Asymmetric Transfer Hydrogenation of Functionalized Acetylenic Ketones

Fang, Zhijia; Wills, Martin

doi:10.1021/jo401284c

Cited by 59 publications

(29 citation statements)

References 111 publications

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“…In the first extension of our studies, we sought to determine what effect an electron-donating group on the side chains of the catalyst might have. Towards this end we prepared the pyridine-containing complex 14, from diol 15 12 and via the dialkyne precursor 16, following the route illustrated in Scheme 2a. Treatment of 14 with slightly more than 1 equivalent of trimethylamine N-oxide (TMAO) 13 resulted in formation of a new species which appears to match the structure 17 in which one CO group was replaced by the pyridine in an intramolecular reaction.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and applications to catalysis of novel cyclopentadienone iron tricarbonyl complexes

et al. 2018

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A series of cyclopentadienone iron tricarbonyl complexes with diverse structures were prepared, in each case using the intramolecular cyclisation of a diyne as a key step. The complexes were generated as enantiomerically enriched through (i) asymmetric synthesis of a C2-symmetric diol following a reported protocol, (ii) resolution of enantiomerically-enriched diastereoisomers formed from a chiral alcohol and (iii) kinetic resolution of a racemic ketone-containing iron tricarbonyl complex. The approaches underline the diversity of the synthetic routes which can be employed in the synthesis of homochiral cyclopentadienone iron tricarbonyl complexes. Although the complexes proved to be effective as catalysts for the reduction of ketones, the alcohol products were formed in low ees (not exceeding ca. 35%), highlighting the challenging nature of asymmetric catalysis using complexes of this type.

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Section: Resultsmentioning

confidence: 99%

Synthesis and applications to catalysis of novel cyclopentadienone iron tricarbonyl complexes

et al. 2018

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“…In agreement with the observations made with non‐tethered catalysts,6q–u acetylenic ketones are excellent substrates, and have been studied and employed extensively in many reported applications. The tethered catalysts have proved valuable and have been used in processes for the synthesis of propargylic alcohols in excellent ee 49,50. They have also proven to be active without any need for pre‐formation of the 16‐electron species, which had been required in previous applications of first‐generation catalysts 6q–u.…”

Section: Application To Other Substrates: Beyond Acetophenone Derivatmentioning

confidence: 99%

“…In one application, the alkyne directing effect could be used twice in a sequence to deliver a diol product, following alkyne reduction (Figure ) 49a…”

Section: Application To Other Substrates: Beyond Acetophenone Derivatmentioning

confidence: 99%

The Development of Phosphine‐Free "Tethered" Ruthenium(II) Catalysts for the Asymmetric Reduction of Ketones and Imines

Nedden

Zanotti‐Gerosa

Wills

2016

The Chemical Record

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120

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In this account, we describe the design, synthesis and applications of tethered versions of the Ru(II)/N-tosyl-1,2-diphenylethylene-1,2-diamine (TsDPEN) class of catalyst that are commonly used for asymmetric transfer hydrogenation and asymmetric hydrogenation of ketones and imines. The review covers key aspects of the reaction mechanisms and examples of applications, including industrial applications to pharmaceutically important target molecules. In addition, closely related catalysts based on Rh(III) and Ir(III) are also described.

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“…A possible explanation that may account for these results is the existence of unfavorable steric hindrance imposed by the rigid linear alkynyl unit, which prevents interactions between catalyst I and substrate 4 (Table 5, entries 1 and 4). To circumvent this reactivity problem, inspired by the work of Wills and co‐workers, we turned our attention to the use of tethered Ru II –TsDPEN catalyst J ,13 known to be a highly active precatalyst for ATH of hindered ketones,13f, 14 imines,14 and acetylenic ketones,15 and Rh III –TsDPEN precatalyst K , a complex developed in our group 16. Unfortunately, neither J nor K reduced substrate 4 a , presumably due to incompatibility in the spatial arrangement of the substrate with the tethered catalyst (Table 5, entries 2–3).…”

Section: Resultsmentioning

confidence: 99%

Efficient Synthesis of Differentiated syn‐1,2‐Diol Derivatives by Asymmetric Transfer Hydrogenation–Dynamic Kinetic Resolution of α‐Alkoxy‐Substituted β‐Ketoesters

Monnereau

Cartigny

Scalone

et al. 2015

Chemistry A European J

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Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α-alkoxy-β-ketoesters in the presence of well-defined, commercially available, chiral catalyst Ru(II) -(N-p-toluenesulfonyl-1,2-diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α-alkoxy-β-hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99 %). Additionally, after extensive screening of the reaction conditions, the use of Ru(II) - and Rh(III) -tethered precatalysts extended this process to more-challenging substrates that bore alkenyl-, alkynyl-, and alkyl substituents to provide the corresponding syn α-alkoxy-β-hydroxyesters with excellent enantiocontrol (up to 99 % ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)-propanoate, which is an important pharmacophore in a number of peroxisome proliferator-activated receptor α/γ dual agonist advanced drug candidates used for the treatment of type-II diabetes.

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Asymmetric Transfer Hydrogenation of Functionalized Acetylenic Ketones

Abstract: A systematic study of the asymmetric transfer hydrogenations of functionalized acetylenic ketones and diketones has been completed, together with a total synthesis of (S,S)-(-)-yashabushidiol B. In several cases, excellent enantioselectivities and yields were achieved.

Cited by 59 publications

References 111 publications

Synthesis and applications to catalysis of novel cyclopentadienone iron tricarbonyl complexes

Synthesis and applications to catalysis of novel cyclopentadienone iron tricarbonyl complexes

The Development of Phosphine‐Free "Tethered" Ruthenium(II) Catalysts for the Asymmetric Reduction of Ketones and Imines

Efficient Synthesis of Differentiated syn‐1,2‐Diol Derivatives by Asymmetric Transfer Hydrogenation–Dynamic Kinetic Resolution of α‐Alkoxy‐Substituted β‐Ketoesters

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