More Like this

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

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

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

   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.

    

   more » « less
2. 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 ( March 2024 , Angewandte Chemie International Edition)

   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.

    

   more » « less
3. Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy

   https://doi.org/10.1002/ange.201601056  

   Prier, Christopher K. ; Hyster, Todd K. ; Farwell, Christopher C. ; Huang, Audrey ; Arnold, Frances H. ( March 2016 , Angewandte Chemie)

   Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A “P411” serine‐ligated variant of cytochrome P450_BM3has been engineered to initiate a sulfimidation/[2,3]‐sigmatropic rearrangement sequence in whole E. coli cells, a non‐natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non‐allylic sulfides.

    

   more » « less
4. Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy

   https://doi.org/10.1002/anie.201601056  

   Prier, Christopher K. ; Hyster, Todd K. ; Farwell, Christopher C. ; Huang, Audrey ; Arnold, Frances H. ( March 2016 , Angewandte Chemie International Edition)

   Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A “P411” serine‐ligated variant of cytochrome P450_BM3has been engineered to initiate a sulfimidation/[2,3]‐sigmatropic rearrangement sequence in whole E. coli cells, a non‐natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non‐allylic sulfides.

    

   more » « less
5. Stereoretentive and regioselective selenium-catalyzed intermolecular propargylic C–H amination of alkynes

   https://doi.org/10.1039/D1SC07067C  

   Maloney, T. Parker ; Dohoda, Alexander F. ; Zhu, Alec C. ; Michael, Forrest E. ( February 2022 , Chemical Science)

   Herein we report an intermolecular propargylic C–H amination of alkynes. This reaction is operationally convenient and requires no transition metal catalysts or additives. Terminal, silyl, and internal alkynes bearing a wide range of functional groups can be aminated in high yields. The regioselectivity of amination for unsymmetrical internal alkynes is strongly influenced by substitution pattern (tertiary > secondary > primary) and by relatively remote heteroatomic substituents. We demonstrate that amination of alkynes bearing α-stereocenters occurs with retention of configuration at the newly-formed C–N bond. Competition experiments between alkynes, kinetic isotope effects, and DFT calculations are performed to confirm the mechanistic hypothesis that initial ene reaction of a selenium bis(imide) species is the rate- and product-determining step. This ene reaction has a transition state that results in substantial partial positive charge development at the carbon atom closer to the amination position. Inductive and/or hyperconjugative stabilization or destabilization of this positive charge explains the observed regioselectivities. 

   more » « less