Ming-Ming Li, Teng-Fei Xiao, Yi-Xiang Geng, Guo-Qiang Xu,* and Peng-Fei Xu*
doi.org/10.1021/acs.orglett.5c02160
ABSTRACT:
Bicyclo[1.1.0]butanes (BCBs), which possess multiple switchable reactive sites, serve as the most direct modular scaffolds for constructing benzene ring bioisosteres. Herein, we describe the precise modulation of BCB reactive sites through Lewis/ Brønsted acid switching to enable the synthesis of challenging spirocycles and bridged frameworks. The divergent reaction outcomes, arising from the precise control of catalysts over the switchable reactive sites of BCBs, are achieved without any substrate modification
Lei Yan, Hui-Qing Yang, Wan-Lei Yu, Xu-Gang Zhang, and Peng-Fei Xu*
https://doi.org/10.1021/jacs.5c03154
ABSTRACT:
Radical asymmetric reactions represent a crucial strategy in asymmetric synthesis, which is characterized by their high reaction efficiency and unique reactivity profiles. Despite significant progress in radical-based asymmetric transformations, the formation of C-N bonds using nonredox metal complexes via the inner-sphere stereocontrol mechanism remains a formidable challenge in the development of novel asymmetric catalytic strategies. This study introduces an innovative and highly efficient asymmetric photochemical bifunctional catalysis that utilizes a combination of magnesium salts and chiral PyBOX-type (pyridinebisoxazoline) C2-symmetric ligands under visible light irradiation. This approach enables the selective α-amidation of β-keto esters via an N-centered radical mechanism, facilitating the synthesis of substituted β-keto amino acid derivatives with a fully substituted stereocenter. The reaction proceeds in good yields (up to 79%) and excellent enantioselectivity (up to 94%). The catalysis proceeds through the in situ formation of prochiral quaternary charge-transfer complexes, which promote the Lewis acid-supported generation of radicals, thereby mediating the subsequent enantioconvergent radical-radical cross-coupling. Notably, the β-keto ester serves a trifunctional role as a sensitizer, reductant, and radical precursor, while the N-protected iminopyridinium ylide functions as both the oxidant and N-centered radical precursor. Experimental and computational mechanistic studies corroborate the enantioconvergent radical-radical cross-coupling process.
Ai-Lian Wang, Huan-Huan Zhao, Hao-Wen Jiang, and Peng-Fei Xu*
https://doi.org/10.1021/acs.orglett.5c01128
In this study, we have devised a strategy that employs oxime carbamate as a bifunctional diamination reagent in combination with SO2 to realize imino-sulfamoylation of alkenes. This protocol is characterized by its mild conditions, operational simplicity, and metal-free nature, while demonstrating broad functional group tolerance for alkenes. Furthermore, the application of this method provides an accessible route to a diverse range of β-amino sulfonamide derivatives.
Yu Zhang, Hong Lu,* Jie Chang, Peng-Fei Xu, Hang Li, Yuan Jin, and Hao Wei*
https://doi.org/10.1002/anie.202500921
Bioisosteric replacement is an important strategy in drug discovery and is commonly practiced in medicinal chemistry; however, the incorporation of bioisosteres typically requires laborious multistep de novo synthesis. The direct conversion of a functional group into its corresponding bioisostere is of particular significance in evaluating structure-property relationships. Herein, we report a functional-group-exchange strategy that enables the direct conversion of aromatic lactones, a prevalent motif in bioactive molecules, into their corresponding cyclic hemiboronic acid bioisosteres. Scope evaluation and product derivatization experiments demonstrate the synthetic value and broad functionalgroup compatibility of this strategy, while the application of this methodology to the rapid remodeling of chromenone cores in bioactive molecules highlights its utility.
Huan-Huan Zhao, Xu-Gang Zhang, Hao-Wen Jiang, Yong-Chun Luo,* and Peng-Fei Xu*
https://doi.org/10.1021/acs.orglett.5c00888
Herein, we report an Fe/Co dual-catalyzed strategy for synthesizing alkenyl unnatural amino acids and peptide modifications. This approach utilizes aspartic acid and glutamic acid derivatives as alkyl radical precursors. It avoids the use of expensive photoredox catalysts and substrate preactivation while preserving the chirality of the amino acids. Furthermore, this strategy enables both modification of peptides and the synthesis of amino-acid-based drug candidates for boron-neutron capture therapy (BNCT).
Hao-Ni Qin, Hao-Wen Jiang, Yi Zhao, Saira Qurban, Ke-Chun Wang and Peng-Fei Xu *
https://doi.org/10.1039/D4SC08085H
Substantial advancements have been achieved in the field of photocatalytic borylation utilizing 4c-7e Lewis base-boryl radicals. However, the utilization of 3c-5e neutral boryl radicals for C–B bond formation remains relatively underexplored due to their inherent instability. In this study, we successfully demonstrated the direct construction of C–B bonds using sodium tetraarylborate as a key reagent. This was accomplished by effectively stabilizing diaryl boryl radicals with nitrile compounds, thereby facilitating the synthesis of valuable boron-containing compounds. Overall, our research elucidates the significant role played by sodium tetraarylborate in enabling an efficient and versatile approach for synthesizing of 1,4,2- diazaborole analogs through a photocatalyzed [3 + 2]-annulation reaction. This mild and adaptable methodology expands synthetic strategies for obtaining diverse derivatives of 1,4,2-diazaboroles, with the RCN–BAr2 complex serving as an effective boron–nitrogen synthon that opens up pathways to multiple boron–nitrogen heterocycles. Furthermore, this breakthrough significantly enhances the applicability of sodium tetraarylborate in photoredox catalysis.
Dong-Sheng Ji,* Xin Zhang, Peiqin Zhang, Xiazhen Bao, Yong Yuan, Congde Huo,* and Peng-Fei Xu*
https://doi.org/10.1021/acs.orglett.4c04715
Herein, we present a visible-light-induced protocol for the synthesis of highly functionalized oxo-bridged oxocine skeletons. This method generates carbenes via visible-light-induced ortho-acyl diazo compounds, which are rapidly intercepted by the oxygen atom of an intermolecular acyl group to form a cyclic 1,3- dipole. The in situ generated highly reactive 1,3-dipole undergoes a facile formal [4 + 3] cycloaddition with alkenyl pyrazolinone, yielding [4.2.1]-oxo-bridged oxocine compounds.
Rong-Rong Ma,Bo-Yang Liu,Lei Yan,Jun-Bing Lin,* and Peng-Fei Xu*
https://doi.org/10.1002/adsc.202401158
The bicyclo[3.3.1]nonane ring represents an attractive yet challenging synthetic targets in the field of organic synthesis, especially in a stereocontrolled fashion. Over the past two decades, organocatalysis has emerged as an enabling technology for the facile construction of enantioenriched molecules with remarkably increasing complexity and diversity, and a myriad of chiral architectures containing bicyclo[3.3.1]nonane units were elegantly assembled through organocatalytic asymmetric transformations. This review summarizes recent advancements on this topic (mainly from 2010–2023), emphasizing the reaction types such as desymmetrization and cascade reactions of different prochiral starting materials toward various chiralbicyclo[3.3.1]nonanes as well as their aza, oxa and thio derivatives. Meanwhile, the synthetic strategy, reaction mechanism, substrate scope and synthetic applications of these catalytic reactions are also discussed. We hope that this review will motivate further development and application of organocatalytic asymmetric synthesis of bicyclo[3.3.1]nonane frameworks.
Hao-Wen Jiang, Hao-Ni Qin, Ai-Lian Wang, Rui Zhang, and Peng-Fei Xu*
https://pubs.acs.org/doi/10.1021/acs.orglett.4c03443
In this study, we investigated the photocatalytic decarboxylation of trimethylamine carboxyborane under mild conditions, successfully generating boryl radicals for subsequent borylation reactions with imines and various alkenes. This method exhibited broad substrate compatibility, including the functionalization of biologically relevant molecules. Our findings expand the utility of trimethylamine carboxyborane beyond its role as a carbon-monoxide- and drug-releasing agent, highlighting its potential in radical chemistry through decarboxylation. This work establishes a robust foundation for further exploration of the synthetic application of trimethylamine carboxyborane.
Ai-Lian Wang, Hao-Wen Jiang, Xu-Yan Han, Yong-Chun Luo,* and Peng-Fei Xu*
https://pubs.acs.org/doi/10.1021/acs.orglett.4c03247
Here, we present a metal-free photosensitized threecomponent reaction for the carboimination of alkenes based on oxime carbonates. Homolysis of oxime carbonates via light-mediated energy transfer enables the simultaneous generation of iminyl radicals and alkoxycarbonyloxyl radicals. The alkoxycarbonyloxyl and alkoxy radicals can act as an effective hydrogen atom transfer reagent, abstracting hydrogen atoms from alkanes and aldehydes, silanes, and phosphine oxide. This strategy exhibits broad functional group tolerance under mild reaction conditions, further broadening the diversity of alkene carboimination.
