cis-3,5-Cyclohexadiene-1,2-diol derivatives: facial selectivity in their Diels-Alder reactions with ethylenic, acetylenic and azo dienophiles

The Diels-Alder reactions of maleimide with the acetonide derivative (6a) of cis-3,5-cyclohexadiene-1,2-diol (1a) in various solvents showed facial selectivities ranging from 1 : 1 to 1 : 9. The same derivative 6a reacted in benzene with ethylenic dienophiles with generally modest facial selectivity, but acetylenic dienophiles added exclusively anti to the oxygen functions of 6a. Dimerization of cyclic acetals 6a and 7 was mainly, but for 6a not exclusively, by anti addition with respect to both the diene and the dienophile partners. Reactions of azo dienophiles with derivatives of 1a were predominantly by anti addition, but the diol itself (1a) gave the syn adduct as the major product.     

Studies into the stereoselectivity of tartrate-derived dienophiles

[reaction: see text] Diels-Alder reactions of 1-(tert-butyldimethylsiloxy)-1,3-butadiene (3) with three C2 symmetric dienophiles derived from tartaric acid have been examined. Complementary diastereoselectivity is observed depending on the nature of the 1,2-diol protecting group incorporated in these dienophiles.     

Propellanes. L. Further support for control by secondary orbital overlap during Diels-Alder reactions of certain propellanes,

In contrast to the behavior of 4-substituted-1,2, 4-triazoline-3, 5-diones which add to the syn-face of the cyclohexadiene with respect to the hetero-ring in propellanes of type 1 , dienophiles containing a C, C double bond instead of an N, N double bond add exclusively to the anti-face of the same substrates. This supports our thesis that these reactions are controlled by secondary orbital interaction between the N, N dienophiles and the hetero-ring of the substrates, an interaction which cannot exist in the C, C dienophiles.     

Dioxopyrrolines. LXII. Diels-Alder reaction of 1-Aryl-4- and 5-methoxycarbonyl-1H-pyrrole-2,3-diones with various 1,3-dienes

Two new dioxopyrrolines (1-aryl-4-methoxycarbonyl-1H-pyrrole-2,3-dione 6 and the 5-methoxycarbonyl isomer 8) behaved as good dienophiles to some kind of 1,3-dienes examined. In most cases, the products were explained by the reaction where the largest lobe of HOMO of dienes reacted to the larger LUMO of dienophiles in an expected cis-endo manner. However, in the reactions of 8 with alkylbutadienes, piperylene and isoprene, abnormality in the reaction was observed, which was well explained by taking account of steric factors.     

The Synthesis of Naphthosultine and Benzodisultines and Their Pyrolysis with Dienophiles: Studies on o‐Naphthoquinodimethane and Bis‐o‐Quinodimethane

Sealed tube reactions of the naphthosultine 8 with a series of electron‐deficient dienophiles (fumaronitrile, N‐phenylmaleimide, dimethyl fumarate, and dimethyl acetylenedicarboxylate) in toluene at 180 °C gave corresponding 1:1 cycloadducts 11–14 in various amounts along with rearranged naphthosulfolene 7 in 67–95% yields. The reaction of 1,2,4,5‐tetra(bromomethyl)benzene with Rongalite (sodium form aldehyde sulfoxylate) and tetrabutylammonium bromide in DMF gave benzodisultines 17 and 18 in a combined yield of 56%. Sealed tube reactions of benzodisultines 17 and 18 with a series of dienophiles in xylene at 200 °C gave corresponding 1:1 and 1:2 cycloadducts 20–27 . The results suggested that thermal extrusion of sulfurdioxide from these sultines led to either o‐naphthoquinodimethane 6 (from 8 ) or bis‐o‐quinodimethane 19 (from 17 and 18 ); sub sequent trapping of these reactive intermediates by dienophiles and SO₂ gave various 1:1 and 1:2 Diels‐Alder ad ducts in modest to excellent yields.     

Chiral thiophene dioxides and thiophene S,N-ylides as dienes for asymmetric diels-aldlr application

2-Menthyltrihalothiophene S,S-dioxides are efficient asymmetric dienes in Diels-Alder reactions with dienophiles to give regio- and stereoisomerically pure adducts. Thus styrene, allyl alcohol, methyl acrylate and acrylamide give solely one adduct while flat dienophiles such as indene and acenaphthylene give two diastereomers. Analogous 1- and 3- chirally substituted thiophenes are of little value in generating pure single adducts. Further transformations of the above adducts into useful enantiomerically pure compounds is briefly discussed.     

Characteristics of the two frontier orbital interactions in the Diels-Alder cycloaddition

Two electron-deficient dienes were reacted with a series of twelve electron-poor and electron-rich dienophiles to give, in some cases, the corresponding Diels-Alder adducts. Clear differences in the roles played by the two frontier orbital interactions emerged. It was demonstrated that in the case of normal Diels-Alder cycloadditions, the FMO theory could predict the relative reactivities between dienophiles, while in the case of inverse-electron demand Diels-Alder reactions, it could not. It was shown that the dissymmetry in electron-rich dienophiles increases their reactivities.     

Diels-Alder cycloadditions of functionalized (Z)-1-benzylidene-2-methylene cyclohexanes: the beneficial effect of high pressure

Diels-Alder cycloaddition reactions have been studied on substituted (Z)-1-benzylidene-2-methylene cyclohexanes 3. The use of very reactive dienophiles allowed the formation of the expected polycyclic structures whereas hyperbaric conditions (16 kbar) were necessary to form the adducts with less reactive dienophiles. An exo stereoselectivity was observed during the reaction with acrylates.     

Synthesis and Chemical Reactivity of 5-Methoxy-2-vinyl-4-azaindoles

2-Vinyl-4-azaindoles are less reactive with dienophiles than 2-vinylindoles. 5-Methoxy-2-vinyl-4-azaindole 2a and its 1-methyl derivative 2a reacts with N-phenylmaleimide to yield cycloadducts only under vigorous conditions. 2b produces a cycloadduct with dimethyl acetylenedicarboxylate, while 2a yields a Michael-type adduct. Reactions with more reactive dienophiles gave only polymeric products.     

Diels-Alder Reactions of [2.2] Paracyclophan-1-ene and [2.2] Paracyclophane-1,9-diene with 3,6-Disubstituted 1,2,4,5-Tetrazines

[2.2] Paracyclophan-1-ene ( 1 ) and [2.2] paracyclophane-1,9-diene ( 6 ) apparently act as dienophiles with inverse electron demand and smoothly react with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate ( 2a ) at room temperature forming dihydropyridazine adducts, which are dehydrogenated to the pyridazino-anellated [2.2] paracyclophanes 5a and 8a , respectively. The molecular structure of 5a is determined by X-ray crystal-structure analysis. Under more rigorous conditions, phenyl-substituted derivatives 5b and 8b are obtained from 1 and 6 , respectively, with 3,6-diphenyl-1,2,4,5-tetrazine. Compounds 1 and 6 are less reactive dienophiles than other strained cyclic olefins as shown by kinetic measurements.     

AM1 semiempirical searching for suitable thiophene derivatives that will enable thiophenes to act as a diene in the diels-alder reactions

The AM1 semiempirical method was used for theoretical searching of activation of thiophene as a diene for the Diels-Alder reaction. The reactivity of thiophene, electron-withdrawing and electron-donating substituted thiophenes, as well as the S-methylthiophenium ion were studied as the diene for Diels-Alder reactions by evaluating their frontier orbital energies and by calculating reaction barriers with activated and deactivated dienophiles. It was demonstrated that slight activation of the thiophene ring can be obtained with both electron-donating and electron-withdrawing groups attached to the thiophene ring. It was predicted that the actual transformation of thiophenes into the corresponding S-methylthiophenium anions is the best means of activating the thiophenes. The calculated activation energies for normal (non-activated) dienophiles are moderate so mild reaction conditions are predicted. If dienophiles are activated with electron-donating substituents, AM1 calculations predict a two step cycloaddition reaction with a very small activation barrier.     

Highly regioselective diels-alder reactions of 2-trimethylsilylmethyl- and 2-trimethylstannylmethyl-1,3-butadiene

2-Trimethylsilylmethyl and 2-trimethylstannylmethyl-1,3-butadiene undergo facile cycloaddition with dienophiles, and show high regioselectivity with unsymmetrical dienophiles.     

New Dienophiles: 1-Acetylvinyl Arenecarboxylates. Reactivity toward cyclopentadiene and exocyclic dienes

The preparations of 1-acetylvinyl arenecarboxylates H₂C=C(COCH₃)OCOR with R = phenyl, p-nitrophenyl, 2,4-dinitrophenyl, α- and β-naphthyl are described (3) . The Diels-Alder reactivity of these dienophiles toward cyclopentadiene is evaluated and compared with that of methyl vinylketone, 3-trimethylsilyloxy-, 3-ethoxy- and 3-acetoxy-3-buten-2-ones. The stereoselectivity of the cycloadditions of these dienophiles with 2,3,5,6-tetramethylidene-7-oxanorbornane (1) and 5,8-dimethoxy-1,4-epoxy-2,3-dimethylidene-1,2,3,4-tetrahydroanthracene (2) is studied. In principle, the dienophiles 3 allow direct functionalization of the position C(9) of the A-ring of daunomycinone analogs by Diels-Alder additions to exocyclic dienes such as 1 and 2 .     

Asymmetric Diels-Alder Cycloadditions with Chiral Carbamoyl Dienophiles

Chiral acylnitroso dienophiles 14 , which were obtained from L -proline and from D -mandelic acid, reacted with cyclohexa-1,3-diene to give the expected diastereoisomers 15 and 16 (Scheme 2 and Table 1). The d.e. values for these Diels-Alder reactions were moderate; they are related to the molecular stiffness of the dienophiles. The absolute configuration of the major cycloadducts was interpreted in terms of HOMO/LUMO interactions, the approach being ‘endo’ and the acylintroso dienophiles reacting from their s-cis-conformation.     

Incorporation of a molecular hinge into molecular tweezers by using tandem cycloadditions onto 5,6-dimethylenenorbornene

Site-selective 1,3-dipolar coupling at the norbornene pi-bond of 5,6-dimethylenenorbornene 1 yields cycloadducts with an end-fused 1,3-diene system which have been reacted with N=N (or C=C) dienophiles to produce ribbon molecules, in which the internal diazacyclohexene (or cyclohexene) subunits are capable of acting as conformational hinges. Direct coupling of 5,6-dimethylenenorbornene with 1,3,4-oxadiazoles or dual coupling with bis(cyclobutene epoxides) afforded bis(1,3-dienes) that diastereoselectively react with dienophiles to produce new, conformationally mobile, molecular tweezers.     

Oxazaborolidinone-catalyzed enantioselective Diels-Alder reaction of acyclic alpha,beta-unsaturated ketones

allo-Threonine-derived O-acyl-B-phenyl-oxazaborolidinones are demonstrated to be powerful and highly enantioselective Lewis acid catalysts for the Diels-Alder reaction of simple acyclic enone dienophiles, expanding the scope of ketone dienophiles and dienes. With 10 to 20 mol % of catalyst, the Diels-Alder adducts are obtained in 76-98% ee with high endo-selectivity. The catalyst exhibits high activity for the reaction with the less reactive beta-substituted dienophiles and the less reactive 1,3-cycohexadiene and 1,3-butadiene derivatives. The application of the catalysts to the Diels-Alder reaction of furan is also described.     

A novel MCR of isocyanates, aldehydes, and dienophiles

[reaction: see text] A novel one-pot procedure for the three-component coupling reaction of isocyanates, aldehydes, and dienophiles (IAD reaction) has been developed. Condensation of isocyanates and aldehydes and subsequent Diels-Alder reactions with electron-deficient dienophiles furnishes endo-selective amino-substituted cyclohexenes in good yield.     

Pi-face-selective Diels-Alder reactions of 3,4-di-tert-butylthiophene 1-oxide and 1-imide and formation of 1,2-thiazetidines

3,4-Di-tert-butylthiophene 1-oxide (1a) reacted with a series of electron-deficient alkenic dienophiles at its syn-pi-face relating to the S=O bond to give [4+2] adducts in excellent yields. The 1-oxide 1a also reacted even with angle-strained dienophiles acenaphthylene and norbornene at its syn-pi-face to afford [4+2] adducts; in the latter case, norbornene reacted exclusively at its exo-pi-face. The oxide 1a reacted with dimethyl acetylenedicarboxylate to produce dimethyl 4,5-di-tert-butylphthalate in high yield with spontaneous extrusion of SO from the initial adduct even at room temperature. Similarly, 3,4-di-tert-butylthiophene 1-(p-toluenesulfonyl)imide (3a) reacted with alkenic dienophiles at its syn-pi-face relating to the S=N bond to give [4+2] adducts in good yields. The reaction of 3a with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) afforded a 1,2-thiazetidine 12a, the first example of S-unoxidized 1,2-thiazetidine, in good yield, through rearrangement of the initial [4+2] adduct. The molecular structure of 12a is discussed on the basis of the X-ray crystallographic analysis. Comparison of the foregoing reactions leads to the conclusion that the 1-oxide 1a is more reactive as a diene than the 1-imide 3a, which is more reactive than 3,4-di-tert-butylthiophene 1,1-dioxide. The origin of the syn-pi-face selectivities of 1a and 3a in Diels-Alder reactions is discussed in terms of the orbital mixing rule and steric effect and also based on B3LYP/6-31G(d) calculations.     

Solvent‐Free Synthesis of Some New PolyAromatic Hydrocarbons by Diels‐Alder Reaction of Tetracyclone

Diels‐Alder reactions of tetracyclone with various dienophiles under solvent free conditions were studied. In the case of cyclic dienophiles that exhibit more steric hindrance, decarbonylation of [4+2] adducts were carried out.     

Radical Cation Diels‐Alder Reactions of Non‐Conjugated Alkenes as Dienophiles by Electrocatalysis

Radical cation Diels‐Alder reactions provide a powerful method for the construction of six‐membered ring systems between both electron‐rich dienes and dienophiles. However, the most recent examples of this class have been limited to β‐methylstyrenes as dienophiles; the use of non‐conjugated alkenes remains challenging. The present study describes the serendipitous development of novel radical cation Diels‐Alder reactions by electrocatalysis that use non‐conjugated alkenes as dienophiles. The key to successful transformation involves highly substituted cyclohexenyl radical cations that are stable enough to be reduced by intermolecular single electron transfer.