Recent Advances in the Chemistry of Isocyanides with Activated Methylene Group

Abstract

This review is devoted to the recent advances in the chemistry of methylene isocyanides with C=C, C≡C, C=O, and C=N bonds. In this paper, we show a variety of [3+2] cycloaddition reactions for isocyanides, carried out both under catalytic and non‐catalytic conditions. In addition, we also focused on diastereo‐ and enantioselectivity data.

BAY-9835: Discovery of the First Orally Bioavailable ADAMTS7 Inhibitor

“…The precipitated solid was filtered off, washed with dichloromethane, and dried in vacuo. 5,[biphenyl]-2-carboxylic acid (46). phenyl]boronic acid (45) (10.82 g, 56.96 mmol) and 2-bromo-3,4-difluorobenzoic acid (44) (9.00 g, 37.97 mmol) were treated with 233.5 mL of 1,4-dioxane.…”

“…Ent -5,6-difluoro-N-{[4-(5-methyl-2-phenyl-1,3-thiazol-4-yl)-2,5dioxoimidazolidin-4-yl]methyl}-4′-(trifluoromethyl)[biphenyl]-2carboxamide (47). 5,[biphenyl]-2carboxylic acid (46) (107 mg, 0.35 mmol) was dissolved in 2.5 mL of DMF. DIPEA (0.26 mL, 1.48 mmol), EDC*HCl (74 mg, 0.38 mmol), and 1-hydroxybenzotriazole hydrate (59 mg, 0.38 mmol) were added and the mixture was stirred at room temperature.…”

Base-Promoted [4 + 2] Annulation Reaction of In Situ-Generated Azadienes from N-Propargylamines with Active Methylene Compounds: Access to Highly Functionalized 2-Pyridones

“…As per the existing literature reports, conventionally the alkylisocyanoacetates ( I) are well established to act as a 1,3 polar species to give [3 + 2] cycloaddition with alkynes, alkenes, imines etc. (Scheme a). For instance, the Zhu group and the Lavilla group have synthesized both imidazole and imidazolium salts from N -propargylamines by using alkylisocyanide derivatives through [3 + 2] annulation (Scheme b).…”

Metal‐Free Electrochemical [3+2] Cycloaddition between α‐Amino Carbonyls and Tosylmethyl Isocyanide en route to Substituted Imidazoles

“…[4] Apart from that, active methylene isocyanides have been realized as useful starting materials en route to multi-functionalized heterocycles. [5] However, these traditional protocols either require transition metals (e.g Cu and Ag) and external oxidants or prefunctionalized moisture-sensitive synthetic handles that restrict practical applicability and incorporation of proper substitution patterns in the synthesized scaffolds (Scheme 1b and 1c). [6] Another possible alternative is photoredox catalysis, which suffers from similar limitations as late-row transition metal complexes are often mandatory as photocatalysts to carry out desired transformations efficiently.…”