Acids, conjugated, addition

Keywords Atom transfer Chiral Lewis acid Conjugate addition ... 

Indoles can also be alkylated by conjugate addition under alkaline conditions. Under acidic conditions, alkylation normally occurs at C3 (see Section 11.1). Table 9.1 includes examples of alkylation by ethyl acrylate, acrylonitrile, acrylamide and 4-vinylpyridine. 

Conjugate acid (Section 1 13) The species formed from a Brpnsted base after it has accepted a proton Conjugate addition (Sections 1010 and 1812) Addition reaction in which the reagent adds to the termini of the con jugated system with migration of the double bond synony mous with 1 4 addition The most common examples include conjugate addition to 1 3 dienes and to a 3 unsaturated car bonyl compounds... 

Isomerization. Maleic acid is isomerized to fumaric acid by thermal treatment and a variety of catalytic species. Isomerization occurs above the 130 to 140°C melting point range for maleic acid but below 230°C, at which point fumaric acid is dehydrated to maleic anhydride. Derivatives of maleic acid can also be isomerized. Kinetic data are available for both the uncatalyzed (73) and thiourea catalyzed (74) isomerizations of the cis to trans diacids. These data suggest that neither carbonium ion nor succinate intermediates are involved in the isomerization. Rather, conjugate addition imparts sufficient single bond character to afford rotation about the central C—C bond of the diacid (75). 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

Physical and Chemical Properties. The (F)- and (Z)-isomers of cinnamaldehyde are both known. (F)-Cinnamaldehyde [14371-10-9] is generally produced commercially and its properties are given in Table 2. Cinnamaldehyde undergoes reactions that are typical of an a,P-unsaturated aromatic aldehyde. Slow oxidation to cinnamic acid is observed upon exposure to air. This process can be accelerated in the presence of transition-metal catalysts such as cobalt acetate (28). Under more vigorous conditions with either nitric or chromic acid, cleavage at the double bond occurs to afford benzoic acid. Epoxidation of cinnamaldehyde via a conjugate addition mechanism is observed upon treatment with a salt of /-butyl hydroperoxide (29). 

The striking effect of the catalyst is exemplified by the reaction of pregna-4, 16-diene-3,20-dione (10) with benzyl mercaptan. In the presence of piperidine only conjugate addition occurs to give (11) whereas with pyridine hydrochloride only the 3-benzyl thioenol ether (12) is formed. In the presence of p-toluenesulphonic acid both reactions take place to yield (13). 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

The use of thiocyanic acid for thiirane synthesis is usually compatible with many functional groups found in natural steroids. The method has found application in androstanes, pregnanes, cholestanes, cholanates and cardeno-lides. However, the presence of a,j5-unsaturated carbonyl groups may decrease the yield of the thiocyanatohydrin due to conjugate addition of thiocyanic acid. Indeed, the 1,4-addition of thiocyanic acid has been carried... 

Conjugate addition of strong nucleophiles to the >C=N—C=C< moiety, followed by ring opening of the resulting saturated 5 4H)-oxazolone. Thus, 57 reacts with simple or peptidic amino acid esters [Eq. (31)]. Similarly, 62 gives 63 in methanolic 7i-propylamine, and... 

Chiral Cu(ll)-complexes ofbis-oxazolines as Lewis acids for catalyzed cycloaddition, carbonyl addition, and conjugate addition reactions 99PAC1407. 

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

Quite a number of asymmetric thiol conjugate addition reactions are known [84], but previous examples of enantioselective thiol conjugate additions were based on the activation of thiol nucleophiles by use of chiral base catalysts such as amino alcohols [85], the lithium thiolate complex of amino bisether [86], and a lanthanide tris(binaphthoxide) [87]. No examples have been reported for the enantioselective thiol conjugate additions through the activation of acceptors by the aid of chiral Lewis acid catalysts. We therefore focussed on the potential of J ,J -DBFOX/ Ph aqua complex catalysts as highly tolerant chiral Lewis acid catalyst in thiol conjugate addition reactions. 

With the success in Lewis acid-catalyzed thiol conjugate addition reactions mentioned above, we further tried to apply the J ,J -DBFOX/Ph-nickel(II) aqua complex catalyst to the catalyzed asymmetric conjugate addition reactions of hydroxyl-amines [88, 89]. However, after some preliminary examinations, we found that... 

The l ,J -DBFOX/Ph-transition metal aqua complex catalysts should be suitable for the further applications to conjugate addition reactions of carbon nucleophiles [90-92]. What we challenged is the double activation method as a new methodology of catalyzed asymmetric reactions. Therein donor and acceptor molecules are both activated by achiral Lewis amines and chiral Lewis acids, respectively the chiral Lewis acid catalysts used in this reaction are J ,J -DBFOX/Ph-transition metal aqua complexes. 

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