A Carbohydrate-Based Julia–Kocienski Reagent for Syntheses of Chain-Extended and C-Linked Saccharides

Abstract

The carbohydrate-derived Julia-Kocienski reagent 2-{[(3aS,4S,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro [3,4-d] [1,3]dioxol-4-yl]methylsulfonyl}-1,3-benzothiazole (6) was prepared from D-ribose and investigated in the eponymous olefination. The base-promoted generation of the Julia anion induced a rearrangement to the corresponding L-lyxose epimer 2- 3-benzothiazole (12), which reacted readily with aldehydes and with a gluconolactone. The latter reaction furnished an exo-glycal-linked C-diglycoside.As part of ongoing investigations into new methodologies for the incorporation of C-linked carbohydrate units into saccharides and glycopeptides, 1 our attention turned to the Julia-Kocienski olefination 2 as a promising and underdeveloped tool in the synthesis of glycoconjugates and longchain carbohydrates. As carbohydrate units integrated into the backbone of larger structures are a common feature in natural products, they present themselves as important synthetic targets. 3 The Kocienski-Lythgoe modifications of the Julia olefination have already been used to great effect in the preparation of such compounds, however, to date research has focused on using the carbohydrate fragment as the carbonyl-containing substrate rather than the reagent itself. Furthermore, such protocols are most commonly applied to the preparation of simple exo-glycals from carbohydrate lactones. 4 These exo-glycals are typically the products of sterically undemanding electron-poor reagents and simple carbonyl methyleneations. 5 The Julia-Kocienski reaction has thereby demonstrated its synthetic compatibility with carbohydrate chemistry.With the hope of utilizing the innate advantages of this versatile methodology, we envisaged the benzothiazole-2-sulfone 6 as a promising candidate for effecting the coupling of a furanose with carbonyl compounds, being, to our knowledge, the first example of a carbohydrate-based Julia reagent. 6 However, the formation of stabilized anions on carbohydrate systems is known to be problematic due to the invariable presence of a leaving group in the β-position. In this case, however, the leaving anion is tethered through the ring system, offering production of the carbanion through conjugate re-addition and subsequent ring closure. A similar approach has been investigated by Secrist et al., who prepared the corresponding triphenylphosphosphonium salt 1 to use its ylide in the Wittig olefination. 7 The ylide reacted readily with aromatic and aliphatic aldehydes to form the chain-extended carbohydrate. Interestingly, in all cases the product had undergone a rearrangement to the L-lyxose epimer 2 via concomitant epimerization of the C4 position through the ring-opened β-elimination product 3 7 (Scheme 1). Furthermore, when the ylide was presented with various ketones it was observed to undergo a self-condensation reaction with the intermediate aldehyde 4 to afford the alkene-linked decafuranose derivative 5. The fact that the self-condensed product contains solely L-lyxose and that no self-condensation is observed w...

Synthesis of C-Glucoside Analogues of Naturally Occurring Phenyl­ethanoid O-Glucosides

“…A furanoside-based sulfone building block was reported previously. 8 The sulfone building block 6 was prepared from ester 8, which, in turn, was prepared in two steps by a known method using tetra-O-benzyl-D-gluconolactone as starting material. 9 Reduction of the ester functionality followed by Mitsunobu reaction of alcohol 9 and 2-mercapto benzothiazole provided sulfide 10.…”