Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition of 1,6-Enynes with Racemic Secondary Allylic Alcohols through Kinetic Resolution.

It has been established that a cationic rhodium(I)/P-phos complex catalyzes the asymmetric [2+2+2] cycloaddition of 1,6-enynes with racemic secondary allylic alcohols to produce the corresponding chiral bicyclic cyclohexenes, possessing three stereogenic centers, as a single diastereomer with excellent ee values. Mechanistic experiments revealed that the present cycloaddition proceeds through the kinetic resolution of the racemic secondary allylic alcohols, in which one enantiomer preferentially reacts with the 1,6-enyne.

Enantioselective Synthesis of Distorted π-Extended Chiral Triptycenes Consisting of Three Distinct Aromatic Rings by Rhodium-Catalyzed [2+2+2] Cycloaddition.

The enantioselective synthesis of distorted π-extended chiral triptycenes, consisting of three distinct aromatic rings, has been achieved with high ee value of 87 % by the cationic rhodium(I)/segphos complex-catalyzed enantioselective [2+2+2] cycloaddition of 2,2'-di(prop-1-yn-1-yl)-5,5'-bis(trifluoromethyl)-1,1'-biphenyl with 6-methoxy-1,2-dihydronaphthalene followed by the diastereoselective Diels-Alder reaction and aromatization. Demethoxy derivatives were also synthesized by the C-O bond cleavage. In this synthesis, the use of the electron-deficient diyne and the electron-rich alkene is crucial to suppress the undesired strain-relieving carbocation rearrangement and stabilize the distorted triptycene structure.

Rhodium-Catalyzed ortho-Bromination of O-Phenyl Carbamates Accelerated by a Secondary Amide-Pendant Cyclopentadienyl Ligand.

It has been established that a newly developed cyclopentadienyl rhodium(III) [CpA RhIII ] complex, bearing an acidic secondary amide moiety on the Cp ring, is able to catalyze the ortho-bromination of O-phenyl carbamates with N-bromosuccinimide (NBS) at room temperature. The presence of the acidic secondary amide moiety on the CpA ligand accelerates the bromination by the hydrogen bond between the acidic NH group of the CpA ligand and the carbonyl group of NBS.

Iridium(III) Catalysts with an Amide-Pendant Cyclopentadienyl Ligand: Double Aromatic Homologation Reactions of Benzamides by Fourfold C-H Activation.

The synthesis, characterization, and catalytic performance of iridium(III) catalysts that bear an amide-pendant cyclopentadienyl ligand ([CpA IrI2 ]2 ) is reported. These [CpA IrI2 ]2 catalysts were obtained from the complexation of a CpA ligand precursor with [Ir(cod)OAc]2 followed by oxidation. Double aromatic homologation reactions of benzamides with alkynes by fourfold C-H activation proceeded in good to high yield with these [CpA IrI2 ]2 catalysts, demonstrating their superior catalytic performance in this challenging transformation.

Rhodium-Catalyzed Highly Diastereo- and Enantioselective Synthesis of a Configurationally Stable S-Shaped Double Helicene-Like Molecule.

An S-shaped double helicene-like molecule (>99 % ee), possessing stable helical chirality, has been synthesized by the rhodium(I)/difluorphos complex-catalyzed highly diastereo- and enantioselective intramolecular double [2+2+2] cycloaddition of a 2-naphthol- and benzene-linked hexayne. The collision between two terminal naphthalene rings destabilizes the helical chirality of the S-shaped double helicene-like molecule, but the introduction of two additional fused benzene rings significantly increases the configurational stability. Thus, no epimerization and racemization were observed even at 100 °C. The enantiopure S-shaped double helicene-like molecule forms a trimer through the multiple C-H⋅⋅⋅π and C-H⋅⋅⋅O interactions in the solid-state. The trimers stack to form columnar packing structures, in which neighboring stacks have opposite dipole directions. The accumulation of helical structures in the same direction in the S-shaped double helicene-like molecule enhanced the chiroptical properties.

Synthesis of Belt- and Möbius-Shaped Cycloparaphenylenes by Rhodium-Catalyzed Alkyne Cyclotrimerization.

A belt-shaped [8]cycloparaphenylene (CPP) and an enantioenriched Möbius-shaped [10]CPP have been synthesized by high-yielding rhodium-catalyzed intramolecular cyclotrimerizations of a cyclic dodecayne and a pentadecayne, respectively. This Möbius-shaped [10]CPP possesses stable chirality and isolated with high enantiomeric purity. It is evident from the reaction Gibbs energy calculation that the above irreversible cyclotrimerizations are highly exothermic; therefore establishing that the intramolecular alkyne cyclotrimerization is a powerful route to strained cyclic molecular strips.

Formal Lossen Rearrangement/Alkenylation or Annulation Cascade of Heterole Carboxamides with Alkynes Catalyzed by CpRhIII Complexes with Pendant Amides.

It has been established that a cyclopentadienyl (Cp) RhIII complex with two aryl groups and a pendant amide moiety catalyzes the formal Lossen rearrangement/alkenylation cascade of N-pivaloyl heterole carboxamides with internal alkynes, leading to alkenylheteroles. Interestingly, the use of sterically demanding internal alkynes afforded not the alkenylation but the [3+2] annulation products ([5,5]-fused heteroles). In these reactions, the pendant amide moiety of the CpRhIII complex may accelerate the formal Lossen rearrangement. The use of five-membered heteroles may deter reductive elimination to form strained [5,5]-fused heteroles; instead, protonation proceeds to give the alkenylation products. Bulky alkyne substituents accelerate the reductive elimination to allow the formation of the [5,5]-fused heteroles.

Rhodium-Catalyzed [2+1+2+1] Cycloaddition of Benzoic Acids with Diynes through Decarboxylation and C≡C Triple Bond Cleavage.

It has been established that an electron-deficient cyclopentadienyl rhodium(III) (CpE RhIII ) complex catalyzes the oxidative and decarboxylative [2+1+2+1] cycloaddition of benzoic acids with diynes through C≡C triple bond cleavage, leading to fused naphthalenes. This cyclotrimerization is initiated by directed ortho C-H bond cleavage of a benzoic acid, and the subsequent regioselective alkyne insertion and decarboxylation produce a five-membered rhodacycle. The electron-deficient nature of the CpE RhIII complex promotes reductive elimination giving a cyclobutadiene-rhodium(I) complex rather than the second intermolecular alkyne insertion. The oxidative addition of the thus generated cyclobutadiene to rhodium(I) (formal C≡C triple bond cleavage) followed by the second intramolecular alkyne insertion and reductive elimination give the corresponding [2+1+2+1] cycloaddition product. The synthetic utility of the present [2+1+2+1] cycloaddition was demonstrated in the facile synthesis of a donor-acceptor [5]helicene and a hemi-hexabenzocoronene by a combination with the chemoselective Scholl reaction.

Aerobic Oxidative Cross-Coupling of Substituted Acrylamides with Alkenes Catalyzed by an Electron-Deficient CpRhIII Complex.

It has been established that an electron-deficient CpRhIII complex, bearing two ester moieties on the Cp ring, [CpERhIII], catalyzes the aerobic oxidative cross coupling of substituted acrylamides with both activated and unactivated alkenes, leading to (2Z,4E)-dienamides, at relatively low temperature (80 °C). Importantly, tertiary, secondary, and primary amide directing groups could equally be used in this catalysis. The mechanistic studies revealed that the electron-deficient nature of the CpERhIII complex facilitates the turnover-limiting vinylic C-H bond cleavage of the acrylamides.

Aerobic Oxidative Olefination of Benzamides with Styrenes Catalyzed by a Moderately Electron-Deficient CpRh(III) Complex with a Pendant Amide.

It has been established that a newly developed moderately electron-deficient cyclopentadienyl (Cp)-Rh(III) complex, bearing ester and pendant amide moieties on the Cp ring [CpARh(III)], is able to catalyze the aerobic oxidative olefination of benzamides, bearing nonspecial carbamoyl groups, with styrenes including disubstituted ones at relatively low temperature (60-80 °C). The presence of both the ester and pendant acidic N-phenylcarbamoyl moieties on the CpA ligand play important roles in facilitation of the catalysis without sacrificing thermal stability of the complex.

Synthesis of a Strained Spherical Carbon Nanocage by Regioselective Alkyne Cyclotrimerization.

The smallest spherical carbon nanocage so far, [2.2.2]carbon nanocage, has been synthesized by the cationic rhodium(I)/H8 -binap complex-catalyzed regioselective intermolecular cyclotrimerization of a cis-1-ethynyl-4-arylcyclohexadiene derivative followed by the triple Suzuki-Miyaura cross-couplings with 1,3,5-triborylbenzene and reductive aromatization. This cage molecule is highly strained, and its ring strain is between those of [6] and [5]cycloparaphenylenes. A significant red-shift of an emission maximum was observed, compared with that of known [4.4.4]carbon nanocage. The sequential cyclotrimerizations of a cis-1,4-diethynylcyclohexadiene derivative with the same rhodium(I) catalyst followed by reductive aromatization failed to afford [1.1.1]carbon nanocage; instead, a ß-graph-shaped cage molecule was generated.

Enantioselective Synthesis of Fully Benzenoid Single and Double Carbohelicenes via Gold-Catalyzed Intramolecular Hydroarylation.

The enantioselective synthesis of fully benzenoid single and double carbo[6]helicenes has been achieved via the gold-catalyzed intramolecular hydroarylation. The single crystal of the racemic double carbo[6]helicene consists of unique layer structures like timbers with halving joints in the woodworking. Furthermore, the double carbo[6]helicenes exhibited relatively large CPL activities among chiral small organic molecules.

Synthesis of Single and Double Dibenzohelicenes by Rhodium-Catalyzed Intramolecular [2+2+2] and [2+1+2+1] Cycloaddition.

Dibenzo[7]helicenes were synthesized with up to 99 % ee by rhodium(I)/binap-catalyzed enantioselective intramolecular [2+2+2] cycloaddition of 2-phenylnaphthalene-linked triynes. Additionally, [2+1+2+1] cycloaddition products, that is, twisted anthracenes, were also synthesized by using difluorphos as ligand. Although these compounds are not configurationally stable at elevated temperature, their Scholl reactions afforded configurationally stable double dibenzo[6]helicenes. The thus-obtained dibenzo[7]helicene exhibited good circularly polarized luminescence property and the double dibenzo[6]helicene showed high fluorescence quantum yield.

Rhodium-Catalyzed Cascade Synthesis of Benzofuranylmethylidene-Benzoxasiloles: Elucidating Reaction Mechanism and Efficient Solid-State Fluorescence.

A new synthetic route to highly fluorescent benzofuranylmethylidenebenzoxasiloles through cationic rhodium(I)/binap complex-catalyzed cascade cycloisomerization of bis(2-ethynylphenol)silanes has been developed involving 1,2-silicon and 1,3-carbon (alkyne) migrations followed by oxycyclization. The present synthesis requires only three steps, starting from commercially available dichlorodiisopropylsilane, which is markedly shorter than our previous synthesis (eight steps starting from commercially available chlorodiisopropylsilane). Theoretical calculations elucidated the mechanism of the above cascade cycloisomerization. This reaction is initiated by the formation of a rhodium vinylidene not through direct 1,2-silicon migration but rather through an unprecedented stepwise 1,5-silicon migration followed by C-Si bond-forming cyclization from a dearomatized allenylrhodium complex. Subsequent 1,3-carbon (alkyne) migration leading to a η3 -allenyl/propargyl-rhodium complex followed by oxycyclization through π-bond (alkyne) activation with the cationic rhodium(I) complex affords the benzofuranylmethylidenebenzoxasilole product. The structure-fluorescence property relationships of the thus obtained benzofuranylmethylidenebenzoxasiloles were investigated, which revealed that good fluorescence quantum yields were generated in the solution state (φF =69-87 %) by introduction of electron-donating alkyl and phenyl groups on two phenoxy groups. In the powder state, 4-methyl- and 4-methoxy-phenoxy derivatives exhibited efficient blue fluorescence (φF =52 % and 46 %, respectively). Especially, the 4-methylphenoxy derivative was thermally stable, and exhibited strong narrow-band fluorescence in the film state (blue, φF =95 %) and redshifted strong narrow-band fluorescence (green, φF =90 %) in the crystalline state as a result of the formation of an offset π-stacked dimer; the latter was confirmed by X-ray crystallographic analysis and by theoretical calculations.

Formal Lossen Rearrangement/[3+2] Annulation Cascade Catalyzed by a Modified Cyclopentadienyl RhIII Complex.

It has been established that a cyclopentadienyl RhIII complex with two phenyl groups and a pendant amide moiety catalyzes the formal Lossen rearrangement/[3+2] annulation cascade of N-pivaloyl benzamides and acrylamides with alkynes leading to substituted indoles and pyrroles. Mechanistic studies revealed that this cascade reaction proceeds via not the Lossen rearrangement to form anilides or enamides but C-H bond cleavage, alkyne insertion, and the formal Lossen rearrangement.

Room Temperature Decarboxylative and Oxidative [2+2+2] Annulation of Benzoic Acids with Alkynes Catalyzed by an Electron-Deficient Rhodium(III) Complex.

It has been established that an electron-deficient (η5 -cyclopentadienyl)rhodium(III) [CpE RhIII ] complex is capable of catalyzing the decarboxylative and oxidative [2+2+2] annulation of benzoic acids with alkynes to produce substituted naphthalenes at room temperature. The appropriate choice of the additive and the solvent is crucial for this transformation. This catalyst system allowed use of oxygen as a terminal oxidant and broadened the substrate scope including both aromatic and aliphatic alkynes. In this catalysis, the electron deficient nature of the CpE RhIII catalyst would cause the strong rhodium-π interaction, which accelerates the decarboxylation as well as the C-H bond cleavage.

Rhodium-Catalyzed Asymmetric [2 + 2 + 2] Cycloaddition of Unsymmetrical α,ω-Diynes with Acenaphthylene.

It has been established that a cationic rhodium(I)/(R)-BINAP complex catalyzes the asymmetric [2 + 2 + 2] cycloaddition of unsymmetrical α,ω-diynes with acenaphthylene at room temperature to give the corresponding chiral multicyclic compounds with high yields and ee values. Interestingly, enantioselectivity highly depended on the structures of α,ω-diynes used. The structural requirements of α,ω-diynes for high enantioselectivity were opposite to those in our previously reported cationic rhodium(I)/(R)-Difluorphos complex-catalyzed asymmetric [2 + 2 + 2] cycloaddition of α,ω-diynes with indene.

Flattening of retinal pigment epithelial detachments after pneumatic displacement of submacular hemorrhages secondary to age-related macular degeneration.

PURPOSE: Pneumatic displacement of submacular hemorrhages (SMHs) with intravitreal injection of sulfur hexafluoride (SF6) gas with or without tissue plasminogen activator (tPA) and prone posturing is an effective minimally invasive treatment. We observed some cases in which simultaneous flattening of hemorrhagic pigment epithelial detachments (PEDs) occurred after prone posturing. This study evaluated the impact of pneumatic displacement using tPA to treat PEDs and visual outcomes in eyes with SMHs secondary to neovascular age-related macular degeneration (AMD). METHODS: This retrospective analysis reviewed the medical records of 32 patients (33 eyes) who underwent pneumatic displacement for AMD-associated SMHs. The SMHs were related to polypoidal choroidal vasculopathy (PCV) in 24 eyes and typical AMD in nine eyes and treated with intravitreal injection of SF6 gas with tPA. We assessed the postoperative best-corrected visual acuities (BCVAs), prevalence and flattening rates of the PEDs, and the number of additional treatments. RESULTS: The mean follow-up period was 35.4 ± 19.8 months. The BCVAs improved significantly in eyes with PCV compared with eyes with typical AMD. Thirty-one (93.9%) of 33 eyes had an accompanying PED. The PEDs flattened in 14 (58.3%) of 24 eyes with PCV but in only one (14.3%) of seven eyes with typical AMD (p = 0.04). A mean of one additional treatment was administered during the first year in 15 eyes with flattened PEDs, which was significantly (p < 0.05) fewer than the 3.6 additional treatments in 16 eyes with persistent PEDs. CONCLUSIONS: PEDs often accompany SMHs secondary to neovascular AMD. Pneumatic displacement of the SMHs using tPA unexpectedly flattened the PEDs, especially in eyes with PCV, and was associated with fewer additional treatments.

[2+2+2] Annulation of N-(1-Naphthyl)acetamide with Two Alkynoates via Cleavage of Adjacent C⁻H and C⁻N Bonds Catalyzed by an Electron-Deficient Rhodium(III) Complex.

It has been established that an electron-deficient cationic CpE-rhodium(III) complex catalyzes the non-oxidative [2+2+2] annulation of N-(1-naphthyl)acetamide with two alkynoates via cleavage of the adjacent C⁻H and C⁻N bonds to give densely substituted phenanthrenes under mild conditions (at 40 °C under air). In this reaction, a dearomatized spiro compound was isolated, which may support the formation of a cationic spiro rhodacycle intermediate in the catalytic cycle. The use of N-(1-naphthyl)acetamide in place of acetanilide switched the reaction pathway from the oxidative [2+2+2] annulation-lactamization via C⁻H/C⁻H cleavage to the non-oxidative [2+2+2] annulation via C⁻H/C⁻N cleavage. This chemoselectivity switch may arise from stabilization of the carbocation in the above cationic spiro rhodacycle by the neighboring phenyl and acetylamino groups, resulting in the nucleophilic C⁻C bond formation followed by ß-nitrogen elimination.

Synthesis, Structures, and Photophysical Properties of Alternating Donor-Acceptor Cycloparaphenylenes.

The synthesis of alternating donor-acceptor [12] and [16]cycloparaphenylenes (CPPs) has been achieved by the rhodium-catalyzed intermolecular cross-cyclotrimerization followed by imidation and/or aromatization. These alternating donor-acceptor CPPs showed positive solvatofluorochromic properties and smaller HOMO-LUMO gaps compared with nonfunctionalized CPPs, which was confirmed by the theoretical study.