Diels-Alder reaction of 1,3-butadiene derivatives with 1-methyl-2(1H)-quinolones having an electron-withdrawing group at the 4-position.

Diels-Alder reactions of 1-methyl-2(1H)-quinolones having an electron-withdrawing group at the 4-position with isoprene, butadiene sulfone, and cyclohexadiene were performed to yield functionalized phenanthridones stereoselectively at atmospheric and at high pressure. Regioselectivity and stereochemistry of a methoxycarbonyl group were studied using the semi-empirical and ab initio MO methods, respectively.     

Synthesis of 5(6H)-phenanthridones using Diels-Alder reaction of 3-nitro-2(1H)-quinolones acting as dienophiles

Diels-Alder reactions of 3-nitro-2(1H)-quinolones with 1,3-butadiene derivatives were carried out to give the phenanthridone derivatives under both atmospheric and high pressure conditions. Furthermore, the reactivity of 3-substituted 2(1H)-quinolones acting as a dienophile with 2,3-dimethyl-1,3-butadiene was examined using molecular orbital (MO) calculation.     

Synthesis of phenanthridones using Diels-Alder reactions of 4-substituted 2(1H)-quinolones acting as dienophiles

Diels-Alder reactions of 2(1H)-quinolones having an electron-withdrawing group at the 4-position with 1,3-butadiene derivatives were carried out to give the phenanthridones richly functionalized under the conditions of atmospheric and high pressure. Furthermore, the reactivities of 4-substituted 2(1H)-quinolones acting as a dienophile were examined using MO calculation.     

Cycloadditions of 1-substituted 1,3-butadienes with 4- or 3-substituted 2(1H)-quinolones acting as dienophiles

Cycloadditions of 1,3-butadiene derivatives having an electron-rich group at the 1-position with 4- or 3-substituted 2(1H)-quinolones were carried out to give the richly functionalized phenanthridines under both atmospheric and high pressure conditions. Furthermore, the reactivity of 4- or 3-substituted 2(1H)-quinolones acting as a dienophile with 1-substituted dienes was examined using MO calculation.     

Synthesis of isoquinoline derivatives by Diels-Alder reactions of 2(1H)-pyridones having an electron-withdrawing group with methoxy-1,3-butadienes

Diels-Alder (DA) reactions of 2(1H)-pyridones having an electron-withdrawing group at the 4-position with 2,3-dimethoxy- and 2-methoxy-1,3-butadienes gave isoquinoline derivatives. Furthermore, an isoquinoline alkaloid (6,7-dimethoxy-2-methyl-1(2H)-isoquinolone) was synthesized by elimination of hydrogen cyanide and dehydrogenation of the DA-adduct having a cyano group at the 4a-position.     

Synthesis of optically active 2-alkoxy-2H-pyran-3(6H)-ones. Their use as dienophiles in Diels-Alder cycloadditions.

Optically active 2-alkoxy-2H-pyran-3(6H)-ones (4a-d) were synthesized in one step by the tin(IV) chloride-promoted glycosylation and rearrangement of the 2-acetoxy-3,4-di-O-acetyl-D-xylal (3) prepared from D-xylose (1). The absolute configuration of the new stereocenter at C-2 was determined by chemical transformation of the dihydropyranones 4a and 4b into the known alkyl pentopyranosides (7a and 7b, respectively). Also, from (1)H NMR experiments using a chiral ytterbium shift reagent, the enantiomeric excesses for 4a (>86%) and 4b (>77%) were established. Enantiomerically pure 4c and 4d were obtained by reaction of 3 with chiral 2-octanol (R and S, respectively). Dihydropyranones 4a-d were employed as dienophiles in Diels-Alder cycloadditions with 2,3-dimethylbutadiene and butadiene. Under thermal conditions, only moderate yields (approximately 50%) of cycloadducts 9a-c and 10a were respectively obtained with good diastereofacial selectivity (>80%). Optimized Lewis acid promoted cycloadditions led to 9a-d and 10a,c in higher yields (approximately 80%) and with higher diastereoselectivities (>94%). The major products were formed by approach of the dienes from the less hindered face of the dihydropyranones, and the minor products (such as 11a) were formed by addition from the opposite side. Furthermore, cycloadduct 9a was stable in an alkaline solution, whereas 11a underwent epimerization under the same conditions.     

Diels-alder reaction of 2(1H)-pyridones acting as dienes

Diels-Alder reactions between N-phenylmaleimide, acting as the dienophile, and 2(1H)-pyridones having a methoxy or a chloro substituent, were carried out, under atmospheric and high pressure conditions, to give the corresponding isoquinuclidine derivatives. Stereoselectivity of the Diels-Alder reactions was studied using molecular orbital calculations.     

Synthetic applications of alpha-fluoroalkylated enones. 1. Use as dienophiles in Diels-Alder cycloadditions

Beta-fluoroalkylated enones are efficient dienophiles in Diels-Alder cycloadditions to prepare various fluorinated cylic compounds. However, the presence of the fluoroalkyl moiety modifies the reactivity and the selectivity of these cycloadditions.     

Tuning the reactivity and chemoselectivity of electron-poor pyrroles as dienophiles in cycloadditions with electron-rich dienes

Activation by Lewis acid catalysis and high pressure allows pyrrole derivatives to react with electron-rich dienes in normal electron demand [4+2] cycloadditions, provided that the aromatic ring is substituted by at least two electron-withdrawing groups. The dienophilic behavior of the heterocycle is expressed through the involvement of either the aromatic carbon-carbon double bond in an all-carbon process or the carbonyl moiety of the substituent in a heterocycloaddition reaction. In this regard, the nature of the heterocyclic substituents is shown to have a dramatic influence and to direct both the reactivity and the chemoselectivity of the cycloaddition.     

Electrostatic interactions between substituents as regioselectivity control elements in Diels-Alder cycloadditions. A DFT study of cycloadditions of 1-methoxy-4-trimethylsiloxy dienes with acrylonitrile

The regioselectivities of Diels-Alder reactions of 1-methoxy-4-trimethylsiloxy-1,3-butadiene and the corresponding o-xylylene with acrylonitrile were explored with density functional theory. The transition state of the reaction of the diene with acrylonitrile was studied in both the gas phase and in a low dielectric (epsilon = 2.247) solvent. The regioselectivities of these reactions are predicted to be controlled by the direct electrostatic interactions between the diene and dienophile substituents. The electron-donating capacities of methoxy and trimethylsiloxy substituents are shown to be very similar and to not contribute to regioselectivity control. A prediction is made that the cycloadditions of the o-xylylene will be unselective, while 1-methoxy-4-trimethylsiloxy-1,3-butadiene will give a small preference ( approximately 5:1) in favor of the proximal methoxy and cyano groups. The thermochromic behavior of trans-disubstituted disiloxy benzocyclobutene was also explored.     

Investigation of the Diels-Alder cycloadditions of 2(H)-1,4-oxazin-2-ones

[Reaction: see text]. A variety of 5-chloro-2(H)-1,4-oxazin-2-ones bearing a range of substituents at their 3- and 6-positions undergo Diels-Alder cycloaddition as a 2-azadiene component with electron-rich, electron-deficient, and electron-neutral dienophiles. These reactions proceed with moderate regio- and stereoselectivity to afford relatively stable and readily isolable bridged bicyclic lactone cycloadducts. Chemical manipulation of these cycloadducts affords highly substituted and functionally rich piperidines. The regio- and stereochemical preferences of the cycloadditions of 5-chloro-2(H)-1,4-oxazin-2-ones are investigated computationally using density functional theory (B3LYP/6-31G).     

Highly selective Diels-Alder reactions of dienophiles with 1, 3-cyclohexadiene mediated by Yb(OTf)(3).2H(2)O and ultrahigh pressures

[reaction: see text] Ultrahigh pressures and catalytic Yb(OTf)(3).2H(2)O were found to mediate Diels-Alder reactions of various electron-deficient dienophiles with 1,3-cyclohexadiene to produce endo-bicyclo[2.2. 2]oct-2-enes in moderate to excellent yield and selectivity. The proposed total synthesis of hapalindole Q based on bicyclo[2.2. 2]oct-2-ene construction by Diels-Alder reaction and subsequent olefin cleavage is outlined. Preliminary results demonstrating the viability of this strategy are presented.     

Diels-Alder reactions of nickel(II) N-confused porphyrins as dienophiles

Diels-Alder reactions of nickel(II) N-confused tetraarylporphyrins as dienophiles with o-benzoquinodimethane yield nickel(II) N-confused isoquinoporphyrins.     

Studies on inverse electron demand hetero Diels-Alder reaction of perfluoroalkyl 2(1H) pyridones with different dienophiles under microwave irradiation

The reaction of N-acetyl perfluoroalkyl substituted 2(1H) pyridones (7) with dimethylacetylenedicarboxylate (DMAD) on neutral alumina under solvent free microwave irradiation conditions extended to undergo an inverse electron demand hetero Diels-Alder reaction, however resulted exclusively in E, Z isomers (3:1) of Michael-type N-adducts (8). The similar reaction in case of 7a under thermal and photochemical conditions also gave the same products.     

Oxygenation of 2,6-di- -butylphenols bearing electron-withdrawing group at 4-position mediated by Co(II)-schiff base complex

4-Acyl-2,6-di- -butylphenols except 3,5-di- -butyl-4-hydroxybenzaldehyde were oxygenated in the presence of Co(Salpr) exclusively at the ortho position to give the corresponding 3,5-di- -butyl-6-hydroperoxy-2,4-cyclohexadienone derivatives in quantitative yield.     

An experimental and computational investigation of the Diels-Alder cycloadditions of halogen-substituted 2(H)-pyran-2-ones

[reaction: see text] Diels-Alder reactions of 3- and 5-halo-subsituted 2(H)-pyran-2-ones with both electron-rich and electron-deficient dienophiles afford stable and readily isolable bridged bicyclic lactone cycloadducts. These cycloadditions proceed with excellent regioselectivity and very good stereoselectivity. In contrast, Diels-Alder reactions of 4-halo-subsituted 2(H)-pyran-2-ones afford cycloadducts which are very prone to loss of bridging CO(2) and the subsequent formation of barrelenes ([2.2.2]cyclooctenes). Furthermore, these cycloadditions proceed with only moderate regio- and stereoselectivity. For both series of the 3- and 5-halo-subsituted 2(H)-pyran-2-ones and 4-halo-subsituted 2(H)-pyran-2-ones, the reactivity patterns do not significantly change between the halogens. The regio- and stereochemical preferences of the cycloadditions of halo-substituted 2(H)-pyran-2-ones are investigated computationally. Calculations were carried out on the transition states leading to the four possible regio- and stereoisomeric cycloadducts by using density functional theory (B3LYP/6-31G). These studies allow prediction of the regio- and stereoselectivity in these reactions which are broadly in line with experimental observations.     

Computational and experimental investigation of the Diels-Alder cycloadditions of 4-chloro-2(H)-pyran-2-one

4-Chloro-2(H)-pyran-2-one undergoes thermal Diels-Alder cycloaddition with electron-deficient dienophiles to afford, without any significant selectivity, 6-endo- and 5-endo-substituted bicyclic lactone cycloadducts. In contrast to 3- and 5-bromo-2(H)-pyran-2-one, 4-chloro-2(H)-pyran-2-one does not undergo thermal cycloadditions with electron-rich dienophiles. The regio- and stereochemical preferences of the cycloadditions of 4-chloro-2(H)-pyran-2-one and other related 2(H)-pyran-2-ones are investigated computationally. Calculations were carried out on the transition states leading to the four possible regio- and stereoisomeric cycloadducts using density functional theory (B3LYP/6-31G). These studies allow prediction of the regio- and stereoselectivity in these reactions which are in line with experimental observations.     

Captodative α,β-unsaturated oxazolines as dienophiles in the asymmetric Diels-Alder reaction

Captodative oxazoline derivative 5a gave rise to four-cycloadducts 6, 7, 8 and 9 in the presence of trifluoroacetic anhydride and cyclopentadiene. Hydrolysis of 6 led to α-phenylthio carboxylic acid 14.     

Synthesis of benzo-halogenated 4-hydroxy-2(1H)-quinolones

Malondianilides 3 derived from dichloro substituted anilines 2 undergo cyclization to afford 4-hydroxy-2(1H)-quinolones 4 in very good yields using methane sulfonic acid-phosphorus pentoxide as catalyst. 3,4-Dichloro anilines 5 can be shown to yield two isomers, 7 and 8 , whereas 3-substituted anilines 9 afford merely 7-substituted 4-hydroxy-2(1H)-quinolones 11.