Palladacycles with a metal-bonded sp3-hybridized carbon as intermediates in the synthesis of 2,2,3,4-tetrasubstituted 2H-1-benzopyrans and 1,2-dihydroquinolines. Effects of auxiliary ligands and substitution at a palladium-bonded tertiary carbon

Article abstract of DOI:10.1021/om0491544

Prompted by the failure to prepare stable oxapalladacycles L ₂Pd-1-C₆H₄-2-OC(R¹)COOEt with PPh₃ ligands (L = PPh₃) and substituents R¹ other than hydrogen, systematic studies on the effects of steric and electronic properties of auxiliary ligands L and substituents R¹ (alkyl, aryl) on the feasibility of formation, stability, and reactivity of the oxapalladacycles were performed. Using N,N,N′,N′-tetramethyl-1,2- ethylenediamine bidentate ligand (L-L = TMEDA), stable palladacycles featuring substituents R¹ (Me, Et, i-Pr, and Ph) were prepared, and the presence of palladium-bonded tertiary sp³-hybridized carbons was confirmed by X-ray crystallographic analyses on palladacycles with i-Pr and Ph substituents R¹. Relying on ³¹P NMR analyses of crude reaction mixtures, ligand displacement reactions of palladacycles (TMEDA)Pd-1-C₆H₄-2-OC(R¹COOEt with monodentate phosphines (PPh₃ and PPh₂Me) were studied, as well as base-mediated ring-closure reactions of arylpalladium-(II) iodo complexes (PPh₃)₂Pd(-1-C₆H₄-2-OCHR ¹COOEt)I and (PPh₂Me)₂Pd(-1-C₆H ₄-2-OCHR¹-COOEt)I. In both series, higher conversions to corresponding palladacycles L₂Pd-1-C₆H₄-2- OC(R¹)COOEt were achieved with PPh₂Me ligands, and both the transformations were negatively affected by an increase in the steric bulk of substituents R¹. Although the palladacycles with monodentate phosphines could not be isolated as stable entities, IR spectroscopic analyses supported the presence of a Csp³-Pd bond. On the basis of these studies, a one-pot conversion of stable arylpalladium(II) iodo complexes with PPh₂Me ligands into 2,2,3,4-tetrasubstituted 2H-1-benzopyrans and 1,2-dihydroquinolines via the insertion of unsymmetrical alkynes into in situ formed palladacycles was developed, providing the heterocycles in good yields (44-80%) as single regioisomers.

Full text of DOI:10.1021/om0491544

Organometallics 2005, 24, 945-961
945
Palladacycles with a Metal-Bonded sp3-Hybridized
Carbon as Intermediates in the Synthesis of
2,2,3,4-Tetrasubstituted 2H-1-Benzopyrans and
1,2-Dihydroquinolines. Effects of Auxiliary Ligands and
Substitution at a Palladium-Bonded Tertiary Carbon
Genliang Lu, Janelle L. Portscheller, and Helena C. Malinakova*
Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive,
Lawrence, Kansas 66045
Received October 30, 2004
Prompted by the failure to prepare stable oxapalladacycles L2Pd-1-C6H4-2-OC(R1)COOEt
with PPh3 ligands (L ) PPh3) and substituents R1 other than hydrogen, systematic studies
on the effects of steric and electronic properties of auxiliary ligands L and substituents R1
(alkyl, aryl) on the feasibility of formation, stability, and reactivity of the oxapalladacycles
were performed. Using N,N,N′,N′-tetramethyl-1,2-ethylenediamine bidentate ligand (L-L
) TMEDA), stable palladacycles featuring substituents R1 (Me, Et, i-Pr, and Ph) were
prepared, and the presence of palladium-bonded tertiary sp3-hybridized carbons was
confirmed by X-ray crystallographic analyses on palladacycles with i-Pr and Ph substituents
R1. Relying on 31P NMR analyses of crude reaction mixtures, ligand displacement reactions
of palladacycles (TMEDA)Pd-1-C6H4-2-OC(R1)COOEt with monodentate phosphines (PPh3
and PPh2Me) were studied, as well as base-mediated ring-closure reactions of arylpalladium-
(II) iodo complexes (PPh3)2Pd(-1-C6H4-2-OCHR1COOEt)I and (PPh2Me)2Pd(-1-C6H4-2-OCHR1-
COOEt)I. In both series, higher conversions to corresponding palladacycles L2Pd-1-C6H4-2-
OC(R1)COOEt were achieved with PPh2Me ligands, and both the transformations were
negatively affected by an increase in the steric bulk of substituents R1. Although the
palladacycles with monodentate phosphines could not be isolated as stable entities, IR
spectroscopic analyses supported the presence of a Csp3-Pd bond. On the basis of these
studies, a one-pot conversion of stable arylpalladium(II) iodo complexes with PPh2Me ligands
into 2,2,3,4-tetrasubstituted 2H-1-benzopyrans and 1,2-dihydroquinolines via the insertion
of unsymmetrical alkynes into in situ formed palladacycles was developed, providing the
heterocycles in good yields (44-80%) as single regioisomers.
Introduction
ligands, frequently represented by monodentate or
bidentate phosphines, has a profound effect on the
reactivity of organometallic species.6 A kinetic study of
thermal decomposition of trans-[PdR′2(PR3)2] complexes
revealed destabilization of the Pd-alkyl bond due to the
interaction between bulky phosphine ligands and the
alkyl groups.7 Structures, reactivity, and stability of
arylpalladium σ-alkyl complexes bearing an electron-
withdrawing group at the transition metal-bonded sp3-
hybridized carbon,4d,8,9 specifically palladium ketone
enolates, R-cyano alkyl complexes, and malonates, that
σ-Alkyl organometallic complexes of palladium rep-
resent key intermediates of the versatile cross-coupling
reactions.1 However, potentially powerful methods for
catalytic asymmetric construction of stereogenic carbon
centers exploiting organopalladium compounds with a
metal-bonded sp3-hybridized stereogenic carbon remain
rare,2 since the majority of synthetically viable inter-
mediates feature primary sp3-hybridized metal-bonded
carbons.3 Additional studies on the preparation, stabil-
ity,4 and reactivity of transition metal organometallics
with secondary and tertiary sp3-hybridized metal-
bonded carbons will be needed to facilitate the design
of new synthetic methodologies.5 The choice of auxiliary
(3) To date, palladium-catalyzed coupling reactions of alkyl elec-
trophiles have remained limited to coupling of primary alkyl halides,
most likely proceeding via intermediates with primary sp3-hybridized
palladium-bonded carbons, see: (a) Wiskur, S. L.; Korte, A.; Fu, G. C.
J. Am. Chem. Soc. 2004, 126, 82-83. (b) Nethernton, M. R.; Fu, G. C.
Angew. Chem., Int. Ed. 2002, 41, 3910-3912. (c) Luh, T.-Y.; Leung,
M.-K.; Wong, K.-T. Chem. Rev. 2000, 100, 3187-3204. (d) Cardenas,
D. J. Angew. Chem., Int. Ed. 1999, 38, 3018-3020. A kinetic study
indicated that, in contrast to primary akyl bromides, oxidative addition
of a secondary alkyl bromide to Pd(P(t-Bu)2Me)2 failed to occur, see:
(e) Hills, I. D.; Netherton, M. R.; Fu, G. C. Angew. Chem., Int. Ed.
2003, 42, 5749-5752. However, nickel-catalyzed coupling to secondary
alkyl halides is known, see: (f) Zhou, J.; Fu, G. C. J. Am. Chem. Soc.
2004, 126, 1340-1341. (g) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003,
125, 14726-14727.
(1) Diederich, F., Stang, P. J., Eds. Metal-Catalyzed Cross-Coupling
Reactions; Willey-VCH Verlag GmbH: Wenheim, 1998.
(2) Palladium-catalyzed asymmetric arylation of ketone, ester, and
amide enolates demonstrates the synthetic utility of such strategies,
see: (a) Buchwald, S. L.; Hamada, T. Org. Lett. 2002, 4, 999-1001.
(b) Hamada, T.; Chieffi, A.; Åhman, J.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 1261-1268. (c) Spielvolgel, D. J.; Buchwald, S. L. J.
Am. Chem. Soc. 2002, 124, 3500-3501. (d) Lee, S.; Hartwig, J. F. J.
Org. Chem. 2001, 66, 3402-3415. (e) Åhman, J.; Wolfe, J. P.;
Troutman, M. V.; Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 1918-1919.
10.1021/om0491544 CCC: $30.25 © 2005 American Chemical Society
Publication on Web 01/27/2005

946 Organometallics, Vol. 24, No. 5, 2005
Lu et al.
operate as intermediates of established catalytic reac-
tions,2 have been investigated by Hartwig and co-
workers.9 An increase in the steric bulk of the auxiliary
phosphine ligands, and the presence of additional sub-
stituents at the palladium-bonded carbon in the alkyl
groups were found to promote alternative coordination
modes, e.g., formation of O-bonded ketone enolates.10
Furthermore, the thermodynamic stability of such
complexes was compromised by an increase in the steric
demands of the alkyl group.9a To date, less attention
has been devoted to comparable studies on the ligand
and substituent effects in palladium ester enolates, and
particularly those featuring di- and trisubstituted metal-
bonded carbons.8,9,10c
As a part of our program exploring applications of
palladacycles with a metal-bonded sp3-hybridized ste-
reogenic carbon in asymmetric organic synthesis,11 we
have been studying the reactivity of stable cyclic arylpal-
ladium ester enolates II (Figure 1). Notably, attempts
Figure 1. Synthetic strategy.
to utilize strategies previously developed11 for the
synthesis of stable palladacycles II and heterocycles III
lacking substituents R1 (R1 ) H) for preparation of
analogous targets II and III with fully substituted
stereogenic carbons (R1 ) alkyl, aryl) proved unsuccess-
ful, as a result of the failure to prepare stable pallada-
cycles II (R1 ) alkyl, aryl) with triphenylphosphine
ligands L.
(4) σ-Alkyl organometallic complexes are prone to decomposition via
â-hydride elimination, see: (a) Collman, J. P.; Hegedus, L. S.; Finke,
R. G. Principles and Applications of Organotransition Metal Chemistry;
University Science Books: Mill Valley, CA, 1987; Chapter 5. However,
a stable alkyl palladium(II) complex featuring â-hydrogens (Ph(CH2)3-
Pd[P(t-Bu)2Me]2Br has been isolated and shown to undergo â-hydride
elimination only upon warming to 50 °C, see: (b) Kirchhoff, J. H.;
Netherton, M. R.; Hills, I. D.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
13662-13663. Thermodynamic stability of alkyl ligands in organome-
tallic complexes decreases in the order methyl > primary > secondary
. tertiary, and isomerization of secondary alkyl complexes into
primary ones was observed, see: (c) Siegbahn, P. E. M. J. Phys. Chem.
1995, 99, 12723-12729. (d) Reger, D. L.; Garza, D. G.; Baxter, J. C.
Organometallics 1990, 9, 873-874. Although steric hindrance between
the metal with its coordination sphere and substituents at the metal-
bonded sp3-hybridized carbon has been invoked to rationalize these
observations, a recent theoretical study pointed to a significant
contribution from electronic factors, demonstrating stabilization of
alkyl organometallics arising from the presence of an electron-
withdrawing group at the metal-bonded carbon, see: (e) Harvey, J. N.
Organometallics 2001, 20, 4887-4895.
Described herein are systematic studies of the effect
of steric and electronic properties of auxiliary ligands
L and substituents R1 on the formation, stability, and
reactivity of palladacycles II (R1 ) alkyl, aryl). Palla-
dacycles II (X ) O, R1 ) alkyl, phenyl) with sterically
unencumbered N,N,N′,N′-tetramethyl-1,2-ethylenedi-
amine auxiliary ligands (L-L ) TMEDA) and pal-
ladium-bonded sp3-hybridized tertiary carbons were
isolated and fully characterized. In contrast, pallada-
cycles II (R1 ) alkyl, phenyl) possessing monodentate
phosphine ligands (L ) PR′xR′′y) were detected only in
situ (1H and 31P NMR) in crude product mixtures arising
from auxiliary ligand displacements on palladacycles II
(L-L ) TMEDA), or from base-mediated ring-closure
reactions of the corresponding arylpalladium(II) iodo
complexes I (Figure 1). Notably the steric properties of
both the auxiliary ligands (L ) PR′xR′′y) and the
substituents R1 significantly affected the progress of
these transformations. Utilizing data from these experi-
ments, a convergent synthetic approach to diverse,
medicinally relevant12 2,2,3,4-tetrasubstituted 2H-1-
benzopyrans III (X ) O, R1, R2 ) alkyl, aryl) and 2,2,3,4-
tetrasubstituted 1,2-dihydroquinolies III (X ) NCOOMe,
R1, R2 ) alkyl, aryl) was developed. Heterocycles III,
which are not easily obtained by traditional synthetic
protocols,13 have been prepared in good to excellent
(5) Malinakova, H. C. Chem. Eur. J. 2004, 10, 2636-2646.
(6) Crabtree, R. H. The Organometallic Chemistry of the Transition
Metals, 3rd ed., John Wiley and Sons: New York, 2001; Chapter 4.
(7) (a) Ozawa, F.; Ito, T.; Yamamoto, A. J. Am. Chem. Soc. 1980,
102, 6457-6463. A computational study reported P-Pd-P angles for
cis-Pd(Et)2[P(t-Bu)2]2 and cis-Pd(Et)2[P(i-Pr)2]2 to be 129.6° and 101.5°,
respectively. Thus, the distortion of the square planar geometry
(deviation from P-Pd-P angle 90°) appears to arise from the notable
steric bulk of the phosphine ligands, see: (b) Cardenas, D. J. Angew.
Chem., Int. Ed. 2003, 42, 384-387.
(8) For representative examples of preparations of stable late
transition metal enolates and other complexes bearing an electron-
withdrawing substituent at the metal-bonded carbon, see: (a) Heath-
cock, C. H. In Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon: Oxford, U. K., 1991; Vol. 2, Chapter 1.9. (b) Naota, T.;
Tannna, A.; Kamuro, S.; Murahashi, S.-I. J. Am. Chem. Soc. 2002,
124, 6842-6843. (c) Ryabov, A. D.; Panyashkina, I. M.; Polyakov, V.
A.; Fisher, A. Organometallics 2002, 21, 1633-1636. (d) Kujime, M.;
Hikichi, S.; Akita, M. Organometallics 2001, 20, 4049-4060. (e)
Hashmi, S. K. A.; Naumann, F.; Bolte, M. Organometallics 1998, 17,
2385-2387. (f) Vicente, J.; Abad, J. A.; Chicote, M.-T.; Abrisqueta, M.-
D.; Lorca, J.-A.; Ramirez de Arelano, M. C. Organometallics 1998, 17,
1564-1568. (g) Rasley, B. T.; Rapta, M.; Kulawiec, R. J. Organome-
tallics 1996, 15, 2852-2854. (h) Garcia-Ruano, J. L.; Gonzalea, A. M.;
Barcena, A. I.; Camazon, M. J.; Navarro-Ranninger, C. Tetrahedron:
Asymmetry 1996, 7, 139-148. (i) Hartwig, J. F.; Andersen, R. A.;
Bergman, R. G. J. Am. Chem. Soc. 1990, 112, 5670-5671. (j) Burkhardt,
E. R.; Doney, J. J.; Slough, G. A.; Stack, J. M.; Heathcock, C. H.;
Bergman, R. G. Pure Appl. Chem. 1988, 60, 1-6. (k) Weinstock, I.;
Floriani, C.; Chiesi-Villa, A.; Guastini, C. J. Am. Chem. Soc. 1986, 108,
8298-8299.
(9) (a) Culkin, D. A.; Hartwig, J. F. Organometallics 2004, 23, 3398-
3416. (b) Culkin, D. A.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123,
5816-5817.
(10) For the discussion of the different bonding modes available to
palladium enolates, see: (a) Tian, G.; Boyle, P. D.; Novak, B. M.
Organometallics 2002, 21, 1462-1465. (b) Albeniz, A. C.; Catalina, N.
M.; Espinet, P.; Redon, R. Organometallics 1999, 18, 5571-5576.
Reference 9a, and references therein. (c) In general, for late transition
metal enolates, coordination to palladium through the carbon atom is
preferred, see ref 10b.
(11) (a) Lu, G.; Malinakova, H. C. J. Org. Chem. 2004, 69, 8266-
8279. (b) Lu, G.; Malinakova, H. C. J. Org. Chem. 2004, 69, 4701-
4715. (c) Portscheller, J. L.; Lilley, S. E.; Malinakova, H. C. Organo-
metallics 2003, 22, 2961-2971. (d) Portscheller, J. L.; Malinakova, H.
C. Org. Lett. 2002, 4, 3679-3681.
(12) For examples of biologically active 2,2-disubstituted 2H-1-
benzopyrans, see: (a) Yu, L. J. Agric. Food Chem. 2003, 51, 2344-
2347. (b) Shin, H. S.; Seo, H. W.; Yoo, S. E.; Lee, B. H. Pharmacology
1998, 56, 111-124. (c) Rovnyak, G. C.; Ahmed, S. Z.; Ding, C. Z.;
Dzwonczyk, S.; Ferrara, F. N.; Humphreys, W. G.; Grover, G. J.;
Santafianos, D.; Atwal, K. S.; Baird, A. J.; McLaughlin, L. G.;
Normandin, D. E.; Sleph, P. G.; Traeger, S. C. J. Med. Chem. 1997,
40, 24-34. For examples of biologically active 2,2-disubstituted 1,2-
dihydroquinolines, see: (d) Elmore, S. W.; Pratt, J. K.; Coghlan, M.
J.; Mao, Y.; Green, B. E.; Anderson, D. D.; Stashko, M. A.; Lin, C. W.;
Falls, D.; Nakane, M.; Miller, L.; Tyree, C. M.; Miner, J. N.; Lane, B.
Bioorg. Med. Chem. Lett. 2004, 14, 1721-1727.

Palladacycles with a Metal-Bonded Carbon
Organometallics, Vol. 24, No. 5, 2005 947
Scheme 1
yields (44-80%), and with a complete regiocontrol, in
one step from stable arylpalladium(II) iodo complexes
I bearing carefully optimized monodentate phosphine
ligands (L). Results described herein contribute to
expanding fundamental understanding of the effects of
auxiliary phosphine ligands on the stability and reactiv-
ity of highly substituted palladium ester enolates,
providing a foundation for future development of asym-
metric and catalytic variants of this synthetic protocol.
Figure 2. Thermal ellipsoid diagrams of complexes 3c
(top) and 3d (bottom). The ellipsoids are drawn at the 50%
probability level.
moisture- and air-stable bright yellow solids in excellent
yields (84-95%), unaffected by steric properties of R1
substituents (Scheme 1). The enolate connectivity in
Results and Discussion
Preparation of Stable Palladacycles with
TMEDA Auxiliary Ligands. Utilizing sterically un-
encumbered N,N,N′,N′-tetramethyl-1,2-ethylenediamine
ligand (TMEDA), a series of stable palladacycles 3a-d
featuring substituents R1 (R1 ) Me, Et, i-Pr, Ph) was
prepared (Scheme 1). Aryl iodides 1a-d, available via
O-alkylation of 2-iodophenol with appropriate R-bromo
esters,14 smoothly participated in oxidative addition
with palladium(0) (Pd2dba3) in the presence of TMEDA,
1
complexes 3a-d was assigned on the basis of the H,
13C NMR, and IR spectroscopic evidence. Thus, palla-
1
dacycle 3a displayed a H NMR signal for the methyl
(Pd-C-CH3) resonance at δ 1.75, a 13C NMR signal for
the Pd-bonded sp3-hybridized tertiary carbon (Pd-Csp3)
at δ 93.5, and the ν(CdO) band in the IR spectrum at
1677 cm-1. Similar data were recorded for complex 3b
1
(R1 ) Et, H NMR signal for the methylene (Pd-C-
1
CH2-) resonance at δ 2.3 (1 H) and δ 2.0 (1 H), 13C NMR
signal for Pd-Csp3 at δ 99.5, and ν(CdO) band in the
IR spectrum at 1670 cm-1), 3c (R1 ) i-Pr, 1H NMR
signal for the methine (Pd-C-CH-) resonance at δ
2.6-2.5 (1 H), 13C NMR signal for Pd-Csp3 at δ 103.4,
and ν(CdO) band in the IR spectrum at 1664 cm-1), and
3d (R1 ) Ph, 13C NMR signal Pd-Csp3 at δ 97.5, and
ν(CdO) band in the IR spectrum at 1676 cm-1).15a
Furthermore, the assigned C-bonded connectivities in
complexes 3c and 3d were confirmed by X-ray crystal-
lographic analyses (Figure 2).15b
providing arylpalladium(II) iodo complexes 2a-d. H
and 13C NMR spectra of complexes 2a and 2d indicated
the presence of diastereomers, presumably arising from
a hindered rotation about the Csp2-Pd bond.11b For the
base-mediated (t-BuOK, 1.2-1.6 mol equiv) conversion
of complexes 2a-d into stable palladacycles 3a-d, the
protocol previously designed for palladacycle 3 lacking
R1 substituent (R1 ) H)11d had to be modified by
replacing THF solvent with benzene. Under these
conditions, the residual t-BuOK was efficiently removed
from the crude reaction mixtures by filtration through
a layer of Celite, preventing decomposition of pallada-
cycles 3a-d during the removal of solvents under
reduced pressure. Palladacycles 3a-d were isolated as
(15) (a) For comparison, the known complex 3 lacking the R1
substituent (R1 ) H) displayed similar spectral characteristics, e.g.,
13C NMR signal for the palladium-bonded sp3-hybridized carbon (Pd-
Csp3) at δ 87.2 and ν(CdO) band in the IR spectrum at 1670 cm-1, see
ref 11d. (b) Both palladacycles possess square planar geometry about
the palladium atom without any distortions from planarity. The sum
of the angles around the palladium atom was 360.1° for both 3c (R1 )
i-Pr) and 3d (R1 ) Ph).
(13) Gribble, G. W., Gilchrist, T. L. Eds. Progress in Heterocyclic
Chemistry; Pergamon: Oxford, 2001; Vol. 13.
(14) Ramakrishnan, V. R.; Kagan, J. J. Org. Chem. 1970, 35, 2901-
2904.

948 Organometallics, Vol. 24, No. 5, 2005
Lu et al.
Scheme 2
NMR analyses (spectra a, c, and e, Scheme 2 and Table
1). Reactions involving substrates 3a and 3c gave rise
to crude mixtures containing complexes [4a] and [4c]
with characteristic 31P NMR signals suggesting the
presence of two palladium-bonded phosphine ligands in
cis orientation ([4a]: δ 30.0 (d, J ) 24.3 Hz, 1 P), 24.5
(d, J ) 25.7 Hz, 1 P), spectrum a, and [4c]: δ 30.8 (d
br, J ) 35-40 Hz, 1 P), 26.7 (d br, J ) 35-40 Hz, 1 P),
spectrum c, Scheme 2 and Table 1). Due to a notable
broadening of signals for complex [4c], the coupling
constants could not be precisely measured. In contrast,
ligand displacement on palladacycle 3d (R1 ) Ph)
afforded complex [4e], likely possessing a single pal-
ladium-bonded phosphine ligand,17 as indicated by a
single broad singlet signal at δ 32.1 (spectrum e, Scheme
2 and Table 1). The line broadening, also observed for
the signal of PPh3, might point to the existence of a
dynamic exchange process involving palladacycle [4e]
and the free ligand. Integration of the 31P NMR spectra
of the crude reaction mixtures revealed that the ratios
of molar equivalents of complexes [4a], [4c], and [4e]
to combined molar equivalents of free ligands L (a
combined integration of signals for PPh3 and P(dO)-
Ph3) were 1:3, 1:4, and 1:5, respectively, indicating that
only a partial conversion of substrates 3a, 3c, and 3d
occurred.18 Accordingly, integration of 1H NMR spectra
confirmed the presence of unreacted complexes 3a
(16%), 3c (11%), and 3d (40%). The disproportionately
low content of detected palladacycle 3c (60% would
correspond to the observed [4c]:L ratio) may reflect
instability of complex 3c, leading to decomposition in
solution. Attempts to isolate complexes [4a], [4c], and
[4e] from the crude mixtures were unsuccessful, and
for this reason the enolate connectivity could not be
unequivocally established (the brackets in [4a-f] des-
ignation of the palladacycles indicate the failure to
completely characterize these entities).
a For the listing of 31P NMR signals for the in situ detected
complexes [4a-f] see Table 1. b Combined integration of 31P
NMR signals for ligands L including signals for PPh3 and
P(dO)Ph3, or PPh2Me and P(dO)Ph2Me, see Table 1. c Molar
ratio of complexes [4] to free ligands L based on integration
of 31P NMR spectra (Table 1).
Replacement of PPh3 with PPh2Me, a ligand with
stronger donor abilities and a smaller cone angle,19
resulted in practically complete conversions of the
selected substrates 3a, 3c, and 3d (spectra b, d, and f,
1
Scheme 2), as indicated by H NMR data.20 The pairs
of doublet signals expected for palladacycles [4b], [4d],
and [4f] featuring two phosphine ligands in cis disposi-
tion were detected in the 31P NMR spectra regardless
of the nature of the R1 substituents (31P NMR signals
for the in situ detected complexes [4b]: R1 ) Me: δ 9.5
Exchange of Auxiliary Ligands in Palladacycles
3a-d. Repeated attempts to prepare the palladacycle
II bearing triphenylphosphine ligands (L ) PPh3, X )
O, Figure 1) and substituent R1 ) Me via the displace-
ment of the TMEDA ligand in palladacycle 3a with
excess PPh3 failed.16 Aiming to qualitatively assess the
effects of steric and electronic properties of auxiliary
monodentate phosphine ligands L and the nature of
substituents R1 on the ligand displacement process,
methylene chloride solutions of palladacycles 3a, 3c, and
3d were treated with PPh3 or PPh2Me (4.0 equiv) at
room temperature under argon for a set time period of
1.5 h. Subsequently, volatile components (TMEDA,
methylene chloride) were removed under reduced pres-
(17) For the synthesis of stable three-coordinate arylpalladium
halide and arylpalladium amido complexes featuring one sterically
demanding phosphine ligand, see: (a) Yamashita, M.; Hartwig, J. F.
J. Am. Chem. Soc. 2004, 126, 5344-5345. (b) Stambuli, J. P.; Bu¨hl,
M.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 9346-9347. Involve-
ment of dimeric arylpalladium halide complexes with a single sterically
demanding phosphine ligand as intermediates in palladium-catalyzed
cross-coupling reactions has been proposed, see: (c) Galardon, E.;
Ramdeehul, J. M.; Brown, J. M.; Cowley, A.; Kuok, K. H.; Jutand, A.
Angew. Chem., Int. Ed. 2002, 41, 1760-1763.
(18) Considering that palladacycles 3 were treated with 4.0 equiv
of PPh3 or PPh2Me ligands, the molar ratio of palladacycles [4] to the
combined free ligands L (a combined integration for P(dO)R3 + PR3),
e.g., [4]:L ) 1:2, would be expected for a complete conversion to
palladacycles [4] with two phosphine ligands per palladium atom
(complexes [4a] and [4c]), and a ratio of [4]:L ) 1:3 would be expected
for a complete conversion to palladacycle [4e] with a single phosphine
ligand per palladium.
1
sure, and crude products were analyzed by H and 31P
NMR in CDCl3 (Scheme 2). Utilizing PPh3 ligands, new
organopalladium complexes possessing palladium-bonded
phosphine ligands were indeed formed according to 31
P
(19) Tollman, C. A. Chem. Rev. 1977, 77, 313-348.
(16) In contrast, an analogous procedure applied to complex 3
lacking the R1 substituent has previously provided quantitative yields
of the corresponding palladacycle II (X ) O, EWG1 ) COOEt, R1 ) H,
L ) PPh3), see ref 11d.
(20) Integration of 1H NMR spectra confirmed the presence of 0%,
3%, and 4% of unreacted complexes 3a, 3c, and 3d, in the crude
reaction mixtures corresponding to spectra b, d, and f in Scheme 2,
respectively.

Palladacycles with a Metal-Bonded Carbon
Organometallics, Vol. 24, No. 5, 2005 949
Table 1. Summary of 31P NMR Data Reported in Scheme 2
chemical
shift δ (ppm)
relative
integration
spectrum
multiplicity
assignment
a
30.0
24.5
-4.9
d, J ) 24.3 Hz
d, J ) 25.7 Hz
s
[4a]
[4a]
PPh3
1 P
1 P
3 P
R1 ) Me
L ) PPh3
b
30.5
9.5
s
P(dO)Ph2Me
[4b]
0.4 P
1 P
R1 ) Me
L ) PPh2Me
d, J ) 30.8 Hz
d, J ) 30.8 Hz
s, br
2.2
[4b]
1 P
-25.3
PPh2Me
1.3 P
c
30.8
26.7
-4.9
d, br, J ) 35-40 Hz
[4c]
[4c]
PPh3
1 P
1 P
4 P
R1 ) i-Pr
L ) PPh3
d, br, J ) 35-40 Hz
s
d
30.5
8.3
s
P(dO)Ph2Me
[4d]
0.3 P
1 P
R1 ) i-Pr
L ) PPh2Me
d, J ) 29.6 Hz
d, J ) 29.5 Hz
s
2.9
[4d]
1 P
-25.3
PPh2Me
1.7 P
e
32.1
29.7
-4.9
s, br
s
s, br
[4e]
P(dO)Ph3
PPh3
1 P
0.5 P
4.5 P
R1 ) Ph
L ) PPh3
f
30.5
10.8
s
P(dO)Ph2Me
[4f]
0.6 P
1 P
R1 ) Ph
d, J ) 34.3 Hz
d, J ) 34.3 Hz
s, br
L ) PPh2Me
3.4
[4f]
1 P
-25.3
PPh2Me
1.1 P
(d, J ) 30.8 Hz, 1 P), 2.2 (d, J ) 30.8 Hz, 1 P), [4d]: R1
) i-Pr: δ 8.3 (d, J ) 29.6 Hz, 1 P), 2.9 (d, J ) 29.5 Hz,
1 P), [4f]: R1 ) Ph: δ 10.8 (d, J ) 34.3 Hz, 1 P), 3.4 (d,
J ) 34.3 Hz, 1 P), Scheme 2 and Table 1). Furthermore,
the observed ratios of molar equivalents of palladacycles
[4b], [4d], and [4f] to the combined molar equivalents
of free ligands L (a combined integration of signals for
PPh2Me and P(dO)Ph2Me) were 1:1.7, 1:2, and 1:1.7,
respectively, as anticipated within experimental error
for complete conversions of complexes 3a, 3c, and
3d.18,21 Disappointingly, isolation and complete charac-
terization of complexes [4b], [4d], and [4f] were thwarted
by the persistent presence of P(dO)Ph2Me in products.
The failure to isolate pure palladacycles [4b], [4d], and
[4f] likely arises from a relatively weak bonding of
phosphine ligands to sterically crowded palladium
centers.
Data summarized in Scheme 2 and Table 1 demon-
strate that a complete displacement of TMEDA ligands
in palladacycles 3 with diverse substituents R1 can be
achieved by a proper choice of monodentate phosphine
ligands, providing semistable complexes [4] with two
phosphine ligands in cis disposition. Evidence support-
ing the involvement of carbon-bonded palladium eno-
lates [4b], [4d], and [4f] was based on IR spectroscopic
data (vide infra).
by in situ generated ester enolates22 of arylpalladium-
(II) iodo complexes I (L ) PR′xR′′y) (Figure 1) was
examined. Arylpalladium(II) iodo complexes 5-8 fea-
turing diverse groups R1 (Me, Et, i-Pr, Ph) and a series
of phosphine ligands L (PPh3, PPh2Me, PPhMe2, PMe3)
were prepared via alternative protocols, relying on
either oxidative addition to aryl iodides 1a-d (method
A),11d or a ligand displacement on complexes 2b-e
(method B)11d (Scheme 3). Method B was chosen in cases
when chromatographic removal of dibenzylidene acetone
(dba) liberated in the oxidative addition proved more
convenient as a part of the preparation of complexes 2,
rather than complexes 5-8. 31P NMR analysis of com-
plexes 5-8 indicated a trans disposition of two non-
equivalent phosphines,23 which was confirmed by X-ray
crystallographic analyses on complexes 6a and 7b.24
To qualitatively compare the influence of steric and
electronic characteristics of monodentate phosphine
ligands L, and the nature of substituents R1 on the rate
of the ring-closure reactions,22 solutions of complexes
5a,b, 7a,b, and 8a,b in THF were treated with t-BuOK
for 20 min at ambient temperature under an atmo-
sphere of dry argon.25 Following the addition of benzene,
(22) The relative thermodynamic stabilities of the iodide (pKaHI
<
1) and potassium ester enolate (A-, pKaHA ) 23) anionic ligands would
be expected to provide a sufficient driving force for the ring closure of
complexes I to yield palladacycles II (Figure 1). However, the nature
of substituents R1 and ligands L could have a profound effect on the
kinetics of the ligand displacement. For the estimate of the pKa for
esters of 2-phenoxycarboxylic acids, see: Bordwell, F. G. Acc. Chem.
Res. 1988, 21, 456-463.
Ligand and Substituent Effects on the Intramo-
lecular Displacement of the Anionic Ligands.
Continuing to pursue the isolation of stable pallada-
cycles II bearing monodentate phosphine ligands L, a
complementary strategy involving an irreversible in-
tramolecular displacement of the anionic iodide ligand
(23) As a result of the presence of a stereogenic carbon in complexes
5-8, the two phosphorus atoms are nonequivalent (diastereotopic),
each giving rise to a doublet signal with J(31P-31P) ) 430-480 Hz,
consistent with trans disposition of the phosphine ligands, see:
Pregosin, P. S.; Kunz, T. W. 31P and 13C NMR of Transition Metal
Phosphine Complexes in NMR 16. Basic Principles and Progress; Diehl,
P., Fluck, E., Kosfeld, R., Eds.; Springer-Verlag: Berlin, 1979. 31P NMR
spectra of complexes 5-8 reveal second-order AB patterns for the two
nonequivalent and strongly coupled phosphorus atoms with a signifi-
cant “roofing effect”. As a consequence, in the spectra of complexes
5a, 6a, and 8a, the weak “outer” signals could not be detected, and
only two singlet signals could be reported.
(21) A notable broadening of the signal of the free PPh2Me ligand
was detected in the products of ligand exchange reactions with
palladacycles 3a (R1 ) Me, spectrum b, Scheme 2) and 3d (R1 ) Ph,
spectrum f, Scheme 2). For comparison, the ligand displacement
reaction of palladacycle 3 (R1 ) H)11d with PPh2Me ligand under the
conditions described in Scheme 2 afforded 31P NMR spectra indicating
the presence of the corresponding palladacycle [4] (R1 ) H) with two
phosphines in cis orientation ([4]: δ 9.52 (d, J ) 31.4 Hz, 1 P), 4.55
(d, J ) 31.2 Hz, 1 P), and [4]:L ratio of 1:1.85), corresponding to a
complete conversion of substrate 3. The signal for excess PPh2Me
ligand showed little peak broadening in CDCl3 solution.
(24) Both complexes possess square planar geometry about the
palladium atom without any distortions from planarity. The sum of
the angles around the palladium atom was 360.1° and 359.6° for 6a
(R1 ) Et, L ) PPh3), and 7b (R1 ) i-Pr, L ) PPh2Me), respectively.

950 Organometallics, Vol. 24, No. 5, 2005
Lu et al.
Scheme 3
Scheme 4
filtration, and removal of volatiles (t-BuOH, THF and
benzene) under reduced pressure,26 the crude products
were analyzed by 31P NMR in CDCl3 (Scheme 4 and
Table 2). Integration of 31P NMR signals in spectra a-f
(Scheme 4) was used to establish the molar ratios of
unreacted complexes 5-8 to palladacycles [4] and to the
combined integral of free ligands L (L represents a
combined integration for both phosphines (PR′xR′′y) and
phosphine oxides (P(dO)R′xR′′y) (Scheme 4 and Table
2).
a For the listing of 31P NMR signals for the in situ detected
complexes [4a-f] and unreacted complexes 5-8, see Table 2.
b Combined integration of 31P NMR signals for ligands L
including signals for PPh3 and P(dO)Ph3, or PPh2Me and
P(dO)Ph2Me, see Table 2. c Ratios of molar percent of sub-
strates 5-8, complexes [4], and free ligands L based on
integration of 31P NMR spectra (Table 2).
Complexes [4a-f], identical to products of the ligand
displacement process (Scheme 2 and Table 1), were
generated as shown by signals in the 31P NMR spectra
(spectra a-f, Scheme 4 and Table 2). Notably, the ring
closure on complex 8a (R1 ) Ph, L ) PPh3) gave rise to
a single broad signal at δ 30.9 for complex [4e], possibly
bearing a single phosphine ligand,17,18 and a signifi-
cantly broadened signal for free PPh3 ligand. These
observations suggested the involvement of the previ-
ously observed dynamic equilibrium in the CDCl3 solu-
tion (compare spectra e in Schemes 2 and 4). Utilizing
substrates 5a (R1 ) Me), 7a (R1 ) i-Pr), and 8a (R1 )
Ph), bearing sterically demanding PPh3 ligands, only
partial conversions were achieved, leaving significant
amounts of unreacted complexes 5a (δ 23.12 (s, 1 P),
23.09 (s, 1 P), 22%),23 7a (δ 23.30 (d, J ) 434.1 Hz, 1
P), 22.42 (d, J ) 434.1 Hz, 1 P), 68%),27 and 8a (δ 23.28
(s, 1 P), 23.25 (s, 1 P), 12%)23,27 in the crude product
mixtures (spectra a, c, and e, Scheme 4 and Table 2).
The corresponding palladacycles [4a] and [4e] were
detected in 33% and 44%, respectively (spectra a and e,
Scheme 4), while only traces of palladacycle [4c],
featuring the most sterically demanding i-Pr substituent
(spectrum c, Scheme 4), were present.27 Unexpectedly,
free PPh3 (32-45%) was generated by the ring-closure
reactions of complexes 5a, 7a, and 8a (spectra a, c, and
e, Scheme 4 and Table 2). The free phosphine ligands
could arise from a partial decomposition of palladacycles
[4a], [4c], and [4e], caused by destabilization due to
steric crowding around the palladium centers. The
amounts of unreacted complexes 5a, 7a, and 8a, and
(25) For comparison, the treatment of arylpalladium(II) iodo complex
I lacking the R1 substituent (X ) O, EWG1 ) COOEt, R1 ) H, L )
PPh3) under the same conditions afforded the corresponding pallada-
cycle II (X ) O, EWG1 ) COOEt, R1 ) H, L ) PPh3) as a stable fully
characterized product in 86% yield, see ref 11d.
(26) Addition of benzene induced a complete precipitation of residual
t-BuOK and KI, which were removed by filtration and thus allowed
for the acquisition of high-quality 31P NMR spectra in CDCl3. However,
a partial oxidation of air-sensitive phosphine ligands and/or partial
decomposition of the semistable organopalladium complexes could not
be avoided under these conditions.
(27) In contrast to alkyl substituents R1 (Me and i-Pr) that are
expected to cause an increasing destabilization of palladacycles [4] due
to the increase in their steric bulk, the phenyl substituent R1 (Ph) could
partially offset the unfavorable steric factors by its electron-withdraw-
ing effects, see refs 4d and 9a.

Palladacycles with a Metal-Bonded Carbon
Organometallics, Vol. 24, No. 5, 2005 951
Table 2. Summary of 31P NMR Data Reported in Scheme 4
chemical
shift δ (ppm)
relative
integration
molar percent
(%)
spectrum
multiplicity
assignment
a
30.0
23.9
23.12
23.09
-5.5
d, J ) 28.0 Hz
[4a]
[4a]
5a
1 P
33
22
45
R1 ) Me
d, J ) 28.0 Hz
1 P
L ) PPh3
s
s
0.7 P
0.7 P
1.3 P
5a
PPh3
b
30.4
9.5
2.2
s
P(dO)Ph2Me
[4b]
[4b]
0.4 P
1 P
1 P
30
70
R1 ) Me
L ) PPh2Me
d, J ) 30.8 Hz
d, J ) 30.8 Hz
c
23.3
22.4
-5.5
d, J ) 434.1 Hz
d, J ) 434.1 Hz
s
7a
0.5 P
0.5 P
0.23 P
68
32
R1 ) i-Pr
L ) PPh3
7a
PPh3
d
30.4
8.4
2.9
7.2
5.5
s
P(dO)Ph2Me
0.3 P
1 P
19
62
R1 ) i-Pr
L ) PPh2Me
d, J ) 29.6 Hz
d, J ) 29.5 Hz
d, J ) 452.1 Hz
d, J ) 452.0 Hz
[4d]
[4d]
7b
1 P
0.3 P
0.3 P
19
7b
e
30.9
23.28
23.25
-4.9
s, br
s
[4e]
8a
1.7 P
0.5 p
0.5 P
1.7 P
44
12
R1 ) Ph
L ) PPh3
s
8a
s, br
PPh3
44
f
30.4
10.8
3.4
s
P(dO)Ph2Me
[4f]
[4f]
0.8 P
1 P
1 P
43
57
R1 ) Ph
d, J ) 34.1 Hz
d, J ) 34.3 Hz
L ) PPh2Me
the contents of palladacycles [4a], [4c], and [4e]
detected in the crude mixtures correlate well with the
anticipated steric and electronic effects of substituents
R1 (Me, i-Pr, Ph).4d,9a,27
recorded on palladacycles 3,15 and on palladacycles of
type 4 lacking the R1 substituent (R1 ) H), and featuring
diverse phosphine ligands,30 for which the existence of
a palladium-bonded sp3-hybridized carbon was unequivo-
cally established.11 Thus, although the involvement of
O-bonded palladium enolates could not be rigorously
ruled out, the presented evidence supports the conclu-
sion that palladacycles [4b], [4d], and [4f] feature a
fully substituted, sp3-hybridized carbon bonded to pal-
ladium.
Synthesis of 2,2,3,4-Tetrasubstituted 2H-1-Ben-
zopyrans and 1,2-Dihydroquinolines. As antici-
pated,11 treatment of palladacycle 3a with dimethyl
acetylenedicarboxylate (dmad) (3.1 equiv, 80 °C in 1,2-
dichloroethane) failed to afford the corresponding ben-
zopyran 9 (Scheme 5), conceivably due to a relatively
tight binding of the bidentate N,N,N′,N′-tetramethyl-
1,2-ethylenediamine (TMEDA) ligand forming a five-
membered chelate ring.31 To facilitate the displacement
of TMEDA ligand, and allow for the attachment of the
alkyne to palladium in the presumed transition state,32
monodentate phosphine ligands (3.0 equiv) were added
to palladacycle 3a, along with dimethyl acetylenedicar-
boxylate (3.1 equiv of dmad, 80 °C in 1,2-dichloroethane,
In contrast, treatment of complexes 5b (R1 ) Me) and
8b (R1 ) Ph), possessing PPh2Me ligands,19 with t-
BuOK under the standard conditions led to a complete
conversion of the substrates, yielding crude products
with higher contents of the corresponding palladacycles
[4b] (70%) and [4f] (57%) (spectra b and f, Scheme 4
and Table 2). However, only an incomplete conversion
of palladium(II) complex 7b (R1 ) i-Pr) possessing an
i-Pr substituent27 was achieved, delivering a crude
product containing palladacycle [4d] (62%) as well as
unreacted complex 7b (19%) (spectrum d, Scheme 4 and
Table 2). A destabilization of palladacycles [4b], [4d],
and [4f] was suggested by the presence of free ligands,
mostly as the phosphine oxide P(dO)Ph2Me in 30%,
19%, and 43% in spectra b, d, and f, respectively
(Scheme 4 and Table 2).28 Attempts at isolation and
complete characterization of complexes [4] from all the
ring-closure experiments (Scheme 4) were unsuccessful
due to the persistent presence of significant quantities
of free ligands and/or ligand oxides. To provide insight
into the bonding mode of palladium enolates in com-
plexes [4b], [4d], and [4f], IR spectroscopic analyses
were performed on the crude reaction mixtures from
experiments shown in spectra b, d, and f (Scheme 4).
The IR spectroscopy revealed ν(CdO) bands at 1687
cm-1 (spectrum b), 1676 cm-1 (spectrum d, ν(CdO) at
1739 cm-1 was observed for the remaining complex 7b),
and 1676 cm-1 (spectrum f), respectively.29 The data are
consistent with the ν(CdO) band observed in IR spectra
(29) The IR spectra of the crude reaction mixtures were measured
in neat films generated upon evaporation of methylene chloride solvent
on the surface of NaCl salt plates.
(30) IR spectra recorded on previously characterized palladacycles
4 lacking substituent R1 (R1 ) H), indicated the presence of ν(CdO)
band of the ester group at 1708 cm-1 for L ) PPh3, and at 1692 cm-1
for L-L ) 1,2-bis(diphenylphosphino)ethane (dppe), see refs 11c and
11d.
(31) Attempted insertion of highly activated dimethyl acetylenedi-
carboxylate (dmad) into palladacycle of type II (R1 ) H, EWG1
)
COOEt, L-L ) 1,2-bis(diphenylphosphino)butane (dppb)) with a bi-
dentate ligand giving rise to a seven-membered chelate ring afforded
only low (<30%) yields of the corresponding benzopyran, requiring
forcing conditions (Portscheller, J. L., Malinakova, H. C. Unpublished
results). It is notable that the replacement of the ester (COOEt) group
with a sterically demanding amide (CONEt2) group in the presence of
the same bidentate ligand (dppb) in palladacycle of type II (R1 ) H,
EWG1 ) CONEt2, L-L ) 1,2-bis(diphenylphosphino)butane (dppb))
facilitated the insertion of dmad, providing the corresponding ben-
zopyran in a good yield (64%), see ref 11d.
(28) For comparison, an intramolecular displacement of the iodide
ligand in complex 8e (R1 ) H, L ) PPh2Me, Scheme 3) under the
conditions of the experiment described in Scheme 4 afforded 31P NMR
spectra indicating a complete conversion of complex 8e, and the
presence of the corresponding palladacycle [4g] (R1 ) H, L ) PPh2-
Me) along with small amounts of the ligand oxide P(dO)Ph2Me, in the
molar ratio 8e:[4g]:L ) 0:87:13. However, isolation and complete
characterization of palladacycle [4g] were not attempted.

952 Organometallics, Vol. 24, No. 5, 2005
Lu et al.
Scheme 5
complexes 7a,b in experiments described in Scheme 4
(spectra c and d), the time for treatment of complexes
7a,b with t-BuOK was extended to 40 min (entries 11-
14, Table 3).36 Gratifyingly, the two-step one-pot protocol
smoothly afforded targeted 2H-1-benzopyrans 9-17 in
good yields (44-80%) as single products, and no traces
1
of regioisomeric heterocycles11,32 were detected by H
NMR analyses of crude reaction mixtures. The highly
selective formation of heterocycles with the two ester
substituents at carbons C-2 and C-3 is consistent with
our previous studies on the insertion of unsymmetrical
alkynes into stable palladacycles of type [4] (R1 ) H, L
) PPh3).11 The regiochemical assignments in benzopy-
rans 10, 12, 14, and 16 possessing a methyl substituent
1
(R2 ) Me) in the C-4 position were based on NOE H
NMR experiments.37 The structure of benzopyran 11
was established by single-crystal X-ray crystallographic
analysis, and the structures of benzopyrans 13, 15, and
17 were assigned accordingly.38
a Tetrafluoroborate salt HPR3BF4 of the ligand was used and
deprotonated in situ by (i-Pr)2EtN.
Scheme 5).33 Testing a series of phosphines with in-
creasing ligand strength and a decreasing cone angle,19
the yield of benzopyran 9 was found to rise from 31%
for the reaction mediated by PPh2Me, to 68% yield
obtained from the reaction mediated by the P(n-Bu)3
ligand (Scheme 5). However, attempts to insert less
activated unsymmetrical alkynes (e.g., MeCtCCOOEt)
into palladacycle 3a under the optimized conditions
(Scheme 5) proved unsuccessful.34 Results similar to
those described above were obtained with palladacycles
3b,c, and further development of this protocol was
abandoned.
The nature of auxiliary phosphine ligands in sub-
strates 5-8 affected yields of benzopyrans 9-17. Thus,
arylpalladium(II) iodo complexes 5a, 6a, and 8a pos-
sessing PPh3 ligands afforded the corresponding ben-
zopyrans 9-16 in low to moderate yields, 20-59%
(entries 1, 3, 5, 7, 9, 11, 13, and 15, Table 3). The failure
to obtain appreciable yields of benzopyrans 14 and 15
(entries 11 and 13, Table 3) from complex 7a (R1 ) i-Pr,
L ) PPh3) is in agreement with the failure to generate
significant amounts of palladacycle [4c] via the ring-
closure reaction of complex 7a (spectrum c, Scheme 4).39
Substrates 5b-8b featuring PPh2Me ligands afforded
benzopyrans 9-15 and 17 in consistently better yields,
57-80% (entries 2, 4, 6, 8, 10, 12, 14, and 19, Table 3).
The described auxiliary ligand effects on synthesis of
benzopyrans 9-17 correlate closely with the previously
observed ligand effects on generation of palladacycles
[4] via the ring-closure (Scheme 4). The content of
palladacycles with PPh2Me ligands, e.g., [4b] (70%),
[4d] (62%), and [4f] (57%) in the crude products of the
ring-closure experiments, was higher than the contents
of palladacycles [4a] (33%), [4c] (0%), and [4e] (44%)
bearing the PPh3 ligand (Scheme 4 and Table 2). In a
single example involving the reaction between complex
8b (R1 ) Ph, L ) PPh2Me) and ethyl 2-butynoate, only
a low yield (44%) of benzopyran 16 was obtained (entry
16, Table 3). Interestingly, further increase in the
Seeking a general method that would permit an
independent variation of substituents at C-2 (R1) and
C-4 (R2) in tetrasubstituted 2H-1-benzopyrans III (Fig-
ure 1), palladium(II) iodo complexes 5-8 were treated
with t-BuOK (1.2 equiv, room temperature, THF, 20-
40 min), followed by the addition of diverse alkynes
(MeOOCCtCCOOMe, MeCtCCOOEt, or MeOC6H4Ct
CCOOEt, 2.5-3.0 equiv) and 1,2-dichloroethane,35 and
heating (80 °C) for 24 h, or until significant quantities
of palladium(0) precipitated (Table 3). According to 31
P
NMR studies on the ring-closure reactions (Scheme 4),
and depending on the choice of auxiliary monodentate
phosphine ligand L, either partial or complete conver-
sion of complexes 5-8 into palladacycles [4], which
would subsequently react with alkynes, was antici-
pated.36 Due to the observed partial conversion of
(37) For example, the 1H NMR NOE analysis of benzopyran 12
indicated that irradiation of the signal for the proton in the methyl
group attached to C-4 position at δ 2.26 (s) led to the NOE enhance-
ment of the signal for the proton at C-5 in the aromatic ring at δ 7.31
(dd).
(32) For the discussion of the mechanism and the origins of
regiocontrol in alkyne insertion reactions with group 10 metalacycles,
see: (a) Bennet, M. A.; Macgregor, S. A.; Wenger, E. Helv. Chim. Acta
2001, 84, 3084-3104. (b) Campora, J.; Palma, P.; Carmona, E. Coord.
Chem. Rev. 1999, 193-195, 207-281.
(33) The ligands were added as tetrafluoroborate salts and depro-
tonated in situ by (i-Pr)2EtN, see: Netherton, M. R.; Fu, G. C. Org.
Lett. 2001, 3, 4295-4298.
(34) Treatment of palladacycle 3a with CH3CtCCOOEt and ligand
[HPMe3]BF4 under the conditions described in Scheme 5 for 24 h did
not give rise to the corresponding benzopyran in concentrations
detectable by TLC.
(35) The addition of 1,2-dichloroethane (DCE) (6 mL) solvent into
the THF (1 mL) solutions of the reactants allowed performing the
alkyne insertion reaction under reflux at elevated temperatures.
Furthermore, the decrease in overall solvent polarity in the DCE/THF
mixtures would be expected to favor migratory insertion of alkynes
into palladacycles of type [4].
(36) The additions of alkyne solutions into the reaction mixtures
containing arylpalladium(II) iodo complexes 5-8 were delayed 20-40
min following the introduction of t-BuOK, to allow for the ring closure
to occur and to consume the t-BuOK, and thus avoid possible base-
induced side-reactions between a full equivalent of base (t-BuOK) and
the alkynes.
(38) Assignment of regiochemistry in benzopyrans 11, 13, 15, and
17 via long-range 1H-13C correlations revealed by HMBC 2D NMR
spectroscopic analysis was complicated due to the overlap of both the
proton and carbon signals for protons and carbons from the two
aromatic rings.
(39) Although the reaction time for the ring closure of arylpalladium-
(II) iodo complex 7a was extended to 40 min (entries 11 and 13, Table
1), benzopyrans 14 and 15 were isolated in only 34% and 26% yields,
respectively, as crude materials with only 85-90% purity by 1H NMR.

Palladacycles with a Metal-Bonded Carbon
Organometallics, Vol. 24, No. 5, 2005 953
Table 3. Regiocontrolled Synthesis of 2,2,3,4-Tetrasubstituted 2H-1-Benzopyrans
entry
substrate
R1
L
time (h)
R2
R3
produt
yield (%)
1
5a
5b
5a
5b
5a
5b
6a
6b
6a
6b
7aa
7ba
7aa
7ba
8a
8b
8c
Me
Me
Me
Me
Me
Me
Et
PPh3
PPh2Me
PPh3
PPh2Me
PPh3
PPh2Me
PPh3
PPh2Me
PPh3
PPh2Me
PPh3
PPh2Me
PPh3
PPh2Me
PPh3
3
1
COOMe
COOMe
Me
COOMe
COOMe
COOEt
COOEt
COOMe
COOMe
COOEt
COOEt
COOMe
COOMe
COOEt
COOEt
COOMe
COOMe
COOEt
COOEt
COOEt
COOEt
COOMe
9
20
63
51
59
59
80
50
63
54
69
b
2
9
3
8
10
10
11
11
12
12
13
13
14b
14
15c
15
16
16
16
16
17
4
24
12
24
11
24
10
24
18
24
18
24
42
24
24
24
24
Me
5
p-MeOC6H4-
p-MeOC6H4-
Me
6
7
8
Et
Me
9
Et
Et
p-MeOC6H4-
p-MeOC6H4-
Me
10
11
12
13
14
15
16
17
18
19
i-Pr
i-Pr
i-Pr
i-Pr
Ph
Ph
Ph
Ph
Ph
Me
57
c
p-MeOC6H4-
p-MeOC6H4-
Me
72
34
44
<5
<5
69
PPh2Me
PPhMe2
PMe3
Me
Me
8d
8b
Me
PPh2Me
p-MeOC6H4-
a Reaction mixture was stirred with t-BuOK for 40 min prior to the addition of the solution of alkyne. b Only 34% yield of crude product
14 in 85-90% purity by 1H NMR was isolated. c Only 26% yield of crude product 15 in 85-90% purity by 1H NMR was isolated.
strength19 of the auxiliary ligands L in complexes 8c
(L ) PPhMe2) and 8d (L ) PMe3) permitted only the
isolation of traces of benzopyran 16, likely reflecting an
unfavorable position of the ligand exchange equilibrium
between ligands L and the alkyne (entries 17 and 18,
Table 3). Results in Table 3 did not point to pronounced
effects of the nature of substituent R1 on the yield of
the corresponding benzopyrans (e.g., compare entries 16
and 19, or 4 and 12, Table 3). However, the observed
correlation between the ligand effects documented by
the experiments in Scheme 4, and the role of the
auxiliary ligands in the preparation of benzopyrans
9-17 (Table 3) suggests that the formation of benzopy-
rans 9-17 proceeds via palladacycles [4a-f] as reactive
intermediates, although the existence of alternative
pathways could not be rigorously ruled out.40
isolated as stable, fully characterized solids. As antici-
pated, 1H, 13C, and 31P NMR spectra of compounds 18-
21 showed significant signal broadening due to the
amide resonance. A sequential treatment of palladium-
(II) complex 21 with t-BuOK (1.2 equiv, room temper-
ature, THF, 40 min) and solutions of alkynes (MeCt
CCOOEt and MeOC6H4CtCCOOEt, 2.5-3.0 equiv) in
1,2-dichloroethane afforded the corresponding tetrasub-
stituted 1,2-dihydroquinolines 22 and 23 in moderate
yields of 55% and 50%, respectively. No traces of
regioisomeric products were detected in the crude reac-
1
tion mixtures by H NMR spectroscopic analyses. The
assignment of regiochemistry for 1,2-dihydroquinoline
1
22 was based on the H NOE experiment,43 and the
structure of 1,2-dihydroquinoline 23 was established by
X-ray crystallographic analysis.
The optimized synthetic protocol was successfully
applied to the synthesis of 1,2-dihydroquinolines 22 and
23 (Scheme 6). N-Alkylation41 of aryl iodide 1842 af-
forded carbamate 19, which was converted by the
established methods11 into aryl palladium(II) complexes
20 and 21 (Scheme 6). Complexes 20 and 21 were
Conclusions
Stable oxapalladacycles 3a-d with sterically unen-
cumbered TMEDA auxiliary ligands and a tertiary sp3-
hybridized palladium-bonded carbon were prepared and
fully characterized. Enolate connectivities in pallada-
cycles 3c and 3d with i-Pr and Ph substituents R1 were
(40) (a) An alternative pathway consisting of a migratory insertion
of the alkyne into palladium(II) complexes 5-8 and subsequent
displacement of the anionic iodide ligand providing seven-membered
palladacycles, which would undergo a reductive elimination, might also
account for the formation of benzopyrans 9-17. Most likely, the extent
of this process would be limited to the portion of complexes 5-8 that
failed to provide palladacycles [4] within the initial 20-40 min period
of treatment with t-BuOK. The formation of palladacycles [4] could
continue after the addition of alkynes, and thus simultaneous operation
of both these pathways cannot be ruled out. For examples of studies
exploring insertion of unsaturated molecules into stable arylpalladium-
(II) halide complexes yielding heterocyclic products, see: (b) Vicente,
J.; Abad, J.-A.; Lopez-Serrano, J.; Jones, P. G. Organometallics 2004,
23, 4711-4722. (c) Vicente, J.; Abad, J.-A.; Fortsch, W.; Lopez-Saez,
M.-J.; Jones, P. G. Organometallics 2004, 23, 4414-4429.
(43) The 1H NMR NOE analysis of 1,2-dihydroquinoline 22 indicated
that irradiation of the signal for the proton in the methyl group
attached to the C-4 position at δ 2.22 (s) led to the NOE enhancement
of the signal for the proton at C-5 in the aromatic ring at δ 7.37 (d).
(41) Bergeron, R. J.; Hoffman, P. J. Org. Chem. 1980, 45, 161-163.
(42) (a) Crich, D.; Sannigrahi, M. Tetrahedron 2002, 58, 3319-3322.
(b) Ko, S. S.; Confalone, P. N. Tetrahedron 1985, 41, 3511-3518.

954 Organometallics, Vol. 24, No. 5, 2005
Lu et al.
Scheme 6
mol % content of palladacycles [4] with PPh2Me ligands
varied from 57 to 70%. Although palladacycles [4] could
not be isolated as pure entities and fully characterized,
IR spectroscopic analyses of crude reaction mixtures
lend support to the presence of palladium-bonded sp3-
hybridized carbon in palladacycles [4b,d,f].10c An ef-
ficient one-pot two-step protocol for the preparation of
2,2,3,4-tetrasubstituted benzopyrans 9-17, and 1,2-
dihydroquinolines 22 and 23 from arylpalladium(II)
complexes 5-8 and 21, and alkynes was devised (Table
3 and Scheme 6), providing the heterocycles in good
yields (44-80%) as single regioisomers. A correlation
between the observed effects of the nature of auxiliary
phosphine ligands on the yields of benzopyrans 9-17,
with the NMR monitoring data described above, sug-
gested that heterocycles 9-17 were generated via a
regiocontrolled migratory insertion of alkynes11 into
palladacycles [4] generated in situ from complexes 5-8.
The presented study provides generally useful insights
into the role played by a proper balance between the
nature of substituents at the palladium-bonded sp3-
hybridized carbon, and the steric and electronic proper-
ties of auxiliary phosphine ligands in palladium-
mediated carbon-carbon bond-forming processes.
Experimental Section
Unless otherwise indicated, all NMR data were collected at
room temperature in CDCl3 with internal CHCl3 as the
reference (δ 7.26 ppm for 1H and 77.00 ppm for 13C) and
external (present in a sealed capillary inserted into the NMR
tube) H3PO4 (δ 0 ppm) as the reference for 31P NMR. IR spectra
were measured in KBr pellets or as thin films on salt (NaCl)
plates. Melting points are uncorrected and were taken in open
capillary tubes. MS were measured under fast atom bombard-
ment (FAB) or electrospray (ES) ionization conditions. Analyti-
cal thin-layer chromatography (TLC) was carried out on
commercial Merck silica gel 60 plates, 0.25 µm thickness, with
fluorescent indicator (F-254) or stained with aqueous KMnO4
solution. Column chromatography was performed with 40-
63 µm silica gel (Merck) or basic alumina (150 mesh, Brok-
mann I). Tetrahydrofuran (THF) was freshly distilled from
sodium/benzophenone. Benzene was distilled from CaH2 and
kept over 3 Å (8-12 mesh) molecular sieves under an
atmosphere of dry argon. 1,2-Dichloroethane and methylene
chloride were kept over 3 Å (8-12 mesh) molecular sieves
under an atmosphere of dry argon; other solvents were used
as received. Unless otherwise specified, all reactions were
carried out under an atmosphere of dry nitrogen or argon in
oven-dried (at least 6 h at 140 °C) glassware. Single crystals
for X-ray analysis were obtained by a slow diffusion of hexanes
into methylene chloride solutions of the palladium complexes,
and by a slow diffusion of hexanes into ether solutions of
heterocycles (a 2H-1-benzopyran and a 1,2-dihydroquinoline).
General Procedure for the Synthesis of Aryl Iodides
1a-d. To a suspension of 2-iodophenol (1.0 mmol) and K2CO3
(5.0 mmol) in acetone (3.3 mL) at room temperature under
argon was added the corresponding R-bromo ester as neat
liquid, and the resulting suspension was refluxed for 16-26
h. The reaction mixtures were filtered, and the solvents were
removed under reduced pressure to provide crude products
that were purified by flash chromatography over silica eluting
with ether/hexane or EtOAc/hexane mixtures to afford aryl
iodides 1a-d as colorless or yellow oils.
1
confirmed by X-ray crystallographic analyses. H and
31P NMR monitoring experiments indicated that ligand
exchange reactions between palladacycles 3a (R1 ) Me),
3c (R1 ) i-Pr), and 3d (R1 ) Ph) and PPh2Me ligands
reached complete conversions to the corresponding
palladacycles [4] possessing the two phosphines in cis
orientation. However, the reactions with PPh3 ligand
under equivalent conditions led only to partial conver-
sions of substrates 3. These observations contrast with
a facile displacement of the TMEDA ligand with PPh3
in palladacycle 3 lacking an R1 substituent (R1 ) H).11d
The choice of monodentate phosphine ligands (L), and
the nature of the substituent R1 in arylpalladium(II)
iodo complexes I proved critical for the successful
generation of palladacycles II (Figure 1) from complexes
I via an intramolecular displacement of iodide. Thus,
31P NMR analyses of the crude product mixtures arising
from the ring-closure reactions of arylpalladium(II) iodo
complexes 5a,b, 7a,b, and 8a,b (L ) PPh3 or PPh2Me,
R1 ) Me, i-Pr, and Ph) run for a set time period of 20
min revealed an incomplete conversion of complexes
bearing PPh3 ligands (5a, 7a, and 8a), and the complex
7b (L ) PPh2Me, R1 ) i-Pr) possessing a sterically
demanding i-Pr substituent,27 while essentially com-
plete conversions were reached with complexes 5b and
8b bearing PPh2Me ligands. The mol % content of
palladacycles [4] with PPh3 ligands in the crude product
mixtures was in the range of 0-44 mol %, while the
Ethyl 2-(2-Iodophenoxy)propionate (1a). Treatment of
2-iodophenol (1.00 g, 4.55 mmol), K2CO3 (3.33 g, 24.1 mmol),
and ethyl 2-bromopropionate (0.90 mL, 1.25 g, 6.91 mmol) for
17 h according to the general procedure described above
eluting with ether/hexane (1:20) afforded aryl iodide 1a (1.425

Palladacycles with a Metal-Bonded Carbon
Organometallics, Vol. 24, No. 5, 2005 955
g, 98%) as a light yellow oil: Rf ) 0.48 (EtOAc/hexane, 1:9);
1H NMR (400 MHz, CDCl3) δ 7.78 (dd, J ) 7.7 Hz, 1.5 Hz, 1
H), 7.24 (ddd, J ) 8.2 Hz, 6.5 Hz, 1.6 Hz, 1 H), 6.75-6.69 (m,
2 H), 4.74 (q, J ) 6.8 Hz, 1 H), 4.27-4.27 (m, 2 H), 1.69 (d, J
) 6.8 Hz, 3 H), 1.24 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz,
CDCl3) δ 171.6, 156.6, 139.8, 129.3, 123.4, 113.5, 87.3, 74.2,
61.3, 18.5, 14.1; IR (neat, cm-1) 1750 (s), 746 (m), 650 (m);
HRMS (FAB) calcd for C11H14IO3 (M + H+), 320.9988, found
320.9971.
Ethyl 2-(2-Iodophenoxy)butyrate (1b). Treatment of
2-iodophenol (3.30 g, 15.0 mmol), K2CO3 (10.0 g, 72.4 mmol),
and ethyl 2-bromobutyrate (4.43 mL, 5.840 g, 30.0 mmol) for
26 h according to the general procedure described above
eluting with EtOAc/hexane (1:20) afforded aryl iodide 1b (4.80
g, 96%) as a light yellow oil: Rf ) 0.52 (EtOAc/hexane, 1:9);
1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J ) 7.8 Hz, 1.6 Hz, 1
H), 7.25 (td, J ) 8.1 Hz, 1.6 Hz, 1 H), 6.73 (td, J ) 7.6 Hz, 1.2
Hz, 1 H), 6.66 (dd, J ) 8.2 Hz, 1.1 Hz, 1 H), 4.60 (t, J ) 5.9
Hz, 1 H), 4.27-4.19 (m, 2 H), 2.07 (pent, J ) 7.3 Hz, 2 H),
1.25 (t, J ) 7.1 Hz, 3 H), 1.17 (t, J ) 7.4 Hz, 3 H); 13C NMR
(125 MHz, CDCl3) δ 171.0, 156.6, 139.7, 129.3, 123.1, 112.6,
86.9, 78.7, 61.2, 26.2, 14.4, 9.7; IR (neat, cm-1) 1746 (s), 801
(m), 735 (m); HRMS (ES) calcd for C12H16IO3 (M + H+),
335.0144, found 335.0129.
Ethyl 2-(2-Iodophenoxy)-3-methylbutyrate (1c). Treat-
ment of 2-iodophenol (0.999 g, 4.542 mmol), and K2CO3 (3.18
g, 23.0 mmol) with a solution of ethyl 2-bromo-3-methylbu-
tyrate (1.436 g, 6.868 mmol) in acetone (2.0 mL) for 19 h
according to the general procedure described above was
followed by the addition of a second portion of the solution of
ethyl 2-bromo-3-methylbutyrate (0.959 g, 4.588 mmol) in
acetone (2.0 mL), and reflux for additional 30 h. Crude product
was purified according to the general procedure, eluting with
ether/hexane (1:20) to afford aryl iodide 1c (1.404 g, 89%) as
a light yellow oil: Rf ) 0.55 (EtOAc/hexane, 1:9); 1H NMR (400
MHz, CDCl3) δ 7.77 (dd, J ) 7.8 Hz, 1.6 Hz, 1 H), 7.22 (td, J
) 7.6 Hz, 1.6 Hz, 1 H), 6.70 (td, J ) 7.6 Hz, 1.2 Hz, 1 H), 6.60
(dd, J ) 8.2 Hz, 1.1 Hz, 1 H), 4.43 (d, J ) 4.7 Hz, 1 H), 4.20 (q,
J ) 7.1 Hz, 2 H), 2.4-2.3 (m, 1 H), 1.23 (t, J ) 7.1 Hz, 3 H),
1.16 (d, J ) 6.8 Hz, 3 H), 1.14 (d, J ) 6.9 Hz, 3 H); 13C NMR
(125 MHz, CDCl3) δ 170.6, 156.6, 139.7, 129.2, 122.9, 112.0,
86.6, 82.1, 61.1, 31.8, 18.9, 17.6, 14.1; IR (neat, cm-1) 1753
(s), 1731 (m), 748 (m); HRMS (FAB) calcd for C13H18IO3 (M +
H+), 349.0301, found 349.0300.
Ethyl 2-(2-Iodophenoxy)-2-phenylacetate (1d). Treat-
ment of 2-iodophenol (1.004 g, 4.56 mmol), K2CO3 (3.15 g, 22.8
mmol), and ethyl 2-bromophenylacetate (1.20 mL, 1.66 g, 6.84
mmol) for 16 h according to the general procedure described
above eluting with ether/hexane (1:20) afforded aryl iodide 1b
(1.751 g, 100%) as a yellow oil: Rf ) 0.48 (EtOAc/hexane, 1:9);
1H NMR (400 MHz, CDCl3) δ 7.81 (dd, J ) 8.1 Hz, 1.6 Hz, 1
H), 7.70-7.68 (m, 2 H), 7.44-7.35 (m, 3 H), 7.23 (td, J ) 8.2
Hz, 1.6 Hz, 1 H), 6.76-6.72 (m, 2 H), 5.68 (s, 1 H), 4.29-4.11
(m, 2 H), 1.18 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz, CDCl3)
δ 169.3, 156.0, 139.9, 134.9, 129.3, 128.9, 128.7 (2 carbons)
127.5 (2 carbons), 123.5, 113.2, 87.2, 79.5, 61.7, 13.9; IR (neat,
cm-1) 1734 (s), 748.5 (m), 697.8 (m); HRMS (FAB) calcd for
C16H16IO3 (M + H+), 382.0144, found 383.0137.
triturated with minimum amounts of ether, yielding pure
palladium(II) iodo complexes 2a-d as yellow solids.
{2-[1-Ethoxycarbonylethoxy]phenyl}iodo(tetra-
methylethylenediamine)palladium (2a). Pd2dba3 (1.00 g,
1.09 mmol), TMEDA (0.50 mmol, 0.385 g, 3.31 mmol), and aryl
iodide 1a (0.770 g, 2.41 mmol) were treated according to the
general procedure described above to afford the palladium
complex 2a (0.830 g, 70%) as a yellow solid: mp 130-131 °C
(ether); Rf ) 0.32 (EtOAc/hexane, 1:1); 1H NMR (500 MHz,
CDCl3) δ 7.35 (dd, J ) 7.2 Hz, 1.7 Hz, 0.2 H), 7.17 (dd, J ) 7.4
Hz, 1.5 Hz, 0.8 H), 6.80-6.73 (m, 1.2 H), 6.68 (td, J ) 7.3 Hz,
1.2 Hz, 0.8 H), 6.60 (d, J ) 7.5 Hz, 0.2 H), 6.41 (dd, J ) 7.8
Hz, 1.1 Hz, 0.8 H), 5.86 (q, J ) 6.8 Hz, 0.2 H), 4.86 (q, J ) 6.8
Hz, 0.8 H), 4.34-4.26 (m, 0.4 H), 4.24-4.15 (m, 1.6 H), 2.82-
2.75 (m, 1 H), 2.73 (s, 2.4 H), 2.71 (s, 2.4 H), 2.70 (s, 0.6 H),
2.66 (s, 0.6 H), 2.63-2.55 (m, 3 H), 2.52 (s, 0.6 H), 2.44 (s, 2.4
H), 2.39 (s, 2.4 H), 2.34 (s, 0.6 H), 1.76 (d, J ) 6.8 Hz, 2.4 H),
1.48 (d, J ) 6.8 Hz, 0.6 H), 1.31 (t, J ) 7.1 Hz, 0.6 H), 1.26 (t,
J ) 7.1 Hz, 2.4 H); 13C NMR (125 MHz, CDCl3) δ 174.0, (173.6),
160.3, (159.6), (139.3), 137.9, (132.8), 131.4, 123.7, (123.6),
(122.6), 121.4, (120.9), 113.7, (74.6), 73.7, 62.1, 60.7, (60.6),
58.6, 50.6, (50.5), 50.2, 49.9, 49.4, (49.3), 20.1, (17.9), (14.4),
14.2 (signals for the minor isomer arising from a hindered
rotation about the Csp2-Pd bond are shown in parentheses);
IR (KBr, cm-1) 1724 (s), 800 (m), 748 (m); HRMS (FAB) calcd
for C17H30N2O5IPd (M + H+), 543.0336, found 543.0327.
{2-[1-Ethoxycarbonylpropoxy]phenyl}iodo(tetra-
methylethylenediamine) palladium (2b). Pd2dba3 (1.00 g,
1.09 mmol), TMEDA (0.50 mmol, 0.385 g, 3.31 mmol), and aryl
iodide 1b (0.807 g, 2.41 mmol) were treated according to the
general procedure described above to afford the palladium
complex 2b (0.707 g, 58%) as a yellow solid: mp 102-104 °C
(ether); Rf ) 0.29 (EtOAc/hexane, 1:1); 1H NMR (500 MHz,
CDCl3) δ 7.17 (d, J ) 7.3 Hz, 1 H), 6.77 (t, J ) 7.2 Hz, 1 H),
6.66 (t, J ) 7.2 Hz, 1 H), 6.25 (d, J ) 7.8 Hz, 1 H), 4.63 (t, J
) 6.3 Hz, 1 H), 4.20 (q, J ) 7.1 Hz, 2 H), 2.81-2.75 (m, 1 H),
2.71 (s, 6 H), 2.66-2.54 (m, 3 H), 2.47 (s, 3 H), 2.42 (s, 3 H),
2.17-2.13 (m, 1 H), 2.12-2.04 (m, 1 H), 1.26 (td, J ) 7.0 Hz,
2.0 Hz, 6 H); 13C NMR (125 MHz, CDCl3) δ 173.3, 159.9, 137.7,
130.3, 123.7, 120.8, 111.2, 77.3, 62.1, 60.6, 58.5, 50.6, 50.2, 49.8,
49.2, 27.2, 14.3, 10.2; IR (KBr, cm-1) 1739 (s), 802 (m), 746
(m); HRMS (ES) calcd for C18H32N2O3IPd (M + H+), 557.0500,
found 557.0511.
{2-[1-Ethoxycarbonyl-2-methylpropoxy]phenyl}iodo-
(tetramethylethylenediamine)palladium (2c). Pd2dba3
(0.962 g, 1.05 mmol), TMEDA (0.47 mmol, 0.362 g, 3.11 mmol),
and aryl iodide 1c (0.771 g, 2.21 mmol) were treated according
to the general procedure described above to afford the pal-
ladium complex 2c (0.833 g, 69%) as a yellow solid: mp 168-
1
170 °C (ether); Rf ) 0.45 (EtOAc/hexane, 1:1); H NMR (400
MHz, CDCl3) δ 7.16 (dd, J ) 7.3 Hz, 1.6 Hz, 1 H), 6.77 (td, J
) 7.2 Hz, 1.6 Hz, 1 H), 6.64 (td, J ) 7.3 Hz, 1.2 Hz, 1 H), 6.16
(dd, J ) 7.9 Hz, 1.0 Hz, 1 H), 4.44 (d, J ) 4.3 Hz, 1 H), 4.19 (q,
J ) 7.2 Hz, 2 H), 2.82-2.75 (m, 1 H), 2.72 (s, 6 H), 2.66-2.51
(m, 3 H), 2.47 (s, 3 H), 2.43 (s, 3 H), 2.40-2.32 (m, 1 H), 1.27
(d, J ) 2.6 Hz, 3 H), 1.26 (t, J ) 7.2 Hz, 3 H), 1.25 (d, J ) 2.0
Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 172.6, 159.8, 137.7,
129.5, 123.7, 120.4, 109.5, 80.2, 62.1, 60.5, 58.6, 50.6, 50.3, 49.7,
49.3, 32.3, 19.8, 18.1,14.3; IR (KBr, cm-1) 1737 (s), 802 (m),
746 (m); HRMS (ES) calcd for C19H34N2O3IPd (M + H+),
571.0657, found 571.0679.
General Procedure for the Synthesis of Palladium-
(II) Iodo Complexes 2a-d. To a solution of tris(dibenzylide-
neacetone)dipalladium(0) (Pd2dba3) (0.500 mmol) in benzene
(25 mL) at room temperature under argon was added neat
N,N,N′,N′-tetramethyl-1,2-ethylenediamine (TMEDA) (1.5
mmol) and the solution of aryl iodides 1a-d (1.05-1.1 mmol)
in benzene (1-2 mL). The reaction mixture was stirred at 55
°C for 30 min. The resulting suspension was filtered through
a plug of Celite, and solvents were removed under reduced
pressure. The crude product was deposited on Celite, intro-
duced on top of a short silica column, and eluted with EtOAc/
hexane (1:5) mixture to remove excess dba, and subsequently
with EtOAc/hexane (1:1) to afford a solid product, which was
{2-[(Ethoxycarbonyl)phenylmethoxy]phenyl}iodo-
(tetramethylethylenediamine)palladium (2d). Pd2dba3
(1.00 g, 1.09 mmol), TMEDA (0.50 mmol, 0.385 g, 3.31 mmol),
and aryl iodide 1d (0.916 g, 2.40 mmol) were treated according
to the general procedure described above to afford the pal-
ladium complex 2d (0.997 g, 75%) as a yellow solid: mp 168-
1
170 °C (ether); Rf ) 0.39 (EtOAc/hexane, 1:1); H NMR (500
MHz, CDCl3) δ 7.90 (d, J ) 7.4 Hz, 1 H), 7.61 (d, J ) 8.1 Hz,
0.6 H), 7.39-7.25 (m, 4.4 H), 6.80 (td, J ) 7.4 Hz, 1.5 Hz, 0.6
H), 6.73 (td, J ) 7.3 Hz, 1.3 Hz, 0.6 H), 6.70 (td, J ) 7.3 Hz,

956 Organometallics, Vol. 24, No. 5, 2005
Lu et al.
1.3 Hz, 0.4 H), 6.64 (dd, J ) 7.9 Hz, 1.2 Hz, 0.6 H), 6.62 (td, J
) 7.5 Hz, 1.3 Hz, 0.4 H), 6.30 (s, 0.4 H), 6.17 (dd, J ) 7.8 Hz,
1.3 Hz, 0.4 H), 6.05 (s, 0.6 H), 4.20-4.12 (m, 2 H), 2.82-2.78
(m, 0.6 H), 2.73 (s, 1.2 H), 2.72 (s, 1.2 H), 2.65 (s, 1.8 H), 2.64-
2.50 (m, 3.4 H), 2.49 (s, 1.2 H), 2.41 (s, 1.8 H), 2.39 (s, 1.2 H),
2.37 (s, 1.8 H), 2.36 (s, 1.8 H), 1.20 (t, J ) 7.1 Hz, 1.8 H), 1.18
(t, J ) 7.1 Hz, 1.2 H); 13C NMR (125 MHz, CDCl3) δ 171.8,
(171.5), 160.2, (159.9), (138.6), 138.5, (137.9), 137.7, (132.7),
132.1, 128.3, (128.2), 128.1 (2 carbons), 128.0, (127.9), 127.4,
123.8, (123.5), (122.5), 122.1, (118.8), 115.7, (80.5), 79.3, (62.2),
62.1, 61.0, (60.9), (58.6), 58.5, (50.6), 50.5, (50.3), 50.2, 49.9,
(49.2), 49.0, (14.2), 14.1 (signals for the minor isomer arising
from a hindered rotation about the Csp2-Pd bond are shown
in parentheses); IR (KBr, cm-1) 1751 (s), 800 (m), 769 (m);
HRMS (ES) calcd for C22H35N3O3IPd (M + NH4+), 622.0758,
found 622.0766.
General Procedure for the Synthesis of Stable Palla-
dacycles 3a-d. To a solution of palladium(II) iodo complexes
2a-d (1.0 mmol) in benzene (14-30 mL) under argon at room
temperature was added t-BuOK (1.2-1.6 mmol, 1.0 M in THF).
The resulting suspension was stirred for 15-20 min, filtered
through Celite, and the solvents were removed under reduced
pressure to afford palladacycles 3a-d as yellow solids.
[1-Ethoxycarbonyl-1-ethinoxy-1,2-phenylene][tetra-
methylethylenediamine]palladium (3a). A solution of pal-
ladium(II) complex 2a (0.800 g, 1.47 mmol) in benzene (20 mL)
was treated with t-BuOK (2.2 mL, 2.2 mmol, 1.0 M in THF)
according to the general procedure described above to afford
palladacycle 3a (0.514 g, 84%) as a yellow solid: mp 154-156
°C dec (benzene); Rf ) 0.34 (EtOAc/hexane, 3:1); 1H NMR (500
MHz, CDCl3) δ 7.03 (d, J ) 7.5 Hz, 1 H), 6.93 (t, J ) 7.2 Hz,
1 H), 6.69 (d, J ) 7.8 Hz, 1 H), 6.60 (t, J ) 7.3 Hz, 1 H), 4.18-
4.07 (m, 2 H), 2.78 (s, 3 H), 2.77 (s, 3 H), 2.73-2.62 (m, 2 H),
2.67 (s, 3 H), 2.52 (s, 3 H), 2.48-2.38 (m, 2 H), 1.75 (s, 3 H),
1.21 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 177.9,
172.2, 136.5, 133.4, 125.5, 117.2, 108.5, 93.5, 61.6, 61.2, 59.7,
50.4, 49.3 (2 carbons), 47.9, 25.7, 14.5; IR (KBr, cm-1) 1677
(s), 802 (m), 750 (m); HRMS (ES) calcd for C17H29N2O3Pd (M
+ H+), 415.1220, found 415.1210.
3 H); 13C NMR (125 MHz, CDCl3) δ 176.5, 174.3, 135.6, 133.2,
125.4, 116.4, 107.8, 103.4, 61.5, 61.2, 59.5, 50.6, 49.6, 49.2, 47.5,
35.8, 24.5, 17.3, 14.6; IR (KBr, cm-1) 1664 (s), 800 (m), 746
(m); HRMS (ES) calcd for C19H33N2O3Pd (M + H+), 443.1534,
found 443.1546.
[1-Ethoxycarbonyl-1-phenylmethinoxy-1,2-phenylene]-
[tetramethylethylenediamine]palladium (3d). A solution
of palladium(II) complex 2d (0.600 g, 0.992 mmol) in benzene
(30 mL) was treated with t-BuOK (1.6 mL, 1.6 mmol, 1.0 M in
THF) according to the general procedure described above to
afford palladacycle 3d (0.446 g, 94%) as a yellow solid: mp
164-166 °C dec (benzene); Rf ) 0.67 (EtOAc/hexane, 3:1); 1H
NMR (500 MHz, CDCl3) δ 7.86 (dd, J ) 8.4 Hz, 1.2 Hz, 2 H),
7.28-7.20 (m, 2 H), 7.12 (t, J ) 7.3 Hz, 1 H), 7.05 (dd, J ) 7.6
Hz, 1.2 Hz, 1 H), 6.95 (td, J ) 7.8 Hz, 1.3 Hz, 1 H), 6.75 (dd,
J ) 7.8 Hz, 1.3 Hz, 1 H), 6.65 (td, J ) 7.5 Hz, 1.3 Hz, 1 H),
4.16-4.07 (m, 2 H), 2.82 (s, 3 H), 2.75 (s, 3 H), 2.73-2.55 (m,
3 H), 2.37 (s, 3 H), 2.22-2.19 (m, 1 H), 1.48 (s, 3 H), 1.09 (t, J
) 7.1 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 174.1, 172.8,
143.9, 136.6, 133.3, 128.7 (2 carbons), 127.6 (2 carbons), 125.8,
125.3, 117.4, 108.6, 97.5, 61.2, 61.1, 59.5, 51.1, 49.3, 49.1, 47.4,
14.1; IR (KBr, cm-1) 1676 (s), 800 (m), 757 (m), 702 (m); HRMS
(ES) calcd for C22H31N2O3Pd (M + H+), 477.1378, found
477.1382.
General Procedure for the Synthesis of Palladium-
(II) Iodo Complexes with Monodentate Phosphine
Ligands. Method A. To a solution of tris(dibenzylidene-
acetone)dipalladium(0) (Pd2dba3) (0.50 mmol) and phosphine
(2.0 mmol) in benzene (20 mL) at room temperature under
argon was added a solution of aryl iodides 1a-d (1.1 mmol)
in benzene (1-2 mL). The mixture was stirred at 60 °C for 30
min. The resulting suspension was filtered through a plug of
Celite, and solvents were removed under reduced pressure.
The crude product was purified by flash chromatography over
silica, eluting with with EtOAc/hexane (1:10) to remove excess
dibenzylideneacetone (dba), and subsequently with EtOAc/
hexane (1:3) to afford palladium (II) complexes 5-8 as yellow
or white solids.
Method B. To a solution of arylpalladium(II) complexes
2b-e (1.0 mmol) in CH2Cl2 (10 mL) under argon at room
temperature was added the corresponding phosphine (2.4-
2.5 mmol) or trimethylphosphonium tetrafluoroborate (2.3
mmol) and diisopropylethylamine (4.6 mmol). The mixture was
stirred at room temperature for the indicated time, solvents
were removed under reduced pressure, and the crude product
was purified by flash chromatography over silica eluting with
EtOAc/hexane (1:20) to remove excess phosphine, and subse-
quently with EtOAc/hexane (1:3) to afford palladium(II)
complexes 6-8 as yellow or white solids.
trans-{2-[1-Ethoxycarbonylethoxy]phenyl}iodobis-
(triphenylphosphine)palladium (5a). Pd2dba3 (0.916 g,
1.00 mmol), PPh3 (1.049 g, 4.00 mmol), and aryl iodide 1a
(0.704 g, 2.200 mmol) were treated according to method A
described above to afford the arylpalladium(II) iodo complex
5a (1.639 g, 86%) as a yellow solid: mp 156-158 °C dec
(EtOAc/hexane, 1:3); Rf ) 0.54 (EtOAc/hexane, 1:3); 1H NMR
(400 MHz, CDCl3) δ 7.59 (q, J ) 5.4 Hz, 6 H), 7.50 (q, J ) 5.4
Hz, 6 H), 7.32-7.20 (m, 18 H), 6.76 (d, J ) 6.3 Hz, 1 H), 6.35
(t, J ) 7.4 Hz, 1 H), 6.05 (t, J ) 7.2 Hz, 1 H), 5.49 (d, J ) 7.9
Hz, 1 H), 4.15-4.07 (m, 1 H), 3.98-3.90 (m, 1 H), 3.67 (q, J )
6.6 Hz, 1 H), 1.38 (d, J ) 6.6 Hz, 3 H), 1.07 (t, J ) 7.1 Hz, 3
H); 13C NMR (100 MHz, CDCl3) δ 172.7, 157.4, 146.8, 136 (t,
J(13C-31P) ) 4.2 Hz), 134.9 (t, J(13C-31P) ) 5.6 Hz), 132.8,
132.5 (d, J(13C-31P) ) 6.1 Hz), 132.3 (d, J(13C-31P) ) 6.7 Hz),
132.2, 129.5 (d, J(13C-31P) ) 16.8 Hz), 127.4 (q, J(13C-31P) )
5.3 Hz), 123.5, 120.9, 110.3, 71.8, 60.7, 18.9, 13.9, several
signals account for more than one carbon; 31P NMR (162 MHz,
CDCl3) δ 23.12 (s, 1 P), 23.09 (s, 1 P);23 IR (KBr, cm-1) 1751
(s), 1730 (s), 1433 (s), 740 (m), 692 (s), 509 (s); HRMS (ES)
calcd for C47H43O3P2Pd (M - I+), 823.1722, found 823.1703.
[1-Ethoxycarbonyl-1-prophinoxy-1,2-phenylene][tet-
ramethylethylenediamine]palladium (3b). A solution of
palladium(II) complex 2b (0.600 g, 1.08 mmol) in benzene (15
mL) was treated with t-BuOK (1.7 mL, 1.7 mmol, 1.0 M in
THF) according to the general procedure described above to
afford palladacycle 3b (0.407 g, 88%) as a yellow solid: mp
132-134 °C dec (benzene); Rf ) 0.44 (EtOAc/hexane, 3:1); 1H
NMR (500 MHz, CDCl3) δ 7.03 (d, J ) 7.6 Hz, 1 H), 6.93 (td,
J ) 7.5 Hz, 0.8 Hz, 1 H), 6.70 (dd, J ) 7.5 Hz, 0.8 Hz, 1 H),
6.57 (td, J ) 7.7 Hz, 0.8 Hz, 1 H), 4.18-4.09 (m, 2 H), 2.79 (s,
3 H), 2.78 (s, 3 H), 2.74-2.67 (m, 2 H), 2.65 (s, 3 H), 2.50 (s, 3
H), 2.46-2.42 (m, 1 H), 2.38-2.35 (m, 1 H), 2.29 (sext, J )
7.4 H, 1 H), 1.99 (sext, J ) 7.1 Hz, 1 H), 1.23 (t, J ) 7.1 Hz,
3 H), 1.13 (t, J ) 7.2 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ
177.1, 173.1, 136.3, 133.3, 125.5, 116.8, 108.2, 99.5, 61.6, 61.2,
59.6, 50.6, 49.4, 49.1, 47.5, 31.7, 14.5, 12.4; IR (KBr, cm-1) 1670
(s), 802 (m), 756 (m); HRMS (FAB) calcd for C18H31N2O3Pd (M
+ H+), 429.1377, found 429.1353.
[1-Ethoxycarbonyl-2-methyl-1-prophinoxy-1,2-phen-
ylene][tetramethylethylenediamine]palladium (3c). A
solution of palladium(II) complex 2c (0.500 g, 0.855 mmol) in
benzene (25 mL) was treated with t-BuOK (1.0 mL, 1.0 mmol,
1.0 M in THF) according to the general procedure described
above to afford palladacycle 3c (0.371 g, 95%) as a yellow
solid: mp 152-154 °C dec (benzene); Rf ) 0.56 (EtOAc/hexane,
1
3:1); H NMR (500 MHz, CDCl3) δ 7.02 (dd, J ) 7.6 Hz, 1.0
Hz, 1 H), 6.92 (td, J ) 7.3 Hz, 1.2 Hz, 1 H), 6.70 (dd, J ) 7.8
Hz, 1.2 Hz, 1 H), 6.55 (td, J ) 7.6 Hz, 1.2 Hz, 1 H), 4.23-4.07
(m, 2 H), 2.80 (s, 3 H), 2.78 (s, 3 H), 2.76-2.66 (m, 2 H), 2.64
(s, 3 H), 2.60-2.53 (m, 1 H), 2.51 (s, 3 H), 2.44 (dt, J ) 13.1
Hz, 3.3 Hz, 1 H), 2.34 (dt, J ) 12.9 Hz, 2.3 Hz, 1 H), 1.35 (d,
J ) 6.9 Hz, 3 H), 1.22 (t, J ) 7.1 Hz, 3 H), 1.03 (d, J ) 6.5 Hz,

Palladacycles with a Metal-Bonded Carbon
Organometallics, Vol. 24, No. 5, 2005 957
trans-{2-[1-Ethoxycarbonylethoxy]phenyl}iodobis-
(methyldiphenylphosphine)palladium (5b). Pd2dba3 (1.374
g, 1.500 mmol), PPh2Me (1.1 mL, 1.184 g, 6.00 mmol), and aryl
iodide 1a (1.056 g, 3.300 mmol) were treated according to
method A described above to afford the palladium complex 5b
(2.075 g, 84%) as a yellow solid: mp 78-80 °C (EtOAc/hexane,
1:3); Rf ) 0.58 (EtOAc/hexane, 1:3); 1H NMR (400 MHz, CDCl3)
δ 7.88-7.84 (m, 2 H), 7.65-7.62 (m, 2 H), 7.58-7.54 (m, 2 H),
7.42-7.39 (m, 4 H), 7.33-7.24 (m, 8 H), 7.19 (t, J ) 7.2 Hz, 2
H), 6.81 (dq, J ) 7.3 Hz, 1.7 Hz, 1 H), 6.62 (t, J ) 7.2 Hz, 1
H), 6.34 (t, J ) 7.2 Hz, 1 H), 5.87 (dd, J ) 8.1 Hz, 1.0 Hz, 1
H), 4.19-4.01 (m, 3 H), 1.95 (d, J ) 6.0 Hz, 3 H), 1.49 (s br, 3
H), 1.48 (t br, J ) 1.3 Hz, 3 H), 1.14 (t, J ) 7.1 Hz, 3 H); 13C
NMR (125 MHz, CDCl3) δ 172.9, 158.1 (t, J(13C-31P) ) 2.4
Hz), 144.6 (t, J(13C-31P) ) 4.7 Hz), 143.3, 136.1 (t, J(13C-31P)
) 17.7 Hz), 135.8 (t, J(13C-31P) ) 4.2 Hz), 134.8 (d, J(13C-
31P) ) 5.0 Hz), 134.7, 134.5 (d, J(13C-31P) ) 13.7 Hz), 133.9
(dd, J(13C-31P) ) 8.6 Hz, 4.2 Hz), 133.7 (d, J(13C-31P) ) 13.5
Hz), 133.4 (dd, J(13C-31P) ) 8.9 Hz, 4.2 Hz), 133.2, 133.1,
132.9, 132.8 (dd, J(13C-31P) ) 8.2 Hz, 4.0 Hz), 132.5 (dd,
J(13C-31P) ) 7.8 Hz, 3.8 Hz), 132.0 (d, J(13C-31P) ) 18.4 Hz),
130.5, 129.9 (d, J(13C-31P) ) 28.0 Hz), 129.3 (d, J(13C-31P) )
9.4 Hz), 128.9, 128.4, 128.1 (dd, J(13C-31P) ) 7.2 Hz, 2.7 Hz),
127.9 (dd, J(13C-31P) ) 7.4 Hz, 2.7 Hz), 127.5 (td, J(13C-31P)
) 7.8 Hz, 2.6 Hz), 125.4, 123.9, 120.9, 110.0, 71.6, 60.9, 19.2,
17.0 (dd, J(13C-31P) ) 21.5 Hz, 9.1 Hz), 14.5 (dd, J(13C-31P)
) 22.7 Hz, 9.2 Hz), 14.1, several signals account for more than
one carbon; 31P NMR (162 MHz, CDCl3) δ 6.84 (d, J ) 451.1
Hz, 1 P), 5.71 (d, J ) 451.0 Hz, 1 P); IR (KBr, cm-1) 1749 (s),
1726 (m), 891 (s), 740 (m), 692 (s); HRMS (FAB) calcd for
C37H39O3P2Pd (M - I+), 699.1409, found 699.1391.
trans-{2-[1-Ethoxycarbonylpropoxy]phenyl}iodobis-
(triphenylphosphine)palladium (6a). Pd2dba3 (0.916 g,
1.00 mmol), PPh3 (1.049 g, 4.00 mmol), and aryl iodide 1b
(0.735 g, 2.20 mmol) were treated according to method A
described above to afford the arylpalladium (II) iodo complex
6a (1.510 g, 78%) as a yellow solid: mp 144-146 °C dec
(EtOAc/hexane, 1:3); Rf ) 0.53 (EtOAc/hexane, 1:3); 1H NMR
(400 MHz, CDCl3) δ 7.62-7.57 (m, 6 H), 7.51-7.47 (m, 6 H),
7.33-7.26 (m, 6 H), 7.23-7.20 (m, 12 H), 6.74-6.72 (m, 1 H),
6.35 (t, J ) 7.4 Hz, 1 H), 6.02 (t, J ) 7.3 Hz, 1 H), 5.53 (t, J )
7.9 Hz, 1 H), 4.21-4.03 (m, 1 H), 3.99-3.88 (m, 1 H), 3.57
(dd, J ) 7.0 Hz, 4.3 Hz, 1 H), 1.90-1.71 (m, 2 H), 1.04 (td, J
) 7.1 Hz, 1.3 Hz, 6 H); 13C NMR (100 MHz, CDCl3) δ 171.9,
157.7 (t, J(13C-31P) ) 2.5 Hz), 146.8 (t, J(13C-31P) ) 3.3 Hz),
136.6 (t, J(13C-31P) ) 4.3 Hz), 134.9 (t, J(13C-31P) ) 5.7 Hz),
132.7 (d, J(13C-31P) ) 19.4 Hz), 132.5 (d, J(13C-31P) ) 5.3 Hz),
132.3 (d, J(13C-31P) ) 4.5 Hz), 132.1 (d, J(13C-31P) ) 18.8 Hz),
129.6 (d, J(13C-31P) ) 20.0 Hz), 127.5 (t, J(13C-31P) ) 5.7 Hz),
123.5, 120.8, 110.6, 76.6, 60.5, 26.0, 14.0, 8.9, several signals
account for more than one carbon; 31P NMR (162 MHz, CDCl3)
δ 22.78 (s, 1 P), 22.73 (s, 1 P);23 IR (KBr, cm-1) 1749 (s), 1730
(m), 740 (m), 692 (s), 509 (m), 491 (m); HRMS (ES) calcd for
C38H45O3P2Pd (M - I+), 837.1896, found 837.1936.
Hz), 134.6 (d, J(13C-31P) ) 12.1 Hz), 133.9 (dd, J(13C-31P) )
8.9 Hz, 3.8 Hz), 133.7 (d, J(13C-31P) ) 11.4 Hz), 133.5 (dd,
J(13C-31P) ) 9.1 Hz, 4.0 Hz), 133.2 (d, J(13C-31P) ) 12.1 Hz),
132.8 (dd, J(13C-31P) ) 8.5 Hz, 3.8 Hz), 132.5 (dd, J(13C-31P)
) 8.0 Hz, 3.2 Hz), 129.9 (d, J(13C-31P) ) 23.8 Hz), 129.3 (d,
J(13C-31P) ) 13.4 Hz), 128.3, 128.1 (dd, J(13C-31P) ) 7.5 Hz,
2.4 Hz), 127.8 (dd, J(13C-31P) ) 7.8 Hz, 2.5 Hz), 127.5 (d,
J(13C-31P) ) 7.6 Hz), 124.0, 120.9, 110.1, 76.4, 60.8, 26.5, 16.5
(dd, J(13C-31P) ) 22.4 Hz, 8.2 Hz), 14.1 (dd, J(13C-31P) ) 24.1
Hz, 13.2 Hz), 14.2, 9.6, several signals account for more than
one carbon; 31P NMR (202 MHz, CDCl3) δ 7.27 (d, J ) 451.0
Hz, 1 P), 5.88 (d, J ) 451.0 Hz, 1 P); IR (KBr, cm-1) 1749 (s),
1730 (m), 892 (s), 740 (m), 729 (m), 692 (s), 503 (m); HRMS
(ES) calcd C38H41O3P2Pd (M - I+), 713.1580, found 713.1572.
trans-{2-[1-Ethoxycarbonyl-2-methylpropoxy]phenyl}-
iodobis(triphenylphosphiine)palladium (7a). Pd2dba3
(1.282 g, 1.400 mmol), PPh3 (1.469 g, 5.600 mmol), and aryl
iodide 1c (1.079 g, 3.100 mmol) were treated according to
method A described above to afford the arylpalladium(II)
complex 7a (2.290 g, 84%) as a yellow solid: mp 140-142 °C
dec (EtOAc/hexane, 1:3); Rf ) 0.51 (EtOAc/hexane, 1:3); 1H
NMR (400 MHz, CDCl3) δ 7.65-7.55 (m, 6 H), 7.54-7.39 (m,
6 H), 7.33-7.20 (m, 18 H), 6.66 (d, J ) 5.5 Hz, 1 H), 6.36 (t, J
) 7.0 Hz, 1 H), 5.96 (t, J ) 7.2 Hz, 1 H), 5.60 (d, J ) 7.8 Hz,
1 H), 4.16-4.10 (m, 1 H), 3.87-3.83 (m, 1 H), 3.45 (d, J ) 4.2
Hz, 1 H), 2.18-2.05 (m, 1 H), 1.14 (d, J ) 6.7 Hz, 3 H), 1.01
(d, J ) 5.1 Hz, 3 H), 1.00 (t, J ) 5.1 Hz, 3 H); 13C NMR (125
MHz, CDCl3) δ 170.9, 158.1 (t, J(13C-31P) ) 2.4 Hz), 146.7 (t,
J(13C-31P) ) 3.2 Hz), 137.2 (t, J(13C-31P) ) 4.4 Hz), 134.9 (dd,
J(13C-31P) ) 8.1 Hz, 4.2 Hz), 132.7 (d, J(13C-31P) ) 15.4 Hz),
132.5 (d, J(13C-31P) ) 15.4 Hz), 132.3 (d, J(13C-31P) ) 14.6
Hz), 132.1 (d, J(13C-31P) ) 14.7 Hz), 129.5 (d, J(13C-31P) )
29.0 Hz), 127.5 (pent, J(13C-31P) ) 3.5 Hz), 123.5, 120.8, 110.8,
80.5, 60.3, 31.6, 18.6, 17.5, 14.1 several signals account for
more than one carbon; 31P NMR (162 MHz, CDCl3) δ 23.30 (d,
J ) 434.1 Hz, 1 P), 22.42 (d, J ) 434.1 Hz, 1 P); IR (KBr,
cm-1) 1747 (m), 1733 (m), 738 (s), 692 (s), 520 (m), 511 (m);
HRMS (ES) calcd for C49H47O3P2Pd (M - I+), 851.2053, found
851.2016.
trans-{2-[1-Ethoxycarbonyl-2-methylpropoxy]phenyl}-
iodobis(methyldiphenylphosphine)palladium (7b). Pal-
ladium(II) complex 2c (0.799 g, 1.400 mmol) and PPh2Me (0.65
mL, 0.70 g, 3.50 mmol) were treated according to method B
described above to afford the aryl palladium(II) iodo complex
7b (0.981 g, 83%) as a pale yellow solid: mp 150-151 °C
(EtOAc/hexane, 1:3); Rf ) 0.61 (EtOAc/hexane, 1:3); 1H NMR
(500 MHz, CDCl3) δ 7.85 (t, J ) 6.9 Hz, 2 H), 7.67-7.64 (m, 2
H), 7.58 (t, J ) 7.3 Hz, 2 H), 7.43-7.25 (m, 12 H), 7.20 (t, J )
7.4 Hz, 2 H), 6.71-6.67 (m, 2 H), 6.39 (t, J ) 7.2 Hz, 1 H),
6.03 (d, J ) 7.9 Hz, 1 H), 4.22-4.10 (m, 2 H), 3.97 (d, J ) 5.3
Hz, 1 H), 2.19-2.12 (m, 1 H), 1.77 (d, J ) 6.5 Hz, 3 H), 1.41
(d, J ) 7.0 Hz, 3 H), 1.19 (t, J ) 7.1 Hz, 3 H), 1.14 (d, J ) 6.9
Hz, 3 H), 1.12 (d, J ) 6.9 Hz, 3 H); 13C NMR (125 MHz, CDCl3)
δ 171.6, 158.8, 144.1, 135.9 (t, J(13C-31P) ) 4.3 Hz), 135.1 (d,
J(13C-31P) ) 11.4 Hz). 133.9 (dd, J(13C-31P) ) 9.4 Hz, 3.4 Hz),
133.6 (dd, J(13C-31P) ) 9.5 Hz, 3.6 Hz), 133.0 (dd, J(13C-31P)
) 8.7 Hz, 3.4 Hz), 132.7 (dd, J(13C-31P) ) 8.1 Hz, 2.9 Hz),
129.9 (d, J(13C-31P) ) 18.1 Hz), 129.4 (d, J(13C-31P) ) 14.6
Hz), 128.1 (dd, J(13C-31P) ) 9.8 Hz, 2.0 Hz), 127.9 (d, J(13C-
31P) ) 8.2 Hz), 127.6 (td, J(13C-31P) ) 8.2 Hz, 1.9 Hz), 124.2,
120.9, 110.1, 80.4, 60.6, 31.9, 18.8, 18.5, 16.1 (dd, J(13C-31P)
) 23.6 Hz, 7.2 Hz), 14.2, 13.8 (dd, J(13C-31P) ) 25.0 Hz, 7.1
Hz), several signals account for more than one carbon; 31P
NMR (202 MHz, CDCl3) δ 7.20 (d, J ) 452.1 Hz, 1 P), 5.54 (d,
J ) 452.0 Hz, 1 P); IR (KBr, cm-1) 1739 (s), 748 (m), 730 (m),
692 (s), 501 (m), 484 (m); HRMS (FAB) calcd for C39H43O3P2-
Pd (M - I+), 727.1737, found 727.1746.
trans-{2-[1-Ethoxycarbonylpropoxy]phenyl}iodobis-
(methyldiphenylphosphine)palladium (6b). Palladium(II)
complex 2b (0.779 g, 1.400 mmol) and PPh2Me (0.65 mL, 0.70
g, 3.50 mmol) were treated according to method B described
above to afford the arylpalladium(II) iodo complex 6b (1.111
g, 93%) as a pale yellow solid: mp 60-62 °C (EtOAc/hexane,
1:3); Rf ) 0.54 (EtOAc/hexane, 1:3); 1H NMR (500 MHz, CDCl3)
δ 7.88-7.85 (m, 2 H), 7.67-7.63 (m, 2 H), 7.58 (td, J ) 8.5
Hz, 1.5 Hz, 2 H), 7.43-7.38 (m, 3 H), 7.33-7.25 (m, 9 H), 7.19
(t, J ) 6.9 Hz, 2 H), 6.76 (dd, J ) 7.3 Hz, 1.6 Hz, 1 H), 6.66 (t,
J ) 7.5 Hz, 1 H), 6.38 (t, J ) 7.2 Hz, 1 H), 5.94 (d, J ) 7.8 Hz,
1 H), 4.20-4.05 (m, 2 H), 4.02 (t, J ) 5.9 Hz, 1 H), 1.91-1.84
(m, 5 H), 1.44 (d, J ) 6.6 Hz, 3 H), 1.17 (t, J ) 7.1 Hz, 3 H),
1.12 (t, J ) 7.5 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 172.3,
158 (t, J(13C-31P) ) 2.6 Hz), 144.4 (t, J(13C-31P) ) 4.9 Hz),
136.2 (d, J(13C-31P) ) 13.1 Hz), 135.9 (d, J(13C-31P) ) 12.9
Hz), 135.7 (t, J(13C-31P) ) 4.2 Hz), 134.9 (d, J(13C-31P) ) 12.1
trans-{2-[(Ethoxycarbonyl)phenylmethoxy]phenyl}-
iodobis(triphenylphosphine)palladium (8a). Pd2dba3 (1.282
g, 1.400 mmol), PPh3 (1.469 g, 5.600 mmol), and aryl iodide
1d (1.185 g, 3.100 mmol) were treated according to method A

958 Organometallics, Vol. 24, No. 5, 2005
Lu et al.
described above to afford the arylpalladium(II) iodo complex
8a (2.266 g, 80%) as a yellow solid: mp 126-128 °C dec
(EtOAc/hexane, 1:3); Rf ) 0.44 (EtOAc/hexane, 1:3); 1H NMR
(500 MHz, CDCl3) δ 7.69-7.66 (m, 6 H), 7.54-7.49 (m, 6 H),
7.39-7.26 (m, 17 H), 7.12-7.10 (m, 6 H), 6.82 (d, J ) 6.5 Hz,
1 H), 6.38 (t, J ) 7.5 Hz, 1 H), 6.1 (t, J ) 7.2 Hz, 1 H), 5.56 (d,
J ) 7.9 Hz, 1 H), 4.38 (s br, 1 H), 4.19-4.13 (m, 1 H), 3.95-
3.87 (m, 1 H), 1.02 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz,
CDCl3) δ 170.7, 157.7 (t, J(13C-31P) ) 2.5 Hz), 147.7 (t, J(13C-
31P) ) 3.4 Hz), 136.5, 135.0 (t, J(13C-31P) ) 5.4 Hz), 134.7 (t,
J(13C-31P) ) 6.3 Hz), 132.6 (d, J(13C-31P) ) 19.1 Hz), 132.4
(d, J(13C-31P) ) 9.5 Hz), 132.3 (d, J(13C-31P) ) 9.0 Hz), 132.1
(d, J(13C-31P) ) 18.9 Hz), 129.5 (d, J(13C-31P) ) 20.8 Hz),
128.7 (d, J(13C-31P) ) 24.8 Hz), 127.9, 127.5 (t, J(13C-31P) )
5.1 Hz), 127.3 (t, J(13C-31P) ) 5.0 Hz), 123.5, 121.1, 110.8,
78.5, 61.1, 13.8, several signals account for more than one
carbon; 31P NMR (162 MHz, CDCl3) δ 23.28 (s, 1 P), 23.25 (s,
1 P);23 IR (KBr, cm-1) 1751 (m), 1733 (m), 740 (m), 692 (s),
509 (s), 493 (m); HRMS (ES) calcd for C52H45O3P2Pd (M - I+),
885.1898, found 885.1898.
trans-{2-[(Ethoxycarbonyl)phenylmethoxy]phenyl}-
iodobis(methyldiphenylphosphine)palladium (8b). Pd2-
dba3 (0.916 g, 1.000 mmol), PPh2Me (0.74 mL, 0.796 g, 4.00
mmol), and aryl iodide 1d (0.840 g, 2.200 mmol) were treated
according to method A described above to afford the arylpal-
ladium(II) complex 8b (1.460 g, 82%) as a yellow solid: mp
72-74 °C (EtOAc/hexane, 1:3); Rf ) 0.53 (EtOAc/hexane, 1:3);
1H NMR (500 MHz, CDCl3) δ 7.89-7.86 (m, 2 H), 7.76 (d, J )
7.0 Hz, 2 H), 7.72-7.68 (m, 2 H), 7.48-7.39 (m, 10 H), 7.32 (t,
J ) 7.0 Hz, 2 H), 7.17 (t, J ) 7.4 Hz, 3 H), 6.98-6.94 (m, 4 H),
6.85 (dd, J ) 7.3 Hz, 1.6 Hz, 1 H), 6.64 (t, J ) 7.3 Hz, 1 H),
6.41 (t, J ) 7.2 Hz, 1 H), 5.94 (d, J ) 8.0 Hz, 1 H), 4.90 (s, 1
H), 4.23-4.08 (m, 2 H), 1.87 (d, J ) 5.5 Hz, 3 H), 1.56 (d, J )
7.1 Hz, 3 H), 1.15 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz,
CDCl3) δ 170.9, 157.9 (t, J(13C-31P) ) 2.8 Hz), 145.3 (t, J(13C-
31P) ) 4.7 Hz), 143.3, 136. 2, 136.1 (d, J(13C-31P) ) 15.9 Hz),
135.9 (d, J(13C-31P) ) 15.8 Hz), 134.9 (d, J(13C-31P) ) 8.1 Hz),
134.7 (d, J(13C-31P) ) 15.5 Hz), 133.9 (dd, J(13C-31P) ) 8.2
Hz, 4.4 Hz), 133.7 (d, J(13C-31P) ) 14.7 Hz), 133.5 (dd, J(13C-
31P) ) 8.6 Hz, 4.6 Hz), 132.9 (dd, J(13C-31P) ) 7.8 Hz, 4.2 Hz),
132.7 (d, J(13C-31P) ) 15.1 Hz), 132.1 (dd, J(13C-31P) ) 7.3
Hz, 3.8 Hz), 130.5, 130.0, 129.7, 129.5, 128.9, 128.8, 128.7,
128.5, 128.3, 128.2 (dd, J(13C-31P) ) 6.9 Hz, 3.1 Hz), 127.8
(dd, J(13C-31P) ) 7.1 Hz, 3.2 Hz), 127.6 (dd, J(13C-31P) ) 7.0
Hz, 3.0 Hz), 127.1 (dd, J(13C-31P) ) 6.6 Hz, 2.9 Hz), 126.9,
125.4, 124.1, 121.3, 110.1, 77.7, 61.4, 16.4 (dd, J(13C-31P) )
20.6 Hz, 9.9 Hz), 14.1 (dd, J(13C-31P) ) 22.9 Hz, 9.9 Hz), 14.1,
several signals account for more than one carbon; 31P NMR
(202 MHz, CDCl3) δ 6.94 (d, J ) 450.6 Hz, 1 P), 6.00 (d, J )
450.5 Hz, 1 P); IR (KBr, cm-1) 1751 (m), 891 (s), 729 (m), 692
(s), 503 (m), 484 (m); HRMS (ES) calcd for C24H41O3P2Pd (M
- I+), 761.1581, found 761.1569.
NMR (400 MHz, CDCl3) δ 7.73-7.66 (m, 4 H), 7.44-7.37 (m,
3 H), 7.33-7.32 (m, 3 H), 7.21-7.14 (m, 3 H), 7.0 (t, J ) 6.7
Hz, 2 H), 6.93 (dd, J ) 7.3 Hz, 1.5 Hz, 1 H), 6.85 (t, J ) 7.3
Hz, 1 H), 6.61 (t, J ) 7.2 Hz, 1 H), 6.28 (d, J ) 7.3 Hz, 1 H),
5.26 (s, 1 H), 4.23-4.10 (m, 2 H), 1.82 (d, J ) 6.6 Hz, 3 H),
1.47 (d, J ) 6.4 Hz, 3 H), 1.42 (d, J ) 6.6 Hz, 3 H), 1.35 (d, J
) 6.5 Hz, 3 H), 1.19 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz,
CDCl3) δ 170.9, 158.2 (t, J(13C-31P) ) 2.8 Hz), 144.5 (t, J(13C-
31P) ) 5.5 Hz), 136.2 (t, J(13C-31P) ) 4.1 Hz), 135.8, 135.7 (d,
J(13C-31P) ) 13.0 Hz), 135.4 (d, J(13C-31P) ) 12.4 Hz), 135.1
(d, J(13C-31P) ) 12.4 Hz), 131.3 (dd, J(13C-31P) ) 8.1 Hz, 3.6
Hz), 130.6 (dd, J(13C-31P) ) 7.8 Hz, 3.5 Hz), 129.3 (d, J(13C-
31P) ) 1.3 Hz), 128.9 (d, J(13C-31P) ) 1.4 Hz), 128.7, 128.5,
127.9 (dd, J(13C-31P) ) 7.3 Hz, 2.3 Hz), 127.6 (dd, J(13C-31P)
) 7.2 Hz, 2.3 Hz), 126.6, 124.1, 121.6, 110.1, 77.6, 61.4, 16.9
(dd, J(13C-31P) ) 22.3 Hz, 9.0 Hz), 15.9 (dd, J(13C-31P) ) 21.9
Hz, 8.5 Hz), 14.9 (dd, J(13C-31P) ) 22.4 Hz, 8.6 Hz), 14.1, 13.7
(dd, J(13C-31P) ) 22.6 Hz, 8.4 Hz), several signals account for
more than one carbon; 31P NMR (162 MHz, CDCl3) δ -8.80
(d, J ) 466.1 Hz, 1 P), -10.50 (d, J ) 465.9 Hz, 1 P); IR (neat,
cm-1) 1747 (s), 908 (s), 740 (m), 715 (w), 694 (m); HRMS (ES)
calcd for C32H37O3P2Pd (M - I+), 637.1265, found 637.1279.
trans-{2-[(Ethoxycarbonyl)phenylmethoxy]phenyl}-
iodobis(trimethylphosphine)palladium (8d). Palladium-
(II) complex 2d (0.605 g, 1.000 mmol), [HPMe3]BF4 (0.377 g,
2.30 mmol), and diisopropylethylamine (0.80 mL, 0.594 g, 4.60
mmol) were treated according to method B described above to
afford arylpalladium(II) iodo complex 8d (0.575 g, 90%) as a
pale yellow solid: mp 154-156°C dec (EtOAc/hexane, 1:3); Rf
) 0.56 (EtOAc/hexane, 1:3); 1H NMR (400 MHz, CDCl3) δ 7.77
(d, J ) 7.4 Hz, 2 H), 7.42 (t, J ) 7.2 Hz, 2 H), 7.34 (t, J ) 7.2
Hz, 1 H), 7.21 (dd, J ) 7.1 Hz, 1.0 Hz, 1 H), 6.95 (t, J ) 7.2
Hz, 1 H), 6.79 (t, J ) 7.1 Hz, 1 H), 6.49 (d, J ) 7.6 Hz, 1 H),
5.59 (s, 1 H), 4.23-4.11 (m, 2 H), 1.36 (d, J ) 6.6 Hz, 9 H),
1.21 (t, J ) 7.1 Hz, 3 H), 1.09 (d, J ) 6.4 Hz, 9 H); 13C NMR
(100 MHz, CDCl3) δ 170.7, 158 (t, J(13C-31P) ) 2.7 Hz), 144.9
(t, J(13C-31P) ) 6.0 Hz), 136.3 (t, J(13C-31P) ) 4.2 Hz), 135.7,
128.7, 128.6, 126.5, 124.0, 121.9, 110.2, 77.4, 61.5, 16.2 (d,
J(13C-31P) ) 9.3 Hz), 16.0 (dd, J(13C-31P) ) 9.0 Hz, 1.7 Hz),
15.8 (d, J(13C-31P) ) 9.0 Hz), 14.1, several signals account for
more than one carbon; 31P NMR (162 MHz, CDCl3) δ -17.79
(d, J ) 480.6 Hz, 1 P), -19.41 (d, J ) 480.5 Hz, 1 P); IR (neat,
cm-1) 1749 (m), 948 (s), 856 (w), 736 (m), 696 (w); HRMS (ES)
calcd for C22H33O3P2Pd (M - I+), 513.0949, found 513.0931.
trans-[2-(Ethoxycarbonylmethoxy)phenyl]iodobis-
(methyldiphenylphosphine)palladium (8e). Palladium(II)
complex 2e11d (0.200 g, 0.379 mmol) and PPh2Me (0.23 mL,
0.247 g, 1.25 mmol) were treated according to method B
described above to afford arylpalladium(II) complex 8e (0.301
g, 98%) as a yellow solid: mp 86-88 °C (EtOAc/hexane, 1:3);
1
Rf ) 0.44 (EtOAc/hexane, 1:3); H NMR (400 MHz, CDCl3) δ
7.58-7.49 (m, 8 H), 7.34-7.23 (m, 12 H), 6.73 (dd, J ) 7.3 Hz,
1.3 Hz, 1 H), 6.58 (t, J ) 7.8 Hz, 1 H), 6.23 (t, J ) 7.3 Hz, 1
H), 5.78 (d, J ) 8.1 Hz, 1 H), 4.25 (q, J ) 7.1 Hz, 2 H), 4.00 (s,
2 H), 1.86 (t, J ) 3.3 Hz, 6 H), 1.29 (t, J ) 7.1 Hz, 3 H); 13C
NMR (125 MHz, CDCl3) δ 169.5, 158.0 (t, J(13C-31P) ) 2.6
Hz), 144.4 (t, J(13C-31P) ) 4.6 Hz), 135.7 (t, J(13C-31P) ) 4.2
Hz), 135.1 (t, J(13C-31P) ) 23.1 Hz), 133.5 (t, J(13C-31P) )
22.9 Hz), 133.1 (t, J(13C-31P) ) 6.4 Hz), 133.0 (t, J(13C-31P)
) 6.0 Hz), 129.5 (d, J(13C-31P) ) 14.7 Hz), 127.8 (t, J(13C-
31P) ) 5.1 Hz), 127.6 (t, J(13C-31P) ) 4.9 Hz), 123.9, 121.0,
109.4, 64.4, 60.9, 16.0 (t, J(13C-31P) ) 108.9 Hz), 14.2; 31P NMR
(162 MHz, CDCl3) δ 6.78 (s, 2 P); IR (neat, cm-1) 1753 (s), 891
(m), 692 (m); HRMS (ES) calcd for C36H37O3P2Pd (M - I+),
685.1253, found 685.1241.
2-Ethoxycarbonyl-3,4-bis(methoxycarbonyl)-2-methyl-
2H-1-benzopyran (9). To a solution of palladacycle 3a (0.050
g, 0.120 mmol) and trimethylphosphonium tetrafluoroborate
[HPMe3]BF4 (0.060 g, 0.366 mmol) in dichloroethane (3.0 mL)
were added diisopropylethylamine (0.065 mL, 0.373 mmol) and
dimethyl acetylenedicarboxylate (dmad) (0.050 mL, 0.407
trans-{2-[(Ethoxycarbonyl)phenylmethoxy]phenyl}-
iodobis(dimethylphenylphosphine)palladium (8c).44 Pal-
ladium(II) complex 2d (0.605 g, 1.000 mmol) and PPhMe2 (0.34
mL, 0.329 g, 2.38 mmol) were treated according to method B
described above to afford arylpalladium(II) complex 8c (0.764
g, 83%) as a white solid: mp 62-64 °C (EtOAc/hexane, 1:3);
Rf (two rotamers) ) 0.56 and 0.38 (EtOAc/hexane, 1:3); 1H
(44) Chromatographic analyses of complex 8c indicated the presence
of two portions of the product with distinct retention factors in TLC.
Preparative TLC separation of these two portions provided samples
with essentially equivalent spectral features in 1H, 13C, and 31P NMR
spectroscopy. However, while well-resolved sharp signals were observed
for one portion (material with Rf ) 0.56 in TLC (EtOAc/hexanes, 1:3),
broad, poorly resolved signals were detected in the spectra of the second
portion (material with Rf ) 0.38 in TLC (EtOAc/hexanes, 1:3). It is
conceivable that as a result of a restricted rotation, complex 8c exists
as two chromatographically separable conformational isomers. The
observed difference in the appearance of NMR spectra of the two
conformational isomers reflects the difference in the degree of rota-
tional freedom in each isomer.

Palladacycles with a Metal-Bonded Carbon
Organometallics, Vol. 24, No. 5, 2005 959
mmol). The mixture was stirred at 80 °C for 24 h, and for an
additional 20 h at room temperature. Solvents were removed
under reduced pressure, and the crude product was separated
by flash chromatography over silica eluting with EtOAc/hexane
(1:9) to afford benzopyran 9 (0.021 g, 52%) as a colorless oil:
61.8, 55.2, 51.4, 21.9, 13.9; IR (KBr, cm-1) 1753 (s), 1730 (s),
1245 (s), 1130 (m), 1026 (m); HRMS (FAB) calcd for C22H23O6
(M + H+), 383.1495, found 383.1506.
2,3-Bis(ethoxycarbonyl)-2-ethyl-4-methyl-2H-1-benzopy-
ran (12). Treatment of complex 6b (0.168 g, 0.200 mmol),
t-BuOK (1.0 M in THF, 0.24 mL, 0.24 mmol), and ethyl
2-butynoate (0.070 mL, 0.068 g, 0.60 mmol) for 24 h at 80 °C
and subsequently for 16 h at room temperature in air according
to the general procedure described above, eluting with EtOAc/
hexane (10:1), afforded 2H-1-benzopyran 12 (0.040 g, 63%) as
a yellow oil: Rf ) 0.30 (EtOAc/hexane, 1:9); 1H NMR (400
MHz, CDCl3) δ 7.31 (dd, J ) 7.7 Hz, 1.5 Hz, 1 H), 7.22 (td, J
) 8.0 Hz, 1.5 Hz, 1 H), 6.94 (td, J ) 7.6 Hz, 1.2 Hz, 1 H), 6.89
(dd, J ) 8.1 Hz, 1.0 Hz, 1 H), 4.27-4.12 (m, 4 H), 2.26 (s, 3
H), 2.21-2.08 (m, 2 H), 1.32 (t, J ) 7.1 Hz, 3 H), 1.21 (t, J )
7.1 Hz, 3 H), 0.99 (t, J ) 7.4 Hz, 3 H); 13C NMR (100 MHz,
CDCl3) δ 170.2, 166.3, 152.6, 135.9, 130.9, 124.8, 123.5, 121.7,
121.4, 116.3, 82.6, 61.5, 60.9, 29.4, 15.4, 14.0, 13.9, 8.1; IR
(neat, cm-1) 1742 (s), 1718 (s), 1253 (s), 754 (m); HRMS (FAB)
calcd for C18H23O5 (M + H+), 319.1545, found 319.1547.
2-Ethoxycarbonyl-2-ethyl-3-methoxycarbonyl-4-(4-
methoxyphenyl)-2H-1-benzopyran (13). Treatment of com-
plex 6b (0.168 g, 0.200 mmol), t-BuOK (1.0 M in THF, 0.24
mL, 0.24 mmol), and methyl (p-methoxy)phenylpropiolate
(0.095 g, 0.50 mmol) for 24 h at 80 °C and subsequently for 16
h at room temperature in air according to the general
procedure described above, eluting with EtOAc/hexane (6:1),
afforded 2H-1-benzopyran 13 (0.055 g, 69%) as a yellow oil
that solidified on standing at room temperature: mp 50-52
°C (CH2Cl2); Rf ) 0.50 (EtOAc/hexane, 1:3); 1H NMR (500 MHz,
CDCl3) δ 7.21 (td, J ) 7.3 Hz, 1.8 Hz, 1 H), 7.14 (dd, J ) 6.7
Hz, 1.9 Hz, 2 H), 6.95 (dd, J ) 8.2 Hz, 0.7 Hz, 1 H), 6.92 (d, J
) 8.7 Hz, 2 H), 6.81 (td, J ) 7.3 Hz, 0.9 Hz, 1 H), 6.77 (dd, J
) 7.7 Hz, 1.8 Hz, 1 H), 4.27-4.15 (m, 2 H), 3.84 (s, 3 H), 3.43
(s, 3 H), 2.30-2.16 (m, 2 H), 1.21 (t, J ) 7.1 Hz, 3 H), 1.07 (t,
J ) 7.4 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 170.2, 166.6,
159.4, 153.1, 140.5, 131.1, 130.1 (2 carbons), 128.4, 127.6,
123.9, 121.9, 121.3, 116.3, 113.6 (2 carbons), 82.9, 61.6, 55.2,
51.4, 29.2, 14.0, 8.1; IR (neat, cm-1) 1739 (s), 1249 (s), 1031
(m); HRMS (ES) calcd for C23H24O6Na (M + Na+), 419.1471,
found 419.1489.
2,3-Bis(ethoxycarbonyl)-4-methyl-2-isopropyl-2H-1-
benzopyran (14). According to the general procedure de-
scribed above, complex 7b (0.171 g, 0.200 mmol) and t-BuOK
(1.0 M in THF, 0.24 mL, 0.24 mmol) were treated for 40 min
at room temperature prior to the addition of 1,2-dichloroethane
(6 mL) and ethyl 2-butynoate (0.070 mL, 0.068 g, 0.60 mmol).
The reaction mixture was heated for 24 h at 80 °C and
subsequently for 16 h at room temperature in air. The crude
product was separated by chromatography over silica, eluting
with EtOAc/hexane (10:1), to afford 2H-1-benzopyran 14 (0.038
g, 57%) as a yellow oil that solidified on standing at room
temperature: mp 56-58 °C (CH2Cl2); Rf ) 0.39 (EtOAc/
hexane, 1:9); 1H NMR (400 MHz, CDCl3) δ 7.26-7.18 (m, 2
H), 6.91 (td, J ) 7.1 Hz, 0.8 Hz, 1 H), 6.88 (dd, J ) 7.5 Hz, 1.1
Hz, 1 H), 4.52-4.05 (m, 4 H), 2.65-2.55 (m, 1 H), 2.11 (s, 3
H), 1.36 (t, J ) 7.1 Hz, 3 H), 1.20 (t, J ) 7.1 Hz, 3 H), 1.10 (d,
J ) 6.7 Hz, 3 H), 1.03 (d, J ) 6.8 Hz, 3 H); 13C NMR (100
MHz, CDCl3) δ 170.4, 166.8, 153.3, 133.8, 130.8, 124.4, 123.8,
121.0, 120.7, 115.8, 84.5, 61.3, 60.9, 34.4, 17.2, 16.8, 15.9, 14.0,
13.9; IR (neat, cm-1) 1747 (m), 1720 (s), 1255 (m), 1244 (m),
1035 (m), 754 (s); HRMS (FAB) calcd for C19H25O5 (M + H+),
333.1702, found 333.1702.
1
Rf ) 0.30 (EtOAc/hexane, 1:3); H NMR (500 MHz, CDCl3) δ
7.29 (td, J ) 8.2 Hz, 1.5 Hz, 1 H), 7.06 (dd, J ) 7.7 Hz, 1.3 Hz,
1 H), 6.95 (t, J ) 7.5 Hz, 1 H), 6.89 (d, J ) 8.1 Hz, 1 H), 4.33-
4.26 (m, 1 H), 4.24-4.17 (m, 1 H), 3.94 (s, 3 H), 3.76 (s, 3 H),
1.74 (s, 3 H), 1.25 (t, J ) 7.1 Hz, 3 H); 13C NMR (100 MHz,
CDCl3) δ 169.2, 166.8, 163.6, 151.8, 136.9, 132.9, 126.4, 122.9,
122.2, 117.2, 117.0, 80.1, 62.0, 52.7, 52.3, 21.6, 13.9; IR (neat,
cm-1) 1741 (s), 1718 (s), 1267 (m), 1245 (m), 1222 (w), 1209
(w); HRMS (ES) calcd for C17H19O7 (M + H+), 335.1131, found
335.1119.
General Procedure for the Synthesis of 2,2-Disubsti-
tuted 2H-1-Benzopyrans. To a solution of arylpalladium-
(II) iodo complexes 5-8 (0.200 mmol) in THF (1 mL) at room
temperature under argon was added t-BuOK (1.0 M in THF,
0.24 mL, 0.24 mmol). The reaction mixture was stirred for 20
min at room temperature, unless a different time period is
indicated. Subsequently, the appropriate alkyne (0.50-0.60
mmol) and 1,2-dichloroethane (6 mL) were added, and the
reaction mixtures were heated to 80 °C for the indicated time
period under argon, and in several cases for an additional 16
h at room temperature in air. Solvents were removed under
reduced pressure, and the crude product was separated by
flash chromatography over silica, eluting with EtOAc/hexane
or ether/hexane mixtures to afford 2,2-disubstitued 2H-1-
benzopyrans 9-17 as colorless or yellow oils or solids.
2-Ethoxycarbonyl-3,4-bis(methoxycarbonyl)-2-methyl-
2H-1-benzopyran (9). Treatment of complex 5b (0.165 g,
0.200 mmol), t-BuOK (1.0 M in THF, 0.24 mL, 0.24 mmol),
and dimethyl acetylenedicarboxylate (dmad) (0.074 mL, 0.086
g, 0.60 mmol) for 1 h at 80 °C according to the general
procedure described above, eluting with EtOAc/hexane (5:1),
afforded 2H-1-benzopyran 9 (0.042 g, 63%) as a yellow oil: Rf
) 0.30 (EtOAc/hexane, 1:3).
2,3-Bis(ethoxycarbonyl)-2,4-bis(methyl)-2H-1-benzopy-
ran (10). Treatment of complex 5b (0.165 g, 0.200 mmol),
t-BuOK (1.0 M in THF, 0.24 mL, 0.24 mmol), and ethyl
2-butynoate (0.070 mL, 0.068 g, 0.60 mmol) for 24 h at 80 °C
and subsequently for 16 h at room temperature in air according
to the general procedure described above, eluting with EtOAc/
hexane (10:1), afforded 2H-1-benzopyran 10 (0.036 g, 59%) as
a yellow oil: Rf ) 0.53 (EtOAc/hexane, 1:3); 1H NMR (400
MHz, CDCl3) δ 7.38 (dd, J ) 7.8 Hz, 1.5 Hz, 1 H), 7.24 (t, J )
7.2 Hz, 1 H), 6.97 (td, J ) 7.7 Hz, 1.2 Hz, 1 H), 6.87 (dd, J )
8.0 Hz, 1.0 Hz, 1 H), 4.26-4.15 (m, 4 H), 2.39 (s, 3 H), 1.69 (s,
3 H), 1.30 (t, J ) 7.1 Hz, 3 H), 1.25 (t, J ) 7.1 Hz, 3 H); 13C
NMR (100 MHz, CDCl3) δ 170.5, 165.6, 151.8, 137.8, 131.2,
125.2, 123.8, 122.2, 121.7, 116.9, 80.5, 61.7, 60.9, 21.9, 15.0,
14.0, 13.9; IR (neat, cm-1) 1751 (s), 1718 (s), 1247 (s), 1051
(m), 1033 (m); HRMS (FAB) calcd for C17H21O5 (M + H+),
305.1389, found 305.1406.
2-Ethoxycarbonyl-3-methoxycarbonyl-4-(4-methoxy-
phenyl)-2-methyl-2H-1-benzopyran (11). Treatment of com-
plex 5b (0.165 g, 0.200 mmol), t-BuOK (1.0 M in THF, 0.24
mL, 0.24 mmol), and methyl (p-methoxy)phenylpropiolate
(0.095 g, 0.50 mmol) for 24 h at 80 °C and subsequently for 19
h at room temperature in air according to the general
procedure described above, eluting with EtOAc/hexane (10:
1), afforded 2H-1-benzopyran 11 (0.061 g, 80%) as a yellow
solid: mp 102-104 °C (CH2Cl2); Rf ) 0.53 (EtOAc/hexane, 1:3);
1H NMR (400 MHz, CDCl3) δ 7.23 (td, J ) 7.6 Hz, 1.8 Hz, 1
H), 7.12 (d br, J ) 7.7 Hz, 2 H), 6.93 (d, J ) 8.3 Hz, 3 H), 6.81
(td, J ) 7.1 Hz, 1.0 Hz, 1 H), 6.76 (dd, J ) 13.4 Hz, 1.7 Hz, 1
H), 4.31-4.09 (m, 2 H), 3.85 (s, 3 H), 3.45 (s, 3 H), 1.82 (s, 3
H), 1.23 (t, J ) 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ
170.3, 166.3, 159.4, 152.4, 141.0, 131.4, 129.9 (2 carbons),
128.5, 128.0, 124.2, 122.5, 121.6, 116.8, 113.6 (2 carbons), 80.6,
2-Ethoxycarbonyl-3-methoxycarbonyl-4-(4-methoxy-
phenyl)-2-isopropyl-2H-1-benzopyran (15). According to
the general procedure described above, complex 7b (0.171 g,
0.200 mmol) and t-BuOK (1.0 M in THF, 0.24 mL, 0.24 mmol)
were treated for 40 min at room temperature prior to the
addition of dichloroethane (6 mL) and methyl (p-methoxy)-
phenylpropiolate (0.095 g, 0.50 mmol). The reaction mixture
was heated for 24 h at 80 °C and for 16 h at room temperature

960 Organometallics, Vol. 24, No. 5, 2005
Lu et al.
in air. The crude product was separated by chromatography
over silica, eluting with EtOAc/hexane (10:1), to afford 2H-1-
benzopyran 15 (0.059 g, 72%) as a yellow oil: Rf ) 0.50 (EtOAc/
hexane, 1:3); 1H NMR (400 MHz, CDCl3) δ 7.22-7.17 (m, 1
H), 7.13 (d, J ) 8.4 Hz, 2 H), 6.97 (d, J ) 8.0 Hz, 1 H), 6.91 (d,
J ) 8.8 Hz, 2 H), 6.77-6.75 (m, 2 H), 4.23-4.16 (m, 2 H), 3.83
(s, 3 H), 3.37 (s, 3 H), 2.76-2.66 (m, 1 H), 1.23 (t, J ) 7.1 Hz,
3 H), 1.16 (d, J ) 6.8 Hz, 3 H), 1.08 (d, J ) 6.8 Hz, 3 H); 13C
NMR (100 MHz, CDCl3) δ 170.3, 166.8, 159.3, 153.7, 139.5,
131.0, 130.1 (2 carbons), 128.2, 127.2, 124.1, 120.9, 120.7,
115.8, 113.6 (2 carbons), 85.2, 61.5, 55.2, 51.5, 34.5, 17.1, 16.6,
14.0; IR (neat, cm-1) 1724 (s), 1247 (s), 1176 (m), 1033 (m);
HRMS (ES) calcd for C24H27O6 (M + H+), 411.1808, found
411.1804.
2,3-Bis(ethoxycarbonyl)-4-methyl-2-phenyl-2H-1-ben-
zopyran (16). Treatment of complex 8b (0.178 g, 0.200 mmol),
t-BuOK (1.0 M in THF, 0.24 mL, 0.24 mmol), and ethyl
2-butynoate (0.070 mL, 0.068 g, 0.60 mmol) for 24 h at 80 °C
and subsequently for 24 h at room temperature in air according
to the general procedure described above, eluting with EtOAc/
hexane (10:1), afforded 2H-1-benzopyran 16 (0.032 g, 44%) as
a yellow oil: Rf ) 0.49 (EtOAc/hexane, 1:3); 1H NMR (500
MHz, CDCl3) δ 7.53 (dd, J ) 8.3 Hz, 1.7 Hz, 2 H), 7.33 (dd, J
) 7.8 Hz, 1.3 Hz, 1 H), 7.29-7.23 (m, 3 H), 7.20 (td, J ) 8.2
Hz, 1.4 Hz, 1 H), 6.97 (dd, J ) 8.1 Hz, 0.9 Hz, 1 H), 6.93 (td,
J ) 7.8 Hz, 1.0 Hz, 1 H), 4.31-4.25 (m, 1 H), 4.22-4.17 (m, 1
H), 4.15 (q, J ) 7.1 Hz, 2 H), 2.41 (s, 3 H), 1.23 (t, J ) 7.1 Hz,
3 H), 1.17 (t, J ) 7.1 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ
169.8, 166.3, 151.9, 138.5, 138.1, 131.1, 128.4, 127.9 (2
carbons), 127.6 (2 carbons), 125.2, 124.0, 123.1, 122.1, 117.3,
83.5, 62.1, 60.9, 15.6, 13.9, 13.8; IR (neat, cm-1) 1755 (m), 1718
(s), 1251 (s), 1031 (m), 756 (w); HRMS (FAB) calcd for C22H23O5
(M + H+), 367.1545, found 367.1544.
2-Ethoxycarbonyl-3-methoxycarbonyl-4-(4-methoxy-
phenyl)-2-phenyl-2H-1-benzopyran (17). Treatment of com-
plex 8b (0.178 g, 0.200 mmol), t-BuOK (1.0 M in THF, 0.24
mL, 0.24 mmol), and methyl (p-methoxy)phenylpropiolate
(0.095 g, 0.50 mmol) for 24 h at 80 °C and subsequently for 18
h at room temperature in air according to the general
procedure described above, eluting with EtOAc/hexane (5:1),
afforded 2H-1-benzopyran 17 (0.061 g, 69%) as a yellow solid:
mp 58-60 °C (CH2Cl2); Rf ) 0.40 (EtOAc/hexane, 1:3); 1H NMR
(500 MHz, CDCl3) δ 7.68 (d, J ) 10.5 Hz, 2 H), 7.33 (t, J ) 6.8
Hz, 2 H), 7.29-7.28 (m, 1 H), 7.23-7.19 (m, 3 H), 7.04 (d, J )
7.9 Hz, 1 H), 6.95 (d, J ) 8.9 Hz, 2 H), 6.81 (td, J ) 6.9 Hz,
0.9 Hz, 1 H), 6.78 (dd, J ) 7.8 Hz, 1.9 Hz, 1 H), 4.33-4.27 (m,
1 H), 4.25-4.18 (m, 1 H), 3.85 (s, 3 H), 3.38 (s, 3 H), 1.22 (t, J
) 7.1 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 169.6, 166.7,
159.6, 152.3, 141.7, 138.1, 131.3, 130.4 (2 carbons), 128.5,
128.4, 128.0, 127.8 (2 carbons), 127.8 (2 carbons), 124.1, 123.2,
121.9, 117.2, 113.6 (2 carbons), 83.7, 62.3, 55.2, 51.5, 13.9; IR
(neat, cm-1) 1753 (m), 1730 (m), 1249 (s), 1054 (w), 1031 (w);
HRMS (ES) calcd for C27H25O6 (M + H+), 445.1651, found
445.1635.
Ethyl 2-[N-(2-Iodophenyl)-N-methoxycarbonyl]amino-
propionate (19). To a suspension of N-methoxycarbonyl-2-
iodoaniline 1842 (3.878 g, 14.00 mmol) and anhydrous K2CO3
(10.0 g, 72.40 mmol) in DMF (40 mL) at room temperature
under argon was added neat ethyl 2-bromopropionate (7.27
mL, 10.14 g, 56.0 mmol), and the resulting suspension was
stirred at 100 °C for 33 h. The reaction mixture was partitioned
between water (50 mL) and ether (3 × 50 mL) and dried
(MgSO4), and the crude product was purified by flash chro-
matography over silica, eluting with EtOAc/hexane (1:3), to
afford aryl iodide 19 (4.04 g, 77%) as a light yellow solid: mp
78-80 °C (EtOAc/hexane, 1:3); Rf ) 0.56 (EtOAc/hexane, 1:3);
1H NMR (500 MHz, CDCl3) δ 7.86 (d, J ) 7.5 Hz, 1 H), 7.63
(dd, J ) 7.8 Hz, 1.2 Hz, 0.8 H), 7.53 (d, J ) 7.6 Hz, 0.2 H),
7.37 (t, J ) 7.6 Hz, 1 H), 7.04 (td, J ) 7.8 Hz, 1.2 Hz, 0.8 Hz),
7.00 (t, J ) 7.9 Hz, 0.2 H), 4.91 (q, J ) 7.6 Hz, 0.8 H), 4.76 (q,
J ) 7.6 Hz, 0.2 H), 4.33-4.22 (m, 2 H), 3.78 (s, 0.6 H), 3.66 (s,
2.4 H), 1.84 (d, J ) 7.1 Hz, 0.6 H), 1.31 (t, J ) 7.1 Hz, 3 H),
1.10 (d, J ) 7.6 Hz, 2.4 H); 13C NMR (125 MHz, CDCl3) δ 173.3,
(171.3), 155.6, (155.1, 154.5), (145.7, 141.3), 140.9, (139.6,
139.3), 139.2, (131.0), 130.6, (129.7), (129.5), 129.4, (129.2),
129.0, (128.6), 103.6, (61.5), 61.3, (61.2), (55.6), 55.5, 53.3,
(53.2), (53.0), (16.8), (15.6), 15.0, (14.3), 14.1 (signals for the
minor isomers arising as a result of the amide resonance are
shown in parentheses); IR (neat, cm-1) 1741 (s), 1712 (s), 767
(m); HRMS (FAB) calcd for C13H16INO4Li (M + Li+), 384.0284,
found 384.0278.
{N-[(1-Ethoxycarbonyl)ethyl]-N-methoxycarbonyl-2-
aminophenyl}iodo(tetramethylethylenediamine)pal-
ladium (20). To a solution of tris(dibenzylideneacetone)-
dipalladium(0) (Pd2dba3) (2.747 g, 3.00 mmol) and aryl iodide
19 (2.263 g, 6.00 mmol) in benzene (100 mL) at room temper-
ature under argon was added neat N,N,N′,N′-tetramethyl-1,2-
ethylenediamine (TMEDA) (1.8 mL, 1.395 g, 12.00 mmol). The
resulting suspension was stirred for 30 min at 60 °C and
filtered through a plug of Celite, and solvents were removed
under reduced pressure. The crude product was purified by
flash chromatography over silica eluting with EtOAc/hexane
(1:5) to remove excess dibenzylideneacetone (dba) and subse-
quently with EtOAc/hexane (2:1) to afford complex 20 (2.805
g, 78%) as a yellow solid: mp 102-104 °C (EtOAc/hexane, 2:1);
1
Rf ) 0.28 (EtOAc/hexane, 3:1); H NMR (500 MHz, CDCl3) δ
7.60 (dd, J ) 7.1 Hz, 2.0 Hz, 0.75 H), 7.52-7.50 (m, 0.25 H),
7.17 (d br, J ) 7.0 Hz, 0.1 H), 7.09-7.07 (m, 0.15 H), 6.87-
6.79 (m, 2.35 H), 6.73 (dd, J ) 7.1 Hz, 1.9 Hz, 0.4 H), 5.78
(pent, J ) 6.6 Hz, 0.75 H), 5.02-4.97 (m, 0.25 H), 4.34-4.25
(m, 0.5 H), 4.23-4.20 (m, 1.5 H), 3.71 (s, 0.25 H), 3.69 (s, 0.75
H), 3.59 (s, 0.5 H), 3.58 (s, 1.5 H), 2.88-2.67 (m, 2 H), 2.71 (s,
1 H), 2.68 (s, 2 H), 2.67 (s, 1 H), 2.64 (s, 2 H), 2.61 (s, 2 H),
2.60 (s, 1 H), 2.48 (s, 0.5 H), 2.43 (s, 1.5 H), 2.36 (s, 0.25 H),
2.43 (s, 0.75 H), 2.30-2.22 (m, 2 H), 1.50 (d, J ) 6.8 Hz, 2.05
H), 1.45 (d, J ) 6.9 H, 0.75 H), 1.33 (t, J ) 7.1 Hz, 2.10 H),
1.27 (t, J ) 7.1 Hz, 0.50 H), 0.96 (d, J ) 6.6 Hz, 0.1 H), 0.91
(d, J ) 6.6 Hz, 0.1 H), 0.87 (t, J ) 7.0 Hz, 0.4 H); 13C NMR
(125 MHz, CDCl3) δ 172.3 (172.8, 172.4), 155.9 (157.8, 157.0,
156.8), 144.9 (148.1, 147.3, 145.7), 140.2 (139.8, 139.4, 139.3),
138.7 (138.9, 138.0, 137.9), 129.2 (129.4, 128.9), 124.2 (124.8,
124.3), 122.8 (123.5, 123.3, 123.1, 122.9), 62.5 (62.7, 62.6), 60.6
(60.8), 58.6 (59.6, 59.1, 58.8, 58.6), 52.2 (52.3, 52.1), 50.9 (51.4,
51.1), 50.2 (50.5, 50.0), 49.9, 49.6 (49.7), 22.6 (21.0, 19.7), 14.4
(14.6, 14.5, 14.3, 14.2, 14.1), 13.3 (multiple signals for the
minor isomers arising from the hindered rotation about the
Csp2-Pd bond and/or the amide resonance are shown in
parentheses); IR (neat, cm-1) 1733 (s), 1701 (s); HRMS (ES)
calcd for C19H33N3O4IPd (M + H+), 600.0551, found 600.0555.
trans-{N-[(1-Ethoxycarbonyl)ethyl]-N-methoxycarbo-
nyl-2-aminophenyl}iodobis(methyldiphenylphosphine)-
palladium (21). To a solution of arylpalladium(II) complex
20 (0.840 g, 1.400 mmol) in methylene chloride (14 mL) at room
temperature under argon was added diphenylmethylphosphine
(0.65 mL, 0.70 g, 3.50 mmol), and the solution was stirred at
room temperature under argon for 2 h. Solvents were removed
under reduced pressure, and the crude product was purified
by flash chromatography over silica eluting with EtOAc/hexane
(1:10) to remove excess phosphine, and subsequently with
EtOAc/hexane (1:1) to afford palladium(II) complex 21 (1.066
g, 96%) as a yellow solid: mp 105-107 °C (EtOAc/hexane, 1:1);
1
Rf ) 0.28 (EtOAc/hexane, 1:3); H NMR (500 MHz, CDCl3) δ
7.89 (s br, 2 H), 7.75 (s br, 2 H), 7.53-7.27 (m, 10 H), 7.25-
6.95 (m, 8 H), 6.89 (s br, 1 H), 6.83 (s br, 1 H), 4.14-3.97 (m,
1.6 H), 3.36 (s br, 1 H), 3.22 (s br, 0.4 H), 2.78 (s br, 2 H),
2.21-1.95 (m, 3 H), 1.90-1.68 (m, 2 H), 1.54-1.10 (m, 8 H);
13C NMR (125 MHz, CDCl3) 171.7 (171.5, 171.1), 156.3, 155.2,
153.7 (153.4), 147.5, 137.3 (d, J(13C-31P) ) 46.6 Hz), 134.5 (d,
J(13C-31P) ) 62.8 Hz), 133.8, 132.3, 130.3 (d, J(13C-31P) ) 50.6
Hz), 129.5 (d, J(13C-31P) ) 8.1 Hz), 128.3, 128.1 (pent, J(13C-
31P) ) 5.0 Hz), 126.4 (d, J(13C-31P) ) 7.0 H), 124.1 (d, J(13C-
31P) ) 19.2 Hz), 60.9, 59.3 (58.7), 51.3 (51.2), 21.0, 17.8 (s br),

Palladacycles with a Metal-Bonded Carbon
Organometallics, Vol. 24, No. 5, 2005 961
14.9 (s br), 14.3 (14.1) (multiple signals for the minor isomers
arising from the amide resonance are shown in parentheses);
31P NMR (161 MHz, CDCl3, 55 °C) δ 4.82 (d br, J ) 443.0 Hz,
1 P), 3.10 (d br, J ) 443.0 Hz, 1 P) (broad signals arise from
the amide resonance); IR (neat, cm-1) 1735 (s), 1701 (s), 891
(m), 692 (m); HRMS (ES) calcd for C39H42NO4P2Pd (M - I+),
756.1624, found 756.1618.
General Procedure for the Synthesis of 2,2-Disubsti-
tuted 1,2-Dihydroquinolines. To a solution of arylpalla-
dium(II) iodo complex 21 (0.200 mmol) in THF (1 mL) at room
temperature under argon was added t-BuOK (1.0 M in THF,
0.24 mL, 0.24 mmol). The reaction mixture was stirred for 40
min at room temperature, the appropriate alkyne (0.50-0.60
mmol) and 1,2-dichloroethane (6 mL) were added, and the
mixtures were heated to 80 °C for 12 h under argon and for
an additional 16 h at room temperature in air. The solvents
were removed under reduced pressure and the crude product
was separated by flash chromatography over silica, eluting
with EtOAc/hexane mixtures, to afford 2,2-disubstituted 1,2-
dihydroquinolines as yellow solids.
t-BuOK (1.0 M in THF, 0.24 mL, 0.24 mmol), and methyl (p-
methoxy)phenylpropiolate (0.095 g, 0.50 mmol) for 12 h at 80
°C and subsequently for 16 h at room temperature in air
according to the general procedure described above, eluting
with EtOAc/hexane (3:1), afforded 1,2-dihydroquinoline 23 as
a yellow solid (0.045 g, 50%): mp 145-147 °C (EtOAc/hexane,
1:3); Rf ) 0.24 (EtOAc/hexane, 1:3); 1H NMR (400 MHz, CDCl3)
δ 7.42 (dd, J ) 8.3 Hz, 0.8 Hz, 1 H), 7.25 (td, J ) 7.2 Hz, 1.5
Hz, 1 H), 7.12 (s br, 2 H), 6.95 (td, J ) 7.8 Hz, 1.0 Hz, 1 H),
6.91 (d br, J ) 8.3 Hz, 2 H), 6.80 (dd, J ) 7.8 Hz, 1.5 Hz, 1 H),
4.20 (qd, J ) 7.1 Hz, 2.2 Hz, 2 H), 3.83 (s, 3 H), 3.80 (s, 3 H),
3.38 (s, 3 H), 1.75 (s, 3 H), 1.25 (t, J ) 7.1 Hz, 3 H); 13C NMR
(100 MHz, CDCl3) δ 170.1, 166.6, 159.4, 154.2, 138.5, 135.2,
130.2 (2 carbons), 130.0, 129.4, 128.8, 127.8, 126.4, 123.8,
122.8, 113.6 (2 carbons), 66.3, 61.9, 55.2, 53.1, 51.5, 20.7, 13.9;
IR (neat, cm-1) 1755 (m), 1724 (s), 1269 (s), 1247 (s), 1064 (m),
761 (m); HRMS (FAB) calcd for C24H25NO7Li (M + Li+),
446.1791, found 446.1790.
Acknowledgment. Support for this work from The
American Chemical Society Petroleum Research Fund,
Kansas NSF EPSCoR, and Kansas Technology Enter-
prise Corporation, and the National Science Foundation
via CAREER Award (CHE-0239123) to H.C.M. is grate-
fully acknowledged. We thank Dr. S. Kumara Vadivel
for contributions to earlier stages of this research, and
to our colleague Dr. Douglas R. Powell for his assistance
with X-ray crystallography.
2,3-Bis(ethoxycarbonyl)-N-methoxycarbonyl-2,4-bis-
(methyl)-1,2-dihydroquinoline (22). Treatment of complex
21 (0.177 g, 0.200 mmol) and t-BuOK (1.0 M in THF, 0.24 mL,
0.24 mmol), and ethyl 2-butynoate (0.070 mL, 0.068 g, 0.60
mmol) for 12 h at 80 °C and subsequently for 16 h at room
temperature according to the general procedure described
above, eluting with EtOAc/hexane (5:1), afforded 1,2-dihydro-
quinoline 22 as a yellow oil (0.040 g, 55%) that solidified on
standing at room temperature: mp 83-85 °C (EtOAc/hexane,
1:5); Rf ) 0.38 (EtOAc/hexane, 1:3); 1H NMR (400 MHz, CDCl3)
δ 7.37 (d, J ) 8.0 Hz, 2 H), 7.26 (td, J ) 7.4 Hz, 1.5 Hz, 1 H),
7.10 (td, J ) 7.7 Hz, 1.1 Hz, 1 H), 4.27-4.14 (m, 4 H), 3.76 (s,
3 H), 2.22 (s, 3 H), 1.62 (s, 3 H), 1.31 (t, J ) 7.1 Hz, 3 H), 1.28
(t, J ) 7.2 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 170.4, 166.2,
154.2, 134.8, 132.8, 130.2, 129.1, 126.2, 124.4, 123.9, 122.7,
Supporting Information Available: Detailed description
of protocols for acquisition of the 31P NMR spectra shown in
Schemes 2 and 4 including full-scale photocopies of spectra
a-f, photocopies of 1H and 13NMR spectra of all new com-
pounds prepared in this study, and 1H NOE difference spectra
of 2H-1-benzopyrans 10, 12, 14, and 16, and 1,2-dihydroquino-
line 22. Includes X-ray crystallographic studies on organopal-
ladium complexes 3c, 3d, 6a, and 7b and heterocycles 11 and
23. This material is available free of charge via the Internet
at http://pubs.acs.org.
66.0, 61.8, 61.0, 52.9, 20.5, 15.5, 14.0, 13.9; IR (neat, cm-1
)
1749 (m), 1722 (s), 1716 (s); HRMS (FAB) calcd for C19H23-
NO6Li (M + Li+), 368.1685, found 368.1691.
2-Ethoxycarbonyl-3-methoxycarbonyl-N-methoxycar-
bonyl-4-(4-methoxyphenyl)-2-methyl-1,2-dihydroquino-
line (23). Treatment of complex 21 (0.177 g, 0.200 mmol) and
OM0491544