Michael addition copper catalysts

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

In addition to a-additions to isocyanides, copper oxide-cyclohexyl isocyanide mixtures are catalysts for other reactions including olefin dimerization and oligomerization 121, 125, 126). They also catalyze pyrroline and oxazoline formation from isocyanides with a protonic a-hydrogen (e.g., PhCH2NC or EtOCOCHjNC) and olefins or ketones 130), and the formation of cyclopropanes from olefins and substituted chloromethanes 131). The same catalyst systems also catalyze Michael addition reactions 119a). 

Copper(II) tetrafluoroborate Cu(BF4)2xH20 has been identified as a new and highly efficient catalyst for Michael addition of thiols to o ,/5-unsaturated carbonyl compounds under solvent-free conditions and in H20 at room temperature. The reactions are very fast and are completed within 2 min to 1 h. The rate of thiol addition is dependent on the steric hindrance at the /3-carbon of the o ,/3-unsaturated carbonyl substrate. In the case of chalcones, the reactions are best carried out in MeOH as solvent.237... 

Scheme 14 Aminoarenethiolato copper(I)-based metallodendrimer G0-20 and its application as catalyst in a 1,4-Michael addition reaction...

A different approach that even obviates the use of a preformed silyllithium reagent takes advantage of the cleavage of the Si-Si bond of a disilane by a copper salt. Hosomi and co-workers185 have reported on the reaction of various enones or enals 250 with hexamethyldisilane or l,l,2,2-tetramethyl-l,2-diphenyldisilane, catalyzed by copper(i) triflate-benzene complex (Scheme 61). The transformation requires heating to 80-100 °C in DMF or DMI and the presence of tri-/z-butylphosphine in order to stabilize the copper catalyst under these harsh conditions. The addition products 251 were obtained with high yield after acidic work-up. The application of the method to alkylidene malonates as the Michael acceptor was recently disclosed.1... 

It is evident from the previous examples that most copper catalysts have been applied only to simple, unsubstituted Michael acceptors so far. Only very recently, chiral, substituted cyclohex-2-enones were used as substrates for copper-catalyzed enantioselective 1,4-additions with phosphoramidites as the chiral ligand. Thus, highly enantioselective kinetic resolutions of several 4- or 5-substituted cyclohex-2-enones were reported by Feringa and co-workers.236,236a In contrast to these Michael acceptors, the corresponding 6-substituted cyclohex-2-enones possess a stereogenic center which can be... 

Michael additions of organolithium, Grignard, and diorganozinc reagents to enones and other rt, -unsaturated carbonyl compounds are catalyzed inter alia by copper, nickel and cobalt salts. The best results are obtained with cop-per(I) catalysts, especially those in which copper is bound to a soft , readily polarizable center (sulfur or phosphorus). 

Spescha et al. [4] used the copper complex 6, which was obtained from a thioglucofuranose derivative, as catalyst for 1,4-additions of Grignard reagents to 3, and observed enantioselectivities of up to 60 % ee. The dihydrooxazolylthiophenolato copper complex 7 was employed by Pfaltz et al. 5] for the enantioselective catalysis of Michael additions to cyclic enones the best results were obtained with tetrahydrofuran as solvent and HMPA as additive. There was a pronounced dependence of the stereoselectivity on the ring size of the substrate 16-37 % ee for 2-cyclopente-none, 60-72 % ee for 3, and 83-87 % ee for 2-cycloheptenone. Alexakis et al. [6] used the heterocycle 8, which is readily accessible from... 

As these examples show, cyclic enones are normally used as substrates for copper-catalyzed enantioselective Michael additions. In some cases, however, good stereoselectivities were also attained with acyclic enones of type 11. Thus, van Klaveren, van Koten et al. [9] employed the copper arenethiolate 13 as catalyst for the 1,4-addition of methylmagnesium iodide to benzylideneacetone and obtained adduct 12 (R = = Me) with 76 % ee. Interestingly, this... 

Vinylogous Mukaiyama-Michael additions of 2-trimethylsilyloxyfuran to 3-alkenoyl-2-oxazolidinones to provide 7-butenolides were shown to be /7-selective. The reaction could be rendered enantioselective in the presence of a (T symmetric copper-bisoxazoline complex <1997T17015, 1997SL568> or a l,T-binaphthyl-2,2 -diamine-nickel(ii) complex as catalyst, as depicted in Equation (16) <2004CC1414>. 

Copper compounds are catalysts for the Michael addition reaction (249), olefin dimerizations (245, 248), the polymerization of propylene sulfide (142), and the preparation of straight-chain poly phenol ethers by oxidation of 2,6-dimethylphenol in the presence of ethyl- or phenyl-copper (209a). Pentafluorophenylcopper tetramer is an intriguing catalyst for the rearrangement of highly strained polycyclic molecules (116). The copper compound promotes the cleavage of different bonds in 1,2,2-tri-methylbicyclo[1.1.0]butane compared to ruthenium or rhodium complexes. Methylcopper also catalyzes the decomposition of tetramethyllead in alcohol solution (78, 81). 

Gomtsyan, A. Org. Lett. 2000, 2, 11. For a reaction with methyl esters with an excess of vinylmagnesium halide and a copper catalyst to give a 3-butenyl ketone by a similar acyl substitution-Michael addition route, see Hansford, K.A. Dettwiler, J.E. Lubell, W.D. Org. Lett. 2003, 5, 4887. Gomtsyan, A. Koenig, R.J. Lee, C.-H. J. Org. Chem. 2001, 66, 3613. 

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