Copper(I)-Catalyzed Dehydrative C-Glycosidation of Unprotected Pyranoses with Ketones

Abstract

We developed a copper­(I)-catalyzed diastereoselective incorporation of ketones into unprotected pyranoses. The reactivity was dependent on the bite angle of the diphosphine ligand in the copper catalyst, and we identified an achiral diphosphine ligand L1 bearing an exceptionally large bite angle as the optimal ligand. A copper­(I)-conjugated Brϕnsted base catalyst containing ligand L1 enabled the C–C bond-forming reaction via in situ-generated copper­(I) enolate, even in the presence of multiple unprotected hydroxy groups. A variety of ketones were introduced with high diastereoselectivity. The product 2,6-cis-pyrans has many applications for the synthesis of biologically active molecules.

Recent Advances in the Chemical Synthesis of C-Glycosides

“…496,497 Recently, Cu(I)-catalyzed dehydrative Cglycosylation of unprotected 2-deoxy sugar 585 with acetophenone 586 in the presence of diphosphine ligand L1 was reported to give C-glycoside 587 in quantitative yield with excellent βselectivity (β/α > 20:1). 498 As an example of the synthesis of Cglycosides between unprotected aldoses and amines through Amadori rearrangement, D-glycero-D-gulo-heptose 588 was reacted with benzyl amine 589 in a mixture of acetic acid and ethanol to produce α-C-glucoside 590 in high yield (95%). 499−502 9.…”

“… − Coupling of glucose 566 with pentane-2,4-dione 568 in the presence of sodium bicarbonate proceeded through Knoevenagel reaction and intramolecular Michael cyclization to give β- C -glucoside 569 in excellent yield. ,, Reactions of other types of unprotected sugar lactols such as 2-acetamido sugars, heptoses, xylose, and galactose with C -nucleophiles such as 1,3-dicarbonyl compounds and 1,3-oxazine-2-thiones in the presence of base (NaHCO 3 , Na 2 CO 3 , NaH, or KOH) or Lewis acid (InCl 3 , CoCl 2 ) also afforded the corresponding C -pyrano- or C -furanoglycosides in good yields with high β-stereoselectivities. ,− As an example of Sc­(OTf) 3 -promoted C -glycosylation of unprotected sugar lactols with aryl compounds, direct glycosylation of glucose 566 with 570 gave β- C -aryl glycoside 571 (65%). − Horner–Wadsworth–Emmons reaction of lactose 572 with β-ketophosphonate 573 under basic conditions provided β- C -glucoside 574 (67%). , Aldol reaction of d -deoxyribose 575 with acetoacetic ester 576 catalyzed by i Pr 2 NEt and 2-pyridone led to hemiketal 577 with high diastereoselectivity (45%, dr > 49:1) . Under the promotion of l -proline and DBU, the Knoevenagel–Michael cascade reaction of d -ribose 578 with dimethyl 3-oxoglutarate 579 gave C -glycoside 580 (86%, dr > 49:1), whereas the aldol-Michael reaction of 578 with acetone 581 provided a mixture of α- and β- C -glycosides 582 and 583 and the hemiketal 584 in a 69% overall yield. − Other amine-mediated aldol-Michael reactions of unprotected ketoses or 2- N -acyl-aldohexoses with acetone 581 have also been reported for the synthesis of C -glycosides. , Recently, Cu­(I)-catalyzed dehydrative C -glycosylation of unprotected 2-deoxy sugar 585 with acetophenone 586 in the presence of diphosphine ligand L1 was reported to give C -glycoside 587 in quantitative yield with excellent β-selectivity (β/α > 20:1) . As an example of the synthesis of C -glycosides between unprotected aldoses and amines through Amadori rearrangement, d - glycero - d - gulo -heptose 588 was reacted with benzyl amine 589 in a mixture of acetic acid and ethanol to produce α- C -glucoside 590 in high yield (95%). − …”

Homogeneous Catalysis: A Powerful Technology for the Modification of Important Biomolecules

“…[51] Ac opper(I)-catalyzed highly diastereoselective approach for the attachment of ketones 57 to unprotected sugars 56 for the synthesis of b-selective alkyl glycosides 58 was developed by Kanai and co-workers (Scheme 15). [52] The reactivity and high nucleophilicity of in-situ-generated Cu I enolates was attributedt ot he use of an achiral diphosphine ligand (L)w ith an unusually large "bite" angle. Interestingly,t he free hydroxy groups in the sugar moiety were well-tolerated.…”

C-Glycosidation of Unprotected Aldopentoses with Ketones Using Proline-Triethylamine as Catalyst

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Reactions of unprotected aldopentoses with ketones catalyzed by proline and triethylamine that afford C-glycoside derivatives are described.C-Glycoside derivatives are important as bioactives, probes, and other functional molecules. [1][2][3][4][5] C-Glycosidation reactions have often been performed on preactivated forms of carbohydrates with protected hydroxy groups or on specific precursors bearing functional groups for the bond-formation at

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“…[6][7][8][9][10] Recently, C-glycosidation reactions of unprotected carbohydrates with ketones other than β-diketones have been developed. [1][2][3][4] For example, we have reported direct C-glycosidation reactions of unprotected di-and trisaccharides with ketones that afford functionalized C-glycoside ketones using pyrrolidine-boric acid catalysis under mild conditions. 4 We have also reported C-glycosidation reactions of 2-N-acyl-aldohexoses with ketones using amine-based catalyst systems.…”