Ferrier Reaction Research Articles

Straightforward access to 2,3- and 3,4-unsaturated derivatives of N-glycolylneuraminic acid

Abstract The facile syntheses of previously unreported 2,3- and 3,4-unsaturated derivatives of N-glycolylneuraminic acid are herein described. The procedure involves a ring-opening of the 4,5-oxazoline of N-acetylneuraminic acid, the acylation of the intermediate free amine, its conversion into the 4,5-oxazoline of N-glycolylneuraminic acid and the subsequent Ferrier reaction or C4 nucleophilic substitution.

Unusual Epimerization in Styryllactones: Synthesis of (-)-5-Hydroxygoniothalamin, (-)-5-Acetylgoniothalamin, and O-TBS-Goniopypyrone.

(−)-5-Hydroxygoniothalamin, (−)-5-acetylgoniothalamin, and (+)-5-hydroxygoniothalamin, isolated from the Goniothalamus genus, are synthesized from triacetyl-O-d-glucal by employing the Ferrier reaction, Mitsunobu reaction, and Jones oxidation as key steps. The synthetic procedure also yields the epimers of (−)-5-hydroxygoniothalamin and (+)-5-hydroxygoniothalamin employing acid-mediated transition-metal-free epimerization at C-5 of styryllactones. Further studies reveal that the epimerization is facilitated by the phenyl group present on the styryllactones. Also, depending on the dihydroxylation reaction conditions, various analogues of saturated styryllactones are synthesized utilizing oxa-Michael reaction conditions.

One-Pot Cascade Transformation of Glucal into Structurally Diverse Drug-Like Scaffolds.

A diversity-oriented synthesis strategy to produce three types of structurally drug-like N-heterocyclic-fused rings has been developed from abundant biomass-derived d-glucal, aniline and water in a stereoselective manner. The overall transformation which entails a cascade of Ferrier reaction and 4π conrotatory imino-Nazarov cyclization was performed in one-pot allowing convenient preparation of scaffolds of high molecular complexity from relatively simple starting materials. While indoline-fused products were readily accessible using ortho-unsubstituted secondary anilines as substrates, reactions with ortho-hydroxyl-anilines furnished fused 1,4-benzoxazines instead. In both cases, InBr3 acted as the Lewis acid catalyst. By altering InBr3 to Ln(OTf)3 , the indoline-fused products could be further converted into tetrahydroquinoline-fused cyclopentenones via ensuing retro-ene rearrangement.

Ferrier Reaction: The first synthesis of 2,3-unsaturated seleno-glycosides by using alkyl(aryl) hydroselenides as the nucleophile and Hf(OTf)4 as the catalyst

By using Hf(OTf)4 as the catalyst, a series of 2,3-unsaturated-Se-glucosides have been synthesized for the first time from tri-O-acetyl-d-glucal, 2,4,6-tri-O-benzyl-d-glucal, 3,4-di-O-acetyl-l-rhamnal and ((2R,3S)-3-acetoxy-2,3-dihydrofuran-2-yl) methyl acetate with PhSeH or alkyl(aryl) hydroselenides as the nucleophile in good yield and high anomeric selectivity.

Glycerol carbonate in Ferrier reaction: Access to new enantiopure building blocks to develop glycoglycerolipid analogues

Glycerol carbonate and tri-O-acetyl-D-glucal were used for the synthesis of glycero-functionalized carbohydrates. Ferrier reaction between the two partners afforded the O-glucoside in 84% yield. Spontaneous crystallization yielded 28% of a pure diastereoisomer with the S configuration as determined by X-ray crystallography. Then, the azido-glycerosugar was prepared in two steps: ring opening of the cyclic carbonate with sodium azide and per-acetylation with an excellent yield of 94%. A library of glycoconjugates were prepared using a 1,3-dipolar cycloaddition in yields ranging from 64 to 99%.

Ferrier reaction in a deep eutectic solvent

A mild and efficient synthesis of 2,3-unsaturated sugar derivatives has been achieved by conducting the Ferrier reaction in a deep eutectic solvent (DES). A wide range of alcohols including primary, secondary, benzylic, and sugar-derived primary alcohols can be used. Advantages include good yields, shorter reaction times and recyclability of DES.

Convergent One-Pot Oxidative [n + 1] Approaches to Spiroacetal Synthesis.

Two one-pot oxidative annulative approaches to spiroacetal synthesis are described. One approach uses a Lewis acid mediated Ferrier reaction in the fragment-coupling stage followed by DDQ-promoted oxidative carbon-hydrogen bond cleavage and cyclization. An alternative approach employs a Heck reaction for fragment coupling followed by DDQ-mediated enone formation and cyclization. These strategies provide convergent routes to common subunits in natural products, medicinal agents, and chemical libraries under mild reaction conditions.

ChemInform Abstract: ZnBr2‐Catalyzed and Microwave‐Assisted Synthesis of 2,3‐Unsaturated Glucosides of Hindered Phenols and Alcohols.

AbstractZnBr2 is shown to be an efficient catalyst for the Ferrier reaction under microwave irradiation.

ZnBr2-Catalyzed and Microwave-Assisted Synthesis of 2,3-Unsaturated Glucosides of Hindered Phenols and Alcohols

Zinc bromide (ZnBr2) under microwave irradiation efficiently catalyzed the Ferrier reaction of hindered phenols and alcohols to afford the corresponding α-2,3-unsaturated glucoside acetates in good yields and with good stereoselectivity. The reaction affords a facile access to new 2,3-dideoxyglucosides of important phenolic and alcoholic constituents of spices.

ChemInform Abstract: Formation of C‐Glycosides by Ferrier Reaction.

AbstractPeracylated glycals, such as (I), are treated with terminal alkynes, e.g. (II), under Lewis acid catalysis to give anomerically pure (E)‐configurated 2‐halo‐hex‐2‐enopyranosides exclusively.

N-Halosuccinimide/AgNO3-Efficient Reagent Systems for One-Step Synthesis of 2-Haloglycals from Glycals: Application in the Synthesis of 2C-Branched Sugars via Heck Coupling Reactions

An expedient one-step synthesis of 2-iodoglycals and 2-bromoglycals from glycals using NIS/AgNO3 and NBS/AgNO3 as reagent systems has been developed. The utility of these 2-haloglycals has been demonstrated by converting them into 2C-branched glycals via the Heck coupling reaction. Ferrier reaction of tri-O-acetyl-2-iodoglycals followed by Heck coupling reaction with methyl acrylate leads to 2C-branched O-glycosides.

Zn(OTf)2-Catalyzed Glycosylation of Glycals: Synthesis of 2,3-Unsaturated Glycosides via a Ferrier Reaction

A mild, catalytic, and efficient protocol has been developed for the synthesis of 2,3-unsaturated glycosides or ‘pseudo-glycals’ using Zn(OTf)2. Stereoselective glycosylation of glycal donor with various acceptors comprising of alcohols, phenols, thiols, and sugar aglycones proceeds smoothly to afford the corresponding 2,3-unsaturaed glycosides in good to excellent yields.

Formation of C-Glycosides by Ferrier Reaction

Peracetylated glycals were treated with terminal alkyne derivatives under Lewis acid catalysis to result in the formation of the pure α- or β- anomerically substituted hex-2-enopyranosides carrying 2(E)-halogenated olefins.

A new route toward 2-acetamido-4-O-methyl-2-deoxy-d-mannopyranose from a Ferrier derivative of tri-O-acetyl-d-glucal, which contributes to aldolase-catalyzed synthesis of laninamivir (CS-8958)

A new route toward 2-acetamido-4-O-methyl-2-deoxy-d-mannopyranose (4-O-methylManNAc), the chemo-enzymatic precursor of 7-O-methylsialic acid and laninamivir, was established. Known p-methoxyphenyl 6-O-(tert-butyldimethylsilyl)-2,3-dideoxy-α-d-erythro-hex-2-enopyranoside was the starting material, and it was derived via Ferrier reaction from tri-O-acetyl-d-glucal. The total yield was 43% over six steps from the starting material. As the key steps, Payne oxidation provided a syn-epoxy alcohol, and the inversion from an aziridine to an oxazoline proceeded stereoselectively. Although the ring opening reaction of the epoxide with an azide gave both the 2- and 3-azido regioisomers, they could be merged into the desired aziridine via independent routes.

A Simple Synthetic Access to Differently 4‐Substituted Neu5Ac2en Glycals Combining Elements of Molecules with Anti‐Neuraminidase Activity

AbstractA protocol for direct access to C‐4‐functionalized Neu5Ac2en derivatives by allylic substitution of an α‐acetoxy group with various nucleophiles is reported. The DANA acetamido group is exchanged for a trifluoroacetylamido group (as in FANA) to avoid the formation of a stable 4,5‐oxazoline. With thiols, the reaction involves an initial attack at the anomeric carbon (Ferrier reaction) under kinetic control, followed by an equilibration of the nucleophile to the thermodynamically more stable 4‐position.

Extending the scope of the Ferrier reaction: fragmentation-rearrangement reactions of selectively substituted 1,2-cyclopropanated glucose derivatives

Two further variations of the Ferrier-type allylic rearrangements of 1,2-cyclopropanated glucose derivatives bearing an acetoxylated carbon at the 1′-position are described. In the first, treatment of the cyclopropanated sugar with a nucleophile (ROH, PhSH, azide) and Lewis acid (BF3·Et2O or Al(OTf)3), gives 2-C-vinyl glucosides in good yields and α-selectivities. Alternatively, treatment with a combination of Lewis acid and acetic acid leads to a novel fragmentation-rearrangement to form a 2,3-dehydro-2-formyl-C-glycoside. [Display omitted]

ChemInform Abstract: Total Synthesis of (‐)‐Tetrodotoxin from D‐Glucose: A New Route to Multi‐Functionalized Cyclitol Employing the Ferrier(II) Reaction Toward (‐)‐Tetrodotoxin.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: An Efficient Synthesis of Cyclophellitol Utilizing Unusual Regioselectivity of Oxirane Ring Opening with Mes2BCH2Li.

Abstract Cyclophellitol has been synthesized from 5,6-enoglucoside efficiently. The carbacyclic skeleton was constructed through a Ferrier reaction mediated by PdCl2. The regioselectivity on the oxirane ring opening with Mes2BCH2Li at the key step is found to be controlled by the hydroxy protecting group.

Total Synthesis of (−)-Tetrodotoxin from d-Glucose: A New Route to Multi-Functionalized Cyclitol Employing the Ferrier(II) Reaction toward (−)-Tetrodotoxin

Abstract Total synthesis of (−)-tetrodotoxin (TTX) from d-glucose is described. As a critical transformation step for synthesizing TTX, a key multi-functionalized cyclitol was prepared from d-glucose employing the Ferrier(II) reaction. Stereospecific introduction of three functionalized branched chains were achieved via Peterson olefination and spiro α-chloroepoxidation of the corresponding carbonyl derivatives.

Spirastrellolide studies. Synthesis of the C(1)–C(25) southern hemispheres of spirastrellolides A and B, exploiting anion relay chemistry

Construction of the C(1)–C(25) southern fragments of both spirastrellolide A and B are described. Highlights of the syntheses include effective use of the three component anion relay chemistry (ARC) tactic recently introduced by our laboratory, a stereoselective spirocyclization via concomitant Ferrier reaction to elaborate the BC spiroketal and use of two dithiane unions to install the A ring as well as C(22)–C(25) fragment. The synthesis proceeded with longest linear sequences of 33 and 32 steps, respectively for spirastrellolide A and spirastrellolide B.