Electron-withdrawing-group enals

In a related paper, Scheldt and co-workers described a stereoselective formal [3 + 3] cycloaddition catalyzed by imidazolinylidine catalyst 256 Eq. 25 [130]. Ultimately this is an intermolecular addition of the homoenolate intermediate to an azomethine ylide followed by intramolecular acylation and presumably follows the same mechanistic path as described previously. Pyridazinones are obtained as single diastereomers in good to high yield from a number of aldehydes. Unfortunately no reaction occurs with the presence of electron-withdrawing groups on the aryl ring of the enal. 

Allylic pinacols. Reduction of ketones bearing an electron-withdrawing group with TiCli in the presence of a,p-enals results in coupling to allylic pinacols in 45 85% yield. Example ... 

Almost all the electrophilic groups or electrophilic intermediates can be employed as the hydride acceptors, e.g., alkylidene malonates, carbophilic transition metals activated alkynes or allenes, enal/enones, aldehyde/ketones, imines, ketenimine/car-bodiimides, metal carbenoids, alkynes carrying electron-withdrawing groups, as well as in situ-generated carbocations (Fig. 3). 

Later, Cid and Ruano reported that aryl-acetonitriles bearing an electron-withdrawing group at the ortho- or poro-position could serve as suitable nucleophiles in organocatalytic Michael reactions with enals [39]. The reaction proceeded with good yields and good enantioselectivities, albeit with low... 

In 2006, Bode and coworkers reported the first enantioselective inverse-electron-demand hetero-Diels-Alder reaction of enals 130 with a,(i-unsaturated imines 131 under the catalysis of carbene precatalyst 123 in combination with Hiinig s base [59]. A broad range of substrates were well tolerated to afford synthetically important dihydropyridinone products 132 in good yields with remarkable enantioselec-tivities (Scheme 38.38). The need to introduce electron-withdrawing groups for enals only lies within the increased electrophilicity of these substrates, which enhances the rate of their reaction with the nucleophilic catalysts. The observed... 

The aforementioned epoxidation has been also performed using imidazolidinone 58 in combination with perchloric acid and (nosylimino)iodo benzene as hyperva-lent iodine oxidant. In this manner, several a,P-unsaturated aliphatic aldehydes were epoxidized in high yields and enantioselectivities (72-93%, 87-97% ee) [65], with only enals possessing an electron-withdrawing group being unreactive under these reaction conditions. 

Asymmetric Diels-Alder Reaction of Unsaturated Aldehydes . The boron atom of acyloxyborane is activated by the electron-withdrawing acyloxy groups, and consequently acyloxyborane derivatives are sufficiently Lewis acidic to catalyze certain reactions. Thus, asymmetric Diels-Alder reactions of a,p-enals with dienes using (1) as a Lewis acid catalyst have been developed. For example, the reaction of cyclopentadiene and methacrolein gives the adduct in 85% yield (endo exo= 11 89) and 96% ee (major exo isomer) (eq 3). Some additional examples are listed in Figure 1. The a-substituent on the dienophile increases the enantioselectivity, while p-substitution dramatically decreases the selectivity. In the case of a substrate having substituents in both a- and p-positions, high enantioselectivity is observed thus the a-substituent effect overcomes that of the p-substituent. 

In 2012, Scheldt and coworkers developed the enantioselective [3 + 2] an-nulation of enals and isatins under NHC/Lewis acid cooperative catalysis. Both electron-withdrawing and electron-donating groups were tolerated, furnishing the spiro-oxindole lactones 56 in good yields and with high enantioselectivities. The spiro-oxindole lactone was converted into maremycin B in five steps and in 17% overall yield (Scheme 20.27). 

In 2013, the Scheidt group reported the NHC-catalysed formal [4 + 2] an-nulation of enals with imidazolidinones to afford enantioenriched bicyclic lactones 105. A Bronsted acid is an essential additive to achieve high chemoselectivity, as is an electron-withdrawing aryl substituent at the 2-position of the imidazolidinone (Scheme 20.46). 

The condensation of the imine, derived from 2-fluoro-3-methylbut-2-enal and benzylamine, with tosyhnethyl isocyanide (TosMIC) prodnced A -benzyl-5-(l-fluoro-2-methylpropenyl)imidazole (Scheme 54) [69]. However, a similar condensation between the imine from 4,4,4-triflnoro-3-methyl-bnt-2-enal and benzylamine with TosMIC was ineffective, presumably due to the strong-electron withdrawing effect of the CFj group which caused unfavorable charge distribution in the a,p-unsaturated Systran of the imine. This prevents the initial TosMIC attack on the iminic C-position and leads to self-decomposition of TosMIC under the reaction conditions. 

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