Michael additions asymmetric, catalytic

Jautze S, Peters R (2010) Catalytic asymmetric Michael additions of a-cyano acetates. Synthesis 365-388... 

By using LaNa3-tris(binaphthoxide) (LSB) 55, catalytic asymmetric Michael addition of thiols to cycloalkenones took place to provide the adduct 56 with high ees in good yields (Eq. 7.41) [48]. 

Figure 4. Catalytic asymmetric Michael addition and epoxidation.

D.3. CATALYTIC ASYMMETRIC MICHAEL ADDITION OF STABILIZED CARBON NUCLEOPHILES... 

TABLE 8D.5. Catalytic Asymmetric Michael Addition of Propyl Radical to A -Cinnamoyloxazolidinone... 

Scheme 6.11 Catalytic asymmetric Michael addition using BINOL-derived two-center catalyst.

For rare examples of catalytic asymmetric Michael addition to a,p-unsaturated aldehydes, see (a) Yamaguchi, M., Shiraishi,T. and Hirama, M. (1993) Angew. Chem., Lnt. Ed. Engl., 32, 1176-1178 ... 

For recent and general reviews on catalytic asymmetric Michael additions, see (a) N. Krause, A. Hoffmann-Roder, Synthesis 2001, 171-196 (b) M. P. Sibi, S. Manyem, Tetrahedron 2000, 56, 8033-8061. 

Modified cinchona alkaloids 18 and 19, derived from quinine and quinidine, respectively, were utilized by Deng and co-workers for the catalytic asymmetric Michael additions of malonates to nitroolefins [49]. These catalysts effectively promoted the conjugate additions of methylmalonate to a variety of aromatic (90-99% yield 96-98% ee), heteroaromatic (97-99% yield 96-98% ee) and aliphatic (71-86% yield 94% ee) -substituted nitroolefins (Table 6.7). As the two alkaloids... 

In 2004, Deng and coworkers reported the first preparatively useful results for the catalytic asymmetric Michael additions of malonates to nitrooleftns. They found that... 

The catalytic asymmetric Michael addition using chiral amine was first reported by Langstrom and Bergson [6]. Treatment of 2-methoxycarbonyl-l-in-danone (6) and acrolein with 0.03 mol % of partially resolved (i )-2-(hydroxyme-thyl)quinuchdine (5,57% ee) in benzene at room temperature gave optically active adduct, [a]546 ° -1-8.83° (c 6.53, CCI4). It clearly indicated that the cluster formed from the base and the enolate reacted with the acceptor. The enantiomeric excess and the absolute configuration of this compound, however, have not yet been determined. 

Several successful examples appeared for the catalytic asymmetric Michael addition reaction. It may be apparent, however, that they are not yet quite satisfactory in terms of stereoselectivity, catalyst efficiency, and applicability. Development of new methods is still required, which would also deepen the fundamental understanding of the Michael addition reaction, a very important reaction in organic synthesis. 

Michael additions. Despite tremendous efforts spent in achieving catalytic asymmetric Michael additions, effective additives of wide applicability are still quite rare. Interestingly, a polyamine ligand 29 promotes the addition of ketone enolates. With JV-methoxy-N-methyl amides of a,p-unsaturated acids as acceptors, the addition of lithium fS)-(a-methylbenzyl)benzylamide proceeds in a highly diastereo- and enantioselective manner, ascribable to a six-centered transition state in which the conjugated amide adopts an s-cis conformation, ... 

Langstrom and Bergson groups carried out the first smdies on the catalytic asymmetric Michael addition of 2-methoxycarbonyl-l-indanone to acrolein with partially resolved (5.57% ee) (f )-2-(hydroxymethyl)quinuclidine as catalyst obtaining certain asymmetric induction in the process h-8.83° [187]. Twenty years... 

The earliest examples of catalytic asymmetric Michael additions involving activated methylenes and enones were conducted with readily available natural amines as catalysts. Wynberg and Helder demonstrated that Cinchona alkaloids such as... 

For reviews on catalytic asymmetric Michael additions, see (a) Yamaguchi M (1999) Conjugate addition of stabilized Ctirbanions. In Jacobsen EN, Pfaltz A, Yamamoto H (eds) Comprehensive asymmetric cattilysis, vol. III. Springer, Berlin, (b) Sibi MP, Manyem S (2000) Tetrahedron 56 8033-8061 (c) Krause N, Hoffmann-Roder A (2001) Synthesis 171-196 (d) Jha SC, Joshi NN (2002) Arkivoc vii 167-196 (e) Christoffers J, Koripelly G, Rosiak A, Rossle, M (2007) Synthesis 1279-1300... 

Scheme 8 Catalytic asymmetric Michael addition reactions of nitroethane to nitroalkenes promoted by a lanthanum catalyst...

Liu, D. Hong, S. W. Corey, E. J. Enantioselective Synthesis of Bridged- or Fused-Ring Bicyclic Ketones by a Catalytic Asymmetric Michael Addition Pathway. /. Am. Chem. Soc. 2006,128,8160-8161. 

As a direct route for the constructing carbon-carbon bonds, catalytic asymmetric Michael additions with various carbon-based nucleophiles including malonic esters, cyanide, electron-deficient nitrile derivatives, a-nitroesters, nitroalkanes, Horner-Wadsworth-Emmons reagent, indoles, and silyl enol ethers have attracted considerable attention. 

The first example of a catalytic asymmetric Michael addition of a Horner-Wadsworth-Emmons reagent to enones was developed by the Shibasaki group using (J )-ALB ent-18 as the catalyst (Scheme 19.28). When sodium tert-butoxide was used as a base instead of butyllithium, the competitive 1,2-addition could be suppressed and the yield of 1,4-addition product increased. 

The first catalytic asymmetric Michael addition of an mygen-centred addition of salicylaldoxime to a,p-unsaturated imides was achieved by the Jacobsen group in 2004 (Scheme 19.34). With p-oxo dimer catalyst [r,R)-[(salan)Al]20 5 as the catalyst, a series of a,p-unsaturated imides worked well. It should be noted that this method could tolerate ester, acetal, and silyl ether functionality, allowing its potential application as an acetate aldol alternative in polyketide natural product synthesis. When combined with efficient N-O bond hydrogenolysis, this (salen)aluminium-catalysed reaction enables the net enantioselective hydration of electron-deficient olefins with no need for purification of the intermediate oxime ethers. 

Catalytic asymmetric Michael addition is an important reaction for creating carbon-carbon bonds with enantioselectivity. This reaction can be combined with other catalytic transformations to build up complex organic structures. A successful example is the enantioselective cascade Michael addition/H -hydrogenation catalyzed by ruthenium hydride borohydride complexes containing P-aminophosphine ligands 26 (Scheme 5.13) [19]. This approach has been extended to pentenones, heptenones, and nitrostyrene Michael acceptors and malonitrile Michael donors. 

The area of asymmetric Michael reaction of 1,3-dicarbonyl to enone can be simply divided into three types (Scheme 9.2). In type I, the Michael acceptor (enone) reacts with the prochiral Michael donor to induce a chiral center on the Michael donor side. In type II, the prochiral Michael acceptor reacts with the Michael donor to give an asymmetric center on the Michael acceptor side. For type III, the prochiral Michael acceptor reacts with the prochiral Michael donor to afford adjacent chiral centers on both sides in one step. Because (3-substituted enone is often used as a Michael acceptor in both type II and type III, the catalytic asymmetric Michael addition is generally divided into two classes 1) Michael addition of vinyl ketone and 2) Michael addition of (3-substituted enone. In the asymmetric Michael addition of class I, vinyl ketone is often employed as a Michael acceptor to react with (3-keto ester for... 

Among metal-BINOL complex catalysts developed by Shibasaki et al., (I )-ALB is found to be the most effective catalyst for the asymmetric Michael addition of malonate to 2-cyclohexen-l-one. In 1998, Shibasaki et al. further fine-tuned the reaction 9onditions by adding the base (e.g., KO-r-Bu) and MS (4 A) to the system. These optimizations accelerate the catalytic asymmetric Michael addition without lowering the enantioselectivity. They suggested that the base was used to activate the Aluminum-Lithium-BINOL (ALB) complex. The 4-A molecular sieve (MS) was used to remove the trace amount of H2O that could otherwise gradually lead to ALB-KO-f-Bu catalyst decomposition. In the presence of ALB (0.3 mol%), KO-f-Bu (0.27 mol%), and 4-A MS, the Michael addition of dimethyl malonate to cyclohex-2-enone proceeded smoothly to give 94% product yield with 99% ee even at room temperature. Particularly noteworthy was that this reaction could be carried out on a 100-g scale without deleterious effect. Later, Xu and co-workers modified and streamlined the work-up procedures... 

Enantioselective total synthesis of ((47J,5iS)-5-Amino-4-(2,4,5-tri-fluorophenyl) cyclohex- l-enyl)-(3-(trifluoromethyl)-5,6-dihydro-[l, 2,4]tri-azolo[4,3-a]pyrazin-7(877)-yl)methanone ABT-341 (708), a DPP4 (dipeptidyl peptidase IV) inhibitor, has been completed in diphenylprolinol silyl ether (707), in the one-pot, multicomponent, reaction of nitroalkene (704), acetaldehyde (703), vinyl phosphonate (706) and amine (705) (Scheme 178) A novel, catalytic, asymmetric Michael addition of azomethine ylide (710) with p-substituted tetraethyl alkyhdene bisphosphates (709) has been realised in the presence of a chiral copper(I)/TF-Bipham-Phos (712) complex. This system provided enantioenriched unnatural i -amino acid derivatives (711) containing gem-bisphosphonates in high yields with... 

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