Iridium-Catalyzed Enantioselective C(sp3)-H Amidation Controlled by Attractive Noncovalent Interactions.

While remarkable progress has been made over the past decade, new design strategies for chiral catalysts in enantioselective C(sp3)-H functionalization reactions are still highly desirable. In particular, the ability to use attractive noncovalent interactions for rate acceleration and enantiocontrol would significantly expand the current arsenal for asymmetric metal catalysis. Herein, we report the development of a highly enantioselective Ir(III)-catalyzed intramolecular C(sp3)-H amidation reaction of dioxazolone substrates for synthesis of optically enriched γ-lactams using a newly designed α-amino-acid-based chiral ligand. This Ir-catalyzed reaction proceeds with excellent efficiency and with outstanding enantioselectivity for both activated and unactivated alkyl C(sp3)-H bonds under very mild conditions. It offers the first general route for asymmetric synthesis of γ-alkyl γ-lactams. Water was found to be a unique cosolvent to achieve excellent enantioselectivity for γ-aryl lactam production. Mechanistic studies revealed that the ligands form a well-defined groove-type chiral pocket around the Ir center. The hydrophobic effect of this pocket allows facile stereocontrolled binding of substrates in polar or aqueous media. Instead of capitalizing on steric repulsions as in the conventional approaches, this new Ir catalyst operates through an unprecedented enantiocontrol mechanism for intramolecular nitrenoid C-H insertion featuring multiple attractive noncovalent interactions.

[1]  Sukbok Chang,et al.  Asymmetric formation of γ-lactams via C–H amidation enabled by chiral hydrogen-bond-donor catalysts , 2019, Nature Catalysis.

[2]  Wing-Yiu Yu,et al.  Ruthenium(II)-Catalyzed Enantioselective γ-Lactams Formation by Intramolecular C-H Amidation of 1,4,2-Dioxazol-5-ones. , 2019, Journal of the American Chemical Society.

[3]  K. Houk,et al.  Computational Exploration of a Pd(II)-Catalyzed γ-C-H Arylation Where Stereoselectivity Arises from Attractive Aryl-Aryl Interactions. , 2018, The Journal of organic chemistry.

[4]  Guoxian Gu,et al.  Highly Enantioselective Synthesis of Chiral γ-Lactams by Rh-Catalyzed Asymmetric Hydrogenation , 2018 .

[5]  M. Baik,et al.  Selective formation of γ-lactams via C–H amidation enabled by tailored iridium catalysts , 2018, Science.

[6]  jin-quan yu,et al.  Enantioselective C(sp3)‒H bond activation by chiral transition metal catalysts , 2018, Science.

[7]  Timothy J. Donohoe,et al.  Hexafluoroisopropanol as a highly versatile solvent , 2017 .

[8]  F. Dean Toste,et al.  Exploiting non-covalent π interactions for catalyst design , 2017, Nature.

[9]  Delong Liu,et al.  Iridium-Catalyzed Asymmetric Hydrogenation of β,γ-Unsaturated γ-Lactams: Scope and Mechanistic Studies. , 2017, Organic letters.

[10]  M. Baik,et al.  Why is the Ir(III)-Mediated Amido Transfer Much Faster Than the Rh(III)-Mediated Reaction? A Combined Experimental and Computational Study. , 2016, Journal of the American Chemical Society.

[11]  D. S. Clark,et al.  An artificial metalloenzyme with the kinetics of native enzymes , 2016, Science.

[12]  Robert J. Phipps,et al.  Ion Pair-Directed Regiocontrol in Transition-Metal Catalysis: A Meta-Selective C-H Borylation of Aromatic Quaternary Ammonium Salts. , 2016, Journal of the American Chemical Society.

[13]  T. Ling,et al.  Advances toward the Synthesis of Functionalized γ-Lactams , 2016 .

[14]  N. Cramer,et al.  Chiral γ-Lactams by Enantioselective Palladium(0)-Catalyzed Cyclopropane Functionalizations. , 2015, Angewandte Chemie.

[15]  M. Kanai,et al.  A meta-selective C-H borylation directed by a secondary interaction between ligand and substrate. , 2015, Nature chemistry.

[16]  Sukbok Chang,et al.  Mechanistic studies on the Rh(III)-mediated amido transfer process leading to robust C-H amination with a new type of amidating reagent. , 2015, Journal of the American Chemical Society.

[17]  Stefan Bräse,et al.  Privileged Scaffolds in Medicinal Chemistry : Design, Synthesis, Evaluation , 2015 .

[18]  C. Bolm,et al.  Light-induced ruthenium-catalyzed nitrene transfer reactions: a photochemical approach towards N-acyl sulfimides and sulfoximines. , 2014, Angewandte Chemie.

[19]  S. You,et al.  Recent development of direct asymmetric functionalization of inert C–H bonds , 2014 .

[20]  N. Chatani,et al.  Catalytic functionalization of C(sp2)-H and C(sp3)-H bonds by using bidentate directing groups. , 2013, Angewandte Chemie.

[21]  Thomas R. Ward,et al.  Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C–H Activation , 2012, Science.

[22]  N. Cramer,et al.  Chiral Cyclopentadienyl Ligands as Stereocontrolling Element in Asymmetric C–H Functionalization , 2012, Science.

[23]  J. Du Bois,et al.  Metal-catalyzed nitrogen-atom transfer methods for the oxidation of aliphatic C-H bonds. , 2012, Accounts of chemical research.

[24]  T. Uchida,et al.  Enantioselective intramolecular benzylic C-H bond amination: efficient synthesis of optically active benzosultams. , 2011, Angewandte Chemie.

[25]  M. Nishio,et al.  The CH/π hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates. , 2011, Physical chemistry chemical physics : PCCP.

[26]  Rui Wang,et al.  Asymmetric synthesis of β-substituted γ-lactams via rhodium/diene-catalyzed 1,4-additions: application to the synthesis of (R)-baclofen and (R)-rolipram. , 2011, Organic letters.

[27]  Eric N. Jacobsen,et al.  Attractive noncovalent interactions in asymmetric catalysis: Links between enzymes and small molecule catalysts , 2010, Proceedings of the National Academy of Sciences.

[28]  S. Blakey,et al.  Enantioselective C-H amination using cationic ruthenium(II)-pybox catalysts. , 2008, Angewandte Chemie.

[29]  J. Du Bois,et al.  A chiral rhodium carboxamidate catalyst for enantioselective C-H amination. , 2008, Journal of the American Chemical Society.

[30]  jin-quan yu,et al.  Pd(II)-catalyzed enantioselective activation of C(sp2)-H and C(sp3)-H bonds using monoprotected amino acids as chiral ligands. , 2008, Angewandte Chemie.

[31]  H. Davies,et al.  Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion , 2008, Nature.

[32]  H. Davies,et al.  Dirhodium tetracarboxylates derived from adamantylglycine as chiral catalysts for enantioselective C-h aminations. , 2006, Organic letters.

[33]  O. Daugulis,et al.  Highly regioselective arylation of sp3 C-H bonds catalyzed by palladium acetate. , 2005, Journal of the American Chemical Society.

[34]  K. W. Jung,et al.  Regio- and Stereocontrol Elements in Rh(II)-Catalyzed Intramolecular C−H Insertion of α-Diazo-α-(phenylsulfonyl)acetamides , 2001 .

[35]  A. Pfaltz,et al.  PhosphinooxazolinesA New Class of Versatile, Modular P,N-Ligands for Asymmetric Catalysis , 2000 .

[36]  S. Kitagaki,et al.  Enantiocontrol in Tandem Carbonyl Ylide Formation and Intermolecular 1,3-Dipolar Cycloaddition of α-Diazo Ketones Mediated by Chiral Dirhodium(II) Carboxylate Catalyst , 1999 .

[37]  H. Davies,et al.  Asymmetric Cyclopropanations by Rhodium(II) N-(Arylsulfonyl)prolinate Catalyzed Decomposition of Vinyldiazomethanes in the Presence of Alkenes. Practical Enantioselective Synthesis of the Four Stereoisomers of 2-Phenylcyclopropan-1-amino Acid , 1996 .

[38]  Ronald Breslow,et al.  Biomimetic Chemistry and Artificial Enzymes: Catalysis by Design , 1995 .

[39]  J. Taunton,et al.  Synthesis of nitrogen-containing polycycles via rhodium(II)-induced cyclization-cycloaddition and insertion reactions of N-(diazoacetoacetyl)amides. Conformational control of reaction selectivity , 1991 .