Cyclopropyl carbinyl radical

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]. 

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. 

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

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 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. 

Butenyl cyclizations are in principle fast reactions proceeding in a 3-exo mode. The rate constant for this type of cyclization is usually in the range of 10" -6 X 10 s. Still, the preparative usefulness of this transformation has remained rather limited because the ring opening of the product cyclopropyl carbinyl radical is usually much faster (A = 10 — 10 s" ) as shown in Scheme 1 [3]. 

Samarium diiodide has also proven to be a useful reagent for this type of transformation with cyclopropyl ketones [11], In this case a ketyl radical is generated adjacent to the cyclopropane ring. Ring opening takes place as readily as with simple cyclopropyl carbinyl radicals. 

The test for radical intermediates in the epoxidation reaction is based on the required rate constant for partitioning of the putative radical intermediate to epoxide as compared to other products. Given that the rate constant for CPCRR of the (trans-2, trans-3-diphcny cyclopropyl)carbinyl radical is > 2 x 10 9 g-l and that the yield of products derived from the radical species IV are <0.1%, the conversion of radical to cis- IX would have a rate constant of >10 2 s"l. The neutral radical species IV cannot be a discrete intermediate in the epoxidation reaction. 

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]. 

Small-ring radical opening is a facile process. This process has been incorporated in the zero bridge cleavage of strained bicycles for one- and two-carbon ring expansions (Scheme 14). Ring expansions of cyclopropyloxy and cyclobutyloxy radicals have been discussed in the previous section. This section focuses on cyclopropyl-carbinyl, ot,j8-epoxyalkyl and cyclobutylcarbinyl radicals. 

Extensive studies have been devoted to these radicals in connection with their structure (classical or nonclassical) and their reactivity (homoallylic rearrangement and 1,2-vinyl migration) and the main results have been reviewed.For instance, the classical nature of the allylcarbinyl, cyclopropyl carbinyl, and cyclobutyl radicals now seems well established. 

In contrast, irradiation of 22c (R = CH, R = CH3) produced bicycHc diketone 25c and alkyHdene phthaKde 26c together with cyclobutanol 23c and the unsaturated alcohol 24c. Compound 26 is the result of secondary photoisomerization of 25. The formation of 25 can be explained by a cyclopropyl-carbinyl rearrangement of ketyl radical VII followed by 1,5-biradical-recombination. Such an inner cyclopropane bond fission may be favored by the better stabilization by R (= CH3) of the new radical center. As found in 22d, replacement of R = CH3 by a Ph group simplified the reaction outcome to provide only 25. 

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