C‐Glycosidations of a 2‐Ketohexosyl Bromide with Electrophilic, Radical, and Nucleophilic Anomeric Carbons

Abstract

The susceptibility of acylated 2‐ketohexosyl halides to C‐homologation is demonstrated with the easily accessible tri‐O‐benzoyl‐α‐D‐arabino‐hexos‐ulosyl bromide 1 as the model compound. C‐Glycosidation with an electrophilic anomeric carbon requires prior carbonyl protection, to avoid carbonyl addition by the C‐nucleophile, for example, as the cyanohydrin. Silver triflate‐promoted reaction with the silylenol ether of acetophenone then efficiently yields the β‐phenacyl product. With thermal (AIBN) or photochemical induction, 1 smoothly generates an anomeric radical − comparatively electrophilic, due to its capto‐dative substitution − which exclusively traps hydrogen in the presence of tributyltin and electron‐deficient alkenes. With allyltributylstannanes, however, it reacts with high stereoselectivity to afford α‐C‐allyl glycosiduloses. The α‐bromoketone functionality in ulosyl bromide 1 is susceptible to Reformatsky conditions: treatment with zinc‐copper couple readily generates the 1,2‐enolate, a most simple anomeric nucleophile, which effectively adds to aldehydes to give α‐C‐hydroxyalkyl glycosiduloses or α‐C‐disaccharides (with sugar aldehydes) with a high degree of double stereoselection. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Recent Advances in the Chemical Synthesis of C-Glycosides

“…136 The Reformatsky-type reaction of 2ketohexosyl bromide 87 with diacetonegalactose-6-aldehyde 88 in the presence of copper-activated zinc followed by βelimination of benzoate using NaHCO 3 gave the corresponding α-C-glycoside 89 in 73% yield. 137…”

“… Reductive samariation of the in situ generated glycosyl iodide 84 with SmI 2 led to an organosamarium­(III) species ( B ) that reacted with aldehyde 85 to give β- C -disaccharide 86 in 66% yield. , It was reported that the 2-deoxyglycosyl phosphonium salt prepared from glycosyl halide was subjected to benzaldehyde through Wittig olefination to afford exo -glycal in moderate yield . The Reformatsky-type reaction of 2-ketohexosyl bromide 87 with diacetonegalactose-6-aldehyde 88 in the presence of copper-activated zinc followed by β-elimination of benzoate using NaHCO 3 gave the corresponding α- C -glycoside 89 in 73% yield …”

Radicals and Carbohydrates

“…The reaction may be effected even with electrophilic glycosyl radicals; α-d-arabino-hexopyranosyl-2-ulose bromide 6 reacts with methyl 2-(tributylstannylmethyl)acrylate albeit in moderate yield. 28 A study of the conformation-anomeric effect-stereoselectivity relationship in the anomeric radical reaction of pentopyranoses has been reported. Selectivity was increased by conformational restriction of the pentopyranose ring in 4 C 1 -chair 7 and completely inverted by flipping the conformation from the 4 C 1 -into the 1 C 4 -chair 8, because of the kinetic anomeric effect.…”

2-Oxoglycosyl (“Ulosyl”) and 2-Oximinoglycosyl Bromides: Versatile Donors for the Expedient Assembly of Oligosaccharides with β-d-Mannose, β-l-Rhamnose, N-Acetyl-β-d-mannosamine, and N-Acetyl-β-d-mannosaminuronic Acid Units

“…Anomeric cyanation of an acylated glycosyl halide has undoubtedly been the most practical C -extension method in terms of simplicity of reagents, workup procedures, and yields . However, exposure of ulosyl bromide 15 to Helferich cyanation conditions (mercuric cyanide in nitromethane for 1−2 d, rt) resulted in complex product mixtures; by contrast, reaction with trimethylsilyl cyanide/BF 3 ·OEt 2 was instantaneous, yet the anomeric bromine was not replaced by cyanide, but the cyanohydrin 77 , isolable in 87% yield, was formed quantitatively (TLC). , (Scheme ). Thus, of the two electrophilic carbons that may be attacked by cyanidedisplacement of bromine at C-1 or carbonyl addition at C-2the latter is strongly preferred, obviously due to the electron-withdrawing effect of the 2-carbonyl that diminishes the polarity of the C−Br bond.…”