AgNTf₂-Mediated Allylation with Allylsilanes at C3a-Position of Hexahydropyrroloindoles: Application to Total Syntheses of Amauromine Alkaloids

Abstract

A protocol for the allylation at the C3a-position of hexahydropyrroloindole using allylsilanes is developed. AgNTf proved to be an efficient activator of halopyrroloindoline substrates. This method is applicable to the introduction of various allyl groups including the reverse prenyl group. The utility of this reaction is demonstrated by total synthesis of amauromine alkaloids. Stepwise bromocyclizations of the bis-indolylmethyl diketopiperazine derivative and subsequent double reverse prenylation furnished (+)-novoamauromine and (-)-epiamauromine.

Total Synthesis of the Proposed Structure of (−)-Novofumigatamide, Isomers Thereof, and Analogues. Part I

“…First, the installation of the prenyl group on endo - 62 was achieved following the protocol described by Tokuyama and co-workers (using prenyltri iso propylsilane 31 as a nucleophile and AgNTf 2 as silver salt), which seemed to be the most appropriate methodology to accomplish this transformation in complex polycyclic substrates. 34 Although only a 31% yield was obtained in this transformation, the result is in agreement with the yields reported in the literature for such complex molecules. 34 Our own experience corroborates this fact since reverse prenylation of comparable substrates with endo relative configurations does not occur when prenyltributylstannane 30 was used as the prenyl source, in spite of the highest nucleophilicity of this reagent (part II of this article; DOI: …”

“… 34 Although only a 31% yield was obtained in this transformation, the result is in agreement with the yields reported in the literature for such complex molecules. 34 Our own experience corroborates this fact since reverse prenylation of comparable substrates with endo relative configurations does not occur when prenyltributylstannane 30 was used as the prenyl source, in spite of the highest nucleophilicity of this reagent (part II of this article; DOI: ( 33 , 34 , 57 ) The subsequent hydrolysis of the methyl ester on endo - 49 following the method described by Nicolaou et al .…”

“…Despite this negative evidence, the latter route toward endo -novofumigatamide ( endo - 11 ) was attempted ( Scheme 6 ). Endo -bromo precursor 38 or the corresponding carbocation formed after treatment with a silver salt proved to be more unstable than those of the corresponding exo diastereomer since reverse prenylation using the conditions described above by Hidetoshi and co-workers 34 led to the isolation of a highly impure fraction of the desired product endo - 39 , which was subsequently treated with TFA to afford the N -Boc-deprotected intermediate endo - 40 . The crude mixture of the previous reaction was submitted to the standard acetylation protocol, but a complex mixture of compounds was obtained, suggesting that all endo intermediates are more unstable, and likely less reactive, than the corresponding exo isomers.…”

Dearomatization Reactions of Indoles to Access 3D Indoline Structures

“…We obtained a separable mixture of the cis-and trans-double-cyclized products 69a and 69b which are, respectively, intermediates for the synthesis of (-)-epi-amauromine and (+)-novoamauromine as described by Tokuyama. 56…”

Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B

“…However, these methods require additional steps after introducing the indole segment by C–N bond formation. In this paper, we describe a novel construction of a C–N1′-linked indolylpyrroloindoline structure by AgNTf 2 -mediated one-pot amination and an indole formation sequence. Furthermore, the utility of this protocol was fully demonstrated by total synthesis of a dimeric indole alkaloid, (+)-pestalazine B ( 3 ).…”