Highly Stereoselective β‐Mannopyranosylation via the 1‐α‐Glycosyloxy‐isochromenylium‐4‐gold(I) Intermediates

Abstract

Abstract While the gold(I)‐catalyzed glycosylation reaction with 4,6‐ O ‐benzylidene tethered mannosyl ortho ‐alkynylbenzoates as donors falls squarely into the category of the Crich‐type β‐selective mannosylation when Ph 3 PAuOTf is used as the catalyst, in that the mannosyl α‐triflates are invoked, replacement of the − OTf in the gold(I) complex with less nucleophilic counter anions (i.e., − NTf 2 , − SbF 6 , − BF 4 , and − BAr 4 F ) leads to complete loss of β‐selectivity with the mannosyl ortho ‐alkynylbenzoate β‐donors. Nevertheless, with the α‐donors, the mannosylation reactions under the catalysis of Ph 3 PAuBAr 4 F (BAr 4 F =tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate) are especially highly β‐selective and accommodate a broad scope of substrates; these include glycosylation with mannosyl donors installed with a bulky TBS group at O3, donors bearing 4,6‐di‐ O ‐benzoyl groups, and acceptors known as sterically unmatched or hindered. For the ortho ‐alkynylbenzoate β‐donors, an anomerization and glycosylation sequence can also ensure the highly β‐selective mannosylation. The 1‐α‐mannosyloxy‐isochromenylium‐4‐gold(I) complex ( Cα ), readily generated upon activation of the α‐mannosyl ortho ‐alkynylbenzoate ( 1 α ) with Ph 3 PAuBAr 4 F at −35 °C, was well characterized by NMR spectroscopy; the occurrence of this species accounts for the high β‐selectivity in the present mannosylation.