Stereoselective Construction of β-chiral Homoallyl Functionalities by Substrate- and Reagent-Controlled Iterative 1,2-Metallate Rearrangements

Homoallylic alcohols possessing chiral β-centers are considered highly valuable in the synthesis of polyketide-based natural products. Therefore, there is a significant demand for new methods that allow for their stereoselective access. In pursuit of this objective, we have successfully combined our substrate-controlled protocol of Hoppe-Matteson-Aggarwal chemistry with iterative 1,2-metallate rearrangements. Notably, this approach has proven effective in introducing not only primary alcohols but also other functional groups such as alkynes and protected amines

Development of the Synthesis of Desepoxy-Tedanolide C

We are presenting the development of our route for the total synthesis of desepoxy-tedanolide C. Through the obtained analytical data, the proposed structure of tedanolide C is questioned and a different configuration for this natural product is proposed. Key steps of the synthesis are a Kiyooka aldol reaction that builds up the tertiary alcohol flanked by three oxygenated carbon atoms and two aldol reactions used for fragment couplings. A Julia-Kocienski olefination was used for installation of the side chain. Besides the successful synthesis, the development for the protecting group setup of the southwestern hemisphere is described in detail as well as another retrosynthetic attempt for building up the target molecule

Very recent advances in vinylogous mukaiyama aldol reactions and their applications to synthesis

It is a challenging objective in synthetic organic chemistry to create efficient access to biologically active compounds. In particular, one structural element which is frequently incorporated into the framework of complex natural products is a β-hydroxy ketone. In this context, the aldol reaction is the most important transformation to generate this structural element as it not only creates new C-C bonds but also establishes stereogenic centers. In recent years, a large variety of highly selective methodologies of aldol and aldol-type reactions have been put forward. In this regard, the vinylogous Mukaiyama aldol reaction (VMAR) became a pivotal transformation as it allows the synthesis of larger fragments while incorporating 1,5-relationships and generating two new stereocenters and one double bond simultaneously. This review summarizes and updates methodology-oriented and target-oriented research focused on the various aspects of the vinylogous Mukaiyama aldol (VMA) reaction. This manuscript comprehensively condenses the last four years of research, covering the period 2016-2019

Photochemical 1,3-Acyl Shifts in Natural Product Synthesis

Photochemical, sigmatropic 1,3-acyl shifts represent a powerful tool to construct quaternary carbon atoms and the backbones of complex natural products which cannot be constructed easily by conventional methods. This review highlights applications of 1,3-acyl shifts to elegant, partly biomimetic total syntheses of natural products by discussing the underlying photochemical equilibrium

Desymmetrization of C2-Symmetric Bis(Boronic Esters) by Zweifel Olefinations

anti-Configured 1,3-dimethyl deoxypropionate motifs are important sub structures in natural products. Herein, we describe a bidirectional approach for the rapid construction of natural products featuring such motifs by using C2-symmetrical 1,3-bis(boronic esters). As for its application in convergent syntheses it was important to establish a selective mono-Zweifel olefination we describe the scope and limitations by using different 1,3-bis(boronic esters) and nucleophiles. This protocol takes advantage of the combination of the Hoppe–Matteson–Zweifel chemistry, which was elegantly put into practice by Aggarwal et al. In order to show its applicability the total syntheses of two natural products, serricornin and (+)-invictolide, were performed. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Asymmetric Total Synthesis of Illisimonin A

The discovery of illisimonin A in 2017 extended the structural repertoire of the Illicium sesquiterpenoids─a class of natural products known for their high oxidation levels and neurotrophic properties─with a new carbon backbone combining the strained trans-pentalene and norbornane substructures. We report an asymmetric total synthesis of (−)-illisimonin A that traces its tricyclic carbon framework back to a spirocyclic precursor, generated by a tandem-Nazarov/ene cyclization. As crucial link between the spirocyclic key intermediate and illisimonin A, a novel approach for the synthesis of tricyclo[5.2.1.01,5]decanes via radical cyclization was explored. This approach was applied in a two-stage strategy consisting of Ti(III)-mediated cyclization and semipinacol rearrangement to access the natural product’s carbon backbone. These key steps were combined with carefully orchestrated C–H oxidations to establish the dense oxidation pattern

Stereoselective Synthesis of Allylic Alcohols via Substrate Control on Asymmetric Lithiation

Allylic alcohols are a privileged motif in natural product synthesis and new methods that access them in a stereoselective fashion are highly sought after. Toward this goal, we found that chiral acetonide-protected polyketide fragments performing the Hoppe–Matteson–Aggarwal rearrangement in the absence of sparteine with high yields and diastereoselectivities rendering this protocol a highly valuable alternative to the Nozaki–Hiyama–Takai–Kishi reaction. Various stereodyads and -triads were investigated to determine their substrate induction. The mostly strong inherent stereoinduction was attributed to a combination of steric and electronic effects

Asymmetries in cloud microphysical properties ascribed to sea ice leads via water vapour transport in the central Arctic

To investigate the influence of sea ice openings like leads on wintertime Arctic clouds, the air mass transport is exploited as a heat and humidity feeding mechanism which can modify Arctic cloud properties. Cloud microphysical properties in the central Arctic are analysed as a function of sea ice conditions during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in 2019–2020. The Cloudnet classification algorithm is used to characterize the clouds based on remote sensing observations and the atmospheric thermodynamic state from the observatory on board the research vessel (RV) Polarstern. To link the sea ice conditions around the observational site with the cloud observations, the water vapour transport (WVT) being conveyed towards RV Polarstern has been utilized as a mechanism to associate upwind sea ice conditions with the measured cloud properties. This novel methodology is used to classify the observed clouds as coupled or decoupled to the WVT based on the location of the maximum vertical gradient of WVT height relative to the cloud-driven mixing layer. Only a conical sub-sector of sea ice concentration (SIC) and the lead fraction (LF) centred on the RV Polarstern location and extending up to 50 km in radius and with an azimuth angle governed by the time-dependent wind direction measured at the maximum WVT is related to the observed clouds. We found significant asymmetries for cases when the clouds are coupled or decoupled to the WVT and selected by LF regimes. Liquid water path of low-level clouds is found to increase as a function of LF, while the ice water path does so only for deep precipitating systems. Clouds coupled to WVT are found to generally have a lower cloud base and larger thickness than decoupled clouds. Thermodynamically, for coupled cases the cloud-top temperature is warmer and accompanied by a temperature inversion at the cloud top, whereas the decoupled cases are found to be closely compliant with the moist adiabatic temperature lapse rate. The ice water fraction within the cloud layer has been found to present a noticeable asymmetry when comparing coupled versus decoupled cases. This novel approach of coupling sea ice to cloud properties via the WVT mechanism unfolds a new tool to study Arctic surface–atmosphere processes. With this formulation, long-term observations can be analysed to enforce the statistical significance of the asymmetries. Furthermore, our results serve as an opportunity to better understand the dynamic linkage between clouds and sea ice and to evaluate its representation in numerical climate models for the Arctic system.</p