Aldehydes as Michael acceptors

However, if we make a small change in the structure by adding two methyl groups 13, our favoured disconnection 13a would be possible only after the discovery of five-valent carbon We shall have to find a way to use unsaturated aldehydes as Michael acceptors. 

The use of ot,p-unsaturated aldehydes as Michael acceptors always represents a challenging situation because of the tendency of enals to undergo 1,2- rather than the desired 1,4- addition reaction. Moreover, working under phase-transfer catalysis conditions incorporates an additional element of difficulty, because of the propensity of enolizable enals to undergo self-condensation side reactions. For this reason, there are only a few examples reporting enantioselective Michael reactions with ot,p-unsaturated aldehydes as Michael acceptors under PTC conditions, both coming from the Maruoka research team and also both making use of chiral tV-spiro quaternary ammonium salts as catalysts. 

Thiamine-catalyzed transformations are reversible, thus TV,/V-dialkyl hydrazones were selected as alternative acyl anion equivalents that were reported to react with electrophiles without acidic activation.41 One especially reactive example, formaldehyde hydrazone resin 13, was constructed from polymer-supported hydrazines and was employed in the first polymer-supported, uncatalyzed acyl anion additions (Fig. 8).38 As test substrates, nitroalkenes (as Michael acceptors) and activated aldehydes were selected. Reactivity of these acyl anion equivalents depended critically not only on the nature of the starting hydrazine, but also on the protocol for hydrazine formation. 

As mentioned above, the enantioselective Michael addition of P-keto esters to a,P-unsaturated carbonyl compounds represents a useful method for the construction of densely functionalized chiral quaternary carbon centers. One characteristic feature of designer chiral phase-transfer catalyst lh in this type of transformation is that it enables the use of a,p-unsaturated aldehydes as an acceptor, leading to the... 

C-Nucleophiles have recently been added asymmetrically to azodicarboxylates as Michael-acceptors, resulting in a-amination of the nucleophilic component. Examples of this type of reaction, which is based on activation of the aldehyde or ketone component by enamine formation, are summarized in Scheme 4.27. Please note that this type of reaction is covered in more detail in chapter 7 of this book. 

The A -diphenylmethylene protection has also been used in the solid-phase mode for the synthesis of either unnatural amino acidst 1 or peptides (Scheme 67)J 1 Thereby, both Merrifield or Wang resins were used and the best base proved to be the organic soluble, nonionic phosphazene bases of Schwesinger, e.g. 2-tert-(butylimino)-2-(ethylamino)-l,3-di-methyl-l,3,2-diazaphosphinane (BEMP). As electrophiles alkyl halides,aldehydes, and Michael acceptors have been used. 

Thus, the zwitterionic enolatoruthenium(II) complex smoothly reacts with electrophiles such as Michael acceptors and aldehydes. 

Bis(phenylsulfonyl)methane has also been employed as an acidic carbon pronucleophile related to malonates and 1,3-diketones with success in the Michael reaction with ot,p-unsaturated aldehydes using 31c as catalyst (Scheme 3.6). The reaction showed a remarkable substrate scope when alkyl-substituted enals were employed but failed when cinnamaldehyde was tested as Michael acceptor. Alternatively, a more acidic cyclic gem-bissulfone has been used as Michael donor, keeping the high yields and enantioselectivities observed for the reaction and also allowing to expand the scope of the reaction to several aromatic enals.In all cases, the chemistry of the sulfonyl group was employed to generate a methyl group after metal-mediated desulfuration or, alternatively. 

There is also an example of a one-pot reaction in which an initial Michael addition of a functionalized aldehyde containing an olefin moiety at the convenient position to a nitroalkene as Michael acceptor was followed by the formation of a 1,3-dipole and a subsequent intramolecular [3 + 2] cycloaddition (Scheme 7.12). In this case, ethyl 7-oxo-2-heptenoate was reacted with a series of nitroalkenes using 31a as catalyst and next A -hydroxylphenylamine was added to the reaction mixture, promoting the formation of the corresponding... 

Dihydrojasmone is also much valued as a scented compound because of its floral and fruity character. A convenient synthetic route is provided by the Stetter reaction (a reaction of aldehydes with Michael acceptors in the presence of thiazohum salts, developed by Hermann Stetter (1917-1993)) of methyl vinyl ketone and heptanal [90], followed by an intramolecular aldol condensation. 

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