Ene adducts

The reaction of hexafluoroacetone azine with cycloheptatriene at 70 °C provides after 8 days a mixture containing 28% of unchanged azine 290 and products formed by three distinct mechanistic pathways, that is, criss-cross cycloaddition product 294, a bis-ene adduct 295 and its oxidation product 296, and [3+6] cycloaddition leading to diaziridine 297, in the ratio 15 38 7 (Scheme 40) <1995JFC(73)203>. 

PTAD spontaneously reacts with various olefins to give the corresponding ene adducts, for example, the reaction with 2-methylbut-2-ene gives a nearly quantitative yield of 645 <1980JOC3467>. When the reaction is run in acetone in the presence of various salts, for example, magnesium perchlorate, in addition to 645, triazolol l, 2-r oxadiazine 646 is formed in 10-30% yield, depending on the reaction conditions (Scheme 105) <1994T1821>. 

The alkene 1-decene (24) was poorly reactive in the carbonyl-ene reaction with ethyl mesoxalate and required a temperature up to 170 °C for a very long time (5 h) [42]. When performed in a homogeneous liquid medium at the same temperature but under the action of MW irradiation the reaction gave a similar result. Reaction time was appreciably shortened by use of GS/MW coupling [30]. Thus, irradiation at 60 W for only 10 min led to the ene adduct 25 in 50% yield (Scheme 7.2). Under these conditions a maximum temperature of 230 °C was measured. To obtain the same yield with conventional heating at 170 °C reaction for 1 h is required. The stereoselectivity of the reaction was not related to the mode of heating. A higher con-... 

Dioxopentane-3-thione reacts178 with allyltributylstannane, Scheme 14, to give the expected thiophilic ene adduct and a [2+2] cycloadduct. 

The presence of EWG on 2,4-dioxopentane-3-thione favours the formation of thiophilic adducts with different allyl substrates.178 In all cases the reaction affords single thiophilic ene adducts and formation of C=C occurs with high E stereoselectivity (Scheme 17). 

The third transformation, by far the most encountered process, is the /3-hydride elimination which is the major and the fastest process in many cases (Scheme 49). The /3-elimination is usually followed by the reductive elimination to give the cycloadduct and regenerate the active metal species. Depending on the regioselectivity of the elimination (Ha or Hb), two dienes, 1,3- and/or 1,4-diene, can be obtained. The products of the latter case formally correspond to Alder-ene adducts (see Chapter 10.12). 

Synthetic activity associated with the carbonyl-ene reaction is extensive. During the past decade, the trend has been to perform these reactions in the presence of a Lewis acid in an enantioselective fashion. Efforts to find a general catalyst that affords homoallylic alcohols in high yields and enantioselectivities are continual. The synthetic utility of this reaction has been validated by its application to the synthesis of a number of natural products (see Section 10.12.6) and many structurally novel motifs that have found a place in drug discovery vide infra). It is the latter application that has resulted in research efforts aimed at large-scale production of carbonyl-ene adducts. 

Chiral bisoxazolines (box) ligands have been attached to a polyethylene glycol (PEG) matrix 25.24 The supported ligands were tested on a variety of reactions for their enantioselectivity. The carbonyl-ene reaction between a-methyl styrene or methylene cyclohexane (26, Equation (15)) and ethylglyoxalate 12 afforded the corresponding ene adduct 27 in 96% and 91% yield and 95% and 85% ee, respectively. 

Silylated primary allylic amines, e.g. CH2=CHCH2N(SiMe3)2, are produced from allylic chlorides and the mixed reagent AgI/LiN(SiMe3)2205. The formation of allylic amines from olefins by the ene reaction is shown in equation 77. The ene adducts 205 from bis(2,2,2-trichloroethyl) azodicarboxylate are converted into 206 by zinc dust in acetone/acetic acid206. 

The cis effect was rationalized by examination of the possible transition states leading to the major and the minor ene adduct (Scheme 2). In transition state 1 (TSO, the interactions between the incoming oxygen and the two allylic hydrogens are more favourable than those in transition state 2 (TS2) where only one allylic hydrogen is present (Scheme 2). 

The anti selectivity increases as the disubstituted side of the double bond becomes more crowded (Scheme 8). This is illustrated with the trisubstituted alkenes 16, 17 and 13. Alkene 16 shows the normal cis effect selectivity where only 10% of the anti ene adduct is formed. However, as the size of the cis alkyl substituent increases from methyl in 16, to isopropyl in 17 and ferf-butyl in 13, the anti selectivity increases from 10% to 42% and to >97%, respectively. The same trend is also noted in substrate 19. A substantial deviation from cis effect selectivity is observed by replacing one methyl group in 18 with a ferf-butyl group in 19. The totally unreactive methylene hydrogens in 18 (cis effect) become reactive in 19, producing the exo ene adduct in 38% yield. 

The role of non-bonded interactions between the ois alkyl substituents during the fornnatlon of the new double bond in the ene adduct... 

For example, in substrates 94 and 96 the major ene adducts (74% and 90%, respectively) are formed by vinylic hydrogen atom abstraction, whereas the minor ene adducts (26% and 10%, respectively) are produced by allylic hydrogen abstraction. The percentage of... 

As discussed in Section II.A.4, photooxygenation of l-aryl-2-methylpropenes in solution proceeds slowly, and affords a complex mixture of products arising mainly from [4 + 2] or [2 + 2] addition to the double bond. The ene pathway is less favourable or even absent. For example, -dimethylstyrene (20) affords the ene adduct in approximately 20% yield, benzaldehyde (from a [2 - - 2] pathway), and mainly two diastereomeric di-endoperoxides (from a [4-1-2] pathway) in a 2/1 ratio (Scheme 48). Similarly, for l-(2-methylpropenyl)naphthalene (137), the 1,4-endoperoxide is mainly formed. ... 

The intrazeolite photooxygenation in a series of isobutenylarenes (20, 137-146), bearing either electron-withdrawing or electron-deficient substituents on the aryl ring, affords rapidly the ene allylic hydroperoxides as the major or even exclusive products (Table 22). The relative yield of the ene adduct was always higher than 85%. 

SCHEME 54. Transition states leading the major ene adducts in solution and within Na-Y... 

Ortiz AL, Echegoyen L (2010) Unexpected and selective formation of an (e, e, e, e)-tetrakis-[60]fullerene derivative via electrolytic retro-cyclopropanation of a D2h-hexakis-[60]fuller-ene adduct. J Mater Chem 21 1362-1364... 

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