Catalytic Enantioselective Conjugate Additions

In the context of catalytic enantioselective conjugate additions, preformed enolates play two different roles as enolates, mainly those of silicon, they add to Michael acceptors under activation by a catalyst. On the other hand, enolates are involved in a second different function as intermediates, if any nucleophile reacts with a,P-unsaturated carbonyl compounds they may be quenched by protonation or reaction with different electrophiles in a stereoselective manner. 

R = Ph, 2-furyl, 2-naphthyl, 3-Ts-lndolyl, 2-MeOCgH4, cyclohexyl, CHMej, CMeg 

A derivatization of zinc enolates like 418, formed in a copper-catalyzed conjugate addition, by trapping as silyl enol ethers 419 was reported by Alexakis group [209]. The addition occurred in very high enantioselectivity when mediated by phosphoramidite 417 or related ligands. Remarkably, the selectivity was distinctly lower when chlorotrimethylsilane was present from the beginning. Therefore, 

For performing consecutive reactions, the isolation of the corresponding boron enolate would be highly desirable. This goal was reached by using phenyl-9-BBN 

436 that reacts with rhodium enolate 435 under formation of the boron enolate 

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Scheme 8.7. Catalytic Enantioselective Conjugate Addition to Cyclohexenone...

More recently, Maruoka and co-workers have reported several new phase-transfer catalysts one of which incorporates a morpholine ring as part of an azoniaspirocyclic core 161 <2007TL4675>. These were employed in the catalytic enantioselective conjugate addition of a-benzylcyanoacetate to acetylenic methyl ketone under phase transfer conditions. 

Catalytic enantioselective conjugate addition and allylic alkylation reactions using Grignard reagents... 

Catalytic enantioselective conjugate addition TABLE 13. The allylic substitution of 3-bromopropenyl esters using Cu/Taniaphos... 

Miller and co-workers, as part of their program in connection to the development of polypeptides as practical and readily modular chiral catalysts and new screening protocols for combinatorial synthesis, have been able to achieve efficient catalytic enantioselective conjugate additions of azides to acyclic enones [15]. As the example in Eq. (5) illustrates, the resulting 3-azidocarbonyls can be easily modified to afford N-containing heterocycles. 

Inexpensive and readily available Grignard reagents and stable dinuclear Cu complexes have been used for the first time in catalytic enantioselective conjugate addition reactions to simple acyclic a -unsaturated methyl esters.95 These reactions have provided access to highly valuable -substituted chiral esters in good yields and with excellent enantioselectivities (up to 99% ee). 

Concerning the catalytic enantioselective conjugate addition reaction, conjugate addition of dialkylzinc to chalcone in the presence of a catalytic amount of the chiral nickel complex derived from norephedrine affords 3-substituted ketones with up to 90% ee (eq 16). ... 

Catalytic Enantioselective Conjugate Addition of Dialkylzincs to Enones. A chiral nickel complex modified with DBNE and an achiral ligand such as 2,2 -bipyridyl in acetonitrile/toluene is an highly enantioselective catalyst for the addition of dialkylzincs to enones. p-Substituted ketones with up to 90% ee are obtained (eq 23). The method is the first highly enantioselective catalytic conjugate addition of an oiganometallic reagent to an enone. 

A sugar-based ligand such as 172 served as a promising chiral ligand for the catalytic enantioselective conjugate addition of cyanide to a, 8-unsaturated A-acylpyrroles as shown in... 

Here is an example, which picks up where we left off a catalytic enantioselective conjugate addition. As you know from Chapter 11, aldehydes and ketones react with secondary amines to form enamines, via iminium ions. But this unsaturated aldehyde can t form an enamine because the iminium ion that is generated by condensation with the cyclic secondary amine... 

Scheme 4.73 The catalytic enantioselective conjugate addition of hydroxylamine benzyl ether to an A -enoylpyrazole.

Moreover, Shibasaki developed a direct catalytic enantioselective conjugate addition of allyl cyanide 37 to a,(3-unsaturated thioamides (Scheme 2.25). A sequential Cu(i)-catalysed intramolecular cyclisation gave rise to enantioenriched fused isothiazoles 41 via Z-olefins 40. 

Shibasaki further developed a direct catalytic enantioselective conjugate addition of terminal allqmes to a,p-unsaturated thioamides under proton-transfer conditions (Scheme 2.26). The combined use of chiral... 

Catalytic Enantioselective Conjugate Addition with Grignard Reagents Lopez, F. Minnaard, A.J. Feringa, B.L. Acc. Chem. Res. 2007, 40, 179. 

Scheme 2.99 Catalytic enantioselective conjugate addition to vinyl sulfones...

Catalytic enantioselective conjugate addition of 1,3-dicarbonyl compounds (199) to nitroalkenes (200) has been attained in the presence of (TfO)2Mg (5 mol%) and (201) as chiral ligand with up to 95%... 

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