Organocatalytic Asymmetric Domino Oxa-Michael-Mannich-[1,3]-Amino Rearrangement Reaction of N-Tosylsalicylimines to α,ß-Unsaturated Aldehydes by Diarylprolinol Silyl Ethers.

An organocatalytic asymmetric enantioselective domino oxa-Michael-Mannich-[1,3]-amino rearrangement reaction of N-tosylsalicylimines with a wide range of α,ß-unsaturated aldehydes utilizing diarylprolinol silyl ether catalysis is described. The catalytic reactions proceed with excellent enantioselectivity (up to 99% ee) to produce the corresponding chair N-tosylimines-chromenes with a yield of up to 99%, tolerating a range of functional groups. This methodology offers a new method with great potential to further extend the synthetic power and versatility of chiral aminocatalysis.

Specific Z-Selectivity in the Oxidative Isomerization of Allyl Ethers to Generate Geometrically Defined Z-Enol Ethers Using a Cobalt(II)(salen) Complex Catalyst.

Enol ether structural motifs exist in many highly oxygenated biologically active natural products and pharmaceuticals. The synthesis of the geometrically less stable Z-enol ethers is challenging. An efficient Z-selective oxidative isomerization process of allyl ethers catalyzed by a cobalt(II) (salen) complex using N-fluoro-2,4,6-trimethylpyridinium trifluoromethanesulfonate (Me3NFPY•OTf) as an oxidant has been developed. Thermodynamically less stable Z-enol ethers were prepared in excellent yields with high geometric control. This methodology also demonstrates the effectiveness in controlling the Z-selective isomerization reaction of diallyl ethers at room temperature. This catalytic system provides an alternative pathway to extend the traditional reductive isomerization of allyl ethers.

Asymmetric synthesis of (-)-solanidine and (-)-tomatidenol.

A concise asymmetric synthesis of two naturally occurring seco-type cholestane alkaloids (-)-solanidine and (-)-tomatidenol from (-)-diosgenin with a linear reaction sequence of 12 steps and 13 steps, respectively, is reported. The synthetic strategy includes the highly controlled establishment of highly functionalized octahydroindolizine ((-)-solanidine) and 1-oxa-6-azaspiro[4.5]decane ((-)-tomatidenol) cores with five stereocenters, respectively, from (-)-diosgenin, featuring two stereoselective cascade transformations including a modified cascade ring-switching process of furostan-26-acid to open the E-ring of (-)-diosgenin and a cascade azide reduction/intramolecular reductive amination to close the E- and F-rings of (-)-solanidine and (-)-tomatidenol. This work should enable further explorations of chemical and biological spaces based on solanidine, tomatidenol and related natural products.

Correction: Asymmetric synthesis of (-)-solanidine and (-)-tomatidenol.

Correction for 'Asymmetric synthesis of (-)-solanidine and (-)-tomatidenol' by Yun Wang et al., Org. Biomol. Chem., 2020, 18, 3169-3176, DOI: .

Robust Privacy-Preserving Recommendation Systems Driven by Multimodal Federated Learning.

Recommendation system (RS) is an important information filtering tool in nowadays digital era. With the growing concern on privacy, deploying RSs in a federated learning (FL) manner emerges as a promising solution, which can train a high-quality model on the premise that the server does not directly access sensitive user data. Nevertheless, some malicious clients can deduce user data by analyzing the uploaded model parameters. Even worse, some Byzantine clients can also send contaminated data to the server, causing blockage or failure of model convergence. In addition, most existing researches on federated recommendation algorithms only focus on unimodality learning, ignoring the assistance of multiple modality data to promote recommendation accuracy. Therefore, this article designs an FL-based privacy-preserving multimodal RS framework. To distinguish various modality data, an attention mechanism is introduced, wherein different weight ratios are assigned to various modal features. To further strengthen the privacy, local differential privacy (LDP) and personalized FL strategies are designed to identify malicious clients and bolster the resilience against Byzantine attacks. Finally, two multimodal datasets are established to verify the effectiveness of the proposed algorithm. The superiority of our proposed techniques is confirmed by the simulation results.

Palladium-Catalyzed Regio- and Stereoselective Cross-Coupling of Vinylethylene Carbonates with Ketimine Esters to Generate (Z)-Tri- and Tetra-substituted Allylic Amino Acid Derivatives.

Herein we report the palladium-catalyzed regio- and stereoselective cross-coupling of vinylethylene carbonates with ketimine esters to construct allylic amino acid scaffolds. This operationally simple protocol furnished (Z)-tri- and tetra-substituted allylic amino acid derivatives in good to excellent yields with distinguished geometric control under mild reaction conditions and proved to be sufficient in large-scale synthesis while retaining excellent reactivity and stereoselectivity, highlighting the practical value of this transformation.

The Chapman rearrangement in a continuous-flow microreactor.

The Chapman rearrangement is of practical significance in pharmaceutical and fine chemical industries. It is a high temperature reaction with an exothermic nature in numerous cases. The conventional batch-wise synthesis is limited by its operational complexities, temperature control difficulties and scale-up hurdles. In this work, a microreactor-based continuous-flow approach was developed to perform the rearrangement in a highly controlled and safer manner. High conversions were obtained within short residence times (≤20 minutes). The detailed kinetics of this reaction, using 2,6-dichloro-phenyl N-phenyl benzimidate and 2-carbomethoxy-phenyl N-phenyl benzimidate as the representative reactants, was explored at varying temperatures to understand the intensified reaction behavior, and was modelled based on the obtained experimental data. The continuous process was scaled up to a 16-fold larger reactor volume by increasing the diameter of the microreactor while maintaining the residence time without further optimization. A very slight variation was observed in the conversion for the larger-sized flow system. Upscaling the batch reaction to a 10 times larger volume, by contrast, resulted in a dramatic decrease in the conversion. The simplicity of scaling up continuous-flow system was clearly demonstrated. A CFD model coupled with the obtained rearrangement kinetics was developed and well validated against the experimental data, which provided a robust platform for guiding the relevant process design and optimization of the continuous-flow processes. The results presented shed new light on the developments and applications of continuous-flow method for the classical Chapman rearrangement that require harsh high temperatures.

Chiral Syn-1,3-diol Derivatives via a One-Pot Diastereoselective Carboxylation/ Bromocyclization of Homoallylic Alcohols.

Chiral syn-1,3-diols are fundamental structural motifs in many natural products and drugs. The traditional Narasaka-Prasad diastereoselective reduction from chiral ß-hydroxyketones is an important process for the synthesis of these functionalized syn-1,3-diols, but it is of limited applicability for large-scale synthesis because (1) highly diastereoselective control requires extra explosive and flammable Et2BOMe as a chelating agent under cryogenic conditions and (2) only a few functional syn-1,3-diol scaffolds are available. Those involving halogen-functionalized syn-1,3-diols are much less common. There are no reported diastereoselective reactions involving chemical fixation of CO2/bromocyclization of homoallylic alcohols to halogen-containing chiral syn-1,3-diols. Herein, we report an asymmetric synthesis of syn-1,3-diol derivatives via direct diastereoselective carboxylation/bromocyclization with both relative and absolute stereocontrol utilizing chiral homoallylic alcohols and CO2 in one pot with up to 91% yield, > 99% ee, and >19:1 dr. The power of this methodology has been demonstrated by the asymmetric synthesis of statins at the pilot plant scale.

Trialkyl Methanetricarboxylate as Dialkyl Malonate Surrogate in Copper-Catalyzed Enantioselective Propargylic Substitution.

The first copper-catalyzed enantioselective propargylation of trialkyl methantricarboxylate with propargylic alcohol derivatives was developed. The tricarboxylate unit in the obtained adducts could be easily transformed into a malonate moiety by treating with in situ generated NaOEt in excellent yield without racemization.

Diastereo- and enantioselective propargylation of benzofuranones catalyzed by pybox-copper complex.

Diastereo- and enantioselective preparation of 2,2-disubstituted benzofuran-3(2H)-one has been realized by a pybox-copper catalyzed reaction between 2-substituted benzofuran-3(2H)-one and propargyl acetate. The utility of this method was demonstrated by further transformation of the terminal alkyne into a methyl ketone without loss of enantiomeric purity.