Cyclopropanated glycals

Nucleosides based upon monocyclic, fused and spirocyclic oxepines have been synthesised via nitrone cycloaddition reactions <07JOC7427>, while oxepine nucleic acids were synthesised from the ring expansion of cyclopropanated glycals <07JACS8259>. 

Scheme 15. Carbohydrate-type oxepine via cyclopropanation of a glycal.

In the previous section, the cyclopropanation of a glycal to form a bicyclic intermediate was followed by a ring-expansion reaction en route to each oxepine. Presented here are routes that afford oxepines either by ring-closing metathesis (RCM) reactions or by cycloisomerization of terminal alkynes. 

Scheme 41 Synthesis a furanose-fused butyrolactone from a glycal-derived cyclopropane...

More recently, another methodology for sugar-fused butyrolactones employing glycal-derived cyclopropane precursors has been described by Chandrasekaran and co-workers (Scheme 44) [215]. In this case, hexofuranose- or hexopyranose-1,2-fused were cyclopropanated into compounds of type 181. After saponification with... 

The cycloaddition of carbenes to glycals is an effective method for the formation of cyclopropanated carbohydrates with high stereoselectivity,60... 

K. J. Henry and B. Fraser-Reid, Cyclopropanation of glycals applications to the synthesis of 2-deoxy-2-vinylglycosides, Tetrahedron Lett., 36 (1995) 8901-8904. 

Studies involving cyclopropanation of glycals with ethyl diazoacetate in the presence of catalytic rhodium acetate or copper powder have also been reported <1995TL8901, 1996TL2533, 20010L2563>. 

Murali, R, Ramana, C V, Nagarajan, N, Synthesis of 1,2-cyclopropanated sugars from glycals, J. Chem. Soc. Chem. Common., 217—218, 1995. 

The synthesis of the required compound 61 commenced with the D-glucal derivative 57 (Scheme 11.16), the cyclopropanation of which gave the (3-derivative 58 as the major compound [63]. Opening the latter gave the intermediate mercurio derivative 59, which was reduced to 60. Final mesylation at the anomeric center followed by spontaneous elimination yielded the branched-glycal 61. This compound was in turn debenzylated [62]. 

Complementing cyclopropanation reactions, the dichlorocyclopropanation of glycals has also been used as a means to introduce methyl groups at sugar C2 positions. An excellent illustration of this strategy was reported in connection with a synthesis of the C29 to C51 fragment of altohyrtin A [64]. 

Other complementary methodologies include the preparation of substituted cyclopropanes from glycals using rhodium acetate carbenoid additions [65,66]. Additionally, acid catalyzed cyclopropane opening reactions in alcoholic solutions afford the 2-C-branched-glycosides. These combined reactions were used to prepare a key intermediate in marine diterpene norrisolide synthesis from D-mannose [67]. 

Timmers, C M, Leeuwenburgh, M A, Verheijen, J C, van der Marel, G A, van Boom, J H, Rhodium(Il) catalyzed asymmetric cyclopropanation of glycals with ethyl diazoacetate, Tetrahedron Asymmetry, 7, 49-52, 1996. 

Compound 110 (obtained by reaction of D-glucal with propargylic alcohol) was subjected to cyclization with Co2(CO)g, which led to a fused tricyclic derivative 111 (O Scheme 48) [97]. [2+2] Cycloaddition of carbenes to glycals is an efficient route leading to cyclopropanated sugars with high stereoselectivity [1]. Such cyclopropanes can be transformed into a number... 

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 15 Spiro anomeric cyclopropanes from dichloro-exo-glycals.

Otherwise, the leaving group may be in the homoallylic situation either in the glycal itself or on a branch carbon atom in both situations the double-bond electrons of the glycal bond to the homoallylic carbon atom to give products with cyclopropane rings fused to furanoid or pyranoid rings, respectively. In this way compounds 76 [105] and 77 [106] are converted to cyclopropa-furanoid and -pyranoid nucleosides (Schemes 25 and 26, respectively). 

Glycals have been extensively used for the synthesis of a wide range of carbohydrate derivatives such as C-, S-/ and N-glycosides, cyclopropanated carbohydrates, and natural products. In particular, the Perrier and the azidonitration reactions, together with Danishefsky s glycal methodology (through epoxides), represent the most widely exploited applications. 

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