Visible-Light-Mediated Decarboxylative Radical Additions to Vinyl Boronic Esters: Rapid Access to γ-Amino Boronic Esters.

The synthesis of alkyl boronic esters by direct decarboxylative radical addition of carboxylic acids to vinyl boronic esters is described. The reaction proceeds under mild photoredox catalysis and involves an unprecedented single-electron reduction of an α-boryl radical intermediate to the corresponding anion. The reaction is amenable to a diverse range of substrates, including α-amino, α-oxy, and alkyl carboxylic acids, thus providing a novel method to rapidly access boron-containing molecules of potential biological importance.

Gold catalysis in total synthesis - recent achievements.

In this critical review the applications of gold catalysed reactions in total synthesis during the years since our last article are reviewed. At the end of this article a literature analysis is conducted to evaluate the progress in this field.

Mechanistic Insights into the Post-Cyclization Isomerization in Gold-Catalyzed 7-exo-dig-Hydroarylations.

The subsequent double-bond isomerization in the synthesis of dibenzocycloheptenes and their heteroaromatic analogues was investigated. In the case of biphenyls, a basic additive completely prevented an isomerization to the thermodynamic product. With electron-rich intramolecular heteroaromatic nucleophiles, the isomerization was still observed, but the kinetic product can be obtained by careful control of the reaction times in most cases. Mechanistic studies demonstrated that a slow isomerization is also possible with the gold catalyst at elevated temperatures, but much faster isomerization rates were observed with acidic additives. An observed initiation period for the gold-catalyzed isomerization indicates that not the homogenous catalyst, but a decomposition product of it may be the catalytically active species.

Synthesis of highly substituted γ-butyrolactones by a gold-catalyzed cascade reaction of benzyl esters.

Easily accessible benzylic esters of 3-butynoic acids in a gold-catalyzed cyclization/rearrangement cascade reaction provided 3-propargyl γ-butyrolactones with the alkene and the carbonyl group not being conjugated. Crossover experiments showed that the formation of the new C-C bond is an intermolecular process. Initially propargylic-benzylic esters were used, but alkyl-substituted benzylic esters worked equally well. In the case of the propargylic-benzylic products, a simple treatment of the products with aluminum oxide initiated a twofold tautomerization to the allenyl-substituted γ-butyrolactones with conjugation of the carbonyl group, the olefin, and the allene. The synthetic sequence can be conducted stepwise or as a one-pot cascade reaction with similar yields. Even in the presence of the gold catalyst the new allene remains intact.

Highly efficient gold-catalyzed synthesis of dibenzocycloheptatrienes.

Dibenzocycloheptatrienes are obtained by a gold-catalyzed 7-exo-dig hydroarylation protocol in a highly efficient manner. The gold-catalyzed reaction usually gives the products in high yields and excellent selectivity. This procedure provides an easy and efficient access to dibenzocycloheptanoids, which are an interesting and unique class of natural products. This was underlined by the first total synthesis of reticuol.

Highly diastereoselective and regioselective copper-catalyzed nitrosoformate dearomatization reaction under aerobic-oxidation conditions.

An unprecedented copper-catalyzed acylnitroso dearomatization reaction, which expands the traditional acylnitroso ene reaction and acylnitroso Diels-Alder reaction to a new type of transformation, has been developed under aerobic oxidation. Intermolecular and intra-/intermolecular reaction modes demonstrate an entirely different N- or O-acylnitroso selectivity. Hence, we can utilize this reaction as a highly diastereoselective access to a series of new pyrroloindoline derivatives, which are important structural motifs for natural-product synthesis.

Dehydrogenative Meyer-Schuster-like rearrangement: a gold-catalyzed reaction generating an alkyne.

Easily accessible propargylic esters are converted to the inverted alkynyl ketones in an oxidative gold-catalyzed reaction. Gagosz's catalyst in combination with PhI(OAc)2 is the best system for this conversion and 18 examples with yields up to 80 % are reported. The results indicate that the triple bond in the product is formed by elimination from a vinylgold intermediate. In a formal sense the new conversion overall is a dehydrogenative Meyer-Schuster rearrangement.

Synthesis of polycyclic indole skeletons by a gold(I)-catalyzed cascade reaction.

The conversion of simple, easily available urea-substituted 3-phenylpropargyl alcohols catalyzed by a simple IPr-gold(I) catalyst in a gold(I)-catalyzed cascade reaction composing of a gold-catalyzed nucleophilic addition and a subsequent gold-catalyzed substitution reaction delivers 1H-imidazo[1,5-a]indol-3(2H)-ones. Other gold(I) catalysts or silver catalysts gave lower yields and often gave other side products. Gold(III) and copper(II) catalysts decomposed the starting material. Twelve examples, including donor and acceptor substituents on the distal nitrogen of the urea substructure, are provided. An X-ray crystal structure analysis confirmed the structural assignment. The mechanistic investigation including isolation and further conversion of intermediates and reactions with enantiopure starting materials indicated that after the nucleophilic-addition step, the substrate undergoes an S(N)1-type benzylic substitution reaction at the indolyl alcohol intermediate or an intramolecular hydroamination reaction of the 2-vinylindole intermediate.

A quantitative 3D motility analysis of Trypanosoma brucei by use of digital in-line holographic microscopy.

We present a quantitative 3D analysis of the motility of the blood parasite Trypanosoma brucei. Digital in-line holographic microscopy has been used to track single cells with high temporal and spatial accuracy to obtain quantitative data on their behavior. Comparing bloodstream form and insect form trypanosomes as well as mutant and wildtype cells under varying external conditions we were able to derive a general two-state-run-and-tumble-model for trypanosome motility. Differences in the motility of distinct strains indicate that adaption of the trypanosomes to their natural environments involves a change in their mode of swimming.

Enantioselective total synthesis and absolute configuration of apiosporic acid.

The first total synthesis of the polyketide apiosporic acid is presented. Key steps are a Julia-Kocienski olefination, a Suzuki-Miyaura cross-coupling, and an intramolecular Diels-Alder reaction. The absolute configuration of the natural product was determined.