Chemistry of fluorinated quinones. Part II proton and fluorine nmr spectra

Proton and fluorine NMR spectra of nineteen fluorinated quinones are presented. Coupling constants were found for HH: $\text{o}$ 10.5, $\text{m}$ 2.2, $\text{p}$ ?0.3-0; for FF: $\text{o}$ 4.5–5.6, $\text{m}$ 0.3–1.7, $\text{p}$1.5–3.0; and HF: $\text{o}$ 8.2–10.1, $\text{m}$ 6.0–8.4, and $\text{p}$ 0.6–0.9.     

Chemistry and biology of biosynthetic Diels-Alder reactions

Nature's repertoire of biosynthetic transformations has recently been recognized to include the Diels-Alder cycloaddition reaction. Evidence now exists that there are enzymes that mediate the Diels-Alder reaction in secondary metabolic biosynthetic pathways. 2002 marked the 100th anniversary of Alder's birth and 75 years since the discovery of the Diels-Alder reaction. It would appear that living systems discovered and made use of this ubiquitously useful ring-forming reaction eons ago for the construction of complex natural products. In this Review an overview is given of all of the known classes of natural products (polyketides, isoprenoids, phenylpropanoids, alkaloids) that have been speculated to arise by a biological Diels-Alder reaction.     

The trifluoromethoxy group as a fluorine twin in the Diels-Alder reactions of halogenated quinones

We describe here a study devoted to the comparison of the relative influence of chlorine, fluorine, and trifluoromethoxy substituents on the regiochemical outcome of the Diels-Alder reaction. For this purpose, we examined the behavior of mixed ‘halogenated’ quinones bearing these groups in their cycloadditions with simple dienes. Contrary to the expectation based on its known electronic properties, the trifluoromethoxy group behaves very much more like a fluorine than a chlorine atom in such reactions. On the basis on an endo transition state demonstrated here for these additions, we tentatively suggest that non-bonded interactions are the main factor controlling the regiochemistry.     

Chemistry of thienopyridines. XXXVIII. Diels-Alder reactions of thienopyridine sulfones. Part 2

Thieno[3,2-b]pyridine 1,1-dioxide ( 2 ) undergoes Diels-Alder condensation with the dienophiles cyclopentadiene, anthracene, and naphthacene in a manner analogous to its isomer thieno[2,3-b]pyridine 1,1-dioxide ( 1 ). Compound 2 dimerizes in refluxing xylene with the loss of sulfur dioxide plus either the loss or transfer of hydrogen to give a small yield (ca. 2%) of pyrido[2′,3′:4,5]thieno[3,2-f]quinoline 7,7-dioxide ( 7 ) and its 5,6-dihydro derivative 12 . Formation of 7 and 12 are compared and contrasted with products reported from dimerization of 1 and of benzo[b]thiophene 1,1-dioxide and its derivatives.     

Addition of radicals to quinones—II. ESR spectra of radicals derived from fluoranil

In systems consisting of thermally decomposing benzoyl peroxide in alkylbenzenes, fluoranil behaves as a selective spin trap. As a result of charge transfer (CT) complex formation between alkylbenzenes and fluoranil, the latter traps secondary radicals formed via H-atom abstraction by phenyl radicals from the alkyl group of the aromatic solvents. Weaker CT interaction leads to the trapping of phenyl radicals. The kinetic isotope effect in H-atom abstraction leads to the same result.     

Regioselectivities of Diels-Alder cycloadditions to methoxy-substituted quinones

Diels-Alder cycloadducts of unsymmetrical electron-rich dienes and methoxybenzoquinones or naphthoquinones produce adducts in which the more nucleophilic diene terminus becomes bonded to the non-methoxylated carbon. These results support the “secondary orbital”, but not the “schizophrenic”, model for donor substituent effects on regioselectivity.     

Enantioselective and structure-selective Diels-Alder reactions of unsymmetrical quinones catalyzed by a chiral oxazaborolidinium cation. Predictive selection rules

The chiral oxazaborolidinium cation 1 promotes Diels-Alder reactions between 2-triisopropylsilyloxy-1,3-butadiene and a number of unsymmetrical 1,4-benzoquinones in a highly enantioselective and structurally selective manner. The basis for the enantioselectivity is explained rationally in terms of a preferred type of transition-state assembly. Selection rules have been developed that allow the prediction of the principal reaction product of Diels-Alder reaction between unsymmetrical diene and quinone components.     

Diels-Alder reactions between dienamides and quinones: stereochemistry of the cycloadditions and cytotoxic activity of the adducts

Tetrahydronaphthoquinones and tetrahydroanthraquinones bearing an amido group have been prepared by Diels-Alder reactions between (E)-1-(N-carbobenzyloxyamino)-1,3-butadiene (2) or (E)-1-(N-benzoyl-N-benzylamino)-1,3-butadiene (5) and benzoquinone or 5-substituted naphthoquinones. The stereochemistry of the cycloadditions was investigated. A high regioselectivity was observed in the reaction of the diene carbamate 2 with 5-methoxy and 5-acetoxy naphthoquinones. This latter gave the unexpected 1,8-regioisomer 3d. The cycloadditions of the dienamide 5 with naphthoquinones 1 (R = OH, OMe, OAc) are regiospecific. Assignment of the structure of the tetrahydroanthraquinone 6b is in good agreement with the known directing effect of the 5-hydroxy group of juglone 1b in analogous Diels-Alder reactions. With 5-methoxy and 5-acetoxy naphthoquinones, the opposite regiochemistry observed is consistent with the electron-donating influence of the methoxy or acetoxy group, making the C-3 carbon atom more electron deficient. Aromatization of the adducts 6b and 7c was accompanied by an unusual elimination of the amido moiety. Thus, 1-hydroxy and 1-methoxy anthraquinones were obtained. Reactions of the dienes 2 and 5 with benzoquinone gave the tetrahydronaphthoquinones 9 and 10 with an endo stereospecificity. Oxidation of 9 by activated manganese dioxide gave the naphthoquinone 11. These compounds were submitted to in vitro cytotoxic assays towards murine L 1210 leukemia cells and clonogenic human tumor cell line MDA-MB 231. The naphthoquinone derivatives 9, 10 and 11 had significant activities with IC50 less than or equal to 0.4 microgram/ml towards these two tumor cell systems.     

Ionic liquid-catalyzed Diels-Alder reaction of levopimaric acid with quinones

Diels-Alder reactions of levopimaric acid with quinones are strongly accelerated in the presence of ionic liquids (imidazolium salts) as catalyst.     

Diels-Alder reactions II: The Reaction Mechanism

The possible mechanisms of the preparatively so productive Diels-Alder reactions are discussed critically on the basis of experimental data. Although most of the facts can be explained readily by a synchronous mechanism, a number of problems remains.     

Asymmetric intramolecular Diels-Alder reactions of N-acyl-camphor-sultam trienes.

Treatment of triene-imides 4 with EtAlCl₂ at ?20° gave crystalline cycloadducts 5 which furnished enantiomerically pure bicyclic alcohols 9 with regeneration of the chiral auxiliary.     

对映选择催化 Diels-Alder 反应

本文综述了对映选择催化 Diels-Alder 反应的进展。     

The effect of pressure on microwave-enhanced Diels-Alder reactions. A case study

It is demonstrated that microwave-assisted Diels-Alder reactions of substituted 2(1H)-pyrazinones with ethylene are significantly more effective utilizing pre-pressurized (up to 10 bar) reaction vessels.     

Enantioselective organocatalytic intramolecular Diels-Alder reactions. The asymmetric synthesis of solanapyrone D

The first direct enantioselective organocatalytic intramolecular Diels-Alder reaction has been accomplished. The use of iminium catalysis has provided a new catalytic strategy for the enantioselective [4 + 2] cycloisomerization of a wide variety of tethered diene-enal systems. The use of imidazolidinones 1 and 2 as the asymmetric catalysts has been found to mediate the enantioselective construction of [4.4.0] and [4.3.0] ring systems. Application of this methodology to the highly efficient asymmetric synthesis of the marine metabolite solanpyrone D has also been accomplished. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. Importantly, this technology has been utilized to execute the first enantioselective, catalytic Type II IMDA reaction.     

Chemistry of O-Benzoquinones and Masked O-Benzoquinones I. Diels-Alder Reactions of O-Benzoquinones with Dimethyl Acetylenedicarboxylate and Phenylacetylene

Diels-Alder reactions of six o-benzoquinones with dimethyl acetylenedicarboxylate has been examined. The yields of adducts vary with the natures of the o-benzoquinones, 3,4-Di-n-propyl-(1c), 3,6-di-n-propyl (1d). 3. 4-diallyl-(1e) and 3, 6-diallyl-o-benzoquinone (1f) are found to give bicyclic a-diketones exclusively without the formation of 1,4-dioxine derivatives, the yields ranging from 20 to 70%. In the case of 4, 5-dimethoxy-o-benzoquinone, dimethyl 4, 5-dimethoxyphthalate is produced in 42% yield, presumably derived from the decomposition of the corresponding initially formed α-diketone. 3, 6-Di-n-propyl-4, 5-dimethoxy-o-benzoquinone deteriorates without addition to dimethyl acetylenedicarboxylate upon heating. The additions of o-benzoquinones 1c , 1d and 1f to phenylacetylene are also studied. The yields of adducts, α-diketones, range from 23% to 82%.     

Exo-selective Diels-Alder reactions of vinylazepines. Origin of divergent stereoselectivity in Diels-Alder reactions of vinylazepines, vinylpiperideines, and vinylcycloalkenes

Diels-Alder reactions of vinylazepines with N-phenylmaleimide afforded exclusively the exo cycloadduct, while high endo stereoselectivity was observed, as previously reported, in analogous reactions of vinylpiperideines. This curious contrast was confirmed by X-ray analysis of cycloadducts not susceptible to epimerization. The stereoselectivity of Diels-Alder reactions of vinylazepines, vinylpiperideines, and vinylcycloalkenes exhibits surprising divergence depending on the detailed diene structure, and DFT calculations (Becke3LYP) were undertaken to shed light on these observations. The model calculations correctly predict the major stereoisomers in these reactions, though they tend to significantly underestimate the stereoselectivity. The results suggest some general considerations in predicting or controlling the stereochemistry of this class of Diels-Alder reactions.     

Self-activated supramolecular reactions: effects of host-guest recognition on the kinetics of the Diels-Alder reaction of open-chain oligoether quinones with cyclopentadiene

Diels-Alder reactions of acyclic oligoether-substituted quinones 1b, 1c, 2b, and 2c with cyclopentadiene were accelerated by the addition of alkali and alkaline earth metal perchlorates, and scandium trifluoromethane sulfonate (k(c)/k(f) = 1.2-23 for univalent cations, 11-1160 for divalent cations, and 1700-192 000 for Sc(3+), where k(c) and k(f) are the rate constants for the metal complexed and uncomplexed quinones, respectively). The shorter-armed 1a, 2a, and 3, however, exhibited no such acceleration effects. The rate accelerations can be rationalized by the FMO consequence in which the bound guest cation withdraws electron density from the quinone dienophile and lowers the LUMO energy suitable for the orbital interaction with the HOMO of cyclopentadiene. Despite the poor cation selectivity, these acyclic oligoether quinones showed larger rate accelerations than the relevant quinocrown ethers 4 (k(c)/k(f) = 1.3-3.0 for univalent cations, 5.0-160 for divalent cations, and 100-2020 for Sc(3+)). The effective electron withdrawal, which leads to the enhanced rate acceleration, can be caused by the direct interaction between the metal cation accommodated in the pseudo-cyclic oligoether linkage and the quinone carbonyl oxygen, as indicated by (1)H NMR spectroscopy. In addition, the larger rate enhancement is rather achieved in the complex with low binding constant K, because the strong encapsulation of metal cation by the oligoether chain diminishes the crucial interaction to the quinone carbonyl oxygen. As a whole, the smaller and higher valent cations tend to bring about notable rate acceleration due to the more enhanced ion-dipole interaction with the quinone carbonyl oxygen. Spectroscopic titration (absorption and (1)H NMR) and kinetic experiments indicated that only the longest di-armed 2c constructs 1:1, and then 1:2, host/guest complexes with Ca(2+), Sr(2+), and Ba(2+). These 1:2 complexes exhibited the most effective acceleration for the respective metal cations.     

The effect of pressure on hydrogen transfer reactions with quinones

The effect of pressure on the oxidation of hydroarenes 3-9 with 2,3-dichloro-5,6-dicyano-1,4-quinone (DDQ; 1 a) or o-chloranil (10), leading to the corresponding arenes, has been investigated. The activation volumes were determined from the pressure dependence of the rate constants of these reactions monitored by on-line UV/Vis spectroscopic measurements in an optical high-pressure cell (up to 3500 bar). The finding that they are highly negative and only moderately dependent on the solvent polarity (DeltaV( not equal ) = -13 to -25 in MTBE and -15 to -29 cm(3) mol(-1) in MeCN/AcOEt, 1:1) rules out the formation of ionic species in the rate-determining step and is good evidence for a hydrogen atom transfer mechanism leading to a pair of radicals in the rate-determining step, as was also suggested by kinetic measurements, studies of kinetic isotope effects, and spin-trapping experiments. The strong pressure dependence of the kinetic deuterium isotope effect for the reaction of 9,10-dihydroanthracene 5/5-9,9,10,10-D(4) with DDQ (1 a) can be attributed to a tunneling component in the hydrogen transfer. In the case of formal 1,3-dienes and enes possessing two vicinal C--H bonds, which have to be cleaved during the dehydrogenation, a pericyclic hydrogen transfer has to considered as one mechanistic alternative. The comparison of the kinetic deuterium isotope effects determined for the oxidation of tetralin 9/9-1,1,4,4-D(4)/9-2,2,3,3-D(4)/9-D(12) either with DDQ (1 a) or with thymoquinone 1 c indicates that the reaction with DDQ (1 a) proceeds in a stepwise manner through hydrogen atom transfer, analogously to the oxidations of 1,4-dihydroarenes, whereas the reaction with thymoquinone 1 c is concerted, following the course of a pericyclic hydrogen transfer. The difference in the mechanistic courses of these two reactions may be explained by the effect of the CN and Cl substituents in 1 a, which stabilize a radical intermediate better than the alkyl groups in 1 c. The mechanistic conclusions are substantiated by DFT calculations.     

Diels-Alder reactions of fluoroallene. An affirmation of homo-lumo control.

The Diels-Alder reactions of fluoroallene proceed with regiospecific addition to the C₂C₃ bond. Mechanistic implications of these results are discussed.