Chiral olefins cyclopropanation

Various approaches to epoxide also show promise for the preparation of chiral aziridines. Identification of the Cu(I) complex as the most effective catalyst for this process has raised the possibility that aziridination might share fundamental mechanistic features with olefin cyclopropanation.115 Similar to cyclo-propanation, in which the generally accepted mechanism involves a discrete Cu-carbenoid intermediate, copper-catalyzed aziridation might proceed via a discrete Cu-nitrenoid intermediate as well. 

Dinuclear Rh(II) compounds are another class of effective catalysts (227). Electrophilic carbenes formed from diazo ketones and dimeric Rh(II) carboxylates undergo olefin cyclopropanation. Chiral Rh(II) carboxamides also serve as catalysts for enantioselective cyclopropanation (Scheme 95) (228). The catalysts have four bridging amide ligands, and... 

Although the diastereocontrolled cyclopropanation generally uses a chiral diazo compound, there is one exception in which a chiral olefin was used to react with an achiral diazo compound. Thus, copper catalysed cyclopropanation of chiral butadiene iron tricarbonyl complex 150 with methyl diazoacetate provided a 1 1 mixture of the trans (151) and cis (152) isomers (equation 132). The diastereomeric excess of both trans and cis are 90% and the decomplexation can be easily achieved by treating the adduct with trimethyl nitroxide in dichloromethane188. 

Llewellyn DB, Arndtsen BA (2005) Synthesis of a library of chiral a-amino acid-based borate counteranions and their application to copper catalyzed olefin cyclopropanation. Tetrahedron Asymmetry 16 1789-1799 Makino T, Baba N, Oda J, Inouye Y (1977) Asymmetric reduction of alpha, beta-unsaturated iminuum salt with A-glucopyranosyl-l,4-dihydronicotin-amides. Chemlnd 1977 277-278... 

This method can also be applied to complexes of conjugated trienes. The uncomplexed double bond may be constructed within the complex via Wittig olefination. Cyclopropanation of the uncomplexed double bond of the resulting tricarbonyliron-triene complexes and oxidative decomplexation leads to dienylcyclopropane products. In this manner chiral dienyl-cyclopropanes 4 and 5 were prepared in high enantiomeric excess (> 90% ee) starting from optically active tricarbonyliron-hexatriene complexes 3 obtained from chirally modified sorbic aldehyde complexes. 

The asymmetric version of the olefin cyclopropanation reaction has also been described with a chiral fran5-Tpp Cu complex (Scheme 8), that led to enantiomeric excess (ee) values in the 80-85% range for both cis and trans isomers in the reaction of styrene and EDA7 ... 

Carbenes with coordination number 1, e.g., alkylidene carbenes. are not considered in this section. They are extensively described in Vol. E19b, p 84. Several examples demonstrate the stereospecificity of their [2 + 1] cycloaddilions to olefins. A few reactions which employ chiral olefins indicate that these are cyclopropanated from the sterically more accessible face (Vol. El9b. p 145). 

A mechanism involving enantioface selective olefin attack upon transient chiral cobalt carbene complexes formed from prochiral diazoalkanes has been proposed to account for the high degree of enantioselectivity observed in cobalt-(ii) catalysed olefin cyclopropanation using chiral diazoalkanes. ... 

While generation of a Mn(V)oxo salen intermediate 8 as the active chiral oxidant is widely accepted, how the subsequent C-C bond forming events occur is the subject of some debate. The observation of frans-epoxide products from cw-olefins, as well as the observation that conjugated olefins work best support a stepwise intermediate in which a conjugated radical or cation intermediate is generated. The radical intermediate 9 is most favored based on better Hammett correlations obtained with o vs. o . " In addition, it was recently demonstrated that ring opening of vinyl cyclopropane substrates produced products that can only be derived from radical intermediates and not cationic intermediates. ... 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

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]. 

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

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%. 

Enantioselective carbenoid cyclopropanation can be expected to occur when either an olefin bearing a chiral substituent, or such a diazo compound or a chiral catalyst is present. Only the latter alternative has been widely applied in practice. All efficient chiral catalysts which are known at present are copper or cobalt(II) chelates, whereas palladium complexes 86) proved to be uneflective. The carbenoid reactions between alkyl diazoacetates and styrene or 1,1 -diphenylethylene (Scheme 27) are usually chosen to test the efficiency of a chiral catalyst. As will be seen in the following, the extent to which optical induction is brought about by enantioselection either at a prochiral olefin or at a prochiral carbenoid center, varies widely with the chiral catalyst used. 

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. 

Diastereoface-differentiating reactions of a carbenoid with an alkene bearing an easily removable, chiral substituent have been used only ocassionally for the enantioselective production of a cyclopropane 216). A recent example is given by the cyclopropanation of the (—)-ephedrine-derived olefin 223 with CH2N2/Pd(OAc)2 after removal of the protecting group, (1/ , 2R )-2-phenylcyclopropane carbaldehyde was isolated with at least 90% e.e. 37). 

In 1966, Nozaki et al. reported that the decomposition of o-diazo-esters by a copper chiral Schiff base complex in the presence of olefins gave optically active cyclopropanes (Scheme 58).220 221 Following this seminal discovery, Aratani et al. commenced an extensive study of the chiral salicylaldimine ligand and developed highly enantioselective and industrially useful cyclopropanation.222-224 Since then, various complexes have been prepared and applied to asymmetric cyclo-propanation. In this section, however, only selected examples of cyclopropanations using diazo compounds are discussed. For a more detailed discussion of asymmetric cyclopropanation and related reactions, see reviews and books.17-21,225... 

The chiral rhodium porphyrin catalyst (90) shows a high turnover rate, though enantioselec-tivity is modest (less than 60% ee). It is, however, noteworthy that cw-selective cyclopropanation of simple olefins (cisjtrans = 2—14.2/1) was realized for the first time with (90).249 250... 

Two strategies have been adopted for asymmetric cyclopropanation. First, there are auxiliary-based methods, involving a covalently attached adjacent chiral moiety on either the olefin or the cyclopropylating agent. The second process, on the other hand, employs a chiral ligand on a metal catalyst. This method is more applicable to route b or c, and this is an issue that warrants further discussion. 

The next major contribution in asymmetric cyclopropanation was the introduction of chiral semicorrin ligands 184 by Fritschi et al.95 This ligand has been used for coordinating with copper and has been found to provide improved enantiocontrol in the cyclopropanation of monosubstituted olefins. Copper(I), coordinated by only one semicorrin ligand, is believed96 to be the catalytically active oxidation state. The copper(I) oxidation state can be reached directly... 

Lo and Fu112 have reported a new type of planar-chiral ligand 203 for the enantioselective cyclopropanation of olefins. As shown in Scheme 5-62, asymmetric cyclopropanation in the presence of chiral ligand 203 proceeds smoothly, giving the cyclopropanation product with high diastereoselectivity and enantioselectivity. 

Some diazoalkanes cyclopropanate olefins in the absence of any catalyst [658-660]. Thus, for instance, upon generation from A -cyclopropyl-A -nitrosourea at 0 °C diazocyclopropane spontaneously cyclopropanates methylenecyclopropanes [658]. Thermal, uncatalyzed cyclopropanations of unactivated olefines with aryldiazome-thanes can already occur at only slightly elevated temperatures (e.g. at 80 °C with 1-naphthyldiazomethane [661]). Henee, for enantioselective cyclopropanations with a chiral catalyst, low reaction temperatures should be chosen to minimize product formation via the uncatalyzed pathway. 

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