With Organometallic Nucleophiles

Dorgan and Jackson [97] extended the work of Thorn and Gallagher [98], reaction of organozinc with glycals to give the corresponding C1 enitols (309 ^ 344), to the synthesis of C-linked glycosyl amino acids. This is exemplified by the conversion of 309 to 347 (Scheme 61).

It has been reported that the glycal 348 undergoes cyclopropanation to give 349 or 350 as the major products, depending on the choice of reagent [99]. Treatment of 348 with ethyl diazoacetate in the presence of rhodium diacetate gave a 59% yield

Scheme 61

of the ester cyclopropane 351 [100]. Hoberg and Claffey showed that treatment of the related glycal 352 under similar conditions gave 353 as the major product in 87% yield, with only trace amounts of the other three possible isomers (Scheme 62) [101].

The formed cyclopropanes have proved to be useful in several cases. For instance, 350 has been ring-expanded to the bicyclo olefin 354 by exposure to TMSOTf [102]. Compound 355 was also found to undergo ring opening to the dihalide 356, albeit in low yield [101]. In addition, 351 was converted to the Fuc-GDP analog 357, a potential transition state based inhibitor (Scheme 63) [103].

Van Boom and Sinay have collaborated to show that the reaction of acetylides with 1,2-anhydro sugars under the influence of zinc chloride catalysis gives the a isomer as the major product. Accordingly, reaction of 358 and 359 under the aforementioned conditions gave 360 in good yield. Standard protecting group manipulations then gave the C-disaccharide 361. The reaction is postulated to proceed via intermediate C [104]. Evans and coworkers have found that allylstannanes serve as good nucleophiles for oxirane opening of the 1,2-anhydro sugars under Lewis acid catalysis. Treatment of 358 with either 362 or 363 in the presence of tributyltin triflate gave good yields of the corresponding 0-allyl-C-glycosides 364 and 365 (Scheme 64) [105].

Scheme 63
Scheme 64

Gervay et al. reported reduction of the diastereomeric epoxides, giving regio-isomeric mixtures of alcohols (369 and 370) (Scheme 65) [106]. Related work (not shown) has been reported by Panza et al. [107].

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