A Cyclization–Rearrangement Cascade for the Synthesis of Structurally Complex Chiral Gold(I)–Aminocarbene Complexes

Abstract

A facile synthesis of chiral cyclic alkyl aminocarbene-gold(I) complexes from gold-free 1,7-enyne substrates was developed. The novel cyclization-rearrangement reaction sequence is triggered by the addition of (Me2S)AuCl to different 1,7-enynes and leads to structurally unique carbene-gold(I) complexes in high yields. These novel complexes are catalytically active and inhibit the proliferation of different human cancer cell lines.

Gold(I) Catalyzed Enyne Cycloisomerization – A Roadmap to Privileged Heterocyclic Scaffolds

“…An aza‐Cope sigmatropic rearrangement afforded the iminium precursor 53 which subsequently yielded the gold(I)−olefin complex 54 . A 1,2‐silyl migration on latter delivered the carbene ( 55 ) as the final product (Figure b) . Inspired by the discovery of metallo‐NHC complexes serving as cancer‐cell growth inhibitors, the synthesized (CAAC)‐Au(I) compound collection was screened for their effect on viability of several cancer cell lines.…”

“…With Ru complexes and NaIO 4 assisted oxidative cleavage of enol-ether 27, the medium-size-lactones 28 were synthesized in 59-68 % yield ( Figure 4b). [19] In another unconventional approach, a bulky triazole gold complex (37) inhibited an intramolecular cyclization of homopropargyl alcohol (29) and thus pushed the latter to form enyne intermediate (31) that followed a cycloisomerization reaction and provided a 2,3-dehydrooxepine (34, Figure 5b). The conditions were established for a one-pot reaction wherein the generated electron-rich oxepine (34) could undergo a Diels-Alder reaction with suitable dienophiles to afford the tricyclic scaffold (35).…”

“…A 1,2-silyl migration on latter delivered the carbene (55) as the final product ( Figure 8b). [29] Inspired by the discovery of metallo-NHC complexes serving as cancer-cell growth inhibitors, [30] the synthesized (CAAC)-Au(I) compound collection was screened for their effect on viability of several cancer cell lines. Indole and phenyl based derivatives of (CAAC)-Au(I) (57, 58, respectively) were found to possess anticancer properties against different cancer cell lines and were active within single digit micromolar IC 50 values.…”

Au-Catalyzed Synthesis and Functionalization of Heterocycles

“…In a related and intriguing example, Kumar and Waldmann et al applied the same principle of cyclisation/rearrangement cascade process for the synthesis of chiral cyclic gold(I) aminocarbene complexes 254 from 1,7-enynes 253 (Scheme 65) [211]. This reaction requires a stoichiometric amount of gold.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…1416) was produced in the reaction of alkyne allylamines (e.g. 1412) in a process involving nucleophilic addition to the alkyne-gold complex to afford the M a n u s c r i p t zwitterion 1413, followed by [3,3] sigmatropic rearrangement and metal migration [1262]. Anti-Bredt NHCgold complexes were used as catalysts for the hydroarylation of alkenes using aniline derivatives [1263].…”