Conjugate addition reactions activated alkenes

Oxazines can also be synthesized by intramolecular addition of oximes to carbon-carbon double bonds. These reactions are not general nitrones and other products can be formed in competition with oxazines. There are examples of conjugate addition to activated alkenes <81TL2557, 91CPB2830> and of acid or Lewis acid-catalyzed addition to simple alkenes <88TL6805> or allenes <89JCS(P1)2415>. 3-Methyl-6-vinyl-5,6-dihydro-4//-1,2-oxazine was isolated in moderate yield from... 

Scheme 5.40 Nickel-catalyzed conjugate addition reaction of arylboronic acids with activated alkenes, as described by Cheng and coworkers [112].

The catalytic enantioselective addition of vinylmetals to activated alkenes is a potentially versatile but undeveloped class of transformations. Compared to processes with arylmetals and, particularly alkylmetals, processes with the corresponding vinylic reagents are of higher synthetic utility but remain scarce, and the relatively few reported examples are Rh-catalysed conjugate additions. In this context, Hoveyda et al. reported very recently an efficient method for catalytic asymmetric allylic alkylations with vinylaluminum reagents that were prepared and used in Thus, stereoselective reactions... 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

The reactivity of a range of alkenes in addition reactions of peroxyl radicals has been reported. Parameters that described the relationship between the activation energy and enthalpy were calculated. An activation energy of 82 kJ moP was determined for the addition of alkylperoxy radicals to isolated C=C bonds, rising by 8.5kJmor when the alkene was conjugated with an aromatic substituent. 

Michael addition of secondary phosphines on conjugated olefins is a well known reaction in organic synthesis. Accordingly, addition of diphenylphosphine on hydrophilic activated alkenes in CH3CN or in... 

The most reactive Michael acceptors, such as alkylidene malonates, gem-dicyanoalkenes and nitroalkenes, react with a-halozinc esters in a conjugate fashion. Beautiful examples were offered by two stereocontrolled conjugate additions to piperidinone 102 and pyrro-lidinone 104 leading to optically active bicyclic lactams 103147 (equation 60) and 105 (equation 61)148. With these electron-poor alkenes a Grignard two-step protocol is to be adopted in order to avoid the single electron transfer reactions from the metal to the Michael acceptor, which should afford olefin dimers. The best solvent is found to be a... 

The conjugate addition of heteronucleophiles to activated alkenes has been used very often in organic synthesis to prepare compounds with heteroatoms [3 to various activating functional groups, e.g. ketones, esters, nitriles, sulfones, sulfoxides and nitro groups. As in the Michael reaction, a catalytic amount of a weak base is usually used in these reactions (with amines as nucleophiles, no additional base is added). 

The Michael reaction is the conjugate addition of a soft enolate, commonly derived from a P-dicarbonyl compound 24, to an acceptor-activated alkene such as enone 41a, resulting in a 1,5-dioxo constituted product 42 (Scheme 8.14) [52]. Traditionally, these reactions are catalyzed by Bronsted bases such as tertiary amines and alkali metal alkoxides and hydroxides. However, the strongly basic conditions are often a limiting factor since they can cause undesirable side- and subsequent reactions, such as aldol cyclizations and retro-Claisen-type decompositions. To address this issue, acid- [53] and metal-catalyzed [54] Michael reactions have been developed in order to carry out the reactions under milder conditions. 

In comparison to the cyclization reactions shown above, intermolecular Meerwein arylations are often more difficult to conduct. Since the aryl radical addition to the alkene is no longer favored by the close proximity of the reacting centers, the probability for a direct recombination of the aryl radical with scavengers Y is significantly increased (Scheme 17). To maintain the desired reaction course from 44 to 45 including steps (1) and (2) [89, 90], Meerwein arylations have for a long time mostly been conducted with activated alkenes, such as acrylates (R = COOR ), vinylketones (R = COR ), styrenes (R = Ph), or conjugated dienes [91,92]. These types of alkenes are known for fast addition of aryl radicals. 

The importance of transition-metal-catalysed reactions lies in their ability to facilitate reactions that would not occur under normal conditions. One such reaction is nucleophilic attack on an isolated double bond. While the presence of a conjugating group promotes the attack of nucleophiles, in its absence no such reaction occurs. Coordination of an alkene to a transition metal ion such as pal-ladium(II) changes its reactivity dramatically as electron density is drawn towards the metal and away from the n orbitals of the alkene. This leads to activation towards attack by nucleophiles just as for conjugate addition and unusual chemistry follows. Unusual, that is, for the alkene the palladium centre behaves exactly as expected. 

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