Asymmetric Michael-Type Addition Reaction

The Michael-type addition reaction of a carbonucleophile with an activated olefin constitutes one of the most versatile methodologies for carbon-carbon bond formation [1]. Because of the usefulness of the reaction as well as the product, many approaches to the asymmetric Michael-type addition reactions have been reported, especially using chirally modified olefins [2-8]. However, the approach directed towards the enantioselective Michael-type addition reaction is a developing area. In this Chapter, the recent progress of the enantioselective Michael-type addition reaction of active methylene compounds and also organometallic reagents with achiral activated olefins under the control of an external chiral ligand or chiral catalysts will be summarized [9]. 

The Michael reaction is an addition of an active methylene compound to an activated olefin, indicating that both Lewis base and Lewis acid are necessary for the activation of the Michael donor as well as the Michael acceptor. The recent focus is centered on the multifunctional catalyst which works as both Lewis base and Lewis acid. 

The recent progress in the Michael addition reaction of active methylene compounds with a, -unsaturated carbonyl compounds has been characterized by the 

The first catalytic asymmetric tandem Michael-aldol reactions were also achieved by the Al-Li-binol complex (ALB), which was prepared from LiAlH4 and binol. The ALB catalysts gave the Michael adducts in up to 99% ee (Eq. (12.2)) [12J. Mechanistic and calculation studies on ALB revealed that ALB is a heterobimetallic complex which acts as a multifunctional catalyst. 

In the presence of a catalytic amount of [(f )-l,l -bi-2-naphthaIenediolato(2)-0,0 ]oxotitanium 2, silyl enol ethers derived from thioesters reacted with cyclo-pentenone to afford the corresponding Michael adducts in high yields and up to 90% ee (Eq. (12.3)) [6]. 

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K. Tomioka, Asymmetric Michael-Type Addition Reaction, in Modem Carbonyl Chemistry, Ed. ... 

The first prominent catalytic asymmetric Michael-type addition reaction of an organolithium reagent was shown by the reaction of 1-naphthy[lithium with 1-fluoro-2-naphthylaldehyde imine in the presence of 6 to afford the binaphthyls in high ee. Only catalytic amounts of 6 (0.05 mol%) effects the reaction to give 82% ee, in which an enantioselective Michael-type addition-elimination mechanism is operative (Eq. (12.12)) [31],... 

The prominent asymmetric Michael-type addition reaction of arylborane was realized using binap-Rh catalyst 38 (Eq. (12.32)) [77, 78],... 

Asymmetric Michael-type addition reactions with participation and/or formation of heterocycles 00MI11. 

To date, several different catalysts, both organocatalysts and metal-based catalysts, are available for the asymmetric Michael-type addition reactions. Indeed, a high level of achievement has been reached in terms of enanatioselectiv-ity and product yield. However, specihc windows for particular substrates, especially in natural product motif synthesis, are stdl in great demand. Thus, the exploration of more gen-eraL as well as more operationally simple (e.g., moisture stable and air stable), catalysts is attainable. Through the further in-depth structural investigation of catalyst-substrate interaction in Michael addition, a more sophisticated, yet more efficient, catalyst can be developed, and thus, the Turn Over Number (TON) can be expected to be increased. These future developments certainly will be fmitfiil to pharmaceutically and industrially related processes. 

The importance of chiral thiols and thioether linkages in biological systems has prompted intense investigation of the use of chiral amines [see e.g. 5-11] and ammonium salts [see e.g. 12] as agents for asymmetric induction in the Michael-type addition reaction. Considerable success has been achieved using chinchona alkaloids and their A-alkyl derivatives (see Chapter 12). 

Asymmetric Michael Reactions. Asymmetric induction has been observed in Michael-type addition reactions that are catalyzed by chiral amines. The Ai-benzyl fluoride salt of quinine has been particularly successful since the fluoride ion serves as a base and the aminium ion as a source of chirality. Drastic improvements in optical purity (1-23%) have resulted by changing from quinine to the N-benzyl fluoride salt (eq 11). ... 

The Michael-type addition reaction of nucleophilic reagents with chirally modified a,jff-substituted carbonyl compounds constitutes the established methodology for the preparation of y9-substituted carbonyl compounds. The disadvantage of this type of asymmetric Michael reaction is the loading and disloading process of the chiral auxiliary on the Michael acceptor. However, this type of the reaction has been well documented to give the adduct with a high level of diastereoselectivity [83, 84]. 

In the early 1980 s Julia and Colonna published a series of papers which, to some extent, filled the gap left by the natural biocatalysts. The Spanish and Italian collaborators showed that a, -unsaturated ketones of type 1 underwent asymmetric oxidation to give the epoxide 2 using a three-phase system, namely aqueous hydrogen peroxide containing sodium hydroxide, an organic solvent such as tetrachloromethane and insoluble poly-(l)-alanine, (Scheme 1) [12]. The reaction takes place via a Michael-type addition of peroxide anion (the Weitz-Scheffer reaction). 

Aluminum salen complexes have been identified as effective catalysts for asymmetric conjugate addition reactions of indoles [113-115]. The chiral Al(salen)Cl complex 128, which is commercially available, in the presence of additives such as aniline, pyridine and 2,6-lutidine, effectively catalyzed the enantioselective Michael-type addition of indoles to ( )-arylcrolyl ketones [115]. Interestingly, this catalyst system was used for the stereoselective Michael addition of indoles to aromatic nitroolefins in moderate enantiose-lectivity (Scheme 36). The Michael addition product 130 was easily reduced to the optically active tryptamine 131 with lithium aluminum hydride and without racemization during the process. This process provides a valuable protocol for the production of potential biologically active, enantiomerically enriched tryptamine precursors [116]. 

Proline was among the first compounds to be tested in asymmetric conjugated reactions, both as a chiral ligand [8] and also as an organic catalyst [3]. The earliest asymmetric intermolecular Michael-type addition, in which proline catalyzed the reaction (arguably via enamine formation) was reported by Barbas and colleagues [9, 10] and by List and co-workers [11]. The reaction, which proceeded in high chemical yield (85-97%) and diastereoselectivity, albeit afforded near-racemic products in dimethyl sulfoxide (DMSO) [11] (Scheme 2.37). The enantio-selectivity of the addition was later ameliorated by Enders, who demonstrated that a small amount of methanol rather than DMSO was beneficial to the enantiose-lectivity of the addition reaction [12]. 

Stereoselectivity. See Asymmetric induction Axial/equatorial-, Cis/trans-, Enantio-, Endo/exo- or Erythro/threo-Selectivity Inversion Retention definition (e.e.), 107 footnote Steric hindrance, overcoming of in acylations, 145 in aldol type reactions, 55-56 in corrin synthesis, 261-262 in Diels-Alder cyclizations, 86 in Michael type additions, 90 in oiefinations Barton olefination, 34-35 McMurry olefination, 41 Peterson olefination, 33 in syntheses of ce-hydrdoxy ketones, 52 Steric strain, due to bridges (Bredt s rule) effect on enolization, 276, 277, 296, 299 effect on f3-lactam stability, 311-315 —, due to crowding, release of in chlorophyll synthesis, 258-259 in metc-cyclophane rearrangement, 38, 338 in dodecahedrane synthesis, 336-337 in prismane synthesis, 330 in tetrahedrane synthesis, 330 —, due to small angles, release of, 79-80, 330-333, 337... 

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