Jprgensen-Hayashi catalyst

Together with the diarylprolinol silyl ethers (Jprgensen-Hayashi catalysts) [54] shown in the first row of Figure 2.3, the chiral imidazolidinones devised by MacMillan are the most usual catalysts for iminium activation. Some representative examples are shown in Figure 2.16. 

The asymmetric vinylogous Michael addition of y-butenolide(buteno-4-lactone) to RCH=CHCH=0 has been reported to proceed with high enantioselectivity and moderate diastereoselectivity in the presence of the Jprgensen-Hayashi catalyst (123a) and AcOLi.236... 

Enders triple cascade reaction for the formation of three new C—C bonds and providing enantiopure cyclohexane derivatives 152 through reaction of a,p-unsaturated aldehydes 95 with activated methylene compounds 151 using his famous Jprgensen-Hayashi catalyst (5)-97 (Scheme 2.45) [75]. 

Domino Sequences Involving Oxindoles as Pronucleophiles Another commonly used approach for the synthesis of spirooxindoles relies on the use of simple oxindoles as pronucleophiles with several Michael acceptors. For example, we developed a highly enantioselective methodology for the synthesis of spirooxindoles by a Michael-Michael-aldol cascade (Scheme 10.19) [30]. Simple 2-oxindole (58) undergoes two consecutive Michael reactions with enals 16 catalyzed by the Jprgensen-Hayashi catalyst I. Next, an intramolecular aldol reaction catalyzed by the same catalyst takes place to afford, after dehydration, the corresponding spirooxindoles 59. 

In 2012, Zhao and coworkers developed an enantioselective strategy for the synthesis of spiroindolenines 94 by a Michael-hemiaminal formation/Pictet-Spengler cascade reaction [54]. The indoles 93 bearing a ketoamido group in 3-position reacted with the enals 16 in the presence of the Jprgensen-Hayashi catalyst (XXIV) to afford the corresponding spiroindolines in excellent yields and enantioselectivities but moderate diastereoselectivities (Scheme 10.33). 

SCHEME 9.15 Tandem reaction promoted by a Jprgensen-Hayashi catalyst. 

SCHEME 9.17 Tandem reaction combining a Jprgensen-Hayashi catalyst with a (S)-proline catalyst. 

Very recently, Lin et al. reported a cascade aminoxylation/aza-Michael/aldol condensation reaction by combining two distinct secondary amine catalysts [23], The (Si-proline was nsed to serve as an enamine catalyst, while the Jprgensen-Hayashi catalyst was exploited to generate achiral imininm ion toward anncleophilic attack (Scheme 9.26). 

Very recently, Sun et al. developed a cascade reaction with a binary catalytic system combining a secondary amine and a palladium catalyst for the synthesis of dihydropyrrole enantioselectively [54]. The reaction began with a Jprgensen-Hayashi catalyst promoted N-Ts propargyl amine-involved aza-Michael addition to cinnamaldehydes and ended with subsequent PdCl and Jprgensen-Hayashi catalyst co-promoted car-bocyclization (Scheme 9.59). The chemistry presented here also involved a DYKAT process and provided an alternative to chiral dihyropyrrole synthesis. 

Using a similar approach, but assisted by Jprgensen/Hayashi prolinol ether catalysts, Fustero et al. [103] and Carter and co-workers [104] have independently documented additional innovative applications of this intramolecular reaction providing a practical route to enantioenriched piperidines from the corresponding co-amino a,p-unsaturated aldehydes (Scheme 11.28). This methodology has been later expanded successfiiUy to the synthesis of quinoUzidine alkaloids such as... 

In 2008, List s group developed an epoxidation using asymmetric counteranion-directed catalysis (ACDC) [177]. In this work, the epoxidation of 1,2-disubstituted enals (33) and (3,(3-disubstituted, a, 3-unsaturated aldehydes (115) was explored. Instead of using a chiral amine (e.g. Jprgensen-Hayashi s catalyst), an achiral amine and a chiral counteranion (a phosphoric acid derived from BINOL), were employed. 

FIGURE 14.7. Resin-supported Jprgensen-Hayashi s and MacMillan s catalysts in the a-selenylation of aldehydes. 

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). 

Planarization in the pyrrolidine enamines increases p-character in the lone pair and renders nitrogen a stronger donor. Enamines derived from imidazolidinones are 10 -1(P times less reactive than those based on the proline-derived Hayashi-Jprgensen catalyst. ... 

Ma has reported a related organocatalytic route to chiral piperidines through an enantioselective Michael addition of aldehydes onto nitroalkenes, followed by intramolecular aminalization, catalyzed by the Hayashi-Jprgensen catalyst in the presence of benzoic acid [34],... 

With respect to the catalysts of choice, the MacMillan imidazolidinones 77 emerged as the most commonly used ones in iminium catalysis, but also cinchona alkaloid-based amines like 115 as well as the Hayashi-Jprgensen catalysts 85 have been highly successful in this field [31,47]. 

An organo-metal synergistic catalysis has been developed (Scheme 19) for the construction of the spirocyclopentene oxindole derivatives (502). Here, the cinnamic aldehyde (498) is first activated through the in situ catalytic formation of the highly electrophilic iminium ion (499) with the Hayashi-Jprgensen prolinol-derived catalyst (325)... 

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