Masanori Shigeno

Stereoselective restructuring of 3-arylcyclobutanols into 1-indanols by sequential breaking and formation of carbon-carbon bonds.

Transition-metal catalyzed reactions involving an elementary step in which a carbon–carbon bond is cleaved provide access to unique organic transformations that would otherwise be difficult to achieve. Of particular interest is the desymmetrization of prochiral substrates through the enantioselective cleavage of a carbon–carbon bond, which produces enantiomerically enriched compounds. We recently described a cascade-type reaction of 3-(2-hydroxyphenyl)cyclobutanones with electron-deficient olefins giving 5-alkylated 3,4-dihydrocoumarins. Mechanistically, the reaction involves two contradictory elementary steps operating in sequence; the first one is breaking of a carbon–carbon bond of the four-membered carbocycle by b-carbon elimination and the second one is a carbon–carbon bond formation by an intermolecular conjugate addition onto the electron-deficient alkene. Such sequences consisting of contradictory elementary steps are worth pursuing from the synthetic as well as mechanistic point of view. Herein, we describe the enantioand diastereoselective synthesis of 1-indanols by restructuring of the carbon framework of 3-arylcyclobutanols. Although construction of chiral quaternary carbon centers remains a significant challenge for synthetic chemists, the present reaction gives rise to two chiral quaternary centers in a highly enantiomerically enriched form in one pot. 3-Ethyl-1-methyl-3-phenylcyclobutanol (1 a), a symmetrical substrate, was heated at 70 8C in 1,4-dioxane in the presence of Cs2CO3 (1.5 equiv) and a rhodium(I) catalyst prepared from [{Rh(OH)ACHTUNGTRENNUNG(cod)}2] (5 mol%) and (R)-BINAP (11 mol%). Restructuring of the carbon framework occurred to afford 3-ethyl-1,3-dimethylindan-1-ol (2 a) as a mixture of diastereomers (cis/trans =79/21) in 98 % combined yield (Scheme 1). The enantiomeric purity of the major cis isomer was 96 % ee. Replacement of the BINAP ligand with (R)-DIFLUORPHOS improved both stereoselectivities, such that the cis/trans ratio became 89:11, and importantly, the enantiopurity of the major isomer increased to 99 % ee. A plausible mechanism is shown in Scheme 1; i) rhodium cyclobutanolate 3 is initially generated by deprotonation of the tertiary hydroxyl group of 1 a by rhodium hydroxide (or alkoxide), which acts as a base, ii) the fourmembered ring carbocycle is opened by b-carbon elimination. The chiral ligand on rhodium induces selective cleavage of one of the two enantiotopic carbon–carbon bonds to generate a chiral quaternary center at the benzylic position, iii) the resulting alkylrhodium species 4 subsequently undergoes 1,4-rhodium shift leading to the formation of arylrhodium intermediate 5, iv) intramolecular 1,2-addition to the carbonyl group occurs to stereoselectively form the [a] M. Shigeno, T. Yamamoto, Prof. Dr. M. Murakami Department of Synthetic Chemistry and Biological Chemistry Kyoto University, Katsura, Kyoto 615-8510 (Japan) Fax: (+81) 75-383-2748 E-mail : murakami@sbchem.kyoto-u.ac.jp Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200902593. Scheme 1. Rhodium-catalyzed reaction of cyclobutanol 1 a.

Palladium-catalyzed sequential carbon-carbon bond cleavage/formation producing arylated benzolactones.

3-(2-Hydroxyphenyl)cyclobutanones react with aryl bromides in the presence of palladium catalysts to afford 4-arylmethyl-3,4-dihydrocoumarins in high yields through a sequence involving carbon-carbon bond cleavage and formation. In the case of the reaction with 2-(2-hydroxyphenyl)cyclobutanones, five- or seven-membered lactones were produced depending on the presence of an additional substituent at the 2-position.

Heating/Cooling Stimulus Induces Three-State Molecular Switching of Pseudoenantiomeric Aminomethylenehelicene Oligomers: Reversible Nonequilibrium Thermodynamic Processes

A 1:1 mixture of pseudoenantiomeric aminomethylenehelicene (P)-tetramer and (M)-pentamer formed three states, namely, the heterodouble helices B and C and the random coil A. At high temperatures, A is the most stable. At low temperatures, C is the most stable, and the structural changes from A to the metastable state B to the product C occur, where B and C have pseudoenantiomeric helical structures. Heating then converts C to A. Essentially, all the molecules change their structure from A to B to C to A. Various nonequilibrium reversible thermodynamic responses appeared depending on thermal conditions: The metastable states A and B can be interconverted with thermal hysteresis without forming C in a far-from-equilibrium manner; three-state hysteresis occurs; states A and B can be frozen at low temperatures and defrosted by warming. An energy and population model for the three-state switching is given, involving inversion of thermodynamic stability and thermal hysteresis.

Two‐Component Fibers/Gels and Vesicles Formed from Hetero‐Double‐Helices of Pseudoenantiomeric Ethynylhelicene Oligomers with Branched Side Chains

A methodology for the formation of fibers/gels and vesicles by molecular assembly and for controlling their properties is presented. Two-component systems of pentamer (P)-5 and tetramer (M)-4 pseudoenantiomeric ethynylhelicenes with decyloxycarbonyl (D) and 4-methyl-2-(2-methylpropyl)-1-pentyloxycarbonyl (bD) side-chains have been examined. Distinct aggregates were formed by changing the solvent for the three combinations of (P)-bD-5/(M)-bD-4, (P)-D-5/(M)-bD-4, and (P)-D-5/(M)-D-4. In toluene, (P)-bD-5/(M)-bD-4, (P)-D-5/(M)-bD-4, and (P)-D-5/(M)-D-4 all formed gels and fibrous assemblies were observed by AFM. The minimum gel-forming concentration (MGC) decreased in the order (P)-bD-5/(M)-bD-4>(P)-D-5/(M)-bD-4>(P)-D-5/(M)-D-4. In diethyl ether, vesicular formation was observed by dynamic light scattering (DLS), AFM, and TEM, and the size of the vesicles decreased in the order (P)-bD-5/(M)-bD-4>(P)-D-5/(M)-bD-4>(P)-D-5/(M)-D-4. Both fiber/gel and vesicle formation were accompanied by enhanced CDs and redshifted UV/Vis absorption bands with a change in color to deep yellow. These are novel two-component oligomeric systems that form assemblies of fibers/gels or vesicles depending on the solvent, and the structures and properties of the assemblies can be fine-tuned by changing the combination of oligomers. In m-difluorobenzene, a homogeneous solution was obtained with (P)-D-5/(M)-bD-4, which again exhibits enhanced CDs and redshifted UV/Vis absorptions. Vapor pressure osmometry analysis showed the formation of a bimolecular heteroaggregate. The study has indicated that pseudoenantiomeric oligomers form hetero-double-helices that hierarchically assemble to form fibers/gels and vesicles.

Side Chain Effect on the Double Helix Formation of Ethynylhelicene Oligomers

Three series of ethynylhelicene oligomers with different side chains were synthesized: (P)-bD-n (n = 2-6) with branched alkyloxycarbonyl side chains; (P)-S-n (n = 2-7) with decylsulfanyl side chains; and (P)-DF-n (n = 4, 6, 8, 10) with alternating decyloxycarbonyl and perfluorooctyl side chains. The double helix formation of these side chain derivatives was compared to that of (P)-D-n with decyloxycarbonyl side chains. CD, UV-vis, and vapor pressure osmometry (VPO) studies showed that (P)-bD-n formed double helices as well as (P)-D-n. CD studies in trifluoromethylbenzene at different temperatures and concentrations indicated that the stability of the aggregate of (P)-bD-6 was similar to that of (P)-D-6. Bulkiness of side chains had little effect on aggregation, which indicated that π-π interactions of the aromatic moiety were essential for double helix formation. (P)-S-n were random coils in all solvents examined except in trifluoromethylbenzene. Whereas (P)-D-7 formed a double helix at 1 × 10(-3) M in toluene, (P)-S-7 was a random coil. This result indicated that the double helix forming ability of (P)-S-n was substantially lower than that of (P)-D-n. Based on the previous observation that (P)-F-n formed a more stable double helix than (P)-D-n, the order of stability may be summarized as follows: (P)-F-n > (P)-D-n and (P)-bD-n >(P)-S-n. The lower stability of (P)-S-n compared to that of (P)-F-n was ascribed to the softness and/or the electron-rich nature at the m-phenylene moiety. (P)-DF-n did not form a stable double helix. It was speculated that a regular alternating arrangement of soft/hard or electron-rich/deficient moieties is important for stable double helix formation. Side chains of ethynylhelicene oligomers can play significant roles in determining the stability of double helices.

Synthesis, Double-Helix Formation, and Higher-Assembly Formation of Chiral Polycyclic Aromatic Compounds: Conceptual Development of Polyketide Aldol Synthesis

Polycyclic aromatic compounds are an important group of substances in chemistry, and the study of their properties is a subject of interest in the development of drugs and materials. We have been conducting studies to develop chiral polycyclic aromatic compounds, i.e., helicenes and equatorenes. These helical molecules showed notable aggregate-forming properties and the capability for chiral recognition exerted by noncovalent bond interactions, which were not observed in compounds with central chirality. Homo- and hetero-double-helix-forming helicene oligomers were developed, and the latter self-assembled to form gels and vesicles. In this article, we describe such hierarchical studies of polycyclic aromatic compounds, which were started from polyketide aldol synthesis.

Molecular Thermal Hysteresis in Helix‐Dimer Formation of Sulfonamidohelicene Oligomers in Solution

Sulfonamidohelicene oligomers up to the nonamer level were synthesized by the repeated coupling reactions of a building block. A tetramer formed a helix dimer in 1,3-difluorobenzene, which unfolded to a random coil with heating. This structural change exhibited thermal hysteresis in which different thermal responses were observed in the course of temperature increase and decrease. The feature of the hysteresis was examined under different heating/cooling modes, and the mechanisms are discussed on the basis of the population change and the presence of an induction period. A proposal regarding the use of thermal hysteresis for sensing a temperature increase/decrease is also given.

Energy Aspects of Thermal Molecular Switching: Molecular Thermal Hysteresis of Helicene Oligomers

Molecular switching is a phenomenon by which a molecule reversibly changes its structure and state in response to external stimuli or energy. Herein, molecular switching is discussed from thermodynamic and kinetic aspects in terms of energy supply with an emphasis on the thermal switching exhibited by helicene oligomers. It includes the inversion of relative thermodynamic stability induced by temperature changes and molecular thermal hysteresis in a closed system. The thermal phenomenon associated with the oligomers involves population/concentration changes between metastable states under nonequilibrium thermodynamic control.

Multiple States of Dimeric Aggregates Formed by (Amido–ethynyl)helicene Bidomain Compound and (Amido–ethynyl–amido)helicene Tridomain Compound

An (amido-ethynyl)helicene bidomain compound and an (amido-ethynyl-amido)helicene tridomain compound were synthesized. The multidomain compounds were designed on the basis of previous findings that amido and ethynyl oligomers form dimeric aggregates with properties orthogonal to each other. Four aggregate states of multidomain compounds, namely, all-dimer, amido-dimer, ethynyl-dimer, and random-coil states, were obtained in different solvents, which were analyzed by circular dichroism (CD), UV/Vis, (1)H NMR, and IR spectroscopy; vapor pressure osmometry (VPO); dynamic light scattering (DLS); and atomic force microscopy (AFM). The amido and ethynyl domains independently aggregated and disaggregated in a two-state manner. Reversible structural changes occurred for a tridomain compound between the ethynyl-dimer/random-coil state and the all-dimer/amido-dimer state with heating and cooling. Two structural change processes with different properties were obtained using a single compound.

Molecular Function of Counting the Numbers 1 and 2 Exhibited by a Sulfoneamidohelicene Tetramer

The sulfoneamidohelicene tetramer in solution exhibits different molecular responses to the same cooling stimulus delivered once and twice under thermal hysteresis conditions. Its random-coil state at a high temperature was cooled and maintained at a given temperature for which its molecules remained in a random coil (first cooling); the resulting solution was heated and cooled, after which a helix dimer formed (second cooling). Such a property can be regarded as a molecular function of counting the numbers 1 and 2.