Michael addition of aldehydes to nitroolefins

Fig. Z5 Proposed transition state models for the Michael addition of aldehydes to nitroolefins...

Hydroxyprolinamides (408) have been reported to catalyse the Michael addition of aldehydes to nitroolefins at 5 mol% loading and an unusually low aldehyde excess (l.Sequiv) with high yn-diastereoselectivity (99 1 dr) and enantioselectivity (<98%... 

Regarding substrate scope, catalysts 22a, 30,37, and 40-44 (Fig. 2.4) are efficient promoters for the Michael addition of aldehydes to p-alkyl substituted nitrooleflns. Taken advantage of the good activity exhibited by catalyst 30 in this process, Alexakis et al. have achieved the total synthesis of the mycotoxin (-)-botryodiplodin [73], process which involves an attractive Michael addition between an aldehyde and an a-substituted nitroolefin (Scheme 2.21). 

A 1,2,3-triazole-based solid-phase click linker was developed with an aldehyde functionality or a regenerative Michael acceptor (REM) functionality (Figure 11.1). In addition, a chiral pyrrolidine catalyst was grafted to the resin with a 1,2,3-triazole linker, enabling enantioselective Michael addition of ketones to nitroolefins... 

Figure 2.8 Some active catalysts in the Michael addition of aldehydes or ketones to nitroolefins in aqueous media.

Primary amine organocatalysts give good yields (up to 93%) and ees (up to 98%) in Michael addition of naphthoquinone to various a ,/3-unsaturated ketones, with several 0 intermediates identified by ESI-MS. A 4-(aminothiourea)prolinol dithioacetal (110) gives up to 98% performance on yieWde/ee in Michael addition of ketones and aldehydes to nitroolefins, at 3 mol% loading and ambient temperature. ... 

A BINAP-derived bifunctional thiophosphoramide gives >98% del>99% ee in Michael addition of cyclohexanones to both aryl- and alkyl-substituted nitroolefins. Imidazolylmethyl ketones undergo one-pot Michael-aldol cascade reactions with Q ,/3-unsaturated aldehydes in DCM at 20 °C using the simple organocatalyst, prolinol... 

As for iminium catalysis, the enamine Michael addition was shown to have a great potential for the fast construction of simple drugs. The group led Benjamin List reported on the highly challenging addition of acetaldehyde to nitroolefins for the synthesis of three different small bioactive natural products (Scheme 11.21). " The Michael adducts 83 obtained using commercial catalyst in 88% to 94% ee and containing both aldehyde and nitro functionality could be transformed by a classic one- to three-step transformation... 

N-terminal L-proline, again in DMSO as solvent [40], In this study the maximum ee in the addition of acetone to trans-2-nitrostyrene was 31%. Alexakis and Andrey successfully employed the bis-pyrrolidine 52 as catalyst for the addition of aldehydes and ketones to trans-fi-nitrostyrene [41], whereas Barbas and Betancort [42] were able to perform the Michael addition of unprotected aldehydes to nitroolefins using the pyrrolidine derivative 53 as catalyst (Scheme 4.24). 

Andrey O, Alexakis A, Tomassini A, Bemardinelli G (2004) The Use of iV-AIkyl-2,2 -Bipyrrolidine Derivatives as Organocatalysts for the Asymmetric Michael Addition of Ketones and Aldehydes to Nitroolefins. Adv Synth Catal 346 1147... 

Cheng and Luo [51] synthesized surfactant-type asymmetric organocatalysts 47 (SATO) for the Michael addition of ketones and aldehydes to nitroolefins in water (Scheme 8.20). High enantioselectivities up to 98% and diastereoselectivities up to 99 2 were observed in water without using any organic solvent or additional additive. These SATO catalysts work in a dual manner that is, they function as asymmetric catalysts to accelerate the reactions and simultaneously act as surfactants, thus helping solubilize the organic substrates. 

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