An Efficient Synthesis of 2- and 2,6-Substituted Piperidines Using Pd-II-Catalyzed 1,3-Chirality Transfer Reaction

An efficient and general method for 2- and 2,6-substituted piperidine syntheses using Pd-II-catalyzed 1,3-chirality transfer reaction has been developed. The various N-protected zeta-amino allylic alcohols cyclize in the presence of PdCl2(CH3CN)(2) to give substituted piperidines with high stereosel...

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Bibliographic Details
Published inJournal of organic chemistry Vol. 74; no. 1; pp. 244 - 253
Main Authors Hande, Sudhir M., Kawai, Nobuyuki, Uenishi, Jun'ichi
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 02.01.2009
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
ALKENES
ASYMMETRIC-SYNTHESIS
RING-CLOSING METATHESIS
ENANTIOSELECTIVE SYNTHESIS
FORMAL SYNTHESIS
BICYCLIC LACTAMS
OXIDATIVE CYCLIZATION
CIS-AMINOPALLADATION
OXYPALLADATION
ALKALOIDS
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Summary:An efficient and general method for 2- and 2,6-substituted piperidine syntheses using Pd-II-catalyzed 1,3-chirality transfer reaction has been developed. The various N-protected zeta-amino allylic alcohols cyclize in the presence of PdCl2(CH3CN)(2) to give substituted piperidines with high stereoselectivities. The syntheses of (S)-(+)- and (R)-(-)-coniine were achieved in 3 steps from the optically pure allylic alcohols (S)-14c and (R)-14c, respectively. Although the rates of reactions were significantly accelerated in CH2Cl2, THF gave the highest stereoselectivity. PdCl2(CH3CN)(2) was found to be the best catalyst for this transformation. A plausible reaction pathway involving the formation of the Pd pi-complex directed by the chiral secondary allylic alcohol followed by syn-azapalladation, and subsequent syn-elimination of PdCl(OH) is proposed.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo801926g