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Asymmetric Phase‐Transfer Catalysis by Quaternary Ammonium Ions Derived from Cinchona ‐Alkaloid Analogs Containing 1,1′‐Binaphthalene Moieties
Author(s) -
Ducry Laurent,
Diederich François
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19990707)82:7<981::aid-hlca981>3.0.co;2-v
Subject(s) - diastereomer , chemistry , enantioselective synthesis , cinchona , moiety , stereochemistry , quinuclidine , catalysis , stereoselectivity , medicinal chemistry , organic chemistry
The synthesis and catalytic properties of a new type of enantioselective phase‐transfer catalysts, incorporating both the quinuclidinemethanol fragment of Cinchona alkaloids and a 1,1′‐binaphthalene moiety, are described. Catalyst (+)‐(a S ,3 R ,4 S ,8 R ,9 S )‐ 4 with the quinuclidine fragment attached to C(7′) in the major groove of the 1,1′‐binaphthalene residue was predicted by computer modeling to be an efficient enantioselective catalyst for the unsymmetric alkylation of 6,7‐dichloro‐5‐methoxy‐2‐phenylindanone ( 1 ; Scheme 1 , Fig. 1 ). Its synthesis involved the selective oxidative cross‐coupling of two differently substituted naphthalen‐2‐ols to afford the asymmetrically substituted 1,1′‐binaphthalene derivative (±)‐ 17 in high yield ( Scheme 3 ). Chromatographic optical resolution via formation of diastereoisomeric camphorsulfonyl esters and functional‐group manipulation gave access to the 7‐bromo‐1,1′‐binaphthalene derivative (−)‐(a S )‐ 11 ( Scheme 4 ). Nucleophilic addition of lithiated (−)‐(a S )‐ 11 to the quinuclidine Weinreb amide (+)‐(3 R ,4 S ,8 R )‐ 8 afforded the two ketones (a S ,3 R ,4 S ,8 R )‐ 27 and (a S ,3 R ,4 S ,8 S )‐ 28 as an inseparable mixture of diastereoisomers ( Scheme 6 ). Stereoselective reduction of this mixture with DIBAL‐H (diisobutylaluminum hydride; preferred formation of the C(8)−C(9) erythro ‐pair of diastereoisomers with 18% de) or with NaBH 4 (preferred formation of the threo ‐pair of diastereoisomers with 50% de) afforded the four separable diastereoisomers (+)‐(a S ,3 R ,4 S ,8 S ,9 S )‐ 29 , (+)‐(a S ,3 R ,4 S ,8 R ,9 R )‐ 30 , (−)‐(a S ,3 R ,4 S ,8 S ,9 R )‐ 31 , and (+)‐(a S ,3 R ,4 S ,8 R ,9 S )‐ 32 ( Scheme 6 ). A detailed conformational analysis, combining 1 H‐NMR spectroscopy and molecular‐mechanics computations, revealed that the four diastereoisomers displayed distinctly different conformational preferences ( Figs. 2 and 3 ). These novel Cinchona ‐alkaloid analogs were quaternized to give (+)‐(a S ,3 R ,4 S ,8 R ,9 S )‐ 4 , (+)‐(a S ,3 R ,4 S ,8 S ,9 S )‐ 5 , (+)‐(a S ,3 R ,4 S ,8 R ,9 R )‐ 6 , and (−)‐(a S ,3 R ,4 S ,8 S ,9 R )‐ 7 ( Scheme 7 ) which were tested as phase‐transfer agents in the asymmetric allylation of phenylindanone 1 . Without any optimization work, (+)‐(a S ,3 R ,4 S ,8 R ,9 S )‐ 4 was found to catalyze the allylation of 1 yielding the predicted enantiomer (+)‐( S )‐ 3b in 32% ee. The three diastereoisomeric catalysts (+)‐ 5 , (+)‐ 6 , and (−)‐ 7 gave access to lower enantioselectivities (6 to 22% ee's), which could be rationalized by computer modeling ( Fig. 4 ).