Danishefsky indole synthesis

Danishefsky and coworkers developed a method for introducing the tcrt-prenyl group at the indole C-2 position based on C-3 chlorination followed by nucleophilic delivery of the ferf-prenyl group from a borane [99]. The intermediate was used in synthesis of gypsetin and breviamide E, both of which contain the 2-(tert-prenyl) substituent. 

Danishefsky and coworkers utilized a nucleophilic displacement of chloride to synthesize 2,3-disubstituted indoles and, more specifically, to realize the total synthesis of gypsetin (not shown) [34, 35]. Tryptamine derivative 68 is transformed into chloroindolenine 69 by f-butyl hypochlorite. The chloroindolenine 69 undergoes attack at C-2 by various nucleophiles, including indole, to produce, after tautomerization, the 2,3-disubstituted indoles (22-79%). The addition of a Lewis acid, Bp3-OEt2 was found to be necessary for high yields for reagents other than prenyl-9-BBN. 

Schkayantz JM, Woo JCG, SUiphaivanh P, Depew KM, Danishefsky SJ (1999) Total synthesis of gypsetin, deoxybrevianamide E, brevianamide E, and tryprostatin B novel constmctions of 2, 3-disubstituted indoles. J Am Chem Soc 121 11964-11975... 

Phalarine (244) (Scheme 44), an indole alkaloid with a novel furanobisindole structure, was isolated from blue canary grass Phalaris coerulescens by Colegate and coworkers in 1999 [93]. Recently, Danishefsky and coworkers reported the first synthesis of this indole alkaloid through a novel rearrangement from azaspiroindo-lenine (derived from 246) to precursor 245 [94, 95] (Scheme 44). 

Gallant M, Link JT, Danishefsky SJ. A Stereoselective synthesis of indole-8-N-glyco-sides An application to the synthesis of Rebeccamycin J. Qrg. Chem. 1993 58 343-349. 

---