LongLarf

A rare approach: A simple rare‐earth‐metal‐catalyzed multicomponent approach to oxazolidinone synthesis is developed from easily available materials, i. e., epoxides, carbonate, and amines. Substrate scope includes a wide range of aromatic and aliphatic amines, as well as mono‐ and di‐substituted epoxides. Preliminary mechanistic studies suggest β‐amino alcohols or amides as intermediates.

Abstract

Three‐component reaction of epoxides, amines, and dimethyl carbonate catalyzed by rare‐earth metal amides has been developed to synthesize oxazolidinones. 47 examples of 3,5‐disubstituted oxazolidinones were prepared in 13–97 % yields. This is a simple and most practical method which employs easily available substrates and catalysts, and is applicable to a wide range of aromatic and aliphatic amines, as well as mono‐substituted epoxides. Scope of disubstituted epoxides is rather limited, which requires further study. Preliminary mechanistic study reveals two possible reaction pathways through intermediates of β‐amino alcohols or amides.

Light as air: Visible light and air were used as easily available and inexpensive reagents for direct metal‐free C−H photooxidation of cyclic tertiary amines towards new antiviral δ‐lactams at ambient conditions. This facile and atom‐efficient method is highly appealing for synthesis of versatile Strychnocarpine alkaloid derivatives (see scheme).

Abstract

Air and visible light have been used in facile direct C−H oxidation of cyclic tertiary amines at ambient conditions, employing organic dyes as photocatalysts and LED. Tolerance of this new environmentally compatible protocol to various side‐chain derivatizations of tryptoline and tetrahydroisoquinoline substrates was demonstrated. The developed method provides a straightforward and sustainable route towards δ‐lactams, which feature strong antiviral properties (EC₅₀ down to 4.6±1.8 μm) against human cytomegalovirus (HCMV). The clear advantages, which are easily available and inexpensive reagents, organic dyes, visible light, air/O₂ and atom efficiency, make this system highly appealing for synthesis of versatile Strychnocarpine alkaloid derivatives with antiviral activity.

Take “Me” on: The first Pd‐catalyzed N‐methylation of nitroarenes with methanol is reported. The generality of the developed protocol is demonstrated in the synthesis of more than 20 N‐methyl‐arylamines under comparably mild conditions.

Abstract

A procedure for the synthesis of N‐methyl‐arylamines directly from nitroarenes using methanol as green methylating agent was developed. The key to success is the use of a specific catalyst system consisting of palladium acetate and the ligand 1‐[2,6‐bis(isopropyl)phenyl]‐2‐[tert‐butyl(2‐pyridinyl)phosphino]‐1H‐Imidazole (L1). The generality of this protocol is demonstrated in the synthesis of more than 20 N‐methyl‐arylamines under comparably mild conditions. Combining this novel methodology with subsequent coupling processes using the same catalyst allows for efficient diversification of aromatic nitro compounds to a broad variety of amines including drug molecules.

Abstract

Tris(pentafluorophenyl)borane‐catalyzed C−C bond functionalization of arylallyl alcohols using donor‐acceptor carbenes is presented. The allylic hydroxyl group is found to assist the product formation by neighboring group participation providing a clue towards mechanistic understanding. This method can also be employed to effect homologation of allyl alcohols to homoallyl alcohols. Overall, this metal‐free transformation presents a novel disconnection strategy towards carbon‐carbon bond scission and formation.

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

Synlett
DOI: 10.1055/s-0037-1611744

Photoredox catalysis is a rapidly evolving platform for synthetic methods development. The prominent use of acridinium salts as a sustainable option for photoredox catalysts has driven the development of more robust and synthetically useful versions based on this scaffold. However, more complicated syntheses, increased cost, and limited commercial availability have hindered the adoption of these catalysts by the greater synthetic community. By utilizing the direct conversion of a xanthylium salt into the corresponding acridinium as the key transformation, we present an efficient and scalable preparation of the most synthetically useful acridinium reported to date. This divergent strategy also enabled the preparation of a suite of novel acridinium dyes, allowing for a systematic investigation of substitution effects on their photophysical properties.
[...]

© Georg Thieme Verlag Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

Reductive electrosynthesis has faced long-standing challenges in applications to complex organic substrates at scale. Here, we show how decades of research in lithium-ion battery materials, electrolytes, and additives can serve as an inspiration for achieving practically scalable reductive electrosynthetic conditions for the Birch reduction. Specifically, we demonstrate that using a sacrificial anode material (magnesium or aluminum), combined with a cheap, nontoxic, and water-soluble proton source (dimethylurea), and an overcharge protectant inspired by battery technology [tris(pyrrolidino)phosphoramide] can allow for multigram-scale synthesis of pharmaceutically relevant building blocks. We show how these conditions have a very high level of functional-group tolerance relative to classical electrochemical and chemical dissolving-metal reductions. Finally, we demonstrate that the same electrochemical conditions can be applied to other dissolving metal–type reductive transformations, including McMurry couplings, reductive ketone deoxygenations, and epoxide openings.

A large family of phosphite‐thioether/selenoether ligands has been easily prepared from accessible L‐(+)‐tartaric acid and D‐(+)‐mannitol and applied in the M‐catalyzed (M = Ir, Rh) asymmetric hydrogenation of a broad number of substrates (46 in total). Its highly modular architecture has been crucial to maximize the catalytic performance. Improving most of the reported approaches, this ligand family presents a broad substrate scope. By selecting the ligand parameters high enantioselectivitites (ee’s up to 99%) have therefore been achieved in a broad range of both, functionalized and unfunctionalized substrates. Interestingly, both enantiomers of the hydrogenation products can be usually achieved by changing the ligand parameters.

High acidity and structural confinement are the pivotal elements in asymmetric acid catalysis. The recently introduced imidodiphosphorimidate (IDPi) Brønsted acids have met with remarkable success in combining those features, acting as powerful Brønsted acid catalysts and “silylium” Lewis acid precatalysts in numerous thus far inaccessible transformations. Substrates as challenging to activate as simple olefins were readily transformed, ketones were employed as acceptors in aldolizations allowing sub ppm level catalysis, whereas enolates of the smallest donor aldehyde, acetaldehyde, did not polymerize but selectively added a single time to a variety of acceptor aldehydes.

We report here that thermodynamic and kinetic isomerization of alkenes can be accomplished by the combination of visible light with Co catalysis. Utilizing Xantphos as the ligand, the most stable isomers are obtained, while isomerizing terminal alkenes over one position can be selectively controlled by using DPEphos as the ligand. The presence of the donor‐acceptor dye 4CzIPN accelerates the reaction further. Transformation of exocyclic alkenes into the corresponding endocyclic products could be efficiently realized by using 4CzIPN and Co(acac)2 in the absence of any additional ligands. Spectroscopic and spectroelectrochemical investigations indicate CoI being involved in the generation of a Co hydride, which subsequently adds to alkenes initiating the isomerization.

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.

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.