Hydroarylation of Allenes

The first carbon addition to allenes catalyzed by gold was described by Hashmi and was the addition of furans to allenones, a reaction that is discussed as a conjugate addition to carbonyls. Then the annulation of 2-allenyl indoles was described (equation 111)and an enantioselective version was later developed for terminal allenes. Then Nelson described the cyclization of an N-substituted pyrrol in the synthesis of (—)-Rhazinilam (equation 112). In that case, gold notably improved the yields and selectivities obtained with Pd(II) or Ag(l), and gave complete retention of the chiral information of the allene. The most recent report is on the hydroarylations of allenes with gold-covered substituted benzenes as substrates. ""... 

Representative procedure for the intramolecular gold-catalyzed hydroarylation of allenes. (R,E)-Methyl 4-[(R)-8-ethyl-5,6,7,8-tetrahydroindolizin-8-yl]-2-methylbut-3-... 

Electron-rich phenyl rings are also suitable nucleophiles for the intramolecular gold-catalyzed hydroarylation of allenes. Thus, dihydroquinoline and chromene derivatives are accessible by treating allenic anilines or allenic aiylethers with a cationic gold catalyst (Scheme 4-14). Because of the limited stability of... 

Scheme 11.7 illustrates that gold and silver triflate-catalyzed intramolecular hydroarylation of allenic anilines and phenols offers an efficient route to dihydroquinoline and chromene derivatives under mild reaction conditions (Watanabe et al. 2007). The hydroarylation takes place at the terminal or central allenic carbon, depending on the substrate structure, leading to a highly selective formation of six-membered rings. 

Fujii, Ohno, and coworkers developed a gold-catalyzed intramolecular aryl C(sp )-H functionalization with allenic anilines for the synthesis of dihydroquinoline (Scheme 12.32) [37]. This intramolecular gold-catalyzed 6-endo hydroarylation of allenic anilines 70 could afford the dihydroquinolines 71 in... 

In the context of the total synthesis of ( )-rhazinilam, an intramolecular hydroarylation of an allene (Scheme 12.23) was investigated.41 The authors report that the Ag(I) complexes were completely ineffective, while AUCI3 delivered 27% of the product and a mixture of 5 mol% AuC13/20 mol% AgOTf gave 82%. The optimum was then reached with 5 mol% Ph3PAuOTf (92% yield). In all cases, the diastereoselectivity was better than 92 8. 

Intermolecular hydroarylations of terminal allenes with highly nucleophilic methoxyarenes are catalyzed by cationic phosphite gold(l) complexes. The addition takes place regioselectively at the unsubstituted allene terminus and affords ( )-allylated benzene derivatives with moderate-to-high yields. 

An asymmetric version of the intramolecular hydroarylation of alkynes (286) to produce fused rings (287) has been developed. With the cationic Pd(II)/(5)-(285) catalyst, the resulting 4-aryl 2-quinolinones were obtained with <98% ee. Asymmetric addition of boronic acids R B(OH)2 to activated cumulenes R C=C=C=C(R )C02Et, catalysed by an NHC-palladium complex, has been shown to yield allenic products R C=C=C(R )CH(R )C02Et with moderate to good enantioselectivities. ... 

Indenes can be synthesized via intramolecular hydroarylation of propargyl acetates catalyzed by NHC gold(I) complexes [127, 128]. The formation of the indenes proceeds via a 1,3-shift to form an allene, followed by the hydroarylation (Scheme 1.8). Notably, this reaction requires strictly anhydrous conditions, because conjugated enones and enals are isolated in the presence of water [129]. Related transformations include reaction with propagyl sulphides or dithioacetals. 

Even though less studied than the O- and A-nucleophiles, other important H-X bonds can participate in hydrofunctionalization catalyzed by gold. Hence, the intermolecular hydroarylation i.e. bond addition) of allenes... 

Alkenes undergo intramolecular hydroarylation under conditions similar to those for allenes. Aromatic compounds bearing alkene side chains afford tetralin derivatives. The intramolecular hydroarylation reaction is catalyzed by RuCls/AgOTf (Scheme 18.10) [9] or Bi(OTf)3 (Scheme 18.11) [10]. The latter process was applied to a tricyclic compound and a seven-membered ring product. The intramolecular hydroarylation of 5-phenylpent-l-ene in the presence of AuCb/AgOTf catalyst affords 1-methyltetralin in 98% yield (Scheme 18.12) [11]. 

A gold(I)-catalyzed hydroarylation of an allene with indole was developed by Toste and Zeldin (Scheme 12.25) [30]. This reaction could be applied toward the total synthesis of flinderoles B 54 and flinderoles C 55, members of a new class of antimalarial bisindole alkaloids isolated from plants of the Flindersia genus. The key intermediate pyrrolidine 53 in the total synthesis of flinderoles B and C could be efficiently constructed as a single diastereomer via Au-catalyzed intramolecular hydroarylation of a pendant allene 52, which was prepared from commercially available tryptophol 51. 

Although less studied than O- and N-nueleophiles, other nueleophilic partners possessing H-X bonds can participate in gold-eatalyzed hydrofunctionalization reactions. Hence, the intermoleeular hydroarylation ie. C(sp2)-H bond addition] of allenes with indoles was reported in the presence of [(IPr) AuCl]. Using the same catalyst, Che and co-workers investigated an interesting cascade terminated by an alkyne hydroarylation step. The intramolecular allene hydroarylation with indoles was also described by Alcaide and Almendros. ... 

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