Asymmetric vinylogous Michael

The asymmetric vinylogous Michael addition of 4-dicyanovinylthiochromans 309 to ot,(3-unsaturated aldehydes proceeds under catalysis by chiral a,a-diarylprolinol salts and exhibits excellent regio-, chemo-, diastereo-, and enantio- selectivities (Equation 46) <2006CC1563>. 

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 19.33 Organocatalytic asymmetric vinylogous Michael (AVM) reaction of 3-alkylidene oxindoles with nitro-olefins promoted by thiourea 17.

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]. 

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. 

The asymmetric vinylogous Michael addition of y-butenolide(buteno-4-lactone) to RCH=CHCH=0 has been reported to proceed with high enantioselectivity and moderate diastereoselectivity in the presence of the Jprgensen-Hayashi catalyst (123a) and AcOLi.236... 

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. 

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. 

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 this context, Woggon and coworkers [21e] appHed an asymmetric vinylogous aldol/Michael reaction in the total synthesis of a-tocopherol (44). They converted enantiomerically pure phytenal and substituted saHcylaldehyde 40 into lactol 42 (Scheme 8.13). Using proHnolether J -41 as the chiral organocatalyst, they obtained the lactol in 60% yield with a diastereomeric ratio of 97 3, which was measured after oxidation to the lactone 43. 

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). 

Styrylisoxazoles. On the basis of their previous achievements using styryhsoxazoles as vinylogous electrophiles in the Michael addition with a variety of soft nucleophUes, Bernardi and Adamo [137] fulfilled the successful application of styrylisoxazoles 138 in the asymmetric vinylogous conjugate addition with... 

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 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]. 

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. 

In contrast to the extensive use of nitroolefins in asymmetric Michael additions [10], the vinylogous analogues, nitrodienes and nitroenynes, are less frequently utilized in the conjugate addition of enolate equivalents, despite the significant synthetic utility of the resulting products which possess carbonyl, nitro, and olefin functionalities. Likewise, studies on the hetero-Michael reaction with these acceptors have been very limited, possibly because of apprehension of the site-selectivity issue [11]. 

B.M. Trost, J. Hitce, Direct asymmetric Michael addition to nitroalkenes vinylogous nudeophiUcity under dinudear zinc catalysis, J. Am. Chem. Soc. 131 (2009) 4572-4573. 

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