Scheme 29

Scheme 30

alcohol olefins such as 170 to Wacker oxidation conditions gave a good yield of the corresponding keto-furanoside 171 and the C-glycoside 172 in a 4:1 ratio (Scheme 33) [47].

D. Wittig Reaction with Stabilized Ylides Followed by Cyclization

1. With Unprotected or Partially Protected Sugars

The situation with stabilized ylides is rather different from that with unstabilized ones because the formed product has the potential to undergo Michael addition to the corresponding C-glycoside. It is not clear what factors control the question of cyclization selectivity, but it is certain that reaction conditions and substrate structure both play an important role for the reaction in question.

It has been shown that free sugars can be converted to the free olefins when exposed to stabilized ylides (173 ^ 174, Scheme 34) [48]. This reaction was later applied by others [49] to the preparation of open-chain sugar «^-unsaturated ester derivatives. As shown in the second equation of Scheme 34, compound 175 was then efficiently converted to 177, a compound that has been previously converted to KDO.

Demailly and coworkers have shown that when Reformatsky ''type'' conditions are applied to this mode of bond formation, a preponderance of open-chain com-

159 160 161 162

Scheme 32

159 160 161 162

Scheme 32

170 171 172

Scheme 33

Scheme 35

pounds such as 179 can be isolated. These results are contrasted to those obtained when the same conditions were applied to the protected sugar derivatives, in which chelation of the lone free hydroxyl with the ester carbonyl causes a template effect favoring stereoselective cyclization to the ^-C-glycoside as shown by 181. In the unprotected case, the formed zinc bromide presumably ties up two vicinal hydroxyl groups, thereby disfavoring cyclization to the C-glycoside (Scheme 35) [50].

2. With Protected Sugars

Similar chemistry was applied to the protected glucosamine derivative 183, and the ^-C-glycoside compound 184 was produced in 50% yield (Scheme 36) [51].

Murai and coworkers used the Wittig reaction on a protected aldehyde to give the Z-olefin in 78% yield along with 15% of the ¿-olefin after acid-catalyzed depro-tection of the acetal. Exposure to base then gave the C-glycoside derivative 187, along with some dimer in 92% combined yield (Scheme 37) [52]. The thioamide-phosphonate was reacted with the manno derivative 188 and gave a good yield of C-glycoside 189 ratio of 21:78). Compound 189 was then converted into the glycine-C-glycosyl compound 190 (Scheme 37) [53].

Davis and coworkers carried out a Wittig-cyclization sequence with the partially protected 2-deoxyamino sugar 191 using an amino acid based phosphonate. Reaction of 191 with the cesium enolate 192 gave a 53% yield of epimers 193 and 194 (1:1 ratio) in which epimerization of the 2-amino group had taken place. The manno isomer 194 was then epimerized to the more stable gluco 193 derivative by simple treatment with f-BuOLi in methanol (Scheme 38) [54].

Scheme 37
Scheme 38
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