Synthesis of (R)-(−)-1-Piperidino-3,3-dimethylbutan-2-ol:  Application in the Molar Scale Asymmetric Ethylation of trans-Crotonaldehyde

A simple three-step preparation of (R)-(−)-1-piperidino-3,3-dimethylbutan-2-ol (amino alcohol catalyst for the Noyori asymmetric alkylation of aldehydes) based on a classical resolution of the racemate is described. Use of this catalyst in a detailed study of the asymmetric ethylation of trans-crotonaldehyde producing trans-(S)-4-hexen-3-ol is also described. The impact of catalyst enantiopurity and loading on the product enantiopurity and yield is studied, which led to optimized conditions for reaction scale-up.