LongLarf

Radical hydrosilylation of electron‐deficient alkenes through cleavage of a trimethylsilyl‐polysilanyl bond has been accomplished. These reactions smoothly occur by direct activation of a trimethylsilyl‐polysilanyl bond through single electron oxidation by a redox catalyst assisted by solvent under visible light irradiation. This catalytic strategy could be also applied to the silylation of highly strained bicyclo[1.1.0]butanes.

Abstract

Oligosilanes are of great interest in the fields of organic photonics and electronics. In this communication, a highly efficient visible‐light‐mediated hydrosilylation of electron‐deficient alkenes through cleavage of a trimethylsilyl‐polysilanyl Si−Si bond is explored. These reactions smoothly occur on readily available organo(tristrimethylsilyl)silanes and other oligosilanes in the presence of an Ir^III‐based photo‐redox catalyst under visible light irradiation. Silyl radicals are generated through single electron oxidation of the oligosilane assisted by the solvent. The introduced method exhibits broad substrate scope and high functional group tolerance with respect to the organo(tristrimethylsilyl)silane and alkene components, enabling the construction of functionalized trisilanes. In addition, this catalytic system can be also applied to highly strained bicyclo[1.1.0]butanes as silyl radical acceptors.

Getting better with H: This Review presents an insight into the catalytic conversion of lignin involving hydrogen, including reductive depolymerization and hydrodeoxygenation of lignin‐derived monomers, with a focus on catalyst systems and reaction mechanisms. The roles of hydrogenation sites and acid sites, strategies for the production of other value‐added chemicals, and future opportunities within this attractive field are discussed.

Abstract

Lignin is the most abundant biopolymer with aromatic building blocks and its valorization to sustainable chemicals and fuels has extremely great potential to reduce the excessive dependence on fossil resources, although such conversions remain challenging. The purpose of this Review is to present an insight into the catalytic conversion of lignin involving hydrogen, including reductive depolymerization and the hydrodeoxygenation of lignin‐derived monomers to arenes, cycloalkanes and phenols, with a main focus on the catalyst systems and reaction mechanisms. The roles of hydrogenation sites (Ru, Pt, Pd, Rh) and acid sites (Nb, Ti, Mo), as well as their interaction in selective hydrodeoxygenation reactions are emphasized. Furthermore, some inspirational strategies for the production of other value‐added chemicals are mentioned. Finally, some personal perspectives are provided to highlight the opportunities within this attractive field.

In with the new: The largely investigated catalytic process affording 5‐aryl‐2‐oxazolidinones by the two‐step assembly of a C₂ precursor with primary amine and carbon dioxide is replaced by the catalyst‐free, direct addition of the amine/CO₂ adduct to the C₂ unit in isopropanol or water.

Abstract

The development of sustainable synthetic routes to access valuable oxazolidinones via CO₂ fixation is an active research area, and the aziridine/carbon dioxide coupling has aroused a considerable interest. This reaction features a high activation barrier and thus requires a catalytic system, and may present some other critical issues. Here, the straightforward gram‐scale synthesis of a series of 5‐aryl‐2‐oxazolidinones was developed at ambient temperature and atmospheric CO₂ pressure, in the absence of any catalyst/co‐catalyst. The key to this innovative procedure consists in the direct transfer of the pre‐formed amine/CO₂ adduct (carbamate) to common aziridine precursors (dimethylsulfonium salts), replacing the classical sequential addition of amine (intermediate isolation of aziridine) and then CO₂. The reaction mechanism was investigated by NMR spectroscopy and DFT calculations applied to model cases.

Bio‐orthogonal modification of dehydroalanine residues in peptides and proteins is achieved by photoredox catalysis with a newly designed water‐soluble Ir^III complex in aqueous media and a variety of zinc benzylsulfinates as reagents.

Abstract

Dehydroalanine (Dha) residues are attractive noncanonical amino acids that occur naturally in ribosomally synthesised and post‐translationally modified peptides (RiPPs). Dha residues are attractive targets for selective late‐stage modification of these complex biomolecules. In this work, we show the selective photocatalytic modification of dehydroalanine residues in the antimicrobial peptide nisin and in the proteins small ubiquitin‐like modifier (SUMO) and superfolder green fluorescent protein (sfGFP). For this purpose, a new water‐soluble iridium(III) photoredox catalyst was used. The design and synthesis of this new photocatalyst, [Ir(dF(CF₃)ppy)₂(dNMe₃bpy)]Cl₃, is presented. In contrast to commonly used iridium photocatalysts, this complex is highly water soluble and allows peptides and proteins to be modified in water and aqueous solvents under physiologically relevant conditions, with short reaction times and with low reagent and catalyst loadings. This work suggests that photoredox catalysis using this newly designed catalyst is a promising strategy to modify dehydroalanine‐containing natural products and thus could have great potential for novel bioconjugation strategies.

Nature, Published online: 09 September 2020; doi:10.1038/s41586-020-2671-4

Nature, Published online: 09 September 2020; doi:10.1038/d41586-020-02541-9

No detours—The direct C(sp³)−H alkynylation of free carboxylic acids in the β‐ and γ‐position is achieved using a Pd‐catalyst with a newly discovered ligand class. The synthetic method features a broad scope including preliminary findings on an enantioselective variant and can be conducted on a preparatively useful scale.

Abstract

In this study we report the identification of a novel class of ligands for palladium‐catalyzed C(sp³)−H activation that enables the direct alkynylation of free carboxylic acid substrates. In contrast to previous synthetic methods, no introduction/removal of an exogenous directing group is required. A broad scope of acids including both α‐quaternary and challenging α‐non‐quaternary can be used as substrates. Additionally, the alkynylation in the distal γ‐position is reported. Finally, this study encompasses preliminary findings on an enantioselective variant of the title transformation as well as synthetic applications of the products obtained.

Dibenzo[a,j]acridines have been synthesized in three steps and high overall yields using a Brønsted acid mediated cycloisomerization as the final key step. Optical‐ and electrochemical properties have been studied by UV/Vis‐ and fluorescence spectroscopy as well as cyclic voltammetry.

A convenient three‐step synthesis of dibenzo[a,j]acridines is reported which relies on regioselective Pd‐catalyzed cross‐coupling reactions of 2,3,5,6‐tetrachloropyridine and subsequent Brønsted acid mediated cycloisomerization. Products are obtained in good yields and the method is broadly applicable. For selected dibenzo[a,j]acridines, photophysical and electrochemical properties were studied.

Advantageous potential of calcium carbide as a solid acetylene reagent in organic chemistry is highlighted in this review. Synthetic opportunities are mapped to expand the synthetic applications of C≡C unit. Particular attention is focused on new approaches elaborated in a recent period.

Acetylene is a key building block for organic chemistry and potentially can be involved in a diverse range of synthetic transformations. However, critical analysis of practical considerations showed that application of gaseous acetylene in regular synthetic labs encounters a number of difficulties. Safety limitations due to flammable and explosive nature of gaseous acetylene and requirements for specialized high‐pressure equipment impose serious drawbacks. Typical reaction conditions involve excess of gaseous reactant, which is simply released to the atmosphere at the end of the reaction, thus generating waste and causing contamination. Calcium carbide brings a new green and sustainable wave into powerful alkyne transformations and significantly expands the repertoire of traditional acetylene chemistry. The novel trend of using calcium carbide instead of gaseous acetylene is synthetically beneficial and opens a novel reactivity for the C≡C unit. This review highlights recent advances in carbide chemistry, demonstrates its advantages and prospects in term of green synthetic approach.

Remarkably stable (ferrocenylmethyl)phosphane oxide was synthesized as the first isolable primary phosphane oxide. Reactivity of this compound and the corresponding phosphane sulfide and selenide, which were also prepared, was studied toward diverse metal precursors and toward unsaturated organic substrates.

Abstract

(Ferrocenylmethyl)phosphane (1) oxidation with hydrogen peroxide, elemental sulfur and grey selenium produced (ferrocenylmethyl)phosphane oxide 1O, sulfide 1S and selenide 1Se, respectively, as the first isolable primary phosphane chalcogenides lacking steric protection. At elevated temperatures, compound 1O disproportionated into 1 and (ferrocenylmethyl)phosphinic acid. In reactions with [(η⁶‐mes)RuCl₂]₂, 1O underwent tautomerization into a phosphane complex [(η⁶‐mes)RuCl₂{FcCH₂PH(OH)‐κP}], whereas 1S and 1Se lost their P‐bound chalcogen atoms, giving rise to the phosphane complex [(η⁶‐mes)RuCl₂(FcCH₂PH₂‐κP)] (Fc=ferrocenyl, mes=mesitylene). No tautomerization was observed in the reaction of 1O with B(C₆F₅)₃, which instead produced a Lewis pair FcCH₂P(O)H₂‐B(C₆F₅)₃. Phosphane oxide 1O added to C=O bonds of aldehydes and ketones and even to cumulenes PhNCE (E=O and S). However, both PH hydrogens were only employed in the reactions with aldehydes and cyanates.

LiAlH₄ catalysis: A combined experimental and theoretical investigation on LiAlH₄ catalyzed imine hydrogenation reveals mechanistic details as well as metal and substrate effects.

Abstract

Commercial LiAlH₄ can be used in catalytic quantities in the hydrogenation of imines to amines with H₂. Combined experimental and theoretical investigations give deeper insight in the mechanism and identifies the most likely catalytic cycle. Activity is lost when Li in LiAlH₄ is exchanged for Na or K. Exchanging Al for B or Ga also led to dramatically reduced activities. This indicates a heterobimetallic mechanism in which cooperation between Li and Al is crucial. Potential intermediates on the catalytic pathway have been isolated from reactions of MAlH₄ (M=Li, Na, K) and different imines. Depending on the imine, double, triple or quadruple imine insertion has been observed. Prolonged reaction of LiAlH₄ with PhC(H)=NtBu led to a side‐reaction and gave the double insertion product LiAlH₂[N]₂ ([N]=N(tBu)CH₂Ph) which at higher temperature reacts further by ortho‐metallation of the Ph ring. A DFT study led to a number of conclusions. The most likely catalyst for hydrogenation of PhC(H)=NtBu with LiAlH₄ is LiAlH₂[N]₂. Insertion of a third imine via a heterobimetallic transition state has a barrier of +23.2 kcal mol⁻¹ (ΔH). The rate‐determining step is hydrogenolysis of LiAlH[N]₃ with H₂ with a barrier of +29.2 kcal mol⁻¹. In agreement with experiment, replacing Li for Na (or K) and Al for B (or Ga) led to higher calculated barriers. Also, the AlH₄ ⁻ anion showed very high barriers. Calculations support the experimentally observed effects of the imine substituents at C and N: the lowest barriers are calculated for imines with aryl‐substituents at C and alkyl‐substituents at N.

Publication date: 20 November 2020

Source: Tetrahedron, Volume 76, Issue 47

Author(s): Moshood O. Ganiu, Binod Nepal, Joshua P. Van Houten, Rendy Kartika

Publication date: 30 October 2020

Source: Tetrahedron, Volume 76, Issue 44

Author(s): Linda Supe, Martin Hein, Viktor O. Iaroshenko, Alexander Villinger, Peter Langer

Synlett
DOI: 10.1055/s-0040-1707263

A highly efficient nucleophilic addition–O-acylation–intramolecular Wittig reaction of β-trifluoromethyl α,β-enones is disclosed. This strategy features mild reaction conditions and provides a practical transition-metal-free method to a set of biologically significant trifluoromethylated furans in high yields with diverse functional groups.
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In rerum natura: Wild‐type cytochrome P450_BM3 catalyzes the oxidation of hydrosilanes to silanols both in vivo and in vitro. Directed evolution was used to generate an efficient and selective biocatalyst that delivers a broad range of aryl‐ and alkyl‐substituted silanols. Computational studies revealed a sequence of H atom abstraction and OH rebound as the mechanism, in analogy to the native C−H hydroxylation activity.

Abstract

Compared to the biological world's rich chemistry for functionalizing carbon, enzymatic transformations of the heavier homologue silicon are rare. We report that a wild‐type cytochrome P450 monooxygenase (P450_BM3 from Bacillus megaterium, CYP102A1) has promiscuous activity for oxidation of hydrosilanes to give silanols. Directed evolution was applied to enhance this non‐native activity and create a highly efficient catalyst for selective silane oxidation under mild conditions with oxygen as the terminal oxidant. The evolved enzyme leaves C−H bonds present in the silane substrates untouched, and this biotransformation does not lead to disiloxane formation, a common problem in silanol syntheses. Computational studies reveal that catalysis proceeds through hydrogen atom abstraction followed by radical rebound, as observed in the native C−H hydroxylation mechanism of the P450 enzyme. This enzymatic silane oxidation extends nature's impressive catalytic repertoire.

Visible‐light‐induced cysteine‐selective bioconjugation has been achieved using fluorescent photosensitizer Q_PEG and photocatalyst Q_CAT . By exploiting the intrinsic photosensitizing capacities of Q_PEG and Q_CAT , a fluorophore Q_PEG and biologically relevant groups could be installed chemo‐ and regioselectively into a series of complex peptides and proteins under biocompatible mild conditions.

Abstract

Bioconjugation methods using visible‐light photocatalysis have emerged as powerful synthetic tools for the selective modification of biomolecules under mild reaction conditions. However, the number of photochemical transformations that allow successful protein bioconjugation is still limited because of the need for stringent reaction conditions. Herein, we report that a newly developed water‐compatible fluorescent photosensitizer Q_PEG can be used for visible‐light‐induced cysteine‐specific bioconjugation for the installation of Q_PEG by exploiting its intrinsic photosensitizing ability to activate the S−H bond of cysteine. The slightly modified Q_CAT enables the effective photocatalytic cysteine‐specific conjugation of biologically relevant groups. The superior reactivity and cysteine selectivity of this methodology was further corroborated by traceless bioconjugation with a series of complex peptides and proteins under biocompatible conditions.