General Information. Commercial reagents were purchased from Aldrich or Strem and used as suppplied. Reactions were conducted using standard drybox techniques. Non-aqueous reagents were transferred under argon via syringe. Organic solutions were concentrated under reduced pressure on a Büchi rotary evaporator. Dioxane was distilled from sodium benzophenone ketyl and then degassed using the freeze-pump-thaw method (4 cycles) prior to use. Chromatographic purification of products was accomplished using forced-flow chromatography on ICN 60 32-64 mesh silica gel 63 according to the method of Still.

C À H bond amination has emerged as a powerful tool for the synthesis of complex nitrogen-containing molecules. Following the early discoveries by Breslow and Gellman, [1] Du Bois and co-workers revolutionized this area of chemistry by developing protocols for practical, efficient, and predictable reactions for oxidative C À H amination.[2] Dirhodium(II) tetracarboxylate catalysts were shown to be particularly effective. Manganese-and ruthenium-porphyrin complexes, [3] silver complexes, [4] and preoxidized nitrogen sources have also been developed as catalysts to carry out this important reaction. [5] Despite these recent advances, general methods for both enantioselective and intermolecular C À H amination remain elusive. Although chiral dirhodium(II) complexes have been developed as catalysts for highly enantioselective metallocarbene reactions, [6] their application to CÀH amination chemistry is yet to produce the same spectacular results. [7] To date, the most effective protocol for asymmetric CÀH amination requires the combination of enantioenriched sulfoxamines as chiral auxiliaries and a chiral dirhodium(II) catalyst.[8] To address the challenge of catalytic asymmetric CÀH amination, we chose to study ruthenium(II)-pybox (pybox = pyridine bisoxazoline) complexes (Scheme 1). Despite reports that show complex 1 exhibited limited reactivity and selectivity in C À H amination reactions, [3f] we felt that the modular nature of the ligand, and the fact that the anionic ligands were independent of the chiral pybox ligand, offered us an opportunity which had not been possible by using either dirhodium(II)-or porphyrin-based catalyst systems.Ruthenium(II)-pybox complexes 1-4 were readily prepared by using the method developed by Nishiyama et al. (Scheme 1).[9] In our initial study, the challenging test substrate sulfamate ester 5[10] was treated with 1.1 equivalents of the oxidant bis(acetoxy)iodobenzene and 5 mol % catalyst 2 to give the desired product of CÀH insertion 6, albeit in modest yield and enantiomeric excess (Table 1, entries 1-3).Based on the study by Fiori and Du Bois, which demonstrates that rhodium-catalyzed C À H amination involves formation of an electrophilic metallonitrene and a build up of positive charge on the carbon center during the insertion process, we rationalized that a cationic catalyst would be more reactive than its neutral analogue.[2e] Halide abstraction from the Scheme 1. Synthesis of ruthenium(II)-pybox complexes. [b] ee [%] [b]

Chiral variants of group IX Cp and Cp* catalysts are well established and catalyze a broad range of reactions with high levels of enantioselectivity. Enantiocontrol in these systems results from ligand design that focuses on appropriate steric blocking. Herein we report the development of a new planar chiral indenyl rhodium complex for enantioselective C–H functionalization catalysis. The ligand design is based on establishing electronic asymmetry in the catalyst, to control enantioselectivity during the reactions. The complex is easily synthesized from commercially available starting materials and is capable of catalyzing the asymmetric allylic C–H amidation of unactivated olefins, delivering a wide range of high-value enantioenriched allylic amide products in good yields with excellent regio- and enantioselectivity. Computational studies suggest that C–H cleavage is rate- and enantio-determining, while reductive C–N coupling from the RhV-nitrenoid intermediate is regio-determining.

An efficient regioselective allylic C–H amidation of mono-, di-, and trisubstituted olefins has been developed. Specifically, the combination of dioxazolone reagents with RhCp* and IrCp* catalysts is reported to promote reactions with complementary regioselectivites to those previously observed in Pd-catalyzed and Ag-promoted Rh-catalyzed reactions. We report that catalyst matching with substrate class is essential for selective reactions. RhCp* complexes are required for high conversion and selectivities with β-alkylstyrene substrates, and IrCp* complexes are necessary in the context of unactivated terminal olefins.

A conceptually novel metallonitrene/alkyne metathesis cascade reaction has been developed for the construction of nitrogen-containing compounds from simple alkyne starting materials. Rhodium(II) tetracarboxylate salts are efficient catalysts for this reaction, in which an electrophilic rhodium nitrene is trapped by an alkyne, resulting in the formation of a new C-N bond and the generation of a reactive metallocarbene for cascade reaction. The reaction is tolerant of both alkyl and aryl substituents on the alkyne, and proceeds at room temperature in a variety of common solvents. The modular nature of the reaction allows for the rapid construction of congested bicyclic systems from remarkably simple alkyne starting materials.