Hexafluoroisopropanol (HFIP)-Mediated Intramolecular Cyclization of Allenamides To Access C1-Vinyl
Dhananjay Chaudhary1, Malleswara Rao Kuram1,2
1Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Abstract:
The construction of biologically interesting N-heterocycles under metal-free conditions is a constant goal in industry and academia. Herein, we have developed an hexafluoroisopropanol (HFIP)-mediated intramolecular cyclization of allenamides, providing tetrahydro-β-carboline derivatives embedded with a C1-vinyl functionality. The metal-free protocol provided tetrahydro-β-carboline derivatives atom-efficiently under room temperature with a broad substrate scope in good to excellent yields. The potential impact of the protocol is further highlighted by synthesizing derivatives of biologically important molecules and diversified scaffolds via postsynthetic modifications.
Related Concept Videos
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Intramolecular Aldol Reaction
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
Halogenation of Alkenes
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
Nucleophilic Aromatic Substitution: Elimination–Addition


