Intramolecular Michael reaction asymmetric

Scheldt and co-workers have also accessed enolate equivalents from enals to furnish cyclopentanes 236 asymmetrically. Formation of the enolate equivalent from enals 235 with the NHC, followed by an intramolecular Michael reaction and 0-acylation, gives the lactone products 236, which are readily opened by either alcohols or amines to generate functionalised cyclopentane derivatives 237 in excellent ee. 

Hechavarria Fonseca MT, List B (2004) Catalytic asymmetric intramolecular Michael reaction of aldehydes. Angew Chem Int Ed Engl 43 3958-3960... 

Asymmetric Michael Addition. An intramolecular Michael reaction catalyzed by (S)-proline leads to the chiral thiadecalin (9) and thiahydrindan (11) and (12). Enone (8) undergoes cyclization in the presence of (S)-proline to give exclusively the trans isomer (9) (eq 4). The thiahydrindandions (11) and (12) are obtained from (10) as a 1 1 mixture of the cis and trans isomers (eq 5). 

Roush, W. R. An asymmetric intramolecular Michael reaction. Construction of chiral building blocks for the synthesis of several alkaloids. Chemtracts Org. Chem. 1988,1, 233-235. 

The intramolecular Michael reaction is useful for the preparation of nitrogen-containing heterocycles. Crucial to the success of this Michael reaction is the accessibility of substrates and nucleophilicity on the part of the nitrogen atom. The ability to control 1,2-asymmetric induction during formation of the heteroring is realized when the substrates are derived form tartaric acid derivatives. 

An asymmetric intramolecular Michael-aldol reaction which leads to nonracemic tricyclic cyclobutanes is performed by using TMSOTf andbis[(/ )-l-phenylethyl]amine as chiral amine, but only moderate enantioselectivities are reached (eq 68). A similar reaction sequence can also be carried out with TMSOTf and HMDS as base, with (—)-8-phenylmenthol as the chiral auxiliary however, the iodotrimethylsilane-HMDS system is more efficient in terms of yield and diastereoselectivity. The combination EtsN/TMSOTf (or some other trialkylsilyl triflates) has been used to accomplish an intramolecular Michael reaction, which was the key step for the synthesis of sesquiterpene (=E)-ricciocarpin A. ... 

Anilide 2a catalysed asymmetric intramolecular Michael reaction of formyl enones to chiral cyclic keto-aldehydes in excellent yields with good stereoselectivity (eqn. (1) in Scheme 6.3). The intramolecular Michael addition of a ketosulfone to an unsaturated ketone (eqn. (2) in Scheme 6.3) catalysed by 15e has heen used as a key step in the synthesis of the carbon tricyclic framework of Lycopodine. The same sulfonylprolinamide served as catalyst in the construction of all-carhon substituted quaternary stereocentre via Robinson-type annulation process (eqn. (3) in Scheme 6.3). 

An organocatalytic (j0rgensen-Hayashi catalyst 1) domino Micliael/Michael/aldol condensation was used to prepare a hexahydronaphtlialenone (+)-121 m route to the natural product (+)-galbulin (Scheme 7.22). In this case, it was proposed that an iminium salt 118 (activated from the re face) and an enamine species 117 were preformed. Following a kinetic asymmetric transformation (KAT) of the racemic precursor 115, the intermediate 119 is first formed through an intermolecular Michael reaction. A second intramolecular Michael reaction occurs and the intermediate 120 forms, and finally an acid-initiated aldol condensation... 

The enantioselective intramolecular Michael reaction is attractive since it provides an efliecient way for the construction of chiral, cyclic carbon skeletons, which are common motifs in natural products. The first organocataly tic asymmetric intramolecular Michael reaction was disclosed by Fonseca and List in 2004 [108]. In the presence of MacMillan... 

Recently, Cobb and co-workers [110] developed the organocatalytic asymmetric intramolecular Michael reaction of nitronates to conjugated esters (Scheme 5.52). By... 

Chen and co-workers [72] reported an asymmetric quadruple amino catalytic domino reaction catalyzed by secondary amines. The reaction consists of a quadruple iminium-enamine-iminium-enamine cascade reaction initiated by a Michael addition of oxindole 114 to the enal and a subsequent intramolecular Michael reaction between the enamine formed in the previous step and the unsaturated oxindole to yield intermediate 116. Next, this intermediate reacts with another molecule of enal via a Michael addition of the oxindole to the enal. The sequence ends with an intramolecular aldol reaction between the preformed enamine and the aldehyde. This organocascade reaction affords highly complex spirooxindoles 118 bearing six contiguous chiral centers in excellent yields and with excellent diastereo- and enantioselectivities (Scheme 10.31). 

The 1,5-anti-aldol reaction was performed with chiral boron enolate of 325 and aldehyde 327, prepared by Evans asymmetric alkylation, cross metathesis, and Wittig homologation (Scheme 72), to afford 324 with a 96 4 diastereoselectivity. Stereoselective reduction of C9-ketone provided the 5y -l,3-diol, which was exposed to catalytic f-BuOK to give 2,6-cis-tetrahyderopyran 333 via an intramolecular Michael reaction. Finally, methyl etherification, deprotection, hydrolysis of ester, and Yamaguchi macrolac-tonization yielded the leucascandrolide macrolide 201 (Scheme 73). 

Intramolecular Michael Reaction of Aldehydes. Imidazolidinone catalyst 1 mediates the asymmetric intramolecular Michael addition of simple aldehydes to enones at rt (eq 15). The reaction is thought to proceed via an enamine mechanism but a dual-activation mechanism involving both enamine and iminium catalysis can also be considered. When a catalytic amount of 1 was used, products were obtained in excellent yield although in low enantioselectivity (eq 15). Better selectivity was observed, however, when catalyst 2 was used (eq 15). 

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. ... 

As shown in Scheme 2.20, selective lithiation of substrate 2-87 by treatment with LDA in THF at -78 °C triggers an intramolecular Michael/intermolecular aldol addition process with benzaldehyde to give a mixture of diastereomers 2-90 and 2-91. 2-91 was afterwards transformed into 2-92, which is used as a chiral ligand for Pd-catalyzed asymmetric allylic substitution reactions [29]. 

Asymmetric intramolecular Michael cyclization.1 Reaction of the ketone 2 with (R)-( + )-l (1 equiv.) generates an enatnine that adds to the unsaturated ester group to give 3a. The yield and the ee of 3 are markedly improved when 5 A... 

Musso has reported the synthesis of diasterane (tricyclo-[3.1.1.I2 4]octane) 15. For this first member of the series of asteranes, the decarboxylation of 16b -> 16c was best achieved via the photolysis of the Barton ester of 16a in the presence of BuSH, as shown in Scheme 5.14 Fukumoto has accomplished asymmetric total synthesis of atisine 17, where the bridged pentacyclic intermediate 18, a precursor for atisine, was synthesized via an intramolecular double Michael reaction starting with 19, Scheme 6.15 Barton protocol was favored during the late stages of the synthesis and the presence of various functionalities was easily accommodated. 

Asymmetric intramolecular double Michael reaction.3 Treatment of the 8-phenylmenthyl ot,(3-unsaturated amide ester (2) with r-butyldimethylsilyl triflate and triethylamine effects this Michael reaction with almost complete diastereose-lectivity to give the indolizidine 3, which was used for synthesis of (- )tylophorine (4). 

Kerr MS, Rovis T (2003) Effect of the Michael Acceptor in the asymmetric intramolecular Stetter reaction. Synlett 2003 1934-1936... 

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