Studies towards the construction of quaternary indolizidines by [2,3]-sigmatropic rearrangement cocatalyzed by ionic liquid

Abstract

Uma abordagem enantiosseletiva eficiente para a preparação de centros quaternários a partir da prolina 5 foi desenvolvida através do rearranjo [2,3]-sigmatrópico de Stevens, co-catalisado por líquido iônico. O rearranjo sigmatrópico foi estereoespecífico porque as migrações- [2,3] foram restritas à mesma face e a estereosseletividade surgiu na etapa preliminar da N-alquilação em 8. O método mostrou melhores rendimentos do que os descritos na literatura. O uso de hexafluorofostato de 1-butil-3-metilimidazólio mostrou uma melhora nos rendimentos do rearranjo de Stevens devido a possível estabilização e/ou ativação das espécies zuiteriônicas em solução, pelo líquido iônico. Diversas indolizidinas foram sintetizadas a partir do derivado (S)-5 da prolina quaternária.An efficient enantioselective approach for preparation of quaternary centers from proline 5 building block has been developed through [2,3]-sigmatropic Stevens rearrangement co-catalyzed by ionic liquid. The sigmatropic rearrangement was stereospecific because the [2,3]-migrations were restricted to the same face, and the stereoselectivity arose from the previous N-alkylation step in 8. The approach showed better yields than described in literature. The use of 1-butyl-3-methylimidazolium hexafluorophosphate showed an improvement in the yields of the Stevens rearrangement due to a possible stabilization and/or activatation of zwiterionic species in solution by the ionic liquid. Several indolizidine moieties were synthesized from quaternary proline derivative (S)-5.

Synthesis of Chiral Cyclopentenones

“…Enantiomerically pure 8a-substituted indolizidine 859 has been efficiently synthesized from L-proline by Duran-Lara et al (Scheme 217). 425 The key step, Pauson−Khand reaction of enyne 858, was achieved with a catalytic amount of dicobalt octacarbonyl and an ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm]•PF 6 ), as cocatalyst.…”

Synthesis of 2‐Aryl‐N‐(EWG‐methyl)‐N‐methylpyrrolidinium Salts as Precursors of Ylides Entering the [1,2] Stevens Rearrangement

“…Selected examples are included in Table 1. [59] Therefore, the formation of oily salts 3 with predominating cis isomer was unexpected and inconsistent with most of the literature data, referring to the synthesis of quaternary derivatives of 2-substituted pyrrolidines [13,[15][16][17][18][24][25][26][27][28][29][30] and other cyclic ammonium salts mentioned above. [1][2][3][4][8][9][40][41][42][43][44][45][46][47][48][49][50][51][52][53] The salts 3 a-d were formed as mixtures of diastereoisomers, with cis isomer usually predominating.…”

“…Other quaternary proline derivatives find application as reagents in organic synthesis. N-Benzylproline (S)-proline t-butyl [12][13][14][15] or methyl [12,[15][16][17][18] ester quaternary derivatives are used in the synthesis of 2-substituted (R)-proline respective esters derivatives. Corresponding ylides generated in the presence of bases undergo the asymmetric [1,2] Stevens [12,13,16] or [2,3] Sommelet-Hauser [12,[14][15][16][17][18] rearrangements.…”

“…Selected examples of prolines C,D obtained from salts A,B are presented in Scheme 1. [13,16] Moreover, the [2,3] Sommelet-Hauser rearrangement of ylides generated from proline derived N-(substituted)allyl ammonium salts is one of the steps in the synthesis of stemofoline derivatives, [19] amathaspiramide F, [20] cephalotaxine, [21] (�)-strictamine [22] and (À )-cephalezomine G. [23] What is important, in all cases rearrangement of ylides generated from proline-derived ammonium salts affords derivatives of proline esters, substituted at C-2 with benzyl, [12,13,16] allyl [12,[15][16][17][18] or aryl [12,14] group. To the best of our knowledge, there are no examples of the rearrangements of these ylides that occur via ring-enlargement.…”

“…Literature data indicate that the majority of 2-substituted pyrrolidinium salts, obtained by quaternization of N-alkyl-2substituted pyrrolidines, are formed as solid mixtures of trans and cis isomers ca 1 : 1 or with trans isomer predominating. [13,[15][16][17][18][24][25][26][27][28][29][30] As mentioned above, proline-derived ammonium salts were synthesized by quaternization of N-(substituted)benzylproline t-butyl [13,15] and methyl [15][16][17][18] esters E as mixtures of diastereoisomers, trans and cis (from 4 : 1 [16] to 100 : 1 [15] ) in the solid state. Predominating trans isomers F were isolated by recrystallization (Scheme 2).…”