Alkenes Lewis acid catalysis

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

The final class of reactions to be considered will be the [4 + 2]-cycloaddition reaction of nitroalkenes with alkenes which in principle can be considered as an inverse electron-demand hetero-Diels-Alder reaction. Domingo et al. have studied the influence of reactant polarity on the reaction course of this type of reactions using DFT calculation in order to understand the regio- and stereoselectivity for the reaction, and the role of Lewis acid catalysis [29]. The reaction of e.g. ni-troethene 15 with an electron-rich alkene 16 can take place in four different ways and the four different transition-state structures are depicted in Fig. 8.16. 

While doubly activated dienophiles gave moderate to good yields under thermal conditions (Table 11), mono activated alkenes such as cyclohexenone (123) failed to react at temperatures up to 150 °C but underwent cycloaddition under Lewis-acid catalysis even if with poor yields (Table 12, entries 1-3) [32],... 

We have a choice of reagents for the -butyl cation a halide with Lewis acid catalysis, and -butanol or isobutene with protic acid catalysis. The least wasteful is the alkene as nothing is lost. Protonation gives the r-butyl cation and two r-butyl groups are added in one operation.3... 

The limitation of the pinacol is the need for symmetry. This section and the next suggest ways of avoiding this problem. Unsymmetrical epoxides are easily made from alkenes and open with Lewis acid catalysis to give the more substituted of the two possible cations.9 Even such a weak Lewis acid as LiBr opens the epoxide 51 to give the tertiary cation 52 which rearranges by ring contraction to the aldehyde 53. The authors prefer to have the bromocompound 54 as an intermediate.10... 

A major problem in the reaction of a,/3-unsaturated carbonyl compounds and alkenes proves to be the competition between hetero Diels-Alder and ene reactions. Intramolecular cycloadditions of 1,6- and 1,7-dienes with ester and cyano groups at the double bond yield the ene product nearly exclusively, but with alkylidene- and benzylidene-ketoesters and 1,3-diketones the Diels-Alder reaction is preferred under thermal conditions, however under Lewis acid catalysis also ene reactions occur [12]. 

The major interaction between these two molecules is between the nucleophilic end of the exo-cyclic alkene and the electrophilic end of the acrylate. These atoms have the largest coefficients in the HOMO and LUMO, respectively, and, in the transition state, bond formation between these two will be more advanced than anywhere else. For most ordinary alkenes and enophiles, Lewis acid catalysis to make the enophile more electrophilic, or an intramolecular reaction (or botft is necessary for an efficient ene reaction. 

Cyanoselenenadon of unactivated alkenes occurs only under harsh conditions, such as strong Lewis acid catalysis (e.g. tin(IV) chloride). The yields are usually good and only trans stereoisomers are observed. Unfortunately, unsymmetrical (terminal and trisubstituted) alkenes yield regioisomeric mixtures. This method provides easy access to unusual trisubstituted carbonitriles starting from relative simple alkenes (equation 20). Several different cyanoselenates are readily available. ... 

In a study by Wicha directed to the synthesis of prostaglandins from the Corey lactone, the use of BFs-EtaO to catalyze the addition of the lithium sulfone anion (470) to aldehydes was demonstrated (equation 109). The use of Lewis acid catalysis results in significantly improved yields for the addition component of the Julia coupling. In this example, the addition of either the lithium or the magnesium sulfone anion proceeded in low yield. With the addition of BF3-Et20, the p-hydroxy sulfone can either be isolated, or directly converted to an alkene in one pot. This sequence was originally developed to deal with the specific problem of a-hydroxy aldehydes, and the difficulty of sulfone anion addition to these adducts. Other problems with addition of the sulfone adduct may be amenable to this solution as well. 

A second application of the use of Lewis acid catalysis in the Julia coupling can be found in the synthesis of trans-Biiktnt isosteres of dipeptides (478 Scheme 62). Initially, attempts to couple aldehydes derived from amino acids (473) resulted in poor overall yield of the alkene. This difficulty was solved by reversing the substituents, and introducing the amino acid portion as the anion of sulfone (476) to the chiral aldehyde (477). The dianion of the sulfone was formed and to it were added 2 equiv. of aldehyde and 1 equiv. of diisobutylaluminum methoxide. The resulting p-hydroxy sulfone was t en on to the reductive elimination step to produce the desired ( )-alkene (478), in 74% overall yield. 

Cyclopropenes may undergo [2 + 2] cycloaddition to themselves, to form dimers, or to other alkenes the reactions may be brought about by photolysis, metal catalysis, Lewis acid catalysis, or simply by heat. Due to the difficulties that can be encountered in completely purifying some cyclopropenes, it is possible that some thermal reactions are actually initiated by small quantities of impurity. The following sections include those reactions occurring under thermal and Lewis acid catalysis. Those brought about by photolysis are covered in Section... 

Vinyl silanes resemble alkenes in reactivity they combine with reactive electrophiles such as bromine without catalysis but need Lewis acid catalysis for reaction with carbon electrophiles. Reaction usually occurs 189 at the silyl end of the alkene so that the intermediate 190 enjoys the P-silyl stabilisation of the carbocation. The silyl group is removed by a nucleophile, usually a halide ion.45... 

An early variant of the Nazarov cyclization119 employed an alkoxycarbonyl substituent and Lewis acid catalysis to facilitate the reaction. The cyclizations were described as temperamental", but did demonstrate the capability to facilitate the cyclization and control the site of the alkene in the cyclized product. For example, cyclization of the a,a -dienone 7 is promoted by the action of trimethylsilyl iodide to afford the /i-keto ester 8 in 48% yield. No studies in stereoinduction have been reported, but, given the recent advances in the design of chiral Lewis acids and the efficient chiral auxiliaries for the reactions of carboxylic acid esters, these substrates are potentially suitable candidates for such studies. 

Similarly, Gonzdlez and Houk predicted that the Diels-Alder reaction of acetylene with 2- abutadiene is more than 2 kcal/mol higher in activation energy than the corresponding ethylene reaction [93]. In the same paper, they also investigated the substituent effects on the reactivities of alkene and alkyne multiple bonds, and the effect of Lewis acid catalysis on these reactions. Another reaction studied computationally was the Diels-Alder reaction of acetylene with a-pyrone [94]. 

To conclude this section, it is important to note that alkenes are not the only hydrocarbon dienophiles that are useful partners in the Diels-Alder reaction. Alkynes and even benzyne are quite useful. As a structure proof of an intermediate in Pandey s synthesis of epiboxidine, the methyl carbamate of pyrrole (34) reacted with dimethyl-2-butynoate (35),in the presence of aluminum chloride (see sec. 11.6.A for a discussion of Lewis acid catalysis) to give a 90% yield of azanorbomadiene (36). A benzyne derivative of pyridine was... 

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