Abstract:
Here we reveal a simple generation of deuterium halide (DX) from common and inexpensive reagents
readily available in a synthetic chemistry laboratory, i.e. prenyl-, allyl-, and propargyl halides, under mild
conditions. We envisaged that in situ generation of an acid, deuterium halide, would be useful for acid catalyzed reactions and could be employed for organocatalytic deuteration. The present work reports a
metal-free method for deuterium labeling covering a broad range of substrate including phenolic com pounds (i.e. flavonoids and stilbenes), indoles, pyrroles, carbonyl compounds, and steroids. This method
was also applied for commonly used drugs such as loxoprofen, haloperidol, stanolone, progesterone,
androstenedione, donepezil, ketorolac, adrenosterone, cortisone, pregnenolone, and dexamethasone. A
gram-scale chromatography-free synthesis of some deuterated compounds is demonstrated in this work.
This work provides a simple, clean and by-product-free, site-selective deuteration, and the deuterated
products are obtained without chromatographic separation. When applying these initiators for other acid catalyzed reactions, the deuterium isotope effects of DX may provide products which are different from
those obtained from reactions using common acids. Although the mechanism of the spontaneous trans formation of prenyl halides to acid is unclear, this overlooked chemistry may be useful for many reactions
