Rapid Access to Chroman‐3‐ones through Gold‐Catalyzed Oxidation of Propargyl Aryl Ethers

Abstract

Ruck‐zuck: Chroman‐3‐one sind wichtige Zwischenstufen in der organischen Synthese und medizinischen Chemie, ihre Synthese erfordert aber mehrere Stufen. Eine goldkatalysierte Alkinoxidation eröffnet einen hoch effizienten Weg zu diesen vielseitigen Heterocyclen in nur zwei Stufen ausgehend von leicht zugänglichen Phenolen (siehe Schema).

Biarylphosphonite Gold(I) Complexes as Superior Catalysts for Oxidative Cyclization of Propynyl Arenes into Indan‐2‐ones

“…We were however particularly surprised by the result obtained in the case of the [ L1 Au]NTf 2 gold complex possessing a phosphite ligand (entry 13) 9. We initially expected it to be a poor catalyst because its high electrophilicity combined with its limited steric crowding around the gold center (% V Bur =32.3)1b, 10 should favor the coordination to the pyridine by‐product. Unexpectedly, not only a respectable 50 % conversion of 6 a was obtained after 6 hours, but the conversion after 0.25 h (21 %) was the best of all the catalysts screened (entry 13 versus entries 5 and 9–12).…”

“…This interesting transformation was supposed to involve the β‐gold vinyloxypyridinium intermediate 4 which could then produce the CH functionalization product 5 by following one of the two pathways depicted in Equation 1 (Path A or B). Given the synthetic importance of indan‐2‐ones (and their derivatives) and the restricted number of studies involving aromatic partners in such oxidative transformations,1b,j we decided to improve and extend this process. In this respect, we took into consideration a series of potential steps and equilibria (Scheme ), which were postulated to influence the efficiency of the oxidative cyclization.…”

“…This result led us to conclude that the net oxidative cyclization process (Scheme ) is kinetically favored by the use of gold catalysts possessing electron poor ligands 11. We therefore decided to design new gold(I) catalysts which possess ligands combining both the electron deficient character of the phosphite L1 and the steric bulk of the biaryl moiety in the t BuXPhos ligand (% V Bur =54.9) 1b. 10 Such catalysts should indeed favor a high reaction rate while limiting their coordination with the pyridine by‐product.…”

An Efficient Gold‐Catalyzed Domino Process for the Construction of Tetracyclic Ketoethers

“…[20] Even AgNTf 2 alone showed a corresponding reactivity, although to a lesser extent and accompanied by the formation of decomposition products (entry 3). The gold I species Me 4 tBuXPhosAuNTf 2 [21] provided 2 a in very high yield (entry 4). Fortunately, AuCl already caused a similarly efficient transformation in only a fraction of the time (entry 5), and its higher oxidized counterpart AuCl 3 led to a further increase in yield in just 10 min (entry 6).…”

“…Platinum(II)chloride and rhodium(II)octanoate turned out to be unreactive (entries 10 and 11). Variation of the oxidant showed that in addition to the hygroscopic N-oxide 3 b also the oxidized Hantzsch ester 3 c, [21] unsubstituted pyridine-N-oxide (3 d), and even the urea hydrogen peroxide complex can be used with less efficiency (entries 12-15), whereas an unselective product formation was observed in the absence of any oxidant (entry 16). Table 2 illustrates the scope of the gold-catalyzed domino reaction under optimized conditions.…”