Synthesis of Three New Bifunctional Glucose-Thiourea Organocatalysts and Their Application in Asymmetric <i>Michael</i> Addition

Abstract

ABSTRACT. Three new glucose-based asymmetric bifunctional organocatalysts containing a 6-aminopyridyl or a 6-methylpyridyl or a cinchona unit were synthesized. Asymmetric Michael addition of pentane-2,4-dione to β-nitrostyrene was catalyzed successfully by these catalysts. In case of the cinchona based glucose-thiourea derivate the S enantiomer of the corresponding Michael adduct was formed with moderate enantiomeric excess in three different solvents.

Synthesis and Applications of Carbohydrate-Based Organocatalysts

“…to give the axial glycosyl bromide as a single anomer (85% yield for the mannose derivative [ 31 ]). A lower yield (69%) was reported [ 33 ] for the bromination of peracetylated glucose using a solution of HBr in acetic acid as described by Deniaud and co-workers [ 34 ].…”

“…Anomeric sugar isothiocyanates were prepared from the corresponding glycosyl bromides by nucleophilic substitution with thiocyanate ion ( Scheme 1 ). The starting carbohydrate can be acetylated with acetic anhydride in pyridine at room temperature to give a mixture of anomers (93% for d -mannose [ 31 ]) or by heating at 100 °C with acetic anhydride in the presence of sodium acetate ( d -mannose 99%, d -lactose 95%, d -galactose 47%, [ 32 ]; and d -glucose 89% [ 33 ]). The bromination was performed by treatment of the sugar acetate with phosphorus bromide in the presence of water (six equiv.)…”

“…The glucosyl thiourea organocatalyst 51 containing a cinchona alkaloid unit ( Scheme 13 ) was also tested in the Michael reaction of pentane-2,4-dione to β-nitrostyrene [ 33 ]. The addition product was obtained in 40–42% yield and 59–64% ee , depending on the solvent used.…”