Intramolecular reactions nucleophilic capture

The TT-allylpalladiLim complexes formed as intermediates in the reaction of 1,3-dienes are trapped by soft carbon nucleophiles such as malonate, cyanoacctate, and malononitrile[ 177-179). The reaction of (o-iodophenyl-methyl) malonate (261) with 1,4-cyclohexadiene is terminated by the capture of malonate via Pd migration to form 262. The intramolecular reaction of 263 generates Tr-allylpalladium, which is trapped by malononitrile to give 264. o-[odophenylmalonate (265) adds to 1,4-cyciohexadiene to form a Tr-allylpalladium intermediate via elimination of H—Pd—X and its readdition, which is trapped intramolecularly with malonate to form 266)176]. 

The ET photochemistry of (IR, 35)-(+)-c/i-chrysanthemol (c/i-127) proceeds via nucleophilic attack of the internal alcohol function on the vinyl group with simultaneous or rapid replacement of an isopropyl radical as an intramolecular leaving group, forming 128. This reaction is a mechanistic equivalent of an Sn2 reaction the mode of attack underscores the major role of strain relief in governing nucleophilic capture in radical cations. 

The 5-nitrosopyrrolopyrimidine (46) is converted by potassium pyrosulfate or triphenylphosphine into the pyrimidinopyrimidine (47). The reaction is thought to go via a nitrene, captured by intramolecular insertion. Nucleophilic attack by ammonia or primary amines at C-6 leads to the same ring enlargement, probably by the mechanism indicated. Treatment of the product (48 R = H)] with nitrous acid produces a compound (47) identical with that from the pyrosulfate reaction (Scheme 15) (72CPB2076). 

Many radical cations derived from cyclopropane (or cyclobutane) systems undergo bond formation with nucleophiles, typically neutralizing the positive charge and generating addition products via free-radical intermediates [140, 147). In one sense, these reactions are akin to the well known nucleophilic capture of carbocations, which is the second step of nucleophilic substitution via an Sn 1 mechanism. The capture of cyclopropane radical cations has the special feature that an sp -hybridized carbon center serves as an (intramolecular) leaving group, which changes the reaction, in essence, to a second-order substitution. Whereas the SnI reaction involves two electrons and an empty p-orbital and the Sn2 reaction occurs with redistribution of four electrons, the related radical cation reaction involves three electrons. 

C-Ring substituted indoles, including 4-nitroindole, are also allylated under these conditions. The reaction is believed to proceed by an Sa I mechanism, with the Zn(03SCF3)2 acting as a Lewis acid catalyst. There may also be some N-H deprotonation by the amine. 1-Methylindole reacts under these conditions, but with reduced yield. The Zn(03SCF3)2-mediated reaction was used in tandem with intramolecular nucleophilic capture to synthesize the flustramine structure [89]. 

This reaction represents capture of the intermediate a complex as the result of intramolecular nucleophilic attack by the carboxylate group ... 

There are also reactions in which electrophilic radicals react with relatively nucleophilic alkenes. These reactions are exemplified by a group of procedures in which a radical intermediate is formed by oxidation of readily enolizable compounds. This reaction was initially developed for /3-ketoacids,311 and the method has been extended to jS-diketones, malonic acids, and cyanoacetic acid.312 The radicals formed by the addition step are rapidly oxidized to cations, which give rise to the final product by intramolecular capture of a carboxylate group. 

The nucleophiles that are used for synthetic purposes include water, alcohols, carboxylate ions, hydroperoxides, amines, and nitriles. After the addition step is complete, the mercury is usually reductively removed by sodium borohydride. The net result is the addition of hydrogen and the nucleophile to the alkene. The regioselectivity is excellent and is in the same sense as is observed for proton-initiated additions.16 Scheme 4.1 includes examples of these reactions. Electrophilic attack by mercuric ion can affect cyclization by intramolecular capture of a nucleophilic functional group, as illustrated by entries 9-11. Inclusion of triethylboron in the reduction has been found to improve yields (entry 9).17... 

The reaction is based upon the two components condensation between an aldehyde or ketone 6 (or their synthetic equivalents) and alcohol 95, which contains an allylsilane (or vinylsilane) moiety. The IMSC reaction is mediated by Lewis or Bronsted acids, which activate the carbonyl group of 6 towards nucleophilic attack. After addition of alcohol 95 on the activated carbonyl, the oxonium cation 96 is formed, which is intramolecularly captured by the pendant allylsilane function, leading to oxygen-containing rings 97 (Scheme 13.38). This process typically requires a stoichiometric (or more) amount of Lewis acid. 

The alkyne insertion reaction is terminated by anion capture. As examples of the termination by the anion capture, the alkenylpalladium intermediate 189, formed by the intramolecular insertion of 188, is terminated by hydrogenolysis with formic acid to give the terminal alkene 192. Palladium formate 190 is formed, and decarboxylated to give the hydridopalladium 191, reductive elimination of which gives the alkene 192 [81]. Similarly the intramolecular insertion of 193 is terminated by transmetallation of 194 with the tin acetylide 195 (or alkynyl anion capture) to give the dienyne 196 [82], Various heterocyclic compounds are prepared by heteroannulation using aryl iodides 68 and 69, and internal alkynes. Although the mechanism is not clear, alkenylpalladiums, formed by insertion of alkynes, are trapped by nucleophiles... 

Under these conditions, silver-assisted electrocyclic ring opening provided the haloallyl cation, which was subsequently trapped by isocyanate anion. Interception of the cationic species with isocyanate was successful since bromide was removed from the reaction mixture as a precipitate (AgBr). Finally, treatment of intermediate 9 with methanol furnished the desired carbamate in 96% yield. This example demonstrates the usefulness of the silver(I)-mediated process. Removal of free halide from the reaction mixture affords a long-lived cationic species that can be captured by a different nucleophile, such as solvent, the silver(I) counteranion, or an intramolecular nucleophile. This reactivity has been exploited in many different ways throughout the years and is examined in greater detail later in this chapter. 

Carbocyclic compounds can be formed by the nucleophilic intramolecular capture of a seleniranium intermediate of an olefinic bond. The carbonium ion which is formed as intermediate can react with another nucleophile or with the solvent. The first examples of these carbocyclization reactions were observed with dienes. Clive [105] reported that the reaction of the diene 203 with phenyl-selenyl chloride in acetic acid afforded the intermediate 204 which reacted with the solvent to give the bicyclic compound 205 (Scheme 31). Carbocyclization reactions were efficiently promoted by phenylselenyl iodide produced by diphenyl diselenide and iodine. As indicated in Scheme 31,Toshimitsu reported that the reaction of 1,5-hexadiene 206, in acetonitrile and water, afforded the acetamido cyclohexane derivative 209, derived from the cyclization of the seleniranium intermediate 207 followed by the reaction of the carbocation 208 with acetonitrile [106]. In several cases, carbocyclization reactions can be more conveniently effected by independently generating the seleniranium intermediates. A simple procedure consists of the reaction of trifluoromethane-sulfonic acid with j9-hydroxyselenides, which can be easily obtained from the... 

All of the reactions you have met so far involve radical attack between two molecules. We ve pointed out some of the drawbacks when C-C bonds are made in this way the radical trap has to be activated (that is, electrophilic to capture nucleophilic radicals) and must often be present in excess and the radical starting material must contain very weak C-X bonds (such as C-Br, C-1, C-Hg). The requirements are much less stringent, however, if the radical reaction is carried out intramolecularly. 

By way of review, the Prins reaction (Scheme 8.20) comprises addition of a carbonyl group to an olefin followed by capture of a nucleophile by the other end of the double bond (20-1). A side reaction consists of addition of carbonyl oxygen (20-2). Yet another photolysis, this one on 19-5, severs the bond between the carbonyl and the adjacent quaternary carbon atom to the unsaturated aldehyde 21-1 (Scheme 8.21) this is admixed with the product of 21-2 from addition via oxygen. Treatment of the mixmre of these products with mild acid leads to intramolecular Prins condensation of the aldehyde in 21-1 with the C13-C14 double bond. Capture of a nucleophile, in this case water, from the less hindered face installs the critical 14a-hydroxyl function. The (9-addition product 21-2 presumably cycles back to 21-1, which the goes on to product. The 12)8-hydroxy product predominates over its 12a-isomer in a 2 1 ratio. 

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