Ligand-controlled asymmetric induction at a transition metal-bonded α-carbon in ester and amide enolates. Diastereoselective formation of oxapalladacycles applied to the synthesis of a chiral nonracemic 2H-1-benzopyran

Article abstract of DOI:10.1021/om030207b

Stable benzannelated oxapalladacycles [-(P-P)Pd-1-C₆H ₄-2-OCHY-] possessing chiral nonracemic bidentate phosphine ligands, (P-P) = (4S,5S)-(+)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane ((S,S)-DIOP) or (2S,4S)-(-)-2,4-bis(diphenylphosphino)pentane ((S,S)-BDPP), and a palladium-bonded stereogenic carbon representing an α-carbon in ester (Y = COOEt) or amide (Y = CONEt₂) enolates, have been synthesized in diastereomeric excess 46-80% exploiting asymmetric induction from the chiral ligands. The stereoselective event involved an intramolecular displacement of the iodide in complexes (P-P)IPd-l-C ₆H₄-2-OCH ₂Y by an in situ generated lithium or potassium ester or amide enolate. Only one enantiomer of each ligand was used, and the absolute sense of stereoinduction could be controlled by the choice of the base (t-BuOK or LDA) to afford both diastereomers of each palladacycle in a diastereomerically enriched form. Treatment of the palladacycles with an excess of t-BuOK allowed for further enrichment in the content of thermodynamic diastereomers. An X-ray structure of the complex [-((S,S)-BDPP)Pd-1C ₆H₄-2-(R)-OCHCOOEt-] was obtained. Ligand exchange reactions of the palladacycles with an achiral 1,2-bis(diphenylphosphino)ethane (dppe) ligand afforded enantiomerically enriched palladacycles [-(dppe)Pd-1-C₆H₄-2-OCHCOOEt-] in the corresponding enantiomeric purities without a loss of the stereochemical information. Reaction of dimethyl acetylenedicarboxylate (dmad) with complex [-((S,S)-DIOP)Pd-l-C₆H₄-2-OCHCONEt₂-], enriched via chromatography to 96% de, afforded (-)-2-N,N-diethylcarbonyl-3,4- bis(methoxycarbonyl)-2H-1-benzopyran in 88.4% ee with only a minimal (8%) racemization of the metal-bonded stereocenter.

Full text of DOI:10.1021/om030207b

Organometallics 2003, 22, 2961-2971
2961
Liga n d -Con tr olled Asym m etr ic In d u ction a t a Tr a n sition
Meta l-Bon d ed r-Ca r bon in Ester a n d Am id e En ola tes.
Dia ster eoselective F or m a tion of Oxa p a lla d a cycles
Ap p lied to th e Syn th esis of a Ch ir a l Non r a cem ic
2H-1-Ben zop yr a n
J anelle L. Portscheller, Sara E. Lilley,† and Helena C. Malinakova*
Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive,
Lawrence, Kansas 66045
Received March 19, 2003
Stable benzannelated oxapalladacycles [-(P-P)Pd-1-C6H4-2-OCHY-] possessing chiral
nonracemic bidentate phosphine ligands, (P-P) ) (4S,5S)-(+)-O-isopropylidene-2,3-dihy-
droxy-1,4-bis(diphenylphosphino)butane ((S,S)-DIOP) or (2S,4S)-(-)-2,4-bis(diphenylphos-
phino)pentane ((S,S)-BDPP), and a palladium-bonded stereogenic carbon representing an
R-carbon in ester (Y ) COOEt) or amide (Y ) CONEt2) enolates, have been synthesized in
diastereomeric excess 46-80% exploiting asymmetric induction from the chiral ligands. The
stereoselective event involved an intramolecular displacement of the iodide in complexes
(P-P)IPd-1-C6H4-2-OCH2Y by an in situ generated lithium or potassium ester or amide
enolate. Only one enantiomer of each ligand was used, and the absolute sense of
stereoinduction could be controlled by the choice of the base (t-BuOK or LDA) to afford both
diastereomers of each palladacycle in a diastereomerically enriched form. Treatment of the
palladacycles with an excess of t-BuOK allowed for further enrichment in the content of
“thermodynamic” diastereomers. An X-ray structure of the complex [-((S,S)-BDPP)Pd-1-
C6H4-2-(R)-OCHCOOEt-] was obtained. Ligand exchange reactions of the palladacycles with
an achiral 1,2-bis(diphenylphosphino)ethane (dppe) ligand afforded enantiomerically enriched
palladacycles [-(dppe)Pd-1-C6H4-2-OCHCOOEt-] in the corresponding enantiomeric purities
without a loss of the stereochemical information. Reaction of dimethyl acetylenedicarboxylate
(dmad) with complex [-((S,S)-DIOP)Pd-1-C6H4-2-OCHCONEt2-], enriched via chromatog-
raphy to 96% de, afforded (-)-2-N,N-diethylcarbonyl-3,4-bis(methoxycarbonyl)-2H-1-benzo-
pyran in 88.4% ee with only a minimal (8%) racemization of the metal-bonded stereocenter.
In tr od u ction
organic substrates5 have been explored. In contrast, an
approach relying on communication of stereochemical
information from chiral auxiliary ligands into achiral
organic substrates giving rise to metal-bonded stereo-
genic carbons has only a few precedents.6,7 Transition
metal enolates, in most cases existing as the Csp3-
(3) For methods based on Csp3-H activation, see: J ones, W. D. In
Topics in Organometallic Chemistry: Activation of Unreactive Bonds
and Organic Synthesis; Murai, S., Ed.; Springer-Verlag: Berlin, 1999;
pp 10-46.
(4) (a) Spencer, J .; Maassarani, F.; Pfeffer, M. Tetrahedron: Asym-
metry 1994, 5 (3), 321-324. (b) Yoneda, A.; Hakushi, T.; Newkome,
G. R.; Fronczek, F. R. Organometallics 1994, 13 (12), 4912-4918.
(5) Cyclometalation at a Csp2-H bond giving rise to the element of
planar chirality has been extensively studied, see: (a) Stevens, A. M.;
Richards, C. J . Organometallics 1999, 18 (7), 1346-1348. (b) Zhao,
G.; Yang, Q.-C.; Mak, T. C. W. Organometallics 1999, 18 (18), 3623-
3636. Stereoinduction at metal-bonded stereocenters (carbon and
sulfur) has only recently been demonstrated, see: (c) Dupont, J .;
Gruber, A. S.; Fonseca, G. S.; Monteiro, A. L.; Ebeling, G. Organo-
metallics 2001, 20 (1), 171-176. (d) Garcia-Ruano, J . L.; Gonzalez, A.
M.; Barcena, A. I.; Camazon, M. J .; Navarro-Ranninger, C. Tetra-
hedron: Asymmetry 1996, 7 (1), 139-148.
(6) (a) For a stereoselective preparation (45% de) of a cycloplatinated
complex featuring a carbon-bonded platinum ketone enolate, see:
Ryabov, A. D.; Panyashkina, I. M.; Polyakov, V. A.; Fisher, A.
Organometallics 2002, 21 (8), 1633-1636. (b) Binotti, B.; Carfagna,
C.; Gatti, G.; Martini, D.; Mosca, L.; Pettinari, C. Organometallics 2003,
22 (5), 1115-1123.
Carbon-carbon bond-forming reactions of intermedi-
ates possessing a transition metal-carbon bond play a
major role in selective syntheses of complex organic
molecules.1 If organometallics with a transition metal-
bonded sp3-hybridized stereogenic carbon could be used
in these transformations,2 a convenient approach to the
creation of stereogenic carbon centers would arise. For
this reason, stereoselective synthesis of complexes with
a transition metal-Csp3 bond has recently received
much attention.3 Classical resolution techniques4 or
diastereoselective cyclometalations of chiral nonracemic
† Undergraduate research participant (NSF-REU), Department of
Chemistry, College of the Ozarks, Point Lookout, MO 65726.
(1) Diederich, F., Stang, P. J ., Eds. Metal-Catalyzed Cross-Coupling
Reactions; Willey-VCH Verlag GmbH: Weinheim, 1998.
(2) For palladium- and nickel-catalyzed approaches to coupling of
two Csp3 centers, see: (a) Aiwen, L.; Zhang, X. Org. Lett. 2002, 4 (14),
2285-2288. (b) Netherton, M. R.; Dai, C.; Neuschu¨tz, K.; Fu, G. C. J .
Am. Chem. Soc. 2001, 123 (41), 10099-10100. (c) Cardenas, D. J .
Angew. Chem., Int. Ed. 1999, 38 (20), 3018-3020. (d) Giovannini, R.;
Stu¨demann, T.; Devasagayaraj, A.; Dussin, G.; Knochel. P. J . Org.
Chem. 1999, 64 (10), 3544-3553. (e) Giovannini, R.; Knochel, P. J .
Am. Chem. Soc. 1998, 120 (43), 11186-11187. (f) Sustmena, R.; Lau,
J .; Zipp, M. Tetrahedron Lett. 1986, 43 (27), 5207-5210.
10.1021/om030207b CCC: $25.00 © 2003 American Chemical Society
Publication on Web 06/06/2003

2962 Organometallics, Vol. 22, No. 14, 2003
Portscheller et al.
bonded forms,8 have been established9 as intermediates
in the synthetically powerful catalytic arylation and
alkenylation of ketones,10 esters,11 amides,12 and cyano
derivatives.13 While catalytic asymmetric arylation of
ketones afforded products in excellent enantiomeric
purities,14 palladium-catalyzed arylation of esters and
amides has been found to be much less stereoselec-
tive.15 Thus, it is rather surprising that studies on the
preparation of stable transition metal ester or amide
enolates16 remain rare in the organometallic literature.
To date, only a few examples of stereoselective synthe-
ses17 of transition metal enolates have been reported,
and methods relying on asymmetric induction from
chiral nonracemic ligands appear virtually unexplored.6
As a part of our program that investigates synthetic
applications of palladacycles, we have recently described
the preparation of racemic oxapalladacycles 1 and
(7) For examples of an enantioselective Csp3-H activation mediated
by irridium centers bearing chiral nonracemic ligands, see: (a) Mobley,
T. A.; Bergman, R. G. J . Am. Chem. Soc. 1998, 120 (13), 3253-3254.
(b) Dorta, R.; Togni, A. Organometallics 1998, 17 (25), 5442-5444.
(8) For representative examples of studies on the preparation and
reactivity of stable transition metal enolates, see: (a) Heathcock, 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 (24), 6842-
6843. (c) Kujime, M.; Hikichi, S.; Akita, M. Organometallics 2001, 20
(19), 4049-4060. (d) Albeniz, A. C.; Catalina, N. M.; Espinet, P.; Redon,
R. Organometallics 1999, 18 (26), 5571-5576, and references therein.
(e) Hartwig, J . F.; Andersen, R. A.; Bergman, R. G. J . Am. Chem. Soc.
1990, 112 (14), 5670-5671. (f) Burkhardt, E. R.; Doney, J . J .; Slough,
G. A.; Stack, J . M.; Heathcock, C. H.; Bergman, R. G. Pure Appl. Chem.
1988, 60 (1), 1-6. (g) Weinstock, I.; Floriani, C.; Chiesi-Villa, A.;
Guastini, C. J . Am. Chem. Soc. 1986, 108 (26), 8298-8299.
(9) Culkin, D. A.; Hartwig, J . F. J . Am. Chem. Soc. 2001, 123 (24),
5816-5817, and references therein.
Sch em e 1
demonstrated their conversion into highly substituted
2H-1-benzopyrans 2 via a regiocontrolled insertion of
unsymmetrical alkynes (Scheme 1).18
Herein, we wish to report that the metal-bonded
stereogenic carbon in stable oxapalladacycles 1 repre-
senting a carbon-bonded ester or amide enolate can be
generated in a stereoselective manner (de up to 80%)
via asymmetric induction from commercially available
chiral nonracemic bidentate phosphine ligands (4S,5S)-
(+)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphos-
phino)butane ((S,S)-DIOP) or (2S,4S)-(-)-2,4-bis(diphen-
ylphosphino)pentane ((S,S)-BDPP). Insertion of di-
methyl acetylenedicarboxylate (dmad) into a diastereo-
merically enriched palladacycle 1 (96% de after chro-
matography) proceeded with only minimal racemization,
providing a chiral nonracemic 2H-1-benzopyran 2 (88.4%
ee, R1 ) R2 ) COOMe, Y ) CONEt2).19 We have system-
atically explored factors that control asymmetric in-
duction in the synthesis of palladacycles 1 and evalu-
ated the configurational stability of the metal-bonded
stereocenter. Absolute sense of stereoinduction could be
controlled by the choice of the base (t-BuOK vs LDA),
and good diastereoselectivity was achieved under both
“kinetic” and “thermodynamic” conditions. Results de-
scribed herein provide a proof of concept for the future
development of a new approach to asymmetric synthesis
of 2H-1-benzopyrans20 and additional diverse applica-
tions of palladacycles 1 to asymmetric organic synthesis.
(10) (a) Fox, J . M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J . Am.
Chem. Soc. 2000, 122 (7), 1360-1370. (b) Kawatsura, M.; Hartwig, J .
F. J . Am. Chem. Soc. 1999, 121 (7), 1473-1478. (c) Hamann, B. C.;
Hartwig, J . F. J . Am. Chem. Soc. 1997, 119 (50), 12382-12383. (d)
Palucki, M.; Buchwald, S. L. J . Am. Chem. Soc. 1997, 119 (45), 11108-
11109.
(11) (a) J orgensen, M.; Lee, S.; Liu, X.; Wolkowski, J . P.; Hartwig,
J . F. J . Am. Chem. Soc. 2002, 124 (42), 12557-12565. (b) Gaertzen,
O.; Buchwald, S. L. J . Org. Chem. 2002, 67 (2), 465-475. (c) Beare, N.
A.; Hartwig, J . F. J . Org. Chem. 2002, 67 (2), 541-555. (d) Lee, S.;
Beare, N. A.; Hartwig, J . F. J . Am. Chem. Soc. 2001, 123 (34), 8410-
8411. (e) Stauffer, S. R.; Beare, N. A.; Stambuli, J . P.; Hartwig, J . F.
J . Am. Chem. Soc. 2001, 123 (19), 4641-4642.
Resu lts a n d Discu ssion
(12) (a) Shaughnessy, K. H.; Hammann, B. C.; Hartwig, J . F. J . Org.
Chem. 1998, 63 (19), 6546-6553.
(13) Culkin, D. A.; Hartwig, J . F. J . Am. Chem. Soc. 2002, 124 (32),
9330-9331.
Syn th esis a n d Str u ctu r e Elu cid a tion of P a lla d a -
cycles 5a -c. Iodopalladium complexes 4a -c possessing
commercially available enantiomerically pure phosphine
ligands (S,S)-DIOP21 and (S,S)-BDPP22 were obtained
by straightforward ligand exchange reactions23 with
known18 complexes 3a and 3b (Scheme 2). Bidentate
(14) (a) Hamada, T.; Chieffi, A.; Åhman, J .; Buchwald, S. L. J . Am.
Chem. Soc. 2002, 124 (7), 1261-1268. (b) Hamada, T.; Buchwald, S.
L. Org. Lett. 2002, 4 (6), 999-1001. (c) Åhman, J .; Wolfe, J . P.;
Troutman, M. V.; Palucki, M.; Buchwald, S. L. J . Am. Chem. Soc. 1998,
120 (8), 1918-1919.
(15) An intramolecular reaction mediated by chiral monodentate or
bidentate phosphines afforded oxindoles in enantiomeric excesses from
4% to 59%. Chiral imidazolidene carbene ligands afforded products
with enantiomeric purities 70-76% ee, see: (a) Lee, S.; Hartwig, J . F.
J . Org. Chem. 2001, 66 (10), 3402-3415. Excellent levels of asymmetric
induction (94-97% ee) in a catalytic arylation of γ-butyrolactones have
been realized when palladium(0) catalyst was replaced with Ni[[(S)-
BINAP](COD), see: (b) Spielvogel, D. J .; Buchwald, S. L. J . Am. Chem.
Soc. 2002, 124 (14), 3500-3501.
(16) For the preparation and characterization of stable transition
metal ester enolates, see: (a) Tian, G.; Boyle, P. D.; Novak, B. M.
Organometallics 2002, 21 (7), 1462-1465. (b) Burkhardt, E. R.;
Bergmann, R. G.; Heathcock, C. H. Organometallics 1990, 9 (1), 30-
44. (c) Kayaki, Y.; Shimizu, I.; Yamamoto, A. Chem. Lett. 1995, 1089-
1090. (d) Stack, J . G.; Simpson, R. D.; Hollander, F. J .; Bergman, R.
G.; Heathcock, C. H. J . Am. Chem. Soc. 1990, 112 (7), 2716-2729.
(17) For a stereoselective synthesis of a stable chiral nonracemic
carbon-bonded “double” ester enolate via an oxidative cyclization of
cyclopropene esters bearing a covalently bonded chiral auxiliary group,
see: (a) Hashmi, A. S. K.; Naumann, F.; Bolte, M. Organometallics
1998, 17 (12), 2385-2387. The influence of metal-centered chirality
on the configuration of the stereogenic carbon in a carbon-bonded
ruthenium ketone enolate has been studied, see: (b) Rasley, B. T.;
Rapta, M.; Kulawiec, R. J . Organometallics 1996, 15 (13), 2852-2854.
(18) Portscheller, J . L.; Malinakova, H. C. Org. Lett. 2002, 4 (21),
3679-3681.
(19) Retention of asymmetry at a palladium-bonded sp3-hybridized
stereogenic carbon in an alkyne insertion reaction has been demon-
strated, see: Spencer, J .; Pfeffer, M. Tetrahedron: Asymmetry 1995,
6 (2), 419-426.
(20) (a) Wipf, P.; Weiner, W. S. J . Org. Chem. 1999, 64 (14), 5321-
5324. (b) Harrity, J . P. A.; Visser, M. S.; Gleason, J . D.; Hoveyda, A.
H. J . Am. Chem. Soc. 1997, 119 (6), 1488-1489.
(21) For representative examples of the application of the (S,S)-
DIOP ligand in asymmetric synthesis, see: (a) Hiroi, K.; Makino, K.
Chem. Lett. 1986, 617-620. (b) Trost, B. M.; Strege, P. E. J . Am. Chem.
Soc. 1977, 99 (5), 1649-1651. (c) Dang, T. P.; Kagan, H. B. J . Chem.
Soc., Chem. Commun. 1971, 10, 481.
(22) For representative examples of the application of the (S,S)-
BDPP ligand in asymmetric synthesis, see: (a) Burgess, K.; Donk, W.
A.; Ohlmeyer, M. J . Tetrahedron: Asymmetry 1991, 2 (7), 613-621.
(b) Bakos, J .; Toth, I.; Heil, B.; Marko, L. J . Organomet. Chem. 1985,
279, 23. (c) MacNeil, P. A.; Roberts, N. K.; Bosnich, B. J . Am. Chem.
Soc. 1981, 103 (9), 2273-2280.
(23) Ludwig, M.; Stro¨mberg, S.; Svensson, M.; Åkermark, B. Or-
ganometallics 1999, 18 (6), 970-975.

Chiral Nonracemic 2H-1-Benzopyran
Organometallics, Vol. 22, No. 14, 2003 2963
Ta ble 1. Effects of Rea ction Con d ition s on
Dia ster eoselectivity in th e Syn th esis of Sta ble
Oxa p a lla d a cycles
Sch em e 2
diastereomeric
ratio
sub-
strate
temp 5.1a -c 5.2a -c de combined
base
(°C)
(%)
(%)
(%) yield (%)
4a
5.1a
35
44
5.2a
65
56
1
2
3
4
5
6
KHMDSa
t-BuOK
-78
rt
30
12
38
26
72
80
94
72
88
72
89
98
ligands with three- and four-carbon tethers were se-
lected because a synthesis of a 2H-1-benzopyran via
alkyne insertion into a racemic palladacycle bearing a
structurally related achiral 1,4-bis(diphenylphosphino)-
butane (dppb) ligand has been described.18
-78
69
63
86
90
5.1bc
24
25
44
54
31
37
14
10
5.2bc
76
75
56
46
LDA
rt
-78
(R*)MeNLib -78
1H and 31P NMR spectra of iodopalladium complexes
4a-c showed temperature-dependent features. 31P NMR
spectra of complexes 4a -c consisted of one major and
one minor pair of doublets corresponding to nonequiva-
lent phosphorus atoms present in two distinct confor-
mations of the seven-membered and six-membered
“chelate” rings.24 Changes in chemical shifts and rela-
tive intensities of the two pairs of doublets were noted
when 31P NMR spectra recorded at 25 and 55 °C were
compared.25
Treatment of iodopalladium complexes 4a -c with
appropriate bases (e.g., t-BuOK or LDA) afforded the
corresponding palladacycles 5a -c in good overall yields
(71-99%) as moisture- and air-stable solids in variable
diastereomeric purities (8-80% de) (vida infra) (Table
1).
Spectroscopic data for complexes 5a -c fully support
the structures depicted in Table 1. Resonances at δ 5.35
and 5.22 (dd, J (1H-31P) ) 10.6 Hz, 8.1 Hz), δ 5.94 and
5.69 (dd, J (1H-31P) ) 8.6-9.9 Hz, 6.8-7.3 Hz), and δ
5.50 and 5.17 (t, J (1H-31P) ) 8.5-8.7 Hz) in the 1H
NMR (500 MHz, CDCl3) spectra of palladacycles 5a , 5b,
and 5c, respectively, were assigned to the methine
protons attached to stereogenic metal-bonded carbons.
The palladium-bonded methine carbons were found to
resonate at δ 97.1 and 98.3 (dd, J (13C-31P) ) 85.0-85.4
Hz, 5.6-5.9 Hz), δ 104.3 (dd, J (13C-31P) ) 89.2-92.0
Hz, 4.3-4.9 Hz), and δ 95.9 and 98.5 (dd, J (13C-31P) )
84.4-85.3 Hz, 5.4-5.7 Hz) in the 13C NMR (125 MHz,
CDCl3) spectra for complexes 5a , 5b, and 5c, respec-
tively. The corresponding H-C correlations were estab-
lished via 2D NMR (HMQC) analyses on complexes 5a ,
5b, and 5c. Two pairs of doublets were detected in 31P
4b
4c
7
8
9
10
11
t-BuOK
rt
0
-78
rt
52
50
12
8
71
88
d
82
91
LDA
-78
77
23
54
5.1c
64
87
42
12
5.2c
36
13
58
88
12
13
14
15
t-BuOK
rt
-78
rt
28
74
16
76
99
99
94
99
LDA
-78
a
b
Reaction time was extended to 2 h. R* ) PhCH(Me)- with
a R configuration. c The assignment of the absolute configuration
is arbitrary. See ref 26. The reaction proceeded with only a
partial conversion of the starting material.
d
NMR (162 MHz, CDCl3) spectra of complexes 5a -c (5a :
δ 10.72 (d, J ) 30.3 Hz), 7.50 (d, J ) 30.1 Hz) and δ
12.28 (d, J ) 30.7 Hz), 3.42 (d, J ) 30.3 Hz); 5b: δ 8.38
(d, J ) 31.1 Hz), 7.61 (d, J ) 31.2 Hz) and δ 8.76 (d, J
) 30.9 Hz), 3.52 (d, J ) 30.8 Hz); 5c: δ 21.74 (d, J )
45.8 Hz), 14.34 (d, J ) 46.0 Hz) and δ 22.34 (d, J )
43.1 Hz), 16.65 (d, J ) 43.0 Hz)). Thus, the indicative
spectral features appeared as two clearly distinguish-
able sets in various ratios in H and 31P NMR spectra
1
recorded for products 5a -c of products 5a -c of the ring-
closure reactions of complexes 4a -c (Table 1). Careful
thin-layer chromatography (silica, EtOAc/hexanes) of
these materials indicated the presence of two com-
pounds with close retention factors (Rf), and variable-
temperature NMR studies did not reveal any temper-
ature-dependent features in 1H and 31P NMR spectra
within the range of temperatures examined (25-55 °C).
On the basis of this evidence, integration of the two 1H
NMR signals corresponding to methine protons at 5.17-
5.94 ppm was employed as a convenient method for
determining the ratios of diastereomers 5.1a -c:5.2a -
c26 shown in Table 1.
(24) For discussions of the conformational equilibrium in palladium,
platinum, rhodium, and irridium complexes bearing the DIOP ligand,
see: (a) Chaloner, P. A. J . Organomet. Chem. 1984, 266 (2), 191-201.
(b) Brown, K.; Chaloner, P. A. J . Organomet. Chem. 1981, 217 (2),
C25-C28. (c) Campi, E. M.; Elmes, P. S.; J ackson, W. R.; Thomson,
R. J .; Weigold, J . A. J . Organomet. Chem. 1989, 371 (3), 393-395. (d)
Brown, J . M.; Chaloner, P. A. J . Am. Chem. Soc. 1978, 100 (13), 4307-
4308.
Crystallization of palladacycle 5c (L ) (S,S)-BDPP,
1
Y ) COOEt) (72% de, 5.1c:5.2c ) 14:86 by H NMR)
via slow diffusion of hexane into a methylene chloride
solution at room temperature afforded diffraction-qual-
ity crystals of a pure major diastereomer, 5.2c, as
confirmed by spectroscopic analyses of the crystalline
material (1H NMR: δ 5.17 (t, J (1H-31P) ) 8.5 Hz)). The
(25) For example, see data for complex 4a : 31P NMR (202 MHz,
CDCl3, 25 °C): δ 11.31 (d, J ) 38.8 Hz, 0.24 P), 11.24 (d, J ) 38.9 Hz,
0.76 P), -3.70 (d, J ) 38.9 Hz, 0.76 P), -6.15 (d, J ) 39.0 Hz, 0.24 P);
31P NMR (202 MHz, CDCl3, 55 °C) δ 11.04 (d, J ) 39.0 Hz, 1 P), -3.62
(d, J ) 39.0 Hz, 0.35 P), -5.53 (d, J ) 39.0 Hz, 0.65 P).

2964 Organometallics, Vol. 22, No. 14, 2003
Portscheller et al.
diastereomeric excess of complex 5.1a up to 80% de was
achieved by employing a chiral nonracemic base gener-
ated in situ via deprotonation of (R)-(+)-N,R-dimethyl-
benzylamine by n-BuLi28 (entry 6, Table 1). The opposite
diastereomer 5.2a was prepared in 30% de when the
ring closure reaction of complex 4a was mediated by
KHMDS at -78 °C (entry 1, Table 1). Application of
t-BuOLi, chiral alkoxide bases (potassium (1R,2S)-
or (1S,2R)-[R-[1-(dimethylamino)ethyl]benzenemeth-
oxide),29 LiHMDS, NaHMDS, and variations in the
nature of solvents (benzene) and additives (AgNO3) did
not prove effective for the ring closure, or did not
significantly improve the observed diastereoselectivities.
Different trends were observed with complex 4b
featuring the amide functionality (entries 7-11, Table
1). Diastereomer 5.2b was isolated in 52% de from the
reaction mediated by t-BuOK at room temperature
(entry 7, Table 1). Surprisingly, reaction at 0 °C afforded
essentially the same result (entry 8, Table 1), and a
further decrease in the reaction temperature to -78 °C
led to incomplete conversion (entry 9, Table 1). The ring
closure mediated by LDA at -78 °C was selective for
the opposite diastereomer, providing complex 5.1b in
54% de (entry 11, Table 1). Attempts to mediate the ring
closure by chiral nonracemic lithium bases (lithium (R)-
or (S)-N,R-dimethylbenzylamides)28 or chiral alkoxide
bases (potassium (1R,2S)- or (1S,2R)-[R-[1-(dimethyl-
amino)ethyl]benzenemethoxide])29 were unsuccessful.
Complex 4c, featuring the (S,S)-BDPP ligand, par-
ticipated in highly diastereoselective ring closure reac-
tions when treated with either t-BuOK or LDA at low
temperatures (entries 13 and 15, Table 1). Notably,
while the ring closure with t-BuOK afforded diastere-
omer 5.1c (74% de), the reaction mediated by LDA
afforded the opposite diastereomer 5.2c (76% de).
The observed differences in diastereoselectivity be-
tween reactions mediated by t-BuOK and LDA at
variable temperatures prompted us to assess the con-
figurational stability of the metal-bonded stereogenic
center in the presence of an excess of t-BuOK (Table 2).
Generation of enolates 6a -c in low equilibrium con-
centrations may allow for either an “enrichment” or an
“erosion” of the diastereomeric purities of palladacycles
F igu r e 1. Crystal structure of complex (+)-(R,S,S)-5.2c.
Ellipsoids represent a 50% probability level.
X-ray crystal structure of complex 5.2c depicted in
Figure 1 indicates the absolute configuration of the
metal-bonded sp3-hybridized stereogenic carbon as R,
allowing for the assignment of the absolute configura-
tion of the diastereomer 5.2c as (R,S,S) and the dia-
stereomer 5.1c (1H NMR: δ 5.50 (t, J (1H-31P) ) 8.4
Hz)) as (S,S,S).
However, attempts to obtain diffraction-quality crys-
tals of palladacycles 5a and 5b were unsuccessful.
Diastereomeric purity of palladacycles 5.1a (78% de)
and 5.1b (50% de) could be further increased by flash
column chromatography over silica, which afforded
diastereomer 5.1a 26 (1H NMR: δ 5.35 (dd, J (1H-31P) )
10.6 Hz, 8.1 Hz) in 94% de, diastereomer 5.1b26 (1H
NMR: δ 5.94 (dd, J (1H-31P) ) 8.7 Hz, 6.8 Hz) in 94%
and 96% de, and a fraction containing the diastereomer
5.2b26 (1H NMR: δ 5.70 (dd, J (1H-31P) ) 9.9 Hz, 7.3
Hz) in 94% de.
In vestiga tion of th e F a ctor s th a t Con tr ol Asym -
m etr ic In d u ction a n d Con figu r a tion a l Sta bility of
th e Meta l-Bon d ed Ster eocen ter s. The choice of the
base and the reaction temperature proved to be the most
important parameters for the control of asymmetric
induction in the preparation of palladacycles 5a -c.
However, no common trends in responses to these
factors could be identified among substrates 4a -c that
differ in the nature of ligands L-L and the electron-
withdrawing group Y. In experiments reported in Table
1, care was taken not to alter the diastereomeric
compositions of the crude products 5a -c upon isola-
tion.27
(27) Workup procedures for the preparations of palladacycles 5a -c
as described in Table 1: Solutions of complexes 4a -c in THF were
treated with the indicated base at the indicated temperature. Crude
reaction mixtures were filtered through a short plug of basic alumina
eluting with ethyl acetate or ethyl acetate/hexanes mixtures with
compositions that allowed for a complete elution of all the organo-
metallic material. Solvents were removed under reduced pressure to
afford the palladacycles 5a -c as yellow solids. The diastereomeric
composition of this material was determined by 1H NMR spectroscopic
analysis.
(28) (a) Cain, C. M.; Cousins, R. P. C.; Coumbarides, G.; Simpkins,
N. S. Tetrahedron 1990, 46 (2), 523-544. (b) Majewski, M.; Gleave,
D. M.; Nowak, P. Can. J . Chem. 1995, 73 (10), 1616-1626. When the
opposite enantiomer of the chiral base, lithium (S)-(-)-N,R-dimethyl-
benzylamide, was applied to the ring closure of complex 4a , a complete
conversion into the palladacycle 5a could not be achieved, even when
an excess of the base was used for a prolonged reaction time. Both
enantiomers of the base, lithium (R)- or (S)-N,R-dimethylbenzylamide,
failed to allow for a complete conversion of complex 4b into palladacycle
5b.
(29) Plaquevent, J .-C.; Perrard, T.; Cahard, D. Chem. Eur. J . 2002,
8 (15), 3301-3307. Attempted formation of palladacycles 5a and 5b
via the treatment of complexes 4a and 4b with chiral alkoxides,
potassium (1R,2S)- and (1S,2R)-[R-[1-(dimethylamino)ethyl]benzene-
methoxide, obtained by the reaction of potassium hydride with
N-methylephedrine in THF, afforded mixtures consisting of unreacted
complexes 4a or 4b and palladacycles 5a or 5b with approximately
1:1 ratios of the diastereomers.
Diastereoselectivity of the preparation of palladacycle
5.1a (Y ) COOEt, L-L ) (S,S)-DIOP) via the treatment
of complex 4a with either t-BuOK or LDA was increased
to 72% de by lowering the reaction temperature to -78
°C (entries 2-5, Table 1). Further improvement in the
(26) In the 1H NMR spectra of the diastereomers designated as 5.1,
the signal for the methine proton attached to the palladium-bonded
carbon is found at lower field than in the spectra of the diastereomers
designated as 5.2 (Table 1). Absolute configurations of the metal-
bonded stereocenters for the diastereomers 5.1a S, 5.1c S, 5.2a R, and
5.2c R as shown in Table 1 were assigned via a combination of X-ray
crystallographic studies on the complex 5.2c, stereospecific ligand
exchange, and specific optical rotations of complexes 7 (see Schemes 3
and 4 in the text). Note that the absolute configurations for the
complexes 5.1b and 5.2b as shown in Tables 1 and 2 have been
assigned arbitrarily.

Chiral Nonracemic 2H-1-Benzopyran
Organometallics, Vol. 22, No. 14, 2003 2965
Ta ble 2. Assessm en t of Con figu r a tion a l Sta bility
of P a lla d iu m -Bon d ed Ster eogen ic Ca r bon s in
Sta ble Oxa p a lla d a cycles
Sch em e 3
diastereomeric
ratio in substrate
diastereomeric
ratio in product
timea
product recovery
5.1 (%) 5.2 (%)
(h) 5.1 (%) 5.2 (%) de (%)
(%)
5a
5a
1
2
3
82
43
43
18
57
57
1
1
3
71
27
38
29
73
62
42
46
24
76
81
69
5bb
5c
5bb
5c
4
5
6
69
27
28
31
73
72
1
1
3
55
18
13
45
82
87
10
64
74
71
76
61
achiral 1,2-bis(diphenylphosphino)ethane (dppe) ligand
without affecting the configurational integrity of the
metal-bonded stereocenter (Scheme 3).32
7
8
9
87
19
19
13
81
81
1
1
3
36
14
12
64
86
88
28
72
76
93
95
90
Enantiomeric purities of complexes (-)-7 (68.2% ee)
and (+)-7 (26.5% ee), determined by HPLC analyses on
a chiral stationary phase (Chiralpak AD), were in
acceptable agreement33 with the diastereomeric ratios
of substrates 5.1a (66% de) and 5.2a (30% de) measured
by 1H NMR spectroscopy (Scheme 3). In both the
reactions, care was taken to ensure that complete
conversion of the complexes 5.1a and 5.2a was achieved.
Enantiomerically enriched palladacycle (-)-7 (74.1%
ee)33 did not racemize to a significant degree when
dissolved in 2-propanol at room temperature, showing
73.1% ee in an HPLC analysis repeated after 7 days, or
when the solution of the complex (-)-7 (74.1% ee)33 in
ethyl acetate was treated with silica for 1 h, yielding
recovered complex (-)-7 in 73.8% ee.
An exchange of (S,S)-BDPP ligand in complex 5.2c
(62% de) for the achiral dppe ligand afforded complex
(+)-7 (62.1% ee by HPLC) (Scheme 4). Assuming that
the ligand exchange proceeded with retention of the
absolute configuration R at the metal-bonded stereo-
genic carbon32 in substrate 5.2c (Figure 1), a correlation
of the signs of optical rotation measured for complexes
7 (Schemes 3 and 4) was used to assign the absolute
configurations of the metal-bonded stereocenters for
a
To solutions of the substrates 5a -c in THF was added 1.1
mol equiv of t-BuOK (1 M solutions in THF). Reaction mixtures
were stirred for the indicated time period at room temperature.
Diastereomeric composition of the recovered palladacycles 5a -c
was determined by 1H NMR. The assignment of the absolute
b
configuration is arbitrary. See ref 26.
5a -c. Thus, treatment of palladacycles 5a -c with 1.1
mol equiv of t-BuOK in THF for at least 1 h30 resulted
in significant shifts in the diastereomeric ratios meas-
ured for the recovered palladacycles (compare entries
1-3, 4-6, and 7-9 in Table 2) favoring the generation
of the “thermodynamic” products 5.2a , 5.2b, and 5.2c.
The equilibration process described in Table 2 allowed
us to raise the maximum diastereomeric purity of pal-
ladacycle 5.2a to 46% de (entry 2, Table 2), and in the
case of palladacycle 5.2b to 74% de (entry 6, Table 2).
In summary, both diastereomers of palladacycles 5a
(in 80% and 46% de), 5b (in 54% and 74% de), and 5c
(in 74% and 76% de) have been prepared via transfer
of asymmetry using only one enantiomer of a chiral
nonracemic ligand and employing either kinetic or
thermodynamic conditions. The structures of the in situ
generated alkaline metal ester and amide enolates
appeared to play a critical role31 in this process, since
the choice of the base allowed us to control the absolute
sense of asymmetric induction.
(32) Stability of a Pd-C bond during a ligand exchange process has
been previously established (see ref 4b) and used for the preparation
of enantiomerically enriched transition metal complexes with achiral
ligands, see refs 4a, 6 and: Ryabov, A. D.; Panyashkina, I. M.;
Polyakov, V. A.; Howard, J . A. K.; Kuzmina, L. G.; Datt, M. S.; Sacht,
C. Organometallics 1998, 17 (16), 3615-3618.
(33) In the case of palladacycle (-)-7, the agreement between the
value of the diastereomeric ratio in substrates 5.1a (determined by
1H NMR) and the enantiomeric excess of complex (-)-7 measured by
chiral phase HPLC analyses was lower than expected. This could have
been caused by the tendency of complex (-)-7 to selectively precipitate
during the removal of solvents under reduced pressure. Although all
the solvents were removed to avoid a net enantiomeric enrichment,
the bulk of the solid material was not homogeneous. This explanation
is supported by a relatively large discrepancy noted for repeated HPLC
analyses of the same sample (up to relative 3%). Conversion of complex
5.1a into the enantiomerically enriched palladacycle (-)-7 was re-
peated several times with the following results: (i) complex 5.1a (60%
de) yielded palladacycle (-)-7 (62% yield, 56.9% ee); (ii) complex 5.1a
(70% de) yielded palladacycle (-)-7 (84% yield, 72.7% ee); (iii) complex
5.1a (80% de) yielded palladacycle (-)-7 (61% yield, 74.1% ee).
Liga n d Exch a n ge Rea ction s of th e Dia ster eo-
m er ica lly En r ich ed P a lla d a cycles. Assign m en ts of
Absolu te Con figu r a tion s. Both enantiomers of pal-
ladacycle 7 have been synthesized via ligand exchange
reactions of palladacycles 5.1a 26 and 5.2a 26 with an
(30) However, no changes in the diastereomeric composition of
palladacycles 5a -c could be detected when the complexes were treated
in neat THF (rt, 1 h), in THF with 0.1 mol equiv of t-BuOK (rt, 1 h),
and in THF with 0.5 mol equiv of t-BuOK (rt, 1 h).
(31) For a discussion of the differences in the structure and the
aggregation state of enolate anions of lithium and potassium metals,
see: Smith, M. B. Organic Synthesis; McGraw-Hill: New York, 1994;
Chapter 9, pp 865-869.

2966 Organometallics, Vol. 22, No. 14, 2003
Portscheller et al.
Sch em e 4
mization of benzopyran (-)-8 accounts for the slight loss
of the stereochemical information in the alkyne inser-
tion reaction cannot be ruled out. This work represents
a rare study on the fate of a nonracemic transition
metal-bonded stereocenter in subsequent carbon-
carbon bond forming reactions.19 At present we are
unable to assign the absolute configurations of benzo-
pyran (-)-8 and palladacycles 5b,26 and work toward
this goal is in progress.
a
Sch em e 5
Con clu sion s
In conclusion, an efficient transfer of asymmetry from
chiral nonracemic ligands into a transition metal-
bonded stereogenic sp3-hybridized carbon has been
demonstrated. The transformation allowed for a dia-
stereoselective (46-80% de) synthesis of novel oxa-
palladacycles representing rare examples of stable
chiral nonracemic palladium ester and amide enolates
with a metal-bonded stereogenic R-carbon. Our studies
revealed that for a selected enantiomer of the ligand,
the absolute sense of stereoinduction could be controlled
by the choice of the base, operating under either kinetic
or thermodynamic conditions. Absolute configurations
of palladacycles 5a and 5c were assigned relying on an
X-ray crystallographic analysis and stereoselective ligand
exchange reactions. A synthetically valuable highly
substituted 2H-1-benzopyran was synthesized in a good
enantiomeric purity (88.4% ee) via a stereoselective
insertion of an alkyne into a diastereomerically enriched
(96% de) palladacycle. In this transformation, the pal-
ladium-bonded stereogenic carbon was incorporated into
a carbon framework with only a minimal loss (8%
racemization) of the stereochemical information. Fur-
ther generalization of this concept with respect to ligand
structures and reaction types of the novel palladacycles
is being pursued in our laboratories.
a
Assignments of the absolute configuration are arbitrary.
palladacycles 5.1a as S and 5.2a as R (Scheme 3, and
Tables 1 and 2).
Syn th esis of a Ch ir a l Non r a cem ic 2H-1-Ben zo-
p yr a n . To explore the applicability of palladacycles 5
for asymmetric organic synthesis, insertion of dimethyl
acetylenedicarboxylate (dmad) into palladacycles 5a -c
was studied.18 Optimum reactivity was observed for
complexes 5b, bearing a sterically demanding amide
functionality.34 The reaction of diastereomer 5.1b en-
1
riched to 96% de (by H NMR) by column chromatog-
raphy, with dmad (ClCH2CH2Cl, 6 h at 100 °C and 16
h at room temperature) afforded benzopyran (-)-818 in
good yield (62%) and only moderately diminished (8%
racemization) enantiomeric excess of 88.4% ee, as
established by HPLC on a chiral stationary phase
(Chiralpak AD) (Scheme 5). The extent of racemization
increased slightly when palladacycle 5.1b enriched to
94% de (by 1H NMR) was treated with dmad for an
extended time at elevated temperature (10 h at 100 °C
and 16 h at room temperature) yielding benzopyran
(-)-8 in 82.1% ee (by HPLC, 12.6% racemization). The
reaction period at room temperature (16 h) allowed for
gradual precipitation of palladium(0) and thus facili-
tated chromatographic purification of benzopyran (-)-8
without significantly affecting its enantiomeric purity.
Thus, benzopyran (-)-8 with 87.2% ee was obtained
when palladacycle 5.1b (96% de by 1H NMR) was
reacted with dmad at elevated temperature (ClCH2-
CH2Cl, 6 h at 100 °C) followed by an immediate isolation
of the product. Decreasing the reaction temperature
from 100 °C to 80 °C eliminated the racemization, but
HPLC analysis of benzopyran (-)-8 detected the pres-
ence of less than 5% unreacted palladacycle 5.1b, which
was difficult to separate by column chromatography.
Although 2H-1-benzopyran (-)-8 proved relatively re-
sistant to racemization35 during chromatographic pu-
rification and extended solution manipulations without
protection from light, the possibility that a slow race-
Exp er im en ta l 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
“internal” (present in a sealed capillary inserted into the NMR
tube) H3PO4 (85%) (δ 0 ppm) as the reference for 31P NMR.
Specific rotation was measured on an AUTOPOL IV polarim-
eter (Rudolph Research Analytical) at room temperature in
methylene chloride. 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 bombardment (FAB) or electron
impact (EI) conditions. Elemental analyses were performed by
Galbraith Laboratories, Knoxville, TN. Analytical 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, Brokmann I). Tetra-
hydrofuran (THF) was freshly distilled from sodium/benzo-
phenone. 1,2-Dichloroethane was freshly distilled from CaH2.
(35) (a) See ref 20a. (b) Van Gemert, B. In Organic Photochromic
and Thermochromic Compounds; Crano, J . C., Guglielmetti, R. J ., Eds.;
Plenum: New York, 1999; Vol. 1, Chapter 3, p 111. Treatment of
benzopyran (-)-8 (82.1% ee) in 1,2-dichloroethane for 6 h at 100 °C in
light or for 6 h at room temperature in light afforded the recovered
benzopyrans (-)-8 in 78.6% ee (4.2% racemization) and 76.8% ee (6.5%
racemization), respectively. Treatment of benzopyran (-)-8 (78.6%)
dissolved in ethyl acetate with silica for 1 h afforded recovered
benzopyran (-)-8 in 76.3% ee (2.9% racemization).
(34) Under the optimized reaction conditions (dmad 2.2 mol equiv,
ClCH2CH2Cl, 6 h at 100 °C and 16 h at room temperature), palladacyle
5a afforded after repeated chromatographic purification a 45% yield
of the corresponding benzopyran18 in 80% purity (by 1H NMR), and
palladacycles 5c and 7 failed to yield the desired organic product.

Chiral Nonracemic 2H-1-Benzopyran
Organometallics, Vol. 22, No. 14, 2003 2967
Benzene was distilled from CaH2 and kept over 3 Å (8-12
mesh) molecular sieves under an atmosphere of dry argon.
Methylene chloride was 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 slow diffusion of hexanes
into a methylene chloride solution of the palladium complex.
Gen er a l P r oced u r e for th e Syn th esis of Iod op a lla -
d iu m Com p lexes 4a -c. A solution of the complex 3a or 3b
(1.0 mmol) and (S,S)-DIOP (1.1 mmol) or (S,S)-BDPP (1.1
mmol) in methylene chloride (55 mL for 4a ,b and 13.5 mL for
4c) was stirred for the indicated time at room temperature
under argon. The solvent was removed under reduced pres-
sure, and the crude product was triturated with small amounts
of ether/hexanes (3:1) to afford pure complexes 4a -c as pale
yellow or orange solids.
0.899 mmol), (S,S)-DIOP (0.492 g, 0.987 mmol), and methylene
chloride (50 mL) were treated according to the general
procedure described above for 1 h to afford complex 4b (0.844
g, 98%) as a yellow solid: mp 139-140 °C dec (EtOAc/hexanes,
1:1); Rf ) 0.26 (EtOAc/hexanes, 1:1); [R]D +54.0 (c 0.74,
1
CH2Cl2); H NMR (500 MHz, CDCl3, 5 °C) δ 7.95 (t, J ) 9.5
Hz, 0.7 H), 7.85-7.82 (m, 2 H), 7.77 (t, J ) 8.6 Hz, 1.3 H),
7.59 (t, J ) 9.0 Hz, 1 H), 7.47-7.37 (m, 10 H), 7.30-7.11 (m,
6 H), 6.50-6.45 (m, 2 H), 6.95-6.89 (m, 1 H), 4.45-4.41 (m, 1
H), 4.25-4.22 (m, 0.3 H), 4.04-3.94 (m, 1.3 H), 3.91-3.84 (m,
1.3 H), 3.59-3.51 (m, 0.7 H), 3.47-3.41 (m, 1 H), 3.35-3.26
(m, 2 H), 3.19-3.14 (m, 1 H), 3.01 (t br, J ) 14.2 Hz, 0.7 H),
2.73-2.67 (m, 0.3 H), 2.43 (t br, J ) 12.2 Hz, 0.7 H), 2.30-
2.18 (m, 1.7 H), 1.25 (s, 3 H), 1.17-1.11 (m, 3 H), 1.08 (t, J )
7.4 Hz, 2 H), 0.99 (s, 2 H), 0.97 (s, 1 H), 0.87 (t, J ) 7.1 Hz, 1
H); 13C NMR (125 MHz, CDCl3) δ 167.7, 158.0, 137.8 (dd,
J (13C-31P) ) 8.8 Hz, 2.6 Hz), 134.8 (d, J (13C-31P) ) 10.6 Hz),
134.3 (t, J (13C-31P) ) 10.9 Hz), 134.0 (d, J (13C-31P) ) 4.3 Hz),
[133.9 (d, J (13C-31P) ) 5.5 Hz)], [133.7], [133.0 (d, J (13C-31P)
) 10.4 Hz)], [132.5 (d, J (13C-31P) ) 10.7 Hz)], [131.8 (d, J (13C-
31P) ) 10.0 Hz)], 131.7 (d, J (13C-31P) ) 10.0 Hz), 131.0 (d,
J (13C-31P) ) 3.4 Hz), [130.9 (d, J (13C-31P) ) 2.4 Hz)], 130.3
(dd, J (13C-31P) ) 23.9 Hz, 1.9 Hz), 129.5 (d, J (13C-31P) ) 2.9
Hz), 128.1 (t, J (13C-31P) ) 10.4 Hz), 128.0 (d, J (13C-31P) )
9.2 Hz), 127.6 (d, J (13C-31P) ) 10.5 Hz), 124.0, 121.5 (t, J (13C-
31P) ) 8.3 Hz), 111.6 (d, J (13C-31P) ) 4.8 Hz), [111.3 (d, J (13C-
31P) ) 4.8 Hz)], 108.2, [107.9], 77.6 (dd, J (13C-31P) ) 7.5 Hz,
2.8 Hz), 76.5 (d, J (13C-31P) ) 2.2 Hz), [68.1], 67.6, [42.4], 42.2,
[40.5], 40.4, 31.4 (dd, J (13C-31P) ) 21.0 Hz, 2.4 Hz), 29.8 (d,
J (13C-31P) ) 23.6 Hz), 26.6, 26.5, [26.4], [14.8], 14.7, [14.2],
13.2, signals for the minor conformer are given in brackets,
several signals account for more than one carbon; 31P NMR
(162 MHz, CDCl3) δ 12.32 (d, J ) 39.4 Hz, 0.69 P), 11.06 (d, J
) 39.0 Hz, 0.31 P), -4.55 (d, J ) 39.0 Hz, 0.31 P), -4.63 (d, J
) 39.4 Hz, 0.69 P); IR (KBr, cm-1) 3050 (m), 2979 (m), 2931
(m), 1663 (s), 739 (s), 692 (s). Anal. Calcd for C43H48INO4P2-
Pd: C, 55.05; H, 5.16; N, 1.49. Found: C, 54.97; H, 5.30; N,
1.50.
(+)-[2-(Eth oxyca r bon ylm eth oxy)p h en yl]iod o[(4S,5S)-
O-isop r op ylid en e-2,3-d ih yd r oxy-1,4-b is(d ip h en ylp h os-
p h in o)bu ta n e]p a lla d iu m (4a ). Complex 3a (0.789 g, 1.49
mmol), (S,S)-DIOP (0.845 g, 1.64 mmol), and methylene
chloride (80 mL) were treated according to the general
procedure described above for 1 h to afford complex 4a (1.33
g, 98%) as a yellow solid: mp 152-153 °C dec (EtOAc/hexanes,
1:2); Rf ) 0.58 (EtOAc/hexanes, 1:1); [R]D +115.2 (c 0.65,
1
CH2Cl2); H NMR (500 MHz, CDCl3, 5 °C) δ 8.05 (t, J ) 9.3
Hz, 1.3 H), 7.99-7.91 (m, 0.3 H), 7.82 (t, J ) 9.4 Hz, 1.7 H),
7.74-7.71 (m, 2.7 H), 7.57-7.36 (m, 10 H), 7.20-7.10 (m, 2
H), 7.03 (t, J ) 7.9 Hz, 1 H), 6.93 (td, J ) 7.6 Hz, 2.3 Hz, 1 H),
6.85 (t, J ) 9.4 Hz, 1 H), 6.48 (t, J ) 7.1 Hz, 1 H), 6.43-6.38
(m, 1 H), 6.03-6.02 (m, 0.3 H), 5.90-5.88 (m, 0.7 H), 4.65 (d,
J ) 15.7 Hz, 0.3 H), 4.49 (d, J ) 15.3 Hz, 0.7 H), 4.37-4.27
(m, 2 H), 4.21 (d, J ) 15.7 Hz, 0.3 H), 4.06 (d, J ) 15.3 Hz, 0.7
H), 3.90-3.82 (m, 1 H), 3.72-3.67 (m, 0.7 H), 3.40-3.29 (m, 1
H), 3.08 (t, J ) 15.4 Hz, 0.7 H), 2.69 (t, J ) 14.4 Hz, 0.7 H),
2.64-2.62 (m, 0.3 H), 2.48-2.44 (m, 0.3 H), 2.28-2.21 (m, 0.7
H), 2.11 (dd, J ) 14.5 Hz, 9.5 Hz, 0.6 H), 1.37 (t, J ) 7.1 Hz,
2 H), 1.33 (t, J ) 7.1 Hz, 1 H), 1.25 (s, 3 H), 1.21 (s, 0.3 H),
1.15 (s, 0.7 H), 0.88 (d, J ) 12.8 Hz, 1.4 H), 0.87 (d, J ) 13.6
Hz, 0.6 H); 13C NMR (125 MHz, CDCl3) δ [169.6], 169.5, 157.7,
[142.0], 141.0, [138.5 (d, J (13C-31P) ) 2.9 Hz)], 137.9 (d, J (13C-
31P) ) 2.9 Hz), 135.4 (d, J (13C-31P) ) 12.4 Hz), [135.3 (d,
J (13C-31P) ) 10.3 Hz)], 134.7 (d, J (13C-31P) ) 13.0 Hz), 133.8,
133.7 (d, J (13C-31P) ) 10.6 Hz), [133.6 (d, J (13C-31P) ) 11.0
Hz)], 133.3 (d, J (13C-31P) ) 9.5 Hz), [133.0 (d, J (13C-31P) )
11.5 Hz)], 132.4 (d, J (13C-31P) ) 10.6 Hz), 131.6 (d, J (13C-
31P) ) 2.4 Hz), 131.0 (d, J (13C-31P) ) 9.0 Hz), [130.8 (d, J (13C-
31P) ) 2.4 Hz)], 130.7 (d, J (13C-31P) ) 2.4 Hz), 130.2 (d, J (13C-
31P) ) 1.4 Hz), 130.1 (d, J (13C-31P) ) 2.4 Hz), 129.9 (d, J (13C-
31P) ) 2.4 Hz), [129.7 (d, J (13C-31P) ) 2.9 Hz)], 128.9 (d, J (13C-
31P) ) 10.5 Hz), 128.7 (d, J (13C-31P) ) 2.6 Hz), [128.5 (d,
J (13C-31P) ) 10.6 Hz)], 128.4 (d, J (13C-31P) ) 10.1 Hz), 127.9
(d, J (13C-31P) ) 9.2 Hz), [127.7 (d, J (13C-31P) ) 10.6 Hz)],
127.0 (d, J (13C-31P) ) 10.4 Hz), 123.9, [123.8], [122.0 (d, J (13C-
31P) ) 8.6 Hz)], 121.8 (d, J (13C-31P) ) 8.4 Hz), [112.3 (d, J (13C-
31P) ) 5.6 Hz)], 111.1 (d, J (13C-31P) ) 5.5 Hz), 108.4, [107.9],
78.3 (dd, J (13C-31P) ) 7.6 Hz, 2.4 Hz), [77.0 (d, J (13C-31P) )
9.2 Hz)], 76.5 (d, J (13C-31P) ) 13.0 Hz), [66.1], 65.2, 60.8,
[60.7], 31.9 (dd, J (13C-31P) ) 21.0 Hz, 3.8 Hz), 31.2 (dd, J (13C-
31P) ) 17.9 Hz, 3.6 Hz), 26.8, [26.7], 26.5, [26.2], 14.4, [14.2],
signals for the minor conformer are given in brackets, several
signals account for more than one carbon; 31P NMR (162 MHz,
CDCl3) δ 11.60 (d, J ) 38.8 Hz, 0.25 P), 11.54 (d, J ) 39.0 Hz,
0.75 P), -3.43 (d, J ) 38.9 Hz, 0.75 P), -5.93 (d, J ) 38.7 Hz,
0.25 P); IR (KBr, cm-1) 3050 (m), 2980 (m), 1755 (s), 738 (s),
692 (s). Anal. Calcd for C41H43IO5P2Pd: C, 54.05; H, 4.76.
Found: C, 54.56; H, 4.93.
(+)-[2-(Eth oxyca r bon ylm eth oxy)p h en yl]iod o[(2S,4S)-
2,4-bis(diph en ylph osph in o)pen tan e]palladiu m (4c). Com-
plex 3a (0.400 g, 0.757 mmol), (S,S)-BDPP (0.366 g, 0.831
mmol), and methylene chloride (10 mL) were treated according
to the general procedure described above for 12 h to afford
complex 4c (0.633 g, 98%) as an orange solid: mp 173-174
°C dec (hexanes); Rf ) 0.57 (EtOAc/hexanes, 1:1); [R]D +79.8
(c 0.54, CH2Cl2); 1H NMR (500 MHz, CDCl3, 5 °C) δ 8.31-
8.27 (m, 2 H), 8.09-8.00 (m, 0.3 H), 7.78 (t, J ) 9.2 Hz, 2 H),
7.70 (t, J ) 8.7 Hz, 1.7 H), 7.67-7.62 (m, 0.3 H), 7.53 (s br,
2.7 H), 7.45 (s br, 0.3 H), 7.41 (t, J ) 7.3 Hz, 1 H), 7.36-7.31
(m, 3 H), 7.17-7.13 (m, 3 H), 6.95 (t, J ) 6.3 Hz, 1.7 H), 6.90-
6.84 (m, 2.7 H), 6.51 (t, J ) 7.3 Hz, 1 H), 6.43 (t, J ) 7.2 Hz,
1 H), 6.20-6.15 (m, 0.3 H), 5.80-5.75 (m, 1 H), 4.41 (d, J )
15.1 Hz, 1 H), 4.36-4.31 (m, 1.7 H), 4.29-4.17 (m, 0.3 H), 3.60
(d, J ) 15.1 Hz, 1 H), 3.20-3.10 (s br, 1 H), 2.85-2.80 (m, 0.7
H), 1.94-1.81 (m, 2.3 H), 1.39 (t, J ) 7.1 Hz, 3 H), 1.29 (dd, J
) 14.5 Hz, 7.0 Hz, 3 H), 0.91 (dd, J ) 11.2 Hz, 7.1 Hz, 3 H);
13C NMR (125 MHz, CDCl3) δ 169.5, [163.9], 158.7, 143.2,
142.3, 137.2 (d, J (13C-31P) ) 12.6 Hz), 136.6 (d, J (13C-31P) )
2.8 Hz), 135.6 (d, J (13C-31P) ) 11.2 Hz), [135.2 (d, J (13C-31P)
) 10.6 Hz)], 134.2 (d, J (13C-31P) ) 9.6 Hz), [134.1 (d, J (13C-
31P) ) 10.9 Hz)], 133.7, 133.4, 131.5 (d, J (13C-31P) ) 7.8 Hz),
131.3 (d, J (13C-31P) ) 2.8 Hz), 131.1, [130.8], 130.2 (d, J (13C-
31P) ) 1.9 Hz), 130.0 (d, J (13C-31P) ) 2.8 Hz), 129.8 (d, J (13C-
31P) ) 1.4 Hz), 128.7 (d, J (13C-31P) ) 8.8 Hz), 128.3 (d, J (13C-
31P) ) 2.6 Hz), 127.8 (d, J (13C-31P) ) 10.7 Hz), 127.4 (d, J (13C-
31P) ) 10.1 Hz), 126.6 (d, J (13C-31P) ) 9.9 Hz), 125.9, [125.6],
123.9, 121.4 (d, J (13C-31P) ) 8.4 Hz), 110.9 (d, J (13C-31P) )
5.2 Hz), [66.1], 64.9, 60.5, [60.4], 35.6 (t, J (13C-31P) ) 6.7 Hz),
26.4 (dd, J (13C-31P) ) 20.4 Hz, 3.8 Hz), 23.3 (dd, J (13C-31P)
) 20.8 Hz, 6.3 Hz), 19.7 (d, J (13C-31P) ) 7.6 Hz), 16.3 (d,
J (13C-31P) ) 5.9 Hz), 14.5, [14.3], signals for the minor
(+)-[2-(N ,N -Die t h ylca r b on ylm e t h oxy)p h e n yl]iod o-
[(4S,5S)-O-isop r op ylid en e-2,3-d ih yd r oxy-1,4-bis(d ip h en -
ylp h osp h in o)bu ta n e]p a lla d iu m (4b). Complex 3b (0.500 g,

2968 Organometallics, Vol. 22, No. 14, 2003
Portscheller et al.
conformer are given in brackets, several signals account for
more than one carbon; 31P NMR (162 MHz, CDCl3) δ 22.57 (d,
J ) 50.3 Hz, 0.13 P), 20.30 (d, J ) 47.9 Hz, 0.87 P), 6.92 (d, J
) 48.1 Hz, 0.87 P), 6.28 (d, J ) 50.2 Hz, 0.13 P); IR (KBr,
cm-1) 3049 (m), 2978 (m), 1756 (s), 1192 (s), 744 (m), 695 (s);
HRMS (FAB) calcd for C39H42IO3P2Pd (M + H+), 870.0954,
found 870.0969. Anal. Calcd for C39H41IO3P2Pd: C, 54.91; H,
4.84. Found: C, 54.95; H, 5.08.
°C dec (EtOAc/hexanes, 1:1); Rf ) 0.50 (EtOAc/hexanes, 1:1);
[R]D +46.8 (c 0.34, CH2Cl2).
An a lytica l d a ta for 5.2a a s a 16:84 m ixtu r e of d ia ster -
eom er s: 1H NMR (500 MHz, CDCl3) δ 8.14 (t, J ) 8.9 Hz,
0.32 H), 8.03 (t, J ) 8.7 Hz, 1.68 H), 7.87 (t, J ) 8.9 Hz, 0.32
H), 7.81 (t, J ) 8.6 Hz, 1.68 H), 7.61 (t, J ) 8.7 Hz, 0.32 H),
7.55 (t, J ) 9.7 Hz, 2 H), 7.49 (t, J ) 8.4 Hz, 2 H), 7.45-7.40
(m, 3 H), 7.36 (q, J ) 6.8 Hz, 2 H), 7.32-7.27 (m, 4 H), 7.24
(td, J ) 7.4 Hz, 1.5 Hz, 1 H), 6.93 (t, J ) 7.0 Hz, 1.68 H),
6.87-6.81 (m, 2 H), 6.59 (td, J ) 8.1 Hz, 3.5 Hz, 0.84 H), 6.45
(td, J ) 7.9 Hz, 0.16 H), 6.16 (tt, J ) 7.1 Hz, 1.6 Hz, 0.84 H),
6.11-6.07 (m, 0.16 H), 5.35 (dd, J ) 10.6 Hz, 8.1 Hz, 0.16 H),
5.22 (dd, J ) 10.1 Hz, 8.5 Hz, 0.84 H), 4.27 (dq, J ) 7.1 Hz,
3.6 Hz, 0.84 H), 4.16-4.05 (m, 1.84 H), 3.99-3.94 (m, 0.16 H),
3.86 (t, J ) 9.5 Hz, 0.84 H), 3.81-3.72 (m, 0.32 H), 3.25 (td, J
) 13.5 Hz, 4.6 Hz, 0.84 H), 3.19 (td, J ) 13.7 Hz, 3.3 Hz, 0.16
H), 3.10 (ddd, J ) 13.6 Hz, 10.9 Hz, 4.0 Hz, 0.84 H), 2.77 (ddd,
J ) 13.7 Hz, 11.2 Hz, 4.7 Hz, 0.16 H), 2.58 (td, J ) 14.0 Hz,
4.1 Hz, 0.84 H), 2.20 (t br, J ) 5.0 Hz, 0.32 H), 1.74 (dd, J )
14.7 Hz, 7.2 Hz, 0.84 H), 1.26 (t, J ) 7.1 Hz, 2.52 H), 1.26 (s,
2.52 H), 1.21 (s, 3 H), 1.00 (t, J ) 7.1 Hz, 0.48 H), 0.94 (s, 0.48
H); 13C NMR (125 MHz, CDCl3) δ 176.0 (q, J (13C-31P) ) 1.3
Hz), 174.6 (t, J (13C-31P) ) 4.8 Hz), 147.9 (dd, J (13C-31P) )
107.1 Hz, 9.9 Hz), 140.5 (dd, J (13C-31P) ) 10.7 Hz, 3.1 Hz),
136.2 (dd, J (13C-31P) ) 38.1 Hz, 2.9 Hz), [136.6 (d, J (13C-31P)
) 14.8 Hz)], 135.2 (d, J (13C-31P) ) 13.2 Hz), [134.1 (d, J (13C-
31P) ) 13.4 Hz)], 133.9 (dd, J (13C-31P) ) 14.8 Hz, 1.4 Hz),
[133.8 (d, J (13C-31P) ) 13.0 Hz)], 133.7 (dd, J (13C-31P) ) 1.4
Hz), 133.4 (d, J (13C-31P) ) 13.5 Hz), 132.4 (d, J (13C-31P) )
1.4 Hz), 132.2 (d, J (13C-31P) ) 10.9 Hz), 132.1 (d, J (13C-31P)
) 0.95 Hz), 131.7 (d, J (13C-31P) ) 10.0 Hz), 131.1 (d, J (13C-
31P) ) 2.4 Hz), [131.0 (d, J (13C-31P) ) 1.9 Hz)], 130.7 (dd,
J (13C-31P) ) 38.6 Hz, 2.4 Hz), [130.7 (t, J (13C-31P) ) 2.4 Hz)],
[130.2], [130.1 (d, J (13C-31P) ) 1.9 Hz)], 129.7, 129.4, 129.3
(d, J (13C-31P) ) 1.8 Hz), 128.8 (d, J (13C-31P) ) 9.9 Hz), [128.6
(dd, J (13C-31P) ) 9.8 Hz, 1.6 Hz)], [128.5 (d J (13C-31P) ) 7.1
Hz)], 128.4 (d, J (13C-31P) ) 10.4 Hz), [128.4 (d, J (13C-31P) )
6.4 Hz)], 128.3 (d, J (13C-31P) ) 9.4 Hz), [126.1], 126.0, 117.5
(q, J (13C-31P) ) 4.3 Hz), 109.2 (d, J (13C-31P) ) 2.1 Hz), [109.1],
108.3, [107.9], 98.3 (dd, J (13C-31P) ) 85.0 Hz, 5.6 Hz), 79.0
(dd, J (13C-31P) ) 9.6 Hz, 5.4 Hz), 76.3 (dd, J (13C-31P) ) 16.7
Hz, 2.4 Hz), 59.3, [59.0], 32.5 (dd, J (13C-31P) ) 24.7 Hz, 6.0
Hz), 27.6 (d, J (13C-31P) ) 14.7 Hz), 26.9, [26.7], 26.6, [26.4],
14.9, [14.5], signals for the minor diastereomer are shown in
brackets, some signals account for more than one carbon; 31P
NMR (162 MHz, CDCl3) δ 12.28 (d, J ) 30.7 Hz, 0.84 P), 10.73
(d, J ) 30.2 Hz, 0.16 P), 7.51 (d, J ) 30.1 Hz, 0.16 P), 3.42 (d,
J ) 30.7 Hz, 0.84 P).
Syn th esis of P a lla d a cycles 5a -c. (-)-[(S)-(Eth oxy-
ca r b on ylm et h in eoxy-1,2-p h en ylen e)][(4S,5S)-O-isop r o-
p ylid en e-2,3-d ih yd r oxy-1,4-b is(d ip h en ylp h osp h in o)b u -
ta n e]p a lla d iu m (5.1a ). To a solution of iodopalladium com-
plex 4a (0.150 g, 0.165 mmol) in THF (7.5 mL) at -78 °C was
added a solution of lithium (R)-(+)-N,R-dimethylbenzylamide29b
(1.1 mL, 0.173 mmol, in THF). The mixture was stirred at -78
°C for 15 min, quenched with 0.1 mL of MeOH, and filtered
through a small plug of basic alumina, eluting with EtOAc.
The solvent was removed under reduced pressure to afford
palladacycle 5.1a (0.126 g, 98%) as a yellow solid in 80% de
(5.1a :5.2a ) 90:10 by 1H NMR). Palladacycle 5.1a with
diastereomeric excess 78% de was further purified by flash
chromatography over silica eluting with EtOAc/hexanes (2:
1
3), to afford complex 5.1a in 94% de, 5.1a :5.2a ) 97:3 (by H
NMR): mp 155-158 °C dec (EtOAc/hexanes, 2:3); Rf ) 0.42
(EtOAc/hexanes, 1:1); [R]D -80.3 (c 0.40, CH2Cl2).
An a lytica l d a ta for 5.1a a s a 97:3 m ixtu r e of d ia ster -
1
eom er s: H NMR (500 MHz, CDCl3) δ 8.14 (t, J ) 8.9 Hz, 2
H), 7.87 (t, J ) 8.9 Hz, 2 H), 7.61 (t, J ) 8.7 Hz, 2 H), 7.53 (t,
J ) 8.9 Hz, 2 H), 7.48 (dd, J ) 7.1 Hz, 1.6 Hz, 1 H), 7.43 (t, J
) 7.9 Hz, 3 H), 7.36 (dd, J ) 14.2 Hz, 7.1 Hz, 4 H), 7.34-7.25
(m, 4 H), 6.87-6.81 (m, 2 H), 6.45 (td, J ) 7.9 Hz, 3.3 Hz, 1
H), 6.11-6.07 (m, 1 H), 5.35 (dd, J ) 10.6 Hz, 8.1 Hz, 0.97 H),
5.22 (dd, J ) 10.6 Hz, 8.1 Hz, 0.03 H), 4.07 (dq, J ) 7.0 Hz,
3.6 Hz, 1 H), 3.99-3.94 (m, 1 H), 3.81 (dq, J ) 7.1 Hz, 3.6 Hz,
1 H), 3.78-3.72 (m, 1 H), 3.19 (td, J ) 13.3 Hz, 3.3 Hz, 1 H),
2.77 (ddd, J ) 13.7 Hz, 11.2 Hz, 4.7 Hz, 1 H), 2.20 (t br, J )
5.0 Hz, 2 H), 1.21 (s, 3 H), 1.00 (t, J ) 7.1 Hz, 3 H), 0.94 (s, 3
H); 13C NMR (125 MHz, CDCl3) δ 176.1, 174.0 (t, J (13C-31P)
) 4.8 Hz), 147.6 (dd, J (13C-31P) ) 106.2 Hz, 10.1 Hz), 140.3
(dd, J (13C-31P) ) 10.1 Hz, 2.9 Hz), 136.2 (dd J (13C-31P) ) 36.3
Hz, 2.9 Hz), 135.6 (d, J (13C-31P) ) 14.6 H), 134.1 (d, J (13C-
31P) ) 13.2 Hz), 133.8 (d, J (13C-31P) ) 13.0 Hz), 132.5 (d,
J (13C-31P) ) 1.0 Hz), 132.2 (d, J (13C-31P) ) 11.0 Hz), 131.1
(d, J (13C-31P) ) 1.4 Hz), 131.0 (d, J (13C-31P) ) 2.0 Hz), 130.8,
130.6 (t, J (13C-31P) ) 2.4 Hz), 130.5, 130.2, 130.1 (d, J (13C-
31P) ) 1.8 Hz), 128.6 (dd, J (13C-31P) ) 10.1 Hz, 1.3 Hz), 128.5
(d, J (13C-31P) ) 7.1 Hz), 128.4 (d, J (13C-31P) ) 6.4 Hz), 126.1,
117.7 (dd, J (13C-31P) ) 8.6 Hz, 4.2 Hz), 109.1 (d, J (13C-31P)
) 2.3 Hz), 107.9, 97.1 (dd, J (13C-31P) ) 85.4 Hz, 5.9 Hz), 78.1
(dd, J (13C-31P) ) 14.9 Hz, 7.7 Hz), 76.7 (d, J (13C-31P) ) 10.3
Hz), 59.0, 31.1 (dd, J (13C-31P) ) 21.4 Hz, 5.5 Hz), 29.9 (d,
J (13C-31P) ) 17.6 Hz), 26.7, 26.4, 14.5, only signals for the
major diastereomer have been detected, some signals account
for more than one carbon; 31P NMR (162 MHz, CDCl3) δ 12.28
(d, J ) 30.7 Hz, 0.03 P), 10.72 (d, J ) 30.3 Hz, 0.97 P), 7.50
(d, J ) 30.1 Hz, 0.97 P), 3.42 (d, J ) 30.3 Hz, 0.03 P).
An a lytica l d a ta for a m ixtu r e of d ia ster eom er s 5.1a :
5.2a (86:14): IR (KBr, cm-1) 3051 (m), 2981 (m), 2931 (w), 1706
(s), 1240 (s), 745 (s), 696 (s); HRMS (FAB) calcd for C41H43O5P2-
Pd (M + H+), 783.1621 found 783.1618.
(-)-[(R or S)-(N,N-Diet h ylca r b on ylm et h in eoxy-1,2-
p h en ylen e)][(4S,5S)-O-isop r op ylid en e-2,3-d ih yd r oxy-1,4-
bis(d ip h en ylp h osp h in o)bu ta n e]p a lla d iu m (5.1b). To a
solution of iodopalladium complex 4b (0.686 g, 0.732 mmol)
in THF (34 mL) at -78 °C was added a solution of LDA (1.5
M in cyclohexane, 0.53 mL, 0.795 mmol). The mixture was
stirred at -78 °C for 15 min, quenched with 0.1 mL of MeOH,
and filtered through a small plug of basic alumina, eluting
with EtOAc/hexanes (1:1). The solvent was removed under
reduced pressure to afford palladacycle 5.1b (0.542 g, 91%) as
a yellow solid in 54% de, 5.1b:5.2b ) 77:23 (by 1H NMR).
Palladacycle 5.1b with diastereomeric excess 50% de was
further purified by flash chromatography over silica eluting
with EtOAc/hexanes (2:3), to afford complex 5.1b in 94% de,
(+)-[(R)-(Eth oxyca r bon ylm eth in eoxy-1,2-p h en ylen e)]-
[(4S,5S)-O-isop r op ylid en e-2,3-d ih yd r oxy-1,4-bis(d ip h en -
ylp h osp h in o)bu ta n e]p a lla d iu m (5.2a ). To a solution of
iodopalladium complex 4a (0.150 g, 0.165 mmol) in THF (7.5
mL) at -78 °C was added a solution of potassium bis-
(trimethylsilyl)amide (KHMDS) (0.5 M in toluene, 0.43 mL,
0.215 mmol). The mixture was stirred at -78 °C for 2 h,
quenched with 0.1 mL of MeOH, and filtered through a small
plug of basic alumina, eluting with EtOAc. The solvent was
removed under reduced pressure to afford palladacycle 5.2a
(0.121 g, 94%) as a yellow solid in 30% de, 5.1a :5.2a ) 35:65
(by 1H NMR). Palladacycle 5.2a with diastereomeric excess
22% de was further purified by flash column chromatography
over silica eluting with EtOAc/hexanes (2:3), to afford complex
5.2a in 68% de, 5.1a :5.2a ) 16:84 (by 1H NMR): mp 152-155
1
5.1b:5.2b ) 97:3 (by H NMR): mp 143-147 °C dec (EtOAc/
hexanes); Rf ) 0.29 (EtOAc/hexanes, 1:1); [R]D -45.8 (c 0.45,
CH2Cl2).
An a lytica l d a ta for 5.1b a s a 97:3 m ixtu r e of d ia ster -
eom er s: 1H NMR (500 MHz, CDCl3) δ 8.06 (ddd, J ) 10.0 Hz,

Chiral Nonracemic 2H-1-Benzopyran
Organometallics, Vol. 22, No. 14, 2003 2969
8.2 Hz, 2.2 Hz, 2 H), 8.00 (t, J ) 8.6 Hz, 2 H), 7.86 (t, J ) 8.6
Hz, 2 H), 7.62 (t, J ) 8.7 Hz, 2 H), 7.49 (td, J ) 7.3 Hz, 1.5
Hz, 1 H), 7.46 (td, J ) 7.6 Hz, 1.5 Hz, 2 H), 7.39-7.35 (m, 4
H), 7.32 (td, J ) 7.7 Hz, 1.7 Hz, 2 H), 7.28 (td, J ) 7.4 Hz, 1.4
Hz, 1 H), 7.21 (td, J ) 7.8 Hz, 1.7 Hz, 2 H), 6.78 (td, J ) 8.2
Hz, 1.4 Hz, 1 H), 6.68 (ddd, J ) 7.9 Hz, 3.0 Hz, 1.2 Hz, 1 H),
6.65 (tdd, J ) 7.9 Hz, 3.4 Hz, 1.4 Hz, 1 H), 6.11 (tt, J ) 7.4
Hz, 1.5 Hz, 1 H), 5.94 (dd, J ) 8.7 Hz, 6.8 Hz, 0.97 H), 5.69
(dd, J ) 9.9 Hz, 7.3 Hz, 0.03 H), 4.00-3.95 (m, 1 H), 3.66-
3.61 (m, 1 H), 3.61-3.17 (s br, 2 H), 3.14 (td, J ) 13.5 Hz, 2.4
Hz, 1 H), 3.05 (t br, J ) 6.5 Hz, 2 H), 2.55 (ddd, J ) 13.9 Hz,
10.8 Hz, 4.7 Hz, 1 H), 2.33 (tt, J ) 15.1 Hz, 5.1 Hz, 1 H), 2.18-
2.11 (m, 1 H), 1.18 (s, 3 H), 1.01 (t, J ) 7.0 Hz, 6 H), 0.90 (s,
3 H); 13C NMR (125 MHz, CDCl3) δ 175.1 (d, J (13C-31P) ) 1.9
Hz), 174.7 (t, J (13C-31P) ) 5.6 Hz), 148.8 (dd, J (13C-31P) )
103.4 Hz, 9.4 Hz), 140.5 (dd, J (13C-31P) ) 10.5 Hz, 2.9 Hz),
136.3 (dd, J (13C-31P) ) 35.3 Hz, 2.9 Hz), 135.0 (d, J (13C-31P)
) 14.0 Hz), 134.2 (d, J (13C-31P) ) 13.5 Hz), 133.2 (d, J (13C-
31P) ) 12.5 Hz), 132.9 (d, J (13C-31P) ) 1.4 Hz), 132.2 (d, J (13C-
31P) ) 11.4 Hz), 131.9 (d, J (13C-31P) ) 1.4 Hz), 131.7 (d, J (13C-
31P) ) 2.4 Hz), 131.4, 131.1, 130.9 (d, J (13C-31P) ) 1.9 Hz),
130.4 (d, J (13C-31P) ) 1.9 Hz), 130.1 (d, J (13C-31P) ) 2.4 Hz),
129.7 (d, J (13C-31P) ) 1.9 Hz), 128.6 (dd, J (13C-31P) ) 11.5
Hz, 10.0 Hz), 128.3 (dd, J (13C-31P) ) 9.4 Hz, 2.6 Hz), 125.7,
117.2 (dd, J (13C-31P) ) 8.2 Hz, 4.2 Hz), 108.6 (d, J (13C-31P)
) 1.9 Hz), 107.7, 104.3 (dd, J (13C-31P) ) 89.2 Hz, 4.3 Hz), 77.9
(dd, J (13C-31P) ) 17.0 Hz, 7.1 Hz), 77.1 (d, J (13C-31P) ) 31.5
Hz), 41.1 (s br, 2 C), 31.7 (dd, J (13C-31P) ) 19.8 Hz, 5.5 Hz),
29.8 (d, J (13C-31P) ) 18.5 Hz), 26.8, 26.4, 13.7 (s br, 2 C), only
signals for the major diastereomer were detected, some signals
account for more than one carbon, broadening of certain
signals is the result of a hindered rotation about the C-N bond
in the amide group; 31P NMR (162 MHz, CDCl3) δ 8.38 (d, J )
31.1 Hz, 1 P), 7.61 (d, J ) 31.2 Hz, 1 P); only signals for the
major diastereomer were detected.
8.2 Hz, 1 H), 3.82-3.77 (m, 1 H), 3.46 (s br 2 H), 3.30-3.21
(m, 2 H), 3.03 (s br, 2 H), 2.67 (td, J ) 14.4 Hz, 4.2 Hz, 1 H),
1.66 (dd, J ) 14.6 Hz, 8.4 Hz, 1 H), 1.27 (s, 3 H), 1.24 (s, 3 H),
1.10 (s br, 6 H); 13C NMR (125 MHz, CDCl3) δ 175.5 (d, J (13C-
31P) ) 1.4 Hz), 174.9 (t, J (13C-31P) ) 5.7 Hz), 148.9, 141.0 (dd,
J (13C-31P) ) 10.7 Hz, 2.6 Hz), 136.7 (dd, J (13C-31P) ) 38.6
Hz, 3.8 Hz), 135.3 (d, J (13C-31P) ) 13.4 Hz), 135.0 (t, J (13C-
31P) ) 1.9 Hz), 133.8 (d, J (13C-31P) ) 13.5 Hz), 133.3 (dd,
J (13C-31P) ) 32.0 Hz, 1.9 Hz), 133.1 (d, J (13C-31P) ) 13.0 Hz),
131.6 (d, J (13C-31P) ) 10.0 Hz), 130.9 (d, J (13C-31P) ) 1.9 Hz),
130.5 (d, J (13C-31P) ) 1.4 Hz), 130.2 (d, J (13C-31P) ) 2.4 Hz),
130.0, 129.7, 128.8 (d, J (13C-31P) ) 9.8 Hz), 128.7 (d, J (13C-
31P) ) 1.9 Hz), 128.3, 128.2 (d, J (13C-31P) ) 2.0 Hz), 127.9 (d,
J (13C-31P) ) 9.5 Hz), 125.7, 117.4 (dd, J (13C-31P) ) 8.6 Hz),
108.6, 108.1, 104.3 (dd, J (13C-31P) ) 92.0 Hz, 4.9 Hz), 79.3
(dd, J (13C-31P) ) 9.5 Hz, 4.3 Hz), 76.4 (dd, J (13C-31P) ) 17.6
Hz, 2.9 Hz), 41.1 (s br, 2 C), 33.3 (dd, J (13C-31P) ) 24.1 Hz,
5.5 Hz), 26.9, 26.8, 26.1 (d, J (13C-31P) ) 15.1 Hz), 13.7 (s, br,
2 C), only signals for the major diastereomer were detected,
several signals account for more than one carbon, broadening
of certain signals is the result of a hindered rotation about
the C-N bond in the amide group; 31P NMR (162 MHz, CDCl3)
δ 8.76 (d, J ) 30.9 Hz, 1 P), 3.52 (d, J ) 30.8 Hz, 1 P); only
the signals for the major diastereomer were detected.
An a lytica l d a ta for a m ixtu r e of d ia ster eom er s 5.1b:
5.2b (69:31): IR (KBr, cm-1) 3051 (m), 2981 (m), 2930 (m),
1582 (m), 1223 (m), 743 (s), 696 (s); HRMS (FAB) calcd for
C
43H48NO4P2Pd (M + H+), 810.2093, found 810.2119.
(+)-[(S)-(Eth oxyca r bon ylm eth in eoxy-1,2-p h en ylen e)]-
[(2S ,4S )-2,4-b is (d ip h e n y lp h o s p h in o )p e n t a n e ]p a lla -
d iu m (5.1c). To a solution of iodopalladium complex 4c (0.150
g, 0.176 mmol) in THF (7.5 mL) at -78 °C was added a solution
of t-BuOK (1.0 M in THF, 0.20 mL, 0.200 mmol). The mixture
was stirred at -78 °C for 15 min and filtered through a small
plug of basic alumina eluting with EtOAc. The solvent was
removed under reduced pressure to afford palladacycle 5.1c
(0.126 g, 99%) as an orange solid in 74% de, 5.1c:5.2c ) 87:13
(by 1H NMR); Rf ) 0.32 (EtOAc/hexanes, 2:3); [R]D +1.1 (c 0.55,
CH2Cl2).
(+)-[(R or S)-(N,N-Diet h ylca r b on ylm et h in eoxy-1,2-
p h en ylen e)][(4S,5S)-O-isop r op ylid en e-2,3-d ih yd r oxy-1,4-
bis(d ip h en ylp h osp h in o)bu ta n e]p a lla d iu m (5.2b). To a
solution of iodopalladium complex 4b (0.151 g, 0.160 mmol)
in THF (7.5 mL) at room temperature was added a solution of
t-BuOK (1.0 M in THF, 0.18 mL, 0.180 mmol). The mixture
was stirred at room temperature for 15 min and filtered
through a small plug of basic alumina eluting with EtOAc/
hexanes (1:1). The solvent was removed under reduced pres-
sure to afford palladacycle 5.2b (0.092 g, 71%) as a yellow solid
in 52% de (5.1b:5.2b ) 24:76 by 1H NMR). In a subsequent
step, a solution of palladacycle 5.2b (0.031 g, 0.038 mmol) with
44% de (5.1b:5.2b ) 28:72 by 1H NMR) in THF (2.5 mL) at
room temperature was resubjected to the closing conditions
by adding a solution of t-BuOK (1.0 M in THF, 0.042 mL, 0.042
mmol). The mixture was stirred at room temperature for 3 h
and filtered through a small plug of basic alumina eluting with
EtOAc/hexanes (1:1). The solvent was removed under reduced
pressure to afford palladacycle 5.2b (0.019 g, 61%) in 74% de,
An a lytica l d a ta for 5.1c a s a 87:13 m ixtu r e of d ia ster -
eom er s: 1H NMR (500 MHz, CDCl3) δ 8.05-8.02 (m, 0.26 H),
7.84 (t, J ) 6.6 Hz, 1.74 H), 7.71 (t, J ) 8.6 Hz, 0.26 H), 7.67-
7.62 (m, 3.48 H), 7.60 (t, J ) 8.8 Hz, 0.26 H), 7.53 (td, J ) 8.6
Hz, 1.5 Hz, 3.26 H), 7.46-7.39 (m, 3 H), 7.38-7.34 (m, 2 H),
7.33-7.30 (m, 1.74 H), 7.28-7.25 (m, 2 H), 7.11 (td, J ) 7.7
Hz, 1.4 Hz, 2 H), 6.85-6.84 (m, 1.74 H), 6.79-6.77 (m, 0.26
H), 6.51 (td, J ) 7.9 Hz, 3.3 Hz, 0.87 H), 6.50 (td, J ) 7.9 Hz,
3.6 Hz, 0.13 H), 6.21-6.15 (m, 0.87 H), 6.12-6.09 (m, 0.13 H),
5.50 (t, J ) 8.7 Hz, 0.87 H), 5.17 (t, J ) 8.5 Hz, 0.13 H), 3.92
(dq, J ) 7.0 Hz, 3.6 Hz, 1 H), 3.69 (dq, J ) 7.1 Hz, 3.6 Hz,
0.87 H), 2.91-2.87 (m, 0.13 H), 2.84-2.78 (m, 0.87 H), 2.77-
2.68 (m, 1 H), 2.08-1.92 (m, 1 H), 1.91-1.78 (m, 1 H), 1.73-
1.66 (m, 0.13 H), 1.91 (dd, J ) 11.0 Hz, 7.0 Hz, 2.61 H), 1.13-
1.07 (m, 3 H), 0.93 (t, J ) 7.1 Hz, 2.61 H), 0.92-0.88 (m, 0.39
H), 0.63 (t, J ) 7.1 Hz, 0.39 H); 13C NMR (125 MHz, CDCl3) δ
176.2, 174.5 (t, J ) 4.3 Hz), 148.8 (dd, J (13C-31P) ) 103.6 Hz,
7.7 Hz), 139.9 (dd, J (13C-31P) ) 9.5 Hz, 2.4 Hz), [137.0 (d,
J (13C-31P) ) 14.2 Hz)], 135.8 (d, J (13C-31P) ) 12.0 Hz), [134.9
(d, J (13C-31P) ) 11.9 Hz)], 134.4 (d, J (13C-31P) ) 12.6 Hz),
[134.3 (d, J (13C-31P) ) 12.7 Hz)], 134.0 (d, J (13C-31P) ) 11.8
Hz), 133.9 (d, J (13C-31P) ) 10.2 Hz), [132.1 (d, J (13C-31P) )
9.2 Hz)], 131.2 (d, J (13C-31P) ) 1.4 Hz), 131.2, 131.1 (dd,
J (13C-31P) ) 6.2 Hz, 2.4 Hz), 130.9, [130.7 (d, J (13C-31P) )
1.9 Hz)], 130.6 (d, J (13C-31P) ) 1.9 Hz), 130.4, 130.3 (dd,
J (13C-31P) ) 13.4 Hz, 2.0 Hz), 130.2 (d, J (13C-31P) ) 2.1 Hz),
130.1 (d, J (13C-31P) ) 2.1 Hz), 129.5 (d, J (13C-31P) ) 1.9 Hz),
[129.1 (d, J (13C-31P) ) 9.5 Hz)], 128.7 (d, J (13C-31P) ) 9.3 Hz),
[128.3 (d, J (13C-31P) ) 8.8 Hz)], 128.2 (d, J (13C-31P) ) 9.6 Hz),
127.9 (d, J (13C-31P) ) 9.0 Hz), [127.8 (d, J (13C-31P) ) 9.7 Hz)],
127.6 (d, J (13C-31P) ) 9.5 Hz), [127.5 (d, J (13C-31P) ) 10.2
Hz)], 125.7, [125.6], 117.5 (dd, J (13C-31P) ) 8.3 Hz, 4.4 Hz),
1
5.1b:5.2b ) 13:87 (by H NMR).
Palladacycle 5.1b with diastereomeric excess 50% de was
further purified by flash chromatography over silica eluting
with EtOAc/hexanes (2:3) to afford a fraction containing
1
complex 5.2b in 94% de, 5.1b: 5.2b ) 3:97 (by H NMR): mp
144-147 °C dec (EtOAc/hexanes, 2:3); Rf ) 0.37 (EtOAc/
hexanes, 1:1); [R]D +31.0 (c 0.51, CH2Cl2).
An a lytica l d a ta for 5.2b a s a 3:97 m ixtu r e of d ia ster -
1
eom er s: H NMR (500 MHz, CDCl3) δ 8.05 (t, J ) 8.5 Hz, 2
H), 7.83 (t, J ) 8.8 Hz, 2 H), 7.56 (t, J ) 7.3 Hz, 2 H), 7.51 (td,
J ) 8.2 Hz, 1.6 Hz, 2 H), 7.43 (ddd, J ) 9.9 Hz, 7.7 Hz, 2.2 Hz,
2 H), 7.33 (td, J ) 7.2 Hz, 1.5 Hz, 1 H), 7.28 (td, J ) 7.9 Hz,
1.4 Hz, 6 H), 7.16 (td, J ) 7.4 Hz, 1 H), 6.86 (td, J ) 7.7 Hz,
1.4 Hz, 2 H), 6.81 (td, J ) 7.5 Hz, 1.3 Hz, 1 H), 6.72 (td, J )
7.9 Hz, 2.8 Hz, 1 H), 6.67 (ddd, J ) 7.8 Hz, 3.1 Hz, 1.0 Hz, 1
H), 6.18 (t, J ) 7.4 Hz, 1 H), 5.93 (dd, J ) 8.6 Hz, 6.8 Hz, 0.03
H) 5.70 (dd, J ) 9.9 Hz, 7.3 Hz, 0.97 H), 4.23 (dt, J ) 13.2 Hz,

2970 Organometallics, Vol. 22, No. 14, 2003
Portscheller et al.
109.0 (d, J (13C-31P) ) 2.5 Hz), [108.6 (d, J (13C-31P) ) 2.5 Hz)],
95.9 (dd, J (13C-31P) ) 84.4 Hz, 5.4 Hz), 58.5, [58.2], 35.4 (t,
J (13C-31P) ) 6.3 Hz), 29.7, [29.1 (dd, J (13C-31P) ) 22.2 Hz,
5.0 Hz)], 28.1 (dd, J (13C-31P) ) 21.9 Hz, 6.0 Hz), 25.6 (dd,
J (13C-31P) ) 16.6 Hz, 1.8 Hz), [19.1 (d, J (13C-31P) ) 7.5 Hz)],
17.9 (d, J (13C-31P) ) 2.5 Hz), [16.9 (d, J (13C-31P) ) 4.9 Hz)],
16.7 (d, J (13C-31P) ) 3.2 Hz), 14.6, [14.0], signals for the minor
diastereomer are given in brackets, several signals account
for more than one carbon; 31P NMR (162 MHz, CDCl3) δ 22.34
(d, J ) 43.1 Hz, 0.13 P), 21.74 (d, J ) 45.8 Hz, 0.87 P), 16.65
(d, J ) 43.0 Hz, 0.13 P), 14.34 (d, J ) 46.0 Hz, 0.87 P).
(+)-[(R)-(Eth oxyca r bon ylm eth in eoxy-1,2-p h en ylen e)]-
[(2S ,4S )-2,4-b is (d ip h e n y lp h o s p h in o )p e n t a n e ]p a lla -
d iu m (5.2c). To a solution of iodopalladium complex 4c (0.148
g, 0.174 mmol) in THF (7.5 mL) at -78 °C was added a solution
of LDA (1.5 M in cyclohexane, 0.13 mL, 0.195 mmol). The
mixture was stirred at -78 °C for 15 min, quenched with 0.1
mL of MeOH, and filtered through a small plug of basic
alumina eluting with EtOAc. The solvent was removed under
reduced pressure to afford palladacycle 5.2c (0.125 g, 99%) as
an orange solid in 76% de, 5.1c:5.2c ) 12:88 (by 1H NMR).
Palladacycle 5.2c with diastereomeric excess 72% de, 5.1c:5.2c
afford complex (-)-7 (0.021 g, 74%) as a yellow solid in 68.2%
ee, 5.1a :5.2a ) 15.87:84.12 (by HPLC): [R]D -78.7 (c 0.40,
CH2Cl2).
(+)-[(R)-Eth oxyca r bon ylm eth in eoxy-1,2-p h en ylen e)]-
[1,2-b is(d ip h en ylp h osp h in o)et h a n e]p a lla d iu m [(+)-7].
Complex 5.2a (0.061 g, 0.077 mmol) with 30% de, 5.1a :5.2a )
35:65 (by 1H NMR), and dppe (0.035 g, 0.087 mmol) were
treated according to the general procedure described above to
afford complex (+)-7 (0.052 g, 98%) as a white solid in 26.5%
ee, 5.1a :5.2a ) 36.73:63.26 (by HPLC): [R]D +33.5 (c 0.54,
CH2Cl2).
(+)-[(R)-Eth oxyca r bon ylm eth in eoxy-1,2-p h en ylen e)]-
[1,2-bis(d ip h en ylp h osp h in o)eth a n e]p a lla d iu m [(+)-7]. To
a solution of 5.2c (0.050 g, 0.069 mmol) with 62% de, 5.1c:
1
5.2c ) 19:81 (by H NMR) in methylene chloride (5 mL), was
added dppe (0.095 g, 0.239 mmol) by a stepwise addition of a
single equivalent over a period of 4 days. Solvents were
removed under reduced pressure, and the resulting solid was
triturated with ether to afford the crude product as a yellow
solid. The crude product was purified by filtration through a
short plug of silica eluting with EtOAc/hexanes (2:1) to afford
complex (+)-7 (0.263 g, 56%) as a pale yellow solid in 62.1%
ee, 5.1c:5.2c ) 18.95:81.05 (by HPLC): [R]D +71.7 (c 0.52,
CH2Cl2).
1
) 14:86 (by H NMR), was crystallized by a slow diffusion of
hexane into a methylene chloride solution of the palladacycle
to afford palladacycle 5.2c as a pure diastereomer: mp 212-
214 °C dec (CH2Cl2/hexanes); Rf ) 0.38 (EtOAc/hexanes, 2:3);
[R]D +99.4 (c 0.18, CH2Cl2).
An a lytica l d a ta for p a lla d a cycle (()-7: mp 213-214 °C
dec (ether); Rf ) 0.70 (EtOAc/hexanes, 1:1); 1H NMR (500 MHz,
CDCl3) δ 7.94-7.90 (m, 2 H), 7.78-7.69 (m, 6 H), 7.50-7.38
(m, 12 H), 6.95 (ddd, J ) 7.9 Hz, 3.4 Hz, 1.3 Hz, 1 H), 6.91
(dd, J ) 7.0 Hz, 1.3 Hz, 1 H), 6.89-6.85 (m, 1 H), 6.31 (dd, J
) 9.9 Hz, 3.8 Hz, 1 H), 6.26 (tt, J ) 7.2 Hz, 1.6 Hz, 1 H), 3.86
(dq, J ) 7.1 Hz, 3.4 Hz, 1 H), 3.22 (dq, J ) 7.1 Hz, 3.6 Hz, 1
H), 2.64-2.48 (m, 1 H), 2.38-2.25 (m, 1 H), 2.06-1.99 (m, 1
H), 1.85-1.74 (m, 1 H), 0.76 (t, J ) 7.1 Hz, 3 H); 13C NMR
(125 MHz, CDCl3) δ 177.4 (d, J (13C-31P) ) 3.0 Hz), 175.4 (t,
J (13C-31P) ) 4.6 Hz), 140.4 (dd, J (13C-31P) ) 10.9 Hz, 2.4 Hz),
134.7 (dd, J (13C-31P) ) 13.6 Hz, 3.0 Hz), 134.0 (t, J (13C-31P)
) 5.4 Hz), 133.5 (d, J (13C-31P) ) 12.9 Hz), 132.6 (d, J (13C-
31P) ) 11.5 Hz), 132.0, 131.4, 131.3 (d, J (13C-31P) ) 7.9 Hz),
131.1 (d, J (13C-31P) ) 9.9 Hz), 131.0, 130.5 (dd, J (13C-31P) )
69.1 Hz, 2.4 Hz), 129.4, 129.0 (dd, J (13C-31P) ) 13.4 Hz, 10.0
Hz), 128.8 (d, J (13C-31P) ) 6.8 Hz), 128.7 (dd, J (13C-31P) )
17.8 Hz, 9.8 Hz), 126.3, 117.9 (dd, J (13C-31P) ) 8.1 Hz, 4.9
Hz), 109.4 (d, J (13C-31P) ) 2.0 Hz), 96.8 (dd, J (13C-31P) ) 85.6
Hz, 5.3 Hz), 58.7, 29.7 (dd, J (13C-31P) ) 26.4 Hz, 17.0 Hz),
28.9 (dd, J (13C-31P) ) 26.7 Hz, 18.2 Hz), 14.1, several signals
account for more than one carbon; 31P NMR (202 MHz, CDCl3)
δ 44.23 (d, J ) 19.3 Hz, 1 P), 41.39 (d, J ) 19.0 Hz, 1 P); IR
(KBr, cm-1): 3049 (w), 2980 (w), 1692 (s), 1434 (m), 1176 (m),
747 (w), 699 (w); HRMS (FAB) calcd for C36H35O3P2Pd (M +
H+), 683.1096, found 683.1073. Anal. Calcd for C36H34O3-
P2Pd: C, 63.30; H, 5.02. Found: C, 63.02; H, 5.13.
An a lytica l d a ta for a p u r e d ia ster eom er 5.2c: 1H NMR
(400 MHz, CDCl3) δ 8.06-8.01 (m, 2 H), 7.71 (t, J ) 8.6 Hz, 2
H), 7.59 (t, J ) 8.6 Hz, 2 H), 7.56-7.53 (m, 5 H), 7.45-7.41
(m, 3 H), 7.37-7.35 (m, 2 H), 7.26 (t, J ) 7.5 Hz, 2 H), 7.13
(td, J ) 7.3 Hz, 1.5 Hz, 2 H), 6.79-6.77 (m, 2 H), 6.50 (td, J )
7.9 Hz, 3.3 Hz, 1 H), 6.14-6.07 (m, 1 H), 5.17 (t, J ) 8.5 Hz,
1 H), 3.91 (dq, J ) 7.1 Hz, 3.6 Hz, 1 H), 2.86 (dq, J ) 7.1 Hz,
3.6 Hz, 1 H), 2.81-2.73 (m, 2 H), 1.85-1.72 (m, 1 H), 1.70-
1.62 (m, 1 H), 1.11 (dd, J ) 14.1 Hz, 7.1 Hz, 3 H), 0.90 (dd, J
) 9.7 Hz, 7.0 Hz, 3 H) 0.62 (t, J ) 7.1 Hz, 3 H); 13C NMR (125
MHz, CDCl3) δ 176.7, 140.9 (dd, J (13C-31P) ) 9.3 Hz, 2.4 Hz),
137.0 (d, J (13C-31P) ) 13.8 Hz), 134.7 (dd, J (13C-31P) ) 70.0
Hz, 12.2 Hz), 132.1 (d, J (13C-31P) ) 9.4 Hz), 130.7 (dd, J (13C-
31P) ) 16.0 Hz, 2.1 Hz), 130.5, 130.2 (d, J (13C-31P) ) 1.9 Hz),
129.1 (d, J (13C-31P) ) 9.5 Hz), 128.3 (d, J (13C-31P) ) 8.8 Hz),
127.7 (dd, J (13C-31P) ) 36.5 Hz, 10.0 Hz), 127.1, 126.8, 125.6,
117.8 (dd, J (13C-31P) ) 8.3 Hz, 4.1 Hz), 108.7 (d, J (13C-31P)
) 2.4 Hz), 98.5 (dd, J (13C-31P) ) 85.3 Hz, 5.7 Hz), 58.2, 35.6
(d, J (13C-31P) ) 5.2 Hz), 29.0 (dd, J (13C-31P) ) 21.7 Hz, 5.5
Hz), 25.8 (dd, J (13C-31P) ) 18.8 Hz, 5.0 Hz), 19.1 (d, J (13C-
31P) ) 7.5 Hz), 16.9 (d, J (13C-31P) ) 4.9 Hz), 14.0, several
signals account for more than one carbon; 31P NMR (202 MHz,
CDCl3) δ 22.32 (d, J ) 43.0 Hz, 1 P), 16.65 (d, J ) 42.7 Hz, 1
P).
(-)-2-N,N-Dieth ylca r bon yl-3,4-bis(m eth oxyca r bon yl)-
2H-1-ben zop yr a n [(-)-8].18 To a solution of palladacycle 5.1b
with 96% de, 5.1b:5.2b ) 98:2 (by 1H NMR) (0.146 g, 0.180
mmol) in methylene chloride (5.5 mL), was added dimethyl
acetylenedicarboxylate (0.048 mL, 0.055 g, 0.390 mmol). The
reaction mixture was stirred for 6 h at 100 °C and subse-
quently for 16 h at room temperature in a 25 mL sealed glass
tube. The crude reaction mixture was purified by flash
chromatography over silica eluting with EtOAc/hexanes (1:2)
to afford pure 2H-1-benzopyran (-)-8 (0.039 g, 62%) as a light
yellow oil in 88.4% ee (by HPLC): [R]D -13.4 (c 1.36 CH2Cl2);
Rf ) 0.56 (EtOAc/hexanes, 1:3); 1H NMR (400 MHz, CDCl3) δ
7.24 (td, J ) 7.8 Hz, 1.4 Hz, 1 H), 7.08 (dd, J ) 7.8 Hz, 1.5 Hz,
1 H), 6.93 (td, J ) 7.6 Hz, 1.0 Hz, 1 H), 6.84 (d, J ) 8.2 Hz, 1
H), 5.95 (s, 1 H), 3.96 (s, 3 H), 3.77 (s, 3 H), 3.70-3.55 (m, 2
H), 3.36-3.23 (m, 2 H), 1.33 (t, J ) 7.1 Hz, 3 H), 1.06 (t, J )
7.1 Hz, 3 H).
An a lytica l d a ta for a m ixtu r e of d ia ster eom er s 5.1c:
5.2c (87:13): IR (KBr, cm-1) 3050 (m), 2975 (m), 2927 (m), 1701
(s), 1480 (m), 1157 (s), 746 (s), 697 (s); HRMS (FAB) calcd for
C39H41O3P2Pd (M + H+), 725.1566, found 725.1541. Anal. Calcd
for C39H40O3P2Pd: C, 64.60; H, 5.56. Found: C, 64.21; H, 5.88.
Gen er a l P r oced u r e for P r ep a r a tion of (+)-[(R)-Eth -
oxycar bon ylm eth in eoxy-1,2-ph en ylen e)][1,2-bis(diph en yl-
p h osp h in o)eth a n e]p a lla d iu m (+)-7 a n d (-)-[(S)-Eth oxy-
carbonylmethineoxy-1,2-phenylene)][1,2-bis(diphenylphos-
p h in o)eth a n e]p a lla d iu m (-)-7. Solutions of complexes 5.1a
or 5.2a (1.0 mmol) and dppe (1.1 mmol) in methylene chloride
(78 mL) were stirred for 16 h at room temperature under
argon. The crude reaction mixtures were purified by flash
chromatography over silica eluting with EtOAc/hexanes (1:1)
to afford pure palladacycles (+)-7 or (-)-7 as white solids.
(-)-[(S)-Eth oxyca r bon ylm eth in eoxy-1,2-p h en ylen e)]-
[1,2-b is(d ip h en ylp h osp h in o)et h a n e]p a lla d iu m [(-)-7].
Complex 5.1a (0.032 g, 0.407 mmol) with 66% de, 5.1a :5.2a )
83:17 (by 1H NMR), and dppe (0.036 g, 0.091 mmol) were
treated according to the general procedure described above to
Ack n ow led gm en t is made to the donors of the
Petroleum Research Fund, administered by the ACS,

Chiral Nonracemic 2H-1-Benzopyran
Organometallics, Vol. 22, No. 14, 2003 2971
chiral-phase chromatographic analyses. Includes HPLC chro-
matograms of (()-7, (+)-7, (-)-7, (()-8, and (-)-8 and
photocopies of 1H and 13C NMR spectra of complexes 4a -c,
5a -c, and 7. This material is available free of charge via the
Internet at http://pubs.acs.org.
to Kansas NSF EPSCoR, and to Kansas Technology
Enterprise Corporation for support of this research. We
thank our colleague Dr. Douglas R. Powell for his
assistance with X-ray crystallography.
Su p p or tin g In for m a tion Ava ila ble: Descriptions of the
X-ray crystallographic study on palladacycle 5.2c and experi-
mental procedures for the experiments in Table 2 and for the
OM030207B