D. A. Evans Carbocations: Stability Structure Chem 206 http://www.courses.fasharvardedu/-chem206/ Other Relevant Background Reading March, Advanced Organic Chemistry, 4th Ed. Chapter 5, pp165-174 Lowery Richardson, Mech. Theory in Org, Chem., 3rd Ed. pp Chemistry 206 383-412. Arnett, Hoeflich, Schriver in Reactive Intermediates Vol 3, Wiley, 1985 Chapter 5, p 189 Advanced Organic Chemistry Saunders, M. and H. A. Jimenez-Vazquez(1991). " Recent studies of carbocations Chem Rev 91: 375 Lecture number 30 Stang, P.J. (1978). " Vinyl Triflate Chemistry: Unsaturated Cations and Carbenes . Acc Chem. Res. 11: 107 Introduction to carbonium I Olah, G.A. and G. Rasul (1997). " Chemistry in superacids 26. From Kekule's tetravalent methane to five-, Six- and seven-coordinate protonated methanes Carbocation stabilization Acc.Chem.Res30(6):245-250 Walling, C (1983). "An Innocent Bystander Looks at the 2-Norbornyl Cation Carbocation Structures by X-ray Crystallography Acc. Chem. Res 16: 448 a Vinyl Allyl Carbonium Ions Exam Question Fall, 2001. The reaction illustrated was recently Snider and co-workers(Org Lett. 2001, 123, 569-572. Prov Reading Assignment for this Lecture nal drawings to support your answer Carey Sundberg, Advanced Organic Chemistry, 4th Ed Part A Chapter 5, Nucleophilic Substitution, 263-350 cH2C2,0°C Laube(1995). X-Ray Crystal Structures of Carbocations Stabilized by Bridging or Hyperconjugation. " Acc. Chem. Res 28, 399(pdf) Carey Sundberg-A, p 337: Provide mechanisms for the following reactions Olah, G A (1995). My search for carbocations and their role in chemistry (Nobel lecture). "Angew. Chem., Int. Ed. Engl. 34, 1393-1405.(CCB library Olah, G.A. (2001). 100 Years of Carbocations and their Significance Chemistry. "J. Org. Chem. 2001, 66, 5944-5957.(pdf HOAC/H2O HOAC/H2O Matthew d. shair Wednesday December 4. 2002
http://www.courses.fas.harvard.edu/~chem206/ OH NH2 NaNO2 Me O Me Me R HOAc/H2O CHO EtAlCl2 OH NH2 CMe3 Me O Me R Me NaNO2 HOAc/H2O O CMe3 D. A. Evans Chem 206 Matthew D. Shair Wednesday, December 4, 2002 Reading Assignment for this Lecture: Other Relevant Background Reading Chemistry 206 Advanced Organic Chemistry Lecture Number 30 Introduction to Carbonium Ions ■ Carbocation Stabilization ■ Carbocation Structures by X-ray Crystallography ■ Vinyl & Allyl Carbonium Ions Carbocations: Stability & Structure March, Advanced Organic Chemistry, 4th Ed. Chapter 5, pp165-174. Lowery & Richardson, Mech. & Theory in Org, Chem., 3rd Ed. pp 383-412. Arnett, Hoeflich, Schriver in Reactive Intermediates Vol 3, Wiley, 1985, Chapter 5, p 189. Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part A Chapter 5, "Nucleophilic Substitution", 263-350 . Walling, C. (1983). “An Innocent Bystander Looks at the 2-Norbornyl Cation.” Acc. Chem. Res. 16: 448. Olah, G. A. and G. Rasul (1997). “Chemistry in superacids .26. From Kekule's tetravalent methane to five-, six- and seven-coordinate protonated methanes.” Acc. Chem. Res. 30(6): 245-250. Saunders, M. and H. A. Jimenez-Vazquez (1991). “Recent studies of carbocations.” Chem. Rev. 91: 375. Stang, P. J. (1978). “Vinyl Triflate Chemistry: Unsaturated Cations and Carbenes.” Acc. Chem. Res. 11: 107. Olah, G. A. (1995). “My search for carbocations and their role in chemistry (Nobel lecture).” Angew. Chem., Int. Ed. Engl. 34, 1393-1405. (CCB library) Laube (1995). “X-Ray Crystal Structures of Carbocations Stabilized by Bridging or Hyperconjugation.” Acc. Chem. Res. 28,: 399 (pdf) Olah, G. A. (2001). “100 Years of Carbocations and their Significance in Chemistry.” J. Org. Chem. 2001, 66, 5944-5957. (pdf) Qumulative Exam Question Fall, 2001. The reaction illustrated below was recently reported by Snider and co-workers (Org. Lett. 2001, 123, 569-572). Provide a mechanism for this transformation. Where stereochemical issues are present, provide clear three dimensional drawings to support your answer. CH2Cl2, 0 °C Carey & Sundberg-A, p 337: Provide mechanisms for the following reactions
D. A. Evans. B Breit Carbocations: Stability Chem 206 Carbocation subclasses Hydride ion affinities(Hi) Carbon- substituted Heteroatom-stabilized Me2-CH_-18 Me3c 231 R3 R2 R3 R2 +21 81 H3C—CH2 -CH R-R3= alkyl or aryl R-R3=alkyl or aryl R-R3= alkyl or aryl The following discussion will focus on carbocations unsubstituted with heteroatoms 287 Classical ys nonclassical carbonium ions PhcH2→ Me-CH, -20 hyperconjugation unsymmetrical symmetrical The effect of beta substituents: Rationalize trivalent increasing nonclassical character -CH 2- Me-CH2-CH2 classical nonclassical 276 270 Stability: Stabilization via alkyl substituents(hyperconjugation) Order of carbocation stability: 3>2>1 Hydride ion affinities versus Rates of Solvolysis >R-C④>Hc>Hce asing number of substituents PhCH2-Br CH=CH-CHr-Br Me2 CH-Br le of hyperconjugation rel rate 100 0.7 The relative stabilities of various carbocations can be measured in the gas phase by their Hydride ion Hl239 256 affinity for hydride ion. +17 R⊕+H R-H+ (CH3)2CH249 ative Solvolysis rates in 80% EtOH, 80C Hydride Affinity =-AG AHI increases-C(+) stability decreases Note:As S-character increases, cation stabilityPhCH2' decreases due to more electronegative carbon Conclusion: Gas phase stabilities do not always correlate with rates of solvolysis J. Beauchamp, J Am. Chem. Soc. 1984, 106, 3917. arey& Sundberg -A, pp 276-
C C C C C C C C C C C C Å Å Å Å R3 R2 R1 R3 R2 O R1 R3 R2 N R R H3C CH2 Me CH2 H2C CH Me2 CH R R R H R R H H R H H H C C + H Ph CH2 Me CH2 PhCH2–Br CH=CH–CH2–Br HI D-HI rel rate Me CH2 Me–CH2 CH2 Hydride Affinity = –DG° C C C C CH3 + CH3CH2 + (CH3)2CH+ (CH3)3C + H2C=CH+ PhCH2 + R R–H Me3 C Me2CH–Br HC C H2C CH CH2 D. A. Evans. B. Breit Chem 206 Carbocation Subclasses Å R–R3 = alkyl or aryl Å R–R3 = alkyl or aryl Å R–R3 = alkyl or aryl Carbon-substituted Heteroatom–stabilized The following discussion will focus on carbocations unsubstitutred with heteroatoms Stability: Stabilization via alkyl substituents (hyperconjugation) Order of carbocation stability: 3˚>2˚>1˚ > > > Due to increasing number of substituents capable of hyperconjugation 314 276 249 231 287 386 239 Hydride ion affinities The relative stabilities of various carbocations can be measured in the gas phase by their affinity for hydride ion. J. Beauchamp, J. Am. Chem. Soc. 1984, 106, 3917. 276 287 +21 386 +81 276 249 –27 231 –18 239 276 –37 –20 256 Hydride ion affinities (HI) Hydride ion affinities versus Rates of Solvolysis Relative Solvolysis rates in 80% EtOH, 80 °C 100 52 0 +17 239 256 A. Streitwieser, Solvolytic Displacement Reactions, p75 Conclusion: Gas phase stabilities do not always correlate with rates of solvolysis 0.7 +10 249 + H 276 270 –7 open The effect of beta substituents: Rationalize trivalent hyperconjugation no bridging unsymmetrical bridging symmetrical bridging classical nonclassical increasing nonclassical character Classical vs nonclassical carbonium ions Note: As S-character increases, cation stability decreases due to more electronegative carbon. + HI HI increases C(+) stability decreases Carey & Sundberg–A, pp 276- Carbocations: Stability
M. Shair. D. Evans Carbocation Generation Stability Chem 206 Carbocation Stability: The pKR+ valt Removal of an energy-poor anion from a neutral precursor via Lewis Acids efinition R+H2O一ROH+H R3C-X LA R3C KR aR+·aH20 LA: Ag, AlCl3, SnCl4, SbCls, SbF5, BF3, FeCl3, ZnCl, PCI, PCl5, POCl3 pKR+ =-log KR arey Sundberg, A, p 277 X: F CL Br L OR Table: pKa+ values of some selected carbenium salts Acidic dehydratization of secondary and tertiary alcohols (4-Meo-CsHg 0.82 6.63 110 R3CoH+Hx120R?c④+xe R: Aryl other charge stabilizing substituents Co2(co)6 X: SO CIO4, FSO3, CF3SO3 From neutral precursors via heterolytic dissociation(solvolysis)-First step in SN1 or E1 reactions E>-CH R3C-X 3C+X⊙ 7.2 Carey Sundberg, A, pp 276- Ability of X to function as a leaving group -N2>-0So2R>-0PO(OR)2>->-Br> CI> OH Carbocation Generation Hydride abstraction from neutral precursors Addition of electrophiles to T-systems R R2C-H Lewis-Acid RaCo R2n RoC-H C Provide a mechanism of this transformation h& B,. be HC=-CH2OH Jcs,cc1971,556
CH2 CHPh R3C R3C R3C R3C X X Fe R3C H H7C3 H7C3 C3H7 R3C H H H Fe Ph3C H H (3-Cl-C6H4 )3C Cr(CO)3 CHPh RS RS H H R2N R2N H H Ph2CH R CPh2 Co2 (CO)6 HC CH2OH R R R3C OH R3C X R R R R R3C X Br H–X H H H2SO4 R R R R H R H R Me O M. Shair, D. Evans Carbocation Generation & Stability Chem 206 Carbocation Stability: The pKR+ value Definition: R + + H2O ROH + H+ KR+ = aROH × aH+ aR+ × aH2O a = activity pKR+ = – log KR+ (4-MeO-C6H4 )3C + 0.82 – 6.63 – 11.0 – 13.3 0.40 0.75 –10.4 –7.4 7.2 4.77 Table: pKR+ values of some selected carbenium salts Hydride abstraction from neutral precursors + Lewis-Acid = etc. Lewis-Acid: Ph3C BF4, BF3, PCl5 Removal of an energy-poor anion from a neutral precursor via Lewis Acids + LA LA–X LA: Ag , AlCl3, SnCl4, SbCl5, SbF5, BF3, FeCl3, ZnCl2, PCl3, PCl5, POCl3 ... X: F, Cl, Br, I, OR Acidic dehydratization of secondary and tertiary alcohols - H2O R: Aryl + other charge stabilizing substituents X: SO4 2-, ClO4 - , FSO3 - , CF3SO3 - From neutral precursors via heterolytic dissociation (solvolysis) - First step in SN1 or E1 reactions solvent Ability of X to function as a leaving group: -N2 + > -OSO2R' > -OPO(OR')2 > -I ³ -Br > Cl > OH2 + ... Carbocation Generation + + + + Addition of electrophiles to -systems chemistry chemistry J.C.S.,CC 1971, 556 Provide a Mechanism of this transformation Carey & Sundberg, A, p 277 Carey & Sundberg, A, pp 276-
D. A. Evans. B. Breit Carbocations: Structure Chem 206 Carbocation Stabilization Through Hyperconjugation Physical Evidence for Hyperconjugation: The Adamantyl Cation pating in the hyperconjugative interaction, e. g C-R, will be lengthened while the C(+)C bond will be shortened First X-ray Structure of an Aliphatic Carbocation ■ FMO Description 1431A Take linear combination of o C-R(filled) and C prorbital (empty FsSb-F-SbFsI F*C-R C-R 10061608A T. Laube, Angew. Chem. Int. Ed. 1986, 25, 349 aC-R gC-R + planar orientation between interacting orbital C-H versus C-C Hyperconjugation The Adamantane Reference The t-Pentyl Cation alculated carbocation (MM-2 agrees with solution 1528A Me 110 1582A 1092A A Stable Carbocation Chemistry, 1997. p 46-47
C C Me H H Me Me Me Me Me H C H H C H H Me Me Me C [F5Sb–F–SbF5] – C H H C H C C R H H H H R D. A. Evans, B. Breit Chem 206 Take linear combination of s C–R (filled) and C pz -orbital (empty): s C–R + s* C–R s C–R s* C–R + Syn-planar orientation between interacting orbitals ■ FMO Description E + + Carbocation Stabilization Through Hyperconjugation C–H versus C–C Hyperconjugation: The t-Pentyl Cation + 1.582 Å + 1.107 Å 1.092 Å R. P von Schleyer in Stable Carbocation Chemistry, 1997, p 46-47 Calculated carbocation agrees with solution structure Physical Evidence for Hyperconjugation: The Adamantyl Cation T. Laube, Angew. Chem. Int. Ed. 1986, 25, 349 First X-ray Structure of an Aliphatic Carbocation 100.6 ° 1.608 Å 1.431 Å + Bonds participating in the hyperconjugative interaction, e.g C–R, will be lengthened while the C(+)–C bond will be shortened. The Adamantane Reference (MM-2) 110 ° 1.530 Å 1.528 Å + Carbocations: Structure
D. A. Evans. K. Scheidt Carbocations: Structure Chem 206 SbF 1421A 1439A C-C1439A 1466A -C2:1446A C31442A 1621A 982° 1622A 1551A T Laube, Angew. Chem. Int. Ed. 1986, 25, 349 eference structure CSP3-Csp2 bond lenath 1342A T. Laube,JAcS1993,115,7240
1.508 Å 1.342 Å Me Me Me F [F5Sb–F–SbF5] – F Me Me Me SbF5 Me Me Me C F5Sb F SbF5 2 SbF5 C Me Me Me F5Sb F SbF5 D. A. Evans, K. Scheidt Chem 206 + T. Laube, Angew. Chem. Int. Ed. 1986, 25, 349 1.621 Å 98.2 ° 1.466 Å + 1.551 Å 1.608 Å 1.622 Å 1.421 Å T. Laube, JACS 1993, 115, 7240 C–C1 : 1.439 Å C–C2 : 1.446 Å C–C3 : 1.442 Å + – + – 1.439 Å reference structure: CSP3–Csp2 bond length Carbocations: Structure
D. A. Evans, K. Scheidt Carbocations: Structure Chem 206 668A 1432A 1408A 1432A 1491A 1442A178 1446A 1210° 1.505A 1439A 121.2 T. Laube,JAcs1993,115,7240 reference structure 1342A CSP2-Csp2 bond length rence structure
1.508 Å 1.342 Å 1.505 Å Cl Cl Cl SbF5 Cl Cl Cl Cl SbClF5 – F Me Ph Me SbF5 C Ph Me Me SbF6 – D. A. Evans, K. Scheidt Chem 206 + + + + + T. Laube, JACS 1993, 115, 7240 1.408 Å 1.491 Å 1.432 Å 1.371 Å 122 ° + 1.446 Å 1.439 Å 1.442 Å 121.0 ° 121.2 ° 117.8 ° + 1.432 Å 1.422 Å 1.725 Å 1.668 Å reference structure: CSP3–Csp2 bond length reference structure: CSP2–Csp2 bond length Carbocations: Structure
D.A. Evans. K Scheidt Carbonium lon X-ray Structures: Bridged Carbocations Chem 206 FsSb-F-SFs「 F5Sb-F--SbF5 T Laube, Angew. Chem. Int. Ed. 1987, 26, 560 1467A1495A 2.092A 1739AM 1467A 1442A One of the longest documented C-c bond lengths 1503A T Laube, JACS 1989.. 9224 hyperconjugation unsymmet
C C C C C C Å Å Me Me Me H Me Me Me Ph Cl AgSbF6 Me H Me Me Me F [F5Sb–F–SbF5] – 2 SbF5 C Me Me Ph F5Sb F SbF5 D. A. Evans, K. Scheidt Carbonium Ion X-ray Structures: Bridged Carbocations Chem 206 – 1.467 Å + 1.855 Å 1.503 Å 1.495 Å T. Laube, JACS 1989, 111, 9224 + 1.467 Å 1.442 Å 1.739 Å** 2.092 Å + + T. Laube, Angew. Chem. Int. Ed. 1987, 26, 560 **One of the longest documented C–C bond lengths. hyperconjugation no bridging unsymmetrical bridging
D. A. Evans, K. Scheidt Carbonium lon X-ray Structures: A Summary Chem 206 1442A 1446A 1408A 2.092A 1739A 439A 1432A A 1508A 1668A 1342A 422A 1725A 1481421A 1467A1495A 1855A 1621A 1622A 1608A Nomenclature: classical vs nonclassical 1503A 1551A hyperconjugation unsymmetrical symmetrical no bridging bridging bridging creasing nonclassical character classical nonclassical
D. A. Evans, K. Scheidt Carbonium Ion X-ray Structures: A Summary Chem 206 1.467 Å 1.855 Å 1.503 Å 1.495 Å 1.467 Å 1.442 Å 2.092 Å 1.739 Å + + + 1.408 Å 1.371 Å 1.432 Å 1.446 Å 1.439 Å 1.442 Å + 1.621 Å 98.2 ° 1.466 Å + 1.551 Å 1.608 Å 1.622 Å 1.421 Å 1.432 Å 1.422 Å 1.725 Å 1.668 Å Cl Cl + 1.508 Å 1.342 Å (ref 1.513 Å)Ph–C(Me)=CH2 1.491 Å C C C Å C C C Å C C C Å C C C Å open trivalent hyperconjugation no bridging unsymmetrical bridging symmetrical bridging classical nonclassical increasing nonclassical character Nomenclature: classical vs nonclassical
D. A. Evans. B Breit Vinyl Allyl Carbocations Chem 206 Vinyl Phenyl Cations: Highly Unstable Allyl& Benzyl Carbocations Evidence suggests that vinyl cations are linear Carbocation Stabilization via -delocalization OTf HOSoly formation of the linear vinyl cation is disfavored due to increasing ring ste the As ring size decreases, the rate of hydrolysis also diminishes. Implying that allyl cation +89 Stabili The Benzyl cation is as stable as a t-Butylcation. This is shown in the A secondary kinetic isotope effect was measured to be KH/Kp=1.5 (quite subsequent isodesmic equations large) indicating strong hyperconjugation and an orientation of the vacant p orbital as shown above P J. Stang J. Am. Chem Soc. 1971, 93, 1513; P J Stang J.C.S. PT ll1977, 1486 o [kcal/mol (CH3)3C+ PhCH3 -(CH3)3CH PhCH2 3.8 Hydride ion affinities(HI) (CH3)3C PhCH2CI-(CH3)3CCI PhCH2 +21 ⊙+81 H3C—CH2-H2C=CH 仓 287 Hydride ion affinities(HI) le3-C +11 H2C= Phenyl Cations Hydride ion affinities versus Rates of Solvolysis 287 PhCHr-Br Me2 CH-Br CH=CH-CH2-Br The ring geometry opposes rehybridization(top) so the vacant orbital retains sp character. Additionally, the empty orbital lies in the nodal plane of the ring, effectively prohibiting conjugative stabilization H 239 249 △-Hl Relative Solvolysis rates in 80% EtOH, 80C A. Streitwieser, Solvolytic Displacement Reactions, p75
OTf D R OTf R H + H3C CH2 H2C CH H2C CH OSolv C C D R R HC C HI D-HI R R PhCH2–Br Me2CH–Br R R Ph CH2 CH=CH–CH2–Br Me3 C D. A. Evans, B. Breit Vinyl & Allyl Carbocations Chem 206 Vinyl & Phenyl Cations: Highly Unstable Evidence suggests that vinyl cations are linear. As ring size decreases, the rate of hydrolysis also diminishes. Implying that the formation of the linear vinyl cation is disfavored due to increasing ring strain. Hyperconjugation P. J. Stang J. Am. Chem Soc. 1971, 93, 1513; P. J. Stang J.C.S. PT II 1977, 1486. A secondary kinetic isotope effect was measured to be KH/KD = 1.5 (quite large) indicating strong hyperconjugation and an orientation of the vacant p orbital as shown above. HOSolv Phenyl Cations The ring geometry opposes rehybridization (top) so the vacant orbital retains sp2 character. Additionally, the empty orbital lies in the nodal plane of the ring, effectively prohibiting conjugative stabilization. 276 287 +21 386 +81 Hydride ion affinities (HI) 287 +11 298 Allyl & Benzyl Carbocations Carbocation Stabilization via p-delocalization ■ Stabilization by Phenyl-groups The Benzyl cation is as stable as a t-Butylcation. This is shown in the subsequent isodesmic equations: (CH3)3C + PhCH3 (CH3 )3CH + PhCH2 DH 0 r [kcal/mol] 3.8 (CH3)3C + PhCH2Cl (CH3 )3CCl + PhCH2 - 0.8 allyl cation 239 Hydride ion affinities (HI) 231 –8 Hydride ion affinities versus Rates of Solvolysis Relative Solvolysis rates in 80% EtOH, 80 °C 100 0.7 52 0 +10 +17 239 249 256 A. Streitwieser, Solvolytic Displacement Reactions, p75
D. A. Evans. B. Breit Cyclopropyl-carbinyl Carbocations Chem 206 Carbocation Stabilization via Cyclopropylgroups Solvolysis rates represent the extend of that cyclopropyl orbital overlap contributing to the stabilization of the carbenium ion which is involved as a See Lecture 5. slide 5-05 for discussion of walsh orbitals Krel=1 A rotational barrier of about 13.7 kcal/mol is observed in -Me nmr in super acids OTS 8(CH3 )=2.6 and 3. 2 ppm OTS following example X-ray Structures support this orientation 1222A 103 1517A 1302A 478A1474A Bridgehead Carbocations 1464A OTs 1541A Tso 1409A 1444A Bridgehead carbocations are highly disfavored due to a strain increase in 1534A achieving planarity. Systems with the greatest strain increase upon passing from ground state to transition state react slow Carbocation Stabilization- Aromaticity Some Huckel aromatic cations(4n+2)T-electrons are isolable as salts with non-nucleophilic anions R R.F.Chds,JACS1986,108,1692 in SbF5-S02CIF
H Me Me C R O R X Me Me Me OTs Me Me OTs OTs TsO X OTs OTs TsO Cl Cl TsO X H H D. A. Evans, B. Breit Cyclopropyl-carbinyl Carbocations Chem 206 Carbocation Stabilization via Cyclopropylgroups A rotational barrier of about 13.7 kcal/mol is observed in following example: NMR in super acids d(CH3) = 2.6 and 3.2 ppm R. F. Childs, JACS 1986, 108, 1692 1.464 Å 1.409 Å 1.534 Å 1.541 Å 1.444 Å 24 ° 1.302 Å 1.222 Å 1.474 Å 1.517 Å 1.478 Å X-ray Structures support this orientation Carbocation Stabilization - Aromaticity Some Hückel aromatic cations (4n+2) p-electrons are isolable as salts with non-nucleophilic anions. Solvolysis rates represent the extend of that cyclopropyl orbital overlap contributing to the stabiliziation of the carbenium ion which is involved as a reactive intermediate: krel = 1 krel = 1 krel = 106 krel = 10-3 krel = 1 krel = 108 + = BF4, SbCl6 ++ ++ generated in SbF5-SO3 in SbF5-SO2ClF stable, isolable salts Bridgehead Carbocations 1 10-7 10-13 104 Bridgehead carbocations are highly disfavored due to a strain increase in achieving planarity. Systems with the greatest strain increase upon passing from ground state to transition state react slowest. why so reactive? See Lecture 5, slide 5-05 for discussion of Walsh orbitals
