Enantioselective synthesis of 3-arylquinazolin-4(3H)-ones via peptide-catalyzed atroposelective bromination

Journal of the American Chemical Society
Matthew E DienerScott J Miller

Abstract

We report the development of a tertiary amine-containing β-turn peptide that catalyzes the atroposelective bromination of pharmaceutically relevant 3-arylquinazolin-4(3H)-ones (quinazolinones) with high levels of enantioinduction over a broad substrate scope. The structure of the free catalyst and the peptide-substrate complex were explored using X-ray crystallography and 2D-NOESY experiments. Quinazolinone rotational barriers about the chiral anilide axis were also studied using density functional theory calculations and are discussed in light of the high enantioselectivities observed. Mechanistic studies also suggest that the initial bromination event is stereodetermining, and the major monobromide intermediate is an atropisomerically stable, mono-ortho-substituted isomer. The observation of stereoisomerically stable monobromides stimulated the conversion of the tribromide products to other atropisomerically defined products of interest. For example, (1) a dehalogenation Suzuki-Miyaura cross-coupling sequence delivers ortho-arylated derivatives, and (2) a regioselective Buchwald-Hartwig amination procedure installs para-amine functionality. Stereochemical information was retained during these subsequent transformations.

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Citations

Dec 10, 2016·Journal of the American Chemical Society·Shaoyu LiBin Tan
Dec 29, 2016·Journal of the American Chemical Society·Anthony J MetranoScott J Miller
Jan 21, 2017·Journal of the American Chemical Society·Lei ZhangBin Tan
Mar 17, 2017·Chemistry : a European Journal·Margery Cortes-ClergetMarc Lecouvey
May 4, 2017·Nature Communications·Sheng-Cai ZhengBin Tan
May 12, 2016·Angewandte Chemie·Vincent C Fäseke, Christof Sparr
Mar 11, 2016·Chemical Communications : Chem Comm·A J MetranoS J Miller
Jan 25, 2018·Chemistry : a European Journal·Yumiko IwasakiOsamu Kitagawa
Aug 1, 2016·Chemical Science·Dipan GhoshJayanta Chatterjee
Dec 20, 2017·Nature Chemistry·Liang-Wen QiBin Tan
Aug 8, 2017·Chemistry : a European Journal·Shumpei TeradaVadim A Soloshonok
May 30, 2019·Organic & Biomolecular Chemistry·Ping-Gui LiLiang-Hua Zou
Jan 31, 2018·Future Medicinal Chemistry·Sean T Toenjes, Jeffrey L Gustafson
Aug 29, 2017·Beilstein Journal of Organic Chemistry·Ryota MiyajiSeijiro Matsubara
Mar 12, 2020·Angewandte Chemie·Joanna Wencel-DelordFrançoise Colobert
May 13, 2017·Organic & Biomolecular Chemistry·P Renzi
May 5, 2020·Chemistry : a European Journal·Tian-Zhen LiFeng Shi
Oct 20, 2020·Chemistry : a European Journal·Vinzenz Thönnißen, Frederic W Patureau
Mar 30, 2021·Chemical Reviews·Jun Kee ChengBin Tan
Jul 8, 2021·Organic & Biomolecular Chemistry·Guosheng FangGang Zhao
Aug 13, 2021·Journal of the American Chemical Society·Junxian YangBin Tan

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