The intriguing structure and dynamic stereochemistry of axially chiral compounds has fueled their use in asymmetric synthesis, chiral recognition, the design of microscopic devices such as molecular motors and switches, drug discovery and other areas. (Wolf, C. (Ed.) Dynamic Stereochemistry of Chiral Compounds, RSC, Cambridge, 2008.) Undoubtedly, the exceptional diversity and the unique stereochemical, electronic, and photochemical properties of both conformationally stable and rapidly racemizing axially chiral biaryls and polyaryls have led to a wide variety of applications. (See e.g., Qiao, X.; Padula, M. A.; Ho, D. M.; Vogelaar, N. J.; Schutt, C. E.; Pascal Jr., R. A. J. Am. Chem. Soc. 1996, 118, 741-745.) It is therefore not surprising that structural analysis along with the study of enantiomerization and diastereomerization processes of mono- and disubstituted naphthalenes have received significant attention. (See e.g., Casarini, D.; Lunazzi, L.; Macciantelli, D. Tetrahedron Lett. 1984, 25, 3641-3642). Alkyl, (See, e.g., Fields, D. L.; Regan, T. H. J. Org. Chem. 1971, 36, 2986-2990.) aryl (See, e.g. House, H. O.; Magin, R. W.; Thompson, H. W. J. Org. Chem. 1963, 28, 2403-2406.) and heteroaryl (See, e.g. Zoltewicz, J. A.; Maier, N. M.; Fabian, W. M. F. Tetrahedron 1996, 52, 8703-8706.) groups have been introduced into the naphthalene framework to study the energy barrier to rotation about the naphthyl-alkyl or naphthyl-aryl bond and intramolecular interactions between proximate alkyl and aryl groups.
In particular, the incorporation of two phenol rings into a rigid C2-symmetric scaffold that is reminiscent of the successful BINOL motif has been of general interest due to potential applications in asymmetric catalysis and enantioselective sensing for a long time. (See e.g., Pritchard, R. G.; Steele, M.; Watkinson, M.; Whiting, A. Tetrahedron Lett. 2000, 41, 6915-6918.)

Although the synthesis of BINOL was first reported in 1873 it took another 100 years until this prime example of a C2-symmetric bidentate atropisomer gained considerable attention. (See von Richter, V. Chem. Ber. 1873, 6, 1249-1260.) Since the mid 1970s, BINOL and its derivatives have found extensive use in asymmetric reactions, molecular recognition studies and other applications. (See e.g., Pu, L. Chem. Rev. 1998, 98, 2405-2494.) The intriguing structure of BINOL and its success as chiral ligand and reagent in asymmetric synthesis has propelled the development of countless analogues that vary in stereoelectronic properties and bite angle. For many years, the synthesis of axially chiral 1,8-bisphenolnaphthalenes has been pursued due to the apparent structural analogy to BINOL and the associated promise in asymmetric catalysis and other areas.
Other attempts to synthesize derivatives of BINOL include the applicants previous work described in U.S. Pat. No. 7,888,509 which included general references to aryl and heteroaryl derivatives of naphthalene and specific examples directed to diacridine derivatives of naphthalene (core structure of diacridine derivative shown below).

However, the incorporation of sufficient steric bulk into the chiral 1,8-bisphenolnaphthalene framework to halt rotation about the aryl-aryl axes and concomitant racemization has proven difficult. (See e.g., Pritchard, R. G.; Steele, M.; Watkinson, M.; Whiting, A. Tetrahedron Lett. 2000.) Accordingly, few stereodynamic 1,8-bisphenolnaphthalenes such as 1,8-bis(3′-formyl-4′-hydroxyphenyl)naphthalene, 1 have been reported to date and used in racemic form. (See e.g., Watkinson, M.; Whiting, A.; McAuliffe, C. A. J. Chem. Soc., Chem. Commun. 1994, 2141.)
Therefore, a need still exists in the art for 1,8-bisphenolnaphthalene derivatives which are isolatable and suitable for use in resolution of enantiomers, enantioselective recognition and asymmetric synthesis.
USPTO Backgrounds
USPTO Backgrounds