Gene Fusion and Directed Evolution to Break Structural Symmetry and Boost Catalysis by an Oligomeric C‐C Bond‐Forming Enzyme

Previous work has demonstrated that variants of a heme protein, Rhodothermus marinus cytochrome c (Rma cyt c), catalyze abiological carbene boron–hydrogen (B–H) bond insertion with high efficiency and selectivity. Here we investigated this carbon–boron bond-forming chemistry with cyclic, lactone-based carbenes. Using directed evolution, we obtained a Rma cyt c variant BORLAC that shows high selectivity and efficiency for B–H insertion of 5- and 6-membered lactone carbenes (up to 24,500 total turnovers and 97.1:2.9 enantiomeric ratio). The enzyme shows low activity with a 7-membered lactone carbene. Computational studies revealed a highly twisted geometry of the 7-membered lactone carbene intermediate relative to 5- and 6-membered ones. Directed evolution of cytochrome c together with computational characterization of key iron-carbene intermediates has allowed us to expand the scope of enzymatic carbene B–H insertion to produce new lactone-based organoborons.

Download Full-text

Five‐Step Synthesis of Yaequinolones J1 and J2

10.26434/chemrxiv.11359553.v1 ◽

2019 ◽

Author(s):

Johannes Schwan ◽

Merlin Kleoff ◽

Philipp Heretsch ◽

Mathias Christmann

Keyword(s):

Bond Forming ◽

Aldol Cyclization

A concise synthesis of yaequinolones J1 and J2 is reported. The route is based on the aryne insertion into the σ- C–N-bond of an unsymmetric imide followed by a diastereoselective aldol cyclization of the resulting N-acylated aminobenzophenone. The chromene motif is generated in the first step by an organocatalytic tandem Knoevenagel-electrocyclization of citral and 2-bromoresorcinol. The approach adheres to the ideality-principle, using almost exclusively strategic bond-forming reactions.

Download Full-text

Radical Capture at Ni(II) Complexes: C-C, C-N, and C-O Bond Formation

10.26434/chemrxiv.8115860.v1 ◽

2019 ◽

Author(s):

Abolghasem (Gus) Bakhoda ◽

Stefan Wiese ◽

Christine Greene ◽

Bryan C. Figula ◽

Jeffery A. Bertke ◽

...

Keyword(s):

Functional Groups ◽

Bond Formation ◽

Dft Studies ◽

Bond Forming ◽

Aryl Amines ◽

Shed Light ◽

Competing Pathways

The dinuclear b-diketiminato NiIItert-butoxide {[Me3NN]Ni}2(μ-OtBu)2 (2), synthesized from [Me3NN]Ni(2,4-lutidine) (1) and di-tert-butylperoxide, is a versatile precursor for the synthesis of a series of NiIIcomplexes [Me3NN]Ni-FG to illustrate C-C, C-N, and C-O bond formation at NiII via radicals. {[Me3NN]Ni}2(μ-OtBu)2 reacts with nitromethane, alkyl and aryl amines, acetophenone, benzamide, ammonia and phenols to deliver corresponding mono- or dinuclear [Me3NN]Ni-FG species (FG = O2NCH2, R-NH, ArNH, PhC(O)NH, PhC(O)CH2, NH2and OAr). Many of these NiII complexes are capable of capturing the benzylic radical PhCH(•)CH3 to deliver corresponding PhCH(FG)CH3 products featuring C-C, C-N or C-O bonds. DFT studies shed light on the mechanism of these transformations and suggest two competing pathways that depend on the nature of the functional groups. These radical capture reactions at [NiII]-FG complexes outline key C-C, C-N, and C-O bond forming steps and suggest new families of nickel radical relay catalysts.

Download Full-text

Bimetallic Radical Redox-Relay Catalysis for the Isomerization of Epoxides to Allylic Alcohols

10.26434/chemrxiv.8178926 ◽

2019 ◽

Author(s):

Ke-Yin Ye ◽

Terry McCallum ◽

Song Lin

Keyword(s):

Ring Opening ◽

High Reactivity ◽

Hydrogen Atom Transfer ◽

Organic Radicals ◽

Epoxide Ring ◽

Allylic Alcohols ◽

Epoxide Ring Opening ◽

Bond Forming ◽

Co Catalysts ◽

The Rich

Organic radicals are generally short-lived intermediates with exceptionally high reactivity. Strategically, achieving synthetically useful transformations mediated by organic radicals requires both efficient initiation and selective termination events. Here, we report a new catalytic strategy, namely bimetallic radical redox-relay, in the regio- and stereoselective rearrangement of epoxides to allylic alcohols. This approach exploits the rich redox chemistry of Ti and Co complexes and merges reductive epoxide ring opening (initiation) with hydrogen atom transfer (termination). Critically, upon effecting key bond-forming and -breaking events, Ti and Co catalysts undergo proton-transfer/electron-transfer with one another to achieve turnover, thus constituting a truly synergistic dual catalytic system.

Download Full-text

Visible-Light Photosensitized Aryl and Alkyl Decarboxylative Carbon-Heteroatom and Carbon-Carbon Bond Formations

10.26434/chemrxiv.7995983.v1 ◽

2019 ◽

Author(s):

Tuhin Patra ◽

Satobhisha Mukherjee ◽

Jiajia Ma ◽

Felix Strieth-Kalthoff ◽

Frank Glorius

Keyword(s):

Energy Transfer ◽

Visible Light ◽

Alkyl Radical ◽

General Strategy ◽

Alkyl Radicals ◽

Bond Forming ◽

Radical Trapping ◽

Carbon Carbon Bond ◽

Radical Generation ◽

Trapping Agent

A general strategy to access both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters has been developed. An energy transfer mediated homolysis of unsymmetrical sigma-bonds for a concerted fragmentation/decarboxylation process is involved. As a result, an independent aryl/alkyl radical generation step enables a series of key C-X and C-C bond forming reactions by simply changing the radical trapping agent.

Download Full-text

Metal-Free Photoredox-Catalyzed C–H/C–H Coupling of Arenes Enabled by Interrupted Pummerer Activation

10.26434/chemrxiv.9158564 ◽

2019 ◽

Author(s):

Miles Aukland ◽

Mindaugas Šiaučiulis ◽

Adam West ◽

Gregory Perry ◽

David Procter

Keyword(s):

Natural Product ◽

Selective Reduction ◽

Cross Coupling ◽

One Pot ◽

Complex Molecules ◽

Pummerer Reaction ◽

Metal Free ◽

Bond Forming ◽

Coupling Partner ◽

Bioactive Natural Product

Aryl–aryl cross-coupling constitutes one of the most widely used procedures for the synthesis of high-value materials, ranging from pharmaceuticals to organic electronics and conducting polymers. The assembly of (hetero)biaryl scaffolds generally requires multiple steps; coupling partners must be functionalized before the key bond-forming event is considered. Thus, the development of selective C–H arylation processes in arenes, that side-step the need for prefunctionalized partners, is crucial for streamlining the construction of these key architectures. Here we report an expedient, one-pot assembly of (hetero)biaryl motifs using photocatalysis and two non-prefunctionalized arene partners. The approach is underpinned by the activation of a C–H bond in an arene coupling partner using the interrupted Pummerer reaction. A unique pairing of the organic photoredox catalyst and the intermediate dibenzothiophenium salts enables highly selective reduction in the presence of sensitive functionalities. The utility of the metal-free, one-pot strategy is exemplified by the synthesis of a bioactive natural product and the modification of complex molecules of societal importance.

Download Full-text

Connecting Remote C–H Bond Functionalization and Decarboxylative Coupling Using Simple Amines

10.26434/chemrxiv.9863363.v1 ◽

2019 ◽

Author(s):

Francisco de Azambuja ◽

Ming-Hsiu Yang ◽

Alexander Bruecker ◽

Paul Cheong ◽

Ryan Altman

Keyword(s):

Organic Molecules ◽

Mechanistic Studies ◽

Bond Functionalization ◽

Bond Forming ◽

Decarboxylative Coupling

The manuscript describes a Pd-catalyzed reaction of benzylic electrophiles that gives para-substituted arene products. Mechanistic studies suggest a mechanism involving a dearomative C–C bond-forming step, followed by base-mediated rearomatization. This mechanism is uncommon and underappreciated in Pd-catalysis and further exploitation of this mechanism should enable access to other organic molecules.

Download Full-text