AN UNUSUAL REARRANGEMENT OF A LITHIATED N-ACYL-TETRAHYDROISOQUINOLINETO AN AMINO-INDAN SKELETON AND STRUCTURAL COMPARISON OF 3-AMINO-2-METHYLINDAN ACIDS AND TETRAHYDRONAPHTHALENE-2-CARBOXYLIC ACIDS AS POSSIBLE BUILDING-BLOCKS FOR PEPTIDE-TURN MIMICS

Lithium aloyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate rearranges to the dilithio derivative of thoxy-2-methyl-1-(pivaloylamino)indan-2- carboxylic acid (2, [1,2]-sigmatropic shift with retention of configur ation) by 1,2-migration resembling the Wittig rearrangement of deproto nated ethers (Scheme 2). The structure, including absolute configurati on of the rearrangement product, was determined by X-ray diffraction. Structural conditions for the rearrangement to occur are tested by sub jecting various other tetrahydroisoquinoline derivatives (6, 7,10, 15) to the metalating conditions. Only one other compound was found to un dergo the same rearrangement (15 --> 16). Possible mechanisms of the r earrangement are discussed (B-G). Due to the presence of a tetrasubsti tuted C-atom, the indan-type beta-amino-acid derivative 2 has a confor mationally locked structure (N-C-C-CO2R dihedral angle 44-degrees). Fo r comparison, the corresponding tetralin-type beta-amino-acid derivati ves 19-22 were prepared, and it was shown by X-ray analysis (of the es ter 21) that these have larger dihedral angles (ca. 60-degrees). It is proposed that beta-amino acids of the type described here could be in corporated into peptides, providing bents of known angles along the pe ptide backbone.