Hegedus-type cyclization

The reaction sequence has also be extended to systems having carbocyclic substituents. A similar zirconocene intermediate prepared from N-allyl-2-bromoaniline was used in the early stages of a synthesis of the A-ring structure of the antitumor antibiotic CC-1065. The second pyrrole ring was installed by a Hegedus-type cyclization. <94J0C192>... 

Hegedus et al. have thoroughly studied the homogeneous hydroamination of olefins in the presence of transition metal complexes. However, most of these reactions are either promoted or assisted, i.e. are stoichiometric reactions of an amine with a coordinated alkene [98-101] or, if catalytic, give rise to the oxidative hydroamination products, as for example in the cyclization of o-allylanilines to 2-alkylindoles [102, 103], i.e. are relevant to Wacker-type chemistry [104]. 

Hegedus proposed the probable course of the cyclization reaction, which follows a Wacker-type reaction mechanism. Coordination of the olefin to Pd(II) results in precipitate 110, which upon treatment with Et3N undergoes intramolecular amination to afford intermediate 111. As expected, the nitrogen atom attack occurs in a 5-exo-trig fashion to afford 112. Hydride... 

Palladium-catalyzed, Wacker-type oxidative cycHzation of alkenes represents an attractive strategy for the synthesis of heterocycles [139]. Early examples of these reactions typically employed stoichiometric Pd and, later, cocat-alytic palladium/copper [140-142]. In the late 1970s, Hegedus and coworkers demonstrated that Pd-catalyzed methods could be used to prepare nitrogen heterocyles from unprotected 2-allylanilines and tosyl-protected amino olefins with BQ as the terminal oxidant (Eqs. 23-24) [143,144]. Concurrently, Hosokawa and Murahashi reported that the cyclization of allylphenol substrates can be accomplished by using a palladium catalyst with dioxygen as the sole stoichiometric reoxidant (Eq. 25) [145]. 

Heck indole synthesis, and Hegedus-Mori-Heckreaction, in general contains at least two types of reactions for indole derivatives. They are the palladium (n) complex-catalyzed oxidative A -heterocyclization of o-allylaniline (developed in 1976) or o-aminostyrenes (reported in 1978) and the palladium-catalyzed intramolecular cyclization of o-halo N-allylaniline (reported in 1980) the latter preparation is also referred to as the Hegedus cyclization. ... 

Because intramolecular cyclization, in general, is entropically favorable, intramolecular aminopalladation of alkenes followed by Pd—H elimination appears to proceed well. However, the basicity of the amine again becomes a crucial factor. The first successful reaction of this type was carried out in 1976 by Hegedus et where less basic ary-... 

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