Novel strategies for the preparation of aminocarbasugar analogues: syntheses of N-substituted aminocyclitols from d-mannose

Two strategies, based on the Pd-catalyzed allylic amination and the epoxidation-nucleophilic opening, have been described for the preparation of aminocarbasugar analogues from an exo-methylene cyclohexane derivative readily accessible in five steps from d-mannose by 6-exo-dig-radical cyclization as the key transformation.

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2-Phenethyl-((3aR,5aS,9aR,9bR)-2,2,8,8-tetramethyl-5a,6,9a,9b-tetrahydro-3aH-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-5-ylmethyl)-amineC22H31NO4Ee = 100%[α]D25=+42.3 (c 0.50, CHCl3)Source of chirality: starting materialAbsolute configuration: l

2-[((3aR,5aS,9aR,9bR)-2,2,8,8-Tetramethyl-5a,6,9a,9b-tetrahydro-3aH-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-5-ylmethyl)-amino]-propan-1-olC17H29NO5Ee = 100%[α]D25=+52.3 (c 0.51, CHCl3)Source of chirality: starting materialAbsolute configuration: l

(1-Phenethyl)-((3aR,5aS,9aR,9bR)-2,2,8,8-tetramethyl-5a,6,9a,9b-tetrahydro-3aH-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-5-ylmethyl)-amineC22H31NO4Ee = 100%[α]D25=+72.6 (c 0.82, CHCl3)Source of chirality: starting materialAbsolute configuration: l

1-((3aR,5aS,9aR,9bR)-2,2,8,8-Tetramethyl-5a,6,9a,9b-tetrahydro-3aH-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-5-ylmethyl)-pyrrolidineC18H29NO4Ee = 100%[α]D25=+36.1 (c 0.64, CHCl3)Source of chirality: starting materialAbsolute configuration: l

4-Benzyl-1-((3aR,5aS,9aR,9bR)-2,2,8,8-tetramethyl-5a,6,9a,9b-tetrahydro-3aH-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-5-ylmethyl)-piperidineC26H37NO4Ee = 100%[α]D25=+27.3 (c 0.49, CHCl3)Source of chirality: starting materialAbsolute configuration: l

1-Benzyl-4-((3aR,5aS,9aR,9bR)-2,2,8,8-tetramethyl-5a,6,9a,9b-tetrahydro-3aH-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-5-ylmethyl)-piperazineC26H36N2O4Ee = 100%[α]D25=+26.7 (c 0.94, CHCl3)Source of chirality:starting materialAbsolute configuration:l

1-(2-Methoxy-phenyl)-4-((3aR,5aS,9aR,9bR)-2,2,8,8-tetramethyl-5a,6,9a,9b-tetrahydro-3aH-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-5-ylmethyl)-piperazineC25H36N2O5Ee = 100%[α]D25=+27.4 (c 1.2, CHCl3)Source of chirality:starting materialAbsolute configuration:l

4-((3aR,5aS,9aR,9bR)-2,2,8,8-Tetramethyl-5a,6,9a,9b-tetrahydro-3aH-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-5-ylmethyl)-morpholineC18H29NO5Ee = 100%[α]D25=+28.1 (c 0.39, CHCl3)Source of chirality:starting materialAbsolute configuration:l

(3aR,4R,5aS,9aR,9bS)-2,2,8,8-Tetramethyl-5-methylene-hexahydro-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-4-olC14H22O5Ee = 100%[α]D25=+199.7 (c 0.7, CHCl3)Source of chirality:starting materialAbsolute configuration:l

(3aR,4R,5R,5aS,9aR,9bS)-epoxy 2,2,8,8-Tetramethyl-5-methylene-hexahydro-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-4-olC14H22O6Ee = 100%[α]D25=+111.4 (c 1.38, CHCl3)Source of chirality:starting materialAbsolute configuration:l

(3aR,4R,5aS,9aR,9bS)-epoxy 2,2,8,8-Tetramethyl-5-methylene-hexahydro-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxin-4-olC14H22O6Ee = 100%[α]D25=+94.8 (c 1.09, CHCl3)Source of chirality: starting materialAbsolute configuration: l

(3aR,4S,5R,5aS,9aR,9bS)-2,2,8,8-Tetramethyl-5-(phenethylamino-methyl)-hexahydro-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxine-4,5-diolC22H33NO6Ee = 100%[α]D25=+30.2 (c 0.99, CHCl3)Source of chirality: starting materialAbsolute configuration: l

(3aR,4S,5S,5aS,9aR,9bS)-2,2,8,8-Tetramethyl-5-(phenethylamino-methyl)-hexahydro-[1,3]dioxolo[4′,5′:3,4]benzo[1,2-d][1,3]dioxine-4,5-diolC22H33NO6Ee = 100%[α]D25=+16.2 (c 0.8, CHCl3)Source of chirality: starting materialAbsolute configuration: l