Bridging the information gap in organic chemical reactions.

The varying quality of scientific reports is a well-recognized problem and often results from a lack of standardization and transparency in scientific publications. This situation ultimately leads to prominent complications such as reproducibility issues and the slow uptake of newly developed synthetic methods for pharmaceutical and agrochemical applications. In recent years, various impactful approaches have been advocated to bridge information gaps and to improve the quality of experimental protocols in synthetic organic publications. Here we provide a critical overview of these strategies and present the reader with a versatile set of tools to augment their standard procedures. We formulate eight principles to improve data management in scientific publications relating to data standardization, reproducibility and evaluation, and encourage scientists to go beyond current publication standards. We are aware that this is a substantial effort, but we are convinced that the resulting improved data situation will greatly benefit the progress of chemistry.

Chromium/Photoredox Dual Catalyzed Synthesis of α-Benzylic Alcohols, Isochromanones, 1,2-Oxy Alcohols and 1,2-Thio Alcohols.

Herein, a Cr/Photoredox-catalyzed general synthetic strategy to access α-benzylic alcohols, isochromanones, oxy alcohols and thio alcohols is unveiled. Alkylation of aldehydes being a crucial C-C bond forming reaction, designing competent catalytic systems would render an attractive and decorated set of diverse alcohol motifs. Considering the challenges associated with classical organometallic chemistry, the strategy of dual catalysis is applied here to generate diverse alcohol motifs in a mild and efficient manner. The amalgamation of photocatalysis with chromium chemistry is chosen for this purpose to generate an environment with low basicity and thus, high chemoselectivity. With alkyl silanes as preferred coupling partners, this catalytic setup produces a broad substrate scope with an excellent functional group tolerance and displays a facile scale-up as well. Its application towards biologically relevant molecules and product diversification contributes to the synthetic utility of this method.

Gadolinium Photocatalysis: Dearomative [2+2] Cycloaddition/Ring-Expansion Sequence with Indoles.

Lanthanide photocatalysts are much less investigated in synthetic chemistry than rare and expensive late transition metals. We herein introduce GdIII photocatalysis of a highly regioselective, intermolecular [2+2] photocycloaddition/ring-expansion sequence with indoles, which could provide divergent access to cyclopenta[b]indoles and indolines. A simple and commercially available Gd(OTf)3 salt is sufficient for this visible-violet-light-induced transformation. The reaction proceeds either through a transient or start-to-end dearomatization cascade and shows excellent regioselectivity (usually >95:5 r.r.), broad scope (59 examples), good functional group tolerance and facile scale-up under mild, direct visible-light-excitation conditions. Mechanistic investigations reveal that direct excitation of the Gd(OTf)3 /indole mixture gives an excited state intermediate, which undergoes the subsequent [2+2] cycloaddition and cyclobutane-expansion cascade.

Rapid Assessment of the Reaction-Condition-Based Sensitivity of Chemical Transformations.

A systematic, user-friendly assessment tool that delivers a clear overview of the sensitivity of reactions to key parameters is highly desirable. Herein, the development of such a method is described. The intuitive, standardized presentation of the results in a radar diagram enables the sensitivity of a protocol to be rapidly assessed. This method was applied to five different visible-light-mediated photochemical reactions, and the results were correlated to the underlying mechanism. Ultimately, we believe that this assessment will help to increase the uptake of new synthetic methods and their reproducibility.

Diastereoselective Allylation of Aldehydes by Dual Photoredox and Chromium Catalysis.

Herein, we report the redox-neutral allylation of aldehydes with readily available electron-rich allyl (hetero-) arenes, ß-alkyl styrenes and allyl-diarylamines. This process was enabled by the combination of photoredox and chromium catalysis, which allowed a range of homoallylic alcohols to be prepared with high levels of selectivity for the anti diastereomer. Mechanistic investigations support the formation of an allyl chromium intermediate from allylic C(sp3)-H bonds and thus significantly extends the scope of the venerable Nozaki-Hiyama-Kishi reaction.

In Water and under Mild Conditions: α-Alkylation of Ketones with Alcohols by Phase-Transfer-Assisted Borrowing Hydrogen Catalysis.

Borrowing hydrogen is a powerful and green technique that allows readily available alcohols to be used as alkylating agents and produces water as the only by-product. Nevertheless, harsh conditions such as high temperatures and organic solvents are usually required. Herein, we present a strategy to perform the α-alkylation of ketones in aqueous media at mild temperatures by combining borrowing hydrogen with phase-transfer catalysis. A broad scope of methyl ketones was functionalized with alkyl and benzyl alcohols in moderate to good yields at 40 °C. The protocol was also highly effective at large scale and room temperature.

Total Synthesis of (+)-Pleuromutilin.

An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key steps of the synthesis include a highly stereoselective SmI2-mediated cyclization to establish the eight-membered ring and a stereospecific transannular [1,5]-hydrogen atom transfer to set the C10 stereocenter. This strategy was also used to prepare (+)-12-epi-pleuromutilin. The chemistry described here will enable efforts to prepare new mutilin antibiotics.

Imidazole-stabilized, electron-deficient boron cations.

The borenium cations [(C7H5N2Ad)B(C6F5)2][AlCl4/Al2Cl7] 2a, and [(C7H5N2Me)B(C6F5)2][B(C6F5)4] 2b were prepared and are shown to feature a high Lewis acidity, the capability to activate hydrogen and to effect the 1,1-carborations of terminal and internal alkynes under mild conditions.