Aldol and Michael reactions

Acrolein reacts slowly in water to form 3-hydroxypropionaldehyde and then other condensation products from aldol and Michael reactions. Water dissolved in acrolein does not present a hazard. The reaction of acrolein with water is exothermic and the reaction proceeds slowly in dilute aqueous solution. This will be hazardous in a two-phase adiabatic system in which acrolein is suppHed from the upper layer to replenish that consumed in the lower, aqueous, layer. The rate at which these reactions occur will depend on the nature of the impurities in the water, the volume of the water layer, and the rate... 

Heck reactions can also be combined with anion capture processes, animations, metatheses, aldol and Michael reactions, and isomerizations. The anion capture process has also been widely used with other Pd-catalyzed transformations. Outstanding examples of many different combinations have been developed by Grigg and coworkers, though not all of them match the requirements of a domino process. All of these reactions will be detailed here, despite the fact the nature of these intermediate transformations would also have permitted their discussion in Chapter 2. 

These retro-Aldol and -Michael reactions can, obviously, follow an isomerization of the aldose to the corresponding ketose, leading thereby to different Aldol fragments or retro-Michael products. Keto-enol exchange as well as the retro-... 

Fig. 2.3 Key reactions in carbohydrate conversion (the arrows represent the retro-Aldol and Michael reactions).

Aldol and -Michael reactions can also proceed on the reaction products of retro-Aldol and -Michael reactions. The reverse (direct) Aldol and Michael reaction can also proceed on various intermediates. Hence, these few reactions can already form a very large variety of possible products. They, indeed, account for most of the reactivity of carbohydrates discussed below, being under pyrolysis, hydrolysis or fermentation conditions. 

Samarium and other lanthanide iodides have been used to promote a range of Mukaiyama aldol and Michael reactions. The syntheses show promise as enantio-selective transformations, but the precise mechanistic role of the lanthanide has yet to be elucidated. 

Le Roux C, Gaspard-Iloughmane H, Dubac J, Jaud J, Vignaux P (1993) New effective catalysts for Mukaiyama-aldol and -Michael reactions bismuth trichloride-metallic iodide systems. J Org Chem 58 1835-1839... 

Crtm-aldol and Michael reactions. CsF is an effective catalyst in reactions of ullyl cool i-lhri s with aldehydes and keloncs lo form i./l-unsaluratcd ketones. 

Combining aldol and Michael reactions in one sequence is very powerful, particularly if one of the reactions is a cyclisation. The Robinson annelation9 makes new rings in compounds like 73 that were needed to synthesise steroids. Disconnection of the enone reveals triketone 74 having 1,3- and 1,5-dicarbonyl relationships. The 1,3-disconnection would not remove any carbon atoms but the 1,5-disconnection at the branchpoint gives a symmetrical 3-diketone that should be good at conjugate addition. 

Aldol and Michael reactions of nitriles.3 Activated nitriles such as ethyl cy-anoacetate react with aldehydes or ketones in the presence of this ruthenium catalyst... 

For aldol and Michael reaction of nitriles, cyclopentadienyl ruthenium enolate complexes shows catalytic activity. The reaction of 2-methylphenylacetonitrile with ethyl acrylate gave the corresponding Michael addition product in 99% yield (Eq. 9.58) [79]... 

In place of active methylene compounds having a nitrile group, malonates, 13-ketoesters, 1,3-diketones, 1,1-disulfones, nitro compounds, Mel drum acid, and anthrone can also be used as the Michael donors for these ruthenium-catalyzed aldol and Michael reactions. The reaction proceeds well in acetonitrile under mild and neutral conditions (Eq. 9.59) [83]. 

Proton abstraction of the polar C-H bond with base is a well-established heteroly-tic C-H bond cleavage to obtain carbanion. Ruthenium complexes can act as a base in nonpolar media to provide highly selective catalyses, as in the Murahashi aldol and Michael reactions. These reactions are highly chemoselective under neutral and mild conditions, where cyanoesters preferentially react over 2,4-pentanedione with nucleophiles (Scheme 14.12) [26]. The mechanistic basis of this reaction is described in Section 14.2.2. 

Low-valent Ru(II) [150] and Rh(I) complexes catalyze aldol and Michael reactions of 2-nitrilo esters. The sequence is thought to be initiated by nitrile complexation to the transition metal. This Lewis acid-activation is followed by an oxidative addition to give a metal hydride and a nitrile complexed enolate as shown in Sch. 36. Examples including diastereoselective Ru(II) catalyzed reactions [151] and enantioselective Rh(I)-catalyzed reactions [152-154] with the large trans-chelating chiral ligand PhTRAP are shown in Tables 8 and 9. 

The basic character of lanthanide alkoxides such as Lu3(Of-Bu)9 seem to effect aldol, cyanosilylation, aldol, and Michael reactions [111]. Complexes 2 and 22, abbreviated as LnMB (Ln = lanthanide, M = alkali metal, B = BR IOL) [112] were thoroughly studied in the catalytic, asymmetric nitroaldol reaction (Henry reaction eq. (10)) [113]. 

Retro-aldol and retro-Michael reactions occur under acidic conditions. The mechanisms are the microscopic reverse of the aldol and Michael reactions, as you would expect. One of the most widely used acid-catalyzed retro-aldol reactions is the decarboxylation of jS-ketoacids, malonic acids, and the like. Protonation of a carbonyl group gives a carbocation that undergoes fragmentation to lose CO2 and give the product. Decarboxylation does not proceed under basic conditions because the carboxylate anion is much lower in energy than the enolate product. 

Tin (II) enolates have been widely used by Mukaiyama and coworkers in aldol and Michael reactions. These enolates are generated by action of Sn(OTf)2 on ketones, esters, N-acy -1,3-oxazolidin-2-ones or -l,3-thiazolidin-2-thiones, thi-olesters or dithioesters in the presence of chiral diamines 2.13 (R = CH2NHAr or CH2N(CH2)5) bearing the (S)-proline skeleton [253, 559, 682]. Diastereoiso-meric and enantiomeric excesses observed in these reactions are often excellent. 

Concerning BiCl3, this weak Lewis acid proved an unexpected catalyst in the Mukaiyama-cross aldol and -Michael reactions from enoxysilanes (ref. 28), because other metallic chlorides (TiCl4, A1C13, SnCl4...) and stronger Lewis acids, are required in stoichiometric proportion for these reactions (ref. 29). On the other hand, more recently, i has been shown that ... 

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