2,2′-Bipyridine-3,3′-dicarboxylic carbohydrate esters and amides. Synthesis and preliminary evaluation as ligands in Cu(II)-catalysed enantioselective electrophilic fluorination

A series of 10 new carbohydrate-substituted bipyridines were prepared from 2,2′-bipyridine-3,3′-dicarboxylic acid, itself easily available from ortho-phenanthroline. As a preliminary exploration of their use as chiral ligands, Cu(II)-catalysed asymmetric electrophilic fluorination of model β-ketoesters using these simple and easily accessible chiral bipyridines was studied. Only modest enantioselectivity was observed in this reaction, although the ee was in a similar range as those provided by known and more elaborate ligands.

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Bis(3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-glucofuranos-3-yl)-2,2′-bipyridine-3,3′-dicarboxylateC36H44N2O14Ee = 100 %[α]D = −67 (c 0.5, CHCl3)Source of chirality: α-d-glucofuranoside

Bis(3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranos-3-yl)-2,2′-bipyridine-3,3′-dicarboxylateC36H44N2O14Ee = 100 %[α]D = +138 (c 0.5, CHCl3)Source of chirality: α-d-allofuranoside

Bis(1-deoxy-2,3:4,5-di-O-isopropylidene-β-d-fructopyranos-1-yl)-2,2′-bipyridine-3,3′-dicarboxylateC36H44N2O14Ee = 100 %[α]D = −12 (c 0.5, CHCl3)Source of chirality: β-d-fructopyranoside

Bis(5-deoxy-1-O-methyl, 2,3-O-isopropylidene-β-d-ribofuranos-5-yl)-2,2′-bipyridine-3,3′-dicarboxylateC30H36N2O12Ee = 100 %[α]D = −45 (c 0.5, CHCl3)Source of chirality: β-d-ribofuranoside

Bis(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl)-2,2′-bipyridine-3,3′-dicarboxylateC36H44N2O14Ee = 100 %[α]D = −46 (c 0.5, CHCl3)Source of chirality: α-d-galactopyranoside

Bis[(2R,5S)-5-methyl-2-(1-methylethyl)cyclohexyl]-2,2′-bipyridine-3,3′-dicarboxylateC32H44N2O4Ee = 100 %[α]D = −50 (c 0.5, CHCl3)Source of chirality: (−) menthol

N,N′- bis-(1-deoxy-2,3:4,5-di-O-isopropylidene-β-d-fructopyranos-1-yl)-2,2′-bipyridine-3,3′-carboxamideC36H47N4O12Ee = 100 %[α]D = −31 (c 1.0, CHCl3)Source of chirality: β-d-fructopyranoside

N,N′-bis-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl)-2,2′-bipyridine-3,3′-carboxamideC36H47N4O12Ee = 100 %[α]D = −19 (c 0.5, CHCl3)Source of chirality: α-d-galactopyranoside

N,N′- bis-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-d-glucopyranos-1-yl)-2,2′-bipyridine-3,3′-carboxamideC40H47N4O20Ee = 100 %[α]D = +30 (c 0.5, CHCl3)Source of chirality: -β-d-glucopyranoside

N,N′-bis-(3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranos-1-yl)-2,2′-bipyridine-3,3′-carboxamideC36H46N4O12Ee = 100 %[α]D = +48 (c 0.5, CHCl3)Source of chirality: α-d-allofuranoside

N,N′- bis-(3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-glucofuranos-1-yl)-2,2′-bipyridine-3,3′-carboxamideC36H46N4O12Ee = 100 %[α]D = −39 (c 0.5, CHCl3)Source of chirality: α-d-glucofuranoside