Alkynes electron-deficient, Michael addition

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. 

Nitroalkanes react with Jt-deficient alkenes, for example, p-nitro ketones are produced from a,P-unsaturated ketones [41], whereas allylic nitro compounds have been prepared via the Michael-type addition of nitroalkanes with electron-deficient alkynes (Table 6.19). The reaction in either dimethylsulphoxide [42] or dimethyl-formamide [43] is catalysed by potassium fluoride in the presence of benzyltriethyl-ammonium chloride the reaction with dimethyl acetylenedicarboxylate is only successful in dimethylsulphoxide [42], Primary nitroalkanes produce double Michael adducts [42,44], A-Protected a-aminoacetonitriles react with alkynes under catalysed solidiliquid conditions to produce the Michael adducts [45] which, upon treatment with aqueous copper(Il) sulphate, are converted into a,p-unsaturated ketones. 

Selected examples of the Michael-type addition of secondary nitroalkanes with electron-deficient alkynes... 

Tsuchii et al. reported a very interesting four-component domino process where an alkyne, two olefins and diphenyl diselenide sequentially react to form a highly functionalized cyclopentane derivative, after a linear addition sequence and 5-exo-trig cyclization [136]. This reaction can be seen as an interrupted polymerization process initiated by the addition of selenyl radical to an electron-deficient alkyne in the presence of a large excess of a Michael acceptor. The identity of each reaction partner is important for the outcome of the reaction. For instance, use of (PhS)2 instead of (PhSe)2 leads to the polymerization product rather than to the cyclization one, while (PhTe)2 did... 

The title compounds are generally obtained in good yields. The unsubstituted 4H-thiochromen-4-one core is accessible by employing trimethyl-silyl acetylene, where the TMS group is cleaved prior to the Michael addition. Alkynes with electron-donating and electroneutral groups are well tolerated, while electron-deficient (hetero)aryl substituents result in substantially lower yields. 

Carbon-carbon bond forming reactions between carbanionic nucleophiles like enolates or deprotonated nitroalkanes and electron deficient alkenes and alkynes belong to the oldest and most versatile transformations known today (225-229). Moreover, stereoselective variants have proven to possess an enormous potential in the syntheses of complex molecules as already exemplified in Sect. 2.4. Whereas the applications depicted in this previous section utilized nucleophiles activated by enamine formation with a chiral secondary amine catalyst to achieve these highly selective C-C bond formations, the present discussirai will focus on the addition of carbon nucleophiles to iminium-activated Michael acceptors. Herein traditional Michael additions using e.g. enolate nucleophiles will be described whereas the use of aromatic Michael donors with iminium-activated acceptors in Friedel-Crafts type reactions will be discussed separately subsequently. 

Increasing importance has to be attributed to modem tandem (or cascade ) techniques—reaction sequences that can be performed as a one-pot procedure because the first reaction step creates the arrangement of functional groups needed for the second to occur. Schemes 5-7 present some in situ preparations for iminium species, which can then react further with appropriate nucleophiles that are alr dy present (preferably in the same molecule). Most elegantly, in situ generation of iminium ions for tandem processes was performed by a 3,3-sigmatropic (aza-Cope-type) rearrangement (Scheme 5), but also by initial Michael-type addition reactions to vinyl-substituted 1,2,3-tricarbonyls (Scheme 6) or to electron-deficient alkynes via enamines (Scheme 7). ... 

Stannyl enol ethers react with electron-deficient alkenes like or, -unsaturated esters and alkynes in the presence of AIBN to give radicalic carbostannylation adducts, y-stannyl ketones, " " in sharp contrast to the Bu4NBr-mediated reaction, which gives simple Michael adducts. In addition, 1,6-enynes, when applied to this carbostannylation, produce five-membered cyclic adducts. For this particular transformation, electron-deficient groups are not needed (Scheme 3-222). 

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