Exo Selectivity Research Articles

NMR Studies on 1,3-Dipolar Cycloaddition of Nitrile Oxides to Norbornenes

The 1,3-dipolar cycloaddition reaction of nitrile oxides to norbornenes substituted with an acrylate-derived moiety was examined. Only adducts to norbornene system were formed with a good exo selectivity and complete site-selectivity. Structures of the products were elucidated by an extensive application of electrospray ionization-mass spectrometry (ESI-MS) and 2D 1H and 13C nuclear magnetic resonance (NMR).

Stereo-Selective Synthesis of 5-Norbornene-2-<i>exo</i>-carboxylic Acid—Rapid Isomerization and Kinetically Selective Hydrolysis

Simple and efficient stereo-selective synthesis of exo-5-norbornene-2-carboxylic acid (NBCA) is reported. Preliminary studies on base promoted isomerization of methyl 5-norbornene-2-carboxylate (MNBC) revealed that rapid isomerization was accomplished with sodium tert-butoxide (tBuONa), and the exo-content at the equilibrium was ca. 60%. The hydrolyses of endo-rich MNBC (endo/exo = 80/20) under various conditions were carried out. The exo selectivity for resulting NBCA was improved when the hydrolysis was conducted with equimolar water at room temperature in the presence of the stronger base (tBuONa) (endo/exo: 18/82). Whereas the use of excess amount of water led to rapid and non-selective hydrolysis affording high endo content of the product. The plausible reaction mechanism involving rapid equilibrium of thermodynamic isomerization and kinetically preferred hydrolysis of exo ester is proposed.

Simple Silver Salts and Palladium Bis(N-heterocyclic carbene) Complexes As Complementary Catalysts for the Nazarov Cyclization

Simple silver salts and dicationic palladium bis(N-heterocyclic carbene) complexes were found to be effective and complementary catalysts for Nazarov cyclizations of divinyl β-keto esters. A sterically hindered palladium bis(NHC) catalyst provided remarkable endo:exo selectivity in cyclizations of cyclohexenyl β-keto esters, whereas AgSbF6 gave improved yields with electron-deficient substrates. The high activities observed with silver salts are significant, given their widespread use as additives in catalytic Nazarov reactions.

Exo‐Selective Asymmetric Diels–Alder Reaction of 2,4‐Dienals and Nitroalkenes by Trienamine Catalysis

Raising the HOMO: 2,4-Dienals can react with nitroalkenes in trienamine-catalyzed asymmetric Diels–Alder reactions (see scheme). Crucial for the success is raising the HOMO energy of the diene through the introduction of appropriate substituents. The reaction exhibits unusually high enantioselectivity and exo selectivity; endo addition is possibly disfavored because of the electrostatic repulsion shown in the scheme.

Exo-Selective Asymmetric Inverse-Electron Demand Hetero-Diels-Alder Reaction Catalyzed by Cu(II)-Hydroxy Oxazoline Ligands

Cu(II) complexes of hydroxy oxazolines derived from (+)-(S)-ketopinic acid catalyze the asymmetric hetero-Diels-Alder cycloaddition of enol ethers and β,γ-unsaturated α-keto esters. The reaction takes place with unprecedented exo selectivity providing 2,4-trans-disubstituted chiral 2,3-dihydropyrans with up to 88% ee.

Unexpected exo selectivity for an intramolecular Diels–Alder reaction involving a doubly-activated δ-pentenolide dienophile

The intramolecular Diels–Alder cyclization of a homochiral doubly-activated δ-pentenolide system is described, proceeding predominantly via an exo transition state to provide an advanced precursor toward unique stereochemical analogs of (+)-symbioimine.

N-(2-Pyridylmethyl)imines as Azomethine Precursors in Catalytic Asymmetric [3 + 2] Cycloadditions

An efficient Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition of N-(2-pyridylmethyl) imines has been developed. In the presence of a Cu(CH(3)CN)(4)PF(6)/bisoxazoline catalyst system, high levels of enantioselectivity (up to 97% ee) and moderate to high exo selectivity were achieved with a wide variety of substituted dipolarophiles, including maleimides, fumarates, fumarodinitrile, enones, and nitroalkenes. The reaction with unsymmetrically substituted dipolarophiles is completely regioselective.

Asymmetric Hydroformylation of an Enantiomerically Pure Bicyclic Lactam: Efficient Synthesis of Functionalised Cyclopentylamines

Customising a bicycle: Rh-catalysed asymmetric hydroformylation of a bicyclic lactam, 2-azabicyclo-[2.2.1]hept-5-en-3-one, was investigated. The use of a chiral diphosphite ligand, (R,R)-Kelliphite, enables excellent selectivity towards one regioisomer combined with excellent productivity and perfect exo selectivity. The products are versatile precursors to highly desired functionationalised cyclopentylamines (see scheme).

Ionic liquids - deanol derivatives as the Diels-Alder reaction solvents

Abstract The Diels-Alder reaction between cyclopentadiene and dienophiles in deanol derivatives containing bis(trifluoromethylsulfonyl)imide anion as media have been studied. The effect of the substituents attached to the cation on the endo:exo selectivity as well as the reaction yield have been evaluated in the absence and presence of Lewis acid catalyst - Y(OTf)3. Catalytic activity of metal triflates and the recycling of chosen catalytic systems have also been investigated

ChemInform Abstract: exo-Selective Diels-Alder Reactions Mediated by Et2AlCl in the Presence of H2O.

Abstract Diels-Alder reactions of 4-triisopropylsilyloxy-2H-thiopyran with N-(2-propenoyl)-2-oxazolidones are promoted by Lewis acids. Unusually high exo selectivity is observed when Et2AlCl in the presence of H2O is used as the Lewis acid. The involvement of the sulfur atom with the bidentate Lewis acid dichlorodiethyl-μ-oxodialuminum is postulated.

ChemInform Abstract: High Degree of Exo Selectivity in Imino Diels-Alder Reactions Catalyzed by tert-Butyldimethylsilyl Triflate.

ChemInform Abstract: High Degree of Exo Selectivity in Imino Diels-Alder Reactions Catalyzed by tert-Butyldimethylsilyl Triflate.

ChemInform Abstract: Diastereoselective Addition Reactions of Racemic Chiral Vinyl Sulfimides.

S-Aryl S-vinyl sulfimides are prepared by a new method via Horner–Wadsworth–Emmons reagents generated in situ. Lewis acid-catalysed Diels–Alder reaction of S-ethenyl-S-phenyl-N-tosylsulfimide with cyclopentadiene leads to the endo anti product with good diastereofacial and endo–exo selectivities. A range of alcohols and amines, with the limitation that they be practically usable in large excess, add to β-aryl vinyl sulfimides with modest diastereoselectivity. The major products of both the cycloaddition and the nucleophilic additions are rationalised by a model invoking addition to the least-hindered face of the s-cisconformation of the vinyl sulfimide.

ChemInform Abstract: Diels-Alder Reaction of Sugar-Derived Cyclic Dienophiles with Cyclopentadiene. Factors Affecting the Reactivity and Stereoselectivity.

[formula: see text] A sugar-derived cyclic dienophile showed a high exo and face selectivity in the Diels-Alder reaction with cyclopentadiene. Structural modifications on the dienophile structure were made, and the outcomes of the cycloaddition reactions were investigated. These results and the spectroscopic data recorded within a series of analogues were used to analyze the factors affecting the reactivity and exo selectivity.

Erbium triflate in ionic liquids: A recyclable system of improving selectivity in Diels–Alder reactions

The efficiency of Er(OTf) 3 in promoting the Diels–Alder reactions between different dienes and dienophiles in ionic liquids has been investigated. Compared with the analogous cycloadditions performed in conventional solvents shorter reaction times are required to obtain good/excellent yields. In most cases an enhancement of regio- and endo:exo selectivity was observed. The role of the ionic liquid, as a function of the cationic part, i.e. the imidazolium based or the pyridinium based, is discussed well. The ILs containing the catalyst can be readily separated from the reaction products and recovered in very high purity for direct reuse, up to six cycles.

1,3-Dipolar Cycloaddition of Azomethine Ylides with α,β-Unsaturated Ketones

The copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with α,β-unsaturated ketones is described. Reaction with 2-cyclopentenone afforded products with endo selectivity, whereas reaction with the trans-acyclic enones gave high exo selectivity. A stereochemical model that depicts the most stable geometry (based on computational studies) in the coordination of the metal atom with the ligand and azomethine species is provided to rationalize the observed selectivities.

Enantioselective Ag(I)-catalyzed [3+2] cycloaddition of azomethine ylides using a chiral ferrocene-based phosphine–phosphoramidite ligand having a stereogenic P-center

A series of chiral ferrocene-based phosphine–phosphoramidite ligands (PPFAPhos) have been employed in the Ag(I)-catalyzed asymmetric [3+2] cycloaddition of azomethine ylides with dimethyl maleate. The results showed that the ligand with a stereogenic P-center in the phosphino moiety displayed the best diastereo- and enantioselectivities, in which up to 99% enantiomeric excesses and 99/1 endo/ exo selectivities have been achieved.

Diels-Alder exo selectivity in terminal-substituted dienes and dienophiles: experimental discoveries and computational explanations.

The Diels-Alder reactions of a series of silyloxydienes and silylated dienes with acyclic alpha,beta-unsaturated ketones and N-acyloxazolidinones have been investigated. The endo/exo stereochemical outcome is strongly influenced by the substitution pattern of the reactants. High exo selectivity was observed when the termini of the diene and the dienophile involved in the shorter of the forming bonds were both substituted, while the normal endo preference was found otherwise. The exo-selective asymmetric Diels-Alder reactions using Evans' oxazolidinone chiral auxiliary furnished a high level of pi-facial selectivity in the same sense as their well-documented endo-selective counterparts. Computational results for these Diels-Alder reactions were consistent with the experimental endo/exo selectivity in most cases. A twist-asynchronous model accounts for the geometries and energies of the computed transition structures.

The Phenylsulfonyl Group as a Temporal Regiochemical Controller in the Catalytic Asymmetric 1,3‐Dipolar Cycloaddition of Azomethine Ylides

Controlling the regioselectivity: The phenylsulfonyl group controlled the regioselectivity in the title reaction to afford pyrrolidine-2,3-dicarboxylates with good regioselectivity and high exo selectivity and enantioselectivity (see scheme). The products are precursors to substituted pyrrolidines and pyrrolines that are not attainable by direct 1,3-dipolar cycloadditions with typical acrylates.

Exo- and Enantioselective Diels-Alder Reactions: Pyrazolidinone Auxiliaries as a Means to Enhanced exo Selectivity

Achiral pyrazolidinone auxiliaries have been investigated in exo- and enantioselective Diels-Alder reactions. The effect of pyrazolidinone N-1 substitution and chiral ligand identity were studied in Yb(OTf)3-catalyzed exo-selective Diels-Alder reactions. An appropriate choice of pyrazolidinone auxiliary and Yb(OTf)3/Pybox chiral Lewis acid led to moderate exo selectivity and high enantioselectivity for the exo-cycloadduct.

Synthesis of bicyclo[3.1.0]hexanones via 1,3-dipolar cycloaddition of diazoalkanes to homochiral α-sulfinyl-2-cyclopentenones

The reactions of diazomethane, diazoethane, and (trimethylsilyl)diazomethane with ( S)-2- p-tolylsulfinylcyclopent-2-en-1-one have been studied. The sulfinyl group increases the reactivity and controls the π-facial and endo/ exo selectivities. The π-facial selectivity can be inverted in the presence of Yb(OTf) 3, which makes possible the stereodivergent synthesis of both diastereoisomeric pyrazolines. Completely stereoselective denitrogenation of optically pure pyrazolines into cyclopropanes was achieved under substoichiometric Yb(OTf) 3 catalysis.