Ryosuke Masuda

Abstract Selenoamides have been recognized as attractive chemical species in various fields; however, derivatives bearing a third heteroatom that can serve as a second reactive center remain limited. In this highlight review, we summarize recent advances regarding the synthesis, structural characterization, and reactivity of selenocarbamoyl compounds that bear main-group substituents such as silyl, germyl, and phosphino groups. Particular emphasis is placed on our recent results pertaining to (selenocarbamoyl)phosphines, which exhibit ambident reactivity at 2 principal sites, i.e. the phosphorus and selenium atoms.

ABSTRACT Despite more than half a century of research on selenoproteins, the central catalytic intermediate, selenocysteine selenenic acid (Sec–SeOH), has remained experimentally elusive. Its isolation has long been impeded by its presumed instability and propensity for thermal deselenation. Here, we report the first isolable Sec–SeOH at ambient temperature. This relies on a bioinspired design of a selenopeptide sequence encapsulated within a protective cradle, together with an oxidant‐free route from the corresponding selenenyl iodides (Sec–SeI), enabling x‐ray structural analysis and chemical characterization. The isolated Sec–SeOH shows unexpected resistance to β‐elimination to dehydroalanine (DHA). Oxidation experiments combined with theoretical calculations demonstrate that conversion to DHA proceeds preferentially via overoxidation to the seleninic acid (Sec–SeO ₂ H), for which β‐elimination is substantially more favorable. Reactivity profiling further highlights the pronounced electrophilicity of Sec–SeOH toward biologically and pharmacologically relevant nucleophiles. These findings redefine the stability–reactivity landscape of Sec–SeOH and provide a foundation for strategies aimed at preventing selenoprotein inactivation. Beyond defining an isolable Sec–SeOH model, the work provides a molecular‐level rationale for how selenoproteins can combine high selenium‐centered reactivity with resistance to irreversible oxidative self‐inactivation.

Abstract Despite considerable research efforts devoted to the applications of selenoamides, derivatives bearing complex functional groups, such as bulky and/or convertible substituents, remain limited so far, probably due to the instability of the selenoamide moiety under several reaction conditions. Herein, we report the synthesis of a selenoformamide possessing both a free hydroxy group and a bulky aryl substituent, achieved via effective N-formylation using acetic formic anhydride and subsequent selenocarbonylation with LiAlHSeH of a sterically encapsulated position. The structure of the selenoamide was established by a single-crystal X-ray diffraction analysis. Although chemoselective transformation of the hydroxy group was found to be challenging, these insights provide a useful platform for further development of selenocarbonyl chemistry.

The synthesis, structural characterization in the solid state, and reactivity of a selenazolidine and a six-membered-ring derivative, i.e., a 1,3-tetrahydroselenazine, that contain a C6F5 substituent are reported. The first crystallographic characterization of a 1,3-tetrahydroselenazine was accomplished by means of single-crystal X-ray diffraction analysis. Despite the structural analogy to C6F5-substituted imidazolidines, these selenium-containing heterocycles exhibit pronounced thermal stability and high resistance toward the formation of the corresponding (amino)(seleno)carbenes, highlighting fundamentally different reactivity patterns between imidazolidines and selenazolidines.