Aldol condensation Michael reaction

Butylation of phenylacetonitrile with aqueous NaOH, as shown in Scheme 25, proceeds faster by use of high DF (>0.5) anion exchange resins.The strongly alkaline conditions degrade the quaternary ammonium ions of the catalyst. Catalyst (64) (1% DVB) is active for alkylation of phenylacetonitrile and benzyl phenyl ketone, and for Williamson ether synthesis, and it is much more stable in base than AERs. AERs in OH form are catalysts for dichlorocyclopropane syntheses from alkenes, chloroform and solid sodium hydroxide, and for dehydration of amides to nitriles. AERs in the appropriate hydroxide, acetate, or cyanide form are catalysts for aldol condensations, Michael reactions, Knoevenagel condensations, cyanoethylations and cyanohydrin syntheses. " ... 

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... 

Examples of commercially applied solid base catalysts are much fewer than for solid acids. Nevertheless, much attention is currently focused on the development of novel solid base catalysts for classical organic reactions such as aldol condensations, Michael additions, and Knoevenagel condensations, to name but a few. 

At 673 K the product distribution over the palladium catalysts (Figure 4) was still highly selective to MIBK (> 80%) however further aldol condensation of acetone with MO to form the three intermediates, phorone, 4,4 -dimethyl hepta-2,6-dione and 2,4-dimethyl hept-2,4-dien-6-one was observed. These species were formed by aldol condensation of acetone with MO at different points in the molecule (10). All can continue to react either by subsequent aldol condensation, Michael addition, or hydrogenation as per Figure 1. There was no detectable isophorone produced, the product of internal 1,6-aldol reaction of... 

Classical organic reactions that have been carried out in water include, among others, the Diels-Alder reaction, the Claisen rearrangement, aldol condensations, Michael additions, and nucleophilic substitutions. In the Diels-Alder reaction, for example, water has been found to increase the reaction rate and to enhance the endoselectivity 120). Two reviews summarize the results for organic reactions in water 121). 

P-Acetamido ketones. A three-component condensation involving a ketone, an aldehyde, and acetonitrile appears to involve aldol and Michael reactions and hydration of nitrilium species, which is quite unusual. 

Aldol and Michael reactions. (C F<>< lyst for these reactions. Thus the aldol cond aldehyde can be conducted at -78°C. Aqi The analogous condensation with imines p Epoxide rearrangement With the t favored during the rearrangement. 

This reaction is related to the Aldol Condensation, Michael Addition, and Wichterle Reaction. 

Enders, D., Joie, C., Deckers, K. (2013). Organocatalytic asymmetric synthesis of tetracyclic pyridocarbazole derivatives by using a Diels-Alder/aza-Michael/Aldol condensation Domino reaction. Chemistry - A European Journal, 19, 10818-10821. 

Since aliphatic nitroalkanes are active methylene compounds, these may be used as starting materials for the preparation of more complex products by typical reactions of methylene compounds such as alkylations, aldol condensations, Michael condensations, and Mannich reactions. 

Other strong base reactions such as Michael additions, aldol condensations, Wittig reactions, Darzens condensations, carbene reactions Oxidations using hypochlorite, hydrogen peroxide, oxygen, permanganate Epoxidations... 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

The method was applied to the synthesis of (-t-)-l9-nortestosterone by the following sequence of reactions. Michael addition of the bisannulation reagent 124 to the optically active keto ester 129 and decarboxylation afforded 130, and subsequent aldol condensation gave 131. Selective Pd-catalyzed oxidation of the terminal double bond afforded the diketone 132 in 78% yield. Reduction of the double bond and aldol condensation gave ( + )-19-nortestosterone (133)[114]. 

Ba.se Catalyzed. Depending on the nature of the hydrocarbon groups attached to the carbonyl, ketones can either undergo self-condensation, or condense with other activated reagents, in the presence of base. Name reactions which describe these conditions include the aldol reaction, the Darzens-Claisen condensation, the Claisen-Schmidt condensation, and the Michael reaction. 

The best method to achieve a high regioselectivity is the use of preformed enolates. A double annulation reaction is possible if, for example, a diketone such as 11 is used as starting material. The product of the Michael addition 12 can undergo two subsequent aldol condensation reactions to yield the tricyclic dienone 13 ... 

The Michael reaction with enamines is exemplified in this procedure. In a second (spontaneous) step of the reaction, an aldol-type condensation occurs resulting in cyclization. Finally, the morpholine enamine of the product forms and is hydrolized by the addition of water to yield a mixture of octalones, which is separated by fractional crystallization. J -Octalone-2 can be reduced by lithium in anhydrous ammonia to the saturated tra/i5-2-decalone (Chapter 3, Section III). 

The first step of the Robinson annulation is simply a Michael reaction. An enamine or an enolate ion from a jS-keto ester or /3-diketone effects a conjugate addition to an a-,/3-unsaturated ketone, yielding a 1,5-diketone. But as we saw in Section 23.6,1,5-diketones undergo intramolecular aldol condensation to yield cyclohexenones when treated with base. Thus, the final product contains a six-membered ring, and an annulation has been accomplished. An example occurs during the commercial synthesis of the steroid hormone estrone (figure 23.9). 

In this example, the /3-diketone 2-methyJ-l,3-cyclopentanedione is used to generate the enolate ion required for Michael reaction and an aryl-substituted a,/3-unsaturated ketone is used as the acceptor. Base-catalyzed Michael reaction between the two partners yields an intermediate triketone, which then cyclizes in an intramolecular aldol condensation to give a Robinson annulation product. Several further transformations are required to complete the synthesis of estrone. 

The intramolecular Michael addition of acyclic systems is often hampered by competing reactions, i.e., aldol condensations. With the proper choice of Michael donor and acceptor, the intramolecular addition provides a route to tram-substituted cyclopentanones, and cyclopentane and cyclohexane derivatives. Representative examples are the cyclizations of /3-oxo ester substituted enones and a,/J-unsaturated esters. 

These reactions imply an aldol condensation following the initial Michael addition. Two examples in which absolute stereocontrol over three or four new stereogenic centers is achieved in a single operation illustrate the potential of these methods. 

Base-induced eliminative ring fission, in which both the double bond and the sulfone function take part, has been observed in thiete dioxides253. The reaction can be rationalized in terms of initial Michael-type addition to the double bond of the ring vinyl sulfone, followed by a reverse aldol condensation with ring opening. The isolation of the ether 270c in the treatment of 6c with potassium ethoxide (since the transformation 267 -> 268 is not possible in this case) is in agreement with the reaction mechanism outlined in equation 101253. 

During 1989-93 lithium perchlorate iethyl ether (LiC104 EtiO, LP-DE) was studied as a reaction medium in organic synthesis when it was observed that cycloadditions, sigmatropic rearrangements, Michael additions and aldol condensations carried out in LP-DE occurred quickly and selectively under mild reaction conditions [33]. In addition, LP-DE allowed the reaction and subsequent work-up to be carried out under essentially neutral conditions. 

Lipase from C.antarctica also catalyzes carbon-carbon bond formation through aldol condensation of hexanal. The reaction is believed to proceed according to the same mechanism as the Michael additions [113]. Lipase from Pseudomonas sp. 

There is some similarity between the cracking of petroleum and the cracking of biomass. However, biomass is more complex chemically both in terms of structrual types and functional groups. In petrochemistry, hydrocarbons are fractionated and they are then functionalized by oxidation, halogenation, nitration and other chemical processes so as to add value. The commodity chemicals are then built up into more complex molecules using such popular synthetic methods as Friedel Craft reactions, Michael and aldol condensations, and Heck and Suzuki couplings. The speciality products of these reactions are then further elaborated into formulations for use in everyday applications ranging from personal care... 

Besides the domino Michael/SN processes, domino Michael/Knoevenagel reactions have also been used. Thus, Obrecht, Filippone and Santeusanio employed this type of process for the assembly of highly substituted thiophenes [102] and pyrroles [103]. Marinelli and colleagues have reported on the synthesis of various 2,4-disubstituted quinolines [104] and [l,8]naphthyridines [105] by means of a domino Michael addition/imine cyclization. Related di- and tetrahydroquinolines were prepared by a domino Michael addition/aldol condensation described by the Hamada group [106]. A recent example of a domino Michael/aldol condensation process has been reported by Brase and coworkers [107], by which substituted tetrahydroxan-thenes 2-186 were prepared from salicylic aldehydes 2-184 and cycloenones 2-185 (Scheme 2.43). 

Domino processes involving Homer-Wadsworth-Emmons (HWE) reactions constitute another important approach. Among others, HWE/Michael sequences have been employed by the group of Rapoport for the synthesis of all-cis-substituted pyrrolidines [143], and by Davis and coworkers to access new specific gly-coamidase inhibitors [144]. Likewise, arylnaphthalene lignans, namely justicidin B (2-281) and retrojusticidin B (2-282) [145], have been synthesized utilizing a domino HWE/aldol condensation protocol developed by Harrowven s group (Scheme 2.65) [146]. 

A SN reaction-based domino route to clerodane diterpenoid tanabalin (2-488) [258] has been described by Watanabe s group (Scheme 2.111) [259]. This natural product is interesting as it exhibits potent insect antifeedant activity against the pink bollworm, Pectinophora gossypiella, a severe pest of the cotton plant The domino sequence towards the substituted trans-decalin 2-487 as the key scaffold is induced by an intermolecular alkylation of the (5-ke toes ter 2-484 with the iodoalkane 2-483 followed by an intramolecular Michael addition/aldol condensation (Robin-... 

Derivatization of the optically active aldehydes to imines has been used for determination of their enantiomeric excess. Chi et al.3 have examined a series of chiral primary amines as a derivatizing agent in determination of the enantiomeric purity of the a-substituted 8-keto-aldehydes obtained from catalysed Michael additions. The imine proton signals were well resolved even if the reaction was not completed. The best results were obtained when chiral amines with —OMe or —COOMe groups were used [2], The differences in chemical shifts of diastereo-meric imine proton were ca. 0.02-0.08 ppm depending on amine. This method has been also used for identification of isomers of self-aldol condensation of hydrocinnamaldehyde. 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

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