Palladium-catalyzed Larock annulation

Jia and coworkers have described a concise total synthesis of dictyodendrins B and C, utilizing palladium-catalyzed Larock annulation for the construction of the highly substituted indole core of compounds 37 and 38 (Scheme 26 2014EJO5735). 

Kadnikov, D.V. and Larock, R.C. (2000) Synthesis of coumarins via palladium-catalyzed carbonylative annulation of internal alkynes by o-iodophenols. Organic Letters, 2, 3643—3646. 

Larock R (2005) Palladium-Catalyzed Annulation of Alkynes. 14 147-182 Larrow JF, Jacobsen EN (2004) Asymmetric Processes Catalyzed by Chiral (Salen)Metal Complexes 6 123-152... 

Larock and co-workers [47] have studied the palladium-catalyzed arylation of 1,3-dienes followed by intramolecular attack by an oxygen nucleophile. o-Iodophenols and o-iodobenzyl alcohol were used as substrates. However these reactions, which are annulation reactions, lead to a 1,2-addition to the conjugated dienes and will not be further treated here. Amides, also, were used as nucleophiles in these reactions. 

Related to the Heck reaction is the Larock annulation of internal alkynes, which is a general route to heterocyclic and carbocyclic systems. Especially attractive is the construction of the pharmaceutically important indole ring system via palladium-catalyzed coupling of 2-iodo-aniline and the corresponding V-methyl, acetyl, and tosyl derivatives with a wide variety of internal alkynes. The catalytic process appears to involve arylpalladium formation, regioselective addition to the carbon-carbon triple bond, and subsequent intramolecular palladium displacement.- ... 

Larock, R. C. Palladium-catalyzed annulation. PureAppl. Chem. 1999, 71,1435-1442. 

Roesch, K. R., Larock, R. C. Synthesis of lsoindolo[2,1-a]indoles by the Palladium-Catalyzed Annulation of Internal Alkynes. Org. Lett. 

The scope and mechanism of palladium-catalyzed annulation of internal alkynes to give 2,3-disubstituted indoles, the effect of substituents on the aniline nitrogen or on the alkynes, as well as the effect of the salts such as LiCl or n-BuaNCl were studied by Larock and coworkers (1998 JOC7652). The mechanism they propose for indole synthesis proceeds as follows (a) reduction of the Pd(OAc)2 to Pd(0) (b) coordination of the chloride to form a chloride-Ugated zerovalent palladium species (c) oxidative addition of the aryl iodide to Pd(0) (d) coordination of the alkyne to the... 

The synthesis of l,6-dihydropyrrolo[2,3- ]indazole derivatives 27 has been described. The indoHc ring system was constructed via a Larock palladium-catalyzed annulation using terminal and internal alkynes (Scheme 17). 

Larock reported a palladium-catalyzed annulation reaction that effectively achieves a bisfunctionalization of a symmetrical alkyne with orf/to-iodobiaryls (Scheme 7) [11]. The transformation has been proposed to involve a 1,4-palladium... 

In addition to the dihydrobenzofurans, benzofurans were systematically studied and prepared as well. In 1995, Larock and co-workers described a palladium-catalyzed annulation of internal allynes with 2-iodoanilines, 2-iodophenols and related derivatives. The corresponding products were isolated in good to excellent yields (Scheme 2.52). 

Larock and cmworkers described a palladium-catalyzed annulation of 1,4-dienes with ort/zo-functionalized aiyl halides in 1993. The reactions go through a (n-allyl)palladium intermediate the corresponding six-membered... 

Meanwhile, a reliable and versatile method of constructing fused heteroaromatic frameworks is palladium-catalyzed annulation between aryl halides bearing a heteroatom-containing nucleophile (—LH in Scheme 25.2) and internal alkynes, developed primarily by Larock s group (X = halogen in Scheme 25.2) [8]. 

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