NOVEL TRICYCLIC CHIRAL COMPOUNDS AND THEIR USE IN ASYMMETRIC CATALYSIS

• US 20110269972A1
• Filed: 09/03/2009
• Published: 11/03/2011
• Est. Priority Date: 09/03/2008
• Status: Active Grant

• Current Assignee: Nanyang Technological University
• Original Assignee: Nanyang Technological University
• Inventors: Xiao, Jian, Loh, Teck Peng
• Granted Patent: US 9,206,090 B2
• Time in Patent Office: Days
• US Class Current: 548/429
• CPC Class Codes: C07B 53/00 Asymmetric syntheses
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention relates to a compound of general Formula (XX), its formation and its use in asymmetric catalysis. In Formula (XX) R and R³¹ are independently —COOR³, —R⁴COOR³, —R⁴CHO, —R⁴COR³, —R⁴CONR⁵R⁶, —R⁴COX, —R⁴OP(═O)(OH)₂, —R⁴P(═O)(OH)₂), —R⁴C(O)C(R³)CR⁵R⁶ and —R⁴CO₂COR³. In addition, R³¹ may also be hydrogen. R³, R⁵ and R⁶ are independently hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group or an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si. R⁴ an aliphatic bridge with a main chain having 1 to about 20 carbon atoms, an alicyclic bridge, an aromatic bridge, an arylaliphatic bridge or an arylalicyclic bridge, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si, and X is halogen. In Formula (XX) R³⁰ is —C(OH)R¹R² or —COOR¹⁴, wherein R¹, R² and R¹⁴ are independently hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group or an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si.

Claims

1-40. -40. (canceled)

41. A hexahydropyrrolo[2,3-b]indole compound of Formula (XX)

42. The compound of claim 41, wherein R³⁰ is —

COOR¹⁴, R¹⁴ being alkyl or a protecting group that is removable in the presence of R by hydrogenolysis1.

43. A hexahydropyrrolo[2,3-b]indole compound of Formula (VII)

44. The compound of claim 43 wherein R¹ and R² are identical.

45. A compound of Formula (VIII)

47. The compound of claim 45, wherein the metal M is selected from the group consisting of Boron, Aluminum, Zinc, Tin, Titanium, Zirconium, Indium, Copper, Iridium, and Lanthanum.

46. A compound of Formula (IX)

48. The compound of claim 46, wherein the metal M is selected from the group consisting of Boron, Aluminum, Zinc, Tin, Titanium, Zirconium, Indium, Copper, Iridium, and Lanthanum.

49. A compound of Formula (VI)

52. The compound of claim 49, wherein R⁹ is (C₁-C₁₀) alkyl.

50. A compound of Formula (IV)

51. The compound of claim 50, wherein Y is removable by hydrogenolysis.

53. The compound of claim 50, wherein R⁹ is (C₁-C₁₀) alkyl.

54. A compound of Formula (IVA)

55. The compound of claim 54, wherein Y is removable by hydrogenolysis.

56. The compound of claim 54, wherein R is aryl-methylenyl.

57. The compound of 50, wherein the nitrogen protecting group Y is one of alkoxycarbonyl, benzhydryl, trifluoroacetyl, t-butoxycarbonyl, a carbamate, an amide, a cyclic imide, an N-Alkyl amine, an N-Aryl amine, an imine, and an enamine

58. The compound of 54, wherein the nitrogen protecting group Y is one of alkoxycarbonyl, benzhydryl, trifluoroacetyl, t-butoxycarbonyl, a carbamate, an amide, a cyclic imide, an N-Alkyl amine, an N-Aryl amine, an imine, and an enamine

59. A compound of Formula (VIA)

60. A method of preparing a compound of Formula (VI)

61. The method of claim 60, wherein providing the compound of Formula (IV) comprises:

contacting a compound of Formula (III)

74. The method of claim 61, wherein the compound of Formula (III) is prepared by a process that comprises an acid catalyzed cyclization of an Na-protected-tryptophan alkyl ester.

62. A method of forming a compound of Formula (VIA)

63. The method of claim 62, wherein R¹⁰ is aryl-methylenyl.

64. The method of claim 62, wherein providing the compound of Formula (IVA) comprises contacting a compound of Formula (IIIA)

75. The method of claim 64, wherein the compound of Formula (IIIA) is prepared by a process that comprises an acid catalyzed cyclization of an Na-protected-tryptophan alkyl ester.

65. A method of preparing a compound of Formula (VII)

66. The method of claim 65, wherein R¹ and R² are identical.

67. A method of preparing a compound of Formula (IV)

70. The method of claim 67, wherein the nitrogen protecting group Y is one of alkoxycarbonyl, benzhydryl, trifluoroacetyl, t-butoxycarbonyl, a carbamate, an amide, a cyclic imide, an N-Alkyl amine, an N-Aryl amine, an imine, and an enamine.

72. The method of claim 67, wherein the alkali base is sodium carbonate.

76. The method of claim 67, wherein the compound of Formula (III) is prepared by a process that comprises an acid catalyzed cyclization of an Na-protected-tryptophan alkyl ester.

68. A method of preparing a compound of Formula (IVA)

69. The method of claim 68, wherein R¹⁰ is aryl-methylenyl

71. The method of claim 68, wherein the nitrogen protecting group Y is one of alkoxycarbonyl, benzhydryl, trifluoroacetyl, t-butoxycarbonyl, a carbamate, an amide, a cyclic imide, an N-Alkyl amine, an N-Aryl amine, an imine, and an enamine.

73. The method of claim 68, wherein the alkali base is sodium carbonate.

77. The method of claim 68, wherein the compound of Formula (IIIA) is prepared by a process that comprises an acid catalyzed cyclization of an Na-protected-tryptophan alkyl ester.

78. A method of preparing a compound of Formula (VIII)

80. The method of claim 78, wherein the metal compound M is selected from the group consisting of BH₃, B₂H₆, B₅H₉, B₁₀H₁₄, AlCl₃, ZnCl₂, Zn(OTf)₂, ZnEt₂, SnCl₂, TiCl₄, Ti(Oi-Pr)₄, Cp₂TiCl₂, ZrCl₄, Cp₂ZrCl₂, InCl₃, In(OTf)₃, Cu(OAc)₂, (IrCp*Cl₂)₂, (Ir(COD)Cl)₂, LnCl₃, and LnCp₂Cl₂.

79. A method of preparing a compound of Formula (IX)

81. The method of claim 79, wherein the metal compound M is selected from the group consisting of BH₃, B₂H₆, B₅H₉, B₁₀H₁₄, AlCl₃, ZnCl₂, Zn(OTf)₂, ZnEt₂, SnCl₂, TiCl₄, Ti(Oi-Pr)₄, Cp₂TiCl₂, ZrCl₄, Cp₂ZrCl₂, InCl₃, In(OTf)₃, Cu(OAc)₂, (IrCp*Cl₂)₂, (Ir(COD)Cl)₂, LnCl₃, and LnCp₂Cl₂.