D.A. Evans Carbocations: Stability, Structure, Rearrangements Chem 206 Here is a typical carbonium ion question that you should be able to handle by http://www.courses.fas.harvardedu/-chem206/ the end of the course. Write out a mechanism for the following transformation Chemistry 206 0% vield Advanced organic Chemistry Lecture number 31 Introduction to Carbonium Ions-2 I Allyl-& Vinylsilanes: The B-Silicon Effect OBF Carbonium Ion Rearrangements A Srikrishna Chem Commun 1994. 2259 Reading Assignment for this Lecture Carey Sundberg, Advanced Organic Chemistry, 4th Ed Question 13 Final Exam, 1999. During Corey s synthesis of Aspidophytine JACS. 19 1), the pivotal intermediate 3 was assembled by the Part A Chapter 5, Nucleophilic Substitution, 263-350 union of 1 the specified conditions. Provide a mechanism for this single-pot Walling C (1983). An Innocent Bystander Looks at the 2-Norbormyl Cation Acc. Chem. Res 16: 448.(handout) CHO Biradeanu(2000). "The Story of the Wagner-Meerwein Rearrangement J. Chem. Ed 77: 858.(handout OHC 1)mixatroom Co2R temp, 5 Ra rb 3) excess Lambert, (1999). " The B effect of silicon and related manifestations of o NaBH3CN conjugation. Acc. Chem. Res 32, 183-190.(handout 2)2 equiv TFAA,0°C Re Rd Other Relevant Background Reading Saunders, M. and H. A Jimenez- Vazquez (1991). "Recent studies of carbocations Chem Rev. 91: 375 Meo OMe Me Matthew d shair December Meo
http://www.courses.fas.harvard.edu/~chem206/ Me Me Me CH2 O BF3•OEt2 N OMe MeO Me NH2 OHC CHO Me3Si CO2R CH2Cl2 Me Me Me OBF4 N Rc Rd Ra Rb Me Me Me OBF4 Me Me Me O H N N MeO MeO Me H CO2R D. A. Evans Chem 206 Matthew D. Shair Friday, December 6, 2002 Reading Assignment for this Lecture: Other Relevant Background Reading Carbocations: Stability, Structure, & Rearrangements Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part A Chapter 5, "Nucleophilic Substitution", 263-350 . Saunders, M. and H. A. Jimenez-Vazquez (1991). “Recent studies of carbocations.” Chem. Rev. 91: 375. Chemistry 206 Advanced Organic Chemistry Lecture Number 31 Introduction to Carbonium Ions–2 ■ Allyl- & Vinylsilanes: The b-Silicon Effect ■ Carbonium Ion Rearrangements Walling, C. (1983). “An Innocent Bystander Looks at the 2-Norbornyl Cation.” Acc. Chem. Res. 16: 448. (handout) Birladeanu (2000). “The Story of the Wagner-Meerwein Rearrangement.” J. Chem. Ed. 77: 858. (handout) Lambert, (1999). “The b effect of silicon and related manifestations of s conjugation.” Acc. Chem. Res. 32, 183-190. (handout) Question 13. Final Exam, 1999. During Corey's synthesis of Aspidophytine (JACS, 1999, 121, 6771), the pivotal intermediate 3 was assembled by the union of 1 and 2 under the specified conditions. Provide a mechanism for this single-pot transformation. + 1) mix at room temp, 5 min 2) 2 equiv. TFAA, 0 °C + 3) excess NaBH3CN 1 2 3 Here is a typical carbonium ion question that you should be able to handle by the end of the course. Write out a mechanism for the following transformation. A. Srikrishna, Chem Commun 1994, 2259 60% yield
M. Shair. D. Evans Carbocation Rearrangements-1 Chem 206 Carbocation [1, 2] Sigmatropic Rearrangements In the most stable ground state conformation, if the relationship between the migrating group(4)and the leaving group(X) is anti, usually inversion is observed in the migration terminus 1, 2 Sigmatropic shifts are the most commonly encountered cationic rearrangements When either an alky l substituent or a hydride is involved, the term Wagner-Meerwein shift is employed to identify this class of rearrangments Biradeanu(2000). The Story of the Wagner-Meerwein Rearrangement. J. Chem. Ed. 77: 858.(handout Stereoelectronic requirement for migration These observations can be ascribed to the principle of least motion: . those elementary reactions will be favored that involve the least change in retention of stereochemistry atomic position and electronic configuration s. Tee JACS1969,91,7144 Principle of least motion in action: bridging TS Migration attends ionization Inversion N 2-electron Huckel transition state Long-lived Carbocations: X departs before Z moves R. Bach J. Am. Chem. Soc. 1979. 101 3118 In the most stable ground state conformation, if the relationship between the migrating group (Z) and the leaving group ()is gauche, usually retention is If migration accompanies ionization, the migration terminus will be inverted. Overlap observed in the migration terminus between the g c-c (migration origin)and the o"c-x(migration terminus will be maximized in an antiperiplanar arrangement. TBSO AIc S L. Schreiber et al Tetrahedron lett. 1989. 30. 3765
Ph Cl H OH Ph O CH3 Z R R X B A C D B A Z R R B A C D B X – A B A C D R R B Z A Z R R A X OH MsO OH TBSO H H B Me3Si H R2 R1 Z R R Et2AlCl A Ph CH3 Cl H OH Ph O NIS B AgBF4 Et2O I H R2 R1 TBSO H O OH H R R A Ph CH3 C O H O Ph Z B Carbocation Rearrangements-1 Chem 206 Carbocation [1,2] Sigmatropic Rearrangements 2-electron Huckel transition state 1,2 Sigmatropic shifts are the most commonly encountered cationic rearrangements. When either an alkyl substituent or a hydride is involved, the term Wagner-Meerwein shift is employed to identify this class of rearrangments. Stereoelectronic requirement for migration.... bridging T.S. retention of stereochemistry In the most stable ground state conformation, if the relationship between the migrating group (Z) and the leaving group (X) is gauche, usually retention is observed in the migration terminus. Long-lived Carbocations: X departs before Z moves. These observations can be ascribed to the principle of least motion: "...those elementary reactions will be favored that involve the least change in atomic position and electronic configuration." In the most stable ground state conformation, if the relationship between the migrating group (Z) and the leaving group (X) is anti, usually inversion is observed in the migration terminus. O. S. Tee JACS 1969, 91, 7144 Principle of least motion in action: Inversion Migration attends ionization R. Bach J. Am. Chem. Soc. 1979, 101, 3118 CH2Cl2, -78˚C S. L. Schreiber et al Tetrahedron Lett. 1989, 30, 3765. If migration accompanies ionization, the migration terminus will be inverted. Overlap between the s C-C (migration origin) and the s* C-X (migration terminus) will be maximized in an antiperiplanar arrangement. M. Shair, D. Evans Birladeanu (2000). “The Story of the Wagner-Meerwein Rearrangement.” J. Chem. Ed. 77: 858. (handout)
M. Shair. D. evans Carbocation Rearrangements-2 Chem 206 Carbocation [1, 2] Sigmatropic Rearrangements Carbocations: Neighboring Group Participation Pinacol rearrangement(vicinal dio Driving force is the gen. of C=O d Groups with accessable electron density (heteroatoms, arenes )and the correct stereoelectronic orientation(anti-periplanar)can"assist"in the ionization of a leaving group CH2NH2 Deamination NO The Cram Phenonium lon Experiments: Cram, JACS 1949, 71, 3865 Demjanov-rearrangement(Driving force: relief of ring strain agner-Meerwein Rearrangements: Application in Total Synthesis Ts H, L-Threo L-Threo 98% chemical fidelity Aco Ph L-Erythro EJ.Corey J. Am. Chem. Soc. 1964, 86, 1652. a-caryophyllene alcohol HMe?MH L-Erythro L-Erythro 98%chemical fidelity Synthesis of (=-lsocomene: Pirrung, JACS 1979, 7130: 1981, 82 Physical Evidence for Neighboring Group Participation Me carbon in C NMR (68.8 ppm Phenonium ion G. Olah JACS1976,98,6784 See Lowry& Richardson, pp 434-439 for discussion of this controversy
CH2NH2 OH OH Me Me H Me OH H Me Me H H Me Me Me HO H Me Me Me H + H2SO4 Me Me Me Me H + CH2 O Me Me Me Me OH H Me Me Me Me Me Me Me Me H OH Me Me Me Me OTs Me H Ph H Me OTs H Me Ph Me H R R X: R R Y Cl SO2ClF HF-SbF5 TsO– TsO– Me Me H H R R R R X Me H H Me Y - R R X: R R Nuc OAc Me H Ph Me H OAc Me H Ph Me H Ph H Me H Me AcO Ph Me H H Me AcO Carbocation Rearrangements-2 Chem 206 Carbocation [1,2] Sigmatropic Rearrangements Wagner-Meerwein Rearrangements: Application in Total Synthesis E. J. Corey J. Am. Chem. Soc. 1964, 86, 1652. a-caryophyllene alcohol Pinacol rearrangement (vicinal diol): Driving force is the gen. of C=O Deamination " NO+ " Demjanov-rearrangement (Driving force: relief of ring strain) equiv to Synthesis of (±)-Isocomene: Pirrung, JACS 1979, 7130; 1981, 82. (±)-Isocumene Carbocations: Neighboring Group Participation Nuc: ■ Groups with accessable electron density (heteroatoms, arenes) and the correct stereoelectronic orientation (anti-periplanar) can "assist" in the ionization of a leaving group. M. Shair, D. Evans The Cram Phenonium Ion Experiments: Cram, JACS 1949, 71, 3865 L-Threo L-Threo D-Threo 98% chemical fidelity L-Erythro 98% chemical fidelity L-Erythro L-Erythro tetrahedral carbon in C13 NMR (68.8 ppm) Physical Evidence for Neighboring Group Participation Phenonium ion G. Olah JACS 1976, 98, 6784. See Lowry & Richardson, pp 434-439 for discussion of this controversy
M. Shair. D. Evans Carbocation Rearrangements- 3 Chem 206 Nonclassical" carbonium ons a In the norbonenyl system, both p orbitals of the double bond can stabilize the vacant p orbital in an end-on orientation Introduction Physical Evidence of Nonclassical Carbonium lon AcOH aturated= Inversion→ sis of 3-B-cholesteryl chloride with acetate proceeds with complete retention Additionally, the B-Cl solvolyzed at an enhanced rate vS the a-cl Under certain conditions the cholesteryl Acetate is obtained cholesteryl F-ace 1467A retention End-on Overlap a These results have been attributed to an end-on overlap between the fille p orbital of the double bond and the vacant p orbital of the cation in a a-type of interaction. This type of stabilization (a 3 center-2 electron bond)results in 1855A what are referred to as "nonclassical carbonium ions C. Shoppee J. Chem. Soc. 1946, 1147S. Winstein J. Am. Chem. Soc. 1954, 76, 18 The Norbornenyl Example HOAC 1503A Full retention 10 times faster hydrolysis thar T Laube JACS 1989. 111. 9224 saturated system
Cl Me H AcOH Me H H OTs KOAc AcOHOAc H OAc AcO Me H Me Me OAc Carbocation Rearrangements-3 Chem 206 Introduction Saturated = inversion ■ Solvolysis of 3-b-cholesteryl chloride with acetate ion proceeds with complete retention Additionally, the b-Cl solvolyzed at an enhanced rate vs. the a-Cl. Under certain conditions, the cholesteryl i-acetate is obtained. C. Shoppee J. Chem. Soc. 1946, 1147S. Winstein J. Am. Chem. Soc. 1954, 76, 18 "Nonclassical" carbonium Ions cholesteryl i-acetate End-on Overlap retention ■ These results have been attributed to an end-on overlap between the filled p orbital of the double bond and the vacant p orbital of the cation in a s-type of interaction. This type of stabilization (a 3 center-2 electron bond) results in what are referred to as "nonclassical carbonium ions". Full retention & 1011 times faster hydrolysis than saturated system end-on overlap The Norbornenyl Example Physical Evidence of Nonclassical Carbonium Ion ■ In the norbonenyl system, both p orbitals of the double bond can stabilize the vacant p orbital in an end-on orientation. M. Shair, D. Evans 1.467 Å + 1.855 Å 1.503 Å 1.495 Å T. Laube, JACS 1989, 111, 9224
M. Shair. D. Evans Carbocation Rearrangements-4 Chem 206 The 2-Norbornyl Cation Nonclassical"carbonium lons: The Facts! An Innocent Bystander Looks at the 2-Norbornyl Cation Walling, C. Acc. Chem. Res. 1983, 16, 448 [F5Sb-F-sbFsF 2 SbF5 HOAC HOAC relative rates T. Laube, Angew. Chem. Int. Ed. 1987, 26, 560 How do we explain the rate difference and stereochemical result? Stabilization of the 2-norbormyl cation is provided by interaction with the C1-C6 bonding o orbital in an end-on orientation 2.092A 1.739A CC→-pC 1467A 1442A Functionalization of Camphor Resonance representation of norbornyl cation Winstein: The delocalized structure is the lowest energy structure Brown: Delocalized structure is the transition state separating localized ions lon Equilibrium Experiments: Field Soloman, JACS 1976, 98, 156 SO3H sO3H
Me Me Me H OBs H HOAc H H OAc H HOAc Me Me Me H OBs H H H + Me Me O Me Me H Me Me Me F OH Me Me SO3H H2SO4 2 SbF5 OH2 Me Me Me Me Me Me H Me Me Me O SO3H [F5Sb–F–SbF5] – OH Me Me Carbocation Rearrangements-4 Chem 206 "Nonclassical" carbonium Ions: The Facts! The 2-Norbornyl Cation 350 1 How do we explain the rate difference and stereochemical result? s C-C p C+ Stabilization of the 2-norbornyl cation is provided by interaction with the C1-C6 bonding s orbital in an end-on orientation relative rates of solvolysis Resonance representation of norbornyl cation Winstein: The delocalized structure is the lowest energy structure Brown: Delocalized structure is the transiltion state separating localized ions "An Innocent Bystander Looks at the 2-Norbornyl Cation" Walling, C. Acc. Chem. Res. 1983, 16, 448. + T. Laube, Angew. Chem. Int. Ed. 1987, 26, 560 Functionalization of Camphor M. Shair, D. Evans 1.467 Å 1.442 Å 2.092 Å 1.739 Å Ion Equilibrium Experiments: Field & Soloman, JACS 1976, 98, 1567 + + DG° = -2.3 kcal/mol