Palladium-catalyzed cross-coupling of 2,5-cyclohexadienyl-substituted aryl or vinylic iodides and carbon or heteroatom nucleophiles

Article abstract of DOI:10.1021/jo981876f

2,5-Cyclohexadienyl-substituted aryl or vinylic iodides have been reacted with carbon nucleophiles (diethyl malonate and 2-methyl-1,3- cyclohexanedione), nitrogen nucleophiles (morpholine, potassium phthalimide, N-benzyl tosylamide, di-tert-butyl iminodicarboxylate, lithium azide, and anilines), a sulfur nucleophile (sodium benzenesulfinate), and oxygen nucleophiles (lithium acetate and phenols) to afford products of cyclization and subsequent cross-coupling in good to excellent yields. In most cases, this process is highly diastereoselective. The reaction is believed to proceed via (1) oxidative addition of the aryl or vinylic iodide to Pd(0), (2) organopalladium addition to one of the carbon-carbon double bonds, (3) palladium migration along the carbon chain on the same face of the ring to form a π-allylpalladium intermediate, and (4) nucleophilic displacement of the palladium.

Full text of DOI:10.1021/jo981876f

J . Org. Chem. 1999, 64, 1875-1887
1875
P a lla d iu m -Ca ta lyzed Cr oss-Cou p lin g of
2,5-Cycloh exa d ien yl-Su bstitu ted Ar yl or Vin ylic Iod id es a n d
Ca r bon or Heter oa tom Nu cleop h iles
Richard C. Larock* and Xiaojun Han
Department of Chemistry, Iowa State University, Ames, Iowa 50011
Received September 15, 1998
2,5-Cyclohexadienyl-substituted aryl or vinylic iodides have been reacted with carbon nucleophiles
(diethyl malonate and 2-methyl-1,3-cyclohexanedione), nitrogen nucleophiles (morpholine, potassium
phthalimide, N-benzyl tosylamide, di-tert-butyl iminodicarboxylate, lithium azide, and anilines), a
sulfur nucleophile (sodium benzenesulfinate), and oxygen nucleophiles (lithium acetate and phenols)
to afford products of cyclization and subsequent cross-coupling in good to excellent yields. In most
cases, this process is highly diastereoselective. The reaction is believed to proceed via (1) oxidative
addition of the aryl or vinylic iodide to Pd(0), (2) organopalladium addition to one of the carbon-
carbon double bonds, (3) palladium migration along the carbon chain on the same face of the ring
to form a π-allylpalladium intermediate, and (4) nucleophilic displacement of the palladium.
In tr od u ction
The intramolecular Heck reaction has been extensively
used in the construction of polycyclic compounds and in
the synthesis of natural products.1 Shibasaki et al.2 have
reported asymmetric Heck reactions of conjugated dienyl-
substituted vinylic triflates (eq 1) and 2,5-cyclohexadi-
enyl-substituted vinylic triflates and iodides (eq 2). The
radical ring-closure reactions of 2,5-cyclohexadienyl-
substituted aryl iodides or vinylic bromides have been
reported by Beckwith et al. (eq 3).3 This methodology has
proven to be a powerful tool for the rapid construction of
polycyclic compounds.
aryl or vinylic iodides and dienyl moieties were present
in the same molecule, the reactions of the resulting
dienyl-substituted aryl or vinylic iodides with external
nucleophiles in the presence of a Pd(0) catalyst might
afford very useful, highly functionalized polycyclic com-
pounds (eqs 5 and 6).7
Resu lts a n d Discu ssion
The starting materials were efficiently prepared by
standard methodology. For example, aryl iodides 1-7
were prepared by the reactions shown in Scheme 1.
We have previously discovered that aryl halides, non-
conjugated dienes, and carbon nucleophiles,4 amines,5 or
heteroatom nucleophiles6 can be coupled in high yields
using Pd(dba)2 as a catalyst (eq 4). We envisioned that if
(2) (a) Shibasaki, M. In Advances in Organic-Metal Chemistry;
Liebeskind, L. S., Ed.; J AI Press: Greenwich, 1996; Vol. 5, pp 119-
151. (b) Kondo, K.; Sodeoka, M.; Mori, M.; Shibasaki, M. Tetrahedron
Lett. 1993, 34, 4219. (c) Sato, Y.; Sodeoka, M.; Shibasaki, M. J . Org.
Chem. 1989, 54, 4738.
(3) Beckwith, A. L.; O’Shea, D. M.; Roberts, D. H. J . Chem. Soc.,
Chem. Commun. 1983, 1445.
(4) Larock, R. C.; Lu, Y. D.; Bain, A. C. J . Org. Chem. 1991, 56,
4589.
(5) Larock, R. C.; Wang, Y., Lu, Y. D.; Russell, C. E. J . Org. Chem.
1995, 59, 8107.
(6) Larock, R. C.; Wang, Y.; Lu, Y. D., work in progress.
(7) For a preliminary communication of this work, see: Han, X.;
Larock, R. C. Synlett, in press.
(1) (a) Gibson, S. E.; Middleton, R. J . Contemp. Org. Synth. 1996,
3, 447. (b) Negishi, E. I.; Coperet, C.; Ma, S.; Liou, S.; Liu, F. Chem.
Rev. 1996, 96, 365. (c) Heumann, A.; Reglier, M. Tetrahedron 1996,
52, 9289. (d) J effery, T. In Advances in Metal-Organic Chemistry;
Liebeskind, L. S., Ed.; J AI Press: Greenwich, 1996; Vol. 5, pp 153-
260. (e) Tsuji, J . Palladium Reagents and Catalysts - Innovations in
Organic Synthesis; Wiley: New York, 1995. (f) de Meijere, A.; Meyer,
F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379.
10.1021/jo981876f CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/25/1999

1876 J . Org. Chem., Vol. 64, No. 6, 1999
Larock and Han
Sch em e 1
Sch em e 2
Vinylic iodides 14-16, 19, 22, and 25 were synthesized
by the reactions shown in Scheme 2.
The reaction of a variety of carbon, nitrogen, oxygen,
and sulfur nucleophiles8,9 with aryl iodide 1 was carried
out under conditions similar to our previous intermo-
lecular versions of this chemistry.4-6 Minimal efforts were
made to optimize each reaction. The results are sum-
marized in Table 1, entries 1-14. Carbon nucleophiles
were observed to give good yields after some modification
of our earlier reported reaction conditions (entries 1 and
2).
Nitrogen nucleophiles have also proven quite success-
ful. The yield of the reaction of iodide 1 with morpholine
could be increased from 31% to 91% by switching to
DMSO as the solvent in the presence of 2 equiv of Na2-
CO3 (entries 3 and 4). The yield of the reaction of 1 with
azide could also be improved from 36% using 1.5 equiv
of NaN3 to 51% using 2 equiv of LiN3 (entries 5 and 6).
The formation of a mixture of regioisomers (29 vs 61 and
62 vs 63) in this reaction might be due to the azide anion
(8) For recent reviews of nucleophilic attack on π-allylpalladium
species, see: (a) Moreno-Manas, M.; Pleixats, R. Adv. Heterocycl. Chem.
1996, 66, 73. (b) Trost, B. M. Pure Appl. Chem. 1996, 68, 779. (c)
Heumann, A.; Reglier, M. Tetrahedron 1995, 51, 975. (d) Godleski, S.
A. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Semmelhack, M. F., Eds.; Pergamon Press: New York, 1991; Vol. 4, p
585.
(9) For the nucleophiles used in this study, see refs 4 and 5. See
also: stabilized carbanion (a) Trost, B. M.; Strege, P. E. J . Am. Chem.
Soc. 1977, 99, 1649. Amines (b) Uozumi, Y.; Tanahashi, A.; Hayashi,
T. J . Org. Chem. 1993, 58, 6826. (c) Tsuda, T.; Kiyoi, T.; Saegusa, T.
J . Org. Chem. 1990, 55, 3388. Azides (d) Murahashi, S. I.; Tanigawa,
Y.; Imada, Y.; Taniquchi, Y. Tetrahedron Lett. 1986, 27, 227. Di-tert-
butyl iminodicarboxylate (e) Connel, R. D.; Rein, T.; Akermark, B.;
Helquist, P. J . Org. Chem. 1988, 53, 3845. Potassium phthalimide (f)
Inoue, Y.; Taquchi, M.; Toyofuku, M.; Hashimoto, H. Bull. Chem. Soc.
J pn. 1984, 57, 3021. Lithium acetate (g) Ba¨ckvall, J . E. Pure Appl.
Chem. 1996, 68, 535. Phenols (h) Deardorff, D. R.; Myles, D. C.;
MacFerrin, K. D. Tetrahedron Lett. 1985, 26, 5615. (i) Deardorff, D.
R. J . Org. Chem. 1988, 53, 189. (j) Deardorff, D. R.; Linde, R. G.;
Martin, A. M.; Shulman, M. J . J . Org. Chem. 1989, 54, 2759. Sodium
benzenesulfinate (k) Trost, B. M.; Organ, M. G.; O’Doherty, G. A. J .
Am. Chem. Soc. 1995, 117, 9662 and references therein.
undergoing backside attack on the π-allylpalladium
intermediate at both ends of the allylic system and/or
[3,3]-sigmatropic rearrangement of the allyl azide.10,11
The formation of a mixture of stereoisomers (29 vs 62
(10) Trost, B. M.; Pulley, S. R. Tetrahedron Lett. 1995, 36, 8737.
(11) (a) Aggarwal, V. K.; Monteiro, N.; Tarver, G. J .; McCague, R.
J . Org. Chem. 1997, 62, 4665. (b) Murahashi, S. T.; Taniguchi, Y.;
Imada, Y.; Tanigawa, Y. J . Org. Chem. 1989, 54, 3292.

Cross-Coupling of Aryl or Vinylic Iodides
J . Org. Chem., Vol. 64, No. 6, 1999 1877
Ta ble 1. P a lla d iu m -Ca ta lyzed Cr oss-Cou p lin g of 2,5-Cycloh exa d ien yl-Su bstitu ted Ar yl a n d Vin ylic Iod id es w ith Va r iou s
Nu cleop h ilesa

1878 J . Org. Chem., Vol. 64, No. 6, 1999
Larock and Han
Ta ble 1 (Con tin u ed )

Cross-Coupling of Aryl or Vinylic Iodides
J . Org. Chem., Vol. 64, No. 6, 1999 1879
Ta ble 1 (Con tin u ed )

1880 J . Org. Chem., Vol. 64, No. 6, 1999
Larock and Han
Ta ble 1 (Con tin u ed )
a
All of the reactions were run in the presence of 10 mol % of Pd(dba)2, 2 mL of DMSO (except entry 2, 5 mL of DMSO; entry 3, 5 mL
b
of DMF; entries 8 and 22, 2 mL of DMF) at 100 °C (except entries 1, 17, 19, and 21, 80 °C). For the assignment of the structures of these
compounds, see the text and Supporting Information. In entries 5, 6, and 15, only the major isomer is shown. c Isomer ratios were determined
by 1H NMR or GC-MS. TBAC ) tetra-n-butylammonium chloride. e The yields are based on the recovery of starting materials. f The
d
product has the same or a very similar 1H NMR spectrum to that of entry 5. After flash chromatography, an inseparable mixture of the
g
product and 1,5-diphenyl-1,4-pentadien-3-one (dba) was obtained. The pure product was obtained after chromatography on a basic alumina
h
column. The reaction afforded an inseparable mixture of two isomers in the ratio of 10:1. Both isomers were obtained in pure form after
hydrolysis of the acetate to the corresponding alcohols.
and 61 vs 63) may result from the palladium-mediated
isomerization of the intermediate π-allylpalladium spe-
cies or a combination of frontside and backside displace-
ment of palladium by azide.11 Although allylic azides can
be readily reduced to allylic amines, which are versatile
intermediates in organic synthesis, the poor selectivity
of this reaction prompted us to search for other protected
primary amine derivatives to employ as nucleophiles.
When potassium phthalimide (entry 7), N-benzyl tosy-
lamide (entry 8), or di-tert-butyl iminodicarboxylate
(entry 9) were used as nucleophiles, the desired products
30-32 were formed each as a single diastereoisomer in
31%, 60%, or 52% yields, respectively. Compounds 31 and
329e should be readily converted to the corresponding
allylic amines under mild conditions. Aniline was chosen
as a nucleophile, because allylic anilines can be employed
in the 3-aza-Cope rearrangement,12 and the initial prod-
uct could potentially prove useful in further intramo-
lecular Heck-type processes. Thus, the reaction of aryl
iodide 1 and aniline afforded compound 33 as a single
diastereoisomer in 90% yield (entry 10).
that the distribution of products is controlled by ther-
modynamics and this whole process is finished in less
than 5 h. Saponification (K2CO3/MeOH) of the insepa-
rable mixture (35a and 35b) afforded two readily sepa-
rable alcohols 64 (84% yield) and 65 (5% yield) (eq 7).
Allylic sulfones are versatile intermediates in organic
synthesis, because sulfones can convert the adjacent
carbon into either a nucleophilic or an electrophilic
center.9k Allylic sulfones can be prepared by π-allylpal-
ladium displacement processes.9k Thus, allylic sulfone 34
was produced in 62% yield as a single diastereoisomer
when sodium benzenesulfinate was used as the nucleo-
phile (entry 11).
Because of the usefulness of allylic phenyl ethers in
the Claisen rearrangement12 and, more importantly, the
potential tandem Heck reaction of the products obtained
when 2-halophenols are used as the nucleophiles, phenol
and 2-bromophenol were reacted with aryl iodide 1 to
afford the desired products 36 and 37 as single diaste-
reoisomers in 62% and 59% yields, respectively.
All of the nucleophiles so far discussed, except lithium
azide and acetate, which are well known for their poor
selectivities in π-allylpalladium chemistry,13 react with
aryl iodide 1 to form the desired products as single
diastereoisomers. However, when aryl iodide 2 was
reacted with diethylmalonate, an inseparable mixture of
four isomers (38, 66, 67, and 68) in the ratio of 66:13:
14:7 was obtained in 60% yield (entry 15). Compounds
38 and 66 (with cis ring fusion between rings B and C)
were no doubt formed by cis addition of the arylpalladium
intermediate to one of the carbon-carbon double bonds
Allylic alcohols and acetates are also versatile inter-
mediates in organic synthesis. The reaction of aryl iodide
1 with 3 equiv of lithium acetate afforded an inseparable
10:1 mixture of two regioisomers in 80% yield in the
presence of 1 equiv of TBAC and 1.5 equiv of LiCl in 2
mL of DMSO at 100 °C for 15 h (entry 12). When the
above reaction was run for 5 or 32 h under otherwise the
same conditions, compound 35 was produced in 74% or
76% isolated yields as an inseparable mixture of the same
two regioisomers in the same 10:1 ratio. This suggests
(12) (a) Blechert, S. Synthesis 1989, 71. (b) Moody, C. J . Adv.
Heterocycl. Chem. 1987, 42, 203. (c) Przheval’skii, N. M.; Grandberg,
II. Russ. Chem. Rev. 1987, 56, 477.
(13) (a) Trost, B. M.; Keinan, E. J . Org. Chem. 1979, 44, 3451. (b)
Trost, B. M. Verhoeven, T. R. J . Am. Chem. Soc. 1980, 102, 4730.

Cross-Coupling of Aryl or Vinylic Iodides
J . Org. Chem., Vol. 64, No. 6, 1999 1881
Sch em e 3
from the top face of the ring, followed by migration and
subsequent backside nucleophilic attack on both ends of
the π-allylpalladium intermediate. Similarly, compounds
67 and 68 (with trans ring fusion between rings B and
C) were probably formed by cis addition of the arylpal-
ladium to one of the carbon-carbon double bonds from
the bottom face of the ring. The poor regioselectivity of
the subsequent nucleophilic substitution of palladium can
be attributed to the greater flexibility present in the 6,7,6-
tricyclic ring of the π-allylpalladium intermediate. How-
ever, when morpholine was used as the nucleophile, the
desired product was formed as a single diastereoisomer
(entry 16). From the results of entries 15/16 and 23/24
we can see that amine nucleophiles (morpholine in entry
16 and aniline in entry 24) are more diastereoselective
than diethylmalonate. It appears that these nitrogen
nucleophiles are more sensitive to the steric hindrance
present in the π-allylpalladium intermediate, but the
reason for this is not clear.
Ester and alcohol functionalities can be tolerated in
the starting aryl iodides employed in this reaction. For
example, aryl iodides 3 and 4 were successfully reacted
with carbon and heteroatom nucleophiles to give the
desired products as single diastereoisomers in good to
excellent yields (entries 17-20). The reaction of ester 3
with LiOAc‚2H2O afforded compound 41 as a single
diastereoisomer in 67% yield (compare entries 12 and 18).
The improved selectivity is presumably due to the
increased steric hindrance toward backside nucleophilic
attack present at the other end of the π-allylpalladium
intermediate (see Scheme 3, intermediate 73).
Because nitrogen-containing moieties are often present
in naturally occurring compounds, it was desirable to
establish if this process would work for substrates with
a free NH group. Reactions of amide-containing aryl
iodide 5 with diethyl malonate or morpholine gave none
of the desired products, probably as a result of the
presence of a relatively acidic amide hydrogen. The
reaction of the secondary amine-containing aryl iodide 6
with diethyl malonate (entry 21) and N-benzyl tosylamide
(entry 22) gave the desired products as single diastere-
oisomers in low yields, whereas aniline gave only a trace
amount of the desired product. However, after protection
of the problematic amine hydrogen in aryl iodide 6 by a
benzyl group, the desired product was formed in 64%
yield as a 75:25 inseparable mixture of two regioisomers
(entry 23) when diethyl malonate was reacted with aryl
iodide 7 and in 59% yield as a single diastereoisomer
(entry 24) when aryl iodide 7 was reacted with aniline.
The poor regioselectivity of the reaction in entry 23 might
be attributed to the conformational mobility present in
the π-allylpalladium intermediate brought about by the
benzyl side chain.
Although vinylic halides have not previously been
employed in intermolecular versions of our migration
chemistry because of the concern that the initial homoal-
lylic palladium intermediate might migrate palladium
back toward the carbon-carbon double bond originating
in the vinylic moiety,14 it appeared that the cyclic dienes
employed here might circumvent this difficulty and afford
unsaturated polycyclic products of considerable utility in
natural product synthesis. To test this hypothesis, vinylic
iodides 14-16, 19, 22, and 25 were allowed to react with
various nucleophiles. Indeed, vinylic iodides can be
employed in this process, and the results are summarized
in Table 1, entries 25-37.
The following observations can be made regarding
these results. Vinylic iodide 14 afforded the desired
products in good yields as single diastereoisomers (entries
25-27). Vinylic iodide 15, with a phenyl group adjacent
to the iodide, also afforded the desired products in good
yields as single diastereoisomers (entries 28-30). When
vinylic iodide 15 was reacted with lithium acetate,
compound 53 was formed in 50% yield as a single
diastereoisomer (compare this with entries 12 and 18).
Most interestingly, vinylic iodide 16 with a hydrogen beta
to the iodide also afforded the desired products in good
yields as single diastereoisomers (entries 31 and 32).
Vinylic iodide 22 afforded the anticipated product 56 in
(14) (a) Larock, R. C.; Mitchell, M. A. J . Am. Chem. Soc. 1976, 98,
6718. (b) Larock, R. C.; Mitchell, M. A. J . Am. Chem. Soc. 1978, 100,
180. (c) Larock, R. C.; Takagi, K.; Hershberger, S. S.; Mitchell, M. A.
Tetrahedron Lett. 1981, 22, 5231.

1882 J . Org. Chem., Vol. 64, No. 6, 1999
Larock and Han
62% yield as a single diastereoisomer when aniline was
used as the nucleophile (entry 33).
From the above results, we can conclude that not only
aryl iodides but also vinylic iodides (even those which
contain a hydrogen beta to palladium) afford the desired
products in good yields, usually as single diastereoiso-
mers. In addition, nucleophiles as diverse as morpholine,
potassium phthalimide, N-benzyl tosylamide, di-tert-
butyliminodicarboxylate, anilines, and phenols give the
desired products as single diastereoisomers in most cases.
Nucleophiles, such as diethyl malonate, usually give the
desired products as single diastereoisomers, unless cer-
tain substrates were used (entries 15, 23, and 36).
Nucleophiles, such as lithium azide and acetate, usually
give the desired products as inseparable mixtures of at
least two isomers (entries 5, 6, and 12). However, some
substrates in which one end of the π-allylpalladium
intermediate is much more sterically hindered than the
other end afford the desired products as single diastere-
oisomers (entries 18 and 30).
Compounds 57 and 58 were produced in 70% and 54%
yields as single diastereoisomers when vinylic iodide 19
was reacted with diethyl malonate or morpholine, re-
spectively (entries 34 and 35). It is indeed interesting that
the four-membered ring can be formed here, because we
have shown previously that cyclobutylcarbinyl palladium
compounds readily ring open and rearrange to π-allylpal-
ladium intermediates.15 Compounds 59 and 60 are formed
in 61% or 71% yields as inseparable mixtures of two
isomers in the ratios 60:40 and 62:38, respectively, when
vinylic iodide 25 was reacted with diethyl malonate or
aniline (entries 36 and 37). The poor selectivity in these
reactions could possibly be due to conformational effects
present in the π-allylpalladium intermediate introduced
by the presence of a tosyl group.
The structures of our cyclization products have been
elucidated by careful examination of their COSY, HMQC,
and NOESY spectra. These data are summarized and
discussed in the Supporting Information. The NOESY
spectral studies indicate that carbon nucleophiles (diethyl
malonate and 2-methyl-1,3-cyclohexanedione), anilines,
and lithium acetate give backside attack on the π-al-
lylpalladium intermediate, whereas sodium benzenesulfi-
nate and phenols afford products of frontside attack. The
stereochemistry of the rest of the compounds were
assigned on the basis of the assumption that soft nucleo-
philes give backside nucleophilic substitution, and hard
nucleophiles attack at palladium in the π-allylpalladium
intermediates and undergo reductive elimination. The
above assignment of hardness or softness to a specific
nucleophile is in agreement with literature data.6,9
This overall coupling process likely proceeds according
to the pathway illustrated in Scheme 3 (exemplified using
iodide 3). Generation and addition of an aryl- or vinylpal-
ladium intermediate to the internal carbon-carbon
double bond, followed by migration of palladium along
the carbon chain on the same face of the ring, results in
the formation of a π-allylpalladium species (73). Inter-
mediate 73 undergoes backside intermolecular nucleo-
philic attack to afford products when soft nucleophiles,
such as diethyl malonate, 2-methyl-1,3-cyclohexanedione,
morpholine, potassium phthalimide, N-benzyl tosyla-
mide, di-tert-butyl iminodicarboxylate, lithium azide,
anilines, and lithium acetate, are used. However, hard
nucleophiles, such as phenols and sodium benzenesulfi-
nate, first attack on the palladium to form intermediate
75, which subsequently undergoes reductive elimination
to afford products of the type 76. The observed regiose-
lectivities of this process are in agreement with literature
observations that the regioselectivity of nucleophilic
attack on the π-allylpalladium intermediates depends
greatly on very small steric differences that exist at the
two termini of the allylic system and that nucleophiles
other than organometallics attack at the less hindered
terminus.6,16 For some nucleophiles, such as lithium
acetate and diethylmalonate, larger steric differences at
the two termini of the allylic system are needed to afford
the desired products as single diastereoisomers.
This work presents a novel method for the highly
diastereoselective synthesis of polycyclic compounds con-
taining allylic functional groups and nicely complements
the recent intramolecular asymmetric Heck chemistry of
Shibasaki, in which beta hydride elimination, rather than
palladium migration, is observed. The facile preparation
of starting materials, good to excellent chemical yields,
and high diastereoselectivity of this process suggest that
this chemistry should find wide application in the total
synthesis of naturally occurring compounds.
Exp er im en ta l Section
Gen er a l. All 1H and 13C NMR spectra were recorded at 300
or 400 and 75.5 or 100 MHz, respectively. Thin-layer chroma-
tography (TLC) was performed using commercially prepared
60 mesh silica gel plates (Whatman K6F) and was visualized
with short wavelength UV light (254 nm) and basic KMnO4
solution [3 g KMnO4 + 20 g K2CO3 + 5 mL NaOH (5%) + 300
mL H2O].
Rea gen ts. All reagents were used directly as obtained
commercially unless otherwise noted. Anhydrous TBAC was
purchased from Lancaster. Palladium chloride was donated
by J ohnson Matthey, Inc. and Kawaken Fine Chemicals Co.,
Ltd. Pd(dba)2 was synthesized by a literature procedure.17 The
preparation of all starting materials is provided in the Sup-
porting Information.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed Re-
a ction s. Pd(dba)2 (14.4 mg, 0.025 mmol), TBAC (or LiCl), base,
nucleophile, organic iodide (0.25 mmol), and solvent (DMSO
or DMF) were added accordingly to an Ar-flushed 2 dram vial.
The vial was flushed with Ar for 2 min and heated in an oil
bath at the indicated temperature for the necessary period of
time. The reaction was monitored by TLC to establish comple-
tion. The reaction mixture was cooled, diluted with ether,
washed with brine solution, dried over anhydrous Na2SO4, and
decanted. The solvent was evaporated in vacuo, and the
product was isolated by flash chromatography (EtOAc/hex-
anes) on a silica gel column. The following compounds were
prepared by the above procedure, and the results are sum-
marized in Table 1.
Com p ou n d 26 (entry 1). The reaction mixture was chro-
matographed using 1:12 EtOAc/hexanes to yield a colorless
liquid: 1H NMR (CDCl3) δ 1.28 (t, J ) 7.2 Hz, 3H), 1.32 (t, J
) 7.2 Hz, 3H), 1.83 (dt, J ) 14.0, 4.0 Hz, 1H), 2.06 (m, 1H),
2.69 (m, 1H), 2.88 (m, 1H), 3.10 (m, 1H), 3.45 (d, J ) 10.0 Hz,
1H), 3.87 (dd, J ) 10.8, 8.4, 1H), 4.12 (dd, J ) 11.2, 3.6 Hz,
1H), 4.22 (q, J ) 6.8 Hz, 2H), 4.27 (q, J ) 7.2 Hz, 2H), 5.74
(dq, J ) 10.0, 1.6 Hz, 1H), 5.85 (dq, J ) 10.0, 2.0 Hz, 1H),
6.80 (d, J ) 7.6 Hz, 1H), 6.91 (td, J ) 7.6, 1.2 Hz, 1H), 7.10
(15) (a) Larock, R. C.; Song, H. Bull. Korean Chem. Soc. 1996, 17,
877. (b) Larock, R. C.; Yum, E. K. Synlett 1990, 529. (c) Larock, R. C.;
Song, H.; Kim, S.; J acobson, R. A. J . Chem. Soc., Chem. Commun. 1987,
834. (d) Larock, R. C.; Varaprath, S. J . Org. Chem. 1984, 49, 3432.
(16) Keinan, E.; Sahai, M. J . Chem. Soc., Chem. Commun. 1984,
648.
(17) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J . J .; Ibers, J . A. J .
Organomet. Chem. 1974, 65, 253.

Cross-Coupling of Aryl or Vinylic Iodides
J . Org. Chem., Vol. 64, No. 6, 1999 1883
(td, J ) 8.0, 1.2 Hz, 1H), 7.13 (d, J ) 8.0 Hz, 1H); 13C NMR
(CDCl3) δ 14.1, 14.2, 30.0, 31.0, 33.0, 33.7, 56.5, 61.4, 61.5,
66.5, 116.8, 120.8, 124.8, 127.4, 128.0, 129.0, 130.8, 154.7,
168.1, 168.2; IR (CHCl3) 1748, 1727 cm-1; HRMS for C20H24O5
calcd 344.1624, found 344.1628.
for C21H17NO3: C, 76.12; H, 5.17; N, 4.23. Found: C, 76.09;
H, 5.43; N, 4.12.
Com p ou n d 31 (entry 8). The reaction mixture was chro-
matographed using 1:5 EtOAc/hexanes to yield a light yellow,
very viscous liquid: 1H NMR (CDCl3) δ 1.88 (ddd, J ) 14.0,
7.6, 3.6 Hz, 1H), 2.13 (dt, J ) 14.0, 6.4 Hz, 1H), 2.42 (s, 3H),
2.49-2.54 (m, 1H), 2.85-2.90 (m, 1H), 3.92 (dd, J ) 10.8, 5.6
Hz, 1H), 3.98 (dd, J ) 11.0, 3.0 Hz, 1H), 4.20 (d, J ) 16.4 Hz,
1H), 4.28-4.32 (m, 1H), 4.68 (d, J ) 16.4 Hz, 1H), 5.22 (dt, J
) 10.0, 2.6 Hz, 1H), 5.78 (dt, J ) 10.0, 2.6 Hz, 1H), 6.74 (td,
J ) 8.0, 0.8 Hz, 2H), 6.84 (td, J ) 7.6, 0.8 Hz, 1H), 7.06 (td, J
) 7.6, 1.2 Hz, 1H), 7.25-7.30 (m, 3H), 7.35 (t, J ) 7.6 Hz,
2H), 7.43 (d, J ) 7.2 Hz, 2H), 7.64 (d, J ) 8.0 Hz, 2H); 13C
NMR (CDCl3) δ 21.5, 30.9, 32.9, 33.3, 48.2, 51.7, 67.1, 116.6,
121.1, 123.2, 127.0, 127.3, 127.5, 127.6, 128.1, 128.5, 129.0,
129.7, 131.9, 137.8, 138.9, 143.2, 154.4; IR (CHCl3) 1360, 1150
cm-1; HRMS for C27H27NO3S calcd 445.1712, found 445.1712.
Com p ou n d 32 (entry 9). The reaction mixture was chro-
matographed using 1:5 EtOAc/hexanes to yield a yellow liquid
(a mixture of the desired product and 1,5-diphenyl-1,4-penta-
dien-3-one). The above mixture was chromatographed further
using basic Alumina (Brockman activity III) with 1:15 EtOAc/
hexanes as an eluent to afford an off-white solid: mp 85-86
°C (EtOAc/hexanes); 1H NMR (CDCl3) δ 1.48 (s, 18H), 2.41 (dd,
J ) 8.4, 4.5 Hz, 2H), 2.75-2.77 (m, 1H), 3.43 (dd, J ) 9.3, 4.5
Hz, 1H), 4.08 (dd, J ) 8.1, 1.8 Hz, 1H), 4.17 (dd, J ) 8.1, 2.7
Hz, 1H), 4.45-4.47 (m, 1H), 5.69 (ddt, J ) 19.2, 10.5, 1.8 Hz,
2H), 6.78 (dd, J ) 8.1, 0.9 Hz, 1H), 6.92 (td, J ) 7.5, 1.2 Hz,
1H), 7.10 (td, J ) 7.5, 0.9 Hz, 1H), 7.31 (d, J ) 7.5 Hz, 1H);
13C NMR (CDCl3) δ 28.0, 30.8, 32.1, 33.8, 50.4, 68.5, 82.3, 116.7,
121.1, 123.3, 127.4, 127.68, 127.70, 131.4, 152.5, 154.9; IR
(CHCl3) 1776, 1736 cm-1; HRMS for C23H31NO5 calcd 401.2202,
found 401.2192. Anal. Calcd for C23H31NO5: C, 68.80; H, 7.78;
N, 3.49. Found: C, 68.78; H, 8.03; N, 3.36.
Com p ou n d 33 (entry 10). The reaction mixture was chro-
matographed using 1:7 EtOAc/hexanes to yield a yellow liquid
(74 mg, the desired product was inseparable from 1,5-diphenyl-
1,4-pentadien-3-one). The mixture was added to LiAlH4 (37
mg, 0.9 mmol) in ether (4 mL) at 0 °C. The resulting mixture
was stirred at 0 °C for 10 min and then at room temperature
for 4 h. After a standard workup, the reaction mixture was
chromatographed using 1:7 EtOAc/hexanes to yield 62.3 mg
of a white solid (90% yield): mp 96-98 °C (EtOAc/hexanes);
1H NMR (CDCl3) δ 1.98 (td, J ) 13.8, 4.2 Hz, 1H), 2.11 (dt, J
) 13.5, 3.6 Hz, 1H), 2.70-2.75 (m, 1H), 3.14 (dt, J ) 11.1, 4.8
Hz, 1H), 3.73 (br s, 1H), 3.84 (dd, J ) 10.8, 9.3 Hz, 1H), 3.95
(dd, J ) 8.1, 3.9 Hz, 1H), 4.14 (ddd, J ) 10.8, 3.6, 0.6 Hz, 1H),
5.82 (ddd, J ) 9.9, 4.2, 1.2 Hz, 1H), 5.99 (ddd, J ) 9.9, 4.5, 1.2
Hz, 1H), 6.62 (dd, J ) 8.4, 0.9 Hz, 2H), 6.72 (tt, J ) 7.4, 0.9
Hz, 1H), 6.85 (ddd, J ) 14.4, 7.5, 1.2 Hz, 2H), 7.07-7.12 (m,
2H), 7.19 (ddt, J ) 8.1, 6.9, 1.8 Hz, 2H); 13C NMR (CDCl3) δ
29.4, 33.6, 33.7, 46.4, 65.6, 113.0, 116.7, 117.5, 120.8, 125.3,
127.4, 128.5, 129.3, 129.4, 130.7, 146.8, 154.6; IR (CHCl3) 3408,
1051 cm-1; HRMS for C19H19NO calcd 277.1467, found 277.1461.
Anal. Calcd for C19H19NO: C, 82.28; H, 6.91; N, 5.05. Found:
C, 82.14; H, 7.13; N, 4.96.
Com p ou n d 27 (entry 2).
The reaction mixture was chromatographed using 1:3 EtOAc/
hexanes to yield a white solid: mp 152-153 °C (EtOAc/
1
hexanes); H NMR (CDCl3) δ 1.11 (s, 3H, H10), 1.59-1.73 (m,
1H), 1.77 (td, J ) 10.0, 3.6 Hz, 1H, H7), 1.93 (dt, J ) 14.1, 5.7
Hz, 1H, H8), 1.98-2.07 (m, 1H), 2.48 (dt, J ) 15.3, 3.9 Hz,
1H, H6), 2.58-2.69 (m, 5H, 4H + H3), 3.31 (dd, J ) 9.3, 5.1
Hz, 1H, H9), 4.06 (dd, J ) 10.8, 2.2 Hz, 1H, H2), 4.15 (dd, J )
10.8, 3.4 Hz, 1H, H1), 5.38 (dd, J ) 3.6, 1.2 Hz, 1H, H5), 5.80
(dt, J ) 10.2, 2.1 Hz, 1H, H4), 6.80 (dd, J ) 8.1, 1.2 Hz, 1H),
6.93 (td, J ) 7.5, 1.2 Hz, 1H), 7.11 (t, J ) 7.8 Hz, 1H), 7.16 (d,
J ) 7.8 Hz, 1H); 13C NMR (CDCl3) δ 11.2, 18.1, 27.7, 31.3,
33.9, 37.3, 37.5, 37.8, 68.3, 70.0, 117.1, 121.1, 123.5, 127.1,
127.5, 127.7, 130.5, 155.2, 208.78, 208.86; IR (CHCl3) 1726,
1692 cm-1; HRMS for C20H22O3 calcd 310.1569, found 310.1578.
Anal. Calcd for C20H22O3: C, 77.39; H, 7.14. Found: C, 77.03;
H, 7.39.
Com p ou n d 28 (entries 3 and 4). The reaction mixture was
chromatographed using straight EtOAc to yield a white solid:
mp 115-116.5 °C (EtOAc/hexanes); 1H NMR (CDCl3) δ 1.94-
2.13 (m, 2H), 2.55-2.73 (m, 5H), 2.87-2.91 (m, 1H), 3.30
(quintet, J ) 4.5 Hz, 1H), 3.73 (t, J ) 4.5 Hz, 4H), 3.95 (dd, J
) 10.8, 7.2 Hz, 1H), 4.10 (dd, J ) 10.8, 3.0 Hz, 1H), 5.80-5.90
(m, 2H), 6.80 (dd, J ) 8.1, 1.2 Hz, 1H), 6.90 (td, J ) 7.5, 1.2
Hz, 1H), 7.10 (tdd, J ) 7.2, 1.5, 0.6 Hz, 1H), 7.20 (d, J ) 7.5
Hz, 1H); 13C NMR (CDCl3) δ 28.8, 30.8, 34.1, 50.1, 56.9, 66.8,
67.4, 116.8, 120.8, 125.0, 127.3, 128.6, 129.5, 130.7, 154.7; IR
(CHCl3) 1115 cm-1; HRMS for C17H21NO2 calcd 271.1572, found
271.1568. Anal. Calcd for C17H21NO2: C, 75.25; H, 7.80; N,
5.16. Found: C, 75.21; H, 8.02; N, 5.07.
Com p ou n d 29 (entries 5 and 6). The reaction mixture was
chromatographed using 1:20 EtOAc/hexanes to yield a white
solid consisting of an inseparable mixture of four isomers (80:
10:5:5): mp 62-64 °C (hexanes); 1H NMR (CDCl3) δ 1.64-
1.76 (m, 0.05H), 1.97-2.14 (m, 1.80H), 2.2-2.6 (m, 0.25H),
2.74-2.81 (m, 0.95H), 2.95-3.05 (m, 0.10H), 3.16-3.24 (m,
0.90H), 3.67-3.82 (m, 0.95H), 3.88-3.93 (m, 0.75H), 4.02-
4.22 (m, 1.25H), 5.84-6.04 (m, 2.0H), 6.78-6.96 (m, 2.0H),
7.09-7.21 (m, 2.0H); 13C NMR (CDCl3) δ major isomer 29.2,
33.5, 33.9, 54.2, 65.2, 116.9, 120.9, 124.5, 126.9, 127.7, 129.2,
131.2, 154.5; IR (CHCl3) 2096 cm-1; HRMS for C13H13N3O calcd
227.1059, found 227.1060. Anal. Calcd for C13H13N3O: C,
68.70; H, 5.77; N, 18.49. Found: C, 68.78; H, 6.05; N, 18.26.
Com p ou n d 30 (entry 7). The reaction mixture was chro-
matographed using 1:5 EtOAc/hexanes to yield a white solid:
mp 150-152 °C (EtOAc/hexanes); 1H NMR (CDCl3) δ 2.36 (dt,
J ) 13.5, 6.3 Hz, 1H), 2.52 (ddd, J ) 13.5, 8.4, 0.75 Hz, 1H),
2.91-2.96 (m, 1H), 3.54 (dd, J ) 10.2, 6.3 Hz, 1H), 4.14 (s,
1H), 4.16 (s, 1H), 4.67-4.73 (m, 1H), 5.71 (dt, J ) 9.9, 2.4 Hz,
1H), 5.97 (dt, J ) 9.9, 2.7 Hz, 1H), 6.82 (dd, J ) 8.4, 1.2 Hz,
1H), 6.96 (td, J ) 7.5, 1.2 Hz, 1H), 7.13 (td, J ) 7.2, 0.9 Hz,
1H), 7.27 (d, J ) 6.9 Hz, 1H), 7.71 (dd, J ) 5.4, 3.0 Hz, 2H),
7.83 (dd, J ) 5.7, 3.0 Hz, 2H); 13C NMR (CDCl3) δ 31.3, 31.5,
33.7, 44.0, 67.7, 116.9, 121.2, 123.1, 123.3, 127.6, 128.1, 128.4,
130.0, 131.9, 134.0, 154.9, 168.1; IR (CHCl3) 1711 cm-1; HRMS
for C21H17NO3 calcd 331.1208; found: 331.1202. Anal. Calcd
Com p ou n d 34 (entry 11).
The reaction mixture was chromatographed using 1:4 EtOAc/
hexanes to yield white needle crystals: mp 155-156 °C
(EtOAc/hexames); 1H NMR (CDCl3) δ 2.18 (ddd, J ) 14.7, 10.2,
6.0 Hz, 1H, H8), 2.36 (dt, J ) 14.7, 4.2 Hz, 1H, H7), 2.64-2.70
(m, 1H, H3), 3.21 (dt, J ) 10.2, 5.1 Hz, 1H, H9), 3.65-3.70 (m,
1H, H6), 3.80 (dd, J ) 11.1, 8.4 Hz, 1H, H2), 4.11 (dd, J ) 11.1,
3.3 Hz, 1H, H1), 5.88 (ddd, J ) 10.2, 3.6, 2.1 Hz, 1H, H5), 6.08

1884 J . Org. Chem., Vol. 64, No. 6, 1999
Larock and Han
(ddd, J ) 10.2, 3.9, 2.0 Hz, 1H, H4), 6.78 (d, J ) 7.8 Hz, 1H),
6.90 (td, J ) 7.4, 1.2 Hz, 1H), 7.10 (t, J ) 7.2 Hz, 2H), 7.57-
7.71 (m, 3H), 7.94 (dd, J ) 6.9 Hz, 2H); 13C NMR (CDCl3) δ
26.8, 29.1, 33.2, 60.0, 66.0, 116.9, 121.0, 121.4, 123.6, 127.8,
128.7, 129.0, 129.2, 133.8, 133.9, 137.5, 154.3; IR (CHCl3) 1035,
1146 cm-1; HRMS for C19H18O3S calcd 326.0977, found 326.0975.
Anal. Calcd for C19H18O3S: C, 69.91; H, 5.56. Found: C, 69.63;
H, 5.51.
1H), 7.10 (dd, J ) 7.8, 1.5 Hz, 1H), 7.15 (dd, J ) 7.5, 1.5 Hz,
1H), 7.28 (d, J ) 7.5 Hz, 1H), 7.31 (d, J ) 7.5 Hz, 1H); 13C
NMR (CDCl3) δ 29.0, 33.5, 33.7, 65.2, 68.8, 116.0, 116.8, 120.8,
121.1, 125.2, 127.5, 128.4, 129.3, 129.6, 130.7, 154.5, 157.6;
IR (CHCl3) 1238, 1065, 1049 cm-1; HRMS for C19H18O2 calcd
278.1307, found 278.1304. Anal. Calcd for C19H18O2: C, 81.99;
H, 6.52. Found: C, 81.61; H, 6.81.
Com p ou n d 37 (entry 14). The reaction mixture was chro-
matographed using 1:9 EtOAc/hexanes to yield a colorless
liquid: 1H NMR (CDCl3) δ 2.00 (ddd, J ) 14.4, 11.7, 3.9 Hz,
1H), 2.29 (dt, J ) 14.1, 3.3 Hz, 1H), 2.81-2.89 (m, 1H), 3.52
(dt, J ) 11.7, 4.5 Hz, 1H), 3.82 (t, J ) 10.2 Hz, 1H), 4.17 (ddd,
J ) 10.8, 3.6, 0.6 Hz, 1H), 4.73 (dd, J ) 8.1, 3.9 Hz, 1H), 5.98
(dd, J ) 9.9, 4.2 Hz, 1H), 6.16 (dddd, J ) 9.9, 4.5, 1.5, 0.9 Hz,
1H), 6.58 (td, J ) 8.4, 0.9 Hz, 2H), 6.91 (td, J ) 9.9, 1.5 Hz,
1H), 6.99 (dd, J ) 8.1, 1.5 Hz, 1H), 7.12 (td, J ) 7.8, 1.5 Hz,
1H), 7.20-7.28 (m, 2H), 7.57 (dd, J ) 7.8, 1.5 Hz, 1H); 13C
NMR (CDCl3) δ 28.9, 33.7, 65.0, 71.4 (2C), 114.2, 116.6, 116.8,
120.8, 122.7, 125.2, 127.5, 127.9, 128.4, 129.4, 131.4, 133.6,
154.4, 154.5; IR (CHCl3) 1242, 1070, 1045 cm-1; HRMS for
Com p ou n d s 35a a n d 35b (entry 12). The reaction mixture
was chromatographed using 1:9 EtOAc/hexanes to yield a light
yellow liquid consisting of a 10:1 mixture of 35a /35b and 1,5-
diphenyl-1,4-pentadien-3-one (dba): 1H NMR (CDCl3) δ 1.93-
2.14 (m, 2H), 2.10 (s, 3H), 2.42-2.55 (m, 0.2H), 2.72-2.80 (m,
1H), 3.14 (dt, J ) 9.9, 4.8 Hz, 0.1H), 3.20 (dt, J ) 12.0, 4.5
Hz, 1H), 3.76 (t, J ) 10.8 Hz, 1H), 3.93 (t, J ) 11.1 Hz, 0.1H),
4.14 (ddd, J ) 10.8, 3.6, 0.9 Hz, 1H), 4.21 (ddd, J ) 10.5, 3.9,
1.5 Hz, 0.1H), 5.07 (dd, J ) 4.0, 2.0 Hz, 0.1H), 5.21 (dd, J )
7.8, 4.2 Hz, 1H), 5.80-5.83 (m, 0.1H), 5.93 (dd, J ) 10.2, 4.2
Hz, 1H), 6.02 (dddd, J ) 10.2, 4.5, 1.5, 0.9 Hz, 1H), 6.83 (dd,
J ) 8.1, 1.0 Hz, 1H), 6.91 (td, J ) 7.2, 1.2 Hz, 1H), 7.11 (td, J
) 7.8, 1.8 Hz, 1H), 7.18 (dd, J ) 7.8, 1.8 Hz, 1H); 13C NMR
(CDCl3) δ 21.2, 21.3, 28.9, 29.2, 30.0, 33.4, 33.6, 35.5, 63.7,
64.8, 66.0, 66.6, 116.7, 116.8, 120.1, 120.8, 123.4, 124.9, 127.56,
127.64, 127.9, 128.3, 128.5, 128.8, 129.4, 130.8, 131.1, 154.4,
170.5 (missing the carbonyl peak of the minor isomer).
Com p ou n d s 64 a n d 65 (eq 8). The mixture of the corre-
sponding acetate and 1,5-diphenyl-1,4-pentadien-3-one (49 mg)
was added to a mixture of MeOH (2.5 mL) and K2CO3 (84.6
mg, 0.6 mmol) at rt. The resulting mixture was stirred at rt
for 2.5 h, and then MeOH was removed in vacuo. Water (30
mL) was added to the residue, and the mixture was extracted
with ether three times (30 mL, 10 mL, 10 mL). The combined
ether layers were dried over Na2SO4 and chromatographed
using 1:3 EtOAc/hexanes to afford the major isomer as a
colorless liquid and the minor isomer as a colorless liquid.
Alcohol 64 (major isomer): 1H NMR (CDCl3) δ 1.83 (br s, 1H),
1.93-2.11 (m, 2H), 2.71-2.77 (m, 1H), 3.24 (dt, J ) 11.4, 5.1
Hz, 1H), 3.79 (dd, J ) 11.1, 9.9 Hz, 1H), 4.12 (ddd, J ) 11.1,
3.6, 0.9 Hz, 1H), 4.18 (dd, J ) 7.8, 3.9 Hz, 1H), 5.84 (dd, J )
9.9, 4.5 Hz, 1H), 6.03 (dddd, J ) 9.9, 4.5, 1.8, 0.9 Hz, 1H),
6.83 (dd, J ) 8.1, 1.2 Hz, 1H), 6.91 (td, J ) 7.2, 1.2 Hz, 1H),
7.11 (td, J ) 7.6, 1.5 Hz, 1H), 7.21 (dd, J ) 7.8, 1.5 Hz, 1H);
13C NMR (CDCl3) δ 28.6, 33.6, 36.9, 63.4, 65.1, 116.8, 120.8,
C
19H17BrO2 calcd 356.0412, found 356.0417.
Com p ou n d s 38 a n d 66-68 (entry 15).
125.4, 127.4, 129.2, 129.3, 131.4, 154.5; IR (CHCl3) 3368 cm-1
;
The reaction mixture was chromatographed using 1:9 EtOAc/
hexanes to yield a white solid consisting of an inseparable 66:
13:14:7 mixture of 38, 66, 67, and 68: 1H NMR (CDCl3) δ 1.19
(t, J ) 7.2 Hz, 2.89H), 1.23-1.31 (m, 5.0H), 2.18-2.29 (m,
1.99H), 2.43-2.57 (m, 1.26H), 2.60 (d, J ) 3.6 Hz, 0.07H),
2.63-2.69 (m, 0.93H), 2.70-2.76 (m, 0.16H), 2.89 (dd, J ) 16.0,
4.4 Hz, 0.30H), 3.06 (dd, J ) 16.0, 11.2 Hz, 0.30H), 3.12-3.22
(m, 1.20H), 3.48 (d, J ) 10.4 Hz, 1.0H), 3.51-3.56 (m, 0.50H),
3.60-3.78 (m, 0.62H), 3.89-4.05 (m, 2.16H), 4.09-4.26 (m,
4.91 H), 4.34 (dd, J ) 11.2, 4.0 Hz, 0.30 H), 4.67-4.76 (m,
2.48H), 5.55-5.59 (m, 1.01H), 5.72-5.79 (m, 0.40H), 5.85-
5.89 (m, 1.0H), 7.08 (d, J ) 7.2 Hz, 1.16H), 7.13-7.26 (m,
4.48H); 13C NMR (CDCl3) δ 13.3, 13.9, 13.98, 14.05, 27.9, 29.3,
34.8, 37.3, 38.8, 39.2, 41.1, 42.3, 43.6, 43.9, 49.9, 56.62, 56.66,
56.72, 61.1, 61.4, 61.5, 63.8, 73.2, 73.8, 74.5, 75.8, 76.6, 125.3,
126.3, 127.3, 127.5, 127.7, 127.9, 128.0, 128.5, 128.6, 128.70,
128.72, 128.79, 128.82, 128.87, 128.93, 130.3, 130.4, 130.8,
139.2, 139.3, 139.6, 139.8, 142.8, 143.4, 167.9, 168.1, 168.3,
169.7; IR (CHCl3) 1748, 1729 cm-1; HRMS for C21H26O5 calcd
358.1780, found 358.1782. After recrystallization of the mix-
ture of 38 plus 66-68, compound 38 was obtained in an almost
pure form: mp 100-104 °C (EtOAc/hexanes); 1H NMR (CDCl3)
δ 1.19 (t, J ) 6.8 Hz, 3H), 1.29 (t, J ) 5.4 Hz, 3H), 2.23 (t, J
) 4.6 Hz, 1H, H10), 2.25 (td, J ) 18.0, 4.8 Hz, 1H, H5), 2.53
(ddq, J ) 18.4, 11.6, 2.0 Hz, 1H, H9), 2.66 (dd, J ) 10.4, 2.4
Hz, H8), 3.14-3.18 (m, 1H, H11), 3.48 (d, J ) 10.4 Hz, 1H, H12),
3.89-4.01 (m, 2H, H3 and H4), 4.09-4.25 (m, 4H), 4.69 (d, J
) 14.0 Hz, 1H, H2), 4.74 (d, J ) 14.0 Hz, 1H, H1), 5.56-5.59
(m, 1H, H7), 5.86-5.90 (m, 1H, H6), 7.09 (d, J ) 7.2 Hz, 1H),
7.16 (td, J ) 7.2, 2.4 Hz, 1H), 7.19-7.24 (m, 2H); 13C NMR
(CDCl3) δ 14.0, 14.1, 29.4, 37.3, 38.9, 41.2, 56.7, 61.5, 61.6,
73.8, 74.5, 125.4, 126.3, 127.8, 128.7, 129.0, 130.4, 139.6, 142.9,
HRMS for C13H14O2 calcd 202.0994, found 202.0996. Alcohol
65 (minor isomer): 1H NMR (CDCl3) δ 1.59 (br s, 1H), 2.21
(dd, J ) 17.6, 8.8 Hz, 1H), 2.37-2.43 (m, 1H), 2.44-2.52 (m,
1H), 3.14-3.19 (m, 1H), 4.03 (t, J ) 10.6 Hz, 1H), 4.04-4.06
(m, 1H), 4.16 (ddd, J ) 10.8, 4.0, 1.2 Hz, 1H), 5.82-5.88 (m,
2H), 6.81 (d, J ) 8.4 Hz, 1H), 6.86 (td, J ) 7.2, 1.2 Hz, 1H),
7.07-7.15 (m, 2H); 13C NMR (CDCl3) δ 29.2, 29.8, 38.4, 64.4,
64.7, 116.6, 120.2, 126.0, 127.4, 127.8, 128.4, 128.7, 153.6; IR
(CHCl3) 3359 cm-1; HRMS for C13H14O2 calcd 202.0994, found
202.0999.
Com p ou n d 36 (entry 13).
The reaction mixture was chromatographed using 1:15 EtOAc/
hexanes to yield an off-white solid: mp 63-65 °C (EtOAc/
hexanes); 1H NMR (CDCl3) δ 2.05 (ddd, J ) 14.2, 11.7, 4.2
Hz, 1H, H8), 2.28 (dtd, J ) 14.1, 3.6, 0.9 Hz, 1H, H7), 2.79-
2.84 (m, 1H, H3), 3.36 (dt, J ) 11.7, 4.5 Hz, 1H, H9), 3.84 (dd,
J ) 11.1, 9.9 Hz, 1H, H1), 4.16 (ddd, J ) 11.1, 3.6, 0.9 Hz, 1H,
H2), 4.73 (dd, J ) 8.1, 4.2 Hz, 1H, H6), 5.96 (ddd, J ) 10.2,
4.5, 0.6 Hz, 1H, H4), 6.13 (dddd, J ) 10.2, 4.5, 1.8, 0.9 Hz, 1H,
H5), 6.83 (dd, J ) 8.1, 0.9 Hz, 1H), 6.89 (td, J ) 7.4, 1.2 Hz,
1H), 6.95 (dd, J ) 7.8, 0.9 Hz, 2H), 6.98 (dt, J ) 7.2, 0.9 Hz,

Cross-Coupling of Aryl or Vinylic Iodides
J . Org. Chem., Vol. 64, No. 6, 1999 1885
168.0 (one carbon missing as a result of overlap). Anal. Calcd
for C21H26O5: C, 70.37; H, 7.31. Found: C, 70.52; H, 7.39.
Com p ou n d 39 (entry 16). The reaction mixture was chro-
matographed using 1:1 EtOAc/hexanes to yield a light yellow
hexanes to yield a white solid: mp 114-116 °C (EtOAc/
hexanes); 1H NMR (CDCl3) δ 1.92 (ddd, J ) 13.0, 8.0, 4.4 Hz,
1H, H8), 2.27 (dtd, J ) 13.2, 5.6, 1.6 Hz, 1H, H9), 2.77 (d, J )
16 Hz, 1H, H1), 2.92 (d, J ) 16 Hz, 1H, H2), 3.42 (dd, J ) 6.0,
4.4 Hz, 1H, H10), 3.59 (d, J ) 10.8 Hz, 1H, H3), 3.65 (d, J )
10.8 Hz, 1H, H4), 3.85-3.89 (m, 1H, H7), 5.61 (dd, J ) 10.0,
1.2 Hz, 1H, H5), 5.91 (dd, J ) 10.0, 2.8 Hz, 1H, H6), 6.58 (dd,
J ) 8.8, 0.8 Hz, 2H), 6.69 (tt, J ) 7.6, 0.8 Hz, 1H), 7.13-7.21
(m, 6H), missing OH and NH; 13C NMR (CDCl3) δ 30.7, 40.9,
43.1, 45.6, 49.3, 68.6, 113.4, 117.5, 123.4, 125.0, 126.6, 126.7,
129.3, 131.4, 133.2, 141.3, 144.8, 147.0; IR (CHCl3) 3530, 3407
cm-1; HRMS for C20H21NO calcd 291.1623, found 291.1624.
Anal. Calcd for C20H21NO: C, 82.44; H, 7.26; N, 4.81. Found:
C, 83.08; H, 7.54; N, 4.75.
1
solid: mp 111-113 °C (EtOAc/hexanes); H NMR (CDCl3) δ
2.33-2.38 (m, 2H), 2.51-2.56 (m, 6H), 3.50-3.56 (m, 1H), 3.66
(t, J ) 4.2 Hz, 4H), 3.81 (dd, J ) 12.0, 3.9 Hz, 1H), 4.08 (br s,
1H), 4.71 (s, 2H), 5.66-5.72 (m, 1H), 5.95-6.02 (m, 1H), 7.10-
7.23 (m, 4H); 13C NMR (CDCl3) δ 29.9, 38.8, 40.6, 50.3, 60.8,
67.4, 73.6, 75.0, 125.9, 126.2, 127.5, 128.3, 128.7, 129.4, 129.6,
139.7; IR (CHCl3) 1118, 1005 cm-1; HRMS for C18H23NO2 calcd
285.1729, found 285.1733. Anal. Calcd for C18H23NO2: C, 75.76;
H, 8.12; N, 4.91. Found: C, 75.81; H, 8.20; N, 4.88.
Com p ou n d 40 (entry 17). The reaction mixture was chro-
matographed using 1:9 EtOAc/hexanes to yield a colorless
liquid: 1H NMR (CDCl3) δ 1.24 (t, J ) 7.2 Hz, 3H), 1.30 (t, J
) 7.2 Hz, 3H), 1.90 (ddd, J ) 14.0, 11.0, 4.0 Hz, 1H), 2.36 (dtd,
J ) 13.6, 4.4, 0.8 Hz, 1H), 2.71-2.74 (m, 1H), 2.98 (d, J )
16.0 Hz, 1H), 3.28 (d, J ) 8.8 Hz, 1H), 3.43 (d, J ) 16.0 Hz,
1H), 3.74 (s, 3H), 3.89 (t, J ) 4.0 Hz, 1H), 4.17 (qd, J ) 7.2,
0.8 Hz, 2H), 4.23 (qd, J ) 7.2, 2.8 Hz, 2H), 5.62 (dt, J ) 10.4,
1.2 Hz, 1H), 5.69 (ddd, J ) 10.0, 2.4, 1.2 Hz, 1H), 7.15-7.18
(m, 2H), 7.20-7.21 (m, 2H); 13C NMR (CDCl3) δ 14.0, 14.1,
26.0, 31.0, 43.1, 44.6, 52.2, 53.6, 56.2, 61.3 (2C), 123.0, 124.8,
126.7, 126.9, 130.1, 130.2, 140.3, 142.7, 168.07, 168.14, 175.0;
IR (CHCl3) 1730 cm-1; HRMS for C22H26O6 calcd 386.1729,
found 386.1728.
Com p ou n d 41 (entry 18). The reaction mixture was chro-
matographed using 1:9 EtOAc/hexanes to yield a light yellow
liquid: 1H NMR (CDCl3) δ 2.05 (s, 3H), 2.08 (ddd, J ) 13.4,
10.0, 4.2 Hz, 1H), 2.62 (dtd, J ) 13.2, 6.8, 1.0 Hz, 1H), 3.00 (d,
J ) 15.9 Hz, 1H), 3.45 (d, J ) 15.9 Hz, 1H), 3.76 (s, 3H), 3.96
(t, J ) 3.9 Hz, 1H), 5.10 (ddt, J ) 9.9, 5.7, 1.5 Hz, 1H), 5.69
(ddd, J ) 10.2, 1.8, 1.2 Hz, 1H), 5.78 (ddd, J ) 10.2, 1.5, 1.2
Hz, 1H), 7.16-7.29 (m, 4H); 13C NMR (CDCl3) δ 21.2, 27.8,
43.0, 44.3, 52.4, 53.7, 66.7, 123.0, 124.8, 127.0, 127.1, 129.2,
131.5, 139.8, 142.2, 170.6, 174.6; IR (CHCl3) 1735 cm-1; HRMS
for C15H14O2 (M+ - C2H4O2) calcd 226.0994, found 226.0996.
Com p ou n d 42 (entry 19).
Com p ou n d 44 (entry 21). The reaction mixture was chro-
matographed using 1:5 EtOAc/hexanes to yield a colorless
liquid: 1H NMR (CDCl3) δ 1.28 (t, J ) 7.2 Hz, 3H), 1.32 (t, J
) 7.2 Hz, 3H), 1.76 (dt, J ) 14.4, 3.6 Hz, 1H), 2.04 (ddd, J )
14.2, 11.2, 5.2 Hz, 1H), 2.58-2.62 (m, 1H), 2.90-2.95 (m, 1H),
3.02-3.06 (m, 1H), 3.04 (dd, J ) 11.2, 9.2 Hz, 1H), 3.25 (dd, J
) 11.2, 3.6 Hz, 1H), 3.48 (d, J ) 10.0 Hz, 1H), 4.22 (q, J ) 7.2
Hz, 2H), 4.27 (q, J ) 7.2 Hz, 2H), 5.75-5.82 (m, 2H), 6.52 (dd,
J ) 8.0, 0.8 Hz, 1H), 6.69 (td, J ) 7.4, 0.8 Hz, 1H), 6.98 (td, J
) 7.6, 1.2 Hz, 1H), 7.05 (d, J ) 7.6 Hz, 1H), missing NH; 13C
NMR (CDCl3) δ 14.1, 14.2, 31.5, 31.9, 33.6, 33.8, 43.5, 56.7,
61.4, 61.5, 114.6, 117.9, 124.2, 126.9, 129.1, 129.4, 130.6, 144.5,
168.2, 168.4; IR (CHCl3) 3412, 1729 cm-1; HRMS for C20H25
NO4 calcd 343.1784, found 343.1782.
-
Com p ou n d 45 (entry 22). The reaction mixture was chro-
matographed using 1:3 EtOAc/hexanes to yield a light yellow,
viscous liquid: 1H NMR (CDCl3) δ 1.84 (ddd, J ) 14.0, 6.8,
4.0 Hz, 1H), 2.13 (ddd, J ) 14.2, 8.0, 6.0 Hz, 1H), 2.41 (s, 3H),
2.45-2.50 (m, 1H), 2.81 (dt, J ) 8.4, 4.0 Hz, 1H), 2.99 (dd, J
) 11.2, 6.4 Hz, 1H), 3.17 (dd, J ) 11.2, 3.2 Hz, 1H), 3.72 (br s,
1H), 4.22 (d, J ) 16.4 Hz, 1H), 4.39-4.44 (m, 1H), 4.70 (d, J
) 16.4 Hz, 1H), 5.17 (dt, J ) 10.0, 2.6 Hz, 1H), 5.79 (dt, J )
10.0, 2.6 Hz, 1H), 6.42 (d, J ) 8.4 Hz, 1H), 6.56-6.62 (m, 2H),
6.93 (td, J ) 7.4, 1.6 Hz, 1H), 7.24-7.29 (m, 3H), 7.34 (t, J )
7.4 Hz, 2H), 7.44 (d, J ) 7.6 Hz, 2H), 7.66 (d, J ) 8.4 Hz, 2H);
13C NMR (CDCl3) δ 21.5, 32.3, 33.2, 33.4, 44.1, 48.1, 51.9, 114.6,
118.1, 122.4, 126.9, 127.0, 127.2, 127.5, 127.6, 128.1, 128.4,
129.7, 134.4, 137.9, 139.1, 143.1, 144.1; IR (CHCl3) 3408, 1335,
1158 cm-1; HRMS for C27H28N2O2S calcd 444.1872, found
444.1868.
Com p ou n d s 46a a n d 46b (entry 23). The reaction mixture
was chromatographed using 1:15 EtOAc/hexanes to yield a
light yellow liquid as an inseparable mixture of two isomers
(65:35): 1H NMR (CDCl3) δ 1.18-1.35 (m, 6H), 1.77 (dt, J )
14.1, 3.3 Hz, 0.65H), 2.00-2.13 (m, 1H), 2.19-2.34 (m, 0.35H),
2.66-2.76 (m, 1H), 2.92-3.27 (m, 3.65H), 3.36-3.53 (m,
1.35H), 4.09-4.31 (m, 4H), 4.41-4.58 (m, 1H), 4.47 (s, 1H),
5.54-5.58 (m, 0.35H), 5.71-5.84 (m, 1.65H), 6.50-6.60 (m,
1.35H), 6.66 (td, J ) 7.5, 0.9 Hz, 0.65H), 6.96-7.02 (m, 1.35H),
7.08 (dd, J ) 6.6, 0.9 Hz, 0.65H), 7.20-7.34 (m, 5H); 13C NMR
(CDCl3) δ 14.0, 14.1, 14.2, 30.0, 32.1, 32.4, 33.1, 33.4, 33.7,
36.9, 50.0, 51.1, 54.5, 55.4, 56.8, 57.2, 61.36, 61.44, 61.49, 61.54,
110.6, 111.6, 115.5, 116.6, 124.7, 124.8, 125.9, 126.4, 126.6,
126.8, 127.1, 127.2, 127.7, 128.4, 128.54, 128.57, 129.1, 129.5,
130.4, 138.4, 138.7, 143.7, 145.2, 168.0, 168.2, 168.4 (four
carbons missing as a result of overlap); IR (CHCl3) 1747, 1728
cm-1; HRMS for C27H31NO4 calcd 433.2253, found 433.2259.
Com p ou n d 47 (entry 24). The reaction mixture was chro-
matographed using 1:15 EtOAc/hexanes to yield a light yellow
oil: 1H NMR (CDCl3) δ 1.93-2.04 (m, 1H), 2.10 (dt, J ) 13.5,
3.0 Hz, 1H), 2.69-2.77 (m, 1 H), 3.10-3.27 (m, 3H), 3.83 (br
s, 1H), 4.00-4.02 (m, 1H), 4.49 (s, 2H), 5.86 (dd, J ) 9.9, 1.2
Hz, 1H), 5.94 (dd, J ) 9.9, 1.2 Hz, 1H), 6.55-6.74 (m, 5H),
6.95-7.04 (m, 2H), 7.16-7.34 (m, 7H); 13C NMR (CDCl3) δ
31.7, 33.4, 34.8, 46.9, 50.4, 55.4, 111.5, 113.1, 116.6, 117.4,
125.2, 126.6, 126.8, 127.2, 128.6, 129.3, 129.4 (2C), 131.1,
138.7, 145.1, 146.9; IR (CHCl3) 3402 cm-1; HRMS for C26H26N2
calcd 366.2096, found 366.2099.
The reaction mixture was chromatographed using 1:3 EtOAc/
hexanes to yield a light yellow liquid: 1H NMR (CDCl3) δ 1.26
(t, J ) 7.2 Hz, 3H, CH3), 1.29 (t, J ) 6.8 Hz, 3H, CH3), 1.88-
1.95 (m, 2H, H5 and H10), 2.17 (dt, J ) 13.2, 5.6 Hz, 1H, H11),
2.72 (d, J ) 15.6 Hz, 1H, H2), 2.73-2.79 (m, 1H, H8), 2.94 (d,
J ) 15.6 Hz, 1H, H1), 3.39 (d, J ) 8.0 Hz, 1H, H12), 3.41 (br s,
1H, H9), 3.62 (d, J ) 10.8 Hz, 1H, H3), 3.68 (d, J ) 10.8 Hz,
1H, H4), 4.16-4.25 (m, 4H, 2 CH2), 5.56 (dd, J ) 10.0, 2.4 Hz,
1H, H6), 5.75 (dd, J ) 10.0, 2.4 Hz, 1H, H7), 7.14-7.18 (m,
4H); 13C NMR (CDCl3) δ 14.02, 14.07, 27.1, 31.7, 41.1, 44.0,
49.6, 56.0, 61.32, 61.34, 68.6, 123.2, 124.9, 126.4, 126.0, 130.8,
132.9, 141.4, 144.6, 168.37, 168.38; IR (CHCl3) 3510, 1728
cm-1; HRMS for C21H26O5 calcd 358.1780, found 358.1789.
Com p ou n d 43 (entry 20).
Com p ou n d 48 (entry 25). The reaction mixture was chro-
The reaction mixture was chromatographed using 1:3 EtOAc/
matographed using 1:9 EtOAc/hexanes to yield a colorless

1886 J . Org. Chem., Vol. 64, No. 6, 1999
Larock and Han
liquid consisting of a 2.3:1 mixture of compound 48 and diethyl
malonate: 1H NMR (CDCl3) δ 1.24-1.31 (m, 6H), 1.58 (ddd, J
) 13.0, 11.1, 4.2 Hz, 1H), 1.67 (d, J ) 1.2 Hz, 3H), 1.84 (dt, J
) 13.2, 0.9 Hz, 1H), 2.26 (d, J ) 15.9 Hz, 1H), 2.85-2.95 (m,
2H), 3.24 (d, J ) 9.3 Hz, 1H), 3.43 (br s, 1H), 3.69 (s, 3H),
4.16-4.25 (m, 4H), 5.12 (d, J ) 0.9 Hz, 1H), 5.60 (dd, J ) 10.2,
2.4 Hz, 1H), 5.70 (dt, J ) 10.2, 1.5 Hz, 1H); 13C NMR (CDCl3)
δ 13.98, 14.0, 16.5, 28.0, 31.6, 45.8, 47.9, 52.0, 52.4, 56.3, 61.2,
61.4, 126.4, 129.0, 131.1, 138.3, 168.2, 168.3, 175.8; IR (CHCl3)
1753, 1730 cm-1; HRMS for C19H26O6 calcd 350.1729, found
350.1729.
hexanes to yield white crystals: mp 108-110 °C (EtOAc/
hexanes); 1H NMR (CDCl3) δ 1.87 (ddd, J ) 13.5, 9.3, 1.5 Hz,
1H, H8), 1.96 (s, 3H, H7), 2.00-2.08 (m, 1H, H9), 3.04 (dd, J )
16.5, 2.1 Hz, 1H, H1), 3.34 (dd, J ) 16.5, 2.4 Hz, 1H, H2), 3.77
(s, 3H, H3), 4.05 (br s, 1H, H10), 5.08 (dd, J ) 9.0, 5.4 Hz, 1H,
H6), 5.91 (br s, 2H, H4 and H5), 7.03-7.31 (m, 10H); 13C NMR
(CDCl3) δ 21.1, 27.8, 47.6, 48.7, 50.7, 52.5, 66.4, 127.0, 127.1,
127.9, 128.2, 128.45, 128.47, 128.5, 131.9, 134.6, 136.3, 136.4,
138.7, 170.4, 175.2; IR (CHCl3) 1729 cm-1; HRMS for C25H24O4
calcd 388.1675, found 388.1670. Anal. Calcd for C25H24O4: C,
77.30; H, 6.23. Found: C, 77.11; H, 6.34.
Com p ou n d 54 (entry 31). The reaction mixture was chro-
matographed using 1:9 EtOAc/hexanes to yield a colorless
liquid: 1H NMR (CDCl3) δ 1.26 (t, J ) 7.2 Hz, 3H), 1.28 (t, J
) 7.2 Hz, 3H), 1.65 (ddd, J ) 13.2, 11.1, 4.2 Hz, 1H), 1.92 (dt,
J ) 13.2, 4.5 Hz, 1H), 2.44 (d, J ) 16.2 Hz, 1H), 2.85-2.95
(m, 2H), 3.25 (d, J ) 9.0 Hz, 1H), 3.46 (br s, 1H), 3.71 (s, 3H),
4.20 (q, J ) 7.2 Hz, 2H), 4.21 (q, J ) 7.2 Hz, 2H), 5.53-5.78
(m, 4H); 13C NMR (CDCl3) δ 14.0, 27.7, 31.7, 44.1, 45.7, 52.0,
52.1, 56.3, 61.3, 128.8, 129.2, 130.9, 133.1, 168.17, 168.26,
175.7 (two carbons missing as a result of overlap); IR (CHCl3)
1735 cm-1; HRMS for C18H24O6 calcd 336.1573, found 336.1570.
Com p ou n d 49 (entry 26). The reaction mixture was chro-
matographed using 1:7 EtOAc/hexanes to yield a light yellow
liquid: 1H NMR (CDCl3) δ 1.65 (ddd, J ) 13.0, 10.2, 4.2 Hz,
1H), 1.71 (d, J ) 0.9 Hz, 3H), 2.16 (dt, J ) 12.9, 4.2 Hz, 1H),
2.29 (d, J ) 16.2 Hz, 1H), 2.93 (dd, J ) 16.2, 1.2 Hz, 1H), 3.45-
3.50 (m, 1H), 3.59 (br s, 1H), 3.72 (s, 3H), 3.99-4.04 (m, 1H),
5.18 (s, 1H), 5.63 (dd, J ) 10.2, 1.5 Hz, 1H), 5.87 (d, J ) 10.2
Hz, 1H), 6.61 (d, J ) 7.5 Hz, 2H), 6.69 (t, J ) 7.5 Hz, 1H),
7.16 (dd, J ) 8.4, 7.2 Hz, 2H); 13C NMR (CDCl3) δ 16.6, 31.2,
45.6, 46.0, 47.9, 52.2, 52.6, 113.5, 117.4, 126.3, 129.3, 130.9,
131.0, 138.6, 147.0, 175.9; IR (CHCl3) 3395, 1728 cm-1; HRMS
for C18H21NO2 calcd 283.1572, found 283.1572.
Com p ou n d 55 (entry 32). The reaction mixture was chro-
matographed using 1:7 EtOAc/hexanes to yield a light yellow
liquid: 1H NMR (CDCl3) δ 1.72 (ddd, J ) 13.0, 10.2, 4.5 Hz,
1H), 2.21 (dt, J ) 12.9, 4.2 Hz, 1H), 2.46 (ddd, J ) 16.2, 3.6,
2.4 Hz, 1H), 2.97 (ddd, J ) 16.2, 5.1, 2.7 Hz, 1H), 3.47-3.52
(m, 1H), 3.58 (br s, 1H), 3.73 (s, 3H), 3.97-4.03 (m, 1H), 5.58-
5.73 (m, 3H), 5.88 (dt, J ) 10.2, 1.2 Hz, 1H), 6.60 (dd, J ) 8.4,
0.9 Hz, 2H), 6.70 (tt, J ) 7.2, 1.2 Hz, 1H), 7.16 (dd, J ) 8.4,
7.2 Hz, 2H); 13C NMR (CDCl3) δ 30.8, 44.0, 45.6, 45.8, 52.2,
52.3, 113.4, 117.5, 129.0, 129.3, 130.8, 131.0, 133.1, 146.9,
175.8; IR (CHCl3) 3395, 1726 cm-1; HRMS for C17H19NO2 calcd
269.1416, found 269.1412.
Com p ou n d 50 (entry 27). The reaction mixture was chro-
matographed using 1:20 EtOAc/hexanes to yield a colorless
liquid: 1H NMR (CDCl3) δ 1.70 (d, J ) 0.9 Hz, 3H), 2.04 (ddd,
J ) 13.2, 10.2, 4.5 Hz, 1H), 2.25-2.35 (m, 2H), 2.92 (d, J )
16.2 Hz, 1H), 3.59 (br s, 1H), 3.74 (s, 3H), 4.79-4.85 (m, 1H),
5.17 (s, 1H), 5.73 (d, J ) 10.2 Hz, 1H), 5.99 (d, J ) 10.2 Hz,
1H), 6.70 (td, J ) 7.5, 0.9 Hz, 1H), 6.83 (dd, J ) 8.1, 0.9 Hz,
1H), 7.26 (td, J ) 7.8, 1.5 Hz, 1H), 7.77 (dd, J ) 7.8, 1.8 Hz,
1H); 13C NMR (CDCl3) δ 16.6, 30.3, 45.5, 48.2, 52.3, 52.5, 71.8,
88.1, 114.1, 122.7, 126.1, 128.6, 129.2, 132.3, 138.6, 139.7,
156.6, 175.4; IR (CHCl3) 1727, 1241, 1063 cm-1; HRMS for
C
18H19IO3 calcd 410.0379, found 410.0378.
Com p ou n d 56 (entry 33). The reaction mixture was chro-
matographed using 1:9 EtOAc/hexanes to yield an off-white
solid: mp 160-162 °C (EtOAc/hexanes); H NMR (CDCl3) δ
Com p ou n d 51 (entry 28). The reaction mixture was chro-
1
matographed using 1:7 EtOAc/hexanes to yield a very viscous,
light yellow liquid: 1H NMR (CDCl3) δ 1.04 (t, J ) 7.2 Hz,
3H), 1.19 (t, J ) 7.2 Hz, 3H), 1.60-1.70 (m, 1 H), 1.73-1.81
(m, 1H), 2.66-2.74 (m, 1H), 3.04 (dd, J ) 16.2, 2.1 Hz, 1H),
3.17 (d, J ) 9.3 Hz, 1H), 3.32 (dd, J ) 16.2, 2.4 Hz, 1H), 3.75
(s, 3H), 3.87-4.17 (m, 5H), 5.82 (dd, J ) 10.2, 1.8 Hz, 1H),
5.88 (dd, J ) 10.2, 1.8 Hz, 1H), 7.04-7.26 (m, 10H); 13C NMR
(CDCl3) δ 13.8, 13.9, 26.2, 31.4, 47.8, 49.0, 50.6, 52.3, 56.2,
61.1, 126.8, 127.8, 128.2, 128.5, 129.8, 130.3, 134.7, 136.47,
136.53, 138.7, 167.9, 168.0, 175.6 (three carbons missing as a
result of overlap); IR (CHCl3) 1729 cm-1; HRMS for C30H32O6
calcd 488.2199, found 488.2205.
1.40-1.56 (m, 2H), 1.70 (d, J ) 12.6 Hz, 2H), 1.84-1.94 (m,
1H), 1.98-2.12 (m, 3H), 2.47-2.61 (m, 2H), 3.38 (t, J ) 11.1
Hz, 1H), 3.77 (br s, 1H), 3.83 (dd, J ) 11.4, 4.8 Hz, 1H), 3.96-
4.05 (m, 2H), 5.49 (t, J ) 3.3 Hz, 1H), 5.74 (dd, J ) 9.9, 4.5
Hz, 1H), 5.91 (dd, J ) 9.9, 5.1 Hz, 1H), 6.62 (d, J ) 7.8 Hz,
2H), 6.69 (t, J ) 7.5 Hz, 1H), 7.18 (t, J ) 7.5 Hz, 2H); 13C
NMR (CDCl3) δ 20.6, 25.3, 29.6, 29.7, 34.8, 37.4, 47.0, 66.9,
71.6, 112.9, 117.2, 124.2, 128.9, 129.3, 129.9, 138.5, 146.8; IR
(CHCl3) 3335 cm-1; HRMS for C19H23NO calcd 281.1780, found
281.1780. Anal. Calcd for C19H23NO: C, 81.10; H, 8.24; N, 4.98.
Found: C, 81.23; H, 8.38; N, 5.00.
Com p ou n d 57 (entry 34). The reaction mixture was chro-
matographed using 1:12 EtOAc/hexanes to yield a colorless
liquid consisting of a 2.9:1 mixture of compound 57 and diethyl
malonate: 1H NMR (CDCl3) δ 1.24 (t, J ) 7.2 Hz, 6H), 1.34
(ddd, J ) 13.6, 11.2, 4.4 Hz, 1H), 1.46 (d, J ) 1.2 Hz, 3H),
1.59 (d, J ) 1.6 Hz, 3H), 2.08 (dtd, J ) 13.6, 4.0, 0.8 Hz, 1H),
2.42 (dt, J ) 14.8, 1.2 Hz, 1H), 2.87-2.95 (m, 1H), 2.99 (d, J
) 15.6 Hz, 1H), 3.26 (d, J ) 9.2 Hz, 1H), 3.64-3.68 (m, 1H),
3.67 (s, 3H), 4.15-4.21 (m, 4H), 5.73 (dt, J ) 10.2, 1.6 Hz,
1H), 5.95 (ddd, J ) 10.2, 2.8, 0.8 Hz, 1H); 13C NMR (CDCl3) δ
14.0, 19.1, 19.3, 27.2, 31.9, 40.6, 41.3, 43.0, 52.0, 56.4, 61.28,
61.30, 125.8, 126.4, 129.48, 129.55, 168.2, 168.3, 175.4 (one
Com p ou n d 52 (entry 29). The reaction mixture was chro-
matographed using 1:1 EtOAc/hexanes to yield a light yellow
oil: 1H NMR (CDCl3) δ 1.72 (ddd, J ) 13.1, 11.1, 4.2 Hz, 1H),
1.88 (dtd, J ) 13.2, 4.2, 1.2 Hz, 1H), 2.22-2.40 (m, 4 H), 2.89-
2.95 (m, 1H), 3.02 (dd, J ) 16.5, 2.1 Hz, 1H), 3.27 (dd, J )
16.5, 3.0 Hz, 1H), 3.54-3.67 (m, 4H), 3.76 (s, 3H), 4.11 (br s,
1H), 5.83 (dd, J ) 10.2, 2.1 Hz, 1H), 5.91 (d, J ) 10.2 Hz, 1H),
7.04-7.27 (m, 10H); 13C NMR (CDCl3) δ 21.7, 47.9, 48.7, 49.3,
50.7, 52.2, 56.0, 67.2, 126.8, 127.8, 128.26, 128.35 (2C), 128.4,
131.2, 131.5, 134.6, 136.4, 136.6, 138.6, 175.5; IR (CHCl3) 1730,
1116 cm-1; HRMS for C27H29NO3 calcd 415.2147, found
415.2146.
carbon missing as a result of overlap); IR (CHCl3) 1730 cm-1
HRMS for C20H28O6 calcd 364.1886, found 364.1890.
;
Com p ou n d 53 (entry 30).
Com p ou n d 58 (entry 35). The reaction mixture was chro-
matographed using 2:1 EtOAc/hexanes to yield a colorless
liquid: 1H NMR (CDCl3) δ 1.43-1.50 (m, 1H), 1.45 (d, J ) 0.8
Hz, 3H), 1.59 (d, J ) 1.6 Hz, 3H), 2.14 (dtd, J ) 13.2, 4.0, 1.2
Hz, 1H), 2.39 (dt, J ) 14.8, 1.2 Hz, 1H), 2.52-2.61 (m, 4H),
2.99 (dd, J ) 14.8, 1.2 Hz, 1H), 3.19-3.23 (m, 1H), 3.69 (s,
3H), 3.70 (t, J ) 4.8 Hz, 4H), 3.73 (br s, 1H), 5.89 (d, J ) 10.4
Hz, 1H), 5.98 (ddd, J ) 10.4, 2.4, 0.8 Hz, 1H); 13C NMR (CDCl3)
δ 19.3, 19.4, 23.0, 41.1, 41.8, 42.7, 49.0, 52.1, 57.0, 67.5, 125.4,
126.9, 130.2, 131.3, 175.5; IR (CHCl3) 1729 cm-1; HRMS for
The reaction mixture was chromatographed using 1:9 EtOAc/
C17H25NO3 calcd 291.1834, found 291.1839.

Cross-Coupling of Aryl or Vinylic Iodides
J . Org. Chem., Vol. 64, No. 6, 1999 1887
Com p ou n d s 59a a n d 59b (entry 36).
as a result of overlap). Anal. Calcd for C26H35NO6S: C, 63.78;
H, 7.20; N, 2.86. Found: C, 63.80; H, 7.29; N, 2.84.
Com p ou n d s 60a a n d 60b (entry 37). The reaction mixture
was chromatographed using 1:7 EtOAc/hexanes to yield an off-
white solid consisting of an inseparable mixture of two isomers
1
(62:38): mp 178-188 °C (EtOAc/hexanes); H NMR (CDCl3)
δ 1.51 (s, 1.86H), 1.62 (s, 1.14H), 1.68 (s, 3H), 1.48-1.74 (m,
1.38H), 1.81-1.85 (m, 0.62H), 2.10-2.21 (m, 1H), 2.40 (s,
1.14H), 2.42 (s, 1.86H), 2.37-2.50 (m, 1H), 2.69 (d, J ) 13.2
Hz, 0.62H), 2.94-2.98 (m, 1H), 3.10 (d, J ) 13.6 Hz, 0.38H),
3.55-3.62 (m, 0.76H), 3.69-3.73 (m, 1.62H), 3.91 (s, 0.62H),
4.37 (d, J ) 14.0 Hz, 0.38H), 4.52 (d, J ) 13.6 Hz, 0.62H),
5.67-5.88 (m, 2H), 6.51 (d, J ) 8.0 Hz, 0.76H), 6.54 (d, J )
8.0 Hz, 1.24H), 6.65 (t, J ) 7.2 Hz, 0.62H), 6.70 (t, J ) 7.2 Hz,
0.38H), 7.11 (t, J ) 8.0 Hz, 1.24H), 7.16 (t, J ) 8.0 Hz, 0.76H),
7.27 (d, J ) 8.0 Hz, 0.76H), 7.31 (d, J ) 8.0 Hz, 1.24H), 7.66
(d, J ) 8.0 Hz, 1.24H), 7.67 (d, J ) 8.0 Hz, 0.76H); 13C NMR
(CDCl3) δ 19.6, 20.0, 20.47, 20.49, 21.6, 24.3, 27.0, 29.1, 29.6,
35.4, 36.9, 43.3, 44.3, 44.5, 46.1, 47.2, 49.9, 112.9, 113.2, 117.50,
117.55, 124.8, 126.3, 126.4, 127.4, 127.67, 127.72, 127.75,
129.28, 129.36, 129.45, 129.54, 129.7, 131.0, 133.6, 134.0,
143.4, 143.5, 146.5, 146.8 (two carbons missing as a result of
overlap); IR (CHCl3) 3390, 1335, 1159 cm-1; HRMS for
The reaction mixture was chromatographed using 1:5 EtOAc/
hexanes to yield a white solid consisting of an inseparable
mixture of two isomers (60:40): 1H NMR (CDCl3) δ 1.07 (d, J
) 14.2 Hz, 0.6H), 1.16-1.24 (m, 6H), 1.64 (s, 3H), 1.69 (s,
1.2H), 1.71 (s, 1.8H), 1.65-1.71 (m, 1H), 1.74-1.78 (m, 1H),
2.13 (t, J ) 12 Hz, 0.6H), 2.29-2.46 (m, 0.4H), 2.38 (s, 1.2H),
2.39 (s, 1.8H), 2.43 (t, J ) 11.6 Hz, 0.4H), 2.58-2.64 (m, 1H),
2.76-2.97 (m 2H), 3.30 (d, J ) 10.4 Hz, 0.4H), 3.35 (d, J )
11.2 Hz, 0.6H), 3.48 (dd, J ) 11.2, 4.4 Hz, 0.4H), 3.63 (ddd, J
) 12.0, 4.4, 1.6 Hz, 0.6H), 4.09-4.18 (m, 4H), 4.36 (d, J ) 13.6
Hz, 0.4H), 4.48 (d, J ) 13.2 Hz, 0.6H), 5.45-5.49 (m, 0.4H),
5.58-5.69 (m, 1.6H), 7.23-7.28 (m, 2H), 7.59-7.62 (m, 2H);
13C NMR (CDCl3) δ 14.08, 14.11, 19.7, 19.8, 20.5, 20.6, 21.6,
24.2, 25.0, 29.7, 30.0, 34.4, 35.2, 36.1, 37.2, 43.1, 44.4, 45.8,
46.6, 56.7, 57.4, 61.6, 61.7, 124.6, 126.4, 127.4, 127.6, 127.7,
127.9, 128.1, 129.1, 129.66, 129.70, 130.1, 133.6, 133.9, 143.3,
143.5, 167.86, 167.92, 167.97, 168.2 (six carbons missing as a
C
C
25H30N2O2S calcd 422.2028, found 422.2030. Anal. Calcd for
25H30N2O2S: C, 71.06; H, 7.16; N, 6.63. Found: C, 69.89; H,
7.24; N, 6.40.
Ack n ow led gm en t. We gratefully acknowledge par-
tial financial support from the Petroleum Research
Fund, administered by the American Chemical Society;
J ohnson Matthey, Inc. and Kawaken Fine Chemicals
Co., Ltd. for the palladium compounds; and Merck for
Academic Development Awards in 1997 and 1998.
result of overlap); IR (CHCl3) 1747, 1728, 1337, 1163 cm-1
;
HRMS for C26H35NO6S calcd 489.2185, found 489.2185. The
mixture was recrystallized from EtOAc/hexanes to afford pure
59a as white crystals: mp 172-174 °C; 1H NMR (CDCl3) δ
1.08 (d, J ) 14.4 Hz, 1H, H9), 1.23 (t, J ) 6.8 Hz, 3H), 1.26 (t,
J ) 7.2 Hz, 3H), 1.68 (s, 3H, H13), 1.69-1.77 (m, 1H, H10), 1.75
(s, 3H, H14), 2.17 (t, J ) 12.0 Hz, 1H, H3), 2.33-2.40 (m, 1H,
H5), 2.44 (s, 3H), 2.68 (d, J ) 13.2 Hz, 1H, H1), 2.83 (dt, J )
13.6, 3.8 Hz, 1H, H11), 2.91 (dt, J ) 10.4, 5.2 Hz, 1H, H8), 3.40
(d, J ) 11.2 Hz, 1H, H12), 3.68 (ddd, J ) 11.6, 4.0, 1.6 Hz, 1H,
H4), 4.13-4.23 (m, 4H), 4.53 (d, J ) 13.6 Hz, 1H, H2), 5.66-
5.74 (m, 2H, H6 and H7), 7.32 (d, J ) 8.2 Hz, 2H), 7.65 (d, J )
8.2 Hz, 2H); 13C NMR (CDCl3) δ 14.1, 19.6, 20.5, 21.5, 24.9,
30.0, 34.3, 35.2, 44.3, 46.5, 56.6, 61.5, 126.4, 127.7, 127.8, 129.0,
129.6, 130.1, 133.6, 143.4, 167.9, 168.1 (two carbons missing
Su p p or tin g In for m a tion Ava ila ble: Procedures for the
preparation of all starting materials; discussion of the 2D
(COSY, HMQC, and NOESY) spectral results for compounds
27, 34, 36, 38, 42, 43, 53, 59a , and 59b; copies of the COSY,
HMQC, and NOESY spectra for the above compounds; a table
summarizing the spectral data for the above compounds; and
copies of the 1H and 13C NMR spectra for compounds 26, 31,
35a and 35b, 64, 65, 37, 38 and 66-68, 40-42, 44-52, 54,
55, 57, 58, 59a a n d 59b, a n d 60a a n d 60b. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O981876F