Lewis acid catalysis Michael addition

A similar approach is followed in a recent study of the Lewis-acid catalysis of a Michael addition in acetonitrile. See Fukuzumi, S. Okamoto, T. Yasui, K Suenobu, T. Itoh, S. Otera, J. Chem. Lett. 1997, 667. 

Similar additions may be performed with the enamine 13. However, with 3-buten-2-one or methyl 2-propenoate Lewis acid catalysis is needed to activate the Michael acceptor chloro-trimethylsilane proved to be best suited for this purpose. A remarkable solvent effect is seen in these reactions. A change from THF to HMPA/toluene (1 1) results in a reversal of the absolute configuration of the product 14, presumably due to a ligand effect of HMPA235. 

Intramolecular conjugate allylation (12, 25).2 Fluoride ion catalyzes intramolecular Michael additions of allyltrimethylsilane to a,p-enones as well as a,p-unsaturated esters, nitriles, and amides Lewis acid catalysis is not effective. The method is particularly suited to cyclopentane annelations.2... 

Among the best specific enol equivalents for Michael addition are silyl enol ethers that are rather beyond the scope of this book but are treated in detail in Strategy and Control. So the silyl enol ether 54 of the ester 53 adds to the enone 55 with Lewis acid catalysis to give a reasonable yield of the ketoester 56 considering that two quaternary centres are joined together.6... 

The best alternatives to enamines for conjugate addition of aldehyde, ketone, and acid derivative enols are silyl enol ethers, Their formation and some uses were discussed in Chapters 21 and 26-28, but these stable neutral nueleophiles also react very well with Michael acceptors either spontaneously or with Lewis acid catalysis at low temperature,... 

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

Michael condensations, together with the Diels-Alder cycloaddition and the aldol reactions, are the most powerful and useful bond-fonning reactions in synthetic organic chemistry. Like the nitro-aldol (Henry) additions, nitroalkanes are particularly appropriate reagents in Michael reactions they act as a-hydrogen donors. Nitroalkanes react easily with typical Michael acceptors such as a,p-unsaturated aldehydes or ketones under base or Lewis acid catalysis. ... 

An alternative and useful method for intramolecular conjugate addition when the Michael donor is a ketone is the formation of an enamine and its reaction with a Michael acceptor. This can be advantageous as enamine formation occurs under reversible conditions to allow the formation of the product of greatest thermodynamic stability. Treatment of the ketone 40 with pyrrolidine and acetic acid leads to the bicyclic product 41, formed by reaction of only one of the two possible regio-isomeric enamines (1.51). Such reactions can be carried out with less than one equivalent of the secondary amine and have recently been termed organo-catalysis (as opposed to Lewis acid catalysis with a metal salt). The use of chiral secondary amines can promote asymmetric induction (see Section 1.1.4). 

Xu, L.-W., Li, L. and Xia, C. G., Transition-metal-based Lewis acid catalysis of aza-type Michael additions of amines to a,/ -unsaturated electrophiles in water, Helv. Chim. Acta, 2004, 87,1522-1526. 

Trimethylsilyl enol ethers of acyclic and alicyclic ketones add to a)S-unsaturated nitroalkanes in Michael fashion under Lewis acid catalysis. Direct hydrolysis of the crude product leads to good yields of 1,4-diones.The ease of access to the starting materials, the high regioselectivity of the addition (the reaction conditions do not cause migration of the double bond in the enol ether), and the simplicity of the manipulations involved underline the usefulness of the method (Scheme 15, p. 83). 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

Other nucleophiles such as nitromethane can also be used for this reaction. Thus, by the catalysis of (fl)-LPB (LaK3tris((/ )-binaphthoxide) (20 mol %), in which La works as a Lewis acid and K-naphthoxide works as a Brpnsted base, nitromethane reacted with chalcone to give the Michael adduct in 85% yield and 93% ee (Scheme 8D.8) [22], Addition of BuOH (120 mol %) gave a beneficial effect on the reactivity as well as the enantioselectivity of this reaction. 

Silica-supported Lewis acids are useful catalysts with microwave irradiation for conjugate additions. The silica-supported catalysts are obtained by treatment of silica with ZnCh [Si(Zn)], Et2AlCl [Si(Al)] or TiCl4 [Si(Ti)] [ 150-152], The Michael addition of methyl a-acetamidoacrylate (196) with indole (2) under Si(M) heterogeneous catalysis assisted by microwave irradiation afforded the alanine derivative 197 within 15 min and/or bis-indolyl 198, depending on the reaction conditions (Scheme 45) [153]. While the bis-indolyl product 198 is only formed when Si(Zn) was used as catalyst, the alanine derivative 197, as a single product is formed under thermal heating in a yield of 12%. The best yields were observed with Si(Al) (Table 5). The product 198 was obtained by elimination of acetamide followed by a-Michael addition between intermediate 199 with a second mole of indole. 

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