Indole synthesis Mori-Ban

The intramolecular version of the Heck reaction has been extremely fruitful, enabling elegant synthesis of many complex molecules [68, 69]. The Mori-Ban indole synthesis (Section 1.10, vide infra) is a good example of such method. In addition, Rawal et al. carried out an intramolecular Heck cyclization of pentacyclic lactam 55 with a pendant vinyl iodide moiety [70]. Employing Jeffery s ligand-free conditions, 55 was converted to a hexacyclic strychnan alkaloid precursor 56 with complete stereochemical control... 

Among early reported Pd-catalyzed reactions, the Mori-Ban indole synthesis has proven to be very useful for pyrrole annulation. In 1977, based on their success of nickel-catalyzed indole synthesis from 2-chloro-fV-allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [122]. Compound 102, easily prepared from 2-bromo-lV-acetylaniline and methyl bromocrotonate, was adopted as the cyclization precursor. Treatment of 102 with Pd(OAc)2 (2 mol%), Ph3P (4 mol%) and NaHCQ3... 

While the Mori-Ban indole synthesis is catalyzed by a Pd(0) species, the Hegedus indole synthesis is catalyzed by a Pd(II) complex. In addition, the Mori-Ban indole synthesis is accomplished via a Pd-catalyzed vinylation (a Heck recation), whereas the Hegedus indole synthesis established the pyrrole ring via a Pd(II)-catalyzed amination (a Wacker-type process). Hegedus conducted the Pd-induced amination of alkenes [430] to an intramolecular version leading to indoles from o-allylanilines and o-vinylanilines [291-293, 295, 250, 251]. Three of the original examples from the work of Hegedus are shown below. 

Pd(Ph3P)4 and Et3N in refluxing acetonitrile to form the intramolecular Heck cyclization product 152 [125]. The mechanism is akin to that of the Mori-Ban indole synthesis (see page 24). In another case, the intramolecular Heck cyclization of enamidone 153 with a pendant thienylbromide moiety furnished the 6-trig-endo product, indolizine 154, in 63% yield, along with the debrominated enamidone 155 in 37% yield [126],... 

Palladium-Catalyzed Cross-Coupling Reactions 2.1 Mori-Ban Indole Synthesis... 

The Mori-Ban indole synthesis [5-12], the intramolecular version of the Heck reaction as applied to the synthesis of indoles, is not a cross-coupling reaction per se, but it is covered here due to its importance in assembling the indole core. 

Recently, Cook s group described their Mori-Ban indole synthesis of substrate 10, easily assembled from 9 [23]. The intramolecular cyclization gave a 1 1 mixture of indole 11 and exo-3-methylene-indoline 12, which was readily converted to 11 upon treatment with acid. By changing the base from K2CO3 to Ag2C03, the Mori-Ban reaction gave exo-3-methylene-indoline 12 exclusively in 90% yield. 

The Mori-Ban indole synthesis is referred to the intramolecular version of the Heck reaction applied to synthesis indoles. The cyclization of o-halo-A-allylanilines to indoles is a general and efficient methodology. For... 

Macor also exploited the Mori-Ban indole synthesis to synthesize several anti-migraine analogues of sumatriptan and homo-tiyptamines as potent and selective serotonin reuptake inhibitors (SSRIs). Noticeably, the presence of the second bromine (the bromine passenger ) on the substrate was not significantly deleterious to the reaction although a small amount of the 7-bromoindole might be sacrificed at the end of the reaction to consume the active palladium catalyst. The approach to 7-bromoindole could provide a general method to access 7-bromoindoles (a rare class of indole derivatives), which then could be further manipulated for the synthesis of more complex 7-substituted indoles. 

In synthesis of eletriptan (Relpax), Pfizer s triptan for the treatment of migraine, Macor again used the Mori—Ban indole synthesis as the key operation to assemble the indole ring. Jeffrey s conditions were once again employed to transform the o-bromo-A allylaniline into the indole core. 

In a synthesis of another anti-migraine agent almotriptan (Axert), the Mori-Ban indole synthesis was the key operation to construct the indole... 

Thankfully, some of the conventional and modem indole synthesis methods do apply to make azaindoles. They include the Larock reaction, Mori-Ban indole synthesis, Bartoli indole synthesis, Batcho-Leimgmber indole synthesis, and Cadogan-Sundberg indole synthesis. 

This reaction is related to the Hegedus Indole Synthesis, Castro Indole Synthesis, and Mori-Ban Indole Synthesis. 

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