Enantioselectivity acyclic enones

Organoboron reagents ate pariictdarly well suited for 1,4-additions of aryl and vinyl groups to enones. Hayasbi et al. developed a highly enantioselective RliQ)/ BlNAP-catalyzed 1,4-addilion of pbenylbotonic add lo cyclic and acyclic enones [24] fSclieme 7.5) and 1-alkenylpbospbonales [25]. 

Aryl-substituted enones such as chalcone and benzalacetone have been used as model substrates in the study of asymmetric 1,4-addition of acyclic enones. Many chiral ligands have been found to afford good enantioselectivities (Scheme 19). Typical results are summarized in Table i 46>50 58-66... 

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... 

Table 1 Enantioselective conjugate addition to acyclic enones...

Woodward and co-workers utilized [Gu(MeCN)4]BF4 and (A)-BINOL-derived thiourethane ligand 87 in the addition reaction of trimethylaluminum to acyclic enones. Both yields and enantioselectivities were moderate (Scheme 44).130... 

The use of copper catalysts based on chiral phosphorus ligands to assist 1,4-additions of dialkylzinc reagents has in recent years produced major breakthroughs, with excellent enantioselectivities. A number of monodentate and bidentate phos-phoramidites, phosphites, phosphonites, and phosphines are now available as chiral ligands for alkyl transfer to a variety of cyclic and acyclic enones. So far. 

However, very few catalyst systems reported to date are highly effective for both p- aryl and p-alkyl acyclic enone substrates in the copper-catalyzed asymmetric 1,4-addition. Ligand 27, developed by Hoveyda, shows high enantioselectivity in the 1,4-addition of dialkylzinc reagents to various acyclic enones (Figure 3.6). " ... 

The above process proceeds with low enantioselectivity when applied to acyclic enones. However the acetals of a,p-enals formed from L-diethyl or L-diisopropyl tartrate react enantioselectively with CHzVZ QHs (2, 134).4 Example ... 

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. 

In this case, the O-benzyl quat hydroxide was used in conjunction with sodium hypochlorite in toluene [65]. Other reports of epoxidations of acyclic enones have appeared, showing 62% ee [66a] or lower enantioselectivity [24e,24h,48b,54a,54c-e,67],... 

Yamaguchi et al. also showed that Rb-L-prolinate catalyzes enantioselective addition of nitroalkanes to several acyclic and cyclic enones [25, 26]. For acyclic enone acceptors the best result, i.e. 74% yield and 68% ee of the S product, was achieved in the addition of 2-nitropropane to -3-penten-2-one (40a, Scheme 4.13) [25]. Screening of several proline derivatives and cyclic amino acids of other ring size resulted in the identification of the O-TBDMS-derivative of 4-hydroxyproline as the best catalyst for addition of nitrocyclohexane to cycloheptenone. In this particular reaction 74% yield and 86% ee were achieved [26]. 

In the metal-free epoxidation of enones and enoates, practically useful yields and enantioselectivity have been achieved by using catalysts based on chiral electrophilic ketones, peptides, and chiral phase-transfer agents. (E)-configured acyclic enones are comparatively easy substrates that can be converted to enantiomeri-cally highly enriched epoxides by all three methods. Currently, chiral ketones/ dioxiranes constitute the only catalyst system that enables asymmetric and metal-free epoxidation of (E)-enoates. There seems to be no metal-free method for efficient asymmetric epoxidation of achiral (Z)-enones. Exocyclic (E)-enones have been epoxidized with excellent ee using either phase-transfer catalysis or polyamino acids. In contrast, generation of enantiopure epoxides from normal endocyclic... 

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... 

The catalyzed reduction was effective for selective reduction of carbonyl groups of enones and ynones without affecting the C-C unsaturated bond (Scheme 43). Acyclic enones 544,1107 endocyclic enones 545,1108,1109 exocyclic enones 546 and 547,1110,1111 and ynones 548-5511112-1115 were enantioselectively reduced under catalytic conditions. The reductions of ynones, for example, 551, to give anti-product 552 via a cyclic chelate 553 were sensitive to the steric size of the distal group of alkyne and to the nature of substituents on the carbonyl carbon. 

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