Indium-Catalyzed Reductive Alkylation of Pyrroles with Alkynes and Hydrosilanes: Selective Synthesis of β-Alkylpyrroles

Abstract

Mixing readily available alkynes, pyrroles, and triethylsilane along with an indium catalyst was found to be an efficient procedure to introduce alkyl groups onto a beta-position of pyrroles in a complete regioselective manner. This is the first demonstration of catalytic beta-alkylation of pyrroles in a single step.

Metalltriflimidate sind bessere Katalysatoren für die organische Synthese als Metalltriflate – der Effekt eines stark delokalisierten Gegenions

“…In(NTf 2 ) 3 war in der Synthese von b-Alkylpyrrolen ein deutlich besserer Katalysator als In(OTf) 3 , In(ONf) 3 , [170] InCl 3 oder HNTf, sowohl bezüglich der Umsetzung als auch bezüglich der Ausbeute (Schema 44). [171] Einige Beobachtungen und Kontrollexperimente stützen den ursprünglich angenommenen Mechanismus, der mit der Bildung einer Isomerenmischung aus a,b'-und b,b'-Dipyrrolylalkan durch eine indiumkatalysierte doppelte Alkylierung des Alkins beginnt. [169] Die beiden Regioisomere gehen dann eine indiumkatalysierte Retroaddition unter Bildung von abzw.…”

Exclusive Synthesis of β‐Alkylpyrroles under Indium Catalysis: Carbonyl Compounds as Sources of Alkyl Groups

“…Herein we disclose a new method for synthesis of b-alkylpyrroles 4 using 6 as alkyl group suppliers. [11] Due to the potent activity of InA C H T U N G T R E N N U N G (NTf 2 ) 3 (Tf = SO 2 CF 3 ) found in our preceding research, [3] research on this topic began with its testing in the reaction of 2-decanone (6 a) and N-methylpyrrole (2 a) with Et 3 SiH (3 a), by the procedure shown as method A: simultaneous treatment of 6, 2, 3 and InA C H T U N G T R E N N U N G (NTf 2 ) 3 (Table 1). Thus, the reaction with InA C H T U N G T R E N N U N G (NTf 2 ) 3 (10 mol %) in 1,4-dioxane at 85 8C for 3 h gave 3-(decan-2-yl)-N-methylpyrrole (4 a) as a single isomer in 92 % yield (entry 1).…”

“…In this context, we recently reported the regiospecific b-alkylation of pyrroles through EAS, by the simple assembly of alkynes 1, pyrroles 2, and Et 3 SiH (3 a) under indium catalysis (Scheme 1). [3] b-Alkylpyrroles are structural motifs found in many natural products [4] and functional organic materials, [5] but b-alkylation of pyrroles by EAS has been a challenging issue, due to dominant a-nucleophilicity of pyrroles. [6] Despite such characteristics of pyrroles, our recent finding, which is the first example of catalytic b-alkylation of pyrroles in one-step, showed that b-alkylpyrroles 4 are formed exclusively, via formation of dipyrrolylalkanes 5 as crucial intermediates.…”

Selective Synthesis of β‐Alkylpyrroles

“…Under indium catalysis, the strategy can be performed readily by a simple mixing of N-substituted pyrroles 39, Et 3 SiH and either alkynes 38 [52] or carbonyl compounds (see below). [53] The alkyne-based reaction, which has been developed prior to the reaction of carbonyl compounds, is the first example of catalytic b-alkylation of pyrroles in a single step.…”

“…Despite that a,b'-dipyrrolylalkanes 51, which possibly lead to a-alkylpyrroles 55 by the elimination of the b-pyrrolyl ring, exist in the reaction mixture before the trapping with nucleophiles, [52][53][54][55][56] a natural question is why no 55 is formed in this strategy. On the basis of experimental results, we can provide the most plausible interpretation for the question.…”