Dehalogenative Deuteration of Unactivated Alkyl Halides Using D₂O as the Deuterium Source

Abstract

The general dehalogenation of alkyl halides with zinc using D2O or H2O as a deuterium or hydrogen donor has been developed. The method provides an efficient and economic protocol for deuterium-labeled derivatives with a wide substrate scope under mild reaction conditions. Mechanistic studies indicated that a radical process is involved for the formation of organozinc intermediates. The facile hydrolysis of the organozinc intermediates provides the driving force for this transformation.

Enantiopure 2,9‐Dideuterodecane – Preparation and Proof of Enantiopurity

“…The combined organic layers were washed with hydrochloric acid (1 mol/L, 90 mL), dried over MgSO 4 and evaporated to yield the title compound 9b (225 mg, 1.58 mmol, 86 %, based on 42 % purity established by 1 H NMR) as a colorless liquid. The spectroscopic data were in accordance with the literature and with those of the product of the catalytic hydrogenation [44] …”

“…13 C{ 1 H} NMR (75 MHz, CDCl 3 ): δ =14.29 (2×CH 3 ), 22.86 (2×CH 2 ), 29.53 (2×CH 2 ), 29.83 (2×CH 2 ), 32.09 (2×CH 2 ) ppm. All spectroscopic data were in accordance with the literature [44] . C 10 H 22 (142.29) (b) Through diimide reduction of 5‐decene (10b) .…”

Recent Advances in the Synthesis of Deuterium‐Labeled Compounds

“…The Br/D exchange reactions of arenes could also occur in a palladium-catalyzed system with a deuterium-labeled formate salt as the deuterium source. [23] Xia et al [24] developed zinc catalysts for the dehalogenation of alkyl halides and obtained deuterium-labeled derivatives using D 2 O as the deuterium donor. They also found that the formation and hydrolysis of organozinc intermediates were beneficial for this reaction.…”

Regioselective α-Deuteration of Michael Acceptors Mediated by Isopropylamine in D2O/AcOD

“…Various electron-poor and electron-rich para -substituted cinnamaldehydes underwent deuteration at the α-position in good yield ( 2a – 2g ). In the case of 2h , deuterium incorporation was observed at both the α position and the positions ortho to the aniline group, likely caused by acid-mediated S E Ar with D + …”

“…In the case of 2h, deuterium incorporation was observed at both the α position and the positions ortho to the aniline group, likely caused by acid-mediated S E Ar with D + . 17 Notably, the reaction could tolerate a S VI -containing substrate and afforded the product 2i in good yield with nearly full H/D exchange. The reaction scope was further explored for other substituted and unsubstituted cinnamaldehydes, which were all tolerated (2j−2o).…”