Cyclopropanation Cu

Enantioselective Cyclopropanation. Cu(OAc>2 has been used as procatalyst in the asymmetric cyclopropanation of alkenes with alkyl diazoacetates with optically pure imines as cocatalyst (eq 18). ... 

Simmons-Smith reaction (Section 7.6) The reaction of an alkene with CH2l2 and Zn—Cu to yield a cyclopropane. 

Similar results are observed in the conjugative addition of CH-acidic methylene compounds with the metal derivatives of 2-nitro-5,10,15.20-tetraphenylporphyrin (6). The nickel porphyrin 6 (M = Ni) yields with an excess of dimethyl malonate the cyclopropane derivative 7 whereas the copper porphyrin 6 (M — Cu) forms with two equivalents of malononitrile the bisadduct 8.111... 

The starting diazo esters 110 were prepared by diazo transfer from the corresponding malonate esters 109. A selection of chiral Hgands in conjunction with 2mol% (with respect to the diazo compound) of [Cu(OTf)2] in (CH2C1)2 was then examined at 65 °C (Scheme 31). All of the Hgands tested were sufficiently reactive to produce diazo decomposition at 65 °C, although the yields of cyclopropanation products were quite variable. Even tertiary... 

Table 5 Results of cyclopropanation reactions with complexes 6a-Cu and 6b-Cu in ionic liquids ...

Similar conclusions concerning the effect of the anion and impurities in the ionic liquid on the cyclopropanation reaction have been drawn in a recently published study [47]. Ionic liquids with the formula [bmim][X], where X = OTf, NTf2, PFe, and BF4, were used. The catalyst used in this study was 6b-Cu(OTf). In all cases, good enantioselectivities (89-97% ee) were obtained and these are similar to those obtained in chloroform. The influence of the presence of halogen anions was tested by the addition of 5% [bmim] [Cl] or [bmim][Br] to [bmim][BF4]. In both cases, a catalytically inactive solution was obtained, showing the detrimental effect of these anions on the reaction. 

The solids were used as catalysts in the benchmark cyclopropanation reaction between styrene and ethyl diazoacetate (Scheme 7). As far as the nature of the clay is concerned, laponite was foimd to be the best support for the catalytic complexes. The best enantioselectivity results (Table 7) were obtained with ligand 6b (69% ee in trans cyclopropanes and 64% ee in cis cyclopropanes) but the recovered solid showed a lower activity and enantioselectivity, which was attributed to partial loss of the chiral ligand from the support. In general, the use of the three chiral ligands led to enantioselectivity results that were intermediate between those obtained in homogeneous phase with CuCl2 and Cu(OTf)2 as catalyst precursors. This seemed to indicate that the sohd behaved as a counterion with an intermediate coordinating abihty to the copper centers. 

In view of this behavior, the next step involved a search for an anionic sohd that was more similar to triflate. Several organic polymers with sulfonic groups were tried as supports [52]. Dowex and Deloxan were used as supports for the enf-6a-Cu(II) complex. The solid catalysts were used in the same cyclopropanation reaction (Scheme 7) and some relevant results are gathered in... 

Table Results of cyclopropanation reactions with 6a-Cu(OTf)2 and 6b-Cu(OTf)2 in solution and exchanged on anionic supports ...

In the case of the reaction between N-acryloyloxazolidin-2-one and cy-clopentadiene, both catalysts showed activities and enantioselectivities similar to those observed in homogeneous phase. However, a reversal of the major endo enantiomer obtained with the immobilized 6a-Cu(OTf)2 catalyst, with regard to the homogeneous phase reaction, was noted. Although this support effect on the enantioselectivity remains unexplained, it resembles the surface effect on enantioselectivity of cyclopropanation reaction with clay supports [58]. 

Scheme 5.3 Cyclopropanation of alkenes and ethyl diazoacetate using Cu-NHC complexes...

A NHC-Cu complex 9 has also been used in the cyclopropanation of 5 and cyclooctene 8 using EDA 6 (Scheme 5.3) [5]. Complex 9 was isolated prior to use and, as in the case of NHC-Ru complex, the cyclopropanation reaction did not display high diastereoselectivity. However, products 7 and 10 were obtained in good to excellent yields depending on the ratio between the alkenes and EDA. Improved yields were obtained when alkenes were used in six- or ten-fold excess. 

As an extension of this methodology, the efficiency of these ligands was also evaluated by these authors for the Cu-catalysed cyclopropanation of styrene derivatives with EDA, providing the corresponding cyclopropanes with similar enantioselectivities of up to 97% ee (Scheme 6.4). ... 

Scheme 6.4 Bis(oxazolines)thiophene ligands for Cu-catalysed cyclopropanations of alkenes with EDA.

Scheme 6.5 Bis(oxazolines)bithiophene ligands for Cu-catalysed cyclopropanation of styrene with EDA.

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... 

Section B gives some examples of metal-catalyzed cyclopropanations. In Entries 7 and 8, Cu(I) salts are used as catalysts for intermolecular cyclopropanation by ethyl diazoacetate. The exo approach to norbornene is anticipated on steric grounds. In both cases, the Cu(I) salts were used at a rather high ratio to the reactants. Entry 9 illustrates use of Rh2(02CCH3)4 as the catalyst at a much lower ratio. Entry 10 involves ethyl diazopyruvate, with copper acetylacetonate as the catalyst. The stereoselectivity of this reaction was not determined. Entry 11 shows that Pd(02CCH3) is also an active catalyst for cyclopropanation by diazomethane. 

A better diastereoselectivity with Cu-catalyzed cyclopropanation was discovered. 

The positively charged phosphonium ligand was intercalated in the hectorite and was used to catalyze olefin hydroformylation.156 Cu(II)-exchanged clays were tested as catalysts in the cyclopropanation reaction of styrene with... 

Smooth and efficient cyclopropanation also occurs with copper(II) triflate and diazomethane. Intra- and intermolecular competition experiments show that, in this case, the less substituted double bond reacts preferentially251. The same is true for CuOTf and Cu(BF4)2, whereas with CuX P(OMe)3 (X = Cl, I), CuS04 and cop-per(II) acetylacetonate, cyclopropanation of the more substituted double bond predominates. An example is given for cyclopropanation of 1. 

The same difference in regioselectivity holds for cyclopropanation with ethyl diazoacetate 25 K It is assumed that Cu(OTf)2 or Cu(BF4)2 are reduced to the Cu(I) salts by the diazo compound the ability of CuOTf to form stable complexes with olefins may then explain why, with these catalysts, cyclopropanation is governed by the steric environment around a double bond rather than by its electron-richness. 

Copper(II) triflate has also been used for the carbenoid cyclopropanation reaction of simple olefins like cyclohexene, 2-methylpropene, cis- or rran.y-2-butene and norbomene with vinyldiazomethane 2 26,27). Although the yields were low (20-38 %), this catalyst is far superior to other copper salts and chelates except for copper(II) hexafluoroacetylaeetonate [Cu(hfacac)2], which exhibits similar efficiency. However, highly nucleophilic vinyl ethers, such as dihydropyran and dihydrofuran cannot be cyclopropanated as they rapidly polymerize on contact with Cu(OTf)2. With these substrates, copper(II) trifluoroacetate or copper(II) hexafluoroacetylaeetonate have to be used. The vinylcyclopropanation is stereospecific with cis- and rra s-2-butene. The 7-vinylbicyclo[4.1.0]heptanes formed from cyclohexene are obtained with the same exo/endo ratio in both the Cu(OTf)2 and Cu(hfacac)2 catalyzed reaction. The... 

Cu(OTf)2 generally gives yields intermediate between those of the other two catalysts, but with a closer resemblance to rhodium. In competition experiments, the better coordinating norbomene is preferred over styrene, just as in the case with Pd(OAc)2. Cu(acac)2, however, parallels Rh2(OAc)4 in its preference for styrene. These findings illustrate the variability of copper-promoted cyclopropanations, and it was suggested that in the Cu(OTf)2-catalyzed reactions of diazoesters, basic by-products, which are formed as the reaction proceeds, may gradually suppress... 

Table 5. Yields of cyclopropanation of various olefins by diazoacetic esters in the presence of Rh2(OAc)4, Pd(OAc)2 or Cu(OTf)/ b...

Cycloheptatriene, as an example of a conjugated triene, is mainly cyclopro-panated at an outer double bond (Scheme 6). This is true for Rh2(OAc)4, Cu(OTf)2 and Pd(OAc)2, but the highest yield is obtained again with the rhodium catalyst72>. Twofold cyclopropanation occurs to only a minor extent, as long as an excess of olefin is applied. With equal amounts of diazo ester and cycloheptatriene, double cyclopropanation increases and even traces of the triply cyelopropanated triene are found with Rh2(OAc)4 and Cu(OTf)2. This behavior essentially parallels the earlier... 

Cu(OTf)2 is an intermediate case (Scheme 9). These findings parallel the catalyst s control over the regioselectivity of cyclopropanation with diazodiphenylmethane 47 (see Sect. 2.1). 

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