Enantioselective Desymmetrization of 1,3‐Disubstituted Adamantane Derivatives via Rhodium‐Catalyzed C−H Bond Amination: Access to Optically Active Amino Acids Containing Adamantane Core

Abstract

In order to synthesize optically active amino acids containing the adamantane core, an enantioselective desymmetrization of adamantanes via rhodium‐catalyzed C−H bond amination was examined. After investigating various conditions, it was found that the coupling reaction between disubstituted adamantane and aryloxysulfonamide was catalyzed by Rh2(S‐TCPTTL)4 to furnish the desired products having up to 85% ee (e.r.=92.4: 7.6) (>99% ee after recrystallization). The synthetic utility of the enantioenriched products as chiral building blocks was demonstrated by transforming one of them into a dipeptide derivative and a Schiff‐base ligand. The absolute configuration of one of the amino acid derivatives was determined unambiguously by X‐ray single‐crystal structure analysis.

Synthesis of 1,2-Disubstituted Adamantane Derivatives by Construction of the Adamantane Framework

“…To date, mostly 1,3-disubstituted achiral adamantane derivatives, utilized as rigid spacers, have been reported. The properties of chiral derivatives can then be exploited in applications where chirality plays a role, such as enantioselective catalysis [30][31][32], the synthesis of enantiopure compounds [33,34], interactions of enantiopure compounds with material [35,36] or light [37], and other physical, chemical, or biological applications [38][39][40]. The low stability of the adamant-1-ene molecule, which has a rather biradical character, does not allow the use of classical alkene chemistry for the formation of 1,2-disubstituted adamantane compounds [41][42][43].…”

“…Molecules 2023, 28, x FOR PEER REVIEW 2 of 30 enantiopure compounds [33,34], interactions of enantiopure compounds with material [35,36] or light [37], and other physical, chemical, or biological applications [38][39][40]. The low stability of the adamant-1-ene molecule, which has a rather biradical character, does not allow the use of classical alkene chemistry for the formation of 1,2-disubstituted adamantane compounds [41][42][43].…”

Catalytic, asymmetric carbon–nitrogen bond formation using metal nitrenoids: from metal–ligand complexes via metalloporphyrins to enzymes

“…170 Another adventurous transformation was recently reported by Yoshida and involved an enantioselective aminative desymmetrisation of 1,3-disubstituted adamantanes using Rh 2 ( S -TCPTTL) 4 . 171 Up to 85% ee was observed and the resulting amino acids built around an adamantane core could be of considerable biological interest.…”