Photodecarboxylative C–H Alkylation of Azauracils with N-(Acyloxy)phthalimides

Abstract

We disclose a transition-metal-free NaI/PPh3-mediated direct C–H alkylation of azauracils using N-(acyloxy)­pthalimides (NHPIs) as readily available alkyl surrogates under visible light irradiation. Detailed mechanistic studies reveal formation of a photoactivated electron donor–acceptor (EDA) complex between NaI/PPh3, TMEDA, and alkyl NHPI ester and establish the crucial role of TMEDA in increasing the activity of the photoredox system. The reaction demonstrates a broad scope, scalability, and appreciable functional group tolerance. A variety of azauracils are shown to undergo alkylation by primary, secondary, and tertiary NHPI esters under mild conditions, furnishing the desired products in good to excellent yields.

Diastereoselective 1,2-difunctionalization of 1,3-enynes enabled by merging photoexcited Hantzsch ester with chromium catalysis

“…This evidence suggests that the electron donor–acceptor (EDA) complex was most likely not formed in the ground state. 41,42 Based on the previous reports, 40,43 the excited-state redox potential of HE* was as negative as −2.28 vs. SCE in DMF, and the reduction of Cr III ( E 1/2 = −0.51 vs. SCE in DMF) and BrCF 2 COOEt ( E 1/2 = −0.57 vs. SCE in DMF) by HE* should be feasible via the photoinduced single electron transfer (SET) process (Fig. 2a).…”

Alkyl radicals from diacyl peroxides: metal-/base-/additive-free photocatalytic alkylation of N-heteroaromatics

“…16 Numerous synthetic procedures on the functionalization of N -heteroaromatics, including alkylation, 17 acylation, 18 arylation, 19 alkoxylation, 20 and other processes, 21 have been developed during the past few decades. 22 Particularly, the direct C–H functionalization of azauracils has gained huge attention recently using sulfur ylides, 23 1,4-dihydropyridines (DHPs), 24 N -alkyl- N -methyl anilines or ethers, 25 and N -(acyloxy)pthalimides (NHPI esters) 26 as alkylating reagents, respectively. However, the metal-free photocatalytic system at room temperature employing alkyl diacyl peroxides as alkyl radical sources has never been established so far.…”

Base-Promoted 1,6-Aza-Michael Addition of Azauracils to para-Quinone Methides

“…We recently reported a transition-metal-free multicomponent reaction between p -QMs, carbon disulfide and amines to access S -diarylmethane dithiocarbamates. 12 In continuation of our interest in metal-free synthetic techniques, 9 12 13 we herein report an organic-base-promoted 1,6-conjugate addition of azauracils with p -QMs to furnish biologically relevant N 4 -diarylmethane azauracils (Scheme 1c ).…”

“…Recently, we became interested in the chemistry of azauracils, 9 a class of privileged nitrogen heterocycles that are recurring motifs in numerous natural products and bioactive compounds (Figure 1 ). 10 Compounds embedded with such motifs are known to serve as antiviral, 10f anticoccidial 10c and 5-HT 1A agonist PET tracer agents.…”

“…Despite the tremendous progress made with regard to the utilization of p-QMs as Michael acceptors for the creation of C-C, 3 C-S, 4 C-P, 5 C-B, 6 and C-Si 7 bonds, examples on the addition of Nheterocycle based N-centered nucleophiles, especially those involving amides/imides are limited (Scheme 1a). 8 Recently, we became interested in the chemistry of azauracils 9 that belong to privileged nitrogen heterocycles and are recurring motifs in numerous natural products, and bioactive compounds (Figure 1). 10 Compounds embedded with such motifs are known to serve as antiviral, 10f anticoccidial 10c and 5-HT1A agonist PET tracer agents.…”