Dipole-Transmissive 1,3-Dipolar Cycloadditions for the Rapid Construction of Polycyclic N-Heterocycles: Synthetic and Mechanistic Investigations.

The investigation of distinctive dipole-transmissive dipolar cycloaddition (DTDC) methodology and the formalisation of this concept is reported. A DTDC procedure was able to be developed by taking advantage of the structural complementarity of azide and diazoalkane 1,3-dipoles. Intramolecular azide-alkene 1,3-DCs followed by spontaneous dipole transmission upon work-up furnished intermediate α-diazoisoindole and α-diazoisoquinoline substrates bearing the key secondary diazoalkane 1,3-dipole. N-Derivatisation of the intermediate α-diazoisoindole and α-diazoisoquinolines with a tethered secondary dipolarophile followed by a subsequent 1,3-DC allowed for rapid construction of a range of functionalised polycyclic N-heterocycles. Integrated experimental and theoretical studies established requirements for product formation and revealed the likely mechanistic basis of divergent reactivity observed.

Pretransmetalation Intermediates in Suzuki-Miyaura Cross-Couplings: Synthesis of Csp3-, Csp2- and Csp-Organopalladium(II) Boronates.

Organopalladium(II) boronates represent fundamental pretransmetalation intermediates in Suzuki-Miyaura cross-couplings. These species are typically kinetically unstable, making them particularly elusive. In this study, a range of unprecedented, kinetically stable alkyl-, alkenyl-, allenyl-, and alkynylpalladium(II) boronates were prepared from various Csp3, Csp2, and Csp electrophiles via a simple, general method. The structures of these complexes were secured by X-ray crystallography, and the chemical competence of a number of these intermediates in transmetalation was demonstrated.

Exploring the Excited States of a Hexa-peri-hexabenzocoronene-Substituted Dipyridophenazine Ligand and Its Metal Complexes.

A hexa-peri-hexabenzocoronene (HBC)-substituted dipyridophenazine (dppz) ligand (dppz-HBC) and its corresponding rhenium [Re(CO)3Cl] and ruthenium [Ru(bpy)2]2+ complexes were synthesized and characterized. The interplay of their various excited states was investigated using spectroscopic and computational techniques. Perturbation of the HBC was seen through a broadening and decreased intensity of the HBC absorption bands that dominate the absorption spectra. A delocalized, partial charge transfer state was shown through emission (520 nm) in the ligand and rhenium complex and is supported by time-dependent density functional theory calculations. Transient absorption measurements revealed the presence of dark states with a triplet delocalized state populated in the ligand, while in the complexes, longer-lived (2.3-2.5 µs) triplet HBC states could be accessed. The properties of the studied ligand and complexes provide insight into the future design of polyaromatic systems and add to the rich history of dppz systems.

O-Acylated Flavones in the Alpine Daisy Celmisia viscosa: Intraspecific Variation.

Flavonoids acylated on their core phenolic groups are rare. The Aotearoa New Zealand endemic alpine daisy Celmisia viscosa is widespread, but its flavonoids have not previously been identified. Leaf extracts yielded a series of 8-O-acylated flavones with combinations of 3-methylbutanoate, 2-methylbutanoate, and 2-methylpropanoate groups and one, two, or three O-methyls, all previously unreported. Regiochemistries of 8-(3″-methylbutanoyl)-5-hydroxy-6,7,4'-trimethoxyflavone (5) and 8-(2″-methylbutanoyl)-5,7,4'-trihydroxy-6-methoxyflavone (10) were defined by X-ray crystallography. LC analyses of leaf extracts from the full geographic range of C. viscosa showed intraspecific variation of these flavones: most had high concentrations of trimethoxy 8-O-acylated flavones, but dimethoxy 8-O-acylated flavones were the most abundant flavonoids in two individuals. Three other viscid (sticky leaved) Celmisa species also contained these rare flavones, but four nonviscid Celmisa had none detectable.

Halimane Diterpenes in the Alpine Daisy Celmisia viscosa: Absolute Configuration, 2,6-Dideoxyhexopyran-3-ulosides, Conformational Flexibility, and Intraspecific Variation.

The methyl-migrated bicyclic skeleton of the halimane diterpenes has been found in a wide range of organisms, including flowering plants, liverworts, marine animals, and bacteria. The discovery of halima-1(10),14-dien-13-ol (3) from the Aotearoa New Zealand endemic alpine daisy Celmisia viscosa is now reported. The full configuration was assigned for the first time by X-ray crystallography, enantiomeric to that of a liverwort isolate. The absolute configuration at C-5 of the halimane is opposite to that at C-5 of the labdane epimanool (1) found in some C. viscosa specimens. Two new 2,6-dideoxyhexopyran-3-uloside halimane derivatives (4 and 5) were also found, and the absolute configuration of 5 was determined by 1H NMR analysis of the Mosher esters. Line broadening in the 13C NMR spectra of these halim-1(10)-enes was due to conformational exchange in the decalin ring A, as shown by molecular modeling and DFT calculations. 1H NMR and GC analyses of leaf extracts of individual plants from across the full geographic range of C. viscosa revealed intraspecific variation of diterpenes: 37 samples had halimadienol as the main diterpene in large amounts and 2 specimens had predominantly epimanool, again in large amounts. Three other viscid (sticky leaved) Celmisia species also contained diterpenes, but none was detectable in four nonviscid Celmisia species.

Revised Structures of Dehydrostenines A and B: Total Syntheses of (±)-Dehydrostenine A and Structure Assigned to Dehydrostenine B.

The first total syntheses of the Stemona alkaloid dehydrostenine A and the structure assigned to dehydrostenine B have been completed from a simple pyrrole substrate in 10 and 11 steps, respectively. Two independent Brønsted-acid-mediated intramolecular Michael additions were exploited to construct the tetracyclic dehydrostenine core. As a result of synthetic studies and associated analysis of the relevant literature, revisions of the structures originally assigned to dehydrostenines A and B are proposed.

Photochemical Activation of a Hydroxyquinone-Derived Phenyliodonium Ylide by Visible Light: Synthetic and Mechanistic Investigations.

We have identified and extensively investigated the photochemical activation and reaction of a hydroxyquinone-derived phenyliodonium ylide in the presence of visible light using experiment and theory. These studies revealed that in its photoexcited state this iodonium is capable of facilitating a range of single-electron transfer (SET) processes, including hydrogen atom transfer (HAT), a Povarov-type reaction, and atom-transfer radical addition chemistry. Where possible, we have employed density functional theory (DFT) to develop a more complete understanding of these photoinduced synthetic transformations.

Transitioning from Intraligand π,π* to Charge-Transfer Excited States Using Thiophene-Based Donor-Acceptor Systems.

A series of electron donor-acceptor compounds are reported in which both the donor and acceptor strengths are systematically altered using mono-, bi-, and terthiophene as donors and benzo[c][1,2,5]thiadiazole (btd), dipyrido[3,2-a:2',3'-c]phenazine (dppz), and the corresponding rhenium(I) complex, [ReCl(CO)3(dppz)], as acceptors. The electronic properties of the compounds are characterized using electrochemistry, electronic absorbance and emission spectroscopies, and transient absorption spectroscopy. The effect of donor and acceptor strengths on frontier molecular orbital localization and on the charge-transfer (CT) character of optical transitions is modeled using density functional theory (DFT) calculations. The electronic absorption spectra of the compounds investigated are dominated by intraligand charge-transfer (ILCT) transitions, where the CT character is shown to increase across the series from mono- to bi- to terthiophene but not significantly across the acceptor series. Emission is shown to originate from the absorbing state. Long-lived nonemissive states have been observed using transient absorption spectroscopy and assigned using triplet-state DFT calculations, which indicate that the lowest energy excited state has more thiophene-localized π,π* character with an increasing number of appended thiophenes.

Synthesis of Arylpalladium(II) Boronates: Confirming the Structure and Chemical Competence of Pre-transmetalation Intermediates in the Suzuki-Miyaura Reaction.

Palladium(II) boronates are recognized as fundamental pre-transmetalation intermediates in Suzuki-Miyaura cross-couplings. While these typically transient species have been detected and studied spectroscopically, it is conspicuous that they have never been isolated since this important reaction was discovered over forty years ago. This study reports the synthesis of a family of unprecedented arylpalladium(II) boronates that are, by design, kinetically stable at ambient temperature, both in solution and in the solid state. These properties enabled unambiguous crystallographic confirmation of their structure for the first time and their chemical competence in a Suzuki-Miyaura reaction was demonstrated.

One-Step Synthesis of C2v-Symmetric Resorcin[4]arene Tetraethers.

The three-component reaction between a resorcinol, 1,3-dimethoxybenzene, and an alkyl aldehyde (R = C1-C11) along with BF3·OEt2 affords a C2v-symmetric resorcin[4]arene tetraether in one step; in most cases, the single isomer can be precipitated from the reaction mixture in moderate to excellent yields (up to 89%). The reaction is tolerant of 2-substituted resorcinols (R' = OH, Cl, Br, Me), allowing a third type of functionality to be regioselectively incorporated during the macrocyclization.

Generation of Microsecond Charge-Separated Excited States in Rhenium(I) Diimine Complexes: Driving Force Is the Dominant Factor in Controlling Lifetime.

A transition-metal-based donor-(linker)-acceptor system can produce long-lived charge transfer excited states using visible excitation wavelengths. The ground- and excited-state photophysical properties of a series of [ReCl(CO)3(dppz-(linker)-TPA)] complexes, with varying donor and acceptor energies, have been systematically studied using spectroscopic techniques (both vibrational and electronic) supported by computational chemistry. The long-lived excited state is 3ILCT in nature for all complexes studied, characterized through transient absorption and emission, transient resonance Raman (TR2), and time-resolved infrared (TRIR) spectroscopy and TDDFT calculations. Modulation of the donor and acceptor energies results in changes of the 3ILCT lifetime by 1 order of magnitude, ranging from 6.1(±1) µs when a diphenylamine donor is used to 0.6(±0.2) µs when a triazole linker and triphenylamine donor is used. The excited-state lifetime may be rationalized by consideration of the driving force within the framework of Marcus theory and appears insensitive to the nature of the linker.

Superphenylphosphines: Nanographene-Based Ligands That Control Coordination Geometry and Drive Supramolecular Assembly.

Tertiary phosphines remain widely utilized in synthesis, most notably as supporting ligands in metal complexes. A series of triarylphosphines bearing one to three hexa-peri-hexabenzocoronene (HBC) substituents has been prepared by an efficient divergent route. These "superphenylphosphines", P{HBC(t-Bu)5}nPh3-n (n = 1-3), form the palladium complexes PdCl2L2 and Pd2Cl4L2 where the isomer distribution in solution is dependent on the number of HBC substituents. The crystalline structures of five complexes all show intramolecular π-stacking between HBC-phosphines to form a supramolecular bidentate-like ligand that distorts the metal coordination geometry. When n = 2 or 3, the additional HBC substituents engage in intermolecular π-stacking to assemble the complexes into continuous ribbons or sheets. The phosphines adopt HBC's characteristics including strong optical absorption, green emission, and redox activity.

Dramatic Alteration of 3ILCT Lifetimes Using Ancillary Ligands in [Re(L)(CO)3(phen-TPA)] n+ Complexes: An Integrated Spectroscopic and Theoretical Study.

The ground and excited state photophysical properties of a series of fac-[Re(L)(CO)3(α-diimine)] n+ complexes, where L = Br-, Cl-, 4-dimethylaminopyridine (dmap) and pyridine (py) have been extensively studied utilizing numerous electronic and vibrational spectroscopic techniques in conjunction with a suite of quantum chemical methods. The α-diimine ligand consists of 1,10-phenanthroline with the highly electron donating triphenylamine (TPA) appended in the 5 position. This gives rise to intraligand charge transfer (ILCT) states lying lower in energy than the conventional metal-to-ligand charge transfer (MLCT) state, the energies of which are red and blue-shifted, respectively, as the ancillary ligand, L becomes more electron withdrawing. The emitting state is 3ILCT in nature for all complexes studied, characterized through transient absorption and emission, transient resonance Raman (TR2), time-resolved infrared (TRIR) spectroscopy and TDDFT calculations. Systematic modulation of the ancillary ligand causes unanticipated variation in the 3ILCT lifetime by 2 orders of magnitude, ranging from 6.0 µs for L = Br- to 27 ns for L = py, without altering the nature of the excited state formed or the relative order of the other CT states present. Temperature dependent lifetime measurements and quantum chemical calculations provide no clear indication of close lying deactivating states, MO switching, contributions from a halide-to-ligand charge transfer (XLCT) state or dramatic changes in spin-orbit coupling. It appears that the influence of the ancillary ligand on the excited state lifetime could be explained in terms of energy gap law, in which there is a correlation between ln( knr) and Eem with a slope of -21.4 eV-1 for the 3ILCT emission.

Strategies, Setbacks, and Successes in the Synthesis of (-)-Spiroleucettadine.

Various strategies toward the synthesis of the marine natural product (-)-spiroleucettadine are described. In the original strategy, a biomimetic inspired oxidation of a 2-imidazoline scaffold uncovered unexpected reactivity, where benzylic oxidation followed by a Baeyer-Villiger reaction was observed. The second generation approach examined oxidative dearomatization of the phenol ring system first, where a competing spirocyclization process was uncovered. Efforts to forge the scaffold via a carbocation mediated benzyl migration were unsuccessful. Highlights of the successful synthesis include two consecutive hypervalent iodine reactions: the first formed the spirocyclic center and the second facilitated installation of an acetate group at the C-5 position to allow for subsequent introduction of the methyl amine side chain.

Walking the Emission Tightrope: Spectral and Computational Analysis of Some Dual-Emitting Benzothiadiazole Donor-Acceptor Dyes.

The synthesis, spectroscopic characterization, and computational modeling of seven benzo[ c][2,1,3]thiadiazole-based donor-acceptor dyes is reported. Using a range of linker units, it is possible to alter the lowest energy transition in terms of intensity (from 8000 to 25000 L mol-1 cm-1) and wavelength (from 350 to 430 nm). Resonance Raman spectroscopy was used in concert with DFT calculations to indicate that the linker unit participates in charge transfer processes. In each compound the excited state behavior appears to be primarily described by a BTD●--Linker-TPA●+ state. Stokes shift versus solvent parameter gradients are on the order of 15000 cm-1, indicating Δµ values are large. Dual emission is observed in six of the seven compounds and it can be modulated as a function of solvent. TD-DFT calculations, including excited state optimizations (linear response and state specific), indicate that the lowest energy emission is charge transfer in character. The high energy emissive state is assigned as n-π*. In nonpolar solvents, only the low energy charge transfer emission band is observed and this band generally has a high quantum yield (Φ ≈ 0.9). For compounds with phenyl and triazolyl linkers, in polar solvents only the high energy n-π* emission is observed. The high energy n-π* emission has a low quantum yield regardless of solvent.

Octahedral [Pd6 L8 ]12+ Metallosupramolecular Cages: Synthesis, Structures and Guest-Encapsulation Studies.

Four planar tripyridyl ligands (Ltripy ), 1,3,5-tris(pyridin-3-ylethynyl)benzene 1 a, 1,3,5-tris[4-(3-pyridyl)phenyl]benzene 2 a, and the hexyloxy chain functionalized derivatives 1,3,5-tris[(3-hexyloxy-5-pyridyl)ethynyl]benzene 1 b, and 1,3,5-tris[4-(3-hexyloxy-5-pyridyl)phenyl]benzene 2 b, were synthesized and used to generate a family of [Pd6 (Ltripy )8 ](BF4 )12 octahedral cages (Ltripy =1 a, b or 2 a, b). The ligands and cages were characterized using a combination of 1 H, 13 C, and DOSY nuclear magnetic resonance (NMR) spectroscopy, high resolution electrospray mass spectrometry (HR-ESI-MS), infrared (IR) spectroscopy, elemental analysis, and in three cases, X-ray crystallography. The molecular recognition properties of the cages with neutral and anionic guests were examined, in dimethyl sulfoxide (DMSO), using NMR spectroscopy, mass spectrometry and molecular modeling. No binding was observed with simple aliphatic and aromatic guest molecules. However, anionic sulfonates were found to interact with the octahedral cages and the binding interaction was size selective. The smaller [Pd6 (1 a, b)8 ]12+ cages were able to interact with three p-toluenesulfonate guest molecules while the larger [Pd6 (2 a, b)8 ]12+ systems could host four of the anionic guest molecules. To probe the importance of the hydrophobic effect, a mixed water-DMSO (1:1) solvent system was used to reexamine the binding of the neutral organic guests adamantane, anthracene, pyrene and 1,8-naphthalimide within the cages. In this solvent system all the guests except adamantane were observed to bind within the cavities of the cages. NMR spectroscopy and molecular modeling indicated that the cages bind multiple copies of the individual guests (between 3-6 guest molecules per cage).

Synthesis of Chromones from 1,1-Diacylcyclopropanes: Toward the Synthesis of Bromophycoic Acid E.

A tandem deprotection-cyclization reaction of 1,1-diacylcyclopropanes is described which allows rapid access to structurally diverse 2,3-disubstituted chromones in good yields, and with straightforward purification. The utility of this reaction is showcased by the construction of the potent antibacterial marine natural product bromophycoic acid E scaffold.

Alteration of Intraligand Donor-Acceptor Interactions Through Torsional Connectivity in Substituted Re-dppz Complexes.

The ground- and excited-state properties of a series of [ReCl(CO)3(dppz)] complexes with substituted donor groups were investigated. Alteration of donor-acceptor communication through modulation of torsional angle and the number and nature of the donor substituents allowed the effects on the photophysical properties to be characterized though both computational and spectroscopic techniques, including time-dependent density functional theory and resonance Raman and time-resolved infrared spectroscopy. The ground-state optical properties show significant variation as a result of donor group modulation, with an increased angle between the donor and acceptor blue-shifting and depleting the intensity of the lowest-energy transition, which is consistently intraligand charge transfer (ILCT) in nature. However, across all complexes studied there was minimal perturbation to the excited-state properties and dynamics. Three excited states on the picosecond, nanosecond, and microsecond time scales were observed in all cases, corresponding to 1ILCT, 3ππ*, and 3ILCT, respectively.

Total Synthesis of (-)-Spiroleucettadine.

One of a number of intriguing new alkaloids isolated from the Leucetta sp. sponge in 2004, spiroleucettadine displayed unique structural features on a restricted scaffold: a trans-fused 5,5-bicyclic ring system together with an amino hemiketal moiety. Attempts to synthesize the initially proposed structure failed, raising questions as to its veracity, and structure revision ensued in 2008; no successful synthetic approach has been reported to date. Herein, we describe the enantiospecific total synthesis of (-)-spiroleucettadine by a highly efficient biomimetic approach starting from l-tyrosine. One of two key hypervalent-iodine-mediated oxidation reactions forged the spirocyclic center, and the other enabled the installation of the methylamine side chain in the penultimate step. Our approach provides synthetic access to a new class of spiroannulated natural products and will enable future studies of the structure-biological-activity relationships of these antibacterial compounds.

The Synthesis of Multifunctionalized 1,3-Oxazin-4-ones from Donor-Acceptor Cyclopropanes.

A series of electronically diverse imines were found to readily react with various donor-acceptor cyclopropyl acid chlorides, with complete regioselectivity, to form 1,3-oxazin-4-ones in moderate yields (25-48% over two steps). Select oxazinones underwent a base induced rearrangement to afford the corresponding cycloheptene-fused oxazinones in good yields (up to 70%).