Lewis acids hemiacetal activation

Kusumoto and coworkers have found that the treatment of hemiacetal 1 with trifluoro- or trichloroacetic anhydride 94 (1 equiv) and trimethylsilyl perchlorate (0.2 equiv) selectively provides the corresponding anomeric ester intermediate 91 [152], Hemiacetal acylation occurs even in the presence of the alcohol acceptor. With Lewis acid assistance, the glycosyl ester intermediate is displaced to provide disaccharide products in good yields. This transformation allowed the synthesis of disaccharides 98 (81%) and 99 (91%). In some cases, acetic anhydride has been used as the electrophilic activator of hemiacetal donors and the reaction with thiol acceptors yields S-linked glycosides [153,154],... 

Fluoral hydrate and hemiacetals are industrial products. They are stable liquids that are easy to handle, and they react as fluoral itself in many reactions. Thus, in the presence of Lewis acids, they react in Friedel-Crafts reactions. They also react very well with organometallics (indium and zinc derivatives) and with silyl enol ethers.Proline-catalyzed direct asymmetric aldol reaction of fluoral ethyl hemiac-etal with ketones produced jS-hydroxy-jS-trifluoromethylated ketones with good to excellent diastereo- (up to 96% de) and enantioselectivities. With imine reagents, the reaction proceeds without Lewis acid activation. The use of chiral imines affords the corresponding 8-hydroxy ketones with a 60-80% de (Figure 2.49). ° ... 

This Lewis acid accomplishes several functions. (1) Noncovalent protection of the 4-N-OH group which is accepted as fourth ligand to boron and thus possibility to take over electron density released from the 7-methoxy group in the critical case of DIMBOA (2) enhancement of the nucleophilic properties of the hemiacetal which was also shown to interact with the Lewis acid (3) promoter function for activation of the trichloroacetimidate glucosyl donor (4) equilibration conditions of any non-favoured diastereomers to the thermodynamically more stable... 

There have been a significant number of reports of the reductive removal of alcohols and ethers from hemiacetals (eq 59), hemiacyliminals (eq 60), and acetals (eqs 61 and 62) 7 These reactions employ a variety of Lewis acids that are best suited for the activation of the leaving group. In many cases the processes are both high yielding and diastereoselective. Either the ether/amide products (eqs 59, 60 and 62) or the alcohol products (eq 61) can be isolated from these reactions. 

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