1. Deuterated-alkylation reagents based on sulfonium salts as cation and radical sources.
- Author
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Ban, Kazuho, Tokunaga, Jin, Yoshimura, Sota, Akai, Shuji, and Sawama, Yoshinari
- Subjects
SULFONIUM compounds ,ALKYLATION ,CARBON-hydrogen bonds ,CYTOCHROME P-450 ,NUCLEOPHILIC substitution reactions - Abstract
The replacement of C–H bonds with more stable C–D bonds at the α-position of heteroatoms, which is the typical metabolic site for cytochrome P450, is important in drug discovery. Recently, we have developed d
n (deuterated)-alkylated sulfonium salts (1a - dn ), which were easily prepared by deuteration (H/D exchange reaction) with D2 O of the corresponding alkyl diphenylsulfonium salts (1a), as electrophilic dn -alkylating reagents (cation sources). Herein, we newly report an improved preparation method of 1a and one-pot synthesis of dn -alkylated compounds via the deuteration of 1a with D2 O and the subsequent nucleophilic substitution under basic conditions. Additionally, dn -alkyl thianthrenium salts (1b - dn ) were also found to work as dn -alkylating reagents (cation sources). Furthermore, 1b - dn served as radical sources under photo-induced reaction conditions with Ir photocatalyst, Hantzsch ester, or triphenylamine to obtain various regioselectively deuterium-incorporated alkyl compounds. These dn -alkylating reagents will contribute to advance the drug discovery. [ABSTRACT FROM AUTHOR]- Published
- 2024
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