Iminium catalysts

The same system was used by Frechet s group of to achieve a multicomponent one-pot cascade reaction with mutually interfering acid and proline-derived pyrrolidine catalysts [31]. The concept is illustrated in Figure 5.1. The protonation of imidazo-lidone (3) by the immobilized PSTA (5) gives the desired iminium catalyst (6), while... 

Miscellaneous Iminium Catalyzed Transformations The enantioselective construction of three-membered hetero- or carbocyclic ring systems is an important objective for practitioners of chemical synthesis in academic and industrial settings. To date, important advances have been made in the iminium activation realm, which enable asymmetric entry to a-formyl cyclopropanes and epoxides. In terms of cyclopropane synthesis, a new class of iminium catalyst has been introduced, providing the enantioselective stepwise [2 + 1] union of sulfonium ylides and ot,p-unsaturated aldehydes.As shown in Scheme 11.6a, the zwitterionic hydro-indoline-derived catalyst (19) enables both iminium geometry control and directed electrostatic activation of sulfonium ylides in proximity to the incipient iminium reaction partner. This combination of geometric and stereoelectronic effects has been proposed as being essential for enantio- and diastereocontrol in forming two of the three cyclopropyl bonds. 

At present, one of the most successful catalysts for enamine activation has been proline (2). Proline is a cheap, widely and commercially available amino acid that can be found in both enantiomeric forms and, as such, represents a remarkable synthetic alternative to many established asymmetric catalysts. Given such attractive features, it has become the catalyst of choice for many enamine-catalyzed processes. However, various more recent studies have demonstrated that proline is not a universal catalyst for transformations that involve the a-functionalization of ketone or aldehyde carbonyls. Indeed, these studies have demonstrated that the iminium catalysts developed by MacMillan (imidazolidinones) and Jprgensen (pyrrolidines) are also highly effective for enamine activation with respect to... 

Chiral Ketone and Iminium Catalysts for Olefin Epoxidation... 

Goncalves, M.H., Martinez, A., Grass, S., Bulman-Page, PC. and Lacour. J. Enantioselective Olefin Epoxidation using Homologous Amine and Iminium Catalysts—a Direct Comparison. Tetrahedron Lett. 2006, 47, 5297-5301. 

Enantioselective organocatalytic cyclopropanations have been performed using directed electrostatic activation conditions.164 Using a new class of iminium catalysts, cyclopropanation has been conducted with enals but not electron deficient alkenes, such as unsaturated nitrile, nitro, or alkylidene malonate systems. 

Calculations [46] and studies of intramolecular oxaziridinium epoxidations [47] suggest that, like their dioxirane counterparts, these epoxidation processes proceed via spiro-transition states. However, the iminium epoxidations are generally more substrate-specific than those using dioxiranes, and models to explain the observed trends in stereocontrol have proved more difficult to construct. One complication is the possibility of formation of diastereomeric oxaziridinium salts from most of the iminium catalysts. Houk has rationalized computationally the observed enantioselectivity with Aggarwal s catalyst 16 [46]. The results of a recent study by Breslow suggest that hydrophobic interactions are important in these processes [48], and aromatic-aromatic interactions between catalyst and substrate may also play a role. 

Kunz RK, MacMillan DWC (2005) Enantioselective organocatalytic cyclopro-panations. The identification of a new class of iminium catalyst based upon directed electrostatic activation. J Am Chem Soc 127 3240-3241 Lacour J, Hebbe-Viton V (2003) Recent developments in chiral anion mediated asymmetric chemistry. Chem Soc Rev 32 373-382 Li X, List B (2007) Catalytic asymmetric hydrogenation of aldehydes. Chem Commun 17 1739-1741... 

Based on the experiences on the Diels-Alder reaction of 2-pyrones [20], Deng et al. have investigated the stereoselective Diels-Alder reaction of 2-pyrones and a,(3-unsaturated ketones. They also found that primary amines lo and lp derived from quinine and quinidine, respectively, werethe optimal iminium catalysts (5 mol%). The acid additive has a crucial effect on the efficiency of the reaction. TFA (20 mol%) gave the best results, and the Michael reaction, as a side reaction, could also be prohibited. 

M.-H. Goncalves, A. Martinez, S. Grass, P.C.B. Page, J. Lacour, Enantioselective olefin epoxidation using homologous amine and iminium catalysts—a direct comparison. Tetrahedron Lett. 47 (2006) 5297. 

Enders et al. elegantly applied diphenylprolinol silyl ether 6a as a catalyst for triple cascade reactions (Scheme 10.18), wherein 6a played the roles ofboth enamine catalyst and iminium catalyst. It should be noted that the four stereocenters were completely controlled[36].Theproposedcatalyticcycleofthe triplecascade isshownin Scheme 10.2. 

Cordova and coworkers showed that prolinol silyl ethers can also operate as iminium catalysts. The Michael addition of 1-fluorobis-(phenylsulfonyl)methane to a,p-unsaturated aldehydes proceeded with high enantioselectivity (Scheme 8.6). The primary Michael adducts were transformed to aldehydes, carbo>g7lic acids, or the sulfonyl groups could... 

Table 2 Iminium catalysts employed in complex natural product syntheses...

The force of this reaction comes from the catalytic integrity of the active star polymers 113 and 115, as they cannot penetrate each other s core. In contrast to that, small molecules and catalysts can freely diffuse to the core of the star polymers 113 to form the desired salt 114, which will then react as optimal iminium catalyst. 

Scheme 26.7 Enantioselective conjugated addition of silanes into a, 8-unsaturated aldehydes catalyzed using copper and chiral iminium catalysts.

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