Asymmetric Phase-Transfer Catalysis by Quaternary Ammonium Ions Derived fromCinchona-Alkaloid Analogs Containing 1,1′-Binaphthalene Moieties

Abstract

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 (+)‐(aS,3R,4S,8R,9S)‐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 (−)‐(aS)‐11 (Scheme 4). Nucleophilic addition of lithiated (−)‐(aS)‐11 to the quinuclidine Weinreb amide (+)‐(3R,4S,8R)‐8 afforded the two ketones (aS,3R,4S,8R)‐27 and (aS,3R,4S,8S)‐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 NaBH4 (preferred formation of the threo‐pair of diastereoisomers with 50% de) afforded the four separable diastereoisomers (+)‐(aS,3R,4S,8S,9S)‐29, (+)‐(aS,3R,4S,8R,9R)‐30, (−)‐(aS,3R,4S,8S,9R)‐31, and (+)‐(aS,3R,4S,8R,9S)‐32 (Scheme 6). A detailed conformational analysis, combining 1H‐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 (+)‐(aS,3R,4S,8R,9S)‐4, (+)‐(aS,3R,4S,8S,9S)‐5, (+)‐(aS,3R,4S,8R,9R)‐6, and (−)‐(aS,3R,4S,8S,9R)‐7 (Scheme 7) which were tested as phase‐transfer agents in the asymmetric allylation of phenylindanone 1. Without any optimization work, (+)‐(aS,3R,4S,8R,9S)‐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).

In the Golden Age of Organocatalysis

“…In alkylation reactions O ‐allyl‐ N‐ anthracenylmethyl (third‐generation) catalysts are usually the most efficient cinchona‐alkaloid catalysts 199. 200 These molecules can be prepared either by multistep synthesis or, more conveniently, in situ 201. The one‐pot procedure is particularly suitable for automated catalyst screening.…”

Phosphole-Containing π-Conjugated Systems: From Model Molecules to Polymer Films on Electrodes

“…The ability of these compounds to function as phase‐transfer catalysts in the asymmetric allylation of 9 a under similar conditions were evaluated. These studies revealed that, without any optimization, 12 a was superior to the other three diastereomeric catalysts 12 b – d , although both the chemical yield and enantiomeric excess of 10 c were unsatisfactory (Scheme ) 8…”

Fortschritte bei asymmetrischen Phasentransferkatalysen

“…Die Eignung dieser Verbindungen als Phasentransferkatalysatoren wurde anhand der asymmetrischen Allylierung von 9 a unter ähnlichen Bedingungen untersucht. Ohne weitere Optimierungen war 12 a zwar den drei Diastereomeren 12 b – d überlegen, Ausbeute wie Enantiomerenüberschuss von Produkt 10 c waren aber unzureichend (Schema ) 8…”