Ene reaction/ -rearrangement

Lewis acid catalyst for Friedel-Crafts, Diels-Alder, [2 + 2] cycloadditions, ene reactions, rearrangements, and other reactions)... 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Claisen or Cope rearrangement Ester cracking Conia ene reaction... 

The retro-ene reaction also is of synthetic importance. While the application of high pressure facilitates the ene reaction, the retro-ene reaction is favored at higher temperatures. Furthermore small-ring strain can shift the equilibrium towards the side of the dienes. The vinylcyclopropane 11 rearranges by a synchronous process to the open-chain diene 12. Formally this process is the reverse of an intramolecular ene reaction ... 

Enantiomers, preferential crystallization of 59 Endo selectivity 798 Ene reactions 808, 809 Enones, synthesis of 732 Enthalpies of formation 102, 103 Enynes, synthesis of 956 Enzymatic kinetic resolution 829 Epimerization 399 Episulphides, oxidation of 237 Episulphones 650, 775 Episulphoxides, photolysis of 742 a,/J-Epoxysulphones reactions of 811, 812 rearrangement of 685 synthesis of 612 / ,y-Epoxysulphones 781 y,<5-Epoxysulphones 627, 628 Epoxysulphoxides reactions of 613 rearrangement of 744 synthesis of 327, 612 Erythronolides 831... 

The cycloaddition of glyoxylic acid with cyclopentadiene in water at pH 6 and 60 °C is slow and occurs with low yield and low diastereoselectivity [18] (Scheme 6.17). Proton (pH = 0.9) [18], copper salts [27] and Bi(OTf)3 [28] accelerate the reaction and increase the diastereoselectivity. The lactones 28 and 29 originate from endo and exo cycloadducts 27, respectively. The proposed rearrangement is depicted in Scheme 6.17 for the major endo adduct 30. A competitive ene reaction that originates 28 and 29 cannot be excluded [28]. 

Keywords Diels-Alder reactions, dipolar cycloadditions, electrocyclic reactions, ene reactions, pericyclic reactions, sigmatropic rearrangements... 

The predictions of the reactivities by the geminal bond participation have been confirmed by the bond model analysis [103-105] of the transition states and the calculations of the enthalpies of activation AH of the Diels-Alder reaction [94], the Cope rearrangement [95], the sigmatropic rearrangement [96], the Alder ene reaction [100], and the aldol reaction [101] as are illustrated by the reactions of the methyl silyl derivatives in Scheme 38 [102], The bond is more electron donating than the bond. A silyl group at the Z-position enhances the reactivity. 

Pinacol Rearrangement in Tandem with the Carbonyl-Ene Reaction. Overman and co-workers have developed protocols in which pinacol rearrangement... 

Selenium dioxide is a useful reagent for allylic oxidation of alkenes. The products can include enones, allylic alcohols, or allylic esters, depending on the reaction conditions. The mechanism consists of three essential steps (a) an electrophilic ene reaction with Se02, (b) a [2,3]-sigmatropic rearrangement that restores the original location of the double bond, and (c) solvolysis of the resulting selenium ester.183... 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

The combination of pericyclic transformations as cycloadditions, sigmatropic rearrangements, electrocydic reactions and ene reactions with each other, and also with non-pericyclic transformations, allows a very rapid increase in the complexity of products. As most of the pericyclic reactions run quite well under neutral or mild Lewis acid acidic conditions, many different set-ups are possible. The majority of the published pericyclic domino reactions deals with two successive cycloadditions, mostly as [4+2]/[4+2] combinations, but there are also [2+2], [2+5], [4+3] (Nazarov), [5+2], and [6+2] cycloadditions. Although there are many examples of the combination of hetero-Diels-Alder reactions with 1,3-dipolar cycloadditions (see Section 4.1), no examples could be found of a domino all-carbon-[4+2]/[3+2] cycloaddition. Co-catalyzed [2+2+2] cycloadditions will be discussed in Chapter 6. 

A simple synthesis of fluorenes as 4-297 was developed by Schafer and coworkers, also using a combination of a Claisen rearrangement and a carbonyl ene reaction (Scheme 4.63) [100]. Heating 4-295 in xylene at 180 °C led to 4-297 as a single diastereomer in 73 % yield the phenol 4-296 can be assumed as an intermediate, but this could not be detected in the reaction mixture. 

Compounds 102 and 103 are products of cyclopropylcarbinyl rearrangements under the reaction conditions, and compound 104 is the product of an ene reaction . Relative reactivities of 96 with furan (7), 2,3-dimethylbutadiene (35), 1,3-cyclohexadiene (26) and cyclopen tadiene (6) were estimated to be 1 2.5 2.5 50, respectively [27]. 

The allene 149 gave by reaction with maleic anhydride (entry 1) and N-phenylmaleimide (entry 2) the [2 + 2] adducts 155a, b as mixtures of two diastereoisomers [36], Nevertheless, their chemical yield was very low and competitive reactions, mostly [4 + 2] cycloadditions on a rearranged al-lylidenecyclopropane and on a primary 1 1 adduct derived from an ene reaction (see Sect. 2.1.2), prevailed. Allenes 149 and 563 cycloadded to tetracyano- and l,l-bistrifluoromethyl-2,2-dicyanoethylene (Table 45, entries 3-6) also selectively at the cyclopropyl substituted double bond in order to remove most of the ring strain [149a],... 

Shortly after these results were published, Giguere and coworkers reported dramatic reductions in reaction times in other MW-assisted syntheses, including Diels-Alder, Claisen rearrangements and ene reactions [2]. These reactions were also performed at elevated pressures, but sealed glass vessels (inside a bath packed with ver-miculite) were used rather than Teflon. 

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