1 PIPERIDINE, ERYTHRO

Kibayashi and coworkers have used enantiometrically pure allylic silyl ethers obtained from amino acids in cycloaddition with nitrones (Eq. 8.49).71 Cyclic nitrone reacts with a chiral allyl ether to give selectively the exo and erythro isomer (de 90%). Optically active alkaloids containing a piperidine ring such as (+)-monomorine,71c (+)-coniine,71a and (-)-oncinotine71b have been prepared from the addition product. 

The chiral center on the piperidine ring retained stereochemical integrity to this point in the synthesis, and provided the basis for a relatively modest level (72 28 threo erythro) of substrate-based stereocontrol in the BH3-THF/H202 hydroboration/oxidation of the... 

ERYTHRO-DIRECTED REDUCTION OF A [J-KETO AMIDE ERYTHRO-1-(3-HYDROXY-2-METHYL-3-PHENYLPROPANOYL)PIPERIDINE (Piperidine, 1-(3-hydroxy-2-methyM-oxo-3-phenylpropyl)-, (R ,R )-( )-)... 

The reaction of methyl phenyldiazoacetate with N-Boc-piperidine (36) is a good illustration of the potential of this chemistry because it leads to the direct synthesis of f/ireo-methylphenidate (37) [27]. The most efficient rhodium car-boxylate catalyst for carrying out this transformation is Rh2(S-biDOSP)2 (2), which results in the formation of a 71 29 mixture of the readily separable threo and erythro diastereomers. The threo diastereomer 37 is produced in 52% isolated yield and 86% ee [Eq. (19)]. Other catalysts have also been explored for this reaction. Rh2(R-DOSP)4 gives only moderate stereoselectivity while Rh2(R-MEPY)4 gave the best diastereoselectivity in this reaction (94% de) [29]. 

Erythro-directed Reduction of B-Keto Amide Erythro-l-(3-hydroxy-2-methyl-3-phenylpropanoyl)piperidine... 

ERYTHRO-DIRECTED REDUCTION OF OF Ap-KETO AMIDE ERYTHRO-1 -(3-HYDROXY-2-METHYL-3-PHENYLPROPANOYL)PIPERIDINE... 

Independently, Davies et al.l also reported the same approach as descrihed above hy Winkler et al. The Rh2(S-DOSP)4-catalyzed decomposition of methyl phenyldiazoacetate (40) in the presence of WBOC-piperidine (41, 4 equivalents) in 2,3-dlmethylbutane at room temperature, followed by treatment with tri-fluoroacetic acid, resulted in the formation of a mixture of threo- and e/yZftro-methylphenidate in 49% yield. However, the Zftreo-isomer was the minor diastereomer and was formed in only 54% ee. A major improvement in enantioselectivity and diastereo-selectivity was achieved hy carrying out the reaction with the Rh2(S-biDOSP)2 catalyst. The ratio of threo to erythro isomers was improved to 2.5 1 (75% yield), respectively. The (27 ,2 7 )-Z/ireo-isomer was formed in 86% ee and isolated in 52% yield. 

Rfmiterol. 4-tHydroxy 2-piperidinylmethyl)-l,2-benzenediol, erythro-a-(3,4-dihydroxyphenyl)-2-piperidine-methanal ery thro- 3,4 -di hydroxy phenyl -2-piperidiny Icarbi -not. Ci2H.7NOj, mol wt 223.28. C 64.55%, H 7.68%, N 6.27%, O 21.50%. Prepn Sankey, Whiting, Ger. pat. 

Substituted piperidines have been obtained from A -piperideine as shown in Scheme 43. An 85 15 mixture of the erythro- and threo-torms of the carbinol (111) is formed " in the synthesis of (rf/)-anabasine (110 R = 3-pyridyl), the use of t-butyl-lithium to form 3-Iithiopyridine from 3-bromopyridine is recommended." A -Piperideine is conveniently generated in solution by the action of potassium superoxide and a crown ether on an ethereal solution of N-chloropiperidine. 

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