Carbohydrate dienes

The olefin metathesis reaction as applied to carbohydrate dienes has been reviewed, as has the use of titanocene(III) and zirconocene(III) chlorides as mild reagents for generating 1-glycosyl radicals from glycosyl halides, and converting them into glycals. ... 

Gurjar and co-workers prepared several novel carbohydrate-based spirocycles and a spirocyclic proline derivative for applications in peptide, nucleoside, and carbohydrate synthesis. Ring-closing metathesis of carbohydrate diene precursor 78 furnished the corresponding spirocycle 80 in 88% yield using a catalytic amount of 3 in dichloromethane. Reaction of proline derivative 79 under similar conditions gave the corresponding spirocyclic peptide 81 in 96% yield. 

A method for the preparation of higher sugars with an aromatic branch has been developed which involves a Michael addition - aldol condensation sequence and uses carbohydrate silylenol ethers, e.g. compound (42), as starting materials. As is demonstrated in Scheme 9, the Michael addition product was obtained as the stable silylenol ether (43). On desilylation, aldol condensation took place to give the cyclic hydroxyketone (44) which aromatised under acetylation conditions. The introduction of an aromatic branch by Diels-Alder cyclisation of a carbohydrate diene is referred to in Chapter 19. 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

The widespread occurrence and biological significance of polyoxygenated carbocycles provided the impetus to apply RCM to sugar-derived dienes. Carbohydrate carbocyclization based on a sequence of Vasella reductive opening of iodo-substituted methyl glycosides [25], and RCM of the dienes available from the resulting unsaturated aldehydes, were used to prepare a series of natural compounds (Schemes 5-7). 

Hultin P. G., Earle M. A. and Sudharshan M. Synthetic Studies with Carbohydrate-Derived Chiral Auxiliaries Tetrahedron 1997 53 14823-14870 Keywords sugar-linked dienes, sugar-linked dienophiles... 

Lopez J. C., Lukacs G. Pyranose-Derived Dienes and Conjugated Enals. Preparation and Diels-Alder Cycloaddition Reactions ACS Symp. Ser. 1992 494 33-49 Keywords carbohydrate, befera-Diels-Alder reactions, stereoselectivity... 

The GC-MS data (Figure 16.11) of the violet zone of B. carterii revealed that the unchanged diterpenes (verticillatriene, cembrene A, and cembrene C) and the nortriterpenes with carbohydrate structure originated from the pyrolyzed triterpenes (Figure 16.12) of the a- and (3-boswellic acids, named 24-norursa-3,12-diene (compound 7), 24-norursa-3,9(ll),12-triene (compound 8), 24-noroleana-3,12-diene (compound 9), and 24-noroleana-3,9(ll),12-triene (compound 10). 

Similarly, the P-phosphono-a,P-unsaturated carbonyl compounds thus synthesized have been used as dienes in a Diels-Alder approach toward the preparation of analogues of myo-inositol 1,4,5-triphos-phate,45 as well as other carbohydrate-related materials.46-48... 

A nice and convergent approach to both compounds makes use of RCM to form the 5-membered building block 71, which mimics the carbohydrate part of the nucleosides. The necessary diene precursor 69 is readily assembled via Evans aldol chemistry. RCM then affords the ring in almost quantitative yield (69->70), leaving the chiral centers and the free hydroxyl group intact. Removal of the chiral auxiliary by reductive cleavage, attachment of the base by means of jt-allylpalladium chemistry, and a final deprotection step complete these highly efficient syntheses [46]. 

Carbohydrates have found widespread use as chiral auxiliaries in asymmetric Diels-Al-der reactions156. A recent example is a study conducted by Ferreira and colleagues157 who used carbohydrate based chiral auxiliaries in the Lewis acid catalyzed Diels-Alder reactions of their acrylate esters 235 with cyclopentadiene (equation 66). Some representative results of their findings, including the ratios of products 236 and 237, have been summarized in Table 9. The formation of 236 as the main product when diethylaluminum chloride was used in dichloromethane (entry 3) was considered to be the result of an equilibrium between a bidentate and monodentate catalyst-dienophile complex. The bidentate complex would, upon attack by the diene, lead to 236, whereas the monodentate complex would afford 236 and 237 in approximately equal amounts. The reversal of selectivity on changing the solvent from dichloromethane to toluene (entry 2 vs 3) remained unexplained by the authors. 

Liebeskind and coworkers have examined the reactivity of (2//-pyran)Mo(CO)2Cp+ cations 210, which may be prepared in optically active form from carbohydrate precursors. Nucleophilic attack on cation 210 occurs at the diene terminus bonded to the ring oxygen to give jr-allyl complexes 51 (Scheme 53)85. Hydride abstraction from 51 gives the cation 54 addition of a second nucleophilie occurs regioselectively to give... 

Chloroacetamidation of unsaturated carbohydrates occurs with substrate dependent stereoselectivity [238]. For iodoac-etamidation of cyclohexene [239], a trans selectivity has been reported. Nitroac-etamidation of the conjugated dienes that were electrolyzed in acetonitrile-containing N2O4, showed a good regio-and a poor stereoselectivity [240]. Anodic... 

A review of Diels-Alder reactions of fullerenes with acyclic and cyclic dienes has been presented. The addition of substituted pyrimidine o-quinodimethanes (75) to [60]fullerenes yields novel organofullerenes (76) bearing a pyrimidine nucleus covalently attached to the Ceo cage (Scheme 26). The Diels-Alder dimerization of cyclopenta[/]phenanthrene (77) with isobenzindene (78) yields the dimer (79) in 85% yield (Scheme 27). Further evidence has been supplied to support an early reorganization of the r-network in the dimerization of 2-methoxycarbonylbuta-1,3-diene. The Lewis acid-catalysed Diels-Alder reactions of acrylate derivatives of new carbohydrate-based chiral auxiliaries with cyclohexadiene show excellent endo. exo... 

The reaction of carbohydrate-derived imines with the Danishefsky diene, ( )-1 -methoxy-3-(trimethylsilyloxy)butadiene, to form heterocycles via the open-chain adducts (for assignment, see pp 456 and 478)130. 

Enyne metathesis can also be used with highly substituted substrates. Catherine Lievre of the Univcrsite de Picardie reports (J. Org. Chem. 2004,69, 3400) that enynes such as 11, readily prepared from carbohydrate precursors, are cyclized by the second generation Grubbs catalyst 2 to the enantiomerically-pure cyclic dienes, exemplified by 12. 

J. C. Lopez and G. Lukacs, Pyranose-derived dienes and conjugated enals—preparation and Diels-Alder cycloaddition reactions, in Cycloaddition Reactions in Carbohydrate Chemistry, 1992, pp. 33-49. 

Further reactions that are highly suited to the synthesis of cyclohexane derivatives, such as cycloaddition processes, 1,3-dipolar additions, and Diels-Alder cyclizations, have been used extensively. In the latter set, carbohydrate-based dienes or dienophiles have been employed and, in addition, intramolecular processes have provided highly suitable means of synthesizing complex polycyclic systems. 

Diels-Alder reactions can be applied to the synthesis of cyclohexane rings by use of carbohydrate-derived dienophiles or dienes, and intramolecular processes allow the controlled elaboration of bicyclic systems. 

An attractive entry to the carbohydrate synthesis is provided by the cycloaddition reaction. Hetero-Diels-Alder reaction, either between an oxa-diene (a,[3-unsaturated aldehyde) and an nucleophilic dienophile, or between activated diene and carbonyl compound (usually an aldehyde), leads to dihydropyrans, which can be subsequently functionalized to sugars in the desired manner (Scheme 3). 

This section includes oxidations of alkanes and cycloalkanes, alkenes and cycloalkenes, dienes, alkynes, aromatic fluorocarbons, alcohols, phenols, ethers, aldehydes, ketones and carbohydrates, carboxylic acids, nitrogen compounds, and organoelement compounds, such as boron, phosphorus, sulfur, selenium, and iodine compounds, and steroids. 

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