Glycals cycloadditions

Oxathiins derived from the cyclic diacylthione (60) and glycals by a cycloaddition reaction yield glycosides on desulfurization, offering an alternative approach to glycosyl transfer <96AG(E)777>. 

When irradiated with light, azidodicarboxylates react with glycals as dienophiles to give Diels-Alder adducts via formal [4 + 2] cycloadditions [334], Upon treatment of... 

Table 5.8 summarizes the glycals that had been converted into 2-aminoglycosides so far. In general, photolytic ds/trans isomerization of trans-azodicarboxylates is necessary to accomplish good yields of the initial cycloadducts [335-337]. However, bis-trichloroethyl azodicarboxylate also reacts under thermal conditions and also gives a more reactive cycloaddition product [338,339]. 

Yet another hetero-dien for cycloaddition reactions of glycals that had been used for the preparation of 2-deoxyglycosides is 2,4-dioxo-3-thioxo-pentane, generated in situ from 3-thiophthalimido-pentane-2,4-dion. The cycloaddition occurs with high... 

This limited methodology must be compared to a new approach for the synthesis of 2-amino 2-deoxycarbohydrates based on the cycloaddition of azodicarboxylates on glycals. This 4 + 2 cycloaddition is initiated by irradiation at 350 nm and seems highly stereoselective. After hydrolysis and reduction, compounds like 43 (Z = Ac) are obtained in good yields [45]. 

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

Dihydrooxadiazines can be made in related fashion and they too offer novel access to important products. For example, the (9-silylated D-glucal 70, irradiated at 350 nm in cyclohexane with dibenzyl azodicarboxylate, affords adduct 74 in 71% yield,74 and this with an acid catalyst can be used as a glycosylating agent to make /J-linked 2-amino-2-deoxy-D-glucosides.75 This chemistry also is applicable to furanoid glycals.74 Scheme 6 outlines the regio- and stereoselectivities of these cycloaddition reactions and their applications in synthetically useful processes. 

A novel reverse electron demand hetero-cycloaddition of glycals 538 with diacylthione 537 has been reported, an example of which is shown in Equation (37) giving products 539 and 540 <1998JOC6673>. It is suggested that this [4+2] cycloaddition may occur in stepwise fashion. 

Amino glycosides.1 Furanoid or pyranoid glycals (2) when irradiated with this azodicarboxylate undergo a [4 + 2]cycloaddition to form a dihydrooxadiazine (3) in 70-80% yield. The adducts on treatment with methanol (TsOH) open with inversion at C, to give hydrazines (4), which furnish 2-amino glycosides (5) on hydrogenolysis and deprotection. 

The [4 + 2] cycloaddition reaction of dibenzyl azodicarboxylate and glycals allows the stereoselective introduction of an amino group at the C-2 of a carbohydrate, the key step in the reaction is shown in Equation (1) <89JA2295>. The nature of the products was determined by x-ray crystallography NMR and IR data proved insufficient as the two possible products from [4 4- 2] and [2 + 2] addition are so similar. X-ray analysis confirmed that the reaction of diethyl azodicarboxylate with cyclopropylfuran gives compound (4), by a [4 4- 2] addition, in 94% yield. Further comparison of the NMR and IR data for all the adducts with spectral data of compound (4) confirmed that [4 + 2] adducts were formed consistently. 

The cycloaddition of glycals (21a-d) and dibenzylazidocarboxylate gives compounds (22a-d) in yields greater than 70% (Scheme 5) <87JA285>. These [4 + 2] adducts are useful intermediates in the preparation of 2-amino-2-deoxy carbohydrates <89JA2295>. The cycloaddition is stereospecific and is controlled by the stereochemistry at the C-3 position stereochemistry has been assigned by nuclear Overhauser enhancement (NOE) studies. 

The double bond in glycals such as (35) contribute two atoms in a photochemical [4 + 2] cycloaddition reaction with dibenzyl azodicarboxylate (Equation (9)). The adducts so formed are useful intermediates in the preparation of carbohydrates with an amino function at the C-2 position... 

A similar cycloaddition reaction occurs between the glycal (36) and the substituted selenium diimide (37) (Equation (10)) <83ZORl622>. 

A practical use of this process has been detailed. Glycal (308) reacted with dibenzoyl azodicarboxylate to deliver the cycloadduct (119) (50%). The elaborated glycal (309) also underwent cycloaddition to give cycloadduct (310) (84%) <89JA5810>. 

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>. 

Diazetidines and/or oxadiazines are obtained from cnol ethers and acyclic diacyldiazenes depending on the structure and the substitution pattern of the alkene (Section 7.2.10.1.). For 3,4-dihydro-2//-pyran (12) and certain glycals it has been found that the cycloaddition of dibenzyl di-azenedicarboxylate 13 to give oxadiazines is favored over the ene products by carrying out the reactions at lower concentration of dihydropyran and under irradiation, which converts ( )-13 to (Z)-1312. 

By the cycloaddition of dibenzyl diazenedicarboxylate and furanoid and pyranoid glycals it is possible to diastereoselectively introduce an amino function at the C-2 position of a carbohydrate29-34. A single diastereomer is produced from furanoid glycals, where the cycloaddition takes place trans to the C-3 hydroxy substituent protected as the silyl ether, e.g., formation of 14-1630. The more reactive bis(2,2,2-trichloroethyl) diazenedicarboxylate can be employed even with less reactive 3-acetyl glycals31. 

Cycloaddition of Dibenzyl Diazenedicarboxylate to Glycals General Procedure29 ... 

Schmidt and his coworkers have cleaved the N—N bond of tetrahydropyridazines (20) with sodium in liquid ammonia as a step in the synthesis of 4-aminolyxose derivatives. Leblanc and coworkers have used carbohydrate-derived glycals as two-electron components in cycloadditions to dibenzyl azodicar-boxylate the adducts (e.g. 21 in Scheme 15) were subjected to methanolysis and the N—N bond was then cleaved using Raney nickel. ... 

Another approach to the tricothecene skeleton proposed by Fraser-Reid takes advantage of carbohydrate enolate chemistry to constmct the A ring [366]. The C ring was formed by intramolecular sulfonate displacement by an appropriate amide enolate. A route to the same skeleton involving [2 + 2] cycloaddition on the double bond of an enone obtained from a glycal has been proposed by Fetizon [367]. Ring expansion of the cyclobutene obtained this way can be effected to constmct the C ring of these compounds. 

The reaction of 5-nitrofuran-2-carboxaldehyde and 2,3,4,6-tetra-O-acetyl-P-o-glucopyrano-sides of ( , )-4-ethoxy-2-[(r rf-butyl)dimethylsilyloxy]butadiene can be highly diastereoselective depending on the nature of the lanthanide Lewis acid used to promote the cycloaddition (Yb(fod)3, La(fod)3). The adducts thus obtained are readily converted into (3-D-glucopyranosyl (1 4)-linked glycals [136b]. 

Glycals can also undergo cycloaddition reactions and their derivatives are of interest for synthetic purposes. Diels-Alder [4+2], Paterno-Biichi [2+2], and 1,3-dipolar additions can be applied to the construction of fused cycloadducts (O Scheme 21) [26,27,28]. 

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... 

Similarly, reaction of 1,4-diacetoxy-l,3-butadiene with methyl glyoxalate afforded glu-curonate glycal [228] and a 2,3-unsaturated isomer. Cycloaddition reactions performed on substrates with inverse electronic properties (e. g., enol ether as a dienofile and unsaturated carbonyl compound as a heterodiene) afford not only the expected products but also ones having high endo selectivity [229,230] as exemplified below by olivose 126 synthesis (O Scheme 43). 

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