Diarylprolinols derivatives

The [3+2] cycloaddition has also been shown to be effective in the reaction of azomethine imines 32 with a,P-unsaturated aldehydes by Chen and co-workers [70], A survey of seven catalysts revealed some interesting trends, with the diarylprolinol derivative 31 giving the highest yields and selectivities (40-95% yield endo. exo 1 4.3-1 49 77-96% ee for exo) with short reaction times (5-24 h) and low catalyst loading (10 mol%) (Scheme 11). The reaction was particularly sensitive to the amount of water present in the reaction medium and the choice of co-acid. This phenomenon is a reoccurring theme in many of the publications in the area of iminium ion catalysis and, as yet, no general explanation has been proposed to account for these observations. 

The equilibria between bicyclic oxazolidines and enamines derived from prolinol derivatives and aldehydes have been studied spectroscopically by Schmid et al. [44] In the case of prolinol, the less stable c db-oxazolidinone is the kinetic product, which is in equilibrium with the aw/f-enamine conformer. The zwitterionic amonium alkoxide, not detected, is the key intermediate in the oxazolidine-enamine equilibrium. For diarylprolinol derivatives, minor amounts of en amine can be detected, and only the e/J[Pg.27]

In addition, Cordova et al. have developed highly enantioselective organocatalytic hydrophosphination reactions of a,p-unsaturated aldehydes. These novel reactions were catalysed by protected chiral diarylprolinol derivatives... 

Another interesting approach to the synthesis of spiro compounds incorporating a cyclopropane was developed by Lattanzi and coworkers. In this work, a-bromo-methylmalonate reacted with 2-arylidene-l,3-indandiones 86 to afford the corresponding spirocyclopropanes 87 in good to excellent yields (74-96%) and moderate to good enantioselectivities (60-85%) when the diarylprolinol derivative XXI was used as the catalyst [50] (Scheme 10.30). 

Cordova [72] in 2007. Both groups reported a hydrophosphination of enals with diphenylphosphine (88) catalyzed by diarylprolinol derivatives 27 (Scheme 33.22). The reactions were performed in the presence of benzoic acid derivatives as co-catalyst, and the originally formed adducts were either reduced to alcohols, which are stable and easier to handle, or oxidized to obtain the phosphine oxide derivatives. In both cases the reaction afforded the phosphine derivatives in good yields and enantioselectivities. 

In 2005 j0rgensen [12] and Hayashi [13] developed almost at the same time diarylprolinol derivatives protected as silyl ethers (Figure 33.4) as a suitable catalysts for rmtne and enamtne activation. 

Type B enamine catalysts have been developed more recently. They include the diarylprolinol ethers (developed by the Hayashi and Jprgensen groups, e.g. 47 and its derivatives) [71-75] as well as the MacMillan imidazolidinone catalysts (e.g. 46) [76-78]. They excel in reactions where hydrogen bonding assistance is either not required or is not essential, such as a-halogenation reactions as well as some conjugate addition reactions (Scheme 12). 

A final class of dipole shown to be effective in iminium ion catalysed [3+2] cycloadditions are azomethine ylides derived from 35 [71] (Scheme 12). Vicario showed that 20 mol% of diarylprolinol 33 catalysed the cycloaddition between a,P-unsaturated aldehydes 34 and imines 35 (THE, 4 °C, 72 h) to give the densely... 

However, formation of this bond through the conjugate addition of a soft sulfur nucleophile to a,P-unsaturated aldehydes is efficiently catalysed using iminium ion catalysis [116], Using diarylprolinol silyl ether 55 the addition of a series of sulfur based nucleophiles to a variety of a,P-unsaturated aldehydes was shown to be effective (73-87% yield 89-97% ee). The products were isolated as their p-hydroxy sulfide derivatives 73 after in situ reduction of the products (Scheme 33). 

A new class of chiral 4-A,A-dialkylaminopyridine acyl-transfer catalysts has been developed that are capable of exploiting both van der Waals (jt) and H-bonding interactions to allow remote chiral information to control stereochemically the kinetic resolutions of secondary alcohols with moderate to excellent selectivity (S = 6-30). Catalysts derived from (.S )- , -diarylprolinol (89 Ar = Ph, 2-naphthyl) in combination with isobutyric anhydride were found to possess high activity and selectivity across a broad range of substrates 89... 

Finally, diarylprolinol 48c has also been employed as catalyst in the enantioselective p-peroxydation of nitroalkenes with tert-butyl hydroperoxide (Scheme 4.65). The catalyst is proposed to engage in a bifunctional activation mode, which on one hand assists the deprotonation of the hydroperoxide and on the other activates the nitroalkene by the formation of one H-bond with the nitro group. Under the optimized conditions, moderate yields and enan-tioselectivities around 85% ee were achieved for a variety of nitrostyrene derivatives. 

One of the first attempts in this field refers to a multicomponent intermolecular sulfa-Michael/amination cascade process in which an a,p-unsatu-rated aldehyde and a thiol were reacted in the presence of a dialkyl azodicarboxylate reagent, giving access to p-amino-y-thioalcohol derivatives with excellent yields and enantioselectivities. Isolation of the final products was accomplished by in situ reduction followed by base-promoted cyclization (Scheme 7.48). 0-Trimethylsilyl diarylprolinol 31c was identified as the best... 

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. ... 

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