Carbazole aminals addition reactions

When naphthyl amines e.g. 23) are used in the Bucherer carbazole synthesis, they are converted by the catalytic action of aqueous bisulfite into tetralonesulfonic acid derivative 13 by the Bucherer reaction. Addition of NaHSOs gives an enamine, which tautomerises to the imine 24 24 is hydrolysed to keto form 13 and subsequent Bucherer carbazole synthesis follows to afford the benzocarbazole product 20. ... 

The diquinone 300 has been shown to react with a variety of primary amines producing carbazole quinones 301, a process which presumably involves an intermediate such as 302 formed by Michael-type addition. Alkyl-, aryl-, and heteroarylamines and amino acids have been utilized. The reaction failed with p-nitro- and p-acetylanilines neutral and acidic amino acids required base catalysis. Hydroxyl-... 

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 conclusion, the fantastically diverse chemistry of indole has been significantly enriched by Pd-catalyzed reactions. The accessibility of all of the possible halogenated indoles and several indolyl triflates has resulted in a wealth of synthetic applications as witnessed by the length of this chapter. In addition to the standard Pd-catalyzed reactions such as Negishi, Suzuki, Heck, Stille, and Sonogashira, which have had great success in indole chemistry, oxidative coupling, amination, and cyclization aie powerful routes to a variety of carbazoles, carbolines, indolocarbazoles, and other fused indoles. 

Sundberg et al. [21] reinvestigated this system by flash photolysis and were able to reproduce the earlier rate constant quoted in cyclohexane. They were able to demonstrate however that this reaction was subject to a considerable solvent effect. As previously mentioned, it was found that photolysis of 2-azido biphenyl in the presence of amines produced 3H-azepines in addition to carbazole. Although secondary amines reduced the yield of carbazole, some heterocycle is still formed even in neat amine. Thus there are two pathways for carbazole formation, one which can be quenched with amines and one pathway which cannot. 

Intramolecular coupling or nucleophilic substitutions sometimes occur upon oxidation of the cation radical the new product frequently then undergoes an additional anodic electron-transfer reaction to yield a new cation radical. For example, tri-p-substituted triphenylamines form stable cation radicals upon oxidation at their first anodic wave. Reynolds et alt (1974) have shown, however, that further oxidation of the cation radicals leads to the appearance of a new reversible redox couple at potentials slightly positive with respect to the first anodic wave. This new couple was shown to occur at potentials where the corresponding carbazole is oxidized, so that the overall process involves conversion of the amine to the carbazole cation radical by reaction scheme (85). 

Prior to the discovery of the aryl-Heck reaction (Chapter 72), the direct Pd-promoted oxidative cyclization of diaryl amines to carbazoles was well known. In 1975 Akennark reported this reaction (Scheme 1, eqnation 1) [1], In addition, A -phenylanthranUic acid gave carbazole-l-carboxylic acid (60%). Miller and Moock used Pd(OAc)j to cyclize 6-anilino-5,8-dimethylisoquinoIine to eUipticine in low yield [2]. The second advance in this chemistry was reported independently by Bittner [3] and Furukawa [4], who described the Pd-mediated (stoichiometric) oxidative conversion of 2-anilino-l,4-benzoquinones and 2-anilino-l,4-naphthoquinones to the corresponding carbazole-l,4-diones and benzo[ ]carbazole-l,6-diones (equations 2, 3). Furukawa s studies included syntheses of several carbazolequinone alkaloids. In 1995 Akermark and colleagues developed catalytic versions (i.e., using tert-butyl hydrogen peroxide [TBHP] or oxygen) of this cyclization (equation 3) [5,6], which elevated the importance of this palladium oxidative cyclization, mainly because of the expense of Pd(OAc)2. Somewhat earlier, Knbiker used cupric acetate as a reoxidant in a synthesis of carbazole-l,4-quinones [7]. 

The gold-catalysed intramolecular amination of allylic alcohols with alkylamines has provided substituted pyrrolidine and piperidine derivatives with excellent yields and selectivities (up to 99% yield and 96% ee)." The reaction mechanism was found to be consistent with the net syn addition of the amine relative to the departing hydroxyl group (Scheme 6). The synthesis of functionalized carbazoles through gold-catalysed deacylative cycloisomerization of 3-acylindole/ynes has been reported. ... 

Minfiensine, a secoiridoid indole alkaloid, was isolated from the African plant Strychnos minfiensis by Massiot and co-workers in 1989. The unique structure feature of the 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9//-carbazole has received much attention for the synthetic efforts and has culminated in several elegant total syntheses. For example. Overman et al. reported on the first and second total synthesis of (-l-)-minfiensine. " In addition, Qin et al. revealed a synthesis of ( )-minfiensine in 2008. Recently, MacMillan and co-workers reported on a nine-step enantiose-lective total synthesis of (-l-)-minfiensine via the key step reaction of organocatalytic Diels-Alder cyclization and amine heterocyclization cascade (Scheme 21.32). For the key step reaction in their approach, reaction of 2-vinylindole 139 and 3 equivalents of propynal in the presence of secondary amine catalyst 140 followed by the addition of NaBH4, stereoselective afforded the tricyclic alcohol 142 via a iminium activated endo-selectiye Diels-Alder cycloaddition and a 5-exo amine heterocy cliz ation. 

---