Ester enolates, Michael addition

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. ... 

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 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. 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

The Pd enolates also undergo intramolecular Michael addition when an enone of suitable size is present in the allyl d-keto ester 744[465]. The main product is the saturated ketone 745, hut the unsaturated ketone 746 and ally-lated product 747 are also obtained as byproducts. The Pd-catalyzed Michael... 

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a p unsaturated carbonyl compounds This reaction called the Michael reaction has been described for anions derived from p diketones m Section 18 13 The enolates of ethyl acetoacetate and diethyl malonate also undergo Michael addition to the p carbon atom of a p unsaturated aldehydes ketones and esters For example... 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

In the Michael addition of achiral enolates and achiral Michael acceptors the basic general problem of simple diastereoselection (see Section D.1.5.1.3.2.), as described in Section 1.5.2.3.2. is applicable. Thus, the intermolecular 1,4-addition of achiral metal enolates to enones, a.jS-unsat-urated esters, and thioamides, results in the formation of racemic syn-1,2 and/or anti-3,4 adducts. 

Four different orientations are possible when the enantiofaces of (E)- and (Z)-enolates and an ( )-enone combine via a closed transition state, in which the olefinic moieties of the donor and the acceptor are in a syn arrangement. It should be emphasized that, a further four enan-tiomorphous orientations of A-D are possible leading to the enantiomers 2 and 3. On the basis of extensive studies of Michael additions of the lithium enolates of esters (X = OR) and ketones (X = R) to enones (Y = R) it has been concluded ... 

The Michael addition of lithium enolates of amides, which have preferentially the Z geometry, under kinetically controlled conditions to a,/i-unsaturated esters provides a highly... 

Thus the product in such cases can exist as two pairs of enantiomers. In a di-astereoselective process, one of the two pairs is formed exclusively or predominantly as a racemic mixture. Many such examples have been reported. In many of these cases, both the enolate and substrate can exist as (Z) or (E) isomers. With enolates derived from ketones or carboxylic esters, (E) enolates gave the syn pair of enantiomers (p. 146), while (Z) enolates gave the anti pair. Addition of chiral additives to the reaction, such as proline derivatives, or (—)-sparteine lead to product formation with good-to-excellent asynunetric induction. Ultrasound has also been used to promote asymmetric Michael reactions. Intramolecular versions of Michael addition are well known. ... 

Domino transformations combining two consecutive anionic steps exist in several variants, but the majority of these reactions is initiated by a Michael addition [1]. Due to the attack of a nucleophile at the 4-position of usually an enone, a reactive enolate is formed which can easily be trapped in a second anionic reaction by, for example, another n,(5-urisalurated carbonyl compound, an aldehyde, a ketone, an inline, an ester, or an alkyl halide (Scheme 2.1). Accordingly, numerous examples of Michael/Michael, Michael/aldol, Michael/Dieckmann, as well as Michael/SN-type sequences have been found in the literature. These reactions can be considered as very reliable domino processes, and are undoubtedly of great value to today s synthetic chemist... 

Using a cyclic enone 2-29b and an ester-TMS enolate 2-30 in the presence of catalytic amounts of SmI2(THF)2, the Michael addition and the Mukaiyama/aldol reaction with the added aldehyde 2-32 led to the diastereomeric adducts 2-33 and 2-34 via 2-31 with a dr =80 20 to 98 2 and 70-77% yield (Scheme 2.7) [13]. The major product is the trans-l,2-disubstituted cycloalkanone. 

Mechanistically, a-methylenecyclopentenone (2-391) reacts with ester enolate 2-392 in a Michael addition to give the enolate 2-393, which is then trapped with an aldehyde 2-394 generating the alcoholate 2-396. This eventually cyclizes through lactonization to afford 2-397 in good yield. The products 2-397 are obtained as single diastereomer thus, it can be assumed that the aldol reaction proceeds via the six-membered chair-like transition state 2-395. 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

Escherichia coli, glutamine synthetase, 28 350 ESR, see Electron spin resonance Ester enolates, Michael addition to ynoates, 38 275, 278... 

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