This Account focuses mainly on our recent endeavors in the area of multicomponent reactions (MCRs) involving zwitterionic species generated by the addition of isocyanides and nucleophilic carbenes such as dimethoxycarbene and N-heterocyclic carbenes to activated alkynes. The strategy employed encompasses the interception of 1:1 zwitterionic species, generated in situ with a wide range of electrophiles. The new MCRs developed offer an efficient and convenient entry into several heterocycles of biological and synthetic importance.

The effect of 4,6-O-benzylidene acetals, 4,6-O-phenylboronate esters, and 4,6-O-polystyrylboronate esters on the stereoselectivity of couplings to galacto-, gluco-, and mannopyranosyl thioglycosides, otherwise protected with benzyl ethers, has been investigated by the benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride (BSP), diphenyl sulfoxide/trifluoromethanesulfonic anhydride (Ph(2)SO), and N-iodosuccinimide/trimethylsilyl trifluoromethanesulfonate (NIS/TMSOTf) methods. The BSP and Ph(2)SO methods give comparable results in all three systems whereas the NIS method affords significantly different stereoselectivities in both the gluco and manno, but not the galacto series. The benzylidene acetal and boronate esters influence the stereochemistry in a similar manner in the beta-selective manno series and the alpha-selective galacto series but show significant differences with the glucose donors. The differences between the glucose, galactose, and mannose series reflect the established differences in reactivity and, especially for mannose, those in the anomeric effect and are best interpreted in terms of changes in the relative energetics between the alpha- and beta-covalent triflate intermediates and the various contact ion pairs with which they are necessarily in equilibrium.

[reaction: see text] The 4-OH groups of both alpha- and beta-methyl glycosides of N-acetylglucosamine, protected with an oxazolidinone spanning the nitrogen and O-3, and bearing benzyl or silyl protection on O-6, show excellent reactivity as acceptors in couplings to a range of glycosyl donors. The enhanced reactivity of these acceptors is attributed in part to the tied back nature of the oxazolidinone, which reduces hindrance around the nucleophilic oxygen. The N-acetyloxazolidinone function also reduces the tendency seen in simple N-acetylglucosamines toward amide glycosylation, and removes the possibility of problematic hydrogen bonding networks. In the beta-, but not the alpha-, series selective hydrolysis of the N-acetyloxazolidinone directly to the N-acetylglucosamine was possible with barium hydroxide, a feature attributed to chelate formation between the acetamide carbonyl group and the glycosidic oxygen in the beta-series.