Catalytic asymmetric heterogeneous aziridination of styrene using CuHY/bis(oxazoline): comments on the factors controlling enantioselectivity Sophia Taylor a , John Gullick a , Paul McMorn a , Donald Bethell b , Philip C. Bulman Page c , Frederick E. Hancock d , Frank King d , and Graham J. Hutchings a, a Department of Chemistry, Cardiff University, P.O. Box 912, Cardiff CF10 3TB, UK b Department of Chemistry, University of Liverpool, Liverpool L69 3BX, UK c Department of Chemistry, Loughborough University, Loughborough, Leics. LE11 3TU, UK d Synetix, P.O. Box 1, Billingham, Teeside TS23 1LB, UK The copper-catalyzed aziridination of styrene is described using both heterogeneous, copper-exchanged zeolite HY, and homogeneous, copper (II) triflate catalysts using both [N-(p-tolylsulfonyl)imino]phenyliodinane ðPhI¼NTsÞ and [N-(p- nosylsulfonyl)imino]phenyliodinane ðPhI¼NNsÞ as nitrene donors. The key differences observed for the two catalysts when modified by chiral bis(oxazoline) ligands are discussed in detail. In particular, the heterogeneously catalyzed asymmetric reaction can give much higher enantioselection than the comparable homogeneously catalyzed reaction. The structure of the bis(oxazoline) ligand is the critical factor, and bis(oxazoline) ligands that are ineffective with the homogeneous catalysts are highly effective for the Cu 2þ cation constrained within the zeolite micropores. The consequences of this observation for the design of chiral ligands for asymmetric heterogeneous catalysis are discussed. The effect of the degree of styrene conversion on the enantioselectivity is described in detail using PhI¼NNs as a nitrene donor. The reaction shows a significant enhancement in ee with conversion at 25  C, and the possible origin of this effect is discussed. KEY WORDS: asymmetric heterogeneous catalysis; aziridination of styrene; CuHy/bis (oxazoline). 1. Introduction Asymmetric catalysis remains a subject of immense interest because the synthesis of pure enantiomers is crucial for pharmaceutical and agrochemical applica- tions. To date, there has been immense progress in the design of homogeneous catalyst methodologies [1–7], and high enantioselection can be achieved in a very broad range of catalyzed reactions. The design of effective heterogeneous asymmetric catalysts has also received significant recent attention [8,9] but, in general, catalysts tend to be very specific for particular reactions and classes of substrates, and there are very few examples of heterogeneously catalyzed reactions giving high enantio- selection. Most work in this area has concentrated on the cinchona alkaloid-modified supported Pt catalysts for alkyl pyruvate hydrogenation, where ees in excess of 95% have been reported [9]. More recent work has focused on the immobilization of homogeneous catalysts, e.g., manganese salen complexes for the asymmetric epoxida- tion of functionalized alkenes [10–12]. Unfortunately, almost invariably, poorer enantioselection is achieved with the immobilized complex compared to the compar- able homogeneous catalysts [12]. However, in 1999, Johnson et al. [13] showed for the first time that a carefully planned immobilization strategy could result in enhanced enantioselection being observed with the immobilized catalyst when it is constrained within the ordered mesopores of MCM-41. They demonstrated this for the allylic amination of cinnamyl acetate using a catalyst based on 1,1 0 -bis(diphenylphosphino)ferrocene anchored to the inner wall of MCM-41 and coordinated to Pd 2þ . The approach was subsequently extended to the enantioselective reduction of ethyl nicotinate [14]. We have concentrated our attention on the hetero- geneous asymmetric aziridination of alkenes [15–18] using Cu 2þ ion-exchanged into zeolite HY modified by chiral bis(oxazoline) (the IUPAC name for 1,3-oxazoline is 4,5-dihydro-1,3-oxazole) ligands (scheme 1]). Azir- idines are important intermediates for pharmaceuticals. We have also observed that, in this catalyzed reaction, higher enantioselection can be obtained with the immo- bilized catalyst than with the homogeneous catalyst, e.g., copper (II) triflate (trifluoromethanesulfonate) [17]. In this paper, we describe the key differences between the homogeneously and heterogeneously catalyzed alkene aziridination reactions using Cu 2þ with two nitrene donors, [N-(p-tolylsulfonyl)-imino]phenyliodinane (the IUPAC name for iodinane is  3 -iodane) ðPhI ¼ NTsÞ and [N-(p-nosylsulfonyl)-imino]phenyliodinane ðPhI¼NNsÞ. In particular, the factors that are important for the enhanced enantioselectivity of the heterogeneous catalyst are discussed. In addition, the effect of conversion on  To whom correspondence should be addressed. E-mail: hutch@cf.ac.uk Topics in Catalysis Vol. 24, Nos. 1–4, October 2003 (# 2003) 43 1022-5528/03/1000–0043/0 # 2003 Plenum Publishing Corporation