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.
Jun-Bing Lin†, Dong-Sheng Ji† & Peng-Fei Xu*
https://doi.org/10.1007/s11426-023-1968-5
Organocatalytic cascade reactions represent a powerful strategy for the rapid construction of complex chiral molecules with multiple stereocenters from simple substrates under mild conditions. The intriguing structural feature and diverse reactivity of catalytically generated dienolate species render them competent and versatile intermediates for the development of practical and valuable cascade reactions. Over the past years, a plethora of innovative and pioneering noncovalent ammonium dienolatemediated cascade reactions have been designed and implemented under the catalysis of chiral organocatalysts, making dienolate activation a general, robust, and complementary method for the functionalization of unsaturated carbonyl compounds and related substances. This review illustrates the recent advances in organocatalytic noncovalent ammonium dienolate-mediated cascade reactions (mainly from 2010 to 2023), including the cascade transformations of ammonium dienolates directly generated from unsaturated ketone/aldehyde, ester/lactone/azlactone, amide/lactam/pyrazolone/oxindole, and alkylidene nitrile compounds. The contents are arranged based on the reaction types of the ammonium dienolates, with an emphasis on cascade 2,5-, 3,5-, and 4,5- difunctionalizations of these intermediates. Furthermore, other cascade reactions involving the 1,3-, 2,3-, and even more complex 3,4,5-reactivities of ammonium dienolates were also discussed. The reaction pathway, reaction stereoinduction, and synthetic applications of the ammonium dienolate-mediated cascade reactions were highlighted throughout the article. As a stimulating and ever-growing research area, the organocatalytic noncovalent ammonium dienolate-mediated cascade reactions are expected to continue demonstrating their magic power for constructing chiral targets in the future and further expanding the boundaries of asymmetric catalysis.
Hao-Wen Jiang, Wan-Lei Yu, Dong Wang, and Peng-Fei Xu*
https://doi.org/10.1021/acscatal.4c00401
Catalytic dehydrogenative borylation of alkenes is arguably the most straightforward approach for synthesizing alkenyl boronates, as it eliminates the need for alkene or boranes prefunctionalizion. While transition-metal catalysis has conventionally been employed for this transformation, competitive side reactions including hydroborylation, overborylation, and regioisomer formation always exist. In this study, we present a radical approach for catalytic dehydrogenative borylation, which involves the synergistic merger of photoredox/HAT/cobalt catalysis, thereby circumventing the necessity for noble metals, sacrificial hydrogen acceptors, and high temperatures. This method employs stable and cost-effective amine borane reagents as feedstocks, resulting in the sole byproduct of H2. This dehydrogenative borylation methodology facilitates the conversion of a diverse array of functionalized alkenes into valuable organoboron reagents. Furthermore, the late-stage borylation of complex molecules demonstrates high levels of site selectivity.
Hong Lu, Yu Zhang, Xiu-Hong Wang, Ran Zhang, Peng-Fei Xu & Hao Wei
https://doi.org/10.1038/s41467-024-48265-6
Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in a ring system without altering the ring size is even more challenging. Here, we introduce a skeletal editing strategy that enables polycyclic arenols, a highly prevalent motif in bioactive molecules, to be readily converted into N-heteroarenes through carbon–nitrogen transmutation. The reaction features selective nitrogen insertion into the C–C bond of the arenol frameworks by azidative dearomatization and aryl migration, followed by ring-opening, and ring-closing (ANRORC) to achieve carbonto-nitrogen transmutation in the aromatic framework of the arenol. Using widely available arenols as N-heteroarene precursors, this alternative approach allows the streamlined assembly of complex polycyclic heteroaromatics with broad functional group tolerance. Finally, pertinent transformations of the products, including synthesis complex biheteroarene skeletons, were conducted and exhibited significant potential in materials chemistry.
Jie Liu, Hao-Wen Jiang, Xiu-Qin Hu,* and Peng-Fei Xu*
https://doi.org/10.1021/acs.orglett.4c01186
Considering the ubiquitous presence of pyridine moieties in pharmaceutical compounds, it holds immense value to develop practical and straightforward methodologies for accessing heterocyclic aromatic hydrocarbons. In recent years, N-alkoxypyridinium salts have emerged as convenient radical precursors, enabling the generation of the corresponding alkoxy radicals and pyridine through single-electron transfer. Herein, we present the first report on visible-light-mediated intermolecular alkoxypyridylation of alkenes employing Nalkoxylpyridinium salts as bifunctional reagents with an exceptionally low catalyst loading (0.5 mol %).
Dong-Sheng Ji,‡Rui Zhang,‡ Xu-Yan Han, Hai-Long Chai, Yucheng Gu, Xiu-Qin Hu and Peng-Fei Xu*
https://doi.org/10.1039/D4QO00148F
Enantioselectively accessing medium-sized ring compounds with multiple stereocenters is still a formidable task due to the unfavorable entropy effect. We have developed a protocol for the enantioselective synthesis of eight-membered lactone derivatives through an organocatalytic Michael/ketalization/fragmentation cascade utilizing ortho-quinone methides and cyclobutanone carbon esters as starting materials. This reaction can be conducted under mild conditions using a wide range of substrates and it exhibits excellent enantioselectivity.
Dong-Sheng Ji,† Rui Zhang,† Xu-Yan Han, Xiu-Qin Hu,* and Peng-Fei Xu*
https://doi.org/10.1021/acs.orglett.3c03861
A protocol was developed to achieve stereodivergent synthesis of stereoisomers of δ-lactam bearing vicinal chiral centers. Organocatalytic cascade reactions were employed to produce the target products as the kinetic products, which exhibited remarkable enantioselectivities. In the presence of DBU, the kinetic product underwent epimerization to form a thermodynamically more stable diastereomer without loss in enantioselectivity. By simply switching the chiral organocatalyst and its enantiomer, we can efficiently obtain four stereoisomers with high enantioselectivities.
Guo-Qiang Xu*, Wei David Wang*, and Peng-Fei Xu*
https://doi.org/10.1021/jacs.3c06169
Owing to its diverse activation processes including single-electron transfer (SET) and hydrogen-atom transfer (HAT), visible-light photocatalysis has emerged as a sustainable and efficient platform for organic synthesis. These processes provide a powerful avenue for the direct functionalization of C(sp3)–H bonds under mild conditions. Over the past decade, there have been remarkable advances in the enantioselective functionalization of the C(sp3)–H bond via photocatalysis combined with conventional asymmetric catalysis. Herein, we summarize the advances in asymmetric C(sp3)–H functionalization involving visible-light photocatalysis and discuss two main pathways in this emerging field: (a) SET-driven carbocation intermediates are followed by stereospecific nucleophile attacks; and (b) photodriven alkyl radical intermediates are further enantioselectively captured by (i) chiral π-SOMOphile reagents, (ii) stereoselective transition-metal complexes, and (iii) another distinct stereoscopic radical species. We aim to summarize key advances in reaction design, catalyst development, and mechanistic understanding, to provide new insights into this rapidly evolving area of research.
