Spiroindolenine synthesis

A recent synthesis of spiroindolenine derivatives has employed a tandem radical-oxidation sequence [86]. Enamides 137 were subjected to a mixture of tributyl-tin hydride and DLP to produce the corresponding indolenine as a single diastereomer (confirmed from 2D NMR experiments). The mechanism is thought to involve the cyclization of the initial aryl radical to the vinyl group in a 6-endo fashion to generate an a-amidoyl radical which is oxidized by DLP to an acyU-minum ion prior to cyclization at the C-3 position of the indole ring. 

Zuleta-Prada H, Miranda LD (2009) Synthesis of spiroindolenine derivatives by a tandem radical-oxidation process. Tetrahedron Lett 50 5336-5339... 

Scheme 6.84 Asymmetric synthesis of six-membered aza-spiroindolenines by Ir-catalyzed intramolecular allylic dearomatization of indoles reported by You.

Table 6.16 Enantioselective synthesis of polycyclic indole derivatives 190 via the in situ formation and migration of spiroindolenine intermediates reported by You.

Scheme 39 Br0nsted acid-catalyzed synthesis of spiroindolenines via [l,5]-hydride shift/cyelization sequence...

In 2012, Zhao and coworkers developed an enantioselective strategy for the synthesis of spiroindolenines 94 by a Michael-hemiaminal formation/Pictet-Spengler cascade reaction [54]. The indoles 93 bearing a ketoamido group in 3-position reacted with the enals 16 in the presence of the Jprgensen-Hayashi catalyst (XXIV) to afford the corresponding spiroindolines in excellent yields and enantioselectivities but moderate diastereoselectivities (Scheme 10.33). 

The synthesis of vindorosine, a highly functionalized pen. a.cyc c Aspidosperma alkaloid is based on intramolecular indole -cyclization of the enamino ketone (A) followed by trapping of the resulting 3,3-spiroindolenine by nucleophilic enol addition at C-2. 

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