Acetonitrile Activation: An Effective Two‐Carbon Unit for Cyclization

Abstract

A novel activation of acetonitrile for the construction of cyclobutenones by [2+2] cyclization was developed. Acetonitrile is utilized for the first time as two‐carbon (C2) cyclization building block. The present protocol successfully inhibits the competitive cycloaddition with the C≡N bond of acetonitrile, but enables the in situ formation of an unsaturated carbon–carbon bond and the subsequent cycloaddition as a C2 unit. This chemistry features simple reaction conditions, high chemoselectivities, wide substrate scope, and offers a new and practical approach to cyclobutenones and cyclobuteneimines.

Clinical Significance of Baseline Neutrophil-to-Lymphocyte Ratio in Patients With Ischemic Stroke or Hemorrhagic Stroke: An Updated Meta-Analysis

“…The characteristics of the included studies are shown in Table 1 (7–10, 12, 13, 23–53). Mortality, functional outcome, risks of ischemic stroke, and post-stroke complication were reported in 20, 17, 7, and 2 articles, respectively.…”

De Novo Protocol for the Construction of Benzo[a]fluorenes via Nitrile/Alkene Activation

“…Recently, Lui et al reported an elegant nickel-catalyzed [2 + 2 + 2] cycloaddition with alkynes to benzene-tethered alkyne–nitrile, which resulted in the construction of functionalized pyridines (Scheme c) . In 2019, Jiao and co-workers described a practical [2 + 2] cycloaddition between acetonitrile and alkynes in which triflic anhydride was used to synthesize cyclobutenones and cyclobuteneimines (Scheme d) . Despite these fruitful efforts, the success of nitrile insertion was limited to acetonitrile/simple nitrile derivatives and required relatively expensive conditions.…”

Metal Free Access to Polysubstituted Pyrimidines via Nitrile Activation and [2+2+2] Cycloaddition

“…But most of them were considered to undergo nitrilium‐ion intermediates (Figure 1b) in presence of Lewis acids (e. g., TfOH, BF 3 ⋅ Et 2 O) [9] . Recently, Jiao's group reported that acetonitrile was activated by Tf 2 O as an effective C2 building unit for synthesis of cyclobutenones / cyclobuteneimines through [2+2] cyclization (Figure 1c) [10] …”