Michael addition of enolate

Deprotection of 2,2-disubstituted-l,3-dithiolanes to give carbonyl compounds can be achieved using Oxone with KBr in aq. MeCN <06TL8559> and a review of silylated heterocycles as formyl anion equivalents includes reference to 64 <06CC4881>. A method for transformation of propargylic dithiolanes 43 into tetrasubstituted furans has been reported <06SL1209> and Michael addition of enolates to the chiral dithiolane dioxide 65 takes place... 

Selective formation of 1,5-dicarbonyl compounds by 1,4-addition (Michael addition) of enolates to enones is facilitated by the use of enol silyl ethers as enolate equivalents [37]. The reaction is catalyzed by... 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

The hindered aluminum tris(2,6-diphenylphenoxide) is an effective promoter of Michael additions of enolates to enones.89... 

A double ir-face selective aptotic Michael addition of the lithium dienolate, derived from the chiral senecioate (119), to cyclopentenone served for the total synthesis of (-)-kushimone (120 Scheme 45).137-138 The selectivity of the key reaction was rationalized by the assumption of a transition state as shown in (121a). A related approach involves the Michael addition of enolates, derived from chiral propionates, to methyl ( )-crotonate (Scheme 46).139 The formation of the threo isomer (122) as the major product indicates a transition state structure as shown in (121b). This method was utilized in the synthesis of the marine natural product 7,20-diisocyanoadociane (123 Scheme 47).140... 

Diastereoselective Michael additions of enolates, prepared from the chiral amides (127) and (128), to prochiral a.p-unsaturated esters were utilized in the synthesis of (+)-dehydroiridodiol (129) and its isomer (130 Scheme 49).143... 

Michael addition.2 This triflate is an effective catalyst for Michael addition of enol silyl ethers to a,P-enones such as methyl vinyl ketone to provide adducts in 60-75% yield, equation (I). This variation is useful in Robinson annelations. 

Using organometallic reagents to make C-C bonds 17 Nucleophilic substitution at saturated carbon 20 Electrophilic addition to alkenes 22 Electrophilic aromatic substitution 29 Conj ugate Michael addition of enolates 39 Radicals... 

Michael addition of enolates to a,[3-unsaturated compounds is a good way of making 1,5-difunction-alfeed compounds, and you should look for these 1,5-relationships in target molecules with a view to making them in this way, Our example is rogletimide, a sedative that can be disconnected to a 1,5-diester. Further 1,5-diCO disconnection gives a compound we made earlier by ethylation of the ester enolate. 

In another study we have constructed a bicyclo[2.2.2]octane library using a tandem Michael addition of enolates of 2-cyclohexenones with various substituted acrylates.7 9 In this way it was possible to prepare a rigid scaffold, from readily available substrates, which could be further elaborated by transformation of the functional groups to give a large array of compounds (Scheme 6). This synthesis required minimal optimisation and... 

Dibutyltin bis(triflate), Bu2Sn(OTf)2, is a mild Lewis acid which catalyzes clean Michael addition of enol silyl ethers [148]. The new catalyst enables use of various labile acceptors such as methyl vinyl ketone and 2-cyclopentenone which do not undergo smooth reaction with conventional Lewis acids. A variety of enol silyl ethers are also employable and thus 2-(trimethylsiloxy)propene, the simplest of this class of compounds, can be used. The adducts of enol silyl ethers of cycloalkanones with vinyl ketones are readily cyclized to give the desired annulated enones free of isomers. Consequently, a practical version of the Robinson annulation has been realized. 

The Michael addition of enolates to vinyl sulfones allows one-pot tandem reactions to be devised to achieve cyclisations as illustrated in Scheme 55. In the first reaction, the enolate (131) is transformed into the cyclic p-hydroxy sulfone (132) in good yield. In the second reaction, the enolate (133) yields the tricyclic compound (134) as a result of a double Michael reaction followed by intramolecular elimination of the benzenesulfonyl group. 

The Michael addition of enolates to vinyl sulfones is facilitated by the introduction of carbanion-stabiIising groups at the a-vinylic position, as illustrated in Scheme 56. 

Diketones are accessible via a number routes, for example by Michael addition of enolate to enone (or precursor Mannich base " ) or by ozonolysis of a cyclopentene precursor. They react with ammonia, with loss of two mole equivalents of water to produce cychc bis-enamines, i.e. 1,4-dihydro-pyridines, which are generally unstable, but can be easily and efficiently dehydrogenated to the aromatic heterocycle. 

Diketones are obtained by Michael addition of enolates or enamines (see above) to a,P-unsaturated carbonyl compounds. 

Another example of organocatalytic Michael addition apphed in total synthesis is that J0rgensen and co-workers [38] developed an asymmetric total synthesis of (/ )-warfarin (104) in 2003 as shown in Scheme 17.17. The key Michael addition of enol 101 to enone 102 was catalyzed by chiral diamine 103 to afford (/ )-warfarin (104) in... 

Dicarbonyl compounds (accessible by Michael addition of enolates or enamines to a,P-unsaturated carbonyl compounds) undergo cyclocondensation with NH3 to afford 1,4-dihydropyridines 158, whose dehydrogenation leads to pyridines 159 ... 

Transprotonation equilibrium plays a vital role in the Michael addition of enolates to methyl-styryl sulfone 536. The primary anion obtained this way cyclizes to the anellation product 538 in quantitative yield. 

---