A Decarboxylative Cross-Coupling Platform To Access 2-Heteroaryl Azetidines: Building Blocks with Application in Medicinal Chemistry

被引：11

作者：

Brewster II, James T. ^{[1
]}

Randall, Samuel D. ^{[1
]}

Kowalski, John ^{[2
]}

Cruz, Cole ^{[1
]}

Shoemaker, Richard ^{[1
]}

Tarlton, Eugene ^{[1
]}

Hinklin, Ronald J. ^{[1
]}

机构：

[1] Pfizer Boulder Res & Dev, Med Chem Div, Boulder, CO 80301 USA

[2] Pfizer Boulder Res & Dev, Drug Metab & Pharmacokinet, Boulder, CO 80301 USA

来源：

ORGANIC LETTERS | 2022年 / 24卷 / 49期

关键词：

REDOX-ACTIVE ESTERS; NICKEL; PHOTOREDOX; ELECTROPHILE; HALIDES; FUNCTIONALIZATION; DISCOVERY; CATALYSIS; RING;

D O I：

10.1021/acs.orglett.2c03852

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Photoredox-transition metal dual catalysis provides a unique platform for constructing sp3-rich chemical matter. Here, we report a nickel-catalyzed cross-coupling of commercially available or easily prepared redox-active NHP azetidine-2-carboxylates with commercially available heteroaryl iodides to yield 2-heteroaryl azetidines. This "off-the-shelf" approach yielded products amenable to diversification giving access to novel saturated heterocyclic scaffolds useful for medicinal chemistry programs. An alternative mechanism for Hantzsch ester within nickel-catalyzed cross-coupling of heteroaryl halides and alpha-amino radicals is also presented.

引用

页码：9123 / 9129

页数：7

共 80 条

[1]

[Anonymous], 2 HETEROARYL AZETIDI

[2]

[Anonymous], DESPITE SIGNIFICANT

[3]

[Anonymous], TOLERANCE DIFFERENT

[4] Recent advances in the chemistry of metallated azetidines [J].

Antermite, Daniele ;

Degennaro, Leonardo ;

Luisi, Renzo .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2017, 15 (01) :34-50

[5] Put a ring on it: application of small aliphatic rings in medicinal chemistry [J].

Bauer, Matthias R. ;

Di Fruscia, Paolo ;

Lucas, Simon C. C. ;

Michaelides, Iacovos N. ;

Nelson, Jennifer E. ;

Storer, R. Ian ;

Whitehurst, Benjamin C. .

RSC MEDICINAL CHEMISTRY, 2021, 12 (04) :448-471

[6] Methods for the Synthesis of Substituted Azetines [J].

Baumann, Andreas N. ;

Eisold, Michael ;

Music, Arif ;

Haas, Geoffrey ;

Kiw, Yu Min ;

Didier, Dorian .

ORGANIC LETTERS, 2017, 19 (20) :5681-5684

[7] Synthesis of azetidines via visible-light-mediated intermolecular [2+2] photocycloadditions [J].

Becker, Marc R. ;

Wearing, Emily R. ;

Schindler, Corinna S. .

NATURE CHEMISTRY, 2020, 12 (10) :898-+

[8] Mechanism and Selectivity in Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Halides with Alkyl Halides [J].

Biswas, Soumik ;

Weix, Daniel J. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (43) :16192-16197

[9] Intramolecular, Visible-Light-Mediated Aza Paterno-Buchi Reactions of Unactivated Alkenes [J].

Blackmun, Dominique E. ;

Chamness, Stephen A. . ;

Schindler, Corinna S. .

ORGANIC LETTERS, 2022, 24 (16) :3053-3057

[10]

Bohacek RS, 1996, MED RES REV, V16, P3, DOI 10.1002/(SICI)1098-1128(199601)16:1<3::AID-MED1>3.3.CO

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