Michael conjugate

Pyrrole-substituted [1-amino ester 394 was synthesized via aza-Michael conjugate addition (Scheme 81) [149]. 

The Michael conjugate addition of an oxygen to an activated double bond has also been exploited in order to obtain 2,5-disubstituted tetrahydrofurans. The diacetoxynonenoate 1 is cyclized with methanolic potassium hydroxide to give the tetrahydrofuranyl derivative 2 in 97 % yield after esterification with diazomethane. The 1,3-asymmetric induction is low as indicated by the cisf trans diastereomeric ratio (67 33) which was determined by a GLC comparison with known material50. 

Diels-Alder reactions with Oppolzer s chiral sultam Diels-Alder reactions with pantolactone as chiral auxiliary Chiral auxiliaries attached to the diene Improved Oxazolidinones SuperQuats Asymmetric Michael (Conjugate) Additions... 

There are other considerations than mere analogy. If R represents some chiral auxiliary, a Diels-Alder reaction on 124 gives a product 125 with two new chiral centres, one, at C-2 in exactly the same place as in the aldol products such as 107. Michael (conjugate) addition to 124 on the other hand gives a compound 122 with only one new chiral centre (C-3) one atom further away from the chiral auxiliary. Another substitution pattern 128 still creates a new chiral centre at C-2 in the Diels-Alder adduct 129 but this time Michael addition does the same. However, the new centre is not created in the conjugate addition step, as that gives the enolate 127, but in the protonation of 127, an inherently less well controlled and probably reversible step. We shall therefore consider Diels-Alder reactions first and tackle the more troublesome Michael additions in the next section. 

Mukaiyama-Michael Addition, Mukaiyama-Michael Conjugate... 

This reaction was first reported by Mukaiyama et al. in 1974. It is a Lewis acid-catalyzed Michael conjugate addition of silyl enol ether to o ,/3-unsaturated compounds. Therefore, it is generally referred to as the Mukaiyama-Michael reaction. Because this reaction is essentially a conjugate addition, it is also known as the Mukaiyama-Michael addition or Mukaiyama-Michael conjugate addition. This reaction is a mechanistic complement for the base-catalyzed Michael addition, j and often occurs at much milder conditions and affords superior regioselectivity. s Besides silyl enol ether, silyl ketene acetals are also suitable nucleophiles in this reaction.For the hindered ketene silyl acetals, the Lewis acid actually mediates the electron transfer from the nucleophiles to o ,/3-unsaturated carbonyl molecules.On the other hand, the Q ,j8-unsaturated compounds, such as 3-crotonoyl-2-oxazolidinone, alkylidene malonates, and a-acyl-a,/3-unsaturated phosphonates are often applied as the Michael acceptors. It has been found that the enantioselectivity is very sensitive to the reactant structures —for example, Q -acyl-Q ,j8-unsaturated phosphonates especially prefers the unique syn- vs anft-diastereoselectivity in this reaction. In addition,... 

A reported diastereoselective synthesis of precursor A of vitamin D3 involved the use of 2-methylcyclopent-2-enone as starting material. The Mukaiyama-Michael conjugate addition of ketene acetal 269 in the presence of trityl hexachloroaniimonate afforded the adduct 270. The lateral chain was introduced, according the procedure of Tsuji, by the treatment of crude 270 with allyl carbonate and palladium dibenzylideneacetone " (Scheme 63). The expected product 271 was obtained in 63% yield from 269. Reduction of 271 with LAH afforded a mixture of diols that was selectively tosylated at the primary hydroxy group. The secondary hydroxy group was protected with the methoxymethyl group and further functional modifications afforded the lactone 272. The reaction of lithium dimethyl methylphosphonate with the lactone 272 completed the synthesis of the AB-des-cholestane derivative 273. 

Enantioselective Michael reactions of thiols provide a convenient route to diverse chiral sulfides. Chen and coworkers have demonstrated that a chiral squaramide catalyst was effective in promoting a sulfa-Michael conjugated addition of various aromatic and aliphatic thiols to a wide range of trans-chalcones (Scheme 10.19) [97]. Moderate to excellent yields and enantioselectivities were achieved. Notably, the reactions between various benzylthiol and trans-chalcones bearing electron-donating or electron-withdrawing substituents proceeded with high enantioselectivities. 

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