Cu-Catalysed Additions

It is believed that the hard Zn(II) cation coordinates to the carbonyl while the soft Cu(I) centre forms a 7i-complex with the enone double bond, forming a bimetallic species (41). Oxidative addition to the enone forms the Cu(III) complex 42, which suffers reductive elimination with concomitant C-C bond formation. After aqueous work-up, 43 delivers the product 39. The reductive elimination is likely to be the rate-determining step.  

There are several reports on the performance of P-stereogenic ligands in enantioselective additions of diethylzinc to enones. Selected results are collected in Table 8.6. 

For both chalcone and substrate 37 many mono- and bidentate ligands give almost complete conversions but good enantioselectivities are difficult to reach. 

Entry 3 corresponds to one of the first reports about enantioselective catalytic Michael additions. For 37 the best results are obtained with MiniPHOS diphosphines (entries 7 and 8). In contrast, other diphosphines such as BisP and DrPAMP provide product 39 in low optical purity (entries 10 and 7 

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Cu-catalysed additions of ZnEt2 to Baylis-Hillman-derived allylic electrophiles with BINOL-based thioether ligand. 

Scheme 2.8 Cu-catalysed addition of w-BuMgCl to cycloheptenone with TADDOL-derived ligands.

Scheme 10.20 Cu-catalysed additions of phenylacetylene to imines with 7V-tosylate-daminoimine ligand.

This regioselectivity is opposite to the one observed by the non-catalysed additions of BH3 THF or 9-BBN to the same alkene, or those catalysed by Rh and Ir catalysts. Chiral NHC ligands (generated from 84) on Cu under the same conditions proceed with high enantioselectivity (enantiomeric ratio 99 1) [71] (Scheme 2.12). 

Scheme 2.2 Cu-catalysed 1,4-additions of ZnEt2 and AlMe3 to ( )-3-nonen-2-one with 1,1 -binaphthalene-derived ligands.

Scheme 2.9 Cu-catalysed 1,4-addition of ZnEt2 to 2-cyclohexenone with thioether-alcohol ligands bearing xylofuranose backbone.

Scheme 2.13 Cu-catalysed 1,4-addition of AlMcj to 4,4-disubstituted cyclohexa-2,5-dienone with thioether ligands.

Scheme 2.18 Cu-catalysed 1,4-additions of RMgl to acyclic enones with arenethio-latocopper (I) complex.

On the other hand, chiral sulfur-containing but noncoordinating ligands such as sulfonamides have been widely used in the asymmetric Michael reaction. In 1997, Sewald et al. reported the use of a series of chiral sulfonamides depicted in Scheme 2.25 in the Cu-catalysed conjugate addition of ZnEt2 to 2-cyclohexenone. Even the use of a stoichiometric amount of catalyst did not allow the enantioselectivity to be higher than 31% ee. 

Scheme 2.26 Cu-catalysed 1,4-additions of Me2CuLi and ZnEt2 to enones with sulfonamide or bis(sulfonamides) ligands.

In addition, the same group has used copper complexes of these ligands as efficient catalysts for enantioselective Cu-catalysed aza-Diels-Alder reactions of A-sulfonyl imines with Danishefsky s dienes, providing the corresponding six-membered heterocycles with enantioselectivities of up to 80% ee. ... 

Benzyl bromides 15 derived from either salicylaldehydes or 2-methylphenols by reaction with alkyl propynoates afford 277-1 -benzopyrans on treatment with tetrahydrothiophene and K2CO3. A sulfonium ylide is proposed which initiates a Michael addition - elimination -substitution sequence. When CS2CO3 is used as the base, 477-1-benzopyrans result almost exclusively, presumably through isomerisation of the 277-1-benzopyran. The protocol thus offers access to both chromene isomers through simple variation of the reaction conditions <06OL3853>. The Cu-catalysed intramolecular O-arylation of a-(2-bromobenzyl)-P-keto esters in refluxing THF offers a useful route to 2-substituted 477-l-benzopyran-3-carboxylates <06JOC6427>. 

Iminocoumarins are formed in high yield from the Cu-catalysed multicomponent reaction of salicylaldehyde, alkynes and sulfonyl azides. It is considered that an initially formed ketimine reacts with the salicylaldehyde hydroxy function and an intramolecular nucleophilic addition to the aldehyde moiety completes the sequence (Scheme 29) <06OL4517>. 

Cyclopropanation of cycloalkenes by this procedure also produced the least sterically hindered bicyclic compound. For example, the copper-catalysed addition of ethyl diazoacetate onto cyclohexene afforded 69% of the exo (111) and 4% of the endo compound (111a) (equation 26). Next to the traditional Cu catalysts, homogeneous... 

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