A Practical Access to Highly Enantiomerically Pure Flavanones by Catalytic Asymmetric Transfer Hydrogenation

Lemke, M.; Schwab, Pia; Fischer, Petra; Tischer, Sandra; Witt, Morris; Noehringer, Laurence; Rogachev, Victor O.; Jäger, Anne; Kataeva, О. N.; Fröhlich, Roland; Metz, Peter

doi:10.1002/anie.201306500

Cited by 51 publications

(35 citation statements)

References 72 publications

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“…It has been reported in literature that racemic flavanone (4) can be enantiospecifically reduced to (2R,4R)-cis-flavan-4-ol (5) with the help of chiral ruthenium complexes [17]. Except for the respective flavan-4-ol (5) this method afforded also unreacted (S)-flavanone (4) with a high enantiomeric excess [17].…”

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Enantioselective reduction of flavanone and oxidation of cis- and trans-flavan-4-ol by selected yeast cultures

Janeczko

Dymarska

Siepka

et al. 2014

Journal of Molecular Catalysis B: Enzymatic

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Section: Introductionmentioning

confidence: 93%

“…Except for the respective flavan-4-ol (5) this method afforded also unreacted (S)-flavanone (4) with a high enantiomeric excess [17]. (S)-flavanone (4) and (2S,4S)-cis-flavan-4-ol (5) were also obtained by means of an enantioselective Ru/NHC-catalyzed hydrogenation of flavone [18].…”

Section: Introductionmentioning

confidence: 98%

Enantioselective reduction of flavanone and oxidation of cis- and trans-flavan-4-ol by selected yeast cultures

Janeczko

Dymarska

Siepka

et al. 2014

Journal of Molecular Catalysis B: Enzymatic

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“…Years later, Metz's group provided a practical catalytic asymmetric transfer hydrogenation of racemic flavanones in a mixture of formic acid and triethylamine, resulting in almost enantiomerically pure flavanones 97 and 4‐hydroxy flavanes 98 through kinetic resolution with rhodium(III) complex 99 by catalytic asymmetric transfer hydrogenation (Scheme ) . Particularly, flavanones with prenylated representatives (R 1 =prenyl), were acquired in high yields and enantiomeric excess with even 0.5 mol% catalyst loading.…”

Section: Asymmetric Synthesis Of Flavanesmentioning

confidence: 99%

Catalytic Asymmetric Syntheses of 2‐Aryl Chromenes

2019

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Chiral chromene motifs are important heterocycles in numerous natural products and bioactive molecules. Among them, flavenes, flavanes, and flavanones, which consist of the 2-aryl-chromene skeleton are observed most frequently. As subgroups of flavonoids, they often occur in various plants and show many biological activities, such as antitumor, antioxidant, antibacterial, anti-inflammatory, and anticoagulant properties. This Minireview summarizes recent reports on catalytic asymmetric synthesis of flavenes, flavanes, and flavanones. derivatives 1, giving the adduct 6. The subsequent intramolecular adol reaction and dehydration providing the desired product 3 (Scheme 2).Almost the same time, professor Córdova and coworkers presented the same domino reaction between 1 a and 2 catalyzed by 4 a, providing a series of 2H-flavenes in high yields and with 83-98% ees (Scheme 3). [5] Notably, by using 2nitrobenzoic acid as an additive, product 3 a could be obtained with 37% yield and 88% ee, comparing to 10% yield and 9% ee when adding no additives. More significantly, another additive, 4 Å molecular sieves, promoted the reaction significantly, increasing the product yield from 37% to 81% with no enantioselectivity erosion. The authors believed that the addition of an organic acid accelerated the adol condensation by activating the benzaldehyde. Also, the organic acid could stabilized the iminium intermediate, facilitating the oxa-Michael addition. The product 7 could be observed by NMR analysis, which gave an obvious evidence to the proposed reaction pathway (Scheme 2).By applying the similar approach, Wang and coworkers developed the asymmetric reaction of 1 and 2 catalyzed by organocatalyst 4 b. [6] Different from Córdova's condition, Wang found that Cl(CH 2 ) 2 Cl was the best solvent to provide the highest enantioselectivity. Lowering the reaction temperature improved ee with prolonged time for completion. The reaction had a broad scope and the functionalized 2H-flavenes were synthesized respectively high yields (53-98%) and with good to excellent levels of enantioselectivities (75-99% ee). However, the electronic nature of the α,β-unsaturated aldehydes 2 had a remarkable effect on the reactivities and ees that 2 bearing electron-withdrawing groups, such as nitro group, generally Scheme 2. Proposed mechanism of the organocatalytic asymmetric oxa-Michael addition/intramolecular adol reaction/dehydration cascade. Scheme 3. Direct organocatalytic asymmetric domino oxa-Michael/aldol condensations between 1 a and α, β-unsaturated aldehydes 2.

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“…Additional attempts of the dynamic kinetic resolution process in which the maximum theoretical yield is 100 %w ould be highly desirable.T he fundamental requirement of DKR is that the two substrate enantiomers can undergo rapid in situ interconversion under the same reaction conditions. [10] Based on Metzsk inetic resolution of flavanones, [11] ad ynamic kinetic resolution version was developed through ac onjugate elimination/conjugate addition pathway in concert with asymmetric ketone transfer hydrogenation step. [12] Therefore,w e surveyed the chromene acetal 4a in our preliminary trials (see Table 4).…”

Section: Angewandte Chemiementioning

confidence: 99%

Kinetic Resolution and Dynamic Kinetic Resolution of Chromene by Rhodium‐Catalyzed Asymmetric Hydroarylation

Yang

Luo

et al. 2019

Angew Chem Int Ed

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Ah ighly efficient kinetic resolution and dynamic kinetic resolution of chromene is reported for the first time and they procced by arhodium-catalyzed asymmetric hydroarylation pathway.T his new approach offers versatile access to various chiral 2,3-diaryl-chromanes containing vicinal stereogenic centers,a sw ell as the recovered chiral flavenes,i nh igh yields with excellent ee values (s factor up to 532). Particularly noteworthy is that this strategy can be further extended to the establishment of adynamic version of the kinetic resolution of chromene acetals and allows complete access to chiral isoflavanes and a-aryl hydrocoumarins.Flavonoids are privileged structural motifs in numerous natural products and pharmaceutical molecules which show many biological activities such as antitumor,a ntioxidant, antibacterial, and anti-inflammatory properties. [1] Flavene, flavane,a nd isoflavane,w hich feature ac hiral center, are subgroups of flavonoids ( Figure 1). Given the prevalence of this structural unit there has been considerable interest in developing methods for the generation of flavene skeletons. Nevertheless,f acile access of their corresponding optically active variants by asymmetric catalysis remains limited. [2] Rhodium-catalyzed asymmetric arylation has been intensively investigated in recent years,however,the alkenes were limited mainly to those activated by proximal electronwithdrawing substituents (represented by carbonyl groups). [3] In fact, examples concerning the rhodium-catalyzed asymmetric arylation of alkenes are rare.I n2 008, Lautens and co-workers reported an asymmetric hydroarylation process in the reaction of ab icyclo[2.2.1]heptane system. [4] Recently,H ayashi and co-workers also reported several successful examples of asymmetric hydroarylations of cycloalkenes. [5] To the alkenylarene substrates,L autens reported the rhodium-catalyzed asymmetric addition of arylboronic acid compounds to simple styrenes and it resulted in Heck-type products,owing to the alkylrhodium intermediate often prefering b-hydride elimination rather than protonation (Scheme 1a). [6] Thea symmetric hydroarylation of styrene was realized by Lam and co-workers where the strongly electron-withdrawing group (nitro) at the paraposition of the arene was aprerequisite to afford the desired hydroarylation product (Scheme 1b). [7] Thus,weselected 2Hchromene skeletons as substrates,i nw hich the arylrhodium intermediates do not have syn b-hydrogen atoms for bhydrogen elimination, and would thus undergo protonation to give hydroarylation products.We embarked on this investigation using the rac-flavene 1aas the benchmark substrate and phenylboronic acid (2a)as the arylating agent (Table 1). To our delight, the arylation product 3aa,w ith vicinal chiral centers,w as obtained as as ingle diastereomer in 48 %y ield with 94 % ee,a nd the recovered 1a was also obtained in 31 %y ield with 95 % ee, catalyzed by the chiral Rh complex in situ generated from 2.5 mol %[ Rh(cod)Cl] 2 and 6mol %( R)-Binap (entry 1). With the hopeful ini...

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A Practical Access to Highly Enantiomerically Pure Flavanones by Catalytic Asymmetric Transfer Hydrogenation

Abstract: A surprisingly selective, non-enzymatic kinetic resolution of readily available, racemic β-chiral ketones enabled the title process, which was applied to a rapid synthesis of several bioactive flavanones in virtually enantiopure form (see scheme; MOM=methoxymethyl, Ts=p-toluenesulfonyl).

Cited by 51 publications

References 72 publications

Enantioselective reduction of flavanone and oxidation of cis- and trans-flavan-4-ol by selected yeast cultures

Enantioselective reduction of flavanone and oxidation of cis- and trans-flavan-4-ol by selected yeast cultures

Catalytic Asymmetric Syntheses of 2‐Aryl Chromenes

Kinetic Resolution and Dynamic Kinetic Resolution of Chromene by Rhodium‐Catalyzed Asymmetric Hydroarylation

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