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1. A Hydride Migration Mechanism for the Mo‐Catalyzed Z‐2‐Selective Isomerization of Terminal Alkenes

   https://doi.org/10.1002/cctc.202301052  

   Jenny, Sarah E.; Serviano, Juan M.; Nova, Ainara; Dobereiner, Graham E. (December 2023, ChemCatChem)

   The catalytic one-bond isomerization (transposition) of 1- alkenes is an emerging approach to Z-2-alkenes. Design of more selective catalysts would benefit from a mechanistic understanding of factors controlling Z selectivity. We propose here a reaction pathway for cis-Mo(CO)4(PCy3)(piperidine) (3), a precatalyst that shows high Z selectivity for transposition of alpha olefins (e.g., 1-octene to 2-octene, 18:1 Z:E at 74% conversion). Computational modeling of reaction pathways and isotopic labeling suggests the isomerization takes place via an allyl (1,3-hydride shift) pathway, where oxidative addition of fac- (CO)3Mo(PCy3)(η2-alkene) is followed by hydride migration from one position (cis to allyl C3 carbon) to another (cis to allyl C1 carbon) via hydride/CO exchanges. Calculated barriers for the hydride migration pathway are lower than explored alternative mechanisms (e.g., change of allyl hapticity, allyl rotation). To our knowledge, this is the first study to propose such a hydride migration in alkene isomerization. 

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2. 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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3. Diels−Alder Reactions of 1‐Alkoxy-1-amino-1,3-butadienes: Direct Synthesis of 6‐Substituted and 6,6-Disubstituted 2‐Cyclohexenones and 6‐Substituted 5,6-Dihydropyran-2-ones

   https://doi.org/10.1021/acs.orglett.1c01031  

   Elkin, P. K.; Durfee, N. D. (June 2021, Organic letters)

   Gaich, T. (Ed.)

   We report the cycloaddition reactions of 1-alkoxy-1- amino-1,3-butadienes. These doubly activated dienes are prepared on a multigram scale from crotonic acid chloride and its derivatives. The dienes undergo Diels−Alder (DA) and hetero-Diels−Alder (HDA) reactions under mild reaction conditions with a variety of electron- deficient dienophiles to afford cycloadducts in good yields with excellent regioselectivities. The hydrolysis of the DA cycloadducts provides 6-substituted and 6,6-disubstituted 2-cylohexenones, which are versatile building blocks for complex molecule synthesis. The corresponding HDA cycloadducts afford 6-substituted 5,6-dihydropyr- an-2-ones. 

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4. Stereodivergent Zweifel Olefination and its Mechanistic Dichotomy

   https://doi.org/10.1002/anie.202309136  

   Manna, Samir; Paul, Swagata; Kong, Wang‐Yeuk; Aich, Debasis; Sahoo, Rupam; Tantillo, Dean J.; Panda, Santanu (September 2023, Angewandte Chemie International Edition)

   Abstract Stereoselective Zweifel olefination using boronate complexes carrying two different reactive π‐systems was achieved to synthesize vinyl heteroarenes and conjugated 1,3‐dienes in good yield and up to 100 % stereoselectivity, which remains unexplored until now. Most importantly, we report the unprecedented formation ofEvs.Z‐vinyl heteroarenes for different heteroarenes under identical conditions. Density functional theory (DFT) investigations unveil the mechanistic dichotomy between olefin and heteroarene activation followed by 1,2‐migration, leading toEorZ‐vinyl heteroarenes respectively. We also report a previously unknown reversal of stereoselectivity by using 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) as an electrophile. The Zweifel olefination using a boronate complex that carries two different olefins was previously unexplored due to significant challenges associated with the site‐selective activation of olefins. We have solved this problem and reported the site‐selective activation of olefins for the stereoselective synthesis of 1,3‐dienes. 

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5. Expanding Reaction Profile of Allyl Carboxylates via 1,2-Radical Migration (RaM): Visible-Light-Induced Phosphine-Catalyzed 1,3-Carbobromination of Allyl Carboxylates

   https://doi.org/10.1021/jacs.2c11867  

   Zhao, Gaoyuan; Lim, Sanghyun; Musaev, Djamaladdin G.; Ngai, Ming-Yu (April 2023, Journal of the American Chemical Society)

   Allyl carboxylates are useful synthetic intermediates in a variety of organic transformations, including catalytic nucleophilic/electrophilic allylic substitution reactions and 1,2-difunctionalization reactions. However, the catalytic 1,3-difunctionalization of allyl carboxylates remains elusive. Herein, we report the first photoinduced, phosphine-catalyzed 1,3-carbobromination of allyl carboxylates, affording a range of valuable substituted isopropyl carboxylates (sIPC). The transformation has broad functional group tolerance, is amenable to the late-stage modification of complex molecules and gram-scale synthesis, and expands the reaction profiles of allyl carboxylates and phosphine catalysis. Preliminary experimental and computational studies suggest a non-chain-radical mechanism involving the formation of an electron donor–acceptor complex, 1,2-radical migration (RaM), and Br-atom transfer processes. We anticipate that the 1,2-RaM reactivity of allyl carboxylates and the phosphine-catalyzed radical reaction will both serve as a platform for the development of new transformations in organic synthesis. 

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