Allylic C-H bond activation and functionalization mediated by tris(oxazolinyl)borato rhodium(I) and iridium(I) compounds

Allylic C-H bond oxidative addition reactions, mediated by tris(oxazolinyl)borato rhodium(I) and iridium(I) species, provide the first step in a hydrocarbon functionalization sequence. The bond activation products To(M)MH(η(3)-C(8)H(13)) (M = Rh (1), Ir (2)), To(M)MH(η(3)-C(3)H(5)) (M = Rh (3), Ir (4)), and To(M)RhH(η(3)-C(3)H(4)Ph) (5) (To(M) = tris(4,4-dimethyl-2-oxazolinyl)phenylborate) are synthesized by reaction of Tl[To(M)] and the corresponding metal olefin chloride dimers. Characterization of these group 9 allyl hydride complexes includes (1)H-(15)N heteronuclear correlation NMR experiments that reveal through-metal magnetization transfer between metal hydride and the trans-coordinated oxazoline nitrogen. Furthermore, the oxazoline (15)N NMR chemical shifts are affected by the trans ligand, with the resonances for the group trans to hydride typically downfield of those trans to η(3)-allyl and tosylamide. These group 9 oxazolinylborate compounds have been studied to develop approaches for allylic functionalization. However, this possibility is generally limited by the tendency of the allyl hydride compounds to undergo olefin reductive elimination. Reductive elimination products are formed upon addition of ligands such as CO and CN(t)Bu. Also, To(M)RhH(η(3)-C(8)H(13)) and acetic acid react to give To(M)RhH(κ(2)-O(2)CMe) (8) and cyclooctene. In contrast, treatment of To(M)RhH(η(3)-C(3)H(5)) with TsN(3) (Ts = SO(2)C(6)H(4)Me) gives the complex To(M)Rh(η(3)-C(3)H(5))NHTs (10). Interestingly, the reaction of To(M)RhH(η(3)-C(8)H(13)) and TsN(3) yields To(M)Rh(NHTs)(H)OH(2) (11) and 1,3-cyclooctadiene viaβ-hydride elimination and Rh-H bond amination. Ligand-induced reductive elimination of To(M)Rh(η(3)-C(3)H(5))NHTs provides HN(CH(2)CH=CH(2))Ts; these steps combine to give a propene C-H activation/functionalization sequence.     

Synthesis and Characterization of Tris(oxazolinyl)borato Copper(II) and Copper(I) Complexes

The reaction of To^MTl (To^M=tris(4,4-dimethyl-2-oxazolinyl)phenylborate) and CuBr₂ in benzene at 60 °C provides To^MCuBr ( 1 ) as an entry-point into tris(oxazolinyl)phenylborato copper chemistry. To^MCuO^tBu ( 2 ) and To^MCuOAc ( 3 ) are prepared by the reactions of To^MCuBr with KO^tBu and NaOAc, respectively. To^MCuO^tBu is transformed into (To^MCuOH)₂ ( 4 ) through hydrolysis. NMR, FT-IR, and EPR spectroscopies are used to determine the electronic and structural properties of these copper(II) compounds, and the solid-state structures were characterized by X-ray crystallography. Reduction of copper is observed upon treatment of To^MCuO^tBu with phenylsilane in an attempt to synthesize monomeric copper(II) hydride. To^MCu ( 5 ) and To^M₂Cu ( 6 ) were independently synthesized and characterized for comparison.     

Nonclassical β-hydrogen elimination of hydrosilazido zirconium compounds via direct hydrogen transfer

Salt metathesis reactions of Cp(2)(NR(2))ZrX (X = Cl, I, OTf) and lithium hydrosilazides ultimately afford hydride products Cp(2)(NR(2))ZrH that suggest unusual β-hydrogen elimination processes. A likely intermediate in one of these reactions, Cp(2)Zr[N(SiHMe(2))t-Bu][N(SiHMe(2))(2)], is isolated under controlled synthetic conditions. Addition of alkali metal salts to this zirconium hydrosilazide compound produces the corresponding zirconium hydride. However as conditions are varied, a number of other pathways are also accessible, including C-H/Si-H dehydrocoupling, γ-abstraction of a CH, and β-abstraction of a SiH. Our observations suggest that the conversion of (hydrosilazido)zirconocene to zirconium hydride and silanimine does not follow the classical four-center mechanism for β-elimination.     

Palladium and rhodium complexes containing 1,3-bis(oxazolinyl)propyl (Probox) ligands: Macrocycles and pincer compounds

New chiral 1,3-bis(4R-phenyl-2-oxazolinyl)propane (Probox^Ph) and achiral 1,3-bis(4,4-dimethyl-2-oxazolinyl)propane (Probox^Me2) ligands have been prepared by Cd(OAc)₂-catalyzed condensation reactions. These ligands, and the known isopropyl derivative Probox^iPr, react with [PdCl₂(NCPh)₂] and [RhCl(η²-C₈H₁₄)₂]₂ to form 16-membered bimetallic macrocycles. Additionally, Probox^Me2 and RhCl₃ react to form a new monoanionic NCN-type pincer complex (κ³-N,C,N-Probox^Me2)RhCl₂. The structures of new palladium and rhodium macrocycles with the Probox ligands are confirmed by X-ray crystallography, and natural abundance ¹⁵N 2D NMR experiments prove oxazoline coordination to the metal centers in solution. Addition of a weakly donating water ligand to (κ³-N,C,N-Probox^Me2)RhCl₂ gives a six-coordinate compound with a mer-Probox configuration, whereas PMe₃ coordination provides a single fac coordinated Probox isomer.     

The effect of topical anesthesia on vocal fold motion

The objective of this study was to determine if topical anesthesia to the larynx and pharynx affects vocal fold motion during dynamic voice evaluation with transnasal flexible endoscopy. Transnasal dynamic laryngeal examinations of 10 patients with no voice complaints were evaluated by five blinded fellowship-trained laryngologists. Each patient was examined before and after application of topical anesthetic. Reviewers rated briskness of right and left vocal fold movement and longitudinal tension on a visual analogue scale. Statistical comparisons were made between individual subject scores before and after anesthetic application. Inter-rater reliability was also assessed. No statistical difference was observed between subject scores before and after anesthetic application. Average intraclass correlation coefficients were 0.643 and 0.591 for pre- and postanesthesia scores, respectively. Application of topical anesthesia to the larynx and pharynx does not affect vocal fold motion.     

Cationic hafnium silyl complexes and their enhanced reactivity in sigma-bond metathesis processes with Si-H and C-H bonds

Reaction of the mixed-ring silyl methyl complex CpCp*Hf[Si(SiMe3)3]Me (4) with B(C6F5)3 in bromobenzene-d5 yielded the zwitterionic hafnium silyl complex [CpCpHfSi(SiMe3)3][MeB(C6F5)3] (7), which is stable for at least 12 h in solution. Addition of PhSiH3 to 7 rapidly produced HSi(SiMe3)3, CpCp*HfH(mu-H)B(C6F5)3, and oligomeric silane products. Reactions of CpCp*Hf(SiR3)Me (SiR3 = SitBuPh2, SiHMes2) with B(C6F5)3 rapidly produced HSiR3 in quantitative yield along with unidentified hafnium-containing species. However, reactions of Cp2Hf(SiR3)Me (SiR3 = Si(SiMe3)3 (8), SitBuPh2 (9), SiPh3 (10)) with B(C6F5)3 quantitatively produced the corresponding cationic hafnium silyl complexes 12-14. The complex Cp2Hf(SitBuPh2)(mu-Me)B(C6F5)3 (13) was isolated by crystallization from toluene at -30 degrees C and fully characterized, and its spectroscopic properties and crystal structure are compared to those of its neutral precursor 9. The sigma-bond metathesis reaction of 13 with Mes2SiH2 yielded HSitBuPh2 and the reactive species Cp2Hf(eta(2)-SiHMes2)(mu-Me)B(C6F5)3 (16, benzene-d6), which was also generated by reaction of Cp2Hf(SiMes2H)Me (11) with B(C6F5)3. Spectroscopic data provide evidence for an unusual alpha-agostic Si-H interaction in 16. At room temperature, 16 reacts with benzene to form Cp2Hf(Ph)(mu-Me)B(C6F5)3 (17), and with toluene to give isomers of Cp2Hf(C6H4Me)(mu-Me)B(C6F5)3 (18-20) and Cp2Hf(CH2Ph)(mu-Me)B(C6F5)3 (21). The reaction with benzene is first order in both 16 and benzene. Kinetic data including activation parameters (deltaH = 19(1) kcal/mol; deltaS = -17(3) eu), a large primary isotope effect (kH/kD = 6.9(7)), and the experimentally determined rate law are consistent with a mechanism involving a concerted transition state for C-H bond activation.     

Activation of arene C[bond]H bonds by a cationic hafnium silyl complex possessing an alpha-agostic Si[bond]H interaction

The reaction of Cp2Hf(SiMes2H)Me (1) with B(C6F5)3 produces zwitterionic Cp2Hf(eta2-SiHMes2)(mu-Me)B(C6F5)3 (2), which is stable for >8 h at -40 degrees C in toluene-d8. Spectroscopic data provide evidence for an unusual alpha-agostic Si-H interaction in 2. At room temperature, 2 reacts with the C-H bonds of aromatic hydrocarbons such as benzene and toluene to produce Cp2Hf(Ph)(mu-Me)B(C6F5)3 (3), isomers of Cp2Hf(C6H4Me)(mu-Me)B(C6F5)3 (4-6), and Cp2Hf(CH2Ph)(mu-Me)B(C6F5)3 (7), respectively. The reaction involving benzene is first-order in both 2 and benzene; rate = k[2][C6H6]. Mechanistic data including activation parameters (DeltaH = 19(1) kcal/mol; DeltaS = -17(3) eu), a large primary isotope effect of 6.9(7), and the experimentally determined rate law are consistent with a mechanism involving a concerted transition state for C-H bond activation.     

Hydrosilane σ-Adduct Intermediates in an Adaptive Zinc-Catalyzed Cross-dehydrocoupling of Si−H and O−H Bonds

Three-coordinate ^PhBOX ZnR (^PhBOX =phenyl-(4,4-dimethyl-oxazolinato; R=Me: 2 a , Et: 2 b ) catalyzes the dehydrocoupling of primary or secondary silanes and alcohols to give silyl ethers and hydrogen, with high turnover numbers (TON; up to 10⁷) under solvent-free conditions. Primary and secondary silanes react with small, medium, and large alcohols to give various degrees of substitution, from mono- to tri-alkoxylation, whereas tri-substituted silanes do not react with MeOH under these conditions. The effect of coordinative unsaturation on the behavior of the Zn catalyst is revealed through a dramatic variation of both rate law and experimental rate constants, which depend on the concentrations of both the alcohol and hydrosilane reactants. That is, the catalyst adapts its mechanism to access the most facile and efficient conversion. In particular, either alcohol or hydrosilane binds to the open coordination site on the ^PhBOX ZnOR catalyst to form a ^PhBOX ZnOR(HOR) complex under one set of conditions or an unprecedented σ-adduct ^PhBOX ZnOR(H−SiR′₃) under other conditions. Saturation kinetics provide evidence for the latter species, in support of the hypothesis that σ-bond metathesis reactions involving four-centered electrocyclic 2σ–2σ transition states are preceded by σ-adducts.     

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

Background  

Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.