Metal-free Deoxygenative Coupling of Alcohol-derived Benzoates and Pyridines for Small Molecules and DNA-encoded Libraries Synthesis

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 Jul 1

PMID 35774170

Authors

Sai Rohini Narayanan Kolusu

Manuel Nappi

Affiliations

Soon will be listed here.

Abstract

Alcohols are among the most widely occurring functional groups found in naturally abundant, biologically relevant organic compounds, which in many cases are considered feedstock chemicals. Herein, we report a metal-free method for the deoxygenative coupling of alcohol-derived benzoates and pyridines promoted by visible light. Given the practical, mild and water-compatible conditions, small molecules and DNA headpieces can be successfully functionalized with a range of primary, secondary and tertiary alcohols. This protocol is distinguished by its wide substrate scope and broad applicability, even in the context of late-stage functionalization and DNA-drug coupling reactions.

Citing Articles

Dearomative intermolecular [2 + 2] photocycloaddition for construction of C(sp)-rich heterospirocycles on-DNA.

Li L, Matsuo B, Levitre G, McClain E, Voight E, Crane E Chem Sci. 2023; 14(10):2713-2720.

PMID: 36908969 PMC: 9993886. DOI: 10.1039/d3sc00144j.

Visible Light Photoredox-Catalyzed Decarboxylative Alkylation of 3-Aryl-Oxetanes and Azetidines via Benzylic Tertiary Radicals and Implications of Benzylic Radical Stability.

Dubois M, Rojas J, Sterling A, Broderick H, Smith M, White A J Org Chem. 2023; 88(10):6476-6488.

PMID: 36868184 PMC: 10204094. DOI: 10.1021/acs.joc.3c00083.

Practical and General Alcohol Deoxygenation Protocol.

Williams O, Chmiel A, Mikhael M, Bates D, Yeung C, Wickens Z Angew Chem Int Ed Engl. 2023; 62(18):e202300178.

PMID: 36840940 PMC: 10121858. DOI: 10.1002/anie.202300178.

References

Kariofillis S, Jiang S, Zuranski A, Gandhi S, Martinez Alvarado J, Doyle A . Using Data Science To Guide Aryl Bromide Substrate Scope Analysis in a Ni/Photoredox-Catalyzed Cross-Coupling with Acetals as Alcohol-Derived Radical Sources. J Am Chem Soc. 2022; 144(2):1045-1055. PMC: 8810294. DOI: 10.1021/jacs.1c12203. View

Ertl P, Schuhmann T . A Systematic Cheminformatics Analysis of Functional Groups Occurring in Natural Products. J Nat Prod. 2019; 82(5):1258-1263. DOI: 10.1021/acs.jnatprod.8b01022. View

Shaw M, Twilton J, MacMillan D . Photoredox Catalysis in Organic Chemistry. J Org Chem. 2016; 81(16):6898-926. PMC: 4994065. DOI: 10.1021/acs.joc.6b01449. View

Kolmel D, Ratnayake A, Flanagan M . Photoredox cross-electrophile coupling in DNA-encoded chemistry. Biochem Biophys Res Commun. 2020; 533(2):201-208. DOI: 10.1016/j.bbrc.2020.04.028. View

Wang P, Chen J, Xiao W . Hantzsch esters: an emerging versatile class of reagents in photoredox catalyzed organic synthesis. Org Biomol Chem. 2019; 17(29):6936-6951. DOI: 10.1039/c9ob01289c. View

Nicastri M, Lehnherr D, Lam Y, DiRocco D, Rovis T . Synthesis of Sterically Hindered Primary Amines by Concurrent Tandem Photoredox Catalysis. J Am Chem Soc. 2020; 142(2):987-998. DOI: 10.1021/jacs.9b10871. View

Gao Y, Wu Z, Yu L, Wang Y, Pan Y . Alkyl Carbazates for Electrochemical Deoxygenative Functionalization of Heteroarenes. Angew Chem Int Ed Engl. 2020; 59(27):10859-10863. DOI: 10.1002/anie.202001571. View

Romero N, Nicewicz D . Organic Photoredox Catalysis. Chem Rev. 2016; 116(17):10075-166. DOI: 10.1021/acs.chemrev.6b00057. View

Prier C, Rankic D, MacMillan D . Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis. Chem Rev. 2013; 113(7):5322-63. PMC: 4028850. DOI: 10.1021/cr300503r. View

10.

Wang J, Lundberg H, Asai S, Martin-Acosta P, Chen J, Brown S . Kinetically guided radical-based synthesis of C(sp)-C(sp) linkages on DNA. Proc Natl Acad Sci U S A. 2018; 115(28):E6404-E6410. PMC: 6048552. DOI: 10.1073/pnas.1806900115. View

11.

Lam K, Marko I . Using toluates as simple and versatile radical precursors. Org Lett. 2008; 10(13):2773-6. DOI: 10.1021/ol800944p. View

12.

Zhang X, MacMillan D . Alcohols as Latent Coupling Fragments for Metallaphotoredox Catalysis: sp-sp Cross-Coupling of Oxalates with Aryl Halides. J Am Chem Soc. 2016; 138(42):13862-13865. PMC: 5464990. DOI: 10.1021/jacs.6b09533. View

13.

Nawrat C, Jamison C, Slutskyy Y, MacMillan D, Overman L . Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling. J Am Chem Soc. 2015; 137(35):11270-11273. PMC: 4632490. DOI: 10.1021/jacs.5b07678. View

14.

Greenwood J, Boyle B, McNally A . Pyridylphosphonium salts as alternatives to cyanopyridines in radical-radical coupling reactions. Chem Sci. 2021; 12(31):10538-10543. PMC: 8356814. DOI: 10.1039/d1sc02324a. View

15.

Gonzalez-Esguevillas M, Miro J, Jeffrey J, MacMillan D . Photoredox-catalyzed deoxyfluorination of activated alcohols with Selectfluor. Tetrahedron. 2020; 75(32):4222-4227. PMC: 7441851. DOI: 10.1016/j.tet.2019.05.043. View

16.

Lackner G, Quasdorf K, Overman L . Direct construction of quaternary carbons from tertiary alcohols via photoredox-catalyzed fragmentation of tert-alkyl N-phthalimidoyl oxalates. J Am Chem Soc. 2013; 135(41):15342-5. PMC: 3856227. DOI: 10.1021/ja408971t. View

17.

Smith J, Harwood S, Baran P . Radical Retrosynthesis. Acc Chem Res. 2018; 51(8):1807-1817. PMC: 6349421. DOI: 10.1021/acs.accounts.8b00209. View

18.

Togo , MATSUBAYASHI , Yamazaki , Yokoyama . Deoxygenative functionalization of hydroxy groups via xanthates with tetraphenyldisilane. J Org Chem. 2000; 65(9):2816-9. DOI: 10.1021/jo991715r. View

19.

Phelan J, Lang S, Sim J, Berritt S, Peat A, Billings K . Open-Air Alkylation Reactions in Photoredox-Catalyzed DNA-Encoded Library Synthesis. J Am Chem Soc. 2019; 141(8):3723-3732. PMC: 6393171. DOI: 10.1021/jacs.9b00669. View

20.

Flood D, Asai S, Zhang X, Wang J, Yoon L, Adams Z . Expanding Reactivity in DNA-Encoded Library Synthesis via Reversible Binding of DNA to an Inert Quaternary Ammonium Support. J Am Chem Soc. 2019; 141(25):9998-10006. PMC: 7033622. DOI: 10.1021/jacs.9b03774. View