C C. Carbanion. Chemical speciates known as initiatiors are required, or photons.

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1 FEE ADICALS C C C C Free adical Carbocation Carbanion Carbene adical eaction Characteristic---three step process 1) Initiation Step----required to get a free radical 2) Propagation Steps--- The reaction of the radical and production of new radicals. 3) Termination steps---equired to remove radicals from the reaction Initiation Step Chemical speciates known as initiatiors are required, or photons. Peroxide heat di-tert-butyl peroxide and dibenzoyl peroxide are commonly used C C C 3 -C-=-C-C 3 C 3 C 3 AIB AzobisIsoButyroitrile heat C 2 C 3 -C C 3 1

2 Propagation---The first formed radical now produces new radicals and reactions C 3 -C C C 3 -X C C 3 -C X C 3 -C-C -C-C -X -C-C-X Termination---any reaction that removes the radical 2 - Stable Free adicals C 3 C 3 C C 3 C 3 C 3 C 3 shape prevents dimerization C=-t-Bu C--t-Bu tbu--tbu -oxide nitrone a nitrone The reaction above produces a stable nitrone radical from a reactive adical. The ES signal of the nitrone can be used to analyze the radical. Tables of nitrone ES spectra with different groups are in the literature 2

3 Free adical early sp 3 hybrid with inversion of stereochemistry Cl 2 Cl C 3 C3 racemic mixture 16% 84% I AIB X X 3

4 alogenation X 2 C 4 C 3 X X energy, kcal/mol X 2 light 2X F 2 Cl 2 Br 2 I C 4 X C 3 X C 3 X 2 C 3 Cl X Fluorination--Propagation energy is so large that the reaction is uncontrollable and explosions result Chlorination--can control the production of Cl radicals by the light source to give a useful process Bromination--The termination step is of low energy and the reactions are very selective for tertiary C bonds Iodination--eaction too difficult to go to completion Bromination is much more selective than chlorination X 2 X X X X Cl 2 relative rates Br 2 22% 33% 30% 15% % 3.8% 0.3% 0.1% relative rates

5 -Br BS, -BromoSuccinimide Mild bromination of allylic and benzylic radicals Initiation C 3 C 3 C C 3 C C Br- Br C 3 from AIB Propagation Br Br -Br Br - Br 2 low concentration Br 2 Br Br Br 2 concentration too low for alkene addition Br 2 Br Br Br Br d [radical substitution]/dt d [addition]/dt = k /Br 2 5

6 adical addition to alkene theory sp LUM SM M The SM orbital of a free radical reacts with the LUM or M of more similar energy with the SM. Electron donating groups raise the SM level and make the radical nucleophilic (SM-LUM). Electron with drawing groups lower thesm and make it electrophilic (SM-M). n the alkene, EWG lower LUM and M; EDG raise M and LUM EDG EWG EDG - C raises SM C EWG - C lowers SM normal LUM M higher LUM M lower LUM M 6

7 SM - LUM ucleophilic radicals contain EDG and add to the LUM of alkenes. k = 4 x 10 4 m -1 s -1 1 Cl 0.1 C 34 Ac 0.02 C 13 Bu CC C C 2 C C 2 C C 2 C 3 C 2 C 3 C 2 C x 10 5 C 4 x 10 6 SM 3 > 2 > C

8 SM-M Electrophilic adicals contain EWG and add to the M of alkenes C C low M 10-3 low SM C 3 1 Bu 30 Pr C 3 16 high M C 2 C 2 Et C 2 C 3 20 neutral reacts with LUM and M levels C 3 C 2 C 3 C (CF 3 ) 3 C Et 3 Si m -1 s -1 most electrophilic radical known 10 8 m -1 s -1 (C 3 ) 3 C- Et 3 Si m -1 s -1 8

9 Atom Transfer eaction IC 2 C 2 Et AIB C Et 2 C I C Bu 3 Sn The iodine atom is transferred from the starting iodo compound to the new radical to form the product. 1) adical Formation C 2 I AIB Bu 3 Sn C 2 k abs = 10 9 M -1 s -1 (Bu 3 Sn ) 2) Cyclization C 2 C 2 5-exo-trig k c = 10 5 M -1 s -1 3) Atom transfer and propagation C 2 C 2 C 2 C 2 I I k = 10 8 M -1 s -1 [I] 9

10 Initiation Bu 3 Sn- AIB Bu 3 Sn 2 3 C C C 3 STEP 1 Bu 3 Sn C Bu 3 Sn C I k x =10 9 m -1 s m -1 s -1 Bu 3 Sn m -1 s -1 Bu 3 Sn C Bu 3 Sn If K x [I] < 10 2 This step stops STEP 2 Bu 3 Sn m -1 s -1 If C too low then addition fails, if too high then step one fails C C set [C] > [Bu 3 Sn] ~ x m -1 s -1 STEP 3 C C C C polymer Bu 3 Sn- Final Product 10 6 m -1 s -1 C [Bu 10 2 m -1 s -1 3 Sn-] 10 6 m -1 s -1 > [C] 1 x 10 6 > 10 x

11 Addition to alkenes Sn Bu 3 5 x 10 4 m - s -1 4 x 10 4 m -1 s -1 E E E m -1 s m -1 s -1 C 2 C 3 C 2 C 3 I 2 x 10 8 m -1 s -1 11

12 Abstrtaction of CF 3 F 3 C C SiEt x 10 8 m -1 s -1 CF 3 CF 3 CF 2 CF 2 SnBu 3 2 x 10 9 m -1 s -1 tbu SiEt x 10 6 m -1 s -1 JCS Perkin 2, 1998, 29 F Si (TMS) m -1 s -1 Dolbier, JC, (1998) 63, 5687 SnBu m -1 s -1 C 3 C 2 C 2 C m -1 s -1 Abstrtaction of X -X SnBu 3 I 7 x 10 9 m -1 s -1 Br, Se m -1 s -1 2-xanthate, nitroso, Cl, S 10 5 m -1 s -1 S 10 6 m -1 s -1 12

13 Clock eactions When a radical intermediate rearranges to another radical intermediate, and both intermediates compete for a reagent, then the values for the rate constants of the reactions involved can be determined. This "clock" allows for the timing of the steps. k X X k (rearrangement) k X * -X *-X X d * / dt = 0 = k [ ] - k X [X][* ] * = k k X [X] d [*X] / dt = k X [X] [* ] d [X] / dt = k X [X] [ ] = * % *-X % -X = k X k [X] The percentages of the products can thus be used to obtain a rearrangement constant or an abstraction constant. ne of the constants must be known and many are known and tabulated. 13

14 Clock reactions in the 5-exo-trig cyclization 5-hexenyl radicals cyclize to give five membered rings exclusively. This is important for the synthesis of 5-membered rings and for obtaining information about the rates of radical reactions k k = 10 5 s -1 k abs k abs Cr 2 Cr 2 Cr 2 = 1 M Cr 1 A/ B = 500 A Cr 1 B % *-X % -X = k X k [X] k X = 5 x 1o 7 m -1 s -1 k k = 1.2 x 10 6 s -1 k abs k abs CCr(C 3 ) CCr(C 3 ) A/ B = A B % *-X % -X = k X k [X] k X = 6.5 x 10 4 m -1 s -1 14

15 Xenon Difluoride eaction C XeF 2 k k = 10 5 s -1 k abs k abs XeF 2 XeF 2 XeF 2 = 0.27 M F A/ B = 0.2 A F B % *-X % -X = k X k [X] k X = 1.2 x 10 6 m -1 s -1 Cyclocarbinyl radical (rapid ring opening) k = 10 8 s -1 k Bu 3 Sn k Bu 3 Sn A / B = A B k = 1.4 x 10 6 m -1 s -1 15

16 Cyclization k values F F F F 3.4 x 10 4 s s -1 2 x 10 3 s -1 cyclization 5-exo 2 x 10 5 s -1 6-endo 5.4 x 10 3 s -1 F 2 C CF 2 C F 2 5-exo 4 x 10 7 s -1 6-endo 5 x 10 6 s -1 Et Et 10 8 s -1 7 x 10 2 s -1 6-exo 5 x 10 3 s -1 7-endo 7 x 10 2 s -1 16

17 Tandem eactions I Bu 3 Sn-SnBu 3 Bu 3 Sn Bu 3 Sn hirsutene 5-exo-trig Cl Cl 17

18 Abstract the delta (δ) hydrogen Br Bu 3 Sn- δ C 2 Et C 2 Et 5-exo C 2 Et C 2 Et C 2 Et C 2 Et Tet Lett (1990) amd 5181 JACS (1998), 110, 5900 ofmann-loeffer eaction δ 1) tbucl hu δ Cl δ δ δ Cl 2) a δ Cl 18

19 Barton Cl hu δ Cl δ A B A B 19

20 Barton Ester Method S -C-Cl S -C- AIB Bu 3 Sn S Sn Bu 3 Barton Ester S -C- SnBu 3 S Sn Bu 3 -C- typical radical reactions (addition and abstraction) C 2 Some common reactions of BrCCl 3 (Br) C 3 I (I) C 2 =CC (C 2 CC) CCl 4 (Cl) 2 () 20

21 Barton-Mcmbie reduction of S --C-SC 3 xanthate AIB Bu 3 Sn- Bu 3 SnS-C-SC 3 Bu 3 Sn S --C-SC 3 Bu 3 Sn S --C-SC 3 Bu 3 Sn S =C-SC 3 Bu 3 Sn- Bu 3 Sn Similar Process S C S C imidazolylthiocarbonic ester S C AIB Bu 3 Sn- S C SnBu 3 21

22 alo-decarboxylations Kochi -C- -C 2 Pb(Ac) -C 4 Pb(Ac) 2 KI Pb(Ac) 4 -C Pb(Ac) 4 KI -I unsdiecker-borodine -C- g Br 2 BrCCl 3 -Br (-C-) 2 g -C 2 g Br 2 BrCCl 3 Peroxide -C 2 CBr 4 C---C S S S S Br SIUE C XeF 2 C Xe 2 -C 2 XeF 2 F -Xe 22

23 earrangements 2 -C C 3 % rearrangement rearrangement increases as the stability of the tert radical increasese. 100 AIB BS 3 C C 3 C-Br C 3 Cl Br 2 C Cl C C 3 C 3 C 3 C 3 C 3 2 C C-Br Br 2 C C C 3 C 3 23

24 Additions to Alkenes Br (no peroxide) Markovnikov addition Br ionic Br (peroxide) Anti Markovnikov additon Br free radical I CCl 4 CCl 3 ICl BrCCl 3 I CCl 3 IBr CCl I 4 CCl 3 CCl 3 CCl CCl 4 3 Cl 75 % trans 4 % cis C 3 C= hu C 3 C= C 3 S AIB C 3 S S 24

25 Aryl adicals --C-C 3 -=--C-C 3 C2 C 3 -nitrosoamide 2 C 3 biphenyl - 2 Diazonium Salt Gomberg-Bachmann biphenyl aryl triazine ZnI 2 ZnI 2 I 2 I Zn? C I C 2 C-C 25

26 Autooxidation--oxidation by oxygen C 3 C 3 C 3 benzoylperoxide C 3 2 C 3 C 3 2 C 3 C 3 cumene hydroperoxide 2 explosive Ethers (TF, diethyl ether, diisopropyl ether) form peroxides on standing when oxygen is present. The initiator is uncertain. The peroxides are unstable and can detonate on agitation. Thus ether that has been standing in a previously opened container for a long period can explode when handled. 26