Suzuki Coupling Reactions in Heterocyclic Chemistry: Synthesis of 3-Substituted Pyrrolines and Pyrroles

Abstract

A simple preparation of N-substituted 3-pyrroline boromic esters from primary amines is described. The Suzuki-Miyaura coupling of these heterocycles with aryl halides proceeds in good yields. Alternatively, oxidation with DDQ or MnO 2 gives the corresponding pyrroles, which can be also engaged in subsequent palladium cross-coupling reactions.

Synthesis of Previously Inaccessible Borylated Heterocycle Motifs Using Novel Boron‐Containing Amphoteric Molecules

“…However, this method is only applicable to the synthesis of the five‐membered oxygen heterocycle 11. Moreover, two strategies for the synthesis of C3‐borylated pyrroles have been described, but they exclusively led to unsubstituted N ‐aryl and N ‐alkyl pyrroles or exhibited poor selectivity 12. 13 Therefore, the development of new procedures for the general and selective synthesis of a variety of C3‐borylated heterocycles is highly desirable, especially for medicinal chemistry, where heterocycles are routinely called upon to map out the accessible chemical space.…”

Synthesis of Previously Inaccessible Borylated Heterocycle Motifs Using Novel Boron‐Containing Amphoteric Molecules

“…[9] However,t he borylation occurs exclusively at the C2 position, with reversal of regioselectivity observed only for pyrroles that bear alarge protecting group on the nitrogen atom and heterocycles that are pre-functionalized with ad irecting group.T ot he best of our knowledge, there are just two literature examples of the selective borylation of NMe and NH pyrroles at the C3 position without the preliminary installation of protecting/directing groups,both of which use the parent unsubstituted rings. [12,13] Therefore,the development of new procedures for the general and selective synthesis of avariety of C3-borylated heterocycles is highly desirable,e specially for medicinal chemistry,w here heterocycles are routinely called upon to map out the accessible chemical space. [11] Moreover,t wo strategies for the synthesis of C3-borylated pyrroles have been described, but they exclusively led to unsubstituted N-aryl and N-alkyl pyrroles or exhibited poor selectivity.…”

“…[11] Moreover,t wo strategies for the synthesis of C3-borylated pyrroles have been described, but they exclusively led to unsubstituted N-aryl and N-alkyl pyrroles or exhibited poor selectivity. [12,13] Therefore,the development of new procedures for the general and selective synthesis of avariety of C3-borylated heterocycles is highly desirable,e specially for medicinal chemistry,w here heterocycles are routinely called upon to map out the accessible chemical space.…”

Synthesis of 3-Aryl-3-pyrrolines and 3-Arylpyrroles via Spontaneous Rearrangement of N-Sulfinyl 2-Aryl-2-vinylaziridines

“…16 Moreover, the corresponding 3-arylpyrroles act as reversible competitive inhibitors of monoamine oxidase B. 17 Besides the aforementioned HBrpromoted rearrangement of 2-aryl-2-vinylaziridines, 13c ring-closing metathesis (RCM), 18 Suzuki coupling reactions, 19 ring contraction of 4-aryl-1,2,5,6-tetrahydropyridines, 20 and dehydration of 3-aryl-3-pyrrolidinols, 16d,21 have also been reported as alternative methods for the preparation of 3-aryl-3-pyrrolines.…”