•We developed a stereoselective spiroketalization using Pd(II)-catalyst.•The mechanism explains the stability of transition state.•The reaction proceeds without activation of the allylic alcohol.We report a highly stereoselective palladium(II)-catalyzed intramolecular cyclization of 1,11-dihydroxyundec-9-en-5-one derivatives via unstable hemiacetal intermediates, in which cyclization occurs without activation of the allylic alcohol to afford spiroketal structures.

We report an asymmetric synthesis of the alkaloid fagomine, which is an inhibitor of mammalian α-glucosidase and β-galactosidase, by means of Sharpless asymmetric dihydroxylation and Pd(II)-catalyzed cyclization, starting from 3-(t-butoxylcarbonylamino)propanol.(2R,3R)-5-[N-(tert-Butoxycarbonyl)amino]-2,3-dibenzyloxypentan-1-olC24H33O5NEe = 74% (det. by 1H NMR of O-methylmandelate ester)[α]D24=+16.8 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)(4R,5R)-Ethyl-7-[N-(tert-butoxycarbonyl)amino]-4,5-dibenzyloxy-2-heptenateC28H37O6N[α]D24=+7.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5R)(4R,5R)-Ethyl-7-[N-(tert-butoxycarbonyl)amino]-4,5-dibenzyloxy-2-hepten-1-olC26H35O5N[α]D24=+14.0 (c 0.27, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5R)(2R,3R,4R)-N-tert-Butoxycarbonyl-3,4-dibenzyloxy-2-vinylpiperidineC26H33O4N[α]D24=-18.6 (c 0.85, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R)(2R,3R,4R)-(N-tert-Butoxycarbonyl-3,4-dibenzyloxy-2-piperidinyl)-methanolC25H33O5N[α]D25-45.6 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R)(2R,3R,4R)-3,4-Dibenzyloxy-1,5-imino-1,2,5-trideoxy-d-arabino hexitolC20H25O3N[α]D26=+11.6 (c 0.80, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R)Fagomine, [1,5-imino-1,2,5-trideoxy-d-arabino hexitol]C6H13O3N[α]D27=+13.4 (c 0.86, H2O)Source of chirality: asymmetric synthesis