Mori-Ban-Heck indole synthesis

An important variation of the Mori-Ban-Heck indole synthesis is Pd-catalyzed oxidative cyclization of A/-aryl enaminones and enamines, as largely developed by Glorius (Scheme 4, equations 1 and 2) [44-46]. The C-2 substituent was easily varied, and the method was extended to imine cyclization (equation 2). Related Pd-catalyzed oxidative cyclizations were described by Li (carbazolones) [47],... 

Scheme 2 Applications of the Mori-Ban-Heck Indole Synthesis Pd2(dba)3...

The aromatic ring version of the Mori-Ban-Heck indole synthesis can be called an aryl-Heck reaction. This palladium-catalyzed cyclization of o-halo diaryl amines has seen many applications in carbazole and carboline synthesis. 

Palladium-Catalyzed Indole Ring Synthesis Mori-Ban-Heck 593... 

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... 

The application of Heck cyclizations to the synthesis of indoles, indolines, and oxindoles was discovered independently by Mori-Ban s [296-298], and Heck s groups [299]. These investigators found that Pd can effect the cyclization of o-halo-lV-allylanilines to indoles under Heck conditions [300], The cyclization of o-halo-/V-allylanilines to indojes is a general and efficient methodology, especially with the Larock improvements where he cyclized o-halo-W-allylanilines and o-halo-N-acryloylanilides into indoles and oxindoles [301]. For example, the conversion of 279 to 280 can be performed at lower temperature, shorter reaction time, and with less catalyst to give 3-methylindole (280) in 97% yield. Larock s improved conditions, which have been widely adopted, are catalytic (2%) Pd(OAc)2, n-Bu4NCl, DMF, base (usually... 

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],... 

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 with the nickel-catalyzed synthesis of indole from 2-chloro-A -allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [111]. Compound 117, easily prepared from 2-bromo-A-acetylaniline and methyl bromocrotonate, was adopted as a cyclization precursor. Treatment of 117 with PdiOAc), (2 mol%), PhjP (4 mol%), and NaHCOj in DMF provided indole 118 via an intramolecular Heck reaction followed by olefin isomerization to afford the fully aromatic product. Although yields fr om the initial report were moderate, they have been greatly improved over the last two decades [112]. 

The incredibly powerful and versatile Heck coupling reaction has found enormous utility in the indole ring synthesis and in the elaboration of this important heterocycle. Due to the enormity of this topic, the section is divided into Heck reactions of indoles, the synthesis of the indole ring as developed by Hegedus, Mori-Ban, and Heck, and the Larock indole ring 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. 

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... 

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. ... 

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... 

In summary, the original discovery by Mori and Ban of a new Pd-catalyzed indole synthesis involving an intramolecular Heck cyclization has been refined by many investigators to become a powerful method for the synthesis of diverse indoles. 

As the first application of Heck reaction in making heterocyclic compounds — namely indole derivatives, the Mori-Ban reaction has been widely used in variety synthesis of indoles. In a program to synthesize CC-1065 analogs, Sundberg prepared indole 19 from o-bromo-JV-allylaniline 18 in an excellent yield using the Jeffrey s conditions. Silver carbonate and sodium carbonate were less effective than triethylamine. 

Starting in 1977, Mori and Ban " at Hokkaido University discovered that Pd can catalyze the intramolecular reaction of o-halo-iV-allylanilines to indoles under Heck reaction conditions. It was the first intramolecuar Heck reaction to the synthesis of heterocycles. For example, the compound 1, which was prepared from methyl a-bromocrotonate (3) and 2-bromo-A-acetylaniline 4, was adopted as a starting material. It was treated with Pd(OAc)2 (2 mol%) and PPhs (4 mol%) in the presence of tetramethylethylenediamine (TMEDA, 200 moI%) under a stream of nitrogen at 125 °C for 5.5 h methyl l-acetyl-3-indolyl acetate was obtained in a yield of 43% via an intramolecular Heck... 

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