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
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.