Deuterium labelling arylation

Noyori et al. recently used ESI-MS to characterize species present in catalytically active solutions during the hydrogenation of aryl-alkyl ketones using their base-free catalyst precursors trans-[Ru((R)-tol-BINAP)((R, RJ-dpenJfHXf/ -BH ] (tol-BI-NAP = 2,2 -bis(ditolylphosphino) -1, T-binaphthyl dpen = 1,2-diphenylethylenedia-mine) in 2-propanol [9b]. Based upon ESI-MS observations, deuterium-labeling studies, kinetics, NMR observations, and other results, the authors proposed that the cationic dihydrogen complex trans-[Ru((R)-tol-BINAP)((R, R)-dpen)(H)( 2-H2)]+ is an intermediate in hydrogenations carried out in the absence of base. 

With deuterium-labeled dimethylaniline as the excited electron donor, primary electron transfer to aryl halides is followed by proton transfer yielding reduced aryl nitro compounds and functionalized dimethylanilines (193). 

As a rather special case, alkyl aldehydes are reduced with titanocen dichloride to the hydrocarbons through a titanium-bonded alkenic intermediate as shown by a deuterium-labeling experiment. Thus, dodecanal was converted to dodecane in 71% yield, along with dodecan-I-ol in 15-20% yield alkyl ketones such as adamantan-2-one and dodecan-6-one afforded alcohols as the major products. No reduction occurred in the case of aryl aldehydes where alkene formation is impossible. ... 

The classic photochemical reaction involving thiophenes is the isomerisation of 2-aryl-thiophenes to 3-aryl-thiophenes the aromatic substituent remains attached to the same carbon and the net effect involves interchange of C-2 and C-3, with C-4 and C-5 remaining in the same relative positions scrambling of deuterium labelling is, however, observed, complicating interpretation of the detailed mechaifism. 

The mass spectra of 1,3-dithianes is more complicated. The electron impact (El) mass spectrometry of 2-aryl and 2-alkyl-l,3-dithianes has been investigated with deuterium labeling studies and these showed the loss of S2H to be a common feature. <690MS(2)6l l, 720MS(7)317>. The El mass spectra of... 

Miller and coworkers have used deuterium labelling to study the mechanism of the electrophilic aromatic substitution reactions of jS-aryl-a,jS-unsaturated diazoalkanes. It had been proposed that the reaction proceeded via an Sti electrocyclic ring closure followed by a [1,5] sigmatropic hydrogen shift (equation 36). 

Deuterium labelling and n.m.r. spectroscopy have been used to study the conformation of thioxanthenium methylides which exist in the e conformation.The stereochemistry (including conformation) of 9-(aryl)thioxanthene 10-oxides and 10,10-dioxides has also been investigated. 

The transformation was found to be stereospecific since [Dj]-trans-215a reacted with (2-naphthyl)magnesium bromide to give [Djj-216 with complete retention of the deuterium label. Under the same reaction conditions, the deuterium atom was completely eliminated from [Dj ]-ds-215b resulting in the unlabeled arylated alkene 216 and [Djj-naphthalene, which is consistent with a possible pathway outlined in Scheme 10.70. 

Investigation on secondary kinetic isotope effects with deuterium labeling on the arene suggests a reaction mechanism in which the C-H bond cleavage is the rate-determining step. This may explain the requirement for the methyl-substituted alkene in order to arrive at a more stabilized neopentyl-like palladium intermediate M. For 2-chlorophenyl as aryl substituent, the superiority of the present pathway was demonstrated over a potential sequence of oxidative insertion,... 

The preceding reactions dealt with the use of chiral auxiliaries linked to the electrophilic arene partner. The entering nucleophile can also serve as a chiral controller in diastereoselective SjjAr reactions. This approach was successfully employed for the arylation of enolates derived from amino acids. To illustrate the potential of the method, two examples have been selected. Arylation of Schollkopf s bislactim ether 75 with aryne 77 as electrophilic arylation reagent was demonstrated by Barrett to provide substitution product 81 with good yield (Scheme 8.18) [62, 63]. Aryne 77 arises from the orf/jo-lithiation of 76 between the methoxy and the chlorine atom followed by elimination of LiCl. Nucleophilic attack of 77 by the lithiated species 78 occurs by the opposite face to that carrying the i-Pr substituent. Inter- or intramolecnlar proton transfer at the a-face of the newly formed carbanion 79 affords the anionic species 80. Subsequent diastereoselective reprotonation with the bulky weak acid 2,6-di-f-butyl-4-methyl-phenol (BHT) at the less hindered face provides the syn product 81. Hydrolysis and N-Boc protection give the unnatural arylated amino acid 82. The proposed mechanism is supported by a deuterium-labeling experiment. Unnatural arylated amino acids have found application as intermediates for the construction of pharmaceutically important products such as peptidomi-metics, enzyme inhibitors, etc. [64, 65]. 

In 2006, Liu and coworkers reported a gold-catalyzed intramolecular cycloaddition of diynes with tethered arenes 118 to synthesize l,3-dihydroindeno[2,l-c]pyran or 2,3-dihydro-l//-indeno[2,l-c]pyridinederivatives 120 (Scheme 12.52) [56]. On the basis of deuterium labeling, they believed that the first reaction step is the intramolecular arylation of one alkyne to form vinylgold(I) intermediate 119,... 

Using a similar concept, Wolfe and Rossi developed a novel palladium-catalyzed stereoselective synthesis of tetrahydrofurans from y-hydroxy alkenes and aryl bromides [27] (Scheme 6.17). After a series of deuterium labeling experiments, the authors suggested that the predominant mechanistic pathway for tetrahydrofiiran formation probably involves a rare syn insertion of an alkene into the Pd-O bond of an intermediate palladium aryl alkoxide [28]. Later, the same group reported similar intramolecular [29] and intermolecular [30] cyclizations to synthesize a series of tetrahydrofurans. 

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