Synthetic Studies of Amide-functionalized Helicene-like Molecules

概要

Helicenes are unique π-conjugated and helical polyaromatic compounds, which consist of ortho-fused benzene or other aromatic rings with nonplanar screw-shaped skeletons. Particularly, heterohelicenes as well as heterohelicene-like molecules, which bear heteroatoms in their fused cyclic system, have attracted much attentions, because these derivatives are expected to show special optical properties and chemical behaviors.

Development of cyclization method is one of the topics for construction of helically twisted molecules, in which the intrinsic steric repulsion is included in the molecular framework. In this thesis, three concise synthetic strategies to access amide-functionalized helicene-like molecules are described. These strategies include the intramolecular amidation (Chapter 2), the one-pot cyclization from the biaryl dicarboxylic acid (Chapter 3), and the palladium-catalyzed domino coupling reaction (Chapter 4). Furthermore, the unique structural features and chiroptical properties of the amide-functionalized helicene-like molecules will be presented.

Chapter 2. Synthesis of an amide-functionalized [7]helicene-like molecule via intramolecular amidation of biphenanthryl monomethylester and its structural analysis The author designed the intramolecular amidation as a key cyclization to amide-functionalized [7]helicene-like molecules. After being prepared the monomethylester from the corresponding dicarboxylic acid, racemic helicene-like molecule was obtained under Curtius reaction conditions with DPPA and subsequent addition of H2O via the intramolecular amidation of the intermediary aniline-type δ-amino acid derivative. This cyclization was readily expanded to the preparation of optically active (P)- and (M)-helicene-like molecule from (S)- and (R)-biphenanthryl monomethylester, respectively.

The helically twisted structure was confirmed by an X-ray analysis. Interestingly, the crystal structure showed unique molecular assembly, in which the M and P enantiomers associated pairwise through the hydrogen-bonding interactions of the amide functional groups. This paired complex furthermore forms alternatingly aligned M, P, M, P columnar packs in the crystal. This columnar packing was found to be caused from the interactions not only through the π-π interaction between the π-faces, which is well known for helicene molecular assembly, but also through the hydrogen-bonding interactions via the amide groups.

Chapter 3. One-pot access to the amide-functionalized [7]helicene-like molecules and phenanthridinone derivatives from biaryl dicarboxylic acids The author envisioned that direct cyclization from the dicarboxylic acid to helicene-like molecules as well as phenanthridinone derivatives would be possible, if the in-situ generated amino group undergoes cyclization with the alternative carboxyl group under Curtius reaction conditions. By the survey of the reaction conditions, use of 2 equivalents of DPPA gave the desired product. These conditions were applicable to the biaryl dicarboxylic acid derivatives to furnish phenanthridinone derivatives bearing a variety of substituents. This reaction conditions can be applicable to the preparation of optically active (M)- and (P)-amide-functionalized [7]helicene-like molecules including sulfur containing derivatives from the corresponding (R)- and (S)-biaryl dicarboxylic acids.

During the survey of the conditions, the author noticed that the phosphate ester derivatives were generated prior to treatment of the basic conditions in the case of the substrates including chalcogen atoms. An X-ray analysis of this phosphate ester derivatives indicated the helically twisted structure.

The racemization barriers of these amide-functionalized helicene-like molecules were also investigated. Experimental and calculated racemization barriers of the prepared derivatives indicated that [7]helicene-like molecules have enough racemization barriers to be stable as optically active forms in ambient temperature, although [5]helicene-like derivatives showed low racemization barriers. The chiroptical properties, the optical rotations and the CD spectra of these amide-functionalized helicene-like molecules were also discussed.

Chapter 4. Preparation of the amide-functionalized [7]helicene-like molecules by palladium-catalyzed domino coupling reactions In the above chapters, the key intramolecular amide bond formations were proceeded from the biaryl substrates prepared in prior to the cyclization. Further straightforward way to access amide-functionalized helicene-like molecules would be the domino process through the biaryl formation and the intramolecular amidation. The author envisioned that the Pd catalyzed domino coupling process previously developed in our laboratory could be applicable to this strategy. After the survey of the reaction conditions, sulfur containing amide-functionalized [7]helicene-like molecule was obtained from the aryl bromide bearing PMB-amide group through subsequent C–C and C–N bond formations (shown in the blue bonds). The PMB-protecting group was readily deprotected to give the amide-functionalized helicene-like molecule.