Photo-Mediated Decarboxylative Giese-Type Reaction Using Organic Pyrimidopteridine Photoredox Catalysts

Abstract

The decarboxylative Giese-type reaction offers a versatile methodology for the radical alkylation of electron-deficient alkenes. Photo-mediated variants often require a pre-activation of carboxylic acids and/or employment of costly transition-metal photocatalysts. Herein, we present a metal-free photocatalyzed decarboxylative Giese-type addition to electron-deficient alkenes using pyrimidopteridine N-oxides as organic photoredox-active catalysts. This protocol comprises mono-, di-, and trisubstituted aliphatic, α-amino, and α-oxy acids as well as a variety of electron-deficient alkenes. Moreover, post-synthetic derivatization and applications are presented.

Iron(III) Complex-Functionalized Gold Nanocomposite as a Strategic Tool for Targeted Photochemotherapy in Red Light

“…Overall, such photoredox chemistry leads to photodecarboxylation and reduction of iron­(III) (Figures and S26). ,,− …”

Recent Advances in Photoredox‐Mediated Radical Conjugate Addition Reactions: An Expanding Toolkit for the Giese Reaction

“…The established organocatalyst tetrapropylpyrimidopteridine N ‐oxide (PrPPTNO, 14 a , [129] E 1/2 =2.29 V versus SCE in MeCN) and its deoxygenated analogue tetrapropylpyrimidopteridine (PrPPT, 14 b , E 1/2 =2.08 V versus SCE in MeCN) are productive in visible‐light photoinitiated Giese reactions (Scheme 30 F). [130] Both species have very high reduction potentials, rivalling that of the current best‐in‐class organocatalysts [Acr‐Mes]ClO 4 . Unlike the chemoselectivity observed in classic Giese reactions, electron‐dense functional groups like alcohols and amines may competitively quench the catalyst and hamper reaction initiation.…”

“…[10,11,49] Thee stablished organocatalyst tetrapropylpyrimidopteridine N-oxide (PrPPTNO, 14 a, [129] E 1/2 = 2.29 Vversus SCE in MeCN) and its deoxygenated analogue tetrapropylpyrimidopteridine (PrPPT, 14 b, E 1/2 = 2.08 Vv ersus SCE in MeCN) are productive in visible-light photoinitiated Giese reactions (Scheme 30 F). [130] Both species have very high reduction potentials,r ivalling that of the current best-in-class organocatalysts [Acr-Mes]ClO 4 .U nlike the chemoselectivity observed in classic Giese reactions,electron-dense functional groups like alcohols and amines may competitively quench the catalyst and hamper reaction initiation. Interestingly, PrPPTNO-mediated Giese reactions are tolerant of substrates containing free alcohols as well as oxidizable aromatic groups.G iese transformations of benzylic carboxylic acids and phenylcarbamic acid do not generate synthetically useful yields of product, highlighting an opportunity for future technological improvements.…”

Direct decarboxylative Giese reactions

“…95 Possessing high excited-state reduction potentials (* E red 1/2 ≈ +2.32 V) 95 b and good stability, these PCs have been investigated by Pospech and co-workers for use in direct DGRs (Scheme 39). 96 They employed catalyst tetrapropyl-pyrimidopteridine N -oxide ( PrPPTNO ), developing conditions that require low PC loadings, substoichiometric amounts of base, short reaction times, and low light intensity. Despite the potential steric hindrance, the reaction conditions proved most effective with secondary and tertiary alkyl carboxylic acid substrates, achieving low to excellent yields (17–92%) with good functional group tolerance.…”