Cyclic Dienophiles Research Articles

Synthesis spiro and fused chromenes via [4 + 2] cycloaddition of salicyl N-tosylimines and cyclic dienophiles

A straight forward synthetic protocol for spiro and fused chromenes has been developed by base promoted oxa-Michael/Mannich reaction of salicyl N-tosylimines and various cyclic dienophiles. 1,4-diazabicyclo[2.2.2]octane (DABCO) promoted [4 + 2] cycloaddition reaction of salicyl N-tosylimines and 3-methyleneoxindoles or 2-arylidene-1,3-indanediones in THF at room temperature afforded functionalized spiro[chromane-3,3′-indolines] or spiro[chromane-3,2′-inden]-1′,3′-diones in moderate to good yields and with high diastereoselectivity. On the other hands, the similar [4 + 2] cycloaddition of salicyl N-tosylimines and 5,6-unsubstituted 1,4-dihydropyridines resulted in tetrahydrochromeno[3,2-b]pyridine derivatives in satisfactory yields.

Lewis acid catalysed polymerisation of cyclopentenone.

A modest structural change of a β-diketiminate-supported aluminium complex leads to dramatic differences in the reactivity towards cyclopentenone. While the bulkier complex efficiently executes Diels Alder transformations the smaller analogue performs unique polymerisation of this substrate. This observation appears to be unprecedented in the chemistry of Lewis acids and cyclic dienophiles as it represents a unique way to polymerise a functionalised olefin.

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles.

In the presence of copper sulfate, three- or four-component reactions of 2-methylindole, aromatic aldehydes and various cyclic dienophiles in refluxing toluene afforded diverse spirotetrahydrocarbazoles. This reaction is an important development of the Levy reaction by using 2-methylindole to replace ethyl indole-2-acetate and successfully provides facile access to important polysubstituted spiro[carbazole-3,3'-indolines], spiro[carbazole-2,3'-indolines], spiro[carbazole-3,5'-pyrimidines] and spiro[carbazole-3,1'-cycloalkanes] in satisfactory yields and with high diastereoselectivity.

Synthesis and ethylene-promoted metathesis of adducts of tandem [4+2]/[4+2] cycloaddition between bis-furyl dienes and maleic acid derivatives

A series of 1,4:5,8-diepoxynaphthalenes, annellated with carbo- and heterocycles, was synthesized based on the tandem intermolecular/intramolecular [4+2] cycloaddition of bis-furyl dienes with moderately to highly reactive cyclic dienophiles (maleic anhydride and maleinimides).

ChemInform Abstract: Organocatalytic Asymmetric Formation of Steroids.

AbstractA facile one‐pot protocol for the synthesis of steroids via Diels—Alder reaction of enals with cyclic dienophiles in the presence of catalytic amounts of Tms‐diphenylprolinol (PRS) is developed.

Organocatalytic Asymmetric Formation of Steroids

AbstractA novel and simple one‐step approach for the construction of optically active steroids in a highly stereoselective manner by using organocatalysis is presented. The reaction of (di)enals with cyclic dienophiles in the presence of a TMS‐protected prolinol catalyst leads to the construction of important 14 β‐steroids. This new reaction allows an easy access to optically active steroids with a variety of substituents in the A ring in high yields and up to greater than 99 % ee. The reaction has been extended to include the construction of B‐ and D‐homosteroids as well as steroids containing heteroatoms in the B ring. The angular substituent at C13 can be varied and alkyl, ester, and sulfone functionalities are introduced with excellent stereoselectivities. Simple synthetic procedures provide access to a range of naturally occurring steroids such as estrone and related analogues.

Organocatalytic Asymmetric Formation of Steroids

A novel and simple one-step approach for the construction of optically active steroids in a highly stereoselective manner by using organocatalysis is presented. The reaction of (di)enals with cyclic dienophiles in the presence of a TMS-protected prolinol catalyst leads to the construction of important 14 β-steroids. This new reaction allows an easy access to optically active steroids with a variety of substituents in the A ring in high yields and up to greater than 99 % ee. The reaction has been extended to include the construction of B- and D-homosteroids as well as steroids containing heteroatoms in the B ring. The angular substituent at C13 can be varied and alkyl, ester, and sulfone functionalities are introduced with excellent stereoselectivities. Simple synthetic procedures provide access to a range of naturally occurring steroids such as estrone and related analogues.

Computational Studies of the Reactivity, Regio-Selectivity and Stereo-Selectivity of Pericyclic Diels-Alder Reactions of Substituted Cyclobutenones

The power of the Diels-Alder reaction was expanded recently through the discovery by Li and Danishefsky that cyclobutenone is an unusually reactive dienophile and that the adducts formed can be converted to products that are formally the Diels-Alder adducts of unreactive dienophiles. However, the effects of substituents on the reactivity as well as the region - and stereo-selectivity of the Diels-Alder reactions of cyclobutenone have not been clearly elucidated yet. This paper reports the results of a computational study at the MP2/6-31G* level of theory into the effects of substituents on the reactivity, regio-selectivity and stereo-selectivity of the Diels-Alder reactions of some substituted cyclobutenones with cyclic and acyclic dienes. It was found that the Diels-Alder reaction of maleic anhydride is far more feasible kinetically than the reaction of cyclobutenone, the activation barrier of the former being more than thrice that of the latter, indicating that maleic anhydride is a far better dienophile than cyclobutenone, which in turn implies that for cyclic dienophiles ring strain is not the dominant factor controlling the kinetics of the Diels-Alder reaction as has been suggested elsewhere. The Diels - Alder reactions of cyclobutenones were all found to follow an asynchronous concerted reaction pathway. In the reactions of the parent (unsubstituted) cyclobutenone with 1,3-butadiene and cyclopentadiene, the endo pathway is the most preferred kinetically, by 2.24 and 1.64 kcal/mol respectively. However, in the reactions of the 4,4-disubstituted cyclobutenones the exo pathway becomes the most preferred in the reactions with both 1,3-buadiene and cyclopentadiene, except for the CN-substituted cyclobutenone where the endo pathway is still the most preferred pathway. In the reactions of the 4-monosubstituted cyclobutenone with 1,3-butadiene, the anti-positions are preferred over the syn positions. The endo-anti position gives the most reactive dienophile kinetically. In the reactions of trans-piperylene with substituted cyclobutenones, the meta-endo position is the most preferred kinetically. In the reactions of isoprene with substituted cyclobutenones, the para-endo substitution gives the lowest activation barriers and therefore the most favorable reaction kinetics. In all the reactions considered in this work, the CN-substituted species have the lowest activation barriers and the most stable products. In the reactions of 4,4-disubstituted cyclobutenones with 1,3-butadiene and cyclopentadiene, the order of activation barriers is CN OH>Cl>CH3.

ChemInform Abstract: Diels—Alder Reactions of 2‐Vinylindoles with Cyclic Dienophiles: Synthesis of [c]‐Annulated Tetrahydrocarbazoles.

AbstractThe reaction proceeds with excellent regioselectivity to give diastereomeric mixtures of pharmaceutically important tetrahydrocarbazole structures annullated with furan or carbocycle moieties, which are readily separable by chromatography.

Phosphonated Bicycles Bearing a N-N Junction

The Diels-Alder reaction between diethyl 1-phosphono-1,3-butadiene and cyclic azo dienophiles, such as 4-phenyl- and 4-methyl-1,2,4-triazoline-3,5- diones and phthalazine-1,4-dione gave access to phosphonated bicyclic cycloadducts bearing a N-N junction. Various functionalizations (dihydroxylation, hydrogenation and phosphonic ester deprotection) have been performed with success. The selective N-N cleavage was not possible for the preparation of large heterocycles. The coordination properties of selected bicycles were tested by ESI-HRMS. © 2013 The Japan Institute of Heterocyclic Chemistry.

4‐Alkenyl‐2‐aminothiazoles: Smart Dienes for Polar [4 + 2] Cycloadditions

AbstractAn exhaustive investigation into the [4 + 2] cycloadditions of 4‐alkenyl‐2‐aminothiazoles with a wide range of dienophiles has been carried out. 4‐Alkenyl‐2‐aminothiazoles act as good in‐out dienes, reacting with dienophiles bearing electron‐withdrawing groups. The heteroannulations, typically conducted under mild conditions, were endo‐selective when cyclic dienophiles were used, and regioselective when the reactions are conducted with unsymmetrical dienophiles. The endo‐selective processes presumably take place by concerted but highly asynchronous mechanisms. In contrast, the low levels of endo selectivity and the lack of stereospecificity in the reactions with certain acyclic dienophiles indicate a stepwise mechanism with a zwitterion as the most plausible intermediate. The course of the reaction changes when the highly reactive PTAD and TCNE are used as dienophiles, since in these cases, only addition products were obtained. Calculations of the HOMO and LUMO energy values of representative 4‐alkenyl‐2‐aminothiazoles, and the results of π‐facial diastereoselective processes by using chiral substrates are also disclosed.

Diels–Alder Reactions of 2-Vinylindoles with Cyclic Dienophiles: Synthesis of [c]-Annulated Tetrahydrocarbazoles

Diels–Alder reactions of 2-vinylindoles with cyclic carbo- and heterodienophiles, in the presence of suitable Lewis acids, led to uncommon [ c ]-carbo- and furoannulated tetrahydrocarbazoles. The obtained compounds encompass a carbonyl group in an angular position, suitable for further transformations, and represent useful intermediates for the synthesis of more complex structures.

Synthetic transformations of higher terpenoids: XXVIII. Diels-Alder reactions of 16-(trimethylsiloxybutadienyl) labdanoids

15,16-Epoxy-16-(3-trimethylsiloxybuta-1,3-dien-1-yl)labdanoids were synthesized, and their reactions with cyclic dienophiles (1,4-benzoquinone, 1,4-toluquinone, 2-bromo-6-methyl-1,4-benzoquinone, and N-methylmaleimide) were studied. The reactions with unsymmetrically substituted benzoquinones were not selective. Methods for the preparation of hybrid compounds containing furan diterpenoid and substituted naphthoquinone, octahydroisoindoletrione, or hexahydroisoindoledione fragments were proposed.

An efficient synthesis of fused polycyclic indole derivatives via Aldol-Hetero Diels-Alder reaction of α,β-Unsaturated Thio-oxindoles with various dienophiles

An efficient and one-pot synthesis of thiopyrano[2,3-b]indole derivatives via Hetero Diels-Alder reaction of α,β-Unsaturated thio-oxindoles with electron poor acetylenes and Cyclic Dienophiles is described. In the proposed method the reaction is performed under neutral and one-pot reaction conditions, and also the substances can be mixed without any activation or modification and without using any catalysts.

Reactivity and stereoselectivity of the Diels–Alder reaction using cyclic dienophiles and siloxyaminobutadienes

Several bicyclic compounds were synthesized by the Diels–Alder reaction using aminodiene and a cyclic dienophile. The stereochemistries of the obtained adducts were determined by X-ray crystallography or NMR analysis. The stereoselectivity of this Diels–Alder reaction was based on the interaction of molecular orbitals between the diene and dienophile. The reactivities of these Diels–Alder reactions were estimated, and the generality of this reaction is discussed.

ChemInform Abstract: Diels-Alder Cycloadditions of Electron-Rich, Electron-Deficient, and Push-Pull Dienes with Cyclic Dienophiles: High-Pressure-Induced Reactions and Theoretical Calculations.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: High Exoselectivity in Diels-Alder Additions of α-Vinylidene and α-Methylene-γ-butyrolactones to Cyclopentadiene.

Abstract Regardless of the conditions, catalytic or thermal, lactones 1 and 8 undergo kinetically controlled Diels-Alder cycloadditions to cyclopentadiene with pronounced exoselectivity. The activation parameters are reported for both reactions. It is suggested that such exoselectivity is a general property of conformationally rigid cyclic cisoid dienophiles.

ChemInform Abstract: Synthesis of a Highly Substituted Cyclopentane: Completely Exo- and Face-Selective Diels-Alder Reaction of Cyclopentadiene with Cyclic Sugar Dienophiles.

ChemInform Abstract: Synthesis of a Highly Substituted Cyclopentane: Completely Exo- and Face-Selective Diels-Alder Reaction of Cyclopentadiene with Cyclic Sugar Dienophiles.

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.

The High Stereoselectivity of the Tandem Sequence Diels—Alder Reaction/Ireland—Claisen Rearrangement Starting from Substituted O‐(E)‐Buta‐1,3‐dienyl Ketene Acetals and Cyclic Dienophiles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.