Method for preparing amine compounds based on novel catalytic curtius rearrangement reaction

Abstract

The invention prepares amine compounds based on novel catalytic Curtius rearrangement reaction. Transition metal catalyzed sp 2 C‑N bond formation is an efficient method for the synthesis of arylamines, catalyzing sp 3 The coupling reaction of C-N bond is also reported from time to time, but at the same time, sp 2 and sp 3 Methods for C‑N bond generation are relatively underdeveloped. The present invention uses resource-rich organic carboxylic acids as carbon sources and easily prepared alkane / aryloxyacyl azides as nitrogen sources, at as low as 0.1 mol% of DMAP and Cu(OAc) 2 Under catalysis, with gas N 2 and CO 2 One-pot generation of protected alkyl, alkenyl, and aryl amines as the only by-product. The reaction can be applied to the late functionalization of natural products and drug molecules, the synthesis of chiral alkylamines, and the rapid construction of different ureas and primary amines. Mechanistic studies reveal that the reaction proceeds through a cascade of carboxylic acid activation, azidation, Curtius rearrangement, and nucleophilic addition.

Description

technical field

[0001] The invention relates to the construction of C-N bonds, in particular to a method for generating alkyl, alkenyl and arylamines based on catalytic decarboxylation to construct C-N bonds. Background technique

[0002] Nitrogen-containing compounds widely exist in alkaloids, amino acids, functional materials and natural products, and are closely related to life science, material science and human health, so the construction of C-N bonds is very important in organic synthesis.

[0003] Since 1990, great progress has been made in the field of transition metal-catalyzed C-N bond coupling, such as copper-catalyzed Ullmann reaction, palladium-catalyzed Buchwald-Hartwig amination reaction and Chan-Lam amination reaction, etc., but these reactions are generally limited to sp 2 Construction of C-N bonds. while sp 3 The construction of C-N bonds mainly relies on traditional methods, such as nitrogen nucleophilic substitution, the Mitsunobu reaction of alcohol...

Examples

Embodiment 1

[0053] Preparation of 2,2,2-trichloroethyl-((1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-)methyl)carbamate ester

[0054] The target product passes through the reaction process and post-processing. Purification by column chromatography afforded 94.0 mg of the target product (93% isolated yield).

[0055] 1 H NMR (400MHz, Chloroform-d) δ7.64(d, J=8.5Hz, 2H), 7.49(d, J=8.4Hz, 2H), 7.03(d, J=2.5Hz, 1H), 6.81(d ,J=9.0Hz,1H),6.66(dd,J=9.1,2.6Hz,1H),5.25(t,J=5.5Hz,1H),4.76(s,2H),4.53(d,J=5.5Hz ,2H),3.81(s,3H),2.42(s,3H); 13 C NMR (101MHz, Chloroform-d) δ168.4, 156.2, 154.7, 139.6, 136.5, 133.7, 131.3, 131.0, 129.9, 129.3, 115.6, 115.1, 112.1, 101.3, 95.7, 74.7, 55.8, 35.4, 13.2; )v 3344, 2929, 1732, 1682, 1591, 1478, 1221, 1045, 811, 721cm -1 ; HRMS (ESI) Calcd.for C21 h 18 Cl 4 N 2 o 4 Na[M+Na] + 524.9913,found 524.9908.

Embodiment 2

[0057] Preparation of 2,2,2-trichloroethyl((R)-3-((3R,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl Hexadecylhydro-1H-cyclopenta[a]phenanthrene-17-)butyl)carbamate

[0058]

[0059] The target product passes through the reaction process and post-processing. Purification by column chromatography afforded 93.2 mg of the target product (87% isolated yield).

[0060] 1 H NMR (400MHz, Chloroform-d) δ4.95(t, J=6.1Hz, 1H), 4.72(s, 2H), 3.84(q, J=3.0Hz, 1H), 3.49–3.42(m, 1H) ,3.34–3.26(m,1H),3.21–3.12(m,1H),2.19(q,J=12.7Hz,1H),2.00–1.94(m,2H),1.92–1.86(m,1H),1.84 –1.78(m,2H),1.72–1.59(m,4H),1.52–1.45(m,6H),1.41–1.33(m,3H),1.31–1.09(m,7H),0.97(d,J= 6.6Hz, 4H), 0.90(s, 3H), 0.65(s, 3H); 13 C NMR (101MHz, Chloroform-d) δ154.6, 95.9, 74.6, 72.1, 68.6, 56.1, 50.6, 42.9, 41.6, 40.0, 39.7, 39.5, 39.0, 36.0, 35.4, 35.2, 34.8, 33.9, 32.9, 30.8 ,28.5,23.8,22.9,20.7,18.7,11.9; IR (neat) v3445,3347,2932,2867,2133,1715,1520,1251,1141,731cm -1 ; HRMS (ESI) Calcd.for C 26 h 42 C...

Embodiment 3

[0062] Preparation of 2,2,2-trichloroethyl(4-(N,N-dipropylsulfamoyl)phenyl)carbamate

[0063]

[0064] The target product passes through the reaction process and post-processing. Purification by column chromatography afforded 67.8 mg of the target product (79% isolated yield). 1 H NMR (400MHz, Chloroform-d) δ7.77 (d, J = 8.7Hz, 2H), 7.57 (d, J = 8.7Hz, 2H), 7.29 (brs, 1H), 4.84 (s, 2H), 3.08 –3.04(m,4H),1.59–1.50(m,4H),0.86(t,J=7.4Hz,6H); 13 C NMR (101MHz, Chloroform-d) δ151.4, 140.9, 135.3, 128.6, 118.6, 95.1, 74.8, 50.2, 22.1, 11.3; IR (neat) v3319, 2966, 1751, 1596, 1533, 1207, 1151, 590cm -1 ; HRMS (ESI) Calcd.for C 15 h 22 Cl 3 N 2 o 4 S[M+H] + 431.0361,found 431.0362.

technical field

[0001] The invention relates to the construction of C-N bonds, in particular to a method for generating alkyl, alkenyl and arylamines based on catalytic decarboxylation to construct C-N bonds. Background technique

[0002] Nitrogen-containing compounds widely exist in alkaloids, amino acids, functional materials and natural products, and are closely related to life science, material science and human health, so the construction of C-N bonds is very important in organic synthesis.

[0003] Since 1990, great progress has been made in the field of transition metal-catalyzed C-N bond coupling, such as copper-catalyzed Ullmann reaction, palladium-catalyzed Buchwald-Hartwig amination reaction and Chan-Lam amination reaction, etc., but these reactions are generally limited to sp 2 Construction of C-N bonds. while sp 3 The construction of C-N bonds mainly relies on traditional methods, such as nitrogen nucleophilic substitution, the Mitsunobu reaction of alcohol...

Examples

Embodiment 1

[0053] Preparation of 2,2,2-trichloroethyl-((1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-)methyl)carbamate ester

[0054] The target product passes through the reaction process and post-processing. Purification by column chromatography afforded 94.0 mg of the target product (93% isolated yield).

[0055] 1 H NMR (400MHz, Chloroform-d) δ7.64(d, J=8.5Hz, 2H), 7.49(d, J=8.4Hz, 2H), 7.03(d, J=2.5Hz, 1H), 6.81(d ,J=9.0Hz,1H),6.66(dd,J=9.1,2.6Hz,1H),5.25(t,J=5.5Hz,1H),4.76(s,2H),4.53(d,J=5.5Hz ,2H),3.81(s,3H),2.42(s,3H); 13 C NMR (101MHz, Chloroform-d) δ168.4, 156.2, 154.7, 139.6, 136.5, 133.7, 131.3, 131.0, 129.9, 129.3, 115.6, 115.1, 112.1, 101.3, 95.7, 74.7, 55.8, 35.4, 13.2; )v 3344, 2929, 1732, 1682, 1591, 1478, 1221, 1045, 811, 721cm -1 ; HRMS (ESI) Calcd.for C21 h 18 Cl 4 N 2 o 4 Na[M+Na] + 524.9913,found 524.9908.

Embodiment 2

[0057] Preparation of 2,2,2-trichloroethyl((R)-3-((3R,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl Hexadecylhydro-1H-cyclopenta[a]phenanthrene-17-)butyl)carbamate

[0058]

[0059] The target product passes through the reaction process and post-processing. Purification by column chromatography afforded 93.2 mg of the target product (87% isolated yield).

[0060] 1 H NMR (400MHz, Chloroform-d) δ4.95(t, J=6.1Hz, 1H), 4.72(s, 2H), 3.84(q, J=3.0Hz, 1H), 3.49–3.42(m, 1H) ,3.34–3.26(m,1H),3.21–3.12(m,1H),2.19(q,J=12.7Hz,1H),2.00–1.94(m,2H),1.92–1.86(m,1H),1.84 –1.78(m,2H),1.72–1.59(m,4H),1.52–1.45(m,6H),1.41–1.33(m,3H),1.31–1.09(m,7H),0.97(d,J= 6.6Hz, 4H), 0.90(s, 3H), 0.65(s, 3H); 13 C NMR (101MHz, Chloroform-d) δ154.6, 95.9, 74.6, 72.1, 68.6, 56.1, 50.6, 42.9, 41.6, 40.0, 39.7, 39.5, 39.0, 36.0, 35.4, 35.2, 34.8, 33.9, 32.9, 30.8 ,28.5,23.8,22.9,20.7,18.7,11.9; IR (neat) v3445,3347,2932,2867,2133,1715,1520,1251,1141,731cm -1 ; HRMS (ESI) Calcd.for C 26 h 42 C...

Embodiment 3

[0062] Preparation of 2,2,2-trichloroethyl(4-(N,N-dipropylsulfamoyl)phenyl)carbamate

[0063]

[0064] The target product passes through the reaction process and post-processing. Purification by column chromatography afforded 67.8 mg of the target product (79% isolated yield). 1 H NMR (400MHz, Chloroform-d) δ7.77 (d, J = 8.7Hz, 2H), 7.57 (d, J = 8.7Hz, 2H), 7.29 (brs, 1H), 4.84 (s, 2H), 3.08 –3.04(m,4H),1.59–1.50(m,4H),0.86(t,J=7.4Hz,6H); 13 C NMR (101MHz, Chloroform-d) δ151.4, 140.9, 135.3, 128.6, 118.6, 95.1, 74.8, 50.2, 22.1, 11.3; IR (neat) v3319, 2966, 1751, 1596, 1533, 1207, 1151, 590cm -1 ; HRMS (ESI) Calcd.for C 15 h 22 Cl 3 N 2 o 4 S[M+H] + 431.0361,found 431.0362.

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