Comparison of Different Polymer‐ and Silica‐Supported 9‐Amino‐9‐deoxy‐epi‐quinines as Recyclable Organocatalysts

Abstract

Results and Discussion Synthesis of supported catalystsIn this study three different supports with wellmarked different properties were chosen:a ni nsoluble organic polymer (cross-linked polystyrene, PS), as oluble organic polymer (poly(ethylene glycol), PEG, M w 5000 Da) and an insoluble inorganic matrix (silica).The general strategy to prepare polystyrene-supported 9-amino-cinchona derivatives involves the introduction of al inker on the quinuclidine ring suitable for radical polymerization. The synthesis of supported catalysts PS-QN is illustrated in Scheme 1. The doubleb ondo fc ommerciallya vailable quinine was converted in atriple bond [11] to afford compound 1,w hich was subjected to copper-catalyzed azidealkyne cycloaddition with azide 2 in order to establish as tyrene moiety ready for polymerization. Alcohol 3 was then converted into amine 4,i solated in 62 %o verall yield after one chromatographic purification step only, [12] and employed in ar adicalc opolymerization under FrØchet-type conditions, with divinylbenzene in the presence of azobisisobutyronitrile (AIBN) as radical initiator and toluenea nd 1-dodecanol as porogenic solvents. [13] Catalysts PS-QNa-c with different catalystl oadings were prepared, taking advantage on different divinylbenzene/4 ratio in the preparation of the materials (see Supporting Information for further details). To study the influence of the linker on the catalytic activity,9 -amino-epiquinine 5,w ithout the styrene moiety,w as also synthesized and copolymerized with divinylbenzene under the same conditions to afford catalyst PS-QNd (Scheme 2).By using the same strategy as described above, quininew as converted into 9-amino-epi-quinine 5 [12] and then demethylated by BBr 3 to afford compound 6,t hat was supported onto Scheme1.Synthesis of polystyrene-supported 9-amino-epi-quinine PS-QNa-c.A LIQUAT336 = trioctylmethylammoniumchloride, DIPEA = N,N-diisopropylethylamine, MsCl = methanesulfonyl chloride, TEA = triethylamine.Scheme2.Synthesis of polystyrene-supported 9-amino-epi-quinine PS-QNd.Scheme3.Synthesis of poly(ethyleneg lycol)-supported 9-amino-epi-quinine PEG-QN.

From Immobilization to Catalyst Use: A Complete Continuous‐Flow Approach Towards the Use of Immobilized Organocatalysts

“…(0.96 g, 75 %). HRMS-ESI (m/z): found for C 18 , and packed with CH 3 CN for 30 min (200 μl min À 1 ). Thereafter, a 3.8 mL solution of (S)-5-benzyl-3-(2-hydroxyethyl)-2,2dimethylimidazolidin-4-one hydrochloride 5 (2.27 × 10 À 1 mol L À 1 ) with triethylamine (0.24 mol L À 1 ) in CH 3 CN was pumped through the reactor at 18 μl.min À 1 .…”

“…To overcome these difficulties, some efforts have been made to support the organocatalysts in a range of solid materials, such as polymers or silica, affording heterogeneous reactions . This strategy has allowed their usage in continuous‐flow reactors, enabling a rapid continuous production of chiral substances and becoming organocatalysis an even greater tool for chemical and pharmaceutical industries …”

“…[10][11][12][13][14][15][16] This strategy has allowed their usage in continuous-flow reactors, enabling a rapid continuous production of chiral substances and becoming organocatalysis an even greater tool for chemical and pharmaceutical industries. [17][18][19][20][21] Despite the exponential growth of the field of asymmetric organocatalysis in the last decades and the advantages of merging it with flow chemistry, this area still remains little explored. In recent years, a small group of homogeneous and heterogeneous asymmetric reactions were successfully con-ducted under continuous-flow conditions, employing certain organocatalysts and modes of catalyst activation.…”

Recent Developments on Supported Hydrogen‐bond Organocatalysts

“…Another example involved a set of 9‐amino‐ epi ‐quinine derivatives which were supported onto three different materials, as shown in Scheme : insoluble cross‐linked polystyrene ( XIII a – c ), soluble polyethylenglycol (PEG, Mw 5000 g mol −1 , XIII d ) and silica as insoluble inorganic matrix ( XIII e – f ) . These compounds (30 mol %) were tested in the Michael addition between isobutyraldehyde ( 1 c ) and trans ‐ 2 a using benzoic acid as additive.…”

Highly active polymeric organocatalyst: Chiral ionic polymers prepared from 10,11‐didehydrogenated cinchonidinium salt

“…Hoffmann and Frackenpohl reported that 3‐ethynyl cinchona alkaloids are more polar and basic than the parent 3‐vinyl compounds . However, the effect of the replacement of the 3‐vinyl group by a 3‐ethynyl group on the catalytic activity of cinchona‐derived organocatalysts has not yet been investigated . An exceptional example was reported by Castle et al who used 3‐alkynyl cinchonidinium salts as catalysts for an asymmetric Aldol reaction.…”