Wenyuan Qian

Towards Sixfold Functionalization of Buckminsterfullerene (C60) at Fully Addressable Octahedral Sites

Selective C(60)-functionalizations that provide access to unusual multifunctional molecules are of interest in the construction of highly organized three-dimensional assemblies. The temporary masking of three of the most reactive sites on C(60) by a bisdiene tether has allowed the facile and high-yielding formation of the fully differentiated trisadduct 1 and the interesting hexaadduct 2.

Tandem Nucleophilic Addition/Diels-Alder Reaction of N-Butadienyl N,O-Ketene Silyl Acetals with C60: Stereoselective Formation of Bicyclic Octahydroquinolino-1,2,3,4-Tetrahydrobuckminsterfullerenes and Combined NMR Spectroscopic and Computational Evaluation of the Functionalization Reactions

We have studied the reactiv- ity of the N,O-ketene N-1,3-butadienyl- N-alkyl-O-silyl acetals 1a - e with C60 proceeding through a tandem process to give the adducts 2a - e. The addition order of these tandem reactions has been evaluated. The initial nucleophilic Michael-like addition of the electron- rich N,O-ketene acetal moiety proceeds unusually fast at 258C, followed by an intramolecularly accelerated Diels - Alder step that is highly diastereoselec- tive. The structures of compounds 2a - e were determined from the 1 H and 13 C NMR shifts and from H - H coupling patterns, while their stereochemistry was deduced from 2D T-ROESY NMR experiments. The proposed mechanism for the nucleophilic addition involves single electron transfer followed by radical anion - radical cation recombi- nation. Computational investigations of the reaction pathways, transition states, and conformational energies have been carried out to corroborate the experi- mental data.

An Orally Available BACE1 Inhibitor That Affords Robust CNS Aβ Reduction without Cardiovascular Liabilities

BACE1 inhibition to prevent Aβ peptide formation is considered to be a potential route to a disease-modifying treatment for Alzheimers disease. Previous efforts in our laboratory using a combined structure- and property-based approach have resulted in the identification of aminooxazoline xanthenes as potent BACE1 inhibitors. Herein, we report further optimization leading to the discovery of inhibitor 15 as an orally available and highly efficacious BACE1 inhibitor that robustly reduces CSF and brain Aβ levels in both rats and nonhuman primates. In addition, compound 15 exhibited low activity on the hERG ion channel and was well tolerated in an integrated cardiovascular safety model.

Pressure-tuning vibrational spectroscopic study of (η5-C5H5)Co(C64H4) Can endohedral fullerenes be formed under pressure?

Abstract The infrared and Raman spectra of the Co(III)-fullerene complex, CpCo(C64H4) (Cp = η5-C5H5), have been examined under high external pressures (up to ∼45 kbar) with the aid of a diamond-anvil cell. The values of the pressure dependencies ( d v d P ) of the vibrational modes are quite normal and range from 0.11–0.58 cm−1 kbar−1. Although only limited data were obtained for the bis-fulleroid, C64H4, the vibrations of the organometallic derivative are, in general, more pressure sensitive than are those of the bis-fulleroid. While there is no evidence for the formation of an endohedral fullerene throughout the pressure range investigated, there is a reversible structural change occurring in the 8.8–13.1 kbar range, most probably associated with rotation of the Cp ligand about the Cpue5f8Co bond.

Accelerating effect of triazolyl and related heteroaryl substituents on SNAr reactions: evidence of hydrogen-bond stabilized transition states.

The remarkable accelerating effect of 1,2,3-triazolyl substituents on SNAr reactions has been investigated through systematic experiments and density functional theory calculations. The lone pair electrons of an ortho-triazolo substituent play a key role in lowering the activation energy for nucleophilic addition via formation of a preferential hydrogen bond with the amine nucleophile at the transition state for addition. In an extension of this finding, a series of related heteroaryl groups with similar electron pair donor properties have also been found to facilitate SNAr reactions. The experimentally determined solvent effect provides further support for this rationale, which was utilized to achieve an ortho-selective substitution on a difluoroarene substrate.