Trapping by Nucleophiles

The existence of n-complex intermediates can be inferred from experiments in which they are trapped by nucleophiles under special circumstances. For example, treatment of the acid 1 with bromine gives the cyclohexadienyl lactone 2. This product results from capture of the n-complex by intramolecular nucleophilic attack by the carboxylate group ... 

In solution, l-(ot-aminoalkyl)benzotriazoles 562 are in equilibrium with iminium cation 563 and hence with their benzotriazole-2-yl isomers 564 (Scheme 89). Protonation or complexation of the benzotriazolyl moiety (e.g., Mg, Zn, B, A1 reagents) facilitates the transformation. Intermediate iminium cations 563 can be trapped by nucleophiles providing synthetic pathways to various amines. Many such reactions are described in CHEC-II(1996) <1996CHEC-11(4)1 >, and some newer results are compiled in reviews <2005T2555>. 

Chromene acetals 39 are accessible from 2-vinyl-substituted phenols via the allylic acetals 38 through oxypalladation of benzyloxypropa- 1,2-diene and a subsequent Ru-catalysed RCM. 2-Substituted chromenes can be derived from the acetals 39 by conversion into the 1-benzopyrylium salts which are then trapped by nucleophiles (Scheme 26) <00TL5979>. In a like manner, 2-aIkoxychromans have been converted into various 2-substituted chromans by sequential treatment with SnCl4 and a silyl enol ether <00TL7203>. 

Disubstituted 2,4-cyclohexadienones (112) undergo photoinduced electrocyclic ring opening to the transient ketene derivatives 113, which can be trapped by nucleophiles to prepare the corresponding carboxylic acid derivatives (114 equation 44)196 197 j le reaction has been employed successfully for the synthesis of various carboxylic acids, esters and amides. 

These can be further oxidized to 1,3-dications and trapped by nucleophiles such as water, alcohols, or chloride ion. 

The ethylene bromonium and 1-bromoethyl cations and their neutral and anionic counterparts have been the subject of a tandem mass spectrometric study of dissociation and gas-phase redox reactions. IR and Raman studies of the bioactive bromonium cation (19), as its hydrogensulfate salt, agree with the results of an X-ray structure determination, and theoretical calculations are also in agreement, except for the details of the NO2 groups. The azaallenium ion (22) is an intermediate in the photolysis of (20) (21) and (22) could both be seen. Flash photolysis of (23) leads to (24), (25), and (26), all of which could be trapped by nucleophiles (27) was not an intermediate. NMR lineshape analysis of the spectmm of (28) leads to reaction rate constants of formation for both the intimate ion pair (29) and the solvent-separated ion pair (30). ... 

The allylic cation (40), formed in a specific acid-catalysed process, is relatively stable thermodynamically, stable enough towards trapping by nucleophiles that the reaction product obtained is almost invariably the naphthalene elimination product. di-Enediynes (42) are formed regiospecifically when the allylic cation (41) is trapped as shown. The walking of methanol around optically active l-methyl-3-ethylallyl... 

The electrophilic intermediate formed during the Beckmann rearrangement may be trapped by nucleophiles other than water. Strictly speaking, these reactions do not fit into the classical rearrangement reaction type. However, due to the fact that the carbon framework changes during the course of the reaction and to the similarities with the classical Beckmann rearrangement process, this topic will be analysed in the present chapter. 

Radical cations of 2-alkylidene-l,3-dithianes can be generated electrochemically by anodic oxidation using a reticulated vitreous carbon (RVC) anode <2002TL7159>. These intermediates readily react with nucleophiles at C-1. Upon removal of the second electron, the sulfur-stabilized cations were trapped by nucleophilic solvents, such as MeOH, to furnish the final cycloaddition products. Hydroxy groups <20010L1729> and secondary amides <2005OL3553> were employed as O-nucleophiles and enol ethers as C-nucleophiles (Scheme 50) <2002JA10101>. 

The oxonium ion generated when dihydropyran is coupled with ethyl glyoxylate in the presence of TiCU can be trapped by nucleophiles offering a useful route to 2,3-disubstituted tetrahydropyrans <99TL1083,4751>. 

The ring expansion of furans by dichlorocarbene addition gives unstable 2,3-dichlorochromenes, which are trapped by nucleophilic displacement reactions (Scheme 13).232 233... 

Elimination of hydrogen halide from dihalocyclopropanes occurs under the influence of strong bases, leading to haiocyclopropenes. Simple halocyclopropenes are unstable but can be trapped by nucleophiles (Scheme 12).191,192 In situations where hydrogen migration is possible, isomerization of the chlorocyclo-propene to alkylidenecyclopropane takes place readily. Thus (27 equation 65) is an excellent precursor... 

The cyclopropyl-allyl rearrangement has been shown to proceed with nucleophilic assistance,87i232<233 and the intermediate allyl cation can be trapped by nucleophiles leading to synthetically useful derivatives. An example is the formation of an unsaturated acetal and the propiolic acid ortho ester (equations 92 and 93).232... 

With 0,-y-unsaturated a -diazo ketones, the resulting [2.1.0]-bicyclic systems (40) were quite unstable and underwent a [2 + 2] cycloreversion to generate ketenes (41), which were then trapped by nucleophiles (Scheme 7). The overall scheme has been named a vinylogous Wolff rearrangement and offers a novel entry to products usually derived from a Claisen rearrangement.102 A recent report describes its application for functionalized angular alkylation in fused ring systems.103 In contrast, the intramolecular re-... 

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... 

On the other hand, a similar activation has been found to be practically possible when carbamates or amides instead of amines themselves are used as the starting materials. The a cation formed from carbamates and amides is sufficiently stable to be trapped by nucleophiles in solution 17). 

The Ru(II)/ROOH system can also be used to oxidize tertiary amines. The intermediate iminium ion is formed, as described earlier for secondary amines, and can be trapped by nucleophiles. Thus, the ruthenium-catalysed oxidation of tertiary amines with hydrogen peroxide in methanol can be performed to give the corresponding a-methoxyamines with high efficiency as illustrated in Fig. 24 [ 137]. Another example is the selective demethylation of tertiary amines in methanol with a combination of Ru(II) and H202, followed by hydrolysis of the intermediate a-methoxylated amines. For example, the methoxylation of N,N-dimethyl-p-toluidine followed by treatment with 2 N HC1 solution gave N-methyl-p-toluidine in 75% yield (Eq. 35) [137]. 

The cation radical intermediates formed from the enamines may be trapped by nucleophiles other than the solvent when these nucleophiles are electrochemically less oxidizable than the enamines. Indeed, the cation radical intermediates formed from morpholino-, piperidino-and pyrrolidinoenamines are trapped by carbanions derived from active methylene compounds such as methyl acetoacetate, acetylacetone and dimethyl malonate with moderate yields (equation 2)3. The products are easily transformed to the corresponding a-substituted ketones by hydrolysis with dilute hydrochloric acid. 

Despite the reactivity of carbazole cation-radicals, that of 9-ethylcarbazole has been trapped by nucleophiles, e.g., I", NO2,475 Thus, iodo and nitro derivatives of 9-ethylcarbazole result, along with 9,9 -diethyl-3,3 -bicarbazole, when 9-ethylcarbazole is oxidized by iodine in the presence of iodide and nitrite.473 Oxidation in the absence of nucleophiles, e.g., by nitrosonium tetrafluoroborate, permits the synthesis of the cation-radical fluoroborate salts of the 3,3 -bicarbazoles476 The reactivity of the cation-radical of 9-vinylcarbazole has been reviewed recently.11,477... 

The doubly charged ion can also be easily trapped by nucleophiles [75,156-159]. The whole of the experimental results described in this section open a puzzle question about the actual mechanism operating in the sensitized photooxygenation of donors with different chemical features. 

The radical cations generated in some electron-transfer reactions can often be trapped by nucleophiles. Many of these reactions are of synthetic value. It has been shown that many phenylalkenes react with electron acceptors under the influence of light to give styry] cations which can be trapped by nucleophilic alcohols or cyanide ions for example, 1-phenylcyclopentene... 

Reaction of (284) with an aldehyde, ketone, or enol ether in the presence of acid results in an electrophilic substitution that produces a -ferrocenylalkyl carbocations that may be trapped by nucleophiles (azides, amines, thiols). This chemistry may be used to prepare enantiomerically pure ferrocene derivatives in a maimer that avoids resolution procedures (Scheme 86)." For example, the enol ether from (-)-menthone affords a kinetic carbocation (302) that may be trapped or allowed to rearrange to the more thermodynamically stable cation (303) and then trapped, thus offering a means of controlling the configuration of the stereocenter adjacent to the ferrocene unit. Use of an enantiomerically pure aldehyde derived from Q -pinene (304) affords a 1 1 carbocationic mixture that similarly isomerizes to a single cation. 

A number of different bases, usually KOH or NaOH [45] with a phase-transfer catalyst [46] or crown ether [47], have been used for generating carbenes which can be trapped by nucleophilic species such as alkoxides, thiolates and, more usually, alkenes. This approach to carbene generation is still popular due to the low cost and the ease of handling the reagents used some examples are given in Figure 6.34 [45, 46, 48]. 

The discovery that sterically crowded -carbon enols are kinetically stable constitutes the milestone towards the elucidation of the electron transfer ability of enolates . Based on this, Schmittel and coworkers started an accurate examination of their redox aptitude, and how it could be reflected on their chemical reactivity. In particular, they pointed out how the predominance of ketones over enols in the neutral keto/enol equilibrium could be inverted upon one-electron oxidation. These findings opened up interesting possibilities for new synthetic procedures. Starting from available ketones, the small amount of enol present in equilibrium can be oxidized by suitable oxidants and the resulting radical cation can be trapped by nucleophiles. For example, l-(p-methoxyphenyl)propan-2-one, which has an enol [l-(p-methoxyphenyl)propen-2-ol] content of only about 0.0001% , reacts with tris(p-methoxyphenyl)aminium hexachloroantimonate in methanol to give the a-methoxyketone 76 °. Comparable yields are obtained with [Fe(phen)3](PFe)3. The products isolated in the reactions are consistent with the mechanism reported in equation 52. 

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