Eric Fillion

N‐Fused Indolines through Non‐Carbonyl‐Stabilized Rhodium Carbenoid CH Insertion of N‐Aziridinyl Imines

Metal-catalyzed methods of functionalizing C H bonds have seen incredible advancements in recent times, allowing for new retrosynthetic disconnections to otherwise unreactive bonds and executing transformations with high chemo-, regio-, and stereocontrol. A more established area of functionalizing C ACHTUNGTRENNUNG(sp3) H bonds has been rhodium-catalyzed C H insertions from carbonyl-stabilized diazo substrates, which has reached a level at which even intermolecular C H insertions with high enantioselectivity have been achieved. Key to the success of the intermolecular methodology was shifting the focus from studying ligand alterations to substrate design, specifically in moving to donor–acceptor carbenoids. Despite the progression, analogous C H insertions of carbenoids without an acceptor (primarily carbonyl functionalities) have remained elusive due to the inherent difficulties with controlling selectivity of the reactive species. Alternatively, a rapidly developing redox-neutral method of functionalizing C ACHTUNGTRENNUNG(sp3) H bonds has been catalyzed variants of the tert-amino effect, which now includes unactivated alkyne and allene acceptors, tertiary aliphatic hydride donors, domino reactions, and enantioselective protocols. Seeking to develop a methodology to give direct access to the privileged N-fused indoline scaffold through C ACHTUNGTRENNUNG(sp3) H bond functionalization, we turned our attention to N-aziridinyl imines 1 (Eschenmoser hydrazones), which potentially offered two distinct reactivity modes to achieve the desired transformation (Scheme 1), namely, hydride acceptor and decomposition to a benzylic carbene. By virtue of the proposed [1,5] hydride shift/cyclization mechanism (Scheme 1, path A), the benzylic carbon would act as a geminal acceptor/donor (effectively a 1,1-dipole) instead of the typical vicinal acceptor/donor; the net result would be the formation of a five-membered ring as opposed to the six-membered ring created with traditionally employed acceptors. Also, cognizant of the ability of the N-aziridinyl imine to function as a carbene precursor (Scheme 1, path B) a competing pathway that could lead to N-fused indoline 2 had to be considered. In this manuscript, we report a general catalytic protocol of non-carbonyl-stabilized rhodium carbenoid C H insertions enabling rapid synthesis of N-fused indolines and complex heterocycles. The ability of hydrazone 1 a to cyclize to tricycle 2 a through C ACHTUNGTRENNUNG(sp3) H bond functionalization was first examined (Table 1). Upon screening Lewis and BrønACHTUNGTRENNUNGsted acids, only varying amounts of starting material and decomposition were observed. However, when heating the reaction ( 70 8C) in the absence of a promoter, the carbene pathway was evident by the formation of the desired product 2 a (by C H insertion) along with aldehyde 3 a, cyclopropanes 4 a, and dimerization products (azine 5 a and alkenes 6 a ; Table 1, entry 1). It was then found that the cyclopropanes could be selectively formed (4 a, trans/cis ratio of 1.6:1) by intermolecular scavenging of the carbene intermediate upon addition of an excess of styrene (Table 1, entry 2). Optimistic about the possibility of mediating the carbene reaction with rhodium, a catalyst screen was performed. It was gratifying to see that the product distribution changed significantly to predominantly form the C H insertion product (Table 1, entry 3) in contrast to a recent report of tosyl hydrazone decomposition, which exclusively formed alkenes through dimerization. Steric effects of dirhodium(II) carboxamidates proved to be beneficial (Table 1, entry 4 versus entries 5 and 6). Additional experiments with [Rh2ACHTUNGTRENNUNG(cap)4] (cap =caprolactamate) probing higher dilution, increased catalyst loading, and slow addition of the substrate resulted in negligible improvement in formation of the C H insertion product 2 a (Table 1, entries 7– 9). The catalyst of choice was determined to be [Rh2ACHTUNGTRENNUNG(5SMEPY)4] (5S-MEPY=methyl-2-oxopyrrolidine-5(S)-carboxylate) on the basis of its slight superiority in terms of selectivity for C H insertion and yield (Table 1, entry 6, 51 %), albeit affording racemic product. Since this [a] S. J. Mahoney, Prof. Dr. E. Fillion Department of Chemistry, University of Waterloo 200 University Avenue West, Waterloo, Ontario Canada N2L 3G1 (Canada) Fax: (+1) 519-746-0435 E-mail : efillion@uwaterloo.ca Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201103155. Scheme 1. General strategy.

Sequential Rh(I)/Pd-Catalyzed 1,4-Addition/Intramolecular Allylation: Stereocontrolled Construction of γ-Butyrolactones and Cyclopropanes

The rhodium-catalyzed conjugate addition of functionalized vinyltin reagents to alkylidene Meldrums acids, followed by Pd-catalyzed intramolecular allylation, is a direct entry into vinyl-substituted gamma-lactones via O-alkylation and vinylcyclopropanes via C-alkylation.

Janus Face Aspect of All-cis 1,2,3,4,5,6-Hexafluorocyclohexane Dictates Remarkable Anion and Cation Interactions In the Gas Phase

Experiments have been carried out in which electrospray ionization has been used to generate ionic complexes of all-cis 1,2,3,4,5,6 hexafluorocyclohexane. These complexes were subsequently mass isolated in a quadrupole ion trap mass spectrometer and then irradiated by the tunable infrared output of a free electron laser in the 800-1600 cm(-1) range. From the frequency dependence of the fragmentation of the complexes, vibrational signatures of the complexes were obtained. Computational work carried out in parallel reveals that the complexes formed are very strongly bound and are among the most strongly bound complexes of Na(+) and Cl(-) ever observed with molecular species. The dipole moment calculated for the heaxafluorocyclohexane is very large (∼7 D), and it appears that the bonding in each of the complexes has a significant electrostatic contribution.

Persistent Intramolecular C-H···X (X = O or S) Hydrogen-Bonding in Benzyl Meldrum's Acid Derivatives.

C-H···X (where X = O or S) intramolecular hydrogen bonding is investigated in three benzyl Meldrums acid derivatives using a combination of solution phase NMR spectroscopy, gas phase infrared multiple photon dissociation spectroscopy, and density functional theory calculations. In one compound, an abnormally large C-H···S hydrogen bond energy of 30.4 kJ mol-1 is calculated with a natural bond orbital analysis. Intramolecular C-H···O hydrogen bonding is found to persist in the gas phase. Gibbs energy decomposition pathways are calculated.

Interaction of B12F122– with All-cis 1,2,3,4,5,6 Hexafluorocyclohexane in the Gas Phase

Clusters of all-cis 1,2,3,4,5,6-hexafluorocyclohexane and the dodecafluorododecaboron dianion, [C6F6H6]n[B12F12]2- (n = 0-4), are investigated in a combined experimental and computational study. DFT calculations and IRMPD spectra in the region of 800-2000 cm-1 indicate that C6H6F6 binds to open trigonal faces of B12F122- via a three-point interlocking binding motif. Calculated binding interactions reveal substantial contributions from C-H···F hydrogen bonding and binding energies that are among the strongest observed for a neutral-anion system.

Synthesis and Characterization of Tricarbastannatranes and Their Reactivity in B(C6F5)3‐Promoted Conjugate Additions

The synthesis and characterization of a series of tricarbastannatranes, in the solid state and in solution, are described. The structures of the complexes [N(CH2 CH2 CH2 )3 Sn](BF4 ), [N(CH2 CH2 CH2 )3 Sn](SbF6 ), [N(CH2 CH2 CH2 )3 Sn]4 [(SbF6 )3 Cl], and [(N(CH2 CH2 CH2 )3 Sn)2 OH][MeB(C6 F5 )3 ] were determined by X-ray crystallography. Furthermore, the B(C6 F5 )3 -promoted conjugate addition of alkyl-tricarbastannatranes to benzylidene derivatives of Meldrums acid was investigated, and detailed mechanistic studies are presented.

Infrared-Driven Charge Transfer in Transition Metal B12F12 Clusters

A combination of infrared multiple photon dissociation (IRMPD) spectroscopy and density functional theory calculations is used to investigate the structures and charge-transfer properties of clusters containing transition metals (TM = Co(II), Ni(II), Cu(I), Zn(II), Rh(III), Pd(II), Ag(I), Cd(II)) and the dodecafluorododecaboron dianion, B12F12(2-). In all cases, IRMPD resulted in transfer of electron density to the metal center and production of B12F12(-). Metals that exhibit the highest degree of charge transfer are found to induce reaction among the B12F12 cages, leading to production of BnFm (up to n = m = 24).

B(C6F5)3-Catalyzed transfer 1,4-hydrostannylation of α,β-unsaturated carbonyls using iPr-tricarbastannatrane

Tris(pentafluorophenyl)borane, B(C6F5)3, has been found to be an effective catalyst to access the hydridoborate anion, [N(CH2CH2CH2)3Sn][HB(C6F5)3], via hydride abstraction from the hypercoordinated tin reagent, iPr-tricarbastannatrane. This process has been applied to the B(C6F5)3-catalyzed transfer 1,4-hydrostannylation of electron-deficient olefins, namely benzylidene barbituric acids. Insights into the mechanism have been obtained via a series of 1H, 2H, 11B, 13C, and 119Sn NMR spectroscopy, mass spectrometry, and labeling experiments.

Mode-Selective Laser Control of Palladium Catalyst Decomposition

It is generally assumed that molecules behave ergodically during chemical reactions, that is, reactivities depend only on the total energy content and not on the initial state of the molecule. While there are a few examples of nonergodic behavior in small (usually electronically excited) species, to date there have been no reports of such behavior in larger covalently bound species composed of several tens of atoms. Here, we demonstrate vibrational mode-selective behavior in a series of palladium catalysts. When we excite solvent-tagged gas-phase Pd catalysts with an infrared laser that is tuned to be resonant with specific molecular vibrations, depending on which vibration we excite, we can select different reaction pathways. We also demonstrate that this behavior can be turned off via chemical substitution.

Infrared-Driven Charge-Transfer in Transition Metal-Containing B12X122– (X = H, F) Clusters

Density functional theory (DFT) calculations and infrared multiple photon dissociation (IRMPD) spectroscopy are employed to probe [TM·(B12H12)]- and [TM·(B12H12)2]2- clusters [TM = Ag(I), Cu(I), Co(II), Ni(II), Zn(II), Cd(II)]. A comparison is made between the charge-transfer properties of the clusters containing the hydrogenated dodecaborate dianions, B12H122-, and the fluorinated analogues, B12F122-, for clusters containing Cd(II), Co(II), Ni(II), and Zn(II). IRMPD of the [TM·(B12H12)]- and [TM·(B12H12)2]2- species yields B12H11- via hydride abstraction and B12H12- in all cases. To further explore the IR-induced charge-transfer properties of the B12X122- (X = H, F) cages, mixed-cage [TM(B12H12)(B12F12)]2- [TM = Co(II), Ni(II), Zn(II), Cd(II)] clusters were investigated. IRMPD of the mixed-cage species yielded appreciable amounts of B12F12- and B12H12- in most cases, indicating that charge-transfer to the central TM cation is a favorable process; formation of B12F12- is the dominant process for the Co(II) and Ni(II) mixed-cage complexes. In contrast, the Zn(II) and Cd(II) mixed-cage complexes preferentially produced fragments of the form B xH yF z-/2-, suggesting that H/F scrambling and/or fusion of the boron cages occurs along the IRMPD pathway.