Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl N-Heteroaryl Ketones with N-Oxide as a Removable ortho-Substituent

Liu, Qixing; Wang, Chunqin; Zhou, Haifeng; Wang, Baigui; Lv, Jiaqi; Cao, Lu; Fu, Yigang

doi:10.1021/acs.orglett.7b03878

Cited by 46 publications

(15 citation statements)

References 27 publications

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“…Azaarene-substituted secondary alcohols, as another kind of α-tertiary carbon-based azaarene derivative, are also important building blocks of numerous pharmaceuticals and biologically active compounds (Rennison et al., 2007). The chiral transition metal-catalyzed asymmetric transfer hydrogenation of aryl N -heteroaryl ketones with sodium formate as a hydrogen source has been developed to access the chiral variants (Liu et al., 2018). However, this strategy is only suitable for aryl N -heteroaryl ketones and is likely not compatible to introduce deuterium on the stereocenters with D 2 O as the deuterium reagent.…”

Section: Resultsmentioning

confidence: 99%

Photoredox-Catalyzed Enantioselective α-Deuteration of Azaarenes with D2O

Shao

et al. 2019

iScience

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Summary The site-specific incorporation of deuterium (D) into small molecules is frequently used to access isotopically labeled compounds with broad utility in many research areas, such as drug development, mechanistic studies, and NMR analyses. Nevertheless, the deuteration of a stereocenter in an enantioselective manner, which could slow the metabolism and improve the bioavailability of bioactive molecules, remains challenging owing to the lack of established catalytic methods. Here, we report an asymmetric α-deuteration strategy for azaarenes with inexpensive D 2 O as the deuterium source. A cooperative visible light-driven photoredox and chiral Brønsted acid–catalyzed system using a Hantzsch ester as the terminal reductant has been developed, which enables racemic α-chloro-azaarenes and prochiral azaarene-substituted ketones to experience a single-electron reduction–enantioselective deuteration process. The transition metal-free method provides important chiral α-deuterated azaarenes in satisfactory yields with good to excellent enantioselectivities (up to 99% ee) and substantial deuterium incorporation.

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Section: Resultsmentioning

confidence: 99%

Photoredox-Catalyzed Enantioselective α-Deuteration of Azaarenes with D2O

Shao

et al. 2019

iScience

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“…A few earlier methods have relied mainly on Ruand Ir-catalyzed asymmetric transfer hydrogenation. 30,31 In addition, the substrates were restricted to ortho-substituted aryl azaarene ketones and N-oxidized azaarene derivatives. On the basis of the prior advances in catalytic asymmetric photoreduction of 1,2-diketones and -keto ketimines, 32 in 2019, Jiang and co-workers 33 developed a direct and more general method for the asymmetric reduction of azaarene-based ketones 37 to chiral alcohols 38 through photoredox asymmetric catalysis using chiral phosphoric acid catalyst 39, (thiophen-2-yl)pyrazine-2,3dicarbonitrile 40 as a photosensitizer, and N-phenylpiperidine (41) as a sacrificial reductant (Scheme 10).…”

Section: Short Review Synthesismentioning

confidence: 99%

Recent Advances in Organocatalyzed Asymmetric Reduction of Prochiral Ketones: An Update

Qin

Han

2021

Synthesis

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Chiral alcohols are important synthetic intermediates or building blocks for the diverse synthesis of drugs, agrochemicals, and natural products. Asymmetric reduction of prochiral ketones has been the most popularly investigated method for accessing chiral alcohols. In this regard, the organocatalyzed asymmetric reduction as a complementary of transition-metal- and enzyme-catalyzed reactions have attracted tremendous interest in the past decades due to the nature of metal-free and easy operation, as well as, principly, the ease of recovery and reuse of catalysts. Following up a comprehensive overview on organocatalyzed asymmetric reduction of prochiral ketones in early 2018, this short review is intended to summarize the recent progress in this area from the beginning of the year 2018 to the end of Aug. 2021.

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“…For example, chiral β‐hydroxysulfones were synthesized from readily available terminal alkynes and sodium sulfinates via oxysulfonylation and asymmetric transfer hydrogenation [10] . To continue our interest in asymmetric transfer hydrogenation of aryl N ‐heteroaryl ketones, [9a,b,h] we report a one‐pot asymmetric stepwise reductive amination of aryl N ‐heteroaryl ketones with benzyl amines without isolation of the unstable ketimines, using p ‐toluenesulfonic acid as a catalyst for the formation of imines, chiral iridium complex as a catalyst and a mixture of formic acid/triethylamine as a reductant for the tandem asymmetric transfer hydrogenation, affording chiral aryl N ‐heteroaryl methylamines in up to 99% ee (Scheme 1d).…”

Section: Introductionmentioning

confidence: 99%