Synthesis of all eight L-glycopyranosyl donors using C-H activation.

The synthesis of all eight rare, but biologically important L-hexoses as the according thioglycosyl donors was achieved through a procedure involving the C-H activation of their corresponding 6-deoxy-L-hexoses. The key steps of the procedure were the silylation of the OH group at C4 followed by an intramolecular C-H activation of the methyl group in γ-position; both steps were catalyzed by iridium. The following Fleming-Tamao oxidation and acetylation gave the suitably protected L-hexoses. This is the first general method for the preparation of all eight L-hexoses as their thioglycosyl donors ready for glycosylation and the first example of an iridium-catalyzed C(sp(3))-H activation on sulfide-containing compounds.

Influence of O6 in mannosylations using benzylidene protected donors: stereoelectronic or conformational effects?

The stereoselective synthesis of ß-mannosides and the underlying reaction mechanism have been thoroughly studied, and especially the benzylidene-protected mannosides have gained a lot of attention since the corresponding mannosyl triflates often give excellent selectivity. The hypothesis for the enhanced stereoselectivity has been that the benzylidene locks the molecule in a less reactive conformation with the O6 trans to the ring oxygen (O5), which would stabilize the formed α-triflate and subsequent give ß-selectivity. In this work, the hypothesis is challenged by using the carbon analogue (C7) of the benzylidene-protected mannosyl donor, which is investigated in terms of diastereoselectivity and reactivity and by low-temperature NMR. In terms of diastereoselectivity, the C-7-analogue behaves similarly to the benzylidene-protected donor, but its low-temperature NMR reveals the formation of several reactive intermediate. One of the intermediates was found to be the ß-oxosulfonium ion. The reactivity of the donor was found to be in between that of the "torsional" disarmed and an armed donor.

ß-Mannosylation with 4,6-benzylidene protected mannosyl donors without preactivation.

Mannosylations with benzylidene protected mannosyl donors were found to be ß-selective even when no preactivation was performed. It was also found that the kinetic ß-product in some cases anomerizes fast to the thermodynamically favored α-anomer under typical reaction conditions.