Cu-complexes, chiral

AUcyl transfer from the magnesium hahde to the chiral Cu complexes generates the Cu complex A, as deduced from NMR experiments. Very likely, this complex functions in a similar manner as previously postulated for organocuprate additions . 

One of the few available examples is represented by the synthesis of cilastatine by a chiral Cu complex promoted cyclopropanation reaction developed by Sumitomo Chemical Co. [78]. Another is the catalytic asymmetric hydrocyanation of vinylarenes developed at DuPont [79]. In this process (Fig. 27) sugar-derived phosphinites are used in combination with a Ni catalyst to prepare enantiomerically enriched precursors of the NSAID naproxen. 

In 2011, Wang and co-workers realized the enantioselective synthesis of Cl-alkylated THIQs 12 by the asymmetrie CDC reaction of Horner-Wadsworth-Emmons (HWE) reagent 11 with Al-aryl THIQs 10 using a chiral Cu complex as the eatalyst. The desired produets were afforded in up to 80% yield, 19 1 dr and 90% ee (Scheme 2.5). A preliminary mechanistic probe indicated that a radical cation intermediate might be involved in the catalytic cycle because a small amount of this species eould be captured by 2,6-di-( Bu)2-4-methylphenol (BHT). 

Starting from an optically active dimer, tetramer, or octamer of 2,3-dihy-droxynaphthalene derivatives, Tsubaki and co-workers realized the synthesis of numerous optically active oligonaphthalene products by second-order asymmetric transformation under amine-copper conditions (Scheme 3.17). On the other hand, Okamoto and co-workers achieved asymmetric oxidative coupling polymerization (AOCP) reactions to synthesize poly(2,3-dihy-droxy-l,4-naphthylene) derivatives (Scheme 3.18). The starting materials of AOCP reactions can be either partially protected tetrahydroxybinaphthale-nes or 2,3-dihydroxynaphthalene. The chiral Cu complexes ligated by (-)-sparteine or bisoxazolines were identified as suitable catalysts for these reactions. However, the enantioselectivity attained in these AOCP reactions was estimated to be low. 

Scheme 2.2S Kinetic resolution of cyclic ketones 107 catalyzed by a chiral Cu complex 99.

Scheme 2.29 Chiral Cu complex 99 catalyzed asymmetrir BV oxidation of racemic hicvclic cyclohutanones. 

Finally, a catalytic enantioselective approach for the formation of allyl a-amino acid derivatives by reaction of N-tosyl-a-imino esters with alkylstannanes catalyzed by chiral Cu complex was developed [162]. 

Chiral Cu(II)-complexes as catalysts in hetero-Diels-Alder reaction 99PAC1407. 

Chiral Cu(ll)-complexes ofbis-oxazolines as Lewis acids for catalyzed cycloaddition, carbonyl addition, and conjugate addition reactions 99PAC1407. 

Inverse electron-demand Diels-Alder reaction of (E)-2-oxo-l-phenylsulfo-nyl-3-alkenes 81 with enolethers, catalyzed by a chiral titanium-based catalyst, afforded substituted dihydro pyranes (Equation 3.27) in excellent yields and with moderate to high levels of enantioselection [81]. The enantioselectivity is dependent on the bulkiness of the Ri group of the dienophile, and the best result was obtained when Ri was an isopropyl group. Better reaction yields and enantioselectivity [82, 83] were attained in the synthesis of substituted chiral pyranes by cycloaddition of heterodienes 82 with cyclic and acyclic enolethers, catalyzed by C2-symmetric chiral Cu(II) complexes 83 (Scheme 3.16). 

Corey et al. [19] simultaneously reported similar studies using a2,2 -bis(oxazolyl)-6,6 -dimethyl-l,l -biphenyl as copper(I)triflate chelate. This hgand afforded a stable monomeric chiral Cu(I) complex providing a highly... 

Corma et al. [55] have prepared chiral Cu(I) complexes with substituted pyrrolidine ligands bearing a triethoxysilyl group (Scheme 24). 

Ghosh et al. [70] reviewed a few years ago the utihty of C2-symmetric chiral bis(oxazoline)-metal complexes for catalytic asymmetric synthesis, and they reserved an important place for Diels-Alder and related transformations. Bis(oxazoline) copper(II)triflate derivatives have been indeed described by Evans et al. as effective catalysts for the asymmetric Diels-Alder reaction [71]. The bis(oxazoline) Ugand 54 allowed the Diels-Alder transformation of two-point binding N-acylimide dienophiles with good yields, good diastereos-electivities (in favor of the endo diastereoisomer) and excellent ee values (up to 99%) [72]. These substrates represent the standard test for new catalysts development. To widen the use of Lewis acidic chiral Cu(ll) complexes, Evans et al. prepared and tested bis(oxazoHnyl)pyridine (PyBOx, structure 55, Scheme 26) as ligand [73]. 

Two mechanisms are possible for the Cu-mediated aziridination using PhI=NTs as a nitrogen source (i) aziridination via Cu-nitrenoid species (L Cu=NTs) and (ii) aziridination via a L (Cu—PhI=NTs) adduct, in which the Cu complex functions as a Lewis acid catalyst. Jacobsen et al. demonstrated that the enantioselectivity of the aziridination using (48) as the chiral auxiliary did not depend on the nitrogen precursors.1 5 This supports the intermediacy of the Cu-nitrenoid... 

Recently, Scott et al. have reported that a Cu complex bearing an axially chiral ligand (49) is an excellent catalyst for aziridination of 2,2-dimethylchromene and cinnamate esters (Scheme 36), though it is also less efficient for the reactions of simple olefins.157,158 On the basis of DFT investigation of the nitrenoid intermediate (50), one of the oxygen atoms of the A -sulfonyl group has been proposed to be interacting with the nitrene N-atom.158... 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

The Lewis acidic properties of chiral Cu(I) complexes have recently been exploited to augment the chemistry of the more developed Cu(II) Lewis acids. As a corollary, much less is known about the chemistry of Cu(I) Lewis acids. They have traditionally been categorized as soft Lewis acids, compared to the borderline-hard Cu(II) Lewis acids (1). 

Arylation of activated double bonds with diazonium salts in the presence of copper catalysts is known as the Meerwin reaction. The reaction is postulated to either proceed through an organocopper intermediate or through a chlorine atom transfer from chiral CuCl complex to the a-acyl radical intermediate. Brunner and Doyle carried out the addition of mesityldiazonium tetrafluoroborate with methyl acrylate using catalytic amounts of a Cu(I)-bisoxazoline ligand complex and were able to obtain 19.5% ee for the product (data not shown) [79]. Since the mechanism of the Meerwin reaction is unclear, it is difficult to rationalize the low ee s obtained and to plan for further modifications. 

Cul, methyllithium, and a camphor-derived /3-amino alcohol (239). Reaction of methylmagnesium iodide and benzylideneacetone in the presence of a small amount of a chiral Cu(I) thiolate complex gives the conjugate addition product in 57% ee (240). 

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