Metal‐Free Synthesis of Pyrrole‐imidazole Alkaloids via a Tandem C−N, C−C coupling Protocol

Abstract

Herein, we present a strategy for the synthesis of pyrrole alkaloid derivatives through a tandem CÀ N, CÀ C coupling reaction employing 2pyrrole formaldehyde and proline as starting materials. This cyclization protocol is successfully applied to polarity-controlled site-selective and stereoselective C(sp 3)À H hydrocarboxylation of proline derivatives, allowing for a remarkably streamlined synthesis of pyrrole alkaloid derivatives which have shown promising biological activities.

Synthesis of bridgehead-azacycles via dual C–N/C–C annulation of α-amino acids, aminals and maleimides

“…Based on these observations and a previous report, 11 we proposed a reaction path (Scheme 5c). Initially, the acid-catalyzed, dipolarophile-induced amidation of α-amino acid with aminal 1 provides intermediate A .…”

“…The resulting crude mixture was purified by column chromatography with neutralised silica gel 100-200 mesh (ethyl acetate : hexane (6 : 4)) to afford the desired product 4a as a white solid in 79% yield. 13,.0 1,19 .0 4,9 .0 11,15 ]nonadeca-4,6,8-triene-2,12,14-trione (4a)…”

“…Secondary α-amino acids (proline, pipecolic acid and sarcosine) play a significant role in organic chemistry. 1–12 These core units are highly desirable due to their wide presence in pharmaceutical ingredients, natural products and bioactive molecules. 1 Additionally, these skeletal structures function as green organo-catalysts in a variety of asymmetric reactions and their use as ligands in metal catalysts is also well established.…”

“…13 However, this route has rarely been investigated with carbonyl-tethered carbon-, nitrogen- and oxygen-based nucleophiles (Scheme 1b). 7,8 Notably, hydrocarboxylative or amidative annulations with various amino-carbonyls are rare 11 and very specific, perhaps due to the straightforward decarboxylation tendency of these α-amino acids. These annulations are distinct from earlier strategies, which can be achieved through α-C–H functionalization using an external dipolarophile.…”

Base-Mediated Coupling Reactions of Benzenesulfonyl Azides with Proline: Synthesis of Proline-Derived Benzenesulfonamides

“…Moreover, here, we use 1,8-diazabicyclo (5.4.0) undec-7-ene (DBU) as a one-pot reagent to complete N -sulfonylation and carboxylic acid esterification, which provides a new idea for their synthesis. As we all know that 1,2-dichloroethane (DCE) is an inert reagent and rarely participates in the reaction, herein encouraged by these works and our group’s previous application of DCE and continuous efforts on tandem reactions, − we report a one-step tandem N -sulfonylation and esterification involving DCE as both the solvent and reactant, where DBU acts as a strong basic reagent to transfer the proton. This reaction atom is economical, raw materials are readily available, and no hazardous reagents are used, and it is well-tolerated for different functional groups and provides a novel idea of esterification.…”