Site‐Selective Oxidative C4 Alkenylation of (NH)‐Pyrroles Bearing an Electron‐Withdrawing C2 Group

Lee

Chemistry An Asian Journal

et al. 2018

Directing group and substrate control strategies have frequently been employed for the regioselective C-H alkenylation of acid- and oxidant-sensitive pyrrole heterocycles. We developed an undirected, aerobic strategy for the C-H alkenylation of N-alkylpyrroles by ligand control. For C2-alkenylation of electron-rich N-alkylpyrroles, an electrophilic palladium catalyst derived from Pd(OAc) and 4,5-diazafluoren-9-one (DAF) was used. Alternatively, a combination of Pd(OAc) and a mono-protected amino acid ligand, Ac-Val-OH, was useful for C5-alkenylation of N-alkylpyrroles possessing electron-withdrawing groups at the C2 position. This approach based on the electronic effects of heterocycles and catalysts can rapidly provide a wide range of alkenyl pyrroles from readily available N-alkylpyrroles and alkenes.

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

C−H Alkenylation of Pyrroles by Electronically Matching Ligand Control

Lee

Chemistry An Asian Journal

et al. 2018

“…Furthermore, authors also demonstrated tandem indole synthesis via successive C‐4/C‐5 double alkenylations followed by electrothermal cyclization (Scheme 23). [35] A regioselective C‐4 palladation on free‐(NH) pyrroles being a challenging task has been the main success. Anyway a C‐2 substituent on pyrrole showed up as the chief controlling component for the perceived regioselectivity.…”

Section: C−h Functionalization Of Pyrrolesmentioning

confidence: 99%

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Hunjan

Panday

Gupta

et al. 2021

The Chemical Record

Self Cite

Among the known aromatic nitrogen heterocycles, pyrrole represents a privileged aromatic heterocycle ranging its occurrence in the key component of “pigments of life” to biologically active natural products to active pharmaceuticals. Pyrrole being an electron‐rich heteroaromatic compound, its predominant functionalization is legendary to aromatic electrophilic substitution reactions. Although a few excellent reviews on the functionalization of pyrroles including the reports by Baltazzi in 1963, Casiraghi and Rassu in 1995, and Banwell in 2006 are available, they are fragmentary and over fifteen years old, and do not cover the modern aspects of catalysis. A review covering a comprehensive package of direct functionalization on pyrroles via catalytic and non‐catalytic methods including their translational potential is described. Subsequent to statutory yet concise introduction, the classical functionalization on pyrroles using Lewis acids largely following an ionic mechanism is discussed. The subsequent discussion follows the various metal‐catalyzed C−H functionalization on pyrroles, which are otherwise difficult to implement by Lewis acids. A major emphasize is given on the radical based pyrrole functionalization under metal‐free oxidative conditions, which is otherwise poorly highlighted in the literature. Towards the end, the current development of pyrrole functionalization under photocatalyzed and electrochemical conditions is appended. Only a selected examples of substrates and important mechanisms are discussed for different methods highlighting their scopes and limitations. The aromatic nucleophillic substitution on pyrroles (being an electron‐rich heterocycle) happened to be the subject of recent investigations, which has also been covered accentuating their underlying conceptual development. Despite great achievements over the past several years in these areas, many challenges and problems are yet to be solved, which are all discussed in summary and outlook.

“…Subjected the cross-coupling products to a second DHR led to C5 substitution with, in the case of the tosylpyrrole, a domino reaction leading to an indole (Scheme 7). The DHR with Pd(OAc)2/Cu(OAc)2 in DMSO of free (NH)-pyrrole occurred in C2 and C5 positions, while N-tosylpyrrole afforded the mono-adduct (Equation (33)) [72]. In contrast, free (NH)-pyrrole with an electron-withdrawing C2 substituent led to alkenylation in C4 position (Equation 34).…”

Section: (33)mentioning

confidence: 99%

“…The fifth publication disclosed a template directing the regioselectivity [112]. Another important report related regioselectivity depending on the substitution [72]. Although these reports concern DHRs of only a few substrates, they represent breakthroughs for researchers involved in the selective synthesis of regioisomers from the same starting material.…”

Section: Conclusion and Remarksmentioning

confidence: 99%

Pd-Catalyzed Intermolecular Dehydrogenative Heck Reactions of Five-Membered Heteroarenes

Bras

Мuzart

2020

Catalysts

The Pd-mediated cross-coupling of (hetero)arenes with alkenes may be an effective method for the formation of a C–C bond from two C–H bonds. Discovered by Fujiwara and co-workers in 1967, this reaction led to a number of reports that we firstly highlighted in 2011 (review with references till June 2010) and for which, we retained the name “dehydrogenative Heck reaction”. The topic, especially the reactions of five-membered heteroarenes, has been the subject of intensive research over the last ten years. The present review is limited to these dehydrogenative Heck reactions published since 2010, underlining the progress of the procedures.