Lewis Acid Catalyzed Electrophilic Aminomethyloxygenative Cyclization of Alkynols with N,O-Aminals

Abstract

Lewis acid enables the electrophilic carbooxygenative cyclization of alkynols with N,O-aminals. The new process proceeds efficiently under very mild conditions via a pathway that is opposite to classical carbo-metalation. These reactions exhibit broad substrate generality and functional group compatibility, leading to a wide variety of 5−8-membered oxacycles bearing diverse functional groups. The cyclization products can be elaborated via simple functional group transformations to generate synthetically useful oxacycles.

Challenge N- versus O-six-membered annulation: FeCl3-catalyzed synthesis of heterocyclic N,O-aminals

“…Noteworthy, in compounds 5a-r, 6a-p and 7, the newly created heterocyclic nucleus represents a new example of cyclic N,O- aminals and carbinolamine derivatives, an interesting class of organic compounds that are common structural motifs embedded within diverse biologically important natural products and pharmaceuticals [32][33][34][35][36][37]. On the other hand, the N,O-aminals are stable and very practical synthetic intermediates commonly employed for the in situ generation of highly electrophilic iminium ions [38][39][40][41].…”

Synthesis of Seven Membered Oxacycles: Recent Developments and New Approaches

“…Another publication relevant to this section comes from Huang and co‐workers, and presents a catalytic use of Zn(OTf) 2 as Lewis acid in the cyclization of alkynols with N ,O‐aminals. [ 16 ]…”

“…Another publication relevant to this section comes from Huang and co-workers, and presents a catalytic use of Zn(OTf ) 2 as Lewis acid in the cyclization of alkynols with N,O-aminals. [16] Following Scheme 6, the mechanism starts when the Zn(OTf ) 2 reacts with the amine 24 to generate the iminium 26. Then, this salt is attacked by the alkyne 23, yielding the allenic intermediate 27.…”

“…Adapted from ref. [16] Finally, the last approach covered in this section was developed by Chang and co-workers, where an intramolecular…”