Proline-derived catalysts

The Corey synthesis began with an asymmetric Diels-Alder reaction between butadiene and 2,2,2-trifluoroethyl acrylate in the presence of the 5-proline-derived catalyst ent-59 to form the adduct ent-69 in excellent yield (97%) and with >97% ee (Scheme 7.10). Ammonolysis of 60 produced amide 61 quantitatively, which underwent iodolacta-mization using the Knapp protocol to generate lactam 62. A-Acylation of 62 with... 

For a recent report on the application of this phenyl transfer protocol using a proline-derived catalyst with dendritic polyether wedges, see X. y. Liu, C. y. 

It is worthy of note that - similarly to the proline catalyzed aldol reaction - the Mannich reaction can also be extended to an enantio- and diastereoselective process in which two stereogenic centers are formed in one step, although using non-chiral starting materials (Scheme 5.16) [22, 23, 26, 27, 28]. In these reactions substituted acetone or acetaldehyde derivatives, rather than acetone, serve as donor. In contrast with the anti diastereoselectivity observed for the aldol reaction (Section 6.2.1.2), the proline-catalyzed Mannich reaction furnishes products with syn diastereoselectivity [23]. A proline-derived catalyst, which led to the formation of anti Mannich products has, however, been found by the Barbas group [29]. 

The asymmetric domino reaction between 2-mercaptobenzaldehyde and a,f)-unsaturated aldehydes proceeds with excellent chemo- and enantio-selectivities to afford 2-substituted 3-formyl-2//-l bcnzothiopyrans, products of a formal Baylis-Hillman reaction, when the. 9-proline derived catalyst 407 is employed (Scheme 123) <2006TL8547>. 

The best results concerning yield and selectivity were obtained with 20 mol% of the TMS-ether (S)-71, which is easily available from the natural amino acid (S)-proline. Using the (R)-proline derived catalyst (R)-71 affords the enantiomeric products ent-12 (Scheme 17). 

Another amine-mediated epoxidation system, discovered by the group of Jorgensen, consists of proline-derived catalysts and is mechanistically distinct... 

Sulfinamide 46, developed by the same group, represents the most recent addition to this family. Here, the original formyl group of the proline derived catalyst 16 was replaced by the t BuSO moiety, which resulted in high enantio selectivities (<97% ee at 0 °C with 10mol% catalyst loading Table 4.10) [Ilf]. The striking feature of this catalyst is its efficiency with imines derived from nonaro matic amines, namely, benzyl, allyl, propyl, isobutyl, and p methoxybenzyl amine (Table 4.10), which renders 46 superior to 43 and dwarfs other catalysts (e.g., 16,19, and 45). Needless to say, this new feature broadens the synthetic arsenal beyond the N aryl substrates and opens new synthetic avenues. In comparison, the valine derived catalyst 47 proved to be less efficient with imines derived from aromatic... 

The Fu and Vedejs catalysts are excellent and work with a range of substrates but good kinetic resolutions can be achieved even with some very simple chiral diamines. A catalyst derived from proline 21 was used at low temperature and low loading to resolve the secondary alcohol 22 very effectively.13 The use of the proline-derived catalysts has been extended to some primary alcohols.14... 

The TIPS-protected L-prolinol derivative A (see Chapter 8) gave superior enantioinduction however, only 44% enantiomeric excess was still obtainable. Tetrazole-derived catalyst B (see Chapter 9) gave the highest yield (98% yield). Figure 5.9 illustrates the difference in reactivity and enantioselectivities between L-proline, and proline-derived catalysts A and B. 

Figure 5.9 Comparison of reactivity and enantioselectivities between L-proIine, and proline-derived catalysts A and B.

This overview about developments in the field of proline-catalysis unfortunately cannot take into full account the vast field of proline-derived catalysts, such as diarylprolinols, 4-silo)yprolines or proline-silyl-ether, to name only a few. These are covered in subsequent chapters of this volume. Furthermore, other great improvements have been made by using immobilised proline catalysts, such as PEG-supported proline or polyelectrolyte-bound pro-line. Going one step further, supported proline catalysts are then applicable in the striving field of continuous-flow reactions. Recent examples include aldol, a-amination reactions and Michael reactions under such conditions. ... 

In 2004, Vignola and List [111] demonstrated the ability of proline-derived catalysts to overcome drawbacks associated with the stoichiometric alkylation of preformed aldehyde enolates when they described an elegant amino acid catalyzed intramolecular a-alkylation reaction of haloaldehydes. The reaction furnished substituted cyclopentanes, cyclopropanes, and pyrrolidines in good yields and good enantio-selectivities (Scheme 8.23), when commercially available (5)-a-methyl proline (LV) as catalyst was used. The presence of a stoichiometric amount of additional base (tertiary amine) was required, not only to trap the hydrogen halide produced in the reaction but also because it has also significant effect on the stereoselectivity of the C—C bond-formation process by stabilizing the ant/ -TS of the /ra 5-enamine intermediate. Nevertheless, an intermolecular version of the reaction remains still elusive, mainly because of the deactivation of the amine catalyst by A -alkylation with the alkyl halide [112]. 

FIGURE 8.1. Proline-derived catalyst h%l LXII and silicon-based secondary amine catalyst LVIII. 

Further extent of asymmetric Sjvl a-alkylation methodology to ketone motifs was disclosed by Cheng and co-workers [129] in 2010. They described the first asymmetric catalytic direct a-alkylation of cyclic ketones catalyzed by functionalized chiral ionic liquids, namely proline-derived catalyst containing benzoimida-zolium moiety (LXI, Figure 8.1), and Brpnsted acid (TFA or phthalic acid). Moreover, described catalytic system enables asymmetric desymmetiization of 3-and 4-substituted cyclohexanones to afford 2,4-trans- and 2,5-cis-substituted products, respectively, with up to 99% yield, greater than 99 1 dr and good enantioselectivities (up to 87% ee). 

Dixon and co-workers [182] published an enantioselective aryloxylation of aldehydes using an inverse-electron-demand hetero-Diels-Alder reaction of in s/tM-generated enamines and o-quinones. After trying different proline-derived catalysts, imidazolidinone 120 gave the best enantioselectivities (Scheme 12.34). 

Sun and co-workers [29] has also made a great contribution to this field, developing novel class of catalysts for the enantioselective hydrosUylation of ketoimines. He reported (5)-proline-derived catalyst obtaining high yields and moderate to high enantioselectivities. Moreover, he developed the first catalyst derived from (L)-pipecolinic acid, able to promote the reaction with high yields and enantioselectivity and, for the first time, the reduction of aliphatic ketimines [30] (Scheme 15.6). This work was also the first to demonstrate the independence of the ketimine geometry on the selectivity of the reaction. 

The group of Metz employed the proline-derived catalyst 159 in combinatiOTi with co-catalyst 160 to catalyze additions of (/ )- and (S )-citronellal (157) to 158 for the selective syntheses of the diastereomeric keto aldehydes 174 and 175. These intermediates could then be used to synthesize the marine sesquiterpenoids (—)-clavukerin A (176) (starting from (S )-157) and ( )-isoclavukerin A (177) (derived from (/ )-157) (Scheme 41) 162). 

CBS Reduction of Ketones (PPG-Sipsy with Caiiery Lonza). Hydride reduction with a proline-derived catalyst (CBS reaction) was applied by Lonza to make 50 kg of an intermediate for Josiphos ligands (79,80). 

Finally, a remarkable four-component tandem Michael-aza-Henry-hemi-aminalisation-dehydration tandem reaction was recently developed by Lin and co-workers on the basis of a dual organocatalysis involving a chiral diaryl prolinol trimethylsilyl ether and a chiral cinchona alkaloid." As shown in Scheme 2.37, the reaction began with the Michael addition of an aldehyde to a nitroalkene catalysed by the L-proline-derived catalyst, giving the corresponding intermediate aldehyde. The latter intermediate... 

Other proline-derived catalysts promoting the selective formation of the fl/iti-diastereomer have been developed, for example, by the groups of Maruoka (axially chiral amino sulfonamides 98, symmetric chiral pyrrolidine-based amino sulfonamides 99) [66, 67] and Cdrdova (diaryl-prolinols 100) [68], among others, involving Coulombic or steric interactions (or both) as well to lock the transition state in the conformation required for stereoselective catalysis (Figure 11.3). 

Scheme 22.20 Formation of ofF-cyde side-product 56 responsible for reducing the efficiency of proline-derived catalysts in the asymmetric aldol reaction.

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