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1. Enantioselective and Regiodivergent Synthesis of Propargyl‐ and Allenylsilanes through Catalytic Propargylic C−H Deprotonation

   https://doi.org/10.1002/anie.202318040  

   Zhu, Jin; Xiang, Hengye; Chang, Hai; Corcoran, James C.; Ding, Ruiqi; Xia, Yue; Liu, Peng; Wang, Yi‐Ming (April 2024, Angewandte Chemie International Edition)

   Abstract We report a highly enantioselective intermolecular C−H bond silylation catalyzed by a phosphoramidite‐ligated iridium catalyst. Under reagent‐controlled protocols, propargylsilanes resulting from C(sp³)−H functionalization, as well the regioisomeric and synthetically versatile allenylsilanes, could be obtained with excellent levels of enantioselectivity and good to excellent control of propargyl/allenyl selectivity. In the case of unsymmetrical dialkyl acetylenes, good to excellent selectivity for functionalization at the less‐hindered site was also observed. A variety of electrophilic silyl sources (R₃SiOTf and R₃SiNTf₂), either commercial or in situ‐generated, were used as the silylation reagents, and a broad range of simple and functionalized alkynes, including aryl alkyl acetylenes, dialkyl acetylenes, 1,3‐enynes, and drug derivatives were successfully employed as substrates. Detailed mechanistic experiments and DFT calculations suggest that an η³‐propargyl/allenyl Ir intermediate is generated upon π‐complexation‐assisted deprotonation and undergoes outer‐sphere attack by the electrophilic silylating reagent to give propargylic silanes, with the latter step identified as the enantiodetermining step. 

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2. Ni- and Pd-Catalyzed Enantioselective 1,2-Dicarbofunctionalization of Alkenes

   https://doi.org/10.1055/a-2108-9549  

   Kang, Taeho; Apolinar, Omar; Engle, Keary M (December 2023, Synthesis)

   Abstract Catalytic enantioselective 1,2-dicarbofunctionalization (1,2-DCF) of alkenes is a powerful transformation of growing importance in organic synthesis for constructing chiral building blocks, bioactive molecules, and agrochemicals. Both in a two- and three-component context, this family of reactions generates densely functionalized, structurally complex products in a single step. Across several distinct mechanistic pathways at play in these transformations with nickel or palladium catalysts, stereocontrol can be obtained through tailored chiral ligands. In this Review we discuss the various strategies, mechanisms, and catalysts that have been applied to achieve enantioinduction in alkene 1,2-DCF. 1 Introduction 2 Two-Component Enantioselective 1,2-DCF via Migratory Insertion 3 Two-Component Enantioselective 1,2-DCF via Radical Capture 4 Three-Component Enantioselective 1,2-DCF via Radical Capture 5 Three-Component Enantioselective 1,2-DCF via Migratory Insertion 6 Miscellaneous Mechanisms 7 Conclusion 

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3. Reactions of Unsymmetric Chiral Dialdehydes with Lysine: Regio‐ and Enantioselective Macrocyclization and Fluorescent Sensing

   https://doi.org/10.1002/ejoc.202401250  

   Mao, Yifan; Li, Yichen; Davis, Stephanie; Pu, Lin (February 2025, European Journal of Organic Chemistry)

   Abstract Three BINOL‐based unsymmetric chiral dialdehydes, (S)‐4, (S)‐5, and (S)‐6, each containing a salicylaldehyde moiety and anortho‐,meta‐ orpara‐substituted benzaldehyde unit, are synthesized and used to react with the enantiomers of an unsymmetric chiral diamine, lysine. These reactions represent the first examples of regioselective as well as enantioselective reactions of an unsymmetric chiral dialdehyde with an unsymmetric chiral diamine to generate unsymmetric chiral macrocycles. The addition of Zn²⁺can further enhance the selectivity for the macrocycle formation. Compounds (S)‐4and (S)‐5are found to exhibit chemoselective and enantioselective fluorescent recognition of lysine in the presence of Zn²⁺. 

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4. alpha- and beta-Functionalized Ketones from 1,3-Dienes and Aldehydes: Control of Regio- and Enantioselectivity in Hydroacylation of 1,3-Dienes

   https://doi.org/10.1021/jacs.1c06245  

   Parsutkar, M. M.; RajanBabu, T. V. (July 2021, Journal of the American Chemical Society)

   Carreira, E. M.; Schoenebeck, F. (Ed.)

   Ketones are among the most widely used intermediates in organic synthesis and their synthesis from inexpensive feedstocks could be quite impactful. Regio- and enantioselective hydroacylation reactions of dienes provide facile entry into useful ketone-bearing chiral motifs with an additional latent functionality (alkene) suitable for further elaboration. Three classes of dienes, 2- or 4-monosubstituted and 2,4-disubstitued 1,3-dienes undergo cobalt(I)-catalyzed regio- and enantioselective hydroacylation giving products with high enantiomeric ratios (er). These reactions are highly dependent on the ligands, and we have identified the most useful ligands and reaction conditions for each class of dienes. 2-Substituted and 2,4-disubstituted dienes predominantly undergo 1,2-addition, whereas 4-substituted terminal dienes give highly enantioselective 4,1- or 4,3-hydroacylation depending on the aldehyde, aliphatic aldehydes giving 4,1-addition and aromatic aldehydes giving 4,3-addition. Included among the substrates are feedstock dienes isoprene ($1.4 /kg) and myrcene ($129/kg) and several common aldehydes. We propose an oxidative dimerization mechanism that involves a Co(I)/Co(III) redox cycle that appears to be initiated by a cationic Co(I) intermediate. Studies of reactions using isolated neutral and cationic Co(I) complexes confirm the critical role of the cationic intermediates in these reactions. Enantioselective 1,2-hydroacylation of 2-trimethylsiloxy-1,3-diene reveals a hitherto undisclosed route to chiral siloxy-protected aldols. Finally, facile syntheses of the anti-inflammatory drug (S)-Flobufen (2 steps, 92% yield, >99:1 er) and the food additive (S)-Dihydrotagetone (1 step, 83% yield; 96:4 er) from isoprene illustrate the power of this method for the preparation of commercially relevant compounds. 

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5. Pd‐Catalyzed Regiodivergent N⁶ versus C^vinyl Arylation of 8‐Vinyl Adenine Nucleosides, Sequential Diarylation, Fluorescence Properties, and Computational Evaluations**

   https://doi.org/10.1002/chem.202501477  

   Akula, Hari K; Ghosh, Goutam; Greer, Alexander; Pradhan, Padmanava; Lakshman, Mahesh K (September 2025, Chemistry – A European Journal)

   Palladium‐catalyzed aryl amination and Heck arylation reactions are complementary transformations, generally requiring a suitable catalyst combination and a base. With substrates containing both an amino group and a vinyl moiety, control of C─N versus C─C reactivity can lead to regiodivergent functionalizations. With this focus, reactions of silyl‐protected 8‐vinyl 2'‐deoxyadenosine and adenosine with aryl bromides and iodides have been studied. Pd(OAc)₂, Pd₂(dba)₃, and preformed dichloro[1,1′‐bis(di‐t‐butylphosphino)ferrocene]palladium (II) (Pd‐118) were evaluated as metal sources. Ligands tested were Xantphos, DPEphos, BIPHEP, and DPPF, with Cs₂CO₃and K₃PO₄as bases. In toluene as solvent, the Pd(OAc)₂/Xantphos/Cs₂CO₃combination was uniquely capable of predominantN⁶arylation. Aryl bromides and iodides gave comparable product yields. Replacement of Cs₂CO₃with K₃PO₄redirected arylation from the nitrogen atom to the vinyl carbon atom, and all other catalyst, ligand, and base combinations gave C^vinylarylation as well. Simply switching from Pd(OAc)₂to Pd₂(dba)₃resulted in loss of theN⁶‐selectivity and C^vinylarylation was favored. Based upon these results, using two structurally similar catalytic systems sequential C^vinylandN⁶arylations of the nucleosides were accomplished. Some of the products were converted to other novel nucleoside analogues. Because some compounds were fluorescent, their photophysical properties were assessed experimentally and computationally. 

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