Unprecedented Chiral Molecular Recognition in a C3-Symmetric Environment

Sung-Gon Kim, Kyung-Hyun Kim, Junyang Jung, Seung Koo Shin,† and Kyo Han Ahn*

J. Am. Chem. Soc. 2002, 124, 591.

Abstract : The enantiomeric recognition of R-chiral primary ammonium ions has been studied with benzenebased tripodal tris(oxazoline) receptors. Contrary to the literature and our expectation, a good level of chiral discrimination is observed with one of the tripodal receptors, which provides a C3-symmetric chiral environment on guest binding. The chiral discrimination has been found to be general in the case of R-aryl substituted guests, suggesting ð-ð interactions as an important factor. This result raises a question with respect to the origin of the chiral discrimination since little steric or electronic difference is expected between the diastereomeric inclusion complexes. Binding studies by NMR titration and isothermal titration calorimetry show that the chiral discrimination results from the different thermodynamic stabilities between the diastereomeric complexes and that the host-guest complex formation is driven by favorable enthalpy changes with a minor negative contribution by entropy changes. The X-ray crystal structures for both of the diastereomeric inclusion complexes are resolved, which unambiguously show the binding mode and provide clues on the origin of the chiral discrimination. Bond angle analyses indicate that the minor complex experiences a larger steric strain, which is discernible when it is viewed from “three-body” interactions between the host and the guest. The guest and oxazoline phenyl rings are well stacked, indicating interplay of the ð-ð interactions. The ð-ð interactions are believed to stabilize host-guest complexes, thereby endowing the highly flexible receptors with a substantial enantio-discrimination.

Crucial Role of Three-Center Hydrogen Bonding in a Challenging Chiral Molecular Recognition

Sung-Gon Kim, Kyung-Hyun Kim, Young Kook Kim, Seung Koo Shin, and Kyo Han Ahn*

J. Am. Chem. Soc. 2003, 125, 13819.

Abstract : The enantio-discrimination of â-chiral primary ammonium ions is achieved by a rational approach that utilizes three-center (bifurcated) hydrogen bonding. The extraction experiments on various selected guests reveal that the bifurcated H-bonding plays a crucial role for the chiral discrimination. The X-ray data obtained for an inclusion complex substantiate such interactions. Using the bifurcated H-bonding, the chiral molecular recognition with our C3-symmetric tripodal oxazoline receptors is extended generally toward ammonium ions of R-, â-, and R,â-chiral amines. Simple molecular models, evoking the bifurcated H-bond ing,  explain the chiral discrimination modes.

Artificial

Receptors That Provides a Preorganized Hydrophobic Environment: A Biomimetic Approach to Dopamine Recognition in Water

Jeongryul Kim, Balamurali Raman, and Kyo Han Ahn*

J. Org. Chem. 2006, 71, 38

Abstract : The recognition of dopamine in water has been achieved with tripodal oxazoline-based artificial receptors, capable of providing a preorganized hydrophobic environment by rational design, which mimics a hydrophobic pocket predicted for a human D2 receptor. The receptors show an amphiphilic nature owing to the presence of hydrophilic sulfonate groups at the periphery of the tripodal oxazoline ligands, which seems to contribute in forming the preorganized hydrophobic environment. The artificial receptors recognized dopamine hydrochloride in water with reasonable selectivity among various organoammonium guests examined. The observed binding behavior of the receptors was explained by evoking guest inclusion in the preorganized hydrophobic pocket-like environment and not by simple ion-pairing interactions. The rationally predicted 1:1 inclusion binding mode was supported by binding studies such as with a reference receptor that cannot provide a similar binding pocket, Job and VT-NMR experiments, electrospray ionization mass analysis, and guest selectivity data. This study implies that an effective hydrophobic environment can be generated even from an acyclic, small molecular artificial receptor. Such a preorganized hydrophobic environment, as being utilized in biological systems, can be effectively used as a complementary binding force for the recognition of organoammonium guests such as dopamine hydrochloride in water.

Tripodal oxazoline-based homochiral coordination cages with internal binding sites

Jeongryul Kim, Dowook Ryu, Yoshihisa Sei, Kentaro Yamaguchi and Kyo Han Ahn*

Chem. Commun., 2006, 1136.

Abstract : Homochiral coordination cages, which have two well-defined internal binding sites for ammonium and organoammonium ions, have been constructed by Pd(II)-mediated self-assembly of preorganized tripodal oxazolines containing pyridine pendant groups.

Molecular Recognition of Anions through Hydrogen Bonding Stabilization of Anion-Ionophore Adducts: A Novel Trifluoroacetophenone-Based Binding Motif

Young Kook Kim, Yun-Ho Lee, Hyang-Yeol Lee, Mi Kyoung Kim, Geun Sig Cha,*, and Kyo Han Ahn*

Org. Lett. 2003, 5, 4003.

Abstract : A novel trifluoroacetophenone-based binding motif has been developed that recognizes anions such as carboxylates through reversible formation of anion-ionophore adducts that are stabilized by intramolecular H-bonding. The intramolecular H-bonding resulted in more than 10-fold enhancement in the binding affinity and an enthalpy gain (¢H°) of 3.0 kcal/mol for the binding of an acetate ion when compared to the case without the intramolecular H-bonding.

Fluorescence modulation in anion sensing by introducing intramolecular H-bonding interactions in host–guest adducts

Yun Mi Chung, Balamurali Raman, Dae-Sik Kim and Kyo Han Ahn*

Chem. Commun., 2006, 186–188

Abstract : Fluorescence signaling in anion binding is modulated from quenching to enhancement by intramolecular H-bonding stabilization of anion–ionophore adducts; the intramolecular H-bonding is suggested to suppress the quenching processes otherwise possible and increase the conformational rigidity of the anionic adducts, leading to fluorescence enhancement in a selective fashion towards cyanide ion, among the various anions examined.

Palladium Pincer Complexes with Reduced Bond Angle Strain: Efficient Catalysts for the Heck Reaction

Myeong Sik Yoon, Dowook Ryu, Jeongryul Kim, and Kyo Han Ahn*

Organometallics 2006, 25, 2409-2411

Abstract : Palladium pincer complexes composed of sixmembered fused metallacycles haVe been synthesized directly from 1,3-bis(2-pyridyloxy)benzene. The pincer complexes show remarkably high turnoVer numbers and frequencies in the Heck reaction.

An Efficient Diastereoselective Synthesis of Chiral Oxazolinylferrocene Compounds

Kyo Han Ahn,* Chang-Woo Cho, Hyon-Ho Baek, Jaiwook Park,* and Sunwoo Lee

J. Org. Chem. 1996, 61, 4937-4943

Abstract : Chiral oxazolinylferrocenes 7 and 8 are synthesized from ethyl ferrocenecarboxylate and amino acid-derived amino alcohols in overall 81-85% yields, through trimethylaluminum-mediated transamidation followed by ring formation with p-toluenesulfonyl chloride and triethylamine. Lithiation of the oxazolinylferrocenes under various reaction conditions and subsequent coupling reactions with electrophiles such as ClPPh2, ClSnBu3, ClSiMe3, PhSSPh, DMF, and CO2 are described. Lithiated intermediates are found to have limited stability, depending on the solvent and the temperature. In THF, the lithiated intermediate rapidly decomposes at 25 °C: In Et2O, it is quite stable at 0 °C but mostly decomposes at 25 °C within 6 h. Lithiation of the oxazolinylferrocenes is directed by the oxazoline moiety and is highly diastereoselective in the case of 8. With s-BuLi in THF-cyclohexane, several ferrocene derivatives 11 are produced with diastereoselectivities of g96:4. s-BuLi and n-BuLi give better selectivities and yields than t-BuLi. With s-BuLi, generally better diastereoselectivities are obtained in THF-cyclohexane than in Et2Ocyclohexanes. When ClPPh2 is used as the electrophile, the s-BuLi in THF-cyclohexane system, however, gives variable yields depending on reaction temperature and time. With n-BuLi in Et2O hexanes at 25 °C, phosphino(oxazolinyl)ferrocene 11a is consistently obtained in moderate yields with a 97:3 diastereoselectivity. Determination of the diastereoselectivity and characterization of new chiral ferrocene compounds including one X-ray crystal structureare described.

Suppressed â-Hydride Elimination in Palladium-Catalyzed Cascade Cyclization-Coupling Reactions: An Efficient Synthesis of 3-Arylmethylpyrrolidines

Chi-Wan Lee, Kyung Seok Oh, Kwang S. Kim,*,† and Kyo Han Ahn*

Org. Lett. 2000, 2, 1213

Abstract : A novel type of palladium-catalyzed cascade cyclization-coupling reaction that proceeds with suppressed â-hydride elimination has been found. One of the N-sulfonyl oxygens is suggested to coordinatively stabilize an alkylpalladium intermediate, thus preventing the intermediate from the usual â-elimination. This is the first sequential palladium-catalyzed coupling reaction where the Suzuki and Heck reactions can compete. The reaction provides an efficient synthetic route to 4-methylene-3-arylmethylpyrrolidines, which are not readily available by other routes.

N-Substituted-3-arylpyrrolidines: Potent and Selective Ligands at Serotonin 1A Receptor

Kyo Han Ahn, Seok Jong Lee, Chang-Ho Lee, Chang Y. Hong and Tae Kyo Park

Bioorganic & Medicinal Chemistry Letters 1999, 9, 1379

Abstract : 3-Arylpyrrolidines are synthesized through the coupling of N-benzyl-3- (methanesulfonyloxy)pyrrolidine with diarylcuprates. Pharmacological evaluation of a series of N-substituted- 3-arylpyrrolidines toward several neurotransmitter receptors indicated that some of them are good ligands for serotonin 1A receptor. Particularly, N-[(N-saccharino)butyl]pyrrolidines were found to be potent and selective ligands. A preliminary biological evaluation for several selected compounds indicated that they are potentially effective antianxiety and antidepressant agents.

Covalent crosslinking of 1-D photonic crystals of microporous Si by hydrosilylation and ring-opening metathesis polymerization

Myeong Sik Yoon, Kyo Han Ahn,* Ronnie W. Cheung, Honglae Sohn, Jamie R. Link, Frédérique Cunin and Michael J. Sailor*

Chem. Commun. 2003, 680.

Abstract : Free-standing porous Si multilayer dielectric mirrors, prepared by electrochemical etching of crystalline Si, are treated with a ruthenium ring-opening metathesis polymerization (ROMP) catalyst followed by norbornene to produce flexible, stable composite materials in which poly(norbornene) is covalently attached to the porous Si matrix.

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