Copper Chloride-Catalyzed and Hydrochloric Acid-Mediated Chemoselective Protiodestannylations of Alkyl (Z)- or (E)-2,3-Bis(trimethylstannyl)-2-alkenoates. Stereoselective Preparation of Alkyl (E)- and (Z)-3-Trimethylstannyl-2-alkenoates

Article abstract of DOI:10.1021/jo9707693

Treatment of alkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoates (7) with a catalytic amount of copper(I) chloride in N,N-dimethylformamide (DMF) containing a small quantity of water provides very good-to-excellent yields of alkyl (E)-3-trimethylstannyl-2-alkenoates (1). On the other hand, stirring of solutions of alkyl (Z)- (7) or (E)-2,3-bis(trimethylstannyl)-2-alkenoates (8) in DMF containing dilute hydrochloric acid produces, efficiently, alkyl (Z)-3-trimethylstannyl-2-alkenoates (2).

Full text of DOI:10.1021/jo9707693

6034
J . Org. Chem. 1997, 62, 6034-6040
Cop p er Ch lor id e-Ca ta lyzed a n d Hyd r och lor ic Acid -Med ia ted
Ch em oselective P r otiod esta n n yla tion s of Alk yl (Z)- or
(E)-2,3-Bis(tr im eth ylsta n n yl)-2-a lk en oa tes. Ster eoselective
P r ep a r a tion of Alk yl (E)- a n d (Z)-3-Tr im eth ylsta n n yl-2-a lk en oa tes
Edward Piers,* Ernest J . McEachern, and Miguel A. Romero
Department of Chemistry, University of British Columbia, 2036 Main Mall, University Campus,
Vancouver, British Columbia, Canada V6T 1Z1
Received April 30, 1997X
Treatment of alkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoates (7) with a catalytic amount of copper(I)
chloride in N,N-dimethylformamide (DMF) containing a small quantity of water provides very good-
to-excellent yields of alkyl (E)-3-trimethylstannyl-2-alkenoates (1). On the other hand, stirring of
solutions of alkyl (Z)- (7) or (E)-2,3-bis(trimethylstannyl)-2-alkenoates (8) in DMF containing dilute
hydrochloric acid produces, efficiently, alkyl (Z)-3-trimethylstannyl-2-alkenoates (2).
Sch em e 1
In tr od u ction
The synthetic uses of alkyl (E)- and (Z)-3-trialkyl-
stannnyl-2-alkenoates of general structures 1 and 2,
along with those of substances readily derived from 1 and
2, are well established.1,2 Up to the present time, the
3-trimethylstannyl-2-alkenoates are shown in Scheme
1.3e Thus, reaction of ethyl 4-cyclohexyl-2-butynoate (3)
with lithium (trimethylstannyl)(cyano)cuprate4 in tet-
rahydrofuran (THF) at -48 to 0 °C, followed by addition
of aqueous NH4Cl-NH4OH (pH ∼8), provided the (Z)-3-
trimethylstannyl-2-alkenoate 4, accompanied by small
amounts (∼5% total) of the corresponding E isomer and
ethyl (E)-4-cyclohexyl-2,3-bis(trimethylstannyl)-2-buten-
oate. Purification of this material by a combination of
flash chromatography5 and distillation afforded 4 in 81%
yield.3e On the other hand, treatment (THF, -78 °C) of
3 with the same cuprate reagent in the presence of dry
ethanol, followed by a suitable workup and chromato-
graphic separation of the small amount (<5%) of 4 from
the major product 5, provided the latter material (81%).3e
Other trimethylstannylcopper(I) reagents can also be
employed to effect conversions analogous to those sum-
marized in Scheme 1.3a-d
Reports6 from this laboratory have described, inter alia,
the efficient palladium(0)-catalyzed addition of hexa-
methyldistannane to R,â-alkynic esters 6. The products
of these processes, alkyl (Z)-2,3-bis(trimethylstannyl)-2-
alkenoates 7, are produced in good-to-excellent yields
(Scheme 2). It has also been disclosed6 that compounds
7 are thermally unstable and, upon heating at 75-90 °C,
rearrange cleanly to the corresponding E isomers 8. We
report herein that treatment of compounds 7 with a
catalytic amount of copper(I) chloride in wet N,N-di-
methylformamide (DMF) at room temperature effects the
chemo- and stereoselective removal of the 2-trimethyl-
most convenient and efficient methods for preparing 1
and 2 in a stereocontrolled fashion entail treatment of
R,â-alkynic esters with suitable trialkylstannylcopper(I)
reagents under carefully defined reaction conditions.1a,3
Examples involving the production of diastereomeric
* Telephone: 604-822-3219. Fax: 604-822-2847. E-mail: epier@
unixg.ubc.ca.
X Abstract published in Advance ACS Abstracts, August 1, 1997.
(1) (a) Piers, E.; Chong, J . M.; Gustafson, K.; Andersen, R. J . Can.
J . Chem. 1984, 62, 1. (b) Piers, E.; Gavai, A. V. J . Chem. Soc., Chem.
Commun. 1985, 1241. (c) Piers, E.; Gavai, A. V. Tetrahedron Lett. 1986,
27, 313. (d) Piers, E.; Friesen, R. W. J . Org. Chem. 1986, 51, 3405. (e)
Piers, E.; Friesen, R. W. Can. J . Chem. 1987, 65, 1681. (f) Piers, E.;
Lu, Y.-F. J . Org. Chem. 1988, 53, 926. (g) Piers, E.; Llinas-Brunet, M.
J . Org. Chem. 1989, 54, 1483. (h) Piers, E.; Gavai, A. V. J . Org. Chem.
1990, 55, 2374. (i) Piers, E.; Gavai, A. V. J . Org. Chem. 1990, 55, 2380.
(j) Piers, E.; Friesen, R. W. Can. J . Chem. 1992, 70, 1204. (k) Piers,
E.; Friesen, R. W.; Rettig, S. J . Can. J . Chem. 1992, 70, 1385. (l) Piers,
E.; Roberge, J . Y. Tetrahedron Lett. 1992, 33, 6923. (m) Piers, E.; Ellis,
K. A. Tetrahedron Lett. 1993, 34, 1875. (n) Piers, E.; Wong, T. J . Org.
Chem. 1993, 58, 3609. (o) Piers, E.; Llinas-Brunet, M.; Oballa, R. M.
Can. J . Chem. 1993, 71, 1484. (p) Piers, E.; Wai, J . S. M. Can. J . Chem.
1994, 72, 146. (q) Piers, E.; Coish, P. D. Synthesis 1995, 47. (r) Piers,
E.; McEachern, E. J .; Burns, P. A. J . Org. Chem. 1995, 60, 2322. (s)
Piers, E.; McEachern, E. J .; Romero, M. A. Tetrahedron Lett. 1996,
37, 1173. (t) Piers, E.; Romero, M. A. J . Am. Chem. Soc. 1996, 118,
1215. (u) Piers, E.; McEachern, E. J . Synlett 1996, 1087.
(2) (a) Harusawa, S.; Osaki, H.; Takemura, S.; Yoneda, R.; Kurihara,
T. Tetrahedron Lett. 1992, 33, 2543. (b) Dodd, D. S.; Pierce, H. D. J r.;
Oehlschlager, A. C. J . Org. Chem. 1992, 57, 5250. (c) Paquette, L. A.;
Lassalle, G. Y.; Lovely, C. J . J . Org. Chem. 1993, 58, 4254. (d) Paquette,
L. A.; Deaton, D. N.; Endo, Y.; Poupart, M.-A. J . Org. Chem. 1993, 58,
4262. (e) Harusawa, S.; Takemura, S.; Osaki, H.; Yoneda, R.; Kurihara,
T. Tetrahedron 1992, 49, 7657. (f) De Brabander, J .; Vandewalle, M.
Synthesis 1994, 855. (g) Elbaum, D.; Porco, J . A. J r.; Stout, T. J .;
Clardy, J .; Schreiber, S. L. J . Am. Chem. Soc. 1995, 117, 211. (h)
Reginato, G.; Capperucci, A.; Degl’Innocenti, A.; Pecchi, S. Tetrahedron
1995, 51, 2129. (i) Hutzinger, M. W.; Oehlschlager, A. C. J . Org. Chem.
1995, 60, 4595.
(3) (a) Piers, E.; Morton, H. E. J . Org. Chem. 1980, 45, 4263. (b)
Piers, E.; Chong, J . M.; Morton, H. E. Tetrahedron Lett. 1981, 22, 4905.
(c) Piers, E.; Chong, J . M.; Morton, H. E. Tetrahedron 1989, 45, 363.
(d) Piers, E.; Tillyer, R. D. J . Org. Chem. 1988, 53, 5366. (e) Piers, E.;
Wong, T.; Ellis, K. A. Can. J . Chem. 1992, 70, 2058.
(4) Piers, E.; Morton, H. E.; Chong, J . M. Can. J . Chem. 1987, 65,
78.
(5) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(6) (a) Piers, E.; Skerlj, R. T. J . Chem. Soc., Chem. Commun. 1986,
626. (b) Piers, E.; Skerlj, R. T. Can. J . Chem. 1994, 72, 2468.
S0022-3263(97)00769-X CCC: $14.00 © 1997 American Chemical Society

Chemoselective Protiodestannylations
J . Org. Chem., Vol. 62, No. 17, 1997 6035
Ta ble 1. Cu Cl-Ca ta lyzed P r otiod esta n n yla tion of Alk yl
Sch em e 2
(Z)-2,3-Bis(tr im eth ylsta n n yl)-2-a lk en oa tesa
substrate
entry (mmol)
CuCl, DMF, H2O, product
mmol mL
mL (yield, %)c
R1 b
1
2
3
4
7a (0.45) Me
0.005
0.004
0.004
0.004
4.0 0.40 1a (91)
4.0 0.40 1b (94)
4.0 0.40 1c (78)
4.0 0.40 1d (87)
4.0 0.40 1e (90)
1.1 0.15 1f (75)
7b (0.35) TBSOCH2
7c (0.44) ClCH2CH2
7d (0.41) Cl(CH2)3
7e (0.39) MOMO(CH2)3 0.004
7f (0.10) C6H5
5
6d
7
0.004
7g (1.49) CH3(CH2)4
0.016 15.0 2.60 1g (91)
a
Unless otherwise noted, all reactions were carried out at room
temperature for 2 h. R2 ) Et for 7a -c and 7e; R2 ) Me for 7d ,
7f, and 7g. c Yield of purified 1. In each case, 1 was accompanied
by minor amounts (2-7%, based on GLC analysis) of the corre-
b
d
sponding alkyl (Z)-3-trimethylstannyl-2-alkenoate. In this case,
Ch a r t 1
the reaction time was 30 min.
11 was readily prepared in two steps from 4-pentyn-1-ol
(see Experimental Section). Thermolysis of each of the
substances 7c (neat, 90 °C, 18 h), 7e (neat, 90 °C, 24 h),
and 7f (neat, 85 °C, 26 h) resulted in the efficient
production of the corresponding E alkenoates 8c, e, and
f (Scheme 3). Of the latter materials, 8c and 8d were
used without purification, while 8f was fully character-
ized.
(b) Cu Cl-Ca ta lyzed P r otiod esta n n yla tion of th e
Alk yl (Z)-2,3-Bis(t r im et h ylst a n n yl)-2-a lk en oa t es
(7a -g). Treatment (room temperature, 2 h) of the
bis(trimethylstannane) 7a with approximately 1 mol %
of CuCl in DMF containing water (∼10% by volume) gave
a mixture of ethyl (E)-3-trimethylstannyl-2-butenoate
(1a ) and the corresponding Z isomer in a ratio of ∼98:2.
Flash chromatography5 of this mixture on silica gel
provided 1a in 91% yield (Table 1, entry 1). In a similar
fashion, the substrates 7b-g were transformed into the
protiodestannylated products 1b-g in very good-to-
excellent yields (Table 1, entries 2-7). In each of the
conversions, the major product was accompanied by a
small amount of the Z isomer, but in no case was the
latter material formed in an amount greater than ∼7%
of the product mixture (see footnote c, Table 1). It should
also be mentioned that, in general, alkyl (E)- and (Z)-3-
trimethylstannyl-2-alkenoates are readily separated by
chromatography on silica gel and, therefore, the acquisi-
tion of either isomer in pure form is easily achieved.
Of the products 1a -g given in Table 1, three (1a ,3c
1b,3c 1d 3e) have been reported previously. Full charac-
terization data for the remaining substances are pre-
sented in the Experimental Section.
Sch em e 3
stannyl function to produce excellent yields of the cor-
responding alkyl (E)-3-trimethylstannyl-2-alkenoates 1.
On the other hand, reaction of 7 or 8 with 1.2 equiv of 1
N hydrochloric acid in DMF also results in the chemose-
lective removal of the R-Me3Sn group, but in these cases
the products are the Z alkenoates 2 (Scheme 2).
On the basis of previous studies,7 it is clear that, in
alkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoates (7), the
alkenyl-tin bond associated with the R-trimethylstannyl
group is much more labile than that related to the
â-Me3Sn function. It has also been established8 that a
trialkylstannyl group attached to a carbon-carbon double
bond readily undergoes (reversible) transmetalation with
copper(I) salts to produce the corresponding alkenylcop-
per(I) intermediate. Finally, there is strong evidence for
the conclusion that intermediates of general structure 14,
derived from the cis addition of Me3SnCu‚SMe2 to R,â-
Resu lts a n d Discu ssion
(a ) Th e Su bstr a tes. The structural formulas of the
alkyl (Z)- (7a -g) and (E)-2,3-bis(trimethylstannyl)-2-
alkenoates (8a -f) employed in this study are given in
Chart 1. Of these substances, the Z isomers 7a -d and
the E isomers 8a , b , and d have been reported pre-
viously.6b Compounds 7e-g were prepared via Pd(0)-
catalyzed addition of hexamethyldistannane to the R,â-
alkynic esters 11-13, respectively (Scheme 3).6b The
substrates 12 and 13 are commercially available, while
(7) Piers, E.; Skerlj, R. T. J . Org. Chem. 1987, 52, 4421.
(8) Farina, V.; Krishnan, B.; Wang, C.; Liebeskind, L. S. J . Org.
Chem. 1994, 59, 5905.

6036 J . Org. Chem., Vol. 62, No. 17, 1997
Piers et al.
Ta ble 2. Hyd r och lor ic Acid -Med ia ted
Sch em e 4
P r otiod esta n n yla tion of Alk yl (Z)- a n d
(E)-2,3-Bis(tr im eth ylsta n n yl)-2-a lk en oa tesa
reaction
substrate
entry (mmol)
1 N HCl, DMF, time,
product
b
R1
mL
mL
min
(yield, %)c
Sch em e 5
1
2
3
4
5
6
7
8
9
7a (0.45) Me
0.55
0.35
0.49
0.49
0.46
0.16
0.55
0.35
0.64
0.25
0.46
0.38
9.0
8.0
8.0
8.0
8.0
3.0
9.0
8.0
10.0
4.0
8.0
6.4
60
5
2a (80)
2b (85)
2c (83)
2d (81)
2e (76)
2f (94)
2a (95)
2b (74)
2c (79)d
2d (91)
2e (82)d
2f (87)
7b (0.35) TBSOCH2
7c (0.41) ClCH2CH2
7d (0.41) Cl(CH2)3
7e (0.39) MOMO(CH2)3
7f (0.13) C6H5
8a (0.45) Me
8b (0.35) TBSOCH2
8c (0.53) ClCH2CH2
60
60
30
10
180
2
60
60
60
180
10 8d (0.20) Cl(CH2)3
11 8e (0.39) MOMO(CH2)3
12 8f (0.33) C6H5
a
b
All reactions were carried out at room temperature. R2 ) Et
for 7a -c, 7e, 8a -c, and 8e; R2 ) Me for 7d , 7f, 8d , and 8f. c Yield
of purified 2. In each case, 2 was accompanied by minor amounts
(entries 1-6, ∼5-20%; entries 7-12, <1-5%, based on GLC
analyses) of the corresponding alkyl (E)-3-trimethylstannyl-2-
d
alkenoate. These numbers refer to combined yields for the
thermal conversion of the (Z)-bis(trimethylstannyl)alkenoates 7c
and 7e, respectively, to the corresponding E isomers, followed by
acid-promoted protiodestannylation of the crude material thus
obtained.
alkynic esters 6, are configurationally quite stable and
undergo protonation of the alkenyl-copper bond with
retention to produce the E alkenoates 1 (Scheme 4).3c On
the basis of these findings, it is reasonable to propose
that the Cu(I)-catalyzed protiodestannylation of sub-
stances of general structure 7 proceeds via the pathway
shown in Scheme 5. Thus, treatment of 7 with CuCl in
DMF would be expected to result in transmetalation of
the R-trimethylstannyl function to afford Me3SnCl and
the alkenylcopper(I) intermediate 15, which would be
protonated by water with retention of configuration to
afford 1. Reaction of the resultant CuOH with HCl
(formed from Me3SnCl + H2O f Me3SnOH + HCl) would
regenerate the CuCl catalyst. The small amount of the
geometric isomer 2 formed from the overall protiodestan-
nylation process (Table 1) is, perhaps, due to a (minor)
pathway involving isomerization of 15 to the copper(I)
allenoate 16, which subsequently protonates on the
central allenic carbon from the side opposite to the bulky
Me3Sn function. Alternatively, the minor amounts of 2
could be formed by HCl-catalyzed protiodestannylation
of 7 (vide infra).
It should be noted that the CuCl-catalyzed protiod-
estannylations of alkyl (E)-2,3-bis(trimethylstannyl)-2-
alkenoates (8, Chart 1) are not synthetically useful
reactions. In general, the conversions are not clean and
the isolated yields of the expected products, alkyl (Z)-3-
trimethylstannyl-2-alkenoates, are poor. Analyses of the
crude reaction mixtures indicate that the two Me3Sn
functions are competitively removed. It thus appears
that the alkenyl-tin bonds associated with the â-Me3Sn
group in the E isomers 8 are more labile than the
corresponding carbon-tin bonds in the Z substrates 7.
This is, perhaps, due to the fact that intramolecular
coordination of the ester carbonyl oxygen in 8 with the
â-Sn atom (vide infra) weakens the alkenyl-tin bond.
(c) Hyd r och lor ic Acid -Med ia ted P r otiod esta n n y-
la tion of Alk yl (Z)- (7a -f) a n d (E)-2,3-Bis(tr im eth -
ylsta n n yl)-2-a lk en oa tes (8a -f). The results of these
experiments are summarized in Table 2. When the
substrate 7a was treated with dilute hydrochloric acid
in DMF at room temperature, a mixture of ethyl (Z)-3-
trimethylstannyl-2-butenoate (2a ) and the corresponding
geometric isomer (1a , see footnote c, Table 2) was
produced in high yield. The ratio of the two products was
∼4:1, respectively, and, after flash chromatography on
silica gel, the major isomer was isolated in 80% yield
(Table 2, entry 1). Similarly, protiodestannylation of the
2,3-bis(trimethylstannyl)-2-alkenoates 7b-f gave the
products 2b-f, respectively, in yields ranging from 76%
(2e, entry 5) to 94% (2f, entry 6). For the reactions
summarized in Table 2, entries 1-6, the amounts of
minor products (alkyl (E)-3-trimethylstannyl-2-alkenoates
1) present in the product mixtures varied from ∼5%
(entry 6) to ∼20% (entry 5).
The hydrochloric acid-mediated protiodestannylation
of the alkyl (E)-2,3-bis(trimethylstannyl)-2-alkenoates
(8a -f) also proceeded smoothly and afforded very good-
to-excellent yields of the corresponding products 2a -f
(Table 2, entries 7-12). Again, the latter materials were
accompanied by small amounts of the E isomers, ranging
from <1% (entry 12) to ∼5% (entries 8 and 11). Interest-
ingly, the quantities of these “side-products” obtained
from treatment of 8 with dilute hydrochloric acid were
generally lower than those derived from destannylation
of 7 via an identical protocol (see Table 2, footnote c).
Of the products 2a -f listed in Table 2, 2a ,3c 2b,3c and
2d 3e were reported previously, while substances 2c, 2e,
and 2f were prepared for the first time during the course
of this study. The preparation of 2c is particularly
noteworthy. Reactions of ethyl 5-chloro-2-pentynoate
with lithium (trimethylstannyl)(phenylthio)cuprate3c or
lithium (trimethylstannyl)(cyano)cuprate,3e under condi-
tions that generally transform alkyl R,â-alkynic esters
into alkyl (Z)-3-trimethylstannyl-2-alkenoates efficiently,
produce 2c in very poor yields. In contrast, as can be
seen from Table 2, the yields of 2c via the protiodestan-
nylation routes are very good. It should also be noted
that the acquisition of products 2b and 2e shows that

Chemoselective Protiodestannylations
J . Org. Chem., Vol. 62, No. 17, 1997 6037
Sch em e 6
Sch em e 8
Sch em e 7
Sch em e 9
the new method can be employed successfully for the
synthesis of compounds containing acid-labile functional
groups.
cation 19. Counterclockwise rotation (least motion12
)
The acid-mediated protiodestannylation of the Z alk-
enoates 7 (Table 2, entries 1-6) probably occurs via a
pathway as outlined in Scheme 6.9 Protonation of 7 on
the oxygen of the ester carbonyl, followed by nucleophilic
attack on the R-Me3Sn function of the resultant inter-
mediate 17, would provide the allenol 18. The stereose-
lective formation of the major product 2 would result from
preferential protonation at C-2 of 18 from the side
opposite to the sterically bulky Me3Sn function.
Protiodestannylation of the E alkenoates 8 may be
mechanistically somewhat more complex. It is certainly
possible that this process proceeds, at least partially, via
a pathway analogous to that presented in Scheme 6.
However, the fact that destannylation of 8 is consistently
more stereoselective (in favor of the Z alkenoate 2, see
Table 2) than that observed for the geometrically isomeric
substrates 7 suggests that an alternative pathway is, at
least to some degree, also operative. The latter possibil-
ity is outlined in Scheme 7.
about the C-2-C-3 bond of 19 places the R-Me3Sn (M in
20, Scheme 7) in an orientation that allows destannyla-
tive regeneration of the double bond to produce, stereo-
selectively, the Z alkenoate 2.
(d ) Stu d ies In volvin g Dim eth yl (Z,Z)- (22), a n d
(E,E)-2,3,8,9-Tetr a k is(tr im eth ylsta n n yl)-2,8-d eca d i-
en ed ioa te (24). The synthetic value of the protiod-
estannylation methods discussed above was demon-
strated further by a brief investigation employing the
substrates 22 and 24, which were prepared as outlined
in Scheme 8. Pd(0)-catalyzed addition6 of 2 equiv of
hexamethyldistannane to dimethyl 2,8-decadiynedioate
(21)6b,13 afforded, in 67% yield, the crystalline Z,Z-
dienedioate 22. Thermolysis (85 °C, 46 h) of the latter
material gave cleanly a mixture of two products. Chro-
matographic separation of these materials furnished the
Z,E dienedioate 23, the partially rearranged product, and
the corresponding E,E isomer 24 in yields of 35 and 52%,
respectively.
Copper(I) chloride-catalyzed protiodestannylation of 22
produced, after chromatographic purification of the crude
product, dimethyl (E,E)-3,8-bis(trimethylstannyl)-2,8-
decadienedioate (25) in 65% yield (Scheme 9). On the
other hand, treatment of 24 with dilute hydrocloric acid
provided, as expected, the Z,Z-dienedioate 26 (96% yield).
Thus, the destannylation methods are applicable to
substrates that are structurally more complex than those
employed in the initial studies (Tables 1 and 2).
It is well established10,11 that a suitably placed oxygen
function will engage in intramolecular coordination with
the tin atom of a trialkylstannyl group. Thus, it is highly
likely10,11 that the ester carbonyl oxygen of 8 is coordi-
nated to the â-trimethylstannyl group as shown in
Scheme 7. Protonation of this substance on the R-carbon
rather than on the carbonyl oxygen would lead to the
(9) For related mechanistic studies and discussions, see: Cochran,
J . C.; Williams, L. E.; Bronk, B. S.; Calhoun, J . A.; Fassberg, J .; Clark,
K. G. Organometallics 1989, 8, 804. Cochran, J . C.; Terrence, K. M.;
Phillips, H. K. Organometallics 1991, 10, 2411.
(10) J astrzebski, J . T. B. H.; Van Koten, G. Adv. Organomet. Chem.
1993, 35, 241.
(12) March, J . Advanced Organic Chemistry, 4th ed.; Wiley: New
York, 1992; p 782 and citations therein.
(13) We are grateful to Ms. Eva Boehringer for a generous sample
of 21.
(11) Piers, E.; Coish, P. D. Synthesis 1995, 47 and citations therein.

6038 J . Org. Chem., Vol. 62, No. 17, 1997
Piers et al.
NH4Cl-NH4OH (pH ∼8) was prepared by the addition of ∼50
mL of aqueous NH3 (30%) to ∼950 mL of saturated aqueous
NH4Cl.
All reactions, except those involving the addition of water
or aqueous HCl, were carried out under an atmosphere of dry
argon using glassware that had been thoroughly flame- and/
or oven-dried (∼120 °C).
Treatment of each of the bis(trimethylstannanes) 25
and 26 with ∼5 equiv of CuCl in DMF14 gave the diesters
27 and 28, respectively. Clearly, the combination of
Pd(0)-catalyzed addition of hexamethyldistannane to R,â-
alkynic esters,6 the new protiodestannylation procedures,
and the previously reported14 copper(I) chloride-mediated
intramolecular oxidative coupling of alkenyltrimethyl-
stannane functions provides an easy synthesis of dia-
stereomeric, structurally novel substances such as 27
and 28.
5-(Meth oxym eth oxy)-1-p en tyn e. To a cold (0 °C), stirred
solution of 4-pentyn-1-ol (3.40 mL, 36.5 mmol) in dry CH2Cl2
(70 mL) was added sequentially diisopropylethylamine (9.49
mL, 54.5 mmol) and chloromethyl methyl ether (4.20 mL, 55.3
mmol). After the mixture had been stirred for 1.5 h, 2 N
aqueous HCl (70 mL) was added and the resulting mixture
was stirred for 15 min. The phases were separated and the
aqueous layer was extracted with Et2O (3 × 50 mL). The
combined organic extracts were washed (brine, 200 mL), dried
(MgSO4), and concentrated. Distillation (70-90 °C (35 Torr))
of the crude oil afforded 4.83 g (97%) of the title compound, a
Con clu sion
The studies outlined above resulted in the development
of new protocols for the synthesis of alkyl (E)- (1) and
(Z)-3-trimethylstannyl-2-alkenoates (2), substances that
have previously been demonstrated to be valuable syn-
thetic intermediates. Compared with previously de-
scribed methods for the synthesis of 1 and 2, involving
stereocontrolled reactions of alkyl 2-alkynoates 6 with
(trimethylstannyl)cuprate reagents under carefully de-
fined experimental conditions, the protocols disclosed
herein offer a number of advantages. Obviously, the new
procedures preclude the neccessity of preparing Me3SnLi
and (trimethylstannyl)copper(I) reagents. The prepara-
tion of 1 involves two experimentally simple steps, a
Pd(0)-catalyzed addition of hexamethyldistannane to
alkyl 2-alkynoates 6 and a chemoselective, CuCl-cata-
lyzed protiodestannylation reaction. The sequences lead-
ing to 2 (6 f 7 f 2 or 6 f 7 f 8 f 2) also employ
experimentally straightforward procedures. In fact, all
the reactions leading to the production of 1 and 2, except
for 7 f 8, are carried out at room temperature and,
therefore, no low-temperature baths are required. Fur-
thermore, the protiodestannylation steps (7 f 1 or 2; 8
f 2) do not require inert atmospheres and the workup
procedures in all of these processes are more convenient
than those required for the cuprate-based methods.
1
colorless oil: IR (neat) 2119, 1150, 1041, 920 cm-1; H NMR
(400 MHz) δ 1.81 (quintet, 2 H, J ) 7 Hz), 1.97 (t, 1 H, J ) 1
Hz), 2.33 (dt, 2 H, J ) 7, 1 Hz), 3.37 (s, 3 H), 3.64 (t, 2 H, J )
7 Hz), 4.62 (s, 2 H); 13C NMR (50.3 MHz) δ 15.2, 28.5, 55.1,
65.9, 68.5, 83.7, 96.4. HRMS calcd for C7H12O2 128.0837, found
128.0838. Anal. Calcd: C, 65.60; H, 9.44. Found: C, 65.40;
H, 9.60.
Eth yl 6-(Meth oxym eth oxy)-2-h exyn oa te (11). To a cold
(-78 °C), stirred solution of 5-(methoxymethoxy)-1-pentyne in
dry THF (5 mL) was added a solution of methyllithium in
diethyl ether (2.10 mL, 3.02 mmol). The mixture was stirred
for 15 min at -78 °C, then warmed to -20 °C, and stirred for
1 h. Ethyl chloroformate (0.30 mL, 3.14 mmol) was added and
stirring was continued at -20 °C for 1 h. After the mixture
had been warmed to room temperature and stirred for 1 h,
saturated aqueous NaHCO3 (5 mL) and diethyl ether (5 mL)
were added. The phases were separated and the aqueous layer
was extracted with Et2O (3 × 10 mL). The combined organic
extracts were washed (brine, 10 mL), dried (MgSO4), and
concentrated. Distillation (95-110 °C (0.6 Torr)) of the crude
oil afforded 410 mg (76%) of 11, a colorless oil: IR (neat) 2236,
1
1713, 1256, 1040, 753 cm-1; H NMR (400 MHz) δ 1.32 (t, 3
H, J ) 7 Hz), 1.88 (quintet, 2 H, J ) 7 Hz), 2.47 (t, 2 H, J )
7 Hz), 3.36 (s, 3 H), 3.61 (t, 2 H, J ) 7 Hz), 4.22 (q, 2H, J ) 7
Hz), 4.61 (s, 2 H); 13C NMR (50.3 MHz) δ 14.0, 15.5, 27.7, 55.2,
61.7, 65.7, 73.4, 88.3, 96.4, 153.7. HRMS calcd for C10H15O4
(M+ - H) 199.0971, found 199.0966. Anal. Calcd for
C10H16O4: C, 59.98; H, 8.08. Found: C, 59.76; H, 8.17.
Eth yl (Z)-6-(Meth oxym eth oxy)-2,3-bis(tr im eth ylsta n -
n yl)-2-h exen oa te (7e). To a stirred solution of ethyl 6-(meth-
oxymethoxy)-2-hexynoate (11) (1.08 g, 5.41 mmol) in dry THF
(40 mL) was added sequentially hexamethyldistannane (1.12
mL, 5.41 mmol) and [Ph3Pd]4Pd (63 mg, 0.054 mmol). The
mixture was heated to reflux for 8 h and then was concentrated
under reduced pressure. Flash chromatography (100 g of silica
gel, 10:1 pentane-Et2O) of the crude oil afforded 2.53 g (89%)
Exp er im en ta l Section
Gen er a l Exp er im en ta l Deta ils. Distillation tempera-
tures, which refer to short-path (Kugelrohr) distillations, and
melting points are uncorrected. 1H NMR and 13C NMR spectra
were recorded by using CDCl3 as the solvent and signal
positions (δ values) were measured relative to the signals for
CHCl3 (δ 7.24) and CDCl3 (δ 77.0), respectively. Tin-proton
coupling constants (J Sn-H) are given as an average of the 117Sn
and 119Sn values. GLC was performed on instruments equipped
with capillary columns (25 m, HP-5) and flame ionization
detectors. TLC was carried out by using commercial aluminum-
backed silica gel 60 plates. Flash chromatography5 was
carried out with 230-400 mesh silica gel (E. Merck).
THF was distilled from sodium/benzophenone, while CH2Cl2
and i-Pr2NEt were distilled from CaH2. Commercial DMF
(99.9%, Fisher Scientific, Inc.) was used without further
purification. J ust prior to use, methyl chloroformate, ethyl
chloroformate, and chloromethyl methyl ether were passed
through a short column of basic alumina (activity I) that had
been dried in an oven (∼120 °C) overnight and then allowed
to cool in a desiccator.
of 7e, a colorless oil: IR (neat) 1703, 1186, 1038, 771, 526 cm-1
;
2
1H NMR (400 MHz) δ 0.209 (s, 9 H, J Sn-H ) 54 Hz), 0.212 (s,
2
9 H, J Sn-H ) 54 Hz), 1.26 (t, 3 H, J ) 7 Hz), 1.59-1.67 (m, 2
H), 2.36-2.42 (m, 2 H), 3.31 (s, 3 H), 3.47 (t, 2 H, J ) 7 Hz),
4.13 (q, 2 H, J ) 7 Hz), 4.56 (s, 2 H); 13C NMR (50.3 MHz) δ
-6.7, 14.5, 30.2, 37.4, 55.1, 60.1, 67.3, 96.3, 149.9, 164.2, 171.7.
HRMS calcd for C15H31O4120Sn2 (M+ - Me) 515.0266, found
515.0255. Anal. Calcd for C16H34O4Sn2: C, 36.41; H, 6.49.
Found: C, 36.51; H, 6.49.
Meth yl (Z)-3-P h en yl-2,3-bis(tr im eth ylsta n n yl)p r op e-
n oa te (7f). To a stirred solution of methyl 3-phenylpropynoate
(12) (1.00 g, 6.25 mmol) in dry THF (50 mL) was added
sequentially hexamethylditin (1.05 mL, 6.25 mmol) and
[Ph3Pd]4Pd (72 mg, 0.063 mmol). The mixture was heated to
reflux for 2 h and then was concentrated under reduced
pressure. Flash chromatography (100 g of silica gel, 95:5
pentane-Et2O) of the crude oil afforded 2.05 g (67%) of 7f, a
crystalline solid: mp 78-79 °C; IR (KBr) 3056, 2987, 1714,
Copper(I) chloride (99.995%+, Aldrich Chemical Co., Inc.)
was used without further purification, while tetrakis(triph-
enylphosphine)palladium(0) was prepared according to the
method described by Coulson.15 Hexamethyldistannane (Or-
ganometallics, Inc.) was distilled prior to use.
A solution of 1 N aqueous HCl was prepared by dissolving
83 mL of concentrated HCl (∼12 M) in 1 L of water. Aqueous
1
1595, 1429, 1219, 1016, 773 cm-1; H NMR (400 MHz) δ 0.11
2
2
(s, 9 H, J Sn-H ) 53 Hz), 0.29 (s, 9 H, J Sn-H ) 54 Hz), 3.35 (s,
3 H), 6.89 (dm, 2 H, J ) 8 Hz), 7.08 (tt, 1 H, J ) 7, 1 Hz),
7.17-7.27 (m, 2 H); 13C NMR (75 MHz) δ -6.7, -6.6, 50.8,
(14) Piers, E.; Romero, M. A. J . Am. Chem. Soc. 1996, 118, 1215.
(15) Coulson, D. R. Inorganic Synthesis 1972, 13, 121.

Chemoselective Protiodestannylations
J . Org. Chem., Vol. 62, No. 17, 1997 6039
125.2, 125.6, 128.0, 147.0, 152.3, 165.6, 172.1. HRMS calcd
for C15H23O2120Sn2 (M+ - Me) 474.9742, found 474.9734. Anal.
Calcd for C16H26O2Sn2: C, 39.40; H, 5.37. Found: C, 39.62;
H, 5.36.
Meth yl (E)-3-P h en yl-3-tr im eth ylstan n ylpr open oate (1f).
This material is a colorless oil: IR (neat) 2950, 1731, 1605,
1
1434, 1165, 1073, 834 cm-1; H NMR (400 MHz) δ 0.19 (s, 9
H, 2J Sn-H ) 52 Hz), 3.53 (s, 3 H), 6.14 (s, 1 H, 3J Sn-H ) 66 Hz),
6.93 (dm, 2 H, J ) 8 Hz), 7.16 (tt, 1 H, J ) 7, 1 Hz), 7.29 (tm,
2 H, J ) 8 Hz); 13C NMR (75 MHz) δ -9.2, 51.0, 124.6, 125.8,
127.5, 128.0, 143.8, 164.6, 168.9. HRMS calcd for C12H15O2120Sn
(M+ - Me) 311.0094, found 311.0086.
Meth yl (Z)-2,3-Bis(tr im eth ylsta n n yl)-2-octen oa te (7g).
To a stirred solution of methyl 2-octynoate (13) (1.00 g, 6.49
mmol) in dry THF (40 mL) was added sequentially hexam-
ethylditin (1.1 mL, 6.49 mmol) and [Ph3Pd]4Pd (75 mg, 0.065
mmol). The resulting mixture was heated to reflux for 3 h
and then was concentrated under reduced pressure. Flash
chromatography (100 g of silica gel, 98:2 pentane-Et2O) of the
crude oil afforded 2.14 g (68%) of 7g, a colorless oil: IR (neat)
Meth yl (E)-3-tr im eth ylsta n n yl-2-octen oa te (1g,) a col-
orless oil, displayed IR (neat) 2958, 2859, 1721, 1596, 1434,
1256, 1169, 771 cm-1; 1H NMR (400 MHz) δ 0.17 (s, 9 H, 2J Sn-H
) 53 Hz), 0.80-0.95 (m, 3 H), 1.22-1.45 (m, 6 H), 2.86 (td, 2
3
1
2930, 2859, 1712, 1433, 1256, 1191, 771 cm-1; H NMR (400
H, J ) 1, 8 Hz, J Sn-H ) 62 Hz), 3.68 (s, 3 H), 5.94 (br s, 1 H,
3J Sn-H ) 74 Hz); 13C NMR (75 MHz) δ -9.1, 14.0, 22.5, 29.3,
2
2
MHz) δ 0.19 (s, 9 H, J Sn-H ) 60 Hz), 0.21 (s, 9 H, J Sn-H ) 58
31.8, 34.7, 50.8, 126.8, 164.7, 174.1. HRMS calcd for C11H21
-
Hz), 0.86 (t, 3 H, J ) 7 Hz), 1.20-1.40 (m, 6 H), 2.29 (t, 2 H,
O2120Sn (M+ - Me) 305.0564, found 305.0554. Anal. Calcd
for: C12H24O2Sn: C, 45.18; H, 7.58. Found: C, 45.51; H, 7.73.
Gen er a l P r oced u r e 2. Hyd r och lor ic Acid -Med ia ted
P r otiod esta n n yla tion of th e Alk yl (Z)- a n d (E)-2,3-Bis-
(t r im et h ylst a n n yl)-2-a lk en oa t es (7a -f, 8a -f, R esp ec-
tively). P r ep a r a tion of th e Alk yl (Z)-3-Tr im eth ylsta n -
n yl-2-a lk en oa tes 2a -f. To a stirred solution of the alkyl 2,3-
bis(trimethylstannyl)-2-alkenoate 7 or 8 in DMF was added 1
N hydrochloric acid. The mixture was stirred at room tem-
perature for the specified length of time and then saturated
aqueous NaHCO3 (one-quarter the volume of DMF) and diethyl
ether (one-quarter the volume of DMF) were added. The
phases were separated and the aqueous layer was extracted
three times with Et2O. The combined organic extracts were
washed (water, brine), dried (MgSO4), and concentrated. The
crude product was purified by flash chromatography on silica
gel.
J ) 7 Hz, J Sn-H ) 58 Hz), 3.67 (s, 3 H); 13C NMR (75 MHz) δ
3
-6.8, -6.7, 14.0, 22.5, 29.8, 31.7, 41.1, 51.0, 148.6, 165.6, 172.4.
HRMS calcd for C14H29O2120Sn2 (M+ - Me) 469.0212, found
469.0214.
Meth yl (E)-3-P h en yl-2,3-bis(tr im eth ylsta n n yl)p r op e-
n oa te (8f). Neat methyl (Z)-3-phenyl-2,3-bis(trimethylstan-
nyl)propenoate (7f) (0.50 g, 1.03 mmol) was heated (85 °C)
under an argon atmosphere for 26 h. Flash chromatography
(50 g of silica gel, 98:2 pentane-Et2O) of the crude oil afforded
0.42 g (84%) of 8f, a crystalline solid: mp 56-57 °C; IR (KBr)
3058, 2981, 2914, 1695, 1552, 1486, 1434, 1236, 1206, 1033,
2
772 cm-1
;
1H NMR (400 MHz) δ -0.16 (s, 9 H, J Sn-H ) 55
Hz), 0.03 (s, 9 H, 2J Sn-H ) 54 Hz), 3.76 (s, 3 H), 6.85 (dm, 2 H,
J ) 8 Hz), 7.15 (tt, 1 H, J ) 8, 1 Hz), 7.26 (tm, 2 H), J ) 8
Hz); 13C NMR (75 MHz) δ -6.9, -6.6, 51.9, 125.5, 126.1, 128.1,
128.2, 147.8, 172.3, 182.2. HRMS calcd for C15H23O2118Sn120Sn
(M+ - Me) 472.9736, found 472.9732. Anal. Calcd for C16H26
-
The quantities of materials used for the individual experi-
ments, the reaction times, and the isolated yields of the
products are summarized in Table 2. Of the products 2a -f
prepared via this general procedure, substances 2a ,3c 2b,3c and
2d 3e were reported previously. The following new alkyl (Z)-
3-trimethylstannyl-2-alkenoates were prepared.
O2Sn2: C, 39.40; H, 5.37. Found: C, 39.70; H, 5.41.
Gen er a l P r oced u r e 1. Cu Cl-Ca ta lyzed P r otiod esta n -
n yla tion of th e Alk yl (Z)-2,3-Bis(tr im eth ylsta n n yl)-2-
a lk en oa tes 7a -g. P r ep a r a tion of th e Alk yl (E)-3-Tr im -
eth ylsta n n yl-2-a lk en oa tes 1a -g. To a stirred solution of
the substrate 7 in DMF were added water and solid CuCl. The
resulting pale green solution was stirred at room temperature
for the specified length of time and then aqueous NH4Cl-
NH4OH (pH ∼8, one-quarter of the volume of DMF) and
diethyl ether (one-quarter of the volume of DMF) were added.
The mixture was stirred, open to the atmosphere, for 10 min.
The phases were separated and the aqueous layer was
extracted three times with Et2O. The combined organic
extracts were washed sequentially with water and brine and
then were dried (MgSO4) and concentrated. The crude product
was purified by flash chromatography on silica gel.
Eth yl (Z)-5-ch lor o-3-tr im eth ylstan n yl-2-pen ten oate (2c),
a colorless oil, exhibited IR (neat) 1704, 1603, 1207, 774 cm-1
;
2
1H NMR (400 MHz) δ 0.17 (s, 9 H, J Sn-H ) 55 Hz), 1.26 (t, 3
3
H, J ) 7 Hz), 2.84 (dt, 2 H, J ) 1, 7 Hz, J Sn-H ) 43 Hz), 3.53
(t, 2 H, J ) 7 Hz), 4.17 (q, 2 H, J ) 7 Hz), 6.39 (t, 1 H, J ) 1
Hz, 3J Sn-H ) 114 Hz); 13C NMR (50.3 MHz) δ -7.3, 14.2, 41.9,
42.9, 60.5, 130.5, 167.6, 170.1. HRMS calcd for C9H1635ClO2120Sn
(M+ - Me) 310.9861, found 310.9866. Anal. Calcd for C10H19
ClO2Sn: C, 36.91; H, 5.89. Found: C, 37.00; H, 5.98.
-
E t h yl (Z)-6-m et h oxym et h oxy-3-t r im et h ylst a n n yl-2-
h exen oa te (2e) was obtained as a colorless oil: IR (neat)
The quantities of materials used for the individual experi-
ments and the isolated yields of the products are summarized
in Table 1. Of the products 1a -g prepared via this general
procedure, substances 1a ,3c 1b,3c and 1d 3e were reported
previously. The following new alkyl (E)-3-trimethylstannyl-
2-alkenoates were prepared.
1
1703, 1600, 1325, 1207, 1041, 774 cm-1; H NMR (400 MHz)
2
δ 0.14 (s, 9 H, J Sn-H ) 54 Hz), 1.25 (t, 3 H, J ) 7 Hz), 1.62-
1.71 (m, 2 H), 2.48 (dt, 2 H, J ) 1, 8 Hz, 3J Sn-H ) 47 Hz), 3.32
(s, 3 H), 3.48 (t, 2 H, J ) 7 Hz), 4.15 (q, 2 H, J ) 7 Hz), 4.57
3
(s, 2 H), 6.34 (t, 1 H, J ) 1 Hz, J Sn-H ) 119 Hz); 13C NMR
(50.3 MHz) δ -7.4, 14.3, 29.1, 36.5, 55.1, 60.3, 66.9, 96.4, 128.3,
167.9, 174.8. HRMS calcd for C12H23O4120Sn (M+ - Me)
351.0614, found 351.0618. Anal. Calcd for C13H26O4Sn: C,
42.77; H, 7.18. Found: C, 42.87; H, 7.24.
Eth yl (E)-5-ch lor o-3-tr im eth ylstan n yl-2-pen ten oate (1c)
was obtained as a colorless oil: IR (neat) 1713, 1599, 1185,
1
2
1034, 773 cm-1; H NMR (400 MHz) δ 0.21 (s, 9 H, J Sn-H
)
54 Hz), 1.27 (t, 3 H, J ) 7 Hz), 3.28 (dt, 2 H, J ) 1, 7 Hz,
Meth yl (Z)-3-ph en yl-3-tr im eth ylstan n ylpr open oate (2f),
a colorless crystalline solid (mp 28-29 °C), displayed IR (KBr)
3J Sn-H ) 55 Hz), 3.60 (t, 2 H, J ) 7 Hz), 4.14 (q, 2 H, J ) 7
Hz), 6.07 (t, 1 H, J ) 1 Hz, J Sn-H ) 69 Hz); 13C NMR (50.3
3
1
1709, 1587, 1319, 1178, 1017, 769 cm-1; H NMR (400 MHz)
2
MHz) δ -8.8, 14.3, 37.1, 43.7, 59.9, 130.7, 163.8, 168.2. HRMS
calcd for C9H1635ClO2120Sn (M+ - Me) 310.9861, found 310.9854.
Anal. Calcd for C10H19ClO2Sn: C, 36.91; H, 5.89. Found: C,
36.98; H, 5.93.
δ 0.18 (s, 9 H, J Sn-H ) 55 Hz), 3.78 (s, 3 H), 6.48 (s, 1 H,
3J Sn-H ) 107 Hz), 7.04-7.09 (m, 2 H), 7.20-7.27 (m, 1 H),
7.28-7.35 (m, 2 H); 13C NMR (50.3 MHz) δ -6.3, 51.7, 126.5,
127.1, 128.1, 129.8, 144.8, 168.2, 173.6. HRMS calcd for
C12H15O2120Sn (M+ - Me) 311.0094, found 311.0085. Anal.
Calcd for C13H18O2Sn: C, 48.05; H, 5.58. Found: C, 47.82; H,
5.68.
E t h yl (E)-6-m et h oxym et h oxy-3-t r im et h ylst a n n yl-2-
h exen oa te (1e), a colorless oil, exhibited IR (neat) 1714, 1598,
1
1368, 1175, 1043, 773 cm-1; H NMR (400 MHz) δ 0.21 (s, 9
2
H, J Sn-H ) 55 Hz), 1.29 (t, 3 H, J ) 7 Hz), 1.68-1.77 (m, 2
Dim eth yl (Z,Z)-2,3,8,9-Tetr a k is(tr im eth ylsta n n yl)-2,8-
d eca d ien ed ioa te (22). To a stirred solution of dimethyl 2,8-
decadiynedioate (21)6b (0.352 g, 1.59 mmol) in dry THF (15
mL) was added sequentially Me3SnSnMe3 (535 µL, 3.17 mmol)
and (Ph3P)4Pd (55 mg, 0.045 mmol). The mixture was refluxed
for 3 h and then was concentrated under reduced pressure.
Flash chromatography (50 g of silica gel, 95:5 pentane-Et2O)
of the crude oil afforded 0.916 g (67%) of the title compound,
3
H), 2.96 (dt, 2 H, J ) 1, 7 Hz, J Sn-H ) 52 Hz), 3.37 (s, 3H),
3.55 (t, 2 H, J ) 7 Hz), 4.17 (q, 2 H, J ) 7 Hz), 4.62 (s, 2 H),
3
5.98 (t, 1 H, J ) 1 Hz, J Sn-H ) 73 Hz); 13C NMR (50.3 MHz)
δ -9.1, 14.3, 29.7, 31.5, 55.1, 59.7, 67.6, 96.4, 128.0, 164.2,
172.2. HRMS calcd for C12H23O4120Sn (M+ - Me) 351.0618,
found 351.0618. Anal. Calcd for C13H26O4Sn: C, 42.77; H,
7.18. Found: C, 42.66; H, 7.24.

6040 J . Org. Chem., Vol. 62, No. 17, 1997
Piers et al.
a colorless crystalline solid: mp 54-55 °C; IR (KBr) 2984,
rial: IR (KBr) 2930, 2856, 1709, 1600, 1436, 1210, 1045, 773
1
2
2919, 1708, 1551, 1430, 1191, 1024, 771 cm-1; H NMR (400
cm-1
;
1H NMR (400 MHz) δ 0.15 (s, 18 H, J Sn-H ) 54 Hz),
2
2
3
MHz) δ 0.20 (s, 18 H, J Sn-H ) 52 Hz), 0.21 (s, 18 H, J Sn-H
)
1.30-1.48 (m, 4 H), 2.40 (t, 4 H, J ) 7 Hz, J Sn-H ) 48 Hz),
3.70 (s, 6 H), 6.32 (s, 2 H, 3J Sn-H ) 119 Hz); 13C NMR (75 MHz)
δ 7.4, 28.8, 39.8, 51.5, 127.7, 168.3, 175.7. HRMS calcd for
C17H31O4120Sn2 (M+ - Me) 539.0266, found 539.0244.
54 Hz), 1.25-1.40 (m, 4 H), 2.29 (t, 4 H, J ) 7 Hz, 3J Sn-H ) 57
Hz), 3.68 (s, 6 H); 13C NMR (75 MHz) δ -6.8, -6.6, 30.2, 40.9,
51.0, 149.0, 165.0, 172.3. HRMS calcd for C17H29O4118Sn120Sn
(M+ - Me7Sn2) 535.0104, found 535.0114. Anal. Calcd for
C24H50O4Sn4: C, 32.85; H, 5.74. Found: C, 33.19; H, 6.05.
Dim et h yl (Z,E)- (23) a n d (E,E)-2,3,8,9-Tet r a k is(t r i-
m eth ylsta n n yl)-2,8-d eca d ien ed ioa te (24). Neat 22 (0.50
g, 0.58 mmol) was heated (85 °C) under an argon atmosphere
for 46 h. Flash chromatography (50 g of silica gel, 95:5
pentane-Et2O) of the crude oil afforded (in order of elution)
0.259 g (52%) of the E,E dienedioate 24, a crystalline substance
(colorless plates, mp 139-140 °C), and 0.174 g (35%) of the
Z,E dienoate (23), a colorless oil.
(E ,E )-1,2-Bis(m e t h oxyca r b on ylm e t h ylid e n e )cyclo-
h exa n e (27). To a warm (60 °C), stirred slurry of CuCl (0.063
g, 0.64 mmol) in 2 mL of DMF was added a solution of the
E,E dienedioate 25 (0.071 g, 0.13 mmol) in 1 mL of DMF. After
the reaction mixture had been stirred for 15 min, it was
allowed to cool to room temperature. Aqueous NH4Cl-NH4OH
(pH ∼8, 3 mL) and water (5 mL) were added sequentially to
the vigorously stirred mixture, which was then extracted with
Et2O (3 × 25 mL). The combined organic extracts were washed
(water, 3 × 25 mL; brine, 25 mL), dried (MgSO4), and
concentrated. Flash chromatography (30 g of silica gel, 9:1
petroleum ether-Et2O) of the remaining oil afforded 19 mg
(66%) of 27, a colorless crystalline substance: mp 32-33 °C;
IR (KBr) 1719, 1635, 1435, 1173, 870 cm-1; 1H NMR (400 MHz)
δ 1.69-1.73 (m, 4 H), 2.92-2.99 (m, 4 H), 3.69 (s, 6 H), 5.81
(s, 2 H); 13C NMR (50.3 MHz) δ 25.7, 30.1, 51.2, 114.6, 160.5,
166.6. HRMS calcd for C12H16O4 224.1049, found 224.1058.
Anal. Calcd: C, 64.27; H, 7.19. Found: C, 64.12; H, 7.15.
(Z,Z)-1,2-Bis(m e t h oxyca r b on ylm e t h ylid e n e )cyclo-
h exa n e (28). To a warm (60 °C), stirred slurry of CuCl (0.048
g, 0.48 mmol) in 2 mL of DMF was added a solution of the Z,Z
dienedioate 26 (53 mg, 0.096 mmol) in 0.5 mL of DMF. The
reaction mixture was stirred for 35 min, was allowed to cool
to room temperature, and then, while being stirred vigorously,
was treated sequentially with aqueous NH4Cl-NH4OH (pH
∼8, 3 mL) and water (5 mL). The mixture was extracted with
Et2O (3 × 20 mL). The combined organic extracts were washed
(water, 3 × 20 mL; brine, 20 mL), dried (MgSO4), and
concentrated. Flash chromatography (30 g of silica gel, 9:1
petroleum ether-Et2O) of the crude product gave 14 mg (65%)
of the title diester 28, a colorless crystalline material: mp 60
°C (dec); IR (KBr) 2947, 2859, 1730, 1665, 1637, 1439, 1336,
Compound 24: IR (KBr) 2987, 2926, 1714, 1691, 1431, 1235,
2
751 cm-1
;
1H NMR (400 MHz) δ 0.13 (s, 18 H, J Sn-H ) 53
Hz), 0.22 (s, 18 H, 2J Sn-H ) 54 Hz), 1.25-1.40 (br m, 4H), 2.40-
2.50 (br m, 4 H, J Sn-H ) 58 Hz), 3.69 (s, 6 H); 13C NMR (75
3
MHz) δ -6.5, -5.9, 30.5, 41.4, 51.8, 144.1, 172.1, 183.9. HRMS
calcd for C23H47O4120Sn4 (M+ - Me) 866.9562, found 866.9549.
Anal. Calcd for C24H50O4Sn4: C, 32.85; H, 5.74. Found: C,
33.22; H, 6.03.
Compound 23: IR (neat) 2986, 2919, 1708, 1693, 1547, 1432,
1226, 1024, 774 cm-1; 1H NMR (400 MHz) δ 0.12 (s, 9 H, 2J Sn-H
) 53 Hz), 0.20 (s, 9 H, 2J Sn-H ) 52 Hz), 0.21 (s, 18 H, 2J Sn-H
)
54 Hz), 1.20-1.31 (m, 2 H), 1.32-1.45 (m, 2 H), 2.28-2.36 (m,
2 H), 2.37-2.48 (m, 2 H), 3.66 (s, 3 H), 3.67(s, 3 H); 13C NMR
(75 MHz) δ -6.8, -6.6, -6.5, -6.0, 30.3, 30.4, 40.8, 41.6, 51.0,
51.8, 143.8, 149.3, 164.5, 172.1, 172.3, 184.3. HRMS calcd for
C24H50O4120Sn4 866.9562, found 866.9529. Anal. Calcd for
C24H50O4Sn4: C, 32.85; H, 5.74. Found: C, 33.22; H, 5.99.
Dim eth yl (E,E)-3,8-Bis(tr im eth ylsta n n yl)-2,8-d eca d i-
en ed ioa te (25). Following general procedure 1 (vide supra),
the Z,Z dienedioate 22 was converted into the title compound
25 with the following quantities of reagents and solvents: 22
(210 mg, 0.243 mmol), CuCl (0.4 mg, 0.004 mmol), DMF (5
mL), and water (0.5 mL). Flash chromatography (30 g of silica
gel, 9:1 petroleum ether-Et2O) of the crude oil afforded 88
mg (65%) of 25, a colorless oil: IR (neat) 2948, 2856, 1719,
1
1283, 1171, 1021, 851 cm-1; H NMR (400 MHz) δ 1.50-1.68
(m, 2 H), 1.86-2.10 (br unresolved m, 2 H), 2.22-2.40 (br
unresolved m, 2 H), 2.51 (br d, 2 H, J ) 12 Hz), 3.60 (s, 6 H),
5.73 (s, 2 H). In a NOE experiment, irradiation of the singlet
at δ 5.73 (vinylic proton) enhances the broad doublet at 2.51
and the broad multiplet at 2.22-2.40; 13C NMR (75 MHz,
CDCl3) δ 29.2, 40.0, 51.1, 113.8, 157.0, 166.1. HRMS calcd
for C12H16O4 224.1049, found 224.1054. Anal. Calcd: C, 64.27;
H, 7.19. Found: C, 64.12; H, 7.24.
1
1595, 1433, 1352, 1155, 771 cm-1; H NMR (400 MHz) δ 0.18
2
(s, 18 H, J Sn-H ) 54 Hz), 1.40-1.50 (m, 4 H), 2.79-3.10 (m,
3
4 H, J Sn-H ) 62 Hz), 3.69 (s, 6 H), 5.94 (t, 2 H, J ) 1 Hz,
3J Sn-H ) 74 Hz). HRMS calcd for C17H31O4120Sn2 (M+ - Me)
539.0266, found 539.0261. Anal. Calcd for C18H34O4Sn2: C,
38.99; H, 6.00. Found: C, 39.26; H, 6.00.
Dim eth yl (Z,Z)-3,8-Bis(tr im eth ylsta n n yl)-2,8-d eca d i-
en ed ioa te (26). Following general procedure 2 (vide supra),
substrate 24 was converted into 26 with the following quanti-
ties of reagents and solvents: 24 (131 mg, 0.151 mmol), 1 N
hydrochloric acid (0.36 mL), and DMF (3 mL). The reaction
temperature was 70 °C and the reaction time in this case was
1 h. Flash chromatography (30 g of silica gel, 95:5 petroleum
ether-Et2O) of the crude oil afforded 81 mg (96%) of the Z,Z
dienedioate 26, a colorless crystalline (mp 75-77 °C) mate-
Ack n ow led gm en t. We gratefully acknowledge the
Natural Sciences and Engineering Research Council of
Canada for financial support and for a Postgraduate
Scholarship (to E.J .M.), Merck Frosst Canada Inc. for
financial assistance, and Bio-Me´ga/Boehringer Ingel-
heim Research Inc. for a Scholarship (to E.J .M.).
J O9707693