Sugar enones

In our group, we have explored the radical addition of alkyl radicals [97] and anomeric radicals [115] to sugar enones 134 having an exo double bond (see Schemes 46 and 47). Comparison of radical and anionic 1,4-addition, shown here, yields strictly equivalent stereoselectivities. The selectivity also depends on the nature of the entering radical, and reversal of stereoselectivity is observed on going from primary alkyl radicals to the larger t-butyl radical [for analogous observations see also Ref. 116]. 

A second group of thio-sugars (i. e. functionalized thiols) is attracting interest as convenient and highly reactive nucleophiles for the stereoselective functionalization of sugar enones in the formation of S -linked thiodisaccharides [64,65,66,67]. 

An n.m.r. study of methyl 4,6-O-benzylidene-ct- and - -Yi-erythro-heitrl-enopyranoside is mentioned in Chapter 20. Iron carbonyl complexes of sugar enones are described in Chapter 16. 

These studies of asymmetric Diels—Alder reactions with a,6-unsaturated sugar enonates permit the following generalizations. 

Dlels-Alder addition of sugar enone (21) and the diene generated from the cyclobutabenzene (22) led mainly to the pentltol-1-ylated derivative (23), from which lactone (24) was prepared by eplmeri-zatlon-lactonizatlon (Scheme 7) sugar derivatives were also described. ... 

Scheme 38 Synthesis of N-glycosyl derivatives, embodying sugar enone derived giycosyi groups, by Ferrier rearrangement.

Scheme 7 Liu s stereoselective synthesis of N-glycosylamines from sugar enones.

FIGURE 10.16 Synthesis of higher sugar enones hy reaction of sngar aldehydes with stabilized sugar ylids or sugar phosphonates. 

The first examples of C-disaccharides obtained applying radical C-glyco-sylation of sugar-derived exocyclic enones was reported by Giese and Witzel.138 The reaction of glucosyl bromide 148 and enone 154 afforded a mixture of stereoisomeric C- glucopyranosyl compounds from which pure 155 was obtained in 22% yield by precipitation (Scheme 52). 

Fig. 34 Approach to higher carbon sugars via the Wittig-type reaction Unusual rearrangement of the enone induced by triflate leaving group. 

In 1985, Vasella and co-workers provided an efficient synthesis of COTC ((4R,5R,6R)-2-crotonyloxymethyl-4,5,6-trihydroxycyclohex-2-enone 52), a gly-oxalase I inhibitor.Methyl a-D-mannopyranoside was transformed in three synthetic steps into the protected all cis-trihydroxycyclohex-2-enone 163 (34 %, overall) which was then transformed into COTC (52) in four steps. Thus, transformations of our "naked sugar" 32 to 137 — 138 — 163 realize a total, asymmetric synthesis of COTC. Another total synthesis of this natural compound has been reported recently by Koizumi and co-workers, as mentioned earlier. 

Optically pure 7-oxanorbom-5-en-2-yl derivatives ("naked sugars") are readily available. Substitution of their centers C(3), C(5) and C(6) can be done with high stereo- and regioselectivity in a predictable fashion. The polysubstituted 7-oxanor-boman-2-ones so-obtained can be transformed into D- or L-carbohydrate derivatives, C-nucleoside precursors or polysubstituted cyclohex-2-enones and cyclohexenols (Scheme 12). Stereoselective rearrangements of the 7-oxanorbom-2-yl systems into polyhydroxylated cyclopentyl derivatives are also possible. 

This conversion of readily available 2-furyl alcohols into unsaturated pyranosuloses proved a very effective route to racemic monosaccharides, through stepwise, selective functionalization of the enone grouping in 325. The shortest synthesis of a natural compound by following this scheme involves palladium-catalyzed hydrogenation of the aldosulose (325, R = Me) obtained from l-(2-furyl)ethanol, resulting209 in cinerulose A, the sugar component of the antibiotic cine-rubin. 

Photochemical reactions of carbohydrates have been discussed.279 Therefore, only examples applicable to the synthesis of branched sugars are briefly described here. Although non-stereoselectivity and low yield are general defects of photoreactions, photoaddition of an alcohol to the enones 125 and 122a proceeded with the same stereo- and regio-selec-tivities as ionic addition ( see Section II,4,c), and in rather better yields,... 

As with epoxides, carbanions can add in a 1,4 fashion to enones or nitrosugars. Nitromethane anion has been used [64], Dithiane anion has been successfully used in the addition to nitroolefins [65] and to enones [66], Accordingly, C-5 branched-chain glucose derivatives 47 and 48 have been prepared from nitroolefin 46 (Scheme 20) [67,68], Sugar-derived enones have been also used as acceptors in free radical reactions to trap alkyl radicals as well as anomeric radicals (see Schemes 29 and 30). 

The photochemically induced radical addition of alcohols to enones has been described by Fraser-Reid [104-109]. Here again, the sense of addition depends on the steric effects of substituents, attack anti to the C-5 substituent being preferred [108,110]. Other uses of sugar-derived enones to trap radicals have been reported [111]. Enolone 77 gave interesting results in terms of selectivity [112]. In this instance, radical addition occurs with an equatorial selectivity, whereas cuprate addition occurs with an axial selectivity [9,62]. 

Nitrone-Nitrile Oxide Cycloaddition. Unsaturated sugars have been used for the simultaneous formation of carbon-carbon and carbon-oxygen bonds in a cir-relation. One of the best ways to achieve this transformation is the cycloaddition of nitrone or nitrile oxides. The cycloaddition of nitrones with olefins has been reviewed [133]. The regioselec-tivity is almost complete when using activated double bonds, such as enone, enelactone (see compound 98, Scheme 35), or esters. 

As mentioned earlier, alkylation of sugar enolates is a method of choice to introduce two different carbon chains in a defined sequence to construct a quaternary chiral center with the desired configuration [11] (see Scheme 39). Several other methods have been proposed, such as the ring opening of spirocyclopropanes [182] or the 1,4-addition of dimethylcuprate on a p-methyl-substituted enone [183]. 

The synthesis of a -amino allylic alcohols is particularly difficult, yet this functionality is important in natural products (such as sphingosine) or as a synthon for further elaboration to amino sugars. In synthetic studies of this moiety204, the corresponding enones, with adjacent stereocenters, have been efficiently reduced to the allylic alcohol in quantitative yields and in both a regiocontrolled (1,2) and a stereocontrolled fashion (equation 53). The syn anti ratio of the product depends upon the hydride reductant and solvent being utilized. A 4 1 ratio was obtained with L-selectride and a 1 6 ratio obtained by the use of DIBAL in toluene. 

Cycloaddition to a-P-unsaturated carbonyl systems represented by different carbohydrate enones yield annulated osides. These bicyclic molecules are used for synthesis of carbocyclic systems using the stereochemical information issued from sugar... 

A few examples of 2 + 2 photocycloadditions of olefins on carbohydrate enones have been recently reported. The main results are described in the preceding review [1] on photochemical reactions of sugars. 

---