Hyperconjugation involving strained carbon-carbon bonds. Structural analysis of ester and ether derivatives and one-bond 13C- 13C coupling constants of α- And β-nopinol

Article abstract of DOI:10.1021/jo3020243

σ_C-C-σ*_C-O interactions involving the strained carbon-carbon bonds of α- and β-nopinol, and their ester and ether derivatives have been demonstrated in the solid state using the variable oxygen probe. These hyperconjugative interactions are manifested as a strong response of the C-OR bond distance to the electron demand of the OR substituent. Although the effects upon the donor C-C bond distances are not large enough to be measurable by X-ray crystallography, they do result in systematic and measurable effects on the ¹³C-¹³C one-bond coupling constants. For the donor C-C bond, coupling constants decrease, consistent with weakening of this bond, while the intervening C-C bond coupling constants increase, consistent with bond strengthening, as the electron demand of OR increases.

Full text of DOI:10.1021/jo3020243

Article
pubs.acs.org/joc
Hyperconjugation Involving Strained Carbon−Carbon Bonds.
Structural Analysis of Ester and Ether Derivatives and One-Bond
13C−13C Coupling Constants of α- and β‑Nopinol
Shinn Dee Yeoh, Colin E. Skene, and Jonathan M. White*
School of Chemistry and Bio-21 Institute, University of Melbourne, Parkville, Victoria 3010, Australia
S
* Supporting Information
ABSTRACT: σC−C−σ*C−O interactions involving the strained carbon−carbon
bonds of α- and β-nopinol, and their ester and ether derivatives have been
demonstrated in the solid state using the variable oxygen probe. These
hyperconjugative interactions are manifested as a strong response of the C−OR
bond distance to the electron demand of the OR substituent. Although the effects
upon the donor C−C bond distances are not large enough to be measurable by X-
ray crystallography, they do result in systematic and measurable effects on the
13C−13C one-bond coupling constants. For the donor C−C bond, coupling constants decrease, consistent with weakening of this
bond, while the intervening C−C bond coupling constants increase, consistent with bond strengthening, as the electron demand
of OR increases.
contributions of the C+−OR valence bond form to the ground-
INTRODUCTION
■
state structure of the molecule containing this fragment.
The electron demand of a given substituent (OR) is
conveniently quantified by the pKa value for the parent acid
(ROH), and a linear relationship between the C−OR bond
distance and pKa (ROH) has been established. The slope is
sensitive to the effects of electron donation into the C−OR σ*
antibonding orbital. The presence of good donor orbitals
vicinal and antiperiplanar to the C−O bond results in a strong
response of the C−OR bond distance to the electron demand
of OR. This reflects increased stabilization of the cation part of
the valence bond form C+−OR. For example, plots of C−OR
bond distance vs pKa (ROH) constructed for 1,8 2,10 and 311
gave the following relationships:
Interactions between donor and acceptor orbitals within a
molecular framework have a profound effect on fundamental
molecular properties including conformational preferences and
chemical reactivity.1 These interactions are dependent on the
intrinsic donor and acceptor abilities of the orbitals involved,
and upon their relative, spatial relationships. These interactions
often give rise to unusual chemical and spectroscopic
properties, and because of their dependence on stereo-
chemistry, they are referred to as stereoelectronic effects.2
Hyperconjugation (or σ−π conjugation)3 is a particularly
important type of donor/acceptor interaction between a filled σ
bonding orbital (σC−X) and an electron-deficient orbital such as
a carbocation p orbital (Figure 1).
Figure 1. Hyperconjugation between σC−X and a carbocation p orbital.
The ease at which a C−X σ-bond donates electrons by
hyperconjugation is an important fundamental property often
referred to as the σ-donor ability. Information on the relative σ-
donor abilities of a range of C−X bonds has been obtained by
various means including Hammett plots,4 measurement of the
charge-transfer bands in donor−acceptor complexes,5 19F and
13C NMR spectroscopy,6 and ab initio calculations on suitable
model systems.7 An X-ray structural method for obtaining
information on σ-donor abilities was introduced by Kirby and
Jones and coined as the variable oxygen probe.8,9 The C−O
bond distance in the C−OR fragment increases with increasing
electron demand of the OR substituent, reflecting increasing
1: rC−O (Å) = 1.493 − (6.49 × 10−3)pKa(ROH)
R2 = 0.985
(1)
2: rC−O (Å) = 1.502 − (5.30 × 10−3)pKa(ROH)
R2 = 0.986
(2)
Received: September 30, 2012
© XXXX American Chemical Society
A
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Scheme 1. Rearrangement of α- and β-Nopinyl Brosylate Derivatives
3: rC−O (Å) = 1.479 − (2.86 × 10−3)pKa(ROH)
R2 = 0.985
C−OR bond distance in these derivatives to the electron
demand of the oxygen substituent (OR) give a measure of σ-
donor abilities of the two types of C−C bond in the four-
membered ring. Of interest also is whether observable
structural effects consistent with the early stages of the
rearrangement (Scheme 1) manifest in the carbon frameworks
of 5 and 6 in response to increasing electron demand of the
OR.
(3)
A strong response of the C−OR bond distance to the
electron demand of OR is demonstrated for 1 which has an
oxygen lone pair (nO) orbital antiperiplanar to the OR
substituent (this is the basis of the well-known anomeric
effect);12 a strong response is also observed for 2 which has a
C−Si bond antiperiplanar to the OR substituent (this is the
basis of the silicon β-effect),13 but a weaker response is obvious
in 3 which has a σC−C bonding orbital, which is a weaker donor
orbital situated antiperiplanar to the OR bond. This structural
RESULTS AND DISCUSSION
■
Treatment of commercially available (1R,5S)-(+)-nopinone (7)
with sodium borohydride gives a quantitative conversion to α-
nopinol 5, while reduction using sodium in wet ether affords a
ca. 1:1 mixture of α- and β-nopinol 5 and 6 (Scheme 2);
separation of the two isomers was readily achieved by dry-flash
chromatography on silica gel.
technique has also been applied to the determination of σC−S
,
14
σC−Se, σC−Te
,
and remote πCC donor abilities.15,16
Examples of participation of C−C or C−H σ bonds resulting
in carbocation stabilization and rearrangement are widespread
in organic chemistry, particularly in terpine chemistry where the
geometry of the molecule is often particularly favorable.17,18
Examples include the pinacol rearrangement, the acid-catalyzed
conversion of pinene hydrochloride to bornyl chloride,19 and
the rearrangement of camphene hydrochloride to isobornyl
hydrochloride.17 Of interest to us is rearrangement of the α-
and β-nopinol system. For example α- and β-nopinyl
bromobenzenesulphonates 1 and 2 undergo a particularly facile
rearrangement to endocamphenilyl 3 and apobornyl bromo-
benzenesulphonates 4, respectively (Scheme 1).20 Rearrange-
ment occurs so rapidly that attempts to prepare the brosylate
derivatives 1 and 2 from α- and β-nopinol 5 and 6 under
standard conditions leads to the isolation of the rearrangement
products 3 and 4 in quantitative yield. The rearrangement
undoubtedly occurs by concerted participation of a strained C−
C bond of the four-membered ring which is antiperiplanar to
the leaving group leading to the formation of a nonclassical ion
intermediate and capture of the intermediate by the brosylate
anion leading to the rearranged products.
Scheme 2. Synthesis of α- and β-Nopinol by Reduction of
Nopinone
The alcohols were converted to the ester and ether
derivatives 5a−h and 6a−h using standard techniques; these
derivatives and the pKa values for their corresponding parent
acids are summarized in Table 1. Attempts to prepare more
electron-demanding sulfonate esters of 5 and 6 (including
mesylate, tosylate, and nosylate) resulted in Wagner−Meerwein
rearrangement into the corresponding analogues of 3 and 4.
The facile rearrangement of 1 and 2 reflects the strong
propensity of the strained C−C bond of the four-membered
ring to participate in the formation and stabilization of the
adjacent carbenium ion.21 The presence of strain raises the
energy of the σC−C electrons, resulting in a better energy match
with the developing carbenium ion p orbital; furthermore,
strain is ultimately released as a result of participation.22
We were interested in determining the σ-donor abilities of
the strained C−C bonds of α- and β-nopinol (5 and 6) from
analysis of accurate crystal structures of ester and ether
derivatives of varying electron demand. The responses of the
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Table 1. Ether and Ester Derivatives of α- and β-Nopinol
pKa (ROH)23
R
α
β
7.15
4.16
3.46
3.43
2.85
2.82
2.17
1.43
4-NO2C6H4
5a
5b
5c
5d
5e
5f
6a
6b
6c
6d
6e
6f
2-Naphthoyl
3-NO2C6H4CO
4-NO2C6H4CO
3,5-(NO2)2C6H3CO
3,4-(NO2)2C6H3CO
2-NO2C6H4CO
2,4-(NO2)2C6H3CO
5g
5h
6g
6h
Figure 2. Thermal ellipsoid plot for α-nopinyl 2-nitrobenzoate (5g).
Ellipsoids are at the 30% probability level.
Crystals of suitable quality for X-ray analysis were obtained
for the α-nopinyl derivatives 5a and 5e−g, while the only
suitable crystal data obtained for the β-nopinyl derivatives were
for 6a−c. Data of insufficient quality for this analysis due to
crystal twinning and/or thermal disorder were obtained for 5,
5d, 5h, and 6d.
Table 3. Selected Bond Distances (Å), Angles (deg), and
Dihedral Angles (deg) for the β-Nopinyl Derivatives 6a−c
6a
6b
6c
Data for 5a, 5e−g, and 6a−c were obtained at 130 K to
minimize the effects of thermal libration. Derivatives 5e and 5f
crystallized with two independent molecules in the asymmetric
unit. Selected bond distances, angles, and dihedral angles for
the α-isomers 5a and 5e−g are presented in Table 2, while a
thermal ellipsoid plot for 5g, with the numbering system
representative of all α-isomers, is presented in Figure 2.
Corresponding data for the β-nopinyl derivatives 6a−c are
presented in Table 3, and a thermal ellipsoid plot for 6c is
presented in Figure 3.
In the α-nopinyl derivatives 5a and 5e−g the C2−C3 and
C3−C4 bonds have essentially eclipsed conformations. As a
result, the two six-membered rings, defined by (C1−C6) and
(C1−C5, C7), adopt basically identical conformations which
are best described as being midway between idealized chair and
boat forms, referred to as a sofa conformation.24 Associated
with the eclipsed conformations about C2−C3 and C3−C4 is
an opening up of the valence angles (Table 2): C1−C2−C3,
mean 113.5°; C2−C3−C4, mean 115.1°; C3−C4−C5, mean
112.5° from the standard tetrahedral angle (109.5°).
C2−O1
C1−C2
C6−C1
1.455(3)
1.504(3)
1.559(3)
1.471(2)
1.517(2)
1.560(2)
1.467(2)
1.511(2)
1.563(2)
C1−C2−C3
C2−C3−C4
C3−C4−C5
C1−C2−C3−C4
C2−C3−C4−C5
C6−C1−C2−C3
C6−C5−C4−C3
O1−C2−C1−C7
O1−C2−C1−C6
111.3(2)
112.4(1)
111.5(1)
114.4(2)
110.8(2)
24.8(3)
115.0(2)
112.5(1)
13.0(2)
114.0(1)
111.4(1)
26.2 (2)
−23.7(3)
−60.8(3)
59.9(3)
−12.3(2)
−55.3(2)
53.7(2)
−24.5 (2)
−62.5(2)
59.6(2)
−82.3(2)
−176.7(2)
−78.2(2)
−173.8(8)
−83.7(1)
−178.3(1)
In the β-isomers 6a−c; however, these bonds are more
“gauche-like”: 6a, C1−C2−C3−C4 = 24.8(3)°; C2−C3−C4−
C5 = −23.7(3)°; 6b, C1−C2−C3−C4 = 13.0(2)°; C2−C3−
C4−C5 = −12.3(2)°; 6c, C1−C2−C3−C4 = 26.2(2)°; C2−
C3−C4−C5 = −24.5(2)° (Table 3). The resulting six-
membered ring defined by C1−C6 is a flattened chair, while
Figure 3. Thermal ellipsoid plot for β-nopinyl 3-nitrobenzoate (6c).
Ellipsoids are at the 30% probability level.
Table 2. Selected Bond Distances (Å), Angles (deg), and Dihedral Angles (deg) for the α-Nopinyl Derivatives
a
a
5e
5f
5a
M1
M2
M1
M2
5g
C2−O1
C1−C2
C1−C7
1.459(2)
1.516(2)
1.552(2)
1.469(3)
1.492(4)
1.548(4)
1.473(3)
1.515(4)
1.539(4)
1.475(3)
1.504(4)
1.556(3)
1.472(3)
1.507(4)
1.550(3)
1.475(3)
1.517(3)
1.547(3)
C1−C2−C3
C2−C3−C4
C3−C4−C5
C1−C2−C3−C4
C2−C3−C4−C5
C6−C1−C2−C3
C6−C5−C4-C3
O1−C2−C1−C7
O1−C2−C1−C6
113.3(1)
113.2(3)
113.8(3)
113.6(2)
113.8(2)
113.4(2)
115.1(1)
112.9(1)
−5.2(2)
2.0(2)
115.4(3)
112.0(3)
−3.9 (4)
0.8(4)
114.8(3)
112.7(3)
−2.8(4)
0.0(5)
115.4(2)
112.0(2)
0.5(3)
115.0(2)
112.6(2)
−3.7 (3)
0.7(3)
115.0(2)
112.8(2)
−5.2 (3)
2.7 (3)
−3.8(3)
−45.2(3)
52.0(3)
171.8(2)
76.9(2)
−42.3(2)
48.8(2)
172.9(1)
78.1(1)
−43.7(4)
50.1(4)
−43.6(4)
49.8(5)
174.7(3)
79.4(3)
−43.3(2)
49.5(3)
−42.6(2)
48.0(2)
172.6(3)
76.7(3)
170.9(2)
76.0(2)
172.6(2)
77.9(2)
a
Derivatives 5e and 5f were crystallized with two independent molecules (M1 and M2) in the asymmetric unit.
C
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the six-membered ring defined by C1−C5 and C7 is in a
flattened boat conformation. The associated bond angles
(Table 3) C1−C2−C3, mean 111.7°, C2−C3−C4, mean
114.4°, and C3−C4−C5, mean 111.5° are relaxed toward the
preferred tetrahedral value compared with the α-nopinyl
derivatives.
The conformation about C1−C2 and the C5−C4 bonds also
differs significantly between the α- and β-derivatives. For the α-
derivatives 5a and 5e−g the average C6−C1−C2−C3 and C6−
C5−C4−C3 dihedral angles are −43.5° and 49.7°, respectively
(Table 2), whereas for the β-nopinyl derivatives 6a−c the
corresponding dihedral angles are −59.5° and 57.7° (Table 3).
The differences in the conformations of the [3.1.1] bicyclic
core for the α- and β-nopinyl derivatives very likely arise from
the minimization of the nonbonded repulsion between the
endo-methyl (C9) and the oxygen substituent on C2. In the α-
nopinyl derivatives, tipping of the C2-oxygen substituent away
from the endo-methyl (C9) is very likely responsible for
flattening of the six-membered ring.
The dihedral angle C7−C1−C2−O1 for the α-nopinyl
derivatives 5a and 5e−g varied from 170.9 to 174.7° (Table 2)
and can be considered to be essentially antiperiplanar. This
geometry allows for close to optimum overlap between the
strained C7−C1 σ-bonding orbital and the O1−C2 σ*-
antibonding orbital (Figure 4, compound 5). In the β-nopinyl
Figure 5. Plot of rC2−O1 vs pKa(ROH) for the α-nopinyl derivatives 5a
and 5e−5g. (The averages of both M1 and M2 values from 5e and 5f
respectively have been used.)
derivatives of cyclopropylmethanol 7 for which a slope of −4.60
was obtained.25
The data set of C2−O1 bond distance and pKa(ROH) for β-
nopinyl derivatives 6a−c can be found in Table 3 and is
presented graphically in Figure 6.
From the plot in Figure 6, the following relationship between
C2−O1 bond distance and the electron demand of the ester
substituent for the β-nopinol derivatives is obtained:
r
C−O (Å) = 1.483 − (3.90 × 10−3)pKa(ROH)
R2 = 0.832
Figure 4. σC−C−σ*C−O interaction for the α-nopinyl and β-nopinyl
derivatives.
(5)
While eq 5 (slope = −3.90) suggests a stronger donor ability
for the antiperiplanar C6−C1 bonds, it is based on a small data
set with more scatter and, at best, gives a very qualitative
indication of the σ-donor ability of the C6−C1 bond.
derivatives 6a−c it is the C6−C1−C2−O1 dihedral angle
(Table 3) that is essentially antiperiplanar. Thus, the strained
C6−C1 σ-bonding orbital is optimally aligned with the C2−O1
antibonding orbital (Figure 4, compound 6).
The structural effects of the σC−C−σ*C−O interaction in the
α-nopinyl derivatives 5a and 5e−g are best demonstrated from
a plot of the C2−O1 bond distances vs the pKa value for the
parent acids for each derivative (Table 1), which is shown in
Figure 5.
The structural data obtained for structures 5a, 5e−g, and
6a−c clearly demonstrate the dependence of the C2−OR bond
distance on the electron demand of the oxygen substituent
(OR) and are consistent with relatively strong σC−C−σ*C−O
interactions involving the strained carbon−carbon bonds of the
four-membered rings. However, the carbon−carbon bond
distances (particularly those involved in the σC−C−σ*C−O
interaction), in both α- and β-nopinol derivatives do not vary
significantly with the electron demand of the OR group (Tables
2 and 3), it appears that the effects are too small, and small
variations in these distances may simply reflect subtle
differences in the crystal packing environments for these
structures. Also, it has been noted before that structural effects
on the σ-donor bond participating in a σ−σ* interaction are
much less that the effects on the σ* acceptor bond.10
From this plot the following relationship between C2−O1
bond distance and the electron demand of the ester substituent
is obtained:
r
C−O (Å) = 1.482 − (3.20 × 10−3)pKa(ROH)
R2 = 0.975
(4)
The slope of eq 4 (−3.20 (aside from the exponent)) is a
measure of the σ-donor ability of the C7−C1 bond of the α-
derivatives (which is antiperiplanar to the C2−OR bond).
Thus, the cyclobutane (C7−C1) bond in the α-nopinyl
derivatives is a stronger σ-donor when compared to the
unstrained C−C bonds of the cyclohexane derivative 3, for
which a gradient of −2.86 was obtained (eq 3) from the
application of variable oxygen probe. On the other hand, the
cyclobutane C−C bond in the α-nopinyl derivatives is a weaker
donor than the more highly strained cyclopropane C−C bond
as indicated by application of the variable oxygen probe to
The apparently small effect on the C−C distances and the
relatively small number of crystalline derivatives prompted us to
investigate the effects that varying electron demand of the OR
substituent would have on the 13C−13C one-bond coupling
constants. 13C−13C one-bond coupling constants have been
shown to vary inversely with carbon−carbon bond distances26
and are sensitive to hyperconjugative effects.25 This solution
b
phase alternative technique would complement the structural
information provided by the X-ray analysis and has the very real
advantage of not requiring good quality crystals.
D
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Figure 6. Plot of rC2−O1 vs pKa(ROH) for the β-nopinyl derivatives 6a−c.
The one-bond 13C−13C (1JC,C) scalar coupling constants are
obtained via INADEQUATE (incredible natural abundance
double quantum transfer experiment).27 The assignment of all
the carbons of α- and β-nopinol 5 and 6 was achieved by
standard two-dimensional techniques, and the substituted
derivatives were assigned by comparison and by matching up
of the 13C−13C coupling constants. Each 13C−13C coupling
constant is determined twice, and these values are averaged.
Coupling constants obtained for α- and β-nopinol derivatives
are presented in Tables 4; atom numbering is that which is
shown in Figures 2 and 3.
Two clear and distinct trends emerged from the analysis of
these 13C−13C coupling constant values for α- (5a−h) and β-
nopinyl derivatives (6a−h). These trends are best interpreted
by the following relationships between the 13C−13C coupling
constant and pKa values of ROH for the α-nopinol derivatives
(eqs 6 and 7) and β-nopinol derivatives (eqs 8 and 9)
1 13
J C−13C (Hz) = 26.697 + (2.48 × 10−1)pKa(ROH)
R2 = 0.951 (C7−C1)
(6)
1 13
J C−13C (Hz) = 38.168 − (1.91 × 10−1)pKa(ROH)
R2 = 0.933 (C1−C2)
Table 4. 13C−13C Coupling Constants for α-Nopinol
Derivatives 5 and 5a−h and β-Nopinol Derivatives 6 and
(7)
1 13
J C−13C (Hz) = 27.163 + (2.33 × 10−1)pKa(ROH)
a
6a−h
R2 = 0.969 (C6−C1)
(8)
pKa (ROH)
compd
J (1,2)
J (7,1)
compd
J (1,2)
J (6,1)
16
5
36.9
36.9
37.2
37.5
37.5
37.6
37.6
37.8
38.0
26.9
28.4
27.9
27.6
27.6
27.3
27.3
27.3
27.0
6
36.6
36.7
37.2
37.4
37.4
37.4
37.6
37.6
37.6
28.2
27.3
27.9
28.0
28.0
27.8
27.9
27.7
28.0
1 13
J C−13C (Hz) = 37.947 − (1.70 × 10−1)pKa(ROH)
7.15
4.16
3.46
3.43
2.85
2.82
2.17
1.43
5a
5b
5c
5d
5e
5f
6a
6b
6c
6d
6e
6f
R2 = 0.940 (C1−C2)
(9)
The slopes of plots for eq 6 and 8 and (2.48 and 2.33 (aside
from the exponent)) give an indication of the sensitivity of the
13C−13C coupling constants of the antiperiplanar bonds of the
α-nopinol (5a-5h) and β-nopinyl derivatives (6a-6h) to the
electron demand of the OR substituent, and importantly
demonstrate that as the electron demand increases (decreasing
pKa (ROH)) then the coupling constants decrease.
5g
5h
6g
6h
a
All spectra recorded in CDCl3 at 298 K. 1JCC coupling constant (Hz)
values 0.2 Hz.
In contrast the 13C−13C coupling constant for the C1−C2
bond (eq 7 and 9) in the α- and β-nopinyl derivatives increase
with increasing electron demand of the OR substituent. These
trends are consistent with the presence of σC−C−σ*C−O
interaction between the antiperiplanar carbon−carbon bond
and the C2−O1 antibonding orbital. This type of interaction
will consequently impart some double-bond character into the
C1−C2 bond as depicted in Figure 9 while weakening the
antiperiplanar bond (C7−C1 for α- and C6−C1 for β-nopinol
derivatives). The contributions of the double-bond no-bond
resonance form increases with increasing electron demand of
OR substituent.
The data in Tables 4 were used to construct plots of selected
13C−13C coupling constants for the ester and ether derivatives
5a−h and 6a−h vs the electron demand of the −OR
substituent as quantified by pKa (ROH). The coupling
constants for the parent nopinols 5 and 6 were not used for
this study as the effects of the oxygen lone pair delocalization
into neighboring C−C bonds would make it impossible to
delineate the effects of lone pair delocalization from the effects
of hyperconjugation.28 Plots of the 13C−13C coupling constants
for the antiperiplanar bonds of the cyclobutane ring for α-and
β-Nopinol vs pKa (ROH) are presented in Figure 7. While
plots of 13C−13C coupling constants of the C1−C2 bonds vs
pKa (ROH) for the α-and β-nopinol derivatives 5a−h and 6a−
h are presented in Figure 8.
CONCLUSION
■
Strong σC−C−σ*C−O interactions involving the strained
carbon−carbon bonds of α- and β-nopinol and their derivatives
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13
13
Figure 7. ( ) Plot of C− C coupling constant C7−C1 vs pKa(ROH) for α-nopinyl derivatives 5a−5h. ( ) Plot of 13C−13C coupling constant
■
▲
C6−C1 vs pKa(ROH) for β-nopinyl derivatives 6a−h.
13
13
Figure 8. ( ) Plot of C− C coupling constant C1−C2 vs pKa(ROH) for α-nopinyl derivatives 5a−h. ( ) Plot of 13C−13C coupling constant
■
▲
C1−C2 vs pKa(ROH) for β-nopinyl derivatives 6a−h.
the 13C−13C one-bond coupling constants as a function of
electron demand for those vicinal bonds involved in this
interaction. Thus the donor C−C bond coupling constants
decrease, consistent with weakening of this bond, while the
intervening C−C bond coupling constants increase, consistent
with bond strengthening, as the electron demand of OR
increases.
Figure 9. σC−C−σ*C−O interaction between C7−C1 donor orbital and
the C2−O1 antibonding orbital in α-nopinol derivatives.
EXPERIMENTAL SECTION
Crystallography. Intensity data were collected on a CCD
diffractometer using either Cu Kα radiation (graphite crystal
■
are demonstrated in the solid state using X-ray crystallography,
and these are manifested as a strong response of the C−OR
bond distance to the electron demand of the OR substituent,
however effects upon the C−C bonds are not large enough to
be measurable by this technique. The σC−C−σ*C−O interaction,
however, does result in systematic and measurable effects on
monochromator λ = 1.54184) or with Mo Kα radiation (graphite
crystal monochromator λ = 0.71073). The temperature during data
collections was maintained at 130.0(2) K.
Crystal data for 5: C9H16O, M = 140.22, T = 130.0(2) K, λ =
0.71069, trigonal, space group P3(2) a = 10.515(2) Å, c =6.565(3) Å,
V = 628.6(3) Å3, Z = 3, Dc = 1.111 mg M−3, μ(Mo Kα) 0.070 mm−1,
F
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F(000) = 308, crystal size 0.4 × 0.08 × 0.07 mm; 3184 reflections
measured, 1215 independent reflections (Rint = 0.0761), twin law:
−1.00 −1.00 0.00 0.00 1.00 0.00 0.00 0.00 −1.00, BASF 0.49, the final
R was 0.0421 [I > 2σ(I)] and wR(F2) was 0.0780 (all data) (without
twin correction: R = 0.21 [I > 2σ(I)] and wR(F2) was 0.35).
Crystal data for 5a: C15H19NO3, M = 261.31, T = 130.0(2) K, λ =
0.71069, orthorhombic, space group P212121, a = 10.2043(6) Å, b =
11.1772(7) Å, c =12.1590(8) Å, V = 1386.8(2) Å3, Z = 4, Dc = 1.252
mg M−3, μ(Mo Kα) 0.087 mm−1, F(000) = 560, crystal size 0.5 × 0.45
× 0.4 mm; 8822 reflections measured, 3170 independent reflections
(Rint = 0.0181), the final R was 0.0380 [I > 2σ(I)] and wR(F2) was
0.1010 (all data).
Crystal data for 5e: C16H18N2O6, M = 334.32, T = 130.0(2) K, λ =
0.71069, orthorhombic, space group P212121, a = 9.7057(8) Å, b =
11.5435(9) Å, c =29.504(2) Å, V = 3305.6(5) Å3, Z = 8, Dc = 1.344 mg
M−3 μ(Mo Kα) 0.104 mm−1, F(000) = 1408, crystal size 0.45 × 0.4 ×
0.06 mm; 17565 reflections measured, 5806 independent reflections
(Rint = 0.0965), the final R was 0.0438 [I > 2σ(I)] and wR(F2) was
0.0731 (all data).
Crystal data for 5f: C16H18N2O6, M = 334.32, T = 130.0(2) K, λ =
0.1.5418, monoclinic, space group P21, a = 7.70798(2) Å, b =
32.9160(6) Å, c =7.4809(2) Å, β = 113.621(3)°, V = 1597.27(7) Å3, Z
= 4, Dc = 1.390 mg M−3, μ(Cu Kα) 0.907 mm−1, F(000) = 704, crystal
size 0.6 × 0.28 × 0123 mm; 7512 reflections measured, 4231
independent reflections (Rint = 0.0278), the final R was 0.0353 [I >
2σ(I)] and wR(F2) was 0.0957 (all data).
Crystal data for 5g: C16H19NO4, M = 289.32, T = 130.0(2) K, λ =
0.71069, monoclinic, space group P21, a = 7.7048(7) Å, b = 9.7610(9)
Å, c = 9.6507(9) Å, β = 98.352(2)°, V = 718.1(1) Å3, Z = 2, Dc = 1.338
mg M−3, μ(Mo Kα) 0.096 mm−1, F(000) = 308, crystal size 0.4 × 0.4
× 0.3 mm; 3810 reflections measured, 2011 independent reflections
(Rint = 0.0339), the final R was 0.0334 [I > 2σ(I)] and wR(F2) was
0.0804 (all data).
a solution of alcohol (1.0 equiv) in anhydrous THF. 4-Fluoroni-
trobenzene (1.05 equiv) was then added to this mixture and the
reaction stirred at rt for 2 h. After quenching by addition of water (1
mL), the solvent was removed in vacuo. The residue was dissolved in
Et2O (20 mL), washed with water (2 × 10 mL), dried (MgSO4),
filtered, and concentrated in vacuo to yield a black oil. Starting material
was removed by column chromatography (gradient system of Et2O/
petroleum ether) to afford the required compound as dark brown oil.
This compound was then later recrystallized to produce good quality
crystals for X-ray crystallography.
General Procedure B: Esterification of Alcohols Using
Benzoyl Chlorides. The alcohol was stirred in anhydrous solvent
(DCM, Et2O, or THF) and pyridine (1 mL) for 30 min and then
treated with benzoyl chloride (1.05 equiv), which was added all at
once at 0 °C. The reaction was stirred at rt for 24 h or until
precipitation of pyridine hydrochloride was complete. Water was
added and the mixture stirred for a further 30 min to hydrolyze the
remaining acid chloride. The mixture was then extracted with Et2O,
and the combined organic extracts were washed with saturated
aqueous copper sulfate (CuSO4) solution, water, saturated aqueous
sodium hydrogen carbonate (NaHCO3) solution, and water, dried
(MgSO4), filtered, and concentrated in vacuo to generally afford solids
of the desired compound which were subsequently recrystallized to
produce crystals of X-ray quality.
α-Nopinol (5). (+)-Nopinone (1 mL, 1.02 g, 7.24 mmol, 1 equiv)
was dissolved in tetrahydrofuran (10 mL) and treated with sodium
borohydride (0.55 g, 14.45 mmol, 2.0 equiv) at 0 °C under nitrogen.
Water (75 mL) was added dropwise over 1 h to the solution, and the
resulting mixture was stirred at 25 °C for 18 h. The resultant mixture
was diluted with water (5 mL) and then extracted with Et2O. The
combined organic extracts were washed with water, dried (MgSO4),
filtered, and concentrated in vacuo to give (1R,2R,5S)-(−)-α-nopinol
in the form of a white crystalline solid (0.42 g, 83%). 1H NMR: δ 4.27
(1H, ddd, J = 9.6, 3.5, 3.5 Hz), 2.33−1.58 (8H, m), 1.21 (3H, s), 1.10
(3H, s), 0.83 (1H, d, J = 9.9 Hz).30 13C NMR: δ 73.2 (CH-OH), 48.0
(CH), 40.9 (CH), 37.4 (quaternary C), 28.2 (CH2), 27.3 (CH3), 25.7
(CH2), 24.7 (CH2), 22.5 (CH3). IR νmax: 3379, 2911, 1457, 1382, 1074
cm−1.
Crystal data for 6a: C16H19NO3, M = 261.31, T = 130.0(2) K, λ =
1.5418, orthorhombic, space group P212121, a = 10.6165(7) Å, b =
10.959(1) Å, c =11.849(1) Å, V = 1378.6(2) Å3, Z = 4, Dc = 1. 259 mg
M−3, μ(Cu Kα) 0.710 mm−1, F(000) = 560, crystal size 0.4 × 0.2 × 0.1
mm; 4874 reflections measured, 2349 independent reflections (Rint
=
0.0491), the final R was 0.0373 [I > 2σ(I)] and wR(F2) was 0.0832 (all
data).
β-Nopinol (6). Et2O (25 mL), water (0.30 mL), and (+)-nopinone
(0.51 mL, 0.50 g, 3.62 mmol) were stirred in ice when sodium metal
(0.38 g, 0.016 mol) was added over 15 min. The mixture was stirred at
0 °C for 4 h. The reaction mixture was slowly quenched with EtOH
and then water. When the sodium metal was fully dissolved, the
organic extracts were washed with water and Et2O, dried with MgSO4,
filtered, and concentrated to afford an approximately 1:2 mixture of α-
(5) and β-nopinol (6). Separation was achieved by column
chromatography on silica gel (gradient system of Et2O/hexane, Rf =
0.88 for α-nopinol (5) and Rf = 0.75 for β-nopinol (6). The β-nopinol
Crystal data for 6b: C20H22O2, M = 294.38, T = 130.0(2) K, λ =
1.5418, monoclinic, space group C2, a = 18.5270(3) Å, b = 7.4890(1)
Å, c =11.4673(2) Å, β = 96.453(2)°, V = 1580.99(4) Å3, Z = 4, Dc =
1.237 mg M−3, μ(Cu Kα) 2.470 mm−1, F(000) = 632, crystal size 0.36
× 0.28 × 0.07 mm, 4698 reflections measured, 2212 independent
reflections (Rint = 0.0219) the final R was 0.0351 [I > 2σ(I)] and
wR(F2) was 0.0986 (all data).
Crystal data for 6c: C16H19NO4, M = 289.32, T = 130.0(2) K, λ =
0.71069, monoclinic, space group P21, a = 7.2654(6) Å, b = 8.3363(7)
Å, c = 12.6898(11) Å, β = 105.698(1)°, V = 739.9(1) Å3, Z = 2, Dc =
1.299 mg M−3, μ(Mo Kα) 0.093 mm−1, F(000) = 308, crystal size 0.5
× 0.45 × 0.35 mm, 3879 reflections measured, 2467 independent
reflections (Rint = 0.0117) the final R was 0.0299 [I > 2σ(I)] and
wR(F2) was 0.0768 (all data).
1
(6) was obtained as a pale yellow oil (0.13 g, 25%). H NMR: δ 4.10
(1H, ddd, J = 7.2, 7.2, ca. 1.9 Hz), 2.61 (1H, bs), 2.06−1.48 (8H, m),
1.21 (3H, s), 1.18 (3H, s). 13C NMR: δ 69.7 (CH−OH), 48.0 (CH),
40.5 (CH), 39.4 (quaternary C), 26.6 (CH3), (CH2), 25.7 (CH2), 23.2
(CH2), 22.5 (CH2), 19.9 (CH3). IR νmax: 3343, 2912, 1462, 1367, 1018
cm−1. HRMS (ESI): calcd C9H16O [M + Na]+ 163.10934, found [M +
Na]+ 163.10944.
α-Nopinyl 4-Nitrophenoxide (5a). Following general procedure A,
potassium hydride (0.03 g, 0.71 mmol) was added to α-nopinol (5)
(0.1 g, 0.71 mmol) in anhydrous THF (2 mL). 4-Fluoronitrobenzene
(0.08 g, 0.75 mmol) was then added to this mixture and stirred for 2 h
to afford product 5a. Crystallization from dichloromethane yielded
brown rectangular blocks (0.14 g, 75%). Mp: =77.3−78.1 °C. 1H
NMR: δ 8.15 (2H, d, J = 9.2 Hz), 6.83 (2H, d, J = 9.2 Hz), 4.90 (1H,
ddd, J = 9.2, 3.2, 3.2 Hz), 2.43−1.81 (7H, m), 1.24 (3H, s), 1.07 (3H,
s), 1.06 (1H, d, J = 9.6 Hz). δ 163.0 140.7, 125.7, 115.0, 79.3, 44.7,
40.7, 37.5, 27.3, 26.9, 24.3, 22.8, 22.5. IR νmax: 2922, 1591, 1494, 1339,
1257 cm−1. HRMS (ESI): calcd C15H19NO3 [M + H]+ 262.14377,
found [M + H]+ 262.14383.
Analytical Analyses. Infrared spectra (IR) were determined on a
Perkin-Elmer Spectrum One, FT ATR-IR spectrometer. High-
resolution mass spectra (HRMS) were obtained via ESI using a
Finnigan Linear Trap Quadrople FT hybrid mass spectrometer linear
ion trap.
Nuclear Magnetic Resonance. Nuclear magnetic resonance
1
(NMR) spectra for H and 13C nuclei were recorded using either a
400 MHz NMR operating at 399.8 and 100.5 MHz, respectively, or on
a 500 NMR spectrometer operating at 500 and 125 MHz, respectively.
The samples for the INADEQUATE analyses were prepared by
dissolving ca. 0.4 g of sample in 0.4 mL of the reported deuterated
chloroform.
Synthesis. Other general experimental details have been reported
elsewhere.29
α-Nopinyl 2-Naphthoate (5b). Following general procedure B, α-
nopinol (5) (0.1 g, 0.71 mmol) in anhydrous DCM (1 mL) and
pyridine was treated with 2-naphthoyl chloride (0.142 g, 1.75 mmol,
General Procedure A: Reaction of Alcohols with 4-
Fluoronitrobenzene. Potassium hydride (1.0 equiv) was added to
G
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The Journal of Organic Chemistry
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1.5 equiv) to afford product 5b which crystallized into white flakes
from toluene (0.17 g, 81%). Mp =108.8−109.3 °C. H NMR: δ 8.73
0.94 (3H). 13C NMR: δ 163.1, 148.6, 147.9, 133.3, 131.1, 127.3, 119.3,
79.4, 44.7, 40.4, 37.1, 27.5, 26.6, 24.2, 22.1, 21.8. IR νmax: 2912, 1724,
1529, 1349, 1295, 732 cm−1. HRMS (ESI): calcd C16H18N2O6 [M +
Na]+ 357.10571, found [M + Na]+ 357.10593.
1
(1H, s), 8.16 (1H, d, J = 7.3 Hz), 7.93 (3H, m), 7.63 (1H, t, J = 7.3
Hz), 7.56 (1H, t, J = 7.3 Hz), 5.68 (1H, ddd, J = 9.2, 2.4, 2.4 Hz),
2.40−1.75 (7H, m), 1.25 (3H, s), 1.14 (3H, s), 1.04 (1H, d, J = 10.2
Hz). 13C NMR: δ 165.9, 135.9, 132.5, 130.6, 129.1, 128.5, 127.8,
127.5, 126.8, 126.3, 125.0, 76.1, 45.2, 40.6, 37.3, 27.4, 26.9, 24.3, 22.9,
22.8. IR νmax: 2918, 1708, 1276, 777, 761 cm−1. HRMS (ESI): calcd
C20H22O2 [M + Na]+ 317.15120, found [M + Na]+ 317.15125.
α-Nopinyl 3-Nitrobenzoate (5c). Following general procedure B, α-
nopinol (5) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 3-nitrobenzoyl chloride (0.14 g, 0.75 mmol)
for 2 h to afford product 5c as a yellow solid (0.16 g, 76%). Mp =
80.1−80.5 °C. 1H NMR: δ 8.84 (1H, s), 8.40 (1H, dd, J = 8.0, 2.3 Hz),
8.35 (1H, d, J = 8.0 Hz), 7.65 (1H, t, J = 8.0 Hz), 5.56 (1H, ddd, J =
9.8, 3.3, 3.3 Hz), 2.51−1.78 (7H, m), 1.26 (3H, s), 1.19 (3H, s,), 1.11
(1H, d, J = 10.3 Hz). 13C NMR: δ 163.4, 147.9, 134.7, 132.4, 129.3,
β-Nopinyl 4-Nitrophenoxide (6a). Following general procedure A,
potassium hydride (0.03 g, 0.71 mmol) was added to β-nopinol (6)
(0.1 g, 0.71 mmol) in anhydrous THF (2 mL). 4-Fluoronitrobenzene
(0.08 g, 0.75 mmol) was then added to this mixture and stirred for 2 h
to afford product 6a which crystallized into brown rectangular blocks
from DCM (0.15 g, 81%). Mp = 75.2−77.0 °C. 1H NMR: δ 8.14 (2H,
d, J = 9.4 Hz), 6.87 (2H, d, J = 9.4 Hz), 4.82 (1H, ddd, J = 6.93, 6.93,
1.8 Hz), 2.26−1.78 (7H, m), 1.62 (1H, d, J = 9.6 Hz), 1.28 (3H, s),
0.93 (3H, s). 13C NMR: δ 163.3, 140.9, 125.8, 115.2, 77.1, 44.4, 40.2,
39.2, 29.6, 26.4, 23.2, 22.8, 20.1. IR νmax: 2917, 1590, 1495, 1300, 1266
cm−1. HRMS (ESI): calcd C15H19NO3 [M + H]+ 262.14377, found
[M + H]+ 262.14377.
β-Nopinyl 2-Naphthoate (6b). Following general procedure B, β-
nopinol (6) (0.1 g, 0.71 mmol) in anhydrous DCM (1 mL) and
pyridine was treated with 2-naphthoyl chloride (0.142 g, 1.75 mmol,
1.5 equiv) to afford product 6b which crystallized into white flakes
126.7, 124.0, 77.0, 44.9, 40.4, 37.2, 27.1, 26.6, 24.1, 22.6, 22.5. IR νmax
:
2921, 1714, 1536, 1346, 1294, 1259, 717 cm−1. HRMS (ESI): calcd
C16H19NO4 [M + Na]+ 312.12063, found [M + Na]+ 312.12083.
α-Nopinyl 4-Nitrobenzoate (5d). Following general procedure B,
α-nopinol (5) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 4-nitrobenzoyl chloride (0.14 g, 0.75 mmol)
for 2 h to afford product 5d as yellow solid (0.15 g, 73%). Mp = 80.1−
80.5 °C. 1H NMR: δ 8.29 (2H, d, J = 8.8 Hz), 8.19 (2H, d, J = 8.8 Hz),
5.55 (1H, ddd, J = 9.8, 3.6, 3.3 Hz), 2.51−1.78 (7H, m), 1.26 (3H, s),
1.17 (3H, s), 1.11 (1H, d, J = 10.3 Hz). 13C NMR: δ 164.0, 150.3,
136.3, 130.5, 123.4, 77.4, 45.2, 40.6, 37.4, 27.4, 26.9, 24.3, 22.9, 22.7.
IR νmax: 2924, 1712, 1523, 1345, 1288, 717 cm−1. HRMS (ESI): calcd
C16H19NO4 [M + H]+ 290.13868, found [M + H]+ 290.13871.
α-Nopinyl 3,5-Dinitrobenzoate (5e). Following general procedure
B, α-nopinol (5) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 3,5-dinitrobenzoyl chloride (0.17 g, 0.75
mmol) for 2 h to afford product 5e as a yellow solid (0.19 g, 80%). Mp
= 100.0−101.8 °C. 1H NMR: δ 9.21 (1H, d, J = 2.1 Hz), 9.14 (2H, d, J
= 2.1 Hz), 5.62 (1H, ddd, J = 10.0, 3.5, 3.3 Hz), 2.52−1.81 (7H, m),
1.28 (3H, s), 1.20 (3H, s), 1.13 (1H, d, J = 10.3 Hz). 13C NMR: δ
161.9, 148.5, 134.6, 129.2, 122.0, 78.7, 45.1, 40.6, 37.5, 27.3, 26.8, 24.2,
22.9, 22.6. IR νmax: 2923, 1719, 1541, 1344, 1286, 719 cm−1. HRMS
(ESI): calcd C16H18N2O6 [M + Na]+ 357.10571, found [M + Na]+
357.10598.
1
from toluene (0.16 g, 76%). Mp = 88.9−90.4 °C. H NMR: δ 8.60
(1H, s), 8.08 (1H, d, J = 10.8 Hz), 7.95 (1H, d, J = 8.0 Hz), 7.85 (2H,
d, J = 8.4 Hz), 7.55 (2H, m), 5.54 (1H, bt, J = 7.6 Hz), 2.44−1.82 (7H,
m), 1.74 (1H, d, J = 8.8 Hz), 1.31 (3H, s), 0.97 (3H, s). 13C NMR: δ
166.2, 135.3, 132.3, 130.6, 129.1, 128.6, 127.9, 127.8, 127.6, 126.3,
125.1, 74.4, 45.0, 40.2, 39.4, 26.3, 23.3, 23.2, 22.3, 20.0. IR νmax: 2922,
1705, 1277, 779, 762 cm−1. HRMS (ESI): calcd C20H22O2 [M + H]+
295.16926, found [M + H]+ 295.16935.
β-Nopinyl 3-Nitrobenzoate (6c). Following general procedure B, β-
nopinol (6) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 3-nitrobenzoyl chloride (0.14 g, 0.75 mmol)
for 2 h to afford product 6c as a yellow solid (0.18 g, 87%). Mp =
1
70.0−71.0 °C. H NMR: δ 8.65 (1H, d, J = 1.6 Hz), 8.28 (1H, d, J =
7.9 Hz), 8.25 (1H, t, J = 7.9 Hz), 7.57 (1H, t, J = 7.9 Hz), 5.37 (1H, br
t, J = 6.7, 6.1, 1.5 Hz), 2.26−1.71 (7H, m), 1.58 (1H, d, J = 10.3 Hz),
1.19 (3H), 0.84 (3H, s). 13C NMR: δ 163.7, 147.9, 134.9, 132.4, 129.3,
126.8, 124.0, 75.5, 44.7, 40.0, 39.3, 26.2, 23.1, 23.0, 22.0, 19.9. IR νmax
:
2927, 1716, 1524, 1347, 1264, 717 cm−1. HRMS (ESI): calcd
C16H19NO4 [M + Na]+ 312.12063, found [M + Na]+ 312.12073.
β-Nopinyl 4-Nitrobenzoate (6d). Following general procedure B,
β-nopinol (6) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 4-nitrobenzoyl chloride (0.14 g, 0.75 mmol)
for 2 h to afford product 6d as a yellow solid (0.18 g, 87%). Mp =
104.3−106.0 °C. 1H NMR: δ 8.26 (2H, d, J = 8.9 Hz), 8.18 (2H, d, J =
8.9), 5.47 (1H, m), 2.34−1.77 (7H, m), 1.64 (1H, d, J = 9.6 Hz), 1.28
(3H, s), 0.94 (3H). 13C NMR: δ 164.1, 150.2, 136.2, 130.4, 123.3,
75.7, 44.9, 40.2, 39.5, 26.3, 23.2, 23.1, 22.2, 20.0. IR νmax: 2919, 1710,
1522, 1346, 1285, 716 cm−1. HRMS (ESI): calcd C16H19NO4 [M +
Na]+ 312.12063, found [M + Na]+ 312.12077.
α-Nopinyl 3,4-Dinitrobenzoate (5f). Following general procedure
B, α-nopinol (5) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 3,4-dinitrobenzoyl chloride (0.17 g, 0.75
mmol) for 2 h to afford product 5f as yellow solid (0.19 g, 76%). Mp =
122.0−123.3 °C. 1H NMR: δ 8.53 (1H, d, J = 1.7 Hz), 8.38 (1H, dd, J
= 8.4, 1.7 Hz), 7.97 (1H, d, J = 8.4 Hz), 5.57 (1H, ddd, J = 9.8, 3.4, 3.3
Hz), 2.50−1.77 (7H, m), 1.25 (3H, s), 1.14 (3H, s), 1.10 (1H, d, J =
10.3 Hz). 13C NMR: δ 162.1, 144.9, 142.5, 135.8, 134.3, 126.1, 125.2,
78.7, 45.1, 40.6, 37.5, 27.4, 26.8, 24.2, 23.0, 22.7. IR νmax: 2919, 1710,
1539, 1367, 1289, 732 cm−1. HRMS (ESI): calcd C16H18N2O6 [M +
Na]+ 357.10571, found [M + Na]+ 357.10595.
α-Nopinyl 2-nitrobenzoate (5g). Following general procedure B,
α-nopinol (5) (0.1 g, 0.71 mmol) in anhydrous DCM (1 mL) and
pyridine was treated with 2-nitrobenzoyl chloride (0.14 g, 0.75 mmol)
for 2 h to afford product 5g as yellow solid (0.18 g, 87%). Mp = 81.0−
81.6 °C. 1H NMR: δ 7.89 (1H, dd, J = 7.8, 1.2 Hz), 7.73 (1H, dd, J =
7.8, 1.8 Hz), 7.66 (1H, dt, J = 1.2 Hz), 7.61 (1H, dt, J = 1.8 Hz), 5.51
(1H, ddd, J = 9.8, 3.5, 3.4 Hz), 2.44−1.80 (7H, m), 1.21 (3H, s), 1.04
(1H, d, J = 10.3 Hz), 0.96 (3H, s). 13C NMR: δ 164.2, 148.0, 132.4,
131.2, 129.4, 127.9, 123.3, 77.7, 44.5, 40.2, 36.9, 27.3, 26.5, 24.0, 21.9,
21.7. IR νmax: 2924, 1721, 1533, 1350, 1290, 736 cm−1. HRMS (ESI):
Calc. C16H19NO4 [M + Na]+ 312.12063, found [M + Na]+ 312.12070.
α-Nopinyl 2,4-Dinitrobenzoate (5h). Following general procedure
B, α-nopinol (5) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 2,4-dinitrobenzoyl chloride (0.17 g, 0.75
mmol) for 2 h to afford product 5h as yellow solid (0.20 g, 84%). Mp
= 110.5−112.2 °C. 1H NMR: δ 8.77 (1H, d, J = 2.1 Hz), 8.52 (1H, dd,
J = 8.4, 2.1 Hz), 7.92 (1H, d, J = 8.4 Hz), 5.56 (1H, ddd, J = 10.0, 3.4,
3.3 Hz), 2.48−1.80 (7H, m), 1.22 (3H, s), 1.05 (1H, d, J = 10.5 Hz),
β-Nopinyl 3,5-Dinitrobenzoate (6e). Following general procedure
B, β-nopinol (6) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 3,5-dinitrobenzoyl chloride (0.17 g, 0.75
mmol) for 2 h to afford product 6e as a yellow solid (0.20 g, 84%). Mp
= 93.0−94.7 °C. 1H NMR: δ 9.06 (1H, s), 8.98 (2H, s), 5.42 (1H, m),
2.28−1.74 (7H, m), 1.60 (1H, d, J = 8.0 Hz), 1.21 (3H, s), 0.86 (3H,
s). 13C NMR: δ 161.8, 148.3, 134.3, 129.0, 121.8, 76.9, 44.6, 40.0, 39.4,
26.1, 23.0, 22.9, 21.9, 19.8. IR νmax: 2926, 1723, 1543, 1343, 1280, 721
cm−1. HRMS (ESI): calcd C16H18N2O6 [M + Na]+ 357.10571, found
[M + Na]+ 357.10605.
β-Nopinyl 3,4-Dinitrobenzoate (6f). Following general procedure
B, β-nopinol (6) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 3,4-dinitrobenzoyl chloride (0.17 g, 0.75
mmol) for 2 h to afford product 6f as yellow solid (0.17 g, 71%). Mp =
1
109.3−111.0 °C. H NMR: δ 8.43 (1H, s), 8.34 (1H, d, J = 8.2 Hz),
7.92 (1H, d, J = 8.2 Hz), 5.41 (1H, m), 2.27−1.74 (7H, m), 1.57 (1H,
d, J = 8.8 Hz), 1.20 (3H, s), 0.85 (3H, s). 13C NMR: δ 162.0, 144.6,
142.2, 135.6, 134.3, 125.8, 125.1, 76.8, 44.6, 40.0, 39.4, 26.1, 23.0, 22.9,
21.9, 19.8. IR νmax: 2913, 1710, 1538, 1366, 1289, 742 cm−1. HRMS
(ESI): calcd C16H18N2O6 [M + Na]+ 357.10571, found [M + Na]+
357.10580.
H
dx.doi.org/10.1021/jo3020243 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
β-Nopinyl 2-Nitrobenzoate (6g). Following general procedure B,
β-nopinol (6) (0.1 g, 0.71 mmol) in anhydrous DCM (1 mL) and
pyridine was treated with 2-nitrobenzoyl chloride (0.14 g, 0.75 mmol)
for 2 h to afford product 6g as a yellow solid (0.17 g, 83%). Mp =
77.0−78.6 °C. 1H NMR: δ 7.85 (1H, dd, J = 7.6, 1.6 Hz, 7.72 (1H, dd,
J = 7.6, 1.9 Hz, 7.64 (1H, dt, J = 1.6 Hz), 7.59 (1H, dt, J = 1.9 Hz),
5.44 (1H, m), 2.31−1.71 (7H, m), 1.50 (1H, d, J = 9.6 Hz) 1.25 (3H,
s), 0.89 (3H, s). 13C NMR: δ 164.7, 148.2, 132.5, 131.4, 129.7, 127.7,
123.5, 76.4, 44.3, 40.0, 39.3, 26.2, 23.0, 22.9, 21.4, 19.9. IR νmax: 2927,
1714, 1530, 1359, 1293, 735 cm−1. HRMS (ESI): calcd C16H19NO4
[M + Na]+ 312.12063, found [M + Na]+ 312.12079.
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Percy, J. M.; Su, M. D. J. Chem. Soc., Perkin Trans. 2 1992, 4, 549.
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285.
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DC, 1993.
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β-Nopinyl 2,4-Dinitrobenzoate (6h). Following general procedure
B, β-nopinol (6) (0.1 g, 0.71 mmol) in anhydrous Et2O (1 mL) and
pyridine was treated with 2,4-dinitrobenzoyl chloride (0.17 g, 0.75
mmol) for 2 h to afford product 6h as yellow solid (0.19 g, 79%). Mp
= 142.0−143.3 °C. 1H NMR: δ 8.75 (1H, s), 8.51 (1H, d, J = 8.4 Hz),
7.93 (1H, dd, J = 8.4, 1.8 Hz), 5.49 (1H, m), 2.32−1.76 (8H, m), 1.49
(1H, d, J = 11.9 Hz), 1.28 (3H, s), 0.92 (3H, s). 13C NMR: δ 163.1,
148.7, 148.2, 133.2, 131.3, 127.2, 119.3, 77.9, 44.4, 40.1, 39.5, 26.3,
23.1, 23.0, 21.5, 20.0. IR νmax: 2924, 1715, 1538, 1352, 1290, 729 cm−1.
HRMS (ESI): calcd C16H18N2O6 [M + Na]+ 357.10571, found [M +
Na]+ 357.10583.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Copies of 13C NMR spectra for compounds 5a−h and 6a−h.
Crystallographic information files (CIF) are available and have
been deposited with the Cambridge Crystallographic Data
Centre and assigned CCDC codes 916415−916422, respec-
tively. This material is available free of charge via the Internet at
http://pubs.acs.org.
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John Wiley & Sons: New York, 2000.
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Am. Chem. Soc. 1983, 105, 733. (b) Vogel, P. Helv. Chim. Acta 1997,
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AUTHOR INFORMATION
Corresponding Author
*E-mail: whitejm@unimelb.edu.au.
Notes
■
The authors declare no competing financial interest.
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