Synthesis of chiral organotin reagents: Synthesis of bicyclo[2.2.1]heptan-2-yl(diphenyl)tin hydrides with cis-disposed, oxygen-containing substituents

Article abstract of DOI:10.1039/a706295h

Alkylation of the methyl 3-triphenylstannylbicyclo[2.2.1]hept-5-ene-2-carboxylate 3 using lithium diethylamide and either methyl iodide or benzyl bromide at -78°C is stereoselective in favour of the endo-alkylated products 10 and 11. Methylation of the saturated ester 12 is also endo-selective in favour of 13. If the unsaturated ester 3 is deprotonated at 0°C rather than at -78°C, the rearranged stannane 17 is obtained as a side-product. The endo-triphenylstannylbicyclo[2.2.1]heptane-2-carboxylate 22 has been prepared from the ester 12 by phenylselenylation, oxidative elimination and reduction using diimide. The triphenylstannanes 13, 17 and 20 have been converted into the alkyl(diphenyl)tin hydrides 27, 28 and 29 and the methoxyalkyltin hydride 36 has also been prepared and characterized. These tin hydrides accelerate the reduction of aryl methyl ketones to 1-arylethanols by phenylsilane, but the reduction product is racemic. Syntheses of the aminobicycloalkyl(triphenyl)stannanes 44, 45 and 48 are described.

Full text of DOI:10.1039/a706295h

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Synthesis of chiral organotin reagents: synthesis of
bicyclo[2.2.1]heptan-2-yl(diphenyl)tin hydrides with cis-disposed,
oxygen-containing substituents
Robert M. Pratt and Eric J. Thomas*
The Department of Chemistry, The University of Manchester, Manchester, UK M13 9PL
Alkylation of the methyl 3-triphenylstannylbicyclo[2.2.1]hept-5-ene-2-carboxylate 3 using lithium
diethylamide and either methyl iodide or benzyl bromide at Ϫ78 ЊC is stereoselective in favour of the endo-
alkylated products 10 and 11. Methylation of the saturated ester 12 is also endo-selective in favour of 13.
If the unsaturated ester 3 is deprotonated at 0 ЊC rather than at Ϫ78 ЊC, the rearranged stannane 17 is
obtained as a side-product. The endo-triphenylstannylbicyclo[2.2.1]heptane-2-carboxylate 22 has been
prepared from the ester 12 by phenylselenylation, oxidative elimination and reduction using diimide.
The triphenylstannanes 13, 17 and 20 have been converted into the alkyl(diphenyl)tin hydrides 27, 28 and 29
and the methoxyalkyltin hydride 36 has also been prepared and characterized. These tin hydrides
accelerate the reduction of aryl methyl ketones to 1-arylethanols by phenylsilane, but the reduction
product is racemic. Syntheses of the aminobicycloalkyl(triphenyl)stannanes 44, 45 and 48 are described.
The (1S,2S,3R,4R)-endo-adduct 2 is the major product from
the diethylaluminium chloride-catalysed Diels–Alder reaction
between the chiral (E)-3-triphenylstannylacrylate 1 and cyclo-
pentadiene.1 The adduct 2 has been converted into the methyl
ester 3 by transesterification and into the saturated alcohol 4, ee
94%, by reduction using diisobutylaluminium hydride followed
by hydrogenation. The alcohol was O-methylated to give the
methyl ether 7, and the alcohol 4 and methyl ether 7 were con-
verted into the bicycloheptyl(diphenyl)tin hydrides 6 and 9 by
Diels–Alder reactions of (Z)-3-(triphenylstannyl)acrylates and
cyclopentadiene.2 However, mixtures of endo- and exo-isomers
were obtained with only modest diastereofacial selectivity being
observed for addition of cyclopentadiene to the (Z)-isomer of
the chiral dienophile 1.1
Results and discussion
Alkylation of methyl 3-triphenylstannylbicyclo[2.2.1]heptane-2-
carboxylates
Alkylation of the lithium enolate of the methyl ester 3 using
methyl iodide or benzyl bromide gave the endo-alkylated
products 10 and 11, in which the methoxycarbonyl group is cis-
disposed with respect to the tin, with stereoselectivities of
у97:3 and 85:15, respectively. Better yields were obtained in
these reactions using lithium diethylamide rather than lithium
diisopropylamide as the base, e.g. 98% rather than 17% for the
methylation, perhaps because of steric interaction with the
bulky, tin-containing, substituent. Hydrogenation of the ester 3
gave the saturated ester 12 which on methylation using lithium
diethylamide and methyl iodide gave the endo-methylated
product 13 with 95:5 stereoselectivity. The saturated ester 13
4
3
O
SnPh3
O
O
SnPh3
H
1
2
H
O
Me
O
O
CO2Me
Me
Me
Me
Ph3Sn
O
O
1
2
3
SnPh2X
SnPh2X
H
H
4
3
SnPh3
SnPh3
SnPh3
CO2Me
CO2Me
OMe
OH
R
CO2Me
12
Me
4 X = Ph
5 X = I
7 X = Ph
10 R = Me
11 R = Bn
8 X = I
13
6 X = H
9 X = H
treatment with iodine followed by reduction of the iodides 5
and 8 using sodium borohydride. Analogous tin hydrides with
different substituents on the oxygen (tert-butyldimethylsilyl,
trityl and 1-naphthoyl) were also prepared. Spectroscopic data
indicated that there is little interaction between the trans-
disposed oxygen functionality and the tin substituents in these
compounds.1
We now report syntheses of bicyclo[2.2.1]heptanyltin iodides
and hydrides with cis-disposed, oxygen-containing, vicinal
substituents together with preliminary studies into the prepar-
ation of amido- and amino-substituted stannanes. Bicyclo-
[2.2.1]heptanylstannanes with vicinal, oxygen-containing
substituents cis-disposed to the tin have been prepared using
was also prepared by hydrogenation of the unsaturated methyl
ester 10.
The structures of these alkylated products were assigned on
1
the basis of spectroscopic data. In the H NMR spectrum of
the unsaturated endo-methylated product 10 the lack of coup-
ling between 3-H and 4-H and the presence of a ‘W’-coupling
of 2.5 Hz between 3-H and the 7-H syn to the double bond
confirmed the retained configuration at C(3).3 The endo-
selectivity of the methylation then followed from the 13C NMR
spectrum which showed three-bond couplings between the tin
and the carboxy carbon and between the tin and the carbon of
the 2-methyl group of 40.5 and 11 Hz, respectively. Since three-
bond couplings to tin are known to follow a Karplus relation-
J. Chem. Soc., Perkin Trans. 1, 1998
727

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ship with respect to torsional angle,4 it follows that the carboxy
group is exo, with a torsional angle of ca. 0Њ with respect to the
C(3)᎐Sn bond, and the 3-methyl group is endo, torsional angle
ca. 110Њ. An NOE enhancement of 6-H of 1.3% on irradiation
of the 3-methyl group is also consistent with the assigned
stereochemistry. Similar features were observed in the NMR
spectra of the other alkylation products 11 and 13.
of spectroscopic data. In its 13C NMR spectrum, three-bond
couplings of 64 and 24 Hz were observed between the tin and
C(7) and between the tin and C(5) suggesting that the tin is in
the endo-position.4,8 This was confirmed by the 1H NMR spec-
trum which showed that 3-H was exo by a coupling of 2.9 Hz
between 3-H and 4-H and no ‘W’-coupling between 3-H and
the syn-7-H. The configuration at C(2) was assigned on the
basis of the three-bond couplings to tin of 30 and 14 Hz
observed in the 13C NMR spectrum for the carboxy carbon and
the carbon of the 2-methyl group, respectively.4 A carbonyl
stretching frequency of 1715 cmϪ1 in the IR spectrum of the
ester 17 was also consistent with a small interaction between the
carbonyl group and the tin indicative of the cis-disposition of
the methoxycarbonyl and triphenylstannyl substituents.
The formation of the endo-ester 17 may be due to partial
elimination of triphenyltin lithium from the enolate 16 at 0 ЊC
to generate the dienyl ester 18. Readdition of the triphenyltin
lithium to this conjugated ester could then either regenerate the
enolate 16 or its epimer at C(3) which would be expected to
react with the methyl iodide from the exo-face to preserve any
interaction between the enolate oxygen and the tin in the transi-
tion structure for alkylation. The isolation of methyl(triphenyl)-
stannane as a side-product is consistent with the involvement of
triphenyltin lithium in this reaction.
The carbonyl stretching frequency in the IR of the methyl-
ated ester 10 was at 1707 cmϪ1, cf. 1731 cmϪ1 for the endo-
methyl ester 3. This shift suggests a small interaction between
the tin and the oxygen of the carbonyl group. This interaction is
consistent with the increases observed in the one-bond coup-
lings between the tin and C(3) and between the tin and the ipso-
aromatic carbon in the 13C NMR spectra of the esters on
1
119/117Sn
methylation, JC(3)
440/421 for 10, cf. 398/381 for 3 and
JC(ipso) Sn 503/481 for 10, cf. 481/458 for 3.5
1
119/117
Organostannanes containing suitably disposed oxygen-
containing functional groups for coordination have been pre-
pared and examined by X-ray crystallography.6 The tetrahedral
geometry of the tin in these compounds was found to be dis-
torted slightly by interaction with the oxygen and increases in
the one-bond coupling to the tin were observed similar to those
reported here. No interaction between the tin and the carboxy
group was indicated by the spectroscopic data obtained for the
bicyclo[2.2.1]heptane carboxylates 2 and 3.1 The detection of
this interaction is therefore indicative of a cis-relationship
between the triphenyltin and methoxycarbonyl substituents as
in the methylated ester 10. Similar features were observed for
the benzylated ester 11 and the saturated endo-methylated ester
13.
Preliminary studies were carried out into an alternative route
to bicyclo[2.2.1]heptanes with endo-methoxycarbonyl and
triphenyltin substituents. Addition of benzeneselenenyl chlor-
ide to the lithium enolate of the ester 12 gave the endo-
phenylselenenyl ester 19 (19%) together with unchanged ester
12 (11%) and the epimerised ester 20 (40%). Differences in the
The preference for endo-alkylation shown by the 3-triphenyl-
stannyl esters 3 and 12 contrasts with the stereoselectivity of
methylation of methyl bicyclo[2.2.1]heptane-3-carboxylate 14
which gives preferentially the exo-methylated product 15.7
Perhaps the tin in the lithium enolate, e.g. 16 derived from the
LiNEt2
SnPh3
SnPh3
12
+
CO2Me
CO2Me
PhSeCl
SePh
19
20
LiNPri2, MeI
MCPBA
+
exo-ester
H
Me
– 78 oC
CO2Me
CO2Me
97 : 3
N2H2
SnPh3
14
15
CO2Me
SnPh3
CO2Me
SnPh3
21
22
O
Li
NMR spectra of the ester 12 and its epimer 20 were consistent
with the assigned structures. For example, the three-bond coup-
ling between the tin and the carboxy carbon was 55 Hz for 20
consistent with a torsional angle between the C(3)᎐Sn and
C(2)᎐CO2Me bonds approaching 0Њ, cf. the coupling of 22 Hz
observed for the endo-ester 12.4 One-bond tin–carbon couplings
were larger for 17 than for 12 in line with some degree of
coordination of the tin by the cis-methoxycarbonyl group.5 The
IR stretching frequency is lower for the exo-ester 20 than for the
H
OMe
16
ester 3, is coordinated by the negatively charged oxygen. This
coordination would have to be disrupted if the alkylation took
place from the exo-direction whereas it can translate into the
weak interaction observed in the alkylated products if the
alkylation takes place from the endo-direction.
When the alkylation of the ester 3 was carried out at 0 ЊC
rather than at Ϫ78 ЊC, the yield of the endo-methylated product
10 was only 21% and an isomer of the alkylated product was
isolated (8%) together with methyl(triphenyl)stannane (17%).
The structure 17 was assigned to the new product on the basis
endo-ester 12, 1715 vs. 1731 cmϪ1
.
Similar data supported the assignment of stereochemistry
to the phenylselenated ester 19. Moreover, oxidation of the
selenide using m-chloroperoxybenzoic acid9 was accompanied
by loss of phenylselenenic acid and gave the unsaturated ester
21. The loss of the hydrogen from C(3) in this elimination con-
firmed the cis-orientation of the phenylselenyl group and 3-H.
It would appear that reactions with other electrophiles of the
enolate generated from the 3-triphenylstannylated ester 12 also
take place trans with respect to the triphenyltin substituent.
Finally reduction of the unsaturated ester 21 by diimide
gave the endo-ester 22 the structure of which was supported by
7
4
3
5
Me
6
1
2
SnPh3
CO2Me
CO2Me
1
spectroscopic data. For example, in the H NMR spectrum a
17
‘W’-coupling of 1.5 Hz was observed between 2-H and the exo-
18
728
J. Chem. Soc., Perkin Trans. 1, 1998

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6-H and a vicinal coupling of 4.5 Hz was observed between 1-H
and 2-H so showing the methoxycarbonyl group to be in the
endo-position. The low carbonyl stretching frequency observed
in its IR spectrum, 1719 cmϪ1 relative to 1731 cmϪ1 observed for
the endo-ester 12, indicates the cis-disposition of the triphenyl-
stannyl and methoxycarbonyl substituents in 22.
This study of the alkylation of esters 3 and 12 had led to the
synthesis of several products 10, 11, 13, 17, 20 and 22, in which
a triphenyltin substituent is cis-disposed with respect to a
methoxycarbonyl group. The conversion of these stannanes
into cis-functionalized tin iodides and tin hydrides was then
investigated.
stretching frequencies of 1708, 1713 and 1711 cmϪ1 observed
for the tin hydrides 27, 28 and 29 were similar to those observed
for the corresponding triphenylstannanes,1 Diastereotopic sub-
stituents attached to the tin of chiral tin hydrides can usually be
distinguished by NMR spectroscopy10,11 and the diastereotopic
phenyl groups of the tin hydrides 27 and 29 gave rise to different
peaks in their 13C NMR spectra although only one set of aro-
matic peaks was apparent for the tin hydride 28. The hydrogens
bound to tin were detected in the 1H NMR spectra of the
tin hydrides 27, 28 and 29 as doublets (J 1.5–2.5 Hz) at δH 6.98
(1JH
(1JH
1906/1820), 6.89 (1JH
1906/1821) and 7.09
1966/1889), respectively, the slightly increased one-
119/117Sn
119/117Sn
119/117Sn
bond coupling to tin for the endo-tin hydride 29 perhaps indi-
cating a slightly stronger interaction between the tin and the
methoxycarbonyl group than for the exo-isomer 27.
Reduction of the methylated exo-ester 13 using diisobutyl-
aluminium hydride gave the alcohol 30 which on treatment with
Syntheses of cis-functionalized tin hydrides
The exo-3-triphenylstannylbicyclo[2.2.1]heptane-2-carboxyl-
ates 13 and 20 were treated with 1 mol equiv. of iodine to give
the alkyl(diphenyl)tin iodides 23 and 24 in excellent yields.2
Ph
I
Ph
I
1
Sn
2
Sn
SnPh3
OH
SnPh3
OR
Ph
OH
Ph
Me
O
4
3
SnPh3
CO2Me
Me
OMe
Me
R
Me
30
32 R = H
31
23 R = Me
24 R = H
25
33 R = Me
Ph
Sn
I
SnPh2H
CO2Me
SnPh2H
OMe
SnPh3
OMe
Me
SnPh2I
Me
Ph
SnPh2H
CO2Me
OMe
R
Me
MeO
Me
O
Me
26
27 R = Me
28 R = H
36
29
34
35
iodine was converted into the tin iodide 31. The one-bond coup-
Hydrogenation of the endo-stannane 17 gave the saturated
stannane 25 which was converted into the tin iodide 26 by
treatment with iodine. Reduction of the tin iodides 23, 24 and
26 with sodium borohydride gave the corresponding tin
hydrides 27, 28 and 29.2
ling of C(2) to the tin observed in the 13C NMR spectrum of the
1
119/117Sn
tin iodide 31, JC(2)
490/467, is larger than that observed
1
119/117Sn
for the hydroxyalkyltin iodide 5, JC(2)
440/418, which is
consistent with some degree of coordination of the tin by the
hydroxy group.5,13 Moreover, the resonance observed in the
119Sn NMR spectrum of the tin iodide 31, at δ Ϫ102, is con-
siderably more upfield than that observed for the iodide 5,
δ Ϫ38.8.1 The diastereotopic phenyl groups in the tin iodide 31
gave rise to different peaks in its 13C NMR spectrum, e.g. at
δ 141.22 and 142.62 for the ipso-aromatic carbons.
However, reduction of the tin iodide 31 using sodium boro-
hydride did not give a tin hydride which could be isolated or
characterised and attempts to eliminate hydrogen iodide from
31 using sodium hydride, perhaps to give an oxastannocycle,
gave only complex mixtures of products.14
Reduction of the unsaturated methylated ester 10 gave the
alcohol 32 which was methylated using sodium iodide and
methyl iodide to give the methyl ether 33. Hydrogenation gave
the saturated methyl ether 34 which was treated with iodine to
give the tin iodide 35. The iodide was reduced using sodium
borohydride to give the tin hydride 36.
Structures were assigned to these products on the basis of
spectroscopic data. Of interest was the degree of coordination
of the methoxycarbonyl group to the tin.6 For the tin iodides, a
significant lowering of the carbonyl stretching frequency was
observed in their IR spectra from 1709, 1715 and 1712 cmϪ1 for
the triphenylstannanes 13, 20 and 25 to 1664, 1665 and 1661
cmϪ1 for the tin iodides 23, 24 and 26, respectively, which is
consistent with a significant coordination of the tin by the
1
methoxycarbonyl substituent in these compounds. In the H
NMR spectra of the exo-tin iodides 23 and 24 a marked
deshielding of the bridgehead proton 1-H was observed relative
to the triphenylstannanes 13 and 20, δ 3.00 and 3.15 for 23 and
24 cf. δ 2.67 and 2.77 for 13 and 20. This may be due to pseudo
trigonal bipyramidal geometry of the tin which would place the
axial iodide close to this bridgehead proton as indicated for the
iodides 23 and 24.
As usually observed for chiral tin halides,10,11 the diastereo-
topic phenyl rings in the diphenyltin iodide 8 for which intra-
molecular coordination of the tin by the methoxy group is not
The structures of the tin iodide 35 and hydride 36 were
assigned on the basis of spectroscopic data. The bridgehead
1
proton, 1-H, in the H NMR spectrum of the iodide 35 was
1
possible, were found to be equivalent by H NMR consistent
deshielded with respect to that of the triphenylstannane 34 by
0.72 ppm, and the diastereotopic phenyl groups in the iodide 35
were distinguishable in its 13C NMR spectrum, e.g. two ipso-
carbons were observed at δ 141.11 and 141.73. These observ-
ations are consistent with some degree of coordination of the
tin by the methoxy group in the tin iodide 35.
with rapid exchange on the NMR time-scale.1 However, the two
phenyl rings in each of the tin iodides 23, 24 and 26 were found
1
to be non-equivalent by both H and 13C NMR spectroscopy.
For example, two ipso-aromatic carbons were observed for the
tin iodides 23, 24 and 26 at δ 140.36/142.37, 140.54/142.42 and
141.03/141.86, respectively.
The one-bond tin–proton coupling observed in the 1H NMR
The coordination of the tin by the methoxycarbonyl sub-
stituents in the tin iodides 23, 24 and 26 which is indicated by
the spectroscopic data discussed above, was not as apparent in
the tin hydrides 27, 28 and 29. For example, the carbonyl
spectrum of the tin hydride 36 was larger than that observed for
1
119/117Sn
the tin hydride 9, JH
1850/1769 cf. 1763/1681, and the
tin in its 119Sn NMR spectrum was somewhat more shielded,
δ Ϫ139 cf. Ϫ118 ppm. The diastereotopic phenyl rings of the tin
J. Chem. Soc., Perkin Trans. 1, 1998
729

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1
hydride 36 also gave rise to distinctly different peaks in its H
and 13C NMR spectra.
SnPh3
CHO
SnPh3
SnPh3
CH=NOH
Tin hydrides with substituents which can coordinate with the
tin in the transition state for hydride transfer can act as hydride
reducing agents. The tin hydrides 27, 28, 29 and 36 were found
to accelerate the reduction of acetophenone and o-hydroxy-
acetophenone by phenylsilane, with better conversions being
obtained for the hydroxyacetophenone. However the 1-aryl-
ethanol so obtained was racemic and reduction of methyl
2-bromo-2-phenylpropanoate using the tin hydride 36 gave
racemic methyl 2-phenylpropanoate. Alkyltin hydrides with
amino substituents which can coordinate with the tin have
also been shown to be useful for the reduction of carbonyl
compounds.15 The preparation of amino-substituted bicyclo-
[2.2.1]heptyl(triphenyl)stannanes was therefore briefly investi-
gated with the synthesis of cis-substituted (aminoalkyl)-
bicycloheptylstannanes in which the amino group can coordin-
ate to the tin being of particular interest.16
NH2
Me
Me
46
Me
48
47
SnPh3
CHO
SnPh3
CH=N–NMe2
Me
49
Me
50
49 was similarly prepared by oxidation of the alcohol 32.
Treatment of this aldehyde with dimethylamine and sodium
cyanoborohydride gave none of the required tertiary amine
although the N,N-dimethylhydrazone 50 was prepared, albeit in
low yield, by treatment with N,N-dimethylhydrazine.
Approaches to aminoalkylbicyclo[2.2.1]heptyl(triphenyl)-
stannanes
The endo-methylated methyl ester 13 was recovered unchanged
from attempts to prepare the dimethylamide 37 by heating the
Conclusions
The work described in this and the preceding papers has
reported aspects of the chemistry of bicyclo[2.2.1]heptan-2-
yl(diphenyl)stannanes. In the present paper, the influence of the
triphenyltin substituent on the stereoselectivity of alkylation of
the esters 3 and 12 is of note. The heteroatom functionality in
the tin iodides 23, 24, 26, 31 and 35 is believed to be associated
with the tin of the tin iodide to a certain extent and the func-
tionalized tin hydrides were found to behave as reducing agents
towards ketones and alkyl halides although the products
obtained were racemic.
It may be that better coordinating groups than the methoxy-
carbonyl and methoxy groups used to date will be required
for effective asymmetric reduction of carbonyl compounds. It
may also be necessary to use bulkier ligands on the tin. In the
present work, the carbon skeleton of the enantiomerically
enriched tin hydrides was assembled using an asymmetric
Diels–Alder reaction. A completely different approach would
start from readily available bicyclic monoterpenes and re-
lated natural products. This approach is presently being
investigated.
SnPh3
SnPh3
SnPh3
CONMe2
CONR1R2
Me
CONR2
38 R = Me
41 R1 = H, R2 = Bn
42 R1,R2 = (CH2)5
37
39 R2 = (CH2)4
40 R2 = (CH2)5
SnPh3
SnPh3
SnPh3
CON(CH2)5
N
N
Me
43
45
44
ester with trimethylaluminium and dimethylamine.17 Analo-
gous attempts to prepare the corresponding benzylamide were
also unsuccessful. However, the esters 3 and 12 could be con-
verted into the amides 38–40 and 41, 42 by treatment with the
appropriate aluminium amide.18 The amide 40 was methylated
by deprotonation using lithium diethylamide at Ϫ30 ЊC fol-
lowed by the addition of methyl iodide at Ϫ78 ЊC, but the endo-
methylated product 43 was only obtained in a modest yield
(16%) together with unchanged starting material (36%) and
methyl(triphenyl)tin (21%). Of note is the IR carbonyl stretch-
ing frequency of the amide 43 which was at 1588 cmϪ1, cf. 1636
cmϪ1 for the amide 40. This is indicative of some degree of
coordination of the tin by the carbonyl oxygen consistent with
the expected stereoselectivity of alkylation.1 Attempts to reduce
the methylated amide 43 to the corresponding tertiary amine
using lithium aluminium hydride were unsuccessful, although
the non-methylated amides 39 and 42 were cleanly reduced to
the endo-dialkylaminomethylbicyclo[2.2.1]heptanylstannanes
44 and 45. It would appear that the combination of a bulky
triphenyltin substituent and a quaternary centre α to the
carbonyl group makes the endo-alkylated amides, e.g. 43, both
relatively inaccessible and difficult to use.
Experimental
For general experimental details see the first paper in this
series.2
Methyl (1S,2R,3R,4R)-2-methyl-3-(triphenylstannyl)bicyclo-
[2.2.1]hept-5-ene-2-carboxylate 10
Butyllithium (1.5 mol dmϪ3 in hexanes; 2.10 cm3) was added
dropwise to a solution of diethylamine (0.41, 3.95 mmol) in
tetrahydrofuran (16 cm3) at 0 ЊC. The solution was stirred for 15
min, and then cooled to Ϫ78 ЊC before the addition of the ester
3 (0.99 g, 1.97 mmol) in tetrahydrofuran (4 cm3). The mixture
was stirred at Ϫ78 ЊC for 1 h and then methyl iodide (0.49 cm3,
7.89 mmol) was added dropwise. After stirring for a further
1.5 h, the reaction mixture was warmed to ambient temperature,
concentrated under reduced pressure and the residue diluted
with ether (20 cm3). The solution was washed with water (20
cm3), then brine (20 cm3), and the organic phase dried (MgSO4)
and concentrated under reduced pressure to give the title
compound 10 (1.0 g, 98%), as an oil, used without further purifi-
cation; [α]D Ϫ10.9 (c 1.33 in CHCl3) (Found: Mϩ Ϫ C6H5,
439.0717. C22H23O2Sn requires M, 439.0720); νmax/cmϪ1 3062,
1707, 1428, 1291, 1273, 1250, 1216, 1100, 1072, 728 and 699;
δH 1.20 (3 H, s, 2-CH3), 1.20 (1 H, d, J 2.5, 3-H), 1.33 (1 H, dd,
J 8.5, 1.5, 7-H), 1.37 (1 H, d, J 8.5, 7-HЈ), 3.13 (1 H, m, 1-H),
3.18 (1 H, m, 4-H), 3.58 (3 H, s, OCH3), 6.10 (1 H, dd, J 5.5, 3,
6-H), 6.39 (1 H, dd, J 5.5, 3, 5-H), 7.4 (9 H, m, ArH) and 7.6
(6 H, m, ArH); δC 24.97 (3JCSn 11), 38.92 (1JCSn 440/421), 47.06,
As a second approach to bicyclo[2.2.1]heptanylstannanes
with cis-disposed amino groups, aspects of the chemistry of the
aldehydes 46 and 49 were briefly investigated. The aldehyde 46
was prepared by oxidation of the alcohol 30 using TPAP19 but
reaction with hydroxylamine20 gave only a low yield, 11%, of the
oxime 47. Nevertheless this oxime was reduced using lithium
aluminium hydride to the amine 48. The unsaturated aldehyde
730
J. Chem. Soc., Perkin Trans. 1, 1998

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48.36, 52.26 (3JCSn 12.5), 52.85, 52.89, 128.11 (3JCSn 48), 128.22,
131.63, 137.44 (2JCSn 35), 140.45 (3JCSn 55.5), 142.55 (1JCSn
503/481) and 181.34 (3JCSn 40.5); m/z 439 (Mϩ Ϫ 77, 100%),
368 (10) and 351 (10).
Methyl (1R,2R,3R,4S)-2-methyl-3-triphenylstannylbicyclo-
[2.2.1]heptane-2-carboxylate 13
Following the procedure outlined for the synthesis of the ester
10, the saturated ester 12 (0.45 g, 0.89 mmol) and methyl iodide
(0.22 cm3, 3.58 mmol) gave the title compound 13 (0.47 g, 98%),
as an oil, used without further purification (Found: Mϩ Ϫ
C6H5, 441.0875. C22H25O2Sn requires M, 441.0877); [α]D Ϫ4.2
(c 6.6 in CHCl3); νmax/cmϪ1 3062, 1709, 1428, 1300, 1277, 1222,
1072, 728 and 699; δH 1.24 (1 H, d, J 10.5, 7-H), 1.40 (3 H, s,
2-CH3), 1.45 (1 H, d, J 2, 3-H), 1.50–1.90 (5 H, m, 5-H2, 6-H2
and 7-HЈ), 2.63 (1 H, m, 1-H), 2.67 (1 H, m, 4-H), 3.65 (3 H, s,
OCH3), 7.35–7.48 (9 H, m, ArH) and 7.58–7.78 (6 H, m, ArH);
δC 22.86, 22.92, 33.62 (3JCSn 66), 38.69, 41.92, 43.69 (1JCSn 455/
435), 46.10 (JCSn 14), 52.91, 53.33 (JCSn 30.5), 128.00 (3JCSn
47.5), 128.07, 137.44 (2JCSn 34), 142.99 (1JCSn 498/476) and
181.55 (3JCSn 55.5); m/z 441 (Mϩ Ϫ 77, 100%).
Chromatography, using light petroleum–ether (100:1) as elu-
ent, of the mixture of products obtained when 3.0 mol equiv. of
lithium diethylamide at 0 ЊC was used to deprotonate the ester
3 gave methyl(triphenyl)tin (0.225 g, 17%) as a white solid
(Found: C, 62.9; H, 5.3. C19H18Sn requires C, 62.5; H, 5.0%);
νmax/cmϪ1 3063, 3047, 3014, 1428, 1075, 726 and 698; δH 0.88
(3 H, s, 2JHSn 56.0/54.0, CH3), 7.5 (9 H, m, ArH) and 7.7 (6 H,
m, ArH); δC Ϫ10.36 (1JCSn 375/358), 128.62 (3JCSn 49.5), 129.03
(4JCSn 11), 136.91 (2JCSn 37.0) and 139.30 (1JCSn 510/487); m/z
351 (Mϩ Ϫ 15, 20%), 307 (100) and 289 (30). Further elution
gave the methylated ester 10 (0.42 g, 21%) followed by methyl
(1S,2S,3S,4R)-2-methyl-3-triphenylstannylbicyclo[2.2.1]heptan-
2-yl-carboxylate 17 (0.15 g, 8%) as an oil (Found: Mϩ,
516.1110. C28H28O2Sn requires M, 516.1111); [α]D ϩ65.8 (c 2.37
in CH2Cl2); νmax/cmϪ1 3062, 1715, 1428, 1331, 1297, 1275, 1212,
1123, 1072, 729 and 700; δH 1.60 (3 H, s, CH3), 1.69 and 1.73
(each 1 H, d, J 8.5, 7-H), 2.00 (1 H, d, J 2.5, 2JHSn 50, 3-H), 3.02
(1 H, m, 1-H), 3.27 (1 H, m, 4-H), 3.57 (3 H, s, OCH3), 6.11
(1 H, dd, J 5.5, 3, 6-H), 6.16 (1 H, dd, J 5.5, 3, 5-H), 7.37 (9 H,
m, ArH) and 7.65 (6 H, m, ArH); δC 27.32 (3JCSn 14), 41.88
(1JCSn 498/487), 47.28 (2JCSn 9), 49.59 (3JCSn 64), 51.66 (3JCSn
22.5), 52.46, 52.78 (2JCSn 16), 128.07 (3JCSn 48), 128.12, 135.67,
137.48 (2JCSn 35.0), 139.07 (3JCSn 24), 142.86 (1JCSn 506/483) and
179.95 (3JCSn 30); m/z (EI) 516 (Mϩ, 10%), 439 (60) and 351
(100).
Phenylselenation of the ester 12
Butyllithium (1.6 mol dmϪ3 in hexanes; 0.47 cm3) was added
dropwise to a solution of diethylamine (0.085 cm3, 0.84 mmol)
in tetrahydrofuran (2 cm3) at 0 ЊC. The solution was stirred for
15 min then cooled to Ϫ78 ЊC before the addition of the ester
12 (0.21 g, 0.42 mmol) in tetrahydrofuran (2 cm3). The mixture
was stirred at Ϫ78 ЊC for 2 h then a solution of benzeneselene-
nyl chloride (0.105 g, 0.545 mmol) in tetrahydrofuran (1 cm3)
was added dropwise. After stirring for a further 2 h, the reaction
mixture was warmed to ambient temperature and concentrated
under reduced pressure. The residue was diluted with ether (10
cm3) then washed with saturated aqueous ammonium chloride
(10 cm3) and brine (10 cm3), dried (MgSO4) and concentrated
under reduced pressure. Chromatography of the residue using
light petroleum–ether (40:1) as eluent gave methyl (1R,2R,
3R,4S)-3-triphenylstannylbicyclo[2.2.1]heptane-2-carboxylate
20 (84 mg, 40%) as an oil (Found: Mϩ Ϫ C6H5, 427.0715.
C21H23O2Sn requires M, 427.0720); νmax/cmϪ1 3062, 1715, 1428,
1215, 1201, 1176, 1073, 728 and 699; δH 1.16 (1 H, d, J 10, 7-H),
1.4–1.6 (3 H, m, CH2 and 7-HЈ), 1.65–1.8 (2 H, m, CH2), 2.05
(1 H, dd, J 9, 2, 2JHSn 55, 3-H), 2.66 (1 H, m, 1-H), 2.77 (1 H, m,
Methyl (1S,2R,3R,4R)-2-benzyl-3-triphenylstannylbicyclo-
[2.2.1]hept-5-ene-2-carboxylate 11
Following the procedure outlined for the synthesis of the
methylated ester 10, but using benzyl bromide as the alkylating
agent, the ester 3 (0.15 g, 0.3 mmol) gave, after chromatography
using light petroleum–ether (20:1) as eluent, the title compound
11 (91 mg, 51%) as a white solid (Found: Mϩ Ϫ C6H5, 515.1034.
C28H27O2Sn requires M, 515.1033); mp 90–94 ЊC; [α]D ϩ10.1
(c 3.60 in CHCl3); νmax/cmϪ1 3061, 1707, 1427, 1330, 1247, 1212,
1179, 1072, 728 and 699; δH 1.26 and 1.40 (each 1 H, d, J 8.5,
7-H), 1.71 (1 H, d, J 2.5, 2JHSn 49, 3-H), 2.65 and 3.12 (each 1 H,
d, J 13, CHHPh), 3.19 (1 H, m, 4-H), 3.28 (1 H, m, 1-H), 3.52 (3
H, s, OCH3), 6.27 (1 H, dd, J 5, 2.5, 6-H), 6.51 (1 H, dd, J 5, 2.5,
5-H), 7.03 (5 H, m, ArH), 7.3 (9 H, m, ArH) and 7.5 (6 H, m,
ArH); δC 37.1 (1JCSn 445/425), 45.44 (JCSn 10), 46.68, 48.09,
51.54 (JCSn 11.5), 52.43, 59.9 (3JCSn 11.5), 126.67, 127.95 (3JCSn
48.5), 128.01, 128.35, 129.10, 132.36, 137.47 (2JCSn 34), 140.90
(3JCSn 55.5), 142.25 (1JCSn 503/481) and 180.01 (3JCSn 40.5); m/z
515 (Mϩ Ϫ 77, 100%).
3
4-H), 2.88 (1 H, d, J 9, JHSn 50, 2-H), 3.55 (3 H, s, OCH3),
7.38–7.46 (9 H, m, ArH) and 7.60–7.80 (6 H, m, ArH); δC
29.67, 33.10 (3JCSn 66.5), 34.47 (1JCSn 442), 36.33, 40.65 (JCSn
11.5), 43.03, 50.18 (2JCSn 30.5), 52.32, 128.11 (3JCSn 47.5),
128.24 (4JCSn 11), 137.43 (2JCSn 34.5), 142.18 (1JCSn 497/475) and
178.74 (3JCSn 55); m/z 427 (Mϩ Ϫ 77, 100%). Further elution
gave methyl (1R,2S,3R,4S)-2-phenylselenyl-3-triphenylstannyl-
bicyclo[2.2.1]heptane-2-carboxylate 19 (52 mg, 19%) as an oil
(Found: Mϩ Ϫ C6H5, 583.0193. C27H27O2SeSn requires M,
583.0198); νmax/cmϪ1 3061, 1702, 1428, 1299, 1264, 1219, 1072,
1053, 1022, 728 and 699; δH 1.15 and 1.38 (each 1 H, d, J 10.5,
7-H), 1.47 (2 H, m), 1.72 (3 H, m), 2.65 (1 H, m, 4-H), 2.88 (1 H,
m, 1-H), 3.29 (3 H, s, OCH3), 7.20–7.40 (12 H, m, ArH) and
7.53–7.74 (8 H, m, ArH); δC 25.74, 33.48 (3JCSn 61.5), 37.78,
Methyl (1R,2S,3R,4S)-3-triphenylstannylbicyclo[2.2.1]heptane-
2-carboxylate 12
2
Palladium (10% on charcoal; 0.21 g, 0.20 mmol Pd) was added
to a solution of the alkene 3 (0.96 g, 1.92 mmol) in ethanol (45
cm3). The mixture was stirred vigorously for 20 h under an
atmosphere of hydrogen then filtered through Celite and the
retained solids washed with ether (4 × 20 cm3). The combined
filtrates were concentrated under reduced pressure to give the
title compound 12 (0.91 g, 95%) as an oil, used without further
purification (Found: Mϩ Ϫ C6H5, 427.0720. C21H23O2Sn
requires M, 427.0700); [α]D Ϫ39.0 (c 3.6 in CHCl3); νmax/cmϪ1
1731, 1428, 1197, 728 and 699; δH 1.36 (1 H, d, J 9.5, 7-H),
1.42–1.58 (5 H, m, 5-H2, 6-H2 and 7-HЈ), 2.34 (1 H, dd, J 6.5, 2,
3-H), 2.62 (2 H, m, 1-H and 4-H), 3.20 (1 H, dd, J 6.5, 3, 2-H),
3.70 (3 H, s, OCH3), 7.36–7.48 (9 H, m, ArH) and 7.6 (6 H, m,
ArH); δC 24.74, 31.12 (1JCSn 419/396), 33.31 (3JCSn 66.5), 40.61,
41.09 (2JCSn 7), 41.65 (2JCSn 15), 51.1 (3JCSn 18), 51.63, 128.59
(3JCSn 47), 128.95 (4JCSn 8.5), 137.38 (2JCSn 34), 138.48 (1JCSn 474/
453) and 175.21 (3JCSn 22); δSn Ϫ99.5; m/z (EI) 427 (Mϩ Ϫ 77,
25%), 351 (40) and 197 (100).
41.39, 42.46 (1JCSn 438/419, JSeC 20), 45.07 (JCSn 12), 52.54,
63.33 (2JCSn 32, 1JSeC 75), 127.96, 128.11, 128.70, 128.98, 137.33
(2JCSn 35), 137.51 (2JSeC 7.5), 142.13, 142.60 (1JCSn 512/489)
and 177.11 (3JCSn 49); m/z 583 (Mϩ Ϫ 77, 3%), 503 (3), 444 (5)
and 368 (30). Further elution gave starting material 12 (25 mg,
11%).
Methyl (1R,4S)-3-triphenylstannylbicyclo[2.2.1]hept-2-ene-2-
carboxylate 21
3-Chloroperbenzoic acid (ca. 75% in water; 36 mg, 0.155 mmol)
was added to the selenide 19 (45 mg, 0.07 mmol) in dichloro-
methane (2 cm3). The solution was stirred at ambient temper-
ature for 5 h then washed with aqueous sodium thiosul-
fate (5 cm3) and brine (5 cm3), dried (MgSO4) and concentrated
under reduced pressure. Chromatography of the residue using
light petroleum–ether (20:1) as eluent gave the title compound
21 (18 mg, 53%) as an oil (Found: Mϩ Ϫ C6H5, 425.0565.
C21H21O2Sn requires M, 425.0564); νmax/cmϪ1 3063, 1715, 1698,
J. Chem. Soc., Perkin Trans. 1, 1998
731

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1429, 1330, 1276, 1255, 1162, 1096, 1075, 729 and 699; δH 1.04–
1.32 (3 H, m, CH2 and 7-H), 1.57 (1 H, d, J 9, 7-HЈ), 1.8 (2 H,
m, CH2), 3.22 (1 H, d, J 1.5, 4-H), 3.31 (3 H, s, OCH3), 3.48 (1
H, m, 1-H), 7.4 (9 H, m, ArH) and 7.45–7.68 (6 H, m, ArH); δC
24.04, 24.53 (JCSn 10.5), 43.48, 47.91 (JCSn 28), 49.25 (JCSn 40.5),
50.73, 128.4, 128.77, 136.86 (2JCSn 38), 139.13, 151.97, 163.03
and 165.36; m/z 425 (Mϩ Ϫ 77, 100%).
an atmosphere of hydrogen for 66 h then filtered through
Celite, and the retained solids washed with ether (4 × 10 cm3).
The combined filtrates were concentrated under reduced pres-
sure to give the title compound 25 (0.117 g, 99%) as an oil, used
without further purification (Found: Mϩ Ϫ 77, 441.0876.
C22H25O2Sn requires M, 441.0877); νmax/cmϪ1 3062, 1712, 1428,
1118, 1072, 728 and 699; δH 1.35 (3 H, s, CH3), 1.25–1.6 (5 H, m,
5-H2, 6-H2 and 7-H), 1.77 (1 H, d, J 8.5, 7-HЈ), 1.86 (1 H, m,
3-H), 2.38 and 2.68 (each 1 H, m), 3.69 (3 H, s, OCH3), 7.37
(9 H, m, ArH) and 7.65 (6 H, m, ArH); δC 26.52, 27.54, 28.35,
39.42, 41.82, 45.69, 46.69, 52.43, 53.41, 127.86 (3JCSn 48),
127.89, 137.31 (2JCSn 35), 143.11 and 180.39; m/z 441 (Mϩ Ϫ 77,
100%) and 351 (15).
Methyl (1R,2S,3S,4S)-3-triphenylstannylbicyclo[2.2.1]heptane-
2-carboxylate 22
Sodium acetate (5.5 mg, 0.065 mmol) and toluene-p-
sulfonohydrazide (12 mg, 0.065 mmol) were added to the α,β-
unsaturated ester 21 (16 mg, 0.03 mmol) in ethanol (2 cm3) at
65 ЊC. Further portions of base and hydrazide were added every
30 min until all the starting material had disappeared (TLC).
After 3 h at reflux the mixture was cooled to ambient temper-
ature and partitioned between ether (5 cm3) and water (5 cm3).
The organic phase was separated, washed with brine (10 cm3),
dried (MgSO4) and concentrated under reduced pressure.
Chromatography of the residue using light petroleum–ether
(2:1) as eluent gave the title compound 22 (6.0 mg, 38%) as an
oil (Found: Mϩ Ϫ C6H5, 427.0724. C21H23O2Sn requires M,
427.0720); νmax/cmϪ1 3062, 1719, 1428, 1206, 1071, 1029, 728
and 699; δH 0.9 (2 H, m), 1.3 (2 H, m), 1.42–1.65 (2 H, m), 2.34
(1 H, d, J 11.5, 2JHSn 60, 3-H), 2.70 and 2.76 (each 1 H, m), 3.28
(1 H, ddd, J 11.5, 4.5, 1.5, 2-H), 3.62 (3 H, s, OCH3), 7.37 (9 H,
m, ArH) and 7.64 (6 H, m, ArH); δC 25.32, 29.73, 30.08, 36.11,
40.94, 42.67, 48.51, 52.22, 128.02 (3JCSn 47.5), 128.06, 137.30
(2JCSn 35.5), 142.76 and 177.81; m/z 427 (Mϩ Ϫ 77, 100%).
(1S,2S,3S,4R)-3-Methoxycarbonyl-3-methylbicyclo[2.2.1]-
heptan-2-yl(diphenyl)tin iodide 26
Iodine (36 mg, 0.14 mmol) was added to a solution of the
triphenylstannane 25 (78 mg, 0.15 mmol) in dichloromethane (2
cm3) and the mixture stirred for 1 h at ambient temperature.
Concentration under reduced pressure gave the title compound
26 (86 mg, 100%) as an oil, used without further purification
(Found: Mϩ Ϫ C6H5, 490.9525. C16H20IO2Sn requires M,
490.9530); [α]D ϩ42.6 (c 6.2 in CHCl3); νmax/cmϪ1 1661, 1429,
1323, 1306, 1126, 730 and 697; δH 0.95 (1 H, m, 5-H), 1.28–1.40
(4 H, m, 6-H and CH3), 1.45–1.64 (3 H, m, 5-HЈ, 6-HЈ and 7-H),
1.80 (1 H, d, J 10, 7-HЈ), 2.16 (1 H, m, 2JHSn 67, 2-H), 2.53 (1 H,
m, 4-H), 3.03 (1 H, m, 1-H), 3.89 (3 H, s, OCH3), 7.33–7.50
(6 H, m, ArH) and 7.65–7.78 and 7.94–8.19 (each 2 H, m, ArH);
δC 26.22, 26.64 (3JCSn 21.5), 28.62 (3JCSn 49), 38.93 (3JCSn 94),
41.14 (2JCSn 20), 47.38 (3JCSn 28.5), 54.35 (1JCSn 562/538), 54.66,
128.35, 128.43, 129.02, 129.16, 135.96 (2JCSn 44.5), 137.05 (2JCSn
49), 141.03, 141.86 and 185.79 (3JCSn 40.5); δSn Ϫ113.98; m/z 586
(Mϩ, 2%), 491 (100) and 441 (80).
(1S,2R,3R,4R)-3-Methoxycarbonyl-3-methylbicyclo[2.2.1]-
heptan-2-yl(diphenyl)tin iodide 23
Iodine (27 mg, 0.105 mmol) was added to a solution of the
triphenylstannane 13 (57 mg, 0.110 mmol) in dichloromethane
(1 cm3) and the mixture stirred for 30 min at ambient temper-
ature. Concentration under reduced pressure then gave the title
compound 23 (63 mg, 100%), as an oil, used without further
purification (Found: Mϩ Ϫ C6H5, 490.9528. C16H20IO2Sn
requires M, 490.9530); νmax/cmϪ1 3065, 3047, 1664, 1430, 1311,
730 and 696; δH 1.10 (1 H, d, J 10.5, 7-H), 1.24 (1 H, dd, J 10,
1.5, 7-HЈ), 1.34 (3 H, s, CH3), 1.38–1.85 (4 H, m, 5-H2 and
6-H2), 1.60 (1 H, d, J 2, 2-H), 2.67 (1 H, m, 4-H), 3.00 (1 H, m,
1-H), 3.84 (3 H, s, CH3), 7.4 (6 H, m, ArH) and 7.8 and 7.9
(each 2 H, m, ArH); δC 22.59, 23.23, 33.18, 39.06, 41.60, 47.53,
52.91, 54.39, 55.37, 128.81, 129.62, 136.62, 137.51, 140.36,
142.37 and 187.38; m/z 491 (Mϩ Ϫ 77, 70%) and 441 (100).
(1S,2R,3R,4R)-3-Methoxycarbonyl-3-methylbicyclo[2.2.1]-
heptan-2-yl(diphenyl)tin hydride 27
Sodium borohydride (4.6 mg, 0.12 mmol) in ethanol (1 cm3)
was added to the tin iodide 23 (63 mg, 0.11 mmol) in dry
ethanol (1 cm3) at ambient temperature. After 30 min, the mix-
ture was concentrated under reduced pressure and the residue
partitioned between saturated aqueous ammonium chloride (5
cm3) and ether (5 cm3). The aqueous phase was extracted with
ether (3 × 10 cm3) and the combined organic extracts dried
(MgSO4) and concentrated under reduced pressure to give
the title compound 27 (50 mg, 100%) as an oil, used without
further purification (Found: Mϩ Ϫ C6H5, 365.0569. C16H21O2Sn
requires M, 365.0564); νmax/cmϪ1 3063, 1836, 1708, 1428, 1301,
1276, 1222, 1171, 1137, 1121, 1092, 1072, 728 and 699;
δH(C6D6) 0.97 (1 H, d, J 8.5, 7-H), 1.12 (3 H, s, CH3), 1.16–1.60
(6 H, overlapping m, 2-H, 5-H2, 6-H2 and 7-HЈ), 2.5 (2 H, m,
(1S,2R,3R,4R)-3-Methoxycarbonylbicyclo[2.2.1]heptan-2-
yl(diphenyl)tin iodide 24
Iodine (31 mg, 0.12 mmol) was added to a solution of the
triphenylstannane 20 (65 mg, 0.13 mmol) in dichloromethane (2
cm3) and the mixture stirred for 5 min at ambient temperature.
Concentration under reduced pressure gave the title compound
24 (72 mg, 100%) as an oil, used without further purific-
ation (Found: Mϩ Ϫ C6H5, 476.9378. C15H18IO2Sn requires M,
476.9374); νmax/cmϪ1 3046, 1665, 1441, 1429, 1298, 1241, 1129,
730 and 696; δH 1.1, 1.46 and 1.7 (each 2 H, m), 2.09 (1 H, dd,
J 9, 1.5, 2-H), 2.79 (2 H, m, 3-H and 4-H), 3.15 (1 H, m, 3JHSn
44, 1-H), 3.84 (3 H, s, OCH3), 7.38 (6 H, m, ArH) and 7.8 and
7.9 (each 2 H, m, ArH); δC 29.85, 32.64 (3JCSn 87.5), 36.96 (JCSn
15.5), 40.62 (JCSn 17.5), 43.49 (1JCSn 520/498), 44.56 (JCSn 7),
1
1-H and 4-H), 3.18 (3 H, s, OCH3), 6.98 (1 H, d, J 1.5, JHSn
1906/1820, SnH), 7.10–7.38 (6 H, m, ArH) and 7.70–8.05 (4 H,
m, ArH); δC(C6D6) 23.08 (JCSn 15), 23.36, 33.82 (JCSn 64.5),
39.19, 42.75 (JCSn 9.5), 43.51 (1JCSn 452/433), 46.76 (JCSn 12.5),
52.86, 53.78, 128.50, 128.92, 138.31, 142.92, 143.13 and 182.36;
m/z 441 (Mϩ Ϫ 1, 100%) and 365 (30).
(1S,2R,3R,4R)-3-Methoxycarbonylbicyclo[2.2.1]heptan-2-yl-
(diphenyl)tin hydride 28
Sodium borohydride (5.5 mg, 0.145 mmol) in ethanol (1 cm3)
was added to a solution of the tin iodide 24 (71 mg, 0.13 mmol)
in ethanol (1 cm3) at ambient temperature. After 15 min the
mixture was concentrated under reduced pressure and the
residue partitioned between saturated aqueous ammonium
chloride (10 cm3) and ether (10 cm3). The aqueous phase was
extracted with ether (3 × 10 cm3) and the combined organic
extracts dried (MgSO4) and concentrated under reduced pres-
sure to give the title compound 28 (54 mg, 98%) as an oil, used
without further purification; νmax/cmϪ1 3061, 3045, 1837, 1713,
1428, 1217, 1202, 1176, 1033, 729 and 699; δH(C6D6) 0.83
3
50.99 (2JCSn 37.5), 55.05, 128.83 and 128.87 (each JCSn 61.0),
2
129.59, 129.67, 136.84 and 137.50 (each JCSn 45), 140.54,
142.42 and 183.95; m/z 477 (Mϩ Ϫ 77, 90%) and 427 (100).
Methyl (1R,2S,3S,4S)-2-methyl-3-triphenylstannylbicyclo-
[2.2.1]heptane-2-carboxylate 25
Palladium (10% on charcoal; 24 mg, 0.025 mmol Pd) was added
to the unsaturated ester 17 (0.118 g, 0.23 mmol) in ethanol
(5 cm3). The resultant suspension was stirred vigorously under
732
J. Chem. Soc., Perkin Trans. 1, 1998

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(1 H, m), 1.1 (2 H, m), 1.25–1.6 (4 H, m), 2.4 (2 H, m, 3-H
and 4-H), 2.51 (1 H, m, 1-H), 3.20 (3 H, s, OCH3), 6.89 (1 H, d,
J 1.5, JHSn 1906/1821, SnH), 7.10–7.35 (6 H, m, ArH) and
17.5), 47.04 (JCSn 31), 48.43 (1JCSn 490/467), 70.40 (3JCSn 68),
128.41, 128.49, 129.00, 129.10, 135.73, 136.16, 141.22 and
142.62; δSn Ϫ102; m/z 463 (Mϩ Ϫ 77, 65%) and 413 (80).
1
7.70–7.95 (4 H, m, ArH); δC(C6D6) 30.13, 33.22, 34.13, 36.80,
41.44, 43.61, 50.58, 52.34, 128.64, 128.94, 138.31 (2JCSn 36),
142.34 and 179.24; m/z 427 (Mϩ Ϫ 1, 100%) and 351 (90).
(1R,2R,3R,4S)-3-Hydroxymethyl-3-methyl-2-triphenylstannyl-
bicyclo[2.2.1]hept-5-ene 32
Diisobutylaluminium hydride (1 mol dmϪ3 in dichloromethane;
4.70 cm3) was added dropwise to a solution of the unsaturated
ester 3 (0.97 g, 1.88 mmol) in dichloromethane (20 cm3) at 0 ЊC.
The solution was warmed to ambient temperature over 19 h
before quenching with methanol (6 cm3) at 0 ЊC. Saturated
aqueous Rochelle’s salt (30 cm3) was added followed by extrac-
tion with dichloromethane (4 × 30 cm3). The organic extracts
were dried (MgSO4) and concentrated under reduced pressure
to give the title compound 32 (0.915 g, 99%) as an oil, used
without further purification (Found: Mϩ Ϫ C6H5, 411.0766.
C21H23OSn requires M, 411.0771); [α]D Ϫ19.2 (c 1.9 in CHCl3);
νmax/cmϪ1 3571, 3425, 3061, 1427, 1073, 1022, 1008, 717 and
(1S,2S,3S,4R)-3-Methoxycarbonyl-3-methylbicyclo[2.2.1]-
heptan-2-yl(diphenyl)tin hydride 29
Sodium borohydride (6.3 mg, 0.165 mmol) in ethanol (1 cm3)
was added to the tin iodide 26 (86 mg, 0.15 mmol) in ethanol
(1 cm3) at ambient temperature. After 15 min, the mixture was
concentrated under reduced pressure and the residue par-
titioned between saturated aqueous ammonium chloride (10
cm3) and ether (10 cm3). The aqueous phase was extracted with
ether (3 × 10 cm3) and the combined organic extracts dried
(MgSO4) and concentrated under reduced pressure to give
the title compound 29 (62 mg, 93%), as an oil, used without
further purification (Found: Mϩ Ϫ C6H5, 365.0564. C16H21O2Sn
requires M, 365.0564); [α]D ϩ6.4 (c 4.9 in C6H6); νmax/cmϪ1
3061, 1839, 1711, 1428, 1287, 1249, 1118, 729 and 699;
δH(C6D6) 1.22 (3 H, s, CH3), 1.30–1.55 (4 H, m), 1.60–1.74
(3 H, m), 2.28 and 2.50 (each 1 H, m), 3.29 (3 H, s, OCH3), 7.09
(1 H, d, J 2.5, 1JHSn 1966/1879, SnH), 7.27–7.39 (6 H, m, ArH)
and 7.80–7.92 and 7.92–8.50 (each 2 H, m, ArH); δC(C6D6)
26.53, 27.22 (3JCSn 14.5), 28.10 (3JCSn 41), 39.10 (3JCSn 70.5),
41.85 (2JCSn 12.5), 44.21 (1JCSn 478/462), 46.79 (3JCSn 28.5),
51.71, 53.48 (2JCSn 11), 127.46–128.27 (overlapping peaks, not
resolved), 137.44 (2JCSn 36), 137.62 (2JCSn 38.5), 141.57, 143.26
(1JCSn 430/408) and 180.54 (3JCSn 28.5); m/z 441 (Mϩ Ϫ 1, 100%)
and 365 (20).
2
699; δH 1.10 (3 H, s, CH3), 1.32 (1 H, d, J 2.5, JHSn 51, 2-H),
1.41 (1 H, d, J 9, 7-H), 1.50 (1 H, br t, J 5, OH), 1.72 (1 H, d, J
9, 7-HЈ), 2.58 (1 H, m, 4-H), 3.18 (1 H, m, 1-H), 3.55 (2 H, m,
CH2OH), 6.15 (1 H, dd, J 5.5, 3, vinylic-H), 6.33 (1 H, dd, J 5.5,
2.5, vinylic-H), 7.4 (9 H, m, ArH) and 7.65 (6 H, m, ArH); δC
24.56 (3JCSn 13.5), 36.94 (1JCSn 413/394), 46.76, 47.36, 47.91,
50.10 (JCSn 12), 72.06 (3JCSn 50.5), 128.39 (3JCSn 47), 128.48,
133.14, 137.18 (2JCSn 34.5), 138.48 (3JCSn 59) and 141.63 (1JCSn
476/455); m/z 411 (Mϩ Ϫ 77, 50%).
(1R,2R,3R,4S)-3-Methoxymethyl-3-methyl-2-triphenylstannyl-
bicyclo[2.2.1]hept-5-ene 33
The alcohol 32 (0.215 g, 0.44 mmol) in tetrahydrofuran (2 cm3)
was added dropwise to a suspension of sodium hydride (60% in
mineral oil; 26 mg, 0.66 mmol) in tetrahydrofuran (3 cm3)
at ambient temperature. The solution was stirred for 1.5 h
before the addition of methyl iodide (0.22 cm3, 3.53 mmol) and
further stirring at ambient temperature for 15 h. After concen-
tration under reduced pressure, the residue was partitioned
between dichloromethane (10 cm3) and brine (10 cm3). The
organic phase was dried (MgSO4) and concentrated under
reduced pressure to give the title compound 33 (0.207 g, 94%) as
an oil, used without further purification (Found: Mϩ Ϫ C6H5,
425.0936. C22H25OSn requires M, 425.0927); νmax/cmϪ1 3062,
1480, 1428, 1098, 1073, 717 and 699; δH 1.10 (3 H, s, CH3),
1.15–1.45 (2 H, m, 2-H and 7-H), 1.86 (1 H, d, J 7-HЈ), 2.50 (1
H, m, 4-H), 2.85 (4 H, m, 1-H and OCH3), 3.13 and 3.29 (each 1
H, d, J 9, CHHOCH3), 6.10 (1 H, dd, J 5.5, 3, vinylic-H), 6.25
(1 H, dd, J 5.5, 2.5, vinylic-H), 7.28–7.50 (9 H, m, ArH) and 7.6
(6 H, m, ArH); m/z 425 (Mϩ Ϫ 77, 100%).
(1S,2R,3R,4R)-3-Hydroxymethyl-3-methyl-2-triphenylstannyl-
bicyclo[2.2.1]heptane 30
Diisobutylaluminium hydride (1 mol dmϪ3 in dichloromethane;
1.17 cm3) was added dropwise to a solution of the ester 13 (0.24
g, 0.47 mmol) in dichloromethane (5 cm3) at 0 ЊC. The solution
was warmed to ambient temperature over 19 h before quench-
ing with methanol (1 cm3) at 0 ЊC. Saturated aqueous Rochelle’s
salt (10 cm3) was added followed by extraction with dichloro-
methane (4 × 15 cm3). The organic extracts were dried (MgSO4)
and concentrated under reduced pressure to give the title
compound 30 (0.23 g, 100%) as an oil, used without further
purification (Found: Mϩ Ϫ C6H5, 413.0933. C21H25OSn requires
M, 413.0927); νmax/cmϪ1 3569, 3411, 3062, 3046, 1427, 1073,
1018, 728 and 699; δH 1.25 (3 H, s, CH3), 1.38 (1 H, m, OH),
1.46 (1 H, d, J 2.5, 2-H), 1.3–1.9 (6 H, overlapping m, 5-H2,
6-H2 and 7-H2), 1.96 (1 H, d, J 2.5, 4-H), 2.62 (1 H, d, J 3, 3JHSn
37.0, 1-H), 3.27 (1 H, dd, J 10.5, 5, CHHOH), 3.36 (1 H, dd, J
10, 2, CHHOH), 7.33–7.43 (9 H, m, ArH) and 7.54–7.72 (6 H,
m, ArH); δC 23.27, 24.19, 33.61, (3JCSn 69), 38.64, 42.48, 43.16
(1JCSn 425/406), 45.00 (JCSn 12.5), 46.74 (JCSn 27), 70.67 (3JCSn
65), 128.14 (3JCSn 46), 136.98 (2JCSn 34) and 141.91 (1JCSn 462/
444); δSn Ϫ109.1; m/z 413 (Mϩ Ϫ 77, 100%).
(1S,2R,3R,4R)-3-Methoxymethyl-3-methyl-2-triphenylstannyl-
bicyclo[2.2.1]heptane 34
Palladium (10% on charcoal; 44 mg, 0.04 mmol Pd) was added
to a solution of the alkene 33 (0.207 g, 0.41 mmol) in ethanol (8
cm3). The resultant suspension was stirred vigorously under an
atmosphere of hydrogen for 66 h then filtered through Celite
and the retained solids washed with ether (4 × 10 cm3). The
combined filtrates were concentrated under reduced pressure to
give the title compound 34 (0.193 g, 93%) as an oil, used without
further purification (Found: Mϩ Ϫ 77, 427.1079. C22H27OSn
requires M, 427.1084); νmax/cmϪ1 1427, 1104, 1073, 727 and 699;
δH 1.25 (3 H, s, CH3), 1.42 (1 H, d, J 2.5, 2-H), 1.38–1.95 (7 H,
overlapping m, 4-H, 5-H2, 6-H2 and 7-H2), 2.55 (1 H, m, 1-H),
2.80 (3 H, s, OCH3), 2.91 and 3.36 (each 1 H, d, J 9,
CHHOCH3), 7.29–7.50 (9 H, m, ArH) and 7.6 (6 H, m, ArH);
m/z 444 (15%), 427 (100) and 306 (30).
{(1S,2R,3R,4R)-3-Hydroxymethyl-3-methylbicyclo[2.2.1]-
heptan-2-yl}(diphenyl)tin iodide 31
Iodine (50 mg, 0.2 mmol) was added to a solution of the
diphenylstannane 30 (0.1 g, 0.2 mmol) in dichloromethane
(2 cm3) and the mixture stirred for 5 min at ambient temper-
ature. Concentration under reduced pressure gave the title
compound 31 (0.11 g, 100%) as an oil, used without further
purification (Found: Mϩ Ϫ C6H5, 463.9658. C15H21IOSn re-
quires M, 463.9659); νmax/cmϪ1 3404, 1428, 998 , 729 and 696;
δH 1.20 (3 H, s, CH3), 1.25–1.90 (6 H, overlapping m, 5-H2, 6-H2
and 7-H2), 1.50 (1 H, d, J 2.5, 2-H), 1.95 (1 H, d, J 2.5,
4-H), 2.72 (1 H, br s, OH), 3.19 (1 H, d, J 3.5, 1-H), 3.24 (1 H,
dd, J 10, 3.5, CHHOH), 3.50 (1 H, d, J 10, CHHOH), 7.35–7.50
(6 H, m, ArH) and 7.70–7.95 (4 H, m, ArH); δC 23.68, 23.87
(3JCSn 26), 33.24 (3JCSn 92.5), 38.83, 42.30 (JCSn 14), 46.56 (JCSn
(1S,2R,3R,4R)-3-Methoxymethyl-3-methylbicyclo[2.2.1]heptan-
2-yl(diphenyl)tin iodide 35
Iodine (91 mg, 0.36 mmol) was added to a solution of the
triphenylstannane 34 (0.19 g, 0.38 mmol) in dichloromethane
J. Chem. Soc., Perkin Trans. 1, 1998
733

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2
(5 cm3) and the mixture stirred for 1 h at ambient temperature.
Concentration under reduced pressure gave the title compound
35 (0.203 g, 97%) as an oil, used without further purification
(Found: Mϩ Ϫ C6H5, 477.9821. C16H23IOSn requires M,
477.9816); [α]D ϩ14.5 (c 4.0 in CHCl3); νmax/cmϪ1 3064, 3047,
1429, 1075, 729 and 697; δH 1.31 (3 H, s, CH3), 1.37–1.95 (7 H,
m, 2-H, 5-H2, 6-H2 and 7-H2), 2.03 (1 H, m, 4-H), 2.99 (3 H, s,
OCH3), 3.09 (1 H, d, J 8, CHHOCH3), 3.23–3.31 (2 H, m,
CHHOCH3 and 1-H), 7.35–7.51 (6 H, m, ArH) and 7.66 and
7.86 (each 2 H, m, ArH); δC 23.64, 24.57 (3JCSn 27), 33.40 (3JCSn
93), 39.16, 42.56 (JCSn 14), 46.41 (2JCSn 17.5), 47.06 JCSn 18.5),
49.40 (1JCSn 500/478), 58.88, 80.74 (3JCSn 64.5), 128.54 (3JCSn 58),
129.19, 129.24, 136.05 (2JCSn 39.5), 136.47 (2JCSn 46.5), 141.11
and 141.73; δSn Ϫ114.7; m/z 477 (Mϩ Ϫ 77, 100%) and 427 (20).
7-H2), 2.21 (1 H, dd, J 5.5, 2.0, JHSn 34, 3-H), 2.85 and 2.90
(each 3 H, s, NCH3), 3.13 (1 H, m, 1-H), 3.17 (1 H, m, 4-H),
3.36 (1 H, dd, J 5.5, 3.5, 3JHSn 75, 2-H), 5.71 (1 H, dd, J 5.5, 3,
vinylic-H), 6.36 (1 H, dd, J 5.5, 2.5, vinylic-H), 7.35 (9 H, m,
ArH) and 7.45–7.62 (6 H, m, ArH); δC 27.36, 36.09, 36.92,
43.86, 46.32, 46.96, 50.28, 128.40, 128.75, 137.12 (2JCSn 34.5),
138.54 and 172.85; m/z 438 (Mϩ Ϫ 77, 12%) and 166 (100).
1-{(1S,2S,3R,4R)-3-Triphenylstannylbicyclo[2.2.1]hept-5-en-2-
ylcarbonyl}pyrrolidine 39
Sodium diethyldihydroaluminate (2 mol dmϪ3 in toluene; 0.15
cm3) and pyrrolidine (99.5%; 0.055 cm3, 0.66 mmol) were heat-
ed in toluene (4 cm3) at 110 ЊC for 1 h. A solution of the ester
3 (0.15 g, 0.3 mmol) in toluene (1 cm3) was then added and
the mixture heated for
a further 24 h. After cooling
(1S,2R,3R,4R)-3-Methoxymethyl-3-methylbicyclo[2.2.1]heptan-
2-yl(diphenyl)tin hydride 36
to ambient temperature, the reaction mixture was quenched
by the slow addition of saturated aqueous ammonium
chloride (2 cm3) and extracted with ether (4 × 10 cm3).
The organic extracts were dried (MgSO4) and concentrated
under reduced pressure. Chromatography of the residue using
dichloromethane as eluent gave the title compound 39 (96 mg,
60%) as an oil (Found: Mϩ Ϫ C6H5, 464.1028. C24H26NOSn
requires M, 464.1036); νmax/cmϪ1 3062, 1638, 1428, 1333, 1321,
1073, 728 and 699; δH 1.26 (1 H, d, J 8, 7-H), 1.31 (1 H, dd, J 8,
1.5, 7-HЈ), 1.66–1.90 (4 H, m, 2 × CH2), 2.17 (1 H, dd, J 6, 2,
2JHSn 34, 3-H), 3.0 (1 H, m, CHHN), 3.14 and 3.17 (each 1 H,
m), 3.21 (1 H, dd, J 6, 3.5, 2-H), 3.4 (3 H, m, CH2N and
CHHN), 5.77 (1 H, dd, J 5.5, 3, vinylic-H), 6.38 (1 H, dd, J
5.5, 2.5, vinylic-H), 7.36 (9 H, m, ArH) and 7.55 (6 H, m,
ArH); δC 24.25, 26.28, 27.47, 38.17, 45.68, 46.12, 46.32, 46.64,
50.31, 128.41, 128.69, 128.77, 137.13 (2JCSn 34.5), 138.38,
138.60 (1JCSn 471) and 171.66; m/z 542 (Mϩ ϩ 1, 2%), 464
(10) and 192 (100).
Sodium borohydride (12 mg, 0.32 mmol) in ethanol (2 cm3) was
added to the tin iodide 35 (0.16 g, 0.29 mmol) in ethanol (2 cm3)
at ambient temperature. After 15 min, the mixture was concen-
trated under reduced pressure and the residue partitioned
between saturated aqueous ammonium chloride (10 cm3) and
ether (10 cm3). The aqueous phase was extracted with ether
(3 × 15 cm3) and the combined organic extracts dried
(MgSO4) and concentrated under reduced pressure to give the
title compound 36 (0.118 g, 95%) as an oil, used without
further purification (Found: Mϩ Ϫ H, 427.1083. C22H27OSn
requires M, 427.1084); νmax/cmϪ1 3062, 1818, 1428, 1104, 728
and 699; δH(C6D6) 1.22 (3 H, s, CH3), 0.95–1.90 (8 H, m, 2-H,
4-H, 5-H2, 6-H2 and 7-H2), 2.48 (1 H, d, J 4, 3JHSn 38, 1-H), 2.86
(1 H, d, J 8.5, CHHOCH3), 2.93 (3 H, s, OCH3), 3.10 (1 H, d,
1
J 8.5, CHHOCH3), 6.49 (1 H, d, J 4, JHSn 1850/1769, SnH),
7.22–7.36 (6 H, m, ArH) and 7.7 and 7.86 (each 2 H, m, ArH);
δC(C6D6) 24.06 (3JCSn 20.5), 24.33, 32.92 (3JCSn 71.5), 39.24,
42.83 (JCSn 7), 42.99 (1JCSn 449/429), 45.43 (2JCSn 28), 46.08
(JCSn 12), 57.24, 81.26 (3JCSn 62.5), 128.01–128.33 (overlapping
peaks, not resolved), 128.48, 128.59, 137.63 (2JCSn 34.5), 137.99
1-{(1S,2S,3R,4R)-3-Triphenylstannylbicyclo[2.2.1]hept-5-en-2-
ylcarbonyl}piperidine 40
1
Sodium diethyldihydroaluminate (2 mol dmϪ3 in toluene; 0.15
cm3) and piperidine (99.5%; 0.66 mmol) in toluene (4 cm3) were
heated at 110 ЊC for 1.5 h. A solution of the ester 3 (0.15 g, 0.30
mmol) in toluene (1 cm3) was then added and the mixture
heated for a further 24 h. After cooling to ambient temperature,
the reaction mixture was quenched by the slow addition of
saturated aqueous ammonium chloride (2 cm3) and extracted
with ether (4 × 10 cm3). The organic phase was dried (MgSO4)
and concentrated under reduced pressure. Chromatography of
the residue using dichloromethane as the eluent gave the title
compound 40 (0.11 g, 66%) as an oil (Found: Mϩ Ϫ C6H5,
478.1191. C25H28NOSn requires M, 478.1193); νmax/cmϪ1 3062,
1636, 1428, 1254, 1222, 1073, 1020, 728 and 699; δH 1.27 (2 H,
m), 1.46 (4 H, m), 1.57 (2 H, m), 2.31 (1 H, d, J 5, 2JHSn 35, 3-H),
3.07 (1 H, m, 1-H), 3.16 (1 H, m, 3JHSn 35, 4-H), 3.30–3.45 (4 H,
m, 2-H, CH2N and CHHN), 3.65 (1 H, m, CHHN), 5.71 (1 H,
dd, J 5.5, 3, vinylic-H), 6.35 (1 H, dd, J 5.5, 2.5, vinylic-H), 7.35
(9 H, m, ArH) and 7.55 (6 H, m, ArH), δC 24.78, 25.84, 26.70,
26.91, 43.47, 43.82, 46.28, 46.43, 47.43, 50.12, 128.31, 128.40,
128.72, 137.16 (2JCSn 34.3), 138.59 (1JCSn 480) and 170.82;
m/z 556 (Mϩ ϩ 1, 10%), 478 (50), 206 (100) and 204 (40).
(2JCSn 37.5), 141.29 and 142.79; δSn(C6D6) Ϫ139.0 (d, JSnH
1860); m/z 427 (Mϩ Ϫ 1, 100%) and 368 (30).
Reduction of 2-hydroxyacetophenone
The tin hydride 27 (31 mg, 0.075 mmol) in methanol (0.5 cm3)
was added to a solution of 2-hydroxyacetophenone (0.10 g,
0.725 mmol) in methanol (1.5 cm3) followed by phenylsilane
(0.27 cm3, 2.18 mmol). The reaction mixture was stirred at
ambient temperature until all of the ketone had disappeared
(4 d, TLC). After concentration of the mixture under reduced
pressure, chromatography of the residue using light petroleum–
ether (1:1) as eluent gave 1-(2-hydroxyphenyl)ethanol (95 mg,
95%) as an oil. In a control experiment, 2-hydroxyaceto-
phenone (71 mg, 0.52 mmol), on being mixed with phenylsilane
(0.195 cm3, 1.56 mmol) in methanol (2 cm3) in the absence of tin
hydride gave only a trace of 1-(2-hydroxyphenyl)ethanol after
7 d.
N,N-Dimethyl (1S,2S,3R,4R)-3-triphenylstannylbicyclo[2.2.1]-
hept-5-ene-2-carboxamide 38
Dimethylamine (2 mol dmϪ3 in tetrahydrofuran; 2.45 cm3) was
added to a solution of trimethylaluminium (2 mol dmϪ3 in
hexanes; 2.39 cm3) in benzene (4 cm3) and the mixture heated
at 80 ЊC for 20 min. The ester 3 (0.3 g, 0.6 mmol) in benzene
(1 cm3) was added and the mixture heated for 15 h. After cool-
ing to ambient temperature, the reaction mixture was quenched
by the slow addition of aqueous hydrogen chloride (0.5 mol
dmϪ3; 5 cm3) and extracted with ether (4 × 10 cm3). The organic
phase was dried (MgSO4) and concentrated under reduced
pressure to give the title compound 38 (0.312 g, 100%) as an
oil, used without further purification (Found: Mϩ Ϫ C6H5,
438.0882. C22H24NOSn requires M, 438.0880); νmax/cmϪ1 3062,
1642, 1428, 1395, 1143, 1073, 997, 729 and 699; δH 1.29 (2 H, m,
N-Benzyl (1R,2S,3R,4S)-3-triphenylstannylbicyclo[2.2.1]-
heptane-2-carboxamide 41
Sodium diethyldihydroaluminate (2 mol dmϪ3 in toluene; 0.15
cm3) and benzylamine (99.5%; 0.065 cm3, 0.595 mmol) were
heated in toluene (3 cm3) at 110 ЊC for 75 min. The ester 12
(0.15 g, 0.30 mmol) in toluene (1 cm3) was then added and the
mixture heated for a further 2 h. After cooling to ambient
temperature, the reaction mixture was quenched by the slow
addition of saturated aqueous ammonium chloride (2 cm3) and
extracted with ether (4 × 10 cm3). The organic phase was dried
(MgSO4) and concentrated under reduced pressure. Chroma-
734
J. Chem. Soc., Perkin Trans. 1, 1998

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tography of the residue using dichloromethane–light petroleum
(9:1) as eluent gave the title compound 41 (0.15 g, 87%) as an
oil (Found: Mϩ Ϫ C6H6, 502.1194. C27H28NOSn requires M,
502.1193); νmax/cmϪ1 3299, 3062, 1644, 1545, 1428, 1238, 1073,
728 and 698; δH 1.32 (1 H, d, J 10, 7-H), 1.39 (1 H, m), 1.45
(1 H, d, J 10, 7-HЈ), 1.6 (3 H, m), 2.39 (1 H, m, 1-H), 2.42 (1 H,
dd, J 6.5, 2, JHSn 42, 3-H), 2.55 (1 H, m, JHSn 37, 4-H), 2.97
(1 H, ddd, J 6, 4, 1.5, 3JHSn 103, 2-H), 4.33 and 4.47 (each 1 H,
dd, J 15, 5.5, CHHN), 5.51 (1 H, br t, J 5.5, NH), 7.22 (5 H, m,
ArH), 7.35 (9 H, m, ArH) and 7.42–7.65 (6 H, m, ArH); δC
24.24, 30.68, 33.25, 41.14, 41.17, 42.51, 43.66, 52.54, 127.22,
127.61, 128.12, 128.43, 128.52, 128.74, 137.23 (2JCSn 33.5),
138.42 and 173.07; m/z 590 (Mϩ ϩ 18, 10%) and 502 (100).
filtered through Celite and the filter washed with ether (4 × 10
cm3). The organic phase was dried (MgSO4) and concentrated
under reduced pressure to give the title compound 44 (46 mg,
85%) as an oil (Found: Mϩ Ϫ C6H5, 450.1249. C24H28NSn
requires M, 450.1244); νmax/cmϪ1 3061, 1428, 1073, 727 and 699;
δH 1.03 (1 H, dd, 2-H), 1.20–1.45 (2 H, m, 7-H2), 1.65–1.90 (4 H,
m), 2.15 (1 H, dd, J 11.5, 8, 3-CH), 2.25–2.50 (5 H, overlapping
m, 3-CHЈ and 2 × CH2N), 2.65 (1 H, m), 3.08 (1 H, m, 1-H and
4-H), 5.95 and 6.24 (each 1 H, m, vinylic-H), 7.4 (9 H, m, ArH)
and 7.54–7.72 (6 H, m, ArH); δC 24.33, 29.09, 29.75, 30.35,
42.16, 45.73, 45.83, 49.45, 54.79, 61.21, 128.48, 128.84, 130.83,
137.42, 137.68 and 139.13; m/z 528 (Mϩ ϩ 1, 10%), 450 (15),
178 (100) and 176 (80).
2
3
1-{(1R,2S,3R,4S)-3-Triphenylstannylbicyclo[2.2.1]heptan-2-
ylcarbonyl}piperidine 42
(1S,2R,3S,4R)-3-(Piperidin-1-ylmethyl)-2-triphenylstannyl-
bicyclo[2.2.1]heptane 45
Sodium diethyldihydroaluminate (2 mol dmϪ3 in toluene; 0.15
cm3) and piperidine (99.5%; 0.065 cm3, 0.66 mmol) in toluene (4
cm3) were heated at 110 ЊC for 1 h. A solution of the ester 12
(0.15 g, 0.30 mmol) in toluene (1 cm3) was then added and the
mixture heated for a further 2 h. After cooling to ambient
temperature, the reaction mixture was quenched by the slow
addition of saturated aqueous ammonium chloride (2 cm3) and
extracted with ether (4 × 10 cm3). The organic phase was dried
(MgSO4) and concentrated under reduced pressure. Chroma-
tography of the residue using dichloromethane–light petroleum
(20:1) as eluent gave the title compound 42 (69 mg, 45%) as an
oil (Found: Mϩ Ϫ C6H5, 480.1343. C25H30NOSn requires M,
480.1349); νmax/cmϪ1 3062, 1633, 1428, 1223, 1073, 728 and 699;
δH 1.10–1.65 (12 H, m), 2.38 (1 H, m, 1-H), 2.56 (1 H, m, 3JHSn
35.5, 4-H), 2.75 (1 H, dd, J 6, 2, 2JHSn 30, 3-H), 3.20–3.74 (3 H,
m, 2 × CHHN and 2-H), 3.47 (1 H, m, CHHN), 3.68 (1 H, m,
CHHN), 7.4 (9 H, m, ArH) and 7.65 (6 H, m, ArH); m/z 557
(Mϩ, 1%), 480 (100) and 208 (100).
Lithium aluminium hydride (12 mg, 0.315 mmol) was added to
a solution of the amide 42 (44 mg, 0.08 mmol) in ether (2 cm3)
at ambient temperature. The solution was stirred for 18 h then
quenched with saturated aqueous ammonium chloride (10 cm3)
and partitioned between ether (10 cm3) and saturated aqueous
Rochelle’s salt (10 cm3). The two-phase mixture was filtered
through Celite and the filter washed with ether (4 × 10 cm3).
The organic phase was dried (MgSO4) and concentrated under
reduced pressure. Chromatography of the residue using
dichloromethane–methanol (20:1) as eluent gave the title com-
pound 45 (31 mg, 72%) as an oil (Found: Mϩ Ϫ C6H5, 466.1553.
C25H32NSn requires M, 466.1557); νmax/cmϪ1 3062, 1428, 1073,
727 and 699; δH 1.2–1.8 (12 H, overlapping m, 5-H2, 6-H2, 7-H2
and 3 × CH2), 2.05–2.55 (10 H, overlapping m, 1-H, 2-H, 3-H,
4-H and 3 × CH2N), 7.35 (9 H, m, ArH) and 7.55 (6 H, m,
ArH); δC 22.71, 24.53, 25.85, 33.73, 36.78, 40.59, 40.65, 41.02,
42.40, 55.23, 62.64, 128.20, 128.50, 137.32 (2JCSn 33) and 139.14;
m/z 544 (Mϩ ϩ 1, 25%), 466 (25), 194 (70) and 192 (65).
1-{(1S,2R,3R,4R)-2-Methyl-3-triphenylstannylbicyclo[2.2.1]-
hept-5-en-2-ylcarbonyl}piperidine 43
(1R,2R,3R,4S)-2-Methyl-3-triphenylstannylbicyclo[2.2.1]-
heptane-2-carbaldehyde 46
Butyllithium (1.5 mol dmϪ3 in hexanes; 0.58 cm3) was added
dropwise to a solution of diethylamine (0.10 cm3, 0.92 mmol) in
tetrahydrofuran (4.5 cm3) at 0 ЊC. The solution was stirred for
15 min then cooled to Ϫ78 ЊC before the addition of the amide
40 (0.10 g, 0.185 mmol) in tetrahydrofuran (2 cm3). The mixture
was stirred at Ϫ78 ЊC for 2.5 h and then methyl iodide (0.115
cm3, 1.84 mmol) was added dropwise. After stirring for a
further 2 h, the reaction mixture was warmed to ambient
temperature, concentrated under reduced pressure and the resi-
due diluted with ether (10 cm3). The solution was washed with
water (10 cm3) then brine (10 cm3), and the organic phase dried
(MgSO4) and concentrated under reduced pressure. Chrom-
atography of the residue using light petroleum–ether (1:1) as
eluent gave methyl(triphenyl)tin (14 mg, 21%). Further elution
gave the title compound 43 (17 mg, 16%) as an oil (Found:
Mϩ Ϫ C6H5, 492.1345. C20H30NOSn requires M, 492.1349);
νmax/cmϪ1 3059, 1588, 1428, 1280, 1249, 1069, 1012, 728 and
699; δH 1.19 (3 H, s, CH3), 1.30 (3 H, m, 3-H and CH2),
1.50–1.80 (6 H, overlapping m, 3 × CH2), 3.12 (2 H, m, 1-H and
4-H), 3.50–3.80 (4 H, overlapping m, 2 × CH2N), 6.08 (1 H,
dd, J 5.5, 3, vinylic-H), 6.42 (1 H, dd, J 5.5, 2.5, vinylic-H),
7.20–7.45 (9 H, m, ArH) and 7.5–7.80 (6 H, m, ArH); m/z 570
(Mϩ ϩ 1, 1%) and 492 (5). Further elution gave starting
material 40 (37 mg, 36%).
N-Methylmorpholine N-oxide (0.11 g, 0.94 mmol) and tetra-
propylammonium perruthenate (8.5 mg, 0.025 mmol) were
added to a solution of the alcohol 30 (0.24 g, 0.48 mmol) and
4 Å molecular sieves (0.5 g) in dichloromethane (3 cm3) at
ambient temperature. The mixture was stirred for 2 h, then
filtered through Celite and the filtrate concentrated under
reduced pressure. Chromatography of the residue using
dichloromethane as eluent gave the title compound 46 (0.17 g,
73%) as an oil (Found: Mϩ Ϫ C6H5, 411.0770. C21H23OSn
requires M, 411.0771); νmax/cmϪ1 3061, 1715, 1427, 1072, 727
and 699; δH 1.14 (2 H, m, 7-H2), 1.24 (3 H, s, CH3), 1.29 (1 H, s,
3-H), 1.40–1.90 (4 H, overlapping m, 5-H2 and 6-H2), 2.28 (1 H,
d, J 3.5, 1-H), 2.60 (1 H, m, 3JHSn 37.5, 4-H), 7.4 (9 H, m, ArH),
7.50–7.80 (6 H, m, ArH) and 9.43 (1 H, s, CHO); m/z 488 (Mϩ,
2%) and 411 (100).
(1S,2R,3R,4R)-3-Aminomethyl-3-methyl-2-triphenylstannyl-
bicyclo[2.2.1]heptane 48
Sodium acetate (22 mg, 0.27 mmol) was added to a solution of
hydroxylamine hydrochloride (10 mg, 0.15 mmol) in ethanol
(4 cm3) and the mixture stirred for 30 min. The aldehyde 46 (60
mg, 0.125 mmol) in a mixture of ethanol (1.5 cm3) and ether
(1.5 cm3) was added. The reaction mixture was stirred at ambi-
ent temperature for 4 d and then extracted with ether (4 × 15
cm3). The organic phase was dried (MgSO4) and concentrated
under reduced pressure. Chromatography of the residue using
dichloromethane as eluent gave the oxime 47 (7 mg, 11%) as an
oil; δH 1.28 (3 H, s, CH3), 1.36 (1 H, J 2, 2-H), 1.45–1.90 (7 H,
overlapping m, OH, 5-H2, 6-H2 and 7-H2), 2.09 (1 H, m, 4-H),
(1R,2R,3S,4S)-3-(Pyrrolidin-1-ylmethyl)-2-triphenylstannyl-
bicyclo[2.2.1]hept-5-ene 44
Lithium aluminium hydride (1 mol dmϪ3 in ether; 1.02 cm3) was
added to a solution of the amide 39 (55 mg, 0.10 mmol) in ether
(2 cm3) at ambient temperature. The solution was stirred for 18
h, then quenched with saturated aqueous ammonium chloride
(10 cm3) and partitioned between ether (10 cm3) and saturated
aqueous Rochelle’s salt (10 cm3). The two-phase mixture was
2.55 (1 H, m, 3JHSn 40, 1-H), 6.20 (1 H, s, CH᎐N), 7.35 (9 H, m,
᎐
ArH) and 7.5 (6 H, m, ArH).
Lithium aluminium hydride (1 mol dmϪ3 in ether; 0.08 cm3)
was added to a solution of the oxime 47 (7 mg, 0.014 mmol) in
J. Chem. Soc., Perkin Trans. 1, 1998
735

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ether (1 cm3). The solution was stirred for 1.5 h, then saturated
aqueous ammonium chloride (2 cm3) was added and the
mixture extracted with ether (3 × 10 cm3). The organic phase
was dried (MgSO4) and concentrated under reduced pressure to
give the title compound 48 (4 mg, 59%) as an oil (Found:
References
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Mϩ Ϫ C6H5, 412.1094. C21H26NSn requires M, 412.1087); νmax
/
cmϪ1 3634, 3384, 3315, 3060, 1579, 1479, 1427, 1260, 1071,
1021, 909, 803, 728 and 700; δH 1.07 (3 H, s, CH3), 1.10–1.50
(3 H, overlapping m, 7-H2 and 2-H), 1.5–1.9 (5 H, overlapping
m, 4-H, 5-H2 and 6-H2), 2.2 (2 H, br s, NH2), 2.55 (3 H, m, 1-H
and CH2N), 7.20–7.40 (9 H, m, ArH) and 7.50–7.70 (6 H, m,
ArH), m/z 412 (Mϩ Ϫ 77, 100%).
5 T. N. Mitchell and B. Godry, J. Organomet. Chem., 1995, 490, 45;
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metallics, 1993, 12, 3051; H. Schumann, B. C. Wassermann and
F. E. Hahn, Organometallics, 1992, 11, 2803.
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(1S,2R,3R,4R)-2-Methyl-3-triphenylstannylbicyclo[2.2.1]hept-
5-ene-2-carbaldehyde 49
N-Methylmorpholine N-oxide (0.44 g, 3.76 mmol) and tetra-
propylammonium perruthenate (66 mg, 0.19 mmol) were added
to a solution of the alcohol 32 (0.92 g, 1.88 mmol) and 4 Å
molecular sieves (2 g) in dichloromethane (15 cm3) at ambient
temperature. The mixture was stirred for 1.5 h, then filtered
through Celite and the filtrate concentrated under reduced
pressure. Chromatography of the residue using dichloro-
methane–light petroleum (3:2) as eluent gave the title com-
pound 49 (0.58 g, 64%) as an oil (Found: C, 66.85; H, 5.35.
C27H26OSn requires C, 66.85; H, 5.4%. Found: Mϩ Ϫ C6H5,
409.0605. C21H21OSn requires M, 409.0614); [α]D Ϫ12.0 (c 3.0
in CHCl3); νmax/cmϪ1 3061, 1714, 1427, 1072, 727 and 699; δH
1.15 (5 H, m, 3-H, 7-H and CH3), 1.29 (1 H, d, J 9, 7-HЈ), 2.94
(1 H, m, 1-H), 3.23 (1 H, m, 4-H), 6.12 (1 H, dd, J 5.5, 3, vinylic-
H), 6.52 (1 H, dd, J 5.5, 3, vinylic-H), 7.4 (9 H, m, ArH), 7.65 (6
H, m, ArH) and 9.60 (1 H, s, CHO); δC 20.67 (3JCSn 12.5), 32.79
(1JCSn 423/403), 47.13, 47.19, 49.04 (3JCSn 14.5), 57.86, 128.19
(3JCSn 49.5), 128.31, 130.00, 137.28 (2JCSn 35.0), 141.44 (3JCSn
55.5), 142.03 (1JCSn 506/483) and 205.17 (3JCSn 37.5); m/z 486
(Mϩ, 5%) and 409 (100).
15 E. Vedejs, S. M. Duncan and A. R. Haight, J. Org. Chem., 1993, 58,
3046.
16 G. van Koten and J. G. Noltes, J. Am. Chem. Soc., 1976, 98, 5393;
J. T. B. H. Jastrzebski, J. Boersma and G. van Koten, J. Organomet.
Chem., 1991, 413, 43; G. van Koten, J. T. B. H. Jastrzebski,
J. G. Noltes, G. J. Verhoeckx, A. L. Spek and J. Kroon, J. Chem.
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Organometallics, 1986, 5, 1551; J. T. B. H. Jastrzebski, J. Boersma,
P. M. Esch and G. van Koten, Organometallics, 1991, 10, 930; J. T. B.
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17 M. F. Lipton, A. Basha and S. M. Weinreb, Org. Synth., Coll. Vol. 6,
1988, 492.
(1S,2R,3R,4R,E)-2-Methyl-3-triphenylstannylbicyclo[2.2.1]-
hept-5-ene-2-carbaldehyde N,N-dimethylhydrazone 50
N,N-Dimethylhydrazine (0.04 cm3, 0.86 mmol) was added to
the aldehyde 49 (0.105 g, 0.215 mmol) in ethanol (2 cm3)
and ether (2 cm3). The solution was stirred at 60 ЊC for 18 h,
then cooled to ambient temperature and concentrated under
reduced pressure. Chromatography of the residue using
dichloromethane–light petroleum (4:1) gave the title compound
50 as an 80:20 mixture of geometric isomers (12 mg, 11%)
(Found: Mϩ Ϫ C6H5, 451.1191. C23H27N2Sn requires M,
451.1196); νmax/cmϪ1 3060, 1480, 1427, 1072, 728 and 700;
δH(major isomer) 1.22 (4 H, m, 3-H and CH3), 1.45 and 1.86
(each 1 H, d, J 8.5, 7-H), 2.33 (6 H, s, 2 × NCH3), 2.76 (1 H,
m, 1-H), 3.26 (1 H, m, 4-H), 6.10 and 6.28 (each 1 H, dd, J 5,
18 T. B. Sim and N. M. Yoon, Synlett, 1994, 827.
19 W. P. Griffith and S. V. Ley, Aldrichimica Acta, 1990, 23, 13.
20 S. R. Sandler and W. Karo, in Organic Functional Group
Preparations, ed. H. H. Wasserman, Academic Press, New York,
2nd edn., 1989, p. 444.
3, vinylic-H), 6.86 (1 H, s, CH᎐N), 7.35 (9 H, m, ArH) and
᎐
7.6 (6 H, m, ArH); m/z 529 (Mϩ ϩ 1, 10%), 451 (90), 179 (100)
and 177 (30).
Acknowledgements
We thank the EPSRC and Zeneca Pharmaceuticals for support
(to R. M. P.) under the CASE scheme and Dr A. Thomas of
Zeneca for many helpful discussions.
Paper 7/06295H
Received 28th August 1997
Accepted 5th November 1997
736
J. Chem. Soc., Perkin Trans. 1, 1998