Cyclopropanation with styrene

Bulky ortlio-methylated phosphine-ligand-coordinating rhodium complex 215 was used for enantiocontroUed and diastereocontrolled cyclopropanation with styrene (Scheme 1.98) [150]. The diastereoselectivity and enantioselectivity of the reaction depended on a substituent on the aromatic ring of the hgand. 

Diazoalkanes are reactive consequently, cycloaddition occurs without transition metal catalysts. Davies and coworkers reported that aryldiazoacetate 294 underwent the formation of cyclopropanes with styrenes to give trisubstituted cyclopropanes 295 in good yields (Scheme 1.143) [208]. The active carbene was generated under thermal conditions. 

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. 

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). 

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. 

Reaction of tris(trimethylsilyl)methyllithium 1631 with styrene oxide affords, via 1632 and 1633, the cyclopropane 1634 in 69% yield [25] (Scheme 10.11). The reactions of tris(trimethylsilyl)methyllithium 1631 have been reviewed [26]. 

The chiral bimetallic complex 1653 reacts with TMSOTf 20 in the presence of excess styrene, via 1654, to give the cyclopropane complex 1655 in high yield [38]. The chromium can be readily removed from 1655 by treatment with I2 in Et20. Analogously, the complex 1656 reacts with styrene in 90% yield, via 1657, to give MegSiOH 4 and phenylcyclopropane 1658 [39] (Scheme 10.17). 

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). 

More recently, Carreira reported a [Fe(TPP)Cl]-catalyzed diastereoselective synthesis of trifluoromethyl-substituted cyclopropane in aqueous media [56]. The carbene precursor trifluoromethyl diazomethane is difficult to be handled, generated in situ from trifluoroethyl amine hydrochloride, and reacts with styrene in the presence of [Fe(TPP)Cl] to give the corresponding cyclopropanes in high yields and with excellent diastereoselectivities (Scheme 12). 

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]. 

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. 

Pd(OAc)2 works well with strained double bonds as well as with styrene and its ring-substituted derivatives. Basic substituents cannot be tolerated, however, as the failures with 4-(dimethylamino)styrene, 4-vinylpyridine and 1 -vinylimidazole show. In contrast to Rh2(OAc)4, Pd(OAe)2 causes preferential cyclopropanation of the terminal or less hindered double bond in intermolecular competition experiments. These facts are in agreement with a mechanism in which olefin coordination to the metal is a determining factor but the reluctance or complete failure of Pd(II)-diene complexes to react with diazoesters sheds some doubt on the hypothesis of Pd-olefin-carbene complexes (see Sect. 11). 

Cyclopropanation of C=C bonds by carbenoids derived from diazoesters usually occurs stereospeciflcally with respect to the configuration of the olefin. This has been confirmed for cyclopropanation with copper 2S,S7,60 85), palladium 86), and rhodium catalysts S9,87>. However, cyclopropanation of c -D2-styrene with ethyl diazoacetate in the presence of a (l,2-dioximato)cobalt(II) complex occurs with considerable geometrical isomerization88). Furthermore, CuCl-catalyzed cyclopropanation of cis-2-butene with co-diazoacetophenone gives a mixture of the cis- and trans-1,2-dimethylcyclopropanes 89). 

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. 

It has already been mentioned that prochirality of the olefin is not necessary for successful enantioselective cyclopropanation with an alkyl diazoacetate in the presence of catalysts 207. What happens if a prochiral olefin and a non-prochiral diazo compound are combined Only one result provides an answer to date The cyclopropane derived from styrene and dicyanodiazomethane shows only very low optical induction (4.6 % e.e. of the (25) enantiomer, catalyst 207a) 9S). Thus, it can be concluded that with the cobalt chelate catalysts 207, enantioface selectivity at the olefin is generally unimportant and that a prochiral diazo compound is needed for efficient optical induction. As the results with chiral copper 1,3-diketonates 205 and 2-diazodi-medone show, such a statement can not be generalized, of course. 

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