Timothy H. Warren

Copper–Nitrene Complexes in Catalytic CH Amination†

The direct catalytic transformation of typically inert carbon– hydrogen bonds into carbon–oxygen, carbon–nitrogen, and carbon–carbon bonds represents a significant challenge in organic synthesis and the chemical industry. Ideally, such reactions would not require the presence of a functional group that is discarded later in the course of the chemical transformation, but would proceed with atom and energy efficiency and be of minimal environmental impact. Chemical species capable of directly promoting this transformation often contain multiple bonds between late transition metals to oxygen, nitrogen, or carbon centers. Nature provides inspiration with enzymes such as cyctochrome P-450, which is efficient at inserting an oxygen atom into hydrocarbon C H bonds through an iron–oxo intermediate ([Fe]=O). The use of iminoiodanes (PhI=NR) has led to the generation of related metal–nitrene intermediates ([M]=NR), which in certain cases, exhibit stoichiometric reactivity with carbon–hydrogen bonds to give amines. Several catalytic protocols based on Rh, Ru, Ag, Au, Cu, and other metals for the amination of benzylic or allylic C H bonds with iminoiodanes bearing electrondeficient N substituents represent useful methodologies for the transformation of C H into C N bonds. 10,11] In these catalytic cases, metal–nitrene species are inferred, but their high reactivity makes their characterization as the active intermediates difficult. This lack of characterization is unfortunate, as a fundamental understanding of metal–nitrene species that mediate catalytic C N bond formation would aid the development of more general systems for C H bond functionalization. In this context, we recently isolated a dicopper complex [{(Me3NN)Cu}2(m-NAr)] (Ar = 3,5-dimethylphenyl) in which a nitrene is bound between two b-diketiminate copper fragments. Solution studies supported the intermediacy of terminal copper–nitrene [Cu] = [(Me3NN)Cu] through the dissociation of a b-diketiminate copper fragment from [{(Me3NN)Cu}2(m-NAr)]. The terminal nitrene could not be directly observed owing to an unfavorable dissociation constant [Eq. (1); [Cu] = [(Me3NN)Cu].

Capture of NO by a Frustrated Lewis Pair: A New Type of Persistent N-Oxyl Radical**

Frustrated Lewis Pairs (FLPs) show a rapidly increasing spectrum of interesting chemical reactions. They have been reported to activate dihydrogen under mild conditions and to serve as metal free hydrogenation catalysts toward specific organic substrates. FLPs add to numerous unsaturated substrates such as alkenes and alkynes, carbonyl compounds, azides and even CO2 or N2O. [3,4] For instance, the intramolecular P/B-FLP 1 adds to nitrosobenzene to form the sixmembered heterocycle 2. Nitric oxide (NO) is an important messenger molecule and regulator in biological systems. We find that the reactive frustrated Lewis pair 1 cleanly and rapidly reacts with this essential small molecule to form the persistent heterocyclicNoxyl radical “P/B-FLP-NOC” (3). Compound 3 represents a novel type of N-oxyl radical related to the ubiquitous TEMPO radical (4) and its congeners (e.g. 5 (PINO) and 6, see Scheme 1). Herein we describe the synthesis, characterization, and O-based reactivity of this novel type of N-oxyl radical derived from a frustrated Lewis pair and nitric oxide. Treatment of a yellow solution of the FLP Mes2PCH2CH2B(C6F5)2 (1) [10] (in situ generated from Mes2PCH=CH2 and Piers borane [HB(C6F5)2] ) in fluorobenzene with 1 equiv NOgas gave rise to an intense green solution fromwhich blue crystals of the P/B-FLP-NOC product 3 were isolated in 58% yield by precipitation with pentane (Scheme 1). X-ray crystal structure analysis of 3 (Figure 1)

N,N-addition of frustrated Lewis pairs to nitric oxide: an easy entry to a unique family of aminoxyl radicals.

The intramolecular cyclohexylene-bridged P/B frustrated Lewis pair [Mes(2)P-C(6)H(10)-B(C(6)F(5))(2)] 1b reacts rapidly with NO to give the persistent FLP-NO aminoxyl radical 2b formed by P/B addition to the nitrogen atom of NO. This species was fully characterized by X-ray diffraction, EPR and UV/vis spectroscopies, C,H,N elemental analysis, and DFT calculations. The reactive oxygen-centered radical 2b undergoes a H-atom abstraction (HAA) reaction with 1,4-cyclohexadiene to give the diamagnetic FLP-NOH product 3b. FLP-NO 2b reacts with toluene at 70 °C in an HAA/radical capture sequence to give a 1:1 mixture of FLP-NOH 3b and FLP-NO-CH(2)Ph 4b, both characterized by X-ray diffraction. Structurally related FLPs [Mes(2)P-CHR(1)-CHR(2)-B(C(6)F(5))(2)] 1c, 1d, and 1e react analogously with NO to give the respective persistent FLP-NO radicals 2c, 2d, and 2e, respectively, which show similar HAA and O-functionalization reactions. The FLP-NO-CHMePh 6b derived from 1-bromoethylbenzene undergoes NO-C bond cleavage at 120 °C with an activation energy of E(a) = 35(2) kcal/mol. Species 6b induces the controlled nitroxide-mediated radical polymerization (NMP) of styrene at 130 °C to give polystyrene with a polydispersity index of 1.3. The FLP-NO systems represent a new family of aminoxyl radicals that are easily available by N,N-cycloaddition of C(2)-bridged intramolecular P/B frustrated Lewis pairs to nitric oxide.

Catalytic CH Amination with Aromatic Amines

Aniline joins the club: A β-diketiminato copper(I) catalyst enables C-H amination of anilines employing low catalyst loadings to preclude oxidation to the diazene ArN=NAr. Electron-poor anilines are particularly resistant towards diazene formation and participate in the amination of strong and unactivated C-H bonds. N-alkyl anilines also take part in C-H amination.

Reaction of CuI with Dialkyl Peroxides: CuII-Alkoxides, Alkoxy Radicals, and Catalytic C–H Etherification

Kinetic analysis of the reaction of the copper(I) β-diketiminate [Cl(2)NN]Cu ([Cu(I)]) with (t)BuOO(t)Bu to give [Cu(II)]-O(t)Bu (1) reveals first-order behavior in each component implicating the formation of free (t)BuO(•) radicals. Added pyridine mildly inhibits this reaction indicating competition between (t)BuOO(t)Bu and py for coordination at [Cu(I)] prior to peroxide activation. Reaction of [Cu(I)] with dicumyl peroxide leads to [Cu(II)]-OCMe(2)Ph (3) and acetophenone suggesting the intermediacy of the PhMe(2)CO(•) radical. Computational methods provide insight into the activation of (t)BuOO(t)Bu at [Cu(I)]. The novel peroxide adduct [Cu(I)]((t)BuOO(t)Bu) (4) and the square planar [Cu(III)](O(t)Bu)(2) (5) were identified, each unstable toward loss of the (t)BuO(•) radical. Facile generation of the (t)BuO(•) radical is harnessed in the catalytic C-H etherification of cyclohexane with (t)BuOO(t)Bu at rt employing [Cu(I)] (5 mol %) to give the ether Cy-O(t)Bu in 60% yield.

C-H Functionalization Reactivity of a Nickel-Imide

We report bifunctional reactivity of the β-diketiminato Ni(III)-imide [Me(3)NN]Ni═NAd (1), which undergoes H-atom abstraction (HAA) reactions with benzylic substrates R-H (indane, ethylbenzene, toluene). Nickel-imide 1 competes with the nickel-amide HAA product [Me(3)NN]Ni-NHAd (2) for the resulting hydrocarbyl radical R(•) to give the nickel-amide [Me(3)NN]Ni-N(CHMePh)Ad (3) (R-H = ethylbenzene) or aminoalkyl tautomer [Me(3)NN]Ni(η(2)-CH(Ph)NHAd) (4) (R-H = toluene). A significant amount of functionalized amine R-NHAd is observed in the reaction of 1 with indane along with the dinickel imide {[Me(3)NN]Ni}(2)(μ-NAd) (5). Kinetic and DFT analyses point to rate-limiting HAA from R-H by 1 to give R(•), which may add to either imide 1 or amide 2, each featuring significant N-based radical character. Thus, these studies illustrate a fundamental competition possible in C-H amination systems that proceed via a HAA/radical rebound mechanism.

Frustrated Lewis pair modification by 1,1-carboboration: disclosure of a phosphine oxide triggered nitrogen monoxide addition to an intramolecular P/B frustrated Lewis pair.

The vicinal frustrated Lewis pair (FLP) mes2P-CH2CH2-B(C6F5)2 (3) reacts with phenyl(trimethylsilyl)acetylene by 1,1-carboboration to give the extended C3-bridged FLP 6 featuring a substituted vinylborane subunit. The FLP 6 actively cleaves dihydrogen. The FLP 3 also undergoes a 1,1-carboboration reaction with diphenylphosphino(trimethylsilyl)acetylene to give the P/B/P FLP 11 that features a central unsaturated four-membered heterocyclic P/B FLP and a pendant CH2CH2-Pmes2 functional group. Compound 11 reacts with nitric oxide (NO) by oxidation of the pendant Pmes2 unit to the P(O)mes2 phosphine oxide and N,N-addition of the P/B FLP unit to NO to yield the persistent P/B/PO FLPNO aminoxyl radical 14. This reaction is initiated by P(O)mes2 formation and opening of the central Ph2P···B(C6F5)2 linkage triggered by the pendant CH2CH2-P(O)mes2 group.

Nitric Oxide Oxidatively Nitrosylates Ni(I) and Cu(I) C-Organonitroso Adducts

Monovalent nickel and copper beta-diketiminato complexes react with ArN=O (Ar = 3,5-Me(2)C(6)H(3), Ph) to give C-nitroso adducts that exhibit three different modes of bonding with varying degrees of N-O bond activation. The addition of ArNO to 2 equiv of [Me(2)NN]Ni(2,4-lutidine) {[Me(2)NN](-) = 2,4-bis(2,6-dimethylphenylimido)pentyl} gives {[Me(2)NN]Ni}(2)(mu-eta(2):eta(2)-ONAr) (1a and 1b), which exhibit symmetrical bonding of the ArN=O moiety between two [Me(2)NN]Ni fragments, with a N-O bond distance of 1.440(4) A in 1a that is significantly longer than those in free C-organonitroso compounds (1.13-1.29 A). [Me(2)NN]Cu(NCMe) reacts with 0.5 equiv of ArNO in ether to give the dinuclear adducts {[Me(2)NN]Cu}(2)(mu-eta(2):eta(1)-ONAr) (2a and 2b), which exhibit eta(2) and eta(1) bonding of the ArN=O moiety with separate [Me(2)NN]Cu fragments possessing N-O distances of 1.375(6) A (2a) and 1.368(2) A (2b). In arene solvents, one beta-diketiminatocopper(I) fragment dissociates from 2 to give [Me(2)NN]Cu(eta(2)-ONAr) (3a and 3b), which may be isolated by the addition of 1 equiv of ArNO to [Me(2)NN]Cu(NCMe). The X-ray structures of 3a and 3b are similar to those of related Cu(I) alkene adducts, with N-O distances in the narrow range 1.333(4)-1.338(5) A. IR spectra of the nitrosobenzene adducts 1b, 2b, and 3b exhibit nu(NO) stretching frequencies at 915, 1040, and 1113 cm(-1), respectively, following the decreasing degree of N=O activation observed in the X-ray structures of species 1, 2, and 3. Both 1a and 3a react with anaerobic NO(g) to give the corresponding N-aryl-N-nitrosohydroxylaminato complexes [Me(2)NN]M(kappa(2)-O(2)N(2)Ar) [M = Ni (4), Cu (5)]. In the reaction of dinuclear 1a with NO, one [Me(2)NN]Ni fragment is trapped as the nickel nitrosyl [Me(2)NN]Ni(NO). Reaction of the monovalent complex [Me(2)NN]Cu(eta(2)-ONAr) with NO(g) to give divalent [Me(2)NN]Cu(kappa(2)-O(2)N(2)Ar) represents an example of oxidative nitrosylation.

Copper(II) Anilides in sp3 C-H Amination

We report a series of novel β-diketiminato copper(II) anilides [Cl2NN]Cu-NHAr that participate in C-H amination. Reaction of H2NAr (Ar = 2,4,6-Cl3C6H2 (Ar(Cl3)), 3,5-(CF3)2C6H3 (Ar(F6)), or 2-py) with the copper(II) t-butoxide complex [Cl2NN]Cu-(t)OBu yields the corresponding copper(II) anilides [Cl2NN]Cu-NHAr. X-ray diffraction of these species reveal three different bonding modes for the anilido moiety: κ(1)-N in the trigonal [Cl2NN]Cu-NHAr(Cl3) to dinuclear bridging in {[Cl2NN]Cu}2(μ-NHAr(F6))2 and κ(2)-N,N in the square planar [Cl2NN]Cu(κ(2)-NH-2-py). Magnetic data reveal a weak antiferromagnetic interaction through a π-stacking arrangement of [Cl2NN]Cu-NHAr(Cl3); solution EPR data are consistent with monomeric species. Reaction of [Cl2NN]Cu-NHAr with hydrocarbons R-H (R-H = ethylbenzene and cyclohexane) reveals inefficient stoichiometric C-H amination with these copper(II) anilides. More rapid C-H amination takes place, however, when (t)BuOO(t)Bu is used, which allows for HAA of R-H to occur from the (t)BuO(•) radical generated by reaction of [Cl2NN]Cu and (t)BuOO(t)Bu. The principal role of these copper(II) anilides [Cl2NN]Cu-NHAr is to capture the radical R(•) generated from HAA by (t)BuO(•) to give functionalized aniline R-NHAr, resulting in a novel amino variant of the Kharasch-Sosnovsky reaction.

Neutral β-diketiminato nickel(II) monoalkyl complexes

Abstract Reaction of NiCl2(2,4-lutidine)2 (1) with Tl[Me2NN] (3) in THF results in the transmetallation of the β-diketiminate ligand from which the tetrahedral {[Me2NN]NiCl}2 (4) was isolated in poor yield. After filtration of the TlCl formed in the reaction between 1 and 3 in THF, addition of Grignard reagents RMgBr results in the isolation of monoalkyl complexes [Me2NN]Ni(R)(2,4-lutidine) (R=Me (5), Et (6), Pr (7)) in 40–70% yield. X-ray structures 5–7 of show these monoalkyls to be somewhat crowded, square planar species. NMR studies of the diamagnetic monoalkyl complexes show that lutidine dissociation/reassociation occurs on the NMR timescale at room temperature. In ethyl and propyl complexes 6 and 7, an equilibrium between the four coordinate [Me2NN]Ni(R)(2,4-lutidine) and a lutidine-free species [Me2NN]Ni(R) (R=Et, Pr) is observed. Broad, high-field 1H resonances consistent with the presence of β-H agostic alkyl groups are observed for the base-free species. The observation of two broad upfield 1H NMR signals at δ −2.7 and −7.3 ppm for the base-free Ni–propyl complex suggests a mixture of primary and secondary β-agostic isomers that reversibly interconvert by β-H elimination/reinsertion. Ethylene slowly inserts into monoalkyls 5–7 demonstrate to give highly branched ethylene oligomers.