Electrophilic cycloaddition

The inside alkoxy effect is useful for predicting the stereoselectivity of nitrile oxide cycloaddition reactions with chiral lylic ethers. The hypothesis states that allylic ethers adopt the inside position and alkyl substituents prefer the sterically less-crowded anti conformation in transition states for these electrophilic cycloadditions . The terms inside and outside are defined in (17) for a hypothetical nitrile oxide cycloaddition transition state. Both ab initio (Gaussian 80 with 3-2IG basis set) and molecular mechanics calculations agree, each predicting the lowest-energy transition state to be the one described, i.e. (18 H outside) just above it lies one where the alkyl group is anti, OR outside and H inside (19 ). As illustrated, the former leads to a product wherein OR and the nitrile oxide oxygen are anti, the latter to one with them syn (Scheme 19). 

The yield of 2 in this reaction can be improved up to 40% by adjusting reaction conditions and using some additives. An alternative route is based on gas-phase oxidation of CH3CF2CF2H by O2 at 500°C, leading to oxetanes 2 in a good yield. Perfluoroalkoxy-substituted oxetanes can be prepared in low yield (<20%) by electrophilic cycloaddition of formaldehyde to perfluorovinyl ethers. Both regioi-somers are formed in this process. 

An electrophilic cycloaddition process was proposed as the mechanism of [3-sultone formation. The initial step is an electrophilic attack of sulfur trioxide on the double bond of fluoroolefin to afford a dipole intermediate (29), which then undergoes intramolecular cyclization (Scheme 2.14). 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

Miscellaneous Reactions. Some hydantoin derivatives can serve as precursors of carbonium—immonium electrophiles (57). 5-Alkoxyhydantoins are useful precursors of dienophiles (17), which undergo Diels-Alder cycloadditions under thermal conditions or in the presence of acid catalysis (58). The pyridine ring of Streptonigrine has been constmcted on the basis of this reaction (59). 

Chemical Properties. The chemistry of ketenes is dominated by the strongly electrophilic j/)-hybridi2ed carbon atom and alow energy lowest unoccupied molecular orbital (LUMO). Therefore, ketenes are especially prone to nucleophilic attack at Cl and to [2 + 2] cycloadditions. Less frequent reactions are the so-called ketene iasertion, a special case of addition to substances with strongly polarized or polarizable single bonds (37), and the addition of electrophiles at C2. For a review of addition reactions of ketenes see Reference 8. 

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

The quiaones have excellent redox properties and are thus important oxidants ia laboratory and biological synthons. The presence of an extensive array of conjugated systems, especially the a,P-unsaturated ketone arrangement, allows the quiaones to participate ia a variety of reactioas. Characteristics of quiaoae reactioas iaclude nucleophilic substitutioa electrophilic, radical, and cycloaddition reactions photochemistry and normal and unusual carbonyl chemistry. 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

It was not their reactivity but their chemical inertness that was the true surprise when diazirines were discovered in 1960. Thus they are in marked contrast to the known linear diazo compounds which are characterized by the multiplicity of their reactions. For example, cycloadditions were never observed with the diazirines. Especially surprising is the inertness of diazirines towards electrophiles. Strong oxidants used in their synthesis like dichromate, bromine, chlorine or hypochlorite are without action on diazirines. Diazirine formation may even proceed by oxidative dealkylation of a diaziridine nitrogen in (186) without destruction of the diazirine ring (75ZOR2221). The diazirine ring is inert towards ozone simple diazirines are decomposed only by more than 80% sulfuric acid (B-67MI50800). 

Benzo[c]furan, 1,3-dihydro-1,3-diphenyl-mass spectrometry, 4, 585 Benzo[c]furan, 1,3-dfmethyl-synthesis, 4, 699, 701 Benzo[c]furan, 1,3-diphenyl-cycloaddition reactions, 4, 67 electrophilic substitution, 4, 604 history, 4, 533... 

Oxazolium hydroxide, anhydro-5-hydroxy-aromaticity, 6, 184 cycloaddition reactions, 6, 209 dimerization, 6, 207 1,3-dipolar cycloaddition reactions with alkynes, 6, 210 electrophilic reactions, 6, 207 mesoionic reactions, 6, 188 reactions, 6, 206-211 synthesis, 6, 225-227... 

The reactions of electrophilic alkenes (alkenes attached to electron-withdrawing groups) with enamines produce one or more of the following products simple alkylation (2), 1,2 cycloaddition (3), and 1,4 cycloaddition (4). Competition with C alkylation by N alkylation is inconsequential and therefore will be largely ignored (5,7). A stepwise ionic mechanism leading to these products necessarily involves the formation of a zwitterion intermediate (1) as the first step, which is then followed either by one of the... 

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