Chapter 6. Polar addition and Elimination Reaction. RCH-CH2Br R C CH 2 H. open carbocation. Br -

Transcription

1 hapter 6 Polar addition and Elimination eaction = open carbocation - syn and anti products kcal/mol Initial Protonation of the central carbon twisted structure and no allylic conjugation allylic conjugation 1 Introduction (Ad E 2) (Ad E 2) Advanced Organic hemistry (hapter 6) 2 1

2 (Ad E 2) (Ad E 3) Addition of ydrogen alides to Alkenes egioselective eaction: Unsymmetrical alkene gives a predominance of one of the two possible addition products. = Y 2 Y + 2 major Y minor egioselective eaction 4 Advanced Organic hemistry (hapter 6) 2

3 egiospecific eaction: One products is formed exclusively. = Y 2 Y egiospecific eaction (Only Product) Addition of ydrogen alides to Alkenes Markownikoff s ule 2 = more favorable Advanced Organic hemistry (hapter 6) 5 Addition of l or to Alkenes: 2 rate k[alkene][] + - fast - - slow + + Advanced Organic hemistry (hapter 6) 6 3

4 The stereochemistry of addition of hydrogen halides to unconjugated alkenes is predominantly ANTI. + - fast - slow Anti stereochemistry is consistent with a mechanism in which the alkene interacts simultaneously with a proton-donating hydrogen halide and a source of halide ion, either a second molecule of hydrogen halide or a free halide ion. The anti stereochemistry is consistent with the expectation that the attack of halide ion occurs from the opposite side of the -bond to which the proton is delivered. Advanced Organic hemistry (hapter 6) 7 owever, reaction can be modified by temperature and solvent. e.g.: 3 + l r.t. 3 l 3 3 anti addition product l 3 3 l 3 syn addition product Advanced Organic hemistry (hapter 6) 8 4

5 A significant variation in the stereochemistry is observed when the double bond conjugated with a group that can stabilize a carbocation intermediate. Because of greater stability of the carbocation (specially in aromatic conjugation) concerted attack by halide ion (Ad E 3 mechanism) is not required and formed ion pair collapses to product faster than rotation takes place, the result will be syn addition. The reaction is first order in l. Advanced Organic hemistry (hapter 6) 9 ompeting eaction with Solvent in Nucleophilic Solvents: Addition of halide salt (e.g., Me 4 N + - ) increases the capture of a carbocation intermediate by halide ion. Advanced Organic hemistry (hapter 6) 10 5

6 ( 3 ) 2 = 2 Ad E 3 mechanism Skeletal earrangement l MeNO 2 l l ( 3 ) ( 3 ) % 60 % -l ( 3 ) 2 = 2 l ( 3 ) [l - - l] - 1,2--Shift [l - - l] ( 3 ) 2-3 ( 3 ) ( 3 ) l [l - - l] - ( 3 ) 2 3 l Advanced Organic hemistry (hapter 6) 11 Addition to onjugated Dienes 1,3-Pentadiene, for example, gives a mixture of products favoring the 1,2-addition product by a ratio of from 1.5:1 to 3.4:1, depending on the temperature and solvent. 3 == 2 Dl 3 -= 2 D + 1-Phenyl-1,3-butadiene: Ad E 2 Mechanism l 3 = 2 D l % % 1,4- Addition Product 1,2- Addition Product Ph== 2 + (Ad E 2) Ph Advanced Organic hemistry (hapter 6) + 3 Allylic and Bezylic Stabilization l Ph= 3 l 3,4- Addition Product 12 6

7 Addition of and l to Norbornene D D idge Ion D D + + D Dl l D + l + l D (1) 57 % (2) 41 % (3) 2 % The excess of 1 over 2 indicates that some syn addition occurs by ion pair collapse before the bridge ion achieves with respect to the chloride ion. Advanced Organic hemistry (hapter 6) 13 D l l D (1) l D l D l (2) 14 Advanced Organic hemistry (hapter 6) 7

8 6.2 Acid atalyzed ydration and elated Addition eactions Ph=D 2 + PhD 2 -D + slow Ph=D 2 O fast 1) General acid catalysis PhD 2 O + Ph=D 2 unreacted 2) Solvent isotope effect (k 2O /k D2O =2-4) Advanced Organic hemistry (hapter 6) ate Limiting Protonation 15 Addition of Nucleophilic Solvents: Effect of Acidity Alkene-acid complex with weaker acids Addition of D to cis- or trans-2-butene (Ad E 3): D 3 = 3 3 = 3 D- D 3 = AcO OAc Advanced Organic hemistry (hapter 6) Anti Addition (stereospecific) 16 8

9 Addition of F 3 SO 3 D to cis- or trans-2-butene (Ad E 2): 3 = 3 + F 3 SO 3 D 3-3 D D AcO D 3-3 OAc non-stereospecific Addition Advanced Organic hemistry (hapter 6) Addition of alogens 1) Is there a discrete positively charged intermediate, or is the addition concerted? 2) If there is a positively charged intermediate, is it a carbocation or a cyclic halonium Ion? For ominations: Anti addition is preferred for alkenes that can not stabilize a carbocation intermediate. Advanced Organic hemistry (hapter 6) 18 9

10 Syn addition is becomes much larger for alkenes conjugated with aryl groups. - Aliphatic Systems: idged ion mechanism (Anti Addition). Aromatic Systems (Electron-eleasing): Stabilization of the carbocation and Ion pair mechanism (Syn Addition). Aromatic Systems (Electron-Attracting): Destabilization of the carbocation and bridged ion mechanism (Anti Addition). Styrene is Borderline. Advanced Organic hemistry (hapter 6)

11 Kinetic of omination 2 rate k1[alkene][ 2] k2[alkene][ 2] k - rate k 3 [Alkene][ 2][ ] 3 - [Alkene][ ][ ] In methanol and high concentration of - kinetic is pseudosecond-order. 2 Similar to the Ad E Advanced Organic hemistry (hapter 6) 21 In non-polar solvents kinetic is third-order. rate k 2 1 [Alkene][ 2] k2[alkene][ 2] Second-order term: 2 2 charge transfer complex ion pair Third-order term: slow Advanced Organic hemistry (hapter 6) 22 11

12 Kinetic of hlorination: Overly 2 ND -Order. First-order in both alkene and l 2. Increasing the reaction rate with alkyl substitution. Advanced Organic hemistry (hapter 6)

13 25 Evidences for cyclic bromonium ion: NM Spectroscopy -ay crystallography Mechanism study 26 13

14 27 hlorination: hlorine is less polarizable, more electronegative and then it is: -Poor bridging group than bromine. -Syn addition is slightly preferred for chlorination. For non-conjugated alkenes, stereo specific anti addition is usually observed for both halogens. ompetitive eactions of ationic Intermediate in hlorination: a) Loss of a Proton 2 l 2 or l l ( 3 ) 2 = 2 + l 2 2 = 2 l 87 % 3 ( 3 ) 2 =( 3 ) 2 + l 2 2 =-( 3 ) 2 l Advanced Organic hemistry (hapter 6) 100 % 28 14

15 b) Alkyl Migration ~ 10% 3 ( 3 ) 3 = 2 + l 2 2 =- 2 l 3 3 ( 3 ) 3 =( 3 ) 3 + l 2 2 =-( 3 ) 3 3 l 46 % Advanced Organic hemistry (hapter 6) 29 Fluorination F 2 eaction with alkenes is violent giving carbon chain degradation products. Electrophilic addition of F 2 to alkenes: a) ef 2 or other electrophilic fluorine derivatives. b) ighly dilute F 2 at low temperature (syn addition, ion pair collapsing). Stereo chemical results and theoretical calculations: Iodination idged Fluoronium Ion is involved. eaction is reversible even in the presence of excess alkene. The addition is stereo specifically anti. Polar or radical mechanism is involved. Advanced Organic hemistry (hapter 6) 30 15

16 alogenation of onjugated Dienes 2 == = % (1,2-addition product) 2 = 2 88 % (1,4-addition product) 1,4-Addition and cationic intermediate with 2 (Stereo specifically syn). 1,2-Addition (Ad E 3 Mechanism) with mild reagents (Stereo specifically anti). Advanced Organic hemistry (hapter 6) Electrophilic Additions Involving Metal Ions Oxymercuration: g + O + = g Advanced Organic hemistry (hapter 6) O Usual nucleophile is the solvent, but other nucleophiles can compete in less nucleophilic solvents. Because of steric effects, reaction can not be accelerated by alkyl substituents on the alkene

17 idged Mercurium Ion = 2 g Nu bridged mercurinium ion Nu g Advanced Organic hemistry (hapter 6) 33 omparison with other bridged intermediates + + or ydrogen idged ation The proton is hard acid and has no unshared electrons. The carbocation or hydrogen bridged is electron deficient and reactive. Advanced Organic hemistry (hapter 6) 34 17

18 + + The positive bromine is softer and has unshared electron pairs which can permit a total of four electrons to participate in the bridged ion. Therefore: a) The ion is more strongly bridged and more stable than hydrogen bridged. b) The bridged ion can be represented as having two covalent bonds to bromine and is electrophilic but not electron deficient. Advanced Organic hemistry (hapter 6) 35 = 2 g bridged mercurinium ion The g 2+ is a soft acid and strongly polarizing. It polarizes the electrons of an alkene to the extent that a three-center, two-electron bond is formed between mercury and the two carbons of the double bond. Therefore: a) A three-center, two-electron bond implies weaker bridging in the mercurinium ion than the three-center, four-electron bonding of the bromonium ion. b) Oxymercuration of simple alkenes is usually a stereo specific anti addition. Advanced Organic hemistry (hapter 6) 36 18

19 eactivity of mercury salts: Solvent ounter ion (F 3 OO) 2 g > ( 3 OO) 2 g > gl 2 Soft anions reduce the reactivity of the g 2+ ion by coordination, which reduce the electrophilicity of the cation. The harder oxygen anions, like NO 3 - and lo4 -, leave the mercuric ion in more reactive state. Advanced Organic hemistry (hapter 6) 37 onformationally biased cyclic alkenes such as 4-t-butylcyclohexene and 4-tbutyl-1-methycyclohexene give exclusively the product of anti-diaxial addition. Methylenecyclohexenes are not very stereoselective, showing a small preference for the axial alcohol, which corresponds to mercuration from the equatorial face

20 6.5 Addition to Alkynes and Allenes ow reactive are alkynes in comparison with alkenes? What is the stereochemistry and regiochemistry of addition? onsidered basic mechanisms: A) + -Y Y Y + Y B) -Y Y - -Y + Y Y + -Y ) + -Y Y Y Mechanisms A and are of the Ad E 2 type while mechanism B would be classified as Ad E 3. Advanced Organic hemistry (hapter 6) 39 Syn Addition of l to Aryl Acetylenes in AcO Advanced Organic hemistry (hapter 6) 40 20

21 Electrophilic Addition Alkyl Acetylenes: It can be Ad E 3( anti addition) or Ad E 2, depend on individual structure and reaction conditions O 3 O 2 3 O 3 Solvent Isotope Effect: MO alculations: + Protonation is rate determining Step kcal/mol is less stable than 3 2 Advanced Organic hemistry (hapter 6) 41 Addition of F 3 OO to Alkynes + F 3 OO F 3 O 2 + F 3 O 2 Syn and anti Addition Products The reaction are proceed through a vinyl cation. alogenation of Phenyl Acetylenes Ar l AcO l 2 Ar l Ar l l + Ar l l + Ar AcO l + Ar AcO l = Advanced Organic hemistry (hapter 6) 21

22 hlorination of Alkyl Acetylenes + l 2 Syn Addition Product + l 2 Anti Addition Product 100 times faster a) T.S. in di-alkyl acetylenes is stabilized by both alkyl substituents. b) T.S. has bridged ion character. l + l 2 l l l 43 Advanced Organic hemistry (hapter 6) omination of Acetylenes a) Alkyl acetylenes Anti Addition Product Mechanism: Termolecular (Ad E 3) b) Aryl acetylenes 2 Ar 2 Syn and Anti Addition Product non-stereospecific Mechanism: Through vinyl cation intermediate 44 Advanced Organic hemistry (hapter 6) 22

23 Effect of - ion Addition on Mechanism Alkyne-bromine complex: a) ollapsing to bridged ion b) dissociation to vinyl cation when the cation is stable. c) eaction with nucleophile ( - ) 2 Ar + 2 Ar a Ar Ar Ar c b Ar Ar + 45 Advanced Organic hemistry (hapter 6) hlorination of 1-exyne in AcO: l-l ( 2 ) 3 3 l 2 AcO l ( 2 ) exyne O 3 O O l 2 l2 ( 2 ) 3 3 1,1-dichlorihexane-2-one hlorination of 1-exene in 2 l 2 : ( 2 ) exyne l ( 2 ) l 2 l l Advanced Organic hemistry (hapter 6) 46 23

24 eaction of Acetylenes with g(oac) 2 in AcO g(oac) goac AcO AcO 2 5 Ph 3-exyne Ph Anti Addition Product g(oac) 2 Ph Ph AcO goac AcO Syn Addition Product Kinetic: First order in both alkyne and g(oac) 2. Advanced Organic hemistry (hapter 6) 47 Summary Addition to Alkynes: Vinyl cation intermediate: non-stereospecific (depending upon the life time of the vinyl cation and concentration of the nuclephiles). idged ion intermediate or alkyne-electrophile complex: stereospecific anti addition Advanced Organic hemistry (hapter 6) 48 24

25 Addition to alkenes is faster than Alkynes. a) Vinyl ation Intermediate: Vinyl cation has around kcal/mol higher energy than cation with sp 2 hybridization. This can be partially compensated by higher G.S. of alkynes. b) idged ion intermediates: Larger rate retardation for the alkyne addition than that for alkenes. Greater destabilization of bridged species by strain and electronic effects in the case of alkynes. favored less favored Advanced Organic hemistry (hapter 6) 49 Electrophilic Addition to Allenes Protonation at terminal sp 2 carbon: == + 2 -= Protonation at central sp carbon: vinyl cation == + -= Advanced Organic hemistry (hapter 6) allyl cation 50 25

26 Initial Protonation of the central carbon: + + Initial Protonation of the central carbon twisted structure and no allylic conjugation allylic conjugation The twisted cation is about 17 kcal/mol higher in energy than the vinyl cation. == + 2 -= Vinyl cation formation is kinetically favored. Advanced Organic hemistry (hapter 6) vinyl cation 51 Addition of to Allenes Addition of 2 to Allenes allylic cation character Nu Nu 52 Advanced Organic hemistry (hapter 6) 26

27 6.6 The E2, E1 and E1cb Mechanism Elimination eactions: 1) + -elimination 2) 2 = + -elimination 3) elimination Advanced Organic hemistry (hapter 6) 53 -Elimination: E2 Mechanism: 2 ' + B B ' =' + Bimolecular T.S. in which abstraction of -proton is concerted with departure of the leaving group. Advanced Organic hemistry (hapter 6) 54 27

28 E1 Mechanism: B 2 ' 2 ' DS is the unimolecular ionization. =' + B E1cb Mechanism: 2 ' + B ' + B =' + E1cb Mechanism: The reaction is unimolecular, like E1 mechanism, but the order is reversed. Advanced Organic hemistry (hapter 6) 55 Variable E2 T.S. Theory Increasing - breaking in the T.S. B B B B E1cb E1cb-like synchrnous E2 E1-like E1 E2 Increasing - breaking in the T.S. Back Advanced Organic hemistry (hapter 6) 56 28

29 57 1. E1 mechanism Advanced Organic hemistry (hapter 6) Ionization is favored by: a) Electro-releasing groups that stabilizing the carbocation b) Good leaving groups c) Solvent of high ionizing strength The base play no role in the DS of the E1 mechanism. After Ionization: ompeting reaction (S N 1 vs. E1). Stronger base favor the E1 path. 2. E1cb mechanisms are limited to reactants having substituents groups that can effectively stabilize the intermediate carbanion

30 6.7 Orientation Effects in Elimination eactions (egiochemistry) E1 Mechanism: Leaving group is completely ionized before - bond breaking. More substituted (more stable) alkene will be formed. In hyperconjugation of - atoms, which has some double bond character, interaction with hydrogen will greatest at more highly substituted carbon Advanced Organic hemistry (hapter 6) 60 30

31 E1cb Mechanism: The direction of elimination is governed by the ease of removal of the - (less hindered side). Less substituted (less stable) alkene will be formed. E2 Mechanism: The direction of elimination is depends on the precise nature of the T.S. E1cb-like End: Less substituted (less stable) alkene will be formed. E1-like End: More substituted (More stable) alkene will be formed. Variable E2 T.S. Theory Advanced Organic hemistry (hapter 6) 61 Synchronous E2 Mechanism: Partial rupture of - and - bonds at T.S. Partial double bond character at T.S More substituted T.S. will have greater stability (lower energy). (Saytzeff ule) Advanced Organic hemistry (hapter 6) 62 31

32 Leaving Group Effect Poorer leaving groups move the T.S. in the E1cb direction. Advanced Organic hemistry (hapter 6) 63 Base Strength Effect A stronger bases leads to an increase in the carbanion character at the T.S. and shifts it in the E1cb direction. 64 Advanced Organic hemistry (hapter 6) 32

33 ( 3 ) I Steric Effects Base K + O( 6 11 ) 3 K + 42 % O(t-Bu) 3 61 % K + O(n-Pr) 3 75 % ( 3 ) 2 = 3 + ( 3 ) 2 2 = 2 58 % 39 % 25 % Advanced Organic hemistry (hapter 6) Stereochemistry of E2 Elimination eactions B: B: syn Study of the stereochemistry a) Diastereomeric reactants anti b) Stereospecifically deuterated substrates Advanced Organic hemistry (hapter 6) 66 33

34 Study of The Stereochemistry a) Diastereomeric reactants Ph OTs Me Me NaOEt EtO Ph Me Me Ph Me OTs Me NaOEt EtO Me Ph Me Advanced Organic hemistry (hapter 6) 67 b) Stereospecifically deuterated substrates D n-bu erythro isomer n-bu anti syn n-bu n-bu E-product D n-bu n-bu n-bu + D n-bu + n-bu Z-product n-bu E-product Z-product Advanced Organic hemistry (hapter 6) 68 34

35 yclic Systems t-bu t-bu E2 rate constant with t-buo - K x x 10-6 D anti Advanced Organic hemistry (hapter 6) D NMe 3 syn 69 Acyclic Systems: Anti elimination is normally preferred with good leaving groups such as - and tosylate. Syn elimination is become important with poorer leaving groups such as F - and trimethyl amine. Extent of syn elimination is increasing with increasing the chain length. e.g. with 2-butyl system syn elimination is small. with 3-hexyl and longer chains syn elimination is prevalent. Advanced Organic hemistry (hapter 6) 70 35

36 Other Factors Presence of free base or ion pair. Ion pair promotes syn elimination. ation assist in departure of the leaving group. syn + O + M + O M Extent of syn elimination is much higher in non-dissociating solvent benzene than in DMSO. Addition of specific metal-ion-complexing agents (crown ethers) would favor dissociation of the ion pair. Advanced Organic hemistry (hapter 6) 71 Steric Effects As the groups become less bulky, the amount of syn elimination diminishes. 1 2 DNMe D 1 2 % syn % anti Ph Ph Ph n-bu MeO-Ph ( 3 ) 2 Me > >95 Advanced Organic hemistry (hapter 6) 72 36

37 NMe NMe 3 B anti path B syn path Advanced Organic hemistry (hapter 6) 73 The proportion of cis and trans isomers of internal alkenes alides usually give predominantly the trans-alkene. Bulkier groups, particularly arensulfonates, give higher proportions of the cis-alkene. O SO 2 Ar trans-alkene O SO 2 Ar cis-alkene B B Advanced Organic hemistry (hapter 6) 74 37

38 6.9 Dehydration of Alcohols Dehydration takes place under acidic rather than basic condition. O 2 ' ' O 2 E1 Mechanism arbocation intermediate: - 2 O 2 ' =' More substituted alkene will be formed eactivity order of alcohols: Advanced Organic hemistry (hapter 6) 3 > 2 > 1 75 arbocation Intermediate: earranged products. 3 ' O ' O 2 3 ' + 2 O 3 ' 2 ' 2 =' Exchange of hydroxyl group: ompeting of S N 1 Advanced Organic hemistry (hapter 6) 76 38

39 6.10 Eliminations Not Involving - Bonds * * anti elimination + syn elimination * eagent % anti % syn NaI/MeO Zn/EtO Advanced Organic hemistry (hapter 6) 77 Iodide-Induced Debromination (everse of alogenation): I I + slow + fast - + I 2 equirement of anti orientation of two bromides. The nucleophilic attack of iodide at one bromide enhances its nucleophilicity and permit formation of the bridged ion. Advanced Organic hemistry (hapter 6) 78 39

40 Zinc-Induced Debromination: Non-Stereospecific Formation of organozinc intermediate: + Zn = + + Zn 2+ Advanced Organic hemistry (hapter 6) 79 Acid-atalyzed Deoxymercuration: I gi g O O -Oxyorganomercurials are much more reactive than simple alcohols. e.g.: 3 (O) 2 gi is converted to propene under acid catalyzed condition at a rate times greater than that for dehydration of 2-propanol under the same condition. Advanced Organic hemistry (hapter 6) 80 40

41 Evidence: trans- and cis-2-methoxycyclohexylmercuric iodide gi OMe gi OMe fast OMe gi gi OMe slow for trans isomer is about 8 kcal/mol less than for the cis isomer. Advanced Organic hemistry (hapter 6) 81 Acid-atalyzed -Elimination of ompound Type M 2 2 O eactivity order: Ig Ph 3 Pb Ph 3 Sn > Ph 3 Si > Bond energies: g-=27 < Pb-=31 < Sn-=54 < Si-=60 < -=96 Advanced Organic hemistry (hapter 6) 82 41

42 Strong carbocation character at the -carbon atom stabilization by metal substituents (electron donation from electron rich -M bond to the adjacent p orbital or as formation bridged species). M M Advanced Organic hemistry (hapter 6) 83 -Elimination involving organosilicon and organotin compounds: n-pr Me 3 Si O n-pr 2 SO 4 n-pr n-pr 3 Ph 3 Sn + O Stereospecifically anti 84 Advanced Organic hemistry (hapter 6) 42

43 Elimination in -halosilanes: 4 9 SiMe 3 NaOMe 4 9 = Fluoride-induced -elimination OO 2 2 SiMe N F OO N = 2 + FSiMe 3 SiMe 3 Nu - Advanced Organic hemistry (hapter 6) = + + Me 3 SiNu 85 Strong carbocation character at the -carbon atom can stabilized by silyl and stannyl substituents. E + + =M 3 -M 3 E =E arbanionic character at -carbon and carbocationic character at -carbon. SiMe 3 + O 3l O 3 Advanced Organic hemistry (hapter 6) 77 % 86 43

44 END OF APTE