Carbazoles intramolecular synthesis

Another intramolecular synthesis of carbazoles 270 employed amino biaryls 269 as the starting materials with 2-picolinic acid as a directing group to facilitate a net C—H amination reaction under copper catalysis in the presence of Mn02 and acetic acid. The directing group is removed spontaneously after the initial amination (140L2892). 

Chang et al. developed an intramolecular synthesis of carbazoles from N-substituted 2-amidobiphenyls via oxidative C-N bond formation (Scheme 8.41). This cyclization could take place readily under both Cu-catalyzed and metal-free conditions. The iodobenzene diacetate or bis(trifluoroacetoxy)iodobenzene undergoes this reaction to provide carbazole products in moderate to low yields. 

Scheme 8.41 Intramolecular synthesis of carbazoles from Nsubstituted 2-amidobiphenyls.

GOMBERG - BACHMANN - GRAEBE - ULLMANN Arylatwn Atykaryl bond formation via diazonium salts Carbazole synthesis by intramolecular aryl-aryl bond formation. 

Zhao and Larock have described the synthesis of carbazoles, indoles, and dibenzofurans 118 via a Ic type cyclization that follows a sequence of Pd-catalyzed cross-coupling of alkynes and aryl iodides 116, then nitrogen-directed palladium migration to an arylpalladium intermediate 117 that undergoes an intramolecular Mizoroki-Heck ring closure <06JOC5340>. 

Applications of the aforementioned methodology are also found in the total synthesis of plagiochin D to link a 16-membered biaryl system [47], as well as to the intramolecular cyclization of di-benzyl halides [45, 48]. Additional examples include dithienothiophene (40) from dithienyl bromide 39 [49] and carbazole 42 from diarylbromide 41 [50]. 

A more recent publication (96F1(43)15) reports the synthesis of tetracyclic derivative azocino[4,3-f>]indole 49 using an intramolecular aldol condensation of carbazole 48. The possible elaboration of effective synthetic methods of the... 

An efficient synthesis of functionalized carbazoles was developed by the palladium-catalyzed annulation of a variety of internal alkynes. This reaction involves arylpalladation of the alkyne, followed by intramolecular Heck olefination, and double bond isomerization. The iodoindole 588 reacts with the alkyne 589 in the presence of a catalytic amount of palladium(O) to give substituted carbazoles 590. In this reaction two new C-C bonds are formed in a single step. Higher reaction temperatures were necessary due to the low reactivity of the iodoindole (566) (Scheme 5.29). 

Table 4 lndolo[3,2-b]carbazoles synthesis by intramolecular cyclization... 

Intramolecular cyclization reactions of highly substituted 2,3-divinylindoles have also been employed for the synthesis of specific carbazole derivatives. Reaction (147) was carried out in the presence of a palladium catalyst, which facilitates aromatization of the dihydrocar-... 

DFT calculations on the intramolecular Diels-Alder reaction of penta-l,3-dienyl acrylates predict stereoselectivities that are in good agreement with the experimen- (g) tal results.85 Another DFT study at the B3LYP/6-31G(d) level of the intramolecular Diels-Alder cycloaddition of 5-vinylcyclohexa-1,3-dienes has been reported. Reaction rates are influenced by dienophile twisting and substituent effects.86 The intramolecular dehydro-Diels-Alder reactions of ynamides (79) provides a new synthesis of benzo[fc]-, tetrahydrobenzo[fc]-, naphtho[l,2-/j -, and dibenzo[a,c]carbazoles... 

Intramolecular Biaryl Bond Formation - Exemplified by the Synthesis of Carbazoles... 

A plausible mechanism for the one-pot synthesis ofcarbazoles is shown in Scheme 5. It consists of two interlinked catalytic cycles. In the first cycle a classical Buchwald-Hartwig amination reaction occurs to generate an intermediate 5 which then enters the second cycle by oxidative addition to Pd(0). The resulting Pd(II) complex then undergoes intramolecular C-H activation to give a six-membered palladacycle which subsequently yields the carbazole by reductive elimination. 

In two papers, Miller and co-workers (45,46) have extended their intramolecular ring B cyclization strategy (47) to the use of aryl nitrenes in the synthesis of pyridocarbazoles. Thus, in the first paper, isoquinoline azide 39 was heated at 180-200°C to aiford ellipticine (1) as the minor product (20%) (Scheme 7). The major product was the isomeric pyrido[3,4-a]carbazole 40 (60%). This result is consistent with the relative nucleophilicities of C-6 and C-8 of isoquinoline. The isomeric azido isoquinoline 41 exhibited comparable re-gioselectivity in the cyclization of the corresponding nitrene to yield isoellipticine (27) as the minor product (Scheme 7). 

As with the corresponding section on p3rroles, indole syntheses have been categorized utilizing a systanatic approach. Intramolecular approaches (t)rpe I) and intermolecular approaches (type II) are classified by the number and location of the new bonds that describe the indole forming step (2 examples shown below). In addition, the synthesis of oxindoles, azaindoles, and carbazoles wUl be treated separately. 

Table 2 Synthesis of carbazoles via intramolecular oxidative coupling of two arene C-H bonds... 

Scheme 29 Pd(II)-catalyzed intramolecular oxidative cyclization for the synthesis of carbazoles O...

A (2 + 2)-cycloaddition product is formed on irradiation of stilbenophane derivatives. A continuation of studies towards the synthesis of cyclophanes has reported the intramolecular cycloaddition of the carbazole derivatives (108). Irradiation through Pyrex in toluene solution affords a mixture of cycloadducts such as the endo,endo-aidduct (109). This is generated in addition to the corresponding exo,endo- and exo-exo-adducts. These products are formed in a ratio of 9 3 1. Single (2- -2)-cycloaddition is also reported. Nishimura and his co-workers have used intramolecular (2-1-2)-cycloaddition reactions of vinyl groups attached to a bisphenol as a path to the synthesis of calix[4]arenes. 

Much research interest in the synthesis of carbazoles is directed at the preparation of natural products. The total syntheses of murrayafoline A 153 and murrayanine have been reported <04S2499>. The key step included a regioselective cycloaddition between oxazolidinone 150 and acrolein which led to benzoxazol-2-one 151 after DDQ oxidation. Ring opening of the oxazol-2-one ring of 151 followed by methylation provided A-phenylaniline 152. A palladium-catalyzed intramolecular cyclization of the latter then produced the natural product 153. Finally, venerable iron-mediated chemistry has been utilized in the total synthesis of furoclausine A 154 <04SL528> and 6-chlorohyellazole 155 <04SL2705>. 

Scheme 45 Synthesis of carbazoles 32 by Buchwald-Hartwig amination and subsequent cyclization by intramolecular Heck-type coupling of the intermediate diarylamines 197...

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