Catalytic deuteration

Under certain conditions surface catalytic deuterations can lead to the exchange of benzylic hydrogens. An example in the steroid field is the exchange of the benzylic hydrogens in estrone methyl ether (42) with deuterium in the presence of palladized charcoal." " According to mass spectrometric analysis, the product (43) contains three deuteriums (83 %), which have been assigned to the 6- and 9a-positions on the basis of NMR evidence." " ... 

Homogeneous catalytic deuteration of various unsaturated 5a-spirostane derivatives is an excellent method for the preparation of side chain labeled analogs. Thus, saturation of the double bonds at positions 20(21), 23 and 24 provided the corresponding deuterated compounds (144), (145) and (146) in high isotopic purity. The preparation of (146) is a rare example of the saturation of an isolated trisubstituted double bond in the steroid field. 

Remarkable success has been achieved by Fryzuk and Bosnich (247) using the complex [Rh(5,5-chiraphos)(COD)]+, where the chiral ligand 25,55-bis(diphenylphosphino)butane, a diphosphine chiral at carbons (25), is readily synthesized from 2R,3R-butane diol. TheZ-isomers of the prochiral a-N-acylaminoacrylic acid substrates were hydrogenated at ambient conditions to / -products with very high enantiomeric excess indeed, leucine and phenylalanine derivatives were obtained in complete optical purity. Catalytic deuteration was shown to lead to pure chiral f3-carbon centers as well as a-carbon centers in the leucine and phenylal-... 

The ion 28 loses H2 by CID with argon to form [(PHOX)Ir(styrene)]+ (29). Compound 29 then undergoes H-D exchange with D2 gas to form the mixture of iso-topomers 29, 29-dh and 29-d2 (Scheme 13.3). When combined, these observations show that the oxidative addition of H2 to 29 is followed by alkene hydride insertion, and that both these steps occur rapidly and reversibly in the gas phase. These results thereby provide gas-phase analogues for catalytic elementary steps that are proposed to occur in solution. Support for this proposed sequence of steps was obtained from a solution-phase catalytic deuteration of styrene. Analysis showed no deuterium incorporation in the unreacted styrene at various conversions, and clean formation of dideuterio ethylbenzene as sole product. 

In the case of actinide systems it was found possible to effect catalytic deuteration of the SiAfc3 groups using D2 and making use of a hydride leaving group.251... 

Asymmetric transfer hydrogenation of benzaldehyde-l-d with (R,R)-28 and (CH3)3COK in 2-propanol gave (R)-benzyl-l-d alcohol quantitatively in 98% ee (Scheme 41) [114], Introduction of electron-donating and electron-accepting groups at the 4 position had little effect on the enantioselectivity. Catalytic deuteration of benzaldehydes was achieved by use of the same complex (R,R)-28 and a 1 1 mixture of formic acid-2-d and triethylamine to give the S deuter-io alcohols in up to 99% ee (Scheme 42) [114], The dt content in the product alcohol was >99%. Only a stoichiometric amount of deuterium source is required to complete the reaction. 

Chiral methyl chiral lactic acid (5). This labeled molecule, useful for study of stereospecificity of enzymic reactions, has been prepared in a way that allows for synthesis of all 12 possible isomers. One key step is the stereospecific debromination of 1, accomplished by conversion to the vinyl-palladium cr-complex 2 followed by cleavage with CF3COOT to give the tritium-labeled 3. The next step is the catalytic deuteration of 3, accomplished with a rhodium(I) catalyst complexed with the ligands norbornadiene and (R)-l,2-bis(diphenylphosphino)propane. This reaction gives 4 with an optical purity of 81%. The product is hydolyzed to 5, which is obtained optically pure by cr3rstallization. 

E2S.15 Two observations must be explained in this catalytic deuteration of C-H bonds. The first is that ethyl groups are deuterated before methyl groups. The second observation is that a given ethyl group is completely deuterated before another one incorporates any deuterium. Let s consider the first observation first. The mechanism of deuterium exchange is probably related to the reverse of the last two reactions in Figure 26.20, which shows a schematic mechanism for the hydrogenation of an olefin by D2. The steps necessary for deuterium substitution into an alkane are shown below and include the dissociative chemisorption of an R-H bond, the dissociative chemisorption of D2, and the dissociation of R-D. This can occur many times with the same alkane molecule to effect complete deuteration. 

Stoichiometric cycloruthenation reactions, as well as the early example of catalytic deuteration of phenol (see above) [38] served for the development of efficient catalytic strategies for C-C bond formations through C-H bond functionalizations. Indeed, ruthenium-catalyzed atom-economical [51] addition reactions of arenes onto C-C multiple bonds, hydroarylations [52-57], were found to be very useful. In an early example, Lewis and Smith disclosed a regioselective alkylation of phenol through in situ formation of its phosphite, and subsequent directed C-H bond functionalization (Scheme 8) [58],... 

Catalytic deuteration of carbon-carbon multiple bonds is thus preferably restricted to small uncomplicated molecules or, as in the formation of [D2]-dihydrouracil from uracil,24 to such as contain a limited number of C-H bonds. Good results can also always be obtained when the substance to be reduced does not contain hydrogen in the allyl position, e.g., withJ1-3-keto steroids,25 and in partial reduction of carbon-carbon triple bonds. Khan20 gives the following description of the last-mentioned reaction ... 

A second objective was to obtain more information about the related efficiencies of films of different metals for the catalytic deuteration of benzene. Beeck and Ritchie (7) investigated the hydrogenation of benzene over both oriented and unoriented films of nickel, and they did some work with iron films, but no information comparable to the extensive data 8) for the hydrogenation of ethylene is available. 

Since some authors did not report information on the above cited side reactions, we carried out some catalytic deuterations of methyl dimorphecolate (methyl 9-hydroxy-octadeca-trara-lO, tra s-12-dienoate), an optically pure precursor of (9/ )-9-HSA. We used an in situ deuterium production method, and we report the new results obtained in section 4 of this Chapter. 

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