Quick Access to Optically Pure 2-(1-Hydroxybenzyl)piperidine and Pyrrolidine

Abstract

Optically pure 2-(1-hydroxybenzyl)piperidine and pyrrolidine were prepared by reaction of oxygenated 2-(p-tolylsulfinyl)benzyl carbanions with the appropriate chlorinated N-sulfinylimines followed by subsequent elimination of the sulfinyl groups. The main reaction is a tandem process involving nucleophilic addition of the sulfinylbenzyl carbanion to the C=N bond followed by intramolecular elimination of the chlorine by the resulting amide. The matched pair of the reagents (exhibiting the same configuration at their respective sulfinyl moieties) evolves with a complete control of the stereoselectivity at the two newly created chiral carbons.

piperidines - pyrrolidines - benzyl carbanion - N-sulfinylimines - tandem A_N/S_Ni reaction

References

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<A NAME="RP10705SS-17">17</A>

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<A NAME="RP10705SS-20">20</A>

Compounds with these configurations had been shown to be the consonant pair in other previously studied reactions (see reference 16).

<A NAME="RP10705SS-21">21</A>

The authors have deposited atomic coordinates for 7 at the Cambridge Crystallographic Data Centre (deposition number CCDC 277170). The coordinates can be obtained on request from the Director Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.

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<A NAME="RP10705SS-23B">23b</A>

See also reference 14a.

<A NAME="RP10705SS-23C">23c</A>

For pyrrodiline 1, see:reference 10.