Transannular hydrogen transfer

An alternative method whereby a fused-ring oxirene may be generated is the epoxidation of a cycloalkyne. Curci et al. have employed methyl(trifluoromethyl)dioxirane (TFD) toward that end, and obtained (215) and c -bicyclo[4.4.0]decan-2-one in ca. 7 1 ratio from cyclodecayne (213) <92TL7929>. These products obviously stem from stereoselective 1,5- and 1,6-transannular insertion pathways. The authors conclude that the products of cycloalkyne oxidations may arise directly from trapping of the oxirene intermediates by transannular hydrogen transfer, as shown in Scheme 46. 

Transannular hydrogen transfer Ketones from ethylenealcohols... 

Transannular hydrogen transfer thus occurs in the overall sequence. Since the reaction of cyclododecyl iodide with Bi2s is certainly not a simple displacement at carbon but also involves transannular hydrogen transfer... 

Another classic study of benzoyl peroxide involved the addition of solvent derived radicals to the para position of the initiator. For example, decomposition of benzoyl peroxide in cyclohexane led to the formation of -cyclohexylbenzoic acid <2) The absence of meta product led to the suggestion (7, 8 ) that para substitu-tion was enhanced by o-lactone formation concerted with addition. An alternative route would involve addition followed by subsequent a-lactone formation ( ) or transannular hydrogen transfer (Fig. 2) (] ). In this case the absence of meta substitution product could be ascribed to reversibility of the addition, and this is known to occur ( ). A preference for para substitution leading to formation of a radical intermediate stabilized by an adjacent carboxylate function would also be expected. 

Large-ring heterocyclic radicals are not particularly well known as a class. Their behavior often resembles that of their acyclic counterparts, except for transannular reactions, such as the intramolecular hydrogen transfer in 1-azacyclononan-1-yl 1 (Scheme 1). As is the case with acyclic ethers, oxepane in the reaction with tert-butoxy radical suffers abstraction of a hydrogen atom from the 2-position in the first reaction step (Scheme 2). 

The isodrine framework was used for synthesis of pagodane in which one of the key steps is Mackenzie s transannular dyotropic hydrogen transfer. Also, a very intriguing ... 

The radical cations of diene systems in cyclic molecules are also capable of reaction as demonstrated by Demnth, Roth and their coworkers. They have studied the influence of phase on the photochemical reactivity of some naturally occurring dienes. Thns the irradiation of the diene 10 in homogeneous solution (acetonitrile/water) in the presence of an electron-accepting sensitizer such as cyanonaphthalene (CN) or DCB brings about fraws,cw-isomerization only. However, when the electron transfer reaction is carried out in the presence of sodinm dodecyl sulphate, transannular hydrogen abstraction reactions yield the two prodncts 11 and 12. Similar reactivity is observed with frans-geranyl acetate 13 and all-trawi-famesyl acetate 14. The authors report that these cyclizations are the flrst examples of biomimetic processes brought about under SET conditions. 

Transannular reactions represent an interesting family of hydrogen transfer processes that can be applied for highly selective and efficient remote functionalization. For instance, Zard reported -functionalization in the longifolene series via Barton decarboxylation of isolongifolic acid (Scheme 21, Eq. 21.1) [97]. A spectacular regio-and stereoselective remote hydroxylation of bicyclic ketone is reported by Winkler... 

No product derived from the transannular hydrogen abstraction is observed in the addition of bromotrichloromethane because bromine atom transfer is sufficiently fast to prevent effective competition from the intramolecular hydrogen abstraction. 

The deprotonation step, either by the sensitizer radical anion or by some adventitious base, is essential for the formation of any amine derived products. This step can be prevented if the a-hydrogens are arranged in a plane orthogonal to the singly occupied nitrogen n-orbital a requirement which is met for the radical cation of l,4-diazabicyclo[2.2.2]octane (DABCO). The low oxidation potential, due to the interaction of the pair of transannular nitrogens, makes this an excellent electron transfer quencher. Yet, no product formation is observed as a result of these interactions, with the possible exception of the zwitterionic adducts formed with highly electrophilic ketones [193]. 

With conditions established to determine the ratio of 44 45 acylation, 137 Pmh-containing peptides were screened as catalysts from the libraries the group had developed for group transfer reactions. Several catalysts, including those hypothesized to form a p-tum [91-93 and references therein], exhibited the capacity to reverse the intrinsic selectivity exhibited by the substrate in comparison to when NMI was the catalyst. When peptide 46 was employed, the preference of 40 for acylation at the 4" over the 11-hydroxyl was inverted from approximately 4 1 44 45 (NMI-catalyzed) to 1 5 44 45 (46-catalyzed). The 11-hydroxyl of 40 has been implicated in a macrolide-stabihzing hydrogen bond with the C9 carbonyl [94, 95]. The stmcture of 45 supports this hypothesis as it was observed to exist not as the C9 ketone, but primarily as transannular hemiketal 47, the structure of which... 

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