LongLarf

Nature Reviews Chemistry, Published online: 10 February 2022; doi:10.1038/s41570-022-00359-9

This Review summarizes advanced photocatalytic systems for value-added chemical production from renewable biomass, with specific attention on the efficient strategies for controlling the generation of key radical intermediates and their subsequent conversion towards desired chemicals.

Catalysis on wheels: The beneficial effects of phosphine oxide additives on cobalt-catalysed reductive etherification enable the cobalt catalyst to “skate” from substrates (left) to products (right). The promoting effect further enables a milder and more general reaction, allowing a lower temperature and syngas (H₂/CO) pressure as well as a broader scope. More information can be found in the Research Article by E. V. Gusevskaya, M. Beller et al. (DOI: 10.1002/chem.202103903).

The carboxyl methyltransferase FtpM can catalyse methylation and dimethylation of a wide range of mono- and dicarboxylic acids, showing high regioselectivity for some diacids. The enzymatic methylation works under aqueous conditions and can therefore be integrated into enzyme cascades as demonstrated by the two-step, one-pot conversion of bioderived HMF to bioplastics precursor FDME.

Abstract

Carboxyl methyltransferase (CMT) enzymes catalyse the biomethylation of carboxylic acids under aqueous conditions and have potential for use in synthetic enzyme cascades. Herein we report that the enzyme FtpM from Aspergillus fumigatus can methylate a broad range of aromatic mono- and dicarboxylic acids in good to excellent conversions. The enzyme shows high regioselectivity on its natural substrate fumaryl-l-tyrosine, trans, trans-muconic acid and a number of the dicarboxylic acids tested. Dicarboxylic acids are generally better substrates than monocarboxylic acids, although some substituents are able to compensate for the absence of a second acid group. For dicarboxylic acids, the second methylation shows strong pH dependency with an optimum at pH 5.5–6. Potential for application in industrial biotechnology was demonstrated in a cascade for the production of a bioplastics precursor (FDME) from bioderived 5-hydroxymethylfurfural (HMF).

Nature, Published online: 08 February 2022; doi:10.1038/s41586-022-04491-w

Automated iterative Csp³-C bond formation

BioTrans2021: We created an artificial enzyme consisting of a non-enzymatic protein (LmrR) containing an unnatural catalytic residue with an aniline side chain (LmrR_pAF). Building on our previous work showing how LmrR_pAF can catalyse a Friedel-Crafts alkylation of indoles, here we show that when α-substituted acroleins are applied as substrates the protein scaffold enables enantioselective protonation with good selectivity.

Abstract

The incorporation of organocatalysts into protein scaffolds holds the promise of overcoming some of the limitations of this powerful catalytic approach. Previously, we showed that incorporation of the non-canonical amino acid para-aminophenylalanine into the non-enzymatic protein scaffold LmrR forms a proficient and enantioselective artificial enzyme (LmrR_pAF) for the Friedel-Crafts alkylation of indoles with enals. The unnatural aniline side-chain is directly involved in catalysis, operating via a well-known organocatalytic iminium-based mechanism. In this study, we show that LmrR_pAF can enantioselectively form tertiary carbon centres not only during C−C bond formation, but also by enantioselective protonation, delivering a proton to one face of a prochiral enamine intermediate. The importance of various side-chains in the pocket of LmrR is distinct from the Friedel-Crafts reaction without enantioselective protonation, and two particularly important residues were probed by exhaustive mutagenesis.

Ene-reductases (ERs) are a promising biocatalyst that reduces unsaturated double bonds cooperatively with transition metals, besides they are amiable with other emergent techniques like photoenzymatic, chemoenzymatic, multi-enzymatic, photoelectrochemical, single reduction chemistry, and radical-mediated transformations. These techniques will influence the enzymologist and synthetic chemist to explore and expand the intriguing chemistries displayed by ERs for academic and industrial purposes.

Abstract

Biocatalysis integrate microbiologists, enzymologists, and organic chemists to access the repertoire of pharmaceutical and agrochemicals with high chemoselectivity, regioselectivity, and enantioselectivity. The saturation of carbon-carbon double bonds by biocatalysts challenges the conventional chemical methodology as it bypasses the use of precious metals (in combination with chiral ligands and molecular hydrogen) or organocatalysts. In this line, Ene-reductases (ERs) from the Old Yellow Enzymes (OYEs) family are found to be a prominent asymmetric biocatalyst that is increasingly used in academia and industries towards unparalleled stereoselective trans-hydrogenations of activated C=C bonds. ERs gained prominence as they were used as individual catalysts, multi-enzyme cascades, and in conjugation with chemical reagents (chemoenzymatic approach). Besides, ERs’ participation in the photoelectrochemical and radical-mediated process helps to unlock many scopes outside traditional biocatalysis. These up-and-coming methodologies entice the enzymologists and chemists to explore, expand and harness the chemistries displayed by ERs for industrial settings. Herein, we reviewed the last five year's exploration of organic transformations using ERs.

Abstract

An elegant P(nBu)₃-triggered synthetic approach has been developed towards multisubstituted 5,6-dihydropyridin-2(1H)-one and pyridin-2(1H)-one derivatives exploiting a domino process involving retro-Claisen/intra-MBH/Wittig/vinylogous aldol transformations as well as retro-Claisen/intra-MBH/ylide hydrolysis/oxidation sequences. This transformation demonstrates chemo- and regioselectivity as well as accessible high diversity enchancement in 17–90% isolated yield.

Synthesis
DOI: 10.1055/a-1702-6193

Selective cleavage of C–C bonds forms one of the greatest challenges in current organic chemistry, due to the relative strength of these bonds. However, such transformations are an invaluable instrument to break down and construct new carbon–carbon bonds. To achieve this, photochemistry can be used as a tool to generate radicals and induce the cleavage of these bonds due to their high reactivity. This review examines some of the most influential contributions in this field since 2010.1 Introduction2 C–C Bond Cleavage2.1 Homogeneous Catalyst2.1.1 N-Centered Radical2.2.2 O-Centered Radical2.2 Heterogeneous Catalyst3 C=C Bond Cleavage3.1 Homogeneous Catalyst3.2 Heterogeneous Catalyst4 C≡C Bond Cleavage4.1 Homogeneous Catalyst4.2 Heterogeneous Catalyst5 Conclusion
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Publication date: 10 February 2022

Source: Chem, Volume 8, Issue 2

Author(s): Hong Deng, Minyan Wang, Yong Liang, Xiangyang Chen, Tianhang Wang, Jonathan J. Wong, Yue Zhao, Kendall N. Houk, Zhuangzhi Shi

For over 100 years, boric acid (BA) has been known to serve as an excellent glass matrix for luminescent chromophores. However, in contrast to a recent report, pure BA does NOT display RTP when excited at 280 nm, and it is demonstrated experimentally that it does not absorb at λ>200 nm. Theoretical studies further reveal that pure BA cannot absorb at λ>175 nm. Thus, an impurity must be responsible for the apparent RTP in the previous report.

Abstract

Boric acid (BA) has been used as a transparent glass matrix for optical materials for over 100 years. However, recently, apparent room-temperature phosphorescence (RTP) from BA (crystalline and powder states) was reported (Zheng et al., Angew. Chem. Int. Ed. 2021, 60, 9500) when irradiated at 280 nm under ambient conditions. We suspected that RTP from their BA sample was induced by an unidentified impurity. Our experimental results show that pure BA synthesized from B(OMe)₃ does not luminesce in the solid state when irradiated at 250–400 nm, while commercial BA indeed (faintly) luminesces. Our theoretical calculations show that neither individual BA molecules nor aggregates would absorb light at >175 nm, and we observe no absorption of solid pure BA experimentally at >200 nm. Therefore, it is not possible for pure BA to be excited at >250 nm even in the solid state. Thus, pure BA does not display RTP, whereas trace impurities can induce RTP.

NHC deoxy-Breslow catalysis offers new umpolung possibilities for electron-poor arene rings. NHC organocatalysis is largely restricted to aldehydes, with other electrophiles proving difficult to harness. It is shown that a pyridinium system can react successfully with an NHC, enabling intramolecular C−C bond formation with a Michael acceptor through a deoxy-Breslow intermediate.

Abstract

Umpolung N-heterocyclic carbene (NHC) catalysis of non-aldehyde substrates offers new pathways for C−C bond formation, but has proven challenging to develop in terms of viable substrate classes. Here, we demonstrate that pyridinium ions can undergo NHC addition and subsequent intramolecular C−C bond formation through a deoxy-Breslow intermediate. The alkylation demonstrates, for the first time, that deoxy-Breslow intermediates are viable for catalytic umpolung of areniums.

Nature Chemistry, Published online: 31 January 2022; doi:10.1038/s41557-021-00869-x

The hydrohalogenation of alkenes generally forms branched alkyl halides. Now, a palladium-catalysed method has been developed for the remote hydrohalogenation of internal and terminal alkenes, enabling the efficient synthesis of linear alkyl halides. The method uses an engineered Pyox ligand with a hydroxy group, which is essential for accelerating the oxidative halogenation.

Palladium-catalyzed decarboxylative cycloadditions, that feature high reactivity, exclusive regioselectivity, excellent functional group compatibility, are powerful strategies for the construction of structurally diverse cyclic compounds. We here systematically summarized the achievements in palladium-catalyzed decarboxylative cycloadditions involving cyclic carbonates, carbamates, and lactones. Mechanistic insights were discussed in detail. The challenges and opportunities of this field were also outlined.

Abstract

Palladium-catalyzed decarboxylative cycloadditions have emerged as highly effective methods for constructing structurally diverse carbo- and heterocycles because of the formation of at least two carbon-carbon or carbon-heteroatom bonds in a single step. It is of great interest to chemists that this type of cycloaddition reactions possesses some special advantages such as high reactivity, exclusive regioselectivity, and good functional group compatibility. Based on these qualities, palladium-catalyzed decarboxylative cycloadditions present strong ability in synthetic chemistry and have been flourished especially in the last five years. In this review, the achievements in palladium-catalyzed decarboxylative cycloadditions involving cyclic carbonates, carbamates, and lactones for accessing oxacyclo-, azacyclo- and carbocyclic compounds are addressed. Mechanistic insights and some synthetic applications toward the synthesis of natural products are discussed. The challenges and opportunities of this field are also outlined.

Synlett
DOI: 10.1055/s-0040-1719872

Reductive radical cyclizations are ubiquitous in organic synthesis and have been applied to the synthesis of structurally complex molecules. N-Heterocyclic motifs can be prepared through the cyclization of α-haloamides; however, slow rotation around the amide C–N bond results in preferential formation of an acyclic hydrodehalogenated product. Here, we compare four different methods for preparing γ-, δ-, ε-, and ζ-lactams via radical cyclization. We found that a photoenzymatic method using flavin-dependent ‘ene’ reductases affords the highest level of product selectivity. We suggest that through selective binding of the cis-amide isomer, the enzyme preorganizes the substrate for cyclization, helping to avoid premature radical termination.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Nature Catalysis, Published online: 28 January 2022; doi:10.1038/s41929-021-00728-5

Metrics are a useful way to assess biocatalyst performance and, when compared to techno-economic targets, can help set goals for further enzyme and bioprocess research and development. Here, we outline some of the remaining challenges to ensure wider acceptance of this approach, both in industry and in academia.