2-C-branched glycosides from 2'-carbonylalkyl 2-O-Ms(Ts)-C-glycosides. A tandem SN2-SN2 reaction via 1,2-cyclopropanated sugars

[reaction: see text] Under basic conditions, 2'-aldehydo (acetonyl) 2-O-Ms(Ts)-alpha-C-glycosides undergo an intramolecular S(N)2 reaction to form 1,2-cyclopropanated sugars, which react with nucleophiles (alcohols, thiols, and azide) at the anomeric carbon to give 2-C-branched glycosides. By way of contrast, the 1,2-cyclopropanes derived from 2'-ketones only react with thiols to give 2-C-branched thioglycosides.     

Efficient methodology for the synthesis of 2-C-branched glyco-amino acids by ring opening of 1,2-cyclopropanecarboxylated sugars

An efficient methodology for the synthesis of 2-C-branched glyco-amino acid derivatives by diastereoselective ring opening of 1,2-cyclopropanecarboxylated sugars in good yields is reported. [reaction--see text]     

Stereoselective synthesis of 2-C-branched (acetylmethyl) oligosaccharides and glycoconjugates: Lewis acid-catalyzed glycosylation from 1,2-cyclopropaneacetylated sugars

1,2-Cyclopropaneacetylated sugars as glycosyl donors reacted with a series of glycosyl acceptors (monosaccharides, amino acids, and other alcohols) in the presence of Lewis acid to produce oligosaccharides and glycoconjugates containing 2-C-acetylmethylsugars. Galactosyl donor gave good to excellent α-selectivities with TMSOTf as a catalyst, whereas galactosyl donor offered moderate to good β-selectivities when BF(3)·Et(2)O was used as a catalyst. However, glucosyl donors produced β-exclusive selectivity under both conditions. The stereoselectivities of glycosylation depend on the reactivity of donor sugars and Lewis acid catalyst, which effectively dictated the glycosylation pathways. The evidence suggests that galactosyl donors (e.g., 7) can undergo S(N)1 pathway with a strong Lewis acid (TMSOTf) and S(N)2 pathway under BF(3)·Et(2)O, whereas the glucosyl donors (e.g., 8 and 10) followed S(N)2 pathway. The stereoselectivity was also consequential to the formation of a C2'-acetal intermediate formed via the 2-C-acetylmethyl group and the anomeric carbonium intermediate in glycosylation.     

Efficient and selective synthesis of glycofuranosyl azides and nucleosides from cyclic 1,2-thiocarbonate sugars

[reaction: see text] Cyclic 1,2-thiocarbonate sugars are convenient starting materials for the selective and efficient preparation of glycofuranosyl azides and nucleosides by regio- and stereoselective thiocarbonate ring-opening.     

Streamlined synthesis of per-O-acetylated sugars, glycosyl iodides, or thioglycosides from unprotected reducing sugars

Solvent-free per-O-acetylation of sugars with stoichiometric acetic anhydride and catalytic iodine proceeds in high yield (90-99%) to give exclusively pyranose products as anomeric mixtures. Without workup, subsequent anomeric substitution employing iodine in the presence of hexamethyldisilane (i.e., TMS-I generated in situ) gives the corresponding glycosyl iodides in 75-95% isolated yield. Alternatively, and without workup, further treatment with dimethyl disulfide or thiol (ethanethiol or thiocresol) gives anomerically pure thioglycosides in more than 75% overall yield.     

Divergent synthesis of 2-C-branched pyranosides and oxepines from 1,2-gem-dibromocyclopropyl carbohydrates

The ring opening of 1,2-(gem-dibromo)cyclopropyl carbohydrates by two different modes leads to either 2-C-(bromomethylene)pyranosides (using base) or 2-bromooxepines (using silver salts), as shown previously by us for a d-glucal-derived cyclopropane. The base-promoted ring opening is extended to encompass additional alcohol, thiol and amine nucleophiles, and diastereoisomeric cyclopropane precursors. Cross-coupling of the 2-C-(bromomethylene)pyranosides leads to extended 2-C-branched pyranosides. Silver-promoted ring expansion of the cyclopropyl carbohydrates in the presence of various alcohols is described. Cross-coupling of the resulting benzyl 2-bromooxepines affords 2-C-substituted oxepines.     

Electrophilic cyclization of 4-thio-but-2-yn-1-ols via 1,2-migration of the thio group: efficient synthesis of 2,4-dihalo-3-thio-substituted furans

A facile and efficient method for the synthesis of 2,4-dihalo-3-thio-furans via the electrophilic cyclization and 1,2-migration of the thio group of 4-thio-but-2-yn-1-ols was developed. As a result of the ready availability of starting materials and the simple and convenient operation, this synthetic route would have potential utility in organic synthesis.     

Traceless Staudinger ligation of glycosyl azides with triaryl phosphines: stereoselective synthesis of glycosyl amides

Alpha-glycosyl amides can be synthesized from the corresponding O-benzyl-alpha-glycosyl azides using a traceless Staudinger ligation with diphenylphosphanyl-phenyl esters 4. All the phosphines employed and their phenol precursors are stable to air at 4 degrees C for months. Fast intramolecular trapping of the reduction intermediates results in the direct formation of the amide link, which, in turn, prevents epimerisation and allows retention of configuration at the anomeric carbon. Yields and alpha-selectivity are high when the reaction is performed in polar aprotic solvents. Removal of the benzyl ether protecting groups is achieved by catalytic hydrogenation. Alpha-glycosyl amides represent a class of virtually unexplored nonhydrolyzable monosaccharide derivatives that may find a useful application as sugar mimics. Conformational studies by NMR spectroscopy confirm that deprotected alpha-glycosyl amides in the gluco, galacto, and fuco series retain the normal pyranose conformation of the monosaccharide. The reaction of phosphines 4 with tetra-O-acetyl-glycosyl azides is nonstereoconservative, and beta-glycosyl amides are obtained in good yields and with complete stereoselectivity starting from both alpha and beta azides.     

Three-component 1,2-carboamination of vinyl boronic esters via amidyl radical induced 1,2-migration

Three-component 1,2-carboamination of vinyl boronic esters with alkyl/aryl lithium reagents and N-chloro-carbamates/carboxamides is presented. Vinylboron ate complexes generated in situ from the boronic ester and an organo lithium reagent are shown to react with readily available N-chloro-carbamates/carboxamides to give valuable 1,2-aminoboronic esters. These cascades proceed in the absence of any catalyst upon simple visible light irradiation. Amidyl radicals add to the vinylboron ate complexes followed by oxidation and 1,2-alkyl/aryl migration from boron to carbon to give the corresponding carboamination products. These practical cascades show high functional group tolerance and accordingly exhibit broad substrate scope. Gram-scale reaction and diverse follow-up transformations convincingly demonstrate the synthetic potential of this method.

Three-component 1,2-carboamination of vinyl boronic esters with alkyl/aryl lithium reagents and N-chloro-carbamates/carboxamides is presented.

Alkenes are important and versatile building blocks in organic synthesis. 1,2-Difunctionalization of alkenes offers a highly valuable synthetic strategy to access 1,2-difunctionalized alkanes by sequentially forming two vicinal σ-bonds.^1a–h Among these vicinal difunctionalizations, the 1,2-carboamination of alkenes, in which a C–N and a C–C bond are formed, provides an attractive route for the straightforward preparation of structurally diverse amine derivatives (Scheme 1a).^2a–c Along these lines, transition-metal-catalyzed or radical 1,2-carboaminations of activated and unactivated alkenes have been reported.^3a–p However, the 1,2-carboamination of vinylboron reagents, a privileged class of olefins,^4a–h to form valuable 1,2-aminoboron compounds which can be readily used in diverse downstream functionalizations,^{5a–c,6a–d} has been rarely investigated. To the best of our knowledge, there are only two reported examples, as shown in Schemes 1b and c. In 2013, Molander disclosed a Rh-catalyzed 1,2-aminoarylation of potassium vinyltrifluoroborate with benzhydroxamates via C–H activation (Scheme 1b).⁷ Thus, the 1,2-carboamination of vinylboron reagents is still underexplored but highly desirable.Open in a separate windowScheme 1Intermolecular 1,2-carboamination of alkenes.1,2-Alkyl/aryl migrations induced by β-addition to vinylboron ate complexes have been shown to be highly reliable for 1,2-difunctionalization of vinylboron reagents (Scheme 1c).^4d–h In 1967, Zweifel''s group developed 1,2-alkyl/aryl migrations of vinylboron ate complexes induced by an electrophilic halogenation.⁸ In 2016, the Morken group reported the electrophilic palladation-induced 1,2-alkyl/aryl migration of vinylboron ate complexes.^9a–k Shortly thereafter, we,^10a–c Aggarwal,^11a–c and Renaud¹² developed alkyl radical induced 1,2-alkyl/aryl migrations of vinylboron ate complexes. In these recent examples, the migration is induced by a C-based radical/electrophile, halogen and chalcogen electrophiles.^13a,bIn contrast, N-reagent-induced migration of vinylboron ate complexes proceeding via β-amination is not well investigated. To our knowledge, as the only example the Aggarwal laboratory described the reaction of a vinylboron ate complex with an aryldiazonium salt as the electrophile, but the desired β-aminated rearrangement product was formed in only 9% NMR yield (Scheme 1c).^13a No doubt, β-amino alkylboronic esters would be valuable intermediates in organic synthesis. Encouraged by our continuous work on amidyl radicals^14a–i and 1,2-migrations of boron ate complexes,^{10a–c,15a–f} we therefore decided to study the amidyl radical-induced carboamination of vinyl boronic esters for the preparation of 1,2-aminoboronic esters. N-chloroamides were chosen as N-radical precursors,^16a–c as these N-chloro compounds can be easily prepared from the corresponding N–H analogues.¹⁷ Herein, we present a catalyst-free three-component 1,2-carboamination of vinyl boronic esters with N-chloroamides and readily available alkyl/aryl lithium reagents (Scheme 1d).We commenced our study by exploring the reaction of the vinylboron ate complex 2a with tert-butyl chloro(methyl)carbamate 3a applying photoredox catalysis. Complex 2a was generated in situ by addition of n-butyllithium to the boronic ester 1a in diethyl ether at 0 °C. After solvent removal, the photocatalyst fac-Ir(ppy)₃ (1 mol%) and THF were added followed by the addition of 3a. Upon blue LED light irradiation, the mixture was stirred at room temperature for 16 hours. To our delight, the desired 1,2-aminoboronic ester 4a was obtained, albeit with low yield (26%,

Simple synthesis of 2-C-branched glyco-acetic acids

Only three steps are required for the selective synthesis of 2-C-branched glyco-acetic acids from glycals by radical addition and decarboxylation.     

Facile,efficient synthesis of polyfunctionalized 2-aminoimidazoles via vinyl azides and cyanamide

A simple and direct synthesis of 2-aminoimidazoles from vinyl azides and cyanamide was developed. An attractive feature of this protocol is that the desired products are generated in a highly efficient and eco-friendly manner without the use of a catalyst. A plausible mechanism has been proposed.     

Pt-catalyzed cyclization/1,2-migration for the synthesis of indolizines, pyrrolones, and indolizinones

Indolizine, pyrrolone, and indolizinone heterocycles are easily accessed via the Pt(II)-catalyzed cycloisomerization or a tandem cyclization/1,2-migration of pyridine propargylic alcohols and derivatives. This method provides an efficient synthesis of highly functionalized heterocycles from readily available substrates. [reaction: see text]     

3,5-Dinitrobenzoic acid catalyzed synthesis of 2,3-unsaturated O- and S-glycosides and tetrahydropyranylation of alcohols and phenols

A simple procedure for the synthesis of 2,3-unsaturated glycosides in acetonitrile and tetrahydropyranylation of alcohols and phenols in dichloromethane in the presence of 3,5-dinitrobenzoic acid is described. A variety of alcohols and thiols are reacted with glycals to give the desired products in high yields with high α-selectivity.     

Efficient and direct synthesis of saccharidic 1,2-ethylidenes, orthoesters, and glycals from peracetylated sugars via the in situ generation of glycosyl iodides with I2/Et3SiH

Peracetylated sugars can be efficiently converted into the corresponding 1,2-ethylidenes, -orthoesters, and -glycals via the in situ generation of glycosyl iodides promoted by I₂/Et₃SiH. The approach is straightforward and avoids isolation of the sensitive iodinated intermediates.     

Facile synthesis of unusual glycosyl carbamates and amino acid glycosides from propargyl 1,2-orthoesters as glycosyl donors

Propargyl 1,2-O-orthoesters are exploited for the synthesis of 1,2-trans O-glycosides of protected amino acids. N-Fmoc- and N-Cbz protected serine/threonine - benzyl/methyl esters reacted well with glucosyl-, galactosyl-, mannosyl- and lactosyl- derived propargyl 1,2-orthoesters affording respective 1,2-trans glycosides in good yields under AuBr(3)/4 ? MS Powder/CH(2)Cl(2)/rt. t-Boc serine derivative gave serine 1,2-orthoester and glycosyl carbamate. Optimized conditions enabled preparation of new glycosyl carbamates from N-Boc protected amines in a single step using gold catalysts and propargyl 1,2-orthoesters in excellent yields.     

A new approach to Amadori ketoses via MoVI-catalyzed stereospecific isomerization of 2-C-branched sugars bearing azido function in a microwave field

A branched-chain aldose bearing an azido group at the C-2 position provides access to the corresponding 1-deoxy-1-azido- and 1-deoxy-1-amino ketoses in a single step via stereospecific isomerization. The isomerization exploited the catalytic effect of molybdate ions and microwave irradiation. The structures of the products were analyzed by NMR spectroscopy, IR, HRMS spectrometry and quantum-chemical DFT calculations. DFT-computed proton-proton coupling constants of the prepared Amadori ketose 1-deoxy-1-amino-d-gluco-heptulose were found to be comparable with the experimentally obtained coupling constants and were in agreement with the ⁴C₁ pyranose form in aqueous solution at room temperature.     

Propargyl 1,2-orthoesters as glycosyl donors: stereoselective synthesis of 1,2-trans glycosides and disaccharides

Propargyl 1,2-orthoesters are identified as glycosyl donors. Various glycosides and disaccharides were synthesized in a stereoselective manner using AuBr₃ as the promoter. AuBr₃ may activate the alkyne resulting in the formation of a 1,2-dioxolenium ion and also behaves as a Lewis acid to facilitate the attack of the glycosyl acceptor. The versatility of the protocol was demonstrated using a panel of aglycones comprising aliphatic, alicyclic, steroidal and sugar alcohols.     

Gold-catalyzed 1,2-migration of silicon, tin, and germanium en route to C-2 substituted fused pyrrole-containing heterocycles

An efficient method for the synthesis of fused pyrroloheterocycles from diverse propargyl-substituted heterocycles in the presence of Au-catalyst has been developed. The cascade transformation proceeds via alkyne-vinylidene isomerization with concomitant 1,2-shift of hydrogen, silyl, and stannyl groups. Remarkably, it was also shown that previously unknown 1,2-migration of a germyl group upon alkyne-vinylidene rearrangement occurs under these reaction conditions. This method allows for mild and efficient synthesis of diverse C-2 substituted N-containing heterocycles.     

Fragmentation of carbohydrate anomeric alkoxyl radicals. A new synthesis of chiral beta-iodo azides, vinyl azides, and 2H-azirines

[reaction: see text] The reaction of 3-azido-2,3-dideoxy-hexopyranose compounds from the d-gluco, d-galacto, d-lacto, and l-arabino carbohydrate series, with (diacetoxyiodo)benzene and iodine, generated 2-azido-1,2-dideoxy-1-iodo-alditols with one carbon less than the starting carbohydrate. These beta-iodo azides could be transformed by dehydroiodination into vinyl azides, which in turn afforded 3-monosubstituted 2H-azirines under thermal conditions. These beta-iodo azides and 2H-azirines may be interesting chiral synthons for the preparation of more complex heterocyclic systems.