Versatile Regioselective Deuteration of Indoles via Transition-Metal-Catalyzed H/D Exchange

Abstract

The promising application of deuterium-labeled compounds, such as the drug deutetrabenazine, warrants efficient, selective, and direct deuteration of organic entities. Here, we present a highly effective regioselective direct C–H deuteration of indole in D2O using Cp*Co­(CO)­I2, [Cp*RhCl2]2, or their combination as a catalyst. This transition-metal-catalyzed system made available mono­(C2)-, di­(C2/C7)-, tri­(C2/C3/C7)-, and even C4-deuterated products from diverse indole substrates, equipped with the removable N1-directing group. The selective H/D exchanges on the rest of the sites of the indoles were also realized by shifting the directing group. Furthermore, an example of this approach was demonstrated to acquire deuteromelatonin from the drug melatonin.

Enantioselective C–H Functionalization toward Silicon-Stereogenic Silanes

“…Besides the enantioselective C–H silylation of dihydrosilanes, Zhao and Zhang recently realized an Ir-catalyzed desymmetric C–H silylation of prochiral diarylsilanol-derived monohydrosilanes (Scheme 16 ). 23 Starting from diarylsilanol 72 , installation of a (hydrido)silyl ether group generates the diarylsilanol derivative 73 , which undergoes subsequent Ir-catalyzed desymmetric intramolecular C–H silylation to deliver the silicon-stereogenic silanol derivative 74 . This approach was inspired by previously reported Rh- and Ir-catalyzed enantioselective dehydrogenative C–H silylations for the synthesis of carbon-stereogenic diarylmethanols by Hartwig and Shi, as well as Ir-catalyzed intramolecular C–H silylation of siloxane-tethered arene by Cui and Xu.…”

Undirected, Pd-catalysed deuteration of indoles with programmable regioselectivity

“…23 Selective deuteration at C2 can currently only be achieved using directed approaches (5): ortho-lithiation 17 or transition-metal catalyzed methods requiring a directing group on the indole nitrogen. [24][25][26] Directing group removal is not always straightforward, 27 andcruciallycan cause isotopic dilution if strong acidic or basic conditions are required. 26,28 Therefore, a directing group free method for C2-deuteration would be highly beneficial.…”

Synthesis of Multideuterated (Hetero)aryl Bromides by Ag(I)-Catalyzed H/D Exchange

“…Direct hydrogen isotope exchange (HIE) is considered to be the most straightforward method for quick access to deuterated arenes . Recently, direct HIE reactions with transition metals including Ir, Pd, Ru, Pt, Fe, Ni, and Co as catalyst have been well explored as a prevalent method for selective deuterium-labeling of aromatic rings (Scheme C). Despite many efforts on the extension of substrate scope, the reported transition-metal-catalyzed H/D exchange protocols still relied on the use of directing groups containing an N or O atom to assist H/D exchange processes and to control site-selectivity.…”