Synthesis of optically active polycyclic N-heterocycles derived from l-prolinamine1. Issue 8 (30th April 2015)

• Record Type: Journal Article
• Authors: Wróblewska, Aneta; Mlostoń, Grzegorz; Heimgartner, Heinz
• Is Part Of: Tetrahedron, asymmetry. Volume 26:Issue 8/9(2015)
• Page Start: 505
• Page End: 509
• Publication Date: 2015-04-30
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2015.03.005
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: The N -Boc-protected ( S )-prolinamine reacts readily with formaldehyde and diverse α-hydroxyimino ketones to give imidazole N -oxides with an enantiomerically pure N -protected (pyrrolidin-2-yl)methyl substituent. Subsequent deprotection yields the corresponding NH derivatives. Upon treatment of these products with Ac2 O at room temperature, a cascade of reactions leads to optically active tricyclic products. In all these processes, the stereogenic center is preserved. In one case, the bis-heterocyclic imidazole N -oxide was transformed into the corresponding optically active imidazole-2-thione via a sulfur-transfer reaction with 2, 2, 4, 4-tetramethylcyclobutane-1, 3-dithione. Abstract : 1-{[(2 S )- N -Boc-pyrrolidin-2-yl]methyl}-4, 5-diphenyl-1 H -imidazole 3-oxide: C25 H29 N3 O3 Ee = 100% [ α ]D 25 = −8 ( c 0.625, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : 1-{[(2 S )- N -Boc-pyrrolidin-2-yl]methyl}-4, 5-dimethyl-1 H -imidazole 3-oxide: C15 H25 N3 O3 Ee = 100% [ α ]D 25 = −24 ( c 0.5, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : 1-{[(2 S )- N -Boc-pyrrolidin-2-yl]methyl}-4-methyl-5-phenyl-1 H -imidazole 3-oxide: C20 H27 N3 O3 Ee = 100% [ α ]D 25 = +99 ( c 0.25, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : N -Phenyl-1-{[(2 S )- N -Boc-pyrrolidin-2-yl]methyl}-5-methyl-1 H -imidazole-4-carboxamide 3-oxide: C21 H28 N4 O4 Ee = 100% [ α ]D 25 = −12 ( c 0.55, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : {[(2 S )-Pyrrolidin-2-yl]methyl}-4, 5-diphenyl-1 H -imidazole 3-oxide: C20 H21 N3 O Ee = 100% [ α ]D 25 = +81 ( c 0.5, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : {[(2 S )-Pyrrolidin-2-yl]methyl}-4, 5-dimethyl-1 H -imidazole 3-oxide: C10 H17 N3 O Ee = 100% [ α ]D 25 = +53 ( c 0.25, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : {[(2 S )-Pyrrolidin-2-yl]methyl}-4-methyl-5-phenyl-1 H -imidazole 3-oxide: C15 H19 N3 O Ee = 100% [ α ]D 25 = +58 ( c 0.25, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : N -Phenyl-{[(2 S )-pyrrolidin-2-yl]methyl}-5-methyl-1 H -imidazole-4-carboxamide 3-oxide: C16 H20 N4 O2 Ee = 100% [ α ]D 25 = +28 ( c 1.0, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : N -Phenyl-{[(2 S )-pyrrolidin-2-yl]methyl}-5-methyl-2-thioxo-2, 3-dihydro-1 H -imidazole-4-carboxamide: C16 H20 N4 OS Ee = 100% [ α ]D 25 = +16 ( c 1.0, DMSO) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : (5a S )-2, 3-Diphenyl-5a, 6, 7, 8-tetrahydro-5 H -pyrrolo[1, 2- c ]imidazo[1, 2- a ]imidazole: C20 H19 N3 Ee = 100% [ α ]D 25 = −35 ( c 0.25, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : (5a S )-2, 3-Dimethyl-5a, 6, 7, 8-tetrahydro-5 H -pyrrolo[1, 2- a ]imidazo[1, 2- a ]imidazole: C10 H15 N3 Ee = 100% [ α ]D 25 = −31 ( c 0.4, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : (5a S )-2-Methyl-3-phenyl-5a, 6, 7, 8-tetrahydro-5 H -pyrrolo[1, 2- c ]imidazo[1, 2- a ]imidazole: C15 H17 N3 Ee = 100% [ α ]D 25 = −229 ( c 0.25, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S ) Abstract : N -Phenyl-[(5a S )-3-methyl-5a, 6, 7, 8-tetrahydro-5 H -pyrrolo[1, 2- c ]imidazo[1, 2- a ]imidazole]-2-carboxamide: C16 H18 N4 O Ee = 100% [ α ]D 25 = −86 ( c 0.375, CH2 Cl2 ) Source of chirality: ( S )-proline Absolute configuration: ( S )