Synthesis 2000; 2000(1): 165-176
DOI: 10.1055/s-2000-6229
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Synthesis of a 9-Fluorenone Derived β-Amino Alcohol Ligand Depicting High Catalytic Activity and Pronounced Non-linear Stereochemical Effects

Katamreddy Subba Reddy* , Lluís Solà, Albert Moyano, Miquel A. Pericàs, Antoni Riera
  • *Unitat de Recerca en Síntesi Asimètrica, Departament de Química Orgànica, Universitat de Barcelona, c/ Martí i Franquès, 1-11, E-08028 Barcelona, Spain; Fax +34 (93) 3 39 78 78; E-mail: mpb@ursa.qo.ub.es
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Publication History

Publication Date:
31 December 2000 (online)

The Jacobsen epoxidation of 9-alkylidenefluorenes 4a (ethylidene), 4b (benzylidene) and 4c (1-naphtylmethylene) with standard (R,R)-manganese salen catalyst has been studied. Both conversion and enantioselectivity depend on the steric bulk of the olefin substituent, best results being recorded with 4b (96% yield, 99% ee). The stereochemical course of the epoxidation of 4a is highly dependent on temperature and solvent, the ee of the resulting epoxide (S)-5a varying from 22% (-18°C, CH2Cl2) to 49% (55°C, MTBE). The lithium perchlorate induced ring-opening of 5a with piperidine in MeCN affords a mixture of regioisomeric amino alcohols 3a/2a arising from the amine attack at the more substituted and less substituted carbons, respectively. The 3a/2a ratio can be modulated by the LiClO4 concentration and the reaction temperature, and varies from 44 : 56 to 91 : 9. An independent, completely regio-controlled synthesis of 3a has been developed involving ring-opening by the more substituted carbon of epoxide 5a with diisopropoxytitanium diazide, reduction of azidoalcohol 10a (H2, Pd/C) and cycloalkylation (1,5-dibromopentane, K2CO3) of the amine alcohol 11a. The amino alcohol 3a exhibits a positive nonlinear stereochemical effect in its action as a ligand for the enantioselective addition of Et2Zn to benzaldehyde. The use of regiochemically pure 3a of > 99% ee has been studied in the addition of Et2Zn to a representative family of aldehydes [19 examples, 93.6% mean ee]. The use of the directly available 9 : 1 mixture of 3a and 2a derived from 46-47% ee 5a as a ligand system for the enantioselective addition of Et2Zn to aldehydes [8 examples, 93.1% mean ee] is also reported.