Stereocontrol, in radical

C. Lesueur, R. Nouguier, M. P. Bertrand, P. Hoffmann, and A. De Mesmaeker, Stereocontrol in radical cyclization on sugar templates. Tetrahedron 50 5369 (1994). 

To broaden our overall knowledge of process kinetics the first chapter of this volume deals with elementary reactions in radical and anionic polymerization it was written by G. V. Schulz, the first recipient of the H. Staudinger Award. It is followed by a discussion on monomer constitution and stereocontrol in radical polymerization by H. G. Elias et al. 

Stack JG, Curran DP, Geib SV, Rebek J, Ballester P (1992) A new chiral auxiliary for asymmetric thermal reactions High stereocontrol in radical addition, allylation, and annulation reactions. J Am Chem Soc 114 7007-7018 Yang NC, Yang DDH (1958) Photochemical reactions of ketones in solution. J Am Chem Soc 80 2913-2914... 

Scheme 11. Acyclic stereocontrol in radical reactions Lewis acid and chiral auxiliaries...

Liu W, Nakano T, Okamoto Y. Stereocontrol in radical polymerization of M,M-dime-thylacrylamide and N,Ar-diphenylacrylamide and thermal properties of syndiotactic poly(methyl acrylate)s derived from the obtained polymers. Polym J. 2000 32 771-777. 

Nagano H, Kuno Y, Omori Y, Iguchi M. Stereocontrol in radical-mediated aHylation of acyclic a-bromo-3-siloxy esters by complexation with lanthanide shift reagents Ln(fod)(3). J Chem Soc Perkin Trans 1. 1996 389—394. 

Sihi MP, JiJG. Acychc stereocontrol in radical reactions p-selectivity with oxazolidi-none auxiliaries. Angew Chem Int Ed. 1996 35 190-192. 

Sihi MP, Ji JG. Acyclic stereocontrol in radical reactions. Diastereoselective radical addition/allylation of N-propenoyloxazolidinone. J Org Chem. 1996 61 6090-6091. 

The N,0- and N,S-heterocyclic fused ring products 47 were also synthesized under radical chain conditions (Reaction 53). Ketene acetals 46 readily underwent stereocontrolled aryl radical cyclizations on treatment with (TMSlsSiH under standard conditions to afford the central six-membered rings.The tertiary N,0- and N,S-radicals formed on aryl radical reaction at the ketene-N,X(X = O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from (TMSlsSiH was investigated and found to provide higher selectivities than BusSnH. 

Metal-catalyzed hydrophosphination has been explored with only a few metals and with a limited array of substrates. Although these reactions usually proceed more quickly and with improved selectivity than their uncatalyzed counterparts, their potential for organic synthesis has not yet been exploited fully because of some drawbacks to the known reactions. The selectivity of Pt-catalyzed reactions is not sufficiently high in many cases, and only activated substrates can be used. Lanthanide-catalyzed reactions have been reported only for intramolecular cases and also sulfer from the formation of by-products. Recent studies of the mechanisms of these reactions may lead to improved selectivity and rate profiles. Further work on asymmetric hydrophosphination can be expected, since it is unlikely that good stereocontrol can be obtained in radical or acid/base-catalyzed processes. 

Our approach was to use the unsaturated bromodeoxylactones in an intramolecular radical reaction, since these compounds possess both the radical precursor and the radical trap within the same molecule. Thus, reacting the unsaturated bromodeoxyheptonolactone 20 (Scheme 14) with tributyltin hydride and a radical initiator, the bicyclic lactone 65 a was obtained in a quantitative yield within 1 h. The stereocontrol in the reaction was determined by the structure of the product, since the compound obtained has two fused cyclopentane rings which can only be cis anellated. The radical A, which is the intermediate, was trapped by the tin hydride. The stereochemistry of the newly formed chiral center is determined by the configuration at C-4 in the educt 20 [45]. 

The conformational barriers in acyclic radicals are smaller than those in closed-shell acycles, with the barrier to rotation in the ethyl radical on the order of tenths of a kilocalorie per mole. The barriers increase for heteroatom-substituted radicals, such as the hydroxymethyl radical, which has a rotational barrier of 5 kcal/mol. Radicals that are conjugated with a n system, such as allyl, benzyl, and radicals adjacent to a carbonyl group, have barriers to rotation on the order of 10 kcal/mol. Such barriers can lead to rotational rate constants that are smaller than the rate constants of competing radical reactions, as was demonstrated with a-amide radicals, and this type of effect permits acyclic stereocontrol in some cases. "... 

Monomer Constitution and Stereocontrol in Free Radical Polymerizations... 

Intuitively, the idea of an influence of the size of the substituent on the stereocontrol in free radical polymerization is very appealing. However, it is not supported by quantitative data. Table I shows the probabilities p of the formation of isotactic and syndiotactic diads at existing iso- and syndiotactic diads for the free radical polymerization of the methacryl type monomers CH2=CH(CH3)COOR in toluene at —78°C. These probabilities have been calculated from published mole fractions of iso- and syndiotactic diads (Xi, X8) and iso-, syndio-, and heterotactic triads (Xu, X88 and Xu) via... 

These findings imply that the use of probabilities for i-ad formation at a given temperature in a given solvent is insufficient to describe the monomer constitutions influence on the stereocontrol in free radical polymerizations. The lack of correlation is either the result of the combined action of more than one parameter (size of substituent, resonance stabilization and/or structure of propagating radicals, etc.) or the result of noncomparable experimental conditions. 

Early studies of the free radical polymerization of methyl methacrylate did not show a solvent influence (18, 22, 23, 24) and consequently no solvent dependent influence of the conversion on the tacticity (23). A solvent dependence on stereocontrol in methyl methacrylate polymerization was however found by Watanabe and Sono (25) as early as 1962. Apparently, their paper has been overlooked. A literature search and a recalculation of most of the published data showed solvent influences on stereocontrol to be the rule and not the exception (6). Later experimental data on methyl methacrylate in about 50 solvents (7) and in 14 solvents (8) confirmed the earlier findings of Watanabe and Sono (25). 

A similar result has been recently found for the free radical polymerization of methyl methacrylate in 14 solvents (32). All differences (Aff. — AHf/8) were found to be positive, but only three of the 14 differences (AH /g — AH. ). Again, isotactic triad formation is favored over heterotactic triad formation and heterotactic triad formation over syndiotactic with increasing temperature as long as the individual modes of addition are considered and not the net result. Except for meth-acrylic acid in alcohols (cf. Lando et al. (28)) no model is known which shows why a certain solvent acts differently from another one with respect to stereocontrol in free radical polymerization. 

These findings suggest a strong influence of conformational effects on the stereocontrol in free radical polymerizations. Conformation analyses are lacking however for the monomers investigated. 

The tandem radical cyclization of tetrayne (97) and its derivatives has been performed to generate the polycyclic pyran (98) via a biradical intermediate.238 The cycloaddition reaction of a biradical species (or diyl) and a multiply bonded species (the diylophile)239 has been observed with unique allene diylophiles.240 The short-lived biradical fonned by the irradiation of the diazene (99) is trapped by an allene diester to form a second biradical species (100). Intramolecular cyclization occurs such that all steric interactions are minimized and so enforces stereocontrol in the formation of the cycloadduct (101) see Scheme 14. A paper reports the rearrangement of 2-vinyhnethylenecyclopropane (102) to 3-methylcyclopentene (103) via the triplet biradical (104), which has been characterized for the first tune by IR spectroscopy.241... 

The C=N bond of simple imines possesses modest reactivity toward intermolecular radical additions, so such acceptors have rarely been exploited. To enhance their reactivity toward nucleophilic radicals, electron-withdrawing groups at the imine carbon have been effective, as demonstrated by Bertrand in radical additions to a-iminoesters prepared from chiral amines [25]. Also, more reactive oxime ethers have been exploited extensively for radical addition, mainly through the longstanding efforts of Naito [26]. In most cases, stereocontrol has been imparted through the substituents on the imino carbon chiral O-substituents on oximes for stereocontrol were ineffective, presumably due to poor rotamer control [27, 28]. 

Diastereoselectivity in radical additions to hydrazones 3 and 7 proved to be quite promising, with diastereomer ratios ranging from 93 7 to 99 1 (Table 3) [47]. In search of optimal stereocontrol, substituents on the oxazolidinone moiety were varied. Thus, isopropyl radical additions to several /V-acylhydrazones 3a-3e were compared for stereoselectivity (Scheme 3). High diastereoselectivities were observed in all adducts 13a-13e, although a rigorous measurement was not obtained on 13c. All of the auxiliaries impart stereocontrol suitable for practical synthetic application [48],... 

The diastereomeric ratios of all these adducts are compiled in Table 7, and illustrate the impact of radical reactivity on stereocontrol. Vinylic radical intermediates formed from 49E and 49F cyclize with consistently lower selectivity than the corresponding alkyl radicals formed from 49D and 49E, which may reflect a shift to an earlier transition state, which could reasonably be expected for the more reactive vinylic radicals. 

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