Gribble indole synthesis

In unpublished work, Gribble and Obaza-Nutaitis (60) have adapted the Saul-nier-Gribble ellipticine synthesis (61) to the synthesis of olivacine (Scheme 14). Keto lactam 85, available from indole in four steps (71% yield) (61), was treated sequentially with methyllithium and lithium triethylborohydride to give diol 86, which, without isolation, was reduced with sodium borohydride to give 1-de-methylolivacine (87). This had been previously converted to olivacine (4) by Kutney and co-workers (62). The success of this synthesis of 87 was due to the fact that Saulnier and Gribble (63) had previously established that the ketone carbonyl of keto lactam 85 is more reactive than the lactam carbonyl group. 

For reviews on the Fischer indole reaction, see Robinson, B. "The Fischer Indole Synthesis" John Wiley and Sons New York, 1982 Hughes, D. L. Org. Prep. Proced. Int 1993,25, 60 Gribble, G. W. Contemp. Org. Synth. 1994, 1. 145 and references cited therein. 

Alford PE, Kishbaugh T, Gribble GW (2010) Nucleophilic addition of hetaryllithium compounds to 3-nitro-l-(phenylsulfonyl)indole synthesis of tetracyclic thieno[3, 2-c]-g-carbo-lines. Heterocycles 80 831-840... 

In Chap. 6, a companion to the preceding chapter, Li and Gribble document Metal-Catalyzed Cross-Coupling Reactions for Indoles , which covers palladium, copper, rhodium, iron, and nickel cross-couplings of indole - a suite of reactions that has assumed great importance in indole synthesis and chemistry. 

Several other groups have made use of the Smith indole synthesis, and a summary of this work is shown in Table 1. Gribble and cowoikers prepared 2-(2-pyridinyl)indoles en route to syntheses of several zwitterionic indolo[2,3-fl] quinolizine alkaloids (Entry 1) [13], and Husson and Hashimoto synthesized a derivative of the alkaloid goni-omitine via a Smith indole synthesis (Entry 2) [14]. Henegar and Hunt reported a very convenient synthesis of 2-trifluoromethylindole (Entry 3) [15], in which TMEDA was found to be necessary. Two bis-indoles were prepared in low yield (Entry 4), bnt this approach failed for n = 1 [16], The bridged indole shown in Entry 5 was synthesized following acid-catalyzed cyclization of the initially formed indole [17]. 

Gribble used the Sundberg indole synthesis to make 2-nitroindole (30) by simply refluxing p-nitro-o-azidonitrostyrene (29) in xylene. This was the first synthesis of 2-nitroindole (30). 

Moskalev, N. V. Gribble, G. W. Synthesis and Diels—Alder reactions of the furo[3,4-b]pyrrole ring system. A new indole ring synthesis. Tetrahedron Lett. 2002, 43, 197—201. 

Ketcha DM, Gribble GW (1985) A convenient synthesis of 3-acylindoles via Friedel Crafts acylation of l-(phenylsulfonyl)indole. A new route to pyridocarbazole-5, 11-quinones and ellipticme. J Org Chem 50 5451-5457... 

Gribble and Saulnier (79) have extended their ellipticine synthesis 43) to the synthesis of 9-methoxyellipticine (2) (Scheme 24). One of the key features of this approach is the regioselective nucleophilic addition to the C-4 carbonyl group of pyridine anhydride 28. The other noteworthy transformation is the conversion of keto lactam 142 to the diol 143 with methyllithium, a process that presumably involves cleavage of the initial adduct to a methyl ketone which undergoes cyclization at the C-3 position of the indolyl anion. Reduction of 143 with sodium borohydride completes the synthesis of 2, in 47% overall yield from 5-methoxyindole (139). Gribble and students 80) have also used this method to synthesize 8-methoxyellipticine (134), 9-fluoroellipticine (144), and the previously unknown 7,8,9,10-tetrafluorellipticine (145), each from the appropriate indole. 

Gribble, G. W. Recent developments in indole ring synthesis-methodology and applications. Perkin 1 2000,1045-1075. 

Practical methodologies for the synthesis of indoles , Humphrey, G. R. and Kuethe, J. T, Chem. Rev., 2006, 106, 2875 Recent developments in indole ring synthesis-methodology and applications , Gribble, G. W., J. Chem. Soc., Perkin Trans. 1, 2000, 1045. 

For a review of recent methods for indole ring synthesis, see Gribble, G.W. J. Chem. Soc., Perkin Trans. I, 2000, 1045. 

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