2. Chiral Supramolecular Systems: Rational Design and Novel Applications.

There has been much progress in the area of asymmetric synthesis, in particular homogeneous asymmetric catalysis, over the past couple of decades. Numerous catalytic systems with excellent chemical selectivity and enantioselectivity are now known. Homogeneous catalytic systems typically rely on inner-sphere control via ancillary ligands to modulate the reactivity and hence selectivity of the metal centers. As illustrated in Fig. 4a, the environment around the vacant site(s) of the metal center can readily change in response to incoming substrates, which can lead to unpredictability in enantio-control. Such an inner-sphere approach is in stark contrast to the outer-sphere control used by Mother Nature in enzymes which typically exhibit excellent chemo-, size-, and enantio-selectivity as a result of the presence of much better-defined chiral pockets via outer-sphere control. We have recently initiated a research program aiming at developing highly enantioselective systems with enzyme-like cavities and functionalities via a combination of both inner- and outer-sphere controls (Fig 4b).

Metal-directed self-assembly has been widely used to construct supramolecular systems such as molecular squares. We envision that the incorporation of axially chiral bridging ligands into such molecular squares could lead to enzyme-like chiral supramolecular systems exploitable for enantioselective recognition, sensing, separation, and catalysis. We have recently synthesized and characterized a family of novel chiral molecular squares [Cl(CO)₃Re(L_1-4)]₄ (where L_1-4 is enantiopure 4,4’-bis(pyridyl)-1,1’-binaphthyl) and observed the first example of enantioselective luminescence sensing by a chiral metallocycle (Scheme II, JACS, 2002, 124, 4554).

In contrast to chiral molecular squares 1-4, chiral organometallic triangles 5-8 with different stability and solubility characteristics were obtained when 4,4’-bis(alkynyl)-1,1’-binaphthalene was treated with cis-Pt(PEt₃)₂Cl₂ in the presence of catalytic amounts of CuI (Scheme III, JACS, 2002, 124, 12948). With the chiral dihydroxy groups in 8, we were able to utilize it for prototypical asymmetric diethylzinc additions to aromatic aldehydes. Ti(IV) complexes of 8 are excellent catalysts for the additions of diethylzinc to aromatic aldehydes to generate chiral secondary alcohols in very high selectivity, yield, and enantioselectivity. The broad substrate scope for catalytic diethylzinc additions using 8 and Ti(OⁱPr)₄ suggests that there is significant flexibility in the dihydroxy groups to accommodate aldehydes of various sizes.

Unexpectedly, treatment of 2,2’-diacetyl-1,1’-binaphthyl-6,6’-bis(ethyne), L₅-H₂, with one equiv of trans-Pt(PEt₃)₂Cl₂ in the presence of catalytic amounts of CuCl in CH₂Cl₂ and HNEt₂ at r.t. afforded a mixture of different sizes of chiral metallomacrocycles [trans-(PEt₃)₂Pt(L₅)]_n, (n=3-8, 9-14). Each of the chiral molecular polygons ranging from triangle to octagon was purified by silica-gel column chromatography and analytically pure 9-14 was obtained in 5%, 18%, 16%, 10%, 5%, and 4% yield, respectively (Scheme IV). These chiral molecular polygons have been extensively characterized by ¹H, ¹³C{¹H}, and ³¹P{¹H} NMR spectroscopy, FAB- and MALDI-TOF-MS, and IR, UV-Vis, and circular dichroism (CD) spectroscopies, and microanalysis (JACS, 2003, 125, 8084). Ongoing research in my group indicates that chiral polygons of much larger size can be readily synthesized in a stepwise fashion. The enormous cavities (4.3 nm in 14) presented by these chiral polygons promise to make them excellent receptors for a variety of guests, thereby providing systematically tunable hosts for enantioselective recognition.

We have also devoted significant efforts to designing other chiral supramolecular assemblies for potential applications in enantioselective processes. Our successful synthesis of well-defined enantiopure 1,1’-binaphthyl-based oligomers and application of these oligomers in enantioselective fluorescence sensing were highlighted on the cover of Nov 1, 2002 issue of J. Org. Chem. We have also synthesized a variety of chiral dendritic architectures and observed interesting generation-dependent luminescence properties in one of these systems (Scheme V).

Representative Publications:

1. “Self-Assembly of Chiral Molecular Polygons.” Jiang, H.; Lin, W. J. Am. Chem. Soc. 2003, 125, 8084-8085 [pdf]. Also see highlight in Science.

2. “A Chiral Metallacyclophane for Asymmetric Catalysis.” Jiang, H.; Hu, A.; Lin, W. Chem. Commun. 2003, 96-97 [pdf].

3. “Self-Assembly of Nanoscale, Porous T-Symmetric Molecular Adamantanoids.” Cui, Y.; Ngo, H.L.; Lin, W. Inorg. Chem. 2002, 41, 5940-5942 [pdf].

4. “The First Organometallic Triangle for Asymmetric Catalysis.” Lee, S.J.; Hu, A.; Lin, W. J. Am. Chem. Soc. 2002, 124, 12948-12949 [pdf]. Also see highlight in Science.

5. “Chiral Macrocycles.” Lee, S.J.; Lin, W. Encyclopedia of Nanoscience and Nanotechnology, in press.

6. “Chiral Ruthenium-Terpyridine Based Metallodendrimers: Facile Synthesis, Characterization, and Photophysical Studies.” Jiang, H.; Lee, S.J.; Lin, W. J. Chem. Soc., Dalton Trans. 2002, 18, 3429-3433 [pdf].

7. “Chiral Hybrid Metal-Organic Dendrimers.” Jiang, H.; Lee, S.; Lin, W. Org. Lett. 2002, 4, 2149-2152 [pdf].

8. “A New Rigid Angular Dicarboxylic Acid for the Construction of Nanoscopic Supramolecules. From a Molecular Rectangle to a 1D Coordination Polymer.” Cui, Y.; Ngo, H.L.; Lin, W. Inorg. Chem. 2002, 41, 1033-1035 [pdf].

9. “A Novel Chiral Molecular Square with Metallo-corners for Enantioselective Sensing.” Lee, S.; Lin, W. J. Am. Chem. Soc. 2002, 124, 4554-4555 [pdf]. Also see highlight in Analytical Chemistry.

10.“Synthesis, Characterization, and Photophysical Properties of Chiral Dendrimers Based on Well-Defined Oligonaphthyl Cores.” Ma, L.; Lee, S.; Lin, W. Macromolecules 2002, 35, 6178-6184 [pdf].

11.“Well-Defined Enantiopure 1,1’-Binaphthyl-Based Oligomers: Synthesis, Structure, Photophysical Properties, and Chiral Sensing” Ma, L.; White, P.S.; Lin, W. J. Org. Chem. 2002, 67, 7577-7586 [pdf] [JOC Cover].