Cyclopropanation 2-symmetric

A review of neighbouring-group effects in natural products includes steroidal examples. The 19-acetoxy-5a-bromo-6-oxo-steroids (228) fragment with base to give the 6-oxo-A -compounds (229) which are regarded as potentially useful intermediates in prostanoid synthesis.The preparation and properties of the 6-spirocyclopropane (230) have been reported. Attempts to cleave the cyclopropane symmetrically were unsuccessful although other cleavages are discussed. ... 

FIGURE 3. Interaction of H Is orbital or C p orbital with the cyclopropane symmetric 3e orbital. 

Chiral C2-symmetric semicorrins (structure 4), developed by Pfaltz [11], were proven to be highly efficient ligands for the copper-catalyzed enantio-selective cyclopropanation of olefins. Variations of the substituents at the stereogenic centers led to optimized structures and very high enantioselectiv-ities [12]. 

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]. 

Other types of new AT-containing ligands have been described as effective chiral inductors for copper-catalyzed asymmetric cyclopropanation. Hence, Fu and Lo [42] prepared a new planar-chiral hgand, namely the C2-symmetric bisazaferrocene (structure 34 in Scheme 18), which was fbimd to be efficient for the cyclopropanation of various olefins with large diastereomeric excesses and ee values up to 95%. 

It is concluded from these results that with this kind of non-C2 symmetric ligand (that led necessarily to poor enantioselectivities in homogeneous phase), it is possible to exploit support effects to change the trans/cis selectivity and to improve the enantioselectivity. This is demonstrated for the trans-cyclopropanes obtained with ligand 10a in styrene. Due to the relative disposition of the ester and phenyl groups in the transition state, support ef-... 

The HO of cyclopropane is degenerate 3e MO 91>. The orbital I is responsible for a symmetric interaction, while orbital II is not. The protonation will take place in the a plane as indicated. The mode of... 

In 1986, Pfaltz et al. introduced a new type of pseudo C2-symmetrical copper-semicorrin complex (68) as the catalyst (Scheme 60).227 228 The complexes (68) are reduced in situ by the diazo compound or by pretreatment with phenylhydrazine to give monomeric Cu1 species (69), which catalyze cyclopropanation. Of the semicorrin complexes, complex (68a) (R = CMe2OH) showed the best enantioselectivity in the cyclopropanation of terminal and 1,2-disubstituted olefins.227,228,17 It is noteworthy that complex (68a) catalyzes cyclopropanation, using diazomethane as a carbene source, with good enantioselectivity (70-75% ee).17... 

The molecular structure of the parent compound was investigated in the vapor and in the solid phase using X-ray, XN and GED methods. The reported data are shown in Table 16. In both phases a clear bond length separation could be detected with a localized three-membered ring and its three adjacent double bonds. The symmetry-equivalent cyclopropane bonds are rather long in C3v-symmetric BUL (1.533-1.542 A), which can be explained by the common electron-withdrawing effect of the 7r-systems in a. svM-ciinal conformation. For comparison, the unaffected bonds in unsubstituted cyclopropane are 1.499 A in the crystal and 1.510 A in the gas phase. Therefore, the bond lengths in BUL... 

Ukaji et al.117 reported an enantioselective cyclopropanation reaction in which moderate enantiomeric excess was obtained when a stoichiometric amount of diethyl tartrate was used as a chiral modifier. Takahashi et al.118 achieved better results using the C2-symmetric chiral disulfonamide 205 as the chiral ligand. 

The methylene triplet adds to ethylene symmetrically through the triplet biradical directly (B). The central methylene group (formed from ethylene) is bent downwards by this process (Fig. 10). At this stage rotation or direct ring closure can occur, with loss of stereochemistry following bond formation to yield cyclopropane. The cyclo-addition of the triplet requires only a small activation energy of about 5 kcal/mole 52). 

The most common byproducts encountered in cyclopropanations with diazoalkanes as carbene precursors are azines and carbene dimers , i.e. symmetric olefins resulting from the reaction of the intermediate carbene complex with the diazoalkane. The formation of these byproducts can be supressed by keeping the concentration of diazoalkane in the reaction mixture as low as possible. For this purpose, the automated, slow addition of the diazoalkane to a mixture of catalyst and substrate (e.g. by means of a pump or a syringe motor) has proven to be a very valuable technique. 

For intermolecular cyclopropanations with unsubstituted diazoacetates the highest asymmetric inductions can be achieved with the copper(I) complexes of C2-symmetric, bidentate ligands developed by Pfaltz (e.g. 1) and Evans (2). The chiral rhodium(II) complexes known today do not generally lead to such high enantiomeric excesses as copper complexes in intermolecular cyclopropanations. For intramolecular cyclopropanations, however, chiral rhodium(II) complexes are usually superior to enantiomerically pure copper complexes [1374]. 

The preparation of cyclopropanes by intermolecular cyclopropanation with acceptor-substituted carbene complexes is one of the most important C-C-bond-forming reactions. Several reviews [995,1072-1074,1076,1077,1081] and monographs have appeared. In recent decades chemists have focused on stereoselective intermolecular cyclopropanations, and several useful catalyst have been developed for this purpose. Complexes which catalyze intermolecular cyclopropanations with high enantiose-lectivity include copper complexes [1025,1026,1028,1029,1031,1373,1398-1400], cobalt complexes [1033-1035], ruthenium porphyrin complexes [1041,1042,1230], C2-symmetric ruthenium complexes [948,1044,1045], and different types of rhodium complexes [955,998,999,1002-1004,1010,1062,1353,1401-1405], Particularly efficient catalysts for intermolecular cyclopropanation are C2-symmetric cop-per(I) complexes, as those shown in Figure 4.20. These complexes enable the formation of enantiomerically enriched cyclopropanes with enantiomeric excesses greater than 99%. Illustrative examples of intermolecular cyclopropanations are listed in Table 4.24. 

It is however not ruled out that the reaction might have proceeded through the formation of a symmetrical intermediate such as phenyl-cyclopropane. 

The reaction of vinylcarbenoids with vinyl ethers can lead to other types of [3 + 2] cycloadditions. The symmetric synthesis of 2,3-dihydrofurans is readily achieved by reaction of rhodium-stabilized vinylcarbenoids with vinyl ethers (Scheme 14.17) [107]. In this case, (J )-pantolactone is used as a chiral auxihary. The initial cyclopropanation proceeds with high asymmetric induction upon deprotection of the silyl enol ether 146, ring expansion occurs to furnish the dihydrofuran 147, with no significant epi-merization during the ring-expansion process. 

Cycloadditions to [6,6]-double bonds of Cjq are among the most important reactions in fullerene chemistry. For a second attack to a [6,6]-bond of a C q monoadduct nine different sites are available (Figure 10.1). For bisadducts with different but symmetrical addends nine regioisomeric bisadducts are, in principle, possible. If only one type of symmetrical addends is allowed, eight different regioisomers can be considered, since attack to both e - and e"-positions leads to the same product. Two successive cycloadditions mostly represent the fundamental case and form the basis for the regioselectivity of multiple additions. In a comprehensive study of bisadduct formations with two identical as well as with two different addends, nucleophilic cyclopropanations, Bamford-Stevens reactions with dimethoxybenzo-phenone-tosylhydrazone and nitrene additions have been analyzed in detail (Scheme 10.1) [3, 9, 10]. 

Seven of these were found after cyclopropanation of e- and trans-n-Cg2(COOEt)4 (n = 2-4) (4-7) with diethylmalonate (Figure 10.6) [20]. In a few cases, such as the Cj-symmetric adduct 8 (e,e,e-addition pattern), the structure can be assigned based on NMR spectroscopy alone. NMR spectroscopy allows for the determination of the point group of the adduct. The e,e,e-addition pattern is the only one that has Cj-symmetry and as a consequence the assignment is unambiguous. The same is true for the Dj-symmetrical adduct 9. Conversely, C2-, C - or Cj-symmetry of trisadducts can arise from different addition patterns. The structural assignment of such adducts requires the additional analysis of their possible formation pathways. 

For example, adduct 12 was formed from e-4, trans-3-6 and trans-2-7. Consequently, it must involve these three positional relationships. Therefore, its structural assignment is unambiguous. Similarly, various trisadducts carrying C2-symmetrical bis(oxazoline) addends could be isolated and structurally assigned [19, 20]. The regioselectivities of these cyclopropanations strongly depend on the precursor bisadduct. Whereas, for example, all possible trisadducts 9,10, 12,14 that can be obtained from trans-3-6 were formed in about equal amounts the cyclopropanation of trans-4-5 is more selective. Among the four isolated isomers 10 was the most abundant. The fifth isomer, with a Cj -symmetrical tmns-4, trans-4, trans-4- addition pattern, was not found. 

Further cyclopropanation of e,e,e-8 leads to the Q-symmetrical tetrakisadduct 15 and the C2 -symmetrical pentakisadduct 16 and the Tfj-symmetrical hexakisadduct 17 (Figure 10.7) [16]. 

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