Enhanced reactivity of tuned imidazolidin-2-one chiral auxiliaries in Diels–Alder reactions

Readily accessible alkyl 1-N-benzoyl-2-oxoimidazolidin-4-carboxylates display enhanced reactivity as efficient chiral auxiliaries in the Diels–Alder reaction of their 3-N-enoyl derivatives.     

Lewis acid mediated asymmetric Diels–Alder reactions of chiral 2-phosphonoacrylates

2-Phosphonoacrylates containing four chiral alcohol auxiliaries were efficiently prepared and evaluated in Lewis acid mediated Diels–Alder reactions. Under the activation of SnCl₄, all reactions performed in CH₂Cl₂ at ?65 °C exclusively afforded the endo (endo-to-carboxylate) cycloadducts with dr’s ranging from 50:50 to >99:1. The best facial selectivity was obtained from the substrate bearing a (?)-phenylmenthyl group, to give adducts as (dr >99:1) or almost as (dr = 99:1) single diastereomers. Detailed strategies for the structural elucidation of the cycloadducts as well as a rationalization of the observed stereoselectivity are described.     

Palladium-catalyzed asymmetric Diels–Alder reactions with novel chiral imino-phosphine ligands

Palladium-catalyzed asymmetric Diels–Alder reactions have been achieved with considerably high enantioselectivity by using chiral imino-phosphine ligands derived from (1S,4R)-(+)-fenchone, (1R,2R,5R)-(+)-2-hydroxy-3-pinanone derivatives, (1S,5R)-(−)-menthone, (1R,4R)-(+)-camphor, and (1S)-(+)-ketopinic acid. A mechanism for the asymmetric induction is proposed on the basis of the stereochemical outcome of the reactions.     

Dynamics of Diels–Alder reactions involving 2-trialkylsilyloxyfurans

Increasing the size of the silyl group on 2-trialkylsilyloxyfurans reduces the rate of Diels–Alder reactions with maleic acid derivatives. While the exo-adduct resulted from the reaction between 2-silyloxyfurans and maleic anhydride, endo-adducts resulted from the reactions with maleate esters. Analysis of transition state structures for the cycloaddition, calculated at the B3LYP/6-31G1 level of theory, revealed significant stretch-mode asynchronicity in the forming bonds, with selectivity arising from steric interactions that affect torsional strain about the shorter of the forming bonds.     

Ring opening of dihydro-2-pyridones and intramolecular Diels–Alder reactions

A new ring-opening reaction of 5,6-dihydro-2-pyridones was discovered. Compounds 1 and 7 were converted to the dienoic amides 2 and 8 by reaction with sodium hydride at room temperature. N-Allylation of compounds 2 and 8 followed by IMDA reaction provided the cis-fused hexahydro-1-indolones 5 and 10, respectively. Treatment of compounds 5 and 10 with DBU in refluxing ethyl acetate gave the conjugated products 6 and 11, which were further transformed to the amides 12–15. The phenylthio group of compound 11 was substituted by a methyl group to give product 16.     

Highly diastereoselective photochemical Diels–Alder reactions: towards the development of a photoactivated chiral auxiliary

Photochemical Diels–Alder additions of maleic anhydride to a homochiral anthracene derivative occur with excellent diastereoselectivity (>95:5) and faster than the corresponding thermal reactions.     

Tandem intramolecular Diels–Alder/retro-Diels–Alder cycloaddition of 2H-chromen-2-one as dienes with the expulsion of CO_2

To study the intramolecular Diels-Alder cycloadditon of 2H-chromen-2-one as a diene, a series of chiral N-allyl-N-benzylamides that contain a 2H-chromen-2-one moiety were designed for the synthesis of benzo[f]isoindol-1-ones via an intramolecular Diels-Alder and a subsequent retro-Diels-Alder cycloaddition with the expulsion of CO₂. Both the yield (80%-89%) and absolute stereocontrol of the tandem reaction were high when an electron-withdrawing group was attached to the dienophile. The double bond in the styrene substructure remained in the products could be further derivatized by dihydroxylation.     

Enantioselective Diels–Alder reactions with left-handed G-quadruplex DNA-based catalysts

Since the discovery of left-handed G-quadruplex(L-G4)structure formed by natural DNA,there has been a growing interest in its potential functions.This study uti...     

Asymmetric Diels–Alder addition of cyclopentadiene to chiral naphthoquinones

Diels–Alder reactions of 1,4-naphthoquinones bearing a chiral auxiliary at C-2, with cyclopentadiene under Lewis acid conditions afforded the corresponding Diels–Alder adducts. High levels of diastereomeric excess were obtained using (R)-pantolactone, (S)-N-methyl-2-hydroxysuccinimide and trans-2-phenylcyclohexanol as auxiliaries. Moderate asymmetric induction was achieved using Oppolzer's camphorsultam and (R)-(+)-4-benzyl-2-oxazolidinone as auxiliaries. X-Ray crystallographic analysis of the pantolactone adduct enabled determination of the stereochemistry of all adducts obtained.     

Diels–Alder reactions of five-membered heterocycles containing one heteroatom

Diels–Alder reactions of five-membered heterocycles containing one heteroatom with an N-arylmaleimide were studied. Cycloaddition of 2,5-dimethylfuran (4) with 2-(4-methylphenyl)maleimide (3) in toluene at 60 °C gave bicyclic adduct 5. Cycloadditions of 3 with 2,5-dimethylthiophene (11) and 1,2,5-trimethylpyrrole (14) were also studied. Interestingly, the bicyclic compound 5 cleanly rearranged, with loss of water, when treated with p-toluenesulfonic acid in toluene at 80 °C to give 4,7-dimethyl-2-p-tolylisoindoline-1,3-dione (6).     

Asymmetric Diels–Alder reactions of optically active oxazolidinone-derived vinylsulfonamides

Chiral vinylsulfonamides bearing an oxazolidin-2-one moiety derived from (R)-2-phenylglycinol and (1R,2S)-norephedrine have been employed as dienophiles in asymmetric Diels–Alder reactions at normal pressure affording d.e.s of up to 99% when EtAlCl₂ or Et₂AlCl were employed as Lewis acids. Theoretical calculations justify the observed enantio- and diastereoselectivity.     

Asymmetric Diels–Alder cycloaddition of a di-P-stereogenic dienophile with cyclopentadiene

The Diels–Alder cycloaddition of the di-P-stereogenic dienophile (S_P,S_P)-1 leads to novel di-P-stereogenic norbornene derivatives and proceeds with moderate diastereoselectivity in the absence of a catalyst. In the presence of TiCl₄, however, the diastereoselectivity was raised to 9:1. The major diastereoisomer has been characterized crystallographically. The separation of the diastereomeric cycloadducts was possible by fractional crystallization in the presence of (?)-O,O-dibenzoyltartaric acid monohydrate.     

Cycloaddition of keteniminium with terminal alkynes toward cyclobuteniminium and their use in Diels–Alder reactions

An efficient access to cyclobutanone derivatives has been developed via a ‘one-pot’ [2+2]/[4+2] sequence involving keteniminium and cyclobuteniminium salts as key intermediates. A broad range of novel cyclobuteniminium salts have been prepared via [2+2] cycloaddition of keteniminium salts and alkynes. The resulting [2+2] adducts were then further transformed by Diels–Alder reaction with various dienes to afford cyclobutanone derivatives in good yields. A density functional theory (DFT) based computational study has been performed to obtain insight into the nature of the cycloaddition reactions and to investigate the difference in reactivity of cyclobuteniminium salts. Finally, the usefulness of cyclobutanone derivatives has been demonstrated by ring expansion reactions affording lactone, lactame, and cyclopentanone derivatives.     

Enthalpies of the Diels–Alder reactions of a series of dienes with tetracyanoethylene and 4-phenyl-1,2,4-triazoline-3,5-dione

Russian Chemical Bulletin - The enthalpies of the Diels–Alder reactions of twenty dienes with two active dienophiles, tetracyanoethylene and 4-phenyl-1,2,4-triazoline-3,5-dione, are compared,...     

Stereoselective hetero Diels–Alder reactions of chiral tricarbonyl (η6-benzaldehyde)chromium complexes

The ZnCl₂-promoted cycloaddition of a series of enantiopure ortho-substituted benzaldehyde–Cr(CO)₃ complexes and Danishefsky's diene gave the corresponding 2-aryl pyranones in good yields and complete enantiospecificity. Some of the mechanistic aspects of the cycloaddition were investigated and the reaction extended to different dienes.     

Asymmetric Diels–Alder reactions of 2-fluoroacrylic acid derivatives. Part 1: The construction of fluorine substituted chiral tertiary carbon

For the construction of chiral monofluorinated tertiary carbons, we have examined the asymmetric Diels–Alder reaction of 2-fluoroacrylic acid derivatives bearing a chiral oxazolidinone moiety. Under diethylaluminum chloride catalyzed conditions at −100°C, the reaction of 1 with isoprene proceeded smoothly with high diastereoselectivity.     

New chiral amino acid-derived α-acyloxynitroso reagents for asymmetric nitroso Diels–Alder reactions

The preparation of new chiral α-acyloxynitroso derivatives 4a–e as chiral dienophiles for the nitroso Diels–Alder reaction is reported. These compounds are obtained from amino acid-derived iodobenzene dicarboxylates and ketoximes, and are stable and easy-to-handle reagents. Initial studies for their nitroso Diels–Alder reactions with cyclohexadiene are also reported.     

Diels–Alder reactions of directly C3-dieneylated chlorophyll derivatives

The [4π?+?2π] cycloaddition of methyl 3-(1,3-butadien-1/2-yl)pyropheophorbides-a with tetracyanoethylene, dimethyl acetylenedicarboxylate, and naphthoquinone gave the corresponding Diels–Alder reaction adducts. The trans-1-substituted 1,3-butadiene was more reactive than its regioisomeric 2-substituent. The oxidation of some cycloadducts gave C3-arylated chlorophyll derivatives, whose ortho-substitution blue-shifted the corresponding Qy absorption maxima in dichloromethane because of the steric repulsion between the aryl and chlorin π-planes.     

Studies directed towards anthracyclinone syntheses: The use of d-glucose as a chiral auxiliary in asymmetric Diels–Alder reactions

Setting up the correct functionality with the correct stereochemistry in the ring-A of anthracycline precursors represents a synthetic challenge. The use of d-glucose as a chiral auxiliary either on the silyloxy diene or naphthoquinone-based dienophile to form the ring-A using asymmetric Diels–Alder reactions as developed by the Stoodley group and is the focus of this review. The endo-transition state is described based on a frontier orbital approach and the HOMO–LUMO energy gaps were estimated using semi-empirical (MNDO) calculations with SPARTAN’08. As anthracyclines are used in chemotherapy, some of their associated biochemistry and clinical effectiveness are also briefly introduced.