Hyellazole synthesis

Indoles substituted at C-3 with butadienyl or styryl groups undergo electrocyclic reactions to give carbazole derivatives. The silyl enol ether (275) can be converted thermally directly into the carbazole (276), as the result of ready elimination of methanol this sequence is crucial for a hyellazole synthesis (Equation (96)) <89CC43>. Several related 3-styrylindole sequences have been developed and differ with respect to the placement of ethyl carbonate groups on the alkene. Both the substrates (277) and (279) undergo photocyclization to the respective benzocarbazoles (278) and (280) as a result of... 

For the quinone imine cyclization of iron complexes to carbazoles the arylamine is chemoselectively oxidized to a quinone imine before the cyclodehydrogenation [99]. The basic strategy of this approach is demonstrated for the total synthesis of the 3-oxygenated tricyclic carbazole alkaloids 4-deoxycarbazomycin B, hyellazole, carazostatin, and 0-methylcarazostatin (Scheme 17). 

Sakamoto et al. reported the synthesis of hyellazole (245) and carazostatin (247) based on the benzannulation of indoles. This method involves an electrocyclization of the 3-(l,3-butadienyl)indoles 685, which derive from the indolin-3-one 686 and the phosphorus ylides 687 (Scheme 5.59). 

The arylamine 709 required for the total synthesis of hyellazole (245) was synthesized by Diels-Alder reaction of l-methoxycyclohexa-l,3-diene (710) and ethyl phenylpropynoate 711. The biphenyl derivative 719 thus obtained was transformed to the arylamine 709 by excecuting a similar reaction sequence as shown in Scheme 5.66. The arylamine 709 was obtained in six steps and 7% overall yield based on 1-methoxycyclohexa-l,3-diene (710) (599,600) (Scheme 5.68). 

Witulski and Alayrac reported the synthesis of clausine C (clauszoline-L) (101) by a rhodium-catalyzed alkyne cyclotrimerization of diyne 1014 and propiolic ester 635 (561). Analogous to the hyellazole (245) synthesis (see Scheme 5.75), the diyne precursor 1014 required for this key cyclotrimerization reaction was obtained starting from readily available 2-iodo-5-methoxyaniline. Using Wilkinson s catalyst, [RhClfPPhsls], crossed-alkyne cyclotrimerization of 1014 and 635 led to N-tosylclausine C (1015) in 78% yield in an isomeric ratio of 3.8 1. Finally, deprotection of the tosyl group with TBAF in refluxing TFIF afforded clausine C (clauszoline-L) (101) (561) (Scheme 5.147). 

R.L. Danheiser and co-workers have used the modified Danheiser benzannuiation for the synthesis of the marine carbazole alkaloid hyellazole. The required diazoketone was prepared from the A/-Boc derivative of 3-acetylindole using a diazo transfer reaction. The diazoketone was irradiated in the presence of the alkyne to afford the desired carbazole annulation product in 56% yield. Finally, in order to install the phenyl group of hyellazole at Cl, the phenolic hydroxyl group was converted to the corresponding triflate and a Stiiie cross-coupiing was performed. 

The iron-mediated arylamine cyclization (mode A in Scheme 12) proceeds via the steps cyclodehydrogenation, aromatization, and concomitant demetalation, and can be achieved with various oxidizing agents (e.g., very active manganese dioxide [92, 93], iodine in pyridine [94—96], and ferroceifium hexafluorophosphate [92,97, 98]). Applications of this procedure to the total symthesis of carbazole alkaloids include for example hyellazole [97] and carazostatin [98] for reviews, see [18-20, 83]. More recent applications of this route to natural product synthesis are described in Sect. 3.1.1. 

In 2002, Witulski and Ala3rac reported a highly efiBcient synthesis of a variety of substituted carbazoles. The marine carbazole hyellazole (399) was synthesized through the regioselective trimerization of diyne 396 and alkyne 397, followed by deprotection in excellent yield (Scheme 2-36). ... 

Bergman, J., and B. Pelcman Synthesis of Carbazoles Related to Carbazomycin, Hyellazole and Ellipticine. Tetrahedron 44, 5215 (1988). 

Kawasaki, T., Y. Nonaka, and M. Sakamoto A New Efficient Synthesis of the 3-Methoxy Carbazole Alkaloid Hyellazole. J. Chem. Soc. Chem. Commun. 43 (1989). 

Moody, C.J., and P. Shah Diels-Alder Reactivity of Pyrano [3,4-6] Indol-3-ones Part 4, Synthesis of Alkaloids Carbazomycin A, B, and Hyellazole. J.C.S. Parkin Trans 1, 2463 (1989). 

The oxidative cyclization of 5-(2-anilino)-substituted (diene)iron complexes provides access to the carbazole alkaloids hyellazole, 6-chlorohyellazole, carazostatin, 7-methoxy-O-methylmukonal, clausine O, clausine H, and clausine Furoannulated carbazole alkaloids, a rare class of natural carbazols that have been isolated from terrestrial plants, are also available by this method. Scheme 4-128 outlines the key step in the synthesis of furoclausine-A, the construction of the carbazole framework. The annulation of the furan ring is carried out subsequently. Final functional group transformations provide the natural product. ... 

Kano, S., Sugino, E., and Hibino, S. (1980) Synthesis of the carbazole alkaloid hyellazole. J. Chem. Soc. Chem. Comnmn., 1241-1242. 

Takano, S., Suzuki, Y, and Ogasawara, K. (1981) A simple synthesis of the blue-green alga alkaloid, hyellazole. Heterocycles, 16,1479-1480. 

Bergman, J. and Pelrman, B. (1988) Synthesis of carbazoles related to carbazomycin, hyellazole and eUipticine. Tetrahedron, 44, 5215-5228. 

Moody, C.J. and Shah, P. (1989a) Synthesis of the carhazole alkaloids carbazomycin A and B and hyellazole. J. Chem. Soc. Perldn Trans. I, 376-377. 

Kawasaki, T., Nonaka, Y, Akahane, M., Maeda, N., and Sakamoto, M. (1993) New approach to 3-oxygenated carbazoles. Synthesis of hyellazole and 4-deoxycarbazomydn B. J. Chem. Soc. Perkin Trans. I, 1777-1781. 

Knolker, H.J., Batun, E., and Hopfmaim, T. (1995) Total synthesis of the marine alkaloid hyellazole. Tetrahedron Lett., 36, 5339-5342. 

Knolker, H.J., Baum, E., and Hopfinann, T. (1999) Transition metal complexes in organic synthesis. Part 53. Iron-mediated synthesis of hyellazole and isohyeUazole. Tetrahedron, 55,10391—10412. 

---