哈佛大学：《高等有机化学》（英文版）Lecture 31 Introduction to Carbonium Ions

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 AcO￾HOAc 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

M. Shair D. Evans Allyl-& Vinylsilanes: The B-Silicon Effect Chem 206 References: Lambert Acc. Chem. Res. 1999.32 183-190 Magnitude of the B-silicon Effect Lambert, JACS1990,112,8120;1996,118,7867 Fleming, Chem. Rev., 1997, 2063 bIolysis(CF3CH2OH Me3C Allyl& vinylsilanes react with electrophiles H OCOCF3 =24x10+12 trapped by solution Nu) 2 eaC./ ZHSiMea Solvolysis(CF3CH2OH) Mechanism -the simple picture: B-Silicon stabilizes carbocation OCOCF =4x104 OCOCF3 RsV 仓 These figures established the B-effect as one of the kinetically strongest in organic chemistry".J.Lambert e sSiMe3 SiMe Data provide no distinction between open and bridged intermediates Proof for a stepwise mechanism provided the following protodesilylation Silicon Effect: the origin of regioselectivity → Me3Si H3S.⑥ A versus both silanes- eld the same Calculation: A more stable than b by 38 kcal mol ds mos kely via a common ediate. a

R3Si A SiMe3 Si H3Si H H CH2 R3Si SiMe3 H2C SiMe3 E R3Si E E E H3C H H CH2 B E E Me3Si SiMe2Ph Me3Si SiMe2Ph Me3C H SiMe3 OCOCF3 H H Me3C H H OCOCF3 SiMe3 H H H Me3Si SiMe2Ph Me3C H Me OCOCF3 H H Me3C H H OCOCF3 Me H Me3Si SiMe2Ph Allyl- & Vinylsilanes: The b-Silicon Effect Chem 206 Allyl– & Vinylsilanes react with electrophiles Mechanism - the simple picture: -Silicon stabilizes carbocation References: Lambert Acc. Chem. Res. 1999, 32, 183-190 Lambert, JACS 1990, 112, 8120; 1996, 118, 7867. Fleming, Organic Reactions 1989, 37, 54. Fleming, Chem. Rev., 1997, 2063. E E E Nu E Nu -Silicon Effect: the origin of regioselectivity sSi–C ® pz empty sSiC pz s E occ pz versus Calculation: A more stable than B by 38 kcal/mol. Jorgensen JACS 1985, 107, 1496. Proof for a stepwise mechanism provided the following protodesilylation experiment: both silanes yield the same product mixture. Hence, the reaction proceeds most likely via a common intermediate, a carbeniumion Magnitude of the -Silicon Effect 1 2 Solvolysis (CF3CH2OH) k1 k2 = 2.4 x 10+12 3 4 Solvolysis (CF3CH2OH) k3 k4 = 4 x 10+4 "These figures established the -effect as one of the kinetically strongest in organic chemistry": J. Lambert Data provide no distinction between open and bridged intermediates M. Shair, D. Evans "R3Si+ " "R3Si+ " (trapped by solution Nu)

M. Shair. D. evans Allyl-& Vinylsilanes: The B-Silicon Effect-2 Chem 206 General: Allylsilanes are more nucleophilic than alkenes The stereochemical consequences for the major product are HOMO is higher in energy due to negative hyperconjugation O anti-addition of E with respect to SiR3 E Examples: x(→cs t-BuCl, TICl4 Me3Si JACS 1982 Electrophile Addition- Stereoelectronics 88:12 R3 Carbonyl Addition of Allylsilanes: Open Transition States oC-Si Me3 Si is not sufficiently Lewis acidic to activate C=o through pre-association; however (RO)2Mesiis Lewis acidic enough to activate C=O through pre-association. These allylsilanes add to RCHO througl closed transition states A1.strain minimized if R= medium size to large and/or ifR=small and rl=H reaction pathway via this reactive R2 conformation could compete major product arises via this Antiperiplanar TS SiMe3 ns by Houk et al. show that the relative energy differences between the and and synclinal transition states are negligible. Both the antiperiplanar models predict a syn selectivity for the newly formed stereogenic centers +Nu上NsMe3 >95:5sy +Nu· NuSiMe3 major(trans) minor(cis) Hayashi,1983,2865

Me3Si Me CH2Cl2 R Me OH R Me OH TiCl4 R O E H R R 1 2 H R R 3 R H R 3 E R 1 R 2 CH2Cl2 R Me OH Me3Si Me TiCl4 R O H R 3 Si H R E R 1 R 3 R 2 R 1 H R Si E R 2 R2 R1 SiMe3 O XnM R1 R2 SiMe3 H R H OR O XnM R R 3 R 2 R 1 Si H R R 3 R 2 R 1 H R Si R Ph Me3Si H R HF Ph CH2Cl2 Ph t-Bu H Me Me Ph Me3Si H t-BuCl, TiCl4 Allyl- & Vinylsilanes: The b-Silicon Effect-2 Chem 206 General: Allylsilanes are more nucleophilic than alkenes HOMO is higher in energy due to negative hyperconjugation ( *) C–Si Houk, JACS 1982, 104, 7162. Electrophile Addition - Stereoelectronics if R = medium size to large and/or R 1 ¹ H Þ major product arises via this reactive conformation if R = small and R 1 = H a reaction pathway via this reactive conformation could compete sCSi E E major (trans) minor (cis) + Nu - NuSiMe3 + Nu - NuSiMe3 The stereochemical consequences for the major product are: Examples: But JACS 1982, 104, 4962. Protodesilylation E:Z 88:12! Eschenmoser, Helv. Chim. Acta 1979, 62, 1922. + > 95:5 syn + ca. 65 : 35 syn Hayashi, TL 1983, 2865. anti addition A1,3-strain minimized sC–Si sC–Si M. Shair, D. Evans sSi–C E p p* sSi–C p ❐ trans-alkene: ❐ anti-addition of E+ with respect to SiR3 Carbonyl Addition of Allylsilanes: Open Transition States Me3Si– is not sufficiently Lewis acidic to activate C=O through pre-association; however (RO)2MeSi– is Lewis acidic enough to activate C=O through pre-association. These allylsilanes add to RCHO througl closed transition states Antiperiplanar TS Synclinal TS Calculations by Houk et al. show that the relative energy differences between the antiperiplanar and and synclinal transition states are negligible. Both the antiperiplanar and synclinal models predict a syn selectivity for the newly formed stereogenic centers

B. Breit. d. evans Allylsilanes: Reactions with Electrophiles Chem 206 Ally silanes add to aldehydes and acetals under Lewis acid promotion Reactions Proceeding through Silicon-Migration Si migration may be promoted by using hindered Si substituents TICl4 Me3Si Felkin Selectivity also holds with this class of nucleophiles A I Meyers, J. Org. Chem. 1998, 63, 5517 Acetals can be used as well diastereoselection: 97: 3 OCH Haco ORcL OZrCl4 Meo2CcO2Me Zrcl4 COm COmE H3CO n-C4Hg (83%) Ar (Pn) he Sakurai Reaction(Enone Conjugate Addition) Ph(Pr)2Si OTICl4 MeO2C CH2Cl2 SiMe3 Can you work out the mechanism?? leming, Org. Reactions 1989, 37, 127-133 17% CO2Me Me BF3"OEz rt 8 h 10 EtAICI2 diastereoselection: >30.1 93%e nek,dog.chem.1993,58,2345 Majetich, Tetrahedron 1987, 43, 5621

Me3Si Ph Me3Si Ph Me3Si Me Me O H Me O H Me OCH3 H3CO n-C4H9 OCH3 H3CO n-C4H9 TiCl4 TiCl4 TiCl4 n-C4H9 OCH3 Me Me OH n-C3H7 Ph OH n-C3H7 Ph n-C4H9 OCH3 Me Me (Pri)3Si MeO2C CO2Me Ar Me O TiCl4 ZrCl4 CH2Cl2 Me3Si Me Me TiCl4 Me O Me3Si TiCl4 CH2Cl2 Me OTiCl4 SiMe3 Me O Me O Me3Si Me O EtAlCl2 CH2Cl2 Me O SiMe3 CH2Cl2 (Pri)3Si Ph(Pri)2Si CO2Me Me PhMe2Si Me H O Me OTiCl4 Si(iPr)3 CO2Me Ar MeO OZrCl4 – SiR3 Me O (Pri)3Si CO2Me CHO Me PhMe2Si Me Ar CO2Me MeO2C SiR3 Me OTiCl4 Si (iPr)3 CO2Me Ar MeO OZrCl4 – SiR3 B. Breit, D. Evans Allylsilanes: Reactions with Electrophiles Chem 206 Allylsilanes add to aldehydes and acetals under Lewis acid promotion regioselectivity: Allyl inversion + + Acetals can be used as well + + (80%) (83%) Felkin Selectivity also holds with this class of nucleophiles The Sakurai Reaction (Enone Conjugate Addition) 75% 17% Fleming, Org. Reactions 1989, 37, 127-133 Majetich, Tetrahedron 1987, 43, 5621 78% Reactions Proceedilng through Silicon-Migration ?? A. I. Meyers, J. Org. Chem. 1998, 63, 5517 diastereoselection: 97:3 85% yield diastereoselection: 96:4 68-70% yield BF3 °OEt2 rt 8 h diastereoselection: >30:1 93% yield Panek, J. Org. Chem. 1993, 58, 2345 Can you work out the mechanism?? Si migration may be promoted by using hindered Si substituents

B Breit. D. Evans Vinylsilanes: Reactions with Electrophiles Chem 206 Stereochemistry of Electrophile Addition to Vinylsilanes Summary Statements Viny l/Ally silanes in Organic Synthesis- Selected Examples 1. Me3C+ is more stable than Me]Si+ in spite of the fact that Si is less Fleming, Org. Reactions 1989, 37, 54 electronegative than c N R RETeNTIoN H Rotation in direction a favored H C-C bond length: 1. A (avoidance of eclipsing interactions, Principle of least motion NuSiMe3 C-Si hyperconjugation is less pronounced than the analogous C-c hyperconjugation do to the impact of the longer C-Si bond lengths 2. Carbonium ions a to Si are less stabilized than carbonium ions p to si. H C(+)a to CICH(OMe)2 TiCl4 Me3Si C-Si hyperconjugation is less pronounced than the analogous C-C hyperconjugation Fleming D 289 3. According to Lambert, silicon has a propensity to stabilize B carbonium ion via hyperconjugation(vertical stabilization)rather than bridging (nonvertical Me3Si c(+)阝 to silicon H-CCSN (CH2O)n Messi TSOH Fleming p 148 4. Silicon has a lower propensity to undergo Wagner-Meerwein like rearrangements than carbon

R1 R2 H El SiMe3 N O O I R1 R2 H SiMe3 El R1 Me3Si R2 H R1 R2 El SiMe3 H El SiMe3 H R O Me Me SiMe3 Et Et ClCH(OMe)2 N H NH Me SiMe3 TsOH TiCl4 TiCl4 R1 R2 H SiMe3 El R1 R2 H I Et Et OMe OMe OH H R Me Me N H N Me Si C Me Me H H H C C Me Me H H H C Me3Si C H H H H Si C Me Me H H Me C Me3Si C H H H H Si C Me Me H H C C Me Me H H H H C Me3Si C H H H H Me Me3Si Me3Si Si C Me Me H H C C H H H H C C H H H H B. Breit, D. Evans Vinylsilanes: Reactions with Electrophiles Chem 206 Stereochemistry of Electrophile Addition to Vinylsilanes RETENTION º + Nu- - NuSiMe3 • Rotation in direction a favored (avoidance of eclipsing interactions, • Principle of least motion a Vinyl/Allylsilanes in Organic Synthesis - Selected Examples Fleming, Org. Reactions 1989, 37, 54. a Fleming p 289 + - 78 °C (73%) (CH2O)n Fleming p 148 2. Carbonium ions to Si are less stabilized than carbonium ions to Si. C to silicon C to silicon C–Si hyperconjugation is less pronounced than the anaologous C–C hyperconjugation do to the impact of the longer C–Si bond lengths. 3. According to Lambert, silicon has a propensity to stabilize b carbonium ion via hyperconjugation (vertical stabilization) rather than bridging (nonvertical stabilization. C to silicon hyperconjugation more important than bridging 4. Silicon has a lower propensity to undergo Wagner-Meerwein like rearrangements than carbon. Summary Statements 1. Me3C+ is more stable than Me3Si+ in spite of the fact that Si is less electronegative than C. C–Si bond length: 1.87 Å C–C bond length: 1.54 Å C–Si hyperconjugation is less pronounced than the anaologous C–C hyperconjugation do to the impact of the longer C–Si bond lengths

M. Shair d. evans Stabilized Cations: Iminium-Ions 1 Chem 206 minium lons Common Methods of generation rel rates: 7000/1 Re or Lewis A Overman et al. TL 1984. 25. 5739 or Lewis Acid Oxidation of amines Hg-x Hg(0) X (4) vinylsilane) (日 vinylsilane) in the case of the(z)vinylsilane is the emerging p orbital coplar bond. Full stabilization of the empty orbital cannot occur with vinylsilane..hence the rate difference Stereoelectronic Effects on nu Addition to Iminium lons PPTS MeOH TMS Hg(OAC)2/EDTA st pumiliotoxin A H COmE Least Motion Argument Nu( favored) Stork et al. JACS 1972. 94. 5109 C=N Stereoelectronic Effects: Lecture 19 For additional related transformations see Aza-Cope Handout, Lecture 11

R1 R2 O N OR2 R1 N R4 R3 H N R1 R2 R4 R3 N N H H MeO2C OH H N Me N Me Hg H H X X – N H H CO2Me OH H R H H NaBH4 HgX2 X - N N H H MeO2C OH H H N R1 R2 R4 R3 N R1 HX N Me H Hg(0) X – Me3 N Si Ph N O H TMS R Me Me N Ph Me3Si N H Ph SiMe3 H H N H Me Me R OH TFA TFA N H Ph H H SiMe3 N H Ph H N H Me Me R TMS OH M. Shair, D. Evans Chem 206 Iminium Ions Common Methods of Generation: Stabilized Cations: Iminium-Ions 1 H + , -H2O H + , -ROH or Lewis Acid or Lewis Acid Stereoelectronic Effects on Nu Addition to Iminium Ions Hg(OAc)2/EDTA one diastereomer Stork et al. JACS 1972, 94, 5109. rds Oxidation of Amines Nu (favored) (E) (Z) Overman et al. TL 1984, 25, 5739. Only in the case of the (Z) vinylsilane is the emerging p orbital coplanar with C-Si bond. Full stabilization of the empty orbital cannot occur with the (E) vinylsilane.....hence the rate difference. rel rates: 7000/1 (Z) vinylsilane) (E) vinylsilane) PPTS, MeOH 80˚C 71 % one double bond isomer Overman et al. JOC 1989, 54, 2591. pumiliotoxin A "Least Motion Argument" steps C=N Stereoelectronic Effects: Lecture 19 For additional related transformations see Aza-Cope Handout , Lecture 11