Search

Phosphinooxazoline (PHOX) ligands are an important class of ligands in asymmetric catalysis. We synthesized ten novel D-fructose-derived spiro-fused PHOX ligands with different steric and electronic demand. The application of two of them was tested in asymmetric allylic alkylation. The ligands are prepared in two steps from readily available 1,2-O-isopropylidene protected β-D-fructopyranoses by the BF3·OEt2-promoted Ritter reaction with 2-bromobenzonitrile to construct the oxazoline moiety followed by Ullmann coupling of the resulting aryl bromides with diphenylphosphine. Both steps proceeded mostly in good to high yields (57–86% for the Ritter reaction and 35–89% for the Ullmann coupling). The Ritter reaction gave two anomers, which could be separated by column chromatography. The prepared ligands showed promising results (er of up to 84:16) in Tsuji–Trost reactions with diphenylallyl acetate as model substrate.

The title new reducing disaccharide (12) was synthesized starting from 1, 6-anhydro-β-lactose. Selective benzoylation of 1, 6-anhydro-4', 6'-O-benzylidene-β-lactose with 4 molar equivalents of benzoyl chloride in pyridine afforded the corresponding 2, 3, 3'-tri-O-benzoate (3) in 41% yield. Sulfonylation of 3 gave 2'-O-mesylate (4) or 2'-O-tosylate (6). Treatment of 4 or 6 with 1.1 molar equivalents of sodium methoxide in boiling MeOH yielded 1, 6-anhydro-4-O-(2, 3-anhydro-4, 6-O-benzylidene-β-D-talopyranosyl)-β-D-glucopyranose (7) in 50 or 66% yield. Further crop of 7 was isolated from the filtrate of 7 as the corresponding diacetate. Heating of a mixture of 7 with excess aq. KOH at 100° for 3 hr cleaved the epoxide ring of 7 trans-diaxially and, after acetylation, 2, 3-di-O-acetyl-1, 6-anhydro-4-O-(2, 3-di-O-acetyl-4, 6-O-benzylidene-β-D-idopyranosyl)-β-D-glucopyranose (9) was isolated in 84% yield. Debenzylidenation of 9 followed by acetylation, and subsequent opening of the 1, 6-anhydro-β-ring with titanium tetrachloride in CHCl3, then treatment with mercuric acetate in glacial AcOH, afforded 1, 2, 3-tri-O-acetyl-4-O-(2, 3, 4, 6-tetra-O-acetyl-β-D-idopyranosyl)-β-D-glucopyranose (11) in 43% yield. Deacetylation of 11 afforded the title compound (12) as a hygroscopic, amorphous powder which gave the crystalline tosylhydrazone.