Regioselective Synthesis of Isonitrile-Containing Densely Functionalized Alkenes from Propynenitriles

Jyoti Jyoti; Rahul Jamra; Deepika Deepika; Shreya Sharma; Chandi C. Malakar; Virender Singh

doi:10.1055/a-2538-1363

Synlett, Table of Contents

Synlett
DOI: 10.1055/a-2538-1363

letter

Emerging Trends in Organic Chemistry: A Focus on India

Regioselective Synthesis of Isonitrile-Containing Densely Functionalized Alkenes from Propynenitriles

Jyoti Jyoti

^aDepartment of Chemistry, Central University of Punjab, Bathinda, 151401, Punjab, India

,

Rahul Jamra

^aDepartment of Chemistry, Central University of Punjab, Bathinda, 151401, Punjab, India

^bDepartment of Chemistry, Dr B R Ambedkar National Institute of Technology (NIT), Jalandhar, 144008, Punjab, India

,

Deepika Deepika

^bDepartment of Chemistry, Dr B R Ambedkar National Institute of Technology (NIT), Jalandhar, 144008, Punjab, India

,

Shreya Sharma

^aDepartment of Chemistry, Central University of Punjab, Bathinda, 151401, Punjab, India

,

Chandi C. Malakar

^cDepartment of Chemistry, National Institute of Technology (NIT), Manipur, Imphal, 795004, Manipur, India

,

Virender Singh ∗

^aDepartment of Chemistry, Central University of Punjab, Bathinda, 151401, Punjab, India

› Author Affiliations

Abstract

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Dedicated to Professor Vinod Kumar Tiwari for his seminal contributions to alkyne–azide cycloaddition chemistry.

Abstract

A transition-metal-free base-mediated approach has been devised for the synthesis of novel densely functionalized alkenes containing isocyanide, nitrile, and ester functionalities. The strategy was found to be applicable to gram-scale synthesis, and a library of functionalized alkenes with significant diversity was developed. The strategy could also be used for the synthesis of trisubstituted pyrrole derivatives by modifying the reaction conditions. The advantages of this approach are its operationally simple procedure, short reaction time (10–30 min), broad substrate scope, high atom economy, metal-free conditions, and high regioselectivity with good to excellent product yields.

Key words

chlorovinyl aldehydes - propynenitriles - isocyanocyanoalkenoates - Michael addition - pyrroles - silver catalysis

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References

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19 Ethyl (3Z)-3-(4-Chlorophenyl)-4-cyano-2-isocyanobut-3-enoate (21A); Typical Procedure An oven-dried, 10 mL, round-bottomed flask was charged with Cs₂CO₃ (0.404 g, 1.24 mmol) and a solution of ethyl isocyanoacetate (A; 0.075 mL, 0.683 mmol) in anhyd DMSO (1.5 mL) at rt, and the mixture was stirred for 2–3 min. 3-(4-Chlorophenyl)prop-2-ynenitrile (21; 0.10 g, 0.62 mmol) was added, and the mixture was stirred at rt for 10 min until the reaction was complete (TLC). The mixture was then poured onto crushed ice, and the organic layer was separated with EtOAc, washed with brine, dried (Na₂SO₄), and concentrated under reduced pressure. The crude product was purified by column chromatography [silica gel (60–120 mesh), EtOAc–hexane (20:80)] to give an off-white solid; yield: 0.144 g (85%); mp 68–70 °C; R_f = 0.48 (EtOAc–hexane, 20:80). IR (neat): 2227 (CN), 1611, 1669 (C=C), 1735 (COOEt) cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 1.21 (t, J = 7.1 Hz, 3 H, CO₂CH₂CH ₃), 4.20 (q, J = 7.1 Hz, 2 H, CO₂CH ₂CH₃), 6.03 (s, 1 H, –C=CH), 7.37 (d, J = 8.2 Hz, 2 H, ArH), 7.41 (s, 1 H, ArH), 7.43 (d, J = 1.9 Hz, 2 H, ArH). ¹³C NMR (150 MHz, CDCl₃): δ = 14.8, 29.8, 69.8, 93.3, 112.5, 118.1, 128.7, 130.3, 133.2, 135.8, 142.0, 151.3, 157.1. HRMS (ESI): m/z [M + H]⁺ Calcd for C₁₄H₁₂ClN₂O₂: 275.0582; found: 275.0590.

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