Organocatalytic Enantioselective Friedel‐Crafts Alkylation Reactions of Pyrroles

Abstract

Substituted and annulated pyrroles containing chiral centers are potentially accessible by means of an organocatalytic enantioselective Friedel-Crafts alkylation (FCA) reaction. They are interesting compounds because of their abundant natural occurrence and their different biological activities. In comparison to indoles, for which a myriad of asymmetric procedures involving the FCA have been developed, pyrroles have been relatively less used as nucleophilic counterparts in this reaction. However, in the last two decades, huge synthetic efforts have been performed around this interesting asymmetric transformation and several methodologies have been devised. In this context, this review article provides a general overview of the organocatalytic enantioselective FCA chemistry of pyrroles, which has not been revised to date. Reactions 2.4. Brønsted Acid Catalyzed Intramolecular FCA Reactions 3.Organocatalytic FCA Reactions with Dihydroindoles 4.Conclusions and Outlook

N‐Functionalization of 4‐amino‐2‐(trifluoromethyl)‐1H‐pyrroles: Synthesis of N‐alkyl derivatives and 1,2,3‐triazol‐4‐yl‐pyrrole scaffolds

“…This shows that pyrrole 1a is reactive toward electrophilic aromatic substitution (S E Ar), because the C ‐alkylation occurred in the presence of a strongly deactivating group (e.g., –CF 3 ) in a short reaction time (2 h), and in the absence of any catalyst. The literature shows that the most commonly applied methods to perform C ‐alkylation of pyrroles use copper‐ and iron‐based catalysts [23–25], organocatalysts [26,27], and ionic liquids [28]. Although the most reactive position for S E Ar in pyrroles is at the 2‐ and 5‐positions, 3‐alkylation can occur in some special cases, and mixtures of products 3‐ and 5‐dialkylated products are usually obtained [29,30].…”

Cellulose-supported hyper-crosslinked l-tryptophan as an efficient chiral catalyst support for improved catalytic performance

“…With the aim of obtaining catalyst supports of high stability, a series of hyper-crosslinked chiral supports were synthesized in the presence of a matrix via a one-step Friedel–Crafts alkylation reaction, using ( l )-tryptophan as the monomer, cellulose and various other materials as the matrix, and 4,4′-bis(chloromethyl)-1,1′-biphenyl as the crosslinker (see Scheme 1). 16,36 In this reaction, the aromatic rings of the amino acids provide crosslinking sites, while the amino acid residues provide binding sites that are available for coordination of the metal catalyst. The amino and carboxyl groups on the surface of the amino silica gel and carboxyl silica gel can react with the crosslinking agent, while the benzene ring of PS can also react with the crosslinking agent; thus, the matrix of the amino silica gel, carboxyl silica gel, and PS can be encapsulated into particles by combining with the crosslinked polymer through covalent bonds.…”

Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions

“… Indeed, our group has focused on developing original synthetic routes to this family of natural products, and we recently reported total syntheses of (±)-dehydrostenine A ( 1 ) and sessilifoliamides B ( 4 ), C, and D . We accessed each of these alkaloids by employing a common strategy in which Brønsted acid-mediated intramolecular Michael addition reactions were judiciously deployed to forge the polycyclic cores of these molecules …”

“…We anticipate that the above-mentioned findings will help to guide the development of new approaches to Stemona alkaloids, related synthetic analogues, and other families of natural products. Furthermore, these findings should also inform approaches to forming annulated pyrrole derivatives via cyclization strategies employing Michael acceptors …”