A simple method for α‐position deuterated carbonyl compounds with pyrrolidine as catalyst

Abstract

A simple, cost-effective method for deuteration of carbonyl compounds employing pyrrolidine as catalyst and D2O as deuterium source was described. High degree of deuterium incorporation (up to 99%) and extensive functional group tolerance were achieved. It is the first time that secondary amines are used as catalysts for H/D exchange of carbonyl compounds, which also allow the deuteration of complex pharmaceutically interesting substrates. A possible catalytic mechanism, based on the hydrolysis of 1-pyrrolidino-1-cyclohexene, for this pyrrolidine-catalyzed H/D exchange reaction has been proposed.

Organocatalytic Deuteration Induced by the Dynamic Covalent Interaction of Imidazolium Cations with Ketones

“…13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 212.5, 41.3 (labeled), 26.9, 24.9. Data in agreement with the literature [9a] …”

Bismuth Subnitrate-Catalyzed Markovnikov-Type Alkyne Hydrations under Batch and Continuous Flow Conditions

“…In most cases, deuteration methods involve halogen/D exchange and are typically mediated by strong bases, which severely limits the functional group tolerance [ 62 ]. Moreover, catalytic H/D exchange reactions are also known; however, these often involve selectivity and/or environmental issues [ 63 , 64 , 65 ]. Inspired by these limitations, we explored a facile methodology to prepare valuable trideuteromethyl ketones by simply switching the reaction medium from MeOH to MeOH- d 4 in bismuth subnitrate-catalyzed alkyne hydrations.…”

B(C6F5)3‐Catalyzed α‐Deuteration of Bioactive Carbonyl Compounds with D2O

“…α ‐Deuteration of bioactive ketones have previously been achieved through Lewis base‐catalyzed conversion of these molecules into enamine or enol intermediates . Representative methods include α ‐C−H deuteration of ondansetron ( A1 ) by pyrrolidine and D 2 O (Scheme A) . 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene (DBU)‐catalyzed α ‐deuteration process represents a notable strategy for isotopic labelling of 2‐acetylphenothiazine ( B1 ) and two other structurally related drugs (Scheme B) .…”