Cyclization, radicals with cyclopropanes

Reaction of alkylthiyl radicals with alkenyl cyclopropanes (44) furnishes intermediate radicals (45) after addition and ring opening. Addition of a further radical acceptor leads to tricyclic [5,5, ] systems via addition followed by cyclization and elimination (Scheme 17).52... 

The concept of ring opening of cyclopropylcarbinyl radicals has been extended to substituted methylenecyclopropanes. As shown in Scheme 4, the crucial step in the reaction sequence is the regioselective addition of a substituted thiyl radical. After opening of the cyclopropane ring, the resulting radical adds to the olefin. Subsequent cyclization and reductive regeneration of the thiyl radical with concomitant liberation of the methylenecyclopentane product complete this transformation [6]. 

When free radicals are added to 1,5- or 1,6-dienes, the initially formed radical (9) can add intramolecularly to the other bond, leading to a cyclic product (10). When the radical is generated from an precursor that gives vinyl radical 11, however, cyclization leads to 12, which is in equilibrium with cyclopropylcarbinyl radical 13 via a 5-exo-trig reaction. A 6-endo-trig reaction leads to 14, but unless there are perturbing substituent effects, however, cyclopropanation should be the major process. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

Concerning the structure, the cyclopropane derivatives 524—526 deviate from the generally observed cycloadducts of cyclic allenes with monoalkenes (see Scheme 6.97 and many examples in Section 6.3). The difference is caused by the different properties of the diradical intermediates that are most likely to result in the first reaction step. In most cases, the allene subunit is converted in that step into an allyl radical moiety that can cyclize only to give a methylenecyclobutane derivative. However, 5 is converted to a tropenyl-radical entity, which can collapse with the radical center of the side-chain to give a methylenecyclobutane or a cyclopropane derivative. Of these alternatives, the formation of the three-membered ring is kinetically favored and hence 524—526 are the products. The structural relationship between both possible product types is made clear in Scheme 6.107 by the example of the reaction between 5 and styrene. 

MISCELLANEOUS REACTIONS OF DIHYDROPYRIDINES Additional tests for net hydride transfers initiated by single-electron transfer include the use of substrates in which such pathways would necessarily involve readily ring-opened cyclopropylmethyl or readily cyclized 5-hexenyl radicals. Products from these radical reactions are not formed in NAD+/ NADH dependent enzymic reductions or oxidations (Maclnnes et al., 1982, 1983 Laurie et al., 1986 Chung and Park, 1982). Such tests have also been applied in non-enzymic reductions. Thus cyclopropane rings in cyclopropyl 2-pyridyl ketones, or imines of formylcyclopropane (van Niel and Pandit, 1983, 1985 Meijer et al., 1984) survive Mg+2 catalysed reduction by BNAH or Hantzsch esters but are opened by treatment with tributylin hydride. 

Radical iodine atom transfer [3 + 2]-cycloaddition with alkene (118) using dimethyl 2-(iodomethyl)cyclopropane-l,l-dicarboxylate (117) forms cyclopentane derivative (119), through the formation of an electron-deficient homoallyl radical, followed by the addition to alkene, and cyclization via 5-exo-trig manner as shown in eq. 4.41. 

Preparation of an oestrone analogue has been made by treatment of a polyene iodide with (TMS)3SiH via a radical cascade involving a 13-endo macrocyclization followed by successive opening of a cyclopropane ring and a 6-exo/5-exo transannular cyclization (equation 52)104. 

Vinyl radicals also add to carbon-carbon double bonds intramolecularly to give 2,6-cw-disubstituted cyclic ethers (Equation (5)).41 In the tin hydride-mediated cyclization of the substrates including alkynes, alkyl radicals attack to carbon-carbon triple bonds leading to uco-alkylidene allylic alcohols (Equation (6)).42 The coupling reaction between alkyl radicals may afford cyclization products. Thus, the reduction of 1,3-diiodopropane derivatives with a tin hydride provides substituted cyclopropanes.4... 

An efficient way of introducing selenium in a radical precursor is the use of selenium containing building blocks. The selenides are particularly appropriate when the reaction sequence involves reaction steps that are incompatible with halides or when the corresponding halides are not stable. In Eq. (7), preparation of the selenenylated alkenyl sulfoxide 35 by alkylation of malonate 33 with the bromide 34 is described [18]. This procedure is not feasible with the corresponding halide due to cyclopropane formation via intramolecular alkylation. Radical cyclization of 35 in a 5-exo mode affords, after elimination of the phenylsulfinyl radical, the methylenecyclopentane 36 in good yield and excellent enantioselec-tivity. 

The reductive cleavage of the proximal cyclopropane bond in bicyclo[3.1.0]heptan-2-ones with samarium(II) iodide involves a one-electron transfer and formation of a radical intermediate which can undergo intramolecular cyclization reactions. ... 

Armesto and his co-workers" have demonstrated that electron-transfer induced cyclization of imines (66) follows the di-jr-methane pathway, via the intermediate radical cation (67), to afford the cyclopropane derivatives (68). The outcome of the reaction is to some extent controlled by the electron-transfer sensitizer used, as can be seen in the reported yields. In the biphenyl substituted example, a cyclopropane derivative (69) is formed in competition with an alter-... 

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