Highly Efficient Biocatalytic Resolution of cis‐ and trans‐3‐Aminoindan‐1‐ol: Syntheses of Enantiopure Orthogonally Protected cis‐ and trans‐Indane‐1,3‐diamine

Abstract

The efficient chemoenzymatic synthesis of enantiopure 1,3-difunctionalized indane derivatives has been achieved. The corresponding cis and trans N-protected amino alcohols were successfully resolved by acetylation using lipase B, which is a biocatalyst isolated from Candida antarctica. All the possible isomers were obtained in very good chemical yields and ee values (>99 %). The utility of these compounds was subsequently shown by the preparation of orthogonally protected cis- and trans-indane-1,3-diamine using a Mitsunobu reaction. Both enantiomers of the trans isomer and a desymmetrized cis diastereomer were prepared in enantiopure form. Complete inversion of configuration during the Mitsunobu reaction was demonstrated by a combination of NMR techniques and molecular modeling. The utility and versatility of the strategy was also demonstrated by the selective deprotection of each nitrogen atom under mild reaction conditions.

Chemoenzymatic preparation of optically active 3-(1H-imidazol-1-yl)cyclohexanol-based ionic liquids: application in organocatalysis and toxicity studies

“…catalysed acetylation towards other 1,3-amino alcohols. 22 Consequently, after a Mitsunobu inversion/deprotection reaction, the configuration of (1R,3R)-trans-alcohol 4 was also confirmed. Once both racemic and optically active salts were obtained, their possible use in organocatalysis was explored by using them as 10 phase transfer catalysts in the model reaction of Michael addition of diethyl malonate to trans-chalcone, and their inhibition properties in the growth of E. coli cells were also evaluated as a test of their biocompatibility.…”

Enzymatic Aminolysis and Ammonolysis Processes in the Preparation of Chiral Nitrogenated Compounds

“…For the trans isomer, both enantiomers could be prepared in enantiopure forms. In the case of the cis diastereoisomer, the corresponding desymmetrized compound was also obtained enantiomerically pure [80].…”

Recent Advances in the Synthesis of Indanes and Indenes

“…Recently, the intramolecular FC acylation reaction was exploited for the synthesis of 3‐aminoindan‐1‐ol and indanediamine derivatives . Cbz‐protected 3‐aminoindanols ( trans / cis =3:1) 8 were obtained in good yield from commercially available 3‐amino‐3‐phenylpropanoic acid through reduction of the 3‐aminoindan‐1‐one intermediate followed by N‐protection (Scheme ).…”

“… Synthesis of enantiopure 3‐aminoindan‐1‐ol and indanediamine derivatives 13 and 14 from 3‐amino‐3‐phenylpropanoic acid …”