Endo-Selective Quenching of Hexahydropyrrolo[2,3-b]indole-Based N-Acyliminium Ions

Abstract

Radical decarboxylation of L-tryptophan-derived (2S,3aR,8aS)-8-arylsulfonyl-1,2-di(methoxycarbonyl)-1,2,3,3a,8,8a-hexahydro-2H-pyrrolo[2,3-b]indoles 8 and 9 in the presence of diphenyl diselenide results in the endo-selective formation of (2R,3aR,8aS)-8-arylsulfonyl-1-methoxycarbonyl-2-phenylselenyl-1,2,3,3a,8,8a-hexahydro-2H-pyrrolo[2,3-b]indoles 10 and 11. These selenides, in conjunction with Lewis acids, serves as precursors to the corresponding N-acyl iminium ions, which undergo selective endo-face quenching by allyltributylstannane, allyltrimethylsilane, propargyltrimethylsilane, and trimethylsilylcyanide. Stereochemical assignments rest on NMR data and crystallographic studies. The endo-selective nature of these reactions is interpreted in terms of minimization of allylic strain at the transition state for nucleophilic attack on the N-acyl iminum ion.

Chemistry of the Hexahydropyrrolo[2,3-b]indoles: Configuration, Conformation, Reactivity, and Applications in Synthesis

“…With an unsubstituted C2 radical and a bulky trap such as diphenyl disulfide, or diphenyl diselenide, almost complete selectivity was obtained for reaction on the endo surface, as in the formation of 109 and 110. 68,69 The stereochemistry of 109 and 110 was readily apparent from the 1 H-NMR coupling motifs, which followed the pattern previously established, and was confirmed by X-ray crystallographic analysis of 110. 68 Radical decarboxylation with trapping by methyl acrylate, 69 leading to the formation of 111, was also highly endo-selective (13:1).…”

“…68,69 The stereochemistry of 109 and 110 was readily apparent from the 1 H-NMR coupling motifs, which followed the pattern previously established, and was confirmed by X-ray crystallographic analysis of 110. 68 Radical decarboxylation with trapping by methyl acrylate, 69 leading to the formation of 111, was also highly endo-selective (13:1).…”

Nucleophilic Additions of Trimethylsilyl Cyanide to Cyclic Oxocarbenium Ions: Evidence for the Loss of Stereoselectivity at the Limits of Diffusion Control

“…A decrease in the ground-state energy of the oxocarbenium ion intermediate due to resonance stabilization from the C-1 phenyl substituent should decrease the rates of nucleophilic addition to the oxocarbenium ions 9a and 9b (k a and k b , Scheme 3) but not affect the rate of nucleophile diffusion between the two diastereotopic faces (k diffusion , Scheme 3). Highly selective additions of Me 3 SiCN to stabilized electrophiles such as N-acyliminium ions 38,39 and other benzylic oxocarbenium ions have also been observed. 40 A competition experiment demonstrated that the disparity between the diastereoselectivities obtained from the additions of allyltrimethylsilane and Me 3 SiCN to oxocarbenium ions lacking the stabilizing phenyl substituents may result from the higher relative reactivity of Me 3 SiCN.…”

“…A decrease in the ground-state energy of the oxocarbenium ion intermediate due to resonance stabilization from the C-1 phenyl substituent should decrease the rates of nucleophilic addition to the oxocarbenium ions 9a and 9b ( k a and k b , Scheme ) but not affect the rate of nucleophile diffusion between the two diastereotopic faces ( k diffusion , Scheme ). Highly selective additions of Me 3 SiCN to stabilized electrophiles such as N -acyliminium ions , and other benzylic oxocarbenium ions have also been observed

…”

“…Understanding the Reactivity of Silyl Cyanides. Because the reactivity of Me 3 SiCN appears to be highly substrate dependent, ,− specific details of our experimental approach to studying its reactivity deserve mention. We chose tetrahydropyran acetals bearing a single alkoxy substituent at the C-4 position as the electrophiles to study the reactivity of this nucleophile .…”