A General Approach for Preparation of Polymer-Supported Chiral Organocatalysts via Acrylic Copolymerization

Abstract

Polymer-supported chiral organocatalysts, as well as most other forms of immobilized catalysts, are traditionally prepared by a postmodification approach where modified catalyst precursors are anchored onto prefabricated polymer beads. Herein, we report an alternative and more scalable approach where polymer-supported chiral enamine and iminium organocatalysts are prepared in a bottom-up fashion where methacrylic functional monomers are prepared in an entirely nonchromatographic manner and subsequently copolymerized with suitable comonomers to give cross-linked polymer beads. All syntheses have been conducted on multigram scale for all intermediates and finished polymer products, and the catalysts have proven successful in reactions taking place in solvents spanning a wide range of solvent polarity. While polymer-supported proline and prolineamides generally demonstrated excellent results and recycling robustness in asymmetric aldol reactions of ketones and benzaldehydes, the simplest type of Jørgensen/Hayashi diarylprolinol TMS-ether showed excellent selectivity, but rather sluggish reactivity in the Enders-type asymmetric cascade. The polymer-supported version of the first-generation MacMillan imidazolidinone had a pattern of reactivity very similar to that of the monomeric catalyst, but is too unstable to allow recycling.

Enantioselectivity, swelling and stability of 4-hydroxyprolinol containing acrylic polymer beads in the asymmetric reduction of ketones

“…2,2 0 -Azobis(2-methylbutyronitrile) (AMBN) was used as the initiator, polyvinyl alcohol as a suspension stabiliser, while KI inhibits the polymerisation in the aqueous phase. 36 The acrylic polymer was isolated by filtration, and the appearance of the fresh catalyst is shown in Figure 2. By having a low degree of cross binder, as for II, a microporous polymer bead is formed.…”

“…Recently, a new method for preparing polymer linked 4-hydroxy-a,a-diphenyl-L-prolinol catalysts was developed. 36,37 Since this protocol is based on a 'bottom up' approach without any chromatographic purifications, the procedure is well suited for large scale synthesis. 28 In order to investigate the scope of the new and readily obtainable polymethacrylate, II (Fig.…”

“…36 The acetophenones 1a-k, 1-acetonaphthone 1l, 2,2,2-trifluoro-1-phenylethanone 4c, borane diethylaniline complex, borane dimethylsulfide complex, (R)-1-(naphthalen-1-yl)ethanol 5l, methyl methacrylate, ethyleneglycol dimethacrylate, 2,2 0 -azobis(2-methylbutyronitrile), polyvinyl alcohol and potassium iodide were purchased from Aldrich. 1-(4-Bromophenyl)-2,2,2-trifluoroethanone 4a was from Apollo, 2,2-difluoro-1-phenylethanone 3c from Alfa Aesar, whereas 2-fluoro-1-phenylethanone 2c was synthesised as described previously.…”

Recent Developments in Asymmetric Organocatalytic Domino Reactions

“…[151] A novel polymer-supported diphenylprolinol silyl ether 332 was synthesized by Hansen et al, and further applied as catalyst to induce a diastereo-and enantioselective three-component domino Michael-Michael-aldol reaction between cinnamaldehyde, n-propanal and nitroalkene 333, affording the corresponding tetrasubstituted cyclohexenecarbaldehyde 334 in 32% yield, as shown in Scheme 87. [152] Once again, although an a,b-unsaturated aldehyde is also implicated as substrate in this reaction, this work is situated in the section dealing with three-component reactions of nitroalkenes because the first Michael addition occurred onto the latter and not on the a,b-unsaturated aldehyde.…”

A reação de Diels-Alder no início do século vinte um

“…Uma modificação relevante é o uso de organocatalisadores suportados em polímeros, 48 como a L-prolina, e as imidazolidinonas de MacMillan, como mostrado no Esquema 10. Outro exemplo é a reação do cicloexadieno com o acrilaldeído, estudada na presença do organocatalisador suportado em montmorillonita (Esquema 11).…”