Cyclopropanations group-selective

A double diastereotopic differentiation strategy on a phosphonoacetate template has been described. The approach utilizes Rh2(OAc)4-catalysed intramolecular cyclopropanation (ICP) employing the (R)-pantolactone auxiliary in the ester functionality of the phosphonoacetate (328).The olefinic diastereofacial selectivity is governed by inherent electronic and steric interactions in the reacting carbene intermediate, while the group selectivity is dictated by the chiral auxiliary. This approach is an effective method to access bicyclic P-chiral phos-phonates (329) (Scheme 87). ... 

Scheme 6.38. (a) Enantioselectivity in intramolecular cyclopropanations [140,141]. (b) Double asymmetric induction in intramolecular cyclopropanations [142]. (c) Group-selective asymmetric cyclopropanation [142]. 

The above-mentioned method is applied to the selective carbon-carbon bond formation between sp carbons [150]. A bromine-zinc exchange reaction of the gcm-dibromo-cyclopropane 96 selectively occurs at the position cis to the phenyl group by treatment with Me4ZnLi2 [151], The reaction of the thus-obtained zincate 97 with VO(OEt)Cl2 leads to the stereoselective formation of l-bromo-l-methyl-2-phenylcyclopropane (98). On the other hand, when the reaction mixture is wanned up to 0 °C, followed by treatment with VO(OEt)Cl2, dimelhylation at the em-positions takes place to give the dimethylcyclopropane (100) via the organozinc 99 as shown in Scheme 2.79)... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

This protective group was used to direct the selective cyclopropanation of a variety of enones. Hydrolysis (HCl, MeOH, H2O, it, 94% yield) affords optically active cyclopropyl ketones. 

This notion is also snpported by the following experimental observations. Because substitution of a cyano gronp on the cyclopropane ring lowers the energy of the Walsh orbital of the cyclopropyl group, the resultant attennation of the interaction of the olefin orbital with the Walsh orbital, if this interaction is indispensable, would reduce the facial selectivity. However, substitution of a cyano gronp on the cyclopropyl group, as in ejco-cyano 59c and endo-cymo 59d, essentially does not modify the syn-preference in dihydroxylation and epoxidation, but even increases the syn preference (59c (98 2) and 59d (>99 <1)) in the case of dihydroxylation. 

The aza-bis(oxazoline) 14, bearing sterically hindering groups, led to very good results in terms of activity and selectivity, comparable to those obtained from corresponding aza-semicorins or bis(oxazolines). For the enantioselec-tive cyclopropanation of styrene, the trans isomer was obtained in 92% ee... 

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-... 

As for cyclopropanation of alkenes with aryldiazomethanes, there seems to be only one report of a successful reaction with a group 9 transition metal catalyst Rh2(OAc)4 promotes phenylcyclopropane formation with phenyldiazomethane, but satisfactory yields are obtained only with vinyl ethers 4S) (Scheme 2). Cis- and trans-stilbene as well as benzalazine represent by-products of these reactions, and Rh2(OAc)4 has to be used in an unusually high concentration because the azine inhibits its catalytic activity. With most monosubstituted alkenes of Scheme 2, a preference for the Z-cyclopropane is observed similarly, -selectivity in cyclopropanation of cyclopentene is found. These selectivities are the exact opposite to those obtained in reactions of ethyl diazoacetate with the same olefins 45). Furthermore, they are temperature-dependent for example, the cisjtrcms ratio for l-ethoxy-2-phenylcyclopropane increases with decreasing temperature. 

Only one report mentions the cyclopropanation with diazodiphenylmethane in the presence of a group VIII metal catalyst. Remarkably enough, the selectivity of the reaction with 5-methylene-bicyclo[2.2.1]hept-2-ene (8) can be reversed completely. With Rh2(OAc)4 as catalyst, the exocyclie double bond is cyclopropanated exclusively (>100 1), whereas in the presence of bis(benzonitrile) palladium(II) chloride the endocyclic C=C bond is attacked with very high selectivity (>50 1)47). 

Some remarks concerning the scope of the cobalt chelate catalysts 207 seem appropriate. Terminal double bonds in conjugation with vinyl, aryl and alkoxy-carbonyl groups are cyclopropanated selectively. No such reaction occurs with alkyl-substituted and cyclic olefins, cyclic and sterically hindered acyclic 1,3-dienes, vinyl ethers, allenes and phenylacetylene95). The cyclopropanation of electron-poor alkenes such as acrylonitrile and ethyl acrylate (optical yield in the presence of 207a r 33%) with ethyl diazoacetate deserve notice, as these components usually... 

The two articles in this current volume describe recent developments with small ring compounds which have not teen compiled in such a context before. T. Hirao discusses selective transformations initiated by transition derivatives in the construction of functionally substituted five-, six- and seven-membered rings as well as open-chair compounds. Cycloadditions onto methylene- and alkylidene-cyclopropane derivatives, described by A. Goti, F. M. Cordero and A. Brandi, not only yield products with spirocyclopropane moieties which can be desirable as such or as potential mimics of gem-dimethyl groupings, but also intermediates which can undergo further transformations with ring-opening of the cyclopropane units. 

The [5 + 2]-cycloadditions of tethered alkyne-VCPs that are 1,2-disubstituted on the cyclopropane ring 5j—1 have been studied and a mechanism has been advanced to explain the regio- and stereoselectivities of the reactions.37 In most cases, the product resulting from cleavage of the less-substituted (sterically less encumbered) carbon-carbon bond is obtained. The [5 + 2]-reaction is stereospecific in that a /ram-rclationship of the substituents on the cyclopropane leads to a m-relationship of the substituents in the product and vice versa (Equations (4) and (5)). For some tethered alkyne-VCPs which contain a functional group that weakens the carbon-carbon bond of the cyclopropane system, the more substituted (weaker) carbon-carbon bond can be cleaved selectively depending on the choice of catalyst. Thus far, the rhodium(l)-catalysts are more selective catalysts than the mthenium(0)-catalysts in the [5 + 2]-reaction of these substituted alkyne-VCPs (Scheme 7).38... 

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