Ruthenium‐Catalyzed Regioselective Deuteration of Alcohols at the β‐Carbon Position with Deuterium Oxide

Abstract

A convenient method for regioselective H/D exchange between D(2)O and alcohols at the β-carbon position using the catalytic system [(p-cymene)RuCl(2)]/ethanolamine/KOH is described. This method is applicable for deuteration of both primary and secondary alcohols. The H/D exchange reactions proceed through an oxidation/modification/reduction reaction sequence. Alcohols are first temporarily oxidized to carbonyl compounds by the hydrogen transfer catalyst. The carbonyl compounds then undergo deuteration at the carbon adjacent to the carbonyl group by keto-enol tautomerization in the presence of D(2)O and a catalytic amount of base. The deuterated carbonyl compounds are then reduced to produce deuterated alcohols. In support of the reaction mechanism, a well-defined bimetallic ruthenium complex was isolated from the reaction of [{(p-cymene)RuCl(2)}(2)] with ethanolamine. The activity of this complex is similar to that of [{(p-cymene)RuCl(2)}(2)]/ethanolamine.

Ruthenium-catalyzed β-alkylation of secondary alcohols with primary alcohols

“…Other solvents were purged with nitrogen for 10 min before use. CpRuCl(dppe) [28], CpRuH(dppe) [29], Cp ⁄ RuCl(COD) [30], Cp ⁄ RuCl(PPh 3 ) 2 [31], RuHCl(CO)(PPh 3 ) 3 [32], RuH 2 (CO)(PPh 3 ) 3 [32], {[(p-cymene) RuCl(NH 2 CH 2 CH 2 O)] 2 H}Cl [33], (p-cymene)RuCl(NH 2 CH 2 CH 2 NTs) Cl [34], (p-cymene)RuCl 2 (PPh 3 ) [35], Ru(OAc) 2 (PPh 3 ) 2 [36], RuCl 2 (PPh 3 ) 2 (2,2 0 -bipyridine) [37], RuCl 2 (NH 2 CH 2 CH 2 NH 2 )(PPh 3 ) 2 [38], RuCl 2 (dppf)(2-PyCH 2 NH 2 ) [39], RuCl 2 (dppb)(2-NH 2 CH 2 Py) [26], RuCl 2 (2-H 2 NCH 2 Py)(PPh 3 ) 2 [26], RuCl 2 (PPh 3 ) 3 [40], RuCl 2 (DMSO) 4 [41], CpRuCl(PPh 3 ) 2 [42], and RuCl 2 (PPh 3 )(2,2 0 :6 0 ,2 00 -terpyridine) [43] were prepared following the procedures described in the literature. All other reagents were used as purchased from Aldrich Chemical Co., Acros Organics, International Laboratory (USA), or Kodak.…”

Ruthenium-Catalyzed Deuteration of Alcohols with Deuterium Oxide

“…It is noted that the energy (29.0 kcal/mol) of the ratedetermining transition state for the hydrogenation/dehydrogenation/dehydrogenation reaction (TS 26-27 , Figure 3) mediated by 14 is substantially lower than those (>35 kcal/mol) for the H/D exchange reaction (TS 15-17, TS 16-16′ , TS [16][17][18][19] in Figure 1) of 14 with D 2 O. The results suggest that hydrogenation of carbonyl compounds and dehydrogenation of alcohol mediated by 14 will proceed more easily than the H/D exchange of the hydride complex 14 with D 2 O.…”

“…47 The solvation and dispersion corrected free energies of the selected structures with respect to the energy reference point are approximately the same as the free energies obtained in the gas-phase calculations. For example, the free energies calculated for TS 15-17 , TS [16][17][18][19] , and TS 23-24 in the gas phase with respect to the reference point are 35.2, 36.5, and 24.1 kcal/mol, respectively, while the solvation and dispersion-corrected free energies are 37.0, 36.1, and 26.1 kcal/mol, respectively. The small differences in the free energies obtained between the two methods do not change the whole picture and conclusions.…”

“…40 All of the calculations were performed with the Gaussian 03 software package. 41 To verify that the relative free energies do not change significantly when the calculations are done with solvation and dispersion effects included, we carried out single-point energy calculations in solvent at the B3LYP-D3 level with the same basis set on the selected optimized structures TS 15-17 , TS [16][17][18][19] , and TS 23-24 . 42 The conductor-like polarizable continuum model (CPCM) was used in the single-point energy calculations, where water was employed as the solvent according to the reaction conditions, and the solute surface was defined by UAKS radii.…”

Hydride‐Rhodium(III)‐N‐Heterocyclic Carbene Catalysts for Vinyl‐Selective H/D Exchange: A Structure–Activity Study

“…Since the pioneering works of Garnett4 and Shilov5 in the 1960s, a plethora of transition‐metal‐based homogeneous catalytic systems for H/D exchange have been developed, including those based on iridium,4c, 6 rhodium,4d, 6g,t, 7 palladium,7h, 8 platinum,4a,b, 5, 7h, 8a,c, 9 ruthenium,7i, 10 cobalt,11 and osmium 7i. 10h, 12 The versatility of these organometallic catalysts is shown by their ability to deuterate different CH groups of aliphatic,2b, 6k,m, 7b,f, 10b,e,i aromatic,2b, 4a, 6k,m,o,s–u, 7b,g,k, 9d, 10e,h,j, 12 and vinylic substrates 6a,n. 7a,d,e,i, 10g However, the control of regio‐ and stereoselectivity still remains an important challenge, especially for the deuteration of olefins in the presence of aromatic groups.…”