Palladium-catalyzed, asymmetric hetero- and carboannulation of allenes using functionally-substituted aryl and vinylic iodides

Article abstract of DOI:10.1021/jo9901992

Aryl and vinylic iodides with a nucleophilic substituent in the ortho or allylic position, respectively, react with 1,2-dienes in the presence of a palladium catalyst and a chiral bisoxazoline ligand to afford five- and six- membered ring heterocycles and carbocycles in good yields and 46-88% enantiomeric excess. The generality of this process has been demonstrated by the use of nucleophilic substituents as varied as tosylamides, alcohols, phenols, carboxylic acids, and stabilized carbanions.

Full text of DOI:10.1021/jo9901992

7
312
J . Org. Chem. 1999, 64, 7312-7322
P a lla d iu m -Ca ta lyzed , Asym m etr ic Heter o- a n d Ca r boa n n u la tion of
Allen es Usin g F u n ction a lly-Su bstitu ted Ar yl a n d Vin ylic Iod id es
J ohn M. Zenner and Richard C. Larock*
Department of Chemistry, Iowa State University, Ames, Iowa 50011
Received February 2, 1999
Aryl and vinylic iodides with a nucleophilic substituent in the ortho or allylic position, respectively,
react with 1,2-dienes in the presence of a palladium catalyst and a chiral bisoxazoline ligand to
afford five- and six-membered ring heterocycles and carbocycles in good yields and 46-88%
enantiomeric excess. The generality of this process has been demonstrated by the use of nucleophilic
substituents as varied as tosylamides, alcohols, phenols, carboxylic acids, and stabilized carbanions.
In tr od u ction
Biologically active molecules, which are chiral, often
We have recently reported the regioselective, pal-
ladium-catalyzed hetero- and carboannulation of allenes
using functionally substituted aryl and vinylic halides.
The nature of the π-allylpalladium intermediates in-
volved encouraged us to examine asymmetric versions
of these annulation processes. Preliminary results of this
work have been published in the form of a communica-
tion.11 We now report, in greater detail, the results of our
investigation.
9
10
exhibit significant variance in biological activity between
1
enantiomers. For this reason, the development of asym-
metric synthetic methodologies has been of prime im-
portance to organic chemists. The enantioselective, pal-
ladium-catalyzed allylic substitution reaction has been
shown to be a useful means of forming new chiral
2
3
4
carbon-carbon, carbon-nitrogen, carbon-oxygen, and
5
carbon-sulfur bonds. Most work in this area has focused
on intermolecular nucleophilic substitution of the sym-
metrical 1,3-diphenyl-π-allylpalladium system and the
development of improved chiral ligands for use in this
Resu lts a n d Discu ssion
The reaction of N-tosyl-2-iodoaniline with 1,2-undeca-
diene was chosen as a model system to optimize condi-
tions for asymmetric induction. We have previously
reported that using as reaction conditions 5 mol % Pd-
6
process. Relatively little work has been done on more
complicated unsymmetrical systems.7
Asymmetric induction in intramolecular π-allylpalla-
dium displacements has received far less attention with
only three examples of this type of process appearing in
(OAc)
2
, 5 mol % PPh
3 2 3
, 3 molar equiv of Na CO , and 1
equiv of n-Bu
4
NCl (TBAC) in DMF at 100 °C for 1 day,
9
the desired product was obtained in 85% yield (eq 1).
Initial attempts at asymmetric induction utilized these
8
the literature. Tsuji reported in 1982 an asymmetric
cyclization of methyl (E)-3-oxo-9-phenoxy-7-nonenoate in
the presence of a chiral diphosphine ligand to give the
cyclized product in up to 48% ee.8 Genet and Grisoni
synthesized an ergot alkaloid synthon in up to 70% ee
using a palladium-chiraphos catalyst,8b and Shibasaki et
al. have recently reported the synthesis of a cis-decalin
derivative in up to 83% ee via an asymmetric π-allylpal-
ladium displacement.8
3
same conditions, but replaced PPh with (R)-BINAP.
a
(6) (a) Brunner, H. In Topics in Stereochemistry; Eliel, E., Wilen, S.
H., Eds.; J ohn Wiley and Sons: New York, 1988; Vol. 18, pp 129-248.
(b) Muller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. Helv. Chim. Acta
1
991, 74, 232-240. (c) Helmchen, G.; Krotz, A.; Ganz, K.-T.; Hansen,
D. Synlett 1991, 257-258. (d) Lowenthal, R. E.; Abiko, A.; Masamune,
S. Tetrahedron Lett. 1990, 31, 6005-6008. (e) Leutenegger, U.;
Umbricht, G.; Fahrni, C.; von Matt, P.; Pfaltz, A. Tetrahedron 1992,
c
4
8, 2143-2156. (f) von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl.
(
1) Bonner, W. A. In Topics in Stereochemistry; Eliel, E., Wilen, S.
H., Eds.; J ohn Wiley and Sons: New York, 1988; Vol. 18, pp 1-96.
2) (a) Trost, B. M.; Dietsche, T. J . J . Am. Chem. Soc. 1973, 95,
1993, 32, 566-568. (g) Frost, C. G.; Williams J . M. J . Tetrahedron Lett.
1993, 34, 2015-2018. (h) Togni, A. Tetrahedron: Asymmetry 1991, 2,
683-690. (i) Bovens, M.; Togni, A.; Venanzi, L. M. J . Organomet. Chem.
1993, 451, C28-C31. (j) Brenchley, G.; Merifield, E.; Wills, M.;
Fedouloff, M. Tetrahedron Lett. 1994, 35, 2791-2794. (k) Togni, A.;
Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.; Tijani, A. J . Am.
Chem. Soc. 1994, 116, 4062-4066. (l) Kubota, H.; Koga, K. Tetrahedron
Lett. 1994, 35, 6689-6692. (m) Minami, T.; Okada, Y.; Otaguro, T.;
Tawaraya, S.; Furuichi, T.; Okauchi, T. Tetrahedron: Asymmetry 1995,
6, 2469-2474. (n) Tokunoh, R.; Sodeoka, M.; Aoe, K.; Shibasaki, M.
Tetrahedron Lett. 1995, 36, 8035-8038. (o) Allen, J . V.; Bower, J . F.;
Williams, J . M. J . Tetrahedron: Asymmetry 1994, 5, 1895-1898.
(7) (a) Auburn, P. R.; Mackenzie, P. B.; Bosnich, B. J . Am. Chem.
Soc. 1985, 107, 2033-2046. (b) Mackenzie, P. B.; Whelan, J .; Bosnich,
B. J . Am. Chem. Soc. 1985, 107, 2046-2053.
(
8
1
4
200-8201. (b) Trost, B. M.; Strege, P. E. J . Am. Chem. Soc. 1977, 99,
649-1651. (c) Fiaud, J .-C.; Legros, J .-Y. J . Org. Chem. 1990, 55,
840-4846. (d) Yamaguchi, M.; Shima, T.; Yamagishi, T.; Hida, M.
Tetrahedron: Asymmetry 1991, 2, 663-666. (e) von Matt, P.; Loiseleur,
O.; Koch, G.; Pfaltz, A.; Lefeber, C.; Feucht, T.; Helmchen, G.
Tetrahedron: Asymmetry 1994, 5, 573-584. (f) Trost, B. M.; Bunt, R.
C. J . Am. Chem. Soc. 1994, 116, 4089-4090. (g) Baldwin, I. C.;
Williams, J . M. J .; Beckett, R. P. Tetrahedron: Asymmetry 1995, 6,
1
9
515-1518. (h) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996,
6, 395-422.
(3) (a) J umnah, R.; Williams, A. C.; Williams, J . M. J . Synlett 1995,
8
6
21-822. (b) Yamazaki, A.; Achiwa, K. Tetrahedron: Asymmetry 1995,
, 51-54. (c) Togni, A.; Burckhardt, U.; Gramlich, V.; Pregosin, P. S.;
(8) (a) Yamamoto, K.; Tsuji, J . Tetrahedron Lett. 1982, 23, 3089-
3092. (b) Genet, J . P.; Grisoni, S. Tetrahedron Lett. 1988, 29, 4543-
4546. (c) Takemoto, T.; Nishikimi, Y.; Sodeoka, M.; Shibasaki, M.
Tetrahedron Lett. 1992, 33, 3531-3532.
Salzmann, R. J . Am. Chem. Soc. 1996, 118, 1031-1037. (d) Constan-
tieux, T.; Brunel, J .-M.; Labande, A.; Buono, G. Synlett 1998, 1, 49-
5
8
6
0.
(
16.
4) Trost, B. M.; Toste, F. D. J . Am. Chem. Soc. 1998, 120, 815-
(9) Larock, R. C.; Berrios-Pe n˜ a, N. G.; Fried, C. A. J . Org. Chem.
1991, 56, 2615-2617.
(5) (a) Eichelmann, H.; Gais, H.-J . Tetrahedron: Asymmetry 1995,
(10) Larock, R. C.; He, Y.; Leong, W. W.; Han, X.; Refvik, M. D.;
Zenner, J . M. J . Org. Chem. 1998, 63, 2154-2160.
, 643-646. (b) Trost, B. M.; Organ, M. G.; O’Doherty, G. A. J . Am.
Chem. Soc. 1995, 117, 9662-9670.
(11) Larock, R. C.; Zenner, J . M. J . Org. Chem. 1995, 60, 482-483.
1
0.1021/jo9901992 CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/15/1999

Hetero- and Carboannulation of Allenes
J . Org. Chem., Vol. 64, No. 20, 1999 7313
Ta ble 1. Op tim iza tion of Con d ition s for th e
En a n tioselective Rea ction of N-Tosyl-2-iod oa n ilin e a n d
1
,2-Un d eca d ien e (eq 1)a
base
mol/ArI solvent temp (°C) yield (%) ee (%)
entry
type
1b
2
3
4
5
Na2CO3
Na2CO3
Ag2CO3
Ag3PO4
Ag3PO4
Ag3PO4
Ag3PO4
Ag3PO4
Ag3PO4
Ag3PO4
Ag3PO4
Ag3PO4
3.0
3.0
1.0
1.0
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMA
THF
100
100
100
100
100
120
80
100
100
100
100
100
87
78
36
36
65
44
63
63
56
71
15
23
5
4
25
25
30
16
0
0
13
7
6
7
c
Under these conditions, the product was obtained in 87%
yield, but only 5% ee (Table 1, entry 1). Removal of TBAC
from the system did not lead to improved enantioselec-
tivity (Table 1, entry 2).
8
9
0
1
2
1
1
1
DMSO
toluene
CH3CN
20
10
Recent reports by Shibasaki et al. have demonstrated
that in the presence of silver salts, significantly enhanced
levels of asymmetric induction can be achieved in chiral
ligand mediated Heck-type reactions of aryl or vinylic
a
Pd(OAc)2 (5 mol %) and of BINAP (5 mol %) were used as the
catalyst. b TBAC (1 equiv) was used in this reaction. Similar
results were obtained using DiPAMP and MeO-BIPHEP as chiral
ligands.
c
halides.12 It is thought that in the presence of Ag , I is
precipitated as AgI, allowing stronger coordination of the
chiral ligand to palladium.1 For this reason, reaction
conditions were altered to include a silver base. Replace-
+
-
products of higher ee than those which form a five-
membered ring, and more electron-rich ligands tend to
give higher asymmetric induction. Best results were
2a
ment of Na
2
CO
3
with a silver salt led to enhanced levels
obtained using the bisoxazoline ligands developed by
Pfaltz and others (Table 2, entries 14-21),6
b-d,19,20
par-
of enantioselectivity (Table 1, entries 3 and 4), although
the overall yield was reduced significantly. We hypoth-
esized that a redox reaction between Pd(0) and Ag(I)
could account for the lower yields and the observed mirror
ticularly compound 1. Further optimization using 1
+
on the reaction vial. Since only 1 equiv of Ag is
3 4
theoretically needed, the amount of Ag PO was reduced
to 0.4 molar equiv (1.2 ion equiv), and under these
conditions the product was obtained in 65% yield and a
slightly higher 30% ee (Table 1, entry 5). Variation of
the reaction temperature had a pronounced effect on the
enantioselectivity (Table 1, entries 5-7). Raising or
lowering the reaction temperature 20 °C caused a reduc-
tion in ee, to the extent of affording an essentially racemic
product at 80 °C. Solvent effects were also very important
both in terms of chemical yield and ee with the original
solvent DMF giving the best results (Table 1, entries
afforded the desired product in 94% yield and 82% ee
(Table 3, entry 1). Only after most of our work had been
completed using ligand 1 did we find that in the presence
20
of chiral ligand 2, these same reaction conditions give
the desired product in 84% yield and an even higher
enantiomeric excess of 88%. However, subsequent results
have suggested that 2 does not generally give higher
levels of asymmetric induction than chiral ligand 1. The
reactions of N-tosyl-2-iodoaniline with the internal al-
lenes 4,5-nonadiene and 1,2-cyclotridecadiene using ligand
8
-12). There was no significant effect on enantioselec-
tivity when Pd(OAc) was replaced by either Pd(dba) or
PdCl in this system.
2
2
2
The final variable examined was the chiral ligand
itself. A variety of chiral ligands were purchased by or
donated to the research group and used in the reaction
of N-tosyl-2-iodoaniline and 1,2-undecadiene (eq 2). The
1
also gave the desired products in high yield and showed
no change in the level of enantioselectivity (Table 3,
entries 2 and 3).
Extension of this process to other nucleophilic sub-
strates has been achieved, although, in general, not to
(
13) Nefkens, S. C. A.; Sperrle, M.; Consiglio, G. Angew. Chem. 1993,
1
05, 1837-1838; Angew. Chem., Int. Ed. Engl. 1993, 32, 1719-1720.
(14) Togni, A. Tetrahedron: Asymmetry 1991, 2, 683-690.
(15) Uozumi, Y.; Hayashi, T. Tetrahedron Lett. 1993, 34, 2335-2338.
(16) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.;
Kondo, M.; Itoh, K. Organometallics 1989, 8, 846-848.
(17) (a) Andrus, M. B.; Argade, A. B.; Pammet, M. G. 210th ACS
National Meeting, Div. Org. Chem. 1995, 420. (b) Andrus, M. B.;
Argade, A. B.; Ankush, B.; Chen, X.; Pammet, M. G. Tetrahedron Lett.
results are summarized in Table 2.
1
995, 36, 2945-2948.
18) Denmark, S. E.; Nakajima, N.; Nicaise, O. J .-C. J . Am. Chem.
Soc. 1994, 116, 8797-8798.
The following observations have been made with
regard to ligand structure. Those ligands which when
coordinated to Pd form a six-membered ring lead to
(
(
19) (a) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339-345. (b) von Matt,
P.; Lloyd-J ones, G. C.; Minidis, A. B. E.; Pfaltz, A.; Macko, L.;
Neuburger, M.; Zehnder, M.; R u¨ egger, H.; Pregosin, P. S. Helv. Chim.
Acta 1995, 78, 265-284.
(
12) (a) Sato, Y.; Sodeoka, M.; Shibasaki, M. Chem. Lett. 1990,
1
1
953-1954. (b) Sato, Y.; Watanabe, S.; Shibasaki, M. Tetrahedron Lett.
(20) (a) Davies, I. W.; Senanayake, C. H.; Larsen, R. D.; Verhoeven,
T. R.; Reider, P. J . Tetrahedron Lett. 1996, 37, 813-814. (b) Davies, I.
W.; Senanayake, C. H.; Larsen, R. D.; Verhoeven, T. R.; Reider, P. J .
Tetrahedron Lett. 1996, 37, 1725-1726.
992, 33, 2589-2592. (c) Sato, Y.; Nukui, S.; Sodeoka, M.; Shibasaki,
M. Tetrahedron 1994, 50, 371-382. (d) Shibasaki, M.; Sodeoka, M. J .
Synth. Org. Chem. J pn. 1994, 52, 955-967.

7
314 J . Org. Chem., Vol. 64, No. 20, 1999
Zenner and Larock
Ta ble 2. Com p a r ison of th e Asym m etr ic In d u ction of Va r iou s Ch ir a l Liga n d s in th e Rea ction of N-Tosyl-2-iod oa n ilin e
a n d 1,2-Un d eca d ien e (eq 2)a
a
All reactions were run in the presence of 5 mol % of Pd(OAc)2, 5 mol % of the chiral ligand, and 1.2 ion equiv of Ag3PO4 in DMF at
1
00 °C for 1 day.
the level of success attained in the model system. For all
substrates, the highest enantiomeric excesses have been
obtained using 1 equiv of the aryl or vinylic iodide, 2
in general a catalyst system comprising 5 mol % Pd(OAc)
2
and 10 mol % 1 affords the desired products in both high
yield and high enantiomeric excess (Table 3; catalysts A
and B), limited optimization of the catalyst system for
each aryl or vinylic halide led to the following observa-
tions. For some substrates, increasing the chiral ligand
1/Pd catalyst ratio from 1:1 to 2:1 led to no improvement
3 4
equiv of the allene, and 1.2 equiv of Ag PO in DMF using
a Pd/1 catalyst, at a temperature low enough to achieve
asymmetric induction, while still allowing the reaction
to go to completion in a reasonable time (Table 3). While

Hetero- and Carboannulation of Allenes
J . Org. Chem., Vol. 64, No. 20, 1999 7315
Ta ble 3. P a lla d iu m -Ca ta lyzed , Asym m etr ic An n u la tion of Allen es Usin g Ch ir a l Bisoxa zolin e Liga n d 1a

7
316 J . Org. Chem., Vol. 64, No. 20, 1999
Zenner and Larock
Ta ble 3 (Con tin u ed )
a
All reactions were run in the presence of 1.2 silver ion equiv of Ag3PO4 in DMF (1.0 mL/0.50 mmol of organic iodide). b Catalyst A:
5
%
mol % of Pd(OAc)2, 10 mol % of ligand 1. Catalyst B: 5 mol % of Pd(OAc)2, 5 mol % of ligand 1. Catalyst C: 5 mol % of Pd(dba)2, 5 mol
c
of ligand 1. Catalyst D: 5 mol % of Pd(dba)2, 10 mol % of ligand 1. Catalyst E: 10 mol % of Pd(dba)2, 10 mol % of ligand 1. Recrystallized
d
product appeared to be >95% ee ([R]D ) -211.0°). The ee of this product has not been determined, since the ee could not be obtained
using Eu(hfc)3.
in asymmetric induction (Table 3; catalysts B, C, and E).
In addition, annulations of allenes using carboxylic acids
or carbanions gave slightly higher ee’s using Pd(dba) as
2
the catalyst (Table 3; catalysts C, D, and E). Annulations
using malonate nucleophiles required 10 mol % of both
the Pd catalyst and the chiral ligand to increase product
yields to acceptable levels (Table 3; catalyst E).
gave the annulation product in 73% yield, but only 55%
ee (Table 3, entry 8). Since chiral ligand 2 had performed
better than 1 in the annulation of 1,2-undecadiene using
N-tosyl-2-iodoaniline, it was tried in the reaction of
2
-iodobenzyl alcohol with 4,5-nonadiene. However, in this
case the reaction was much slower, lower yielding and
afforded the product in the same 55% ee. While the same
aryl iodide reacted with 1,2-cyclotridecadiene to afford
the desired product in 77% ee, the yield was only 29%
Aryl and vinylic iodides containing oxygen nucleophiles
have been used to form six-membered ring heterocycles
in fair to excellent ee values. The reaction of 2-iodo-4-
acetylphenol and 1,2-undecadiene afforded the desired
benzofuran derivative in excellent yield, but only 52% ee
(Table 3, entry 9).
The reaction of 2-iodobenzoic acid with the terminal
allene 1,2-undecadiene gave good selectivity, but in this
system substituents on the aromatic ring of the substrate
did cause significant variation in the ee (Table 3, entries
(
Table 3, entry 4). Experimental conditions for asym-
metric induction were not optimized for this system.
-Iodobenzyl alcohol reacts with 1,2-undecadiene to give
1
1-14).
2
The reaction of 2-iodobenzoic acid and 4,5-nonadiene
the desired product in 72% yield and 73% ee (Table 3,
entry 5). Substitution in the 5-position of 2-iodobenzyl
alcohol had little effect on the enantioselectivity (Table
gave the desired product in only low yield, although the
ee remained reasonably high (Table 4, entry 1) (eq 3).
Due to the low overall yield, further optimization of this
reaction was attempted (Table 4). Solvent effects were
found to be most crucial, both in terms of product yield
and ee. Unfortunately, those solvents which facilitate
product formation seem to do so at the expense of
enantioselectivity.
3
, entries 6 and 7).
In general, for all functionalized aryl iodides, except
N-tosyl-2-iodoaniline, internal allenes gave lower levels
of enantioselectivity than terminal allenes. For example,
the reaction of 2-iodobenzyl alcohol with 4,5-nonadiene

Hetero- and Carboannulation of Allenes
J . Org. Chem., Vol. 64, No. 20, 1999 7317
Ta ble 4. Effect of Solven t on P r od u ct Yield a n d
Sch em e 1
En a n tioselectivity in th e Rea ction of 2-Iod oben zoic Acid
a
a n d 4,5-Non a d ien e (eq 3)
temp
(°C)
time
(d)
yield (%)
ee
(%)
entry
solvent
(E/Z ratio)b
1
2
3
4
5
6
7
8
9
0
1
2
3
DMF
CH2Cl2
CH2Cl2
ClCH2CH2Cl
CHCl3
THF
THF
DMF/THF (1:1)
Toluene
Tetramethylurea
DMSO
40
40
rt
40
40
40
rt
40
40
40
40
40
40
3
2
1
2
3
3
5
17
3
3
16
69
35
45
30
36
44
39
48
30
43
61 (6:1)
40 (6:1)
81 (7:1)
84 (8:1)
87
87
39
71 (6:1)
30
0
1
1
1
1
3
3
3
CH3CN
CH3NO2
65
45 (4:1)
23
38
a
All reactions were run in the presence of 5 mol % of Pd(OAc)2,
5
mol % of ligand 1, and 1.2 ion equiv of Ag3PO4. b If no E/Z ratio
is specified, only the E isomer was obtained.
between diastereomers is accomplished via a π-σ-π
7
process. This interconversion is known to occur rapidly
The formation of six-membered ring heterocycles using
vinylic iodides bearing alcohol or carboxylic acid func-
tionality in the allylic position followed the same trends
found with the aryl analogues (Table 3, entries 15-20).
Entries 18 and 19 (Table 3) demonstrate a quite signifi-
cant temperature effect in the reaction of (Z)-3-iodo-2-
methyl-2-propen-1-ol and 1,2-undecadiene. This reaction
at 40 °C afforded a product in 88% ee; higher than we
had observed in any other annulation process. Unfortu-
nately, at this lower temperature, the reaction was very
sluggish and even after a reaction time of 15 days the
product was isolated in only a 21% yield.
Carboannulation has also been carried out enantiose-
lectively using this methodology. Using as the substrate
diethyl 2-iodophenylmalonate, it again was found that
terminal allenes led to products of higher optical purity
than internal symmetrical allenes (Table 3, entries 21
and 22).
in terminal π-allylpalladium species, and this is no
doubt of paramount importance to eventual enantio-
discrimination.7b Bosnich’s work has suggested that the
major π-allylpalladium intermediate gives rise to the
major enantiomer observed. In light of this, we speculate
that steric interactions between the benzyl groups of
chiral ligand 1 and the terminal alkyl substituent of the
π-allylpalladium intermediate lead to a preference for one
diastereomer 4a over the other, which goes on to form
the major observed enantiomer. Therefore, enantioselec-
tivity is achieved due to minimization of steric interac-
tions. Assuming backside nucleophilic displacement of 4a ,
this mechanistic model predicts an (S) absolute config-
uration for the observed product. An X-ray crystal
structure determination of 7-bromo-3,4-dihydro-4-meth-
ylene-3-n-octyl-1H-2-benzopyran (Table 3, entry 7) has
confirmed the predicted (S) absolute configuration.
In the case of internal allenes, if the π-allyl system
maintains a syn-syn conformation, a symmetrical π-al-
lylpalladium species is generated in which steric interac-
tions cannot be minimized (Scheme 2). This system would
then resemble a 1,3-disubstituted π-allylpalladium in-
termediate for which factors leading to enantioselectivity
The mechanism of this reaction has been outlined in
our earlier publication and is reproduced in Scheme 1.11
The first step is undoubtedly reduction of Pd(II) to Pd-
0), followed by oxidative addition of the organic halide.
(
The addition of aryl or vinylic palladium compounds to
allenes is known to produce π-allylpalladium compounds,
which readily undergo intramolecular nucleophilic sub-
in the intermolecular nucleophilic attack have been well
described elsewhere.1
9,22
Those studies conclude that
stitution.9
,10,21
+
In the presence of Ag , the iodide is
nucleophilic attack occurs at the end of the π-allyl system
removed as AgI, allowing the formation of a 16 electron,
positively charged Pd intermediate to which the bidentate
chiral ligand is coordinated.12 This system then resembles
those investigated by Bosnich in which interconversion
(22) (a) Reiser, O. Angew. Chem., Int. Ed. Engl. 1993, 32, 547-549.
b) Sprinz, J .; Kiefer, M.; Helmchen, G.; Reggelin, M.; Huttner, G.;
(
Walter, O.; Zsolnai, L. Tetrahedron Lett. 1994, 35, 1523-1526. (c)
Breutel, C.; Pregosin, P. S.; Salzmann, R.; Togni, A. J . Am. Chem. Soc.
1994, 116, 4067-4068. (d) Dawson, G. J .; Williams, J . M. J .; Coote, S.
J . Tetrahedron Lett. 1995, 36, 461-462. (e) Dawson, G. J .; Williams,
J . M. J .; Coote, S. J . Tetrahedron: Asymmetry 1995, 6, 2535-2546. (f)
Brown, J . M.; Hulmes, D. I.; Guiry, P. J . Tetrahedron 1994, 50, 4493-
4506. (g) Boog-Wick, K,; Pregosin, P. S.; Trabesinger, G.; Organome-
tallics 1998, 17, 3254-3264. (h) Nordstr o¨ m, K.; Macedo, E.; Moberg.
J . Org. Chem. 1997, 62, 1604-1609.
(21) (a) Ahmar, M.; Barieux, J .-J .; Cazes, B.; Gor e´ , J . Tetrahedron
1
987, 43, 513-526. (b) Cazes, B.; Colovray, V.; Gor e´ , J . Tetrahedron
Lett. 1988, 29, 627-630. (c) Friess, B.; Cazes, B.; Gor e´ , J . Tetrahedron
Lett. 1988, 29, 4089-4092. (d) Walkup, R. D.; Guan, L.; Kim, Y. S.;
Kim, S. W. Tetrahedron Lett. 1995, 36, 3805-3808. (e) Walkup, R. D.;
Guan, L.; Mosher, M. D.; Kim, Y. S.; Kim, S. W. Synlett 1993, 88-90.
(
f) Davies, I. W.; Scopes, D. I. C.; Gallagher, T. Synlett 1993, 85-87.

7
318 J . Org. Chem., Vol. 64, No. 20, 1999
Zenner and Larock
Sch em e 2
We hypothesize that coordination of the bisoxazoline
chiral ligand may further shift this equilibrium toward
the syn-anti isomer since this stereoisomer is relatively
free of steric interactions between the benzyl substituents
of the bound ligand and the substituents on the π-allyl
system (7). To examine this possibility, we formed the
3
(
η -5-phenylnon-4-enyl)palladium(II)-2 complex (11) in
CD
di-µ-chlorodi(η -5-phenylnon-4-enyl)dipalladium(II) and
in CD CN at 80 °C gave no evidence of coordination.
3
CN. Initial attempts to form this complex by stirring
3
2
3
3
Therefore, di-µ-chlorodi(η -5-phenylnon-4-enyl)dipalla-
dium(II) (9) was first stirred with AgOTf, precipitating
AgCl and leading to the formation of (η -5-phenylnon-4-
3
enyl)palladium(II) triflate (10). This species was then
stirred with ligand 2 in CD CN at 80 °C (eq 5). Analysis
3
at which there exists steric interactions between the
π-allyl substituent and the substituent on the oxazoline
ring.19 As the π-bound Pd(0)-alkene primary product is
formed, this strain is alleviated (Scheme 2, path A). The
above-described mechanism of asymmetric induction
would predict an (R) absolute configuration for the
products of internal allene annulation. However, the
optical rotations of the products we have obtained from
1
internal allenes, as well as the H NMR splitting patterns
in the presence of a chiral lanthanide shift reagent,
appear more consistent with the (S) configuration ob-
served for products arising from the annulation of
terminal allenes. A determination of the X-ray crystal
structure of (E)-3-bromo-5,6a,7,8,9,10,11,12,13,14,15,16-
dodecahydrobenzo[d]cyclotrideca[b]pyran (Table 3, entry
of the resulting complex 11 by 1H NMR spectroscopy
verified that in the ligand-bound π-allylpalladium species
this equilibrium is further shifted, favoring the syn-anti
over the syn-syn isomer in a ratio of 3:1. This same
experiment using ligand 1 resulted in a 3.8:1 mixture of
syn-anti and syn-syn isomers. These results have prece-
dent in the work of Gor e´ and co-workers, who reported
an 85:15 (E/ Z) ratio of products from the intermolecular
displacement of a 1-n-heptyl-2-phenyl-π-allylpalladium
1
0) has shown the absolute configuration is in fact (S).
Therefore, we hypothesize that, in the case of a 1,2,3-
trisubstituted π-allylpalladium system, the steric bulk
of the substituent in the 2-position may lead to an
equilibrium which favors the syn-anti (7) over the syn-
syn (6) configuration (Scheme 2).23
21a
intermediate by sodium diethylmalonate (eq 6).
To confirm this suspicion, we synthesized and isolated
3
di-µ-chlorodi(η -5-phenylnon-4-enyl)dipalladium(II) as a
mixture of oil and crystals.24 Proton and C NMR
analysis of the viscous oil component showed a 1:1
mixture of syn-syn and syn-anti isomers, while the
crystals were essentially pure syn-syn isomer. A solution
of syn-syn isomer in chloroform equilibrated over time,
or at elevated temperature, to a 1:1 mixture of syn-syn
and syn-anti isomers (eq 4).
13
Again, if as suggested by Bosnich7 and others,4c the
major π-allylpalladium intermediate present in solution
gives rise to the major enantiomer observed, backside
nucleophilic attack must occur preferentially at the anti
terminus of the π-allyl system in order to give the
(
23) (a) Faller, J . W.; Thomsen, M. E.; Mattina, M. J . J . Am. Chem.
Soc. 1971, 93, 2642-2653. (b) Lukas, J .; Ramakers-Blom, J . E.; Hewitt,
T. G.; De Boer, J . J . J . Organomet. Chem. 1972, 46, 167-177. (c)
A° kermark, B.; Hansson, S. J . Am. Chem. Soc. 1990, 112, 4587-4588.
(24) Larock, R. C.; Mitchell, M. A. J . Am. Chem. Soc. 1978, 100,
1
80-188.

Hetero- and Carboannulation of Allenes
J . Org. Chem., Vol. 64, No. 20, 1999 7319
observed product of (S) absolute configuration at the
stereogenic center and (E) configuration about the double
bond (Scheme 2, path C). The higher reactivity of the
anti-substituted carbon, required by this mechanistic
path, has precedent in work by Åkermark (eq 7).2
plates (Whatman K6F), and visualization was effected with
short wavelength UV light (254 nm) or basic KMnO
3 g of KMnO + 20 g of K CO + 5 mL of NaOH (5%) + 300
mL of H O]. All melting points are uncorrected.
4
solution
[
4
2
3
2
Rea gen ts. All reagents were used directly as obtained
commercially unless otherwise noted. All palladium reagents
were donated by J ohnson Matthey Inc. and Kawaken Fine
Chemicals Co., Ltd. 2-Iodoaniline, 2-iodobenzyl alcohol, 2-io-
dobenzoic acid, 2-iodobenzyl chloride, propargyl alcohol, p-
toluenesulfonyl chloride, diethyl malonate, 1-decene, 4-octene,
3c
3 3
cyclododecene, bromoform, MeLi, Et N, PCC, and Eu(hfc)
were purchased from Aldrich Chemical Co., Inc. 5-Bromo-2-
iodobenzoic acid, 2-iodo-5-methylbenzoic acid, and 2-iodo-4,5-
dimethoxybenzoic acid were obtained from Trans World Chemi-
cals, Inc.
3
Allen es. 1,2-Undecadiene, 4,5-nonadiene, and 1,2-cyclot-
ridecadiene were prepared by treating the corresponding 1,1-
dibromocyclopropanes with methyllithium according to a
literature procedure.27 The appropriate 1,1-dibromocyclopro-
panes were prepared from the corresponding alkenes using a
Di-µ-chlorodi(η -5-(2′-hydroxymethylphenyl)non-4-enyl-
)
2
dipalladium(II) has been prepared by the reaction of
-(chloromercurio)benzyl alcohol, 4,5-nonadiene, and Li -
2
2
4
PdCl
4
,
but this π-allylpalladium compound rapidly
decomposed at room temperature. Therefore, we were
unable to attempt to correlate the ratio of syn-syn and
syn-anti isomers to the ee of the annulation product
28
literature procedure.
N-Tosyl-2-iod oa n ilin e. Tosylation of 2-iodoaniline (25
mmol) was carried out by treating 2-iodoaniline with tosyl
chloride (25 mmol) in pyridine (8 mL) and heating for 3 h at
(
E)-4-n-butylidene-3,4-dihydro-3-n-propyl-1H-2-benzo-
8
0 °C.29 The product was purified by recrystallization from
pyran. Alternatively, nucleophilic attack at the end of the
π-allyl system, which is relatively free of steric interac-
tions in the syn-syn isomer (Scheme 2, path B), also leads
to the observed (S) enantiomer. We have as yet been
unable to determine the precise mechanism at work in
these systems.
1
ethanol, followed by washing several times with hexanes:
NMR (CDCl
H
3
) δ 2.4 (s, 3 H), 6.95 (ddd, 1 H, J ) 7.5, 7.5, 1.5
Hz), 7.34 (d, 2 H, J ) 7.8 Hz), 7.37 (ddd, 1 H, J ) 8.1, 7.5, 1.5
Hz), 7.47 (dd, 1 H, J ) 8.1, 1.5 Hz), 7.65 (d, 2 H, J ) 8.1 Hz),
7.79 (dd, 1 H, J ) 8.1, 1.5 Hz), 8.0 (bs, 1 H); 13C NMR (CDCl )
3
δ 21.6, 122.4, 126.8, 127.4, 129.4, 129.6, 135.8, 137.4, 139.1,
2
1
1
3
44.2 (one sp signal missing due to overlap); IR (CHCl
3
) 3300,
The regioselectivity of this annulation process is gener-
ally quite high, often better than that observed under
-
1
285, 1233 cm . Anal. Calcd for C13
.22. Found: C, 41.77; H, 3.47.
H12INO S: C, 41.82: H,
2
3
our previously reported conditions using PPh as the
4
-Hyd r oxy-3-iod oa cetop h en on e. Prepared using a modi-
ligand.9 The reaction of aryl or vinylic iodides and 1,2-
undecadiene forms five- or six-membered ring products
by nucleophilic attack exclusively at the more substituted
end of the π-allylpalladium intermediate (Table 3; entries
,10
30
fication of a procedure by Schreiber and Stevenson. To a
solution of 4-hydroxyacetophenone (37.6 mmol) in concentrated
ammonium hydroxide (250 mL) was added with rapid stirring
to a solution of potassium iodide (185 mL, 30.7 g) and iodine
(37.90 mmol) in water (76 mL). After overnight stirring at
room-temperature, the mixture was filtered through Celite.
The filtrate was acidified to pH 1. The heterogeneous solution
was cooled to 5 °C and filtered. The solid collected was
dissolved in ether and treated with activated carbon. Filtra-
tion, concentration, and purification by column chromatogra-
phy afforded 4-hydroxy-3-iodoacetophenone in 56% yield. After
1
, 4-7, 11-15, and 18-21). The regioselectivity of attack
at the more sterically congested π-allyl terminus may be
explained on the basis of two electronic factors: (1) the
net positive charge on the π-allylpalladium species being
more localized at the alkyl-substituted terminus25 and
(
2) the observation that electron-rich palladium(0)-ligand
complexes favor coordination to the more electron-
deficient, less-substituted double bond of the observed
recrystallization from MeOH/H
tained in 49% yield: mp 153-155 °C (mp 154-156 °C); H
NMR (CDCl ) δ 2.55 (s, 3 H), 5.91 (s, 1 H), 7.02 (d, 1 H, J )
2
O (2:1) the product was ob-
1
product.7,26 For these reasons, the transition state leading
to the observed product may be favored.
3
8
.4 Hz), 7.87 (dd, 1 H, J ) 8.3, 2.0 Hz), 8.30 (d, 1 H, J ) 2.1
Hz).
5
-Br om o-2-iod oben zyl Alcoh ol. Prepared in 55% yield by
Con clu sion
borane reduction of the corresponding benzoic acid following
a literature procedure: H NMR (CDCl ) δ 2.25 (bs, 1 H), 4.62
The palladium-catalyzed, asymmetric hetero- and car-
boannulation of allenes using functionally substituted
aryl and vinylic iodides has been achieved in moderate
to high levels of enantiomeric excess. The generality of
this process has been demonstrated by the use of a wide
variety of aryl and vinylic iodides, internal nucleophiles
and allenes. This generality, combined with the proce-
dural ease with which these reactions are carried out,
make this an attractive route to enantiomerically en-
riched hetero- and carbocycles. The results of this study
include the highest ee’s reported for a palladium-
catalyzed, intramolecular, allylic substitution reaction.
31 1
3
(s, 2 H), 7.13 (dd, 1 H, J ) 8.1, 2.1 Hz), 7.61 (d, 1 H, J ) 2.1
Hz), 7.64 (d, 1 H, J ) 8.1 Hz); 13C NMR (CDCl
) δ 68.7, 94.6,
123.0, 131.1, 132.2, 140.3, 144.6; IR (CHCl ) 3250 cm
-Iod o-5-m eth ylben zyl Alcoh ol. Prepared in 83% yield
by borane reduction of the corresponding benzoic acid following
3
-
1
3
.
2
a literature procedure:3 H NMR (CDCl
1 1
) δ 2.02 (bs, 1 H), 2.26
3
(
1
s, 3 H), 4.58 (s, 2 H), 6.76 (dd, 1 H, J ) 8.1, 1.5 Hz), 7.21 (d,
13
H, J ) 1.5 Hz), 7.61 (d, 1 H, J ) 8.1 Hz); C NMR (CDCl
3
)
)
δ 21.0, 69.1, 93.3, 129.3, 130.2, 138.5, 138.8, 142.2; IR (CHCl
3
-
1
3230 cm
.
Dieth yl 2-Iod op h en ylm a lon a te. Prepared by treatment
of ethyl 2-iodophenylacetate with NaH and diethyl carbonate
Exp er im en ta l Section
Gen er a l. All 1H and 13C NMR spectra were recorded at 300
and 75.5 MHz, respectively. Thin-layer chromatography was
performed using commercially prepared 60-mesh silica gel
(27) Landor, P. D. The Chemistry of Allenes; Academic Press: New
York, 1982; Vol. 3, p 867.
(
28) Skattebol, L. Acta Chem. Scand. 1963, 17, 1683-1693.
(29) Modified from a procedure by Ratcliffe (Ratcliffe, J . J . Chem.
Soc. 1951, 1140-1141).
(30) Schreiber F. G.; Stevenson, R. J . Chem. Soc., Perkin Trans. 1
(
25) (a) He, Y. M.S. Thesis, Iowa State University, 1992. (b) Berrios-
Pe n˜ a, N. G. Ph.D. Dissertation, Iowa State University, 1989.
26) Hartley, F. R. Chem. Rev. 1969, 69, 799-844.
1977, 90-92
(31) Yoon, N. M.; Pak, C. S.; Brown, H. C.; Krishnamurthy, S.;
Stocky, T. P. J . Org. Chem. 1973, 38, 2786-2792.
(

7
320 J . Org. Chem., Vol. 64, No. 20, 1999
Zenner and Larock
according to a literature procedure:32 1H NMR (CDCl
) δ 1.28
397.2075, found 397.2069. Anal. Calcd for C24
72.51; H, 7.86. Found: C, 70.70; H, 7.80.
(E)-N-Tosyl-3-n -b u t ylid en e-2,3-d ih yd r o-2-n -p r op ylin -
d ole (Ta ble 3, en tr y 2). Obtained as a clear, colorless oil in
95% yield from the reaction of N-tosyl-2-iodoaniline and 4,5-
nonadiene after purification by column chromatography using
3
2
H31NO S: C,
(
t, 6 H, J ) 7.2 Hz), 4.25 (dq, 4 H, J ) 7.2, 1.5 Hz), 5.12 (s, 1
H), 7.01 (dt, 1 H, J ) 7.8, 1.5 Hz), 7.37 (dq, 1 H, J ) 7.8, 1.2
Hz), 7.47 (dd, 1 H, J ) 7.8, 1.5 Hz), 7.87 (dd, 1 H, J ) 7.8, 1.5
Hz); C NMR (CDCl
1
3
3
) δ 14.0, 29.4, 62.0, 101.6, 128.5, 129.6,
1
29.7, 136.4, 139.6, 167.7; IR (neat) 1736, 1217, 1175 cm-1
;
HRMS for C13
H
15IO
4
calcd 362.0015, found 362.0013.
10:1 hexanes/EtOAc: [R]
D
) -32.5° (c ) 0.045, dichloroethane)
[
80% ee, based on integration of two aromatic peaks corre-
(
Z)-3-Iod o-2-m eth ylp r op en -1-ol. Prepared in 42% yield
from propargyl alcohol by treating with MeMgI and CuI in
THF/Et O and subsequent addition of I according to a
literature procedure: H NMR (CDCl ) δ 1.80 (t, 1 H, J ) 6.3
Hz), 1.98 (s, 3 H), 4.24 (d, 2 H, J ) 6.3 Hz), 5.98 (s, 1 H);
NMR (CDCl ) δ 21.5, 67.6, 74.7, 145.8; IR (neat) 3354, 1134
1
sponding to H-7 and Ts in the presence of Eu(hfc)
3
]; H NMR
(
CDCl ) δ 0.84 (t, 3 H, J ) 7.5 Hz), 0.89 (t, 3 H, J ) 7.5 Hz),
3
2
2
3
3 1
1.31-1.45 (m, 4 H), 1.60-1.74 (m, 1 H), 1.78-1.92 (m, 1 H),
2.21-2.27 (m, 2 H), 2.30 (s, 3 H) 4.53 (td, 1 H, J ) 5.4, 1.5
Hz), 5.28 (td, 1 H, J ) 7.4, 1.5 Hz), 7.04 (td, 1 H, J ) 7.7, 0.9
Hz), 7.10 (d, 2 H, J ) 8.4 Hz), 7.22 (td, 1 H, J ) 7.5, 0.9 Hz),
3
1
3
C
3
-
1
cm
.
7
.38 (d, 1 H, J ) 7.5 Hz), 7.47 (d, 2 H, J ) 8.4 Hz), 7.72 (d, 1
(
Z)-3-Iod o-2-m eth ylp r op en oic Acid . Prepared from (Z)-
-iodo-methylpropen-1-ol by first oxidizing with PCC to give
Z)-3-iodo-2-methylpropenal. This compound was not charac-
terized due to its rapid decomposition. (Z)-3-Iodo-2-methyl-
propenal was immediately converted to the acid by NaClO
13
H, J ) 8.1 Hz); C NMR (CDCl
3
1
3
) δ 13.6, 14.0, 16.8, 21.4, 22.6,
0.0, 40.2, 67.4, 117.6, 124.5, 127.0, 128.5, 129.3, 130.9, 134.6,
43.5, 144.2 (three sp2 signals missing due to overlap); IR
3
(
(
1
neat) 3060, 3030, 2950, 2920, 2860, 1592, 1490, 1450, 1353,
168 cm ; HRMS for C22
2
/
-
1
H
27NO
2
S calcd 369.1763, found
S: C, 71.51; H, 7.37.
H
2
O
2
-mediated oxidation according to a literature procedure:
3
1
4 1
369.1766. Anal. Calcd for C22
Found: C, 70.02; H, 7.40.
(E)-N-Tosyl-5a ,6,7,8,9,10,11,12,13,14,15-u n d eca h yd r o-
cyclotr id ec[b]in d ole (Ta ble 3, en tr y 3). Obtained as a white
solid in 95% yield from the reaction of N-tosyl-2-iodoaniline
and 1,2-cyclotridecadiene after purification by column chro-
H
27NO
2
H NMR (CDCl
3
) δ 2.11 (s, 3 H), 7.10 (s, 1 H), 11.3 (bs, 1 H);
3
C NMR (CDCl
3
) δ 22.46, 86.67, 137.6, 172.0; IR (CHCl
3
) 2980,
-
1
1
693 cm
.
(Z)-1-Iod o-3-m eth yl-1-bu ten -3-ol. To a three-neck round-
bottom flask with condenser was added 14.74 mmol of 1 M
MeMgBr in ether. (Z)-Ethyl 3-iodopropenoate in 5 mL of ether
was then slowly added dropwise. The resultant solution
warmed to reflux and then turned orange. This solution was
heated at reflux for an additional 60 min. After quenching with
water, the aqueous mixture was extracted with ether (3 × 25
matography using 10:1 hexanes/EtOAc: mp 147-149 °C; [R]
D
)
-37.0° [81% ee, based on integration of two aromatic peaks
1
corresponding to H-7 and Ts in the presence of Eu(hfc)
3
]; H
NMR (CDCl
3
) δ 1.0-1.35 (m, 16 H), 1.63-1.77 (m, 2 H), 2.08-
2
5
.23 (m, 1 H), 2.27 (s, 3 H), 2.52-2.68 (m, 1 H), 4.63 (m, 1 H),
.37 (dd, 1 H, J ) 10.4, 5.1 Hz), 6.99 (t, 1 H, J ) 8.0 Hz), 7.10
4
mL). The combined organic phase was dried over MgSO ,
concentrated, and purified via flash column chromatography
9:1 hexanes/EtOAc) to afford (Z)-1-iodo-3-methyl-1-buten-3-
(
d, 2 H, J ) 8.1 Hz), 7.19 (t, 1 H, J ) 8.0 Hz), 7.51 (d, 1 H, J
(
) 8.0 Hz), 7.56 (d, 2 H, J ) 8.1 Hz), 7.76 (d, 1 H, J ) 8.0 Hz);
1
ol: H NMR (CDCl
3
) δ 1.41 (s, 6 H), 2.40 (s, 1 H), 6.21 (d, J )
13
C NMR (CDCl
7.8, 28.3, 36.9, 66.9, 115.9, 123.8, 123.9, 124.8, 126.9, 128.7,
29.4, 130.3, 134.6, 136.0, 143.6, 144.7; IR (neat) 1356, 1184
3
) δ 18.5, 21.4, 24.2, 24.9, 25.2, 25.4, 26.4, 27.1,
1
3
8
2
.4 Hz, 1 H), 6.64 (d, J ) 8.4 Hz, 1 H); C NMR (CDCl
9.47, 72.27, 75.83, 146.43.
Gen er a l P r oced u r e for th e En a n tioselective, P a l-
3
) δ
2
1
-1
cm ; HRMS for C26
Anal. Calcd for C26
H
H
33NO
33NO
2
S calcd 423.2232, found 423.2232.
S: C, 73.72; H, 7.85. Found: C,
la d iu m -Ca ta lyzed An n u la tion of Allen es. To a 1-dram vial
were added the palladium reagent (0.019 mmol), the appropri-
ate organic iodide (0.375 mmol), Ag PO (0.150 mmol), the
3 4
appropriate allene (0.750 mmol), and 0.75 mL of a DMF/chiral
ligand stock solution containing the desired amount of bisox-
azoline ligand 1 (0.019 or 0.038 mmol). The vial is then flushed
2
7
3.72; H, 7.85.
-Acet yl-2,3-d ih yd r o-3-m et h ylen e-2-n -oct ylb en zofu -
5
r a n (Ta ble 3, en tr y 4). Obtained as a pale yellow oil in 95%
yield from the reaction of 2-iodo-4-acetylphenol and 1,2-
undecadiene after purification by column chromatography
2
with N , capped with a screw cap containing a Teflon liner,
using 10:1 hexanes/EtOAc: [R]
D
) -61.2° (c ) 0.30, CHCl
52% ee, chiral HPLC]; H NMR (CDCl ) δ 0.87 (t, 3 H, J )
.0 Hz), 1.20-1.60 (m, 12 H), 1.70-1.90 (m, 2 H), 2.57 (s, 3
3
)
and placed in an oil bath at the desired temperature for the
specified period of time (see Table 3). The vial was then
removed from the oil bath, and the reaction mixture was
columned directly on silica gel using hexanes/EtOAc as elu-
ents. Determination of the enantiomeric excess of the products
1
[
6
3
H), 4.98 (d, 1 H, J ) 3.0 Hz), 5.25 (m, 1 H), 5.54 (d, 1 H, J )
.0 Hz), 6.84 (d, 1 H, J ) 9.0 Hz), 7.86 (dd, 1 H, J ) 9.0, 2.1
3
13
Hz), 8.01 (d, 1 H, J ) 2.1 Hz); C NMR (CDCl
3
) δ 14.0, 22.6,
4.3, 26.3, 29.2, 29.3, 29.4, 31.8, 36.1, 87.4, 101.6, 110.0, 121.6,
26.4, 130.5, 132.0, 146.0, 166.0, 196.4; HRMS for C19
was accomplished using the chiral NMR shift reagent Eu(hfc)
Optical rotations were determined at 20 °C using a J asco DIP-
3
.
2
1
26 2
H O
3
70 digital polarimeter.
calcd 286.1933, found 286.1929. This compound slowly decom-
poses and thus was not submitted for elemental analysis.
3,4-Dih yd r o-4-m et h ylen e-3-n -oct yl-1H -2-b en zop yr a n
(Ta ble 3, en tr y 5). Obtained as a clear, colorless oil in 72%
yield from the reaction of 2-iodobenzyl alcohol and 1,2-
undecadiene after purification by column chromatography
using 30:1 hexanes/EtOAc: [R]
ethane) [73% ee, based on integration of the vinylic hydrogens
3 3
in the presence of Eu(hfc) ]; H NMR (CDCl ) δ 0.88 (t, 3 H, J
Sp ectr a l Da ta . N-Tosyl-2,3-d ih yd r o-3-m eth ylen e-2-n -
octylin d ole (Ta ble 3, en tr y 1). Obtained as a pale yellow
oil in 94% yield from the reaction of N-tosyl-2-iodoaniline and
1
,2-undecadiene after purification by column chromatography
using 10:1 hexanes/EtOAc: [R] ) -19.4° (c ) 0.040, dichlo-
roethane) [82% ee, based on integration of two aromatic peaks
D
D
) -15.6° (c ) 0.30, dichloro-
1
corresponding to H-7 and Ts in the presence of Eu(hfc)
3
]; H
) δ 0.86 (t, 3 H, J ) 6.9 Hz), 1.1-1.5 (m, 12 H),
1
NMR (CDCl
3
1
4
.70-1.85 (m, 1 H), 1.95-2.15 (m, 1 H), 2.32 (s, 3 H), 4.55-
.67 (m, 1 H), 4.85 (d, 1 H, J ) 2.0 Hz), 5.34 (d, 1 H, J ) 2.0
) 7.0 Hz), 1.20-1.40 (m, 12 H), 1.70-1.80 (m, 2 H), 4.27 (dd,
1 H, J ) 7.2, 6.6 Hz), 4.71 (d, 1 H, J ) 15.3 Hz), 4.82 (d, 1 H,
J ) 15.3 Hz), 5.02 (s, 1 H), 5.59 (s, 1 H), 6.98-7.03 (m, 1 H),
Hz), 7.03 (ddd, 1 H, J ) 7.5, 7.5, 0.6 Hz), 7.13 (d, 2 H, J ) 8.1
Hz), 7.27 (t, 1 H, J ) 7.8 Hz), 7.29 (d, 1 H, J ) 7.8 Hz), 7.53
7.18-7.24 (m, 2 H), 7.61-7.65 (m, 1 H); 13C NMR (CDCl
) δ
3
1
3
(
d, 2 H, J ) 8.1 Hz), 7.74, (d, 1 H, J ) 7.8 Hz); C NMR
14.1, 22.7, 25.6, 29.3, 29.5, 29.6, 31.9, 65.7, 77.2, 106.9, 123.9,
3
(CDCl
3
) δ 14.1, 21.5, 22.6, 22.8, 29.6, 29.4, 29.6, 31.8, 37.2,
6.6, 102.6, 116.9, 120.7, 124.3, 127.1, 129.4, 129.8, 130.3,
34.4, 143.8, 143.9, 145.1; HRMS for C24 S calcd
124.3, 126.8, 127.6, 131.6, 134.4, 142.0 (one sp carbon missing
due to overlap); IR (neat) 1103 cm ; HRMS for C18
258.1984, found 258.1980.
-
1
6
1
H26O calcd
H
31NO
2
3
,4-Dih yd r o-7-m eth yl-4-m eth ylen e-3-n -octyl-1H-2-ben -
zop yr a n (Ta ble 3, en tr y 6). Obtained as a clear, colorless
oil in 56% yield from the reaction of 2-iodo-5-methylbenzyl
alcohol and 1,2-undecadiene after purification by column
(
32) Krapcho, A. P.; Diamanti, J .; Cayen, C.; Bingham, R. Org.
Synth. 1967, 47, 20.
33) Duboudin, J . G.; J ousseaume, B. J . Organomet. Chem. 1979,
68, 1-11.
34) Dalcanale, E.; Montanari, F. J . Org. Chem. 1986, 51, 567-569.
(
chromatography using 30:1 hexanes/EtOAc: [R]
D
) -17.1° (c
1
(
) 0.026, EtOAc) [67% ee, based on integration of the vinylic

Hetero- and Carboannulation of Allenes
J . Org. Chem., Vol. 64, No. 20, 1999 7321
1
hydrogens in the presence of Eu(hfc)
(
3
]; H NMR (CDCl
3
) δ 0.87
the reaction of 2-iodobenzoic acid and 1,2-undecadiene after
purification by column chromatography using 10:1 hexanes/
t, 3 H, J ) 6.9 Hz), 1.20-1.60 (m, 12 H), 1.70-1.80 (m, 2 H),
2
1
5
1
2
1
.32 (s, 3 H), 4.25 (dd, 1 H, J ) 7.5, 6.3 Hz), 4.64 (d, 1 H, J )
5.0 Hz), 4.72 (d, 1 H, J ) 15.0 Hz), 4.97 (d, 1 H, J ) 1.2 Hz),
EtOAc: [R]
D
) -79.5° (c ) 0.068, dichloroethane) [67% ee,
based on integration of aromatic H-8 in the presence of Eu-
1
.54 (s, 1 H), 6.83 (s, 1 H), 7.03 (d, 1 H, J ) 8.4 Hz), 7.53 (d,
(hfc)
3
]; H NMR (CDCl ) δ 0.86 (t, 3 H, J ) 6.9 Hz), 1.20-1.55
3
H, J ) 7.8 Hz); 1 C NMR (CDCl
3
) δ 14.6, 21.7, 23.2, 26.1,
(m, 12 H), 1.60-1.75 (m, 1 H), 1.80-2.00 (m, 1 H), 5.00 (t, 1
H, J ) 7.2 Hz), 5.33 (s, 1 H), 5.71 (s, 1 H), 7.42-7.48 (dq, 1 H,
J ) 8.1, 2.4 Hz), 7.57-7.61 (m, 2 H), 8.11 (d, 1 H, J ) 7.8 Hz);
3
9.8, 30.1, 30.1, 32.4, 33.0, 66.1, 77.8, 106.3, 124.3, 125.2, 128.3,
29.3, 134.8, 138.0, 142.4; IR (neat) 1106 cm-1; HRMS for
1
3
C
19
H
28O calcd 272.2140, found 272.2138.
-Br om o-3,4-d ih yd r o-4-m eth ylen e-3-n -octyl-1H-2-ben -
zop yr a n (Ta ble 3, en tr y 7). Obtained as a clear, colorless
oil in 64% yield from the reaction of 5-bromo-2-iodobenzyl
alcohol and 1,2-undecadiene after purification by column
C NMR (CDCl
3
) δ 14.0, 22.5, 25.2, 29.1, 29.3, 31.7, 34.6, 81.9,
7
113.3, 123.5, 123.8, 129.0, 129.9, 133.9, 136.2, 138.6, 164.1 (one
sp signal missing due to overlap); IR (CHCl
3
-1
3
) 1720, 1114 cm ;
HRMS for C18 calcd 272.1776, found, 272.1771.
24 2
H O
7-Meth yl-4-m eth ylen e-3-n -octyl-1-isoch r om an on e (Table
3, en tr y 12). Obtained as a clear, colorless oil in 69% yield
from the reaction of 2-iodo-5-methylbenzoic acid and 1,2-
undecadiene after purification by column chromatography
chromatography using 30:1 hexanes/EtOAc: [R]
D
) -8.7° (c
)
0.034, EtOAc) [67% ee, based on integration of the vinylic
1
hydrogens in the presence of Eu(hfc)
3
]; H NMR (CDCl
3
) δ 0.88
(
4
t, 3 H, J ) 6.9 Hz), 1.22-1.59 (m, 12 H), 1.69-1.78 (m, 2 H),
using 10:1 hexanes/EtOAc: [R]
D
) -70.7° (c ) 0.033, dichlo-
.25 (t, 1 H, J ) 6.6 Hz), 4.60 (d, 1 H, J ) 15.3 Hz), 4.68 (d, 1
roethane) [63% ee, based on integration of aromatic H-8 in
1
H, J ) 15.3 Hz), 5.05 (s, 1 H), 5.58 (s, 1 H), 7.17 (d, 1 H, J )
.2 Hz), 7.32 (dd, 1 H, J ) 8.4, 1.8 Hz), 7.48 (d, 1 H, J ) 8.4
3 3
the presence of Eu(hfc) ]; H NMR (CDCl ) δ 0.87 (t, 3 H, J )
1
6.6 Hz), 1.20-1.55 (m, 12 H), 1.66 (m, 1 H), 1.92 (m, 1 H),
2.43 (s, 3 H), 4.99 (t, 1 H, J ) 6.9 Hz), 5.28 (s, 1 H), 5.66 (s, 1
1
3
Hz); C NMR (CDCl
3
) δ 14.2, 22.7, 25.5, 29.3, 29.6, 31.9, 32.5,
6
(
5.2, 77.2, 107.5, 121.6, 125.7, 127.3, 130.1, 130.7, 136.4, 141.2
H), 7.42 (dd, 1 H, J ) 8.1, 0.9 Hz), 7.49 (d, 1 H, J ) 8.1 Hz),
3
-1
13
one sp carbon missing due to overlap); IR (neat) 1111 cm
HRMS for C18 25BrO calcd 336.1089, found 336.1091.
E)-4-n -Bu t ylid en e-3,4-d ih yd r o-3-n -p r op yl-1H -2-b en -
;
3
7.94 (s, 1 H); C NMR (CDCl ) δ 14.1, 21.2, 22.6, 25.3, 29.2,
H
29.3, 29.4, 31.8, 34.8, 82.1, 112.4, 123.3, 123.8, 130.2, 133.6,
-1
(
134.9, 138.6, 139.3, 164.5; IR (CHCl
3
) 1715, 1183 cm ; HRMS
zop yr a n (Ta ble 3, en tr y 8). Obtained as a clear, colorless
for C19 calcd 286.1933, found 286.1939.
26 2
H O
oil in 73% yield from the reaction of 2-iodobenzyl alcohol and
6,7-Dim e t h oxy-4-m e t h yle n e -3-n -oct yl-1-isoch r om a -
n on e (Ta ble 3, en tr y 13). Obtained as a clear, colorless oil
in 78% yield from the reaction of 2-iodo-4,5-dimethoxybenzoic
acid and 1,2-undecadiene after purification by column chro-
4
,5-nonadiene after purification by column chromatography
using 30:1 hexanes/EtOAc: [R] ) -71.6° (c ) 0.030, dichlo-
roethane) [55% ee, based on integration of the vinylic hydrogen
D
1
in the presence of Eu(hfc)
3
]; H NMR (CDCl
3
) δ 0.90 (t, 3 H, J
matography using 10:1 hexanes/EtOAc: [R]
D
) -52.6° (c )
)
7.8 Hz), 0.95 (t, 3 H, J ) 7.8 Hz), 1.30-1.65 (m, 6 H), 2.36
0.027, dichloroethane) [71% ee, based on integration of the
1
(
dq, 2 H, J ) 7.5, 2.1 Hz), 4.28 (dd, 1 H, J ) 6.9, 5.7 Hz), 4.64
d, 1 H, J ) 14.7 Hz), 4.70 (d, 1 H, J ) 14.7 Hz), 5.51 (t, 1 H,
3 3
vinylic hydrogens in the presence of Eu(hfc) ]; H NMR (CDCl )
(
δ 0.87 (t, 3 H, J ) 6.9 Hz), 1.20-1.55 (m, 12 H), 1.60-1.75
(m, 1 H), 1.85-1.95 (m, 1 H), 3.95 (s, 3 H), 4.00 (s, 3 H), 4.98
(t, 1 H, J ) 6.9 Hz)), 5.25 (s, 1 H), 5.59 (s, 1 H), 6.97 (s, 1 H),
J ) 6.9 Hz), 7.06 (dd, 1 H, J ) 6.9, 1.5 Hz), 7.18-7.28 (m, 2
1
3
H), 7.41 (dd, 1 H, J ) 6.9, 1.5 Hz); C NMR (CDCl
3
) δ 14.0,
4.1, 19.0, 23.5, 31.0, 36.3, 65.4, 79.4, 124.2, 126.3, 126.8, 127.9,
28.1, 132.6, 133.7, 136.3; IR (neat) 1082 cm-1; HRMS for
1
1
7.55 (s, 1 H); 13C NMR (CDCl
3
) δ 14.1, 22.7, 25.4, 29.2, 29.4,
31.9, 35.0, 56.2, 56.3, 82.2, 105.3, 111.2, 111.6, 116.4, 130.7,
138.8, 150.0, 154.0, 164.3 (one sp3 signal missing due to
C
16
H
22O calcd 230.1671, found 230.1672.
-
1
(
E)-5,6a ,7,8,9,10,11,12,13,14,15,16-Dod eca h yd r oben zo-
overlap); IR (neat) 1714, 1653, 1140, 1061 cm ; HRMS for
calcd 332.1988, found 332.1997.
7-Br om o-4-m eth ylen e-3-n -octyl-1-isoch r om an on e (Table
[
d ]cyclotr id ec[b]p yr a n (Ta ble 3, en tr y 9). Obtained as a
20 28 4
C H O
clear, colorless oil in 29% yield along with a trace of an
unknown impurity from the reaction of 2-iodobenzyl alcohol
and 1,2-cyclotridecadiene after purification using 30:1 hexanes/
3, en tr y 14). Obtained as a clear, colorless oil in 67% yield
from the reaction of 5-bromo-2-iodobenzoic acid and 1,2-
undecadiene after purification by column chromatography
EtOAc: [R]
D
) -148.9° (c ) 0.017, dichloroethane) [77% ee,
based on integration of the vinylic hydrogen in the presence
using 10:1 hexanes/EtOAc: [R]
D
) -47.1° (c ) 0.024, dichoro-
1
of Eu(hfc)
.75 (m, 2 H), 2.10-2.25 (m, 1 H), 2.55-2.70 (m, 1 H), 4.38
dd, 1 H, J ) 8.7, 3.6 Hz), 4.60 (d, 1 H, J ) 14.1 Hz), 4.68 (d,
H, J ) 14.1 Hz), 5.64 (dd, 1 H, J ) 11.1, 5.1 Hz), 7.09 (d, 1
H, J ) 6.3 Hz), 7.19-7.30 (m, 2 H), 7.53 (d, 1 H, J ) 7.2 Hz);
3 3
]; H NMR (CDCl ) δ 1.20-1.60 (m, 16 H), 1.62-
ethane) [48% ee, based on integration of aromatic H-8 in the
1
1
3 3
presence of Eu(hfc) ]; H NMR (CDCl ) δ 0.87 (t, 3 H, J ) 6.9
(
1
Hz), 1.15-1.45 (m, 12 H), 1.60-1.70 (m, 1 H), 1.80-1.95 (m,
1 H), 5.00 (t, 1 H, J ) 6.9 Hz), 5.37 (s, 1 H), 5.72 (s, 1 H), 7.46
(d, 1 H, J ) 8.4 Hz), 7.72 (dd, 1 H, J ) 8.4, 2.1 Hz), 8.25 (d, 1
1
3
13
C NMR (CDCl
3
) δ 22.4, 24.6, 24.8, 25.3, 26.0, 26.1, 27.3, 27.8,
H, J ) 2.1 Hz); C NMR (CDCl ) δ 14.1, 22.6, 25.3, 29.1, 29.3,
3
2
1
2
8.7, 33.1, 66.1, 80.1, 124.5, 126.6, 126.7, 127.2, 129.4, 132.6,
33.1, 136.8; IR (neat) 1081 cm ; HRMS for C20
84.2140, found 284.2138.
31.8, 34.7, 82.0, 114.1, 123.1, 125.1, 125.7, 132.8, 135.0, 137.0,
-
1
3
H
28O calcd
3
137.8, 162.9 (one sp signal missing due to overlap); IR (CHCl )
-1
1710, 1150 cm ; HRMS for C18
350.0890.
2
H23BrO calcd 350.0881, found
(
S)-(E)-3-Br om o-5,6a,7,8,9,10,11,12,13,14,15,16-dodecah y-
d r oben zo[d ]cyclotr id ec[b]p yr a n (Ta ble 3, en tr y 10). Ob-
tained as a pale yellow oil in 33% yield along with a trace of
an unknown impurity from the reaction of 5-bromo-2-iodoben-
zyl alcohol and 1,2-cyclotridecadiene after purification using
5,6-Dih yd r o-3-m eth yl-5-m eth ylen e-6-n -octyl-2H-p yr a n -
2-on e (Ta ble 3, en tr y 15). Obtained as a clear, colorless oil
in 41% yield from the reaction of (Z)-3-iodo-2-methyl-2-
propenoic acid and 1,2-undecadiene after purification using
3
0:1 hexanes/EtOAc: [R]
oil was crystallized from hexane to give white needles: [R]
211.0° (c ) 0.008, CDCl ) [>95% ee, no resolution of the
vinylic hydrogen was observed in the presence of Eu(hfc) ];
D
) -118.0° (c ) 0.021, CDCl
3
). This
10:1 hexanes/EtOAc: [R]
D
) -93.5° (c ) 0.014, dichloroethane)
D
)
[80% ee, based on integration of the methyl hydrogens in the
1
-
3
3 3
presence of Eu(hfc) ]; H NMR (CDCl ) δ 0.88 (t, 3 H, J ) 6.6
3
Hz), 1.22-1.55 (m, 12 H), 1.66-1.79 (m, 1 H), 1.80-1.93 (m,
1 H), 1.99 (s, 3 H), 4.99 (dd, 1 H, J ) 8.1, 5.7 Hz), 5.13 (s, 1
1
H NMR δ 1.2-1.6 (m, 16 H), 1.62-1.80 (m, 2 H), 2.12-2.25
(
4
m, 1 H), 2.48-2.62 (m, 1 H), 4.35 (dd, 1 H, J ) 8.4, 3.3 Hz),
H), 5.22 (s, 1 H), 6.77 (s, 1 H); 13C NMR (CDCl
3
) δ 14.1, 17.1,
.56 (d, 1 H, J ) 14.7 Hz), 4.64 (d, 1 H, J ) 14.7 Hz), (5.64
22.7, 24.8, 29.3, 29.5, 31.9, 36.1, 80.8, 115.9, 127.2, 138.7, 139.5,
3
(
)
2
ddd, 1 H, J ) 10.8, 5.1, 0.3 Hz), 7.26 (s, 1 H), 7.39 (d, 2 H, J
164.7 (one sp carbon missing due to overlap); IR (neat) 1716,
1
3
-1
1.2 Hz); C NMR (CDCl
3
) δ 22.2, 24.6, 24.8, 25.3, 25.9, 26.1,
24 2
1110 cm ; HRMS for C15H O calcd 236.1776, found 236.1770.
7.2, 27.8, 28.6, 32.9, 65.5, 80.0, 120.6, 127.6, 128.9, 129.8,
30.1, 131.6, 132.3, 138.9; IR (CHCl
(E)-5-n -Bu t ylid en e-5,6-d ih yd r o-3-m et h yl-6-n -p r op yl-
2H-p yr a n -2-on e (Ta ble 3, en tr y 16). Obtained as a clear,
colorless oil in 59% yield (96:4 E/Z) from the reaction of (Z)-
3-iodo-2-methyl-2-propenoic acid and 4,5-nonadiene after pu-
rification using 10:1 hexanes/EtOAc: [R]
dichloroethane) [46% ee, based on integration of the allylic
-
1
1
3
) 2932, 1478, 1465 cm
;
7
9
HRMS for
C H O Br calcd 362.1245, found 362.1245;
20 27
8
1
C
20
H
27O Br calcd 364.1226, found 364.1223.
-Meth ylen e-3-n -octyl-1-isoch r om a n on e (Ta ble 3, en -
tr y 11). Obtained as a clear, colorless oil in 50% yield from
4
D
) -97.5° (c ) 0.027,

7
322 J . Org. Chem., Vol. 64, No. 20, 1999
Zenner and Larock
methyl hydrogens in the presence of Eu(hfc)
3
]; 1H NMR
) δ 0.93 (t, 3 H, J ) 6.9 Hz), 0.94 (t, 3 H, J ) 7.2 Hz),
Hz), 4.0-4.4 (m, 4 H), 5.59 (t, 1 H, J ) 7.5 Hz), 7.21-7.33 (m,
(CDCl
3
2 H), 7.51 (d, 1 H, J ) 7.2 Hz), 7.63 (dd, 1 H, J ) 6.9, 1.8 Hz);
1
1
2
6
.30-1.52 (m, 4 H), 1.58-1.72 (m, 1 H), 1.78-1.90 (m, 1 H),
.00 (s, 3 H), 2.19 (qt, 2 H, J ) 14.7, 7.5 Hz), 4.84 (t, 1 H, J )
.9 Hz), 5.55 (t, 1 H, J ) 7.8 Hz), 7.03 (s, 1 H); 13C NMR
(E isomer) H NMR (CDCl
3
) δ 0.79 (t, 3 H, J ) 6.9 Hz), 1.00
(t, 3 H, J ) 7.2 Hz), 1.16 (t, 3 H, J ) 7.2 Hz), 1.31 (t, 3 H, J
) 6.9 Hz), 1.15-1.50 (m, 4 H), 1.51 (m, 2 H), 2.15-2.35 (m, 2
H), 3.92 (m, 1 H), 4.0-4.4 (m, 4 H), 5.93 (t, 1 H, J ) 7.5 Hz),
7.21-7.33 (m, 2 H), 7.37 (dd, 1 H, J ) 6.6, 2.1 Hz), 7.59 (dd,
1 H, J ) 7.2, 1.5 Hz). This product mixture was not further
characterized.
(CDCl
3
) δ 13.7, 13.9, 17.5, 18.4, 22.6, 29.4, 38.1, 81.9, 126.1,
30.4, 132.3, 133.7, 165.3; IR (neat) 1714, 1105 cm- ; HRMS
calcd 208.1463, found 208.1467.
E)-6,7,8,9,10,11,12,13,14,15,15a -Un d eca h yd r o-3-m eth -
1
1
for C13
20 2
H O
(
ylcyclotr id ec[b]p yr a n -2-on e (Ta ble 3, en tr y 17). Obtained
as a clear, colorless oil in 52% yield (98:2 E/Z) from the reaction
of (Z)-3-iodo-2-methyl-2-propenoic acid and 1,2-cyclotrideca-
Di-µ-ch lor o-d i(η -5-p h e n yln on -4-e n yl)d ip a lla d iu m -
3
(II) (9). Obtained as a 1:1 mixture of the syn-syn and syn-
anti isomers from the reaction of 4,5-nonadiene, Li PdCl and
2
4
diene after purification using 10:1 hexanes/EtOAc: [R]
D
)
PhHgCl in CH CN according to a literature procedure:22 (syn-
3
-
202.6° (c ) 0.022, dichloroethane) [61% ee, based on integra-
syn) H NMR (CDCl ) δ 0.78 (t, 6 H, J ) 6.9 Hz), 1.20-1.40
1
3
1
tion of the methyl hydrogens in the presence of Eu(hfc)
3
]; H
(m, 4 H), 1.40-1.58 (m, 4 H), 3.73 (m, 2 H), 7.36-7.43 (m, 3
NMR (CDCl
3
) δ 1.18-1.66 (m, 16 H), 1.80 (qt, 2 H, J ) 13.2,
H), 7.63-7.65 (m, 2 H); 13C NMR (CDCl ) δ 13.9, 22.0, 31.5,
3
6
4
.3 Hz), 2.01 (s, 3 H), 2.07-2.22 (m, 1 H), 2.28-2.42 (m, 1 H),
81.7, 127.4, 127.8, 128.3, 130.0, 133.6; (syn-anti) H NMR
1
.91 (t, 1 H, J ) 5.1 Hz), 5.56 (dd, 1 H, J ) 11.1, 6.0 Hz), 7.02
(CDCl ) δ 0.78 (t, 3 H, J ) 6.9 Hz), 0.99 (t, 3 H, J ) 7.2 Hz),
3
1
3
(s, 1 H); C NMR (CDCl
3
) δ 17.6, 21.4, 24.7, 24.8, 26.2, 26.4,
1.20-1.40 (m, 2 H), 1.40-1.58 (m, 2 H), 1.58-1.70 (m, 2 H),
1.80-1.92 (m, 2 H), 3.73 (m, 2 H), 7.36-7.43 (m, 3 H), 7.63-
2
6.6, 28.0, 35.5, 82.4, 126.2, 130.0, 133.3, 133.6, 165.1 (two
3
-1
sp carbons missing due to overlap); IR (neat) 1714, 1125 cm
HRMS for C17 calcd 262.1933, found 262.1932.
,6-Dih yd r o-3-m et h yl-5-m et h ylen e-6-n -oct yl-2H -p yr -
a n (Ta ble 3, en tr y 18). Obtained as a clear, colorless oil in
;
7.65 (m, 2 H).
H
26
O
2
3
(
η -5-P h en yl-n on -4-en yl)p a lla d iu m (II) tr iflu or om eth -
5
3
a n esu lfon a te (10). Di-µ-chlorodi(η -5-phenyl-non-4-enyl)di-
palladium(II) and AgOTf were stirred at 80 °C in CD CN for
.25 h. The starting π-allylpalladium chloride dimer was a 1:1
3
7
1
0% yield from the reaction of (Z)-3-iodo-2-methyl-2-propen-
-ol and 1,2-undecadiene after purification using 30:1 hexanes/
0
ratio of syn-anti to syn-syn isomers. A white precipitate of AgCl
EtOAc: [R]
D
) -11.5° (c ) 0.031, dichloroethane) [79% ee,
was observed immediately upon mixing. 1H NMR spectral
based on integration of the allylic methyl hydrogens in the
analysis of an aliquot of the resulting solution indicated it was
a 1.4:1 mixture of syn-anti and syn-syn isomers based on
integration of the methyl peaks. For the two stereoisomers all
three syn-methyl groups are found at 0.78 ppm, while the anti-
1
presence of Eu(hfc)
Hz), 1.15-1.45 (m, 12 H), 1.45-1.55 (m, 1 H), 1.65-1.75 (m,
H), 1.71 (s, 3 H), 3.95-4.15 (m, 3 H), 4.72 (s, 1 H), 4.73 (s, 1
3 3
]; H NMR (CDCl ) δ 0.88 (t, 3 H, J ) 6.9
1
1
3
H), 5.97 (s, 1 H); C NMR (CDCl
3
) δ 14.3, 18.8, 22.7, 25.6,
methyl group is found at 1.02 ppm. Spectral data for the
2
9.4, 29.7, 29.7, 32.0, 32.1, 66.4, 75.4, 107.3, 122.4, 136.1, 142.9;
product mixture: 1H NMR (CD
1
3
CN) δ H NMR (CDCl
3
) δ 0.78
-
1
3
IR (CHCl ) 1653, 1616, 1102 cm ; HRMS for C13H22O calcd
(
t, 9 H, J ) 6.9 Hz), 1.02 (t, 3 H, J ) 7.2 Hz), 1.27-1.54 (m, 12
1
94.1471, found 194.1468.
,6-Dih yd r o-2,2-d im et h yl-5-m et h ylen e-6-n -oct yl-2H -
H), 1.55-1.70 (m, 2 H), 1.80-1.90 (m, 2 H), 3.99 (m, 2 H),
7
5
.44-7.49 (m, 5 H).
p yr a n (Ta ble 3, en tr y 20). Obtained as a clear, colorless oil
in 62% yield from the reaction of (Z)-4-iodo-2-methyl-3-buten-
3
(
η -5-P h en yln on -4-en yl)palladiu m (II) tr iflu or om eth an e-
3
su lfon a te-Liga n d 2 (11). (η -5-Phenylnon-4-enyl)palladium-
2
-ol and 1,2-undecadiene after purification using 30:1 hexanes/
EtOAc: [R] ) +46.0° (c ) 0.036, CHCl ) (ee undetermined);
H NMR (CDCl ) δ 0.88 (t, 3 H, J ) 7.2 Hz), 1.20-1.45 (m, 18
(II) trifluoromethanesulfonate and 2 were stirred in CD CN
3
D
3
at 80 °C for 16 h. The mixture was cooled to room temperature
1
3
1
and an aliquot removed and analyzed by H NMR spectros-
H), 1.50-1.70 (m, 1 H), 1.75-1.90 (m, 1 H), 4.22 (m, 1 H), 4.83
copy. Determination of the ratio of syn-anti and syn-syn
isomers was based upon integration of the methyl peaks. See
the Supporting Information for a 1H NMR spectrum of this
complex.
(
)
2
d, 2 H, J ) 9.6 Hz), 5.69 (d, 1 H, J ) 9.9 Hz), 6.07 (d, 1 H, J
1
3
3
9.9 Hz); C NMR (CDCl ) δ 14.2, 22.7, 24.6, 25.4, 29.4, 29.6,
9.7, 29.7, 31.9, 32.0, 69.6, 72.3, 108.7, 125.5, 136.6, 143.0; IR
-
1
(neat) 1177, 1089 cm ; HRMS for C16
H28O calcd 236.2140,
(
η3-5-P h en yln on -4-en yl)palladiu m (II) tr iflu or om eth an e-
found 236.2139.
su lfon a te-Liga n d 1. This complex was formed as described
Diet h yl 3-Met h ylen e-2-n -oct yl-1,1-in d a n ed ica r b oxy-
la te (Ta ble 3, en tr y 21). Obtained as a pale yellow oil in 67%
yield from the reaction of diethyl 2-iodophenylmalonate and
3
for the preparation of (η -5-phenylnon-4-enyl)palladium-2.
1
The H NMR spectral data were recorded at 65 °C to eliminate
1
peak broadening. See the Supporting Information for a
NMR spectrum of this complex.
H
1
,2-undecadiene after purification using 10:1 hexanes/
EtOAc: [R] ) 48.8° (c ) 0.29, dichloroethane) [75% ee, based
on integration of the vinylic hydrogens in the presence of Eu-
D
1
(
hfc)
H, J ) 7.2 Hz), 1.29 (t, 3 H, J ) 6.9 Hz), 1.21-1.52 (m, 14 H),
.62-3.72 (m, 1 H), 4.02-4.34 (m, 4 H), 5.11 (d, 1 H, J ) 1.2
Hz), 5.52 (d, 1 H, J ) 1.8 Hz), 7.25-7.33 (m, 2 H), 7.45-7.48
3
]; H NMR (CDCl
3
) δ 0.87 (t, 3 H, J ) 6.9 Hz), 1.22 (t, 3
Ack n ow led gm en t. We gratefully acknowledge the
U.S. Department of Education for financial support in
the form of a GAANN (Graduate Assistance in Areas of
National Need) Fellowship and Prof. Andreas Pfaltz for
his generous contribution of bisoxazoline chiral ligands.
In addition, we thank the following for their contribution
of chiral ligands used in this study: Prof. M. B. Andrus,
Dr. I. Davies (Merck & Co.), Prof. S. E. Denmark, Prof.
T. Hayashi, Hoffman LaRoche, Prof. H. Nishiyama,
Prof. A. Togni, Prof. B. M. Trost, Prof. L. M. Vananzi,
Prof. M. Wills, and Prof. J . M. J . Williams.
3
1
3
(
m, 1 H), 7.59-7.63 (m, 1 H); C NMR (CDCl
3
) δ 14.0, 14.2,
4.2, 22.7, 27.1, 29.3, 29.5, 29.7, 30.4, 31.9, 50.8, 61.3, 61.7,
8.1, 105.0, 120.8, 127.4, 128.5, 128.8, 140.3, 140.8, 149.8,
1
6
1
69.3, 169.6; IR (neat) 1734, 1615, 1190 cm- ; HRMS for
calcd 386.2457, found 386.2448.
Diet h yl 3-n -Bu t ylid en e-2-n -p r op yl-1,1-in d a n ed ica r -
1
24 34 4
C H O
boxyla te (Ta ble 3, en tr y 22). Obtained as a pale yellow oil
in 79% yield (7:1 Z/E) from the reaction of diethyl 2-iodophe-
nylmalonate and 4,5-nonadiene after purification using 10:1
hexanes/EtOAc: [R]
D
) 28.0° (c ) 0.037, dichloroethane) [47%
Su p p or tin g In for m a tion Ava ila ble: NMR spectral data
H and C) of all key intermediates and new annulation
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
ee, based on integration of the vinylic hydrogen in the presence
(1
13
1
of Eu(hfc)
3
]; (Z isomer) H NMR (CDCl
.9 Hz), 0.98 (t, 3 H, J ) 7.2 Hz), 1.19 (t, 3 H, J ) 7.2 Hz),
.29 (t, 3 H, J ) 6.9 Hz), 1.15-1.50 (m, 4 H), 1.55 (qt, 2 H, J
14.7, 7.2 Hz), 2.36-2.47 (m, 2 H), 3.54 (dd, 1 H, J ) 8.4, 4.8
3
) δ 0.86 (t, 3 H, J )
6
1
)
J O9901992