Thermal intramolecular ene reaction

Coverage in this chapter is restricted to the use of alkenes or alkynes as enophiles (equation 1 X = Y = C) and to the use of ene components in which a hydrogen is transferred. Coverage in Sections 1.2 and 1.3 is restricted to ene components in which all three heavy atoms are carbon (equation 1 Z = C). Thermal intramolecular ene reactions of enols (equation 1 Z = O) with unactivated alkenes are presented in Section 1.4. Metallo-ene reactions are covered in the following chapter. Use of carbonyl compounds as enophiles, which can be considered as a subset of the Prins reaction, is covered in depth in Volume 2, Chtqiter 2.1. Addition of enophiles to vinylsilanes and allylsilanes is covered in Volume 2, Chapter 2.2, while addition of enophiles to enol ethers is covered in Volume 2, Chapters 2.3-2.S. Addition of imines and iminium compounds to alkenes is presented in Volume 2, Part 4. Use of alkenes, aldehydes and acetals as initiators for polyene cyclizations is covered in Volume 3, Chapter 1.9. Coverage of singlet oxygen, azo, nitroso, S=N, S=0, Se=N or Se=0 enophiles are excluded since these reactions do not result in the formation of a carbon-carbon bond. 

Conia and coworkers have developed an extensive series of thermal intramolecular ene reactions of unsaturated ketones which occur on extended heating (30 min to several hours) at 300-400 C in pyrex. The initial step of the reaction is reversible tautomerization of the ketone (163) to give enol... 

The thermal intramolecular ene reaction of (269) leads to (—)-a-kainic acid (270) after subsequent transformations of functional groups (Scheme 134). ... 

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 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 ene reaction is strongly catalyzed by Lewis acids such as aluminum chloride and diethylaluminum chloride204 Coordination by the aluminum at the carbonyl group increases the electrophihcity of the conjugated system and allows reaction to occur below room temperature, as illustrated in Entry 6. Intramolecular ene reactions can be carried out under either thermal (Entry 3) or catalyzed (Entry 7) conditions 205 Formaldehyde in acidic solution can form allylic alcohols, as in entry 1. Other carbonyl ene reactions are carried out with Lewis acid catalysts. Aromatic aldehydes and acrolein undergo the ene reaction with activated alkenes such as enol ethers in the presence of Yb(fod)3 206 Sc(03SCF3)3 has also been used to catalyze ene reactions.207... 

The only example of the generation of a monocyclic heterocycle by y-bond formation is provided by the thermally promoted conversion of the bisallenyl selenide (143) into the selenophene (144) (78TL1493). The cyclization is conveniently formulated as proceeding via an intramolecular ene reaction. Another electrocyclic process appears to be involved in the conversion of allyl phenyl selenide (145) into 2-methyl-2,3-dihydrobenzo[6]seleno-phene (146) (71TL49). The origin of the minor amount of 2-methylbenzoselenophene (147) which is also formed has not been established. Access to 3-keto-2,3-dihy-drobenzo[h]selenophenes (148) (71KGS333) and 2-arylidene-3-keto-2,3-... 

Intramolecular ene reaction of 1,7-dienes.1 The ZnBr2-catalyzed reaction of the activated 1,7-diene 1 gives the frans-disubstituted cyclohexane 2 (>98% selectivity.) Under the same conditions, the chiral 1,7-diene 3 [from (R)-citronellal] is converted into two diastereomeric frww-disubstituted cyclohexanes, 4 and 5 in the ratio 96.5 3.5. Slightly higher diastereoselectivity obtains with (C2H5)2A1C1 (96% de), but the thermal ene reaction gives 4 and 5 in the ratio 86 14. 

Type II intermolecular ene reaction of thioaldehydes was reported by Vedejs and coworkers492 and already mentioned by Schaumann1. Type in has recently appeared and involves the formation of a C—S bond instead of a C—C bond, as in the case of type I. Type III intramolecular ene reaction has been reported for thioketones and for thioaldehydes. The group of Motoki489 examined the thermal cyclization of o-(2-substituted allyloxy) thiobenzophenones 137 leading to 1,5-oxathiocine derivatives 138 (equation 148). 

Intramolecular ene reactions of 1,7-dienes with doubly activated enophiles (123 X, Y = CO2R, CN, COMe) proceed readily either thermally or with Lewis acid catalysis to give (124) and stereoisomers. In an elegant series of studies, Tietze and coworkers have explored the stereochemistry... 

Excellent yields of ene adducts have been obtained in Lewis acid catalyzed intramolecular ene reactions of homoallylic glyoxylates. Treatment of (120) with SnCU in nitromethane provides (121) in 85% yield. Similar treatment of (122) gives (123) in 50-60% yield, which was converted to actino-bolin. Allylic glyoxylates decompose in the presence of Lewis acids but give modest yields of ene adducts in thermal reactions (Scheme 19). ... 

The ene reaction where both partners are simple alkenes is quite useful when the partners are linked so as to provide for an intramolecular ene reaction. There is a preference for the formation of cw-disubstituted cyclopentane and frans-disubstituted cyclohexane systems resulting from thermally induced, intramolecular ene reactions. For example, levels of transjcis control of 92 8 to > 99 1 were found for the intramolecular cyclization of methyl 2-cyano-9-methyl-3,8-decadienoate23 24. Furthermore, the same tran. -stereochemical relationship was obtained when the reaction was carried out at room temperature in the presence of zinc(II) bromide with control consistently at the 99 1 level for R and R2 either methoxycarbonyl or cyano groups24, This preference for trans fusion does not appear to be greatly altered by added substituents on the chain connecting the reacting partners (vide infra). 

The situation with intramolecular ene reactions that form five-membered rings is less well defined, with some systems providing cis substitution under thermal conditions26 (with some special exceptions25) while tram substitution is favored in the presence of Lewis acids, such as zinc(II) bromide. The presence of substituents and/or heteroatoms within the chain does not alter this bias for trans substitution27. In both cases the tram configuration is favored, but to a greater extent in the presence of zinc(ll) bromide (see Table 1). 

There are numerous examples of internal direction from indigenous stereogenic centers in ene reactions, especially intramolecular variants that form rings. For example, levels of 94% de for the zinc bromide induced and 76% de for the thermally induced (180 °C) intramolecular ene reaction with methyl 2-methoxycarbonyl-5,9-dimethyl-2,8-decadienoate have been found28, 0. 

Type II intramolecular ene reactions of unsaturated aldehydes and ketones have been extensively investigated. Ene reactions occur thermally or with Lewis acid catalysis to give 3-methylenecyclohexan-ols52-96-109 or 3-methylenecycloheptanols.110-114 3-Methylenecyclopentanols cannot be formed in type II reactions. However, Lewis or Brpnsted acid induced cyclization of y,8-unsaturated aldehydes and ketones gives zwitterionic intermediates that lose a proton to give unsaturated cyclopentanols85122 or rearrange to cyclopentanones.115-121... 

An intramolecular ene reaction between the silene and the H-C-C=0 moieties of 64 presumably occurs in the second step of the thermal rearrangement252 of the silicon analogue of a phenyl allyl ether discussed in Section III.A.2.C. 

Hansson, T, O. Sterner, B. Wickberg, and R. Bergman The Thermal Isomerization of the Sesquiterpene Isovelleral and Merulidial. A Reversible Ring Opening of the cw-Methylcyclopropanecarbaldehyde Group via an Intramolecular Ene Reaction. J. Org. Chem., 57, 3822 (1992). 

Hansson, T, R. Bergman, O. Sterner, and B. Wickberg The Mechanism of the Thermal Rearrangement of the Marasmane Sesquiterpene (+) Isovelleral. Cyclopropane Ring Closure via an Intramolecular Ene Reaction. J. Chem. Soc., Chem. Commun., 1260 (1990). 

Sol 2. (c) The reactant undergoes intramolecular ene reaction under thermal conditions. In this reaction, allyl hydrogen is transferred to alkyne system instead of the transfer of propargylic hydrogen to alkene part, which may give allene derivative. 

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