Palladium-catalyzed hydrophenylation of bicyclic alkenes

Article abstract of DOI:10.1016/S0040-4020(02)01277-2

Palladium-catalyzed hydrophenylation reactions of bicyclic alkenes were investigated. These reactions were found to be completely chemo- and stereoselective, giving only exo products on the less substituted double bonds of bicyclic alkenes in moderate to good yields. For unsymmetrical bicyclic alkenes, regioselectivities of 52:48 to 100:0 were observed with various substituents on the bicyclic alkenes.

Full text of DOI:10.1016/S0040-4020(02)01277-2

Tetrahedron 58 (2002) 9527–9540
Palladium-catalyzed hydrophenylation of bicyclic alkenes
*
Peter Mayo and William Tam
Department of Chemistry and Biochemistry, Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry,
University of Guelph, Guelph, Ont., Canada N1G 2W1
Received 15 August 2002; revised 2 October 2002; accepted 4 October 2002
Abstract—Palladium-catalyzed hydrophenylation reactions of bicyclic alkenes were investigated. These reactions were found to be
completely chemo- and stereoselective, giving only exo products on the less substituted double bonds of bicyclic alkenes in moderate to good
yields. For unsymmetrical bicyclic alkenes, regioselectivities of 52:48 to 100:0 were observed with various substituents on the bicyclic
alkenes. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Palladium-catalyzed coupling reactions of olefins represent
1
an important strategy for carbon–carbon bond formation.
2.1. Palladium-catalyzed hydrophenylation of 2,3-
disubstituted norbornadienes (1a–1c)
Both the inter- and intramolecular Heck-type hydroarylation
and hydroalkenylation have been well studied and the
asymmetric variant of these reactions has also been
Only very few examples of the study of chemo- and
stereoselectivity of transition metal-catalyzed cyclo-
additions and addition reactions of substituted norborn-
adienes can be found in the literature, and in all cases, the
only substituted norbornadiene that has been used in these
studies was the 2,3-dicarbomethoxynorbornadiene 1a
(Scheme 1). For example, the Pd-catalyzed [3þ2] cyclo-
addition of palladium–trimethylenemethane (Pd–TMM)
complex with 1a occurs exclusively on the electron-
deficient, tetrasubstituted double bond (with stereo-
2
–6
reported.
However, to our knowledge, no systematic
study on the chemo-, stereo- and regioselectivities of
palladium-catalyzed hydrophenylation of substituted
bicyclic alkenes has been reported in the literature. There
are several questions about the palladium-catalyzed hydro-
phenylation of substituted bicyclic alkenes that we would
like to address: (i) the chemoselectivity (for the substituted
norbornadienes 1 and 2, will hydrophenylation occur on the
C vC or C vC double bond, Fig. 1); (ii) the stereo-
1
4
selectivity exo/endo¼80:20). On the other hand, the
opposite chemoselectivity was observed in the Co-catalyzed
Pauson–Khand [2þ2þ1] cycloaddition of propyne and
5
6
2
3
selectivity (exo vs endo products); and (iii) the regio-
selectivity of unsymmetrical systems (2–4, Fig. 1). In the
past few years, we have been focusing on the synthesis of
substituted norbornadienes and norbornenes and studying
different cycloaddition reactions and addition reactions to
1
5
1a, and in the Ru-catalyzed carbonylative cyclization of
7
–13
these bicyclic alkenes.
In this paper, we would like to
report our study on the chemo-, stereo- and regio-
selectivities of these bicyclic alkenes in the palladium-
catalyzed hydrophenylation reactions.
Figure 1. Substituted bicyclic alkenes.
Keywords: palladium; hydrophenylation; heck coupling; bicyclic alkenes;
chemoselectivity; stereoselectivity; regioselectivity.
*
Corresponding author. Tel.: þ1-519-824-4120x2268; fax: þ1-519-766-
1
499; e-mail: wtam@uoguelph.ca
Scheme 1. Literature examples of addition reactions of norbornadiene 1a.
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01277-2

9528
P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
Figure 2. Assignment of stereochemistry of 8 and 9.
with potassium formate (HCOOK) and using DMF as
solvent at 258C (conditions B) improved the yield of 8c to
33% (Table 1, entry 4). Further improvement of the yield to
58% was achieved by the addition of tetrabutylammonium
Scheme 2. Possible hydrophenylation products.
1
6
allylic carbonates, in which the reactions occurred
exclusively on the less substituted, less electron-deficient
double bond.
chloride (Bu NCl, conditions C, Table 1, entry 5).
4
The chemoselectivity and stereochemistry of the hydro-
1
Four possible hydrophenylation products are possible
with 2,3-disubstituted norbornadienes (Scheme 2). Hydro-
phenylation can occur on the less substituted double bonds
of the norbornadienes to give exo product 8 or endo product
phenylation products 8a and 8c were easily assigned by H
1
NMR. Since the H NMR of the products do not contain any
vinylic protons of the norbornadiene and therefore products
10 and 11 are not possible (Scheme 2). Examining the
a
9
, or occur on the more substituted double bonds of the
coupling pattern of H in 8 and 9 is sufficient to distinguish
these exo and endo stereoisomers (Fig. 2). As the dihedral
norbornadienes, to give exo product 10 or endo product 11.
In order to study the chemo- and stereoselectivities of the
palladium-catalyzed hydrophenylation of 2,3-disubstituted
norbornadienes, several 2,3-disubstituted norbornadienes
a
b
angle between H and H in the exo isomer 8 is close to 908,
18
the coupling constant between H and H is close to 0 Hz.
a
b
1
0,17
(
hydrophenylation reactions were studied (Table 1).
1a–1c) were prepared
and their palladium-catalyzed
Although four possible hydrophenylation products could be
formed, single isomers were produced in all cases. Thus,
excellent chemoselectivities were observed and hydro-
phenylations only occurred on the less hindered double
bond of the norbornadienes regardless of the electronic
nature of the substituents on the norbornadienes. The
hydrophenylations were also highly stereoselective, giving
only the exo products in moderate to good yields. With 2,3-
disubstituted norbornadienes 1a and 1b (X¼COOMe and
SiMe ), Pd-catalyzed hydrophenylations occurred smoothly
3
using Pd(OAc) (20 mol%), PPh (40 mol%), formic acid
2
3
(
HCOOH) and piperidine in THF at 608C (conditions A)
afforded the products 8a and 8b in 91 and 80% yields,
respectively (Table 1, entries 1 and 2). With 2,3-dibromo-
norbornadienes 1c, under conditions A, less than 10% of the
hydrophenylation product 8c was isolated and a compli-
cated mixture of inseparable products was obtained instead
(
Table 1, entry 3). Replacing the formic acid and piperidine
Table 1. Pd-catalyzed hydrophenylation of 2,3-disubstituted norborna-
dienes 1a–1c
a
b
c
Entry
X
Conditions
Product
Yield (%)
1
2
3
4
5
COOMe
A
A
A
B
C
8a
8b
8c
8c
8c
91
80
,10
33
SiMe
Br
3
Br
Br
58
a
Reaction conditions: A¼Pd(OAc)
08C. B¼Pd(OAc) , PPh , HCOOK, DMF, 258C. C¼Pd(OAc)
HCOOK, Bu NCl, DMF, 258C.
No other isomers were detected by H NMR (400 MHz) in the crude
reaction mixture.
Isolated yields after column chromatography.
2
, PPh
3
, HCOOH, piperidine, THF,
6
2
3
2 3
, PPh ,
4
b
c
1
Scheme 3. Proposed mechanism.

P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
9529
a
c
Thus, H of the exo isomer 8 is a dd as it only couples to H
d
Table 2. Pd-catalyzed hydrophenylation of 2-substituted norbornadienes
2a–2c
b
and H but not with H . On the other hand, the
a
b
corresponding dihedral angle between H and H in the
endo isomer 9 is approximately 428 and would give a
1
8,19
a
coupling constant of ,5 Hz.
isomer 9 would be expected to have a ddd pattern as it
couples to H , H as well as H . Since H in all the products
a and 8c showed a dd coupling pattern (8a: d 3.05 ppm, dd;
b: d 2.55 ppm, dd; 8c: d 3.03 ppm, dd), they all therefore
must possess the exo stereochemistry.
Thus, H of the endo
c
d
b
a
a
b
c
Entry
X
Conditions
Product ratio 21/19
Yield (%)
8
8
d
1
2
3
4
5
COOMe
COOMe
COOMe
Si BuMe
nHexyl
A
C
D
A
A
21a/19a¼nd
, 10
N.R.
56
60
57
d
e
21a/19a¼nd
21a/19a¼62:38
21b/19b¼67:33
21c/19c¼62:38
t
The excellent levels of chemoselectivities can be explained
by the mechanism proposed in Scheme 3. Addition of PhI to
the active Pd(0) complex will lead to the formation of
Pd-complex 10. Coordination of the less substituted double
bond (C vC ) of a 2,3-disubstituted norbornadiene to the
2
a
Reaction conditions: A¼Pd(OAc) , PPh , HCOOH, piperidine, THF,
2
3
6
PPh , HCOOK, Bu NCl, THF, 608C.
08C. C¼(OAc) NCl, DMF, 258C. D¼Pd(OAc)
2
, PPh
3
, HCOOK, Bu
4
2
,
3
4
5
6
b
c
d
e
1
Determined by H NMR (400 MHz) in the crude reaction mixture.
Combined (21þ19) isolated yields after column chromatography.
nd¼not determined.
Pd-complex 10 would lead to the formation of the olefin
complex 11, whereas coordination of the more substituted
double bond (C vC ) would provide the olefin complex 12.
Due to the steric hindrance of the X substitutents on the
norbornadiene with the ligands on the Pd, complex 12 is
highly disfavored. syn-Carbopalladation of the favorable
Pd-complex 11 across the C vC double bond would
N.R.¼no reaction was observed as indicated by TLC.
2
3
position of the substituent X, and exo/endo refers to the
stereochemistry of the Ph group), e.g. syn-exo-19 vs anti-
exo-21; syn-exo-23 vs anti-exo-25.
5
6
provide the intermediate 13. Substitution of one of the
ligands on the Pd-complex 13 with the formate (HCOO)
group would generate intermediate 15. Elimination of CO2
followed by reductive elimination would provide the
observed product 8 and regenerate the Pd(0) catalyst.
In order to carry out this study, 2-substituted norbornadienes
1
0
2a–2c were synthesized and their Pd-catalyzed hydro-
phenylation reactions were studied (Table 2). Similar to
hydrophenylation of 2,3-disubstituted norbornadienes
1a–1c, high levels of chemo- and stereoselectivities were
2.2. Palladium-catalyzed hydrophenylation of 2-
substituted norbornadienes (2a–2c)
observed with 2-substituted norbornadienes 2a–2c.
Although eight possible isomers could be formed in the
reactions (Scheme 4), only the two regioisomers 19 and 21
were formed in all cases (Table 2). Thus, hydrophenylation
of 2-substituted norbornadienes occurred only on the exo-
face of the less substituted double bond of the norborn-
adienes, regardless of the electronic nature of the substituent
Unlike hydrophenylation of symmetrical 2,3-disubstituted
norbornadienes 1a–1c in which only four possible hydro-
phenylation products are possible (Scheme 2), for unsym-
metrical 2-substituted norbornadienes 2, eight
hydrophenylation products are theoretically possible
X. Low levels of regioselectivities were observed (,2:1)
t
(
substituted double bond (C vC ) to give products 19–22
Scheme 4). Hydrophenylation could occur on the less
with all the substituents tested (X¼COOMe, Si BuMe or
2
n
5
6
hexyl). With 2-silyl-substituted norbornadiene 2b and
2-alkyl-substituted norbornadiene 2c, Pd-catalyzed hydro-
(
chemoselectivity), or on the more substituted double bond
to give products 23–26. In either case, both exo and endo
products are possible e.g. 19 vs 20, 21 vs 22 etc.
phenylations occurred smoothly using Pd(OAc)2
(20 mol%), PPh (40 mol%), formic acid (HCOOH) and
3
(
stereoselectivity). Other than chemo- and stereoselectiv-
piperidine in THF at 608C (conditions A) providing
products 21b/19b and 21c/19c in 60 and 57% yields,
respectively (Table 2, entries 4 and 5). With 2-ester-
substituted norbornadiene 2a, under conditions A, less than
ities, regioselectivity is also another question that we would
like to address for unsymmetrical systems. Either syn or anti
products could be formed (syn/anti with respect to the
10% of the hydrophenylation products were isolated and a
complicated mixture of inseparable products was obtained
instead (Table 2, entry 1). Although no reaction was
observed using conditions C (Table 2, entry 2), carrying out
the reaction using conditions D (Pd(OAc) , PPh , HCOOK
2
3
and Bu NCl in THF at 608C) improved the yield of 21a/19a
4
to 56% (Table 2, entry 3).
The chemo-, stereo- and regiochemistry of the hydro-
1
phenylation products were easily assigned by H NMR.
1
Since the H NMR of the products contain only one (not
two) vinylic proton of the norbornadiene and therefore only
isomers (19–22) are possible (Scheme 4). To distinguish
between exo and endo isomers (e.g. 19 vs 20), a similar
method to that used for the assignments of the structure of 8
and 9 (Fig. 2) was used (examining the coupling pattern of
a
Scheme 4. Possible hydrophenylation products.
H ). Regioisomers 19 and 21 were found to be the products

9530
P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
Figure 3. Assignment of regiochemistry of 21 and 19.
formed in the Pd-catalyzed hydrophenylation of all of the
2-substituted norbornadienes 2a–2c. To determine which
1
isomer (19 or 21) was the major product, H NMR and/or
b
HCOSY experiments were used. In the major product 21, H
c
d
e
is a doublet (coupled only to H but not with H ) and H is
f
also a doublet (coupled only to the vinylic proton H , but not
a
b
with H ). In the minor product 19, H is a singlet (not
a
e
c
f
coupled to H ) and H is a dd (coupled only to H and H but
d
not with H ) (Fig. 3).
2.3. Palladium-catalyzed hydrophenylation of 2-
substituted norbornenes (3a–3f)
Scheme 6. Proposed mechanism.
may not be a direct hydrophenylation product. It could be
formed from compound 28 via epimerization of the exo
proton a to the CHO group under the reaction conditions.
The regiochemistry of the Pd-catalyzed hydrophenylation of
both 3a and 3b can be explained by the mechanism shown in
Scheme 6. Coordination of Pd complex 10 with 3a would
lead to the formation of Pd-complex 32. Carbopalladation
Since hydrophenylation of 2-substituted norbornadienes
2
the norbornadienes, regardless of the electronic nature of the
substituent X, we would like to determine if hydrophenyl-
ation can ever occur on the substituted double bond of
norbornene 3. The results of the hydrophenylation of
a–2c occurred only on the less substituted double bond of
2
-substituted norbornenes 3a–3f are shown in Scheme 5.
will occur in such a way that the d-Ph group will add to the
1
dþC of the norbornene, as in Heck-type reactions, to give
3
Pd-catalyzed hydrophenylation of both 3a and 3b were
highly regioselective, with the Ph group adding only to C3.
Pd-catalyzed hydrophenylation of 3a using Pd(OAc) , PPh ,
intermediate 33 which will eventually lead to the formation
of the observed regioisomer 27.
2
3
formic acid (HCOOH) and piperidine in THF at 608C
conditions A) afforded product 27 as the only isolated
2-Bromonorbornene 3c did not undergo the expected
hydrophenylation (30, Scheme 5) under the reaction
conditions and coupling product 31 was formed instead.
Coupling product 31 could be formed via two different
mechanisms (Scheme 7). The Ph group could either end up
attached to C or on C of 3c. The coupling product 31 with
(
product in 28% yield. No improvement of the yield was
observed using other conditions (B–D, Tables 1 and 2). Pd-
catalyzed hydrophenylation of 3b using HCOOK (condition
D, Table 2) provided two stereoisomers 28 and 29 in a ratio
of 76:24 with a combined yield of 55%. For all the Pd-
catalyzed hydrophenylation reactions that we have studied
so far, the hydrophenylations are always syn-exo-addition
processes (both Ph and H added syn across the double bond
on the exo face of the bicyclic structure), thus compound 29
2
3
the Ph group attached to C2 could be formed via
intermediate 37 (path A, this intermediate has been
2
0
proposed in the cyclotrimerization of 3c). The coupling
product 31 with the Ph group attached to C could be formed
via hydrophenylation of 3c with Pd complex 10 (path B).
3
Scheme 5. Hydrophenylation of 2-substituted norbornenes 3a–3f.
Scheme 7. Proposed mechanism for the formation of 38/31.

P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
9531
Scheme 8. Synthesis of deuterium labelled compound 36.
syn-exo-Addition of 10 across the C vC double bond
2
3
would lead to the formation of 40. syn-Coplanar base
2
0
induced HBr elimination would give 41 and upon addition
of HCOOH would eventually generate the product 31 with
the Ph group attached to C3.
In order to distinguish these two mechanisms, we have
prepared the deuterated compound 36 via hydrogenation of
2
halide exchange and trapping the resulting anion with D O
,3-dibromonorbornadiene 1c followed by mono lithium–
0
1
2
(
Scheme 8). The structure of the deuterated compound 36
1
13
2
1
was proven by H, C and H (deuterium) NMR. H NMR
showed that there is no vinylic H in the deuterated
compound 36, C NMR showed a triplet of the alkene
2
carbon attached to the deuterium (D), and H (deuterium)
Scheme 10. Examples of some previous studies on the remote substituent
effects of 2-substituted 5-norbornenes from our research group.
1
3
Scheme 10(b)) and Co-mediated Pauson–Khand reactions
(regioselectivity up to 74:26, Scheme 10(c)) were observed.
To the best of our knowledge, there is no systematic study
on the effect of a remote substitutent on the regioselectivity
of the Pd-catalyzed hydrophenylation reactions of unsym-
metrical norbornene systems has been reported in the
literature.
NMR showed only one peak of D. With the deuterated
compound 36 (Scheme 7), path A will lead to the formation
of a deuterated product 38, with the Ph group attached to C2,
whereas path B will give a non-deuterated product 31 with
the Ph group attached to C . When the deuterated compound
3
3
6 was subjected to the Pd-catalyzed hydrophenylation
conditions, we obtained a 60:40 mixture of the deuterated
product 38 and the non-deuterated product 31 (Scheme 9).
Since we obtained both 38 and 31, both mechanisms (path A
and path B) may be operating in the reaction of 3c to form
In order to study the remote substituent effects on
regioselectivity in the Pd-catalyzed hydrophenylation
reactions of 2-substituted 5-norbornenes, exo-2-substituted
5-norbornenes 4a–4d, endo-2-substituted 5-norbornenes
4e–4h and 5-norbornen-2-one 4i were prepared (see
3
1 (Scheme 5). Unlike 2-substituted norbornenes 3a–3c,
with an electron-withdrawing substitutent attached to the
double bond of the norbornenes, which reacted with PhI
under Pd-catalysis, 2-substituted norbornenes 3d–3f were
found to be inert under the reaction conditions (Scheme 5).
2
4
preceding paper). Four different hydrophenylation pro-
ducts are theoretically possible in the coupling between
iodobenzene and a 2-substituted 5-norbornene (Scheme 11).
Carbon–carbon bond formation could occur between the Ph
group with one of the two olefinic carbons (C or C ) of the
2
2
.4. Palladium-catalyzed hydrophenylation of
-disubstituted 5-norbornenes (4a–4i)
5
6
2-substituted 5-norbornene 4, and exo and endo coupling
products are also possible. Based on the above studies of
norbornenes and norbornadienes, we anticipated that only
the exo-coupling products 46 and 47 would be formed. It has
proven to be true and in all the 2-substituted 5-norbornenes
that we examined, only the exo-coupling products 46 and 47
were obtained.
The study of long-range stereoelectronic effect of a remote
substituent in controlling regio- and stereoselectivities on
nucleophilic and electrophilic additions to p-bonds has
2
1
attracted considerable interest. On the other hand, very
few examples of the study of remote substituent effects on
transition metal-catalyzed reactions can be found in the
1
1a,13,22,23
literature.
We have recently reported the remote
The results of the palladium-catalyzed hydrophenylation
reactions of exo-2-substituted norbornenes 4a–4d (Y¼H)
with iodobenzene are shown in Table 3, entries 1–9, and
those of endo-2-substituted norbornenes 4e–4h (X¼H) are
shown in entries 10–13. Hydrophenylation of 4a (X¼
substituent effects on the regioselectivity in some metal-
catalyzed and non-metal-catalyzed reactions of 2-substi-
9
,11a,12,13,24
tuted 5-norbornenes (Scheme 10).
For example,
the remote substituents showed strong long-range stereo-
electronic effect on oxymercuration reactions (regio-
selectivity up to 94:6, Scheme 10(a)), whereas moderate
levels of long-range stereoelectronic effect on Ru-catalyzed
COOMe, Y¼H, entry 1) under conditions A, (Pd(OAc)
2
[
2þ2] cycloadditions (regioselectivity up to 88:12,
Scheme 9. Coupling reaction of 36.
Scheme 11. Possible hydrophenylation products.

9532
P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
Table 3. Pd-catalyzed hydrophenylation of 2-substituted 5- norbornenes
a–4i
4
Figure 4. Determination of regio- and stereochemistry of the coupling
products.
a
b
c
Entry
X
Y
Conditions
46/47
Yield (%)
the exo-OAc-norbornene 4d, a complicated mixture of
products was obtained from the Pd-catalyzed coupling
between 2-norbornenone 4i (X¼Y¼O, ketone) and PhI
using formic acid (HCOOH) with Pd(OAc) , PPh , and
piperidine in THF at 608C (entry 14). When potassium
formate (HCOOK) was used instead of formic acid
(HCOOH), a much cleaner reaction was observed and the
highest regioselectivity was obtained (85:15, entry 15).
1
2
3
4
5
6
7
8
9
COOMe
OH
OTBS
OTBS
OTBS
OTBS
OTBS
OAc
OAc
H
H
H
H
H
H
H
H
H
H
H
H
H
A
A
A
C
E
(a) 62:38 74
(b) 67:33 87
(c) 72:28 83
(c) 66:34 87
(c) 74:26 82
(c) 72:28 92
(c) 74:26 76
2
3
F
G
A
C
A
A
A
A
A
C
d
d
–
–
(d) 71:29 41
(e) 75:25 70
(f) 62:38 85
(g) 58:42 89
(h) 67:33 81
10
11
12
13
14
15
COOMe
OH
OTBS
OAc
The regiochemistry and stereochemistry of the coupling
products were determined by various NMR techniques. The
exo stereochemistry of the products was proven by the
d
d
X¼Y¼O (ketone)
–
(i) 85:15 38
–
b
1
X¼Y¼O (ketone)
coupling pattern of H in H NMR spectra (Fig. 4). For
b
example, in 46c, as the dihedral angles between H and the
c
bridge head proton H in the exo product are close to 908,
a
Reaction conditions: A¼Pd(OAc)
08C. C¼Pd(OAc) , PPh , HCOOK, Bu
Pd(OAc) (PPh
, HCOOH, piperidine, THF, 608C. F¼Pd(OAc)
PPh (PPh
, HCOOH, piperidine, DMF, 608C. G¼Pd(OAc)
HCOOH, piperidine, DMF, 258C.
2
, PPh
3
, HCOOH, piperidine, THF,
6
2
3
4
NCl, DMF, 258C. E¼
their coupling constants would be very small (J,0–2 Hz).
For the endo product 49c, the dihedral angles between H
2
3
)
2
2
-
b
(
3
)
2
2
3
)
2
,
c
and H are approximately 428 and would give coupling
25
b
1
Determined by H NMR (400 MHz) and/or GC in the crude reaction
mixture.
constants of ,5 Hz. In all the coupling products (major
and minor) that we obtained, all the H are doublets of
b
c
Combined (46þ47) isolated yields after column chromatography.
d
d
e
Complicated mixture of products was obtained.
doublets (dd) (coupled only with H and H but not with the
c
bridge head proton H ), therefore all the coupling products
1
9
(
20 mol%), PPh (40 mol%), HCOOH (5 equiv.), piperidine
3
must possess exo stereochemistry. The regiochemistry of
the coupling products was then determined by NMR
(
7 equiv.) in THF at 608C) gave two regioisomers 46a and
2
6
4
7a in a ratio of 62:38. With oxy-substituents (OH, OTBS
and OAc), the regioselectivities increased slightly (67:33 to
4:26). We have examined several different reaction
GOESY experiments (a gradient NOE experiment). For
a
example, in the major regioisomer 46c, H showed þve
e
b
7
NOE effect with H but not with H , whereas for the minor
isomer 47c, H showed þve NOE effect with H but not
a
b
conditions with 4c (X¼OTBS, Y¼H, entries 3–7). Using
e
Pd(OAc) (PPh ) instead of Pd(OAc) and PPh under the
3
with H . In all of the cases that we examined, the major
isomers were the ones with the Ph group attached to C
5
2
3 2
2
same solvent (THF) and temperature (608C) provided
almost identical yields and regioselectivities (entries 3 and
(regioisomers 46).
5
). With Pd(OAc) (PPh ) as catalyst in DMF similar
2 3 2
regioselectivities were observed (entries 6 and 7) and a
higher yield was obtained when the reaction was carried out
at 608C (entry 6) than at room temperature (entry 7). We
have also examined the use of other solvents using the
catalytic system Pd(OAc) and PPh (not shown in Table 1).
A proposed mechanism to account for the formation of the
2
3
Very little effect was observed on the yield as well as the
regioselectivity with different solvents (hexanes, Et O,
2
CH Cl and toluene). Using potassium formate (HCOOK)
2
2
instead of formic acid (HCOOH) in the coupling reaction of
c with PhI led to a lower regioselectivity (entry 4). With
4
X¼OAc (4d), a complicated mixture of products was
obtained using formic acid (HCOOH) with Pd(OAc) , PPh ,
2
3
and piperidine in THF at 608C (entry 8). The same catalytic
system using potassium formate (HCOOK) instead of
formic acid (HCOOH) provided a much cleaner reaction
of 4d and the regioselectivity was 71:29 with a combined
yield of 41% (entry 9). Similar trends in regioselectivities
were observed in the palladium-catalyzed hydrophenylation
reactions of endo-2-substituted norbornenes 4e–4h (X¼H)
with iodobenzene (entries 10–13). Regioselectivities of
5
8:42 to 75:25 were observed. The lowest regioselectivity
was observed with Y¼OTBS (4g) and the highest regio-
selectivity was observed with Y¼COOMe (4e). Similar to
Scheme 12. Proposed mechanism.

P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
9533
major product 46 is shown in Scheme 12. Coordination of
the double bond of 2-substituted 5-norbornene 4 to the
Pd-complex 10 would lead to the formation of the olefin
complex 50. According to our previous density function
theory (DFT) study of 2-substituted 5-norbornene systems,
McMaster University, Hamilton, Ontario. Elemental
analyses were performed by Canadian Microanalytical
Service Ltd., British Columbia or by Quantitative Technol-
ogies Inc., New Jersey.
C of 2-substituted 5-norbornenes (4a–4i) is always more
6
4.2. Materials
9
b
‘
negative’ than C5. Thus the d-Ph group in the Pd-complex
5
0 will have the preference to add to the dþC of the double
Unless stated otherwise, commercial reagents were used
without purification. The palladium catalysts were pur-
chased from Strem Chemicals and were stored in an inert
atmosphere dry box. THF was purified by distillation from
potassium/benzophenone under dry nitrogen. DMF and
5
bond, to give intermediate 51 which will eventually lead to
the formation of the major regioisomer 46 with the Ph group
attached to C5.
piperidine were purified by distillation from CaH under dry
2
1
7
10
28
29
3
. Conclusions
nitrogen. Norbornadienes 1a, 1c, 2a, 2c and
1
2
12
29
24
norbornenes 3d, 3e, 3f, 4a–4i were prepared
according to literature procedures.
We have studied the palladium-catalyzed hydrophenylation
reactions of substituted norbornadienes and norbornenes.
The reactions with symmetrical 2,3-disubstituted norborn-
adienes (1a–1c) were found to be completely chemo-
4.3. Synthesis of substituted norbornadienes and
norbornenes
(
100:0) and stereoselective (100:0), with the palladium-
catalyzed hydrophenylation reactions occurring only on the
less substituted or less sterically hindered double bonds
regardless of the electronic nature of the substituents. The
reactions with unsymmetrical 2-substituted norbornadienes
4.3.1. 2,3-Bis(trimethylsilyl)bicyclo[2.2.1]hepta-2,5-
diene (1b). To a flame-dried round-bottom flask containing
1
0
2-bromo-3-trimethylsilyl)bicyclo[2.2.1]hepta-2,5-diene
t
(1.00 g, 4.11 mmol) and THF (12.0 mL) was added BuLi
(7.50 mL, 12.8 mmol, 1.7 M in pentane) dropwise at 2788C
under nitrogen. The reaction mixture was stirred at 2788C
for 1 h. The lithiated norbornadiene was trapped with
TMSCl (2.6 mL, 20.5 mmol) at 2788C and stirred for
30 min. The reaction mixture was reacted at 08C for 1 h
(
2a–2c) were also found to be completely chemo- (100:0)
and stereoselective (100:0), with low levels of regio-
selectivity (up to 67:33). Palladium-catalyzed hydrophenyl-
ation of 2-substituted norbornadienes 3a and 3b, with an
electron-withdrawing group attached to the double bond of
the norbornenes, was highly regioselective, whereas
before being quenched with saturated NaHCO
O. The aqueous layer was extracted with Et O, washed
with saturated NaCl, then H O and dried over MgSO . The
and
3
2
-substituted norbornenes that do not contain an electron-
H
2
2
withdrawing group attached to the double bond were found
to be inert in the hydrophenylation. We have also
investigated the long-range electronic effect of a remote
substituent on unsymmetrical norbornenes 4a–4i in the
palladium-catalyzed hydrophenylation reaction. Moderate
levels of regioselectivities (remote substituent effects) were
observed (58:42 to 85:15) with various remote substituents
on the norbornenes.
2
4
crude product was purified by column chromatography
(hexanes) to give norbornadiene 1b (0.964 g, 4.08 mmol,
99%) as a colourless liquid. R 0.66 (hexanes); IR (neat)
f
3065 (m), 2957 (s), 2898 (m), 2864 (m), 1523 (s), 1405 (m),
1301 (s), 1249 (s), 1193 (m), 1169 (s), 1052 (s), 1011 (s),
966 (s), 898 (s) cm2 ; H NMR (CDCl
1
1
, 400 MHz) d 6.60
3
(t, 2H, J¼1.9 Hz), 3.92 (m, 2H), 1.63 (m, 2H), 0.15 (s, 18H);
1
3
C NMR (APT, CDCl , 100 MHz) d 165.0, 141.9, 71.5,
3
58.0, 0.09. HRMS calcd for C H Si : m/z 236.1417, found
m/z 236.1428.
1
3
24
2
4
. Experimental
4
.1. General information
4.3.2. 2-(tert-Butyldimethylsilyl)bicyclo[2.2.1]hepta-2,5-
diene (2b). Bicyclo[2.2.1]hepta-2,5-diene (5.0 mL,
46.3 mmol) was added to a flame-dried round-bottom
All reactions were carried out in an atmosphere of dry
nitrogen at ambient temperature unless otherwise stated.
Standard column chromatography was performed on 230–
t
flask containing BuOK (2.86 g, 25.5 mmol) and THF
(30 mL) at 2788C. nBuLi (10.0 mL, 25.0 mmol, 2.5 M in
hexanes) was then added to the flask via a dropping funnel
and the temperature was maintained below 2658C. The
reaction mixture was warmed to 2408C over 1 h. TBSCl
(3.61 g, 23.9 mmol) in THF (8 mL) was then added via a
cannula to the reaction mixture at 2788C. The reaction
mixture was stirred at 2408C for 30 min and at 258C for
30 min. After quenching the reaction with water, the
aqueous layer was extracted with diethyl ether and the
combined organic layers were washed sequentially with
4
00 mesh silica gel (obtained from Silicycle) by use of flash
2
7
column chromatography techniques. Analytical thin-layer
chromatography (TLC) was conducted on Merck precoated
silica gel 60 F254 plates. All glassware was flame dried
under an inert atmosphere of dry nitrogen. Infrared spectra
were taken on a Bomem MB-100 FTIR spectrophotometer.
1
13
H and C NMR spectra were recorded on a Bruker-400
1
spectrometer. Chemical shifts for H NMR spectra are
reported in parts per million (ppm) from tetramethylsilane
with the solvent resonance as the internal standard (chloro-
form: d 7.26). Chemical shifts for C NMR spectra are
reported in parts per million (ppm) from tetramethylsilane
with the solvent as the internal standard (deuterochloro-
form: d 77.0). High-resolution mass spectra were done by
McMaster Regional Centre for Mass Spectrometry at
water and saturated NaCl, and dried over MgSO . The
4
1
3
solvent was removed by rotary evaporation and the crude
product was purified by vacuum distillation (758C, 5 Torr)
to give norbornadiene 2b (4.23 g, 20.5 mmol, 82%) as a
clear, colourless liquid. R
0.80 (hexanes); IR (neat) 3065
(m), 2931 (s), 2856 (s), 1539 (s), 1471 (s), 1389 (m), 1361
f

9534
P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
(
(
1
s), 1299 (s), 1248 (s), 1206 (m), 1190 (m), 1022 (m), 1008
1
warmed to 2408C and stirred for 1 h, then re-cooled to
2788C. The reaction mixture was transferred to a solution
of DMF (1.80 mL, 23.2 mmol) in THF (5 mL) at 2788C via
cannula over 45 min and rinsed with THF (2£0.5 mL). The
reaction mixture was warmed to room temperature and
s), 929 (m) cm2 ; H NMR (CDCl , 400 MHz) d 7.06 (d,
1
3
H, J¼2.8 Hz), 6.68 (m, 2H), 3.75 (br s, 1H), 3.63 (br s,
1
H), 1.89 (d, 1H, J¼5.9 Hz), 1.86 (d, 1H, J¼5.9 Hz), 0.85
1
3
(
CDCl , 100 MHz) d 155.2, 153.5, 143.3, 142.2, 74.2, 54.3,
s, 9H), 0.038 (s, 3H), 0.0077 (s, 3H); C NMR (APT,
quenched with saturated NH Cl (30 mL), the layers were
4
3
5
m/z 206.1491, found m/z 206.1499.
2.0, 26.7, 17.2, 26.2, 26.7. HRMS calcd for C H Si:
1
separated and the aqueous layer was extracted with CH Cl
2
3
22
2
(3£30 mL). The combined organic layers were washed with
brine (30 mL) and dried (MgSO ). The solvent was removed
4
4.3.3. 2-Ethoxycarbonylbicyclo[2.2.1]hept-2-ene (3a). A
solution of norbornene (520 mg, 5.52 mmol) in THF (1 mL)
by rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes¼1:9) to give 3b
(209.0 mg, 1.70 mmol, 16%) as a clear, transparent liquid.
t
was added to a flame-dried flask containing KO Bu (310 mg,
.76 mmol) in THF (2 mL) at 2788C via cannula and rinsed
2
R 0.40 (EtOAc/hexanes¼1:9). Spectral data were identical
f
3
1
with THF (2£0.25 mL). The temperature was maintained
to those reported in the literature.
below 2608C during this addition. nBuLi (1.1 mL,
.75 mmol, 2.5 M in hexanes) was added to the reaction
2
4.3.5. 2-Bromobicyclo[2.2.1]hept-2-ene (3c). A solution of
norbornene (3.84 g, 40.7 mmol) in THF (5 mL) was added
mixture over 15 min, with the temperature maintained
below 2708C. The reaction mixture was warmed to 2408C
and stirred for 1 h, then re-cooled to 2788C. A solution of
LiBr (360 mg, 4.14 mmol) in THF (2 mL) was added to the
reaction mixture via cannula and rinsed with THF
t
to a flame-dried flask containing KO Bu (1.24 g, 11.0 mmol)
in THF (6 mL) cooled to 2788C via cannula and rinsed with
THF (2£0.5 mL). The temperature was maintained below
2728C during this addition. nBuLi (4.40 mL, 11.0 mmol,
2.5 M in hexanes) was added to the reaction mixture over
45 min, with the temperature maintained below 2728C. The
reaction mixture was slowly warmed to 2408C and stirred
for 1.5 h, then re-cooled to 2708C. 1,2-Dibromoethane
(0.950 mL, 11.0 mmol) was added to the reaction mixture
dropwise over 30 min, with the temperature maintained
between 240 and 2508C. The reaction mixture was
warmed to 2408C and stirred for 2 h, then it was warmed
(
2£0.25 mL). The temperature was maintained below
608C during this addition. The reaction mixture was
warmed to 2408C and stirred for 45 min, then re-cooled to
788C. The reaction mixture was transferred to a solution
of ethyl chloroformate (0.470 mL, 4.92 mmol) in THF
2
2
(
(
1 mL) at 2788C via cannula and rinsed with THF
2£0.25 mL). The reaction mixture was stirred at 2788C
for 15 min, then warmed to room temperature and stirred for
45 min. After quenching with water (10 mL), the layers
were separated and the aqueous layer was extracted with
to room temperature and quenched with saturated NH Cl
4
(30 mL). The layers were separated and the aqueous layer
was extracted with 1:9 CH Cl /hexanes (3£30 mL). The
Et O (3£10 mL). The combined organic layers were
2
2
2
washed with brine (10 mL) and dried (MgSO ). The
4
combined organic layers were washed with brine (30 mL)
and dried (MgSO ). The solvent was removed by rotary
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography
4
evaporation and the crude product was purified by column
chromatography (hexanes) to give 3c (622.7 mg,
3.60 mmol, 33%) as a clear, transparent liquid. R 0.83
f
(
2
(
1
EtOAc/hexanes¼1:19) to give 3a (93.0 mg, 0.559 mmol,
0%) as clear, transparent liquid. 0.31
EtOAc/hexanes¼1:19); IR (neat) 2977 (s), 2874 (m),
743 (w), 1712 (s), 1596 (w), 1449 (w), 1370 (w), 1342
w), 1279 (s), 1260 (s), 1220 (w), 1160 (s), 1117 (w), 1079
a
R
f
(Hexanes); IR (neat) 2970 (s), 2950 (s), 2920 (s), 2872 (s),
1577 (s), 1469 (w), 1448 (m), 1305 (s), 1274 (m), 1252 (w),
1208 (w), 1158 (s), 1122 (m), 1037 (s), 1032 (m) 1017
(
(
s), 1023 (w) cm2 ; H NMR (CDCl , 400 MHz) d 6.91 (d,
1
1
(w) cm ; H NMR (CDCl , 400 MHz) d 6.02 (d, 1H,
3
21
1
3
1
2
2
1
H, J¼3.1 Hz), 4.18 (ABX , 2H), 3.25 (d, 1H, J¼1.0 Hz),
J¼3.1 Hz), 2.89 (m, 2H), 1.64–1.70 (m, 2H), 1.58–1.61 (m,
C NMR (APT, CDCl ,
3
3
1
3
.99–3.01 (m, 1H), 1.61–1.79 (m, 2H), 1.47 (dt, 1H, J¼8.4,
.0 Hz), 1.28 (t, 3H, J¼7.1 Hz), 1.19 (dd, 1H, J¼8.5,
.0 Hz), 1.09 (dd, 1H, J¼5.1, 2.3 Hz), 1.06 (dd, 1H, J¼5.4,
1H), 1.11–1.22 (m, 3H);
100 MHz) d 134.8, 125.5, 50.5, 48.1, 43.9, 25.9, 24.4.
2
This is a known compound in the literature.
3
1
3
2
.8 Hz); C NMR (APT, CDCl , 100 MHz) d 164.9, 146.6,
3
1
were identical to those reported in the literature.
41.0, 60.0, 48.2, 43.4, 41.8, 24.6, 24.5, 14.3. Spectral data
3
4.3.6. 2,3-Dibromobicyclo[2.2.1]hept-2-ene (35). A flame-
dried, round-bottom flask was charged with norbornadiene
0
1c (310.2 mg, 1.24 mmol), ethanol (10 mL), 5% Pd/C
(1.9 mg, 0.893 mmol), and a balloon of H was attached
to the flask. The reaction mixture was stirred at 258C for
24 h and filtered. The solvent was removed by rotary
evaporation and the crude product was purified by column
chromatography (hexanes) to give the product 35 (257 mg,
4
.3.4. 2-Formylbicyclo[2.2.1]hept-2-ene (3b). A solution
of norbornene (3.80 g, 40.4 mmol) in THF (5 mL) was
2
t
added to a flame-dried flask containing KO Bu (1.25 mg,
1
1.2 mmol) in THF (6 mL) at 2788C via cannula and rinsed
with THF (2£0.5 mL). The temperature was maintained
below 2608C during this addition. nBuLi (4.40 mL,
1
1.02 mmol, 82%) as a clear, colourless liquid. R 0.82
f
1
1.0 mmol, 2.5 M in hexanes) was added to the reaction
(hexanes); H NMR (CDCl , 400 MHz) d 3.00 (s, 2H),
3
mixture over 45 min, with the temperature maintained
below 2708C. The reaction mixture was warmed to 2408C
and stirred for 1.5 h, then re-cooled to 2788C. A solution of
LiBr (1.30 mg, 14.9 mmol) in THF (4 mL) was added to the
reaction mixture via cannula over 30 min and rinsed with
THF (2£0.5 mL). The temperature was maintained below
1.77–1.79 (m, 1H), 1.68–1.71 (m, 2H), 1.26–1.33 (m, 2H),
1
3
1.22 (dd, 1H, J¼8.4, 1.5 Hz); C NMR (APT, CDCl3,
100 MHz) d 125.5, 51.6, 46.9, 25.7. This is a known
compound in the literature.
3
3
4.3.7. 2-Bromo-3-deuterobicyclo[2.2.1]hept-2-ene (36).
t
BuLi (0.60 mL, 1.0 M in pentane, 0.60 mmol) was added
2
708C during this addition. The reaction mixture was

P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
9535
to a solution of norbornene 35 (83.4 mg, 0.331 mmol) in
THF (2 mL) cooled to 2788C. The reaction mixture was
stirred at 2788C for 30 min, then D O (0.50 mL,
27.6 mmol) was added and the reaction mixture was stirred
at 2788C for 45 min. The reaction mixture was then
(hexanes); IR (neat) 3062 (w), 3025 (w), 2956 (s), 2900 (m),
2867 (m), 1601 (w), 1496 (m), 1446 (m), 1405 (w), 1248 (s),
2
1 1
1172 (w), 1023 (s) cm ; H NMR (CDCl , 400 MHz) d
3
2
0
0
7.17–7.33 (AA MM X, 5H), 3.19 (m, 1H), 3.09 (d, 1H,
J¼1.3 Hz), 2.55 (dd, 1H, J¼8.9, 4.7 Hz), 1.74 (ddd, 1H,
J¼11.9, 4.7, 3.8 Hz), 1.54 (dt, 1H, J¼8.7, 1.2 Hz), 1.49
(ddd, 1H, J¼11.9, 9.3, 2.6 Hz), 1.24 (dm, 1H, J¼8.6 Hz),
warmed to 258C, quenched with H O (5 mL), and extracted
2
with Et O (4£5 mL). The combined extractions were dried
2
1
3
(MgSO ), the solvent was removed by rotary evaporation
and the crude product was purified by column chromato-
0.22 (s, 9H), 0.20 (s, 9H); C NMR (APT, CDCl ,
4
3
100 MHz) d 160.5, 160.3, 146.4, 128.2, 127.6, 125.5,
55.4, 48.9, 44.5, 43.4, 33.0, 0.9, 0.6. Anal. calcd for
C H Si : C, 72.54; H, 9.61. Found C, 72.81; H, 9.28.
graphy (hexanes) to give the product 36 (50.8 mg,
.292 mmol, 88%) as a clear, colourless liquid. R 0.84
f
0
19 30
2
(
hexanes); IR (neat) 2958 (s), 2915 (s), 2872 (s), 1712 (w),
1
1
558 (m), 1467 (m), 1447 (m), 1378 (w), 1294 (s), 1272 (w),
252 (w), 1162 (m), 1120 (w), 1083 (s), 1032 (m) cm2 ; H
4.4.3. exo-2,3-Dibromo-5-phenylbicyclo[2.2.1]hept-2-ene
(8c) (Table 1, entry 5). A flame-dried vial was charged with
norbornadiene 1c (65.5 mg, 0.262 mmol), DMF (2 mL),
iodobenzene (30 mL, 0.268 mmol), PPh3 (14.2 mg,
0.0541 mmol), tetrabutylammonium chloride (TBAC,
1 1
NMR (CDCl , 400 MHz) d 2.89 (s, 2H), 1.61–169 (m, 2H),
3
1.60 (dt, 1H, J¼8.3, 2.3 Hz), 1.17 (ddd, 2H, J¼10.4, 3.7,
2
1
2
1
3
.4 Hz), 1.12 (dm, 1H, J¼8.3 Hz); C NMR (APT, CDCl ,
3
00 MHz) d 134.5 (t, J ¼26.5 Hz), 125.3, 50.4, 48.0, 43.7,
CD
75.3 mg, 0.271 mmol), KO CH (77.5 mg, 0.921 mmol),
2
Pd(OAc) (6.5 mg, 0.0290 mmol). The reaction mixture was
2
2
5.8, 24.3. H (deuterium) NMR (CDCl , 65 MHz) d 6.37
3
(
s).
stirred for 24 h at room temperature. After quenching with
water (15 mL), the reaction mixture was extracted with 1:9
CH Cl /hexanes (8£15 mL), and the combined organic
4
4
.4. Pd-catalyzed hydrophenylation reactions
2
2
layers were dried (MgSO ). The solvent was removed by
4
.4.1. exo-2,3-Bis(methoxycarbonyl)-5-phenylbicyclo-
rotary evaporation and the crude product was purified by
column chromatography (Hexanes) to give the product 8c
(50.1 mg, 0.153 mmol, 58%) as a clear, colourless liquid. Rf
0.47 (hexanes); IR (neat) 3061 (w), 3026 (w), 2982 (s), 2951
(s), 2874 (w), 1586 (s), 1497 (s), 1463 (m), 1448 (s), 1294
[
2.2.1]hept-2-ene (8a) (Table 1, entry 1). A flame-dried
vial was charged with norbornadiene 1a (58.6 mg,
.281 mmol), THF (2 mL), PPh (27.8 mg, 0.106 mmol),
0
3
Pd(OAc) (12.1 mg, 0.0539 mmol), iodobenzene (30 mL,
2
0
acid (50 mL, 1.33 mmol). The reaction mixture was stirred
for 24 h at 608C. After quenching with water (5 mL), the
2
1 1
.268 mmol), piperidine (180 mL, 1.82 mmol), and formic
(s), 1278 (m), 1264 (m), 1066 (s) cm ; H NMR (CDCl ,
3
0
0
400 MHz) d 7.20–7.35 (AA MM X, 5H), 3.11 (m, 1H), 3.07
(dd, 1H, J¼3.3, 1.6 Hz), 3.03 (dd, 1H, J¼8.3, 4.8 Hz), 1.98
(ddd, 1H, J¼11.6, 8.9, 1.9 Hz), 1.84–1.91 (m, 2H), 1.71 (dt,
reaction mixture was extracted with Et O (4£5 mL), and the
2
1
3
combined organic layers were dried (MgSO ). The
4
1H, J¼8.9, 1.8 Hz); C NMR (APT, CDCl , 100 MHz) d
3
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography
(
0
(
143.4, 128.5, 127.6, 127.5, 126.9, 126.2, 57.5, 52.0, 44.30,
44.27, 38.8. Anal. calcd for C H Br : C, 47.60; H, 3.69.
Found C, 47.36; H, 3.75.
1
3
12
2
EtOAc/hexanes¼1:4) to give the product 8a (73.0 mg,
.255 mmol, 91%) as orange–white crystals. Rf 0.41
EtOAc/hexanes¼1:4); IR (neat) 3060 (w), 3026 (w),
991 (m), 2952 (s), 2879 (w), 2844 (w), 2257 (w), 1736
s), 1625 (s), 1602 (m), 1486 (m), 1448 (m), 1436 (s), 1340
s), 2275 (s), 1259 (s), 1193 (m), 1155 (s), 1093 (s), 1020
4.4.4. exo-2-Methoxycarbonyl-5-phenylbicyclo[2.2.1]-
hept-2-ene (21a) and exo-2-methoxycarbonyl-6-phenyl-
bicyclo[2.2.1]hept-2-ene (19a) (Table 2, entry 3). A flame-
dried vial was charged with norbornadiene 2a (40.7 mg,
0.271 mmol), THF (2 mL), iodobenzene (30 mL,
0.268 mmol), PPh3 (14.3 mg, 0.0545 mmol), tetrabutyl-
ammonium chloride (TBAC, 76.9 mg, 0.277 mmol),
KO CH (78.3 mg, 0.931 mmol), Pd(OAc)2 (6.3 mg,
2
0.0281 mmol). The reaction mixture was stirred for 2 d at
room temperature. After quenching with water (5 mL), the
2
(
(
(
(
1
2
1
1
2
1
1
m) cm
0
;
H NMR (CDCl , 400 MHz) d 7.19–7.35
3
0
AA MM X, 5H), 3.813 (s, 3H), 3.811 (s, 3H), 3.38 (m,
H), 3.36 (br s, 1H), 3.05 (dd, 1H, J¼8.4, 5.4 Hz), 1.93–
1
3
.03 (m, 2H), 1.68–1.74 (m, 2H); C NMR (APT, CDCl ,
3
00 MHz) d 165.2, 165.1, 145.6, 145.1, 143.9, 128.5, 127.5,
26.1, 52.0, 51.6, 45.9, 44.8, 43.5, 33.1. HRMS calcd for
C H O : m/z 286.1205, found m/z 286.1222.
1
reaction mixture was extracted with Et O (4£5 mL), and
7
18
4
2
the combined organic layers were dried (MgSO ). The
4
4
.4.2. exo-2,3-Bis(trimethylsilyl)-5-phenylbicyclo[2.2.1]-
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography
(EtOAc/hexanes¼1:9) to give an inseparable mixture of
21a and 19a (34.6 mg, 0.152 mmol, 56%, 21a/19a¼62:38
hept-2-ene (8b) (Table 1, entry 2). A flame-dried vial was
charged with norbornadiene 1b (61.4 mg, 0.260 mmol),
THF (2 mL), PPh3 (28.6 mg, 0.109 mmol), Pd(OAc)2
1
(
12.3 mg,
0.0548 mmol),
.268 mmol), piperidine (180 mL, 1.82 mmol), and formic
iodobenzene
(30 mL,
measured by integration on 400 MHz H NMR spectrum
0
and GC) as
a
clear, colourless liquid. Rf 0.51
acid (50 mL, 1.33 mmol). The reaction mixture was stirred
for 24 h at 608C. After quenching with water (5 mL), the
reaction mixture was extracted with 1:9 CH Cl /hexanes
(EtOAc/hexanes¼1:9); IR (neat) 3061 (w), 3026 (m),
2977 (s), 2950 (s), 2876 (m), 1720 (s), 1600 (s), 1495 (m),
1435 (m), 1346 (m), 1278 (s), 1258 (s), 1234 (m), 1191 (m),
2
2
1156 (s), 1089 (s) cm2 ; H NMR (CDCl , 400 MHz) d
1 1
(
(
4£5 mL), and the combined organic layers were dried
3
MgSO ). The solvent was removed by rotary evaporation
4
7.26–7.32 (m, 4H), 7.18–7.22 (m, 1H), 7.15 (d, 0.38H,
J¼3.2 Hz), 7.09 (d, 0.62H, J¼3.1 Hz), 3.77 (s, 1.14H), 3.76
(s, 1.86H), 3.35 (m, 1H), 3.13 (br s, 0.62H), 3.08 (ddd,
0.38H, J¼7.8, 6.2, 0.9 Hz), 2.84 (dd, 0.62H, J¼8.8, 4.7 Hz),
and the crude product was purified by column chromato-
graphy (hexanes) to give the product 8b (65.3 mg,
0
.208 mmol, 80%) as a clear, colourless liquid. R 0.79
f

9536
P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
2
1
.80 (dd, 0.38H, J¼8.9, 4.9 Hz), 1.86–1.96 (m, 1H),
0.38H), 2.89 (br s, 0.38H), 2.85 (d, 0.62H, J¼1.4 Hz), 2.71–
1
3
.57–1.79 (m, 3H); C NMR (APT, CDCl , 100 MHz)
3
2.80 (m, 2H), 2.11–2.19 (m, 2H), 1.72–1.78 (m, 1.38H),
1.65 (ddd, 0.62H, J¼11.3, 8.9, 2.2 Hz), 1.57–1.61 (m, 1H),
1.44–1.54 (m, 3H), 1.32–1.37 (m, 6H), 0.89–0.93 (m, 3H);
major isomer (21a): d 165.1, 148.9, 144.8, 142.6, 128.3,
27.6, 125.8, 51.4, 48.2, 45.4, 44.0, 43.3, 33.0; minor isomer
19a): d 165.2, 148.2, 144.7, 142.4, 128.4, 127.5, 125.9,
1
(
1
3
C NMR (APT, CDCl , 100 MHz) d major isomer (21c): d
3
5
m/z 228.1150, found m/z 228.1128.
1.4, 50.0, 45.5, 43.3, 42.4, 33.0. HRMS calcd for C H O:
1
152.2, 146.6, 128.6, 128.2, 127.6, 125.4, 48.6, 45.7, 45.6,
45.4, 33.4, 31.8, 30.3, 29.2, 27.5, 22.6, 14.1; minor isomer
5 16
(19c): 152.2, 146.6, 128.9, 128.2, 127.5, 125.4, 51.6, 45.7,
4
[
.4.5. exo-2-tert-Butyldimethylsilyl-5-phenylbicyclo-
2.2.1]hept-2-ene (21b) and exo-2-tert-butyldimethyl-
43.7, 42.7, 36.2, 31.8, 29.8, 29.3, 27.6, 22.6, 14.1. Anal.
calcd for C H : C, 89.70; H, 10.30. Found C, 89.98; H,
10.12.
1
9 26
silyl-6-phenylbicyclo[2.2.1]hept-2-ene (19b) (Table 2,
entry 4). A flame-dried vial was charged with norborn-
adiene 2b (57.4 mg, 0.278 mmol), THF (2 mL), PPh3
4.4.7. 2-endo-Ethoxycarbonyl-3-exo-phenylbicyclo-
[2.2.1]heptane (27). solution of norbornene 3a
(12.2 mg, 0.0734 mmol) in THF (1 mL) was added to a
flame-dried vial containing Pd(OAc)2 (3.6 mg,
(
0
27.9 mg,
.0535 mmol), iodobenzene (30 mL, 0.268 mmol), piper-
idine (180 mL, 1.82 mmol), and formic acid (50 mL,
0.106 mmol),
Pd(OAc)2
(12.0 mg,
A
1
6
.33 mmol). The reaction mixture was stirred for 24 h at
08C. After quenching with water (5 mL), the reaction
0.0160 mmol) and PPh (7.9 mg, 0.0301 mmol) via cannula
3
and rinsed with THF (2£0.5 mL). Iodobenzene (30 mL,
0.268 mmol), piperidine (30 mL, 0.30 mmol), and formic
acid (20 mL, 0.53 mmol) were added. The reaction mixture
was stirred for 23 h at 608C. After quenching with water
mixture was extracted with Et O (4£5 mL), and the
2
combined organic layers were dried (MgSO ). The solvent
4
was removed by rotary evaporation and the crude product
was purified by column chromatography (hexanes) to give
an inseparable mixture of 21b and 19b (47.4 mg,
0
on 400 MHz H NMR spectrum and GC) as a clear,
(4 mL), the reaction mixture was extracted with Et O
2
(4£4 mL) and dried (MgSO ). The solvent was removed by
4
.167 mmol, 60%, 21b/19b¼67:33 measured by integration
rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes¼1:49) to give the
product 27 (5.1 mg, 0.0209 mmol, 28%) as a clear, colour-
1
colourless liquid. R 0.70 (hexanes); IR (neat) 3061 (w),
f
3
1
1
027 (m), 2956 (s), 2927 (s), 2890 (s), 2855 (s), 1554 (m),
494 (m), 1470 (s), 1463 (s), 1361 (m), 1297 (w), 1248 (s),
less liquid. R 0.27 (1:19 EtOAc/hexanes); IR (neat) 2960
f
(m), 2865 (w), 1724 (s), 1265 (s), 1178 (m), 1094 (m), 1029
1
048 (s) cm2 ; H NMR (CDCl , 400 MHz) d 7.27–7.33
1
1
(m) cm
0
21
;
H NMR (CDCl , 400 MHz) d 7.17–7.30
3
3
0
(
m, 4H), 7.16–7.20 (m, 1H), 6.60 (d, 0.67H, J¼3.0 Hz),
(AA MM X, 5H), 4.16 (ABX , 2H), 3.21 (d, 1H,
3
6
0
2
1
1
0
.50 (d, 0.33H, J¼2.9 Hz), 3.10 (br s, 0.67H), 2.99 (br s,
.67H), 2.93 (m, 0.66H), 2.71 (dd, 0.67H, J¼8.7, 4.7 Hz),
.63 (dd, 0.33H, J¼8.7, 4.8 Hz), 1.71–1.80 (m, 1H), 1.55–
.64 (m, 2H), 1.38–1.42 (m, 1H), 0.923 (s, 6.03H), 0.915 (s,
.49H), 0.914 (s, 1.48H), 0.070 (s, 4.02H), 0.069 (s, 0.99H),
J¼5.8 Hz), 2.84 (ddd, 1H, J¼6.0, 4.2, 1.9 Hz), 2.67 (m,
1H), 2.49 (dm, 1H, J¼4.1 Hz), 1.79 (dm, 1H, J¼9.9 Hz),
1.52 (m, 1H), 1.46 (m, 1H), 1.42 (m, 1H), 1.41 (m, 1H), 1.39
1
3
(m, 1H), 1.27 (t, 3H); C NMR (APT, CDCl , 100 MHz) d
3
174.3, 145.9, 128.4, 126.9, 125.8, 60.4, 55.7, 48.8, 42.9,
41.0, 38.3, 30.1, 24.2, 14.4. HRMS calcd for C H O : m/z
244.1463, found m/z 244.1458.
1
3
.064 (s, 0.99H); C NMR (APT, CDCl , 100 MHz) d
3
16 20 2
major isomer (21b): d 148.9, 148.8, 146.4, 128.2, 127.6,
25.5, 49.7, 46.1, 46.0, 43.4, 33.8, 26.8, 16.9, 21.8; minor
isomer (19b): 148.9, 148.8, 146.3, 128.3, 127.6, 125.5, 52.6,
5.9, 43.78, 43.75, 33.1, 26.8, 16.9, 25.8, 26.1. HRMS
calcd for C19H28Si: m/z 285.2038, found m/z 285.2011.
1
4.4.8. 2-endo-Formyl-3-exo-phenylbicyclo[2.2.1]heptane
(28) and 2-exo-formyl-3-exo-phenylbicyclo[2.2.1]hep-
tane (29). A flame-dried vial was charged with norbornene
4
3b (33.0 mg, 0.270 mmol), THF (2 mL), iodobenzene
(40 mL, 0.357 mmol), PPh3 (14.2 mg, 0.0541 mmol),
4
.4.6. exo-2-Hexyl-5-phenylbicyclo[2.2.1]hept-2-ene
(
(
21c) and exo-2-hexyl-6-phenylbicyclo[2.2.1]hept-2-ene
19c) (Table 2, entry 5). A flame-dried vial was charged
with norbornadiene 2c (47.1 mg, 0.267 mmol), THF
Pd(OAc)2 (6.0 mg, 0.0267 mmol), KO CH (27.0 mg,
2
0.321 mmol). The reaction mixture was stirred for 4 d at
608C. After quenching with water (5 mL), the reaction
(
2 mL), PPh (27.9 mg, 0.106 mmol), Pd(OAc) (12.3 mg,
3
.0548 mmol), iodobenzene (30 mL, 0.268 mmol), piper-
mixture was extracted with Et O (4£5 mL), and the
2
2
0
idine (180 mL, 1.82 mmol), and formic acid (50 mL,
1
6
combined organic layers were dried (MgSO ). The
4
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography
(EtOAc/hexanes¼1:19) to give an inseparable mixture of
28 and 29 (29.8 mg, 0.149 mmol, 55%, 28/29¼76:24
.33 mmol). The reaction mixture was stirred for 15 h at
08C. After quenching with water (5 mL), the reaction
mixture was extracted with Et O (4£5 mL), and the
2
1
combined organic layers were dried (MgSO ). The solvent
4
measured by integration on 400 MHz H NMR spectrum
was removed by rotary evaporation and the crude product
was purified by column chromatography (hexanes) to give
an inseparable mixture of 21c and 19c (38.4 mg,
and GC) as
a
clear, colourless liquid. Rf 0.30
(EtOAc/hexanes¼1:19); IR (neat) 2957 (m), 2874 (m),
2807 (w), 2717 (w), 1717 (s), 1602 (w), 1497 (w), 1400 (w),
1266 (s), 1071 (m), 1031 (m) cm2 ; H NMR (CDCl ,
1
1
0
on 400 MHz H NMR spectrum and GC) as a clear,
.151 mmol, 57%, 21c/19c¼62:38 measured by integration
3
1
400 MHz) d 9.88 (s, 0.76H), 8.98 (d, 0.24H, J¼3.6 Hz),
7.14–7.30 (m, 5H), 3.26 (d, 0.24H, J¼10.0 Hz), 3.24 (d,
0.76H, J¼3.7 Hz), 2.85–2.86 (m, 1.52H), 2.73 (dm, 0.24H,
J¼10.0 Hz), 2.67 (br s, 0.24H), 2.62 (br s, 0.24H), 2.57 (d,
0.76H, J¼4.2 Hz), 1.98 (dm, 0.24H, J¼10.6 Hz), 1.82 (dd,
0.76H, J¼10.0, 0.7 Hz), 1.69 (m, 1H), 1.34–1.64 (m, 4H);
colourless liquid. R 0.86 (hexanes); IR (neat) 3060 (m),
f
3
1
(
025 (m), 2959 (s), 2927 (s), 2871 (s), 2857 (s), 1600 (m),
494 (m), 1463 (m), 1448 (m), 1378 (w), 1262 (w), 1076
w) cm2 ; H NMR (CDCl , 400 MHz) d 7.29–7.31 (m,
1
1
3
4
H), 7.26–7.28 (m, 1H), 5.77 (br s, 0.62H), 5.69 (br s,

P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
9537
1
3
C NMR (APT, CDCl , 100 MHz) major isomer (28): d
3
mixture was stirred for 1 d at 608C, then passed through a
plug of silica gel (EtOAc/hexanes¼1:49). The solvent
was removed by rotary evaporation and the crude
product was purified by column chromatography
(EtOAc/hexanes¼1:19) to give an inseparable mixture of
2
3
1
03.6, 145.4, 128.5, 126.8, 125.9, 63.8, 46.0, 42.9, 39.0,
8.2, 30.3, 24.2; minor isomer (29): d 204.1, 140.6, 128.7,
27.7, 126.3, 60.2, 50.4, 41.2, 38.3, 36.6, 30.6, 28.2. HRMS
calcd for C H O: m/z 200.1201, found m/z 200.1213.
5 16
1
4
6a and 47a (46.7 mg, 0.203 mmol, 74%, 46a/47a¼62:38
1
4.4.9. 2-Phenylbicyclo[2.2.1]hept-2-ene (31). A flame-
dried vial was charged with norbornene 3c (46.3 mg,
measured by integration on 400 MHz
spectrum) as a colourless, transparent liquid. R 0.22
H
NMR
f
0
0
.268 mmol), THF (2 mL), iodobenzene (90 mL,
.804 mmol), PPh3 (27.8 mg, 0.106 mmol), piperidine
(EtOAc/hexanes¼1:49); IR (neat) 3087 (w), 3060 (w),
3025 (w), 2952 (s), 2878 (m), 1729 (s), 1602 (w), 1494 (m),
1448 (m), 1435 (m), 1358 (m), 1305 (w), 1262 (w), 1195 (s),
(
180 mL, 1.82 mmol), formic acid (50 mL, 1.33 mmol),
1174 (s), 1042 (m) cm2 ; H NMR (CDCl , 400 MHz) d
1 1
and Pd(OAc)2 (11.8 mg, 0.0526 mmol). The reaction
mixture was stirred for 5 d at 608C. After quenching with
water (10 mL), the reaction mixture was extracted with
CH Cl (4£10 mL) and dried (MgSO ). The solvent was
3
7.15–7.31 (m, 5H), 3.70 (s, 1.86H), 3.68 (s, 1.14H), 2.82
(dd, 0.38H, J¼8.7, 5.7 Hz), 2.77 (dd, 0.62H, J¼8.7, 6.0 Hz),
2.70 (br s, 0.38H), 2.64 (d, 0.62H, J¼3.8 Hz), 2.53 (dd,
0.38H, J¼9.1, 4.8 Hz), 2.44–2.48 (m, 1.62H), 1.98 (dd,
0.38H, J¼5.4, 4.4 Hz), 1.95 (dd, 0.62H, J¼5.4, 4.2 Hz),
2
2
4
removed by rotary evaporation and the crude product was
purified by column chromatography (hexanes) to give the
product 31 (22.0 mg, 0.129 mmol, 48%) as a clear, colour-
1
3
1.41–1.92 (m, 5H); C NMR (APT, CDCl , 100 MHz)
3
1
less liquid. R 0.64 (hexanes); H NMR (CDCl , 400 MHz)
f
major isomer (46a): d 176.4, 146.6, 128.28, 126.9, 125.6,
51.7, 46.4, 45.6, 42.5, 41.4, 38.6, 35.0, 34.3; minor isomer
(47a): 176.1, 146.1, 128.26, 127.0, 125.7, 51.7, 47.1, 47.0,
46.9, 37.8, 36.4, 34.1, 33.4. HRMS calcd for C H O : m/z
3
0
0
d 7.16–7.43 (AA MM X, 5H), 6.29 (d, 1H, J¼3.2 Hz), 3.32
br s, 1H), 2.99 (m, 1H), 1.73–1.83 (m, 2H), 1.53 (dm, 1H,
J¼8.3 Hz), 1.25 (ddd, 1H, J¼8.2, 1.4, 1.0 Hz), 1.11–1.19
(
1
5 18 2
1
3
(
m, 2H); C NMR (APT, CDCl , 100 MHz) d 147.8, 135.8,
230.1307, found m/z 230.1328.
3
1
is a known compound in the literature.
29.7, 128.4, 126.6, 124.8, 47.9, 43.3, 43.1, 26.8, 24.8. This
4
3
4.4.12. 2-exo-Hydroxy-5-exo-phenylbicyclo[2.2.1]hep-
tane (46b) and 2-exo-hydroxy-6-exo-phenylbicyclo-
[2.2.1]heptane (47b) (Table 3, entry 2). Pd(OAc)2
(12.5 mg, 0.0557 mmol), PPh3 (28.3 mg, 0.108 mmol),
4.4.10. 2-Deutero-3-phenylbicyclo[2.2.1]hept-2-ene (38).
A flame-dried vial was charged with norbornene 36
(
(
35.8 mg, 0.206 mmol), THF (2 mL), iodobenzene
120 mL, 1.07 mmol), PPh (21.5 mg, 0.0820 mmol), piper-
iodobenzene
(0.090 mL,
0.80 mmol),
piperidine
(0.180 mL, 1.81 mmol), and formic acid (0.050 mL,
1.3 mmol) were added to a solution of norbornene 4b
(29.5 mg, 0.268 mmol) in THF (2 mL). The reaction
mixture was stirred for 3 d at 608C. After quenching with
water (4 mL), the reaction mixture was extracted with 1:9
CH Cl (4£4 mL) and dried (MgSO ). The solvent was
3
idine
0
(180 mL,
1.82 mmol),
Pd(OAc)2
.0419 mmol), and formic acid (36 mL, 0.95 mmol) were
(9.4 mg,
added. The reaction mixture was stirred for 3 d at 608C.
After quenching with water (5 mL), the reaction mixture
was extracted with Et O (4£5 mL) and dried (MgSO ). The
2
4
2
2
4
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography (hexanes).
removed by rotary evaporation and the crude product was
purified by column chromatography (EtOAc/hexanes¼1:4)
to give an inseparable mixture of 46b and 47b (44.1 mg,
1
H NMR revealed the presence of the excess iodobenzene as
well as the products 38 and 31 (38/31¼60:40), so Zn dust
0.234 mmol, 87%, 46b/47b¼67:33 measured by integration
1
(15.9 mg, 0.234 mmol) was added to a solution of the
products in 1:1 EtOH/saturated NH Cl (2 mL) to remove the
on 400 MHz H NMR spectrum) as a yellow semi-solid. R
f
0.31 (EtOAc/hexanes¼1:4); IR (neat) 3382 (br s), 3087 (w),
3060 (w), 3025 (w), 2957 (s), 2896 (m), 1653 (w), 1600 (w),
1494 (m), 1449 (m), 1345 (w), 1266 (w), 1151 (w), 1081
(m), 1064 (s), 1032 (m) cm2 ; H NMR (CDCl , 400 MHz)
4
excess iodobenzene. The reaction mixture was stirred at
2
(
58C for 24 h and then extracted with Et O (4£5 mL), dried
2
1 1
MgSO ), and filtered to give an inseparable mixture of 38
4
3
and 31 (6.0 mg, 0.0351 mmol, 17%, 38/31¼60:40 measured
d 7.15–7.31 (m, 5H), 3.96 (d, 0.33H, J¼6.7 Hz), 3.93 (d,
0.67H, J¼6.7 Hz), 2.64 (dd, 0.67H, J¼8.2, 5.6 Hz), 2.57
(dd, 0.33H, J¼8.2, 6.7 Hz), 2.42 (s, 0.33H), 2.41 (s, 0.67H),
2.33 (s, 0.33H), 2.28 (d, 0.67H, J¼3.8 Hz), 1.88 (ddd,
1
by integration on 400 MHz H NMR spectrum) as a clear,
colourless liquid. Spectral data for 38: R 0.67 (hexanes); H
1
f
0
0
.32 (s, 1H), 3.00 (s, 1H), 1.74–1.83 (m, 2H), 1.52–1.53
NMR (CDCl , 400 MHz) d 7.17–7.43 (AA MM X, 5H),
3
3
(
(
1
(
0.67H, J¼13.2, 6.8, 2.4 Hz), 1.78 (ddd, 0.33H, J¼13.2, 6.8,
1
3
13
m, 1H), 1.24–1.29 (m, 1H), 1.12–1.22 (m, 2H); C NMR
APT, CDCl , 100 MHz) visible peaks: d 128.4, 126.6,
24.8, 47.9, 43.3, 43.0, 26.8, 24.8; H (deuterium) NMR
CDCl , 65 MHz) d 6.35 (s). HRMS calcd for C H D: m/z
2.2 Hz), 1.35–1.72 (m, 6H); C NMR (APT, CDCl ,
3
100 MHz) major isomer (46b): d 146.6, 128.2, 127.0,
125.56, 74.6, 45.9, 44.9, 43.0, 42.0, 33.3, 31.9; minor isomer
(47b): 146.2, 128.3, 127.0, 125.62, 75.2, 50.8, 42.4, 41.5,
37.9, 35.8, 32.6. HRMS calcd for C H O: m/z 188.1201,
3
2
3
13 13
1
71.1158, found m/z 171.1145.
1
3 16
found m/z 188.1200.
4
.4.11. 2-exo-Methoxycarbonyl-5-exo-phenylbicyclo-
2.2.1]heptane (46a) and 2-exo-methoxycarbonyl-6-exo-
[
phenylbicyclo[2.2.1]heptane (47a) (Table 3, entry 1).
Pd(OAc)2 (12.4 mg, 0.0552 mmol), PPh3 (27.9 mg,
4.4.13. 2-exo-(tert-Butyldimethylsilyloxy)-5-exo-phenyl-
bicyclo[2.2.1]heptane (46c) and 2-exo-(tert-butyldi-
methylsilyloxy)-6-exo-phenylbicyclo[2.2.1]heptane (47c)
(Table 3, entry 5). A solution of norbornene 4c (57.7 mg,
0.257 mmol) in THF (1 mL) was added to a flame-dried vial
containing Pd(OAc) (PPh ) (36.4 mg, 0.0486 mmol) via
0
(
1
(
.106 mmol), iodobenzene (90 mL, 0.804 mmol), piperidine
0.180 mL, 1.81 mmol), and formic acid (0.050 mL,
.33 mmol) were added to a solution of norbornene 4a
42.0 mg, 0.276 mmol) in THF (2 mL). The reaction
2
3 2
cannula and rinsed with THF (2£0.5 mL). Iodobenzene

9538
P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
(
90 mL, 0.80 mmol), piperidine (0.180 mL, 1.81 mmol),
THF (1 mL) was added to a flame-dried vial containing
Pd(OAc)2 (12.2 mg, 0.0543 mmol) and PPh3 (28.3 mg,
0.108 mmol) via cannula and rinsed with THF (2£0.5 mL).
Iodobenzene (0.090 mL, 0.80 mmol), piperidine (0.180 mL,
1.81 mmol), and formic acid (0.050 mL, 1.3 mmol) were
added. The reaction mixture was stirred for 16 h at 608C.
After quenching with water (4 mL), the reaction mixture
and formic acid (50 mL, 1.3 mmol) were added. The
reaction mixture was stirred for 16 h at 608C. After
quenching with water (4 mL), the reaction mixture was
extracted with Et O (4£4 mL), and the combined organic
2
layers were dried (MgSO ). The solvent was removed by
4
rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes¼1:19) to give an
inseparable mixture of 46c and 47c (64.0 mg, 0.212 mmol,
8
1
was extracted with EtOAc (4£4 mL) and dried (MgSO ).
4
The solvent was removed by rotary evaporation and the
crude product was purified by column chromatography
(EtOAc/hexanes¼1:19) to give an inseparable mixture of
2%, 46c/47c¼74:26 measured by integration on 400 MHz
H NMR spectrum) as a colourless, transparent liquid. Rf
0
.44 (EtOAc/hexanes¼1:9); IR (neat) 3088 (w), 3063 (w),
026 (w), 2956 (s), 2930 (s), 2894 (s), 2856 (s), 1653 (w),
604 (w), 1494 (w), 1471 (m), 1361 (m), 1256 (s), 1180 (w),
46e and 47e (44.1 mg, 0.191 mmol, 70%, 46e/47e¼75:25
1
3
1
1
4
3
5
2
1
3
(
(
4
1
3
measured by integration on 400 MHz
spectrum) as a colourless, transparent liquid. R 0.27
H
NMR
f
152 (m), 1089 (s), 1018 (m) cm21; H NMR (CDCl ,
1
(EtOAc/hexanes¼1:19); IR (neat) 3060 (w), 3025 (w),
2954 (s), 2878 (m), 1736 (s), 1601 (w), 1494 (m), 1448 (m),
1435 (m), 1351 (m), 1305 (m), 1201 (s), 1168 (s), 1117 (w),
3
00 MHz) d 7.15–7.31 (m, 5H), 3.85 (d, 0.26H, J¼6.7 Hz),
.82 (dd, 0.74H, J¼8.5, 1.0 Hz), 2.62 (dd, 0.74H, J¼8.5,
.3 Hz), 2.52 (dd, 0.26H, J¼8.6, 6.2 Hz), 2.37 (s, 0.26H),
.36 (s, 0.74H), 2.26 (s, 0.26H), 2.20 (d, 0.74H, J¼3.7 Hz),
.78 (ddd, 0.74H, J¼12.8, 6.6, 1.9 Hz), 1.60–1.69 (m,
.26H), 1.43–1.46 (m, 2H), 0.90–0.91 (m, 9H), 0.07–0.08
1042 (m) cm2 ; H NMR (CDCl , 400 MHz) d 7.15–7.31
1 1
3
(m, 5H), 3.74 (s, 0.75H), 3.73 (s, 2.25H), 2.91–2.82 (m,
2H), 2.73 (d, 0.25H, J¼3.4 Hz), 2.68 (br s, 0.75H), 2.42–
1
3
2.45 (m, 1H), 1.59–1.89 (m, 5H), 1.35–1.41 (m, 1H); C
NMR (APT, CDCl , 100 MHz) major isomer (46e): d 175.4,
1
3
m, 6H); C NMR (APT, CDCl , 100 MHz) major isomer
3
3
46c): d 147.0, 128.2, 127.1, 125.48, 75.0, 46.3, 45.0, 43.9,
146.8, 128.2, 126.9, 125.5, 51.56, 46.43, 45.2, 43.3, 40.9,
37.9, 34.3, 33.0; minor isomer (47e): d 175.2, 146.2, 128.2,
127.1, 125.6, 51.64, 46.5, 46.39, 41.7, 38.0, 37.5, 37.4, 31.1.
Anal. calcd for C H O : C, 78.23; H, 7.88. Found C,
1.9, 33.4, 32.0, 25.94, 18.13, 24.6; minor isomer (47c): d
46.7, 128.3, 127.1, 125.52, 75.5, 51.0, 42.5, 42.3, 38.5,
5.7, 32.8, 25.90, 18.10, 24.7. Anal. calcd for C H OSi:
1
9
30
15 18 2
C, 75.43; H, 10.00. Found C, 75.63; H, 10.16.
77.93; H, 7.99.
4
(
.4.14. 2-exo-Acetoxy-5-exo-phenylbicyclo[2.2.1]heptane
46d) and 2-exo-acetoxy-6-exo-phenylbicyclo[2.2.1]hep-
tane (47d) (Table 3, entry 9). Pd(OAc)2 (6.5 mg,
.029 mmol), tetrabutylammonium chloride (81.4 mg,
.293 mmol), potassium formate (165.6 mg, 1.97 mmol),
4.4.16. 2-endo-Hydroxy-5-exo-phenylbicyclo[2.2.1]hep-
tane (46f) and 2-endo-hydroxy-6-exo-phenylbicyclo-
[2.2.1]heptane (47f) (Table 3, entry 11). A solution of
norbornene 4f (29.8 mg, 0.270 mmol) in THF (1 mL) was
0
0
added to a flame-dried vial containing Pd(OAc) (12.1 mg,
2
and iodobenzene (40 mL, 0.36 mmol) were added to a
solution of norbornene 4d (41.2 mg, 0.271 mmol) in DMF
0.0539 mmol) and PPh (28.1 mg, 0.107 mmol) via cannula
3
and rinsed with THF (2£0.5 mL). Iodobenzene (0.090 mL,
0.80 mmol), piperidine (0.180 mL, 1.81 mmol), and formic
acid (0.050 mL, 1.3 mmol) were added. The reaction
mixture was stirred for 21 h at 608C. After quenching with
(
2 mL). The reaction mixture was stirred for 96 h at room
temperature. After quenching with water (4 mL), the
reaction mixture was extracted with 1:9 CH Cl /hexanes
2
2
(
4£4 mL) and dried (MgSO ). The solvent was removed by
water (4 mL), the reaction mixture was extracted with Et O
2
4
rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes¼1:19) to give an
inseparable mixture of 46d and 47d (25.5 mg, 0.111 mmol,
4
1
(4£4 mL). The extractions were combined, and the solvent
was removed by rotary evaporation. The crude product was
purified by column chromatography (EtOAc/hexanes¼1:4)
to give an inseparable mixture of 46f and 47f (43.1 mg,
1%, 46d/47d¼71:29 measured by integration on 400 MHz
H NMR spectrum) as a colourless, transparent liquid. Rf
0.229 mmol, 85%, 46f/47f¼62:38 measured by integration
1
0
.31 (EtOAc/hexanes¼1:19); IR (neat) 3086 (w), 3060 (w),
026 (m), 2965 (s), 2878 (m), 1740 (s), 1602 (w), 1495 (m),
471 (m), 1449 (m), 1376 (s), 1360 (s), 1302 (m), 1240 (s),
on 400 MHz H NMR spectrum) as a yellow solid. R 0.37
f
3
1
1
(EtOAc/hexanes¼1:4); IR (neat) 3366 (br s), 3085 (w),
3059 (w), 3025 (w), 2954 (s), 2877 (m), 2493 (br w), 1601
(m), 1494 (m), 1472 (w), 1449 (m), 1344 (m), 1303 (m),
1266 (m), 1147 (m), 1121 (w), 1085 (m), 1054 (s), 1019
2
1
1
152 (w), 1048 (s), 1032 (s), 1015 (s) cm ; H NMR
(
CDCl , 400 MHz) d 7.15–7.31 (m, 5H), 4.79 (ddd, 0.29H,
3
2
1
1
J¼7.0, 1.2, 1.0 Hz), 4.73 (dd, 0.71H, J¼7.2, 2.7 Hz), 2.70–
(s) cm ; H NMR (CDCl , 400 MHz) d 7.23–7.32 (m,
3
2
2
.72 (m, 1H), 2.69 (s, 0.29H), 2.44–2.48 (m, 1.71H), 2.04 (s,
.13H), 2.03 (s, 0.87H), 1.95 (m, 0.71H), 1.85 (ddd, 0.29H,
4H), 7.15–7.19 (m, 1H), 4.28–4.36 (m, 1H), 3.56 (dd,
0.62H, J¼8.9, 6.0 Hz), 2.90 (dd, 0.38H, J¼11.6, 5.4 Hz),
2.47 (ddd, 0.38H, J¼12.9, 9.1, 2.3 Hz), 2.40 (s, 0.62H), 2.39
(s, 0.38H), 2.33–2.35 (m, 1H), 2.11 (ddd, 0.38H, J¼13.1,
10.1, 4.8 Hz), 2.03 (ddd, 0.62H, J¼9.6, 4.2, 1.9 Hz), 1.93
(ddd, 0.62H, J¼12.0, 9.2, 2.3 Hz), 1.76 (m, 0.62H), 1.61–
1.65 (m, 2H), 1.56 (d, 0.38H, J¼4.1 Hz), 1.31–1.37 (m,
1H), 1.08 (dt, 0.38H, J¼13.0, 3.4 Hz), 0.97 (dt, 0.62H,
1
3
J¼13.6, 6.8, 1.8 Hz), 1.50–1.76 (m, 5H); C NMR (APT,
CDCl , 100 MHz)majorisomer(46d):d 170.9, 146.3,128.28,
3
1
27.0, 125.69, 77.2, 45.9, 42.0, 41.9, 40.3, 33.1, 32.7, 21.4;
minor isomer (47d): d 170.7, 145.6, 128.33, 127.1, 125.74,
7.6, 47.8, 42.2, 39.0, 37.8, 35.8, 33.3, 21.4. HRMS calcd for
C H O : m/z 230.1307, found m/z 230.1285.
7
1
5 18 2
1
3
J¼12.9, 3.6 Hz); C NMR (APT, CDCl , 100 MHz) major
3
4
[
.4.15. 2-endo-Methoxycarbonyl-5-exo-phenylbicyclo-
2.2.1]heptane (46e) and 2-endo-methoxycarbonyl-6-
exo-phenylbicyclo[2.2.1]heptane (47e) (Table 3, entry
0). A solution of norbornene 4e (41.4 mg, 0.272 mmol) in
isomer (46f): d 147.1, 128.3, 127.3, 125.4, 72.9, 49.2, 39.5,
38.4, 37.7, 36.3, 35.5; minor isomer (47f): d 147.1, 128.3,
127.0, 125.5, 72.4, 47.1, 43.4, 43.0, 40.9, 35.3, 29.4. HRMS
calcd for C H O: m/z 188.1201, found m/z 188.1208.
1
1
3 16

P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
9539
4
.4.17. 2-endo-(tert-Butyldimethylsilyloxy)-5-exo-phenyl-
(ddd, 0.67H, J¼14.6, 10.3, 4.6 Hz), 2.095 (s, 0.99H), 2.092
(s, 2.01H), 1.92 (ddd, 0.33H, J¼12.2, 8.8, 2.2 Hz), 1.80 (m,
0.33H), 1.56–1.68 (m, 2H), 1.34–1.38 (m, 1H), 1.21 (dt,
0.67H, J¼13.5, 3.4 Hz), 1.11 (dt, 0.33H, J¼13.4, 3.7 Hz);
C NMR (APT, CDCl , 100 MHz) major isomer (46h): d
3
bicyclo[2.2.1]heptane (46g) and 2-endo-(tert-butyldi-
methylsilyoxy)-6-exo-phenylbicyclo[2.2.1]heptane (47g)
(Table 3, entry 12). A solution of norbornene 4g
1
3
(
56.5 mg, 0.252 mmol) in THF (1 mL) was added to a
flame-dried vial containing Pd(OAc)2 (11.7 mg,
.0521 mmol) and PPh (27.3 mg, 0.104 mmol) via cannula
171.2, 146.8, 128.3, 126.9, 125.62, 75.0, 46.7, 42.7, 40.7,
38.1, 34.99, 30.4, 21.2; minor isomer (47h): d 171.1, 146.3,
128.3, 127.2, 125.56, 75.2, 46.4, 38.8, 37.2, 37.1, 36.0,
34.96, 21.2. Anal. calcd for C H O : C, 78.23; H, 7.88.
0
3
and rinsed with THF (2£0.5 mL). Iodobenzene (0.090 mL,
0.80 mmol), piperidine (0.180 mL, 1.81 mmol), and formic
acid (0.050 mL, 1.3 mmol) were added. The reaction
1
5 18 2
Found C, 78.05; H, 7.97.
mixture was stirred for 17 h at 608C. After quenching with
water (4 mL), the reaction mixture was extracted with Et O
4.4.19. 5-exo-Phenylbicyclo[2.2.1]heptan-2-one (46i) and
6-exo-phenylbicyclo[2.2.1]heptan-2-one (47i) (Table 3,
entry 15). Pd(OAc)2 (6.4 mg, 0.029 mmol), tetrabutyl-
ammonium chloride (80.4 mg, 0.289 mmol), potassium
formate (78.7 mg, 0.936 mmol), and iodobenzene
(0.040 mL, 0.36 mmol) were added to a solution of
norbornene 4i (29.0 mg, 0.268 mmol) in DMF (2 mL).
The reaction mixture was stirred for 3 d at room
temperature. After quenching with water (4 mL), the
reaction mixture was extracted with EtOAc (4£4 mL) and
2
(
4£4 mL). The extractions were combined, and the
solvent was removed by rotary evaporation. The crude
product was purified by column chromatography
(
EtOAc/hexanes¼1:19) to give an inseparable mixture of
4
measured by integration on 400 MHz H NMR spectrum) as
6g and 47g (67.9 mg, 0.224 mmol, 89%, 46g/47g¼58:42
1
a colourless, transparent liquid. R 0.36 (hexanes); IR (neat)
f
3
1
1
7
3
5
027 (w), 2955 (s), 2930 (m), 2884 (m), 2857 (m), 1653 (m),
471 (m), 1361 (w), 1257 (m), 1151 (m), 1122 (w), 1095 (s),
068 (s), 1029 (w) cm ; H NMR (CDCl , 400 MHz) d
3
.24–7.32 (m, 4H), 7.15–7.19 (m, 1H), 4.18–4.23 (m, 1H),
.62 (dd, 0.42, J¼8.8, 6.3 Hz), 2.88 (dd, 0.58H, J¼9.1,
.2 Hz), 2.53 (ddd, 0.58H, J¼12.2, 9.5, 2.0 Hz), 2.28–2.31
2
1 1
dried (MgSO ). The solvent was removed by rotary
4
evaporation and the crude product was purified by column
chromatography (EtOAc/hexanes¼1:9) to give an insepar-
able mixture of 46i and 47i (19.1 mg, 0.103 mmol, 38%,
1
(
(
1
m, 2H), 1.99 (ddd, 0.58H, J¼13.4, 9.6, 4.5 Hz), 1.86–1.93
m, 0.84H), 1.75 (m, 0.42H), 1.59 (dd, 0.42H, J¼3.1,
46i/47i¼85:15 measured by integration on 400 MHz H
NMR spectrum and GC) as a colourless, transparent liquid.
R 0.24 (EtOAc/hexanes¼1:9); IR (neat) 3060 (w), 3027
.5 Hz), 1.57 (dd, 0.58J, J¼3.2, 1 Hz), 1.51 (dt, 0.58H,
f
J¼12.5, 4.9 Hz), 1.29 (t, 0.42H, J¼1.1 Hz), 1.27 (t, 0.58H,
J¼1.1 Hz), 1.24 (t, 0.42H, J¼1.0 Hz), 1.06 (ddd, 0.58H,
J¼12.8, 3.6, 2.9 Hz), 0.93–0.94 (m, 9H), 0.07–0.08 (m,
(m), 2964 (s), 2909 (m), 2884 (m), 1756 (s), 1601 (m), 1494
(m), 1469 (m), 1449 (m), 1407 (m), 1294 (w), 1174 (m),
1126 (w), 1092 (w) cm2 ; H NMR (CDCl , 400 MHz) d
1 1
3
1
3
6
H); C NMR (APT, CDCl , 100 MHz) major isomer
7.30–7.37 (m, 2H), 7.20–7.27 (m, 3H), 3.15 (dd, 0.15H,
J¼8.2, 6.3 Hz), 3.03 (dd, 0.85H, J¼8.5, 6.1 Hz), 2.83 (m,
0.15H), 2.81 (m, 0.85H), 2.75 (m, 0.15H), 2.72 (d, 0.85H,
3
(
46g): d 147.65, 128.2, 127.1, 125.3, 72.4, 43.4, 43.3, 41.4,
37.6, 34.7, 29.6, 25.9, 18.2, 24.8; minor isomer (47g): d
147.74, 128.2, 127.4, 125.2, 72.9, 50.0, 47.0, 39.2, 39.1,
36.5, 34.9, 25.9, 18.2, 24.65, 24.69. Anal. calcd for
1
3
J¼4.3 Hz), 1.92–2.23 (m, 5H), 1.72–1.75 (m, 1H);
C
NMR (APT, CDCl , 100 MHz) major isomer (46i): d 217.5,
3
C H OSi: C, 75.43; H, 10.00. Found C, 75.41; H, 10.02.
19 30
145.1, 128.46, 126.8, 126.1, 50.4, 46.0, 45.1, 41.7, 35.1,
32.3; visible peaks of minor isomer (47i): d 143.6, 128.48,
4
.4.18. 2-endo-Acetoxy-5-exo-phenylbicyclo[2.2.1]hep-
tane (46h) and 2-endo-acetoxy-6-exo-phenylbicyclo-
2.2.1]heptane (47h) (Table 3, entry 13). A solution of
127.0, 126.3, 56.5, 44.5, 41.0, 36.4, 35.8, 32.3. Anal. calcd
for C H O: C, 83.83; H, 7.58. Found C, 83.59; H, 7.76.
1
3 14
[
norbornene 4h (36.3 mg, 0.238 mmol) in THF (1 mL) was
added to a flame-dried vial containing Pd(OAc) (12.4 mg,
2
Acknowledgements
0
.0552 mmol) and PPh (27.4 mg, 0.104 mmol) via cannula
3
and rinsed with THF (2£0.5 mL). Iodobenzene (0.090 mL,
We thank the Natural Sciences and Engineering Research
Council (NSERC) of Canada, Boehringer Ingelheim
0
.80 mmol), piperidine (0.180 mL, 1.81 mmol), and formic
acid (0.050 mL, 1.3 mmol) were added. The reaction
(Canada) Ltd. and the University of Guelph for the generous
mixture was stirred for 18 h at 608C. After quenching with
water (4 mL), the reaction mixture was extracted with Et O
financial support of our program. Peter Mayo thanks
NSERC for postgraduate scholarships (PGS A and PGS B).
2
(
4£4 mL) and dried (MgSO ). The solvent was removed by
4
rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes¼1:9) to give an
inseparable mixture of 46h and 47h (44.6 mg, 0.194 mmol,
References
8
1%, 46h/47h¼67:33 measured by integration on 400 MHz
1
H NMR spectrum) as a colourless, transparent liquid. Rf
1. For recent reviews, see: (a) Beletskaya, I. P.; Cheprakov, A. V.
Chem. Rev. 2000, 100, 3009, and references cited therein.
(b) Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314.
2. (a) Larock, R. C.; Johnson, P. L. J. Chem. Soc., Chem.
Commun. 1989, 1368. (b) Arcadi, A.; Marinelli, F.; Bernocchi,
E.; Cacchi, S.; Ortar, G. J. Organomet. Chem. 1989, 368, 249.
(c) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34,
7493.
0
.38 (EtOAc/hexanes¼1:19); IR (neat) 3087 (w), 3061 (w),
026 (w), 2964 (s), 2879 (w), 1732 (s), 1602 (w), 1494 (w),
448 (m), 1376 (m), 1360 (m), 1303 (w), 1208 (s), 1140 (w),
091 (w), 1047 (m), 1027 (m) cm ; H NMR (CDCl ,
3
00 MHz) d 7.15–7.32 (m, 5H), 4.99–5.06 (m, 1H), 3.39
3
1
1
4
2
1
1
(
2
dd, 0.33H, J¼8.8, 6.0 Hz), 2.88 (dd, 0.67H, J¼8.9, 5.6 Hz),
.67 (d, 0.33H, J¼4.4 Hz), 2.63 (s, 67H), 2.39 (s, 0.33H),
.88 (s, 0.67H), 2.31 (ddd, 0.67H, J¼12.6, 9.0, 2.3 Hz), 2.15
2
3. (a) Larock, R. C.; Babu, S. Tetrahedron Lett. 1987, 28, 5291.

9540
P. Mayo, W. Tam / Tetrahedron 58 (2002) 9527–9540
(
b) Burns, B.; Grigg, R.; Ratananukul, P.; Sridharan, V.;
Stevenson, P.; Worakun, T. Tetrahedron Lett. 1988, 29, 4329.
. (a) Brunner, H.; Kramler, K. Synthesis 1991, 1121.
endo stereochemistry of bicyclic alkanes, see: (a) Flautt, T. J.;
Erman, W. F. J. Am. Chem. Soc. 1963, 85, 3212.
(b) Mazzocchi, P. H.; Stahly, B.; Dodd, J.; Rondan, N. G.;
Domelsmith, L. N.; Rozeboom, M. D.; Caramella, P.; Houk,
K. N. J. Am. Chem. Soc. 1980, 102, 6482. See also Refs. 8b,12,
13.
4
(
(
b) Sakuraba, S.; Awano, K.; Achiwa, K. Synlett 1994, 291.
c) Moinet, C.; Fiaud, J.-C. Tetrahedron Lett. 1995, 36, 2051.
5
6
. Ozawa, F.; Kobatake, Y.; Kubo, A.; Hayashi, T. J. Chem. Soc.,
Chem. Commun. 1994, 1323.
20. Cossu, S.; De Lucchi, O.; Paulon, A.; Peluso, P.; Zonta, C.
Tetrahedron Lett. 2001, 42, 3515.
. (a) Hay, L. A.; Koenig, T. M.; Ginah, F. O.; Copp, J. D.;
Mitchell, D. J. Org. Chem. 1998, 63, 5050. (b) Jia, C.; Piao, D.;
Kitamura, T.; Fujiwara, Y. J. Org. Chem. 2000, 65, 7516.
21. For recent reviews, see: (a) Cieplak, A. S. Chem. Rev. 1999,
99, 1265. (b) Ohwada, T. Chem. Rev. 1999, 99, 1337.
(c) Mehta, G.; Chandrasekhar, J. Chem. Rev. 1999, 99, 1437.
22. MacWhorter, S. E.; Sampath, V.; Olmstead, M. M.; Schore,
N. E. J. Org. Chem. 1988, 53, 203.
(
c) Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda, K.;
Irie, M.; Fujiwara, Y. J. Am. Chem. Soc. 2000, 122, 7252.
. (a) Yip, C.; Handerson, S.; Jordan, R.; Tam, W. Org. Lett.
7
8
9
1999, 1, 791. (b) Yip, C.; Handerson, S.; Tranmer, G. K.; Tam,
W. J. Org. Chem. 2001, 66, 276.
. (a) Tranmer, G. K.; Keech, P.; Tam, W. Chem. Commun. 2000,
23. Lautens, M.; Tam, W.; Edwards, L. G. J. Chem. Soc., Perkin
Trans. 1 1994, 2143.
24. Mayo, P.; Tam, W. Tetrahedron 2002, 58, 9513–9525.
25. The exo and endo cycloadducts 46 and 47 were modeled for
energy minimization at PM3 level (CS Chem 3D Pro Version
3.5.1) using MOPAC for the assessment of the dihedral angles
863. (b) Tranmer, G. K.; Tam, W. J. Org. Chem. 2001, 66,
5113.
. (a) Mayo, P.; Poirier, M.; Rainey, J.; Tam, W. Tetrahedron
Lett. 1999, 40, 7727. (b) Mayo, P.; Orlova, G.; Goddard, J. D.;
Tam, W. J. Org. Chem. 2001, 66, 5182.
a
b
between H and H . These dihedral angles were then compared
to the Karplus curve for the determination of the theoretical
coupling constants.
1
1
0. Tranmer, G. K.; Yip, C.; Handerson, S.; Jordan, R. W.; Tam,
W. Can. J. Chem. 2000, 78, 527.
26. GOESY: Gradient enhanced nuclear Overhauser enhancement
spectroscopy, see: (a) Stonehouse, J.; Adell, P.; Keeler, J.;
Shaka, A. J. J. Am. Chem. Soc. 1994, 116, 6037. (b) Stott, K.;
Stonehouse, J.; Keeler, J.; Hwang, T-L.; Shaka, A. J. J. Am.
Chem. Soc. 1995, 117, 4199. (c) Dixon, A. M.; Widmalm, G.;
Bull, T. E. J. Magn. Reson. 2000, 147, 266.
1. (a) Jordan, R. W.; Tam, W. Org. Lett. 2000, 2, 3031. (b) Jordan,
R. W.; Tam, W. Org. Lett. 2001, 3, 2367.
1
1
1
2. Mayo, P.; Hecnar, T.; Tam, W. Tetrahedron 2001, 57, 5931.
3. Mayo, P.; Tam, W. Tetrahedron 2001, 57, 5943.
4. Trost, B. M.; Balkovec, J. M.; Angle, S. R. Tetrahedron Lett.
1
986, 27, 1445.
27. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
28. Lautens, M.; Edwards, L. G.; Tam, W.; Lough, A. J. J. Am.
Chem. Soc. 1995, 117, 10276.
1
5. Schore, N. E. Comprehensive Organometallic Chemistry II,
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon:
Oxford, 1995; Vol. 12, p 721.
29. Verkruijsse, H. D.; Brandsma, L. Recl. Trav. Chim. Pays-Bas
1986, 105, 66.
1
1
6. Morisaki, Y.; Kondo, T.; Mitsudo, T. Org. Lett. 2000, 2, 949.
7. Michieletto, I.; Fabris, F.; De Lucchi, O. Tetrahedron:
Asymmetry 2000, 11, 2835.
30. Gassman, P. G.; Mansfield, K. T. J. Am. Chem. Soc. 1968, 90,
1517.
1
8. The exo and endo cycloadducts 8 and 9 were modeled for
energy minimization at PM3 level (CS Chem 3D Pro Version
31. Rousseau, G.; Le Perchec, P.; Conia, J. M. Synthesis 1978, 67.
32. (a) Cossu, S.; De Lucchi, O.; Paulon, A.; Peluso, P.; Zonta, C.
Tetrahedron Lett. 2001, 42, 3515. (b) Gassman, P. G.;
Gennick, I. J. Org. Chem. 1980, 45, 5211.
3
.5.1) using MOPAC for the assessment of the dihedral angles
a
b
between H and H . These dihedral angles were then compared
to the Karplus curve for the determination of the theoretical
coupling constants.
33. Gassman, P. G.; Gennick, I. J. Org. Chem. 1980, 45, 5211.
34. Kleinfelter, D. C.; Dye, T. E.; Mallory, J. E.; Trent, E. S.
J. Org. Chem. 1967, 32, 1734.
1
9. Similar methods have been used for the assignment of exo and