Sergio González-Granda

Bio: Sergio González-Granda is an academic researcher from University of Oviedo. The author has contributed to research in topics: Chemistry & Catalysis. The author has an hindex of 2, co-authored 5 publications receiving 9 citations.

Alcohol Dehydrogenases and N-Heterocyclic Carbene Gold(I) Catalysts: Design of a Chemoenzymatic Cascade towards Optically Active β,β-Disubstituted Allylic Alcohols

Abstract: The combination of gold(I) and enzyme catalysis is used in a two-step approach, including Meyer-Schuster rearrangement of a series of readily available propargylic alcohols followed by stereoselective bioreduction of the corresponding allylic ketone intermediates, to provide optically pure β,β-disubstituted allylic alcohols. This cascade involves a gold N-heterocyclic carbene and an enzyme, demonstrating the compatibility of both catalyst types in aqueous medium under mild reaction conditions. The combination of [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene][bis(trifluoromethanesulfonyl)-imide]gold(I) (IPrAuNTf2 ) and a selective alcohol dehydrogenase (ADH-A from Rhodococcus ruber, KRED-P1-A12 or KRED-P3-G09) led to the synthesis of a series of optically active (E)-4-arylpent-3-en-2-ols in good yields (65-86 %). The approach was also extended to various 2-hetarylpent-3-yn-2-ol, hexynol, and butynol derivatives. The use of alcohol dehydrogenases of opposite selectivity led to the production of both allyl alcohol enantiomers (93->99 % ee) for a broad panel of substrates.

Laccase-mediated Oxidations of Propargylic Alcohols. Application in the Deracemization of 1-arylprop-2-yn-1-ols in Combination with Alcohol Dehydrogenases

Abstract: Financial supports from the Spanish Ministry of Economy and Competitiveness (MEC,Project CTQ2016-75752-R) and the Asturian Regional Government(FC-GRUPIN-IDI/2018/000181)are gratefully acknowledged.

Unmasking the Hidden Carbonyl Group Using Gold(I) Catalysts and Alcohol Dehydrogenases: Design of a Thermodynamically-Driven Cascade toward Optically Active Halohydrins

Abstract: A concurrent cascade combining the use of a gold(I) N-heterocyclic carbene (NHC) and an alcohol dehydrogenase (ADH) is disclosed for the synthesis of highly valuable enantiopure halohydrins in an aqueous medium and under mild reaction conditions. The methodology consists of the gold-catalyzed regioselective hydration of easily accessible haloalkynes, followed by the stereoselective bioreduction of the corresponding α-halomethyl ketone intermediates. Thus, a series of alkyl- and aryl-substituted haloalkynes have been selectively converted into chloro- and bromohydrins, which were obtained in good to high yields (65–86%). Remarkably, the use of stereocomplementary commercial or made-in-house overexpressed alcohol dehydrogenases in Escherichia coli has allowed the synthesis of both halohydrin enantiomers with remarkable selectivities (98 → 99% ee). The outcome success of this method was due to the thermodynamically driven reduction of the ketone intermediates, as just a small excess of the hydrogen donor (2-propanol, 2-PrOH) was necessary. In the cases that larger quantities of 2-PrOH were applied, higher amounts of other by-products (e.g., a vinyl ether derivative) were detected. Finally, as an extension of this cascade transformation and exploration of the synthetic potential of chiral halohydrins, the synthesis of both enantiomers of styrene oxide has been developed in a one-pot sequential manner in very high yields (88–92%) and optical purities (97 → 99% ee).

Merging Gold(I) Catalysis with Amine Transaminases in Cascade Catalysis: Chemoenzymatic Transformation of Propargylic Alcohols into Enantioenriched Allylic Amines

Abstract: The compatibility between gold(I) catalysts and amine transaminases has been explored to transform racemic propargylic alcohols into enantioenriched allylic amines in a straightforward and selective manner. The synthetic approach consists of a gold(I)-catalysed Meyer-Schuster rearrangement of a series of 2-arylpent-3-yn-2-ols and a subsequent stereoselective enzyme-catalysed transamination of the resulting α,β-unsaturated prochiral ketones. The design of cascade processes involving sequential or concurrent approaches has been studied in our search for ideal reaction conditions to produce the desired amines. Thus, the N-heterocyclic carbene complex [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]-[bis(trifluoromethanesulfonyl)-imide]gold(I) ([Au(IPr)(NTf2)] (A) in aqueous medium was found to be an ideal catalyst, while selective, made-in-house and commercial amine transaminases permitted the asymmetric synthesis of both (E)-4-arylpent-3-en-2-amine enantiomers in good isolated yields (53–84%) and excellent stereoselectivities (97 to >99% enantiomeric excess).

Combination of gold and redox enzyme catalysis to access valuable enantioenriched aliphatic β-chlorohydrins.

Abstract: The synthesis of enantioenriched β-chlorohydrins is highly appealing due to their relevance as building-blocks in organic synthesis. However, the approximation to aliphatic derivatives is particularly challenging due to the difficulties to get access to the α-chloroketone precursors. Herein, we propose a straightforward and scalable approach combining in a concurrent manner gold(I) and redox enzyme catalysis through a hydration-bioreduction cascade. A total of nine aliphatic β-chlorohydrins bearing different functional groups were obtained with very high yields (63-88%) and stereoselectivities (>99% ee).

Biocatalysis with Laccases: An Updated Overview

Abstract: Laccases are multicopper oxidases, which have been widely investigated in recent decades thanks to their ability to oxidize organic substrates to the corresponding radicals while producing water at the expense of molecular oxygen. Besides their successful (bio)technological applications, for example, in textile, petrochemical, and detoxifications/bioremediations industrial processes, their synthetic potentialities for the mild and green preparation or selective modification of fine chemicals are of outstanding value in biocatalyzed organic synthesis. Accordingly, this review is focused on reporting and rationalizing some of the most recent and interesting synthetic exploitations of laccases. Applications of the so-called laccase-mediator system (LMS) for alcohol oxidation are discussed with a focus on carbohydrate chemistry and natural products modification as well as on bio- and chemo-integrated processes. The laccase-catalyzed Csp2-H bonds activation via monoelectronic oxidation is also discussed by reporting examples of enzymatic C-C and C-O radical homo- and hetero-couplings, as well as of aromatic nucleophilic substitutions of hydroquinones or quinoids. Finally, the laccase-initiated domino/cascade synthesis of valuable aromatic (hetero)cycles, elegant strategies widely documented in the literature across more than three decades, is also presented.

Biocatalytic axidation of alcohols

Abstract: Enzymatic methods for the oxidation of alcohols are critically reviewed. Dehydrogenases and oxidases are the most prominent biocatalysts, enabling the selective oxidation of primary alcohols into aldehydes or acids. In the case of secondary alcohols, region and/or enantioselective oxidation is possible. In this contribution, we outline the current state-of-the-art and discuss current limitations and promising solutions.

Enzymatic strategies for asymmetric synthesis

Abstract: Enzymes, at the turn of the 21st century, are gaining a momentum. Especially in the field of synthetic organic chemistry, a broad variety of biocatalysts are being applied in an increasing number of processes running at up to industrial scale. In addition to the advantages of employing enzymes under environmentally friendly reaction conditions, synthetic chemists are recognizing the value of enzymes connected to the exquisite selectivity of these natural (or engineered) catalysts. The use of hydrolases in enantioselective protocols paved the way to the application of enzymes in asymmetric synthesis, in particular in the context of biocatalytic (dynamic) kinetic resolutions. After two decades of impressive development, the field is now mature to propose a panel of catalytically diverse enzymes for (i) stereoselective reactions with prochiral compounds, such as double bond reduction and bond forming reactions, (ii) formal enantioselective replacement of one of two enantiotopic groups of prochiral substrates, as well as (iii) atroposelective reactions with noncentrally chiral compounds. In this review, the major enzymatic strategies broadly applicable in the asymmetric synthesis of optically pure chiral compounds are presented, with a focus on the reactions developed within the past decade.

Recent trends in synthetic enzymatic cascades promoted by alcohol dehydrogenases

Abstract: Alcohol dehydrogenases have fascinated chemists over the span of a few decades to catalyze oxidation and reduction reactions and have been increasingly incorporated as biocatalysts in scaled-up industrial processes for the production of valuable chiral compounds under mild and environmentally friendly conditions. In this review, we discuss recent advances on alcohol dehydrogenases coupled in cascade reactions with other enzyme classes, chemocatalysts, or organocatalysts to obtain high value–added products. The examples include deracemization processes for the synthesis of chiral diols and amino alcohols, whole-cell and co-expression systems, and chemoenzymatic and organoenzymatic cascades, with a vision for future developments.

Where Chemocatalysis Meets Biocatalysis: In Water.

Abstract: Chemoenzymatic catalysis, by definition, involves the merging of sequential reactions using both chemocatalysis and biocatalysis, typically in a single reaction vessel. A major challenge, the solution to which, however, is associated with numerous advantages, is to run such one-pot processes in water: the majority of enzyme-catalyzed processes take place in water as Nature's reaction medium, thus enabling a broad synthetic diversity when using water due to the option to use virtually all types of enzymes. Furthermore, water is cheap, abundantly available, and environmentally friendly, thus making it, in principle, an ideal reaction medium. On the other hand, most chemocatalysis is routinely performed today in organic solvents (which might deactivate enzymes), thus appearing to make it difficult to combine such reactions with biocatalysis toward one-pot cascades in water. Several creative approaches and solutions that enable such combinations of chemo- and biocatalysis in water to be realized and applied to synthetic problems are presented herein, reflecting the state-of-the-art in this blossoming field. Coverage has been sectioned into three parts, after introductory remarks: (1) Chapter 2 focuses on historical developments that initiated this area of research; (2) Chapter 3 describes key developments post-initial discoveries that have advanced this field; and (3) Chapter 4 highlights the latest achievements that provide attractive solutions to the main question of compatibility between biocatalysis (used predominantly in aqueous media) and chemocatalysis (that remains predominantly performed in organic solvents), both Chapters covering mainly literature from ca. 2018 to the present. Chapters 5 and 6 provide a brief overview as to where the field stands, the challenges that lie ahead, and ultimately, the prognosis looking toward the future of chemoenzymatic catalysis in organic synthesis.