Efficient and Convenient Heterogeneous Palladium‐Catalyzed Regioselective Deuteration at the Benzylic Position

Abstract

The Pd/C-catalyzed efficient and regioselective hydrogen-deuterium (H-D) exchange reaction on the benzylic site proceeded in D2O in the presence of a small amount of H2 gas. The use of the Pd/C-ethylenediamine complex [Pd/C(en)] as a catalyst instead of Pd/C led to the efficient deuterium incorporation into the benzylic site of O-benzyl protective groups without hydrogenolysis. These H-D exchange reactions provide a post synthetic and D(2)-gas-free deuterium-labeling method on a wide variety of benzylic sites using D2O as the deuterium source and heterogeneous Pd/C or Pd/C(en) as a reusable heterogeneous palladium catalyst under mild and neutral conditions.

A simple, efficient, and selective deuteration via a flow chemistry approach

“…These values are highly competitive as compared with the literature methods mentioned above. 12,13 A pressure in the 40-60 atm range and flow rate in the range 0.7-2 mL min À1 did not influence the yield or the degree of deuterium incorporation. It is important to note that the reactions were carried out in a single run and the products were analyzed without any further purification.…”

“…However, these time-consuming methods do not produce highpurity D 2 and they also require high pressure, the use of a special catalyst or an excess amount of a strong base or acid. [11][12][13][14] Flow chemistry approaches are commonly used in organic synthesis. 15,16 Among flow chemistry techniques, the best-characterized and most widely used reaction is heterogenous hydrogenation.…”

Rapid, regioselective deuteration of dimethyl-2,2′-bipyridines via microwave-assistance

“…The H-D exchange reactions in D 2 O solutions were thus studied using various inorganic catalysts at different reaction temperatures for 24 h. The results from these exchange reactions are summarized in Table 1. Of the catalysts, Pd/C, 14 and Na 2 CO 3 , known H-D exchange reaction catalysts for heterocyclic compounds, 8d, 10 and bipyridines, 6c, 13b did however not give any H-D exchange of compound 1 in D 2 O solutions (Entries 1-4). In all cases, increasing the reaction temperature did not yield significant advantages over the reaction conducted at lower temperature (Entries 1-4).…”

A Practical Method for p-Methoxybenzylation of Hydroxy Groups Using 2,4,6-Tris(p-methoxybenzyloxy)-1,3,5-triazine (TriBOT-PM)

“…The residue was purified by column chromatography (hexaneEtOAc, 38:1 to 19:1) to afford 2i (173.8 mg, 84%) as a clear colorless oil. 9,11,18 To a solution of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (104.1 mg, 0.400 mmol) and TriBOT-PM (117.5 mg, 0.240 mmol) in THF (1.33 mL), CSA (13.9 mg, 0.0598 mmol) was added at r.t. The mixture was heated to reflux and additional TriBOT-PM was added after 3.5 h (78.3 mg, 0.160 mmol) and 6.5 h (19.6 mg, 0.0400 mmol), respectively.…”