Vinylogous Michael reactions

The iron catalysis of vinylogous Michael reactions is not only restricted to dimerizations. The y-donor 46b can be converted with MVK (41a) to give the 1,7-dioxo-constituted product 49 when the catalyst is Fe(III) (Scheme 8.21) [75]. If NaOMe in MeOH is applied as the catalyst, reaction of the dienolate of donor 46b in the a-position with acceptor 41a proceeds via a normal Michael reaction and 1,5-dioxo-constituted product 50 is obtained. 

Scheme 8.21 Base-catalyzed Michael and iron-catalyzed vinylogous Michael reactions.

Scheme 8.22 Synthesis of a naphthobenzofuran derivative by vinylogous Michael reaction.

Christoffers, J. Catalysis of the Michael reaction and the vinylogous Michael reaction by ferric chloride hexahydrate. Synlett 200, 723-732. 

Scheme 3.9 Vinylogous Michael reaction of dicyanoacrylates with a,P-unsaturated aldehydes.

Remarkably, the reaction also tolerated the use of differently substituted a-alkyl-p-ketoesters as Michael donors, leading to the formation of compounds containing two contiguous stereogenic centers, one of them a quaternary one, in good diastereo- and enantioselectivities (Scheme 4.6). Masked cyclic 1,3-diketones such as 2-hydroxy-1,4-naphthoquinols have also been successfully applied in this context also showing the extraordinary performance of catalyst 68a in terms of both yields and enantioselectivities. There is also one example of a vinylogous Michael reaction between a,a-disubstituted dicyanoacrylates and nitroalkenes for which Takemoto s catalyst has also been identified as the most efficient promoter of the reaction. Moreover a solid-supported version of this catalyst has also been developed by Takemoto himself and tested in the reaction of diethylmalonate with nitrostyrene with success. ... 

A vinylogous Michael reaction has also been reported using enolizable doubly activated alkylidenes as Michael donors and acrolein as Michael acceptor (Scheme 4.39). In this case, the reaction furnished regioselectively the corresponding a-addition products, the unsaturation remaining in the final adduct at the p-position. After optimizing the reaction conditions, modified... 

Scheme 6.15 Enantioselective vinylogous Michael reactions catalyzed by chiral Bronsted bases.

Despite of the significant progress made in asymmetric Michael reactions, most of the catalytic methodologies are applicable only for the functionalization of electron-dehcient olehns at the (3 position. The enantioselective construction of C—C bonds at the y position of olefins has met with limited success. Recently, with the exploitation of the vinylogy concept [121], the asymmetric vinylogous Michael reaction has emerged as an effective strategy to address this synthetic issue [3e,122]. 

SCHEME 5.63. Direct vinylogous Michael reaction of a,a-dicyanoalkenes. 

Zhang, Y. Shao, Y.-L. Xu, H.-S. Wang, W. J. Organocatalytic Direct Asymmetric Vinylogous Michael Reaction of an a,P-Unsaturated y-Butyrolactam with Enones. Org. Chem. 2011,76,1472-1474. 

After MacMillan s pioneering work on the VMM-type reaction, a number of oiganocatalysts were applied to similar reaction systems. Among these, direct vinylogous Michael reaction attracted much attention. For example, Alexakis reported that diphenylprolinol silyl ether 142 and aminal-pyrrolidine catalyst 143 are effective for the direct reaction of angelica lactone 140a with a,p-enal 137b (Scheme 59) [101]. In this case, it was also mentioned that furan-2(5H)-one itself does not work as a suitable nucleophile. 

SCHEME 60 Enantioselective direct vinylogous Michael reaction of chalcone. 

H. Huang, F. Yu, Z. Jin, W. Li, W. Wu, X. Liang, J. Ye, Asymmetric vinylogous Michael reaction of a,p-unsaturated ketones with y-butenolide rmder multifimctional catalysis, Chem. Commrm. 46 (2010) 5957-5959. 

In a related study, the same researchers used guanidine 52 for the enantioselective vinylogous Michael reaction of furanone 53 with various aromatic and aliphatic nitroalkenes (Scheme 10.50) [143]. In addition, several additional asymmetric transformations catalyzed by axially chiral guanidines were reported by Terada and coworkers between 2009-2012 (Schemes 10.51-55) [144-148]. 

Scheme 10.50 Enantioselective vinylogous Michael reaction of furanone 53.

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