Copper-Catalyzed Asymmetric Propargylation of Cyclic Aldimines

Abstract

The copper-catalyzed asymmetric propargylation of cyclic aldimines is reported. The influence of the imine trimer to inhibit the reaction was identified, and equilibrium constants between the monomer and trimer were determined for general classes of imines. Asymmetric propargylation of a diverse series of N-alkyl and N-aryl aldimines was achieved with good to high asymmetric induction. The utility was demonstrated by a titanium catalyzed hydroamination and reduction to generate the chiral indolizidines (-)-crispine A and (-)-harmicine.

Catalytic Asymmetric Reactions Involving the Seven‐Membered Cyclic Imine Moieties Present in Dibenzo[b,f][1,4]oxazepines

“…Very recently, Fandrick and co‐workers reported the copper‐catalyzed asymmetric propargylation of aldimines with use of a propargylborolane as a propargylic agent . The authors performed the propargylation of a series of cyclic imines, two of which were seven‐membered cyclic imines of type 1 .…”

Copper(II) Triflate Catalyzed Regioselective and Enantioselective Propargylation of Isatin Derivatives by Using Allenylboronic Acid Pinacol Ester

“…The advancements made so far in the development of the new methodology for functionalized tertiary alcohols use a stoichiometric amount of propargyl metal species. [1c], However, recent trends in this area of organic transformations have used allenylboronic acid pinacol ester as the starting material for regioselective propargylation and allenylation by using organocatalysts[5b], [5e], and different metals, such as Ag, Zn, and Cu as Lewis acids . However, the site selection for the formation of propargyl and allenyl substitutes remain a challenging task because of the formation of stable allenyl and less stable propargyl intermediates .…”

“…However, the site selection for the formation of propargyl and allenyl substitutes remain a challenging task because of the formation of stable allenyl and less stable propargyl intermediates . With these upsurge developments for regioselective and enantioselective propargylation, the substrate scope has been restricted to aldehydes,[5e], [8b], [9a], ketones,[1a], [7a], imines,[7b], [9d], , and keto esters. [5b] However, the regioselective and enantioselective propargylation of isatin, i.e., alpha‐keto lactams have rarely been explored …”

“…Accordingly, we have outlined a simple, cost‐effective protocol for regioselective propargylation of isatin derivatives by using allenylboronic acid pinacol ester as a nucleophile with copper as a Lewis acid catalyst[9a], [9b], [9d], in aqueous media. The exciting properties were observed in aqueous media, like high reactivity, high yields, low reaction time even though the isatin derivatives were not soluble in the reaction media.…”

“…The protocol developed is very atom efficient and yielded propargyl alcohols in excellent yields with high regioselectivity without the aid of any ligand precursor, which is required for site selection for ketones. [9a], [9c] The enantioselective synthesis of propargylic alcohols is also explored with retention in regioselectivity with an enantiomeric ratio up to 12:88. To the best of our knowledge, this general catalytic protocol for the regioselective propargylation of isatins with allenylboronic acid pinacol ester has not been reported before.…”