Acyclic enones, enantioselective conjugate addition

Table 1 Enantioselective conjugate addition to acyclic enones...

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. 

Highly enantioselective conjugate addition of Et2Zn to acyclic and cyclic enones has been performed in the presence of copper/phosphorus containing catalysts.117-119... 

The preparation of silyl enol ethers from carbonyl compounds represents one of the major uses of TMSOTf. Recently, the stereochemistry and regiospeciflcity of such transformation has been addressed for aldehydes and Q -(lV-alkoxycarbonylamino) ketones, respectively. On the other hand, enantiopure silyl enol ethers can be formed by addition of TMSOTf to zinc enolates, which are obtained from the copper-catalyzed enantioselective conjugate addition of dialkyIzinc reagents to cyclic (eq 36) and acyclic enones. ... 

A highly enantioselective conjugate addition of nitromethane and nitroethane to acyclic enones has been recently achieved using chiral cyclohexanediamine-derived primary amine thiourea 48 (Scheme 2.57) [168], With respect to the electrophile, the reaction shows a broad substrate scope and not only 1-aryl- but also 1-alkyl enones afford the corresponding chiral y-nitroketones with good yields and excellent enantioselectivities (92-99% ee). 

Chiral binaphthylthiophosphoramide 52b and binaphthylselenophosphoramide 53 have been developed by Shi and co-workers, and high enantioselectivity (up to 97%) has been achieved in the asymmetric conjugate addition of acyclic enones under the optimized conditions.58... 

Phosphite-pyridine ligands (191) derived from racemic biphenyl units and homochi-ral BINOL have been developed for enantioselective (<96% ee) Cu(I)-catalysed conjugate additions of Et2Zn to a variety of acyclic enones, such as ArCH=CHCOR.229 Ligand (192) was equally successful (90-99% ee).230... 

A new class of phosphaferrocene-oxazoline ligands has been disclosed by Fu and co-workers30 and applied to the copper-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones with good enantioselectivity. The substitution pattern on the phosphoryl ring as well as on the oxazoline was shown to have an enormous impact on the selectivity. Ligands 26 and 27, which share the same absolute configuration in the oxazoline, provide the (5)-l,4-adduct preferentially. This observation led to the conclusion that the stereochemistry at the oxazoline, and not the planar... 

Other C-C bond-forming reactions have been successfully developed using SCCO2 and liquid CO2 as reaction media. Examples include the synthesis of cyclopentenones via cobalt-catalyzed cocyclizations of alkynes with alkenes and carbon monoxide (Pauson-Khand reaction) (Scheme 30) , enantioselective nickel-catalyzed hydrovinylation of styrenes (Scheme 31) , and the palladium-catalyzed hydroarylation of acyclic jS-substimted-o , j8-enones with aryl iodides (formal conjugate addition) (Scheme 32). ... 

Once in the modern organocatalysis era and with the mechanistic rationale for the iminium activation concept in hand, many different and more efficient methodologies have been developed for this particular reaction. For example, and still focused on the use of secondary amines as catalysts, imidazolidine 53a and proline-tetrazole 2a catalysts have been developed for the conjugate addition of malonates to acyclic enones (Scheme 3.17). For the 53a-catalyzed reaction, this proceeded well in terms of yields and enantioselectivities for a wide range of differently substituted arylideneacetones and for cyclohexenone but yields tend to decrease when more bulky substituents were placed around the carbonyl moiety. Importantly, the enantioselectivity of the reaction was very dependent upon the nature of the malonate reagent, observing that dibenzyl malonate and diethylmalonate furnished the best results. The most... 

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