Yuya Hu

A unique highly branched tetraterpene constitutes the epicuticular layer of this Collembola. The structure was elucidated by combination of NMR‐techniques and chemical synthesis of degradation products. A Y‐shaped structure is formed by joining two terpene building blocks made up by six and two prenyl units, respectively. Viaticene is the first member of a new tetraterpene compound class.

The cuticles of springtails are extremely wear‐ and friction‐resistant, super‐hydrophobic, non‐fouling, and self‐cleaning. As such, the chemistry of the lipids covering these cuticles is of great interest as a model for biomimetic super‐hydrophobic surfaces, although only few of these lipids have been structurally elucidated. Hypogastrura viatica, a surface‐dwelling springtail, produces highly branched tetraterpene hydrocarbons with an unprecedented [6+2]‐terpene connectivity as components of the epicuticular lipid layer. The structure of the major lipid component, viaticene A, was elucidated through isolation, spectroscopic analysis, chemical derivatization, synthesis, as well as stereochemical analysis of the core unit obtained from ozonolysis of the isolated lipid. Viaticenes A and B represent a new class of irregular tetraterpenoid natural products.

Convenient enantioselective synthesis of bioactive hydroxy fatty acids and fatty acid esters of hydroxy fatty acids was developed, based on the organocatalytic synthesis of chiral epoxides.

The recent discovery of a novel class of endogenous lipids, named Fatty Acid esters of Hydroxy Fatty Acids (FAHFAs), that present antidiabetic and anti‐inflammatory activities, has attracted the interest on hydroxy fatty acids (HFAs) and their derivatives. We present herein the development of a convenient and general methodology for the asymmetric synthesis of HFAs and FAHFAs. The enantioselective organocatalytic synthesis of asymmetric terminal epoxides starting from monoprotected α,ω‐diols and their subsequent ring opening by a Grignard reagent are the key‐steps for our methodology, allowing the introduction of the hydroxy group at different positions of the long chain by proper selection of the starting diol and the Grignard reagent. MacMillan's third generation imidazolidinone organocatalyst has been employed for the epoxide formation, ensuring products in high enantiomeric purity. Furthermore, an approach for the synthesis of deuterated HFAs and FAHFAs was developed, leading to deuterated derivatives, which can be useful in biological studies and in mass spectrometry studies as internal standards.

Copper to the rescue: A general method for the synthesis of propargylic sulfones featuring quaternary stereocenters has been developed. The method relies on a copper‐catalyzed sulfonylation of propargylic cyclic carbonates using sodium sulfinates. It provides the first example of such a transition‐metal‐catalyzed enantioselective propargylic substitution reaction with sulfur‐centered nucleophiles and gives access to functionalized tertiary sulfones.

Abstract

Tertiary propargylic sulfones are of significant importance in organic synthesis and medicinal chemistry, but to date no general asymmetric synthesis approach has been developed. We disclose a versatile copper‐catalyzed sulfonylation of propargylic cyclic carbonates using sodium sulfinates that allows the construction of propargylic sulfones featuring elusive quaternary stereocenters. This method provides the first successful example of such an enantioselective propargylic sulfonylation, features high asymmetric induction, wide functional group tolerance, and scalability, and enables attractive product diversification.

You will be upgraded: Isobutanol is a desirable gasoline alternative because of its compatibility with modern engine technology, high energy density, and high octane number. In this work, the first homogeneous non‐noble metal catalyst for sustainable production of isobutanol by upgrading of (bio)ethanol and widely available methanol is disclosed. The reaction proceeds at very low catalyst loading with a remarkable turnover number (9233) and up to 96 % isobutanol selectivity.

Abstract

Isobutanol serves as an ideal gasoline additive owing to its good compatibility with current engine technology, high energy density, and high octane number. Herein, an efficient and selective Mn‐catalyzed upgrading of ethanol with methanol into isobutanol is reported. This is the first example of deoxygenative coupling of lower alcohols to isobutanol by using a homogeneous non‐noble‐metal catalyst. This transformation proceeded at very low catalyst loading with a high turnover number (9233) and up to 96 % isobutanol selectivity.

A rare reductive coupling of nitro compounds with organohalides has been realized. The reaction proceeds via a partial reduction of the nitro group to a nitrenoid intermediate. Therefore, not only aromatic but also aliphatic nitro compounds are efficiently transformed into mono‐alkylated amines, with organohalides as the alkylating agent. On account of the nitrenoid’s innate reactivity, a catalyst is not required, resulting in a high tolerance for aryl halide substituents in both starting materials.

A novel enantioselective Cu‐catalyzed arylation of benzylic C‐H bonds using alkylarenes as a limiting reagent has been developed, where a chiral bisoxazoline ligand bearing an acetate ester moiety plays a key role in both reactivity and enantioselectivity. The reaction provides an efficient access to various chiral 1,1‐diarylalkanes in good yields with good to excellent enantioselectivities, and displays excellent functional group tolerance.

Site-selective and versatile aromatic C−H functionalization by thianthrenation

Site-selective and versatile aromatic C−H functionalization by thianthrenation, Published online: 13 March 2019; doi:10.1038/s41586-019-0982-0

A highly site-selective aromatic C–H functionalization reaction that does not require a particular directing group or arene substitution pattern provides functionalized arenes that can participate in various transformations.

: A direct decarboxylative strategy for the generation of aza‐o‐quinone methides (aza‐o‐QMs) by N‐heterocyclic carbene (NHC) catalysis has been discovered and explored. This process requires no stoichiometric additives in contrast with current approaches. Aza‐o‐QMs react with trifluoromethyl ketones via a formal [4+2] manifold to access highly enantioenriched dihydrobenzoxazin‐4‐one products, which can be converted to dihydroquinolones via an interesting stereoretentive aza‐Petasis‐Ferrier rearrangement sequence. Complementary DFT studies provided an accurate prediction of the reaction enantioselectivity, and lend further insight to the origins of stereocontrol. Additionally, a computed potential energy surface around the major transition structure suggests a concerted asynchronous mechanism for the formal annulation.

The addition of water to non‐activated carbon‐carbon double bonds catalyzed by fatty acid hydratases (FAHYs) allows for highly regio‐ and stereoselective oxyfunctionalization of renewable oil feedstock. So far, the applicability of FAHYs has been limited to free fatty acids, mainly owing to the requirement of a carboxylate function for substrate recognition and binding. Here, we describe for the first time the hydration of oleic acid (OA) derivatives lacking this free carboxylate by the oleate hydratase from Elizabethkingia meningoseptica (OhyA). Molecular docking of OA to the OhyA 3D‐structure and a sequence alignment uncovered conserved amino acid residues at the entrance of the substrate channel as target positions for enzyme engineering. Exchange of selected amino acids gave rise to OhyA variants which showed up to an 18‐fold improved conversion of OA derivatives, while retaining the excellent regio‐ and stereoselectivity in the olefin hydration reaction. Our study expands the range of applications of this enzyme class beyond the hydration of free fatty acids and provides the first report on an engineered FAHY with enhanced catalytic activity for OA derivatives.

Tertiary allylic alcohols are conveniently converted into either (Z)‐ or (E)‐configured alfa,beta‐unsaturated gamma‐amino acids by treatment with secondary amines under Pd catalysis at ambient conditions. Key to control the stereoselective course of these formal allylic aminations is the presence of a suitable diphosphine ligand, with dppp [1,3‐diphenylphosphino)propane, L12] providing high yields and selectivities for the (Z) isomers, whereas the DPEPhos derivative L1´ allows for selective formation of the corresponding (E) isomeric products. This ligand‐controlled, stereodivergent protocol thus shows promise for the stereoselective preparation of allylic amination products from a common substrate precursor.

Fluorine‐containing β‐amino acids and their derivatives have attracted significant attentions due to their importance in life sciences. Herein the previously unknown difluoroketenimine, as the analogue of the elusive difluoroketene, has been generated by the reaction of difluorocarbene and isocyanide, which further undergoes [2+2] cycloaddition with imine. The three‐component reaction affords α,α‐difluoro‐β‐amino amides in good yields. Mechanistic studies reveal unique property of the difluoroketenimine in the [2+2] cycloaddition with imine.

α-Fluorination of carbonyls with nucleophilic fluorine

α-Fluorination of carbonyls with nucleophilic fluorine, Published online: 04 March 2019; doi:10.1038/s41557-019-0215-z

Introducing fluorine into organic compounds enables their electronic properties to be tuned and can also significantly alter their function. Now, the α-fluorination of amides has been achieved using nucleophilic fluorinating agents using a polarity reversal strategy. This new method has been used to synthesize a fluorinated analogue of the blockbuster antidepressant drug, citalopram.

A series of thirty‐three N,N‘‐diaryl, dialkyl and alkyl‐aryl ureas have been prepared in pyridine or toluene via reaction of silyl‐amines with CO2. This protocol is shown to provide facile access to 13C‐labeled ureas, as well as chiral and macrocyclic ureas. These reactions proceed via initial generation of the corresponding silyl‐carbamates, which subsequently react with silylamine under thermal conditions to afford the thermodynamically favored urea and disilyl‐ether.