公开(公告)号：US20200131213A1

公开(公告)日：2020-04-30

申请号：US16485931

申请日：2018-02-13

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07F15/00

摘要： We report the design of a catalytic, bifunctional template that binds heterocyclic substrate via reversible coordination instead of covalent linkage, allowing remote site-selective C—H olefination of heterocycles. The two metal centers coordinated to this template play different roles; anchoring substrates to the proximity of catalyst and cleaving the remote C—H bonds respectively. Using this strategy, we demonstrate remote site-selective C—H olefination of heterocyclic substrates which do not have functional group handles for covalently attaching templates. For instance the olefination can be an alkenylation of a 3-phenylpyridine with an acrylate alkyl ester selective for the meta position of the phenyl group with respect to the pyridine, or can be an alkenylation of a quinoline with an acrylate alkyl ester selective for the 5-position of the quinoline.

公开(公告)号：US11186563B2

公开(公告)日：2021-11-30

申请号：US16086535

申请日：2017-03-20

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07B53/00 ,  C07D401/06 ,  C07D209/48 ,  C07D213/06 ,  C07D215/12 ,  C07D263/10 ,  C07D413/06 ,  C07D491/048 ,  B01J31/18

摘要： Chiral acetyl-protected aminoethyl quinoline (APAQ), pyridine and imazoline ligands are disclosed that enable Pd (II)-catalyzed enantioselective arylation or heteroarylation of ubiquitous prochiral β-methylene C—H bonds of aliphatic amides offers an alternative disconnection for constructing β-chiral centers. Systematic tuning of the ligand structure reveals that a six-membered instead of a five-membered chelation of these types of ligands with the Pd(II) is important for accelerating the C(sp3)-H activation thereby achieving enantioselectivity for quinoline and pyridine ligands.

公开(公告)号：US10858383B2

公开(公告)日：2020-12-08

申请号：US16485931

申请日：2018-02-13

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07F15/00 ,  C07D213/04 ,  C07D215/06

摘要： We report the design of a catalytic, bifunctional template that binds heterocyclic substrate via reversible coordination instead of covalent linkage, allowing remote site-selective C—H olefination of heterocycles. The two metal centers coordinated to this template play different roles; anchoring substrates to the proximity of catalyst and cleaving the remote C—H bonds respectively. Using this strategy, we demonstrate remote site-selective C—H olefination of heterocyclic substrates which do not have functional group handles for covalently attaching templates. For instance the olefination can be an alkenylation of a 3-phenylpyridine with an acrylate alkyl ester selective for the meta position of the phenyl group with respect to the pyridine, or can be an alkenylation of a quinoline with an acrylate alkyl ester selective for the 5-position of the quinoline.

公开(公告)号：US10696635B2

公开(公告)日：2020-06-30

申请号：US16094707

申请日：2017-04-18

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07C6/02 ,  C07D213/68 ,  C07D401/14 ,  C07D405/14 ,  C07D231/12 ,  C07D231/56 ,  C07D401/12 ,  C07D405/12 ,  C07D239/42 ,  C07D409/12 ,  C07D409/14 ,  C07D241/12 ,  C07D413/12 ,  C07D217/12 ,  C07D213/36 ,  C07D213/26 ,  B01J23/44 ,  C07D213/30 ,  C07D213/40 ,  C07D213/55 ,  C07D213/72 ,  C07D215/38 ,  C07D217/18 ,  C07D217/24 ,  C07D239/26

摘要： A class of mono-protected 3-amino-2-hydroxypyridine (MPAHP) ligands that enable the meta-C—H arylation of anilines, phenols, phenylacetic acids, and biologically relevant heterocyclic compounds using norbornene as a transient mediator is disclosed, such as in the formation of a reaction product of Formula IA: The applicability of this meta-arylation methodology in the pharmaceutical industry is illustrated for heteroaryl substrates and heteroaryl iodide coupling partners, a feat made possible by using the MPAHP ligand. The enabling nature of MPAHP ligands to achieve other meta-C—H functionalization processes is also illustrated by the development of a meta-C—H amination reaction and a meta-C—H alkynylation reaction.

公开(公告)号：US20190119212A1

公开(公告)日：2019-04-25

申请号：US16094707

申请日：2017-04-18

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07D213/68 ,  C07D213/40 ,  C07D215/38 ,  C07D217/24 ,  C07D405/12 ,  C07D409/12 ,  C07D401/12 ,  C07D213/30 ,  C07D213/55 ,  C07D239/26 ,  C07D231/12 ,  C07D213/72 ,  C07D239/42 ,  C07D231/56 ,  C07D217/18 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  B01J23/44

摘要： A class of mono-protected 3-amino-2-hydroxypyridine (MPAHP) ligands that enable the meta-C—H arylation of anilines, phenols, phenylacetic acids, and biologically relevant heterocyclic compounds using norbornene as a transient mediator is disclosed. The applicability of this meta-arylation methodology in the pharmaceutical industry is illustrated for heteroaryl substrates and heteroaryl iodide coupling partners, a feat made possible by using the MPAHP ligand. The enabling nature of MPAHP ligands to achieve other meta-C—H functionalization processes is also illustrated by the development of a meta-C—H amination reaction and a meta-C—H alkynylation reaction.

公开(公告)号：US11021427B2

公开(公告)日：2021-06-01

申请号：US15733763

申请日：2019-04-17

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu ,  Pengxiang Shen

IPC分类号： C07C51/353 ,  C07C67/343 ,  C07C201/12 ,  C07C253/30 ,  C07F9/40 ,  C07D333/24 ,  C07D209/49 ,  C07D209/48 ,  B01J31/22 ,  B01J27/232 ,  C07D307/54

摘要： The invention includes procedures for stereoselective β-acylation of carboxylic acids having a β-carbon atom. For example, stereoselective acylation procedures include the following reactions: (I)

公开(公告)号：US10759743B2

公开(公告)日：2020-09-01

申请号：US16344092

申请日：2017-10-19

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07C211/35 ,  C07C211/03 ,  C07C269/04 ,  C07D215/12 ,  C07C209/68 ,  C07D213/40 ,  C07D213/61 ,  C07B37/04 ,  B01J31/22 ,  C07D213/64 ,  C07D241/42 ,  C07D319/18 ,  C07D333/22 ,  C07D471/04

摘要： Pd(II)-catalyzed g-G(sp3)-H arylation or heteroarylation of primary amines is realized by using 2-hydroxynicotinaldehyde as a catalytic transient directing group. Importantly, the catalyst and the directing group loading can be lowered to 2% and 4% respectively, thus demonstrating high efficiency of this newly designed transient directing group. Heterocyclic aryl iodides are also compatible with this reaction. Furthermore, swift synthesis of 1,2,3,4-tetrahydronaphthyridine derivatives is accomplished using this reaction.

公开(公告)号：US20190315710A1

公开(公告)日：2019-10-17

申请号：US16086535

申请日：2017-03-20

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07D401/06 ,  C07D413/06 ,  C07D263/10 ,  C07D215/12 ,  C07D209/48 ,  C07D213/06 ,  C07D491/048 ,  C07B53/00 ,  B01J31/18

摘要： Chiral acetyl-protected aminoethyl quinoline (APAQ), pyridine and imazoline ligands are disclosed that enable Pd (II)-catalyzed enantioselective arylation or heteroarylation of ubiquitous prochiral β-methylene C—H bonds of aliphatic amides offers an alternative disconnection for constructing β-chiral centers. Systematic tuning of the ligand structure reveals that a six-membered instead of a five-membered chelation of these types of ligands with the Pd(II) is important for accelerating the C(sp3)-H activation thereby achieving enantioselectivity for quinoline and pyridine ligands.

公开(公告)号：US20190241508A1

公开(公告)日：2019-08-08

申请号：US16344092

申请日：2017-10-19

申请人： The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07C269/04 ,  C07D319/18 ,  C07D213/61 ,  C07D213/64 ,  C07D213/40 ,  C07D215/12 ,  C07D241/42 ,  C07D333/22 ,  C07C209/68 ,  C07D471/04 ,  B01J31/22

CPC分类号： C07C269/04 ,  B01J31/2239 ,  B01J2231/44 ,  B01J2531/824 ,  C07B37/04 ,  C07C209/68 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/18 ,  C07D213/40 ,  C07D213/61 ,  C07D213/64 ,  C07D215/12 ,  C07D241/42 ,  C07D319/18 ,  C07D333/22 ,  C07D471/04 ,  C07C211/40 ,  C07C271/22

摘要： Pd(II)-catalyzed g-G(sp3)-H arylation or heteroarylation of primary amines is realized by using 2-hydroxynicotinaldehyde as a catalytic transient directing group. Importantly, the catalyst and the directing group loading can be lowered to 2% and 4% respectively, thus demonstrating high efficiency of this newly designed transient directing group. Heterocyclic aryl iodides are also compatible with this reaction. Furthermore, swift synthesis of 1,2,3,4-tetrahydronaphthyridine derivatives is accomplished using this reaction.

公开(公告)号：US20180009739A1

公开(公告)日：2018-01-11

申请号：US15547014

申请日：2016-01-28

申请人： Jin-Quan YU ,  The Scripps Research Institute

发明人： Jin-Quan Yu

IPC分类号： C07C233/15 ,  C07D209/48 ,  C07B43/06 ,  C07C233/59 ,  C07C231/12 ,  C07D307/77 ,  C07D209/04

CPC分类号： C07C233/15 ,  C07B43/06 ,  C07C231/12 ,  C07C233/59 ,  C07C2602/10 ,  C07D209/04 ,  C07D209/42 ,  C07D209/48 ,  C07D307/77 ,  C07D307/84

摘要： An alternative approach to formation of a C-C bond at a meta-position of an aromatic compound is disclosed that employs an ethylenically unsaturated bicyclic compound as a transient mediator to achieve meta-selective C-H activation with a simple and common ortho-directing group. The use of a pyridine-based ligand assists in relaying the palladium catalyst to the meta-position by the unsaturated bicyclic compound following initial ortho-C-H activation.