Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1‐azi‐glycoses

Abstract

Dedicated to Duilio Arigoni on the occasion of his 65th birthday (1.X.93)In the context of the hypothesis postulating a heterolytic cleavage of a C-N bond during thermolysis of alkoxydiazirines (Scheme I ) , we report the preparation of the diazirines4,5,7, and 8, the kinetic parameters for the thermolysis in MeOH of the diazirines 1 and 4-9, and the products of their thermolysis in an aprotic environment. The diazirines 4,5,7, and 8 (Schemes 2-5) were prepared from the known hemiacetals 10,19,34 (prepared from 31 in an improved way), and 42 according to an established method. The oximes 11,20,35, and 43 were obtained from the corresponding hemiacetals as (E/Z)-mixtures; 43 was formed together wlth the cyclic hydroxylamine 44. Oxidation of 11,35, and 43 (N-chlorosuccinimide/l,8-diazabicyclo[5.4.0]undec-7-ene (NCS/DBU) or NaIO,) gave good yields of the (Z)-hydroximolactones 12, 36, and 45, while the oxime 20 led to a mixture of the (E)-and (2)-hydroximolactones 21 and 22, which adopt different conformations. Their configuration was assigned, inter alia, by a comparison with the enol ethers 28 and 29, which were obtained, together with 30, from the reaction of the diazirine 5 with benzaldehyde and PBu,. Treatment of the hydroximolactone 0-sulfonates 13,23,37, and 46 with NH,/MeOH afforded the diaziridines 15,25,38, and 47 in good yields, while the (E)-sulfonate 24 decomposed readily. Oxidation of the diaziridines gave 4, 5, 7, and 8, respectively. Thermolysis of the diazirines 1 and 4-9 in MeOH yielded the anomeric methyl glycosides 50/51,16/17,26/27,52/53,39/40,48/49, and 54/55, respectively. A comparison of the kinetic data of the thermolysis at four different temperatures shows the importance of conformational and electronic factors and is compatible with the hypothesis of a heterolytic cleavage of a C-N bond. An early transition state is evidenced by the absence of torsional strain by an annulated 1,3-dioxane ring. Thermolysis of 1 in MeCN at 23" led mostly to the diastereoisoineric (Z,Z)-, (E,E)-, and (E,Z)-lactone azines 56, 57, and 58 (Scheme 6), which convert to 56 under mild conditions, and to 59 (3%). The benzyloxyglucal59 was obtained in higher yields (IS%), together with 44% of 5658, by thermolysis of solid 1. Similarly, thermolysis at higher temperatures of4 in toluene, THF, or dioxane and of 9 in CH2C12 or THF yielded the (Z,Z)-lactone azines 60 and 61, respectively, the latter being accompanied by the dihydro-oxazole 62.Introduction. -Diazirines [I] are important precursors of carbenes, and the mechanism of their thermolysis attracted considerable attention, which focused on the concertedness of the cleavage of the two C-N bonds and the homo-or heterolytic nature of the bond breaking [2-71. The mechanism and the kinetics of the thermolysis of (a1koxy)alkyldiazirines (see [8] and earlier papers of the series [9-131) have not been studied, but we hypothesized that thermolysis of 1-azisugars, such as 1, i.e. cyclic (alkoxy)alkyldiazirines, is initiated by heterolysis of one of the C( 1)-N bonds, accord-

Glycosylidene Carbenes. Part 25. Glycosidation of ginkgolides B and A

“…Deprotection of 5-8 yielded 9-12, respectively (see below). and 16 (Scheme 2, cf below), and increasing amounts (1 1 -32 Ya) of by-products derived from 2, such as lactone azines [18] Under similar conditions, glucosidations in lP-dioxane, toluene, CH,Cl,, or CHC1, with 1 equiv. of 2 led to a mixture of 5-8 in yields reaching 30%, in the best case.…”

“…It proved to be a 98:2 mixture of the two trans-diastereoisomers, as evidenced by the two sets of signals for the hydrazi group in the 'H-NMR spectra (CJ [18]). The diazirine 34 was prepared by oxidizing 33 with I, in CH2C12.…”

“…Rapid filtration through silica gel gave 34 (97%) as a colorless foam. It had a half-life T'/, at 25" of 85 min, higher than 2 = 33 min [18]), and kept well for months at -78" in solution (THF or CH,Cl,), or in the solid state.…”

“…This diazirine was synthesized from 2,3,6-tr~-O-benzyl-4-~-(2,3,4,6-tetra-O-benzyl-~-~-galactosyl)-~-g~ucopyranose [21] following the established method [18] [22]. The oxime 30 was obtained as (E/Z)-mixture (70:30, 94 %) and oxidized with MnO, [23] …”

Glycosylidene Carbenes. Part 16. Glycosidation of methyl 6‐O‐trityl‐α‐D‐altropyranoside

“…The disaccharides 5-10 were separated by repeated flash chromatographies and characterized as the diacetdtes 11-16. The azines 17 [9], and the benzylated 2-(benzyloxy)glucal 18 [9] [lo] were obtained as by-products. Attempts to isolate other by-products, particularly demethylated saccharides as they were observed in the glycosidation of 3 [4], trisaccharides, or epoxides failed4).…”