Vinylogous Michael addition reaction

J. Wang, C. Qi, Z. Ge, T. Cheng, R. li. Efficient direct asymmetric vinylogous Michael addition reactions of y-butenolides to chalcones catalyzed by vicinal primary-diamine salts, Chem. Commun. 46 (2010) 2124-2126. 

The first highly regio-, chemo-, diastereo-, and enantio-selective vinylogous Michael addition of oqa-dicyanoalkenes to oq/S-unsaturated aldehydes employs salts of a,a-diarylprolinol (103) (20 mol%) as organocatalysts. The reaction presumably involves the formation of an iminium species from the aldehyde as the first step of the cascade.153... 

Regioselective addition of 2-methoxyfuran and 2-trimethylsilyloxyfuran to chromium(O) alkynylcarbene complexes furnished interesting dienyne and dienediyne carboxylates <07AGE2610>. The reaction likely proceeded through a formal vinylogous Michael addition adduct, as illustrated in the following example. 

Sharpless bis-cinchona alkaloids such as [DHQD]2PYR (163a) have proved to serve as highly efficient catalysts for the asymmetric vinylogous Michael addition of the electron-deficient vinyl malonitriles 164 as the nucleophilic species to nitroole-fins 124 [50], This process exhibited exclusive y-regioselectivity and high diastereo-and enantioselectivity. Only the anti-products 165 were observed in all reactions (Scheme 9.57). Of note, 1-tetralone did not react with nitroolefins under these... 

Scheme 10.22 Vinylogous Michael addition and domino Michael-retro-Michael reaction.

Compound (120) was prepared from 8,10-dihydrosweroside aglucone (32), which could be alkylated in aprotic solvent in the presence of a strong base to (33). However, under the same conditions, but in the absence of the alkylating agent, a sequence of four base-catalyzed reactions (dimerization by a vinylogous Michael addition, intramolecular aldolization, lactonization and cyclization by hetero Michael addition) gave the final product (120). Detailed analysis of its formation would exceed the frame of this paper [result to be published]. 

Application of solid-state chemistry for quantitative multistep cascades in a ball mill is also demonstrated by reaction of enamine ketone 291 with 1,2-dibenzoylethene 292 (Scheme 3.78). Pyrrole derivative 293 was obtained by Kaupp et al. in quantitative yield through four reaction steps (vinylogous Michael addition, imine/enamine rearrangement, cyclization, and elimination), without the use of add catalysts [18]. 

Li and co-workers [129] developed the first enantioselective organocatalytic direct vinylogous Michael addition of y-butenolides 130 to chalcones catalyzed by the vicinal primary-diamine salt 56 (Scheme 5.64). The reaction proceeded smoothly to afford the highly valuable chiral y-butenolides 131 with good yields and high... 

Most recently, Terada and co-workers [132] realized the first organocatalytic asymmetric direct vinylogous Michael addition of a-tert-butylthio-substituted furanones to nitroalkenes. The reaction was catalyzed by axially chiral guanidine 133, leading to densely functionalized y-butenolides 130a in high iy/j-diastereo- and enantioselectivities. However, no example has showed for the unsubstituted -y-butenolide (Scheme 5.65). 

S. Oxindole Derivatives. Most recently, Curti et al. [140] disclosed the first example of a direct, organocatalytic asymmetric vinylogous Michael addition of 3-alkylidene oxindole to nitroalkenes. Bifunctional cinchona alkaloid/thiourea catalyst 69 could effectively promote the reaction, solely aHbrding the 7-substituted 3-alkylidene oxindoles 146 with excellent regio-, diastereo-, and enantioselectivities (Scheme 5.71). Importantly, both aromatic and aliphatic substituted nitroalkenes were applicable for such a reaction. 

Scheme 35 Vinylogous Michael addition-cyclization cascade reaction to form spiro-oxindoles...

Other nucleophiles, such as dicyanoolefins, have been submitted to orga-nocatalysed Michael additions with a,p-unsaturated aldehydes by Loh et al., in 2008. Therefore, a pool of water-compatible catalysts, namely dialkyl-(. -prolinols, was developed for the enantioselective direct vinylogous Michael addition of vinylmalononitriles to a,p-unsaturated aldehydes in aqueous medium. In all the reactions tested, only the ufM/i-Michael addition products were obtained. Notably, the best results in both yields and enantioselectivities were obtained by using the catalyst bearing a hexyl group, as shown in Scheme 1.11. 

This type of catalyst was also employed by Christmann et al. to promote the asymmetric intramolecular Diels Alder reaction of tethered a,p-unsaturated dialdehydes in the presence of benzoic acid as a co-catalyst through vinylogous enamine activation. The corresponding cycloadducts were obtained in good yields and excellent enantioselectivities of up to 98% ee, as shown in Scheme 6.6. When one of the aldehyde functions was replaced by an a,p-unsaturated ketone as the acceptor, no formal [4 -I- 2] cycloaddition was observed instead, a direct enantioselective vinylogous Michael addition occurred. 

In 2010, Xie reported a vinylogous Michael addition of 3-cyano-4-methylcou-marins to a,P-unsaturated ketones using primary amine catalysts derived from cinchona alkaloids to promote the reaction. The final compounds were afforded in good yields and good enantioselectivities [88]. 

A different kind of vinylogous Michael addition of y-substituted deconjugated buteno-lides (444) to -nitrostyrenes was catalysed by the modified cinchona-derived thiourea (440). The reaction proceeded at -36 C and gave the adducts (445) with >20 1 dr and <98% ec.294... 

The Michael reaction is of central importance here. This reaction is a vinylogous aldol addition, and most facts, which have been discussed in section 1.10, also apply here the reaction is catalyzed by acids and by bases, and it may be made regioselective by the choice of appropriate enol derivatives. Stereoselectivity is also observed in reactions with cyclic educts. An important difference to the aldol addition is, that the Michael addition is usually less prone to sterical hindrance. This is evidenced by the two examples given below, in which cyclic 1,3-diketones add to o, -unsaturated carbonyl compounds (K. Hiroi, 1975 H, Smith, 1964). 

Torgov introduced an important variation of the Michael addition allylic alcohols are used as vinylogous a -synthons and 1,3-dioxo compounds as d -reagents (S.N. Ananchenko, 1962, 1963 H. Smith, 1964 C. Rufer) 1967). Mild reaction conditions have been successful in the addition of ],3-dioxo compounds to vinyl ketones. Potassium fluoride can act as weakly basic, non-nudeophilic catalyst in such Michael additions under essentially non-acidic and non-basic conditions (Y. Kitabara, 1964). 

When the enamine is in conjugation with a carbonyl function, as in a-aminomethylene aldehydes (528,529), ketones (530), or esters (531), a Michael addition is found in vinylogous analogy to the reactions of amides. An application to syntheses in the vitamin A series employed a vinyl lithium compound (532). 

Chen and co-workers utilized the chiral bifunctional catalysts to directly access vinylogous carbon-carbon bonds via the asymmetric Michael addition of a,a-dicy-ano-olefms to nitro-olefms [102]. The scope of the reaction was explored with a variety of substituted a,a-dicyano-olefins and P-substituted nitro-olefms (Scheme 50). The authors propose the catalysf s tertiary amine functionality depro-tonates the cyano-olefm, activating the nucleophile to add to the -face of the pre-coordinated nitro-olefm. 

The base-catalyzed Michael addition of oxazolin-5-ones to alkynic ketones produces 4-(3-oxopropenyl) derivatives (405) (79CB3221). The latter compounds are cleaved on warming with oxalic acid dihydrate in acetic acid to y-diketones (406). The mechanism of this transformation corresponds to a vinylogous Dakin-West reaction (Scheme 90). 

Intermolecular Michael addition [4.1] Intermolecular aldol reaction [6.2.1] Intramolecular aldol reaction [6.2.2] Aldol-related reactions (e.g. vinylogous Mukaiyama-type aldol) [6.2.3]... 

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