Submit Manuscript  

Article Details

Polymer-supported (-)-8-phenylmenthyl Auxiliary as an Effective Solidphase Chiral Inductor in the Addition of Nucleophiles to N-acyliminium Ions

[ Vol. 20 , Issue. 8 ]


Oscar Forero-Doria, Leonardo S. Santos*, Fabiane M. Nachtigall and Nagula Shankaraiah   Pages 696 - 702 ( 7 )


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.

Materials and Methods: 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.


(˗)-8-Phenylmenthyl chiral auxiliary, solid-phase synthesis, asymmetric nucleophilic addition, alkaloids, MALDIMS, on-line monitoring.


Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Talca University, Talca, Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Talca University, Talca, Instituto de Innovacion Basada en Ciencia, University of Talca, Talca, Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad

Read Full-Text article