Highly Diastereoselective Synthesis of Medium-Sized Carbocycle-Fused Piperidines via Sequential Hydride Shift Triggered Double C(sp3)-H Bond Functionalization.

Herein we report a diastereoselective synthesis of medium-sized carbocycle-fused piperidines via [1,n (n = 6, 7)]-[1,5]-sequential hydride shift triggered double C(sp3)-H bond functionalization. When cinnamylidene malonates having N,N-dibenzyl propylamine moiety were treated with 5 mol % of Yb(OTf)3, a [1,6]-[1,5]-sequential hydride shift/cyclization process proceeded to afford seven-membered carbocycle-fused piperidines with excellent diastereoselectivities. This sequential system was applicable to the synthesis of eight-membered carbocycle-fused piperidines by an unprecedented [1,7]-[1,5]-sequential hydride shift/cyclization process.