Stereoselectivity alkene cyclopropanation

The complex [Fe(D4-TmAP)Cl] with Halterman s porphyrin ligand can effect asymmetric alkene cyclopropanation with diazoacetate in high product yield and high stereoselectivity [57]. The reaction occurs smoothly at room temperature without the need for addition of CoCp2, affording the cyclopropyl esters... 

It has been pointed out earlier that the anti/syn ratio of ethyl bicyclo[4.1,0]heptane-7-carboxylate, which arises from cyclohexene and ethyl diazoacetate, in the presence of Cul P(OMe)3 depends on the concentration of the catalyst57). Doyle reported, however, that for most combinations of alkene and catalyst (see Tables 2 and 7) neither concentration of the catalyst (G.5-4.0 mol- %) nor the rate of addition of the diazo ester nor the molar ratio of olefin to diazo ester affected the stereoselectivity. Thus, cyclopropanation of cyclohexene in the presence of copper catalysts seems to be a particular case, and it has been stated that the most appreciable variations of the anti/syn ratio occur in the presence of air, when allylic oxidation of cyclohexene becomes a competing process S9). As the yields for cyclohexene cyclopropanation with copper catalysts [except Cu(OTf)2] are low (Table 2), such variations in stereoselectivity are not very significant in terms of absolute yields anyway. 

Stereoselective inns-cyclopropanation. Rhodium(II) carboxylates are generally the preferred catalysts for cyclopropanation of alkenes with diazoacetates (7,313 9,406,10,340) even though they show only low tram-selectivity. The tram-selectivity can be markedly enhanced by use of rhodium(II) acetamide. Use of rhodium(II) 2,4,6-triarylbenzoates favors ds-stereoselectivity.1... 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

The stereoselectivity of cyclopropane ester formation could also be effected by using reagents supported on linear or cross-linked polymers. The most important effects were noted with chloromethylated polymers cross-linked with divinylbenzene. The role of hyperconjugation in determining the stereochemistry of nucleophilic cyclopropanation of electrophilic alkenes has been studied and predicted In terms of equation 57 the... 

The predictable inversion of configuration that accompanies 8 2 substitution reactions can be used to convert stereoselectively labeled vicinal dihaloalkanes into stereoselectively labeled cyclopropanes. The dihaloalkanes can, themselves, be prepared by halogenation of stereoselectively labeled alkenes. Two examples are shown in Figure 8 and Figure 9 . 

A little-used route to stereoselectively labeled cyclopropanes is nucleophilic addition to the corresponding cyclopropene. Access to both labeled and unlabeled cyclopropenes from the corresponding 1-alkynes allows preparation of both diastereomers of the labeled product. This route is one of the few that would allow easy preparation of a 1,1-disubstituted-cyclopropane-2-d. Cyclopropanation of the corresponding alkene would in principle achieve the same goal but preparation of such alkenes with a label in a defined stereochemical position is not easy. An example of the approach is shown in Figure 10. ... 

New evidence as to the nature of the intermediates in catalytic diazoalkane decomposition comes from a comparison of olefin cyclopropanation with the electrophilic metal carbene complex (CO)jW—CHPh on one hand and Rh COAc) / NjCHCOOEt or Rh2(OAc)4 /NjCHPh on the other . For the same set of monosubstituted alkenes, a linear log-log relationship between the relative reactivities for the stoichiometric reaction with (CO)5W=CHPh and the catalytic reaction with RhjfOAc) was found (reactivity difference of 2.2 10 in the former case and 14 in the latter). No such correlation holds for di- and trisubstituted olefins, which has been attributed to steric and/or electronic differences in olefin interaction with the reactive electrophile . A linear relationship was also found between the relative reactivities of (CO)jW=CHPh and Rh2(OAc) NjCHPh. These results lead to the conclusion that the intermediates in the Rh(II)-catalyzed reaction are very similar to stable electrophilic carbenes in terms of electron demand. As far as cisjtrans stereoselectivity of cyclopropanation is concerned, no obvious relationship between Rh2(OAc) /N2CHCOOEt and Rh2(OAc),/N2CHPh was found, but the log-log plot displays an excellent linear relationship between (CO)jW=CHPh and Rh2(OAc) / N2CHPh, including mono-, 1,1-di-, 1,2-di- and trisubstituted alkenes In the phenyl-carbene transfer reactions, cis- syn-) cyclopropanes are formed preferentially, whereas trans- anti-) cyclopropanes dominate when the diazoester is involved. 

Stereochemical data support the occurence of these intermediates, as also shown by Doyle et al. (1984 b) They compared reactivities and stereoselectivities of cyclopropanations of phenyldiazomethane and eleven different open-chain alkenes containing a terminal double bond or a double bond in the chain, and a cyclic alkene (cyclopentene) catalyzed by the binuclear complex Rh2(OCOCH3)4 (8.127, see later in this section), with the reactivities and stereoselectivities of cyclopropanations of the same alkenes with (benzylidene)(pentacarbonyl)tungsten [(CO)5W(CHC6H5)], i.e., a stable metal-carbene. An almost perfect linear relationship of the cyclopropane derivatives of the eleven alkenes with the two carbene sources was obtained. On this basis, Doyle and his coworkers concluded that the reaction starts with an initial association of the alkene 71-bond with the electrophilic center of the metal-carbene complex, followed by o-bond formation with backside displacement... 

Stereoselectivity of cyclopropanation with 22 alkenes and regioselectivity of monosubstituted buta-l,3-dienes are highest for a copper(i) catalyst, intermediate for two Rh catalysts and lowest for a PdCl2 complex. On the basis of these comparisons, Doyle et al. were able to define and determine simple linear relationships, namely an index S of relative stereoselectivity (1984 a), and R of relative regioselectivity (1982 b). More data on stereo- and regioselectivities were summarized by Doyle (1986). We shall return to the mechanism of stereoselectivity of cyclopropanation later in this section in the context of dihydrofuran formation. 

Intramolecular cyclopropanation is a simple and convenient method to produce bicyclic or tricyclic cyclopropanes when electrophiles, such as carbene precursors, and nucleophiles, such as alkenes, are present in the same molecule. The most significant advancement of this method is the formation of [3.1.0] and [4.1.0] bicyclic compounds from the cyclopropanation of allylic and homoallylic diazocarbonyl compounds. Some of the high stereoselective macrocyclic cyclopropanes, with up to 20-membered ring, can also be synthesized with this method. Among the catalysts used in these reactions, rhodium catalysts are most frequently used for their high yields and stereoselectivities. Their exceptional enantiocontrols in a variety of diazo-alkene substrates make them very popular in bioactive molecular synthetic applications. 

The stereoselectivity of cyclopropanation is highly affected by the stereogenic centers close to the alkene unit. Aggarwal et al. reported that A -chiral allylic amine 96 underwent stereoselective cyclopropanation to give 97 in 95% yield (Scheme 1.50) [85]. The obtained product 97 was almost a single isomer. 

Charette and coworkers investigated the stereoselectivity of gem-zinc carbenoids in the reaction with allylic alcohols 100 and 101 (Scheme 1.52). Configuration at the allylic stereogenic center and alkene geometry affected the stereoselectivity of cyclopropanation [87]. 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

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