CN115232091A - Method for converting amide into alpha-substituted amine compound - Google Patents
Method for converting amide into alpha-substituted amine compound Download PDFInfo
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- CN115232091A CN115232091A CN202110447085.8A CN202110447085A CN115232091A CN 115232091 A CN115232091 A CN 115232091A CN 202110447085 A CN202110447085 A CN 202110447085A CN 115232091 A CN115232091 A CN 115232091A
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- -1 amine compound Chemical class 0.000 title claims abstract description 64
- 238000000034 method Methods 0.000 title claims abstract description 27
- 150000001408 amides Chemical class 0.000 title claims abstract description 21
- 229910052751 metal Inorganic materials 0.000 claims abstract description 55
- 239000002184 metal Substances 0.000 claims abstract description 55
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 239000000654 additive Substances 0.000 claims abstract description 28
- 230000000996 additive effect Effects 0.000 claims abstract description 25
- 239000000126 substance Substances 0.000 claims abstract description 12
- 150000001216 Samarium Chemical class 0.000 claims abstract description 10
- 238000007306 functionalization reaction Methods 0.000 claims abstract description 10
- 150000001225 Ytterbium Chemical class 0.000 claims abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 238000006467 substitution reaction Methods 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 239000003153 chemical reaction reagent Substances 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 229910052769 Ytterbium Inorganic materials 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 229910052772 Samarium Inorganic materials 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 claims description 6
- 125000002524 organometallic group Chemical group 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 150000001336 alkenes Chemical class 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052804 chromium Inorganic materials 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 150000004795 grignard reagents Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 125000001979 organolithium group Chemical group 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- 239000010703 silicon Substances 0.000 claims description 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 1
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims 1
- 239000007787 solid Substances 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000003921 oil Substances 0.000 description 15
- 239000000758 substrate Substances 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 239000000945 filler Substances 0.000 description 10
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- 238000006254 arylation reaction Methods 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 238000010791 quenching Methods 0.000 description 9
- 230000000171 quenching effect Effects 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 239000012467 final product Substances 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- SPPZBAGKKBHZRW-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-naphthalen-2-yl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C=CC=C2)C2=C1 SPPZBAGKKBHZRW-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000005890 dearylation reaction Methods 0.000 description 2
- 238000006392 deoxygenation reaction Methods 0.000 description 2
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229960001705 buclizine Drugs 0.000 description 1
- MOYGZHXDRJNJEP-UHFFFAOYSA-N buclizine Chemical compound C1=CC(C(C)(C)C)=CC=C1CN1CCN(C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)CC1 MOYGZHXDRJNJEP-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- DERZBLKQOCDDDZ-JLHYYAGUSA-N cinnarizine Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C\C=C\C1=CC=CC=C1 DERZBLKQOCDDDZ-JLHYYAGUSA-N 0.000 description 1
- 229960000876 cinnarizine Drugs 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229960001474 meclozine Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004957 naphthylene group Chemical group 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
- FBOUYBDGKBSUES-VXKWHMMOSA-N solifenacin Chemical compound C1([C@H]2C3=CC=CC=C3CCN2C(O[C@@H]2C3CCN(CC3)C2)=O)=CC=CC=C1 FBOUYBDGKBSUES-VXKWHMMOSA-N 0.000 description 1
- 229960003855 solifenacin Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/023—Preparation; Separation; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/60—Preparation of compounds containing amino groups bound to a carbon skeleton by condensation or addition reactions, e.g. Mannich reaction, addition of ammonia or amines to alkenes or to alkynes or addition of compounds containing an active hydrogen atom to Schiff's bases, quinone imines, or aziranes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/24—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to three ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
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Abstract
The invention discloses a method for converting amide into an alpha-substituted amine compound, which uses a mixed system of divalent metal samarium salt and/or metal ytterbium salt, a metal simple substance and a metal additive to promote the direct deoxidation functionalization reaction of the amide compound and convert the amide compound into the alpha-substituted amine compound. The method has simple reaction operation and can be carried out under mild conditions.
Description
Technical Field
The present invention relates to a process for converting amides to alpha-substituted amines.
Background
Amides are common functional groups in organic chemistry, are nitrogen-containing compounds which are under development, and are widely used in fine chemical industry, agricultural chemistry and pharmaceutical industry. The carbonyl carbon of amides is less reactive and its conversion to important amine compounds by deoxy functionalization of the carbonyl group is a long-standing challenge for synthetic chemists. To date, methods involving electrophilic activation and controlled hydride reduction have been reported to achieve amide deoxygenation to build new covalent bonds. Nevertheless, the weak electrophilicity of the carbonyl carbon in the amide often requires strong acids/bases or special amides with directing groups, or multi-step operations, the use of water/air sensitive organometallic reagents, etc., which limits their use to some extent.
In 1992, the first passage through Smi was reported by the N.Sonoda group 2 the/Sm system effects the deoxydimerization of amides, and the authors believe that the reaction system may involve an alpha-amino carbene intermediate (J.Am.chem.Soc.1992, 114, 8729). However, this reaction gives only the dimerized product and is a mixture of cis and trans isomers, with a large proportion of the substrate yield being at a moderate level.
Disclosure of Invention
The invention aims to provide a method for converting amide into an alpha-substituted amine compound and a method for synthesizing a 1, 1-diarylmethylamine compound.
In the present invention, there is provided a method for producing an α -substituted amine compound, which comprises promoting the reaction of an amide compound with an organometallic reagent and C, using a mixed system of a divalent metal samarium salt and/or metal ytterbium salt, a metal simple substance and a metal additive 6-14 Aromatic hydrocarbon, 5-to 10-membered heterocyclic hydrocarbon, 5-to 15-membered heteroaromatic hydrocarbon, C 2-20 Olefins or C 1-20 Alkane is subjected to deoxidation functionalization reaction to obtain an alpha-substituted amine compound,
wherein, the metal simple substance is one or the combination of more than two of Sm, mg, zn, in and Yb;
the metal additive is metal salt and/or complex compound of one or more than two of Pd, rh, ir, ru, ni, ag, cu, fe, co, mn and Cr;
the organometallic reagent is selected from: organoboron reagents, grignard reagents, organolithium reagents, organosilicon reagents.
In another preferred embodiment, the method uses a mixed system of divalent samarium and/or ytterbium metal salt, simple metal and metal additive to promote the amide compound, the organometallic reagent and C 6-14 Aromatic hydrocarbon, 5-to 8-membered heterocyclic hydrocarbon, 5-to 15-membered heteroaromatic hydrocarbon, C 2-6 Olefins or C 1-6 The alkane is subjected to deoxidation functionalization reaction to obtain the alpha-substituted amine compound.
In another preferred example, the method comprises the following steps:
the method uses a mixed system of divalent metal samarium salt and/or metal ytterbium salt, a metal simple substance and a metal additive to promote the deoxidation functionalization reaction of an amide compound 1 and a reaction reagent 2 to obtain an alpha-substituted amine compound 3,
in each formula, LG is selected from: boron groups (such as pinacol borate ester group) and [ MgBr ] in organic boron reagent] + 、[MgCl] + 、Li + Silicon base and hydrogen;
R 1 and FG are each independently selected from: substituted or unsubstituted C 6-14 Aryl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 2-20 Alkenyl, substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted 5-10 membered heterocyclyl; wherein said substitution means substitution by one or more substituents selected from the group consisting of: c 1-4 Alkyl radical, C 2-4 Alkenyl, halogen, C 1-4 Haloalkyl, cyano, C 1-4 Alkoxy, - (CH) 2 ) m -CN、-NR 6 R 7 、-SiR 8 R 9 R 10 O (5-8 membered heterocyclic group), -O (C) 3-6 Cycloalkyl), -S (C) 1-4 Alkyl), 5-10 membered heteroaryl, C 6-14 An aryl group; or the adjacent substituent and the two connected carbon atoms form a 5-10 membered heterocyclic ring; it is provided withIn, R 8 、R 9 、R 10 Each independently is C 1-4 Alkyl radical, C 6-14 An aryl group; r 6 、R 7 Each independently is hydrogen, C 1-4 Alkyl radical, C 6-14 An aryl group; the above 5-to 10-membered heteroaryl group, C 6-14 Aryl is optionally substituted with one or more substituents selected from the group consisting of: 5-10 membered heteroaryl, C 6-14 Aryl radical, C 1-4 Alkoxy radical, C 1-4 An alkyl group;
R 2 、R 3 each independently selected from: substituted or unsubstituted C 1-4 Alkyl, substituted or unsubstituted C 1-4 An alkoxy group; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-4 Alkoxy radical, C 1-4 Alkyl radical, C 2-4 Alkenyl, halogen, C 1-4 Haloalkyl, cyano;
or R 2 、R 3 Taken together with the attached N to form a substituted or unsubstituted 5-12 membered heterocyclic ring (monocyclic, fused, bridged), optionally having 1,2 or 3 heteroatoms selected from S, O or N, other than N; the substitution on the heterocycle means substitution with one or more substituents selected from the group consisting of: c 1-4 Alkyl radical, C 1-4 Alkoxy, halogen, cyano, C 1-4 Haloalkyl, - (5-to 15-membered heteroaryl), = (5-to 15-membered heteroaryl), - (CH) 2 ) m -(C 6-14 Aryl) (R) 4 ) n1 、-C 2-4 Alkenyl- (C) 6-14 Aryl) (R) 5 ) n2 Wherein m is 0, 1,2 or 4; n1, n2 are independently 1,2, 3 or 4; each R 4 Each R 5 Independently is C 1-4 An alkyl group.
In another preferred embodiment, R 1 Selected from the group consisting of: substituted or unsubstituted C 6-14 Aryl, substituted or unsubstituted 5-10 membered heteroaryl; wherein said substitution means substitution with one or more substituents selected from the group consisting of: c 1-4 Alkyl, halogen, C 1-4 Haloalkyl, cyano, C 1-4 An alkoxy group; or adjacent substituents form a 5-to 10-membered heterocyclic ring with the two carbon atoms to which they are attached.
In another preferred embodiment, R 1 Is selected from the followingGroup (2): substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5-9 membered heteroaryl (e.g., furyl, benzofuryl, pyrrolyl, thienyl, indolyl).
In another preferred embodiment, R 1 Substituted means substituted with one or more substituents selected from the group consisting of: methyl, chloro, fluoro, trifluoromethyl, cyano, methoxy, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, ethoxy, propoxy, bromo; or adjacent substituents form a 5-7 membered heterocyclic ring with the two carbon atoms to which they are attached, said heterocyclic ring having 1,2 or 3 heteroatoms selected from S, O or N.
In another preferred embodiment, R 2 、R 3 Each independently selected from: substituted or unsubstituted C 1-4 An alkyl group; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-4 An alkoxy group;
or R 2 、R 3 Taken together with the attached N to form a substituted or unsubstituted 5-12 membered heterocyclic ring (monocyclic, fused or bridged), optionally having 1,2 or 3 heteroatoms selected from S, O or N, other than N; the substitution on the heterocycle means substitution by one or more substituents selected from the group consisting of: c 1-4 Alkyl, - (5-to 15-membered heteroaryl), = (5-to 15-membered heteroaryl), - (CH) 2 ) m -(C 6-14 Aryl) (R) 4 ) n1 、-C 2-4 Alkenyl- (C) 6-14 Aryl) (R) 5 ) n2 Wherein m is 0, 1,2 or 4; n1, n2 are independently 1,2, 3 or 4; each R 4 Each R 5 Independently is C 1-4 An alkyl group.
In another preferred embodiment, FG-LG is FG-BPin.
In another preferred embodiment, the silicon group is selected from: trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl and diphenylmethylsilyl.
In another preferred embodiment, FG is selected from: substituted or unsubstituted C 6-14 Aryl, substituted or unsubstituted 5-15 membered heteroaryl;
wherein said substitution means substitution with one or more substituents selected from the group consisting of: c 1-4 Alkyl radical, C 2-4 Alkenyl radical, C 1-4 Alkoxy, halogen, C 1-4 Haloalkyl, - (CH) 2 ) m -CN、-NR 6 R 7 、-SiR 8 R 9 R 10 O (5-8 membered heterocyclic group), -O (C) 3-6 Cycloalkyl), -S (C) 1-4 Alkyl), 5-10 membered heteroaryl, C 6-14 An aryl group; or the adjacent substituent and the two connected carbon atoms form a 5-10 membered heterocyclic ring; r is 8 、R 9 、R 10 Each independently is C 1-4 An alkyl group; r 6 、R 7 Each independently is C 6-14 An aryl group; the above 5-to 10-membered heteroaryl group, C 6-14 Aryl is optionally substituted with one or more substituents selected from the group consisting of: 5-10 membered heteroaryl, C 6-14 Aryl radical, C 1-4 An alkoxy group.
In another preferred embodiment, the divalent samarium salt is Smi 2 、SmBr 2 、SmCl 2 One or a combination of two or more of them; the divalent ytterbium metal salt is YbI 2 、YbBr 2 、YbCl 2 One or a combination of two or more of them.
In another preferred embodiment, the metal additive is used in an amount of 0.001mol% to 500mol% based on the amount of the amide compound.
In another preferred embodiment, the divalent samarium or ytterbium metal salt is used in an amount of 0.001mol% to 500mol% based on the amide compound.
In another preferred embodiment, the amount of the metal simple substance is 0.001mol% to 500mol% of the amount of the amide compound.
In another preferred embodiment, the amount of the metal additive is preferably 10mol% to 50mol% of the amount of the amide compound.
In another preferred embodiment, the divalent samarium or ytterbium metal salt is preferably used in an amount of 200mol% to 300mol% based on the amide compound.
In another preferred example, the amount of the metal simple substance is preferably 200mol% to 300mol% of the amount of the amide compound.
In another preferred embodiment, the reaction temperature is from-80 ℃ to 200 ℃, preferably from 40 ℃ to 100 ℃, more preferably from 70 ℃ to 90 ℃.
In another preferred embodiment, the reaction is carried out in an organic solvent selected from the group consisting of: tetrahydrofuran, methanol, toluene, acetonitrile, carbon tetrachloride, chloroform, 1, 4-dioxane, 1, 2-dichloroethane, ethylene glycol dimethyl ether, dimethyl sulfoxide, N-dimethylformamide and N-methylpyrrolidone.
In another preferred embodiment, the metal additive is selected from the group consisting of: feCl 3 、Fe(OTf) 3 、Rh 2 (OAc) 4 、Rh 2 (OCt) 4 、Sc(OTf) 3 、NiI 2 、Ni(COD) 2 /PPh 3 、Ni(COD) 2 、CoCl 2 、CuI、Pd(PPh 3 ) 4 、Pd 2 (dba) 3 /Xantphos、Pd 2 (dba) 3 /PPh 3 、Pd(OAc) 2 /Xantphos。
The invention discloses a method for converting amide into an alpha-substituted amine compound by using a mixed system of divalent metal samarium salt (or metal ytterbium salt), a metal simple substance and a metal additive for the first time. The use of metal additives is the key to realizing the efficient deoxidation functionalization reaction of the amide.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Drawings
FIG. 1 shows the NMR spectrum of compound 3aa obtained in example 1.
FIG. 2 shows the NMR carbon spectrum of compound 3aa obtained in example 1.
Detailed description of the invention
The inventors of the present application have extensively and intensively studied and developed a direct deoxidation functionalization reaction of amide using a mixed system of a divalent metal samarium salt (or metal ytterbium salt), a metal simple substance and a metal additive. The reaction operation is simple, the reaction is carried out under mild conditions, and the amide can be converted into the alpha-substituted amine compound. On the basis of this, the present invention has been completed.
Term(s)
The term "C 1-6 "means having 1,2, 3, 4, 5 or 6 carbon atoms," C 3 -C 10 "means having 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, and so forth.
The term "alkyl" denotes a saturated linear or branched hydrocarbon moiety, such as-CH 3 or-CH (CH) 3 ) 2 . The term "alkoxy" denotes a radical formed by the attachment of an alkyl group to an oxygen atom, e.g. -OCH 3 ，-OCH 2 CH 3 . The term "cycloalkyl" denotes a saturated cyclic hydrocarbyl moiety including monocyclic, fused and bridged ring structures, such as cyclohexyl. The term "heterocyclyl" refers to a cyclic hydrocarbon group having 1,2, 3, or 4 heteroatoms selected from O, N, S, including monocyclic, fused and bridged ring structures, such as morpholine rings. The term "aryl" denotes a hydrocarbyl moiety comprising one or more aromatic rings including, but not limited to, phenyl, benzyl, phenylene, naphthyl, naphthylene, pyrenyl, anthracenyl, phenanthrenyl. The term "heteroaryl" denotes aryl groups containing at least one ring heteroatom (e.g., having 1,2, 3, or 4 heteroatoms selected from O, N, S), including monocyclic, fused ring structures, such as benzisothiazolyl, thiazolyl, thienyl, furyl, pyrrolyl, indolyl, benzimidazolyl and the like.
Unless otherwise specified, alkyl, alkoxy, cycloalkyl, heterocyclyl, heteroaryl, and aryl groups described herein include both substituted and unsubstituted moieties. Possible substituents on alkyl, alkoxy, cycloalkyl, heterocyclyl, heteroaryl, and aryl include, but are not limited to: c 1 -C 6 Alkyl radical, C 1 -C 6 Haloalkyl, C 2 -C 6 Alkenyl radical, C 2 -C 6 Alkynyl, C 3 -C 10 Cycloalkyl radical, C 3 -C 10 Cycloalkenyl radical, C 1 -C 6 Alkoxy, aryl, hydroxy, halogen, amino.
Use of
The alpha-aryl substituted amine compound can be used for treating diseases such as urticaria caused by allergens. Therefore, the compound can be used for preparing medicaments for preventing and treating tumors.
The alpha-aryl substituted amine compound can be independently administered or jointly administered with other pharmaceutically acceptable compounds (such as other anti-tumor drugs). Representative antineoplastic agents include (but are not limited to): letrozole, solifenacin, cetirizine, cinnarizine, meclizine, buclizine.
The invention has the advantages that:
(1) A process for converting amides to alpha-substituted amines is provided.
(2) Provides a preparation method of a novel 1, 1-diaryl methylamine compound.
(3) The method of the invention develops a mixed system of divalent metal samarium salt (or metal ytterbium salt), metal simple substance and metal additive to realize direct deoxidation functionalization reaction of amide. The reaction operation is simple, the reaction is carried out under mild conditions, and the amide can be converted into the alpha-substituted amine compound. From a synthetic point of view, this conversion is an extremely simple way of carrying out the challenging amide deoxygenation conversion, which is a long-term goal of organic chemists.
The invention is described in detail below by way of examples, it being necessary to point out here: the following examples are intended to illustrate the present invention and should not be construed as limiting the scope of the invention, which is intended to include the insubstantial modifications and adaptations of the invention set forth above by those skilled in the art.
Example 1
In this example, the reaction product of naphthalene-2-boronic acid pinacol ester as arylating agent and tetrahydrofuran as solvent in SmI 2 Sm, and catalyzing the dearylation reaction of the substrate 1 a. The reaction formula is as follows:
the reaction is as follows: under nitrogen atmosphere, 1a (17.5mg, 0.1mmol) and 2a (25.4mg, 0.2mmol) were each charged into a sealed tube, and then Sm (30.0mg, 0.2mmol), smI were added successively 2 (2.2 mL, 0.22mmol). After stirring at 80 ℃ for eighteen hours, it was quenched by addition of saturated sodium bicarbonate (4 mL), extracted with ethyl acetate (3X 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography using basic alumina as the packing to give the deoxyarylated product 3aa in 56% yield.
The NMR spectrum and NMR spectrum of 3aa are shown in FIGS. 1 and 2, respectively.
1 H NMR(400MHz,CDCl 3 )7.89(s,1H),7.80(d,J＝7.6Hz,1H),7.73(dd,J＝8.4,2.8Hz,2H),7.62(d,J＝8.4Hz,1H),7.52(d,J＝7.6Hz,2H),7.45–7.34(m,2H),7.25(t,J＝7.6Hz,2H),7.14(t,J＝7.2Hz,1H),4.32(s,1H),2.51–2.42(m,4H),1.83–1.74(m,4H)ppm.
Example 2
In the embodiment, the naphthalene-2-boronic acid pinacol ester is used as an arylating reagent, and tetrahydrofuran is used as a solvent to catalyze the deoxidation and arylation reaction of the substrate 1a at different temperatures. The reaction formula is as follows:
the reaction is as follows: under nitrogen atmosphere, 1a (17.5mg, 0.1mmol) and 2a (25.4mg, 0.2mmol) were each charged into a sealed tube, and then Sm (30.0mg, 0.2mmol), smI were added successively 2 (2.2mL, 0.22mmol). Stirring for eighteen hours at different temperatures, adding saturated sodium bicarbonate (4 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain the final product.
Table 2: effect of different temperature conditions on the Deoxyarylation results
a GC yield.
Example 3
In this example, the reaction product of naphthalene-2-boronic acid pinacol ester as arylating agent and tetrahydrofuran as solvent in SmI 2 Sm is used for catalyzing deoxidation and arylation of the substrate 1a by adding different metal additives. The reaction formula is as follows:
the reaction is as follows: under nitrogen atmosphere, 1a (17.5mg, 0.1mmol) and 2a (25.4mg, 0.2mmol) were each charged into a sealed tube, followed by Additive (5 mmol%), sm (30.0mg, 0.2mmol), and SmI 2 (2.2mL, 0.22mmol). Stirring at 80 deg.C for eighteen hours, adding saturated sodium bicarbonate (4 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain the final product.
Table 3: effect of different additives on Deoxyarylation results
b 0.2 Isolated yield on mmol scale
Example 4
In this example, different substituted pinacolato arylborates were used as arylating reagents, tetrahydrofuran as solvent, pd (PPh) 3 ) 4 As additive in Sm and SmI 2 Catalyzing the deoxidation and arylation reaction of the catalytic substrate 1a (the reaction formula is as follows):
the reaction is as follows: nitrogen atmosphereUnder the action of a sealed tube, 1a (35.0 mg, 0.2mmol) and 2 (0.4 mmol) are respectively added, and then Pd (PPh) is added 3 ) 4 (11.6mg,5mmol％),Sm(60.0mg,0.4mmol),SmI 2 (4.4mL, 0.44mmol). Stirring at 80 deg.C for eighteen hours, adding saturated sodium bicarbonate (8 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain deoxyarylated product 3. The experimental results are shown below:
3aa, yellow solid, 86% yield, mp 78-79 ℃. 1 H NMR(400MHz,CDCl 3 ):δ7.89(s,1H),7.80(d,J＝7.6Hz,1H),7.73(dd,J＝8.4,2.8Hz,2H),7.62(d,J＝8.4Hz,1H),7.52(d,J＝7.6Hz,2H),7.45–7.34(m,2H),7.25(t,J＝7.6Hz,2H),7.14(t,J＝7.2Hz,1H),4.32(s,1H),2.51–2.42(m,4H),1.83–1.74(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 ):δ144.0,141.8,133.4,132.6,128.4,128.1,127.8,127.6,127.5,126.8,125.9,125.8,125.7,125.4,76.6,53.7,23.6ppm；IR(neat)ν2962,2874,1598,1506,1359,1127,810,729cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 21 H 22 N 288.1750；found288.1747.
3ab, yellow solid, 84% yield, mp 70-71 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.40(d,J＝7.6Hz,4H),7.19(t,J＝7.2Hz,4H),7.09(t,J＝7.6Hz,2H),4.10(s,1H),2.42–2.33(m,4H),1.75–1.66(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ144.3,128.3,127.5,126.7,76.5,53.6,23.5ppm.
3ac, yellow oil, 88% yield, 1 H NMR(400MHz,CDCl 3 ) 1 HNMR(400MHz,CDCl 3 )δ7.40(t,J＝7.2Hz,4H),7.27–7.20(m,4H),7.16(t,J＝7.2Hz,1H),4.13(s,1H),2.45–2.33(m,4H),1.80–1.69(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ128.8,128.6,128.5,127.4,75.7,53.6,23.5ppm(Four carbons is missing because of overlapping)；IR(neat)ν2960,2873,1599,1487,1268,1088,756,698cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 17 H 19 ClN 272.1192；found:272.1201.
3ad, yellow oil, 65% yield, 1 H NMR(400MHz,CDCl 3 )δ7.59(d,J＝8.0Hz,2H),7.51(d,J＝8.0Hz,2H),7.44(d,J＝7.6Hz,2H),7.27(t,J＝8.0Hz,2H),7.18(t,J＝7.6Hz,1H),7.45–7.34(s,1H),2.46–2.39(m,4H),1.82–1.73(m,4H)ppm； 13 C NMR(151MHz,CDCl 3 )δ148.3,143.3,129.0(q,J＝31.7Hz),128.6,127.7,127.5,127.2,125.4(q,J＝3.0Hz),124.2(q,J＝271.8Hz),76.0,53.5,23.5ppm； 19 F NMR(376MHz,CDCl 3 )δ-62.4(s,3F)ppm；HRMS(ESI)m/z:[M+H] + calcd for C 18 H 19 F 3 N 306.1474；found:306.1464.
3ae, yellow oil, 80% yield, 1 H NMR(400MHz,CDCl 3 )δ7.47(d,J＝6.8Hz,2H),7.37(d,J＝7.2Hz,2H),7.26(t,J＝7.2Hz,2H),7.15(t,J＝7.2Hz,1H),7.08(d,J＝7.6Hz,2H),4.17(s,1H),2.52–2.43(m,4H),2.27(s,3H),1.85–1.74(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ129.1,128.4,127.40,127.36,126.8,76.3,53.7,23.5,21.0ppm(Three carbons is missing because of overlapping)；IR(neat)ν2922,2854,1602,1510,1361,1126,799,697cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 18 H 22 N 252.1752；found:252.1747.
3af, yellow solid, 66% yield, mp 58-59 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.48–7.38(m,6H),7.25(t,J＝7.2Hz,2H),7.15(t,J＝7.2Hz,1H),4.13(s,1H),2.46–2.38(m,4H),1.80–1.73(m,4H),0.21(s,9H)ppm； 13 C NMR(101MHz,CDCl 3 )δ144.8,144.2,138.5,133.4,128.3,127.5,126.80,126.77,76.6,53.7,23.5,-1.1ppm；IR(neat)ν2965,1596,1450,1361,1247,1131,831,722cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 20 H 28 NSi 310.1991；found:310.1986.
3ag, yellow solid, 77% yield, mp 50-51 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.44(d,J＝7.6Hz,2H),7.36(d,J＝8.4Hz,2H),7.25–7.23(m,2H),7.15(t,J＝7.2Hz,1H),6.80(d,J＝8.4Hz,2H),4.11(s,1H),3.74(s,3H),2.46–2.37(m,4H),1.82–1.72(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ158.3,144.5,136.5,128.4,128.3,127.3,126.6,113.7,75.8,55.1,53.7,23.5ppm；IR(neat)ν2928,2853,1603,1509,1452,1360,1147,698cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 18 H 22 NO 268.1702；found:268.1696.
3ah, yellow solid, 80% yield, mp 84-85 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.46(d,J＝7.6Hz,2H),7.38(d,J＝8.4Hz,2H),7.27(t,J＝7.6Hz,2H),7.17(t,J＝7.6Hz,1H),6.97(d,J＝8.8Hz,2H),5.37(q,J＝3.2Hz,1H),4.13(s,1H),3.94–3.87(m,1H),3.57–3.61(m,1H),2.49–2.38(m,4H),2.05–1.93(m,1H),1.86–1.81(m,2H),1.73–1.80(m,4H),1.69–1.55(m,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ155.9,144.5,137.4,128.34,128.31,128.2,127.3,126.6,116.16,116.12,96.3,75.84,75.79,61.99,61.97,53.6,30.4,25.2,23.5,18.8ppm；IR(neat)ν2938,2873,1608,1509,1453,1356,1073,699cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 22 H 28 NO 2 338.2118；found:338.2115.
3ai, white solid, 80% yield, mp 40-41 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.45(d,J＝7.6Hz,2H),7.28(dd,J＝17.6,8.4Hz,4H),7.18(t,J＝7.2Hz,5H),7.03(d,J＝7.6Hz,4H),6.95–6.89(m,4H),4.09(s,1H),2.46–2.37(m,4H),1.81–1.72(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ147.8,146.2,144.4,138.6,129.1,128.3,128.2,127.5,126.7,124.1,123.8,122.5,76.0,53.7,23.5ppm IR(neat)ν2963,1587,1488,1311,1271,1028,750,694cm -1 .；HRMS(ESI)m/z:[M+H] + calcd for C 29 H 29 N 2 405.2328；found:405.2325.
3aj, yellow solid, 67% yield, mp 52-53 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.50–7.37(m,4H),7.31(d,J＝8.0Hz,2H),7.25(t,J＝7.6Hz,2H),7.15(t,J＝7.2Hz,1H),6.64(dd,J＝17.6,10.8Hz,1H),5.69(d,J＝17.2Hz,1H),5.16(d,J＝10.8Hz,1H),4.15(s,1H),2.47–2.36(m,4H),1.82–1.72(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ144.1,144.0,136.5,136.1,128.4,127.6,127.4,126.8,126.3,113.3,76.2,53.6,23.5ppm；IR(neat)ν2956,2874,1597,1486,1451,1362,899,697cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 19 H 22 N 264.1755；found:264.1747.
3ak, white solid, 55% yield, mp 97-98 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.47(d,J＝8.0Hz,2H),7.43(d,J＝7.2Hz,2H),7.25(t,J＝8.0Hz,2H),7.23–7.12(m,3H),4.17(s,1H),3.62(s,2H),2.34–2.48(m,4H),1.82–1.72(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ144.3,143.8,128.4,128.2,128.1,127.9,127.3,126.9,117.9,75.9,53.5,23.5,23.1ppm；IR(neat)ν2974,2857,2086,1598,1486,1024,823,792cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 19 H 21 N 2 277.1701；found:277.1699.
3al, yellow oil, 91% yield, 1 H NMR(400MHz,CDCl 3 )δ7.45(d,J＝7.6Hz,2H),7.24(t,J＝7.2Hz,2H),7.19–7.10(m,3H),7.05(d,J＝7.6Hz,1H),6.87(dd,J＝8.4,2.4Hz,1H),4.11(s,1H),3.73–3.65(m,1H),2.42(d,J＝6.4Hz,4H),1.79–1.71(m,4H),0.76–0.68(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ158.9,145.8,144.2,129.1,128.3,127.5,126.7,120.1,114.4,112.9,76.4,53.6,50.6,23.5,6.14,6.13ppm；IR(neat)ν2965,2874,1584,1443,1357,1255,1018,775cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 20 H 24 NO 294.1861；found:294.1852.
3am, colorless oil, 59% yield, 1 H NMR(400MHz,CDCl 3 )δ7.43(d,J＝6.8Hz,2H),7.37(s,1H),7.28–7.21(m,3H),7.20–7.12(m,2H),7.08–7.01(m,1H),4.11(s,1H),2.44(s,3H),2.43–2.36(m,4H),1.72–1.79(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ145.0,143.9,138.2,128.8,128.3,127.5,126.8,125.7,124.8,124.3,76.3,53.6,23.5,15.8ppm；IR(neat)ν2964,2872,1587,1492,1361,1128,779,703cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 18 H 22 NS 284.1478；found:284.1468.
3an, yellow oil, 77% yield, 1 H NMR(400MHz,CDCl 3 )δ7.48(d,J＝7.2Hz,2H),7.27(t,J＝7.2Hz,2H),7.18(t,J＝7.2Hz,1H),6.68(d,J＝2.0Hz,2H),6.29(t,J＝2.4Hz,1H),4.09(s,1H),3.77(s,6H),2.51–2.37(m,4H),1.82–1.75(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ160.6,146.8,144.0,128.3,127.4,126.8,105.4,98.5,76.6,55.2,53.6,23.5ppm；IR(neat)ν2960,2835,1593,1454,1201,1151,827,706cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 19 H 24 NO 2 298.1802；found:298.1802.
3ao, white solid, 72% yield, mp 73-74 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.45(d,J＝7.2Hz,2H),7.28(t,J＝7.2Hz,2H),7.18(t,J＝7.2Hz,1H),7.02(d,J＝1.6Hz,1H),6.91(dd,J＝8.0,1.2Hz,1H),6.70(d,J＝8.0Hz,1H),5.88(dd,J＝9.2,1.2Hz,2H),4.09(s,1H),2.48–2.37(m,4H),1.83–1.76(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ147.6,146.2,144.4,138.5,128.3,127.3,126.7,120.4,107.9,107.7,100.8,76.0,53.6,23.5ppm；IR(neat)ν2917,2874,1486,1373,1245,1107,1039,693cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 18 H 20 NO 2 282.1496；found:282.1489.
3ap, yellow oil, 67% yield, 1 H NMR(400MHz,CDCl 3 )δ7.92(t,J＝7.6Hz,1H),7.46(d,J＝7.6Hz,2H),7.40(d,J＝8.0Hz,1H),7.29(t,J＝7.4Hz,2H),7.25–7.17(m,2H),4.65(s,1H),2.52–2.38(m,4H),1.84–1.76(m,4H)ppm； 13 C NMR(151MHz,CDCl 3 )δ159.5(d,J＝249.2Hz),142.2,135.3(d,J＝12.1Hz),130.3(qd,J＝33.2,9.1Hz),129.5(d,J＝4.5Hz),128.5,127.7,127.4,123.4(q,J＝271.8Hz),121.3–121.1(m),112.9(dq,J＝25.7,4.5Hz),67.0,53.4,23.5ppm； 19 F NMR(376MHz,CDCl 3 )δ-62.6(s,3F),-116.5(m,1F)ppm；IR(neat)ν2976,1585,1454,1367,1328,1126,742,698cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 18 H 18 F 4 N 324.1367；found:324.1370.
3aq, white solid, 68% yield, mp 135-136 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.18(d,J＝8.0Hz,2H),7.80–7.72(m,1H),7.65(d,J＝8.4Hz,2H),7.60–7.54(m,1H),7.49(d,J＝7.6Hz,2H),7.38–7.27(m,4H),7.20(t,J＝7.6Hz,1H),4.26(s,1H),2.53–2.43(m,4H),1.86–1.75(m,4H)ppm； 13 CNMR(101MHz,CDCl 3 )δ163.0,150.6,148.1,143.4,142.1,128.5,128.0,127.8,127.5,127.1,125.6,124.9,124.4,119.8,110.5,76.2,53.5,23.5ppm；IR(neat)ν2957,1617,1452,1361,1242,1053,1014,740cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 24 H 23 N 2 O 355.1815；found:355.1805.
3ar, colorless solid, 83% yield, mp 44-45 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.45(d,J＝7.2Hz,2H),7.39(s,1H),7.31(t,J＝7.2Hz,3H),7.22(t,J＝7.2Hz,1H),6.46(s,1H),4.18(s,1H),2.51–2.43(m,4H),1.83–1.74(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ143.4,142.9,139.2,128.4,128.3,127.6,126.9,109.8,66.8,53.4,23.4ppm；IR(neat)ν2967,2920,1598,1499,1450,1125,1020,727cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 15 H 18 NO 228.1387；found:228.1383.
3as, colorless solid, 91% yield, mp 50-51 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.48(d,J＝7.2Hz,2H),7.31(t,J＝7.6Hz,2H),7.25–7.17(m,3H),7.16(dd,J＝4.4,1.2Hz,1H),4.35(s,1H),2.49–2.43(m,4H),1.82–1.75(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ145.3,143.5,128.3,127.6,127.1,126.9,125.4,120.9,71.5,53.5,23.5ppm；IR(neat)ν2927,2873,1600,1493,1451,1362,1027,698cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 15 H 18 NS 244.1162；found:244.1155.
3at, yellow solid, 89% yield, mp 126-127 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.48(d,J＝7.6Hz,2H),7.30(t,J＝7.6Hz,2H),7.21(t,J＝7.6Hz,1H),7.16(d,J＝4.8Hz,1H),7.12(d,J＝3.2Hz,1H),7.01(d,J＝3.6Hz,1H),6.97(t,J＝3.6Hz,2H),6.90(d,J＝3.6Hz,1H),6.84(d,J＝3.6Hz,1H),4.43(s,1H),2.56–2.42(m,4H),1.84–1.72(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ148.2,143.0,137.2,136.6,136.2,135.7,128.4,127.8,127.5,127.3,124.5,124.24,124.19,123.7,123.5,122.6,71.3,53.4,23.5ppm；IR(neat)ν2951,2850,1599,1452,1354,1249,831,697cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 23 H 22 NS 3 408.0909；found:408.0909.
3au, white solid, 86% yield, mp 75-76 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.23(s,1H),8.14(d,J＝7.6Hz,1H),7.72(d,J＝8.0Hz,2H),7.62(d,J＝7.2Hz,2H),7.58–7.49(m,5H),7.47–7.38(m,3H),7.37–7.30(m,3H),7.25(t,J＝7.2Hz,3H),7.13(t,J＝7.6Hz,1H),4.35(s,1H),2.55–2.46(m,4H),1.86–1.77(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ144.8,141.0,140.2,140.0,139.9,136.8,136.3,128.9,128.3,127.5,127.4,127.1,127.0,126.6,125.80,125.77,123.44,123.37,120.3,119.8,119.0,109.73,109.70,76.7,53.9,23.6ppm(One carbon is missing because of overlapping)；IR(neat)ν2962,1599,1487,1452,1230,1027,763,696cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 35 H 31 N 2 479.2472；found:479.2482.
3av, yellow solid, 83% yield, mp 74-75 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.85–7.79(m,1H),7.70–7.63(m,1H),7.59–7.47(m,4H),7.31–7.19(m,5H),7.14–7.05(m,4H),6.91–6.83(m,4H),4.33(s,1H),3.87–3.77(m,6H),2.60–2.47(m,4H),1.88–1.79(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ155.6,146.2,144.2,141.1,139.7,133.6,129.0,128.4,128.3,127.4,126.8,126.7,126.2,125.4,122.8,116.5,114.6,76.5,55.4,53.7,23.5ppm(One carbon is missing because of overlapping)；IR(neat)ν2951,1600,1501,1487,1380,1237,1072,736cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 35 H 35 N 2 O 2 515.2704；found:515.2693.
3aw, white solid, 72% yield, mp 194-195 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.71(d,J＝6.4Hz,4H),8.63(d,J＝8.4Hz,2H),7.65(d,J＝8.4Hz,2H),7.57–7.47(m,8H),7.27(t,J＝7.2Hz,2H),7.17(t,J＝7.6Hz,1H),4.26(s,1H),2.53–2.43(m,4H),1.83–1.14(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ171.44,171.40,149.0,143.6,136.2,134.8,132.4,129.2,128.9,128.5,128.4,127.7,127.5,127.0,76.3,53.6,23.5ppm；IR(neat)ν2964,1588,1517,1445,1367,1023,764,687cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 32 H 29 N 4 469.2393；found:469.2387.
Example 5
In this example, 2a is used as arylating reagent, tetrahydrofuran is used as solvent, and Pd (PPh) is used 3 ) 4 As additive in Sm and SmI 2 Catalyzing the deoxidation and arylation reaction of various substrates 1 under the catalysis (the reaction formula is as follows):
the reaction is as follows: under nitrogen atmosphere, 1 (xx mg,0.2 mmol) and 2a (102.0 mg,0.4 mmol) were added to a sealed tube, followed by Pd (PPh) 3 ) 4 (11.6mg,5mmol％),Sm(60.0mg,0.4mmol),SmI 2 (4.4mL, 0.44mmol). Stirring at 80 deg.C for eighteen hours, adding saturated sodium bicarbonate (8 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain deoxyarylated product 3. The experimental results are shown below:
3ba, colorless solid, 94% yield, mp 98-99 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.81(s,1H),7.78(d,J＝7.6Hz,1H),7.76–7.72(m,2H),7.58(d,J＝8.4Hz,1H),7.46(d,J＝7.6Hz,2H),7.44–7.35(m,2H),7.29–7.23(m,2H),7.15(t,J＝7.2Hz,1H),4.38(s,1H),2.36(s,4H),1.62-1.53(m,4H),1.48-1.39(m,2H)ppm； 13 C NMR(101MHz,CDCl 3 )δ143.1,140.8,133.4,132.6,128.3,128.0,127.8,127.5,126.7,126.5,126.1,125.8,125.4,76.9,53.3,26.2,24.7ppm(One carbon is missing because of overlapping)；IR(neat)ν2964,2854,1598,1492,1442,1360,1147,733cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 22 H 24 N 302.1907；found:302.1903.
3ca, colorless oil, 71% yield, 1 H NMR(400MHz,CDCl 3 )δ7.81(s,1H),δ7.79–7.71(m,3H),7.63(d,J＝8.4Hz,1H),7.49(d,J＝7.6Hz,2H),7.45–7.36(m,2H),7.26–7.23(m,2H),7.15(t,J＝7.2Hz,1H),4.76(s,1H),2.63(t,J＝5.6Hz,4H),1.69–1.58(m,8H)ppm； 13 C NMR(101MHz,CDCl 3 )δ144.0,141.8,133.4,132.6,128.3,127.99,127.96,127.8,127.5,126.7,126.4,126.2,125.8,125.4,75.6,54.0,29.1,26.9ppm；IR(neat)ν2921,2851,1598,1491,1450,1361,1148,742cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 23 H 26 N 316.2071；found:316.2060.
3da, colorless solid, 92% yield, mp 125-126 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.83(s,1H),7.78(d,J＝7.6Hz,1H),7.73(d,J＝8.4Hz,2H),7.59(dd,J＝8.8,1.6Hz,1H),7.48(d,J＝7.2Hz,2H),7.45–7.34(m,2H),7.26(t,J＝7.2Hz,2H),7.15(t,J＝7.2Hz,1H),4.35(s,1H),3.72(t,J＝4.4Hz,4H),2.42(d,J＝4.8Hz,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ142.1,139.8,133.4,132.7,128.5,128.3,127.9,127.7,127.5,127.1,126.6,126.0,125.73,125.65,76.8,67.2,52.7ppm；IR(neat)ν2970,2856,1488,1285,1109,1066,1031,754cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 21 H 22 NO 304.1698；found:304.1696.
3ea, yellow solid, 58% yield, mp 97-98 ℃. 1 H NMR(400MHz,CDCl 3 )major isomer:δ7.93(s,1H),7.85(s,1H),7.76–7.81(m,2H),7.75–7.70(m,3H),7.55(d,J＝7.6Hz,1H),7.42–7.37(m,2H),7.24–7.22(m,1H),7.12(t,J＝7.2Hz,1H),5.12(s,1H),3.25–3.11(m,2H),1.84–1.70(m,3H),1.38–1.46(m,3H),1.06(d,J＝7.2Hz,3H),1.01(d,J＝7.6Hz,3H)ppm；minor isomer:δ7.93(s,1H),7.85(s,1H),7.76–7.81(m,2H),7.75–7.70(m,3H),7.55(d,J＝7.6Hz,1H),7.42–7.37(m,2H),7.24–7.22(m,1H),7.12(t,J＝7.2Hz,1H),5.31(s,1H),3.25–3.11(m,2H),1.84–1.70(m,3H),1.38–1.46(m,3H),1.06(d,J＝7.2Hz,3H),1.01(d,J＝7.6Hz,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ143.7,141.6,141.4,133.50,133.48,132.62,132.59,128.3,128.0,127.68,127.67,127.5,126.6,126.5,126.4,126.11,126.09,125.74,125.72,125.40,125.37,70.4,70.3,48.0,47.7,31.4,16.2,16.1,14.6ppm；IR(neat)ν2923,2849,1597,1504,1364,1144,742,699cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 21 H 22 NO 304.1698；found:304.1696.
3fa, yellow oil, 72% yield, 1 H NMR(400MHz,CDCl 3 )major isomer:δ7.90–7.71(m,3H),7.63(s,1H),7.56(d,J＝8.4Hz,1H),7.48–7.40(m,3H),7.35(dd,J＝14.0,6.8Hz,1H),7.27(dd,J＝15.6,8.0Hz,1H),7.19(t,J＝7.2Hz,1H),5.74(s,1H),2.92(dd,J＝22.4,10.8Hz,1H),2.55(dd,J＝23.6,11.2Hz,1H),1.94–1.77(m,3H),1.73–1.47(m,5H),1.37–1.18(m,4H),1.06–0.78(m,2H)ppm；minor isomer:δ7.90–7.71(m,3H),7.63(s,1H),7.56(d,J＝8.4Hz,1H),7.48–7.40(m,3H),7.35(dd,J＝14.0,6.8Hz,1H),7.27(dd,J＝15.6,8.0Hz,1H),7.19(t,J＝7.2Hz,1H),5.71(s,1H),2.92(dd,J＝22.4,10.8Hz,1H),2.55(dd,J＝23.6,11.2Hz,1H),1.94–1.77(m,3H),1.73–1.47(m,5H),1.37–1.18(m,4H),1.06–0.78(m,2H)ppm； 13 C NMR(101MHz,CDCl 3 )δ143.4,141.0,138.3,136.1,133.2,133.0,132.4,132.3,130.5,129.2,128.7,128.3,128.0,127.7,127.5,127.4,127.1,127.0,126.9,126.8,126.7,126.1,125.8,125.7,125.6,125.3,64.0,63.8,63.3,63.2,49.0,43.54,43.51,33.3,33.2,33.0,32.9,30.74,30.71,26.39,26.37,26.1,25.86,25.85ppm；IR(neat)ν2918,2850,1598,1505,1444,1239,1030,701cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 21 H 22 NO 304.1698；found:304.1696.
3ga, white solid, 77% yield, mp 108-109 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.80(s,1H),7.77(d,J＝7.6Hz,1H),7.73(d,J＝8.4Hz,2H),7.60(dd,J＝8.8,1.2Hz,1H),7.47(d,J＝7.6Hz,2H),7.44–7.34(m,2H),7.25(t,J＝7.6Hz,2H),7.14(t,J＝7.2Hz,1H),4.36(s,1H),4.22(dd,J＝17.6,4.4Hz,2H),2.59(dd,J＝27.6,11.2Hz,2H),2.23(d,J＝11.2Hz,2H),2.17–2.08(m,2H),1.94–1.84(m,2H)ppm； 13 C NMR(101MHz,CDCl 3 )δ142.43,140.1,133.4,132.7,128.5,128.3,127.8,127.7,127.5,127.0,126.6,125.9,125.6,125.5,76.2,74.88,74.86,57.6,57.4,28.7,28.6ppm；IR(neat)ν2960,1598,1504,1450,1327,1133,992,877cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 23 H 24 NO330.1851；found:330.1852.
3ha, white solid,45.3mg,52% yield, mp 158-159 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.91(s,1H),7.87(d,J＝8.0Hz,1H),7.83(d,J＝8.0Hz,1H),7.80(d,J＝8.4Hz,3H),7.67(d,J＝8.8Hz,1H),7.56(d,J＝7.2Hz,2H),7.50–7.41(m,3H),7.32(t,J＝7.6Hz,3H),7.22(t,J＝7.6Hz,1H),4.54(s,1H),3.60(t,J＝4.4Hz,4H),2.78–2.63(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ164.0,152.7,142.3,140.0,133.4,132.7,128.6,128.4,128.04,128.00,127.8,127.6,127.4,127.1,126.6,126.0,125.8,125.7,123.9,123.8,120.5,76.3,51.9,50.3ppm；IR(neat)ν2953,1593,1486,1420,1379,1257,1003,733cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 28 H 26 N 3 S 436.1844；found:436.1842.
3ia, yellow oil, 83% yield, 1 H NMR(400MHz,CDCl 3 )δ7.81(s,1H),7.78–7.71(m,3H),7.56(dd,J＝8.8,1.2Hz,1H),7.46–7.38(m,4H),7.27(t,J＝7.6Hz,2H),7.21–7.16(m,1H),5.08(s,1H),3.48(t,J＝6.4Hz,4H),3.27(s,6H),2.83(t,J＝6.4Hz,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ142.2,140.0,133.3,132.6,128.5,128.2,127.9,127.8,127.5,127.1,126.9,126.6,125.8,125.6,72.2,71.5,58.7,50.9ppm；IR(neat)ν2872,1598,1491,1450,1363,1114,814,701cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 23 H 28 NO 2 350.2119；found:350.2115.
3ja, colorless solid, 87% yield, mp 65-66 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.92(s,1H),7.85(d,J＝7.6Hz,1H),7.80(d,J＝8.4Hz,2H),7.66(dd,J＝8.4,1.2Hz,1H),7.54(d,J＝7.6Hz,2H),7.51–7.41(m,2H),7.32(t,J＝7.2Hz,2H),7.21(t,J＝7.2Hz,1H),4.29(s,1H),2.30(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ143.2,141.0,133.4,132.6,128.5,128.2,127.8,127.5,126.9,126.2,125.9,125.8,125.5,78.1,44.8ppm(One carbon is missing because of overlapping)；IR(neat)ν2989,2857,1597,1494,1362,1250,812,734cm - 1 .HRMS(ESI)m/z:[M+H] + calcd for C 19 H 20 N 262.1597；found:262.1590.
3ka, white solid, 73% yield, mp 95-96 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.91(s,1H),7.85(d,J＝7.6Hz,1H),7.80(d,J＝8.4Hz,2H),7.65(dd,J＝8.4,1.2Hz,1H),7.43–7.38(m,4H),7.14(d,J＝7.6Hz,2H),4.26(s,1H),2.32(s,3H),2.30(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ141.2,140.2,136.5,133.5,132.6,129.2,128.2,127.8,127.6,127.5,126.0,125.83,125.75,125.5,77.8,,44.8,21.0ppm；IR(neat)ν2990,2857,1597,1509,1362,1250,858,742cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 20 H 22 N 276.1738；found:276.1747.
3la, white solid, 66% yield, mp 89-90 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.82(s,1H),7.79(d,J＝8.0Hz,1H),7.75(d,J＝8.8Hz,2H),7.53(dd,J＝8.8,1.6Hz,1H),7.48–7.35(m,4H),7.24(d,J＝8.4Hz,2H),4.21(s,1H),2.22(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ141.8,140.4,133.4,132.7,132.5,129.1,128.6,128.4,127.8,127.6,126.2,126.0,125.7,125.5,77.3,44.7ppm；IR(neat)ν2951,2819,1591,1503,1462,1363,1026,743cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 19 H 19 NCl296.1206；found:296.1201.
3ma, white solid, 91% yield, mp 58-59 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.82(s,1H),7.78(d,J＝8.0Hz,1H),7.74(d,J＝8.4Hz,2H),7.54(d,J＝8.4Hz,1H),7.49–7.31(m,4H),6.94(t,J＝8.4Hz,2H),4.19(s,1H),2.21(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ161.7(d,J＝246.4Hz),140.7,139.0(d,J＝3.0Hz),133.4,132.6,129.1(d,J＝8.1Hz),128.3,127.7,127.6,126.1,126.0,125.6,125.5,115.2(d,J＝20.2Hz),77.1,44.7ppm； 19 F NMR(376MHz,CDCl 3 )δ-115.7(m,1F)ppm；IR(neat)ν2976,2856,1601,1481,1235,1094,1039,775cm - 1 .HRMS(ESI)m/z:[M+H] + calcd for C 19 H 19 NF 280.1504；found:280.1496.
3na, white solid, 77% yield, mp 70-71 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.84(s,1H),7.79(d,J＝8.0Hz,1H),7.76(d,J＝8.4Hz,2H),7.62(d,J＝8.0Hz,2H),7.54(t,J＝8.9Hz,3H),7.47–7.37(m,2H),4.28(s,1H),2.23(s,6H)ppm； 13 C NMR(151MHz,CDCl 3 )δ147.4,140.0,133.4,132.8,130.1,129.1(q,J＝33.2Hz),128.5,128.0,127.8,127.6,126.5,126.1,125.9,125.5(q,J＝3.0Hz),124.2(q,J＝271.8Hz),77.6,44.6ppm； 19 F NMR(376MHz,CDCl 3 )δ-62.4(s,3F)ppm；IR(neat)ν2953,1617,1507,1323,1265,1121,1016,733cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 20 H 19 NF 3 330.1475；found:330.1464.
3oa, white solid, 50% yield, mp 115-116 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.81(d,J＝9.6Hz,2H),7.78(d,J＝8.4Hz,2H),7.64(d,J＝8.4Hz,2H),7.57(d,J＝8.4Hz,2H),7.52(dd,J＝8.4,1.2Hz,1H),7.50–7.41(m,2H),4.31(s,1H),2.25(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ148.9,139.4,133.4,132.8,132.4,128.6,128.4,127.8,127.6,126.6,126.2,126.0,125.3,118.8,110.7,77.6,44.6ppm；IR(neat)ν2956,2851,2223,1605,1502,1361,1025,752cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 20 H 19 N 2 287.1550；found:287.1543.
3pa, yellow solid, 81% yield, mp 62-63 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.87–7.83(m,2H),7.81(d,J＝8.4Hz,2H),7.60(dd,J＝7.2,2.0Hz,1H),7.56(dd,J＝8.8,1.6Hz,1H),7.53–7.43(m,2H),7.42–7.36(m,1H),7.02(t,J＝8.8Hz,1H),4.23(s,1H),2.26(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ156.9(d,J＝248.5Hz),140.5(d,J＝4.0Hz),139.9,133.3,132.7,129.6,128.5,127.8,127.6,127.2(d,J＝7.1Hz),126.3,126.1,125.8,125.4,120.8(d,J＝17.2Hz),116.5(d,J＝20.2Hz),76.7,44.6ppm； 19 F NMR(376MHz,CDCl 3 )δ-118.0(m,1F)ppm；IR(neat)ν2975,2862,1598,1494,1253,1023,828,745cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 19 H 18 NFCl 314.1106；found:314.1106.
3qa, colorless oil, 41% yield, 1 H NMR(400MHz,CDCl 3 )δ7.86–7.76(m,4H),7.53–7.42(m,3H),7.21–7.11(m,2H),4.19(s,1H),2.24(s,6H)ppm； 13 C NMR(151MHz,CDCl 3 )δ151.2(ddd,J＝251.0,9.1,3.0Hz),140.1–139.8(m),139.2,138.5(dt,J＝251.0,15.1Hz),133.4,132.9,128.6,127.8,127.6,126.6,126.3,126.0,125.2,111.4(dd,J＝18.1,3.0Hz),76.6,44.4ppm； 19 F NMR(376MHz,CDCl 3 )δ-134.0(dd,J＝18.8,7.5Hz,2F),-162.5(m,1F)ppm；IR(neat)ν2953,2865,1617,1524,1345,1030,744,701cm -1 .HRMS(EI)m/z:[M] + calcd for C 19 H 16 NF 3 315.1224；found:315.1229.
3ra, white solid, 73% yield, mp 73-74 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.90(s,1H),7.84(d,J＝8.0Hz,1H),7.79(d,J＝8.0Hz,2H),7.63(d,J＝8.4Hz,1H),7.50–7.37(m,4H),6.86(d,J＝8.4Hz,2H),4.24(s,1H),3.76(s,3H),2.29(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ158.4,141.3,135.3,133.4,132.5,128.7,128.2,127.7,127.5,125.9,125.7,125.4,113.7,77.3,55.1,44.8ppm(One carbon is missing because of overlapping)；IR(neat)ν2936,1604,1504,1301,1277,1172,1020,820cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 20 H 22 NO 292.1704；found:292.1696.
3sa, colorless oil, 76% yield, 1 H NMR(400MHz,CDCl 3 )δ7.86(s,1H),7.81(d,J＝8.0Hz,1H),7.77(d,J＝8.4Hz,2H),7.61(d,J＝8.4Hz,1H),7.47–7.39(m,2H),7.07(s,1H),7.01(d,J＝8.0Hz,1H),6.78(d,J＝8.4Hz,1H),4.19(s,1H),3.88(s,3H),3.82(s,3H),2.26(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ149.0,147.9,141.1,135.9,133.5,132.6,128.2,127.8,127.5,126.0,125.9,125.7,125.5,120.0,110.9,110.5,77.7,55.9,55.8,44.8ppm；IR(neat)ν2983,2817,1589,1510,1464,1230,1024,786cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 21 H 24 NO 2 322.1802；found:322.1802.
3ta, white solid, 71% yield, mp 114-115 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.88(s,1H),7.84(d,J＝8.0Hz,1H),7.80(d,J＝8.4Hz,2H),7.61(d,J＝8.4Hz,1H),7.51–7.40(m,2H),7.11–7.04(m,1H),6.96(d,J＝8.0Hz,1H),6.74(d,J＝8.0Hz,1H),5.90(d,J＝11.6Hz,2H),4.18(s,1H),2.28(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ147.7,146.4,141.1,137.4,133.4,132.6,128.2,127.8,127.5,125.92,125.91,125.6,125.5,120.9,108.0,107.8,100.8,77.7,44.7ppm；IR(neat)ν2975,2855,1599,1482,1436,1236,1022,774cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 20 H 20 NO 2 306.1488；found:306.1489.
3ua, yellow oil, 83% yield. 1 H NMR(400MHz,CDCl 3 )δ7.90(s,1H),7.85(d,J＝8.0Hz,1H),7.82–7.77(m,2H),7.66(d,J＝8.8Hz,1H),7.51–7.40(m,2H),7.17(s,2H),4.14(s,1H),3.67(s,3H),2.28(s,12H)ppm； 13 C NMR(101MHz,CDCl 3 )δ155.7,141.2,138.4,133.4,132.6,130.6,128.2,127.8,127.7,127.5,126.0,125.9,125.7,125.5,77.8,59.5,44.9,16.2ppm；IR(neat)ν2946,2859,1599,1481,1220,1011,907,732cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 22 H 26 NO320.2019；found:320.2009.
3va, white solid, 93% yield, mp 137-138 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.01(s,2H),7.88(d,J＝8.0Hz,2H),7.84–7.82(m,1H),7.81(t,J＝4.0Hz,3H),7.73(dd,J＝8.8,1.2Hz,2H),7.52–7.42(m,4H),4.48(s,1H),2.37(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ140.7,133.4,132.7,128.3,127.8,127.5,126.3,125.91,125.85,125.6,78.1,44.9ppm；IR(neat)ν2925,2854,1598,1503,1361,1268,834,764cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 23 H 22 N 312.1750；found:312.1747.
3wa, colorless solid, 76% yield, mp 87-88 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.98(s,1H),7.86–7.82(m,3H),7.75(dd,J＝8.8,1.6Hz,1H),7.52(t,J＝6.4Hz,2H),7.50–7.44(m,2H),7.28–7.23(m,1H),7.20(td,J＝7.6,0.8Hz,1H),6.72(s,1H),4.63(s,1H),2.36(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ157.6,154.9,137.0,133.2,133.0,128.2,127.9,127.6,127.3,126.2,126.0,125.9,123.8,122.6,120.7,111.4,104.7,70.4,44.0ppm(One carbon is missing because of overlapping)；IR(neat)ν2976,2858,1598,1505,1452,1362,1148,739cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 21 H 20 NO302.1547；found:302.1539.
3xa, yellow oil, 51% yield, 1 H NMR(400MHz,CDCl 3 )δ7.88(s,1H),7.85–7.80(m,3H),7.67(d,J＝8.4Hz,1H),7.49–7.43(m,2H),7.39(s,1H),6.35–6.25(m,2H),4.49(s,1H),2.27(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ154.7,141.9,137.6,133.3,132.9,128.0,127.9,127.5,127.0,126.3,125.9,125.8,110.0,107.9,69.8,43.9ppm；IR(neat)ν2946,2861,1598,1503,1457,1361,1011,733cm -1 .HRMS(EI)m/z:[M] + calcd for C 17 H 17 NO 251.1310；found:251.1305.
3ya, yellow oil, 67% yield, 1 H NMR(400MHz,CDCl 3 )δ7.88(s,1H),7.86–7.80(m,3H),7.69(dd,J＝8.4,1.6Hz,1H),7.52–7.43(m,2H),7.23(dd,J＝5.2,1.2Hz,1H),7.01(d,J＝3.6Hz,1H),6.91(dd,J＝5.2,3.6Hz,1H),4.68(s,1H),2.31(s,6H)ppm； 13 C NMR(101MHz,CDCl 3 )δ147.3,139.4,133.3,132.8,128.2,127.9,127.6,126.7,126.2,126.0,125.9,125.8,125.1,124.9,72.5,44.2ppm；IR(neat)ν2947,2859,1599,1505,1454,1359,1017,695cm -1 .HRMS(EI)m/z:[M] + calcd for C 17 H 17 NS 267.1082；found:267.1085.
example 6
In this example, 2n is used as arylating reagent, tetrahydrofuran is used as solvent, pd (PPh) 3 ) 4 As additive in Sm and SmI 2 Catalyzing the deoxidation and arylation reaction of the catalytic substrate 4 (the reaction formula is as follows):
the reaction is as follows: under nitrogen atmosphere, 4 (79.8mg, 0.2mmol) and 2n (102.0mg, 0.4mmol) were each charged into a sealed tube, and Pd (PPh) was added successively 3 ) 4 (11.6mg,5mmol％),Sm(60.0mg,0.4mmol),SmI 2 (4.4mL, 0.44mmol). Stirring at 80 deg.C for eighteen hours, adding saturated sodium bicarbonate (8 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain the final product. The experimental results are shown below:
5, white solid, 62% yield, mp 96-97 ℃. 1 H NMR(400MHz,CDCl 3 )δ7.50–7.34(m,4H),7.30–7.11(m,7H),7.05(d,J＝7.6Hz,1H),6.85(t,J＝7.6Hz,1H),6.63(d,J＝9.6Hz,2H),6.32–6.20(m,1H),4.18(s,1H),3.73(s,3H),3.72(s,3H),3.66–3.10(m,4H),2.66–2.27(m,4H)ppm； 13 CNMR(101MHz,CDCl 3 )δ160.9,160.8,160.72,160.70,148.9,145.00,144.96,142.0,139.8,134.0,132.1,132.0,130.6,128.98,128.95,128.44,128.42,128.1,127.9,127.82,127.80,127.0,125.3,122.6,105.8,105.7,98.6,98.5,76.22,76.17,55.2,51.7ppm；IR(neat)ν2805,1594,1574,1452,1246,1149,1004,741cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 32 H 32 N 3 O 2 S 522.2208；found:522.2210.
Example 7
In this example, 2a is used as arylating reagent, tetrahydrofuran is used as solvent, and Pd (PPh) is used 3 ) 4 As additive in Sm and SmI 2 Catalyzing the deoxidation and arylation reaction of the catalytic substrate 6 (the reaction formula is as follows):
the reaction is as follows: under a nitrogen atmosphere, 6 (82.8mg, 0.2mmol) and 2a (102.0mg, 0.4mmol) were addedPutting into a sealed tube, and sequentially adding Pd (PPh) 3 ) 4 (11.6mg,5mmol％),Sm(60.0mg,0.4mmol),SmI 2 (4.4mL, 0.44mmol). Stirring at 80 deg.C for eighteen hours, adding saturated sodium bicarbonate (8 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain the final product. The experimental results are shown below:
7, orange solid, 90% yield, mp 108-109 deg.C 1 H NMR(400MHz,CDCl 3 )δ8.34(s,1H),7.81(s,1H),7.78–7.68(m,3H),7.59(d,J＝8.4Hz,1H),7.46(d,J＝7.2Hz,2H),7.43–7.36(m,2H),7.34(d,J＝7.6Hz,1H),7.23(t,J＝7.2Hz,2H),7.17–7.04(m,4H),7.03–6.95(m,1H),4.42(s,1H),3.41–3.23(m,2H),2.84–2.67(m,4H),2.61–2.42(m,2H),2.38–2.26(m,2H),2.12–2.02(m,2H)ppm； 13 C NMR(101MHz,CDCl 3 )157.51,157.48,146.4,142.7,142.6,140.40,140.39,139.44,139.40,139.38,137.68,137.65,137.1,133.3,132.5,132.4,132.1,130.8,128.8,128.3,128.1,127.8,127.64,127.63,127.4,126.8,126.4,126.3,125.8,125.4,121.9,75.89,75.86,53.5,31.7,31.3,31.11,31.09,30.9ppm；IR(neat)ν2897,1635,1585,1477,1437,1242,1173,813,731cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 36 H 32 N 2 Cl 527.2251；found:527.2249.
Example 8
In this example, 2a is used as arylating reagent, tetrahydrofuran is used as solvent, and Pd (PPh) is used 3 ) 4 As additive in Sm and SmI 2 Catalyzing the deoxidation and arylation reaction of the catalytic substrate 8 (the reaction formula is as follows):
the reaction is as follows: under nitrogen atmosphere, 8 (49.4mg, 0.2mmol) and 2a (102.0mg, 0.4mmol) were charged into a sealed tube respectivelySuccessively adding Pd (PPh) 3 ) 4 (11.6mg,5mmol％),Sm(60.0mg,0.4mmol),SmI 2 (4.4mL, 0.44mmol). Stirring at 80 deg.C for eighteen hours, adding saturated sodium bicarbonate (8 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain the final product. The experimental results are shown below:
11, yellow oil, 51% yield, 1 H NMR(400MHz,CDCl 3 )δ7.84–7.73(m,4H),7.59(d,J＝8.4Hz,1H),7.47–7.38(m,2H),7.01(s,1H),6.94(d,J＝7.6Hz,1H),6.77(d,J＝8.4Hz,1H),4.29(s,1H),4.22–4.17(m,4H),2.48–2.29(m,4H),1.64–1.56(m,4H),1.49–1.41(m,2H)ppm； 13 C NMR(101MHz,CDCl 3 )δ143.3,142.3,141.1,136.6,133.4,132.6,128.0,127.8,127.5,126.3,126.1,125.8,125.4,120.9,117.0,116.6,76.2,64.3,64.2,53.2,26.2,24.7ppm；IR(neat)ν2928,1589,1501,1361,1280,1106,811,734cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 24 H 26 NO 2 360.1959；found:360.1958.
example 9
In this example, 2a is used as arylating reagent, tetrahydrofuran is used as solvent, and Pd (PPh) is used 3 ) 4 As additive in Sm and SmI 2 Catalyzing the deoxidation and arylation reaction of a catalytic substrate 9 (the reaction formula is as follows):
the reaction is as follows: under nitrogen atmosphere, 9 (61.4mg, 0.2mmol) and 2a (102.0mg, 0.4mmol) were respectively added into a sealed tube, and Pd (PPh) was added successively 3 ) 4 (11.6mg,5mmol％),Sm(60.0mg,0.4mmol),SmI 2 (4.4mL, 0.44mmol). After stirring at 80 ℃ for eighteen hours, it was quenched by addition of saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3X 10 mL), anhydrous sulfuric acidSodium is dried, filtered and concentrated, and then column chromatography purification is carried out by taking alkaline alumina as a filler to obtain the product of the deoxyarylation. The experimental results are shown below:
12, colorless oil, 75% yield, 1 H NMR(400MHz,CDCl 3 )δ6.95(s,1H),6.84(d,J＝7.6Hz,1H),6.70(d,J＝8.0Hz,1H),6.67(s,2H),5.91(d,J＝8.0Hz,2H),4.31(s,1H),3.84(s,6H),3.80(s,3H),2.51(t,J＝5.6Hz,4H),1.85–1.75(m,2H),1.69–1.63(m,4H),1.55–1.46(m,4H)ppm； 13 C NMR(101MHz,CDCl 3 )δ152.9,147.5,146.2,140.4,138.1,136.3,121.3,108.2,107.8,104.4,100.8,76.8,60.8,55.9,52.9,28.1,27.8,25.5ppm；IR(neat)ν2919,1589,1502,1417,1233,1123,1036,731cm -1 .HRMS(ESI)m/z:[M+H] + calcd for C 24 H 32 NO 5 414.2274；found:414.2275.
example 10
This example uses 2a as the arylating reagent, tetrahydrofuran as the solvent, pd (PPh) 3 ) 4 As additive in Sm and SmI 2 Catalyzing the dearylation reaction of the catalytic substrate 10 (the reaction formula is as follows):
the reaction is as follows: under nitrogen atmosphere, 10 (56.2mg, 0.2mmol) and 2a (102.0mg, 0.4mmol) were added into a sealed tube, and Pd (PPh) was added successively 3 ) 4 (11.6mg,5mmol％),Sm(60.0mg,0.4mmol),SmI 2 (4.4mL, 0.44mmol). Stirring at 80 deg.C for eighteen hours, adding saturated sodium bicarbonate (8 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain the final product. The experimental results are shown below:
13, yellow oil, 59% yield, 1 H NMR(400MHz,CDCl 3 )δ8.16(d,J＝6.0Hz,2H),7.78(d,J＝8.4Hz,2H),7.66(d,J＝7.2Hz,2H),7.59(d,J＝8.0Hz,2H),7.53–7.37(m,7H),7.29(t,J＝7.2Hz,1H),6.80(s,2H),4.31(s,1H),3.87(s,6H),3.78(s,3H),3.77–3.69(m,4H),2.56–2.38(m,4H)ppm； 13 CNMR(101MHz,CDCl 3 )δ153.2,141.0,140.2,140.1,140.0,138.8,136.7,136.6,133.8,128.9,128.4,127.6,127.1,127.0,126.0,125.8,123.4,123.2,120.2,119.9,119.6,110.0,109.9,104.4,77.1,67.2,60.7,56.1,52.8ppm；IR(neat)ν2952,2832,1589,1489,1453,1229,1117,746cm -1 .HRMS(ESI)m/z:[M+Na] + calcd for C 38 H 36 N 2 O 4 Na 607.2577；found:607.2567.
example 11
In this example, 2a is used as arylating reagent, tetrahydrofuran is used as solvent, and Pd (PPh) is used 3 ) 4 As additive in Sm and SmI 2 Catalyzing the deoxidation and arylation reaction of a catalytic substrate 1 (the reaction formula is as follows):
the reaction is as follows: under nitrogen atmosphere, 1 (xx mg,0.2 mmol) and 2a (102.0 mg,0.4 mmol) were added to a sealed tube, followed by Pd (PPh) 3 ) 4 (11.6mg,5mmol％),Sm(60.0mg,0.4mmol),SmI 2 (4.4mL, 0.44mmol). Stirring at 80 deg.C for eighteen hours, adding saturated sodium bicarbonate (8 mL), quenching, extracting with ethyl acetate (3X 10 mL), drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography with basic alumina as filler to obtain the final product. The experimental results are shown below:
14, yellow oil, 74% yield, 1 H NMR(400MHz,CDCl 3 )δ7.37–7.28(m,6H),7.27–7.21(m,6H),7.20–7.15(m,1H),4.20(s,1H),3.48(s,2H),2.63–2.20(m,8H),1.29(s,9H)ppm； 13 C NMR(101MHz,CDCl 3 )δ149.8,142.2,141.4,134.8,132.4,129.2,128.9,128.54,128.48,127.9,127.0,125.0,75.4,62.6,53.2,51.8,34.4,31.4ppm.
15, yellow oil, 73% yield, 1 H NMR(400MHz,CDCl 3 )δ7.38–7.28(m,4H),7.27–7.19(m,4H),7.19–7.12(m,2H),7.12–6.98(m,3H),4.20(s,1H),3.47(s,2H),2.99–2.32(m,8H),2.31(s,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ142.1,141.3,137.7,137.6,132.4,130.0,129.2,128.54,128.48,128.0,127.81,127.75,127.0,126.4,75.4,63.0,53.2,51.7,21.4ppm.
16, white solid, 80% yield, 1 H NMR(400MHz,CDCl 3 )δ7.43–7.37(m,4H),7.34(d,J＝7.6Hz,2H),7.31–7.21(m,6H),7.21–7.18(m,1H),7.17–7.11(m,2H),6.49(d,J＝15.6Hz,1H),6.26(dt,J＝15.6,6.8Hz,1H),4.23(s,1H),3.15(d,J＝6.4Hz,2H),2.70–2.25(m,8H)ppm； 13 C NMR(101MHz,CDCl 3 )δ142.7,136.9,132.9,128.5,128.4,127.9,127.4,126.8,126.5,126.2,76.1,61.0,53.4,51.8ppm.
all documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.
Claims (10)
1. A method for preparing an alpha-substituted amine compound, the method comprisingPromoting the amide compound, the organic metal reagent and C by using a mixed system of divalent samarium and/or ytterbium metal salt, a simple metal and a metal additive 6-14 Aromatic hydrocarbon, 5-to 10-membered heterocyclic hydrocarbon, 5-to 15-membered heteroaromatic hydrocarbon, C 2-20 Olefins or C 1-20 Alkane is subjected to deoxidation functionalization reaction to obtain an alpha-substituted amine compound,
wherein, the metal simple substance is one or the combination of more than two of Sm, mg, zn, in and Yb;
the metal additive is metal salt and/or complex compound of one or more than two of Pd, rh, ir, ru, ni, ag, cu, fe, co, mn and Cr;
the organometallic reagent is selected from: organoboron reagents, grignard reagents, organolithium reagents, organosilicon reagents.
2. The method of claim 1, wherein the method comprises the steps of:
the method uses a mixed system of divalent metal samarium salt and/or metal ytterbium salt, a metal simple substance and a metal additive to promote the deoxidation functionalization reaction of an amide compound 1 and a reaction reagent 2 to obtain an alpha-substituted amine compound 3,
in each formula, LG is selected from: boron group, [ MgBr ] in organoboron reagents] + 、[MgCl] + 、Li + Silicon base and hydrogen;
R 1 FG is each independently selected from: substituted or unsubstituted C 6-14 Aryl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted C 3-10 Cycloalkyl, substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted C 2-20 Alkenyl, substituted or unsubstituted 5-10 membered heterocyclyl; wherein said substitution means substitution with one or more substituents selected from the group consisting of: c 1-4 Alkyl radical, C 2-4 Alkenyl, halogen, C 1-4 Haloalkyl, cyano, C 1-4 Alkoxy, - (CH) 2 ) m -CN、-NR 6 R 7 、-SiR 8 R 9 R 10 -O (5-to 8-membered heterocyclic group), -O (C) 3-6 Cycloalkyl), -S (C) 1-4 Alkyl), 5-10 membered heteroaryl, C 6-14 An aryl group; or the adjacent substituent and the two connected carbon atoms form a 5-10 membered heterocyclic ring; wherein R is 8 、R 9 、R 10 Each independently is C 1-4 Alkyl radical, C 6-14 An aryl group; r 6 、R 7 Each independently of the other is hydrogen, C 1-4 Alkyl radical, C 6-14 An aryl group; the above 5-to 10-membered heteroaryl group, C 6-14 Aryl is optionally substituted with one or more substituents selected from the group consisting of: 5-10 membered heteroaryl, C 6-14 Aryl radical, C 1-4 Alkoxy radical, C 1-4 An alkyl group;
R 2 、R 3 each independently selected from: substituted or unsubstituted C 1-4 Alkyl, substituted or unsubstituted C 1-4 An alkoxy group; the substitution means substitution by one or more substituents selected from the group consisting of: c 1-4 Alkoxy radical, C 1-4 Alkyl radical, C 2-4 Alkenyl, halogen, C 1-4 Haloalkyl, cyano;
or R 2 、R 3 Taken together with the attached N to form a substituted or unsubstituted 5-12 membered heterocyclic ring (monocyclic, fused, bridged), optionally having 1,2 or 3 heteroatoms selected from S, O or N, other than N; the substitution on the heterocycle means substitution by one or more substituents selected from the group consisting of: c 1-4 Alkyl radical, C 1-4 Alkoxy, halogen, cyano, C 1-4 Haloalkyl, - (5-to 15-membered heteroaryl), = (5-to 15-membered heteroaryl), - (CH) 2 ) m -(C 6-14 Aryl) (R) 4 ) n1 、-C 2-4 Alkenyl- (C) 6-14 Aryl) (R) 5 ) n2 Wherein m is 0, 1,2 or 4; n1, n2 are independently 1,2, 3 or 4; each R 4 Each R 5 Independently is C 1-4 An alkyl group.
3. The method of claim 2, wherein the step of preparing the composition comprisesIn that R 1 Selected from the group consisting of: substituted or unsubstituted C 6-14 Aryl, substituted or unsubstituted 5-10 membered heteroaryl; wherein said substitution means substitution with one or more substituents selected from the group consisting of: c 1-4 Alkyl, halogen, C 1-4 Haloalkyl, cyano, C 1-4 An alkoxy group; or adjacent substituents form a 5-to 10-membered heterocyclic ring with the two carbon atoms to which they are attached.
4. The method of claim 2, wherein R is 2 、R 3 Each independently selected from: substituted or unsubstituted C 1-4 An alkyl group; the substitution means substitution with one or more substituents selected from the group consisting of: c 1-4 An alkoxy group;
or R 2 、R 3 Taken together with the attached N to form a substituted or unsubstituted 5-12 membered heterocyclic ring (monocyclic, fused, bridged), optionally having 1,2 or 3 heteroatoms selected from S, O or N, other than N; the substitution on the heterocycle means substitution with one or more substituents selected from the group consisting of: c 1-4 Alkyl, - (5-to 15-membered heteroaryl), = (5-to 15-membered heteroaryl), - (CH) 2 ) m -(C 6-14 Aryl) (R) 4 ) n1 、-C 2-4 Alkenyl- (C) 6-14 Aryl) (R) 5 ) n2 Wherein m is 0, 1,2 or 4; n1, n2 are independently 1,2, 3 or 4; each R 4 Each R 5 Independently is C 1-4 An alkyl group.
5. The method of claim 2, wherein FG is selected from the group consisting of: substituted or unsubstituted C 6-14 Aryl, substituted or unsubstituted 5-15 membered heteroaryl;
wherein said substitution means substitution by one or more substituents selected from the group consisting of: c 1-4 Alkyl radical, C 2-4 Alkenyl radical, C 1-4 Alkoxy, halogen, C 1-4 Haloalkyl, - (CH) 2 ) m -CN、-NR 6 R 7 、-SiR 8 R 9 R 10 O (5-8 membered heterocyclic group), -O (C) 3-6 Cycloalkyl), -S (C) 1-4 Alkyl), 5-to 10-memberedHeteroaryl, C 6-14 An aryl group; or the adjacent substituent and the two connected carbon atoms form a 5-10 membered heterocyclic ring; r is 8 、R 9 、R 10 Each independently is C 1-4 An alkyl group; r 6 、R 7 Each independently is C 6-14 An aryl group; the above 5-to 10-membered heteroaryl group, C 6-14 Aryl is optionally substituted with one or more substituents selected from the group consisting of: 5-10 membered heteroaryl, C 6-14 Aryl radical, C 1-4 An alkoxy group.
6. The method according to claim 1 or 2, wherein the divalent samarium salt is Smi 2 、SmBr 2 、SmCl 2 One or a combination of two or more of them; the divalent ytterbium metal salt is YbI 2 、YbBr 2 、YbCl 2 Or a combination of two or more thereof.
7. The method according to claim 1 or 2, wherein the metal additive is used in an amount of 0.001mol% to 500mol% based on the amount of the amide compound;
the dosage of the divalent samarium salt or ytterbium salt is 0.001-500 mol% of that of the amide compound; and/or
The dosage of the metal simple substance is 0.001mol% -500mol% of the dosage of the amide compound.
8. The process according to claim 1 or 2, wherein the reaction temperature is from-80 ℃ to 200 ℃, preferably from 40 ℃ to 100 ℃, more preferably from 70 ℃ to 90 ℃.
9. The process according to claim 1 or 2, wherein the reaction is carried out in an organic solvent selected from the group consisting of: tetrahydrofuran, methanol, toluene, acetonitrile, carbon tetrachloride, chloroform, 1, 4-dioxane, 1, 2-dichloroethane, ethylene glycol dimethyl ether, dimethyl sulfoxide, N-dimethylformamide and N-methylpyrrolidone.
10. The method of claim 1, wherein the metal additive is selected from the group consisting of: feCl 3 、Fe(OTf) 3 、Rh 2 (OAc) 4 、Rh 2 (Oct) 4 、Sc(OTf) 3 、NiI 2 、Ni(COD) 2 /PPh 3 、Ni(COD) 2 、CoCl 2 、CuI、Pd(PPh 3 ) 4 、Pd 2 (dba) 3 /Xantphos、Pd 2 (dba) 3 /PPh 3 、Pd(OAc) 2 /Xantphos。
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