title: Rh-Catalyzed Intermolecular Reactions of α-Alkyl-α-Diazo Carbonyl Compounds with Selectivity over β-Hydride Migration.
abstract: Rh-carbenes derived from α-diazocarbonyl compounds have found broad utility across a remarkable range of reactivity, including cyclopropanation, cyclopropenation, C-H insertions, heteroatom-hydrogen insertions, and ylide forming reactions. However, in contrast to α-aryl or α-vinyl-α-diazocarbonyl compounds, the utility of α-alkyl-α-diazocarbonyl compounds had been moderated by the propensity of such compounds to undergo intramolecular β-hydride migration to give alkene products. Especially challenging had been intermolecular reactions involving α-alkyl-α-diazocarbonyl compounds. This Account discusses the historical context and prior limitations of Rh-catalyzed reactions involving α-alkyl-α-diazocarbonyl compounds. Early studies demonstrated that ligand and temperature effects could influence chemoselectivity over β-hydride migration. However, effects were modest and conflicting conclusions had been drawn about the influence of sterically demanding ligands on β-hydride migration. More recent advances have led to a more detailed understanding of the reaction conditions that can promote intermolecular reactivity in preference to β-hydride migration. In particular, the use of bulky carboxylate ligands and low reaction temperatures have been key to enabling intermolecular cyclopropenation, cyclopropanation, carbonyl ylide formation/dipolar cycloaddition, indole C-H functionalization, and intramolecular bicyclobutanation with high chemoselectivity over β-hydride migration. Cyclic α-diazocarbonyl compounds have been shown to be particularly resilient toward β-hydride migration and are the first class of compounds that can engage in intermolecular reactivity in the presence of tertiary β-hydrogens. DFT calculations were used to propose that for cyclic α-diazocarbonyl compounds, ring constraints relieve steric interaction for intermolecular reactions and thereby accelerate the rate of intermolecular reactivity relative to intramolecular β-hydride migration. Enantioselective reactions of α-alkyl-α-diazocarbonyl compounds have been developed using bimetallic N-imido-tert-leucinate-derived complexes. The most effective complexes were found by computation and X-ray crystallography to adopt a "chiral crown" conformation in which all of the imido groups are presented on one face of the paddlewheel complex in a chiral arrangement. Insight from computational studies guided the design and synthesis of a mixed ligand paddlewheel complex, Rh2(S-PTTL)3TPA, the structure of which bears similarity to the chiral crown complex Rh2(S-PTTL)4. Rh2(S-PTTL)3TPA engages substrate classes (aliphatic alkynes, silylacetylenes, α-olefins) that are especially challenging in intermolecular reactions of α-alkyl-α-diazoesters and catalyzes enantioselective cyclopropanation, cyclopropenation, and indole C-H functionalization with yields and enantioselectivities that are comparable or superior to Rh2(S-PTTL)4. The work detailed in this Account describes progress toward enabling a more general utility for α-alkyl-α-diazo compounds in Rh-catalyzed carbene reactions. Further studies on ligand design and synthesis will continue to broaden the scope of their selective reactions.
authors.affiliation: DuPont Crop Protection, Stine-Haskell Research Center , Newark, Delaware 19711, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: DeAngelis
authors.affiliation: Brown Laboratories, Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Panish
authors.affiliation: Brown Laboratories, Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Fox
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D003979:Diazonium Compounds / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D003979:Diazonium Compounds; D009942:Organometallic Compounds; C030011:carbene; D006859:Hydrogen; D012238:Rhodium; D008697:Methane