Glycosylidene Carbenes. Part 5. Synthesis of Glycono‐1,5‐lactone Tosylhydrazones as Precursors of Glycosylidene Carbenes

Dedicated to the memory of Jorge F. Lo¬pez-Herrera Acylation and sulfonylation of the N,N'-unsubstituted glucosylidenespirodiaziridines 1A/1B 95 : 5 with Ac 2 O, 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). 15 N-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.Introduction. ± The reactivity of glycosylidene diaziridines has not been wellexplored. Apart from an investigation of their formation [1], with special emphasis on the stereoselectivity of the addition of NH 3 and MeNH 2 to the precursor glyconolactone oxime sulfonates [2], only the oxidation of these diaziridines with iodine and Et 3 N or Me 3 N in MeOH, Et 2 O, or CH 2 Cl 2 [3] to N-unsubstituted-glycosylidene diazirines was investigated. These diazirines have been studied as precursors of glycosylidene carbenes [3 ± 5].The reactivity of 3-alkyldiaziridines has been explored more extensively. Their reaction with electrophiles is strongly influenced by the nature of the electrophile and by the N-substituents. Attack of electrophiles on the diaziridines I leads to diaziridinium ions II (Scheme 1). For R 3 H, deprotonation of II afforded substituted diaziridines III [6 ± 10]. Alternatively, diaziridine ring opening of II led to the hydrazonium ions IV, which were transformed into hydrazones V (R 4 H) [11] [12] and into azomethine imines VI (R 3 H) [13]. Hydrolysis of IV afforded ketones VII and hydrazines VIII [13a] [14] [15]. This transformation to hydrazines constitutes a valuable method for the selective preparation of otherwise hardly accessible N -alkyland N,N'-dialkylhydrazines [16]. The reaction of 1,3,3-trimethyldiaziridine with AcCl led to a 4 : 1 mixture of N-methyl-N'-isopropylidene-acethydrazide and 2-acetyl-1,3,3trimethyldiaziridine [17].Except for the oxidation with I 2 , we found no reaction of glycosylidene diaziridines, nor of any other 3-alkoxydiaziridine with electrophiles. We have examined the reactions of glycosylidene-diaziridines with acylating and sulfonylating reagents, and describe the results of these experiments.Results and Discussion. ± 1. Acylation and Sulfonylation...

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See 1 more Smart Citation

Glycosylidene Carbenes. Part 32

Mangholz

Briner

Bernet

et al. 2003

“…The ready isomerization of the (E,Z)-lactone azine 58 to the (Z/Z)-isomer 56 and the exclusive formation, at higher temperatures, of the (Z,Z)-isomers from the diazirines 4 and 9 demonstrate the relative stability of these isomers, which is in keeping with the preferred (Z)-configuration of lactone hydrazones [46] [94], lactone semicarbazones [95], lactone oximes [44] [60] [96j, and lactam oxirnes [97], but differs from the preferred conformation of ester azines [98]. The conformation of acyclic alkoxyazines is presumably similar to the one of acyclic imino ethers [99] and characterized by a N=C-0-C angle of O", which leads to a stabilizing n(0)-donor-+a*(C-N)-acceptor interaction ('generalized anomeric effect').…”

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

Vasella

Witzig

Waldraff

et al. 1993

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-

“…-The nucleophilic character of glycosylidene carbenes has been evidenced, among others, by their reaction with electron-poor alkenes (for reviews, see [2-41). Thus, glycosylidene carbenes derived from the diazirines 1 [ 5 ] , 2 [ 6 ] , and 3 [7], and from the 4-toluenesulfonohydrazide sodium salts 4 [8] and 5 [9] add readily to electronpoor alkenes, leading to spirocyclopropanes. Yields of the products derived from the pivaloylated diazirine 1 were higher than those obtained from the benzylated diazirine 2, showing that the nature of the protecting groups influences the (nucleophilic) reactivity of these alkoxycarbenes 2).…”

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Glycosylidene Carbenes. Part 24 Reactivity modulation by protecting groups of the addition of glycosylidene carbenes to electron‐rich alkenes

Waldraff

Bernet

Vasella

1997

The reactivity of glycosylidene carbenes derived from pivaloylated vs. benzylated diazirines 1 and 2 towards enol ethers have been examined. The pivaloylated 1 led to higher yields of spirocyclopropanes than the benzylated 2. Among the enol ethers tested, dihydrofuran 6 proved most reactive, yielding 71 -72% of the spiro-linked tetrahydrofuran 7, while the benzylated diazirine 2 afforded only 33% of the analogue 8 (Scheme 1). Other enol ethers proved much less reactive. The addition of 1 and 2 to the dibydropyran 10 and the 2,3-dihydro-5-methylfuran 15 gave low yields of single cyclopropanes (+ 12, 14, andl6), and the glycals 17 and 18, and (E)-1-methoxyoct-1-ene (23) did not react. The main products of these reactions were the azines (Z,Z)-11 and (Z,Z)/(E,E)-lJ.Similarly, 1 and 2 reacted poorly with (Z)-1-methoxyoct-1-ene (M), leading to the cyclopropanes 25/26/27 and 28/29/30/31 (Scheme 2). Main products were again the azines (Z,Z)-11 and (Z,Z)/(E,E)-13. The structure of 7 and 25 was established by X-ray analysis (Figs. 1 and 2). The mechanism of addition of glycosylidene carbenes to enol ethers is discussed. AM1 Calculations indicate that the LUMO,,,,,,,/HOMO,,,,.,,,,,,, interaction is dominant at the beginning of the reaction, while the transition states are characterized by a dominant interaction of the doubly occupied, sp2-hybridized orbital of the carbene with the LUMO of the enol ether. The relative reactivity of the carbenes towards either the enol ethers or the diazirines determine type and yields of the products.