Conjugate addition reactions Potassium /-butoxide

Iodine-Mercury(II) oxide, 149 Lithium diisopropylamide-Potassium /-butoxide, 164 Molybdenum carbonyl, 194 Phenyliodine(III) diacetate, 242 Sulfuryl chloride, 284 Conjugate addition reactions Michael reactions Alumina, 14... 

The asymmetric Michael reaction can be catalysed by enantiomerically pure crown ethers in the presence of base. For instance the addition of cyclic donor (11.16) with acceptor (11.22) occurs with up to 99% ee using an enantiomerically pure crown ether in the presence of potassium tert-butoxide. In fact, enantiomerically pure crown ethers have been used to catalyse other Michael reactions, including the use of crown ether (11.45) in the conjugate addition reaction between the ester (11.46) and Michael acceptor (11.47). The reaction is remarkably rapid (one minute at —78°C). 

Lithium butyldimethylzincate, 221 Lithium sec-butyldimethylzincate, 221 Organolithium reagents, 94 Organotitanium reagents, 213 Palladium(II) chloride, 234 Titanium(III) chloride-Diisobutylalu-minum hydride, 303 Tributyltin chloride, 315 Tributyl(trimethylsilyl)tin, 212 3-Trimethylsilyl-l, 2-butadiene, 305 Zinc-copper couple, 348 Intramolecular conjugate additions Alkylaluminum halides, 5 Potassium t-butoxide, 252 Tetrabutylammonium fluoride, 11 Titanium(IV) chloride, 304 Zirconium(IV) propoxide, 352 Miscellaneous reactions 2-(Phenylseleno)acrylonitrile, 244 9-(Phenylseleno)-9-borabicyclo[3.3.1]-nonane, 245 Quina alkaloids, 264 Tributyltin hydride, 316 Conjugate reduction (see Reduction reactions)... 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium fert-butoxide induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocyclic double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cyclization-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization [73]. 

With unsymmetrical ketones, a mixture of regioisomeric enolates may be formed, resulting in a mixture of Michael adducts. Deprotonation in a protic solvent is reversible and leads predominantly to the thermodynamically favoured, more-substituted enolate. Reaction with a Michael acceptor then gives the product from reaction at the more-substituted side of the ketone carbonyl group. The 1,5-dicarbonyl compound 24 is the major product from conjugate addition of 2-methylcyclohexanone to methyl acrylate using potassium tert-butoxide in the protic solvent tert-butanol (1.39). In contrast, the major product from Michael addition... 

As part of a projected synthesis of corrins, a simple synthesis of y-substi-tuted y-butyrolactams via the conjugate addition of hydrogen cyanide to unsaturated ketones is described contrary to a much earlier report, the )S-cyanohydrin (101) is not produced, but a mixture of the two butyro-lactams (102) and (103) is isolated, (103) being convertible into (102) by reaction with basic cyanide solution. Reaction of one of those, (102), with potassium t-butoxide in t-butyl alcohol gave, inter alia, the semi-corrinoid (104), These transformations are outlined in Scheme 35. 

One of the many benefits of the conjugate addition approach stems from the ability of the product to self-catalyze the reaction. Carreira and Fettes reported on an oxa-conjugate addition in the synthesis of leucascandrolide A in 2002 [22]. Exposure of hydroxy enone 15 to a catalytic quantity potassium ferf-butoxide under thermodynamic conditions provided the A ring pyran 16 in good yield (63 %) and with a dr of 10 1 favoring the 2,6-cis product (Scheme 4). 

The application of strong bases to hydrocarbons which contain a sp3 hybridized carbon and a conjugated system may abstract a proton and form a fully conjugated carbanion. This reaction has several synonyms such as deprotonation, proton abstraction or metalation reactions. The most common bases are alkyl lithium derivatives, e.g., butyl lithium21 24). Sometimes the addition of tetramethylethylenediamine (TMEDA) or potassium ferf-butoxide is required especially when dianions and polyanions are prepared 24e,f). Ether solvents or hydrocarbon solvents are most common. This process can be demonstrated by the preparation of anthraene dianion 22 from 9,10-dihydroanthracene (1)25). The metalation reaction can also be carried out in the NMR tube. 

The monocyclopropanation of conjugated dienes is relatively easily realized, in comparison to unconjugated dienes (Section 1.2.1.4.2.1.3.), since the remaining double bond is deactivated after the addition of the first molecule of dichlorocarbene. It is also possible to prepare diadducts by using excess of carbene source to diene and by the correct selection of method for the generation of the carbene. The chloroform/base/phase-transfer catalyst method is suitable for the synthesis of either mono- or diadducts, while the chloroform/potassium tert-butoxide method allows the monoadducts to be obtained, often in high yields. The examples of the reactions of 16,and 1849,84,85 illustrate the problems. 

When isomerization of the double bond of the intermediate cyclopropene into the exo methylene position is energetically unfavored, double elimination followed by double addition of base can occur. Thus, reaction of (cu/tra i )-l,l-dichloro-2-methyl-3-vinylcyclopropane (9) with potassium terf-butoxide plus methoxide in dimethyl sulfoxide gave a mixture of cis- and trans-, -dimethoxy-2-methyl-3-vinylcyclopropane (10). Both double bonds formed via elimination appear to be conjugated with the vinyl group and do not migrate to the exo position. The similar reaction of l,l-dichloro-2-[( )-propenyl]cyclopropane (11) gave a small amount of 1-/ert-butoxy-2-(prop-2-enylidene)cyclopropane (13) in addition to products of double addition. Without added methoxide, 13 was the only product isolated. ... 

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