Chem 206 D. A. Evans Acyclic Conformational Analysis-1 The product ? Stereoselection: 8/1 H 2 O 2 , - OH BH 3 , THF Problem 61. The following stereoselective hydroboration has been reported by Kishi in his synthesis of monensin (JACS 1979, 101, 259). Provide the stereostructure of the major product and rationalize the stereochemical outcome as indicated in the directions. Me OCH 2 Ph Me O Problem 68. The following stereoselective enolate alkylation has been reported by Kim (Tetrahedron Lett. 1986, 27, 943). Provide the stereostructure of the major product and rationalize the stereochemical outcome as indicated in the directions. The product ? Stereoselection: >40:1 TsO CO 2 Me C 4 H 9 Me LiNR 2 Problem 722. Carbonium ion A has been calculated to be 38 kcal/mol more stable than carbonium ion B (Jorgensen JACS 1985, 107, 1496). The profound stabilization of carbonium ions by silicon in this fashion is referred to as the "beta-silicon effect". For example, the S N 1 solvolysis reaction of 1 is 10 +12 times as fast as the corresponding reaction of 2. The solvolysis of 2 leads to the olefin. For a good review see: Lambert Acc. Chem. Res. 1999, 32, 183-190 A CH 2 CH 2 R 3 Si vs B CH 2 CH 2 R 3 C Part A: Identify the HOMO– LUMO interactions in the S N 1 reactions of 1 and 2. 1-LUMO 1-HOMO 2-LUMO 2-HOMO Me 3 C H SiMe 3 OCOCF 3 H H 1 Me 3 C H Me OCOCF 3 H H 2 Solvolysis (CF 3 CH 2 OH) k 1 k 2 = 2.4 x 10 +12 D. A. Evans Monday, September 25, 2006 h t t p : / / w w w . c o u r s e s . f a s . h a r v a r d . e d u / c o l g s a s / 1 0 6 3 Chemistry 206 Advanced Organic Chemistry Lecture Number 4 Conformational Analysis-1 ! Ethane, Propane, Butane & Pentane Conformations ! Simple Alkene Conformations ! Reading Assignment for week A. Carey & Sundberg: Part A; Chapters 2 & 3 R. W. Hoffmann, Angew. Chem. Int. Ed. Engl. 2000, 39, 2054-2070 Conformation Design of Open-Chain Compounds (handout) The Ethane Barrier Problem F. Weinhold, Nature 2001, 411, 539-541 "A New Twist on Molecular Shape" (handout) F. M. Bickemhaupt & E. J. Baerends, Angew. Chem. Int. Ed. 2003, 42, 4183- 4188,"The Case for Steric Repulsion Causing the Staggered Conformation in Ethane" (handout) F. Weinhold,, Angew. Chem. Int. Ed. 2003, 42, 4188-4194,"Rebuttal of the Bikelhaupt–Baerends Case for Steric Repulsion Causing the staggered Connformation of Ethane" (handout)
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Chem 206D. A. Evans Acyclic Conformational Analysis-1
The product ?Stereoselection: 8/1H2O2, -OH
BH3, THF
Problem 61. The following stereoselective hydroboration has been reported by Kishi in his synthesis of monensin (JACS 1979, 101, 259). Provide the stereostructure of the major product and rationalize the stereochemical outcome as indicated in the directions.
Me
OCH2Ph
Me
O
Problem 68. The following stereoselective enolate alkylation has been reported by Kim (Tetrahedron Lett. 1986, 27, 943). Provide the stereostructure of the major product and rationalize the stereochemical outcome as indicated in the directions.
The product ?Stereoselection: >40:1
TsOCO2Me
C4H9
Me
LiNR2
Problem 722. Carbonium ion A has been calculated to be 38
kcal/mol more stable than carbonium ion B (Jorgensen JACS 1985,
107, 1496). The profound stabilization of carbonium ions by silicon in
this fashion is referred to as the "beta-silicon effect". For example,
the SN1 solvolysis reaction of 1 is 10+12 times as fast as the
corresponding reaction of 2. The solvolysis of 2 leads to the olefin.
For a good review see: Lambert Acc. Chem. Res. 1999, 32, 183-190
A
CH2 CH2R3Si
vs
B
CH2 CH2R3C
Part A: Identify the HOMO–LUMO interactions in the SN1
reactions of 1 and 2.
1-LUMO
1-HOMO
2-LUMO
2-HOMO
Me3C
H
SiMe3
OCOCF3
HH
1
Me3C
H
Me
OCOCF3
HH
2
Solvolysis (CF3CH2OH)
k1
k2
= 2.4 x 10+12
D. A. EvansMonday, September 25, 2006
http://www.courses.fas.harvard.edu/colgsas/1063
Chemistry 206
Advanced Organic Chemistry
Lecture Number 4
Conformational Analysis-1
! Ethane, Propane, Butane & Pentane Conformations
! Simple Alkene Conformations
! Reading Assignment for week
A. Carey & Sundberg: Part A; Chapters 2 & 3
R. W. Hoffmann, Angew. Chem. Int. Ed. Engl. 2000, 39, 2054-2070Conformation Design of Open-Chain Compounds (handout)
The Ethane Barrier Problem
F. Weinhold, Nature 2001, 411, 539-541"A New Twist on Molecular Shape" (handout)
F. M. Bickemhaupt & E. J. Baerends, Angew. Chem. Int. Ed. 2003, 42, 4183-4188,"The Case for Steric Repulsion Causing the Staggered Conformation
in Ethane" (handout)
F. Weinhold,, Angew. Chem. Int. Ed. 2003, 42, 4188-4194,"Rebuttal of the Bikelhaupt–Baerends Case for Steric Repulsion Causing the staggered
Connformation of Ethane" (handout)
Chem 206D. A. Evans Acyclic Conformational Analysis-1
+1.4 kcal mol -1+1.0 kcal mol -1
Incremental Contributions to the Barrier.
+1.0 kcal mol -1
1 (H!Me)
2 (H!H)
3 (H!H)
propane
ethane
" E (kcal mol -1)Eclipsed atomsStructure
For purposes of analysis, each eclipsed conformer may be broken up into its component destabilizing interactions.
Ethane Rotational Barrier: The FMO View
One explanation for the rotational barrier in ethane is that better overlap is possible in the staggered conformation than in the eclipsed conformation as shown below.
F. Weinhold, Angew. nature 2001, 411, 539-541"A New Twist on Molecular Shape"
!* C–HLUMO
! C–HHOMO
In the staggered conformation there are 3 anti-periplanar C–H Bonds
! C–HHOMO
!* C–HLUMO
! C–H
!" C–H
In the eclipsed conformation there are 3 syn-periplanar C–H Bonds
!" C–H
! C–H
Following this argument one might conclude that:
C C
C CC
H
C
H
C C
HH
H H
H
H
Me
Me
Me
! The staggered conformer has a better orbital match between bonding and antibonding states.
! The staggered conformer can form more delocalized molecular orbitals.
J. P. Lowe was the first to propose this explanation"A Simple Molecuar Orbital Explanation for the Barrier to Internal
Rotation in Ethane and Other Molecules"J. P. Lowe, JACS 1970, 92, 3799
Estimate the rotational barrier about the C1-C2 bond in isobutane
Chem 206D. A. Evans Acyclic Conformational Analysis: Butane
! G˚ = –2.3RT Log10K
! G° = –RT Ln K
Relationship between !G and Keq and pKa
Recall that: or
! G˚298 = –1.4 Log10Keq
At 298 K: 2.3RT = 1.4 (!G in kcal Mol–1 )
pKeq = – Log10KeqSince
pKeq
0–1–2
0–1.4
1.010100
!G˚Keq
! G˚298 = 1.4 pKeq
–2.8 kcal /mol
Hence, pK is proportional to the free energy change
! E = ?
eclipsed conformation
staggered conformation
Using the eclipsing interactions extracted from propane & ethane we should be able to estimate all but one of the eclipsed butane conformations
Butane
Me
C
Me
CH
H HH H H
HH
Me
Me
Eclipsed atoms ! E (kcal mol -1)
+1.0 kcal mol -11 (H"H)
+2.8 kcal mol -12 (H"Me)
# E est = 3.8 kcal mol -1
The estimated value of +3.8 agrees quite well with the value of +3.6 reported by Allinger (J. Comp. Chem. 1980, 1, 181-184)
+3.6
+5.1
+0.88Ref = 0
G
E1
E2
n-Butane Torsional Energy Profile
H
C
Me
HHH
Me
C
Me
H H
H
Me
H
Me
C
Me
H
C
H
H
HH
HH
H
Me
Me
ene
rgy
A
Barrier?
Acyclic Conformational Analysis: ButaneD. A. Evans Chem 206
eclipsed conformation
staggered conformation
! E = +5.1 kcal mol-1
From the torsional energy profile established by Allinger, we should be able toextract the contribution of the Me"Me eclipsing interaction to the barrier:
Butane continued
Me
C
H
CH
H MeH Me H
HMe
H
H
Let's extract out the magnitide of the Me–Me interaction
2 (H!H) + 1 (Me!Me) = +5.1
1 (Me!Me) = +5.1 – 2 (H!H)
1 (Me!Me) = +3.1
+3.1
Incremental Contributions to the Barrier.
+2.0
1 (Me!Me)
2 (H!H)
" E (kcal mol -1)Eclipsed atoms
Eclipsed Butaneconformation
From the energy profiles of ethane, propane, and n-butane, one may extractthe useful eclipsing interactions summarized below:
Hierarchy of Eclipsing Interactions
! E kcal mol -1
+1.0
+1.4
+3.1
C C
X Y
H
H
H
H
X Y
H H
H Me
Me Me
Nomenclature for staggered conformers:
CH
H H
H
Me
Me
CH
H Me
H
H
Me
C
H
Me H
H
H
Me
trans or tor (anti)
gauche(+)
or g+
gauche(-)
or g-
Conformer population at 298 K:
70% 15% 15%
R
C
R
R
C
R
R
CR
sp
sc
(Klyne, Prelog, Experientia 1960, 16, 521.)
sc
acac
ap
CR
R
C
RR
C
R
R
0°
+60°
+120°
180°
-60°
-120°
Torsion angle Designation Symbol
0 ± 30°
+60 ± 30°
+120 ± 30°
180 ± 30°
-120 ± 30°
-60 ± 30°
± syn periplanar
+ syn-clinal
+ anti-clinal
antiperiplanar
- anti-clinal
- syn-clinal
± sp
+ sc (g+)
+ ac
ap (anti or t)
- ac
- sc (g-)
Energy Maxima
Energy Minima
E2
G
E1
A
E1
G
n-ButaneConformer
Acyclic Conformational Analysis: PentaneD. A. Evans Chem 206
n-Pentane
Me Me
H H
H H
Me H
H H
H Me Me H
H Me
H H
Me Me
Me Me
Me MeMe Me
Me
Me Me
Me
Rotation about both the C2-C3 and C3-C4 bonds in either direction (+ or -):