Scalable synthesis of a new enantiomerically pure π-extended rigid amino indanol

• Published in: Tetrahedron letters 2012-01, Vol.53 (1), p.15-18
• Main Authors: Rendina, Victor L., Goetz, Samantha A., Neitzel, Angelika E., Kaplan, Hilan Z., Kingsbury, Jason S.
• Format: Article
• Language: English
• Subjects: 3 H-Benz(e)indene; Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Amino indanol; Asymmetric catalysis; Bis(oxazoline); Blocking; Chemistry; Conversion; Crystal structure; Distortion; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Organic chemistry; Parents; Preparations and properties; Purification; Ritter reaction; Synthesis (chemistry); Tetrahedrons
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2011.10.144

A convenient route to a benzo-fused amino indanol chiral controller is disclosed. The synthesis is based on a newly optimized entry to 3 H-benz(e)indene that can be performed on decagram scale with no purification of intermediates. Subsequent oxidation, classical resolution, and Ritter steps give the target synthon in >98% ee. The resolution features ( S)-naproxen as an inexpensive and highly crystalline resolving agent. Conversion of the amino alcohol to its bis(oxazolinyl)-propane is also reported. A solid state structure of the CuCl 2–box complex shows preservation of the distorted square planar geometry found in the parent CuCl 2(indanyl-box) despite greater steric crowding by the blocking groups.