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Acylation and sulfonylation of the N,N′-unsubstituted glucosylidenespirodiaziridines 1A/1B 95 : 5 with Ac2O, BzCl, FmocCl, TsCl, (naphthalen-2-yl)sulfonyl, and (2,4,6-triisopropylphenyl)sulfonyl chloride, and concomitant rearrangement gave the acylated and sulfonylated gluconolactone hydrazones 2B–2G in 40–83% yield (Scheme 2). Similarly, the galacto and manno analogues 3A/3B 95 : 5 and 5A/5B 55 : 45 and the mannofuransoylidene-diaziridine 30 were acetylated and tosylated to give 4A, 4B, 6, 31A, and 31B (55–73% yield; Schemes 2 and 5). 15N-Labelling of 11A/11B and 14A/14B showed that the pseudoequatorial NH of the gluco diaziridines 1 and the pseudoaxial NH of the galacto diaziridines 3 were preferentially acetylated and tosylated (Scheme 3). Sulfonylation of the N-methylated diaziridines 19A/19B 72 : 28, 22A/22B 85 : 15, 25A/25B 85 : 15, 28A/28B 80 : 20, and 33A/33B/33C/33D 76 : 4 : 12 : 8 yielded the N-methyl-N-tosylglyconolactone hydrazones 20, 23, 26, 29, and 34 (44–66%; Schemes 4 and 5). The methylated N-atom of the diaziridines proved more reactive, irrespective of the configuration at C(2) and C(4). The products were readily hydrolysed to glyconolactones.

The diastereoselectivity of the addition of NH3 and MeNH2 to glyconolactone oxime sulfonates and the structures of the resulting N-unsubstituted and N-methylated glycosylidene diaziridines were The 15N-labelled glucono- and galactono-1,5-lactone oxime mesylates 1* and 9* add NH3 mostly axially (>3 : 1; Scheme 4), while the 15N-labelled mannono-1,5-lactone oxime sulfonate 19* adds NH3 mostly equatorially (9 : 1; Scheme 7). The 15N-labelled mannono-1,4-lactone oxime sulfonate 30* adds NH3 mostly from the exo side (>4 : 1; Scheme 9). The configuration of the N-methylated pyranosylidene diaziridines 17, 18, 28, and 29 suggests that MeNH2 adds to 1, 9, 19, and 23 mostly to exclusively from the equatorial direction (>7 : 3; Schemes 5 and 8). The mannono-1,4-lactone oxime sulfonate 30 adds MeNH2 mostly from the exo side (85 : 15; Scheme 10), while the ribo analogue 37 adds MeNH2 mostly from the endo side (4 : 1; Scheme 10). Analysis of the preferred and of the reactive conformers of the tetrahedral intermediates suggests that the addition of the amine to lactone oxime sulfonates is kinetically controlled. The diastereoselectivity of the diaziridine formation is rationalized as the result of the competing influences of intramolecular H-bonding during addition of the amines, steric interactions (addition of MeNH2), and the kinetic anomeric effect. The diaziridines obtained from 2,3,5-tri-O-benzyl-D-ribono- and -D-arabinono-1,4-lactone oxime methanesulfonate (42 and 48; Scheme 11) decomposed readily to mixtures of 1,4-dihydro-1,2,4,5-tetrazines, pentono-1,4-lactones, and pentonamides. The N-unsubstituted gluco- and galactopyranosylidene diaziridines 2, 4, 6, 8, and 10 are mixtures of two trans-substituted isomers (S/Rca. 19 : 1, Scheme 2). The main, (S,S)-configured isomers S are stabilised by a weak intramolecular H-bond from the pseudoaxial NH to ROC(2). The diaziridines 12, derived from GlcNAc, cannot form such a H-bond; the (R,R)-isomer dominates (R/S 85 : 15; Scheme 3). The 2,3-di-O-benzyl-D-mannopyranosylidene diaziridines 20 and 22 adopt a 4C1 conformation, which does not allow an intramolecular H-bond; they are nearly 1 : 1 mixtures of R and S diastereoisomers, whereas the OH5 conformation of the 2,3:5,6-di-O-isopropylidene-D-mannopyranosylidene diaziridines 24 is compatible with a weak H-bond from the equatorial NH to OC(2); the (R,R)-isomer is favoured (R/S ≥7 : 3; Scheme 6). The mannofuranosylidene diaziridine 31 completely prefers the (R,R)-configuration (Scheme 9).

The syntheses of glycosides from the diazirine 1 and a range of alcohols under thermal and/or photolytic conditions are described. Yields and diastereoselectivities depend upon the pKHA values of the alcohols, the solvent, and the reaction temperature. The glycosidation of weakly acidic alcohols (MeOH, EtOH, i-PrOH, and t-BuOH, 1 equiv. each) in CH2Cl2 at room temperature leads to the glycosides 2–5 in yields between 60 and 34% (Scheme 1 and Table 1). At −70 to −60°, yields are markedly higher. In CH2Cl2, diastereoselectivities are very low. In THF, at −70 to −60°, however, glycosidation of i-PrOH leads to α-D-/β-D-4 in a ratio of 8:92. More strongly acidic alcohols, such as CF3CH2OH, (CF3)2 CHOH, and (CF3)2C(Me)OH, and the highly fluorinated long-chain alcohols CF3(CF2)5(CH2)2OH (11) and CHF2(CF2)9CH2OH (13) react (CH2Cl2, r.t.) in yields between 73 and 85% and lead mainly to the β-D-glucosides β-D-6 to β-D-8, β-D-12, and β-D-14 (d.e. 14–68%). Yields and diastereoselectivities are markedly improved, when toluene, dioxane, 1,2-dimetoxyethane, or THF are used, as examined for the glycosidation of (CF3)2C(Me)OH, yielding (1,2-dimethoxyethane, 25°) 80% of α-D-/ β-D-8 in a ratio of 2:98 (d.e. 96%; Table 4). In EtCN, (CF3)2C(Me)OH yields up to 55% of the imidate 10. Glycosidation of di-O-isopropylideneglucose 15 leads to 16 (CH2Cl2, r.t.; 65%, α-D/ β-D = 33:67). That glycosidation occurs by initial protonation of the intermediate glycosylidene carbene is evidenced, for strongly acidic alcohols, by the formation of 10, derived from the attack of (CF3)2MeCO− on an intermediate nitrilium ion (Scheme 4), and for weakly acidic alcohols, by the formation of α-D-9 and β-D-9, derived by attack of i-PrO− on intermediate tetrahydrofuranylium ions. A working hypothesis is presented (Scheme 3). The diastereoselectivities are rationalized on the basis of a protonation in the σ plane of the intermediate carbene, the stabilization of the thereby generated ion pair by interaction with the BnOC(2) group, with the solvent, and/or with the alcohol, and the final nucleophilic attack by RO− in the π plane of the (solvated) oxonium ion.

Phenol, 4-methoxyphenol, 4-nitrophenol, methyl orsellinate (1), and 2,6-di(tert-butyl)-4-methylphenol (BHT; 2) have been glycosylated by thermal reaction (20-60°) with various glycosylidene-derived diazirines

A preparation of glycosylphosphonates (27, 28, 36, 38, and 39) from 2-azido-2-deoxy-glycoses (26,35, and 37) and the synthesis of the non-isosteric phosphonate analogue 3a of lipid X(2) are described. The 2-azido group was introduced by azidonitration. Treatment of the 1-O-acetyl-2-azido-2-deoxy-β-D-galactopyranose 22 with 1.5-3 equiv. of P(OMe)3 and 1.2-2.5 equiv. of TfOSiMe3 gave mainly recovered starting material. In P(OMe)3 as the solvent, the dimethyl phosphoramidate 24 was obtained by way of a Staudinger reaction, even in the presence of TfOSiMe3. Treatment of the benzylated α-D-galacto-trichloroacetimidate 26, however, with P(OMe)3 and TfOSiMe3 gave a 1:1 mixture of the α- and β-D-galacto-phosphonates 27 and 28, while the acetylated α-D-gluco- imidate 35 led to the α-D-gluco-configurated phosphonate 36. The stereoselectivity of the phosphonate formation is related to the relative ease of formation of oxonium-ion intermediates from 26 and 35. Starting from the phosphonate 36, deacetylation, benzylidenation, reduction of the azido group, acylation with (R)-3-(benzyloxy)tetradecanoic acid and deprotection yielded the desired compound 3a which was crystallized in the presence of 2 equiv. of (aminomethylidyne)trimethanol (Tris.). The structure of the phosphonates was deduced from their 1H-, 13C-, and 31P-NMR spectra.

A new approach towards the synthesis of glycosides based upon a (formal) insertion of glycosylidene carbenes into OH bonds is presented. The synthesis and characterization of the glycosylidene-derived diazirines 25–28, precursors of glycosylidene carbenes, are described. The diazirines were prepared by the rapid, high-yielding oxidation of the diaziridines 20 and 22–24 with I2/Et3N. The diaziridines, the first examples of C- alkoxy-diaziridines, were formed in high yields by the reaction of the [(glycosylidene)-amino]methanesulfonates 14 and 17–19 with a saturated solution of NH3 in MeOH. The diazirines are highly reactive compounds, losing N2 at room temperature or below. The reaction of the gluco-configurated diazirine 25 with i-PrOH yielding a mixture of the α- and β-D-glucosides 29 and 30 illustrates the potential of glycosylidene-derived diazirines as a new type of glycosyl donors.