Ene reaction thermal

Diastereoselective ene reactions. Thermal cyclization via an intramolecular ene-tvpc reaction of the (7.)-1,6-diene 1 results in a mixture of trans-1 and cis-2 in the ratio 75 25. This reaction is markedly accelerated by addition of (C2H5)2AIC1, with only trans-1 being formed. The (E)-isomer of I is also cyclized thermally to give... 

Thermal and photochemical electrocyclic reactions are particularly useful in the synthesis of alkaloids (W. Oppolzer, 1973,1978 B K. Wiesner, 1968). A high degree of regio- and stereoselectivity can be reached, if cyclic olefin or enamine components are used in ene reactions or photochemical [2 + 2]cycloadditions. 

The method for preparing (-)-menthol (73) from (+)-citroneUal (68), which can be fractionally distilled from citroneUa oU, is cyclization by the ene-reaction. The reaction can be done thermally or using alumina and silica catalysts (145—147). 

The 27T-electrons of the carbon-nitrogen double bond of 1-azirines can participate in thermal symmetry-allowed [4 + 2] cycloadditions with a variety of substrates such as cyclo-pentadienones, isobenzofurans, triazines and tetrazines 71AHC(13)45). Cycloadditions also occur with heterocumulenes such as ketenes, ketenimines, isocyanates and carbon disulfide. It is also possible for the 27r-electrons of 1-azirines to participate in ene reactions 73HCA1351). 

Thermal cycli2alion of dienones enals, ynones, diones keloesters, etc, to monocyclic spirocycfc bicyclic derivatives, (ene reaction of unsalurated enol)... 

The ene reaction as a reaction principle has been first recognized and systematically investigated by Alder It is a thermal addition reaction of a double bond species 2—the enophile—and an alkene 1—the ene—that has at least one allylic hydrogen. The intramolecular variant is of greater synthetic importance than is the intermolecular reaction. 

Diels-Alder reactions of vinylpyrazoles 45 and 46 only occur with highly reactive dienophiles under severe conditions (8-10 atm, 120-140 °C, several days). MW irradiation in solvent-free conditions also has a beneficial effect [40b] on the reaction time (Scheme 4.11). The indazole 48, present in large amounts in the cycloaddition of 45 with dimethylacetylenedicarboxylate, is the result of an ene reaction of primary Diels-Alder adduct with a second molecule of dienophile followed by two [l,3]-sigmatropic hydrogen shifts [42]. The MW-assisted cycloaddition of 46 with the poorly reactive dienophile ethylphenyl-propiolate (Scheme 4.11) is significant under the classical thermal reaction conditions (140 °C, 6d) only polymerization or decomposition products were detected. 

Most carbonyl-ene reactions used in synthesis are intramolecular and can be carried out under either thermal or catalyzed conditions,43 but generally Lewis acids are used. Stannic chloride catalyzes cyclization of the unsaturated aldehyde 5. 

Scheme 10.2 gives some examples of ene and carbonyl-ene reactions. Entries 1 and 2 are thermal ene reactions. Entries 3 to 7 are intermolecular ene and carbonyl-ene reactions involving Lewis acid catalysts. Entry 3 is interesting in that it exhibits a significant preference for the terminal double bond. Entry 4 demonstrates the reactivity of methyl propynoate as an enophile. Nonterminal alkenes tend to give cyclobutenes with this reagent combination. The reaction in Entry 5 uses an acetal as the reactant, with an oxonium ion being the electrophilic intermediate. 

Another thermal route which has been particularly useful for the generation of silaaromatics (silabenzene, silatoluene, 4-substituted silaaromatics, etc.) and silafulvenes is the ene reaction of allylsilanes, as illustrated [Eq. (4)]. 

A second category of silene reactions involves interactions with tt-bonded reagents which may include homonuclear species such as 1,3-dienes, alkynes, alkenes, and azo compounds as well as heteronuclear reagents such as carbonyl compounds, imines, and nitriles. Four modes of reaction have been observed nominal [2 + 2] cycloaddition (thermally forbidden on the basis of orbital symmetry considerations), [2 + 4] cycloadditions accompanied in some cases by the products of apparent ene reactions (both thermally allowed), and some cases of (allowed) 1,3-dipolar cycloadditions. 

The tandem-Knoevenagel-ene reaction is a powerful tool to synthesize five-and six-membered carbocycles.2 5 The process is exemplified by the diastereoselective synthesis of 4a. Compound 4a has been obtained In both enantiomeric forms and as a racemate according to the procedure described here. The sequence includes the Knoevenagel reaction of citronellal, 1, and dimethyl malonate, 2, followed by the intramolecular ene cyclization of the chiral 1,7-diene 3 to yield the trans 1,2-disubstituted products 4a and 4b. Whereas the thermal cyclization of 3 at 160°C provides 4a and 4 b in a ratio of only 89.7 10.3, the Lewis acid... 

Thermal ene reactions of 3-(alk-2-enyl)benzylamino-2-(methoxycarbonyl) acrolein derivatives have been reported to give the substituted 4,5-dihydro-lff-azepines 3 (R = H, Me, Ph, 2-furyl, CC Et) in good yield <00T1299>. 

The Conia-ene reaction is a thermal cyclization of an alkyl ketone with an alkyne to give the corresponding a-vinylated ketone.98 The catalytic version of this reaction has been reported to generalize the process to more functionalized substrates.99 The intramolecular carbocupration of alkyne 94 has been investigated under basic conditions in the presence of a catalytic amount of copper iodide (Scheme 28).100 The cyclic product 95 is obtained in high yield. 

A diastereoselective intramolecular thermal carbonyl-ene reaction of a single enantiomer of keto ester 7 afforded the C5-C14 fragment of the jatrophane skeleton (Scheme 3).11 The key reaction was performed under thermal conditions (180 °C, 3 days) to afford only the m-compounds 8 and 9 in a 5 1 diastereomeric ratio. The kinetic preference for the m-isomers was explained by the less strained m-annulated transition states. 

The Alder-ene reaction has traditionally been performed under thermal conditions—generally at temperatures in excess of 200 °C. Transition metal catalysis not only maintains the attractive atom-economical feature of the Alder-ene reaction, but also allows for regiocontrol and, in many cases, stereoselectivity. A multitude of transition metal complexes has shown the ability to catalyze the intramolecular Alder-ene reaction. Each possesses a unique reactivity that is reflected in the diversity of carbocyclic and heterocyclic products accessible via the transition metal-catalyzed intramolecular Alder-ene reaction. Presumably for these reasons, investigation of the thermal Alder-ene reaction seems to have stopped almost completely. For example, more than 40 papers pertaining to the transition metal-catalyzed intramolecular Alder-ene reaction have been published over the last decade. In the process of writing this review, we encountered only three recent examples of the thermal intramolecular Alder-ene reaction, two of which were applications to the synthesis of biologically relevant compounds (see Section 10.12.6). 

The [4+ 4]-homolog of the [4 + 2]-Alder-ene reaction (Equation (48)) is thermally forbidden. However, in the presence of iron(m) 2,4-pentanedioate (Fe(acac)3) and 2,2 -bipyridine (bipy) ligand, Takacs57 found that triene 77 cyclizes to form cyclopentane 78 (Equation (49)), constituting an unprecedented formal [4 + 4]-ene cycloisomerization. The proposed mechanism for this transformation involves oxidative cyclization followed by /3-hydride elimination and reductive elimination to yield the cyclized product (Scheme 18). 

Weinreb et al86 have also studied the participation of allenes in imino-ene and carbonyl-ene reactions. Gycloisomerization of imine 133 in the presence of stannic chloride gave exclusively the m-substituted cyclopentyl isomer 135 (Scheme 27). The thermal imino-ene reaction of 136 was equally effective. More highly substituted... 

Racemic methyl cucurbate and racemic methyl epijasmonate were synthesized via a thermal Alder-ene reaction (Scheme 40).99 The newly formed stereocenters are controlled by the existing protected hydroxyl group of 166 in an anti/syn relationship. 

In the transition state a boat like structure appears and there will be a suprafacial cis addition to the termini of the n bond. The ene reaction does not have a symmetrical transition state and it is a thermally allowed concerted reaction. Its transition state involves a suprafacial interaction of six electrons (4 from the k bonds and two from the o bond) So it is a Huckel system and transition state is aromatic. In the terminatlogy of Woodward and Hoffmann it can be regarded as o2s + n2s + 7t2s reaction. 

The effect of ring substituents on the rate constants, deuterium kinetic isotope effects and Arrhenius parameters for ene-additions of acetone to 1,1-diphenylsilane have been explained in terms of a mechanism involving fast, reversible formation of a zwitterionic silene-ketone complex, followed by a rate-limiting proton transfer between the a-carbonyl and silenic carbon. A study of the thermal and Lewis acid-catalysed intramolecular ene reactions of allenylsilanes with a variety of... 

The bond reorganization process shown in Eq. (1) is formally known as an Alder-ene reaction, where X=H. The classic example involving the thermal reaction of an alkene having allylic hydrogen(s) (an ene) with an electron-deficient unsaturated compound (an enophile) was first reported by Alder in 1943 [1]. 

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