We have developed two green, practical, and efficient procedures, including a one-pot one, to synthesize isothiocyanates from amines and carbon disulfide via desulfurization with sodium persulfate. Water is used as the solvent. Basic conditions are necessary for good chemoselectivity for isothiocyanates. Structurally diverse linear and branched alkyl amines and aryl amines are readily converted to isothiocyanates by the two procedures in satisfactory yields. Halogens, benzylic C–H bonds, methylthio, nitro, ester, alkenyl, electron-rich or -deficient (hetero)aryls, acetylenyl, and even phenolic and alcoholic hydroxyls are well tolerated. The one-pot procedure in water can also be used to realize the preparation of chiral isothiocyanates from chiral amines, and the modification of bioactive structures with free amino groups. In large-scale preparation, simple and practical purification procedures independent of column chromatography are developed.

^◊ The co-authors are based on the chronical order worked on this project The Wolff–Kishner reduction, discovered in the early 1910s, is a fundamental and effective tool to convert carbonyls into methylenes via deoxygenation under strongly basic conditions. For over a century, numerous valuable chemical products have been synthesized by this classical method. The reaction proceeds via the reversible formation of hydrazone followed by deprotonation with the strong base to give an N-anionic intermediate, which affords the deoxygenation product upon denitrogenation and protonation. By examining the mechanistic pathway of this century old classical carbonyl deoxygenation, we envisioned and subsequently developed two unprecedented new types of chemical transformations: a) alcohol deoxygenation and b) C–C bond formations with various electrophiles including Grignard-type reaction, conjugate addition, olefination, and diverse cross-coupling reactions. 1 Introduction 2 Background 3 Alcohol Deoxygenation 3.1 Ir-Catalyzed Alcohol Deoxygenation 3.2 Ru-Catalyzed Alcohol Deoxygenation 3.3 Mn-Catalyzed Alcohol Deoxygenation 4 Grignard-Type Reactions 4.1 Ru-Catalyzed Addition of Hydrazones with Aldehydes and Ketones 4.2 Ru-Catalyzed Addition of Hydrazone with Imines 4.3 Ru-Catalyzed Addition of Hydrazone with CO₂ 4.4 Fe-Catalyzed Addition of Hydrazones 5 Conjugate Addition Reactions 5.1 Ru-Catalyzed Conjugate Addition Reactions 5.2 Fe-Catalyzed Conjugate Addition Reactions 6 Cross-Coupling Reactions 6.1 Ni-Catalyzed Negishi-type Coupling 6.2 Pd-Catalyzed Tsuji–Trost Alkylation Reaction 7 Other Reactions 7.1 Olefination 7.2 Heck-Type Reaction 7.3 Ullmann-Type Reaction 8 Conclusion and Outlook

The efficacy of messenger RNA (mRNA)-based vaccines or therapies relies on delivery vehicles that can transport them into the cytosol of cells. Lipid nanoparticles (LNPs) are the most clinically advanced carrier for mRNA. The chemical structure of an ionizable lipid is critical for the delivery efficiency of the LNPs. Herein, we synthesize a new ionizable lipid containing fluorinated alkyl chains (F-L319) and evaluate its mRNA delivery efficiency compared to its hydrocarbon counterpart (L319). While LNPs formulated with F-L319 alone showed decreased mRNA encapsulation and delivery efficiencies in comparison to the L319-LNP, we found that combining the appropriate ratios of F-L319 and L319 as hybrid ionizable lipids in LNPs (hybrid-LNPs) greatly enhanced mRNA delivery efficiency both in vitro and in vivo. Upon intravenous injection, the hybrid-LNP showed targeted mRNA expression in the spleen. Mechanistic studies indicate that the enhanced mRNA delivery of the hybrid-LNP is attributed to both improved mRNA encapsulation and cellular uptake. Collectively, fluorination of ionizable lipids represents a promising strategy to improve the delivery efficiency of LNPs.