Synthesis of highly substituted 2-spiropiperidines

2-Spiropiperidines are a highly desirable, yet under represented structure in drug discovery. 2-Spiropiperidines were synthesised in either a two-pot or one-pot reaction. In the two-pot reaction, the addition of a Weiler dianion to N -Boc imines, followed by deprotection and in situ condensation with a cyclic ketone generated functionalised 2-spiropiperidines in good to excellent yields. In the one-pot reaction, the addition of Chan's diene to N -Boc imines under Maitland-Japp conditions, followed by the addition of sodium bicarbonate and a cyclic ketone formed functionalised 2-spiropiperidines in moderate to good yields. Highly substituted novel 2-spiropiperidines, which are scaffolds suitable for drug discovery or natural products synthesis, were synthesized in a simple one-pot or two-pot procedure.