Copper-salen complex

Catalyst screening experiments resulted in the discovery that copper(salen) complex 33 was a highly effective catalyst for the conversion of alanine derivative 16b into (f )-a-methyl phenylalanine 17 under the conditions shown in Scheme 8.16. The presence of just 1 mol% of catalyst 33 was sufficient to induce the formation of compound 17 with up to 92% ee and in >70% yield [33]. Allyl bromide, 1-chloromethylnaphthalene and ethyl iodide also reacted with substrate 16b to give the corresponding (H)-a-methyl a-amino acids in the presence of 2 mol % of complex 33 [34], Complex 33 also catalyzed the asymmetric mono-alkylation of glycine-derived substrate 34 by benzylic or allylic halides, to give (H)-a-amino acid derivatives 35 with 77-81% ee. and in greater than 90% yield, as shown in Scheme 8.17. 

Figure 8.2 Gauche- and anti-conformations of a copper(salen) complex.

The X-ray structure of complex 42a [42] showed it to be square planar, and essentially superimposable on the X-ray structure of Cu(salen) complex 33 [45], Complex 42a was found to be catalytically active, and gave (R)-a-methyl-phenylala-nine methyl ester in 83% yield and with 80% ee - results which are essentially identical to those obtained using complex 33. Changing the substrate to compound 38f [which was optimal for the use of copper(salen) complex 33] further increased the enantioselectivity of the reaction to 85%. Experimentally, complex 42a has an advantage compared to copper(salen) complex 33 as it does not require chromatographic purification on Sephadex-LH20 to obtain a pure catalyst. 

COPPER-SALEN COMPLEX AS A PHASE TRANSFER CATALYST... 

CATALYTIC, ASYMMETRIC SYNTHESIS OF o,a-DISUBSTITUTED AMINO ACIDS USING A CHIRAL COPPER-SALEN COMPLEX AS A PHASE TRANSFER CATALYST... 

Observation of the stereoselective manner of chiral substrates binding to these asymmetric metal-salen complexes was not confined to [VO(l,3)] or chiral epoxides. Recently we showed how asymmetric copper salen complexes, [Cu(l)] and [Cu(4)] (Fig. 1), could also discriminate between chiral amines (R-IS-methylbenzylamine, MBA) as evidenced by multi-frequency CW and pulsed EPR, ENDOR, HYSCORE and DPT [45]. The discrimination of the MBA enantiomers was directly observed by W-band EPR. By simulating the W-band EPR spectra of the individual diastereomeric adduct pairs (i.e. R,R -[Cu(4)]+R-MBA and R,/ -[Cu(4)]-l-5-MBA), accurate spin-Hamiltonian parameters could be extracted for each adduct. The EPR spectmm of the racemic combinations (i.e. ra -[Cu(4)]+rac-MBA) was then simulated using a linear combination of the g/A parameters for the homochiral (R,R -[Cu(4)]+R-MBA) and heterochiral (R,R -[Cu... 

Abdel Azzem, M., Z.F. Mohamed, and H.M. Fahmy (1995). Electrocatalytic reduction of some imino compounds on a glassy carbon electrode electrochemically modified with a new copper-salen complex. J. Electroanal. Chem. 399,121-125. 

A few Lewis acids have been shown to catalyze the Yonemitsu-type reactions of indoles, aldehydes, and several CH acids (Scheme 13.79). Dimethyhnalonate 358 was successfully reacted with indole 327 and several aldehydes 357 under solvent-free ultrasound irradiation conditions to provide the desired products 359 in moderate yields [135]. Ytterbium triflate was used as the Lewis-acidic catalyst in this case. A copper-salen complex was utilized in water at elevated temperature to facilitate the Yonemitsu-type reaction of indoles 360, aldehydes 361, and malonodinitrile 21 [136]. In close similarity copper(II) acetate was used in polyethylene glycol at elevated temperatures to provide Yonemitsu-type products 366 in moderate to high yields (48-98%) [137]. 

The development of catalysts for the efficient oxidation of catechol and its derivatives in water is topic of ongoing work in this laboratory. Towards this end, polyethylene glycol side-chains were incorporated in a pentadentate salen ligand to enhance the water solubility of the complexes derived thereof. A dinuclear copper(II) complex is found to catalyze the oxidation of 3,5-di-tert.-butylcatechol into 3,5-di-tert-butyl-o-benzoquinone more than twice as fast in aqueous organic solution as in purely organic solvents (ly,at/knon= 140,000). Preliminary data are discussed. 

In our ongoing efforts to develop oxidation catalysts that are functional in water as environmentally berrign solvent, we synthesized a water-soluble pentadentate salen ligand with polyethylene glycol side chairts (8). After coordination of copper(II) ions to the salen ligand, a dinuclear copper(II) complex is obtained that is soluble in water, methanol and mixtures of both solvents. The aerobic oxidation of 3,5-di-tert.-butylcatechol (DTBC) into 3,5-di-terr.-butylqitinone (DTBQ) was used as a model reaction to determine the catalytically active species and initial data on its catalytic activity in 80% methanol. 

Synthesis of complex 1. The pentadentate salen catalyst 1 was synthesized as described (9). In short, the tosylated 2-[2-(2-methoxyethoxy)-ethoxy]-ethanol 2 (10) was reacted with 2,4-dihydroxybenzaldehyde 3 to yield 4-alkoxy salicylaldehyde 4 after chromatographic purification (eq. 1). Subsequent condensation of 4 with 1,3-diaminopropanol yielded water-soluble salen ligand 5 in sufficient purity and 89% yield (11). The formation of an azomethine bond is indicated by a shift of the NMR signal for the carbonyl carbon from 194.4 ppm in aldehyde 4 to 166.4 ppm for the imino carbon in 5. The pentadentate ligand 5 was then treated with copper(ll) acetate in methanol to obtain the dinuclear copper(ll) complex 1 as a green solid (eq. 2) (11). 

A dinuclear salen complex was investigated as catalyst for the aerobic oxidation of 3,5-di-ferf.-butylcatechol into 3,5-di-teri.-butylquinone in organic and aqueous organic solution. The actual catalyst composition varies in both solvent systems. Formation of a mononuclear species competes with formation of a dinuclear copper(ll) catalyst. The aerobic oxidation of 8 into 9 is 140,000-fold accelerated over background in aqueous methanol, and is about twice as fast as the same reaction in pure methanol. 

Metal-Catalyzed. Cyclopropanation. Carbene addition reactions can be catalyzed by several transition metal complexes. Most of the synthetic work has been done using copper or rhodium complexes and we focus on these. The copper-catalyzed decomposition of diazo compounds is a useful reaction for formation of substituted cyclopropanes.188 The reaction has been carried out with several copper salts,189 and both Cu(I) and Cu(II) triflate are useful.190 Several Cu(II)salen complexes, such as the (V-f-butyl derivative, which is called Cu(TBS)2, have become popular catalysts.191... 

C. R. Jacob, S. R. Varkey, and R. Ratnasamy, Zeolite encapsulated copper (X2-Salen) complexes, Appl. Catal. A 168, 353-364 (1998). 

Attempts to aziridinate alkenes with iron catalysts in an asymmetric manner have met with only limited success to date [101], In an early report on the use of various chiral metal salen complexes, it was found that only the Mn complex catalyzed the reaction whereas all other metals investigated (Cr, Fe, Co, Ni etc.) gave only unwanted hydrolysis of the iminoiodinane to the corresponding sulfonamide and iodoben-zene [102], Later, Jacobsen and coworkers and Evans et al. achieved good results with chiral copper complexes [103]. 

Since both nickel(II) and copper(II)(salen) complexes have been found to form asymmetric phase-transfer catalysts, the use of other metal(salen) complexes was investigated. Cobalt(salen) complexes 42a-d provided an opportunity to probe the influence of the oxidation state of the metal on the catalytic activity of the complex [42]. Hence, each of these complexes was prepared and tested as a catalyst for the benzylation of substrate 16a, according to the conditions specified in Scheme 8.18. 

The normal U-shaped Hammett plots were found for both the catalysed [by a copper(II)salen complex (31)] and uncatalysed asymmetric alkylation of enolates by substituted benzyl bromides,126 indicating that both reactions occur via an. S N2 mechanism (Scheme 15). Because both reactions were faster when electron-withdrawing substituents were on the benzyl bromide, it was concluded that there was more bond formation than bond rupture in the. S N2 transition states. Because the curvature of the Hammett plot was greater for the catalysed reaction, it was concluded that the catalysed reaction has a later transition state with a greater negative charge on Ca. The role of the catalyst was to increase the nucleophilic character of the enolate anion. 

An hDA reaction between Danishefsky s diene and glyoxylate esters proceeds in the presence of bisoxazoline-lanthanide complexes with moderate levels of enantioselectivity <2000TL2203>. A similar reaction between Danishefsky s diene and a-keto esters proceeds with excellent enantioselectivity in the presence of bisoxazoline-copper <2001TL6231, 2003EJ0317, 2004TA1987> or Cr(m), Co(n and m)-salen complexes <2004TA3189>. 

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