Discrimination of β‐Ketoesters by Ruthenium(II)–Binap‐Catalyzed Asymmetric Hydrogenation

Krämer, Rainer; Brückner, Reinhard

doi:10.1002/anie.200700021

Cited by 23 publications

(6 citation statements)

References 65 publications

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“…This justifies the assumption that the two remaining Weinreb amides shown in Table have analogous 3D structures. This would mean that the rule “hydrogenations catalyzed by Ru complexes of S ‐BINAP establish dashed C–OH bonds – provided the product is drawn with the orientation shown for 2 –” applies not only to such hydrogenations of β‐keto esters and β‐keto amides,[7b] but to β‐keto Weinreb amides as well.…”

Section: Resultsmentioning

confidence: 99%

“…This pioneering reaction did not attract many followers until we reported that an H 2 pressure of 5 bar is sufficient for Ru‐catalyzed asymmetric hydrogenations of β‐keto amides to go to completion at room temp. within less than 1 d . These conditions are generalizable:, by using the dinuclear Ru II complex [Et 2 NH 2 ] + {[RuCl( S )‐BINAP] 2 (µ‐Cl) 3 } – (0.5 mol‐%), with ethanol as the solvent, a hydrogen pressure of 4 bar, and reaction times of 14–36 h, β‐hydroxy amides become available with over 91 % ee .…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Enantiomerically Pure β‐Hydroxy Ketones via β‐Keto Weinreb Amides by a Condensation/Asymmetric‐Hydrogenation/Acylation Sequence

Diehl

Brückner

2016

Eur J Org Chem

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An established route to enantiomerically pure β‐hydroxy ketones proceeds through the asymmetric hydrogenation of β‐keto esters, an ester/amide exchange, and the use of the resulting β‐hydroxy amide for the acylation of an organometallic compound. We shortened this route by showing that β‐keto Weinreb amides are hydrogenated with up to 99 % ee in the presence of [Me2NH2]+{[RuCl(S)‐BINAP]2(µ‐Cl)3}– (0.5 mol‐%) at room temp./5 bar. These Weinreb amides were prepared by seemingly obvious yet unprecedented condensations of lithiated N‐methoxy‐N‐methylacetamide with carboxylic chlorides (51–87 % yield). The resulting β‐hydroxy Weinreb amides were used for the acylation of organolithium and Grignard reagents. They thus gave enantiomerically pure β‐hydroxy ketones (28 examples). A selection of these compounds gave anti‐1,3‐diols after another C=O bond hydrogenation, or syn‐1,3‐diols by a Narasaka–Prasad reduction.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of Enantiomerically Pure β‐Hydroxy Ketones via β‐Keto Weinreb Amides by a Condensation/Asymmetric‐Hydrogenation/Acylation Sequence

Diehl

Brückner

2016

Eur J Org Chem

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“…A Reformatsky-type reaction of 18 mediated by SmI 2 , followed by oxidation of the resulting hydroxy ester, afforded the corresponding bketoester 20. Gratifyingly, catalytic asymmetric hydrogenation of 20 with 1 mol % [23] afforded 21 in 90 % yield, with an excellent de value of > 99 %. Protection of 21 with TBSOTf, followed by basic hydrolysis resulted in A.…”

Section: Resultsmentioning

confidence: 99%

Formal Synthesis of the Anti‐Angiogenic Polyketide (−)‐Borrelidin under Asymmetric Catalytic Control

Madduri¹,

Minnaard²

2010

Chemistry A European J

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Borrelidin (1) is a polyketide that possesses extremely potent anti-angiogenesis activity. This paper describes its formal total synthesis by the most efficient route to date. This modular approach takes optimal benefit of asymmetric catalysis and permits the synthesis of analogues; in addition, the high yields and selectivities obtained eliminate the need for separation of stereoisomers. The upper half of borrelidin has been accessed by iterative copper-catalysed asymmetric conjugate addition of methylmagnesium bromide, whereas synthesis of the lower half of the molecule was achieved by relying on asymmetric hydrogenation and cross-methathesis as key steps.

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“…Subsequently, only limited examples were reported with these difficult substrates 10,48. The amide moiety tended to have a stronger coordination ability than esters,49 so we speculated that γ‐keto amides might be easier to hydrogenate. In the presence of CeCl 3 •7H 2 O as the additive, N , N ‐dimethyl‐4‐oxo‐4‐phenylbutanamide ( 34a ) was hydrogenated to give 35a in 85% ee (Scheme ) 50.…”

Section: γ‐ and δ‐Functionalized Ketones And Simple Ketonesmentioning

confidence: 97%

A Decennary Journey towards the Efficient Asymmetric Hydrogenation of Highly Functionalized Ketones

Lü

Zhang

2016

The Chemical Record

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Around 2006, our group launched a long-term project on the asymmetric hydrogenation of functionalized ketones by using ruthenium complexes with SunPhos ligands. In this review, we recount the burgeoning and blossoming of this project. At the outset, we attempted some benchmark reactions with an array of monofunctionalized ketones, including α- and β-keto esters/amides, β-keto sulfones, phosphonates, and α-hydroxy ketones. For α-keto esters and amides, we discovered that CeCl •7H O was an efficient additive for both activity and enantioselectivity. The element iodine was found to be a valid additive for β-keto sulfones. β,γ-Unsaturated α-keto acids and esters were also hydrogenated to the saturated chiral blocks with good enantioselectivity and a high turnover number. For the α-substituted β-keto esters and phosphonates, exceptionally high stereoselectivity was achieved through dynamic kinetic resolution. Based on these incipient successes, we diverted to bifunctionalized ketone substrates, such as γ-heteroatom-substituted β-keto esters and δ-ketal-β-keto esters. For the δ-ketal-β-keto esters, CaCO was added to stabilize the δ-ketal groups, which ensured the formation of δ-ketal-β-hydroxy esters in good yields and high ee values. More interestingly, γ-halo-γ,δ-unsaturated-β-keto esters were hydrogenated to afford highly enantiopure chiral allyl alcohols under mild and neutral conditions. The distance effect of the directing groups was investigated in β-, γ-, and δ-keto amides; the last two were hydrogenated with the Ru-SunPhos-diamine system. To implement the pinpoint recognition of two carbonyl groups in similar chemical propinquity, we compared the reaction rates of different β-keto acid derivatives. THF was found to be a helpful coordinative solvent to control the chemo- and enantioselectivity for more challenging polycarbonyl substrates, such as 3-oxo glutaric acid derivatives, β,δ-diketo carboxamides, and γ-heteroatom-substituted β-diketones. The effects of solvents and heteroatoms in these substrates were also studied. Applications of these hydrogenation reactions were also exemplified by the employment of the products for important pharmaceutical syntheses.

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Discrimination of β‐Ketoesters by Ruthenium(II)–Binap‐Catalyzed Asymmetric Hydrogenation

Cited by 23 publications

References 65 publications

Synthesis of Enantiomerically Pure β‐Hydroxy Ketones via β‐Keto Weinreb Amides by a Condensation/Asymmetric‐Hydrogenation/Acylation Sequence

Synthesis of Enantiomerically Pure β‐Hydroxy Ketones via β‐Keto Weinreb Amides by a Condensation/Asymmetric‐Hydrogenation/Acylation Sequence

Formal Synthesis of the Anti‐Angiogenic Polyketide (−)‐Borrelidin under Asymmetric Catalytic Control

A Decennary Journey towards the Efficient Asymmetric Hydrogenation of Highly Functionalized Ketones

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