Substituted benzyl ethers as radical stable protecting groups

4,6-O-[1-Cyano-2-(2-iodophenyl)ethylidene] Acetals. Improved Second-Generation Acetals for the Stereoselective Formation of β-d-Mannopyranosides and Regioselective Reductive Radical Fragmentation to β-d-Rhamnopyranosides. Scope and Limitations

“…7 However, neither system is really compatible with the presence of benzyl ethers and like, owing to essential hydrogen atom abstraction step from the acetal. 8 One rare exception to this rule is the high yield cleavage of a benzylidene acetal of a 1,2-diol in the presence of benzyl ethers with NBS on a significant scale and in excellent yield reported in the course of a synthesis of a cyclosporine component. 9 It should be noted, however, that the rate of hydrogen atom abstraction from the acetal position of 1,3-dioxolanes is approximately an order of magnitude faster than that from the comparable position in 1,3-dioxanes, 10 which accounts for the selectivity over benzylic hydrogen atom abstraction in this example.…”

The 4,6-O-[α-(2-(2- Iodophenyl)ethylthiocarbonyl)benzylidene] Protecting Group: Stereoselective Glycosylation, Reductive Radical Fragmentation, and Synthesis of β-d-Rhamnopyranosides and Other Deoxy Sugars

“…3,4 L-Rhamnose itself, but not L-mannose, is readily available and is therefore the obvious starting point for the β-L-rhamnopyranosides, 5 (1) Pozsgay, V. In Carbohydrates in Chemistry 7,8 Unfortunately, the reaction is not suitable for use in the presence of benzyl and allyl-type protecting groups due to the competing cleavage of these groups, which significantly reduces yields and complicates isolation. 9 This incompatibility precludes the use of the NBS cleavage in the synthesis of β-D-rhamnosides from the corresponding β-D-mannnosides as ethers are the protecting groups of choice for the 2-and 3-hydroxy groups in direct β-mannosylation. A further disadvantage of the NBS reaction is the obvious need to remove the bromide atom in a subsequent reduction.…”

“…The cleavage of 4,6- O -benzylidene-protected sugars to their 4- O -benzoyl-6-bromo-6-deoxy congeners by N -bromosuccinimide is an established reaction in carbohydrate chemistry. , Unfortunately, the reaction is not suitable for use in the presence of benzyl and allyl-type protecting groups due to the competing cleavage of these groups, which significantly reduces yields and complicates isolation . This incompatibility precludes the use of the NBS cleavage in the synthesis of β- d -rhamnosides from the corresponding β- d -mannnosides as ethers are the protecting groups of choice for the 2- and 3-hydroxy groups in direct β-mannosylation.…”

Synthesis of the ?-Rhamnopyranosides and the 6-Deoxy-?-mannoheptopyranosides

“…The well-known Hanessian-Hullar reaction involving the oxidative fragmentation of a 4,6-O-benzylidene acetal with N-bromosuccinimide to give a 4-O-benzoyl-6-bromo-6-deoxy sugar, [13][14][15][16][17][18][19] with its many applications in carbohydrate chemistry, would be well-suited for this task were it not for its incompatibility with benzyl ethers. [20] We note in passing that this restriction is lifted for the fragmentation of five-membered cyclic benzylidene acetals, [21] owing to the documented more rapid abstraction of hydrogen from 1,3-dioxolanes than from 1,3-dioxanes. [22] Robert's variant on the Hanessian-Hullar reaction, [23,24] in which a catalytic thiol and a radical initiator convert a 4,6-O-benzylidene acetal directly into a 4-O-benzoyl-6deoxy sugar, suffers from the same problem but teaches the essential lesson that the intermediate dioxanyl radical fragments with high contrathermodynamic selectivity to give the required primary radical at the 6-position, to which we will return later (Scheme 2).…”