AN UNUSUAL REARRANGEMENT OF A LITHIATED N-ACYL-TETRAHYDROISOQUINOLINE TO 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 1-lithio-6,7-dimethoxy-3-methyl-2-pivaloyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate rearranges to the dilithio derivative of 5,6-dimethoxy-2-methyl-1-(pivaloylamino)indan-2-carboxylic acid (2, [1,2]-sigmatropic shift with retention of configuration) by 1,2-migration resembling the Wittig rearrangement of deprotonated ethers (Scheme 2). The structure, including absolute configuration of the rearrangement product, was determined by X-ray diffraction. Structural conditions for the rearrangement to occur are tested by subjecting various other tetrahydroisoquinoline derivatives (6, 7,10, 15) to the metalating conditions. Only one other compound was found to undergo the same rearrangement (15 --> 16). Possible mechanisms of the rearrangement are discussed (B-G). Due to the presence of a tetrasubstituted C-atom, the indan-type beta-amino-acid derivative 2 has a conformationally locked structure (N-C-C-CO2R dihedral angle 44-degrees). For comparison, the corresponding tetralin-type beta-amino-acid derivatives 19-22 were prepared, and it was shown by X-ray analysis (of the ester 21) that these have larger dihedral angles (ca. 60-degrees). It is proposed that beta-amino acids of the type described here could be incorporated into peptides, providing bents of known angles along the peptide backbone.