Mechanistic Insights into the Post‐Cyclization Isomerization in Gold‐Catalyzed 7‐exo‐dig‐Hydroarylations

Abstract

The subsequent double-bond isomerization in the synthesis of dibenzocycloheptenes and their heteroaromatic analogues was investigated. In the case of biphenyls, a basic additive completely prevented an isomerization to the thermodynamic product. With electron-rich intramolecular heteroaromatic nucleophiles, the isomerization was still observed, but the kinetic product can be obtained by careful control of the reaction times in most cases. Mechanistic studies demonstrated that a slow isomerization is also possible with the gold catalyst at elevated temperatures, but much faster isomerization rates were observed with acidic additives. An observed initiation period for the gold-catalyzed isomerization indicates that not the homogenous catalyst, but a decomposition product of it may be the catalytically active species.

Gold catalysis in total synthesis – recent achievements

“…Without acidic additive a mixture of 40 and the compound bearing an exo-methylene group was obtained. 22 AgNTf 2 and HNTf 2 alone were not catalytically active in this reaction. The total synthesis was completed after two steps furnishing Reticuol in 42% yield over 6 steps (Scheme 6b).…”

Direct synthesis of aryl-annulated [c]carbazoles by gold(i)-catalysed cascade reaction of azide-diynes and arenes

“…This result suggested that the second arylation was accelerated by the additional methoxy group located at the para -position to the reacting carbon. 26 We then examined the kinetic isotope effect (eqn (4) in Scheme 6 ). The competition reaction using N -Boc-pyrroles 9F (2.5 equiv.)…”

Gold-catalyzed hydroarylation reactions: a comprehensive overview

“…Hashmi and his co-workers proposed the synthetic pathway of dibenzocycloheptane derivatives via gold-catalyzed post-cyclization isomerization (Scheme 10). 25 The 7- exo-dig hydroarylation reaction occurred with compound 20 and 5 mol% [L 6 Au(NTf 2 )] catalyst, 5 mol% of 2,6-di- tert -butylpyridine in deuterated benzene at 80 °C for 0.5–72 h and formed the desired product 21 in 41–95% yields. Compound 20 contained a di-substituted methoxyphenyl ring and gave a good yield of 95% after 3 h. When tert -butyloxycarbonyl (Boc)-protected pyrrole or indole ring was used, the tetracyclic molecule 21 was synthesized in moderate and high amounts, respectively (71% and 98%).…”