Deracemization of racemic alcohols combining photooxidation and biocatalytic reduction

Wang, Jianfeng; Peng, Yongzhen; Xu, Jian; Wu, Qi

doi:10.1039/d2ob01386j

Cited by 11 publications

(7 citation statements)

References 40 publications

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“…Furthermore, ( R )- 3ba was readily converted to ( S )- 3ba with an entirely reverse chirality under standard photoenzymatic conditions (Scheme e). These results ruled out the possibility of a photocatalytic oxidation/enzymatic reduction mechanism for the deracemization of rac - 3ba . − The synthetic importance of this amino alcohol motif was emphasized by the reaction of ( S )- 3ba and 1,1′-carbonyldiimidazole ( 5 ), and the oxazolidinone product 6 can be easily produced in 99% yield and >99% ee (Scheme f).…”

Section: Resultsmentioning

confidence: 99%

Photoredox/Enzymatic Catalysis Enabling Redox-Neutral Decarboxylative Asymmetric C–C Coupling for Asymmetric Synthesis of Chiral 1,2-Amino Alcohols

Liu,

Zhu,

et al. 2023

JACS Au

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Photocatalysis offers tremendous opportunities for enzymes to access new functions. Herein, we described a redox-neutral photocatalysis/enzymatic catalysis system for the asymmetric synthesis of chiral 1,2-amino alcohols via decarboxylative radical C–C coupling of N-arylglycines and aldehydes by combining an organic photocatalyst, eosin Y, and carbonyl reductase RasADH. Notably, this protocol avoids using any sacrificial reductants. A possible reaction mechanism proposed is that the transformation proceeds through sequential photoinduced decarboxylative radical addition to an aldehyde and a photoenzymatic deracemization pathway. This redox-neutral photoredox/enzymatic strategy is promising not only for effective synthesis of a series of chiral amino alcohols in a green and sustainable manner but also for the design of other novel C–C radical coupling transformations for the synthesis of bioactive molecules.

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Section: Resultsmentioning

confidence: 99%

Photoredox/Enzymatic Catalysis Enabling Redox-Neutral Decarboxylative Asymmetric C–C Coupling for Asymmetric Synthesis of Chiral 1,2-Amino Alcohols

Liu,

Zhu,

et al. 2023

JACS Au

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“…Die Autoren zitierten weitere Referenzen innerhalb der Hintergrundinformationen [56–108] . Ablagenummern: (https://www.ccdc.cam.ac.uk/services/structures?id=doi:10.1002/anie.202402885) 2313487 (für 2‐Amino‐5‐mesityl‐3‐methylpyridin), 2313446 (für 1‐AlPh 2 ), 2313488 (für 2‐AlMe 2 ), 2313489 (für 2‐AlEt 2 ), 2313490 (für 2‐Al i Bu 2 ), 2313491 (für 2‐Al t Bu 2 ), 2313492 (für 2‐AlPh 2 ), 2313493 (für 2‐AlCl 2 ), 2313485 (für 2‐Al(CH=CH 2 ) 2 ), 2313494 (für 2‐Al(C≡C‐TMS) 2 ), 2313495 (für 3‐AlMe 2 ), 2313496 (für 3‐AlPh 2 ) enthält zusätzliche kristallographische Daten für diesen Artikel.…”

Section: Hintergrundinformationenunclassified

Aktivierung von Diorganyl‐bis(pyridylimino)isoindolid‐Aluminiumkomplexen mit sichtbarem Licht und deren organometallische Radikalreaktivität

Wenzel,

Werner,

Allgaier

et al. 2024

Angewandte Chemie

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We report on the synthesis and characterization of a series of (mostly) air‐stable diorganyl bis(pyridylimino) isoindolide (BPI) aluminum complexes and their chemistry upon visible‐light excitation. The redox non‐innocent BPI pincer ligand allows for efficient charge transfer homolytic processes of the title compounds. This makes them a universal platform for the generation of carbon‐centered radicals. The photo‐induced homolytic cleavage of the Al–C bonds was investigated by means of stationary and transient UV/Vis spectroscopy, spin trapping experiments, as well as EPR and NMR spectroscopy. The experimental findings were supported by quantum chemical calculations. Reactivity studies enabled the utilization of the aluminum complexes as reactants in tin‐free Giese‐type reactions and carbonyl alkylations under ambient conditions, which both indicated radical‐polar crossover behavior. A deeper understanding of the physical fundamentals and photochemical process was provided, furnishing in turn a new strategy to control the reactivity of bench‐stable aluminum organometallics.

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“…Until now, only one example of a cascade reaction for the deracemization of racemic alcohols combining photoinduced oxidation and enzymatic reduction mediated by whole-cells containing (R)-selective KtCR or (S)-selective RasADH has been reported (Scheme 1G). 17 However, a photooxidation step catalyzed by SAS in water with supplemental acetonitrile (30%, v/v) furnished ketones in mostly nonquantitative yield (53− 97%), which can be expected to clearly impact the % ee-values of the desired alcohols if the reactions were conducted in a one-pot manner. To our surprise, the authors reported enantiomeric excesses for the obtained products with values in the 95−99% range, which does not match the obtained results of the photooxidation step, and suggests a two-pot reaction sequence carried out with indirect separation of the unreacted racemic alcohols.…”

Section: ■ Introductionmentioning

confidence: 99%

“…In turn, direct photobiocatalytic deracemization of sec -alcohols toward enantiopure alcohols is still in its infancy. Until now, only one example of a cascade reaction for the deracemization of racemic alcohols combining photoinduced oxidation and enzymatic reduction mediated by whole-cells containing ( R )-selective KtCR or ( S )-selective RasADH has been reported (Scheme G) . However, a photooxidation step catalyzed by SAS in water with supplemental acetonitrile (30%, v/v) furnished ketones in mostly nonquantitative yield (53–97%), which can be expected to clearly impact the % ee-values of the desired alcohols if the reactions were conducted in a one-pot manner.…”

Section: Introductionmentioning

confidence: 99%

One-Pot Sequential Two-Step Photo-Biocatalytic Deracemization of sec-Alcohols Combining Photocatalytic Oxidation and Bioreduction

Rudzka,

Antos,

Reiter

et al. 2024

ACS Catal.

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Chiral alcohols are versatile building blocks and are of particular interest in the asymmetric synthesis of nonracemic active pharmaceutical ingredients, agrochemicals, fragrances, flavors, natural products, etc. Herein, we report on a "one-pot sequential two-step" concurrent oxidation−reduction photobiocatalytic process to synthesize enantiomerically enriched alcohols. In this regard, an efficient photocatalytic system based on irradiation with 440 nm blue LEDs in the presence of 9-fluorenone as a metalfree photocatalyst and molecular oxygen as the terminal oxidant in dry DMSO as the hydrogen peroxide-neutralizing agent was used to oxidize a broad range of racemic (hetero)benzylic alcohols into prochiral ketones quantitively (>99% conv.). The in situ formed carbonyl compounds were subsequently converted into the corresponding chiral alcohols via a sequential biocatalytic transhydrogenation catalyzed by lyophilized E. coli cells overexpressing highly stereoselective and stereocomplementary recombinant alcohol dehydrogenases (ADHs) originated from Rhodococcus ruber (E. coli/ADH-A) or Rhodococcus erythropolis (E. coli/ReADH) to obtain (S)-alcohols and Lactobacillus kef ir (E. coli/Lk-ADH) or KRED-110 to obtain (R)-alcohols, respectively. Overall, the elaborated photobiocatalytic deracemization of racemic alcohols using a 9-fluorenone-O 2 -blue LED-DMSO-E. coli/ADH system carried out on a semipreparative scale (0.25 mmol; 63 mM final conc. in 4 mL) at room temperature yielded nonracemic aryl alcohols with 82−99.9% conv., in up to 92% isolated yield, with 97−99.9% ee and complementary chirality.

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Deracemization of racemic alcohols combining photooxidation and biocatalytic reduction

Abstract: We described a cascade reaction for deracemization of racemic alcohols combing photooxidation and enzymatic reduction under mild condition without the isolation of intermediate ketones. By using different ketoreductases, a variety...

Cited by 11 publications

References 40 publications

Photoredox/Enzymatic Catalysis Enabling Redox-Neutral Decarboxylative Asymmetric C–C Coupling for Asymmetric Synthesis of Chiral 1,2-Amino Alcohols

Photoredox/Enzymatic Catalysis Enabling Redox-Neutral Decarboxylative Asymmetric C–C Coupling for Asymmetric Synthesis of Chiral 1,2-Amino Alcohols

Aktivierung von Diorganyl‐bis(pyridylimino)isoindolid‐Aluminiumkomplexen mit sichtbarem Licht und deren organometallische Radikalreaktivität

One-Pot Sequential Two-Step Photo-Biocatalytic Deracemization of sec-Alcohols Combining Photocatalytic Oxidation and Bioreduction

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