Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 1135 122

1. Fluorine

The analysis of the syn-addition of molecular fluorine to ethylene at the MP2/6-31 C G level with IRC calculations indicates that F2 approaches the CDC bond vertically at the middle to form a perpendicular complex 38 as the intermediate. The latter complex then re-orientates to a rhombic-type transition state 39 to give the final syn-addition product 4084. This analysis rules out the involvement of the square-type complex 41 proposed earlier. However, these calculations do not clarify the F2 addition to electron-deficient alkenes, such as acrylonitrile84.

Further experimental support for a four-centre, concerted addition across the CDC bond as the major mechanism has been obtained by the study of the molecular dynamics of the addition of F2 to cis-d2-ethylene and the subsequent decomposition dynamics of the vibrationally excited 1,2-difluoroethane-d2 product isolated in Ar or Xe matrixes at 12K85.

The long sought epifluoronium ion 42 has now been identified in gaseous phase as a (relatively) stable species86.

Alkoxyxenon fluorides (ROXeF), generated from XeF2 on reaction with alcohols, react with indene as positive oxygen electrophiles when BF3.Et2O is used as catalyst. By contrast, with proton catalysts they react as apparent fluorine electrophiles87.

Vicinal difluorides have been obtained on reaction of XeF2 with triphenylethylene, 9- benzylidenefluorene and tetraphenylethylene in CH2Cl2 in the presence of HF at r.t. By contrast, no reaction was observed with CsSO4F ( 30 °C) unless MeOH had been added. In the latter case, Markovnikov-type fluoromethoxy adducts were isolated88.

1146 Pavel Kocovskˇy´

The stereochemistry of fluoroalkoxylation of 1-phenylbenzocycloalkenes 43 with CsSO4F in alcohols (MeOH, EtOH, PriOH) is ring-size dependent. Thus, predominant syn-addition for the five-membered ring, mainly anti addition for the six-membered ring, and an almost exclusive syn process for the seven-membered ring have been reported. The -bond disruption in the substrate has been identified as the rate-determining step89.

The major product of the thermal addition of CF3OF to trichloroethylene in the gas phase was identified as CF3OCHCl CCl2F. Other products, i.e. CHClF CCl2F and CF3O(CHCl CCl2)nOCF3 (n 2), are formed in minor amounts90.

2. Chlorine

The geometries of eleven chloronium ions were calculated using 3-21G MO and were classified as being either bridged (‘onium’) or open structures, depending on the parent olefin. Rather surprisingly, the chloronium ion derived from 2,3-dimethyl-2-butene (Me2CDCMe2) was found to be an open species, presumably due to the antisymmetric exchange repulsion between an occupied MO of the alkene and the ClC p lone pair electrons91.

The pre-equilibrium molecular complex formed in a mixture of ethylene and chlorine has been characterized using a pulsed nozzle FT microwave spectrometer. The rotational spectrum demonstrated the existence of a C2v-symmetrical complex 44: the Cl2 molecule lies along the C2 axis of ethylene that is perpendicular to the molecular plane and interacts weakly with the -bond92.

Chlorination of a variety of vinyl compounds RCHDCH2 (R D Me, Bui, But , CH2Cl, CH2Br, CH2OH, Br, COMe, CO2H, CN) in alcohols gives a mixture of 2-alkoxy-1- chloro compounds, 1-alkoxy-2-chloro compounds and vicinal dichlorides, the relative proportions of which are dependent on the substituent R, reaction temperature, molar ratio and elapse time93. Similarly, chlorination, alkoxychlorination and/or acetoxychlorination was observed with 2-methyl-but-2-ene94 and 4-substituted cyclopentenes95.

Non-conjugated olefins have been found to undergo anti-dichlorination with a MnO2 Me3SiCl mixture via a non-chain radical mechanism with MnCl4 serving as the reactive species. Conversion of MnCl4 to MnCl2 during the reaction seems to be an efficient radical-quenching process96.

Chlorination of ethylene with Cl2 in C2H4Cl2 solution has been studied with and without FeCl3 catalysis at 293 308 K. Simultaneous addition and substitution was detected97. The yields of the styrene low-temperature halogenation products with DMFžCl2 or DMFžBr2 have been found to exceed the yields using free halogen in DMF solution98.

Liquid-phase chlorination of butadiene in the presence of Bu3N affords a mixture of 1,2- and 1,4-addition products. Kinetic measurements suggest two independent mechanisms: the 1,2-adduct is formed by the attack of Bu3NžCl2 on the butadienežCl2 -complex, whereas formation of the 1,4-adduct involves Bu3N-stabilization of the -complex99 101.

A quantum chemistry study of the reaction of chloroprene with Cl2 has revealed two transition states for substitutive chlorination, which is consistent with two consecutive processes: chlorination to give a carbocation followed by abstraction of the originally allylic proton. On the other hand, a single transition state was observed for additive chlorination. The potential barriers for the former process lay below that for the latter102.

Electrophilic chlorination of the trichlorodienone 45 has been found to give two isomeric products resulting from 2,5- and 4,5-addition of chlorine; both processes involve the same intermediate 46103 105.

Chlorination of (Z)-1-silyl-1,2-difluoroalkenes 47 carried out in the presence of fluoride ions is followed by a stereospecific desilylation which occurs with an overall retention of configuration (47 ! 48)106. The mechanism is believed to involve syn-addition of chlorine and the fluoride-mediated elimination of Me3SiF and Cl .

3. Bromine

An MNDO calculation of six bromonium ions derived from ethylene, propene, 2-butene, isobutylene, 2-methyl-2-butene and tetramethylethylene, 49 54 shows energy minima corresponding to symmetrical bridged ions for symmetrically substituted systems 49 51 and highly asymmetric bridged ions for non-symmetrically substituted species 52 54107.

Semiempirical methods at various levels have been used to elucidate the structure of the bromonium ion arising from 2-methylpropene 52 in gas phase108. The computed structure turned out to be dependent upon the method employed and the inclusion of the electron correlation and of polarization107,109. The computed structure becomes more symmetric (i.e. more bridged) as the quality of the computation method improves. However, the potential energy surface along the C(2) C(1) Br mode is very flat and may be easily disturbed by the incoming nucleophile110. These factors appear to be significant in the interpreting of the Markovnikov rule109. On the other hand, the PPM3 and lower level ab initio molecular orbital calculations, carried out for thirteen bromonium ions, suggest the non-symmetrical Markovnikov-type structures for 52 and other non-symmetrical ions resulting from donor acceptor relations111. By contrast, geometries of thirteen mercuronium ions, for example 55, have been found to be dictated by steric repulsion between the AcO group and the substituent, rather than the electronic effects111.

A Fukui-type correlation emphasizing the role of the conservation of orbital symmetry has been presented, with formation of bromonium ion as an example. Walsh MOs of bromonium ion have also been discussed with reference to further reactions of bromonium ion with bromide ion, resulting in the formation of trans-dibromide112.

The first theoretical calculations of bromination in solution110 (in CH2Cl2, in MeOH and in vacuo), using the polarizable continuum model and Bader’s procedure, demonstrated that the Br atom in bromonium ion shares a positive charge equal to or larger than that on the carbon atoms, both in vacuo and in polar solvents. This indicates that the basic character of the -complex does not imply a complete electron transfer from ethylene to BrC and that a partial character of -complex is present. The charge distribution does not exclude a nucleophilic attack of Br or Br3 on the bridged Br (which has previously been proposed to account for the reversibility of the bromonium ion formation113). In vacuo, trans-ethylene bromonium bromide 56 is more stable than the cis-complex 57 by 12 kcal mol 1, showing that the attack on carbon is favoured over that on bromine in the preparatory step. However, the energy difference is greatly reduced in polar solvents (to 2.9 kcal mol 1 in MeOH)110.

Adamantantylidenadamantane (AdDAd) is unique among olefins in that its structure impedes the Br2 addition from proceeding beyond the stage of bromonium ion114,115. An investigation of the AdDAd Br2 system in 1,2-dichloroethane using stopped-flow and UV spectrometric techniques has shown that an equilibrium is instantaneously established with 2:1, 1:1, 1:2 and 1:3 olefin Br2 aggregates (Scheme 1)116. Conductivity measurements have confirmed that the 1:1 species is a molecular charge-transfer complex (CTC) while the other three are ionic in nature. The 1:2 and 1:3 species have been identified as the bromonium tribromide and the bromonium pentabromide salts, respectively. The CTC 59 turned out to be surprisingly stable. However, the formation of both 59 and 60 is too fast to be monitored, so that it was impossible to check experimentally if 60 is formed directly from olefin 58 and Br2 or by a Br2-assisted ionization of the first formed 59. Nevertheless, on the basis of the previously proven involvement of CTCs on the reaction coordinate

SCHEME 1

for the ionic bromination of cyclohexene in the same solvent, it seems very likely that 60 arises from 59. The bromonium pentabromide 61 was found at equilibrium in appreciable amounts at sufficiently high analytical concentrations of Br2 and was proven to be formed

from 60 and Br2 with the formation constant K013 D [61]/[60][Br2] D 22.4 l mol 1. This value is close to that for the formation of Bu4NC Br5 from Bu4NC Br3 and Br2

(14.3 l mol 1), which confirms the involvement of bromonium pentabromide ion pairs in olefin bromination at high concentration of Br2117.

The complication stemming from the equilibrium shown in Scheme 1 was later circumvented by the conversion of 60 to the crystalline triflate 62, which was isolated and subjected to a detailed NMR and X-ray analysis118. An unprecedented, rapid and direct transfer of BrC was observed from 62 to acceptor olefins, such as cyclohexene-d10 to give the corresponding trans-2-bromocyclohexyl trifluoromethansulphonate-d10, indicating that an intermolecular BrC transfer from ion to olefin must be considered as competitive with the various product-forming steps during olefin bromination118.

The bromination of dibenzoazepine 63 in 1,2-dichloroethane gives the trans-dibromide 64 as the only product. The reaction was monitored spectrophotometrically and found to exhibit a third-order kinetics (second-order in Br2). A significant conductivity has also been found during the course of bromination. Both spectrophotometric and conductometric measurements are consistent with the presence of Br3 salt intermediates at a maximum concentration of ca 2% of that of the initial reactants. The X-ray structure of dibromide 64 shows a considerable strain at carbons bearing bromine atoms. The strain appears to be responsible for an easy, spontaneous debromination of 64, as well as for high barrier for the formation of 64 from the bromonium-tribromide intermediate. That makes possible the cumulation of the intermediate itself during the bromination of 63119.

Further convincing evidence for the reversibility of bromonium-ion formation has been gained from the 5H-dibenzo[b,f]azepine model system113,120,121 (for discussion of previous results, see elsewhere2), from kinetic measurements of bromination of tetraisobutyl ethylene (TIBE)122 and from elucidation of trans-2-bromotriflate 65123. The latter compound was solvolysed at r.t. in AcOH and MeOH containing varying concentration of

LiBr and in the presence of cyclopentene as a scavenger olefin. The kinetics, determined by monitoring the formation of strong acids (TfOH or HBr), show that the rate of solvolysis of 65 is dependent on [Br ] (at a constant ionic strength). In the presence of Br , the products are trans-1,2-dibromides and bromo-solvates of both cyclohexene and cyclopentene. The cyclopentenyl products have been shown to arise from the electrophilic addition of Br2/Br3 to cyclopentene, while trans-1,2-dibromocyclohexane 67 is formed by Br capture of the bromonium ion 66 on carbon. The Br2 required for bromination of cyclopentene results from attack by Br on the bromonium ion 66 on BrC . On the basis of the ratio of the cyclopentyl products to 67, Br capture of the solvolytically produced bromonium ion 66 (by attack on BrC ) is 4 5 times more prevalent than attack on carbon in AcOH, and ca 25 times more preferred in MeOH123.

:Br

A dynamic NMR investigation of the AdDAd/Br2 system has also provided additional kinetic and thermodynamic evidence for reversible formation of the bromonium ion/Brn pairs. The data revealed that the rate-limiting step for the reversal of a bromonium ion into reagents involves an intermediate having 1:1 (olefin/Br2) stoichiometry very likely the charge-transfer complex. Although AdDAd cannot proceed past the stage of bromonium ion formation (in which it differs from other olefins), the stages of the reaction up to that point must be considered normal. Therefore, the conclusions arrived at with the AdDAd system should be viewed as general124.

Stable bromonium and iodonium ions 69 71 of AdDAd and bicyclo[3.3.1]nonylidenebicyclo[3.3.1]nonane have been characterized by X-ray diffraction125. The data have

demonstrated that the three-membered halonium ring is almost symmetrical with the fol-

that the halonium ion has two perpendicular planes of symmetry. Addition of the parent olefin causes line broadening of signals of the carbons above and below the plane that includes the central C C bond and is perpendicular to the above two planes. This effect has been attributed to the transfer of XC to acceptor molecule. Rate constants for this process have been determined; activation parameters for the exchange between 69 and

transfer proceeds via an unsymmetrical 1:1 halonium ion/olefin charge-transfer complex intermediate and a D2d-symmetrical transition state125.

Greater retardation observed for the bromination of sterically congested adamantylidenealkenes AdDCRR0 (R D H or Me, R0 D H, Me, Pri, But or neo-Pent) compared to isopropylidenealkenes Me2CDCRR0 has been attributed to a change of mechanism, namely to the inhibition of nucleophilic solvent assistance in the ionization step and/or return resulting from a slow product-forming step126.

The early stage of electrophilic bromination of tetraisobutylethylene (TIBE) has been examined to detect the formation constant (Kf) for the 1:1 charge-transfer complex (in CH2Cl2, AcOH and MeOH). Based on the Kf values, the thermodynamic parameters for CTC formation from TIBE C Br2 are H D 4.2 š0.2 kcal mol 1 and S D9.5 š0.7 e.u. TIBE reacts with Br2 to afford substitution products, two of which are an initially formed allylic bromide and a more slowly formed diene bromide127.

The reversibility of the ionization step in olefin bromination (vide supra)121 implies that the product-determining step can also be partially rate-determining128. The occurrence of isomerization of cis-stilbene to trans-stilbene accompanying bromination can be rationalized129 as follows: a strained cis-bromonium species is first isomerized to a trans-bromonium tribromide ion pair (through an open ˇ-bromocarbocation). The latter ion pair then releases molecular bromine, producing trans-stilbene129. The reversibility of bromonium ion and ˇ-bromocarbocation formation has been further elucidated with p- substituted stilbenes in 1,2-dichloroethane in the 10 1 to 10 4 M concentration range128. Observed dibromide ratios showed that an open ˇ-bromocarbocation is the intermediate of the bromination of 72a and 73a (stabilized by p-CH3), whereas bridged and partially bridged ions are involved with all other olefins 72b 72d and 73b 73d. This also determines the extent of reversibility: open ˇ-bromocarbocations do not significantly revert to the olefin, whereas symmetrically bridged bromonium ions, particularly those generated from 72d and 73d, are the most prone to reversal. This trend corresponds to a gradual mechanistic shift of rate determination from the ionization step to the product-forming

(a) R1 = H, R2 = Me

energy

b

a

reaction coordinate

FIGURE 1. Reaction coordinate diagram for the bromination of trans-p-methylstilbene (a) and trans-p-p0 -bis(trifluoromethyl)stilbene. (b). Reprinted with permission from G. Bellucci, R. Bianchini, C. Chiappe, R. S. Brown and H. Slebocka-Tilk, J. Am. Chem. Soc., 113, 8012 (1991). Copyright (1991) American Chemical Society

(Figure 1), which is reflected in the dramatic difference in the reaction rate (73a was found to react 107 faster than 73d)128,130.

While bromination of cis-stilbene (72e) in CHCl3 gives d,l-dibromide at higher Br2 concentration, preferential formation of meso-dibromide has been observed at lower concentrations131. Moreover, at low concentrations, the addition is accompanied by a cis trans isomerization of the unreacted olefin (72e ! 73e). This behaviour can be rationalized by assuming the reversibility of the formation of the bromonium ions and by their isomerization131.

An increase by two in the number of alkyl substituents on the double bond has been found to increase in both the Kf and kobsd roughly by a factor of 103, indicating

that substituent effects are much more influential on kobsd than on Kf. This may be rationalized by reversible ionization of CTCs to bromonium-bromide ion pairs132 134,

which should result in a decreased ionization rate and, therefore, in a decrease in the kobsd for bromination132.

An unusually large inverse secondary deuterium kinetic isotope effect (1.53 2.75, depending on the reaction conditions) has been reported for bromination of the sterically congested olefin 74. This behaviour can be rationalized by decreased steric hindrance due, in particular, to the endo-placement of the deuterium atoms relative to the double bond135.

D D D D

D D D D

D D

D D

D D

D D

(74)

Bromination of 5H-dibenz[b,f]azepine-5-carbonyl, studied at 5, 25 and 50 °C, has demonstrated that the charge-transfer complex ionization cannot be rate-limiting. The collapse of bromonium-tribromide intermediate (having a large negative enthalpy of formation) has been suggested as the most likely rate-determining step136.

In order to determine the lifetimes of bromonium ions 75, the product ratios for Br2 or NBS addition to a series of olefins (cyclopentene, cyclohexene, tetramethylethylene and styrene) in MeOH containing varying concentrations of N3 or Br have been elucidated137. From the 76/77 ratio, the partitioning constant ratios (kN/kMeOH) for the four olefins have been found as 5.9, 4.9, 9.3 and 2.7 M 1, respectively. The amount of 76 is unexpectedly low (in view of high nucleophilicity of N3 as compared to MeOH) which suggests that both N3 and MeOH capture a highly reactive intermediate in a non-activation-limited process. Assuming that the N3 reacts with the intermediate with a diffusion-limited rate constant 1010 M 1 s 1, the respective lifetimes of the ions produced from bromination of the four olefins are 5.9 ð 10 10, 5.0 ð 10 10, 9.3 ð 10 10 and 2.7 ð 10 10 s, respectively. These values have been interpreted as suggesting the following: (1) the cyclic olefins produce ions that live about 100 times longer than a secondary

1154 Pavel Kocovskˇy´

carbocation; (2) tetramethylethylene gives a bromonium ion that lives ca 10 times longer than a tertiary carbocation; (3) styrene gives an ion (bromonium or ˇ-bromocation) that is ca 40-fold longer-lived than the 1-phenetyl cation137.

Negative activation energies (ca 60 kJ mol 1) have been found for the liquid-phase bromination of unsaturated compounds in non-polar solvents and are believed to originate from the association of small amounts of HBr and H2O present in the system138.

While bromonium ions are not formed in gas phase82,139, they are well established intermediates in bromination of olefins in solution. Hence, solvents are of crucial importance for promoting the addition. Kinetic criteria including kinetic solvent isotope effects (ROH vs ROD; R D Me, Et) have been used to estimate the magnitude of the electrophilic and nucleophilic involvement of protic solvents, electrostatic medium effects and the occurrence of internal return in the bromination of olefins140,141. The values obtained are consistent with reversible formation of highly congested bromonium ions in protic solvents. The different magnitude of return in protic and aprotic media has also been rationalized by solvent involvement. It appears that in protic media, the main driving force is electrophilic assistance to Br departure, as shown by the kinetic solvent isotope effect (KSIE). This participation provides an important contribution to the reaction rate, regardless of the degree of substitution on the olefin. Nucleophilic assistance to positive charge development also contributes but to a smaller extent and depends on the olefin structure: bulky substituents or those that are capable of stabilizing a positive charge by delocalization can attenuate this effect. In halogenated solvents, the driving force is probably bromine assistance to the charge-transfer complex (CTC) ionization (analogous to electrophilic solvent assistance). This results in the formation of Br3 so that the product-forming step is energetically more expensive and the bromonium ion formation is reversible. Larger steric effects have been observed for adamantylidene derivatives AdDCR2 (as an extreme) than for other olefins, where the steric congestion is smaller. Thus the experimental rates for addition to AdDCR2 are smaller than ionization rates (in contrast to other olefins) due to the high degree of reversibility of the formation of bromonium ions140.

Bromination and oxymercuration have been found to have different rate-limiting steps: formation of the bromonium ion for the former reaction and attack by solvent on mercuronium ion for the latter142.

A new examination of the bromination and chlorination of acenaphthylene revealed that the relative amount of the syn-adduct increased as the solvent polarity decreased. At 4 6 °C the syn-dibromide remained unchanged for a year, and hexane was found to be the best solvent for its preparation143.

Stereoselectivity found for electrophilic additions to norbornene and 1-methoxy-2- cyclohexene is believed to originate from secondary orbital interactions rather than from orbital distorsion at the reaction centre144. Rather different results have been obtained from an ab initio MO study of the norbornene hydroboration145.

Tuning of the regioselectivity of electrophilic additions by substituents attached to the norbornene derivatives 79 has been reported. Strong preference for nucleophilic attack at C(5) has been confirmed146. Bromination of 80 at 20 °C has been found to afford a single product, tetrabromide 81, arising via a Wagner Meerwein rearrangement with accompanying aryl migration147 150. Unlike the reaction with Seand S-electrophiles (see below), bromination of 82 with Br2 or NBS was found to induce skeletal rearrangement and fragmentation151.

The preference for bromination of CDC vs activated aromatic ring has been elucidated with the aid of model compounds 83 and 84. Bromination of 83 has been found to occur first at the double bond; with excess of Br2, subsequent bromination of the aromatic ring has been observed. By contrast, 84 is first brominated in the aromatic nucleus before the