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1. 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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2. Ligand control in chemo, regio-and enantioselective cycloaddition of alkynes and 1,3-dienes

   Singh, D.; Parsutkar, M. M.; RajanBabu, T. V. (March 2022, Abstracts of papers American Chemical Society)

   Asymmetric synthesis of substituted 1,4 cyclohexadienes and cyclobutenes has received great attention in recent years. Strategies such as base metal catalyzed cycloaddition bypass the need of harsh reaction conditions which are often required for synthesis of such motifs. These strategies using base-metals as catalysts are also valuable in constructing substituted cyclic motifs from readily available and inexpensive materials such as dienes and alkynes. Such reactions can be cost effective and environmentally friendly. In past decade, low valent cobalt has shown promising reactivity in forming new C-C and C-X (e. g., X= Si, B, N) bonds in high stereoselectivity. Through our studies, we found that cationic cobalt(I) complexes can catalyze intermolecular cycloaddition reactions of alkyne and 1,3-dienes in regio-and enantioselective manner. We also discovered that the involvement of 4-pi electrons or 2-pi electrons of 1,3-dienes can be controlled by the judicious choice of ligands employed on cobalt leading to [4+2] and [2+2] cycloaddition products respectively in high regio- and stereoselectivity. This excellent selectivity complimented with moderate to good yields provided us with broadly applicable protocol for synthesis of diversely substituted enantiopure cyclic motifs with enantiomeric excesses upto 99%. The scope of this method has been expanded over simple aliphatic and aromatic 1,3-dienes and alkynes bearing various functional groups. The methodical development of this transformation along with the ligand effects and possible mechanisms will be discussed in detail. 

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3. Ligand control in chemo, regio-and enantioselective cycloaddition of alkynes and 1,3-dienes

   Singh, D.; Parsutkar, M. M.; RajanBabu, T. V. (March 2022, Abstract of Papers, ACS Spring National Meeting, , March 20-24, 2022. Abstract: CAPlus AN: 2022:2171183)

   Asymmetric synthesis of substituted 1,4 cyclohexadienes and cyclobutenes has received great attention in recent years. Strategies such as base metal catalyzed cycloaddition bypass the need of harsh reaction conditions which are often required for synthesis of such motifs. These strategies using base-metals as catalysts are also valuable in constructing substituted cyclic motifs from readily available and inexpensive materials such as dienes and alkynes. Such reactions can be cost effective and environmentally friendly. In past decade, low valent cobalt has shown promising reactivity in forming new C-C and C-X (e. g., X= Si, B, N) bonds in high stereoselectivity. Through our studies, we found that cationic cobalt(I) complexes can catalyze intermolecular cycloaddition reactions of alkyne and 1,3-dienes in regio-and enantioselective manner. We also discovered that the involvement of 4 pi electrons or 2 pi electrons of 1,3-dienes can be controlled by the judicious choice of ligands employed on cobalt leading to [4+2] and [2+2] cycloaddition products respectively in high regio- and stereoselectivity. This excellent selectivity complimented with moderate to good yields provided us with broadly applicable protocol for synthesis of diversely substituted enantiopure cyclic motifs with enantiomeric excesses upto 99%. The scope of this method has been expanded over simple aliphatic and aromatic 1,3-dienes and alkynes bearing various functional groups. The methodical development of this transformation along with the ligand effects and possible mechanisms will be discussed in detail. 

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4. Enantioselective Synthesis of Functionalized Arenes by Nickel‐Catalyzed Site‐Selective Hydroarylation of 1,3‐Dienes with Aryl Boronates

   https://doi.org/10.1002/anie.202004982  

   Marcum, Justin S.; Taylor, Tiffany R.; Meek, Simon J. (June 2020, Angewandte Chemie International Edition)

   Abstract A catalytic method for the site‐selective and enantioselective synthesis of functionalized arenes by the intermolecular hydroarylation of terminal and internal 1,3‐dienes with aryl pinacolato boronates is reported. The reactions are promoted by 5.0 mol % of a readily available monodentate phosphoramidite‐Ni complex in ethanol, affording a variety of enantioenriched products in up to 96 % yield and 99:1 er. Mechanistic studies indicate that Ni–allyl formation is irreversible and related to the nature of the arylboronate. 

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5. An I2-catalyzed, Visible-Light Photoredox-Mediated Radical Conversion of a-Nitrocarbonyls to Nitrile Oxides. Catalytic Access to Isoxazolines and Isooxazoles from Alkenes and Alkynes

   https://doi.org/10.26434/chemrxiv-2024-16d7c  

   Giri, Samyadev; Giri, Ramesh (September 2024, ChemRxiv)

   A visible light-mediated, I2-catalyzed intermolecular transformation of alkenes, conjugated dienes, styrenes and alkynes to isooxazoline and isoxazole motifs with a-nitrocarbonyls and analogs is reported. The reaction is also applicable to 1,1-disubstituted terminal, 1,2-disubstituted internal and trisubstituted alkenes, and tolerates a range of functional groups including epoxides, heterocycles, phosphates, free alcohols and thiocyanates. Mechanistic studies reveal that a-nitrocarbonyls are first converted to -carbonyl radicals followed by their conversion to acyl nitrile oxides, which subsequently undergo [3 + 2] dipolar cycloaddition reactions with the unsaturated molecules. 

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