Lin Pu

Fluorescent probes for selective recognition of chiral amino alcohols, amino acids and diamines in fluorous phase and applications in asymmetric reaction screening.

A series of bisBINOL-based fluorescent probes, which contain two BINOL units linked by an alkane chain of varying length, were synthesized and characterized. It was found that the chain length of the alkane linker has strong effect on the fluorescence response of these compounds toward amino acids. Among them, compound (S,S)-6 that contains a six-carbon alkyl chain linker exhibits highly chemoselective and enantioselective fluorescence enhancement with arginine in the presence of Zn²⁺, but other compounds show much less selective fluorescence response. Spectroscopic studies have been conducted to investigate the mechanism of this process.

Three BINOL‐based unsymmetric chiral dialdehydes, (S)‐4, (S)‐5, and (S)‐6, each containing a salicylaldehyde moiety and an ortho‐, meta‐ or para‐substituted benzaldehyde unit, are synthesized and used to react with the enantiomers of an unsymmetric chiral diamine, lysine. These reactions represent the first examples of regioselective as well as enantioselective reactions of an unsymmetric chiral dialdehyde with an unsymmetric chiral diamine to generate unsymmetric chiral macrocycles. The addition of Zn²⁺ can further enhance the selectivity for the macrocycle formation. Compounds (S)‐4 and (S)‐5 are found to exhibit chemoselective and enantioselective fluorescent recognition of lysine in the presence of Zn²⁺.

Highly fluorinated naphthyl aldehyde 1 and binaphthyl aldehyde (R)-2 were designed and synthesized for fluorous-phase-based sensing. Greatly enhanced sensitivity and chemoselectivity in going from 1 to (R)-2 in the fluorescent detection of cysteine has been discovered. This is attributed to the increased structural rigidity of the axially chiral binaphthyl unit in (R)-2 upon reaction with cysteine to form the corresponding thiazolidine product. The fluorous-phase-based detection of cysteine not only can allow the analysis to be conducted in a phase away from the interference of other organic and inorganic species but also results in significantly increased fluorescence response.

1,1'-Bi-2-naphthol (BINOL) has been extensively used as the chirality source in the fields of molecular recognition, asymmetric synthesis, and materials science. The direct electrophilic substitution at the aromatic rings of the optically active BINOL has been developed as one of the most convenient strategies to structurally modify BINOL for diverse applications. High regioselectivity has been achieved for the reaction of BINOL with electrophiles. Depending upon the reaction conditions and substitution patterns, various functional groups can be introduced to the specific positions, such as the 6-, 5-, 4-, and 3-positions, of BINOL. Ortho-lithiation at the 3-position directed by the functional groups at the 2-position of BINOL have been extensively used to prepare the 3- and 3,3'-substituted BINOLs. The use of transition metal-catalyzed C-H activation has also been explored to functionalize BINOL at the 3-, 4-, 5-, 6-, and 7-positions. These regioselective substitutions of BINOL have allowed the construction of tremendous amount of BINOL derivatives with fascinating structures and properties as reviewed in this article. Examples for the applications of the optically active BINOLs with varying substitutions in asymmetric catalysis, molecular recognition, chiral sensing and materials are also provided.

The dynamic covalent chemistry of imines is utilized to conduct a regioselective as well as enantioselective synthesis of an unsymmetric (C₁) chiral macrocycle from the reaction of an unsymmetric (C₁) chiral dialdehyde, (S)-4, that contains a salicylaldehyde unit and a benzaldehyde unit, with lysine, an unsymmetric (C₁) chiral diamine. The enantioselectivity is further enhanced in the presence of Zn²⁺. Compound (S)-4 in combination with Zn²⁺ is found to be a highly chemoselective as well as enantioselective fluorescent probe for lysine. It can be used to detect specific enantiomers of this amino acid.

The first near IR fluorescent probe for the chemoselective and enantioselective recognition of arginine in aqueous solution is reported in this work. This probe, made of a 1,1’‐binaphthyl‐based chiral aldehyde unit and a rhodamine‐based near IR chromophore, in combination with La³⁺ exhibits highly chemoselective as well as enantioselective fluorescent enhancement with arginine at λ=764 nm upon excitation at λ=690 nm. Little or no fluorescent response is observed toward the chirality miss‐matched arginine enantiomer or other common amino acids and their enantiomers. This probe also allows visual discrimination of the arginine enantiomers because of its fast and distinct color change upon interaction with the substrate.

It is discovered that one enantiomer of a chiral substrate can greatly enhance the fluorescence of one molecular probe at one emitting signal (λ₁ = 517 nm), while the opposite enantiomer of the substrate greatly enhances the fluorescence of the same probe at a distinctively different emission (λ₂ = 575 nm). This probe is made of a 1,1'-binaphthyl-based chiral dialdehyde that in combination with Zn²⁺ under slightly acidic conditions shows a chemoselective and enantioselective fluorescent response to histidine. The opposite enantioselective fluorescent responses of the probe at two emissions allow it to be used to determine both the concentration and the enantiomeric composition of the substrate using a single probe. The mechanistic study has revealed two very different reaction pathways when the two enantiomers of the substrate are treated with the probe. These reaction pathways generate two different products, one dimeric and another polymeric, with very different emissions.