An Efficient One-Pot Synthesis of Novel Fused Pyrroles and Indoles by Dipolar Cycloaddition under Microwave and Conventional Conditions

Abstract

The straightforward synthesis of families of novel tricyclic and tetracyclic pyrrolino and indolino heterocycles in a onepot [3+2]-cycloaddition reaction is described. The process enables the synthesis of diversified pyrroles or pyrrolines in high yields in a single step. Microwave and conventional thermal conditions were explored, with remarkable acceleration observed under the microwave conditions.

Mechanistic Insights into the Reaction of N‐Propargylated Pyrrole‐ and Indole‐Carbaldehyde with Ammonia, Alkyl Amines, and Branched Amines: A Synthetic and Theoretical Investigation

“…The 3‐(phenylpropyn1yl)‐1 H ‐pyrrole‐2‐carbaldehyde ( 23 ) and the 1‐(3‐phenylpropynlyl)‐1 H ‐indole‐2‐carbaldehyde ( 25 ) were synthesized by a palladium‐catalyzed Sonogashira coupling reaction (Scheme ). After successful synthesis of coupling products 23 , [17e] and 25 ,, [17e] they were treated with propargylamine at the reflux temperature of methanol. The cyclization products 24 and 26 were obtained in 65 % and 38 % yields, respectively (Scheme ).…”

“…Synthesis of 1‐(3‐Phenylprop‐2‐ynyl)‐1H‐pyrrole‐2‐carbaldehyde (23) :, [17e] Cuprous iodide (3.8 mg, 0.02 mmol) of palladium acetate (4.5 mg, 0.02 mmol), and triphenylphosphane (13.1 mg, 0.05 mmol) were placed in a two necked round‐bottomed flask under nitrogen atmosphere. In another flask, 1‐(prop‐2‐ynyl)‐1 H ‐pyrrole‐2‐carbaldehyde ( 9 ) (0.266 g, 2.0 mmol) and iodobenzene (0.24 mL, 2.18 mmol) and diisopropylamine (1 mL, 7.0 mmol) were dissolved in dry THF (20 mL), and then added to the mixture prepared above.…”

Using Continuous Processes to Increase Production

“…Microwave-assisted chemistry has been powerful for drug discovery and organic synthesis. − In what are essentially HTST conditions, microwave (MW) processes can dramatically speed up and improve the yield of reactions . For instance, under microwave irradiation the proline adduct 49 was formed by dipolar cycloaddition in significantly higher yield than by reaction under thermal conditions (Scheme ) . Under microwave irradiation esterification of Boc- l -proline with dimethyl carbonate to afford 50 was about 80 times faster than esterification at 90 °C, the boiling point of dimethyl carbonate. , Using stop-flow conditions citalopram 51 was prepared in almost quantitative yield .…”

Synthesis of Pyrrole-Fused C,N-Cyclic Azomethine Imines and Pyrazolopyrrolopyrazines: Analysis of Their Aromaticity Using Nucleus-Independent Chemical Shifts Values

“…Pyrrole aldehyde 8 was synthesized by application of the Vilsmeier reaction . Treatment of aldehyde 8 with propargyl bromide followed by Sonogashira coupling afforded the alkyne derivatives 9 and 10 (Scheme ). N -Propargylpyrrole-2- N ′-acyl and tosyl hydrazones 12a – h were synthesized by the reaction of N -propargyl-2-formylpyrrole with various hydrazines substituted by tosyl or acyl groups in excellent yields (Scheme ).…”