chemistry 206 - keeel...carey & sundberg, advanced organic chemistry, 4th ed. part a chapter 5,...
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Chem 206D. A. Evans Carbocations: Stability & Structure
Other Relevant Background Reading
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.
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
D. A. EvansMondayDecember 11, 2006
Reading Assignment for this Lecture:
Chemistry 206
Advanced Organic Chemistry
Lecture Number 33
Introduction to Carbonium Ions
! Carbocation Stabilization
! Carbocation Structures by X-ray Crystallography
! Vinyl & Allyl Carbonium Ions
Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part A Chapter 5, "Nucleophilic Substitution", 263-350 .
Laube (1995). “X-Ray Crystal Structures of Carbocations Stabilized by Bridging or Hyperconjugation.” Acc. Chem. Res.1995, 28,: 399 (electronic pdf)
Olah, G. A. (2001). “100 Years of Carbocations and their Significance in Chemistry.” J. Org. Chem. 2001, 66, 5944-5957. (handout)
Walling, C. (1983). “An Innocent Bystander Looks at the 2-Norbornyl Cation.” Acc. Chem. Res. 1983, 16, 448. (handout)
Birladeanu, L. (2000). "The Story of the Wagner-Meerwein Rearrangement.” J. Chem. Ed. 2000, 77, 858. (handout)
http://www.courses.fas.harvard.edu/colgsas/1063
Problem 17: The reaction illustrated below was recently reported by Snider and co-workers (Org. Lett. 2001, 123, 569-572). Provide a mechanism for this transformation. Wherestereochemical issues are present, provide clear three dimensional drawings to supportyour answer.
Me
O
Me Me
R EtAlCl2
CH2Cl2, 0 °C
Me
O
Me
R
Me
Carey & Sundberg-A, p 337: Provide mechanisms for the following reactions.
OH
NH2 NaNO2
HOAc/H2O
CHO
OH
NH2 NaNO2
HOAc/H2O
CMe3
O
CMe3
The Gathering at The Gathering at JDRJDR’’s s 70th70th Birthday CelebrationBirthday Celebration19881988
DervanDervan, Ireland, Evans, Bergman, Grubbs, JDR, Myers, Dougherty, Hammond, Ireland, Evans, Bergman, Grubbs, JDR, Myers, Dougherty, HammondRecent organic faculty at CIT, present and departedRecent organic faculty at CIT, present and departed
Chem 206D. A. Evans John D. Roberts, Institute Professor of Chemistry, Emeritus, Caltech
B.A., 1941, University of California (Los Angeles)Ph.D. 1944, University of California (Los Angeles)
John D. Roberts was born in 1918.
He became Prof. at MIT and then Prof. at Caltech where he is still active. His work has been centered on mechanisms of organic reactions.
One of the joys of being a professor is when an exceptional student comes along and wants to work
with you.
J.D. Roberts, The Right Place at the Right Time. p. 63.
John D. Roberts graduated from the University of California at Los Angeles where he had received A. B. (hons) degree in 1941 and the Ph. D. degree in 1944. In 1945-1946 he was a National Research Council Fellow and Instructor at Harvard. Later on, he went to MIT in 1946 as an Instructor. He had introduced the terms "nonclassical" carbocations and "benzyne" into organic chemistry. He had won numerous awards; he is a member of the National Academy of Sciences (1956) and the American Philosophical Society (1974). He received the Welch Award (1990, with W. E. Doering), the National Medal of Science (1990), and the ACS Arthur C. Cope Award (1994). Since 1939 his research has been concerned with the mechanisms of organic reactions and the chemistry of small-ring compounds. His current work involves applications of nuclear magnetic resonance spectroscopy to physical organic chemistry.
Roberts made major research and pedagogic contributions to mechanisticorganic chemistry. He pioneered the use of 14C and other isotopic labels tofollow molecular rearrangements as, for example, in the complex and subtle solvolysis of cyclopropyl-carbinyl systems. He introduced the terms"nonclassical" carbocations and "benzyne" into organic chemistry, and usedisotopic labeling to establish the intermediacy of each. Roberts was early torecognize NMR's potential, and used 1H NMR to study nitrogen inversion,long-range spin-spin coupling and conformational isomerism, and later 13Cand 15N NMR to study other reactions, including the active sites of certainenzymes. Roberts' superb short books on "Nuclear Magnetic Resonance"(1959), "Spin-Spin Splitting in High Resolution NMR" (1961) and "Notes onMolecular Orbital Calculations" (1961) did much to popularize and clarifythese subjects for organic chemists. His highly successful text "BasicPrinciples of Organic Chemistry" (1964), written with Marjorie Caserio,introduced spectroscopy early to undergraduates. Roberts received manyawards, including the Roger Adams (1967) and Priestley (1987) Medals. Anexcellent photographer, Roberts graciously supplied several of thephotographs for the MSU collection.
D. A. Evans. B. Breit Chem 206Carbocations: Stability
Carbocation Subclasses
R3 R2
R1
!
R–R3 = alkyl or aryl
R3 R2
O!
R–R3 = alkyl or aryl
R1
R3 R2
N!
R–R3 = alkyl or aryl
R R
Carbon-substituted Heteroatom–stabilized
The following discussion will focus on carbocations unsubstitutred with heteroatoms
C C
C!
C C
C!
C C
C
!C C
C
!
opentrivalent
hyperconjugationno bridging
unsymmetrical bridging
symmetrical bridging
classical nonclassical
increasing nonclassical character
Classical vs nonclassical carbonium ions
Stability: Stabilization via alkyl substituents (hyperconjugation)
R
R
R
H
R
R
H
H
R
H
H
H
Order of carbocation stability: 3˚>2˚>1˚
>> > Due to increasing number of substituents capable of hyperconjugation
C C+H
314
276
249
231
287
386
239
Hydride ion affinities
The relative stabilities of various carbocations can be measured in the gas phase by theiraffinity for hydride ion.
J. Beauchamp, J. Am. Chem. Soc. 1984, 106, 3917.
+ H
Note: As S-character increases, cation stability decreases due to more electronegative carbon.
+ HI
!HI increases " C(+) stability decreases
Hydride Affinity = –!G°
Carey & Sundberg–A, pp 276-
C C C C
CH3+
CH3CH2+
(CH3)2CH+
(CH3)3C+
H2C=CH+
PhCH2+
R R–H
Me CH2
276 249
–27
231
–18Me2 CH Me3 C
Hydride ion affinities (HI)
H3C CH2
276
H2C CH
287
+21
HC C
386
+81
Ph CH2
239 276
–37 –20Me CH2
256
CH CH2H2C
Me CH2
276 270
–7Me–CH2 CH2
The effect of beta substituents: Rationalize
Hydride ion affinities versus Rates of Solvolysis
PhCH2–Br CH=CH–CH2–Br
Relative Solvolysis rates in 80% EtOH, 80 °C
100 52
0 +17
239 256HI
!-HI
A. Streitwieser, Solvolytic Displacement Reactions, p75
Conclusion: Gas phase stabilities do not always correlate with rates of solvolysis
Me2CH–Br
0.7
+10
249
rel rate
M. Shair, D. Evans Chem 206Carbocation Generation & Stability
Carbocation Stability: The pKR+ value
Definition: R+ + H2O ROH + H+
KR+ =aROH ! aH+
aR+ ! aH2O
a = activity
pKR+ = – log KR+ Carey & Sundberg, A, p 277
(4-MeO-C6H4)3C Ph3C (3-Cl-C6H4)3C Ph2CH
Fe
CH2
Fe
CHPh CHPh
Cr(CO)3
R CPh2
Co2(CO)6
+
H7C3
H7C3
C3H7
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
Carey & Sundberg, A, pp 276-
most stable
least stable
Hydride abstraction from neutral precursors
R3C H + Lewis-Acid
R3C H =
HH
H
RS
RS
H
H
R2N
R2N
H
Hetc.
Lewis-Acid: Ph3C BF4, BF3, PCl5
Carbocation Generation
R3C
H
Removal of an energy-poor anion from a neutral precursor via Lewis Acids
R3C X + LA LA–X
LA: Ag , AlCl3, SnCl4, SbCl5, SbF5, BF3, FeCl3, ZnCl2, PCl3, PCl5, POCl3 ...X: F, Cl, Br, I, OR
R3C +
Acidic dehydratization of secondary and tertiary alcohols
R3C OH- H2O
R: Aryl + other charge stabilizing substituents
X: SO42-, ClO4
-, FSO3-, CF3SO3
-
+ R3C +H–X X
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 ! -Br > Cl > OH2
+ ...
R3C X R3C + X
Addition of electrophiles to !-systems
R
R
R
R
H R
R
R
R
H chemistry
R RH R
H
R chemistry
Br
H2SO4
Me
O
HC C CH2OH
J.C.S.,CC 1971, 556
Problem 897: Provide a Mechanism of this transformation
D. A. Evans, B. Breit Chem 206Carbocations: Structure
+
C C
R
H
HH
HC
H
HC
H
R
Carbocation Stabilization Through Hyperconjugation
Take linear combination of ! C–R (filled) and C pz-orbital (empty):
! C–R
!" C–R
+
! FMO Description
CH
H
E
! C–R
+
!" C–R
Syn-planar orientation between interacting orbitals
CH
H
D. A. Evans, K. Scheidt Chem 206Carbonium Ion X-ray Structures: Bridged Carbocations
1.467 Å
1.442 Å
1.739 Å**2.092 Å
+
+[F5Sb–F–SbF5]–
T. Laube, Angew. Chem. Int. Ed. 1987, 26, 560
Me
Me
Me
H
MeMe
H
Me
Me
Me
F
**One of the longest documented C–C bond lengths.
C C
C!
C C
C
!
hyperconjugationno bridging
unsymmetrical bridging
2 SbF5
F5Sb F SbF5–
1.467 Å
+
1.855 Å
1.503 Å
1.495 Å
T. Laube, JACS 1989, 111, 9224
Me
Me
Ph Cl
C
Me
Me
Ph
+
AgSbF6
D. A. Evans, K. Scheidt Chem 206Carbonium Ion X-ray Structures: A Summary
1.467 Å
1.855 Å
1.503 Å
1.495 Å
1.467 Å
1.442 Å
1.739 Å2.092 Å
+
+
+
1.408 Å
1.432 Å1.371 Å
1.446 Å
1.439 Å
1.442 Å
+
98.2 °1.621 Å
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!
C C
C!
C C
C
!C C
C
!
opentrivalent
hyperconjugationno bridging
unsymmetrical bridging
symmetrical bridging
classical nonclassical
increasing nonclassical character
Nomenclature: classical vs nonclassical
Chem 30D. A. Evans Chapter 18: Chemistry of Aryl & Vinyl Halides
Me
R
X H CMe
RFavorable
H2C
R
XUnfavorable CC R
H
H
–X–
–X–
Substitution (SN1)
Substitution Reactions
Sp hybridized Carbonis more electronegative
CSp2 Carbonium Ions do exist!
1.221 Å
Si
Si
1.946 Å
Si Si
CMe3
Me
Me Me
Me
Normal CC triple bond lengths are ~1.21 Å
D. A. Evans, B. Breit Chem 206Vinyl & Allyl Carbocations
D
R
OTf
R C CD
RR
OTf OSolv
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
H+
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.
H3C CH2
276
H2C CH
287
+21HC C
386
+81
Hydride ion affinities (HI)
H2C CH
287
+11
298
Allyl & Benzyl Carbocations
R
R
R
R
Carbocation Stabilization via !-delocalization
allyl cation
! Stabilization by Phenyl-groups
The Benzyl cation is approximately as stable as a t-Butylcation.
(CH3)3C + PhCH3 (CH3)3CH + PhCH2
!H0r
[kcal/mol]
3.8
(CH3)3C + PhCH2Cl (CH3)3CCl + PhCH2– 0.8
Ph CH2
239
Hydride ion affinities (HI)
231
Me3 C–8
Hydride ion affinities versus Rates of Solvolysis
PhCH2–Br Me2CH–Br CH=CH–CH2–Br
Relative Solvolysis rates in 80% EtOH, 80 °C
100 0.7 52
0 +10 +17
239 249 256HI
!-HI
A. Streitwieser, Solvolytic Displacement Reactions, p75
D. A. Evans Chem 206The Johnson Longifolene Synthesis
Volkman, Andrews, Johnson, JACS 1975, 97, 4777
The plan ( According to Volkman):
Me Me
Me
CH2
H
Me Me
Me
HO
Me Me
Me
Me Me
Me
Me Me
Me
H
Me Me
Me
H
HO
longfifolene
TFA, K2CO375%
Me Me
Me
HO
Me Me
Me
H
NaBH3CN
ZnBr2
94%
Me Me
CH2
H
H
H+
91%
Me Me
Me
ZnBr2NaBH3CN
longfifolene
steps
Ho, Nouri, Tantillo, JOC 2005, 70, 5139-5143
W. S. Johnson!s total synthesis of the sesquiterpenoid longifolene is a classic example of the power of cationic polycyclizations for constructing complex molecular architectures. Herein we revisit the key polycyclization step of this synthesis using hybrid Hartree-Fock/density functional theory calculations and validate the feasibility of Johnson!s proposed mechanism. We also explore perturbations to the 3-center 2 electron bonding array in a key intermediate that result from changing the polycyclic framework in which it is embedded.
The Cationic Cascade Route to Longifolene
FIGURE 1. Relative energies (kcal/mol) of stationary points for the mechanism shown in Scheme 2 (B3LYP/6-31G(d) zero-point corrected energies in italics, B3LYP/6-31G(d) free energies at 0 °C in bold, and CPCM-B3LYP/6-31G(d) energies in water underlined).
D. A. Evans, B. Breit Chem 206Cyclopropyl-carbinyl & Bridgehead Carbocations
Carbocation Stabilization via Cyclopropylgroups
C
A rotational barrier of about 13.7 kcal/mol is observed in
following example:H
Me
Me NMR in super acids!(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
R
O1.222 Å
1.474 Å
1.517 Å
1.478 Å
X-ray Structures support this orientation
See Lecture 5, slide 5-05 for discussion of Walsh orbitals
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:
Me
Me
OTs
OTs
Cl
Cl
krel = 1 krel = 1
krel = 106 krel = 10-3
OTs
OTs
krel = 1
krel = 108
Why??
Carey–A, p 286
Me
Me
Me
OTs
TsO TsO TsO
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?
TsO
why so reactive?
–TsO
D. A. Evans, J.Tedrow Chem 206A Stable Hypervalent Carbon Compound ?
+
2.428 Å
2.452 Å
1.483 Å
2.428 Å
2.452 Å
+
OMe OMeCO2Me
Me3O+BF4– O OC
OMeMeOMe Me
+
B2F7–
"The relevant C–O distances are longer than a covalent C–O bond (1.43 Å) but shorter than the sum of the van der Waals radii (3.25 Å)."
"The Synthesis and Isolation of Stable Hypervalent Carbon Compound (10-C-5) Bearing a 1,8-Dimethoxyanthrecene Ligand"
Akibe, et al. JACS 1999, 121, 10644-10645
For a recent monograph on hypervalent Compounds see:"Chemistry of Hypervalent Compounds", K. Akiba, Wiley-VGH, 1999