Of cyclopropyl carbinyl

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

The intermediacy of free radicals is further supported by the observation of 5-exo cyclizations and the ring opening of cyclopropyl carbinyl radicals. 

With vinylcyclopropanes thioselenation proceeds via ring-opening of cyclopropyl-carbinyl radicals. An example of the thioselenation of isocyanides by means of a (PhS)2-(PhSe)2 mixed system is shown in Scheme 15.69 the product is a useful building block for TS-lactarn derivatives, e.g. carbacephems. 

In summary, the results discussed above reveal that an ether oxygen in a medium or a bicyclic ring system may offer significant anchimeric assistance in reactions in solvolytic displacement reactions. Because of inductive effects, steric effects, field effects, and internal return, anchimeric assistance, when present, is often difficult to demonstrate kinetically. Products formed from bicyclic and tricyclic oxonium ions probably more often result from participation after carbocation formation. Participation by oxygen apparently occurs to the exclusion of transannular hydride shifts in medium ring systems, but other types of participation such as homoallylic or formation of cyclopropyl carbinyl cations will most likely occur to the exclusion of ether oxygen participation. 

With 6-alkenoic acids the intermediate radical partially cyclizes to a cyclopentyl-methyl radical in a 5-exo-trig cycHzation [139] (Eq. 6) [138 a, 140] (see also chap. 6). To prevent double bond migration with enoic acids the electrolyte has to be hindered to become alkaline by using a mercury cathode. Z-4-Enoic acids partially isomerize to -configurated products. Results from methyl and deuterium labelled carboxylic acids support an isomerization by way of a reversible ring closure to cyclopropyl-carbinyl radicals. The double bonds of Z-N-enoic acids with N > 5 fully retain their configuration [140]. 

Aziridinocyclopropanes 163 derived from 2-phenylsulfonyl-l,3-dienes undergo BF3-induced rearrangement to bicyclic amines 165, which feature the skeleton of the tropane alkaloids. The reaction proceeds via cyclopropyl carbinyl cation 164, an intermediate also invoked in the analogous epoxide rearrangements. Trapping by fluoride ion is a competing pathway <96TL3371>. 

An early - but mechanistically interesting - construction of a bicyclo[3.1.0]oxa-hexane by a domino radical cyclization was presented by Luh s group [50]. The addition of tributyl tin and AIBN to a solution of bromides 3-111 in refluxing benzene gave 3-114 as single diastereoisomers in acceptable yields via the intermediates 3-112 and 3-113 (Scheme 3.29). It is important that the cyclopropyl carbinyl radical intermediate has the correct stability and reactivity, which is achieved by the a-silyl substituent. 

The unusual nature of the cyclopropyl carbinyl cation allows yet another mode of attack to form cyclobutane products. Because this mode of attack releases little strain, normally some special structural features are required to direct the reaction along this pathway. 

Table 6.22 Calculated barriers (kJ/mol) for the ring opening of the cyclopropyl-carbinyl radical.11...

Triethylamine as the electron donor was also used by Mattay and co-workers in tandem fragmentation cyclization reactions of a-cyclopropylketones. The initial electron transfer on the ketone moiety is followed by the fast cyclopropyl-carbinyl-homoallyl rearrangement, yielding a distonic radical anion. With an appropriate unsaturated side chain within the molecule both annealated and spi-rocyclic ring systems are accessable in moderate yields (Scheme 41) [62]. 

Using methods such as those discussed for the norbornyl cation, nonclassical structures have now been established for a number of carbocations. " Representative examples are shown below. The 7-phenyl-7-norbornenyl cation 19 exists as a bridged strucmre 20, in which the formally empty p orbital at C7 overlaps with the C2—C3 double bond. This example is of a homoallylic cation. The cyclopropyl-carbinyl cation 21, historically one of the first systems where nonclassical ions were proposed, has been shown to exist in superacids mainly as the nonclassical bicyclo-butonium ion 22, although it appears as if there is a small amount of the classical 21 present in a rapid equilibrium. Cations 23 and 24 are examples of p-hydridobridged... 

The trishomocyclopropenium species 91 has been an important cation in terms of the development of the concept of homoaromaticity. It also provides an example of a different mode of cyclopropyl homoconjugation to that encountered in the systems discussed thus far. In 91, the cyclopropane is formally interacting with the remote positive charge in an edge-on manner. All of the previous examples discussed have involved a cyclopropyl carbinyl-type interaction with the conjugating group being joined to the cyclopropane. 

From solvolytic studies of iso topically labeled substrates it was shown that cyclopropyl-carbinyl-cyclobutyl interconversion is stereospecific51 52. The stereospecific interconversion of cyclobutyl cations to the corresponding cyclopropylcarbinyl cation was also cleanly observed in superacid medium, and was used to prepare otherwise unstable cis-(a-methylcyclopropyl)carbinyl cation 1753. Thus ionization of d.s-2-chloro- or cw-3-chloro-l-methylcyclobutane in SbF5-S02ClF at -135 °C yielded the ris-isomer which rapidly rearranged irreversibly into the trans-isomer 18 at about -100 °C. The trows-isomer 18 is the only cation obtained when the preparation was carried out at -80 °C, or when prepared from the cyclopropylmethyl carbinol20b 38 50ac (equation 24). 

In reaction (214), the addition of RS to the C(6) position is followed by a very rapid and irreversible cyclopropyl carbinyl radical rearrangement [reaction (215) Carter et al. 2000]. The resulting radical is comparatively long-lived and can be reduced by the thiol [reaction (216)]. Thus in this example, the minor pathway is detected, while the other, being reversible, remains unobserved. 

The rigid geometry of the adamantyl nucleus has also been utilized to quantitatively evaluate the stereoelectronic requirements of cyclopropylcarbinyl cations. The bisected conformation of the cyclopropyl cation, 97, is known to be preferred strongly relative to the perpendicular conformation, 98 280 The adamantyl derivate 99 incorporates a cyclopropyl carbinyl system locked in the... 

Alkylation reactions which introduce a double bond adjacent to the cyclopropane ring provide intermediates which may undergo useful rearrangements to the cyclobutanone system. As shown in Scheme 20, reactions of 1-vinylcyclopropanol (108) with acid, positive halogens, peracids or carbonium ions lead to cyclobutanones via the cyclopropyl carbinyl cation 109. 76>... 

K.A. Wiberg, Application of the Pople-Santry-Segal CNDO method to the cyclopropyl-carbinyl and cyclobutyl cation and to bicyclobutane, Tetrahedron 24 (1968) 1083. 

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