Radical Deuteration with D₂O: Catalysis and Mechanistic Insights

Abstract

Selective incorporation of deuterium atoms into molecules is of high interest for labeling purposes and for optimizing properties of drug candidates. A mild and environmentally benign method for the deuteration of alkyl iodides via radical pathway using DO as source of deuterium has been developed. The reaction is initiated and mediated by triethylborane in the presence of dodecanethiol as a catalyst. This method is compatible with a wide range of functional groups and provides the monodeuterated products in good yields and with a high level of deuterium incorporation. It opens promising opportunities for the development of enantioselective radical reactions. Moreover, a revision of the mechanism of the deoxygenation reaction of xanthates using RB and water (Wood deoxygenation) is presented.

Phosphonium Phenolate Zwitterion vs Phosphonium Ylide: Synthesis, Characterization and Reactivity Study of a Trimethylphosphonium Phenolate Zwitterion

“…The 1 H, 13 C and 31 P NMR data of 1 suggested a dipolar structure. Particularly, the 31 P NMR spectrum showed a characteristic signal for tetravalent phosphorus at 16.7 ppm in CD 3 CN (17.9 ppm in D 2 O or DMSO-d6).…”

“…1 H NMR (400 MHz, CD 3 CN): δ 6.77 (t, J = 8.8 Hz, 1H), 6.41 (dd, J 1 = 9.2 Hz, J 2 = 2.8 Hz, 1H), 6.17 (dd, J 1 = 17.2 Hz, J 2 = 2.8 Hz, 1H), 3.74 (s, 3H), 1.94 (d,J = 14.4 Hz,9H). 13…”

“…[9] Here we report a new trimethylphosphonium phenolate zwitterion 1 (Scheme 1c). [12,13] Thus a new catalytic deuteration process using 1 as the catalyst and CD 3 CN as deuterium source was revealed to selectively afford several deuterium-labelled products with high deuteration. [11] Recognizing the little knowledge on this type of products, a subsequent study was conducted to reveal the reactivity.…”

“…Notably, the development of new hydrogen isotope exchange reactions to access isotopically labeled organic molecules is of current interest in organic chemistry due to the value of deuterated compounds in the study of reaction mechanisms, mass-dependent analysis and biological processes. [12,13] Thus a new catalytic deuteration process using 1 as the catalyst and CD 3 CN as deuterium source was revealed to selectively afford several deuterium-labelled products with high deuteration. In addition, 1 also demonstrated an interesting reactivity similar to a phosphonium ylide and could be used as an olefination reagent to convert aldehydes into terminal alkenes.…”

Diversity‐Oriented Desulfonylative Functionalization of Alkyl Allyl Sulfones

“…Site‐specific incorporation of deuterium is important since deuterium‐labeled compounds are widely applied in synthetic and medicinal chemistry (kinetic isotope effect measurements, pharmacokinetic and pharmacodynamics research) . Radical deuteration using D 2 O as the D‐source represents a promising approach due to the low cost of D 2 O and the high functional group tolerance of radical chemistry. Recently, MacMillan and Renaud developed radical deuterations with D 2 O as the formal D‐donor using phenol or thiol type HAT‐reagents, that readily exchange their protons with D 2 O.…”