- Modified fry cyanation of a chiral pyridinium salt: Asymmetric syntheses of (-)-coniine and (-)-solenopsin A
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The synthesis of chiral 2-cyano-Δ4-tetrahydropyridine 5 was carried out in 85 % yield through a modified two-step Fry reductive cyanation of pyridinium salt (+)-3c that used lithium triethylborohydride as the hydride donor. An alkylation-reduction sequence provided 2-alkyl-substituted tetrahydropyridines (+)-10a and (+)-10b in 72-75 % yield after chromatographic purification. This protocol has been applied to the asymmetric syntheses of piperidine alkaloids (-)-coniine and (-)-solenopsin A. The two-step reductive cyanation of chiral pyridinium salt (+)-3c afforded α-amino nitrile 5 in 85 % yield, which underwent an alkylation-reduction sequence followed by removal of the chiral moiety to yield the hemlock alkaloid (-)-coniine as its mandelate salt (>99:1 er). This reaction sequence was also used for the synthesis of the trans-2,6-disubstituted piperidine alkaloid (-)-solenopsin A. Copyright
- Vu, Van Ha,Jouanno, Laurie-Anne,Cheignon, Adele,Roisnel, Thierry,Dorcet, Vincent,Sinbandhit, Sourisak,Hurvois, Jean-Pierre
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p. 5464 - 5474
(2013/09/02)
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- A direct and general method for the reductive alkylation of tertiary lactams/amides: Application to the step economical synthesis of alkaloid (-)-morusimic acid D
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Full details of the direct and general method for the reductive alkylation of tertiary lactams and amides to give tertiary sec-alkylamines are presented. This one-pot method consists of in situ activation of a lactam or an amide with Tf2O/DTBMP, addition of a Grignard reagent, and reduction of the resulting iminium intermediates. Alkyl, benzyl, and aryl Grignard reagents and several reductants or reducing conditions (LiAlH4, NaBH4, Hantzsch ester, Bu3SnH, Pd(OH)2/C, H2) could be used effectively. Reductive alkylations of substituted lactams demonstrated good to excellent 1,3-asymmetric induction to provide the corresponding di- or trisubstituted pyrrolidine/piperidine in 6:1 (LiAlH4), 11:1 (Et 3SiH), and 20:1 (catalytic hydrogenation) cis/trans diastereoselectivity, respectively. The versatility of this methodology was demonstrated by its application in the concise stereoselective synthesis of piperidine alkaloid (-)-morusimic acid.
- Xiao, Kai-Jiong,Wang, Yu,Huang, Ying-Hong,Wang, Xiao-Gang,Huang, Pei-Qiang
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p. 8305 - 8311
(2013/09/24)
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- Versatile one-pot reductive alkylation of lactams/amides via amide activation: Application to the concise syntheses of bioactive alkaloids (±)-bgugaine, (±)-coniine, (+)-preussin, and (-)-cassine
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Direct entry: One-pot reductive alkylation of lactams/amides with Grignard reagents has been realized via lactam/amide activation with Tf2O. This method opens a direct entry to α-alkylated amines. The versatility of the method is illustrated by the concise syntheses of bioactive alkaloids (±)-bgugaine, (±)-coniine, (+)-preussin, and (?)-cassine.
- Xiao, Kai-Jiong,Wang, Yu,Ye, Ke-Yin,Huang, Pei-Qiang
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supporting information; experimental part
p. 12792 - 12796
(2011/02/22)
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- Application of Electro-Oxidative α-Cyanation of Aza-Rings to the Synthesis of Gephyrotoxin 223AB
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Six and five-membered cyclic α-cyanoamines have been prepared efficiently from N-benzylpiperidine and N-benzylpyrrolidine.These α-cyanoamines were successfully used in the synthesis of gephyrotoxin 223AB.
- Yang, Teng-Kuei,Yeh, Shun-Tsai,Lay, Yen-Yuan
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p. 1711 - 1716
(2007/10/02)
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- Efficient and Convenient Method for Synthesis of Solenopsin A and Its Analogues Using 1-Benzyl-2,6-dicyanopiperidine
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An efficient synthetic sequence proposed here provides a new method for preparation of not only solenopsin A, i.e., trans-2-methyl-6-undecylpiperidine, but also coniine, i.e., 2-propylpiperidine, and other 2,6-dialkylpiperidine alkaloids: A reaction of 1-benzyl-2,6-dicyanopiperidine (1) with alkyl halides selectively gives 2-alkyl- and 2,6-dialkyl-1-benzyl-2,6-dicyanopiperidines (2 and 3), decyanation of which affords respectively 2-alkyl- and 2,6-dialkyl-1-benzylpiperidines (4 and 5) in high yields.
- Takahashi, Kazumasa,Kurita, Hideki,Ogura, Katsuyuki,Iida, Hirotada
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p. 4368 - 4371
(2007/10/02)
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