Camphor-derived sulfonylhydrazines: catalysts for Diels-Alder cycloadditions

Camphor-derived sulfonylhydrazines proved to be very active for organocatalyzed Diels-Alder cycloadditions with cyclopentadiene. Good chemical yields and enantiomeric excesses up to 89% and 88% are obtained for endo/exo adducts.     

Investigation of the exo and endo isomers of dioxolane-type benzylidene derivatives of carbohydrates by 13C NMR spectroscopy

The absolute configurations of nine 2,3-O-benzylidene-α-L-rhamno- and α-D-mannopyranoside diasteteomeric pairs were determined and the ¹³C NMR spectra of further thirteen α-L-rhamno- and α-D-mannopyranosides, having various substituents, were completely assigned.Four ¹³C shifts were found suitable for the determination of the absolute configuration of the dioxolane skeleton. (1) The chemical shift of the acetal carbon in the endo isomers is between 103.9 and 104.7 ppm whereas for the exo isomers this region extends from 102.8 to 103.4 ppm; (2) The formation of the dioxolane ring causes a deshielding effect for the bridgehead carbons, in the exo isomers this effect is more pronounced for C-3 whereas in the endo isomers for C-2. For C-4, shielding effect was found in the exo isomers and deshielding effect in the endo ones; (3) The chemical shift of the quaternary carbon of the phenyl group is greater in the exo isomers than in the endo ones; (4) The difference between the shift of the acetal carbon and that of the quaternary carbon of the phenyl group in the exo isomers is greater than 35.4 ppm, in the endo isomers is less than 33.7 ppm.     

[4 + 2] Cycloaddition reactions of hexachlorotropone

The cycloaddition of hexachlorotropone to selected olefins, including 1,3-dienes, has been examined. Unlike tropone, which undergoes [6 + 4] cycloadditions with 1,3-dienes, only [4 + 2] processes were observed with hexachlorotropone. Its apparent preference for exo-addition (contrast tetrachlorocyclopentadienone) probably results from thermodynamic control of the endo : exo product ratios.     

Influence of the side chain protecting group on the stereoselectivity of the 1,3-dipolar cycloaddition of d-talo-configured nitrones

Two new five-membered cyclic d-talo-configured nitrones were synthesized from d-mannose, and examined in 1,3-dipolar cycloadditions with vinyl acetate and vinylene carbonate. The stereoselectivity of the cycloadditions depends greatly on the protecting group of the vicinal diol attached to the nitrone C-5 carbon atom. Methyl protection resulted in limited syn/anti-selectivity, giving mixtures of the two isomeric exo-syn and exo-anti isoxazolidines in comparable amounts. On the other hand, the cyclohexylidene-substituted nitrone reacted more selectively in favour of the syn isomer. The difference in the diastereoselectivity was attributed to the specific spatial orientation of the nitrone C-5 substituent.     

Stereoselective additions to the exocyclic CC bond of some α-alkylidene-(+)-camphor derivatives

Stereoselective additions to the exocyclic CC double bond of some (1R,3E,4S)-3-alkylidene-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and (1R,4E,5S)-4-alkylidene-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones were studied. All additions took place predominantly from the less hindered endo-face of the methylidene compounds to give the corresponding exo-adducts as the major isomers. Thus, catalytic hydrogenations afforded the α-alkylated (1R,3R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and (1R,4R,5R)-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-ones in 28–100% de. Similarly, 1,3-dipolar cycloadditions of 2,4,6-trisubstituted benzonitrile oxides gave the corresponding spiro cycloadducts in 66–100% de. The structures were determined by 2D NMR techniques, NOESY spectroscopy and X–ray diffraction.     

8-Azabicyclo[3.2.1]oct-3-en-2-ones via asymmetric 1,3-dipolar cycloaddition of a homochiral 3-oxidopyridinium betaine

8-Azabicyclo[3.2.1]oct-3-en-2-ones were prepared by asymmetric 1,3-dipolar cycloadditions of homochiral pyridinium betaine 4. Excellent diastereofacial selectivity was achieved for the major 6-exo cycloadducts. The absolute stereochemistry of cycloadduct 7 was confirmed by a single-crystal X-ray diffraction study.     

A new route to the synthesis of isoxazoline derivatives from dihydropyran via cycloaddition reaction in ionic liquid

A new approach to the synthesis and 1,3-dipolar cycloadditions of nitrones has been described from 2,3-dihydro-4H-pyran and various hydroxylamines, with electron-deficient alkynes for the synthesis of isoxazoline derivatives. Significant rate acceleration and improved yields of exclusively exo isoxazolines in 1-butyl-3-methylimidazolium based ionic liquids have been observed. Novel isoxazolines may be used as a precursor for the synthesis of variety of peptides.     

Domino Diels-Alder reactions of N-methoxyethyl-7-oxa-norbornadiene-2,3-dicarboximide: an elusive, highly reactive dienophile

Flash vacuum pyrolysis (FVP) has been used to generate the novel 7-oxa-norbornadiene-2,3-dicarboxylic imide that in situ gave an unprecedented cycloaddition reaction cascade with the imidofuran, a side-product of FVP. Stereoselectivity of cycloadditions was studied with the aid of density functional calculations, which fully support observed exo/endo-selectivity.     

Hetero Diels-Alder reaction: a novel strategy to regioselective synthesis of pyrimido[4,5-d]pyrimidine analogues from Biginelli derivative

A number of potent pyrimido[4,5-d]pyrimidine analogues have been efficiently synthesized by hetero Diels-Alder cycloaddition of 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid methyl ester, a Biginelli compound with N-arylidine-N′-methylformamidines and N-arylidine guanidine in dry toluene. Structures of the newly obtained cycloadducts were established on the basis of elemental and spectral (IR, NMR and Mass) data. The molecular mechanism of the observed cycloaddition reaction has been investigated theoretically by means of PM3 semiempirical method. Transition state structure determinations and activation energy calculations have shown the preference for the endo approach over the exo approach of dienophile towards the diene fragments used, which is consistent with the experimental results. The studied cycloadditions proceed via an asynchronous concerted mechanism. It was demonstrated that FMO theory could reasonably predict the relative reactivities between dienes as well as indicating that these reactions belong to normal Diels-Alder type cycloadditions.     

Cycloadditions of chiral carbonyl ylides with imine dipolarophiles as a route to enantiomerically pure α-amino-β-hydroxy acids

The preparation of enantiomerically pure threo-β-amino-α-hydroxy acids via 1,3-dipolar cycloadditions of imine dipolarophiles with the chiral isomünchnone derived from (5R)-5-phenylmorpholin-3-one 1 is described. The cycloadducts were obtained with excellent diastereofacial- and exo-selectivity. Subsequent hydrolysis and chemoselective exocyclic amide cleavage afforded the threo-β-amino-α-hydroxy acids with recovery of the initial chiral auxiliary.     

Hydrogen-Bond-Assisted Diels–Alder Kinetics or Self-Healing in Reversible Polymer Networks? A Combined Experimental and Theoretical Study

Diels–Alder (DA) cycloadditions in reversible polymer networks are important for designing sustainable materials with self-healing properties. In this study, the DA kinetics of hydroxyl-substituted bis- and tetrafunctional furans with bis- and tris-functional maleimides, both containing ether-functionalized spacers, is investigated by modelling two equilibria representing the endo and exo cycloadduct formation. Concretely, the potential catalysis of the DA reaction through hydrogen bonding between hydroxyl of the furans and carbonyl of the maleimides or ether of the spacers is experimentally and theoretically scrutinized. Initial reaction rates and forward DA rate constants are determined by microcalorimetry at 20 °C for a model series of reversible networks, extended with (i) a hydroxyl-free network and hydroxyl-free linear or branched systems, and (ii) polypropylene glycol additives, increasing the hydroxyl concentration. A computational density-functional theory study is carried out on the endo and exo cycloadditions of furan and maleimide derivatives, representative for the experimental ones, in the absence and presence of ethylene glycol as additive. Additionally, an ester-substituted furan was investigated as a hydroxyl-free system for comparison. Experiment and theory indicate that the catalytic effect of H-bonding is absent or very limited. While increased concentration of H-bonding could in theory catalyze the DA reaction, the experimental results rule out this supposition.     

Evaluation of ethyl 2-carbomethoxyethenesulfinates as 2-hydroxymethyl enethiol equivalents in the Diels-Alder reaction

Z- and E-ethyl 2-carbomethoxyethenesulfinates 1 and 2 hold the potential to be enethiol equivalents by way of Diels-Alder cycloaddition chemistry followed by reduction. To pursue this, both dieneophiles were subjected to thermal and Lewis acid mediated [4+2] cycloadditions with a number of dienes. Yields of cycloadduct ranged from 34 to 94%, with cycloadditions of the aromatic dienes proceeding in moderate yields, presumably due to the reversibility of the reactions. Many cycloadducts were obtained as a mixture of sulfur epimers, but these isomers were unified in the subsequent reduction step. Using either LAH or DIBAL, the cycloadducts were reduced providing β-mercapto (or sulfanyl) carbinols in 32-97%. The sequence of two reactions places sulfur and hydroxy functional groups in set relative stereochemistry within a 6-membered ring.     

The predictable behaviour of cations deriving from endo-4-chlorotetracyclo[3.3.0.0.2,8O.3,6]octane.

Silver cation-initiated ionization of the title compound in aqueous dioxane gives the exo and endo-tetracyclo[3.3.0.0.^2,8O.^4,6]octane-3-ols (35 and 65%). Thermal isomerization in chloroform gives the exo and endo isomers of 4-chlorobicyclo[3.2.1]octa-2,6-dienes (3.5 and 1.5%) and 6-chlorotricyclo[3.2.1.0.^2,7]oct-3-ene (90 and 5%). The behaviour of the cations involved is compatible with MINDO/3 calculations.     

Iron carbonyl complexes of 2,3,5,6-tetrakis(methylene)-7-oxabicyclo[2.2.1]heptane. Crystal and molecular structure of (C10H10O)Fe(CO)3 and (C9H10CO)Fe2(CO)6

The reaction of 2,3,5,6-tetrakis(methylene)-7-oxabicyclo[2.2.1]heptane (I) with iron carbonyls in various solvents yields the (η⁴-1,3-diene)Fe(CO)₃ isomers (II: exo; III: endo) and the bimetallic isomers bis[(η⁴-1,3-diene)Fe(CO)₃] (IV: bis(exo); V: endo,exo). In weakly coordinating solvents, a parallel rearrangement of I occurs through CO bond cleavage of the allylic ether by Fe₂(CO)₉ yielding an unsaturated ketone (VI) bonded to two Fe(CO)₃ groups through a trimethylenemethane and a 1,3-diene system, respectively. The geometries of III and VI have been ascertained by X-ray crystal structure determinations.     

Rhodium catalyzed,one-pot,three component redox-neutral process towards fused ring heterocycles

A three component, rhodium-catalyzed isomerisation/1,3-dipolar cycloaddition reaction is described for the synthesis of fused ring heterocycles as endo/exo isomers, with the formation of three new bonds and four stereocenters.     

Fully regio- and endo-stereoselective synthesis of new polycyclic allylic sulfides via a Diels-Alder reaction. Synthetically useful transformations of these sulfides

Thermal and Lewis acid catalyzed cycloadditions of (Z)-1,2-diheterosubstituted-1,3-dienes to a variety of dienophiles are described. Both endo/exo and regioselectivity have been investigated. In all cases cycloaddition reactions exhibited full regio- and endo-stereoselectivity. The obtained cycloadducts are new polycyclic allylic sulfides carrying much structural and stereochemical informations. Work on transformation of the adducts, mainly to the corresponding new 1,3-dienes and aromatic compounds, is also presented.     

Porphyrines synthètiques porteuses de chaines laterales peptidiques - II : Synthèse et etude comparée des cis et trans (mésotétraphénylporphyrinyl)-3-propénamides

The synthesis and structural properties are reported for mesotetraphenylporphyrin cis and trans 3-propenamide, obtained by condensation of amines or C-protected amino-acids with corresponding carboxylic acids by means of the BOP reagent. The mesotetraphenylporphyrin cis 3-propenoic acid yields cis endo and cis exo atropoisomers. These structural attributions were based on their spectral properties (NMR and circular dichroism). Cis endo and cis exo isomers may be equilibrated in refluxing toluene. The trans 3- propenoic mesotetraphenylporphyrin acid yields only one isomer.     

A novel transformation of 1-exo-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones with sulfoxonium ylide to highly strained 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans

When 1-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones (1) were treated with dimethylsulfoxonium methylide, 1-endo isomers (endo-1) gave 1-substituted 3-aroyl-1,2,4a,9b-tetrahydrodibenzofuran-4-ols (2) exclusively as expected. On the other hand, 1-exo isomers (exo-1) underwent a novel transformation to 1-substituted 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans (3), together with 2.     

High pressure and thermal Diels-Alder reactions of 5-nitro[2.2]paracyclophanepyran-6-one

The Diels-Alder reactions of 5-nitro[2.2]paracyclophanepyran-6-one with 1,3-butadienes and 1,2-dihydro-3-vinyl-naphthalene were examined under thermal and high-pressure conditions. The cycloadditions with 1,3-butadienes occurred in good yield and anti-exo diastereoselectively only under high-pressure conditions; the one with 1,2-dihydro-3-vinyl-naphthalene afforded comparable yields of mixtures of anti/syn adducts under normal and high-pressure conditions. A structural analysis of the reaction products by ¹H and ¹³C NMR spectroscopy is presented.     

Selective Modification of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) through Diels–Alder Cycloadditions on Dehydroalanine Residues

We report the late-stage chemical modification of ribosomally synthesized and post-translationally modified peptides (RIPPs) by Diels–Alder cycloadditions to naturally occurring dehydroalanines. The tail region of the thiopeptide thiostrepton could be modified selectively and efficiently under microwave heating and transition-metal-free conditions. The Diels–Alder adducts were isolated and the different site- and endo/exo isomers were identified by 1D/2D ¹H NMR. Via efficient modification of the thiopeptide nosiheptide and the lanthipeptide nisin Z the generality of the method was established. Minimum inhibitory concentration (MIC) assays of the purified thiostrepton Diels–Alder products against thiostrepton-susceptible strains displayed high activities comparable to that of native thiostrepton. These Diels–Alder products were also subjected successfully to inverse-electron-demand Diels–Alder reactions with a variety of functionalized tetrazines, demonstrating the utility of this method for labeling of RiPPs.