An Asymmetric Synthesis of 2-Substituted Piperidines through Ozonolysis of Cyclopentenes and Reductive Aminocyclization

Kawaguchi, Mamoru; Hayashi, Osarnu; SAKAI, Noriyuki; Hamada, Masayuki; Yamamoto, Yukio; Oda, Jun’ichi

doi:10.1080/00021369.1986.10867869

Cited by 4 publications

(4 citation statements)

References 3 publications

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“…Conversion of salt to free amine gave 6.1 g (20% of theoretical yield) product having [␣] D ϭ ϩ3.9. This rotation is the same as reported by Kawaguchi et al (1986) for (S)-(ϩ)-2-methylpiperidine. Therefore, the absolute conÞgu-ration of our methylpiperidine was (S)-.…”

Section: Methodssupporting

confidence: 75%

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Optically Active Arthropod Repellents for Use Against Disease Vectors

Klun

Gupta

2000

J Med Entomol

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Optically inactive 1-[3-cyclohexen-1-ylcarbonyl] piperidine and 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine are repellents against blood-feeding arthropods. Pure stereoisomers of these compounds were synthesized and characterized for use in bioassays. Initial laboratory tests with the malaria vector Anopheles stephensi Liston showed that this species was repelled differentially by the stereoisomers of 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine. Two stereoisomers were twice as repellent as the other stereoisomers. These results indicate that stereoisomerism influences repellent efficacy in this class of compounds.

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Section: Methodssupporting

confidence: 75%

“…Optical rotation for the product was [␣] D ϭ Ϫ3.9. This rotation was the same as reported by Kawaguchi et al (1986) for 2-methylpiperidine having an absolute conÞguration of (R)-. Therefore, the conÞguration of our product was (R)-.…”

Section: Methodssupporting

confidence: 67%

Optically Active Arthropod Repellents for Use Against Disease Vectors

Klun

Gupta

2000

J Med Entomol

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“…The Corey method that uses NaCN and MnO 2 [19,20], oxidation using Ag 2 O [21][22][23], use of NaClO 2 -NaH 2 PO 4 -trimethylethylene [20,[24][25][26], and oxidation by Ru compounds [27] and CAN-t-BuOOH [28] must be mentioned among several well-recommended approaches.…”

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confidence: 99%

Synthesis of 10-Carbonyl and 10-Carboxylic Derivatives of para-Mentha-1,8-Diene-5,6-Diol

et al. 2015

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The synthesis of 10-carbonyl and 10-carboxylic derivatives of para-mentha-1,8-diene-5,6-diol (1) that exhibited high anti-Parkinson's activity was described. The synthesis of these compounds was an important programmatic component in a study of the metabolism of 1.Our previous discovery [1, 2] that (4S,5R,6R)-para-mentha-1,8-diene-5,6-diol (1) exhibited high anti-Parkinson's activity stimulated further studies of it. The absolute configuration of 1 affected its anti-Parkinson's activity [1]. It was important to include all functional groups (double bonds and hydroxyls) in the molecule [3]. Metabolism studies represent a key phase of pharmacokinetic investigations. As a rule, mass spectra of monoterpenoids are very difficult to relate reliably to their structures without mass spectrometric data of the pure compounds, which makes it necessary to synthesize them.According to literature data on the metabolism of para-menthane monoterpenoids [4][5][6][7], the formation of products from methyl hydroxylation and further oxidation to carbonyl compounds were expected. We synthesized earlier hydroxyderivatives 2 [8] and 3 [9]. The methods for synthesizing these and other similar alcohols were recently reviewed by us in detail [10].The goal of the present work was to synthesize 10-carbonyl and 10-carboxylic derivatives of 1. The first task was to prepare 2-[(1S,5R,6R)-5,6-dihydroxy-4-methylcyclohex-3-enyl]acrylaldehyde (3). The simplest approach seemed to involve oxidation of triol 2. However, its reaction with MnO 2 formed reaction mixtures with <30% of target aldehyde 3 according to PMR and GC-MS data.We used bromide 4 as a key intermediate in the synthesis of triol 2 [8]. Also, bromides are known to be capable of transforming into the corresponding aldehydes via alkylation of nitro compounds followed by Nef hydrolysis [11,12] or Kornblum oxidation by 14]. However, instead of the expected reaction with EtNO 2 , 4 underwent an intramolecular heterocyclization to form bicyclic product 5 in quantitative yield (Scheme 1). We prepared previously 5 in 15% yield via the reaction of 4 with n-BuLi [8]. Thus, the newly found version for performing the intramolecular cyclization turned out to be much more effective. Kornblum oxidation of 5 via reaction with DMSO in CCl 4 formed a complicated product mixture with total contents of identified 3 and 5 of <7%. 1) N. N. VorozhtsovOH OH 1 3 5 9 7 OH OH OH OH OH O 1 2 3

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“…piperidines has been also performed through ozonolysis of prochiral cyclopentenes and subsequent aminocyclization. 3 ) In the present report, we describe a further application of this methodology to the preparation of piperazines, dioxothiomorpholines and aza- 8 X: 5 SCHEME 1. Syntheses of Piperazines, Dioxothiomorpholines and Thiomorpholines.…”

mentioning

confidence: 99%