Heteroarene Phosphinylalkylation via a Catalytic, Polarity-Reversing Radical Cascade

Abstract

A polarity-reversing radical cascade strategy for alkene di-functionalization by vicinal C-C and C-P bond-formation has been developed. This approach to concurrently adding phosphorous and a heteroarene across an olefin is enabled by photocatalytic generation of electrophilic P-centered radicals. Upon chemoselective addition to an olefin, the resulting nucleophilic C-centered radical selectively combines with electrophilic heteroarenes, such as pyridines. This multi-component coupling scheme for phosphinylalkylation complements classic two-component methods for hydrophosphinylation of alkenes and C-H phosphinylation of arenes. Included competition and photo-quenching experiments provide insight into the selectivity and mechanism of this polarityreversal pathway.

Organoboron Mediated Homolytic Aromatic Substitution of N-Methoxypyridinium Salts

“…The reaction with cholesteryl iodide (3 equivalents) afforded the desired lutidine 27 in 37% with an excellent level of stereocontrol. Similar yields were obtained in reactions involving the 4-chloro and 4-bromo-Nmethoxypyridinium salts 1j and 1k with secondary and tertiary radicals (28)(29)(30)(31)(32)(33). Highly electrophilic pyridinium salts such as 2,4and 2,6-dichloro derivatives 1l and 1m afforded the corresponding products 35-37 in good yields.…”

“…The reaction involving iodides and xanthates described above, open the possibility to develop a three-component coupling process involving a radical precursor, an alkene, and a Nmethoxypyridinium salt. This approach is expected to complement the related photoredox catalyzed approaches involving N-methoxypyridinium salts, [31][32][33] lepidinium and quinaldinium trifluoroacetate, [55] as well as quinoxalin-2(1H)ones. [56] Products presented in Scheme 7 results from such a twostep carbopyridinylation reaction.…”

“…In a related manner, three component coupling reactions involving N-methoxypyridinium salts were developed by Baik, Hong and co-workers [31] using a Mn(III)/Ag(I) oxidizing system and by Nagib and co-workers using an iridium based photocatalyst. [32,33] Scheme 1. Radical addition to N-alkoxypyridinium salts.…”

Photochemical C–H Silylation and Hydroxymethylation of Pyridines and Related Structures: Synthetic Scope and Mechanisms

“…35 A milder version of this photochemical process was recently disclosed by DiRocco, Krska and co-workers by using 4 [Ir(dF-CF3-ppy)2(dtbpy)]PF6 as the photocatalyst an benzoyl peroxide (PBO) as the terminal oxidant. 39 Based on the dual reactivity of N-alkoxypyridinium ions (NAPs), 40,41,[42][43][44][45] as alkoxy radical precursors that are good hydrogen abstractors 46,47,48 and as electrophilic partners in Minisci reactions, as previously reported by Hong and co-workers [49][50][51][52][53][54][55]56 we hypothesized that NAPs should be good partner with silanes or methanol to accomplish photocatalytic C-H silylation and hydroxymethylation, respectively (Scheme 1).…”

Transition-Metal-Free, Intermolecular Azidoheteroarylation of Alkenes: Efficient Access to β-Azidoalkylated Quinoxalinones and Preliminary Antifungal Evaluation Against Magnaporthe grisea

“…Recently, Nagib and co-authors disclosed the first heteroarene phosphinylalkylation reaction by constructing vicinal C-C and C-P bonds across the C=C, in which electrophilic heteroarenes such as pyridines were employed as coupling partners. 18 Given the biological significance of phosphorus, we then questioned whether diethyl phosphite could also be used as radical precursor for this cascade reaction. Gratifyingly, the desired phosphinylalkylated quinoxalin-2(1H)-one 6 could be isolated in 65% yield under the following conditions: hex-1-ene (1a; 2.0 equiv) and 1methylquinoxalin-2(1H)-one (2a; 1.0 equiv), diethyl phosphite (4.0 equiv), Li 2 CO 3 (2.0 equiv), phenyliodine(III) diacetate (4.0 equiv), EtOAc (0.2 M), at 60 °C for 12 hours.…”