NMR and Stereochemistry
Chem 8361/4361:
Interpretation of Organic Spectra
© 2009–2013 Andrew Harned & Regents of the University of Minnesota
General flow for solving structures
C10H20O
Exact Mass: 156.1514
Molecular Weight: 156.2652
Molecular weight/formula (MS)
Functional groups (IR, NMR)
Carbon connectivities (substructures) (NMR)
OH
Me
Positions of functional groups
within framework (gross structure)
(2D NMR, coupling constants)
Stereochemical issues
How can this
be solved???
Me
Me
HO
HO
OH
Relative
Stereochemistry
(Diastereomers)
Can be determined with many of the tools we have
already discussed, along with some new ones
Bifulco, G.; Dambruoso, P.; Gomex-Paloma, L.; Riccio, R. Chem. Rev. 2007, 107, 3744.
NMR Spectroscopy
Strategies for determining relative stereochemistry
Chemical Shifts
– Diastereotopic protons will have different chemical shifts, this will
only tell you that diastereomers are present, cannot necessarily tell
which is which by inspection only by comparison to known
structures
– Geometry may place certain protons in shielding/deshielding
portions of functional groups
Coupling Constants
– In acyclic systems, usually cannot tell which is which by
inspection
– Often must convert to rigid/cyclic structure
Both require some knowledge of 3D structure –> Make model(s)
NMR Spectroscopy
Proximity of Protons
Nuclear Overhauser Effect (nOe)
– Through space interactions between nuclei,
whether or not they are directly coupled
– Magnitude decreases as inverse of sixth power
of distance
1
nOe ∝
C
A
H3C
CH3
vs.
irradiate more H's give better results
H
C
B
H
H
H
C
H 2C
– Strongly irradiate one, get larger # in excited state
– The other then shifts to lower state to compensate
and peak increases in intensity
– Useful for determining stereochemistry
– Need rigid system
H
C
L
3–4 Å typical
L6
H
HB
HA
H
H 3C
C
CO2H
irr. A
17% enhancement in C
irr. B
no enhancement in C
NMR Spectroscopy
Proximity of Protons
Nuclear Overhauser Effect (nOe)
• nOe Difference: Subtract original spectrum from the irradiated spectrum
– This leaves only the enhanced protons
NMR Spectroscopy
Proximity of Protons
Nuclear Overhauser Effect (nOe)
• nOe Difference: Subtract original spectrum from the irradiated spectrum
NMR Spectroscopy
44913_07_p341-380 11/30/04 1:21 PM Page 359
Proximity of Protons
Nuclear Overhauser Effect (nOe)
Problem 7.4E
• nOe Difference:
Subtract original spectrum from the irradiated spectrum
1 irradiated
NOE Difference Spectra, 600 MHz
8 irradiated
2 irradiated
10
9,10 irradiated
4
5
2
5.2
5.3
5.4
2
5.5
2
6 irradiated
OH
6
8
6
1
3
7
9
9,10
Geraniol
1.7
ppm
6
4.5
1.6
ppm
9 10 8
1
5.0
8
4.0
3.5
3.0
2.5
2.0
1.5
ppm
NMR Spectroscopy
Proximity of Protons
Nuclear Overhauser Effect (nOe)
HB
C HA
– 2D experiments
NOESY: Nuclear Overhauser Effect Spectroscopy
L
ROESY: Rotating-frame Overhauser Effect
3–4 Å typical
Spectroscopy
– Look like COSY, but cross-peaks are for through space interactions
• cross peaks not observed past ~5 Å
C
Theoretical maximum NOE
NOESY vs. ROESY
– For MW <~600 max. NOE is always positive
– For MW 700–1200 max. NOE goes through zero
– For MW >1200 max. NOE is negative
– ROE is always positive, but works best for
MW 700–1200
– If given choice for small moleculs, run NOESY
Figure from: http://www.columbia.edu/cu/chemistry/groups/nmr/NOE.htm
NMR Spectroscopy
Proximity of Protons
O
Nuclear Overhauser Effect (nOe)
H
N
Boc
vinylMgBr
OH
N
Boc
KOt-Bu
O
CH3
O
N
H
H
J = 6.6 Hz
J. Org. Chem. 2008, 73, 2898
1,3-Diol Stereochemistry
Derivatization as Acetonide
13C
OH
NMR Analysis of acetonide carbons
OH
R2
R1
– 1,3-Diols are very common motifs in natural products
a 1,3-diol
– Determining the relative stereochemistry can be difficult because many
are on acyclic or macrocyclic carbon chains with unknown conformations
– Rychnovsky reasoned that converting the 1,3-diols to an acetonide would
make the system rigid
– Furthermore it was expected that syn-diols would prefer a chair
conformation, while anti-diols would prefer a twist-boat conformation
– These two would then lead to differences in the 13C NMR spectrum
R1
R2
R2
O
O
R1
O
R1
CH3
O
R2
O
R2
H
syn-1,3-diol acetonide
CH3
Chair
CH3
O
CH3
O
H
H
O
R1
anti-1,3-diol acetonide
Rychnovsky, S. D.; Rogers, B. N.; Richardson, T. I. Acc. Chem. Res. 1998, 31, 9–17
H
Twist-boat
1,3-Diol Stereochemistry
Derivatization as Acetonide
13C
NMR Analysis of acetonide carbons
R1
R2
R2
O
O
~93% below
100 ppm
O
R1
CH3
O
R1
R2
O
R2
H
syn-1,3-diol acetonide
CH3
Chair
O
CH3
O
CH3
O
H
H
~96% above
100 ppm
R1
anti-1,3-diol acetonide
Twist-boat
equatorial Me
axial Me
Chart adapted from: Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett. 1990, 31, 945–948
H
1,3-Diol Stereochemistry
Derivatization as Acetonide
13C
NMR Analysis of acetonide carbons
– Acetonides of polyproprionate polyols display similar chemical shift patterns
Me
(Me) H
R2
R1
(H) Me
O
O
R2
30.0 ± 0.15
O
R1
CH3
O
H
H
syn-polypropionate
polyol
R2
O
O
19.4 ± 0.21
R2
H
O
(Me) H
CH3
24.6 ± 0.76
(H) Me
O
R1
anti-polypropionate
polyol
some variance with stereochemistry,
98.1 ± 0.83 but most below 100 ppm
Chair
Me
R1
CH3
CH3
H
Twist-boat
100.6 ± 0.25 some variance, but most above 100 ppm
Evans, D. A.; Rieger, D. L.; Gage, J. R.Tetrahedron Lett. 1990, 31, 7099–7100.
Case Study
Macrolactins, Part 1
– The macrolactins were isolated from a deep sea bacterium and displayed interesting
biological activity; gross structure determined, but stereochemistry unknown
OH
OH
Me
O
O
1) Me3SiO
NSiMe3
Dihydromacrolactin F
2) TMSOTf, –78 ºC
(~0.7 mg)
O
O
HO
H3C
HO
O
CH3
CH3 = 99%
Dihydromacrolactin F (9 mg available)
O
13C
H3C
O
H3C
~0.1 mg, 25 min 13C NMR
13C NMR = 19.8, 30.2 ppm
OH
OR
CO2Me
O
O
1) H2, Pd/C
2) MeOH, HCl
Macrolactin B
(~9 mg)
OH
3) TMSOTf, –78 ºC
O
HO
HO
Macrolactin A (R = H)
Macrolactin B (R = β-glucosyl) (40 mg available)
H3C
O
CH3
CH3 = 99%
13C
H3C
H3C
O
13C
>0.1 mg
NMR = 24.8 ppm
Rychnovsky, S. D.; Skalitzky, D. J.; Pathirana, C.; Jensen, P. R.; Fenical, W. J. Am. Chem. Soc. 1992, 114, 671–677
NMR Spectroscopy
Quantitative NMR
Determining Ratios
• This is fairly trivial for lower ratios (under ~20:1)
• Integrating separated peaks of the same type works well
• Can be done for diastereomers, structural isomers, and mixtures of
compounds
example:
CO2Et
CO2Et
Cu(OAc)2•H2O (5 mol%)
(S)-SEGPHOS (5 mol%)
TMDS (1 equiv), THF, rt
1
CO2Et
CO2Et
57% yield
12:1 dr, 94% ee
Oswald,
L.;L.;
Peterson,
J. A.;
H. W.H.
Org.
10.1021/ol901560r
Oswald,C.C.
Peterson,
J.Lam,
A.; Lam,
W.Lett.
Org.2009,
Lett.DOI:
2009,
4504–4507.
12
NMR Spectroscopy
Quantitative NMR
Determining Ratios
• What about higher ratios?
• “Pure by NMR” generally understood to be 95% or above
• Thought to mean this is the number that can be distinguished from noise
• But 13C satellites account for 1.108% (ratio of 178.5:1)
1:1 mixture
Claridge, T. D. W.; Davies, S. G.; et al. Org. Lett. 2008, 10, 5433–5436.
NMR Spectroscopy
Quantitative NMR
Determining Ratios
• The 13C satellites can be used as an internal standard for diastereomeric ratios
up to 1000:1 (99.8% de)
• BUT you must run NMR experiment under quantitative conditions
a) use delays of 5T1 (about 25 s should be good); this ensures that >99%
of nuclei have relaxed fully before next pulse
b) other processing procedures should be used (see paper below)
• Collect spectrum and integrate the minor isomer relative to the 13C – 1H
satellite of the major isomer
• Integrate 3C – 1H satellite as 1
• When the height of the 13C – 1H satellite of the major isomer is greater than the
12C – 1H resonance of the minor, the ratio is >180:1 (>98.9%)
Claridge, T. D. W.; Davies, S. G.; et al. Org. Lett. 2008, 10, 5433–5436.
NMR Spectroscopy
Quantitative NMR
1.0000 13C
178.5 12C
= 9.7243 : 1
1 13C
18.3561 minor
% de =
8.7243
10.7243
Claridge, T. D. W.; Davies, S. G.; et al. Org. Lett. 2008, 10, 5433–5436.
= 81.35
NMR Spectroscopy
Quantitative NMR
1.0000 13C
178.5 12C
= 1113 : 1
1 13C
0.1603 minor
% de =
1112
1114
Claridge, T. D. W.; Davies, S. G.; et al. Org. Lett. 2008, 10, 5433–5436.
= 99.82
Absolute
Stereochemistry
(Enantiomers)
Seco, J. M.; Quinoa, E.; Riguera, R. Chem. Rev. 2004, 104, 17.
NMR Spectroscopy
Enantiomer Determination
Determination of Absolute Configuration
– Several different methods available
– Two main strategies:
1) chiral solvating agent – chiral solvent or additive (e.g. shift reagent)
– no covalent linkage
– very small differences in δ between the two enantiomers
– many times requires both enantiomers of substrate;
not always available
2) chiral derivatizing agent – chiral auxiliary
– covalent linkage
– diastereomeric derivatives made using two enantiomers of
auxiliary
– does not require both enantiomers of substrate
NMR Spectroscopy
Enantiomer Determination
Chiral Derivatizing Agents
The sign (+ or –) of
ΔδL1 and ΔδL2 allows
for determination of
configuration of A
O
F3C
Ph
O
OH
OMe
(R)-MTPA
(Mosher's Acid)
MeO
H
OH
Ph
(R)-MPA
(Derived from
mandelic acid)
– Two main derivitizing agents (both enantiomers needed)
– These are the most common, others available but will not discuss, see review
(same principles)
NMR Spectroscopy
Enantiomer Determination
Chiral Derivatizing Agents
O
F3C
Ph
O
OH
OMe
(R)-MTPA
(Mosher's Acid)
MeO
H
OH
Ph
(R)-MPA
(Derived from
mandelic acid)
1) Polar or bulky group to fix a particular conformation
2) A functional group to allow for attachment of substrate
3) A group able to produce an efficient and space-oriented
anisotropic effect
– Shields/deshields L1 and L2 in each diastereomer
NMR Spectroscopy
Enantiomer Determination
Mosher Analysis with MTPA
H
O
F3C
(R)-MTPA
Ph
O
C
L2
1H, 13C,
or 19F
1H, 13C,
or 19F
L1
OMe
H
HO
C
L2
CF3, C=O, C–H all in same plane
L1
H
O
(S)-MTPA
F3C
MeO
O
Ph
C
L2
L1
– Working conformational model, actual conformation may vary
– Ph of (R)–MTPA shields L2
– Ph of (S)–MTPA shields L1
NMR Spectroscopy
Enantiomer Determination
Modified Mosher Analysis
– Original method used 19F due to limitations in instruments
– Modified method uses 1H or 13C
HC
HB
Cδ
C δ'
HZ
Cγ
Cγ'
HY
Cβ
Cβ'
HX
HZ
HY
HX
Shields HA, B, C
HA
(OMe)
(Ph)
(R)–MTPA
Ph
OMe
(S)–MTPA
O
H
O
HC
OMTPA
Δδ < 0
(–)
C
H
Shields HX, Y, Z
CF3
Δδ > 0
(+)
Δδ = δS – δR
HB
HA
Majority of examples with alcohols, but has been used with other groups
(see review)
NMR Spectroscopy
Enantiomer Determination
HZ
Modified Mosher Analysis
HY
– Example
Δδ < 0
HX
(+0.011)
Me
Me
H
Mosher
Analysis
(–0.002)
H (–0.006)
(–0.006) H
H
(+0.008)
H
H (+0.022)
H (+0.030)
(–0.015) H
H (+0.084)
(–0.011) H
HO
H (+0.088)
OH
Me
HO
OMTPA
Me
(–0.034)
H
(–0.144)
Me
H
OMTPA
HO
(–)
Me
OH
C
H
(+)
HC
OMTPA
(–)
C
H
Δδ > 0
(+)
HB
HA
NMR Spectroscopy
Enantiomer Determination
HZ
Modified Mosher Analysis
Δδ < 0
HY
– Example
HC
OMTPA
(–)
Δδ > 0
C
(+)
H
HX
HA
(–0.007)
(–0.009) Me
(–0.009)
(+0.100)
Me
Mosher
Analysis
OH
Me
(–0.007) Me
H
H
MTPAO
H
OH
(–0.002) H
(+0.049)
(+0.111)
H (+0.009)
Me
(+0.047) Me
OH
H
C
(–)
(+)
Me
OH
OH
Me
(–0.058)
Me
Me
(–0.083)
Me
(–0.008)
Me
(+0.047)
(–0.004) Me
Me
Me
(+0.055)
OMTPA
HB
NMR Spectroscopy
Enantiomer Determination
HZ
Modified Mosher Analysis
Δδ < 0
HY
– Example
(–)
H
Mosher
Analysis
Me
Previous
Example
(–0.020)
H (–0.010) H
Me
(–0.021)
H
H (–0.288)
H (–0.131)
(–0.004) Me
H
OH
H (+0.003)
(+0.012) Me
OMTPA
(+0.014) H
H
H
(+0.011) H
Me
(+0.030)
(+)
H
(+)
(+0.097)
C
(–)
C
(+0.064)
H
OMTPA
(–)
C
H
HX
(–0.012)
(–0.006)
OMTPA
HC
OMTPA
Δδ > 0
(+)
HB
HA
NMR Spectroscopy
Enantiomer Determination
HZ
Modified Mosher Analysis
HY
– Conformational model will break down on occasion
Δδ < 0
(–)
OMe
(S)-MTPA-Cl
Et3N, DMAP
CH2Cl2
O
OMe O
OH
9
Me
O
H
-5
+10
+35
H Me
+10
Me
+10
-40
OMOM
+5
Values in Hz
-15
OMOM
OMe
Me
Me OMOM
(R)-MTPA ester
OMe
CF3
O
OMOM
Ph
(R)-MTPA-Cl
O
Et3N, DMAP
CH2Cl2
9
Me
O
OMe
OMe O
OMe
OMOM
OMe
Me OMOM
(S)-MTPA ester
-40
+40
H
O
Ph
OMe O
OMOM
O
OMe
O
9
Me OMOM
MTPA
+5
O
C
H
HX
CF3
O
HC
OMTPA
Δδ > 0
(+)
HB
HA
NMR Spectroscopy
Enantiomer Determination
HZ
Modified Mosher Analysis
HO
O
HO
CO2H
O
-0.12
-0.07
H
*
O
-0.03
H
OH
MTPAO
H +0.02
+0.01 +0.09
+0.01
+0.01
CO2H
O
HO
H
-0.03
O
O
HO
O
Me
OH
HO
OH
HO
O
HO
H
CO2H
O
O
O
H
OH
HO
CO2H
O
HO
O
O
HO
O
Me
HO
OH
C
H
-0.02
-0.06
O
HO
(–)
HX
-0.01
OH
Δδ < 0
HY
– Sometime need to make derivative
HC
OMTPA
Δδ > 0
(+)
HB
HA
NMR Spectroscopy
Enantiomer Determination
HZ
Modified Mosher Analysis
HY
– Diols possible as well
HX
HC
OMTPA
Δδ < 0
(–)
C
H
Δδ > 0
(+)
HB
HA
OMTPA
CO2H
OMTPA
(+0.01)
(+0.02)
OMTPA
(–0.07)
(+0.05)
(+0.02)
(–0.08)
(+0.00)
OMTPA
OH
OH
Case Study
Macrolactins, Part 2
OH
OMTPA
O
O
MTPACl
HO
O
O
MTPAO
HO
MTPAO
OMTPA
Dihydromacrolactin F
1) BSA
2) DIBAL-H
3) MTPACl
4) OsO4/NaIO4
5) NaBH4
O
MTPAO
CF3
MeO2C
Fragment A
Authentic samples of each fragment
were made and subjected to full
Mosher analysis and then compared
to degraded material
CO2Me
Fragment B
OMe
O
Ph
HO
MeO2C
1a) O3
1b) Jones Ox.
2) CH2N2
OMTPA
CO2Me
Fragment C
OH
Dihydromacrolactin F
(absolute configuration)
O
HO
O
confirmed by synthesis
J. Am. Chem. Soc. 1996,
118, 13095–13096
HO
Rychnovsky, S. D.; Skalitzky, D. J.; Pathirana, C.; Jensen, P. R.; Fenical, W. J. Am. Chem. Soc. 1992, 114, 671–677
Absolute
Stereochemistry
(a bit of UV)
Crews, P.; Rodríguez, J.; Jaspars, M. Organic Structure Analysis;
Oxford University Press: New York, 1998; pp 349–371.
Electromagnetic spectrum
Increasing Energy & Frequency
Increasing Wavelength
Taken from: http://www4.nau.edu/microanalysis/
Microprobe/Xray-Spectrum.html
Different effects observed
in different areas
• UV – electronic transitions
• IR – bond vibrations
• Microwaves – rotational motion
• Radiowaves – nuclear spin transitions
Overview of methods
Taken from: Crews, P.; Rodriguez, J.; Jaspars, M. Organic Structure Analysis; Oxford University Press: New York, 1998, p 5.
Intro to UV-Vis
• UV range: 200–400 nm
• Visible range: 400–800 nm
• Below 200 nm strongly absorbed by air (O2 & CO2) or solvents;
must use vacuum techniques to determine (commercial instruments
available)
• Observe electronic transitions: excitation of an electron from
bonding or nonbonding orbital to antibonding orbital
• Four types of transitions:
σ
σ∗
All occur below 200 nm
π
π∗
Some examples in normal range
n
π∗
Most common, but weak
n
σ∗
Few examples in normal range
Intro to UV-Vis
Useful Terminology:
• λmax – wavelength where maximum absorbance is observed
• Bathochromic (Red) shift – increasing λmax
• Hypsochromic (Blue) shift – decreasing λmax
• Molar extinction coefficient (ε) – gives an indication of the
peak intensity at λmax (how strongly it absorbs the light)
Beer-Lambert Law:
A = εlc
A = absorbance
ε = extinction coefficient
l = cell path in cm
c = concentration (M/L)
See Pretsch and Lambert
for tables
Chiral Chromophores
By using plane polarized light with UV wavelengths we can obtain
information about the stereochemistry of chiral molecules.
• Recall that chiral, molecules will rotate plane polarized light
[α] =
100α
lc
[Φ] = [α] (MW/100)
[α] = specific rotation at a given wavelength
c = concentration (g/100ml)
α = amount of rotation
[Φ] = molar rotation
l = cell path in dm
Measuring [α] or [Φ] over a range of wavelengths results in a optical rotatory
dispersion (ORD) plot – S-shaped curve
Plain curve – chiral compound with no chromophore
Cotton effect (CE) occurs with compounds containing
a chromophore
+ CE: peak is at higher λ than trough
– CE: peak is at lower λ than trough
Zero crossover occurs at λmax
Opposite enantiomers display opposite ORD curves
of identical magnitude
Chiral Chromophores
If circularly polarized light is used instead, a circular dichroism (CD)
plot is obtained instead
Left- and right-handed circularly polarized light is differentially absorbed
by chiral molecules and yields elliptically polarized light
[θ] = 3300Δε
[θ] = molar ellipticity
Δε = difference between ε of left- and right-handed circularly polarized light
Plotting [θ] or Δε vs. wavelength gives CD plot
– Gaussian curve
• can be positive or negative
• can be easier to interpret when more than one
chromophore is present
Sounds like an
easy way to
determine
stereochemistry.
But...
The Catch
How do you interpret the data!!!
Rules have been established to interpret the signs of the ORD
and CD spectra for carbonyl-containing molecules.
Allow for determining constitution, conformation, or configuration...
But you need to know two of these
So in order to determine the absolute configuration of a molecule
you need to know its structure (including any relative
stereochemistry) and know its conformation
Often need to have a known molecule of similar composition/
stereochemistry for comparison
Nonrigid molecules, need not apply
The Octant Rule
Developed from rigid cyclohexanones, but
has been extended to other systems
Begin by trisecting carbonyl with three planes
1) Substituents in back lower right and back upper left make + contribution
2) Substituents in back lower left and back upper right make – contribution
3) Substituents in any of the planes dividing the octants make no contribution
Review: Kirk, D. N. Tetrahedron 1986, 42, 777–818.
The Octant Rule
O
4
3
1
t-Bu
Me
The t-butyl group will
fix the conformation
t-Bu
H
Me
O
H
O
(3S,4R)-4-tert-butyl-3-methylcyclohexanone
Draw ring on octant
Has negative Cotton effect
Methyl is in back upper right quadrant
• consistent with negative CE
a
t-Bu
Me
C5
C4
C3
C6
O
C2
Add t-Bu and Me
C5
C4
C3
C6
O
C2
Konopelski, J. P.; Sundararaman, P.; Barth, G.; Djerassi, C. J. Am. Chem. Soc. 1980, 102, 2737–2745
The Octant Rule
H
O
3
5
10
1
H
5
Me
9
3
11a
C9
C6
C5
C10
C1
C4
O
C2
Predicted to have positive CE
Me
Me
H
O
C8
1
O
Me
C7
9
1
3
1
9
H
5
10
Me
11b
9
O
C1
C10
5
3
C9
C2
O
C5
C8
C4
C6
C7
Predicted to have negative CE
The Octant Rule
OH
Me
OH
Me
OH
OH
H
O
H
O
H
Cafestol
Me
Me
O
H
16
Known to have positive CE
H
18
The Exciton Chirality Method
What if the molecule of interest does not have a ketone or
another molecule with which to compare?
If two chromophores are located near each other, the excited state is delocalized
between the two – splitting the excited
state. This is known as exciton coupling
or Davydov splitting.
Excitations of the two split energy levels
generates CEs of mutually opposite
signs.
The signs of the first and second CE will
tell the spatial relationship between the
chromophores.
Often requires making a derivative to
install the chromophores.
The Exciton Chirality Method
HO
O
Me
Brevetoxin
O
O
H
Me
Me
O
Me
O
H
H
Me
O
O
O
H
Me
H
O
H
O
O
Br
O
O
Br
O H
H
O
O
O
H
O
Me
Lin, Y.-Y.; Risk, M.; Ray, S. M.; Van Engen, D.;
Clardy, J.; Golik, J.; James, J. C.; Nakanishi, K. J.
Am. Chem. Soc. 1981, 103, 6773–6775.
The Exciton Chirality Method
O
Sugar
OH
MeO
OH
Sugar =
H
O
MeO
O
OH
O
O
Phorbaside A
H
Cl
• Absolute configuration of
macrolide determined by
other means
• Correlations onto sugar
suggested L-configuration
but were weak
OH
MeO
O
MeO
HO
O
HO
1) HCl, MeOH, 100 ºC
2) Pyr, 2-napthoyl chloride
NCO
3) Pyr,
OH
L-rhamnose
O
N
H
O
O
MeO
O
OMe
MacMillan, J. B.; Xiong-Zhou, G.; Skepper, C. K.; Molinski, T. F. J. Org. Chem. 2008, 73, 3699–3706.
The Exciton Chirality Method
Do not necessarily need two aromatics
One partner can be an allylic or homoallylic olefin
230 nm: benzoate π→π*
Harada, N.; Iwabuchi, J.; Yokota, Y.; Uda, H.; Nakanishi, K. J. Am. Chem. Soc. 1981, 103, 5590–5591.
The Exciton Chirality Method
O
OH
Me
OMe
O
O
Ph
Me
OH
Me
O
O
Me
OMe
O
Me
OMe
O
O
H
N
O
OH
OMe H
O
OH
O
H
Me
OH
O
Me
Me
Ganefromycin α
1) NH4OH
2) CH2N2
3) EDC, DMAP
NMe2
HO2C
O
Ph
Me
OH
Me
OH
Me2N
O
NH
OMe H
H
N
O
O
OMe
O
O
H
Me
OH
O
Me
Me
Andersson, T.; Berova, N.; Nakanishi, K.; Carter, G. T. Org. Lett. 2000, 2, 919–922.
The Exciton Chirality Method
Configurations of Functional Groups
1-Aryl-1,2-diols
OH
B
HO
Ar
OH
R
R
OH
O
H
O
CHCl3, 4Å MS
B
negative chirality
Superchi, S.; Casarini, D.; Summa, C.; Rosini, C. J. Org. Chem. 2004, 69, 1685–1694.
Allylic Amines
O
O
O
H2N
N
O
O
Skowronek, P.; Gawronski, J. Tetrahedron Lett. 2000, 41, 2975–2977.
The Exciton Chirality Method
Configurations of Functional Groups
Chiral Sulfoxides
O
O
N
NH2
O
O
Ar (S) R
Or
O
O
Pb(OAc)4
O
CHCl3
N
O
Ar
S
R
N
Or
O
N
O
Ar
S
R
N
O
S
Ar (R) R
Three possible rotamers!
Major from modeling
Gawronski, J.; Grajewski, J.; Drabowicz, J.; Mikolajczyk, M. J. Org. Chem. 2003, 68, 9821–9822.