Chiral alkenes, stereoselective cyclopropanation

D. Stereoselective Cyclopropanation of Alkenes using Chiral Auxiliaries. . . 266... 

The stereoselective cyclopropanation of chiral alkenes can be divided into two classes cyclic and acyclic alkenes. Furthermore, within each class, a subdivision exists involving those that contain a proximal basic group that can direct the cyclopropanation reaction of zinc carbenoids and the others that do not. The discrimination of reactivity between alkenes that possess a proximal basic group and those that do not was first highhghted early on when Simmons and Smith noticed that the cyclopropanation of l-(o-methoxyphenyl)-l-propene was more efficient than that of the related meta and para isomers (equation 46). ... 

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. 

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 range of alkenes that may be used as substrates in these reactions is vast Suitable catalysts may be chosen to permit use of ordinary alkenes, electron deficient alkenes such as a,(3-unsaturated carbonyl compounds, and very electron rich alkenes such as enol ethers. These reactions are generally stereospecific, and they often exhibit syn stereoselectivity, as was also mentioned for the photochemical reactions earlier. Several optically active catalysts and several types of chiral auxiliaries contained in either the al-kene substrates or the diazo compounds have been studied in asymmetric cyclopropanation reactions, but diazocarbonyl compounds, rather than simple diazoalkanes, have been used in most of these studies. When more than one possible site of cyclopropanation exists, reactions of less highly substituted alkenes are often seen, whereas the photochemical reactions often occur predominantly at more highly substituted double bonds. However, the regioselectivity of the metal-catalyzed reactions can be very dependent upon the particular catalyst chosen for the reaction. 

The reactions of these iron carbene reagents with alkenes to give cyclopropanes are stereospecific. They also exhibit high syn stereoselectivity in many cases. Optically active derivatives have been reported that have chiral ligands on iron or chiral alkoxy groups on the prospective caibene center and which have been resolved with the iron itself as a chiral center. Resulting from this work have been some highly enantioselective cyclopropanations. 

The [2+1] cycloaddition between metal carbenoid intermediates and alkenes is a very powerful method for the stereoselective synthesis of cyclopropanes [1-3]. Indeed, the vast majority of chiral catalysts developed for carbenoid chemistry were specifically designed for asymmetric cyclopropanation [1-3]. In recent years, however, a number of other enantioselective cydoadditions have been reported. 

Stereoselectivity) is observed however, for ethylidene complexes of Fe(CO)(PR3)Cp (69) the products reflect trans selectivity. This difference in stereoselectivity has been suggested to be dependent upon which conformer is more reactive. The reaction of a chiral-at-iron cationic carbene complex (70) with styrene or vinyl acetate affords optically active cyclopropane products with high enantioselectivity (Scheme 24). h >3 intramolecular cyclopropanation, as in the case of (71), proceeds moderately well for the formation of norcarane-type ring systems however, intramolecular C-H insertion is a competing pathway when the alkene is highly... 

Historically one of the first asymmetric methods to be explored, cyclopropanation came of age32 with box and salen ligands on Cu(I). Diazo compounds, particularly diazoesters 138, react with Cu(I) to give carbene complexes 140 that add to alkenes, particularly electron-rich alkenes to give cyclopropanes 141. The reaction is stereospecific with respect to the alkene -1runs alkenes giving trans cyclopropanes - and reasonably stereoselective as far as the third centre is concerned. Any enantioselectivity comes from the chiral ligand L. You have already seen the Ru carbene complexes are intermediates in olefin metathesis (chapter 15). 

The reactions of diazoalkanes 9.21 with alkenes lead to pyrazolines 9.22, which are thermally transformed into cyclopropanes. Similar transformations occur during thermal reactions of diazoesters. The use of diazoesters of chiral alcohols did not give useful results, so chiral residues have been introduced on the olefin dipolarophile. Meyers and coworkers [327] carried out the reaction of diazomethane 9.21 (R = R = H) and diazopropane 9.21 (R = R = Me) with chiral lactams 1.92 (R = i-Pr or ferf-Bu, R = Me). These 1,3-dipolar cycloadditions are regioselective, but only CH2N2 leads to an interesting stereoselectivity (Figure 9.9). Morever, when the RM substituent of lactam 1.92 is H, the reaction is no longer stereoselective. 

Intramolecular cyclopropanations with unsaturated diazo ketones have also been reported. Furthermore, enantioselective cyclopropanation with diazomethane can be achieved in up to 75% ee. In detailed mechanistic discussions, a copper(I) species, complexed with only one semicorrin ligand, and formed by reduction and decomplcxation, is suggested as the catalytical-ly active species, cisjtrans Stereoselection and discrimination of enantiotopic alkene faces should take place within a copper-carbene-alkene complex25-54"56. According to these interpretations, cisjtrans selectivity is determined solely by the substituents of the alkene and of the diazo compound (especially the ester group in diazoacetates) and is independent of the chiral ligand structure (salicylaldimine or semicorrin)25. 

By stereoselective additions of carbenes or carbene equivalents to alkenes optically pure cyclopropanes are obtained. " In concerted [2+1] cycloadditions the stereochemistry of the alkene is conserved in the products. (Z)-configurated alkenes lead stereospecifically to cis-cyclopropanes. So far, compared to [2+1] cycloadditions involving alkenes bearing the chiral auxiliary, asymmetric reactions involving chiral carbene precursors proved to be less efficient. 

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