Sugar aldehydes Wittig reaction

The second synthesis of 654 and 655 makes use350,351 of the Wittig reaction. The (methylthio)methyl ether 656 is converted into the chloromethyl ether 657, which reacts with triphenylphosphine to yield a crystalline phosphonium salt (658). Reaction of 658 with phenyllithium gives a phosphorane, treatment of which with acryl-aldehyde leads to ethers 654 and 655 in —50% yield. Pure trtms-diene 654 was obtained352 in a reversed way consisting in preparation of a sugar ether acrylaldehyde (660) by replacement of the p-tolylsulfonyl group in 659, followed by reaction of 660 with methylenetriphenyl-phosphorane. 

Chiral aldehydes such as N-protected a-aminoaldehydes and a-alkoxyalde-hydes as well as chiral butadienes derived from sugars by a Wittig reaction have also been used in the hetero Diels-Alder reactions successfully with the inducing stereogenic centers remaining in the obtained cycloadducts. 

Wittig reactions of a-alkoxy aldehydes and sugar lactols, such as pentose ketal (48), with stabilised ylides usually proceed with low ( )-selectivity. However, Harcken and Martin have discovered that treatment of these aldehydes with (methoxycarbonylmethylene)tributyl phosphorane (49) and a catalytic quantity of benzoic acid produces the heptenonate (50) with a E Z ratio of 95 5. The stereoselectivity of the reactions between aldehydes and spirophosphoranes (51) has been examined and the phosphoranes found to favour the formation of (Z)-a,p-unsaturated aldehydes and amides. ... 

While the use of allylic ethers provides convenient routes to the formation of ketones and aldehydes, the Wittig reaction, as illustrated in Figure 7.14, may be utilized in the formation of ester functionalized C-glycosides. This approach is either a or (S selective and works with benzylated, acetylated and unprotected sugars. A particular advantage is that reaction intermediates can be intercepted and utilized. Moreover, glycosidic activation is not required for this type of reaction. 

As shown above, many of the methods that are available to form carbon-carbon bonds rely on the reaction of a carbanion with a suitable electrophile. Keto-sugars are readily available by simple oxidation of hydroxyl groups. Thus, the reaction of carbohydrate-derived ketones or aldehydes with carbanions has been extensively explored. However, keto groups are suitable substrates in olefinations, such as Wittig reactions, leading to versatile intermediates for the construction of complex structures. This section will detail some application of keto-sugars in total syntheses along these two main lines. 

Sun and Fraser-Reid reported a synthesis of methyl (-)-nonactate starting from D-ribose, C-4 of which (sugar numbering) provided C-6 (nonactin numbering) of the tetrahydrofuran ring (Scheme 36) (64). The ribose-derived aldehyde 260, was converted to the ketone 261 by a Wittig reaction followed by hydrolysis of the enol ether. Raney nickel catalysed hydrogenation of the ketone 261... 

A number of analogues of showdomycin have been prepared from aldehyde sugars by the Wittig reaction illustrated for xylodialdose derivatives in Scheme 2. ... 

An interesting approach to carbobicyclic polyhydroxylated compounds was proposed by Jarosz.43 It was based on a Lewis acid transformation of sugar allyltins 82 into dieno-aldehydes 83 with the fi-geometry across the internal double bond exclusively. The Wittig-type reaction of 83 afforded a triene, which underwent cyclization under high pressure, providing derivatives of bicyclo[4.3.0]nonane 84. Alternatively, dienoaldehyde 83 was converted into the phosphonate 85, which afforded the bicyclo[4.4.0]-decene derivatives (86) upon reaction with an aldehyde and simultaneous cyclization of the resulting triene.43 (Fig. 29). 

The anomeric appendage of imino sugars has been exploited to generate mimics of glycoconjugates. An example is reported in Fig. 42 for the synthesis of nojirimycinyl C-(L)-serine 109,73 in which the ozonolysis of the allylic appendage generates the aldehydes 106, on which the aminoacidic moiety was inserted by Wittig-Horner reaction. 

The C-glycosylation procedures generally exploit the electrophilic character of the anomeric carbon of the sugar. The new C-C bond can be formed by reaction of the aldehydic function of the sugar with an organometallic or a Wittig... 

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