2858-66-4Relevant academic research and scientific papers
Enantioselective Rhodium-Catalyzed Allylation of Aliphatic Imines: Synthesis of Chiral C Aliphatic Homoallylic Amines
Li, Wei-Sian,Kuo, Ting-Shen,Hsieh, Meng-Chi,Tsai, Ming-Kang,Wu, Ping-Yu,Wu, Hsyueh-Liang
, p. 5675 - 5679 (2020/08/10)
Reported herein is a method for the efficient syntheses of optically active 1-alkyl homoallylic amines in yields up to 95%, 13.5:1 dr, and 98% ee under mild, aqueous reaction conditions, via the Rh-catalyzed asymmetric allylation of aliphatic aldimines. This method provides a streamlined synthetic platform for the preparation of indolizidine and piperidine alkaloids, thus demonstrating its usefulness.
Strategies for the Asymmetric Construction of Pelletierine and its Use in the Synthesis of Sedridine, Myrtine, and Lasubine
Zaidan, Raed K.,Evans, Paul
, p. 5354 - 5367 (2019/06/25)
Three methods for the asymmetric synthesis of both enantiomers of pelletierine 6 are reported. Bella's proline-based Mannich process gave (R)- and (S)-Cbz-protected 6 in good yields from Δ1-piperideine 14 and in reasonable enantiomeric excess (74–80 % ee). An intramolecular aza-Michael, cinchona-based, organocatalytic method is also reported. With commercially available 9-amino quinine (24a) and quinidine (24b) catalysts, Cbz-protected α,β-unsaturated ketone 23 also gave (R)- and (S)-Cbz-protected 6 in good yields and enantiomeric excess (90–99 % ee). This material was used to synthesize both optically active forms of deoxyhalofuginone (26), an analogue of febrifugine which is of interest as an anti-fibrotic agent. Finally, a resolution of racemic pelletierine using (R)- and (S)-mandelic acid 27 is reported. This scalable method gave both enantiomers of Cbz- and Boc-protected 6 in excellent enantiomeric excess (≥ 99 %). Both highly enantioenriched forms of 6 (obtained from the resolution study) were used to synthesize several alkaloids. Firstly, (–)-(S)-Cbz-protected pelletierine 17 was used to prepare naturally occurring sedridine (32) and its epimer allosedridine (8). Then the preparation of both enantiomers of the quinolizidine myrtine (33) by an olefination-intramolecular aza-Michael sequence is reported. Finally, the synthesis of the epimeric quinolizidine alkaloids, lasubine I (34) and lasubine II (35), from (+)- and (–)-Boc-protected pelletierine (29) respectively, is discussed.
Polymer-supported (-)-8-phenylmenthyl auxiliary as an effective solidphase chiral inductor in the addition of nucleophiles to N-acyliminium Ions
Forero-Doria, Oscar,Santos, Leonardo S.,Nachtigall, Fabiane M.,Shankaraiah, Nagula
, p. 696 - 702 (2018/02/27)
Aim and Objective: According to our interest in developing new methods for the construction of intricate molecules, a reliable polymer-supported (-)-8-phenylmenthyl chiral auxiliary for the addition of different nucleophiles to chiral-supported N-acyliminium precursors were developed. Material- and Method-: Merrifield resin was employed to anchor (-)-8-phenylmenthol, which was prepared by nitration of (-)-8-phenylmenthyl chloroacetate followed by reduction of nitro group and subsequent Merrifield resin coupling. Treatment of a suspension of polymer-supported chloroformate and piperidinone in the presence of Et3N resulted in attachment of the substrate onto the solid-support. Treatment of the resulting resin with LiEt3BH/MeOH afforded methoxypiperidine in 87% yield. Then, the addition of allyltrimethylsilane, TMSCN, 2-(trimethylsiloxy)propene and triisopropylsilyloxyfuran and others to the N-acyliminium ion derived from chiral 2-methoxypiperidine carbamate was studied. Results: The stereochemical outcome of the addition of nucleophiles to the supported N-acyliminium ion derived from 2-methoxypiperidine carbamate was proposed through the Si-face, affording after resin cleavage 2-substituted piperidines in 70%-84% yields and selectivities ranging from 4:1-11.1. Moreover, the key intermediates of chiral piperidines have been employed for the synthesis of simple chiral alkaloids such as (R)-pipecolic acid, (R)-pelletierine, (S)-coniine and (R,R)-myrtine. Conclusion: The proposed supported-chiral auxiliary for asymmetric approach may be expected to result not only in efficient solid-phase syntheses of a wide range of alkaloids but also in the development of useful new solid-phase methodologies, particularly for the asymmetric additions to iminium precursors. This work describes the first example of solid-phase synthesis by using supported (-)-8-phenylmenthyl as an effective chiral inductor and would be useful for the synthesis of chiral building block libraries.
Asymmetric synthesis of (+)- and (-)-deoxyfebrifugine and deoxyhalofuginone
Zaidan, Raed K.,Smullen, Shaun,Evans, Paul
supporting information, p. 6433 - 6435 (2015/11/16)
Both enantiomers of deoxyfebrifugine (4) and deoxyhalofuginone (5), analogues of the quinazolinone-containing biologically active compounds febrifugine (1) and halofuginone (3), have been prepared in a six-step reaction sequence featuring an organocatalyzed Mannich reaction as the key stereo-inducing step. The compounds were isolated as their dihydrobromide salts in 29-42% overall yield and in 74-80% enantiomeric excess.
Syntheses of (-)-pelletierine and (-)-homopipecolic acid
Chiou, Wen-Hua,Chen, Guei-Tang,Kao, Chien-Lun,Gao, Yu-Kai
supporting information; experimental part, p. 2518 - 2520 (2012/04/23)
Enantiomeric syntheses of (-)-homopipecolic acid and (-)-pelletierine have been achieved by chiral resolution of tropanol followed by Baeyer-Villiger oxidation. The methodology provides a practical route for the synthesis of optically pure piperidines. The Royal Society of Chemistry 2012.
Biomimetic organocatalytic asymmetric synthesis of 2-substituted piperidine-type alkaloids and their analogues
Monaco, Mattia R.,Renzi, Polyssena,Scarpino Schietroma, Daniele M.,Bella, Marco
supporting information; experimental part, p. 4546 - 4549 (2011/10/31)
Natural substances such as pelletierine and its analogues have been prepared in up to 97% ee and good yield by a protective-group-free, biomimetic approach. Usage of benzonitrile or acetonitrile as solvents effectively prevents product racemization.
Improved protocol for asymmetric, intramolecular heteroatom Michael addition using organocatalysis: Enantioselective syntheses of homoproline, pelletierine, and homopipecolic acid
Carlson, Erik C.,Rathbone, Lauren K.,Yang, Hua,Collett, Nathan D.,Carter, Rich G.
, p. 5155 - 5158 (2008/09/21)
(Chemical Equation Presented) An improved protocol for the construction of enantioenriched pyrrolidine, indoline, and piperidine rings using an organocatalyzed, intramolecular heteroatom Michael addition is described. Application to the enantioselective synthesis of homoproline, homopipecolic acid, and pelletierine has been accomplished.
A new asymmetric entry to 2-substituted piperidines. A concise synthesis of (+)-coniine, (-)-pelletierine, (+)-δ-coniceine, and (+)-epidihydropinidine
Takahata, Hiroki,Kubota, Minoru,Takahashi, Seiki,Momose, Takefumi
, p. 3047 - 3054 (2007/10/03)
A new asymmetric route to 2-substituted piperidines involving the Sharpless asymmetric dihydroxylation (AD) of 5-hexenylazide 1 and an intramolecular aminocyclization as crucial steps and its application to the asymmetric synthesis of four piperidine alkaloids, (+)-coniine 2, (-)-pelletierine 3, (+)-δ-coniceine 4, aND (+)-epidihydropinidine 5 is presented.
Synthesis of enantiomeric β-amino ketones via 1,3-dipolar cycloaddition and chromatographic resolution
Louis, Chantal,Mill, Sibel,Mancuso, Vincent,Hootele, Claude
, p. 1347 - 1350 (2007/10/02)
The cycloaddition reactions of 3,4,5,6-tetrahydropyridine 1-oxide 1 with the homochiral alkynyl sulfoxides 6a-e proceed in high yield to afford, with low asymmetric induction, mixtures of diastereomeric isoxazolines that are readily separated by column chromatography.The resolved isoxazolines can be subsequently converted, by hydrogenolysis, to enantiomeric β-amino ketones.
