Radical stereoselectivity fragmentation

Crich and Gastaldi investigated the nucleophilic trapping of a dihydronaphthalene radical cation by octyl alcohol and noted that the stereoselectivity of the reaction, while not high, was a function of the substrate stereochemistry (Scheme 19) [134]. In terms of the general mechanism for fragmentation... 

A Iky I-1.7>-hutadienes.311 A radical reaction of tri-n-butyltin hydride with a-(llydmxymclhyl)allyl lolyl sullbncs (I) results in stereoselective formation of allyltin intermediates, which fragment to 2-substilutcd 1. .Vbutadicnes when heated. 

The fragmentation of nitrate esters to carbon radicals under thermal or photochemical conditions has been exploited by Batsanov and co-workers in the stereoselective construction of 8-lactones [95JCS(P1)1281]. Treatment of 205 with tin hydride in refluxing benzene gave the 6-exo-trig cyclization product 206 in good yield and high stereoselectivity. 

Substrates A3 (Q = O) have been employed not only as starting materials for fragmentation reactions but also to probe novel stereoselectivity concepts. The photochemical transformation of axial chirality into central chirality was achieved by Carreira et al., who employed chiral, enantiomerically pure allenes in intramolecular [2 + 2]-photocycloaddition reactions (Scheme 6.27) [79]. The reaction of enantiomerically pure (99% ee) cyclohexenone 71, for example, yielded the two diastereomeric products 72a and 72b, which differed only in the double bond configuration. Apparently, the chiral control element directs the attack at the allene to its re face. The double bond isomerization is due to the known configurational liability of the vinyl radical formed as intermediate after the first C—Cbond formation step (see Scheme 6.2, intermediate C). 

In combination with the range of standard transformations of alcohols, alkenes, and vinylsulfides, these silicon-tethered additions of functionalized radicals offer a versatile and stereoselective approach to amino alcohol synthesis. Whereas vinyl and 2-oxoethyl radicals have not yet been demonstrated as competent participants in the various intermolecular additions reported in the literature, the temporary tether approach allows such functionalized fragments to be installed in an efficient and stereoselective manner. Synthesis of the aminosugar daunosamine from achiral precursors shows how this concept, employing hydrazone radical acceptors, can be merged with asymmetric catalysis to achieve practical synthetic advances. 

The mechanism of these transformations seems to be substrate-dependent and only the cycloisomerization of aryl and primary iodides was thought to proceed as shown in Scheme 31. The stereoselectivity of the isomerization of 110 to 111 is better accommodated with the intermediacy of l-methyl-5-hexenyl radical59. Later, it was proposed that the isomerization of 6 to 109 also proceeds via a radical-mediated atom transfer process initiated by homolytic fragmentation of an ate-complex intermediate 112 (Scheme 32)60. 

Kilburn has extensively studied radical cascades centered on the use of methylenecyclopropane derivatives. An addition-fragmentation process ap-parented to pathway c opened new routes for the synthesis of carbocycles. In a recent work, a Sml2-promoted cascade of propargyl ether 73 has been used to give bicyclic ether 78 with good diastereoselectivity (Scheme 24), thus providing a short route to the monoterpenoid paeonilactone B. The observed stereoselectivity in the 74 75 cyclization step was shown to be critically dependent on the presence of HMPA [84]. 

Ueda et al. reported a tandem radical addition-cycUzation reaction in aqueous media [184]. This reaction was initiated by single-electron transfer from indium to an alkyl iodide. Fragmentation of the iso-propyl iodide radical anion generated the iso-propyl radical, which triggered the addition/cyclization tandem. Final SET and in situ hydrolysis delivered cyclic sulfonamides in good yield but low stereoselectivity. 

Similarities between mass spectral and thermal fragmentations are particularly common in certain reaction types. Electrocyclic reactions, for example, are frequently similar in the two processes. The thermal process has in general a higher stereoselectivity (because of the higher aromaticity in even-electron systems). Retro-Diels-Alder reactions are typical examples for the similarity of the two processes. Internal displacement reactions may also be similar in the two processes, mainly in the case of internal radical displacements. The relationship between mass spectra and thermal fragmentation is complex, and it is useful to discuss it for separate classes of compounds. 

The authors opted to install the bromotetrahydropyran A-ring last due to its possible instability under radical, strongly basic, and/or acidic conditions. The D-ring was envisioned to arise from a stereoselective epoxidation followed by cyclization to afford the tetrahydrofuran framework. Key to achieving this plan was accessibility to structure 56 (Scheme 10). This fragment in turn was envisioned to be assembled by coupling the anion derived from 57 with epoxide 58. Compound 58 could presumably be accessed via stereoselective cyclizations from diol 59. 

D. Crich and A. A. Bowers, 4,6-0-[l-Cyano-2-(2-iodophenyl)ethylidene] acetals. Improved second generation acetals for the stereoselective formation of /J-D-mannopyranosides and regioselective reductive radical fragmentation to /J-D-Rhamnopyranosides. scope and limitations, J. Org. Chem., 71(2006)3452-3463. 

Phenol-ketone novolacs 1487, 1488 Phenol-nitrile complexes 377 Phenol radical cations 1101 fragmentation of 289-291 Phenols—see also Biphenols, Bis-phenols, Hydroxybenzenes, Polyphenols acidities of, gas-phase 310-312 acylation of 629-632, 933, 934 Lewis acid catalyzed 631 montmoriUonite-catalyzed 632 pyridine-catalyzed 631 adsorption of 944 alkylation of 606-629, 941 Brdnsted acid catalyzed 612 Lewis acid catalyzed 607-611 solid acid catalyzed 612-621 stereoselective 621-626 under supercritical conditions 621 as antioxidants 139-143, 840-901 ort/io-substituted 845 thermochemistry of 139, 140, 179 autoxidation of 1118, 1119 bromination of 649-651 jr-cation interaction of 322 chlorination of 649 comparison with isoelectronic methyl, amino and fluoro aromatic derivatives 226... 

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