Synlett

In recent years, rhodium catalysis has evolved as a powerful tool for chemo- and stereocontrolled syntheses of chiral molecules through C–H functionalization. In particular, chiral cyclopentadienyl rhodium (CpRh) complex-catalyzed asymmetric C–H functionalization reactions have gained ever-increasing attention in organic synthesis. However, the design and synthesis of novel chiral Cp ligands remain challenging due to the difficulty of imparting chiral elements into the Cp moiety. In this account, we introduce our research progress in the syntheses of chiral cyclopentadienyl ligands and their applications in rhodium-catalyzed asymmetric C–H functionalization reactions.1 Introduction2 SCpRh-Catalyzed Enantioselective C–H Functionalization Reactions3 CpmRh-Catalyzed Enantioselective C–H Functionalization Reactions4 BOCpRh-Catalyzed Enantioselective C–H Functionalization Reactions5 BCSCpRh-Catalyzed Enantioselective C–H Functionalization Reactions6 Conclusion

A simple and efficient one-pot protocol has been developed for the synthesis of 1H-tetrazole and 1-methyltetrazole derivatives from aldehydes under mild and metal-free conditions using ammonium azide or methyl azide, respectively. A number of tetrazole derivatives were obtained in moderate to high yields (75–92%) in green solvents at a moderate temperature. These reactions presumably proceed through the formation of a nitrile in situ. The mild conditions and the easy workup and purification make this method highly valuable.

Benzylic C(sp3)–H oxidation is a useful process that can give aryl carbonyl compounds as valuable building blocks. Here, we report a study on the use of bromo(diphenyl)methane as a Br source for a phototriggered benzylic oxidation. The reaction conditions are mild and compatible with a variety of substrates. Mechanistic studies suggest that the reaction might involve a peroxyl radical intermediate formed by a reaction between a benzylic C radical and molecular oxygen.

The indolizinium natural product ficuseptine, produced by the tropical fig tree Ficus septica, has been reported to have antibacterial properties. Herein, the synthesis of ficuseptine, ten analogues with differing aryl substituents, and two aryl regioisomers is reported. Despite several previous total syntheses, synthetically prepared ficuseptine has not been subjected to biological testing to confirm its activity. In our hands, ficuseptine was moderately active in Gram-positive B. spizizenii, with an MIC of 32 μg/mL, which was maintained for most aryl substituents. The position of the aryl rings was crucial, however, since regioisomeric ficuseptine analogues, mimicking related natural products, were found to be inactive. Finally, all ficuseptine derivatives were inactive (MIC >128 μg/mL) against Gram-negative E. coli. Understanding these structure–activity relationships (SAR) is helpful for future studies to understand the molecule’s mechanism of action or further develop its antibacterial properties.

We report a simple and efficient two-carbon homologation method to directly convert aldehydes into difluoromethyl alkynes by using readily accessible and stable diphenyl(2,2,2-trifluoroethyl)phosphine oxide [Ph2P(=O)CH2CF3]. The conditions for this reaction are compatible with a broad range of aldehydes. Deuterium-labeling experiments suggest that the reaction probably involves a key rearrangement of aryl difluoroallenes generated in situ.

Synlett 2025; 36: V-DOI: 10.1055/s-0043-1773509Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents

The cross-coupling of two distinct C(sp3
)–O bonds provides a highly valuable pathway for the construction of C(sp3
)–C(sp3
) bonds, but it remains underdeveloped. Recently, we reported an innovative photoinduced Zr-catalyzed carbomagnesiation for the reductive coupling of ethers with high cross-selectivity. Mechanistic investigation reveals that photoexcitation of low-valent zirconocene facilitates the activation of C(sp3
)–O bonds of benzylic ethers. This leads to the formation of functionalized benzylic Grignard reagents for downstream coupling with aliphatic ethers through an SN2-like pathway.1 Introduction2 Concept of Our Design on this Work3 Photoinduced Zr-Catalyzed Cross-Coupling of Ethers4 Photoinduced Zr-Catalyzed Cross-Coupling of Benzylic Magnesium Alkoxide with Ethers5 Our Methods for Mechanism Investigation6 Conclusion

A one-pot, three-component coupling procedure has been developed for the synthesis of [(benzothiazol-2-ylamino)(aryl)methyl]isoquinolinols via the reaction of hydroxyisoquinolines, aryl/heteroaryl/aliphatic aldehydes with 2-aminobenzothiazoles under catalyst- and solvent-free conditions. The developed 2′-aminobenzothiazolomethylation procedure is suitable to execute even on a gram scale and has a broad scope. The 2′-aminobenzothiazolomethylated products (Betti bases) were formed through the initial nucleophilic C-attack of hydroxyisoquinolines on aldehydes to generate the ortho-quinone methide (o-QM) as an intermediate, followed by 1,4-aza-Michael addition of 2-aminobenzothiazoles. Betti bases have significance in medicinal chemistry due to their wide range of pharmacological applications and they are useful ligands and catalysts in asymmetric synthesis.

Synlett 2025; 36: V-DOI: 10.1055/s-0043-1773507Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents

The quest for general and highly efficient and enantioselective catalytic route to chiral alcohols remains a formidable challenge in asymmetric synthesis. Here, we highlight our recent work of asymmetric transfer hydrogenation (ATH) of N-methyliminodiacetyl (MIDA) acylboronates, showcasing a versatile platform for the efficient synthesis of enantiomerically enriched secondary alcohols. Acyl-MIDA-boronates harboring diverse (het)aryl, alkyl, alkynyl, alkenyl, and carbonyl substituents can be hydrogenated, yielding various α-borylated alcohols with high ee values. Crucially, the boron moiety can be easily transformed into other groups, allowing access to previously unattainable carbinols adorned with two structurally similar substituents. The enantioselectivity-directing role of BMIDA is elucidated by computational analyses, which stems from the CH–O electrostatic attraction between the η6-arene-CH of the catalyst and the σ-bonded oxygen atoms within BMIDA. This work represents the first asymmetric transformation on acylboronates and expands the domain of asymmetric transfer hydrogenation.