Hydrophobically directed aldol reactions: polystyrene-supported L-proline as a recyclable catalyst for direct asymmetric aldol reactions in the presence of water

摘要

A simple synthetic methodology for the preparation of a polystyrene-udsupported L-proline material is reported, and thisudmaterial has been used as catalyst in direct asymmetric aldoludreactions between several ketones and arylaldehydes to furnishudaldol products in high yields and stereoselectivities.udScreening of solvents showed that these reactions take placeudonly in the presence of water or methanol, at lower levels ofudconversion in the latter case. This solvent effect, coupledudwith the observed high stereoselectivities, has been ex-udIntroductionudIn the last decade organocatalysis has became a field ofudgreat interest.[1] Organocatalysts are metal-free small organicudmolecules that are able to function as efficient andudselective catalysts for a large variety of enantioselectiveudtransformations. In this context, -proline and its derivativesudhave emerged as powerful organocatalysts.[2] -Prolineudcan be regarded as the simplest “enzyme” and it has beenudsuccessfully applied in many reactions, such as Robinsonudannulations,[3] aldol reactions,[4] Mannich reactions,[5]udMichael reactions,[6] direct electrophilic α-aminations,[7] Diels–udAlder reactions,[8] Baylis–Hillman reactions,[9] aza-Morita-udBaylis–Hillman reactions,[10] α-selenenylation,[11] oxidation,[ud12] chlorination,[13] and others.[14]udAmong all these processes, -proline-mediated aldol reactionsudaffording β-hydroxy ketones have been investigatedudin great depth. Indeed, the aldol reaction is one of the mostudimportant C–C bond-formation methods in organic synthesis.[ud15] Proline and its derivatives operate by bifunctional catalysisudand play the role of a simplified version of the type Iud[a] Dipartimento di Chimica Organica “E.Paternò”, Università diudPalermo,udViale delle Scienze, Pad. 17, 90128 Palermo, ItalyudFax: +39-091-596825udE-mail: mgrutt@unipa.itud© 2007 Wiley-VCH Verlag GmbH 4688 & Co. KGaA, Weinheim Eur. J. Org. Chem. 2007, 4688–4698udplained in terms of the formation of a hydrophobic core inudthe inner surface of the resin, whereas the hydrophilic prolineudmoiety lies at the resin/water interface. Such a microenvironmentudboth promotes the aldol reaction and increases theudstereoselectivity. Recycling investigations have shown thatudthis material can be reused, without loss in levels of conversionudand stereoselectivity, for at least five cycles.