Abstract
Nitrogen‐substituted alkynes, such as ynamines and ynamides, are versatile synthetic building blocks. Ynimines bearing additional nucleophilic and electrophilic centers relative to ynamines and ynamides are expected to have high synthetic potential. However, their chemical reactivity remains unexplored owing mainly to the lack of synthetic accessibility. We report herein a versatile copper‐catalyzed synthesis of ynimines from readily available O‐acetyl ketoximes and terminal alkynes. A wide range of O‐acetyl ketoximes derived from diaryl ketones, aryl alkyl ketones and dialkyl ketones underwent cross‐coupling with a diverse set of terminal alkynes to afford the ynimines in good to excellent yields. An unprecedented [5+1] heteroannulation reaction exploiting the reactivity of the ynimine generated in situ was subsequently developed for the synthesis of medicinally important heterocycles, including isoquinolines, azaindoles, azabenzofurans, azabenzothiophenes and carbolines.
Highlights
Stimulated by the development of efficient and practical methods to prepare ynamides (Scheme 1a),[1] stabilized form of ynamines,[2] at the turn of this century, the synthetic potential of this multifunctional building block has been exploited extensively and many powerful transformations have been developed over the last two decades.[3]
The elegant Cu-catalyzed oxidative cross-coupling between imines and terminal alkynes developed by Evano is without doubt the most atom economic way to access ynimines
We report an operationally simple, general and scalable synthesis of ynimines 1 by way of Cu-catalyzed aza-Sonogashira cross coupling between O-acetyl oximes 2 and terminal alkynes 3
Summary
Title: Copper-Catalyzed Aza-Sonogashira Cross-Coupling to Ynimines: Development and Application to the Synthesis of Heterocycles. This manuscript has been accepted after peer review and appears as an Accepted Article online prior to editing, proofing, and formal publication of the final Version of Record (VoR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article
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