Acetanilides intramolecular cyclization

Several efficient procedures have been developed that allow the cross-dehy-drogenative synthesis of heterocycles via intramolecular cyclization of acetanilide radicals. Fagnou and co-workers developed a palladium-catalyzed intramolecular coupling of arenes and alkanes in air. A new sp -sp C-C... 

Hartwig has reported an intramolecular/intermolecular process affording the 3-aryloxindoles 105 (Scheme 32).115 The intermolecular arylation of acetanilide derivative 104 is slower than the intramolecular arylation to form the oxindole. Thus, the overall transformation starts with cyclization followed by intermolecular arylation of indole. In order to slow down the intermolecular process and speed up the intramolecular reaction, chloroarene and bromine-substituted acetanilide precursors are used according to their respective reactivity with palladium(O) in the oxidative addition process. 

The cyclization of a-chloroacetanilides reported by Buchwald may also involve C-H activation (also Scheme 5). As mentioned above, acetanilides are among the most reactive substrates in this reaction. The presence of a base (Et3N), and 2-PhC6H4PBu2 as the ligand, are conditions more typical of cross-coupling of halides and therefore the sequence may start this way, followed by intramolecular... 

Finally, ortho- 2,2-dibromovinyl)-aniline or -acetanilide can successfully be applied in a sequential cyclizing amination-cross coupling reaction with diethyl phosphonate to furnish the indolyl phosphonic ester 136 or the N-acetyl 2-aryl indole 137 as recently shown by Bisseret and coworkers [ 105] (Scheme 50). This sequence can be also performed with corresponding phenol derivatives furnishing benzofurans. For the N-acetyl 2-aryl indole 137 it can be shown that the Suzuki coupling occurs prior to the intramolecular animation as a consequence of the gradual difference in reactivity between trans-and czs-carbon-bromine bonds. 

In 2014, Rh(III)-catalyzed intramolecular annulation of alkyne-tethered acetanilides for the synthesis of fused tricyclic indoles 3 via C-H activation was developed by the groups of Liu, Jia, and Li [6a-c]. The reactions have a good substrate scope, utilize molecular oxygen as the cooxidant, and proceed with complete regioselectivity. It is interesting to note that only the sterically hindered ortho-C-H bond of the arene moiety participated in C-C bond formation (Eq. (5.3)). Similarly, the cyclization of anilides with allyl carbonates also proceeded to form 2-substituted indoles 4 (Eq. (5.4)) [6d]. 

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