Cyclopropanation of styrene

Fig. 3.8 Cyclopropanation of styrene in the presence of alcohol ligands. [Yang, Z. Lorenz, ).C. Shi, Y. Tetrahedron Lett. 1998, 39, 8621. Reprinted with permission from Elsevier Ltd.)...

Ruthenium porphyrin complexes are also active in cyclopropanation reactions, with both stoichiometric and catalytic carbene transfer reactions observed for Ru(TPP)(=C(C02Et)2> with styrene. Ru(Por)(CO)orRu(TMP)(=0)2 catalyzed the cyclopropanation of styrene with ethyidiazoacetate, with aiiti.syn ratios of 13 1... 

These two compounds with S configuration on their oxazohne rings were tested as copper(I) catalysts for the cyclopropanation of styrene, the hgand 9 with S axial chirality being much more enantioselective than 10 with the R configuration. Thus, the catalytic system CuOTf-(S,S)-bis(oxazolyl)-binaphthyl (9, R = Bu) led to excellent enantioselectivities, particularly for the cyclopropanation of styrene with (-menthyldiazoacetate 95% ee for the trans-cyclopropane and 97% ee for the cis, with trans/cis = 68/32. 

The aza-bis(oxazoline) 14, bearing sterically hindering groups, led to very good results in terms of activity and selectivity, comparable to those obtained from corresponding aza-semicorins or bis(oxazolines). For the enantioselec-tive cyclopropanation of styrene, the trans isomer was obtained in 92% ee... 

Pyridine-based N-containing ligands have been tested in order to extend the scope of the copper-catalyzed cyclopropanation reaction of olefins. Chelucci et al. [33] have carefully examined and reviewed [34] the efficiency of a number of chiral pyridine derivatives as bidentate Hgands (mainly 2,2 -bipyridines, 2,2 6, 2 -terpyridines, phenanthrolines and aminopyridine) in the copper-catalyzed cyclopropanation of styrene by ethyl diazoacetate. The corresponding copper complexes proved to be only moderately active and enantios-elective (ee up to 32% for a C2-symmetric bipyridine). The same authors prepared other chiral ligands with nitrogen donors such as 2,2 -bipyridines 21, 5,6-dihydro-1,10-phenanthrolines 22, and 1,10-phenanthrolines 23 (see Scheme 14) [35]. 

Chelucci et al. [41] synthesized further chiral terpyridines derived from (-)-yd-pinene, (-i-)-camphor, and (-l-)-2-carene and tested their ability to chelate copper or rhodium for the asymmetric cyclopropanation of styrene. The copper catalysts were poorly efficient and selective in this reaction. The corresponding rhodium complexes led to the best result (64% ee) with the ligand derived from (-l-)-2-carene (ligand 33 in Scheme 17). 

In dichloromethane, this complex with alow catalyst loading (1 mol%) achieved the cyclopropanation of styrene with ethyldiazoacetate in high di-astereoselectivity (trans/cis = 90/10) and enantioselectivity (up to 97% ee for the major isomer). 

Metalloporphyrins have proved their efficiency as ruthenium carbonyl hg-ands for the enantioselective cyclopropanation of styrene [50,51]. 

Woo et al. [54] prepared new chiral tetraaza macrocyclic hgands (48 in Scheme 23) and their corresponding iron(II) complexes and tested them, as well as chiral iron(II) porphyrin complexes such as Fe (D4 -TpAP) 49, in asymmetric cyclopropanation of styrene. 

Clarke and Shannon also supported copper bis(oxazoline) complexes onto the surfaces of inorganic mesoporous materials, such as MCM-41 and MCM-48, through the covalent binding of the ligand, modified by alkoxysilane functionalities [59]. The immobilized catalysts allowed the cyclopropanation of styrene with ethyldiazoacetate to be performed as for the corresponding homogeneous case, and were reused once with almost no loss of activity or selectivity. 

The copper complexes of these ligands were tested in the cyclopropanation of styrene with ethyl diazoacetate (Scheme 7) and the ene reaction between a-methylstyrene and ethyl glyoxylate (Scheme 8). hi both cases moderate enantioselectivities were obtained but these were lower than those foimd with the parent hgand. 

Aryldiazomethane can also be used for iron porphyrin-catalyzed alkene cyclopropanation [55]. For example, the treatment of p-tolyldiazomethane with styrene in the presence of [Fe(TTP)] afforded the corresponding arylcyclopropapane in 79% yield with a high transicis ratio of 14 1 (eq. 1 in Scheme 11). Interestingly, when bulkier mesityldiazomethane was used as carbene source, ds-selectivity was observed (cisitrans = 2.0 1). Additionally, mesityldiazomethane was found to react with frans-p-styrene, the latter was found not to react with EDA or trimethyl-silyldiazomethane under the similar reaction conditions, to give l-mesityl-2-methyl-3-phenylcyclopropane in 35% yield. Trimethylsilyldiazomethane is also an active carbene source for [Fe(TTP)]-catalyzed cyclopropanation of styrene, affording l-phenyl-2-trimethylsilylcyclopropane in 89% yield with transicis ratio of 10 1 (eq. 2 in Scheme 11). 

Interestingly, the cyclopropanation of styrenes with EDA catalyzed by the half sandwich iron complex [CpFe(CO)2(THF)] BF4 afforded cyclopropanes in good yields and with ds-selectivity cisitrans = 80 20) [62]. With phenyldiazomethane as a carbene source, excellent cA-selectivity (92-100%) was achieved (Scheme 15) [63]. 

Scheme 5.2 Cyclopropanation of styrene and ethyl diazoacetate using ruthenium-NHC complexes...

The use of stoichiometric ruthenium-NHC complexes generated in situ from [Ruljd-COCKp-cymene)], an imidazohnm salt [4] or an imidizol(idin)ium-2-carboxylate [4] has been applied in the cyclopropanation of styrene 5 with ethyl diazoacetate (EDA) 6 (Scheme 5.2). No base was necessary when imidazolium-2 carboxylate were employed. The diastereoselectivity was low and the cis/trans ratio was around 50/50 (Table 5.1). Although the diastereoselectivity was moderate, the reaction was highly chemoselectivity as possible side reactions (homologation, dimerisation and metathesis) were totally or partially suppressed. 

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

In 2004, ruthenium-catalysed asymmetric cyclopropanations of styrene derivatives with diazoesters were also performed by Masson et al., using chiral 2,6-bis(thiazolines)pyridines. These ligands were prepared from dithioesters and commercially available enantiopure 2-aminoalcohols. When the cyclopropanation of styrene with diazoethylacetate was performed with these ligands in the presence of ruthenium, enantioselectivities of up to 85% ee were obtained (Scheme 6.6). The scope of this methodology was extended to various styrene derivatives and to isopropyl diazomethylphosphonate with good yields and enantioselectivities. The comparative evaluation of enantiocontrol for cyclopropanation of styrene with chiral ruthenium-bis(oxazolines), Ru-Pybox, and chiral ruthenium-bis(thiazolines), Ru-thia-Pybox, have shown many similarities with, in some cases, good enantiomeric excesses. The modification... 

On the other hand, Doyle et al. have developed methyl 2-oxoimidazolidine-4(carboxylate ligands, containing 2-phenylcyclopropane attached at the 1-iV-acyl site, such as the (4(5),2 (7 ),3 (7 )-HMCPIM) ligand. The resulting dirhodium complex led, for the cyclopropanation of styrene with EDA, to the corresponding cyclopropane with 68% ee and 59% yield, but with almost... 

On the other hand, other chiral dirhodium(II) tetracarboxylate catalysts based on azetidine- and aziridine-2-carboxylic acids have been prepared by Zwanenburg et al. and submitted to the cyclopropanation of styrene with... 

Scheme 6.18 Rh-catalysed cyclopropanation of styrene with sulfonamide ligands derived from aziridine- and azetidine-2-carboxylic acids.

In another reaction dendritic pyridine derivatives such as 82 or 83 were tested as co-catalysts for enantioselective cyclopropanation of styrene with ethyl diazoacetate [102]. Using catalyst 82, enantiomer ratios of up to 55 45 were obtained. However, with catalyst 83 bearing larger branches yields and selectivities did not increase. The relatively low selectivities were rationalized by the presence of a large number of different conformations that this non-rigid system may adopt. 

Metal complexes of tetra-4-ferf-butylphthalocyanine [PcM, M = Mn(III)OAc, Cu(II), Co(II), Ni(II), Fe(II) (C5H5N)2, Rh(III)Cl] have also been tested for their stereoselective potential in the cyclopropanation of styrene with ethyl diazoacetate 101K The Co(II) and Rh(I) complexes, already highly active at room temperature, produced the 2-phenylcyclopropanecarboxylic esters in a E Z isomer ratio of 1.0-1.2 which compares well with the value obtained with the rhodium(III) porphyrin 47 a (1.2). In the other cases, E.Z ratios of 2.0-2.2 were observed, except for M = Fe(II) (C5HsN)2 where it was (3.0) the E.Z ratio of the purely thermal reaction was 2.0. 

Katsuki et al. have reported that the CoIII(salen) ((98) X = I, Y = t-Bu) bearing an apical halide ligand shows high trara-selectivity in the cyclopropanation of styrene and its derivatives, albeit with moderate enantioselectivity (Scheme 71).267 The enantioselectivity is influenced, however, by the natures of the apical ligand and the 5,5 -substituents, and high enantio- and traMs-selectivity has been realized by their appropriate tuning ((98) X = Br, Y = OMe).268 It is noteworthy that the CoIII(salen) complex bearing substituents at C3 and C3 shows no catalytic activity. 

Certain transition metal complexes catalyze the decomposition of diazo compounds. The metal-bonded carbene intermediates behave differently from the free species generated via photolysis or thermolysis of the corresponding carbene precursor. The first catalytic asymmetric cyclopropanation reaction was reported in 1966 when Nozaki et al.93 showed that the cyclopropane compound trans- 182 was obtained as the major product from the cyclopropanation of styrene with diazoacetate with an ee value of 6% (Scheme 5-56). This reaction was effected by a copper(II) complex 181 that bears a salicyladimine ligand. 

For example, the asymmetric cyclopropanation of styrene with BDA catalyzed by CuOTf 83 yields cyclopropane with a trans cis ratio of 94 6 and 99% ee for the trans-isomer.31... 

The popularity of Cu(acac)2, where acac = acetylacetonato, as a precatalyst in alkene cyclopropanation using diazoesters has led to the investigation of chiral 1,3-dicarbonyls as a source of asymmetric induction in this process. Mathn et al. (26) report a selective cyclopropanation of styrene with a dimedone-derived diazocarbonyl in the presence of a camphor-derived diketone, Eq. 12. The reaction is con-... 

Scheme 5. Various oxazoline ligands and selectivities in the cyclopropanation of styrene.

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