Diphenylprolinol silyl ether catalyst

Cordova " and Wang showed new variants of cyclopropanation reaction using diphenylprolinol silyl ether catalysts. The reaction required... 

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. 

The diphenylprolinol silyl ether 45a catalyst was developed by the Hayashfs group for the addition of a-unbranched aldehydes to aryl and alkyl substituted nitroolefins [35]. This catalyst, as well as the perfluoroalkyl derivative 45b [36],... 

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. 

The 0-TBS-hydro>y-diphenylprolinol silyl ethers 14, analogues of the Jorgensen-Hayashi catalyst 3a, were tested in 2008 by List and coworkers for the challenging catalytic asymmetric Michael reactions of acetaldehyde with nitroalkenes. While 4-hydroxy-proline derivative 14a displayed diminished activity, but slightly better enantioselectivity with respect to 3a, the 3-hydroxy-proline derivative 14b gave in this case very poor results (Scheme 11.12). 

Riguet reported a methodology involving an enantiose-lective organocatalytic Friedel-Crafts alkylation followed by an Ugi 4-center 3-component reaction [57]. In the first reaction, the Friedel-Crafts reaction, 5-hydroxyfuran-2(5F/)-one (53) was used as an electrophile to alkylate indoles 52 to give the intermediate 54, using a diphenylprolinol silyl ether 56 as catalyst (Scheme 7.22). Then, adducts 54—obtained from Friedel-Crafts reaction—were used in a one-pot manner... 

A number of highly efficient asymmetric domino nitro-Michael additions of C-nucleophiles catalysed by organocatalysts were described in 2008. One of the most employed organocatalysts for these types of reactions is diphenylprolinol silyl ether. This catalyst was used by Hong et al. to develop a highly diastereo-and enantioselective domino reaction occurring between 7-oxohept-2-enoate and nitroalkenes (Scheme 1.61). ° The reaction afforded highly functionalised... 

After MacMillan s pioneering work on the VMM-type reaction, a number of oiganocatalysts were applied to similar reaction systems. Among these, direct vinylogous Michael reaction attracted much attention. For example, Alexakis reported that diphenylprolinol silyl ether 142 and aminal-pyrrolidine catalyst 143 are effective for the direct reaction of angelica lactone 140a with a,p-enal 137b (Scheme 59) [101]. In this case, it was also mentioned that furan-2(5H)-one itself does not work as a suitable nucleophile. 

The simplest enoUzable aldehyde, acetaldehyde, was until recently not examined in organocatalytic reactions due to its high reactivity as electrophile or as nucleophile leading to intractable mixture of products resulting from side reactions. The groups of List [63] and Hayashi [64] reported independently the use of acetaldehyde as donor in Michael addition to nitroalkenes (Scheme 34.24). They both selected diphenylprolinol silyl ether (6) as the best catalyst but employed different solvents (acetonitrile or DMF/Pr OH for LisL and 1,4-dioxane for Hayashi) at room temperature. Similar selectivities were observed under both conditions but higher yields were obtained with Hayashi s conditions. 

MacMillan s group advanced the iminium activation strategy to intramolecular Diels-Alder reactions with good diastereoselectivity (up to 20 1) and enantioselectivity [61]. The strategy was applied in the total synthesis of (-i-)-hapalindole Q [62]. A novel binaphthyl-based diamine was utilized to catalyze Diels-Alder reaction of a,P-unsaturated aldehydes with unprecedented high exo selectivity [63]. It was reported that the same reaction was also catalyzed by diphenylprolinol silyl ether and an acid as cocatalyst [64]. However, with the same reactants and the same catalyst, an ene reaction took place instead without an acid additive. Diels-Alder reactions of 2-vinylindoles and a,p-unsaturated aldehydes were also developed [65]. 

Gotoh H, Ishikawa H, Hayashi Y. Diphenylprolinol silyl ether as catalyst of an asymmetric, catalytic, and direct Michael reaction of nitroalkanes with a,(3-unsaturated aldehydes. Org. Lett. 2007 9(25) 5307-5309. 

Hayashi Y, Gotoh H, Masui R, Ishikawa H. Diphenylprolinol silyl ether as a catalyst in an enantioselective, catalytic, formal aza [3+3] cycloaddition reaction for the formation of enantioenriched piperidines. Angew. Chem. Int. Ed. 2008 47 (21) 4012-+015. 

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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