Cyclopropylcarbinyl derivatives

The l3C NMR spectrum of the C4H7+ cation in superacid solution shows a single peak for the three methylene carbon atoms (72) This equivalence can be explained by a nonclassical single symmetric (three-fold) structure. However, studies on the solvolysis of labeled cyclopropylcarbinyl derivatives suggest a degenerate equilibrium among carbocations with lower symmetry, instead of the three-fold symmetrical species (13). A small temperature dependence of the l3C chemical shifts indicated the presence of two carbocations, one of them in small amounts but still in equilibrium with the major species (13). This conclusion was supported by isotope perturbation experiments performed by Saunders and Siehl (14). The classical cyclopropylcarbinyl cation and the nonclassical bicyclobutonium cation were considered as the most likely species participating in this equilibrium. 

There have been a very large number of investigations of carbocationic reactions of cyclobutyl, cyclopropylcarbinyl and allylcarbinyl derivatives under so-called stable-ion as well as solvolytic conditions. Bartlett (1965) has stated Among nonclassical ions the ratio of conceptual difficulty to molecular weight reaches a maximum with the cyclopropylcarbinyl-cyclobutyl system . The term nonclassical was first used by Roberts and Mazur (1951) to describe the nature of tricyclobutonium ion [32] suggested to be involved in reactions of cyclopropylcarbinyl derivatives. Later Roberts and coworkers (Mazur et al., 1959) favoured a set of rapidly equilibrating nonclassical bicyclo-butonium ions [34] instead of a single non-classical species. Essentially all experimental evidence on indicates that the species is a nonclassical... 

In selecting the various cyclopropylcarbinyl structural types for the review, the main concern was to systematize the available literature in convenient, structurally readily recognizable sections. However, these sections in many cases also correspond to divisions in mechanistic types. Cyclopropylcarbinyl derivatives contained as part structures in... 

A number of studies have been carried out on systems in which more than one cyclopropane ring is attached to a potential carbocation center. One of the first of these was by Hart and coworkers " with simple open-chain cyclopropylcarbinyl derivatives. Some of their relative rate data for hydrolysis in 80 % aqueous dioxane are as follows. 

The partial data presented above seem to indicate that substituents which are capable of stabilizing a carbocationic center at a bridgehead position will favor the formation of cyclobutyl derivatives, whereas such a substitution on the methylene carbons results in cyclopropylcarbinyl derivative formation. This is consistent with the observation that the acid-catalyzed methanolysis of 3-/ -bicyclobutanecarbonitrile (35) yields 58 % and 42 % of... 

In order to establish the preferred direction of approach, the bicyclobutane moiety must be incorporated in a rigid system to prevent ring flips which equilibrate the axial and equatorial positions in the cyclobutanic products. The tricyclic system 7 is in principle an ideal substrate for this purpose. However, it reacts with acids to give mainly the corresponding cyclopropylcarbinyl derivatives. In the reaction of its carbomethoxy derivative 38 with HCIO4 in MeOH, Razin and Eremenko have obtained 0.8 % of the bicyclic product 39, indicating that the addition mode is indeed cis diequatorial. This... 

As was pointed out earlier, either central bond cleavage or addition to a side bond can account for the formation of the various products obtained in electrophilic addition reactions. It is highly likely that, in reactions where the cyclobutane ring is retained in the product, it is the central bond which is cleaved. However, when cyclopropylcarbinyl derivatives are obtained, both attack on a side bond as well as cleavage of the central bond followed by skeletal rearrangements are conceivable mechanistic pathways. The literature does record one report which purportedly disproves the side bond fission process in the reaction of chlorosulfonyl isocyanate with bicyclobutane The results of this study, however, have been reinterpretedleaving the question moot. 

The rates of solvolysis of cyclopropylcarbinyl derivatives are strongly enhanced. Thus, the ethanolysis of cyclopropylcarbinyl benzenesulfonate 488), Ar=Phenyl, is 500 times as fast as that of ethyl benzenesulfonate (4S9)383. The rate acceleration of 488), Ar=j3-Naphthyl, is 1220 in methanol, and 139000 in acetic acid384. Electron supply by the cyclopropyl group increases with increasing electron demand at the cationic center.The p+ value for the cyclopropyl derivatives 491), -2.78, is consider-... 

The stereochemistry just described also applies to the transformations of optically active (521) which ionizes to give two distinct bisected cyclopropylcarbinyl cations in a 3 1 ratio407. The tertiary cyclopropylcarbinyl derivative (522), on the other hand, solvolyzes without equilibration of the C(CH3)2 groups4087. A cyclopropylcarbinyl rearrangement with inversion at the migrating carbon is also necessary for... 

Product formation from cyclopropylcarbinyl derivatives is often controlled by stabilization of the positive charge in the various cationic intermediates. Methyl or... 

Numerous routine synthetic applications have appeared which make use of the stereoselective ring-opening of cyclopropylcarbinyl derivatives to E-olefins. The allylcarbinyl-cyclopropylcarbinyl interconversion is frequently used for the protection of double bonds in steroids during synthetic procedures for the preparation of homosteroids and may be involved in the fluorination of A -3-tri-methylsiloxy-steroids. ... 

Another one of the more extensively investigated carbocation systems derives from SnI reactions on homoallyl, cyclobutyl, or cyclopropylcarbinyl derivatives. Solvolyses of all three of these systems give very interesting product mixtures. Let s examine just a few... 

Cyclopropylcarbinyl radicals (5) are alkyl radicals but they undergo rapid ring opening to give butenyl radicals." The rate constant for this process has been measured by picosecond radical kinetic techniques to be in the range of 10 M s for the parent to lO Af s for substituted derivatives. This process has been observed in bicyclo[4.1,0]heptan-4-ones. ... 

In an elegant summary, Bly and Koock (95) explain the diverse products and results observed in the solvolysis of all homoallenic systems as shown in Scheme VI. Upon reaction, homoallenic derivatives which solvolyze with TT-electron participation form an initial cyclopropylcarbinyl-type ion, 127. 

Cu(II) EPR signal in nitriles as solvent as well as by polarographic measurements 144>. Similarly, the EPR signal disappeared when Cu(OTf)2 was used for catalytic cyclo-propanation of olefins with diazoesters 64). In these cases, no evidence for radical-chain reactions has been reported, however. The Cu(acac)2- or Cu(hfacac)2-eatalyzed decomposition of N2CHCOOEt, N2C(COOEt)2, MeCOC(N2)COOEt and N2CHCOCOOEt in the presence of cyclopropyl-substituted ethylenes did not furnish any products derived from a cyclopropylcarbinyl - butenyl rearrangement128. These results rule out the possible participation of electron-transfer processes and radical intermediates which would arise from interaction between the olefin and a radical species derived from the diazocarbonyl compound. 

Scheme 3 - Product distribution from solvolysis of cyclopropylcarbinyl cyclobutyl and allylcarbinyl derivates.

The Nature of the Intermediate in Carbonium-Ion Type Interconversion Reactions of Cyclobutyl, Cyclopropylcarbinyl and Allylcarbinyl Derivatives. J. Amer. chem. Soc. 73, 3542 (1951). 

Furthermore, the chloro ester 1-Me also readily reacted with the nitrile ylide 37 at room temperature, however, the pyrrole derivative 40 was the only isolated product (Scheme 9) [26 a]. The latter was obviously formed from the primary cycloadduct 38 by a cyclopropylcarbinyl to homoallyl rearrangement [1]. 

The mechanism of this reaction is still not clear, but the key steps are probably a cyclopropylcarbinyl to cyclobutyl ring enlargement [45] with subsequent ring enlargement of the cyclobutane derivative 46. In fact, such cyclobutane derivatives 46c,d could easily be prepared in 86 and 94% yield, respectively, by stirring dichloromethane solutions of 42c,d in the presence of AI2O3 at 20 °C, and 46 c, d quantitatively isomerized into 47 c, d upon heating in DMSO at 100 °C for 2 h. 

Artemisyl, Santolinyl, Lavandulyl, and Chrysanthemyl Derivatives.— The presence of (41) in lavender oil has been reported earlier. Poulter has published the full details of his work (Vol. 5, p. 14) on synthetic and stereochemical aspects of chrysanthemyl ester and alkoxypyridinium salt solvolyses (Vol. 3, pp. 20—22) and discussed its biosynthetic implications. Over 98% of the solvolysis products are now reported to be artemisyl derivatives which are formed from the primary cyclopropylcarbinyl ion (93) which results from predominant (86%) ionization of the antiperiplanar conformation of (21)-)V-methyl-4-pyridinium iodide the tail-to-tail product (96 0.01%) may then result from the suprafacial migration of the cyclopropane ring bond as shown stereochemically in Scheme 3. This is consistent with earlier work (Vol. 7, p. 20, ref, 214) reporting the efficient rearrangement of the cyclobutyl cation (94) to (96) and its allylic isomer, via the tertiary cyclopropylcarbinyl cation (95). ... 

Further studies on the cholesteryl/i-cholesteryl system were reported by Dodson and Reigel4 and particularly by Winstein and his coworkers5-6. This early work showed that the interconversion of the two cholesteryl derivatives, one of which has an open or homoal-lyF form 1 and the other a cyclopropylcarbinyl form 3, could be understood in terms of the intermediate 2 (equation 1). Electron delocalization in 2 was suggested to occur across the intervening carbon atom rather than between adjacent carbon atoms as in normal conjugated systems. 

Access to homotropenylium ions can be achieved by two general routes. The first involves the addition of an electrophile to a cyclooctatetraene or cyclooctatetraene derivative, an approach which can be considered to correspond to a homoallyl route (Scheme 4). In this route the electrophile is generally attached stereoselectively to the endo position on C(8)18 7,1 74. The second approach involves the ionization of a bicyclo[5.1.0]octadienyl derivative. This is the cyclopropylcarbinyl approach (Scheme 4). This route has the potential of generating a wide range of differently substituted cations however, the starting materials can be difficult to access75 . 

Solvolytic studies provided the first structural indication for almost every carbocation-ic intermediate and the C4H,+ ion is no exception. Roberts observed that the solvolysis of cyclopropylcarbinyl or cyclobutyl systems and the diazotative deamination reactions of cyclopropylcarbinyl amine or cyclobutyl amine gave similar product mixtures consisting of cyclopropylcarbinyl, cyclobutyl and allylcarbinyl derivatives in essentially the same ratio1,2. A common cationic intermediate of C3v structure, the tricyclobutonium ion 1, was... 

In 1951 Roberts observed that most cationic reactions of cyclopropylcarbinyl and of cyclobutyl derivatives give the same products in nearly the same ratio.73 For example, cyclopropylcarbinyl and cyclobutyl amines on deamination form the products shown in Equation 6.31.74 Moreover, when allylcarbinyl tosylate (63)... 

On the other hand, there is now a good deal of evidence that the solvolysis of most cyclobutyl derivatives does lead directly to the cyclopropylcarbinyl cation. For example, orbital symmetry considerations (Section 11.3) indicate that the conversion of cyclobutyl cations into cyclopropylcarbinyl cations should occur by disrotatory ring opening as shown in Figure 6.11 but any steric factors that would hinder such a process decelerate most cyclobutyl solvolyses. Thus 86 See note 84(b). 

If two different C4H7 + ions may exist, which is the more stable The fact that most cyclobutyl derivatives seem to solvolyze directly to the cyclopropylcarbinyl cation strongly suggests that that ion is the more stabilized. Nuclear magnetic resonance studies, however, give conflicting information. The spectrum of the unsubstituted cyclopropylcarbinyl cation in superacid solution is most... 

Evidence has been obtained467 for the involvement of a tertiary cyclopropylcarbinyl cationic intermediate in the rearrangement of presqualene diphosphate to squalene. 16-Oximino-17a-benzyl-17//-hydroxy derivatives in the androstane and estrane series have been converted into 16-oxo-17//-benzyl-17a-hydroxy derivatives with inversed configuration at C(17), on treatment with titanium trichloride. It has been suggested468 that the rearrangement occurs through the key intermediate (401) (see Scheme 97). 

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