Deoxygenation of carbohydrates by thiol-catalysed radical-chain redox rearrangement of the derived benzylidene acetals

Abstract

Five- or six-membered cyclic benzylidene acetals, derived from 1,2- or 1,3-diol functionality in carbohydrates, undergo an efficient thiol-catalysed radical-chain redox rearrangement resulting in deoxygenation at one of the diol termini and formation of a benzoate ester function at the other. The role of the thiol is to act as a protic polarity-reversal catalyst to promote the overall abstraction of the acetal hydrogen atom by a nucleophilic alkyl radical. The redox rearrangement is carried out in refluxing octane and/or chlorobenzene as solvent at ca. 130 degrees C and is initiated by thermal decomposition of di-tert-butyl peroxide (DTBP) or 2,2-bis(tert-butylperoxy)butane. The silanethiols (Bu(t)O)3SiSH and Pr(i)3SiSH (TIPST) are particularly efficient catalysts and the use of DTBP in conjunction with TIPST is generally the most effective and convenient combination. The reaction has been applied to the mono-deoxygenation of a variety of monosaccharides by way of 1,2-, 3,4- and 4,6-O-benzylidene pyranoses and a 5,6-O-benzylidene furanose. It has also been applied to bring about the dideoxygenation of mannose and of the disaccharide alpha,alpha-trehalose. The use of p-methoxybenzylidene acetals offers no great advantage and ethylene acetals do not undergo significant redox rearrangement under similar conditions. Functional group compatibility is good and tosylate, epoxide and ketone functions do not interfere; it is not necessary to protect free OH groups. Because of the different mechanisms of the ring-opening step (homolytic versus heterolytic), the regioselectivity of the redox rearrangement can differ usefully from that resulting from the Hanessian-Hullar (H.-H.) and Collins reactions for brominative ring opening of benzylidene acetals. When simple deoxygenation of a carbohydrate is desired, the one-pot redox rearrangement offers an advantage over H.-H./Collins-based procedures in that the reductive debromination step (which often involves the use of toxic tin hydrides) required by the latter methodology is avoided.

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

“…Since, multiple deoxygenations had been observed by Dang et al [30] on trehalose derivatives previously, we figured that we could access the rhamnose-based trisaccharide directly from a suitably derivatized manno- trisaccharide bearing the three 4,6- O- benzylidene protecting groups by a single global deoxygenation step. Accordingly, we coupled the monomeric units 2 , 3b [45] and 4 to reach the mannose-based trisaccharide 12 (Scheme 4).…”

“…Deoxygenation at the C-6 position of D-mannose derivatives bearing conventional or Crich’s modified 4,6- O -benzylidene protection [19–23] has been the principal philosophy behind the synthesis of the D-rhamnose [19–23 30,33–39] motif. This is a natural choice not only because it allows simultaneous selective blockage of the O-4 and O-6 positions but also sets up the model on which various deoxygenation protocols may be tried.…”

“…Compound 3a which is the phenyl thioglycoside analogue of 4 was also accessed similarly. Both the compounds were next converted to their rhamnoside counterparts 6 and 7 [44], respectively by treatment with di- tert -butyl peroxide (DTBP) and triisopropylsilanethiol (TIPST) under reflux in octane over 2–3 h [30] in overall 74% and 64% yields, respectively, over two steps. It is worth noting here that during column chromatographic purification after AcOH-mediated cleavage of the orthobenzoate derivative some losses were incurred due to the migration of the 2- O -benzoyl group to the O-3 position.…”

Regioselective Ring Opening of 1,3‐Dioxane‐Type Acetals in Carbohydrates

“…Dang et al have reported a thiol‐catalyzed radical‐chain redox rearrangement of benzylidene acetals, resulting in deoxygenation at one of the diol termini and formation of a benzoate ester at the other side . By using a combination of di‐ tert ‐butyl peroxide (DTBP) as a radical initiator and triisopropylsilanethiol (TIPST) as a polarity‐reversal catalyst, glucoside 159 was regioselectively converted into the 6‐deoxy‐4‐ O ‐benzoyl derivative 192 (Scheme ).…”

Thiyl radicals and induction of protein degradation

“…Hydrogen abstraction by thiyl radicals from organic substrates had been documented decades ago [48, 49], and thiols had been added to synthetic processes to facilitate hydrogen transfer via “polarity reversal catalysis” [50, 51]. Here, a primary organic radical (R 1 • ) abstracts a hydrogen from a thiol, yielding a thiyl radical, which, in turn, reacts via hydrogen abstraction with a second organic substrate, R 2 -H. The net reaction is hydrogen transfer between R 1 • and R 2 -H, catalyzed by the thiol.…”