Martin indole synthesis

A concise total synthesis of the indole alkaloid dihydrocorynantheol (101) (Scheme 19), that features two RCM steps and a zirconocene-catalyzed carbo-magnesation [68], is a further example of Martin s interest in applying RCM as a key reaction for the construction of alkaloid frameworks [69]. The first RCM step was applied to bis-allyl amide 96. The resulting intermediate 97 was directly subjected to carbomagnesation and subsequent elimination to deliver 98 in 71% yield from 96. Amide 98 was then transformed into acrylamide 99 in... 

Huffman JW, Dai D, Martin BR, Compton DR. Design, synthesis and pharmacology of cannabimimetic indoles. Bioorg Med Chem Lett 1994 4 563-566. 

Martin effected the synthesis of several 3,5-diarylated indoles by a tandem Stille-Suzuki sequence [131]. The latter reaction involves exposure of 3-(3-pyridyl)-5-bromo-l-(4-toluenesulfonyl)indole with arylboronic acids (aryl = 3-thienyl, 2-furyl, phenyl) under typical conditions to give the expected products in 86-98% yield [131], Carrera engaged 6- and 7-bromoindole in Pd-catalyzed couplings with 4-fluoro- and 4-methoxyphenylboronic acids to prepare 6- and 7-(4-fluorophenyl)indole (90% and 74% yield) and 6-(4-methoxyphenyl)indole (73% yield) [29]. Banwell and co-workers employed 7-bromoindole in a Suzuki coupling with 3,4-dioxygenated phenylboronic acids en route to the synthesis of Amaryllidaceae alkaloids [132], Yields of 7-arylated indoles are 93-99%. Moody successfully coupled 4-bromoindole... 

Murakami et al. reported (575) a total synthesis of murrayaquinone A (107) by oxidation of l-hydroxy-3-methylcarbazole (23) with Fremy s salt, as previously described by Martin and Moody (632). The hydroxycarbazole 23 required for this synthesis was obtained via the Fischer indolization of the O-methanesulfonyl phenylhydrazone 614 (575) (see Scheme 5.38). The oxidation of l-hydroxy-3-methylcarbazole (23) with Fremy s salt afforded murrayaquinone A (107) as the major product, along with a 5% yield of isomeric carbazole-l,2-quinone 876 (575) (Scheme 5.108). 

A concise total synthesis of the indole alkaloid dihydrocorynantheol 148 (Scheme 27) that features two RCM steps and a zirconocene-catalyzed carbomagnesation is a further example of Martin s interest in applying RCM as a key... 

Pyrroles, H.M.L. Davies. Synthesis of Porphyrins with Exocy-clic Rings from Cycloalkenopyrroles, T.D. Lash. Palladium-Catalyzed Coupling Reactions of Indoles, A.R. Martin and Q. Zheng. Cycloaddition Reactions of Indole Derivatives, U. Pindur. Transition-Metal Mediated Synthesis of Carbazole Derivatives, H. J. Knoiker. Synthesis of [b]-Annelated Indoles by Thermal Electrocyclic Reactions, S. Hibino and E. Sugi-no. Total Synthesis of (-) and ent (-) Duocarmycin SA, D.L. Boger. Index. I... 

Oxidation of the protected 5-aminoindole 129 with Dess-Martin periodinane (DMP) produced the indole-quinone 130. This methodology was employed in a new total synthesis of the Actinomycetes metabolite BE-10988 (131), which is a promising topoisomerase II inhibitor <02JA2221>. 

The total synthesis of the complex bioactive indole alkaloid ditryptophenaline, having two contiguous quaternary stereocenters related by C2 symmetry, was accomplished in the laboratory of L.E Overman.In the late stages of the synthetic effort the complex diol substrate was oxidized to the dicarboxylic acid using a two-step procedure first, a Dess-Martin oxidation to the dialdehyde followed by the Pinnick oxidation. The mild reaction condition ensured that the integrity of the stereocenters at the a-positions was preserved. 

Martin effected the synthesis of several 3,5-diarylated indoles by a tandem... 

Bos, M., Jenck, E., Martin, J. R., Moreau, J.-L., Sleight, A. J., Wichmann, J., Widmer, U. Novel agonists of 5HT2C receptors. Synthesis and biological evaluation of substituted 2-(indol-l-yl)-l-methylethylamines and 2-(indeno[l,2-h]pyrrol-l-yl)-l-methylethyl-amines. Improved therapeutics for obsessive compulsive disorder. 7. Med. Chem. 1997,40,2762-2769. 

Dutta AK, Ryan W, Thomas BF, Singer M, Compton DR, Martin BR, Razdan RK (1997) Synthesis, pharmacology, and molecular modeling of novel 4-alkyl oxy indole derivatives related to cannahimimetic aminoalkyl indoles (AAIs). Bioorg Med Chem 5 1591-1600... 

Maulide et al. developed a unified method for the direct transfer of ylides and the metal-free arylation of carbonyl compounds. This was applied in the synthesis of pyrrole 76 from 75 upon treatment with Martin s sulfurane in toluene at room temperature. The dearomatization of both indole and pyrrole could be effected with a variety of electron-donating or -withdrawing groups in good to excellent yields (13JA7312). 

In terms of the application of selective alkene RCM for multiple ring formation, Martin et al. reported a very interesting example in their total synthesis of indole alkaloid ( )-pseudotabersonine (44) [57]. In this case, a highly functionalized tetraene substrate (45) underwent double RCMs in the presence of Hoveyda-Grubbs II catalyst to afford a mixture of two diastereomers (46) (Fig. 14). During this process the high regioselectivity for alkene RCM was achieved, which was worthy of note. 

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