Deuterium labelling nucleophilic addition

A deuterium-labeling study of a reaction of this type demonstrated syn stereoselectivity in both the oxypalladation and P-elimination, which indicates that the cyclization occurs by internal migration, rather than by an anti nucleophilic capture.113 This particular system also gives products from double-bond migration that occurs by reversible Pd(II)-D addition-elimination. 

In light of these kinetic studies, a decrease in the concentration of the ligand is predicted to favor the a-deprotonation pathway. On the contrary, further studies show that the a/yS deprotonation ratio is independent of this concentration. This observation, associated with deuterium-labeling studies, suggests the involvement of the a-deprotonation in the formation of the ally lie alcohols at low concentration of ligand. Conversely, the presence of highly coordinating solvents such as HMPA, which break up ion pairs, suppresses both a-deprotonation and nucleophilic addition (Scheme 14) . ... 

The same ethylidene ruthenium complex, as well as its iron congener, is alternatively obtained through direct protonation of the dimetallacycles 64a (M = Fe) and 64b (M = Ru) (64). In this case, the carbonyl alkyne carbon-carbon bond is broken irreversibly to give the cationic /x, 17s-vinyl complexes 65a and 65b, which undergo nucleophilic attack by hydride (NaBFLi) to produce complexes of methylcarbene (63a,b) (Scheme 21a). Deuterium-labeling experiments prove that the final compounds arise from initial hydride addition to the /3-vinylic carbon of 65. However, isolation of small amounts of the 7j2-ethylene complex 66 indicates that hydride attack can also occur at the a-vinylic carbon (64). 

The reaction of vinylic phenyliodium salts (57) with cyanide anions could be mistaken for a simple substitution reaction.59 However, the presence of both allylic (58) and vinylic (59) nitrile products suggests a more complex picture. Deuterium labelling experiments show that the allylic product is formed via the Michael addition of cyanide to the vinylic iodonium salt, followed by elimination of iodobenzene and a 1,2-hydrogen shift in the 2-cyanocycloalkylidene intermediate (60). H-shift occurs from the methylene carbon in preference to the methine carbon. The effects of substitution and different nucleophiles were examined. 

Bauld and coworkers studied the [2+2] cycloaddition of A-vinyl carbazoles 86a and electron-rich styrenes 86b catalyzed by iron(III) catalysts A or B in the presence of 2,2 -bipyridine as a ligand, which was reported originally by Ledwith and coworkers (Fig. 21) [142, 143]. Deuterium-labeling studies provided support for the stepwise nature of the process, consisting of reversible SET oxidation of the electron-rich olefin to a radical cation 86 A. Nucleophilic addition of excess 86 leads to distonic radical cation 86B, which cyclizes to cyclobutane radical cation 86C. Back electron transfer affords cyclobutanes 87 and regenerates the catalyst. Photoelectron transfer catalysis gave essentially the same result, thus supporting the pathway. 

The mechanism of this reaction was investigated in detail by Wakatsuki [13] by isolation of intermediates, deuterium-labeling experiments and theoretical calculations. The postulated catalytic cycle involves first the protonation of a Ru(II)-alkyne species to give a Ru(IV)-vinylidene intermediate via a Ru(IV)-vinyl species. The nucleophilic addition of water to the a-carbon of the vinylidene ligand followed by reductive elimination affords the aldehyde (Scheme 8.3). 

The mechanism of formation of benzvalene from cyclopentadienyl-lithium and dichloromethane has been studied in detail. On employing dideuteriodichloro-methane, the deuterium label is found to be stereospecifically located at the C-1 position of the product, in contrast to earlier reports. These data are compatible with two routes (i) chlorocyclopropanation of the cyclopentadienyl-lithium and subsequent nucleophilic displacement of the chloro-substituent and (ii) attack of the cyclopenta-dienyl anion on the dichloromethane to produce a cyclopentadienyl carbenoid A distinction between these two routes comes from a study of the reaction with indenyl-lithium. The exclusive formation of 1- and 2-deuterionapthalene (0.6 1) as byproducts is compatible only with the carbenoid path (Scheme 6) in which 1,2-cheletropic addition affords benzobenzvalene uniquely labelled at C-1, as is observed. 

Oxygen nucleophiles The enantioselective addition of water to enones in an aqueous environment, catalysed by a copper complex with an achiral ligand, non-covalently bound to DNA has been reported to produce the corresponding )8-hydroxy ketones with <82% ee. Deuterium labelling demonstrated that the reaction is diastereospecific, with only the S yn-hydration product formed, for which outcome, there is no equivalent in conventional homogeneous catalysis ... 

Nucleophilic attack of stabilized carbon nucleophiles on coordinated olefins is also known. Hegedus developed the alkylation of olefins shown in Equation 11.31. The (olefin)palladium(II) chloride complexes did not react with malonate nucleophiles, but the triethylamine adduct does react with this carbon nucleophile to provide the alkylation product. This reaction has recently been incorporated into a catalytic alkylation of olefins by Widenhoefer. - Intramolecular reaction of the 1,3-dicarbonyl compounds with pendant olefins in the presence of (GHjCNl PdCl occurs to generate cyclic products containing a new C-C bond (Equation 11.32). Some intermolecular reactions with ethylene and propylene have also been developed by this group. Deuterium labeling studies (Equation 11.32) have shown that the addition occurs by external attack on the coordinated olefin. ... 

A wide range of transition metal-allyl complexes are known to react with many types of nucleophiles. In most cases, these reactions occur between cationic allyl complexes and amines or stabilized, anionic carbon nucleophiles. The reaction typically occurs between the nucleophile and the form of the allyl complex, and attack usually occurs at the face of the allyl ligand opposite the metal. However, there are exceptions to these trends. For example, several experiments suggest that unstabilized carbon nucleophiles react first at the metal center, and C-C bond formation occurs between the alkyl and the allyl group by reductive elimination. In addition, a recent study has shown through deuterium labeling that attack of malonate anion on a molybdenum-allyl complex occurs with retention of configuration. ... 

A deuterium-labeling experiment was carried out to probe the reaction mechanism. The results indicated that the H/D exchange at the ort/io-position is reversible. A proposed mechanism is shown in Scheme 16. An iminium species 39, which is proposed as the CO source, is generated in situ from DMF via a multistep process under Cu(ll) catalyst with O2. The reaction of cyclometalated complex 20 with 39 resulted in the formation of 40, which is oxidized by Cu(ll) under O2 to give 41. An intramolecular nucleophilic addition gives the intermediate 42, which is followed by oxidation and hydrolysis to afford the phthalimide 38. 

An elimination-addition mechanism has also been invoked for the nucleophilic substitution of cyclohexenyliodonium salts with acetate ion. For example, the reaction of either the 4- or 5-substituted cyclohex-l-enyl(phenyl)iodonium tetra-fluoroborate (31 or 32 respectively) with tetrabutylainmonium acetate in aprotic solvents gives the ipso and cine acetate substitution products (33 and 34 and vice-versa, respectively) in almost the same ratio (Scheme 23). These results were consistent with an elimination-addition mechanism involving 4-substituted cyclohexyne 35 as a common intermediate. The presence of a cyclohexyne intermediate was confirmed by deuterium labelling and trapping studies leading to [4-l-2]-cycloaddition products. 

During the formation of ylide 2 in the presence of EtOLi the acetate moiety has been lost. As the reagent is a nucleophile, it is reasonable to consider that the removal of the acetate group takes place by a classical addition-elimination process induced by ethoxide. Thus, nucleophilic attack of the EtOLi on the carboxylate in 1 would form intermediate 11 that by elimination of ethyl acetate gives ylide 2 (Scheme 31.5). This mechanistc proposal is fully in agreement with the retention of the deuterium label in the reaction products 10 when starting from the a-deuterated salt 9. 

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