Diels-Alder reactions of masked o-benzoquinones: new experimental findings and a theoretical study of the inverse electron demand case

Diels-Alder reactions of the masked o-benzoquinone (MOB) 2 with vinylene carbonate (3), the bicyclic derivatives 4, 5, and 6, and the intramolecular version of the 2-hydroxymethylfuran-MOB Diels-Alder reaction are described. In addition, a theoretical study of the Diels-Alder reactions of MOBs with enol and thioenol ethers is presented.     

内分子DIELS-ALDER反应合成DRIMANE类倍半萜化合物DRIMENIN, POLYGODIAL及CINNAMOLIDE的全合成

近年来有不少报道从事于生理活性Drimane类倍半萜的合成,较多采用了分子间Diels-Alder反应来建立Drimane的骨架。本文首次采用内分子Diels-Alder反应作为关键反应合成了Drimane类化合物。同时还在引入了手性诱导基团后,首次完成了从无手性的原料化合物β-紫罗兰酮至光学活性(-)-drimenin1的不对称合成。     

A novel and facile stereocontrolled synthetic method for polyhydro-quinolines and pyridopyridazines via a diene-transmissive Diels-Alder reaction involving inverse electron-demand hetero Diels-Alder cycloaddition of cross-conjugated azatrienes

Cross-conjugated azatrienes bearing an electron-withdrawing sulfonyl or benzoyl group on the nitrogen atom underwent, on heating or in the presence of a Lewis acid (TMSOTf), an initial inverse electron-demand hetero Diels-Alder reaction with electron-rich dienophiles (vinyl ether, vinyl thioether, and allenyl ether) to produce 1:1 cycloadducts with high endo selectivity. The initial cycloadducts thus obtained underwent a second Diels-Alder reaction stereoselectively on the newly formed diene unit with electron-deficient dienophiles to give the crossed bis-cycloadducts, octahydroquinolines, with high diastereo-π-facial selectivity. The N-sulfonylazatrienes tethering an ortho-cinnamyloxyphenyl dienophile at the triene terminal underwent an initial intramolecular hetero Diels-Alder reaction of the inverse electron-demand type. The subsequent second Diels-Alder reaction of the formed mono-cycloadducts completed the diene-transmissive hetero Diels-Alder protocol to give benzopyrano[3,4-c]quinolines in a highly stereoselective manner.     

Synthesis and thermal modulation of the fluorescence of a pyrene-arylmaleimide dyad and its Diels-Alder adduct

The fluorescence of a pyrene-arylmaleimide dyad and its Diels-Alder adduct can be thermally modulated through reversible Diels-Alder reaction of arylmaleimide unit with furan. Moreover, the fluorescence intensities of the Diels-Alder adduct of dyad 1 with furan vary linearly with the temperatures of the corresponding solutions, demonstrating that these molecules are interesting compounds for studies of fluorescent molecular thermometers.     

Accurate prediction of rate constants of Diels-Alder reactions and application to design of Diels-Alder ligation

Bioorthogonal reactions are useful tools to gain insights into the structure, dynamics, and function of biomolecules in the field of chemical biology. Recently, the Diels-Alder reaction has become a promising and attractive procedure for ligation in bioorthogonal chemistry because of its higher rate and selectivity in water. However, a drawback of the previous Diels-Alder ligation is that the widely used maleimide moiety as a typical Michael acceptor can readily undergo Michael addition with nucleophiles in living systems. Thus, it is important to develop a nucleophile-tolerant Diels-Alder system in order to extend the scope of the application of Diels-Alder ligation. To solve this problem, we found that the theoretical protocol M06-2X/6-31+G(d)//B3LYP/6-31G(d) can accurately predict the activation free energies of Diels-Alder reactions with a precision of 1.4 kcal mol(-1) by benchmarking the calculations against the 72 available experimental data. Subsequently, the electronic effect and ring-strain effect on the Diels-Alder reaction were studied to guide the design of the new dienophiles. The criteria of the design is that the designed Diels-Alder reaction should have a lower barrier than the Michael addition, while at the same time it should show a similar (or even higher) reactivity as compared to the maleimide-involving Diels-Alder ligation. Among the designed dienophiles, three substituted cyclopropenes (i.e. 1,2-bis(trifluoromethyl)-, 1,2-bis(hydroxylmethyl)- and 1,2-bis(hydroxylmethyl)-3-carboxylcyclopropenes) meet our requirements. These substituted cyclopropene analogs could be synthesized and they are thermodynamically stable. As a result, we propose that 1,2-bis(trifluoromethyl)-, 1,2-bis(hydroxylmethyl)- and 1,2-bis(hydroxylmethyl)-3-carboxylcyclopropenes may be potential candidates for efficient and selective Diels-Alder ligation in living systems.     

Mechanism of scandium ion catalyzed Diels-Alder reaction of anthracenes with methyl vinyl ketone

Rates of Diels-Alder cycloadditions of anthracenes with methyl vinyl ketone (MVK) are accelerated significantly by the presence of scandium triflate [Sc(OTf)3]. Sc(OTf)3 also promotes photoinduced electron-transfer reactions from various electron donors to MVK significantly. Comparison of the promoting effect of Sc(OTf)3 in photoinduced electron-transfer reactions of MVK with the catalytic effect of Sc(OTf)3 in the Diels-Alder reaction of 9,10-dimethylanthracene with MVK has revealed that the MVK-Sc(OTf)3 complex is a reactive intermediate in both the Diels-Alder and photoinduced electron-transfer reactions. The observed second-order rate constants of the Sc(OTf)3-catalyzed Diels-Alder reactions of anthracenes with MVK are by far larger than those expected from the observed linear Gibbs energy relation for the Diels-Alder reactions of anthracenes with stronger electron acceptors than MVK, which are known to proceed via electron transfer. This indicates that the Sc(OTf)3-catalyzed Diels-Alder reactions of anthracenes with MVK does not proceed via an electron-transfer process from anthracences to the MVK-Sc(OTf)3 complex.     

Efficient synthesis of a 4,5-epoxy-2-cyclohexen-1-one derivative bearing a spirolactone via a Diels-Alder reaction with high pi-facial selectivity: a synthetic study towards scyphostatin

The Diels-Alder reaction of spirolactones with cyclopentadiene afforded the adduct with high pi-facial selectivity; a hydrophilic analogue of scyphostatin was synthesized from the Diels-Alder adduct.     

Silyl-substituted 1,3-butadienes for Diels-Alder reaction, ene reaction and allylation reaction

Silyl-substituted 1,3-butadienes are useful building blocks and are readily applied in several types of reactions such as Diels-Alder reaction, ene reaction and allylation. They can also participate in different tandem reactions such as Diels-Alder/allylation, ene/allylation, ene/allylation/Diels-Alder reaction, ene/allylation/ene reaction and ene/allylation/Diels-Alder/allylation reaction. This feature article reviews the synthesis of silyl-substituted 1,3-butadienes, and their applications in the reaction types mentioned above, involving a tandem Diels-Alder/ene/allylation process. This article also introduces some reactions of alkenylsilanes and allylsilanes for comparison and discussion about the tandem reaction. The tandem reactions described in this article are a powerful tool to construct complicated multicyclic compounds with high selectivity and high efficiency.     

Synthesis of the ravidomycin ring system

Synthesis of the tetracyclic aromatic ring system of the ravidomycin family of anti-tumor agents is reported. The synthesis is a sequential Meerwein and Diels-Alder route with the crucial regiochemistry of the Diels-Alder reaction controlled with a chlorine atom.     

Asymmetric synthesis of (+)-cis-nemorensic acid from a chiral Diels-Alder adduct of 2,5-dimethylfuran

(+)-cis-Nemorensic acid was synthesized from a chiral Diels-Alder adduct prepared by a catalytic enantioselective Diels-Alder reaction with 2,5-dimethylfuran and 2,2,2-trifluoroethyl acrylate.     

A substituent effects study reveals the kinetic pathway for an interfacial reaction

This paper describes the use of a substituent effects study to understand the mechanistic basis for an interfacial Diels-Alder reaction that does not proceed with standard second-order kinetics. Cyclopentadiene (Cp) undergoes a Diels-Alder reaction with a chemisorbed mercaptobenzoquinone to yield an immobilized Diels-Alder adduct. The pseudo-first-order rate constants are not linearly related to the concentration of diene, but they reach a limiting value with increasing concentrations of diene. The results of a substituent effects study support a mechanism wherein the electrochemical oxidation of hydroquinone produces two states of quinone. The first form, Q*, either reacts with Cp or isomerizes to Q, a form that is significantly less reactive with the diene. The interfacial reaction reaches a maximum rate when the concentration of diene is sufficiently high so that Q* undergoes complete Diels-Alder reaction and does not isomerize to Q. This work provides an example of the use of physical organic chemistry to understand an interfacial reaction.     

A total synthesis of xestodecalactone a and proof of its absolute stereochemistry: interesting observations on dienophilic control with 1,3-disubstituted nonequivalent allenes

A concise total synthesis of xestodecalactone A, utilizing a Diels-Alder strategy is described. The focal Diels-Alder reaction relied on an "ynoate" dienophile to rapidly assemble the required resorcylinic acid scaffold. During this study, Diels-Alder cycloaddition reactions involving 1,3-disubstituted nonequivalent allene dienophiles were studied, and some surprising results were encountered.     

Characteristics of the two frontier orbital interactions in the Diels-Alder cycloaddition

Two electron-deficient dienes were reacted with a series of twelve electron-poor and electron-rich dienophiles to give, in some cases, the corresponding Diels-Alder adducts. Clear differences in the roles played by the two frontier orbital interactions emerged. It was demonstrated that in the case of normal Diels-Alder cycloadditions, the FMO theory could predict the relative reactivities between dienophiles, while in the case of inverse-electron demand Diels-Alder reactions, it could not. It was shown that the dissymmetry in electron-rich dienophiles increases their reactivities.     

Diels-Alder reactions with dienes bearing a remote stereogenic center. Conformational model for diastereofacial selectivity

In Diels-Alder reactions of 1-acyloxydienes, the 1-O-methylmandeloxy group has the distinct advantage of serving dual functions. Not only is it an effective chiral auxiliary for Diels-Alder stereocontrol, but also it provides rather reliable determination of the absolute stereochemistry of the Diels-Alder adduct, via the Dale-Mosher NMR model, subject only to the ability to resolve the proper NMR resonances. Study of the Diels-Alder reactions of such chiral 1-acyloxydienes has led us to a transition structure model which uniquely explains the origin of the observed stereoselectivities and is supported by experimental evidence, including X-ray structures showing the conformations of three Diels-Alder adducts. The model may also have wider applicability in conformational analysis and control of selectivity in other reactions.     

Synthesis of [60]fullerene-functionalized rotaxanes

Synthesis of [60]fullerene (C₆₀)-functionalized rotaxanes via Diels-Alder reactions with C₆₀ is described. Diels-Alder reaction of C₆₀ and sulfolene moiety as masked diene attached on the wheels of rotaxanes results in high yields of C₆₀ incorporation. Rotaxanes are prepared by tin-catalyzed urethane-forming end-capping reaction with isocyanate of pseudorotaxane having the wheel carrying C₆₀ functionality as introduced by the Diels-Alder reaction. The Diels-Alder reaction was accomplished as end-capping reaction between C₆₀ and pseudorotaxane bearing sultine moiety as masked diene on the axle terminal. A variety of C₆₀-containing [2]rotaxanes was prepared in moderate to good yields by these Diels-Alder protocols.     

Anthracene cycloadducts as highly selective chiral auxiliaries

A new chiral auxiliary was designed and easily prepared from a Diels-Alder cycloadduct of an enantiomerically pure anthracene with maleimide. Excellent diastereoselectivities in Diels-Alder reactions, conjugate additions, and aldol reactions employing these auxiliaries are now reported.     

Synthesis and Diels-Alder reactions of homochiral 2-sulfinylmaleates with cyclopentadiene

Enantiomerically pure 2-p-tolylsulfinylmaleates 1, 2 and 3 have been readily prepared by Knoevenagel reaction between (S)-menthyl p-toluenesulfinate and glyoxylic acid. Their asymmetric Diels-Alder reactions with cyclopentadiene have been studied under a wide range of uncatalyzed and catalyzed conditions and the stereochemical results have been explained by assuming a steric control approach, in term of S-cis or S-trans favoured conformations. Uncatalyzed Diels-Alder reactions of 1 and some Lewis acid catalyzed Diels-Alder reactions of 2 show high facial and endo selectivities. The facial selectivity of dienophile 2 highly depends on the Lewis acid, whereas reactivity of 1 and 3 is very sensitive to the solvent. These sulfinylmaleates 1, 2 and 3 act as synthetic equivalents of chiral acetylenedicarboxylates in Diels-Alder reactions after basic elimination of the sulfinylic moiety in the resulting adducts.     

Regioselective Diels-Alder reactions of 3-indolylquinones

6-(3-Indolyl)quinolinequinone derivatives gave regioselective Diels-Alder reactions with a variety of dienophiles, yielding polycyclic carbazole derivatives. One-pot reactions, proceeding through a cascade of reactions including regioselective Michael and Diels-Alder steps, gave heptacyclic derivatives starting from indoles and 2,5,8(1H)-quinolinetriones. Double Diels-Alder reactions of 6-(3-indolyl)quinolinequinones and dihalobenzoquinones gave eleven-cycle products in one step.     

A direct route to fluostatin C by a fascinating Diels-Alder reaction

The Diels-Alder reactions between vinylindenes (5 or 6) as the dienes with quinoneketals (7 or 8) or with methacrolein as the dienophiles were investigated. The remarkable regioselectivities of these Diels-Alder adducts suggested that the regiopreferences of these dienes and dienophiles in these cases are not a fixed property of each component of the cycloaddition but are mutually contigent. This paper shows how the Diels-Alder reaction between 6 and 8 was applied to the inaugural total syntheses of fluostatin C and E.     

Use of bis(oxazoline)-metal complexes as chiral catalysts for asymmetric Diels-Alder reactions using 2-acetyl-1,4-naphthoquinone as a dienophile

Asymmetric Diels-Alder reactions of 1,4-naphthoquinone and 2-acetyl-1,4-naphthoquinone with cyclopentadiene catalyzed by bis(oxazoline)-metal complexes afforded the corresponding Diels-Alder adducts. Moderate levels of enantiomeric excess were obtained and a number of different reaction conditions evaluated.