Catalysts diarylprolinol

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). 

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. 

J0rgensen [111] and Vicario [112] independently described the conjugate addition of both triazole and tetrazole based nucleophiles to a,P-unsaturated aldehyde substrates as an alternative method for C-N bond formation. These reactions were catalysed by the diarylprolinol and imidazolidinone scaffolds with equal efficiency showing the complementarity and efficacy of both these catalyst architectures. In addition, Jprgensen has also shown succinimide to be an effective Michael donor (see Sect. 2.3.5 Scheme 49 for further details) [113]. 

Cordova has also shown hydrogen peroxide to be an effective oxidant in the epoxidation of a,P-unsatnrated aldehydes using diarylprolinol ether 30 as the catalyst (Fig. 9) [146, 147], Within these reports it was also shown that the resulting epoxy aldehydes could be used directly in either Wittig or Mannich reactions, providing synthetically useful one-pot protocols to prepare densely functionalised building blocks for further elaboration. 

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... 

The Michael-type addition of thiols to a,p-unsaturated aldehydes has been reported to proceed very efficiently using O-TMS protected diarylprolinol 31c as catalyst (Scheme 3.32). The low configurational stability of the adducts at r.t. led the authors to modify the reaction conditions, which finally involved carrying out the reaction at -24 °C and reducing the adducts in situ, furnishing the corresponding y-thio alcohols in excellent yields and enantioselectivities. Both alkyl- and aryl-substituted enals could be used as suitable Michael... 

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. 

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. ... 

Diarylprolinol silyl ether catalyst was able to promote enantioselective allqrlations of a,p-unsaturated aldehydes with stabilised carbcations as electrophiles. Dienamine intermediates were trapped by the electrophile in two positions. The y-disubstituted aldehydes were not good substrates for y-substitution. However, linear unbranched and p-substituted a,p-unsaturated aldehydes preferred y-substitution. ot-Substituted aldehydes were unreactive under secondary amine catalysis (Scheme 8.45). 

Then, the hydride ion is selectively transferred to the f-olefin from the least sterically hindered face to produce the corresponding isomer of the product. Furthermore, although a kinetic preference for (he (Z)-iminium ion formation has been demonstrated, the ( )-iminium ion intermediates, which dominate the equilibrium ratio, react with nucleophiles faster than the ( -isomers when diarylprolinol and imidazohnone-based chiral catalysts are anployed in conjugate additions to a,P-unsaturated aldehydes [20]. 

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