Activated cyclopropanes, opening with

The growing importance of cyclopropane derivatives (A. de Meijere, 1979), as synthetic intermediates originates in the unique, olefin-like properties of this carbocycle. Cyclopropane derivatives with one or two activating groups are easily opened (see. p. 69f.). Some of these reactions are highly regio- and stereoselective (E. Wenkert, 1970 A, B E. J. Corey, 1956 A, B, 1975 see p. 70). Many appropriately substituted cyclopropane derivatives yield 1,4-difunctional compounds under mild nucleophilic or reductive reaction conditions. Such compounds are especially useful in syntheses of cyclopentenone derivatives and of heterocycles (see also sections 1.13.3 and 4.6.4). 

Therefore acceptor cyclopropanes 1 will be ring opened by nucleophiles N to provide products like 2 (homo Michael addition) as depicted in Eq. 1. On the other hand, electrophiles E+ cleave donor activated cyclopropanes 3 affording adducts 4 or 5 which demonstrates that the cyclopropane serves as a homoenolate equivalent in this sequence (Eq. 2). Seebach consequently classified these methods as umpolung with the cyclopropane trick 4. ... 

Activated cyclopropanes 33 react with nucleophilic selenium species to give the ring-opened products 34 in moderate to good yields (Scheme 33) [56]. This reaction has been used for natural product synthesis [57]. 

The opening of activated cyclopropanes with nitrogen nucleophiles has been widely applied to the synthesis of pynolizidine and pyrroline alkaloids by Danishefsky this subject has been reviewed. A number of pyrroline annulations have been based on this principle, illustrated in equation (35a). > Similar opening can be accomplished with halides, cuprates, and sulfur or selenium nucleophiles. ... 

So far, optical rotations of compounds have been discussed where the optical activity is associated with the particular structure of the cyclopropane ring. This means that the rotations are generated by a chiral arrangement of (achiral) ligands attached to the (achiral) molecular skeleton. For certain substituent patterns of I, in particular, the rotations are induced by atomic asymmetry. This is true for III and IV. The effect of the (achiral) cyclopropane moiety (viewed as a ligand) on open-chain molecules with an asymmetric carbon atom can be seen from the rotations of (S)-( —)-l-methyl-1-(1-ethoxyethyl) cyclopropane (80) and its counterpart 81 with only acyclic substituents. ... 

Reductive opening with zinc only occurs with vicinal diactivated cyclopropanes whereas lithium in liquid ammonia also works with compounds having one activating substituent. In this case the bond overlapping most effectively with a C=0 group is broken The degree of stereoselectivity, however, is largely dependent on the proton source present and on the reaction temperature (equation 35) as well as on the nature of more remote substituents . ... 

During the reaction of the doubly activated allyl halides with primary and secondary amines no 2-amino-substituted cyclopropane derivatives could be isolated, but instead ring-opened products are formed. Primary amines give rise to the formation of aldimines (332) while secondary amines afford formally substitution products (333) . The formation of these products can be explained by ring cleavage of non-isolable electrophilic 2-aminocyclopropanes (331) as outlined in equation 104. 

An elegant route to 11-deoxyprostaglandins uses a 1,5 attack of an enolate on such an activated cyclopropane. The ring-opening of activated cyclopropanes by intramolecul-arly situated nucleophiles has also been achieved An interesting case of intramolecular 1,7 attack on an activated vinylcyclopropane was observed upon treatment with dimsyl sodium-Me2SO at 90°C (equation 18) . 

The reaction of doubly activated allyl halides with active methylene compounds does not produce cyclopropanes, although they do occur as intermediates. Ring opening of the initially formed cyclopropanes gives products in which the position of the substituents are rearranged. 

Zinc in a protic solvent has also been applied to the reductive ring opening of activated cyclopropane derivatives. Usually the most activated cyclopropyl bond was cleaved. Treatment of arylcyclopropyl aryl ketones 7 with zinc in ethanol alforded aryl propyl ketones in excellent yields. The reduction of 1,2-dibenzoylcyclopropane (7f) with zinc/zinc(II) chloride produced 1,3-dibenzoylpropane (81) in quantitative yield. Dimethyl 2-benzoyl-3-phenylcyclop-ropane-l,l-dicarboxylate (7e) was converted to the corresponding (2-benzoyl-1-phenylethyl)malonate (8e) when heated with zinc in methanol. ... 

The cleavage with hydrogen bromide has been applied to the ring opening of a number of cyclopropanes incorporated into a polycyclic system. Treatment of tricyclo[3.3.0.0 ]octan-3-one (36) with hydrogen bromide in dichloromethane gave two bromo-substituted bicycles 37 and 38 as the result of the cleavage of the two different activated cyclopropane bonds. ... 

Electron-withdrawing groups such as carbonyl functions render the cyclopropane ring susceptible to attack by nucleophiles. These ring-opening reactions of activated cyclopropanes by nucleophiles have been reviewed. Diethylcyclopropane-1,1-dicarboxylates la, b reacted with secondary amines such as diethylamine and piperidine to yield diethyl (2-aminoethy )malonates 2a, The nucleophilic attack of primary amines usually occurred at the ester function... 

The addition of amines to activated cyclopropanes with opening of the three-membered ring was also applied for the preparation of bicyclic systems with the nitrogen as bridgehead atom. These transformations involved the intramolecular nucleophilic attack of a primary amine which was generated by the Gabriel method. 

The susceptibility of nucleophiles to ring-opening reactions is often increased after the activated cyclopropane structure has been incorporated into a polycyclic system due to the additional strain. 3-enaqueous tetrahydrofuran. When 3-cnt/o-methoxytricyclo[3.2.0.0 ]heptan-6-one was dissolved in methanol, the corresponding ring-opened dimethoxy derivative 22 (R = Me) was isolated in high yield. 

Lithium benzeneselenolate reacted with acetylcyclopropane (5, R = H R = Me) and other mono-activated cyclopropanes to ring-opened products 6 with a benzeneselanyl substituent at the terminal carbon atom. ... 

Certain activated cyclopropanes with a spiroannulated ring reacted with trichloroacetyl chloride to give ring-opened products with a chloro substituent in the terminal position of the side chain. ... 

Cobalt(Il) in Vitamin can act as a nucleophile and has the capability to open activated cyclopropane rings. A number of cyclopropane derivatives with one or two electron-withdrawing groups at the same carbon atom were reacted with vitamin B, j to give adducts in which cobalt(lll) was linked to one of the methylene groups. Photolysis in aqueous isopropyl alcohol under anaerobic conditions led to the displacement of the metal by hydrogen. 

When 2-methoxycyclopropyl ketones 1 were treated with aqueous acid, the bond between the functional groups was cleaved and <5-oxoaldehydes 2 were obtained in good yield.The formation of these products can be rationalized by the addition of water across the activated cyclopropane bond and elimination of methanol from the hemiacetal intermediate. Usually, the generation of the cyclopropane derivative from the alkyl 2-chloro-3-methoxypropyl ketone and the subsequent ring-opening reaction was performed without isolation of the cyclopropane. ... 

However, this sequence can be reversed. - Thus, the activated cyclopropane can be de-protonated by lithium diisopropylamide, reacted with an appropriate ketone and opened by various methods such as treatment with acid or desilylation with fluoride. Using this reaction sequence, y-lactones 52 with various substituents can be obtained by the intramolecular attack of the ketone oxygen on the siloxy-substituted carbon followed by oxidation with pyridinium chlorochromate. The cyclic hemiacetal intermediates 53 can be converted to the tetrahyd-rofuran derivatives 55 by deoxygenation with triethylsilane/boron trifluoride. 

Selective ring opening of cyclopropanes. Ring opening by nucleophiles of suitably activated cyclopropanes has gained importance during recent years. Sodium or potassium cyanide can be used for this purpose. An example is the conversion of 1 or 2 into 3, ant/-7-cyano-eni/o-5-bromobicyclo[2.2.1]heptane-2-one, by reaction with potassium cyanide in the presence of catalytic amounts of sodium methoxide (equation T). The intermediate 2 can be isolated in high yield by reaction of 1 with 1 equiv. of sodium hexamethyldisilazide (4, 407) in ether. ... 

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