Alkynes Michael addition

In certain cases, Michael reactions can take place under acidic conditions. Michael-type addition of radicals to conjugated carbonyl compounds is also known.Radical addition can be catalyzed by Yb(OTf)3, but radicals add under standard conditions as well, even intramolecularly. Electrochemical-initiated Michael additions are known, and aryl halides add in the presence of NiBr2. Michael reactions are sometimes applied to substrates of the type C=C—Z, where the co-products are conjugated systems of the type C=C—Indeed, because of the greater susceptibility of triple bonds to nucleophilic attack, it is even possible for nonactivated alkynes (e.g., acetylene), to be substrates in this... 

Cyanation of vinylic organometallic compounds Addition to activated alkynes (Michael)... 

In a, P-unsaturated carbonyl compounds and related electron-deficient alkenes and alkynes, there exist two electrophilic sites and both are prone to be attacked by nucleophiles. However, the conjugated site is considerably softer compared with the unconjugated site, based on the Frontier Molecular Orbital analysis.27 Consequently, softer nucleophiles predominantly react with a, (i-unsaturated carbonyl compounds through conjugate addition (or Michael addition). Water is a hard solvent. This property of water has two significant implications for conjugate addition reactions (1) Such reactions can tolerate water since the nucleophiles and the electrophiles are softer whereas water is hard and (2) water will not compete with nucleophiles significantly in such... 

The Michael addition of nitro compounds to electron-deficient alkynes affords allylic nitro compounds in good yields, in which KF-/j-Bu4NC1 in DMSO is used as a base and solvent (Eq. 4.118).161... 

A new three-component approach to the highly substituted 2,5-dihydro-l,2,4-oxadiazoles 359 has been reported from the reaction of nitriles 354 under mild conditions with iV-alkylhydroxylamines 355 in the presence of electron-deficient alkynes 356 (Scheme 60) <20050L1391>. This synthesis is proposed to proceed via the initial formation of the alkyl or arylamidoximes 357, which then undergo a sequential double Michael addition to the electron deficient alkyne. The intermediate alkyl or arylamidoximes 357 can be isolated and then reacted with the alkyne to produce the product. The initial Michael adduct 358 is stable in cases where R2 is H. 

Michael additions of 7r-allyl species to alkynes were employed for the synthesis of elaborated carbocycles as in the ruthenium-catalyzed cycloisomerization of 1,6-enynes (Equation (188)).1... 

Alkyne dipolarophiles such as methyl propiolate or DMAD reacted with ylides derived from [l,2,3]triazolo[l,5-tf]-pyridines, but the mechanism proposed involved a Michael addition and subsequent nucleophilic attack rather than a concerted [4+2] cycloaddition <1996T10519> (see Section 11.13.8). 

Similarly, alkenylzirconium species prepared by the hydrozirconation of alkynes add in a conjugated fashion to enones. Formation of an intermediate zincate prior to transmetalation to the copper species facilitates the Michael addition (Scheme 2.62) [135]. This methodology has been applied to the preparation of protected misoprostol 129 (Scheme 2.63) [136, 137]. 

Among the catalytic asymmetric alkyne additions to the sp carbon center, such as carbonyl, imines, and iminiums, truly metal-catalyzed alkyne addition to alkenes is rare. By using a PINAP derivative (Figure 5.4), Cu-catalyzed Michael addition... 

A plausible mechanism for the ring expansion (Scheme 65) proceeds via an intermediate zwitterion A, resulting from Michael addition of the tertiary nitrogen to the alkyne. Cleavage of the C(l)-N bond occurs via formation of the six-membered transition state B in which a molecule of alcohol facilitates the Sn reaction. 

Another approach for the synthesis of networks relies on the polycondensation of multifunctionalized polyesters with the appropriate multifunctionalized agent, provided that one of the partner is at least tri-functionalized. Toward this end, several reaction have been reported, such as the Michael addition of amines onto acrylates [184], the coupling of ketones and oxyamines [185], the click copper(II)-catalyzed azide-alkyne cycloaddition [186], and esterification reactions [25, 159, 187]. Interestingly, if esterification reactions are used, the crosslinks are then degradable. 

This reaction achieves an umpolung cyclization in vhich a terminal alkyne is hydrated and undergoes an intramolecular Michael addition according to the mechanism depicted in Scheme 6.34. 

Macrolactone synthesis 6,51, 71, 72, 94, 124,131,163,187,195 McMurry coupling 43 Medium ring synthesis 43,45,75, 77 Metathesis, Alkene (see Grubbs) Metathesis, Alkyne (see alkyne metathesis) Michael addition Intramolecular 166,166, 167,201 Intermolecular 57,84, 153, 166,204... 

The base-catalyzed Michael addition of oxazolin-5-ones to alkynic ketones produces 4-(3-oxopropenyl) derivatives (405) (79CB3221). The latter compounds are cleaved on warming with oxalic acid dihydrate in acetic acid to y-diketones (406). The mechanism of this transformation corresponds to a vinylogous Dakin-West reaction (Scheme 90). 

Pyrrole and 1-alkylpyrroles generally react with ir-deficient alkenes and alkynes to give Michael addition products (see Section 3.05.1.2.6), but Diels and Alder (3lLA(490)267) reported that 1-methylpyrrole also gave a 1 2 adduct with DM AD formulated as (229), which could be derived from a [w4+w2] cycloaddition of a second molecule of DM AD with the initially formed Michael adduct (cf. Section 3.05.2.3). Subsequent work, however, has shown structure (229) for the 1 2 adduct to be incorrect, the true structure being (230) (63AHC(i)i25, 78AHC(23)265). The formation of the dihydroindole (230) requires the initial... 

As is to be expected, an alkynic ketone undergoes a Michael addition with a carbanion, leading eventually to a pyranone (50JA1022). Using malonic esters, a 3-alkoxycarbonyl derivative results, which is hydrolyzed to the 2-oxopyran-3-carboxylic acid under alkaline conditions, but to the pyranone by sulfuric acid. Rapid ester exchange is observed with the initial products, the alcohol used as solvent determining the nature of the alkyl group in the 3-carboxylic esters (Scheme 90). 

In the case of a ketone with two active methylene groups, such as dibenzylketone, the reaction can take two courses. The pyranone results from Michael addition to the alkyne followed by normal ring closure. The second product, a resorcinol, arises from either Michael condensation followed by an intramolecular Claisen condensation or the order of these two reactions may be reversed (60JCS5153). 

The products of the reaction of 4-hydroxy-6-methylpyran-2-one with alkynic esters show some dependence on the solvent used. Dimethyl butyndioate yields the bicyclic pyranone (325) in the absence of solvent and using Triton B as the catalyst. Michael addition is envisaged to yield the intermediate dione (324) which cyclizes in the normal manner... 

Resin-bound amines can be converted into imines [710,711] or enamines by reaction with carbonyl compounds (Entries 6 and 7, Table 3.39). Resin-bound enamines have also been prepared by Michael addition of resin-bound secondary amines to acceptor-substituted alkynes [712], by Hg(II)-catalyzed addition of resin-bound secondary amines to unactivated alkynes [713], by addition of C-nucleophiles to resin-bound imino ethers [714], and by chemical modification of other resin-bound enamines [712,713,715], Acceptor-substituted enamines ( push-pull alkenes) are not always susceptible to hydrolytic cleavage by TFA alone and might require aqueous acids to undergo hydrolysis [716]. 

As with Michael additions to activated alkenes, the initial adducts with activated alkynes can be trapped by various processes. An aldol reaction can occur if a carbonyl is properly situated in the starting material (Scheme 71).123 However, the use of methyl ethynyl ketone (509) and its homologs in the Robinson annulation process to give cyclohexadienones (510 equation 110) usually proceeds in poor... 

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