimides toward highly stereoselective Diels–Alder reactions. An unconventional mechanism of stereocontrol is operative, wherein the organocatalyst is actively involved in both the photochemical pathway, by leveraging the formation of the reactive photoenol, and the stereoselectivity‐defining event.     

Highly Stereoselective Diels–Alder Reactions Catalyzed by Diboronate Complexes**

A highly enantioselective catalytic system for exo-Diels–Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDB). Activated by various Lewis or Brønsted acids, BPDB can catalyze highly stereoselective asymmetric exo-Diels–Alder reactions of monocarbonyl-based dienophiles. When 1,2-dicarbonyl-based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels–Alder reactions. BPDB can be prepared as crystalline solids on a large scale and are stable under ambient condition. Single-crystal X-ray analysis of the structure for acid-activated BPDB indicated that its activation involves cleavage of a labile B←N bond.     

Chiral Dawson‐Type Hybrid Polyoxometalate Catalyzes Enantioselective Diels–Alder Reactions

Can achiral organocatalysts linked to chiral polyanionic metal oxide clusters provide good selectivity in enantioselective C?C bond formations? The answer to this question is investigated by developing a new active hybrid polyoxometalate‐based catalyst for asymmetric Diels–Alder reaction. Chirality transfer from the chiral anionic polyoxometalate to the covalently linked achiral imidazolidinone allows Diels–Alder cycloaddition products to be obtained with good yields and high enantioselectivities when using cyclopentadiene and acrylaldehydes as partners.     

Reactivity of 2-methylene-1,3-dicarbonyl compounds: catalytic enantioselective Diels–Alder reaction

The catalytic enantioselective Diels–Alder reaction of 1,1-dicarbonylethenes 3 with cyclopentadiene in the presence of Ti-TADDOLs, Mg–Ph-box and Mg–Ph-mox complexes was investigated. Although both exo- and enantioselectivity with Ti-TADDOL catalysts were poor, they were much improved using Mg–Ph-box or Mg–Ph-mox complexes as chiral catalysts. Thus, 3 was an efficient two-point binding dienophile and the non-C₂-symmetric Ph-mox 8 could be used as a chiral ligand.     

Efficient Method for the Synthesis of Functionalized Basic Maleimides

A three‐step procedure involving Diels–Alder condensation of maleic anhydride with furane, formation of N‐substituted imide upon reaction with appropriate diamine, and a final retro Diels–Alder regeneration of the maleic carbon–carbon double bond is proposed for an unequivocal synthesis of N‐substituted basic maleimides. The novel method is characterized by mild reaction conditions, easy work‐up, high yields, and no need for additional catalysis.     

Stacking and Electrostatic Interactions Drive the Stereoselectivity of Silylium‐Ion Asymmetric Counteranion‐Directed Catalysis

Computational analysis shows that the enantioselectivity of asymmetric Lewis‐acid organocatalysis of the Diels–Alder cycloaddition of cyclopentadiene to cinnamates arises from stacking interactions that favor the addition of the diene to the more hindered face of the dienophile, while electrostatic interactions control the diastereoselectivity by selectively stabilizing the endo transition state. These results not only explain the stereoselectivity of these silylium‐ion‐ACDC reactions but should also guide the development of more effective ion‐pairing asymmetric organocatalysts.     

Cyclodextrins in Polymer Modification: Diels–Alder Addition of Cyclopentadiene/Methylated‐β‐Cyclodextrin Complex on Unsaturated Polyester and Formation of a New Type of Polypseudorotaxane

Summary: Cyclopentadiene ( 1 ) was incorporated as a guest into the cavity of randomly methylated‐β‐cyclodextrin (me‐β‐CD) as a host, yielding the stable, water compatible cyclopentadiene/me‐β‐CD complex ( 1a ). We successfully attempted to use the synthesised complex in a Diels–Alder addition with a water‐soluble unsaturated polyester ( 2 ) derived from poly(ethylene glycol) and maleic anhydride. The reaction yielded a new type of polypseudorotaxane ( 3 ). Examination of the polypseudorotaxane ( 3 ) and a model inclusion complex of the starting unsaturated polyester with me‐β‐CD ( 2a ) showed that cyclodextrins are threaded onto the main chain in both cases. The cyclohexene moiety formed after the Diels–Alder addition does not act as a stopper, a dethreading process being evidenced and discussed.

The polypseudorotaxane synthesized here.     

Asymmetric Diels–Alder and ene reactions promoted by a Ti(IV) complex bearing a C2-symmetric tridentate ligand

A new Ti(IV) complex obtained from the C₂-symmetric amino diol (1R,5R)-3-aza-3-benzyl-1,5-diphenyl pentan-1,5-diol, (1R,5R)-1, is used effectively as a Lewis acid promoter in asymmetric Diels–Alder reactions. Using various Evans' oxazolidinones as dienophiles and cyclopentadiene as the diene high yields of the adducts with moderate enantioselectivity, under different reaction conditions are achieved. The effects of solvent, temperature and ligand on the enantioselectivity of the Diels–Alder products are reported. Molecular modelling studies provide an understanding of the diastereofacial selectivity of the Diels–Alder reactions. Asymmetric carbonyl-ene reactions between various glyoxylate esters and α-methyl styrene are also described.     

Synthesis of Fused Tricyclic Systems from Cycloalkadienones via Diels–Alder Reaction: Sharpless Oxidation of bis Adducts

The Diels–Alder reaction between 2,7‐cyclooctadienone and cyclopentadiene goes to completion to produce a bis adduct and mono adduct under InCl₃ conditions. 2,6‐Cycloheptadienone undergoes sequential Diels–Alder reactions in the presence of AlCl₃ with cyclohexadiene and cyclopentadiene to produce the bis adduct. The bis adducts were oxidatively cleaved to produce the [5.8.5] and [5.7.6] tricyclic systems.     

Stereodivergent Synthesis of Piperidine Alkaloids by Ring‐Rearrangement Metathesis/Reductive Lactam Alkylation of Nitroso Diels–Alder Cycloadducts

A general methodology for the stereoselective synthesis of 2‐(2‐hydroxyalkyl)piperidine alkaloids by ring‐rearrangement metathesis of nitroso Diels–Alder cycloadducts is reported. The approach is illustrated by the formal synthesis of porantheridine and the total synthesis of andrachcinidine through a diastereodivergent allylation of an N‐alkoxy bicyclic lactam. The asymmetric synthesis of the latter alkaloid provides new insights into the configurational stability of cycloadducts between chloronitroso reagents and cyclopentadiene.     

Asymmetric Photocatalysis by Intramolecular Hydrogen‐Atom Transfer in Photoexcited Catalyst–Substrate Complex

3‐(2‐Formylphenyl)‐1‐pyrazol‐1‐yl‐propenones undergo an asymmetric photorearrangement to benzo[d]cyclopropa[b]pyranones with up to >99 % ee, which is catalyzed by a bis‐cyclometalated rhodium catalyst in the presence of visible light. Mechanistic experiments and DFT calculations support a mechanism in which a photoexcited catalyst/substrate complex triggers an intramolecular hydrogen‐atom transfer followed by a highly stereocontrolled hetero‐Diels–Alder reaction. In this reaction scheme, the rhodium catalyst fulfills multiple functions by 1) enabling visible‐light π→π* excitation of the catalyst‐bound enone substrate, 2) facilitating the hydrogen‐atom transfer, and 3) providing the asymmetric induction for the hetero‐Diels–Alder reaction.     

Enantioselective Synthesis of Arene cis‐Dihydrodiols from 2‐Pyrones

An enantioselective chemical synthesis of arene cis‐dihydrodiols has been realized from 2‐pyrones through sequential ytterbium‐catalyzed asymmetric inverse‐electron‐demand Diels–Alder (IEDDA) reaction of 2‐pyrones and retro‐Diels–Alder extrusion of CO₂. By using this strategy, a series of substituted arene cis‐dihydrodiols can be obtained efficiently with high enantioselectivity (>99 % ee in many cases). Based on this strategy, efficient and concise asymmetric total syntheses of (+)‐MK7607 and 1‐epi‐(+)‐MK7607 were accomplished.     

Diversified Cycloisomerization/Diels–Alder Reactions of 1,6‐Enynes through Bimetallic Relay Asymmetric Catalysis

We report the combination of transition‐metal‐catalyzed diversified cycloisomerization of 1,6‐enynes with chiral Lewis acid promoted asymmetric Diels–Alder reaction to realize asymmetric cycloisomerization/Diels–Alder relay reactions of 1,6‐enynes with electron‐deficient alkenes. A broad spectrum of chiral [5,6]‐bicyclic products could be acquired in high yields (up to 99 %) with excellent diastereoselectivy (>19:1 dr) and enantioselectivity (up to 99 % ee).     

Molecular recognition in the palladium complex promoted asymmetric synthesis of a keto-ester heterofunctionalized P-chiral phosphine

A chiral organopalladium complex promoted asymmetric Diels–Alder reaction between 1-phenyl-3,4-dimethyl-phosphole and methyl-trans-4-oxo-2-pentenoate gives the corresponding keto-carboxylate heterofunctionalized P-chiral phosphine ligand in which the keto group is stereoselectively located in the exo position of the phosphanorbornene skeleton.