4 Reaction Mechanisms Part (iii) Free-radical Reactions By D. CRICH Department of Chemistry University College London 20 Gordon Street London WC1H OAJ 1 Introduction The material included in this chapter reflects to a large extent the author's interest in the use of free radicals as reactive intermediates in preparative organic chemistry and is divided into two sections. The first section contains a summary of the more interesting uses of free-radical intermediates in synthesis published in the past year and the second a description of those mechanistic studies and physical measure- ments published during the same period which will prove useful to chemists planning the incorporation of free-radical steps into their own reaction sequences. The use of physical methods for the observation of free radicals per se and the measurement of thermochemical data pertaining to free radicals their formation and their reactions has been omitted.2 Synthesis Intramolecular Processes.-One of the most interesting developments in the field of free-radical cyclizations in 1986 was the macrocyclization of alkyl radicals generated by the action of tri-n-butyltin hydride on alkyl halides onto crp-unsaturated ketones and esters (Scheme l).' Best yields were obtained for the formation of 14-and 20-membered rings. The inclusion of an E-alkene or a triple bond into the alkyl chain had no detrimental effect upon the cyclization yields. A more cumbersome approach to macrocyclic ketones involved photochemical or thermal decomposition of cyclic tetraacyl diperoxides in the absence of solvent.* Bu,SnH AlBN wc Scheme 1 Nicolaou established an ingenous route to some brevetoxin model compounds involving the sodium naphthalenide mediated transannular cyclization of macrodithionolides (Scheme 2).3 ' N.A. Porter D. R. Magnin and B. T. Wright J. Am. Chem. SOC.,1986,108 2787. * M. Feldhues and H. J. Schafer Tetrahedron 1986,42 1285. K. C. Nicolaou C.-K. Huang M. E. Duggan K. B. Reddy B. E. Marron and D. G. McGarry J. Am. Chem. Soc. 1986 108 6800. 65 66 D. Crich a% Me - . .. I I1 0 0 0 H H H SMe H Reagents i sodium naphthalenide; ii Me1 Scheme 2 With the exception of these highlights the now familiar 5/6-exo-trig/ dig processes continued to dominate the field of free-radical cyclizations.Nevertheless some significant advances were made in this area. Parsons et al. have succeeded in fusing a five-membered ring onto a p-lactam by means of a free-radical cyclization (Scheme 3).4 Interestingly the inclusion of a methyl group at the azetidione 4-position led to higher yields of carbapenam possibly due to a Thorpe-Ingold effect. Winkler and Sridar made elegant use of the original Julia observation of the reversibility of the cyclization of 5-hexenyl radicals stabilized by two-electron withdrawing groups to obtain a good yield of cis-anti-cis linear triquinanes from an appropriately functionaliZed 1,5-~yclooctadiene (Scheme 4).' The use of a simple alkyl radical generated from an iodide with tri-n-butyltin hydride led to mixtures of cis-and trans-bicyclo[6,3,0]undec-3-enesand linear triquinanes.68% (@/a= 5.8/1) 10% Scheme 3 CN H n 45 "/o 15 '/o Scheme 4 Curran introduced the cyclization of 5-hexynyl iodides to iodomethylene cyclo- pentanes (Scheme 5).6 This process which relies on the very rapid (3lo9mol-' dm3 s-' at 80 "C) and efficient abstraction of an iodine atom from the substrate by a vinyl radical has the significant advantage of requiring only a catalytic quantity of stannane as initiator. In a similar manner 5-hexenyl iodides were cyclized to iodomethylcyclopentanes although these reactions were not so clean reflecting the less efficient chain-transfer step.' Use was made of the fact that 2-sila-5-hexenyl J. Knight P.J. Parsons and R. Southgate J. Chem. Soc. Chem. Commun. 1986 78. -5 J. D. Winkler and V. Sridar J. Am. Chem. Soc. 1986 108 1708. 'D. P. Curran M.-H. Chen and D. Kim.J. Am. Chem. Soc. 1986 108 2489. ' D. P. Curran and D. Kim Tetrahedron Lett. 1986 27 5821. Reaction Mechanisms -Part (iii) Free-radical Reactions radicals cyclize predominantly in the 6-endo-trig mode to effect a stereoselective synthesis of steroidal side-chains from 17-alkylidene-16-(bromomethyl)dimethyl-silyloxy steroids.' 5-Hexenyl radicals can be generated and subsequently cyclized by the treatment of homoallylic iodides with tri-n-butyltin hydride in the presence of an excess of a Michael acceptor such as acrylonitrile (Scheme 6).9 Scheme 5 I Scheme 6 Tandem cyclizations have again been put to good use by Curran.This time for the preparation of angular triquinanes (Scheme 7)." The influence of minor modifications to the substitution pattern of the precursor on cyclization stereochemistry is noteworthy here. Tsang and Fraser-Reid demonstrated that appropriately placed aldehydes can function as internal traps for alkyl radicals in the presence of tri-n-butyltin hydride (Scheme 8).11 The popular a-methylene- y-lactones can be prepared by 5-exo-dig cyclization of homopropargyloxycarbonyl radicals generated from the phenylseleno carbonate with tri-n-butyltin hydride (Scheme 9).12 It was also possible to cyclize a homoallyloxycarbonyl radical in the 5-exo-trig mode leading to a y-lactone after chain tran~fer.'~ X X Bu,SnH b + AIBN 80°C Br I I x=o 66% 1 3 X = OCH2CH2O 65% 2.5 1 Scheme 7 M.Koreeda and I. A. George J. Am. Chem. SOC.,1986 108 8098. 2. CekoviE and R. SaiEiE Tetrahedron Lett. 1986 27 5893. 10 D. P. Curran and S. C. Kuo J. Am. Chern. SOC.,1986 108 1106. R. Tsang and B. Fraser-Reid J. Am. Chem. SOC.,1986 108 2116; 1986 108 8102. 12 M. D. Bachi and E. Bosch Tetrahedron Lett. 1986 27 641. 13 D. H. R. Barton and D. Crich J. Chem. SOC.,Perkin Trans. 1 1986 1603. 68 D. Crich phT'% 0 Bu,SnH OMe ____,Ho{& OMe !%oMe H k I 1 8O/O 73'/o Scheme 8 Scheme 9 A novel approach to radical cyclizations involved the fragmentation of tertiary alkoxy radicals generated from hydroperoxides with ferrous sulphate giving sub- stituted 5-hexenyl radicals which subsequently underwent ring closure (Scheme lO).I4 The main problem with this entry into the 5-hexenyl system was the lack of regioselectivity in the fragmentation of the alkoxy radical.OOH MeC0,H W 3 8 '10 30% 8Yo 18% Scheme 10 A key step in the synthesis of isoamijiol by the Pattenden group was the generation of a ketyl radical anion from a ketone with sodium naphthalenide and its subsequent cyclization onto an w-acetylenic bond (Scheme 1 l)? Ketyl radical anions generated in the same manner were cyclized onto allenes by Crandall and Mualla.I6 Various cobalt complexes have again been demonstrated to be efficient in promoting the cyclization of alkyl and aryl halides onto appropriately placed double bonds." The Reagent i sodium naphthalenide Scheme 11 Z.CekoviE and R. SaiEiE Tetrahedron Lett. 1986 27 5981. Is G. Pattenden and G. M. Robertson Tetrahedron Lett. 1986 27 399. 1b J. K. Crandall and M. Mualla Tetrahedron Lett. 1986 27 2243. " H. Bhandal G. Pattenden and J. J. Russell Tetrahedron Lett. 1986 27 2299; V. F. Patel G. Pattenden and J. J. Russell ibid. 1986 27 2303. Reaction Mechanisms -Part (iii) Free-radical Reactions cobalt complexes need only be present in catalytic quantities with regeneration by either chemical or electrochemical means. The use of a cobalt complex in stoicheiometric amounts leads after cyclization to an organocobalt( 111) species which can be transformed with oxygen and sodium borohydride to the corresponding alcohol.In the field of remote functionalization Breslow has been able to functionalize for the first time on the P-face of a steroid using a 6P-ester (Scheme 12)." In this manner it was possible after elimination and ozonolysis to effect cleavage of the cholesterol side-chain to the 20-ketone. Three papers" describing the use of excep- tionally active catalysts for the remote functionalization of various steroidal alcohols and esters were later retracted.20 Reagents i PhlCl2 CH2C12 Bu'OH NaHCO, hv; ii -HCI; iii O3 Scheme 12 Intermolecular Processes.-Several interesting developments have been made in the field of carbon-carbon bond formation by intermolecular radical addition to multiple bonds. The use of a catalytic quantity of tri-n-butyltin chloride and sodium cyanoborohydride as overall reductant enabled Stork to employ a variety of activated alkenes including methyl and phenyl vinylsulphone and diethyl vinylphosphonate as radical traps in his radical cyclization with subsequent intermolecular carbon- carbon bond forming sequence.21 Particularly noteworthy was the use of an a-trimethylsilyl-aP-unsaturated ketone as radical trap in this sequence leading to an a-silyl ketone which was subsequently rearranged to give a regiospecific trimethyl- silyl enol ether (Scheme 13).22 It has been demonstrated that 2-carboethoxyallyl-tri-n-butylstannane( 1) under-goes SH2' reactions with alkyl radicals much more rapidly than simple allyl-tri-n- b~tylstannane.~~ The N-tertiary butyl carboxamide group also proved to be a good U.Maitra and R. Breslow Tetrahedron Lerr. 1986 27 3087. 19 R. Breslow and M. P. Mehta J. Am. Chem. Soc. 1986 108 2485; 1986 108 6417; 1986 108 6418. 2o R. Breslow Chem. Eng. New; December 8 1986 p. 2; J. Am. Chem. Soc. 1987 109 1605. G. Stork and P. M. Sher J. Am. Chem. Soc. 1986 108 303. 22 G. Stork P. M. Sher and H.-L. Chen J. Am. Chem. Soc. 1986 108 6384. 23 J. E. Baldwin R. M. Adlington D. J. Birch J. A. Crawford and J. B. Sweeney J. Chem. Soc. Chem. Commun. 1986 1339. 70 D. Crich OEt Q-(OEt I + 'I OSiMe3 Reagents i 10% Bu3SnCI NaBH3CN CH,=CH(SiMe3)CO(CH2)4Me; ii 140 "C Scheme 13 activating group for the S,2' reactions of allylstannanes. At the same time it was demonstrated that 1 -or 3-substituted allylstannanes are scrambled under free-radical conditions.In the reaction of carboxylic/thiohydroxamic mixed anhydrides (which this author proposes to call 0-acyl thiohydroxamates) with allylic sulphides the presence of an activating group as in (2) was found to be f~ndamental.~~ COzEt ASCMe, / Tertiary-butyldiphenylmethylhydrazones have been shown to be superior to triphenylmethylhydrazones for the formation of alkyl radicals by a deprotonation alkylation and subsequent azo decomposition sequence.25 In order to form the radical the intermediate azo-compound was heated in benzene at reflux. Diphenyl diselenide N-bromo- and N-chloro-succinimide and P-nitrostyrene were used to trap radicals formed in this manner. Low-temperature deprotonation of triphenyl- methylhydrazones and treatment of the resulting anion first with an aldehyde or ketone and then phosphorus trichloride prior to warming to room temperature results in the formation of alkenes possibly via a 4-membered ring (Scheme 14).26 24 D.H. R. Barton and D. Crich J. Chem. SOC.,Perkin Trans. I 1986 1613. 25 J. E. Baldwin R. M. Adlington and I. M. Newington J. Chem. Soc. Chem. Commun. 1986 176. 26 J. E. Baldwin R. M. Adlington J. C. Bottaro J. N. Kolhe I. M. Newington and M. W. D. Perry Tetrahedron 1986 42 4235. Reaction Mechanisms -Part (iii) Free-radical Reactions Reagents i MeLi THF/TMEDA -55 "C; ii PhCHO; iii XI, -78°C; iv -104 20°C Scheme 14 With the aid of alkylmercury(I1) chlorides as radical sources Russell has carried out the substitution of phenylacetylenes themselves containing an appropriate radical leaving group at the terminal position by a proximal addition elimination sequence (Scheme 15).27 The irradiation of alkylmercury( 11) chlorides in the presence of an activated terminal alkene results in the formation of a bishomoalkylmercury( 11) chloride via a radical chain-reaction (Scheme 16) .28 Similarly alkylmercury( 11) chlorides can be added across activated acetylenes.Ph-CEC-I + R-Hg-ClZ Ph-C=C-R Scheme 15 0 Scheme 16 Dicyanogen triselenide was introduced as an efficient trap for alkyl radicals leading to the formation of alkyl selen~cyanates.~~ Homolytic substitution of nitrogenous heterocycles was a popular subject in 1986.The importance of protonation of the heterocycle in increasing the rate of addition and in drastically changing the regioselectivity of addition was demonstrated by Mini~ci.~' Thus phenyl radicals generated from dibenzoyl peroxide add to 4-cyanopyridine giving a 0.23/1 ratio of ortho/ meta substitution products whereas addition to the 4-cyanopyridinium cation gave an ortho/ meta ratio of 1.71/ 1. Formylation of heteroaromatic bases can be 27 G. A. Russell and P. Ngoviwatchai Tetrahedron Lett. 1986 27 3479. 28 G. A. Russell W. Jiang S. S. Hu and R. K. Khanna J. Org. Chem. 1986 51 5498. 29 D. H. R. Barton D. Bridon Y. HervC P. Potier J. Thierry and S. Z. Zard TetrcLedron 1986,42,4983. 30 F. Minisci E. Vismara F. Fontana G. Morini M.Serravalle and C. Giordano J. Org. Chem. 1986 51 441 1. 72 D. Crich achieved by reaction of the base hydrochloride with trioxane tertiary butyl- hydroperoxide and ferrous ion followed by an aqueous work-~p.~' The dibenzoyl peroxide-initiated substitution of the lepidinium cation with cyclohexene leads not to the 243'-cyclohexenyl)lepidinium cation but rather to the (241'-cyclo-hexeny1)lepidinium cation.32 A mechanistic rationale for this observation involving addition of the benzoyloxy radical to cyclohexene substitution of the lepidinium cation by the adduct and finally elimination of benzoic acid was proposed. Homolytic substitution of protonated heteroaromatic bases was also achieved by photolysis in the presence of 0-acyl thiohydroxamates as radical sources (Scheme 17).33 The efficiency of substitution of protonated heteroaromatic bases with benzyl radicals is temperature-dependent.34 The ratio of dibenzyl to benzylated base increases significantly with temperature leading to the speculation that the addition of benzyl radicals to protonated bases is reversible.NHCOPh NHCOPh + G[-O-N? S Reagents camphor-10-sulphonic acid DMF hv Scheme 17 3 Mechanism and Physical Aspects The kinetic product of vinyl radical cyclization onto a 6-alkene is the 5-exo-trig At high stannane concentration the a-methylenecyclopentylmethyl radical so formed can be effectively trapped. At lower stannane concentration this radical undergoes rearrangement via a cyclopropylmethyl radical to the thermodynamically more favoured P-methylenecyclohexyl radical the product of an apparent 6-endo-trig process (Scheme 18).First-order rate constants were measured for steps a and b (Scheme 18) and found to be 1.2 x 10' and 1.6 x lo5s-' respectively at 60 "C. Aryl radicals were also found to cyclize rapidly in a 5-exo-trig mode onto 8-alkenes (5 x lo's-' at 50°C for the parent 2-(3'-buteny1)phenyl radical).36 Here again however in certain cases the kinetic 5-exo-trig cyclized radicals have been shown to undergo rearrangement by a pathway analogous to that outlined in Scheme 18 to the apparent 6-endo-trig produ~t.~' The nature of substituents at position-6 on the aromatic ring had a pronounced effect on the efficiency of this rearrangement. 31 C.Giordano F. Minisci E.Vismara and S. Levi J. Org. Chem. 1986 51 536. 32 E. Vismara M. Serravalle and F. Minisci Tetrahedron Lett. 1986 27 3187. 33 D. H. R. Barton B. Garcia H. Togo and S. Z. Zard Tetrahedron Lett. 1986 27 1327; E. Castognino S. Corsano D. H. R. Barton and S. Z. Zard ibid. 1986 27 6337. 34 F. Minisci E. Vismara G. Morini F. Fontana S. Levi M. Serravalle and C. Giordano J. Org. Chem. 1986 51 476. 35 A. L. J. Beckwith and D. M. O'Shea Tetrahedron Lett. 1986 27 4525; G. Stork and R. Mook ibid. 1986 27 4529. 36 A. N. Abeywickrema and A. L. J. Beckwith J. Chem. Soc. Chem. Commun. 1986,464. 37 K. A. Parker D. M. Spero and K. C. Inman Tetrahedron Lett. 1986 27 2833. Reaction Mechanisms -Part (iii) Free-radical Reactions b Ilow[Bu,SnH] Scheme 18 Thus with a 6-formyl group the rearrangement product was the only one observed whilst with a 6-hydroxymethyl group no rearrangement was found.Giese has studied the rate of 1,2-formyl migration in P-formyl radicals and found it to be of a similar order to 1,2-vinyl migration in P-vinyl radicals3* Two useful papers describing the relative reactivities of variously substituted alkyl halides alkyl phenyl sulphides and alkyl phenyl selenides towards tri-n-butylstannyl radicals and tri- n-butylgermyl radicals were published.39 In general it was found that for a specific alkyl group the order of reactivity is Br > PhSe > C1 > 4-NC-C6H4S > PhS > 4-Me-C6H4S > MeS and that for a given halide or chal- cogen X the order of reactivity of the alkyl fragment is EtOCOCH2X > RCH,0CH2X > RC02CHzX> RCH2X.It was also found that the tri-n-butyl- germyl radical abstracts halogen (with the exception of chlorine) and chalcogen more rapidly than the tri-n-butylstannyl radical and adds more rapidly to alkenes. Nevertheless with the possible exception of reactions involving a radical rearrange- ment or cyclization step the use of germanes instead of stannanes does not necessarily lead to higher yields in chain reactions due to the relatively poor hydrogen-donor capability of germanes. Pentamethyldisilane has been proposed as a hydrogen donor in radical chain-reactions with alkyl halides;40 in terms of reactivity towards alkyl radicals it was found to be intermediate between tri-n-butylgermanium hydride and triethylsilane.The rate of inversion of the parent cyclopropyl radical has been estimated by means of specific deuterium labelling to be greater than 10” s-l at 71 0C.41 Pyramidal alkyl radicals show similar selectivity towards alkenes in addition reactions as planar alkyl radicals.42 The selectivity of addition of a series of alkylated ethyl bromoacetates to two pairs of alkenes has been ~tudied.4~ With the exception of the parent radical it was found that the carboethoxyalkyl radicals added more rapidly to propyl-2-propenyl ether than to 1-octene but also more rapidly to 1-methylcyclohexene than to 1-octene. Both selectivities increased with increasing steric bulk at the radical centre which was explained in terms of increased radical persistance and hence lower exothermicity of addition.38 B. Giese N. Heinrich H. Horler W. Koch and H. Schwarz Chem. Ber. 1986 119 3528. 39 A. L. J. Beckwith and P. E. Pigou Aust. J. Chem. 1986 39 77; 1986 39 1151. 40 J. Lusztyk B. Maillard and K. U. Ingold J. Org. Chem. 1986 51 2457. 41 L. J. Johnston and K. U. Ingold J. Am. Chem. Soc. 1986 108 2343. 42 B. Giese and J. A. Gonzalez-Gomez Chem. Ber. 1986 119 1291. 43 V. Ghodoussi G. J. Gleicher and M. Kravetz J. Org. Chem. 1986 51 5007. 74 D. Crich The reaction of alkylcobaloximes with various radicals has been portrayed for some years now as an example of SH2 at carbon; two more examples of this process involving the reaction of propargy14 and benzylcobaloximes4’ with sulphonyl chlorides have appeared.Evidence has been presented however for an alternative mechanism involving addition of the attacking radical onto a ligand giving a resonance-stabilized nitroxide radical followed by elimination to give the apparent S,2 product (Scheme 19).46The reaction of small strained propellanes with bromotri- chloromethane tetrachloromethane and aldehydes in the presence of dibenzoyl peroxide does however appear to be a good candidate for a reaction involving an SH2 step at carbon.47 Interestingly the use of acetaldehyde led to a 2/1 adduct (Scheme 20). A review on the homolytic reactions of small strained bicycloalkanes has appeared.48 Beckwith has demonstrated that SH2 at sulphur in chiral sulphoxides takes place with complete inversion of c0nfiguration.4~ I I OH OH Scbeme 19 OH (PhCO,), + MeCHO -Me~&c!H-Me Scheme 20 Benzyl vinyl ethers are formed on reaction of 1-aryl-2-bromomethyloxiranes with tri-n-butyltin hydride and a radical initiator.” By means of 180-labelling studies the 1,2-acetoxy migration in 2-acetoxyalkyl radicals was shown to be a 1,2-shift involving only the acetoxy oxygen as opposed to a 2,3-shift involving the carbonyl oxygen.’l A particularly interesting example of this radical rearrangement is the formation of 2-deoxyglucose tetraacetate upon treatment of acetobromoglucose with tri-n-butylstannane (Scheme 2 1).52 This particular example appears to have gone pre- viously unnoticed and doubtless depends on the order and rate of addition of the reactants.The mechanism of addition of tri-n-butylstannyl iodoacetates to alkenes giving y-lactones has been in~estigated~~ and shown to proceed via two discrete 44 B. D. Gupta and S. Roy Tetrahedron Lett. 1986 27 4905. 45 B. D. Gupta M. Kumar 1. Das and S. Roy Tetrahedron Lett. 1986 27 5773. 46 R. C. McHatton J. H. Espenson and A. Bakac J. Am. Chem. Soc, 1986 108 5885. 41 K. B. Wiberg S. T. Waddell and K. Laidig Tetrahedron Lett. 1986 27 1553. 48 K. U. Ingold and J. C. Walton Acc. Chem. Rex 1986 19 72. 49 A. L. J. Beckwith and D. R. Boate J. Chem. SOC.,Chem. Commun. 1986 189. 50 M. Cook 0.Hares A. Johns J. A. Murphy and C. W. Patterson J. Chem. SOC.,Chem. Commun. 1986 1419. P. KoEovski I. Sta~,and F. TureEek Tetrahedron Lett.1986 27 1513. 52 B. Giese Silicon Germanium Tin and Lead Compounds 1986 9 99. 53 M. Degueil-Castaing B. De Jaso G. A. Kraus K. Landgrebe and 9. Maillard Tetrahedron Leu. 1986 27 5927. Reaction Mechanisms -Part (iii) Free-radical Reactions Scheme 21 steps; a radical chain-process involving addition of the carbon-iodine bond across the alkene followed by a two-electron cyclization of the so-formed stannyl y-iodocarboxylate to the lactone. Unlike their acyclic counterparts which are quenched by oxygen at the terminal position six-membered cyclic pentadienyl radicals react with molecular oxygen at the central position leading eventually to cross-conjugated cyclohexadienone~.~~ This disparity was explained in terms of reduced steric strain in the adduct radical.Newcomb and Park used 0-acyl thiohydroxamates in the measurement of rates of hydrogen abstraction by alkyl radicals from various hydrogen donors and found them to be a clean and convenient radical source for use in this kind of quantitative Beckwith measured the rates of reaction of primary alkyl radicals with the stable nitroxide (3) and found them to be of the order 8.9 x lo8mol-' dm3 s-' at 60 0C.56 Warkentin used the same nitroxide (3) to calibrate the rate of ring-opening of the cyclopropylmethyl radical in the range 30-90 0C.57 X The capto-dative effect continues to be a subject of much interest. Newcomb investigated the effect of captodative substituents on the rate of cyclization of 5-hexenyl radicals (4).58 Thus it was found that at 50°C the 6-cyano-5-hexenyl radical [(4) X = H Y = CN] and the 6-methoxy-5-hexenyl[(4) X = H Y = OMe] cyclized 275-and 2.4-times more rapidly respectively than the standard 5-hexenyl radical whilst in the capto-dative substituted radical [(4) X = CN Y = OMe] cyclization was accelerated by a factor of 41 5 at 50 "C providing some slight evidence for a capto-dative effect.Neumann on the other hand found little or no evidence for merostabilization of 4,4'-disubstituted triarylmethyl radicals as measured by the extent of change in the position of the radical-dimer equilibrium according to the 54 A. L. J. Beckwith D. M. O'Shea and D. H. Roberts J. Am. Chem. Soc. 1986 108 6408. 55 M. Newcomb and S.-U. Park J. Am. Chem.SOC.,1986 108 4132. 56 A. L. J. Beckwith V. W. Bowry M. O'Leary G. Moad E. Rizzardo and D. H. Solomon J. Chem. Soc. Chem. Commun. 1986 1003. 57 L. Mathew and J. Warkentin J. Am. Chem. Soc. 1986 108 7981. 58 S.-U. Park S. K. Chung and M. Newcomb J. Am. Chem. SOC.,1986 108 240. 76 D. Crich nature (capto dative and capto-dative) of the aryl sub~tituents.~~ Viehe et al. noticed a significant drop in the minimum temperature required for the cleavage of symmetri- cally substituted 1,Shexadienes to ally1 radicals when the substituents were capto- dative in nature rather than simply one or the other.60 Katritzky et al. made the interesting suggestion that merostabilization is likely to be much more pronounced in polar media than in non-polar media as a result of the higher polarization of capto-dative substituted radicals as compared to more symmetrically substituted ones.61 The 'reverse effect' is a concept introduced by Ballester to describe the accelerating effect of persistent radicals in a molecule upon the reactions of other substituents in the same molecule.62 For example benzylic bromination with bromine and AIBN in tetrachloromethane at reflux of the di( pentachlorophenyl)-4-methyltetra-chlorophenylmethyl radical was found to be approximately eight times more rapid than bromination of the analogous triarylmethane under the same conditions.Similarly the reaction of diethylmalonate and potassium carbonate in dioxane at 90 "C with the di(pentachlorophenyl)-4-bromomethyltetrachlorophenylmethyl radical was nine times faster than with the triarylmethane.Finally the controversial idea of there being two types of chemistry associated with the succinimidyl radical one belonging to a .rr-type radical and one to a a-type radical has now been withdrawn.63 59 W. P. Neumann W. Uzick and A. K. Zarkadis J. Am. Chem. SOC. 1986 108 3762. 60 M. Van Hoecke A. Borghese J. Penelle R. MerCnyi and H. G. Viehe Tetrahedron Letl. 1986 27,4569. 61 A. R. Katritzky M. C. Zerner and M. M. Karelson J. Am. Cbem. SOC.,1986 108 7213. 62 M. Ballester J. Veciana J. Riera J. Castacer C. Rovira and 0.Armet J. Org. Chem. 1986 51 2472. 63 P. S. Skell U. Luning D. S. McBain and J. M. Tanko J. Am. Cbem. Soc. 1986 108 121.