Functionalized 1,8-Diarylnaphthalenes: Applications in Enantioselective Sensing and Stereoselective Cycloadditions

Abstract

The unique structure of 1,8-diarylnaphthalenes provides an excellent opportunity to design sensors with a chromophoric binding pocket and the ability to transform a binding event with a chiral substrate into a strong and quantifiable signal. Since both arene rings readily rotate about the two chiral axes, 1,8-bis(3'-formyl-4'-hydroxyphenyl)naphthalene exists as a mixture of enantiomeric anti-conformers that rapidly interconvert via a meso syn-isomer. Diimine formation between this stereodynamic probe and chiral substrates disturbs this equilibrium and strongly favors the population of a single diastereomer through intramolecular hydrogen bonding. The cofacial arrangement of the two salicylaldehyde rings favors intramolecular pi-pi interactions and subsequent generation of intense Cotton effects at high wavelengths. This sensor provides information about the absolute configuration and enantiomeric composition of a wide range of amino alcohols and amino acids based on well-defined and understood central-to-axial chiral amplification processes.

The incorporation of moderate bulk in the form of methyl groups into the ortho-positions of 1,8-bis(3'-formyl-4'-hydroxyphenyl)naphthalene resulted in the formation of conformational isomers that are stable to interconversion and separable at room temperature. The axially chiral stereoisomers of 1,8-bis(2'-methyl-4'-hydroxy-5'-formylphenyl)naphthalene were isolated via formation of diastereomers with chiral amino alcohols, chromatographic separation and hydrolysis. The Gibbs activation energy for atropisomerization was calculated as 103.7 (102.4) kJ/mol for the conversion of the anti-(syn-) to the syn-(anti-) isomer. The diimine derivatives were also investigated and it was found that they undergo an asymmetric transformation of the first kind, which significantly facilitates the preparation of enantiopure atropisomers on the gram scale. The energy barrier for the conversion of the (M,M,S,S)-isomer to the syn-isomer was determined as 115.7 kJ/mol and proved to be significantly higher than the rotational barriers of the (P,P,S,S) and (P,M,S,S)-diastereomers.

An analogous 1,8-diarylnaphthalene skeleton was developed to examine stereoselective cycloadditions. 1,8-Dipyridylnaphthalene had previously been shown to preorganize fumaric acid for quantitative photoaddition in the solid state. Extensive screening of conditions suitable for cocrystallization of 1,8-dipyridylnaphthalene and trans-cinnamic, mesaconic or trans,trans-muconic acids showed that the desired packing motif and the stoichiometry in the solid state based on non-covalent interactions cannot always be controlled. A series of templates for the covalent attachment and preorganization of olefinic substrates was then synthesized in an attempt to overcome these limitations. It was found that immobilization of trans-cinnamic acid to 1,8-bis(4'-anilino)naphthalene provided an alternative means for stereoselective photodimerization. The use of this recoverable template effectively biases the [2+2]dimerization of trans-cinnamic and trans-3-(3,4-dimethylphenyl)acrylic acids towards cis,trans,cis-cyclobutanetetracarboxylic acids, and proceeded with high yield and excellent stereoselectivity.