Diphenylprolinols silyl enamines

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. 

ThefoUowingdominoreactiondevelopedbyj0rgensenandco-workers [44a] involves enamine activation of aldehydes by diphenylprolinol silyl ether promoting an enantioselective Michael addition onto quinones, followed by an intramolecular hemiacetaliza-tion (Scheme 16.22). The resulting dihydrobenzofiirans were obtained with high yields... 

Enamine-intermolecular Addition Cascades It was suggested that the intermediate y-nitroaldehyde 91 in Scheme 1.31 might react with an aldehyde via an oxo-Henry sequence, and subsequent hemiacetalization would provide tetrahydropy-ran derivatives. Uehara et al. [50] and Iskikawa et al. [51] realized this hypothesis independently through a four-component reaction in one pot to furnish highly substituted tetrahydropyran derivatives 102 with excellent diastereo- and enantioselec-tivity (up to 98 2 dr and 99% ee) (Scheme 1.35). These two methods are complementary because anti-Michael products were synthesized using catalyst 101 [50], while syn-Michael products were obtained with diphenylprolinol silyl ether catalyst 34 [51]. 

In addition to imininm-initiated cascade reactions, two of the steps in enamine-activated cascade reactions can also be enforced by cycle-specific catalysis. It is well known that diphenylprolinol silyl ether catalyst 34 is optimal for diverse enamine-mediated transformations to fnmish prodncts with high enantioselectivities. However, similar to imidazolidinone catalysts, it proved to be less effective or ineffective for bifunctional enamine catalysis. Cycle-specific catalysis via an aza-Michael/Mannich sequence by combining 34 and either enantiomer of proline was thus developed to generate 206 in about 60% yields with excellent diastereo- and enantioselectivities (Scheme 1.89) [139]. 

The combination of diphenylprolinol silyl ether catalyst 34 with a primary amine catalyst was used to promote the double a-functionalization of aldehydes [140], A combination of enamine or iminium catalysis with N-heterocyclic carbene catalysis [141] and hydrogen-bonding catalysis [142] was also developed. 

Since the early example of a proline-catalyzed asymmetric domino Michael-aldol reaction reported by Bui and Barbas in 2000 [57], a number of these reactions have been successfully developed by several groups. For example, Wang et al. have reported the synthesis of chiral densely functionalized cyclopentenes on the basis of a domino Michael-aldol reaction followed by dehydration between aromatic enals and dimethyl 2-oxoethylmalonate [67]. High yields (63-89%) and enantiose-lectivities (91-97% ee) were obtained by using (S)-diphenylprolinol silyl ethers as catalysts. On the other hand, the condensation of P-nitroketones 36 onto enals in the presence of 8 was shown by Hong et al. to afford the corresponding domino Michael-aldol products 37 through the iminium-enamine activation mode [68]. 

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