Heteroannulation reaction

Bagley MC, Chapaneri K, Dale JW, Xiong X, Bower J (2005) One-pot multistep Bohlmann-Rahtz heteroannulation reactions synthesis of dimethyl sulfomycinamate. J Org Chem 70 1389-1399... 

Several investigators have developed the reductive cyclization of o-nitrostyrenes into an efficient synthesis of indoles. Thus, research by the groups of Watanabe [458, 459], SOderberg [460, 461], and Cenini [462, 463] have established this reductive Pd-catalyzed A/ -heteroannulation reaction as a viable route to simple indoles and fused indoles (372) as shown below. Ohta... 

Iodocarboxylic acid 1003 and 1,4-pentadiene undergo a palladium-catalyzed heteroannulation reaction producing the tetrahydropyran-2-one 1004 in poor yield (Equation 394) <2000JOC1525>. 

A novel type of heteroannulation reaction has been reported by Wamhoff, Schmidt et al. <91TL4473, 93JOC6976). Uracil-iminophosphoranes (108) are converted into pyrimido[4,5-rf]pyrimidine betaines (109) in a one-pot three-component reaction with isocyanates and hetarenes (double bonds) (Equation (14)). 

Metal-mediated electrophilic cyclizations of o-ethynylanilines leading to indoles have also been reported. For example, the gold(III)-catalyzed heteroannulation of bis-aniline 119 produced 2,2 -biindole 120 <04S610>. A similar heteroannulation reaction was reported utilizing copper triflate as the catalyst <04JOC1126>. 

Unconjugated 1,4-cyclohexadiene (350) undergoes heteroannulation. Reaction of 350 with 349 is explained by carbopalladation to give 351. Dehydropalladation... 

Pd-mediated heteroannulation of alkynes with resin-bound o-iodoaniHnes 16 gives trisubstituted indoles with good yields. Zhang and coworkers have used Rink amide AM resin as solid support and the iodoanihne was linked by formation of an amide bond (1997TL2439 Scheme 7). After the heteroannulation reaction, cleavage with trifluoroacetic acid gave the indoloamide functionalized compounds 17. 

Jana and Sinha have described the total synthesis of ibogaine, epiibo-gaine, and their analogs utilizing the Larock heteroannulation reaction for the creation of the suitably substituted indole (Scheme 25 2012T7155). 

In addition, the above multicomponent process was used to prepare the indole A -carboxamide derivatives 23 via Larock heteroannulation reaction. 

Larock heteroannulation reaction was further extended and an intramolecular Larock indole synthesis of 2-chloroanilines bearing tethered acetylenes 106 was developed for the elaboration of a variety of polycyclic indole skeletons 107, for example, in 108-112. This intramolecular indolization method unveiled an unusual >sy -anidopalladation pathway of a tethered alkyne. The major side product is the dechlorinated starting material as a result of a reductive process. 

Allylpalladium complexes with BOX-type ligands and glucopyrano-oxazoline-palladium catalysts were used as catalysts for enantioselective allylic substitution (277). A chiral bisoxazoline ligand (BOXBZ) developed by Pfaltz has been used for asymmetric carbo- and heteroannulation reactions (278). An axial binaphthyl-based ligand possessing oxazolyl substituents (BOXAX) was developed by Hayashi and co-workers and successfully applied for the asymmetric Wacker-type cyclization (279). 

SCHEME 31 Heteroannulation reaction between arynes and N-aryl-a-aminoketones [54]. 

The reaction of 5-alkyl/arylamino-6-chloropyrazine-2,3-carbonitriles 37 with phenylacetylene 18, catalyzed by Pd-Cu, in the presence of sodium lauryl sulfate as a surfactant in water leads to the formation of highly substituted pyrazino-pyrroles 38 in good to high yields (Scheme 12) [43]. This palladium-catalyzed heteroannulation reaction... 

Castle et al. reported the efficient synthesis of tryptophan derivatives with different substituents on the indole ring [45]. Their strategy involves a PTC 45 mediated alkylation of 14 with propargyl bromide 54 first. The key intermediate 55 was then transformed into the central tryptophan residue 58 of celo-gentin C (59) in two more steps, involving a hydrolysis of the Schiff base and amine-protection first, followed by a palladium-catalyzed heteroannulation reaction (Scheme 9). 

In a heteroannulation reaction, optically active y-hydroxy-a,p -acetylenic esters undergo regiospecific hydration in the presence of Zeise s dimer, [PtCl2(C2H4)]2, to generate, by tandem hydration/annulation reaction, optically active tetronic acids in 74-92% yields [131] (Scheme 72). 

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