The Mori-Ban indole synthesis

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],... 

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. 

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... 

This reaction was first reported by Mori and Ban in 1976. It is a synthesis of indole derivatives by an intramolecular Heck Reaction of o-halo-fV-aUylanilines catalyzed by a low-valent metal complex and is known as the Mori-Ban indole synthesis. In this reaction, the low-valent metal can be nickel or palladium, but the ortho halogen must be bromine or iodine. Often the o-iodo-fV-allylaniline is more reactive than corresponding o-bromo substrate. In addition, it has been found that the catalyst can be deactivated under the reaction conditions, thus aperiodic provision of fresh catalyst normally gives higher overall yields than that using the same total amount of catalyst at once. ... 

Other references related to the Mori-Ban indole synthesis are cited in the literature. ... 

In addition to the numerous applications of the Mori-Ban indole synthesis, there have been developed several new methods that extend and improve the original procednre. A Pd-catalyzed one-pot A-alkylation/Heck cyclization was published by both Jprgensen [23] and Beck [24] for the Mori-Ban indolization, and Kurth discovered a one-pot, three-component assembly to afford indoles (Scheme 2, equation 1) [25], Kaim and Grimaud reported a... 

There are many variations and improvements on the application of Heck cyclization to the synthesis of indoles (the Mori-Ban indole synthesis) in the past three decades. The cyclization of o-halo-A -allylanilines to indoles is a general and efficient methodology that has been improved by Larock. These improvements include cyclozations of o-halo-A -allylanilines and o-halo-A -acryloylanilines into indoles and oxindoles. For example, the conversion of 16 to 17 can be performed at lower temperature, shorter reaction time, and with less catalyst to give 3-methylindole 17 in 87% yield. 

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