Deuterium-labelled acetylenes

As corroborated by deuterium labeling studies, the catalytic mechanism likely involves oxidative dimerization of acetylene to form a rhodacyclopen-tadiene [113] followed by carbonyl insertion [114,115]. Protonolytic cleavage of the resulting oxarhodacycloheptadiene by the Bronsted acid co-catalyst gives rise to a vinyl rhodium carboxylate, which upon hydrogenolysis through a six-centered transition structure and subsequent C - H reductive elimina-... 

Scheme 14 Top Plausible catalytic cycle as supported by deuterium labeling. Bottom ESI mass spectrum of a reaction mixture aliquot diluted 5000-fold in methanol from the hydrogen-mediated coupling of gaseous acetylene to an a-ketoester (Ar = p-N02Ph)...

Insertion of the alkyne into the Pd-H bond is the first step in the proposed catalytic cycle (Scheme 8), followed by insertion of the alkene and /3-hydride elimination to yield either the 1,4-diene (Alder-ene) or 1,3-diene product. The results of a deuterium-labeling experiment performed by Trost et al.46 support this mechanism. 1H NMR studies revealed 13% deuterium incorporation in the place of Ha, presumably due to exchange of the acetylenic proton, and 32% deuterium incorporation in the place of Hb (Scheme 9). An alternative Pd(n)-Pd(iv) mechanism involving palladocycle 47 (Scheme 10) has been suggested for Alder-ene processes not involving a hydridopalladium species.47 While the palladium acetate and hydridopalladium acetate systems both lead to comparable products, support for the existence of a unique mechanism for each catalyst is derived from the observation that in some cases the efficacies of the catalysts differ dramatically.46... 

A further piece of evidence to elucidate the catalytic pathway of silylformylation was provided by a pair of deuterium-labeled reactions. The results revealed that the scrambling of hydrogen atoms between a hydrosilane and a terminal acetylene is minimal during the reaction and that the hydrogen atom of the formyl group and the vinylic hydrogen are derived from the hydrosilane and the acetylenic proton, respectively (Eq. 8) [15 bj. 

This was explained by the involvement of a vinylidene complex that is also in agreement with the migration of the acetylenic hydrogen to C-2 observed by deuterium labeling. The stereoselective reaction requires the use of EtjN and a slight excess of the alkyne. 

An alternative mechanism calls for hydrogen atom transfer by the reverse of eq 14 with no organome-tallic intermediates. Attempts to distinguish between these two possible pathways of hydrogen addition employed deuterium labeling. Stereoselectivity in the addition of LCoH to double and triple bonds was observed. Early work indicated Co—D cis addition to olefins and acetylenes.232 Later experiments showed... 

Further, hydrolysis of some carbides with D20 leads to important fundamental compounds with deuterium labeling. For example, dideuterio-acetylene is obtained from CaC2f50 tetradeuteriomethane from A14C3,51 and perdeuterated allene from Mg2C3 at about 350° 52... 

Parallel chemical oxidation of deuterium labeled biphenylacetylene with metachloro-perbenzoic acid yielded the same product as was obtained in the enzymatic reaction. These observations exclude the possible oxidation of the acetylenic terminal C—H bond, because such a reaction would not be compatible with complete conservation of the deuterium atom. Thus, the formation of a ketene derivative was postulated (Scheme 5). However, the nature of the intermediate from which the ketene derivative is formed remains to be elucidated. An oxirene structure was suggested in parallel to alkene epoxidation however, oxirenes are very unstable species due to electronic and steric factors It is currently believed that a complex between the acetylenic n electrons and cytochrome P450 iron-oxene moiety is formed, leading to the formation of the ketene. ... 

GrafvonderSchulenburg, W., Hopf, H. and Walsh, R. (1999). AUcyl Migration Aptimdes in the Vinybdene-Acetylene Rearrangement and Isotope Effect in the Vinyhdene Formation Process from a Deuterium-Labeled Cyclopropene. Angewandte Chemie International Edition, 38 1128-1130. 

Recently Miyaura and co-workers have reported a trans-hydroboration of terminal alkynes using [Rh(COD)Cl]2[P( Pr)3]4 or [Ir(COD)Cl]2[P( Pr)3]4 (eq 13). Mechanistic studies via deuterium labeling show that after the oxidative addition of the alkyne to the metal, the acetylenic deuterium undergoes migration to the carbon resulting in the formation of a vinylidene metal complex. Oxidative addition of borane to the metal complex and 1,2-... 

The first of these was a study by Shevlin and Wolf who showed that photochemical addition of carbon suboxide to cyclopropene resulted in the formation of vinyl acetylene and acetylene. They postulated the intermediacy of bicyclobutanylidene as a source of the former and tetrahedrane as a source of the latter (Figure 65). The postulated intermediacy of tetrahedrane was supported by two labeling studies. In the first cyclopropene-3,3-d2 containing 87.1 3.2% deuterium was used. The resulting acetylene was analyzed for... 

Then, in a second experiment, carbon suboxide labeled at the central atom with was photolyzed in the presence of cyclopropene-3,3-d2. The resulting acetylenes were reduced to the corresponding ethylenes with chromous chloride and these were then separated on the basis of deuterium content by gas chromatography. The content of each ethylene was then analyzed and, again, found to be very close to that expected for a tetrahedrane intermediate (Table 3). 

Two chemical syntheses of stereospecifically labeled serines (91, 92) relied on the stereospecific reduction of the acetylene 76 followed by anti addition of MeOBr (91) or HOBr (92) to the product 77. The second of these syntheses (92) is shown in Scheme 21. It involved catalytic reduction of the anthracene adducts of the propiolates 76, Ha = H, and 76 with hydrogen and deuterium, respectively, followed by a retro Diels-Alder reaction. The products were the (Z)-isomer 77, Ha = H, and the (f)-isomer 7, Hg = H, respectively. Reaction of these with Af-bromosuccinimide in sulfuric acid gave three parts of the bromohydrins 78 together with one part of the alternative regioisomers. 

Since no intermediates could be detected in the in vitro studies of the oxidation of acetylenic derivatives, it was assumed that very short-lived intermediates were probably formed. In order to further characterize this pathyway, studies with deuterium and labeled biphenylacetylene (acetylenic hydrogen and internal acetylenic carbon, respectively) were initiated. The mass and nuclear magnetic resonance spectra of the resulting biphenyl acetic acid derivative showed that ... 

The only obvious thermal isomerization of acetylene is transposition of the atoms at either end of the triple bond. This type of dyotropic process was observed in the parent molecule using deuterium and carbon labeling. Thus, flash vacuum pyrolysis of [l- C,l- H]acetylene at temperatures above 700°C resulted in protium appearing at Cl of the recovered acetylene (Scheme 3.1). 

Heavy water is the cheapest available deuterium source. However, it has one inconvenience. Being inevitably employed in excess, it necessitates extraction or at least drying of the reaction mixture as part of the workup protocol. In contrast, deuterium chloride in diethyl ether can be employed in stoichiometric doses. But also this reagent suffers from a drawback. It reacts, if slowly, with the ethereal solvent. Therefore, the indefinitely storable phenylacetylene-ry-c may often become the deuteration reagent of choice. Due to its high intrinsic acidity and its needle-like slim shape, this terminally deuterated acetylene transfers the isotope label most effectively and in general irreversibly. 

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