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

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 Ph3PAuOTf 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., −NTf2, −SbF6, −BF4, and −BAr4F) 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 Ph3PAuBAr4F (BAr4F=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 Ph3PAuBAr4F at −35 °C, was well characterized by NMR spectroscopy; the occurrence of this species accounts for the high β-selectivity in the present mannosylation.