Nitrogen substituted alkynes such as ynamines and ynamides are versatile synthetic building blocks in organic chemistry. 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 due mainly to the lack of synthetic accessibility. We report herein a versatile Cu-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 undergo cross-coupling with a diverse set of terminal alkynes to afford the ynimines in good to excellent isolated yields. An unprecedented [5+1] heteroannulation reaction exploiting the reactivity of the in situ generated ynimine is subsequently developed for the synthesis of medicinally important heterocycles including isoquinolines, aza-indoles, aza-benzofurans, aza-benzothiophenes and carbolines. We anticipate that this robust synthesis of ynimines would open an avenue for the exploration of this functionally rich building block .