Influence of steric symmetry and electronic dissymmetry on the enantioselectivity in palladium-catalyzed allylic substitutions

Article abstract of DOI:10.1021/jo026889e

Chiral P,N-ligands with pseudo-C₂ and pseudo-C_s symmetry based on chiral pyrrolidine and phospholane rings or on dinaphthatodihydroazepino and dinaphthatodihydrophosphepino moieties were prepared and assessed in the palladium-catalyz

Full text of DOI:10.1021/jo026889e

In flu en ce of Ster ic Sym m etr y a n d Electr on ic Dissym m etr y on th e
En a n tioselectivity in P a lla d iu m -Ca ta lyzed Allylic Su bstitu tion s
J ean-Luc Vasse, Robert Stranne, Raivis Zalubovskis, Carole Gayet, and Christina Moberg*
Department of Chemistry, Organic Chemistry, Royal Institute of Technology,
SE-100 44 Stockholm, Sweden
kimo@kth.se
Received December 20, 2002
Chiral P,N-ligands with pseudo-C2 and pseudo-Cs symmetry based on chiral pyrrolidine and
phospholane rings or on dinaphthatodihydroazepino and dinaphthatodihydrophosphepino moieties
were prepared and assessed in the palladium-catalyzed allylic substitutions of allylic acetates.
Higher selectivity was achieved with pseudo-C2-symmetric ligands based on the binaphthyl skeleton
than with the analogous C2-symmetric P,P- and N,N-analogues. Pseudo-C2-type ligands had
properties superior to those of pseudo-meso-type ligands when 1,3-diphenyl-2-propenyl acetate was
used as a substrate, whereas the reverse situation was found for 3-cyclohexenyl acetate. Chirally
flexible ligands, prepared by substitution of one of the rigid binaphthyl skeletons for a flexible
biphenyl system, were found to induce chirality to the same extent as a 1:1 mixture of the rigid
ligands.
In tr od u ction
Control of the steric and electronic properties of chiral
ligands employed in asymmetric metal catalysis is a
requirement for efficient transfer of chirality, and factors
responsible for those properties thus need to be consid-
ered in ligand design and preparation.1 Ligands with C2
symmetry have been extensively employed in asymmetric
catalysis.2 The success of such ligands originates in a
reduction of the number of catalyst-substrate interac-
tions and, as a consequence, the number of competing
reaction pathways. There is, however, no fundamental
rule stating that ligands with 2-fold rotational symmetry
must always exert enantiocontrol superior to those
lacking elements of symmetry. In bidentate C2-symmetric
ligands, the two donor atoms have, by definition, to be
identical, and therefore, the enantiodiscrimination in
asymmetric reactions involving such ligands relies solely
on the steric properties of the enantiocontrolling catalytic
intermediates. Introduction of electronic dissymmetry
destroys the rotational symmetry, and in C2-symmetric
ligands differences in trans influence and π-back-dona-
tion of the donor atoms can thus not be exploited.
F IGURE 1. Ligands with C2 or pseudo-C2 symmetry (A) and
Cs or pseudo-Cs symmetry (B).
ing a reduced number, with symmetrical substrates often
one single, of diastereoisomeric π-allyl palladium com-
plexes, whereas with asymmetric ligands, electronic dis-
symmetry may contribute to control nucleophilic attack.
We wished to exploit the behavior of “sterically sym-
metric” ligands (possessing a mirror plane or a 2-fold
rotational axis) which are being electronically desymme-
trized. Systematic studies have previously been made of
the effect of electronic properties of ligands on the
enantioselectivity,4 but the ligands studied have at the
same time usually been “sterically dissymmetric”, con-
taining differently substituted donor atoms. To our
knowledge, the effect of pure electronic dissymmetry has
previously been studied in only a few cases. A pseudo-
C2-symmetric ligand was shown to afford higher enan-
tioselectivity than truly C2-symmetric analogues,5 and a
“pseudo-meso” ligand with the asymmetry in the ligand
backbone was found to induce chirality in the catalytic
process.6
The palladium-catalyzed substitution of symmetrical
allylic acetates and carbonates constitutes one example
of reactions where C2- as well as C1-symmetric ligands
have been shown to result in high enantioselectivity.3
Nucleophilic attack occurs on an intermediate π-allyl
palladium complex outside the coordination sphere of the
metal and is directed via ligand-substrate interactions.
Ligands with C2 symmetry have the advantage of provid-
Two types of structures, A and B (Figure 1), fulfilling
our needs may be distinguished. The arrangement A has
(3) (a) Frost, C. G.; Howarth, J .; Williams, J . M. J . Tetrahedron:
Asymmetry 1992, 3, 1089-1122. (b) Trost, B. M.; Van Vranken, D. L.
Chem. Rev. 1996, 96, 395-422. (c) Trost, B. M.; Lee, C. In Catalytic
Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley: New York, 2000;
pp 593-649.
(1) (a) Ojima, I. Catalytic Asymmetric Synthesis; VCH Publishers:
New York, 1993. (b) Noyori, R. Asymmetric Catalysis in Organic
Synthesis; J ohn Wiley & Sons: New York, 1994. (c) Seyden-Penne, J .
Chiral Auxiliaries and Ligands in Asymmetric Synthesis; J ohn Wiley
& Sons: New York, 1995. (d) J acobsen, E. N.; Pfaltz, A.; Yamamoto,
H. Comprehensive Asymmetric Catalysis; Springer: Berlin, 1999; Vols.
1-3.
(4) Saitoh, A.; Misawa, M.; Morimoto, T. Synlett 1999, 483-485.
(5) (a) Robert, F.; Gaillard, N.; Sinou, D. J . Mol. Catal. A 1999, 144,
473-476. (b) Robert, F.; Delbecq, F.; Nguefack, C.; Sinou, D. Eur. J .
Inorg. Chem. 2000, 351-358.
(2) Whitesell, J . K. Chem. Rev. 1989, 89, 1581-1590.
(6) Trost, B. M. Acc. Chem. Res. 1996, 29, 355-364.
10.1021/jo026889e CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/27/2003
3258
J . Org. Chem. 2003, 68, 3258-3270

Enantioselectivity in Palladium-Catalyzed Allylic Substitutions
CHART 1
C2 symmetry when L1 is equal to L2 and C1 symmetry
when L1 is different from L2, whereas B is achiral (meso
compound) when L1 is equal to L2 but asymmetric when
L1 is different from L2. In a preliminary study, we
reported results from initial investigations of the two
types of ligands where we demonstrated that a ligand of
type B exhibited higher reactivity and resulted in higher
enantioselectivity in reactions of a substrate reacting via
an anti-anti π-allyl palladium complex, while those with
structure A were preferred for syn-syn complexes.7 We
now report on further studies of the use of ligands with
different steric and electronic symmetry properties in
palladium catalyzed allylation reactions.
connected with different linkers to allow for structural
diversity and variation of the steric and geometric
parameters (ligands 1-15, Chart 1).
For the construction of 1-substituted trans-dialkyl-
phospholanes, two synthetic strategies have been de-
scribed. One involves reaction of a lithio trans-2,5-
dialkylphospholane, obtained from a trans-2,5-dialkyl-
1-phenylphospholane via P-aryl bond cleavage with
lithium11 or from lithium bis(trimethylsilyl)phosphide
and a cyclic sulfate,12 with a suitable electrophile, whereas
the key step in the second strategy is the reaction of the
cyclic sulfate of an (R*,R*)-1,4-alkanediol with an ap-
propriate lithiophosphido derivative.13 For the prepara-
tion of the pyrrolidine part of the ligands a variety of
suitable methods are available, including N-alkylation
of a preformed pyrrolidine as well as alkylation of a
primary amine with an electrophile derived from 2,5-
hexanediol.14 The route finally selected for the prepara-
tion of 1 and 2 started with 2-bromoaniline (16), which
was treated with (S,S)-2,5-hexanediol cyclic sulfate (17,
Scheme 1), obtained via Baker’s yeast reduction of
hexane-2,5-dione.15 Bromine lithium exchange of the
resulting pyrrolidine (18, 71%) followed by reaction with
Resu lts
Liga n d Design a n d P r ep a r a tion . Ligands based on
rigid, conformationally restricted scaffolds, which have
proven to exhibit high enantiodiscrimination in catalytic
reactions, were selected for the present study. Trans-2,5-
disubstituted five-membered nitrogen and phosphorus8
heterocycles on one hand and dinaphthatodihydroaze-
pino9 and dinaphthatodihydrophosphepino derivatives10
on the other hand were considered to satisfy our require-
ments and were selected as appropriate chiral motifs for
the construction of suitable N,N-, N,P-, and P,P-ligands.
The two moieties containing the heteroatom donors were
(11) (a) Burk, M. J .; Feaster, J . E.; Harlow, R. L. Tetrahedron:
Asymmetry 1991, 2, 569-592. (b) Morimoto, T.; Ando, N.; Achiwa, K.
Synlett 1996, 1211-1212.
(12) Burk, M. J .; Pizzano, A.; Mart´ın, J . A.; Liable-Sands, L. M.;
Rheingold, A. L. Organometallics 2000, 19, 250-260.
(13) (a) Burk, M. J . J . Am. Chem. Soc. 1991, 113, 8518-8519. (b)
Burk, M. J .; Feaster, J . E.; Nugent, W. A.; Harlow, R. L. J . Am. Chem.
Soc. 1993, 115, 10125-10138.
(7) Stranne, R.; Vasse, J .-L.; Moberg, C. Org. Lett. 2001, 3, 2525-
2528.
(8) Burk, M. J . Acc. Chem. Res. 2000, 33, 363-372.
(9) Bourghida, M.; Widhalm, M. Tetrahedron: Asymmetry 1998, 9,
1073-1083.
(14) Pichon, M.; Figade`re, B. Tetrahedron: Asymmetry 1996, 7, 927-
964.
(10) Guiry, P. J .; McCarthy, M. Tetrahedron 2001, 57, 3809-3844.
(15) Lieser, J . K. Synth. Commun. 1983, 13, 765-767.
J . Org. Chem, Vol. 68, No. 8, 2003 3259

Vasse et al.
SCHEME 1
analogue of 3 was recently prepared via a similar
procedure.17
Ligands 5 and 6,7 based on 4,5-dihydro-3H-dinaphatho-
[1,2-c:2′,1′-e]azepino and 4,5-dihydro-3H-dinaphatho[1,2-
c:2′,1′-e]phosphepino skeletons, were prepared as previ-
ously described via a route analogous to that used for
the preparation of 3 and 4, by reaction of (R)-2,2′-bis-
(bromomethyl)-1,1′-binaphthyl ((R)-24),19 obtained to-
gether with its enantiomer from BINOL via resolution,20
with (2-aminoethyl)phosphonic acid diethyl ester (21)
followed by reduction to the primary phosphine. Protec-
tion with borane followed by alkylation of the protected
phosphine with (R)-24 or (S)-24 gave the desired ligands
as their borane adducts. Attempts to alkylate on phos-
phorus prior to protection, using 24 and a variety of
bases, resulted in lower yields of products. Selective
deprotection at nitrogen gave proligands 5-BH3 and
6-BH3 (59 and 61%, respectively, from 24), which could
be fully deprotected or used directly in the catalytic
reactions.
To enable comparison of the asymmetric ligands with
C2-symmetric analogues, the P,P- and N,N-ligands 7 and
8 were also synthesized. The former ligand (7) was
obtained from reaction of (S)-24 with ammonium phos-
phinate21 (to give 25, 42%), followed by reduction with
phenylsilane22 to give 26,23 isolated as its borane adduct
(43%, Scheme 3). Disubstitution of ethylene glycol dito-
sylate with 26-BH3 resulted in a low yield of product,
and as this route can give access to only one diastereo-
isomer it was not considered useful. Instead, conjugate
addition of 26-BH3 to diethyl vinylphosphonate (27) gave
28-BH3 (83%), which was subjected to LAH reduction
to give 29-BH3 (71%). Treatment of 28-BH3 with an
additional 1 equiv of borane gave the bisborane adduct
of 29, which afforded protected ligand 7 (51%) after
reaction with (S)-24. An alternative procedure affording
7, employing reaction of bis(1,2-dichlorophosphine)ethane
with bis(lithiomethyl)-1,1′-binaphthyl, was also recently
described.24 Ligand 8 was prepared in one step from (R)-
2,2′-bis(bromomethyl)-1,1′-binaphthyl and 1,2-diamino-
ethane according to a published procedure (Scheme 4).25
Meso ligands 9 and 10,25 which were desired in order to
enable comparison of the reactivity of the asymmetric
ligands with that of analogues with different steric
properties, were prepared via treatment of (R)-24 with
29-2BH3 and 31, respectively, the latter obtained by
reacting (S)-24 with a large excess of 1,2-diaminoethane.
To assess the importance of the length and structure
of the tether connecting the coordinating parts of the
ligands, the N,N-ligands 11-13 were prepared via reac-
tion of (R)-2,2′-bis(bromomethyl)-1,1′-binaphthyl with the
SCHEME 2
diethylchlorophosphite yielded a phosphinite, which was
isolated as its borane adduct 19-BH3 (72%). Deprotection
using DABCO16 (to yield 19), subsequent reduction (LAH/
TMSCl), and lithiation of the phosphine (20) obtained
afforded a monolithiophosphide that was reacted with
(S,S)-2,5-hexanediol cyclic sulfate or (R,R)-2,5-hexanediol
cyclic sulfate. A second litiation completed the ring
closure, yielding 1 and 2, respectively (20 and 12% yield
from 19-BH3), isolated as their borane adducts. Com-
pound 1 and its four-membered ring analogue were
recently prepared in low yields by an alternative proce-
dure.17
Ligands 3 and 4, with more electron-rich phosphorus
and nitrogen atoms, were obtained via reaction of (2-
aminoethyl)phosphonic acid diethyl ester (21) with (S,S)-
2,5-hexanediol cyclic sulfate (17) to yield 22 (47%), which
was reduced by LAH18 to the corresponding phosphine
(23). Lithiation and treatment with a (S,S)- or (R,R)-2,5-
hexanediol cyclic sulfate, followed by BH3‚Me2S, afforded
the desired borane protected ligands 3 (17% from 22) and
4 (21% from 22, Scheme 2); 2 equiv of BH3‚Me2S was
required as the first equivalent was trapped by the
electron-rich nitrogen atom. The four-membered ring
(19) (a) Hall, D. M.; Turner, E. E. J . Chem. Soc. 1955, 1242-1251.
(b) Xiao, D.; Zhang, Z.; Zhang, X. Org. Lett. 1999, 1, 1679-1681.
(20) Cai, D.; Hugues, D. L.; Verhoeven, T. R.; Reider, P. L.
Tetrahedron Lett. 1995, 36, 7991-7994.
(21) Boyd, E. A.; Boyd, M. E. K.; Kerrigan, F. Tetrahedron Lett. 1996,
37, 5425-5426.
(22) Soulier, E.; Yaouanc, J .-J .; Laurent, P.; des Abbayes, H.;
Cle´ment, J .-C. Eur. J . Org. Chem. 2000, 3497-3503.
(23) Racemic 26 has previosly been prepared by a route which was
considered less convenient as it involved the use of PH3: Bitterer, F.;
Herd, O.; Ku¨hnel, M.; Stelzer, O.; Weferling, N.; Sheldrick, W. S.; Hahn,
J .; Nagel, S.; Ro¨sch, N. Inorg. Chem. 1998, 37, 6408-6417.
(24) Chi, Y.; Zhang, X. Tetrahedron Lett. 2002, 43, 4849-4852.
(25) (a) Mazaleyrat, J .-P.; Cram, D. J . J . Am. Chem. Soc. 1981, 103,
4585-4586. (b) Mazaleyrat, J .-P. Tetrahedron: Asymmetry 1997, 8,
2709-2721.
(16) Brisset, H.; Gourdel, Y.; Pellon, P.; Le Corre, M. Tetrahedron
Lett. 1993, 34, 4523-4526.
(17) Marinetti, A.; J us, S.; Labrue, F.; Lemarchand, A.; Genet, J .-
P.; Ricard, L. Synthesis 2001, 2095-2104.
(18) Gali, H.; Prabhu, K. R.; Karra, S. R.; Katti, K. V. J . Org. Chem.
2000, 65, 676-680.
3260 J . Org. Chem., Vol. 68, No. 8, 2003

Enantioselectivity in Palladium-Catalyzed Allylic Substitutions
SCHEME 3
SCHEME 5
reduced by LAH to afford 37 and, after protection, 37-
2BH3. Reaction with (S)-22 afforded 14-2BH3, which was
chemoselectively deprotected to the desired compound
14-BH3. Protected ligand 15-BH3 was obtained via an
analogous procedure from 38-2BH3. As expected, in the
1H NMR spectra of 5 and 6, the methylene protons in
the azepino and phosphepino rings gave rise to separate
AB patterns, whereas in 14-BH3 a singlet was observed
from the methylene protons of the nitrogen part of the
ligand, demonstrating that interconversion of the atro-
pisomers, via rotation around the biphenyl axis, is rapid
on the NMR time scale.
SCHEME 4
Allylic Alk yla tion s w ith 1,3-Dip h en yl-2-p r op en yl
Aceta te. Deprotection of the BH3-protected ligands was
achieved either with DABCO prior to the catalytic
reaction or in situ with palladium acetate,27 at the same
time employed as the palladium source for the catalytic
reaction.28 Pseudo-C2-symmetric ligand 1 and pseudo-
meso ligand 2 were employed in the alkylation of rac-
(E)-1,3-diphenyl-2-propenyl acetate (39) with malonate
using palladium acetate as the palladium source in the
presence of bis(trimethylsilyl)acetamide (BSA) and KO-
Ac29 (eq 1). Surprisingly, from both reactions the product
was obtained with 37% ee, but with different absolute
configurations of the major isomer (Table 1, entries 1 and
2). The reason for this might be that the nitrogen atom
is too electron-poor to take part in coordination to the
metal and that the ligand coordinates in a monodentate
(26) (a) Hall, D. M.; Lesslie, M. S.; Turner, E. E. J . Chem. Soc. 1950,
711-713. (b) Williams, D. J .; Macy, P. K.; Hezs, D. R. Org. Prep. Proced.
Int. 1985, 17, 270-274.
appropriate diamine (32-34, Scheme 4). Finally, the
chirally flexible ligands 14 and 15 were prepared by
procedures similar to those applied for the preparation
of 7 and 9, employing 2,2′-bis(bromomethyl)-1,1′-biphe-
nyl26 (35) in place of either binaphthyl derivative (Scheme
5). Thus, treatment of 35 with 21 afforded 36, which was
(27) Riegel, N.; Darcel, C.; Ste´phan, O.; J uge´, S. J . Organomet.
Chem. 1998, 567, 219-233.
(28) Wimmer, P.; Widhalm M. Tetrahedron: Asymmetry 1995, 6,
657-660.
(29) Trost, B. M.; Murphy, D. J . Organometallics 1985, 4, 1143-
1145.
J . Org. Chem, Vol. 68, No. 8, 2003 3261

Vasse et al.
TABLE 1. Alk yla tion of 1,3-Dip h en yl-2-p r op en yl Aceta te
TABLE 3. Alk yla tion of 1,3-Dip h en yl-2-p r op en yl Aceta te
w ith Ma lon a te (Eq 1) Usin g N,P -Liga n d s 5 a n d 6:
In flu en ce of th e Cou n ter ion
w ith Ma lon a te (Eq 1) Usin g N,P -Liga n d s 1-4
entry
ligand
Pd source
time (h)
convn (%)
ee (%)
entry ligand Pd source
salt
time (h) yield (%) ee (%)
1
2
3
4
1-BH3
2-BH3
3-2BH3
4-2BH3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
1
1
7
7
100
100
100
100
37 (R)
37 (S)
81 (S)
67 (R)
1
2
3
4
5
6
7
8
5-BH3 Pd(OAc)2 KOAc
6-BH3 Pd(OAc)2 KOAc
5-BH3 Pd(OAc)2 NaOAc
6-BH3 Pd(OAc)2 NaOAc
5-BH3 Pd(OAc)2 CsF
6-BH3 Pd(OAc)2 CsF
5-BH3 Pd(OAc)2 LiOAc
6-BH3 Pd(OAc)2 LiOAc
6
24
6
100
40
100
40
98 (S)
37 (R)
98 (S)
37 (R)
98 (S)
37 (R)
98 (S)
4 (S)
24
6
12
6
100
100
100
60
TABLE 2. Alk yla tion of 1,3-Dip h en yl-2-p r op en yl Aceta te
w ith Ma lon a te (Eq 1) Usin g N,P -Liga n d s 5 a n d 6:
Va r ia tion of Tem p er a tu r e a n d Liga n d Meta l Ra tio
8
T
time yield
ee
entry ligand
Pd source
5-BH3 Pd(OAc)2
6-BH3 Pd(OAc)2
Pd/L (°C) (h) (%)
(%)
to obtain the free ligands, was required. This was
achieved using two equivalents of DABCO in toluene
(Table 2).7 When an excess of 5 was employed, results
identical to those obtained with a Pd/ligand ratio of 1:1
were obtained (entry 6). The catalytic reaction in the
presence of 2 equiv of 6 afforded the product having
opposite absolute configuration with higher ee (59%,
entry 7) than that obtained using a 1:1 ratio. These
results suggest that the catalytically active species
derived from 5 does not change with the metal/ligand
ratio, but that a 2:1 complex with only phosphorus
binding to palladium is involved in the reaction employ-
ing an excess of 6. That type of complex is expected to
yield the product with opposite absolute configuration
(see Mechanistic Considerations).
1
2
3
4
5
6
7
1:1
1:1
1:1
20
20 72
0
6
100 98 (S)
95 37 (R)
10 98 (S)
0
5-BH3 Pd(OAc)2
5-BH3 Pd(OAc)2
6-BH3 Pd(OAc)2
5
6
8
1:1 -20 24
1:1 -20 24
0
[(η3-C3H5)PdCl]2 1:2
20
20
8
8
100 98 (S)
100 59 (S)
[(η3-C3H5)PdCl]2 1:2
fashion. This assumption is supported by the results from
the same catalytic reaction employing monodentate
(R,R)-2,5-dialkyl-1-phenylphospholane, which was re-
ported to give the product with 37% ee.30
With symmetrical substrates, the nucleophilic addition
constitutes the enantiodiscriminating step. To achieve
high enantioselectivity with racemic substrates, the rate
of interconversion between diastereomeric allyl com-
plexes must be rapid relative to the nucleophilic addition.
Decreased enantioselectivity may also be achieved due
to the presence of unsymmetrical ion pairs leading to
memory effects.31 It is therefore not surprising that the
nature of the ion pair containing the nucleophilic anion,
and thus the counterion of the nucleophile, may influence
the enantioselectivity of the catalytic reaction.32 The
effect of that ion on the reactions employing ligands 5
and 6 was therefore studied. The results are reported in
Table 3. Reactions employing pseudo-C2-symmetric ligand
5 were found to be insensitive to whether lithium,
sodium, potassium, or cesium was employed as the
counterion, and good conversion and high enantioselec-
tivity was always achieved (entries 1, 3, 5, and 7). In
contrast, the nucleophilic species turned out to play an
important role upon the outcome of reactions involving
the pseudo-meso ligand 6. Replacing KOAc (entry 2) with
NaOAc (entry 4) or CsF (entry 6) did not affect the
enantioselectivity (37% ee of the (R)-product), whereas
in the presence of LiOAc (entry 8) merely 4% ee was
achieved. It has also previously been observed that the
smaller cation lithium affords higher amounts of the ent-
product.6 This is probably due to increased rate of
nucleophilic attack. In the reactions with ligand 6,
increased reactivity was observed with nucleophiles
having cesium and lithium as counterions.
Different results were obtained when ligands 3 and 4
were employed in the same catalytic process. In these
reactions, the protected ligands and palladium acetate
were used. The pseudo-C2-symmetric ligand 3 afforded
the product from reaction of rac-(E)-1,3-diphenyl-2-pro-
penyl acetate with malonate with 81% ee and with the
(S)-product dominating (Table 1, entry 3), whereas the
(R)-product was obtained with lower selectivity, 67% ee,
using 4 as the ligand (entry 4). Full conversion was
achieved with both ligands within 6-7 h.
The behavior of binaphthyl derivatives 5 and 6, em-
ployed as their borane protected adducts, differed to an
even larger extent. With pseudo-C2-symmetric ligand 5
total conversion was achieved after 6 h at ambient
temperature and an enantiomeric excess of 98% in favor
of the (S)-enantiomer was observed (Table 2, entry 1),
whereas 3 days of stirring were necessary to obtain 95%
conversion to the product with moderate enantioselec-
tivity (37% of the (R)-enantiomer) when the pseudo-meso
ligand 6 was used (entry 2). The catalytic reaction was
also attempted at lower temperature. However, at 0 °C
low conversion was observed for the more reactive ligand
(entry 3), without alteration of the enantiomeric excess,
and at -20 °C no reaction occurred (entries 4 and 5).
To allow a study of the influence of the ratio between
metal and ligand on the outcome of the catalytic process,
deprotection of the ligand precursors 5-BH3 and 6-BH3,
Allylic substitutions using C2-symmetric P,P-ligand 7
and N,N-ligand 8 were next studied. Attempts to depro-
tect 7 using a large excess of diethylamine removed the
(31) Lloyd-J ones, G. C.; Stephen, S. C. Chem. Eur. J . 1998, 4, 2539-
2549.
(30) Yan, Y.-Y.; RajanBabu, T. V. Org. Lett. 2000, 2, 199-202.
3262 J . Org. Chem., Vol. 68, No. 8, 2003
(32) Trost, B. M.; Bunt, R. C. J . Am. Chem. Soc. 1998, 120, 70-79.

Enantioselectivity in Palladium-Catalyzed Allylic Substitutions
TABLE 4. Alk yla tion of 1,3-Dip h en yl-2-P r op en yl
Aceta te w ith Ma lon a te (Eq 1) Usin g N,N- a n d
P ,P -Liga n d s 7-13
TABLE 5. Alk yla tion of 1,3-Dip h en yl-2-p r op en yl Aceta te
w ith Ma lon a te (Eq 1) Usin g Ch ir a lly F lexibleLiga n d s 14
a n d 15
entry ligand
Pd source
time (h) convn (%) ee (%)
T
time convn
ee
entry
ligand
14-BH3
14-BH3
15-BH3
15-BH3
Pd source (°C) (h)
(%)
(%)
1
2
3
4
5
6
7
8
7
[(η3-C3H5)PdCl]2
3
4
2
90
100
100
20
2
0
98
0
73 (S)
94 (S)
99 (R)
7-2BH3 Pd(OAc)2
8
9-2BH3 Pd(OAc)2
10
11
12
13
1
2
3
4
5
Pd(OAc)2 20
Pd(OAc)2
Pd(OAc)2 20
Pd(OAc)2
4
24
5
24
4
60
40
55
55
65
87 (S)
87 (S)
78 (S)
81 (S)
79 (S)
[(η3-C3H5)PdCl]2
5
4
[(η3-C3H5)PdCl]2
24
72
72
72
5
[(η3-C3H5)PdCl]2
[(η3-C3H5)PdCl]2
[(η3-C3H5)PdCl]2
5-BH3/6-BH3 1:1 Pd(OAc)2 20
94 (R)
Ch ir a lly F lexible Liga n d s. The addition of a chiral
enantiopure diamine to a racemic mixture of ruthenium-
(II) complexes with chirally flexible (proatropisomeric)
biphenylphosphine ligands has been shown to result in
a mixture of diastereomeric complexes undergoing slow
stereomutation to finally yield one single diastereomer.34
We considered that, instead of combining one rigid and
one flexible ligand, the incorporation of one rigid and one
chirally flexible moiety in the same ligand35 would give
rise to a system which, according to the reaction condi-
tions, would exhibit either pseudo-C2 or pseudo-Cs con-
figuration. We thus decided to design ligands bearing one
fixed element of chirality and a potentially flexible
element capable of adopting either (R) or (S) absolute
configuration. For this purpose, two ligands, 14 and 15,
were designed (Scheme 5). Each ligand is able to adopt
two configurations, as rotation around the single bond
connecting the aromatic rings in the biphenyl part of the
molecules is possible, although the rate of interconversion
between this two diastereoisomeric conformations may
be different.
The two ligands were assessed in the palladium-
catalyzed allylic substitution of 1,3-diphenyl-2-propenyl
acetate with dimethylmalonate and the results compared
with those obtained from a catalytic reaction employing
a 1:1 mixture of the pseudo-C2 and pseudo-meso ligands
(Table 5). The 1:1 mixture of 5 and 6 gave the product
with (S) absolute configuration in 79% enantiomeric
excess (entry 5), showing the reactivity of 5 to be seven
times higher than that of 6. Ligand 15, being chirally
flexible at the phosphorus part of the molecule, behaved
essentially like the 1:1 mixture of 5 and 6 (78% ee at room
temperature, 81% ee at 5 °C), indicating that intercon-
version between the two diastereomeric conformations
is slow compared to the rate-determining step of the
catalytic reaction (Table 5, entries 3 and 4). Use of 14
led to higher enantioselectivity (87% at room temperature
as well as at 5 °C), although not higher than expected
for a than the 1:1 mixture of ent-5 and 6 (entries 1 and
2). These results suggest that the barrier to interconver-
sion between the diastereomeric conformations is high
compared to the activation barriers leading to nucleo-
philic addition, and thus that reactions using 14 and 15
do not occur under Curtin-Hammet conditions.
borane according to 1H NMR, but a well resolved 31P
NMR spectrum could not be recorded. The ligand ob-
tained was, however, assessed in the palladium-catalyzed
allylic substitution. After 4 h, the reaction was complete
and a product with an enantiomeric excess of 73% (S)
was isolated (Table 4, entry 1). We suspected that a
significant amount of mono-oxidized ligand was present,
which is probably detrimental for the reaction as the
oxidized ligand might coordinate in a monodentate
fashion yielding a complex leading to the opposite enan-
tiomer, thus decreasing the ee of the catalytic reaction.
It has previously, indeed, been demonstrated that oxida-
tion of one phosphorus atom in dppe yields a ligand which
coordinates in a monodentate fashion.33 We therefore
decided to repeat the method applied to the P,N-ligands,
using Pd(OAc)2 to generate the catalyst from P,P-ligand
7-2BH3. Under these conditions, the catalytic reaction
was complete after 4 h and the (S) enantiomer was
obtained with 94% excess (entry 2). It was still difficult
to completely avoid oxidation of the ligand, and this is
probably the reason that higher enantioselectivity was
achieved when P,N-ligand 5 was used, as oxidation of
phosphorus in that case leads to a monodentate N-ligand
which probably is inactive in the catalytic process. It is
interesting to note that 5, having pseudo-C2 symmetry,
required nearly twice as long reaction time as C2-
symmetric 7 for full conversion, suggesting the formation
of about equal amounts of two complexes from the former,
of which only one reacts. The N,N-ligand 8, which has
previously not found use in catalytic applications,10 was
found, in addition to high enantioselectivity, to exhibit
remarkably high reactivity, affording full conversion to
product within less than 2 h at room temperature (entry
3). Meso ligands 9 and 10, obviously resulting in racemic
products, were found to exhibit considerably lower reac-
tivity than the C2- or pseudo-C2-symmetric ligands, P,P-
ligand 9 requiring 4 h at room temperature for 20%
conversion, whereas only 2% of product was obtained
after 24 h using N,N-ligand 10 (entries 4 and 5).
The reactivity and selectivity of the catalytically active
complex was found to be strongly affected by the struc-
ture of the spacer connecting the binaphthyl moieties.
Thus, whereas no product was obtained upon use of 11
(entry 6), derived from (S,S)-diaminocyclohexane, the
diastereomer 12 afforded 98% yield of a product consist-
ing mainly of the (R) enantiomer (94% ee) within 72 h at
ambient temperature (Table 4, entry 7). A catalytic
reaction employing ligand 13, resulting in a six-mem-
bered chelate with palladium, resulted in precipitation
of palladium, and no product was isolated (entry 8).
Cyclic Su bstr a tes. The study of this new class of
ligands was also extended to sterically less demanding
substrates. Thus, 3 and 4 were tested as ligands in the
(34) (a) Mikami, K.; Korenaga, T.; Teruda, M.; Ohkuma, T.; Pham,
T.; Noyori, R. Angew. Chem., Int. Ed. 1999, 38, 495-497. (b) Mikami,
K.; Aikawa, K.; Korenaga, T. Org. Lett. 2001, 3, 243-245.
(35) This concept has been used for the design of ligands used in
Rh-catalyzed hydroformylations: Nozaki, K.; Sakai, N.; Nanno, T.;
Higashijima, T.; Mano, S.; Horiuchi, T.; Takaya, H. J . Am. Chem. Soc.
1997, 119, 4413-4423.
(33) Amatore, C.; J utand, A.; Thuilliez, A. Organometallics 2001,
20, 3241-3249.
J . Org. Chem, Vol. 68, No. 8, 2003 3263

Vasse et al.
TABLE 6. Alk yla tion of 3-Cyclop en ten yl Aceta te (n ) 1)
a n d 3-Cycloh exen yl Aceta te (n ) 2) w ith Ma lon a te (Eq 2)
Usin g Liga n d s 3-6
was not achieved with the present catalytic systems and
no enantioselectivity was thus observed.
entry ligand
n
Pd source T (°C) time (h) convn (%) ee (%)
1
2
3
4
5
6
7
8
3-2BH3
4-2BH3
5-BH3
6-BH3
3-2BH3
4-2BH3
5-BH3
6-BH3
2
2
2
2
1
1
1
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
20
20
40
40
20
20
20
20
120
192
24
24
25
17
24
24
0
73
40
24 (R)
12 (R)
26 (R)
13 (S)
12 (R)
27 (R)
26 (R)
70
100
100
100
100
Nitr ogen Nu cleop h iles. Benzylamine was explored
as a nucleophile in the substitution of 1,3-diphenyl-2-
propenyl acetate using 5 as a ligand (eq 4). Whereas
essentially no enantioselectivity (4% ee) was achieved at
room temperature, a 39% ee of the product with (R)
absolute configuration was surprisingly observed when
the reaction was run at 45 °C, at which temperature full
conversion was achieved within 48 h. This suggests that
the rate-determining step is not the same at the two
temperatures. Under the same conditions, ligand 6
resulted in 10% conversion to a racemic product. When
potassium phthalimide was used as nitrogen source no
reaction with 1,3-diphenyl-2-propenyl acetate was ob-
served, even at 50 °C.
palladium mediated substitution of rac-3-cyclohexenyl
(40) and rac-3-cyclopententyl acetate (41) with dimethyl
malonate as the nucleophile (eq 2), employing metal/
ligand ratios of 1:1 (Table 6). From the reaction with
cyclohexenyl acetate, using pseudo-C2-symmetric ligand
3, no product was isolated even after a reaction time of
120 h (entry 1). The pseudo-meso ligand 4 exhibited
higher reactivity, resulting in 73% conversion to the (R)-
product with 24% ee after 192 h (entry 2). The same
substrate was transformed to the (R)-product employing
ligands 5 (40% conversion after 24 h, 12% ee, entry 3)
and 6 (70% conversion after 24 h, 26% ee, entry 4).
Interestingly, in contrast to the situation with 1,3-
diphenyl-2-propenyl acetate, use of pseudo-meso ligands
4 and 6 thus resulted in somewhat higher enantioselec-
tivity and higher reactivity in the substitution of cyclo-
hexenyl acetate than use of the diastereoisomeric com-
pounds 3 and 5. With cyclopentenyl acetate as the
substrate, a smaller difference in reactivity between the
two types of ligands was observed, 3 requiring 25 h for
full conversion and 4 17 h, and both ligands led to the
same level of enantioselectivity ((S)-product with 13% ee,
entry 5, and (R)-product with 12% ee, entry 6 respec-
tively). With ligands 5 and 6 full conversion to the (R)-
product (27 and 26% ee, respectively) was achieved after
24 h (entries 7 and 8).
Mech a n istic Con sid er a tion s
Several features concerning the mechanism of pal-
ladium-catalyzed allylic alkylations are known.3 The first
step is the oxidative addition of the allylic acetate to Pd-
(0), which has been shown to be a reversible process.38
For symmetrically substituted substrates, the enantio-
discriminating step is the attack of the nucleophile on
the π-allyl palladium complex, from the side trans to
phosphorus, to form a palladium(0) olefin complex.
Depending on whether this step is endothermic or
exothermic, the reactivity of the reacting π-allyl palla-
dium(II) complex or the stability of the π-olefin pal-
ladium(0) complex resulting from nucleophilic attack
should be considered in order to rationalize the enantio-
discrimination of the catalytic process.39 Late, product-
like, transition states have recently been suggested as a
result of experimental40 as well as theoretical studies,41
although under different conditions, an early transition
state has been demonstrated.42 In processes with late
transition states, the enantiodiscrimination is assumed
to be a result of the most favorable conversion of the allyl
complex into an olefin complex, as recently illustrated
by for example Morimoto.43 The steric as well as the
electronic properties of the ligand-metal complex are
Su bstr a te w ith En a n tiotop ic Lea vin g Gr ou p s. We
have also explored the possibility for the two ligands 5
and 6 to desymmetrize a meso-diacetyl compound em-
ploying 3,5-cyclopentenyl bisurethane 42 as substrate (eq
3). High enantioselectivity has been observed in this type
of process with different types of ligands, including the
C2-symmetric Trost diphosphine3c as well as some asym-
metric ligands.36 In this particular reaction, the enan-
tiodetermining step is the oxidative addition of the allylic
acetate to Pd(0).37 Although electronic dissymmetry
might be expected to influence the ionization of the
acetate, discrimination of the enantiotopic leaving groups
(38) Amatore, C.; Gamez, S.; J utand, A. Chem. Eur. J . 2001, 7,
1273-1280.
(39) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339-345.
(40) Brown, J . M.; Hulmes, D. I.; Guiry, P. J . Tetrahedron 1994,
50, 4493-4506.
(36) (a) Okauchi, T.; Fujita, K.; Ohtaguro, T.; Ohshima, S.; Minami,
T. Tetrahedron: Asymmetry 2000, 11, 1397-1403. (b) Evans, D. A.;
Campos, K. R.; Tedrow, J . S.; Michael, F. E.; Gagne´, M. R. J . Am.
Chem. Soc. 2000, 122, 7905-7920.
(37) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J . Am. Chem. Soc.
1992, 114, 9327-9343.
(41) Hagelin, H.; A° kermark, B.; Norrby, P.-O. Chem. Eur. J . 1999,
5, 902-909.
(42) Mackenzie, P. B.; Whelan, J .; Bosnich, B. J . Am. Chem. Soc.
1985, 107, 2046.
(43) Saitoh, A.; Achiwa, K.; Tanaka, K.; Morimoto, T. J . Org. Chem.
2000, 65, 4227-4240.
3264 J . Org. Chem., Vol. 68, No. 8, 2003

Enantioselectivity in Palladium-Catalyzed Allylic Substitutions
SCHEME 6
stabilities. Nucleophilic attack on these two complexes
is assumed to represent the major reaction routes, as the
anti-anti and anti-syn complexes would give rise to either
products with Z-olefinic bonds, not observed in the
product mixtures, or to the opposite enantiomer, and
therefore can be present only in a low amount, or at least
lead to product only to a minor extent. Nucleophilic
attack trans to phosphorus is generally preferred45 but
occurs readily only for one of the complexes, as formation
of an olefin complex is sterically unfavorable for the other.
The observation that the major product has (S) absolute
configuration when ligands with Pr chirality (3, 5, 7, 14,
15) are employed and that the opposite enantiomer is
preferentially formed from reactions employing a ligand
with Mr chirality (8, 12) is in accordance with the
proposed model.43 Likewise, from pseudo-meso ligand 6
the formation of two major allyl palladium complexes is
assumed to occur, although in this case this assumption
has less strong support from experimental data. The two
syn-syn complexes are believed to have different energies
due to different sterical situations, the formation of
product via nucleophilic attack trans to phosphorus on
the complex assumed to be the most stable one being in
accordance with experiments. These suggestions are also
in accordance with the formation of products with dif-
ferent absolute configurations from the two types of
ligands (3 and 5 on one hand, and 4 and 6 on the other),
and with the fact that 5 exhibits only about half the
reactivity of C2-symmetric ligand 7.
The low reactivity of 11 and 13 as compared to 8 and
12 probably originates in different steric situations.
Inspection of molecular models suggests that a smaller
chiral pocket is available for the substrate in the former
ligands, resulting in more labile metal complexes; at-
tempted reaction employing 13 even resulted in the
precipitation of palladium.
The results obtained upon alkylation of cyclic sub-
strates can be rationalized analogously. Only two π-allyl
palladium complexes are possible, as only two diastere-
omeric anti-anti complexes may form. Nucleophilic attack
trans to phosphorus on the complexes leading to products
with (R) absolute configuration is expected to be favored,
in accordance with the results from experiments employ-
ing ligands 4, 5, and 6, although from the reaction of
cyclopentenyl acetate using ligand 3, the opposite enan-
tiomer was isolated with low ee. The model also suggests
that larger enantiodiscrimination for cyclic substrates
should occur for nucleophilic attack at the complex with
the pseudo-meso ligands 4 and 6 as compared to those
with ligands 3 and 5, although this is observed experi-
mentally only in the alkylation of cyclohexenyl acetate.
The observation of products with different absolute
configuration from reactions employing a 1:1 and 1:2 6/Pd
ratio is in accordance with a change from a pseudo-meso
structure of the palladium allyl complex to one with Pr
chirality.
crucial for the enantioselectivity, although the origin of
the enantiocontrol using aminophosphine ligands has
been claimed to depend mainly on steric factors, elec-
tronic factors being important only for cyclic substrates.44
The situation for the two types of ligands presented
here is illustrated in Scheme 6. A late transition state
for the step involving addition of the nucleophile is
assumed, although the same conclusions would result
from a consideration of processes with early transition
states. As the ligands are devoid of symmetry, up to eight
diastereomeric allyl palladium complexes may form from
1,3-diphenyl-2-propenyl acetate. In the case of the pseudo-
C2 ligand 5, two out of these, the M- and W-shaped (endo,
exo) syn-syn complexes, are assumed to have similar
Only few ligands induce high enantioselectivity in
alkylations of small aliphatic substrates. One factor
which seems to be crucial in reactions with this type of
substrate is the bite angle, but other factors may be
important as well. We are presently undertaking further
(44) Widhalm, M.; Nettekoven, U.; Kalchhauser, H.; Mereiter, K.;
Calhorda, M. J .; Fe´lix, V. Organometallics 2002, 21, 315-325.
(45) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336-345.
J . Org. Chem, Vol. 68, No. 8, 2003 3265

Vasse et al.
temperature was allowed to slowly raise to 0 °C. The flask
was cooled to -78 °C, and BH3‚SMe2 (2.4 mL, 2 M in THF,
4.8 mmol) was added. The flask was degassed, and the reaction
mixture was stirred overnight at room temperature. The slurry
was filtered through a short plug of silica and concentrated.
The crude product was purified by column chromatography
on silica gel (pentane/diethyl ether 97:3) to give an oil, which
was further purified by recrystallization from pentane at -78
°C to give 19-BH3 (882 mg, 72%) as a white solid: mp 35-36
studies of the present type of ligands in order to optimize
the structure for a wider range of substrates.
Con clu sion s
N,P-, N,N-, and P,P-ligands with pseudo-C2, pseudo-
Cs, C2, and Cs symmetry were prepared and evaluated
in palladium-catalyzed allylic alkylations; in ligands with
pseudo-Cs symmetry, the chirality originates in different
donor atoms only. With substrates preferring syn-syn
conformation, C2- and pseudo-C2-symmetric ligands proved
to induce higher enantioselectivity than those having
pseudo-Cs symmetry (those with Cs symmetry evidently
resulting in racemic products), whereas the reverse
situation was found for a cyclohexenyl substrate, forced
to have an anti-anti structure. Depending on the sub-
strate, a ligand with either pseudo-C2 or pseudo-Cs
symmetry should thus be selected for the allylic alkyl-
ation. The nature of the spacer connecting the two donor
parts of the bidentate ligands proved to be crucial for the
selectivity as well as for the reactivity of the catalysts.
°C; [R]25 +163.6 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ
D
7.76 (ddd, J ) 11.3, 7.8, 1.6 Hz, 1H), 7.42 (app t, J ) 7.7 Hz,
1H), 7.13-7.04 (m, 2H), 4.28-4.18 (m, 1H), 4.18-3.96 (m, 4H),
3.82-3.71 (m, 1H), 2.32-2.21 (m, 1H), 2.13-2.02 (m, 1H),
1.69-1.57 (m, 1H), 1.50-1.40 (m, 1H), 1.34 (ddd, J ) 14.1,
7.0, 0.4 Hz, 6H), 1.07 (d, J ) 5.9 Hz, 3H), 0.75 (d, J ) 6.4 Hz,
3H), 1.02-0.30 (br, 3H); 13C NMR (125 MHz, CDCl3) δ 151.0
(d, J CP ) 9.9 Hz), 133.5 (d, J CP ) 8.8 Hz), 132.3 (d, J CP ) 1.2
Hz), 127.3 (d, J CP ) 74.5 Hz), 124.4 (d, J CP ) 7.3 Hz), 122.0
(d, J CP ) 9.0 Hz), 63.0 (d, J CP ) 5.2 Hz), 62.6 (d, J CP ) 5.3
Hz), 59.1, 53.3, 32.5, 31.7, 18.9, 18.5, 16.4 (d, J CP ) 6.3 Hz),
16.3 (d, J CP ) 6.4 Hz); 31P NMR (202 MHz, CDCl3) δ 130.7 (br
m). Anal. Calcd for C16H29BNO2P: C, 62.15; H, 9.45; N, 4.53.
Found: C, 61.96; H, 9.50; N, 4.50.
Dieth yl (2R,5R)-[2-(2,5-Dim eth ylp yr r olid in yl)p h en yl]-
p h osp h in ite (19). DABCO (123.4 mg, 1.1 mmol) was added
to a degassed solution of 19-BH3 (309.2 mg, 1.0 mmol) in
toluene (600 µL) at -78 °C. The mixture was degassed and
warmed to room temperature before the flask was sealed and
heated at 45 °C for 48 h. The flask was cooled to room
temperature, and the toluene was removed at reduced pres-
sure. The residue was washed with degassed hexanes (3 × 1
mL). The organic phases were combined and concentrated at
reduced pressure to give 289 mg of an air-sensitive oil which
was used without further purification: 1H NMR (400 MHz,
CDCl3) δ 7.74-7.72 (m, 1H), 7.35-7.28 (m, 1H), 7.06-7.01 (m,
2H), 4.19 (br s, 1H), 4.07-3.95 (m, 1H), 3.94-3.84 (m, 1H),
3.83-3.70 (m, 2H), 3.62-3.50 (m, 1H), 2.23 (br s, 1H), 2.09
(br s, 1H), 1.54-1.43 (br m, 2H), 1.31 (ddd, J ) 14.1, 7.0, 0.3
Hz, 3H), 1.19 (ddd, J ) 14.1, 7.0, 0.4 Hz, 3H), 1.03 (br s, 3H),
Exp er im en ta l Section
Gen er a l Rem a r k s. All air-sensitive reactions were per-
formed in oven-dried glassware under argon or nitrogen
atmosphere using freshly distilled solvents. Tetrahydrofuran
and diethyl ether were distilled from sodium-benzophenone
under nitrogen. Methylene chloride was distilled from CaH2
or P2O5. Hexanes, dimethylformamide, and methanol were
dried over molecular sieves, unless otherwise stated. Column
chromatography was performed using EM silica gel 60 (230-
1
400 mesh), Merck silica gel 60 H, or SDS silica gel 60 A. H
NMR spectra were recorded at 500, 400, or 300 MHz, 13C
spectra at 125 and 100 MHz, and 31P spectra at 202 MHz. The
1H and 13C chemical shifts are reported relative to CHCl3, and
the 31P chemical shifts are reported relative to H3PO3 (exter-
nal). Melting points are uncorrected. Elemental analyses were
performed by Analytische Laboratorien, Lindlar, Germany.
HRMS analyses were performed at the University of Lund,
Sweden. Handling of the cyclic sulfates and the manipulation
of the primary phosphines should be conducted with ca u tion
(well ventilated fume hood). Compounds 5,7 6,7 8,14 and 38-
0.79 (br s, 3H);13C NMR (125 MHz, CDCl3) δ 149.9 (d, J CP
)
21.8 Hz), 136.6 (d, J CP ) 23.0 Hz), 130.4 (d, J CP ) 3.9 Hz),
130.1, 123.0 (d, J CP ) 2.1 Hz), 122.1, 62.7 (d, J CP ) 16.1 Hz),
61.2 (d, J CP ) 7.9 Hz), 58.7, 58.6, 32.6, 32.0, 19.6, 18.5, 17.2
(d, J CP ) 5.6 Hz), 17.0 (d, J CP ) 5.1 Hz); 31P NMR (202 MHz,
CDCl3) δ 152.3; GC-MS 295 (M+), 266, 252, 238, 224, 172,
158.
7
2BH3 were prepared via previously described procedures.
1-[(2R,5R)-2,5-Dim eth ylph osph olan ylbor an e]-2-[(2R,5R)-
2,5-d im eth ylp yr r olid in yl]ben zen e (1-BH3). Chlorotrim-
ethylsilane (38 µL, 3.0 mmol) was added dropwise to a
degassed slurry of LAH (114 mg, 3.0 mmol) in THF (10 mL)
at -78 °C with stirring. The suspension was stirred for 3 h at
room temperature. Phosphonite 19 (289 mg, 1.0 mmol) in
degassed THF (2 mL) was slowly added at -78 °C. The
reaction mixture was allowed to reach room temperature
slowly, and stirring was continued for an additional 15 h. The
reaction was quenched by the addition of degassed absolute
MeOH (640 µL) followed by degassed THF (15 mL) at -78 °C.
The reaction mixture was stirred at room temperature for 1 h
and 20 min and then filtered. The filter cake was washed with
degassed THF (3 mL). The solvents were carefully removed
at reduced pressure. The residue, consisting of 20, was
dissolved in 5 mL of degassed THF, and n-butyllithium (300
µL, 2.5 M in hexane, 0.75 mmol) was added dropwise at -78
°C. The resulting yellow solution was stirred at room temper-
ature for 1 h. (2S,5S)-Hexanediol cyclic sulfate ((S,S)-17, 135
mg, 0.75 mmol) in degassed THF (1 mL) was added at -78
°C. The solution was stirred at room temperature for 1.5 h.
n-Butyllithium (300 µL, 2.5 M in hexane, 0.75 mmol) was
added dropwise at -78 °C, resulting in a yellow color. The
reaction mixture was then stirred at room temperature for 18
h. BH3‚Me2S (375 µL, 2 M in THF, 0.75 mmol) was added at
-78 °C and the reaction mixture stirred at room temperature
(2R,5R)-1-(2-Br om op h en yl)-2,5-d im et h ylp yr r olid in e
(18). (2S,5S)-Hexanediol cyclic sulfate ((S,S)-17, 2.0 g, 11.1
mmol) was mixed with 2-bromoaniline (16, 9.56 g, 55.5 mmol).
The flask containing the mixture was degassed and sealed
before it was heated for 22 h at 75 °C. The reaction mixture
was cooled to room temperature and the resulting solid treated
with 5 M NaOH (150 mL), followed by extraction with pentane
(4 × 75 mL). The combined organic phases were dried over
Na2SO4 and concentrated at reduced pressure. The crude
product was purified by column chromatography on silica gel
(pentane) to give 18 (2.0 g, 71%) as a colorless oil: [R]25D +132.4
(c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.51 (dd, J ) 7.9,
1.5 Hz, 1H), 7.20 (td, J ) 7.7, 1.5 Hz, 1H), 6.97 (dd, J ) 8.0,
1.3 Hz, 1H), 6.81 (td, J ) 7.6, 1.5 Hz, 1H), 4.44 (m, 1H), 3.79
(m, 1H), 2.22 (m, 1H), 2.10 (m, 1H), 1.57 (m, 1H), 1.47 (m,
1H), 1.1 (J ) 5.8 Hz, 3H), 0.75 (d, J ) 6.3 Hz, 3H); 13C NMR
(125 MHz, CDCl3) δ 145.8, 133.6, 127.1, 123.8, 122.6, 119.8,
55.4, 53.6, 33.1, 32.6, 19.5, 19.4. Anal. Calcd for C12H16NBr:
C, 56.71; H, 6.34; N, 5.51. Found: C, 56.65; H, 6.36; N, 5.62.
Dieth yl (2R,5R)-[2-(2,5-Dim eth ylp yr r olid in yl)p h en yl]-
p h osp h in ite-Bor a n e (19-BH3). tert-Butyllithium (5.1 mL,
1.7 M in pentane, 8.6 mmol) was added dropwise (5 min) at
-95 °C to a degassed solution of 18 (1.0 g, 3.9 mmol) in diethyl
ether (20 mL). The mixture was stirred for 45 min before
diethyl chloro phosphite (0.69 mL, 4.7 mmol) was added at
-78 °C and then stirred for an additional 5 h, while the
3266 J . Org. Chem., Vol. 68, No. 8, 2003

Enantioselectivity in Palladium-Catalyzed Allylic Substitutions
for 2 h. The reaction was quenched by the addition of water
(100 µL). The mixture was diluted with CHCl3 (25 mL) and
filtered through a plug of Na2SO4. Concentration of the solvent
resulted in a white sticky material that was purified by column
chromatography on silica gel (CHCl3/hexanes 4:6) to give
1-BH3 (60 mg, 20%) as a white solid. An analytically pure
3 h, whereafter an additional amount of n-butyllithium (0.39
mL, 2.5 M, 0.98 mmol) was added at -78 °C. The reaction
mixture was allowed to reach room temperature and then
stirred at this temperature for a further 19 h. BH3‚SMe2 (1.56
mL, 2 M, 3.12 mmol) was added, and the reaction mixture was
stirred at ambient temperature for 1 h. Liquid chromatography
on neutral alumina (column 2.5 × 15 cm, eluent: 100 mL of
hexane followed by 200 mL of hexane/Et2O 2:1) yielded 61 mg
sample was obtained by recrystallization from hexanes: mp
1
118-119 °C; [R]25 +35.3 (c 1.0, CHCl3); H NMR (400 MHz,
D
CDCl3) δ 7.73 (ddd, J ) 9.7, 7.9, 1.6 Hz, 1H), 7.39 (split t, J )
7.7 Hz, 1H), 7.15-7.11 (m, 2H), 4.01-3.89 (m, 1H), 3.75-3.63
(m, 1H), 3.50-3.34 (m, 1H), 2.55-2.42 (m, 1H), 2.33-2.04 (m,
4H), 1.75-1.60 (m, 1H), 1.59-1.42 (m, 3H), 1.36 (dd, J ) 15.8,
6.9 Hz, 3H), 1.02 (d, J ) 6.0 Hz, 3H), 0.88 (dd, J ) 13.9, 7.3
Hz, 3H), 0.75 (d, J ) 6.5 Hz, 3H), 1.15-0.25 (br, 3H); 13C NMR
(17%, white crystals) of 3-2BH3: [R]25 -55.9 (c 1.0, CHCl3);
D
1H NMR (400 MHz, CDCl3) δ 3.65-3.59 (m, 1H), 3.12-3.03
(m, 1H), 2.88-2.76 (m, 2H), 2.46-2.32 (m, 2H), 2.23-2.01 (m,
5H), 1.91-1.82 (m, 1H), 1.9-0.9 (br, 3H), 1.79-1.69 (m, 1H),
1.48-1.34 (m, 3H), 1.32 (d, J ) 6.5 Hz, 3H), 1.24 (dd, J ) 6.9,
2.4 Hz, 3H), 1.20 (d, J ) 6.8 Hz, 3H), 1.14 (d, J ) 6.9 Hz, 3H),
0.36 (br q, J ) 109.2, 80.9 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 65.2, 63.6, 50.7 (d, J CP ) 6.9 Hz), 34.9 (d, J CP ) 3.3 Hz),
34.2, 33.7 (d, J CP ) 37.1 Hz), 32.0 (d, J CP ) 3.5 Hz), 28.9, 28.6,
17.5 (d, J CP ) 27.7 Hz), 16.0, 15.8 (d, J CP ) 4.7 Hz), 15.2, 13.4
(d, J CP ) 2.7 Hz); 31P NMR (202 MHz, CDCl3) δ 38.1 (br s).
Anal. Calcd for C14H34B2NP: C, 62.50; H, 12.74; N, 5.21.
Found: C, 62.37; H, 12.57; N, 5.25.
(125 MHz, CDCl3) δ 151.4 (d, J CP ) 2.1 Hz), 136.0 (d, J CP
)
10.9 Hz), 130.9 (d, J CP ) 2.5 Hz), 125.5 (d, J CP ) 6.0 Hz), 125.1-
(d, J CP ) 38.7 Hz), 123.6 (d, J CP ) 10.5 Hz), 59.9, 52.9, 35.1
(d, J CP ) 37 Hz), 33.7 (d, J CP ) 4.2 Hz), 32.9 (d, J CP ) 7.6 Hz),
32.2, 30.7, 29.7 (d, J CP ) 35.7 Hz), 19.3, 17.1, 15.8 (d, J CP
)
4.1 Hz), 14.6 (d, J CP ) 3.7 Hz); 31P NMR (202 MHz, CDCl3) δ
41.2 (br m). Anal. Calcd for C18H31BNP: C, 71.30; H, 10.30;
N, 4.62. Found: C, 71.14; H, 10.34; N, 4.51.
2-[(2S,5S)-2,5-Dim eth ylph osph olan yl-bor an e]-1-[(2R,5R)-
2,5-d im eth ylp yr r olid in ylbor a n e]eth a n e (4-2BH3). Com-
pound 4-2BH3 was synthesized using the procedure employed
for the preparation of 3-2BH3 by using (2R,5R)-hexanediol
cyclic sulfate instead of (2S,5S)-hexanediol cyclic sulfate (21%
of 4-2BH3, white crystals): [R]25D -26.7 (c 1.0, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 3.18-3.09 (m, 1H), 3.66-3.58 (m, 1H),
2.94-2.86 (m, 1H), 2.77-2.68 (m, 1H), 2.42-2.25 (m, 2H),
2.20-2.00 (m, 5H), 1.9-0.9 (br, 3H), 1.85-1.73 (m, 2H), 1.52-
1.35 (m, 3H), 1.31 (d, J ) 6.6 Hz, 3H), 1.26 (dd, J ) 13.9, 6.8
Hz, 3H), 1.23 (dd, J ) 16.2, 6.9 Hz, 3H), 1.17 (d, J ) 6.9 Hz,
3H), 0.35 (br q, J ) 102.2, 86.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 65.3, 63.3, 50.2 (d, J CP ) 6.8 Hz), 34.6 (d, J CP ) 3.5
Hz), 34.4, 33.8 (d, J CP ) 36.1 Hz), 33.1 (d, J CP ) 35.1 Hz), 28.8,
28.7, 17.8 (d, J CP ) 27.1 Hz), 16.2, 15.5, 15.2 (d, J CP ) 4.5 Hz),
13.7 (d, J CP ) 2.8 Hz); 31P NMR δ (202 MHz, CDCl3) 38.4 (br
m). Anal. Calcd for C14H34B2NP: C, 62.50; H, 12.74; N, 5.21.
Found: C, 62.60; H, 12.87; N, 5.13.
1-[(2S,5S)-2,5-Dim eth ylph osph olan ylbor an e]-2-[(2R,5R)-
2,5-d im eth ylp yr r olid in yl]ben zen e (2-BH3). Ligand 2 was
prepared analogously to 1 from 19 using (2R,5R)-hexanediol
cyclic sulfate: yield 12%, as a white solid; mp 96-97 °C; [R]25
D
+141.9 (c 0.8, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.68 (ddd,
J ) 9.2, 7.9, 1.6 Hz, 1H), 7.35 (split t, J ) 9.6 Hz, 1H), 7.13-
7.07 (m, 2H), 3.78-3.60 (m, 3H), 2.36-2.04 (m, 5H), 1.64-
1.41 (m, 4H), 1.37 (dd, J ) 16.3, 7.2 Hz, 3H), 1.08 (d, J ) 5.9
Hz, 3H), 0.85 (dd, J ) 13.5, 7.2 Hz, 3H), 0.67 (d, J ) 6.5 Hz,
3H), 1.03-0.21 (br, 3H); 13C NMR (125 MHz, CDCl3) δ 151.8
(d, J CP ) 1.5 Hz), 135.7 (d, J CP ) 10.0 Hz), 130.5 (d, J CP ) 2.3
Hz), 124.5 (d, J CP ) 5.6 Hz), 123.7 (d, J CP ) 39.2 Hz), 122.9
(d, J CP ) 10.3 Hz), 61.1, 51.9, 36.3 (d, J CP ) 36.1 Hz), 34.5 (d,
J CP ) 2.9 Hz), 33.9 (d, J CP ) 5.0 Hz), 32.3, 31.3 (d, J CP ) 34.3
Hz), 30.5, 19.4, 17.2, 16.0 (d, J CP ) 4.4 Hz), 15.9 (d, J CP ) 3.9
Hz); 31P NMR (202 MHz, CDCl3) δ 42.1 (br m). Anal. Calcd
for C18H31BNP: C, 71.30; H, 10.30; N, 4.62. Found: C, 71.10;
H, 10.38; N, 4.55.
(S)-4,5-Dih yd r o-5-h yd r oxy-3H-d in a p h th o[1,2-c:2′,1′-e]-
p h osp h ep in e 5-Oxid e (25). Diisopropylethylamine (2.6 mL,
14.9 mmol) was added to a suspension of ammonium phos-
phinate (340 mg, 4.1 mmol) in dichloromethane (25 mL) at 0
°C. After the mixture was stirred for 20 min, chlorotrimeth-
ylsilane (1.9 mL, 15 mmol) was added at 0 °C. The mixture
was stirred for 2 h at room temperature, a solution of (S)-2,2′-
di(bromomethyl)-1,1′-binaphthyl ((S)-24, 1.19 g, 2.7 mmol) in
dichloromethane (5 mL) was added at 0 °C, and the mixture
was stirred for additional 24 h. The reaction was carefully
quenched with water (5 mL) at 0 °C, and the organic phase
washed twice with aqueous HCl (10%, 5 mL) and with water
(5 mL). The organic layer was dried over magnesium sulfate
and concentrated to give, after flash chromatography on silica
gel using CH2Cl2/MeOH (95:5) as eluent, 25 as a brown pale
solid (392 mg, 42%): [R]20D -97.6 (c 1.0, CHCl3); 1H NMR (400
MHz, CDCl3) δ 7.84 (d, J ) 8.4 Hz, 4H), 7.45 (d, J ) 8.2 Hz,
2H), 7.36 (t, J ) 6.7 Hz, 2H), 7.13 (m, 4H), 3.02 (quint, J )
16.9 Hz, 4H); 13C NMR (100 MHz, CDCl3) δ 133.7, 132.7, 132.1,
Diet h yl [2-(2R,5R)-(2,5-Dim et h ylp yr r olid in yl)et h yl]-
p h osp h in ite (22). A degassed mixture of (2S,5S)-hexanediol
cyclic sulfate ((S,S)-17, 600 mg, 3.33 mmol) and (2-aminoethyl)-
phosphonic acid diethyl ester (21, 1.80 g, 9.94 mmol) was
heated at 75 °C for 48 h. Water (5 mL) and NEt3 (1 mL) were
added, and the mixture was extracted with pentane. The
organic phase was dried (MgSO4) and concentrated under
reduced pressure to give 416 mg (47%) of 22 as a yellow oil,
which was used further without additional purification: 1H
NMR (400 MHz, CDCl3) δ 4.06 (m, 4H), 3.00 (br s, 2H), 2.86
(m, 1H), 2.60 (m, 1H), 2.06-1.82 (m, 4H), 1.37-1.27 (m, 8H),
0.94 (d, J ) 6.3 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 61.4
(dd, J CP ) 10.3 Hz), 54.9, 40.8, 30.7, 25.6 (d, J CP ) 137.9 Hz),
16.5, 16.4 (d, J CP ) 6.0 Hz); 31P NMR (202 MHz, CDCl3) δ 31.8.
1-[(2R,5R)-2,5-Dim eth ylph osph olan ylbor an e]-2-[(2R,5R)-
2,5-d im eth ylp yr r olid in ylbor a n e]eth a n e (3-2BH3). LAH
(151 mg, 3.98 mmol) was slowly added to a degassed solution
of phosphonite 22 (349 mg, 1.33 mmol) in diethyl ether (10
mL, stirring at 0 °C for 10 min). After being stirred at 0 °C for
30 min, the reaction mixture was allowed to reach room
temperature and then stirred at this temperature for a further
2 h. The reaction was quenched with a saturated aqueous
solution of Na2SO4 and the organic phase dried over Na2SO4.
Removal of the solvents under reduced pressure gave 23 (125
mg) as a yellow oil, which was diluted with degassed THF (5
mL). n-Butyllithium (0.39 mL, 2.5 M, 0.98 mmol) was added
at -78 °C. The reaction mixture was allowed to reach room
temperature and, after being stirred at this temperature for
a further 30 min, added to a solution of (2S,5S)-hexanediol
cyclic sulfate ((S,S)-17, 142 mg, 0.79 mmol) in THF (15 mL)
at -78 °C. The reaction mixture was allowed to reach room
temperature and then stirred at this temperature for a further
130.2, 129.1, 128.2, 128.1, 126.9, 126.3, 125.5, 35.2 (d, J HP
)
90 Hz); 31P NMR (202 MHz, CDCl3) δ 67.7.
(S)-4,5-Dih yd r o-3H -d in a p h t h o[1,2-c:2′,1′-e]p h osp h ep -
in e-Bor a n e (26-BH3). A mixture of phosphinic acid 25 (365
mg, 1.06 mmol) and phenylsilane (0.26 mL, 2.12 mmol) was
heated at 90 °C for 6 h under argon, and the excess of
phenylsilane was removed under reduced pressure. THF (1
mL) was added followed by a solution of BH3‚Me2S (2N in THF,
0.6 mL), and the mixture was stirred for 2 h at room
temperature. The solvent was removed under reduced pres-
sure, and the residue was purified by flash chromatography
on silica gel using CH2Cl2/hexane (50:50) as eluent to give 26-
BH3 as a white solid (148 mg, 43%): [R]20 ) +195 (c 1.0,
D
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.93-7.86 (m, 4H), 7.51
J . Org. Chem, Vol. 68, No. 8, 2003 3267

Vasse et al.
(dd, J ) 8.6, 1.6 Hz, 1H), 7.43-7.39 (m, 2H), 7.27-7.21 (m,
3H), 7.13 (d, J ) 8.0 Hz, 1H), 7.08 (d, J ) 8.6 Hz, 1H), 5.15
(dm, J ) 375 Hz, 1H), 3.03 (ddd, J ) 18.7, 13.3, 5.8 Hz, 1H),
2.95 (dt, J ) 14.5, 3.6 Hz, 1H), 2.84 (d, J ) 13.4 Hz, 1H), 2.67
(ddd, J ) 10.5, 12.2, 14.1 Hz, 1H), 0.9-0.0 (br, 3H).
Dieth yl (S)-2-[(S)-4,5-Dih yd r o-3H-d in a p h th o[1,2-c:2′,1′-
e]p h osp h ep in obor a n e]eth ylp h osp h on a te (28-BH3). KO-
t-Bu (5 mg, 0.045 mmol) was added to a solution of the
phosphine-borane 26-BH3 (148 mg, 0.45 mmol) and diethyl
vinylphosphonate (27, 74 mg, 0.45 mmol) in THF (1 mL), and
the reaction mixture was stirred for 12 h at room temperature.
Evaporation of the solvent and purification of the residue by
flash chromatography on silica gel using CH2Cl2/MeOH (98:
Hz, 2H), 7.15 (d, J ) 8.4 Hz, 2H), 2.83 (m, 6H), 2.61 (dd, J )
16.8, 13.0 Hz, 2H), 1.90 (m, 2H), 1.68 (m, 2H), -0.1- -0.8 (br,
6H). 13C NMR (100 MHz, CDCl3) δ 134.2, 133.7, 133.6, 133.4,
132.7, 132.5, 130.3, 130.0, 129.7, 129.4, 128.9, 128.8, 128.6,
127.7, 127.2, 127.1, 127.0, 126.8, 126.4, 126.2, 29.9 (d, J ) 32.2
Hz), 29.3 (d, J ) 29.8 Hz), 17.0 (d, J ) 26.4 Hz); 31P NMR
(202 MHz, CDCl3) δ 50.3 (br); HRMS (FAB+Na) m/z calcd for
C
46H42B2NaP2 701.2846, found 701.2853.
1-[(S)-4,5-Dih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]p h osp h e-
p in obor a n e]-2-[(R)-4,5-d ih yd r o-3H-d in a p h th o[1,2-c:2′,1′-
e]p h osp h ep in ob or a n e]et h a n e (9-2BH3). Compound
9-2BH3 was prepared by the method described for 7-2BH3
using 29-2BH3 (25 mg, 0.062 mmol) and (R)-2,2′-di(bromom-
ethyl)-1,1′-dinaphthyl ((R)-24, 27 mg, 0.062 mmol): yield 48%
2) as eluent gave 28-BH3 (183 mg, 83%) as a colorless oil:
1
[R]20 +126 (c 0.1, CHCl3); H NMR (400 MHz, CDCl3) δ 7.76
1
D
(20 mg, white solid); H NMR (400 MHz, CDCl3) δ 7.90 (d, J
(m, 4H), 7.37 (d, J ) 8.8 Hz, 1H), 7.30 (d, J ) 7.1 Hz, 1H),
7.28 (d, J ) 7.5 Hz, 1H), 7.23 (d, J ) 8.5 Hz, 1H), 7.10-7.00
(m, 3H), 6.95 (d, J ) 8.5 Hz, 1H), 3.92 (m, 4H), 2.72 (d, J )
13.1 Hz, 1H), 2.61 (m, 2H), 2.44 (dd, J ) 12.8, 16.4 Hz, 1H),
1.88-1.52 (m, 4H), 1.14 (dt, J ) 9.9, 7.1 Hz, 6H), 0.7-0.1 (br,
3H); 13C NMR (100 MHz, CDCl3) δ 133.8, 133. 2, 133.1, 132.2,
132.0, 130.1, 130.0, 129.9, 129.8, 129.0, 128.9, 128.4, 128.3,
127.1, 126.8, 126.5, 126.3, 125.9, 125.7, 62.0 (d, J ) 6.5 Hz),
29.7 (d, J ) 46.0 Hz), 28.7 (d, J ) 29.5 Hz), 20.0, 18.6, 16.4 (d,
J ) 6 Hz), 16.1 (d, J ) 5.2 Hz); 31P NMR (202 MHz, CDCl3) δ
50.3 (br), 30.5 (dt, J ) 56.5, 8.1 Hz).
2-[(S)-4,5-Dih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]p h osp h e-
p in obor a n e]eth ylp h osp h in e (29-BH3). LAH (44 mg, 1.11
mmol) was added in small portions to a solution of 28-BH3
(180 mg, 0.37 mmol) in THF (3 mL) at 0 °C. After 30 min of
stirring, saturated aqueous sodium sulfate (40 µL) was added
with caution. The crude product was filtered through a plug
of silica to give, after evaporation of the solvent, 29-BH3 (101
mg, 71%) as a white solid which was directly used in the next
step: 1H NMR (400 MHz, CDCl3) δ 8.01-7.88 (m, 4H), 7.58
(d, J ) 8.3 Hz, 1H), 7.48 (m, 2H), 7.41 (d, J ) 8.2, 1H), 7.30-
7.22 (m, 3H), 7.15 (d, J ) 8.4, 1H), 2.94 (d, J ) 12.9 Hz, 1H),
2.85 (dt, J ) 195.0, 6.8 Hz, 2H), 2.82 (m, 2H), 2.62 (dd, J )
16.0, 12.9 Hz, 1H), 1.87-1.69 (m, 4H), 0.94-0.05 (br, 3H).
) 8.6 Hz, 2H), 7.87 (d, J ) 8.3 Hz, 2H), 7.83 (d, J ) 8.1 Hz,
2H), 7.67 (d, J ) 8.3 Hz, 2H), 7.50 (d, J ) 8.4 Hz, 2H), 7.41 (d,
J ) 7.8 Hz, 2H), 7.38 (d, J ) 7.8 Hz, 2H), 7.22 (d, J ) 8.6 Hz,
2H), 7.16 (m, 4H), 7.07 (t, J ) 9.8 Hz, 4H), 2.86 (d, J ) 13.1
Hz, 2H), 2.72 (dd, J ) 15.1, 3.2 Hz, 2H), 2.64 (d, J ) 15.1 Hz,
2H), 2.57 (dd, J ) 16.4, 12.9 Hz, 2H), 1.74 (m, 2H), 1.67 (m,
2H), 0.75- -0.1 (br, 6H); 13C NMR (100 MHz, CDCl3) δ 134.2,
133.7, 133.6, 133.4, 132.7, 132.4, 130.2, 129.6, 129.4, 128.9,
128.8, 128.7, 127.4, 127.2, 127.0, 126.8, 126.4, 126.2, 30.4 (d,
J ) 32.9 Hz), 28.6 (d, J ) 35.9 Hz), 17.2 (d, J ) 27.4 Hz); 31P
NMR (202 MHz, CDCl3) δ 50.7 (br); HRMS (FAB+Na) m/z
calcd for C46H42B2NaP2 701.2846, found 701.2853.
2-[(S)-4,5-Dih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]a zep in o]-
eth yla m in e (31). Ethylenediamine (1.8 g, 30 mmol) and
triethylamine (1.39 g, 13.7 mmol) in toluene (0.5 mL) were
added to (S)-2,2′-dibromoethyl-1,1′-binaphthyl ((S)-24, 104 mg,
0.236 mmol). The flask was sealed and heated to 60 °C for 24
h. Water and diethyl ether were added. The organic layer was
separated and dried (Na2SO4) and concentrated under vacuum
to give 31 (72 mg, 90%): 1H NMR (400 MHz, CDCl3) δ 7.83
(d, J ) 8.21 Hz, 4H), 7.46-7.28 (m, 6H), 7.19-7.10 (m, 2H),
3.55 and 3.10 (AB, J ) 12.2 Hz, 4H), 2.85-2.72 (m, 2H), 2.66-
2.56 (m, 1H), 2.38-2.28 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 135.0, 133.4, 133.1, 131.3, 128.3, 128.2, 127.7, 127.4, 125.7,
125.4, 58.0, 55.4, 39.7.
2-[(S)-4,5-Dih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]p h osp h e-
p in obor a n e]eth ylp h osp h in e-Bor a n e (29-2BH3). A solu-
tion of BH3‚Me2S (2 N in THF, 0.14 mL) was added to a
solution of 29-BH3 (101 mg, 0.26 mmol) in THF (2 mL), and
the mixture was stirred for 1 h at room temperature. The
solvent was removed under reduced pressure and the residue
1-[(R)-4,5-Dih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]a zep in o]-
2-[(S)-4,5-d ih yd r o-3H -d in a p h t h o[1,2-c:2′,1′-e]a zep in o]-
et h a n e (10). Compound (R)-24 (74.7 mg, 0.170 mmol) and
triethylamine (1 mL) were added to compound 31 (57 mg, 0.168
mmol) in toluene (1 mL), and the mixture was heated at 60
°C for 24 h. After the mixture was cooled to room temperature,
the solvent was evaporated and the remaining solid was
dissolved in chloroform. The organic phase was washed with
filtered through a plug of silica to give 29-2BH3 (83 mg, 81%)
1
as a white solid: [R]20 +100.2 (c 1.0, CHCl3); H NMR (400
D
MHz, CDCl3) δ 8.08-7.99 (m, 4H), 7.62 (d, J ) 8.1 Hz, 1H),
7.55 (d, J ) 7.6 Hz, 1H), 7.51 (d, J ) 8.2 Hz, 1H), 7.47 (d, J )
6.5 Hz. 1H), 7.32-7.27 (m, 3H), 7.20 (d, J ) 7.8 Hz, 1H), 4.76
(dm, J PH ) 370 Hz, 1H), 4.63 (dm, J PH ) 370 Hz, 1H), 3.00 (d,
J ) 12.8 Hz, 1H), 2.87 (m, 2H), 2.71 (app t, J ) 14.8 Hz, 1H),
1
water and dried (Na2SO4): yield 35%. The H NMR spectrum
of the product obtained was in agreement with that published.25b
(1S,2S)-1,2-Bis[(R)-4,5-dih ydr o-3H-din aph th o[1,2-c:2′,1′-
e]a zep in o]cycloh exa n e (11). (R)-2,2′-Dibromoethyl-1,1′-bi-
naphthyl ((R)-24, 443.5 mg, 1.0 mmol) and (1S,2S)-1,2-
diaminocyclohexane (57.5 mg, 0.5 mmol) were mixed with
toluene (5 mL) and triethylamine (420 µL, 3.0 mmol). The
resulting slurry was degassed at -78 °C and then warmed to
room temperature before the flask was sealed and heated at
60 °C for 60 h. The flask was cooled to room temperature, and
THF (5 mL) was added. The liquid was decanted, and the
residue was washed with THF (2 × 5 mL). The combined
liquids were filtered through a glass frit (P2) and concentrated
at reduced pressure. The crude product was recrystallized from
CHCl3/tert-butyl methyl ether to give 11 (164 mg, 49%) as a
white powder: mp 293-294 °C; [R]25D -185.5 (c 1.0, CHCl3);1H
NMR (400 MHz, CDCl3) δ 7.87 (d, J ) 8.1 Hz, 4H), 7.74 (d, J
) 8.2 Hz, 4H), 7.44-7.37 (m, 12H), 7.24-7.20 (m, 4H), 3.70
and 3.52 (AB, J ) 12.3 Hz, 8H), 2.85 (br d, J ) 8.5 Hz, 2H),
1.91 (br d, J ) 13.1 Hz, 2H), 1.76-1.66 (br m, 2H), 1.39-1.28
(br m, 2H), 1.24-1.16 (br m, 2H); 13C NMR (75 MHz, CDCl3)
δ 135.3, 134.6, 132.7, 131.5, 128.3, 128.2, 128.1, 127.4, 125.4,
125.0, 66.0, 51.7, 28.9, 25.8; MS (EI, direct inlet) 670 (M+),
2.16 (m, 2H), 1.97 (m, 1H), 1.78 (m, 1H), 0.2-0.9 (br, 6H); 13
C
NMR (100 MHz, CDCl3) δ 134.3 (d, J ) 3.0 Hz), 133.7 (d, J )
4.4 Hz), 133.6, 133.4, 132.7 (d, J ) 1.5 Hz), 132.4 (d, J ) 2.3
Hz), 130.1, 129.9, 129.8, 129.5, 129.5, 128.9, 128.6, 128.6, 127.3
(d, J ) 2.2 Hz), 127.2, 127.0, 126.9, 126.5, 126.3, 30.2 (d, J )
32.3 Hz), 29.1 (d, J ) 30.0 Hz), 19.9 (dd, J ) 26.0, 3.7 Hz),
10.9 (d, J ) 34.5 Hz); 31P NMR (202 MHz, CDCl3) δ 50.5, -46.7
(t, J ) 470 Hz).
1,2-Bis[(S)-4,5-d ih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]p h os-
p h ep in obor a n e]eth a n e (7-2BH3). Sodium hydride (4.2 mg,
0.175 mmol) was added in one portion to a solution of
phosphine-borane 29-2BH3 (30 mg, 0.075 mmol) and (S)-2,2′-
di(bromomethyl)-1,1′-diphenyl ((S)-24, 33 mg, 0.075 mmol) in
THF (0.3 mL) and the mixture was stirred for 2 h at room
temperature. The solid was filtered off and the filtrate
concentrated to give, after flash chromatography on silica gel
using CH2Cl2/hexane (1:1) as eluent, 7-2BH3 (26 mg, 51%) as
a white solid: [R]20 +39.5 (c 1.0, CHCl3); 1H NMR (400 MHz,
D
CDCl3) δ 8.05 (d, J ) 8.3 Hz, 2H), 7.95 (app q, J ) 7.3 Hz,
6H), 7.52-7.43 (m, 8H), 7.27-7.21 (m, 4H), 7.19 (d, J ) 8.0
3268 J . Org. Chem., Vol. 68, No. 8, 2003

Enantioselectivity in Palladium-Catalyzed Allylic Substitutions
391, 377, 308, 293, 266. HRMS (FAB+H) m/z calcd for
yield 62% (white solid, 62 mg); [R]20 +52.5 (c 1.0, CHCl3); 1H
D
C
50H43N2 671.3426, found 671.3434.
NMR (400 MHz, CDCl3) δ 7.97 (d, J ) 8.3 Hz, 1H), 7.88 (t, J
) 8.9 Hz, 3H), 7.54 (d, J ) 8.3 Hz, 1H), 7.50-7.36 (m, 10H),
7.22-7.09 (m, 5H), 3.74 (br d, J ) 12.7 Hz, 1H), 3.55 (br d, J
) 11.8 Hz, 1H), 3.30 (br, 2H), 3.02 (m, 2H), 2.86 (d, J ) 12.9
Hz, 1H), 2.79 (s, 1H), 2.77 (d, J ) 4.3 Hz, 1H), 2.68 (dd, J )
16.8, 13.1 Hz, 1H), 2.49 (qd, J ) 12.9, 4.2 Hz, 1H), 2.01 (qd, J
) 11.3, 6.3 Hz, 1H), 1.7-1.2 (br, 3H), 0.7-0.0 (br, 3H); 13C
NMR (100 MHz, CDCl3) δ 141.2, 134.2, 134.2, 133.9, 133.6,
133.5, 132.6, 132.5, 130.5, 130.4, 130.1, 130.0 (d, J ) 6 Hz),
129.7, 129.3, 128.9, 128.8, 128.8, 128.7, 128.7, 128.5, 128.0,
127.2, 127.1, 126.8, 126.4, 126.2, 55.8, 55.1, 53.9, 30.5 (d, J )
34 Hz), 29.2 (d, J ) 30 Hz), 18.6 (d, J ) 27 Hz). Anal. Calcd
for C38H38B2NP: C, 81.31; H, 6.82; N, 2.50. Found: C, 81.19;
H, 6.67; N, 2.35.
(1R,2R)-1,2-Bis[(R)-4,5-dih ydr o-3H-din aph th o[1,2-c:2′,1′-
e]a zep in o]cycloh exa n e (12). Compound 12 was prepared
analogously to 11 using (1R,2R)-1,2-diaminocyclohexane: yield
51% (white powder); mp 286-288 °C; [R]25 -314.8 (c 1.0,
D
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J ) 8.0 Hz, 4H),
7.85 (d, J ) 8.2 Hz, 4H), 7.47-7.39 (m, 12H), 7.27-7.23 (m,
4H), 3.85 and 3.59 (AB, J ) 11.7 Hz, 8H), 2.97 (br d, J ) 8.1
Hz, 2H), 1.88 (br d, J ) 10.7 Hz, 2H), 1.71-1.63 (br m, 2H),
1.33-1.15 (br m, 4H); 13C NMR (75 MHz, CDCl3) δ 135.7,
134.6, 132.8, 131.3, 128.5, 128.23, 128.17, 127.5, 125.4, 125.0,
66.7, 51.8, 29.0, 25.7; MS (EI, direct inlet) 670 (M+), 391, 377,
308, 293, 265; HRMS (FAB+H) m/z calcd for C50H43N2 671.3426,
found 671.3423.
1-[4,5-Dih yd r o-3H-d iben zo[c-e]a zep in o]-2-[(S)-4,5-d i-
h yd r o-3H -d in a p h t h o[1,2-c:2′,1′-e]p h osp h ep in ob or a n e]-
eth a n e (14-BH3). Compound 14-BH3 was prepared from
14-2BH3 (56 mg, 0.1 mmol) and DABCO (12 mg, 0.1 mmol)
by stirring under argon atmosphere for 12 h at room temper-
ature. Flash chromatography on silica gel using CH2Cl2/AcOEt
(98:2) as eluent gave 14-BH3 in 86% yield (47 mg, white
solid): [R]20D +80.1 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 7.91-7.84 (m, 4H), 7.51 (d, J ) 8.3 Hz, 1H), 7.44-7.34 (m,
7H), 7.28 (td, J ) 7.3, 1.3 Hz, 2H), 7.22 (d, J ) 6.6 Hz, 2H),
7.20-7.16 (m, 2H), 7.14 (d, J ) 6.6 Hz, 1H), 7.06 (dd, J ) 8.6
Hz, 1H), 3.32 (s, 4H), 2.93 (dd, J ) 13.3, 2.0 Hz, 1H), 2.86 (dd,
J ) 14.6, 5.1 Hz, 1H), 2.81 (m, 2H), 2.76 (dd, J ) 14.6, 9.3 Hz,
1H), 2.66 (dd, J ) 17.1, 13.3 Hz, 1H), 1.92 (m, 1H), 1.74 (m,
1H), 0.9-0.0 (br, 3H); 13C NMR (100 MHz, CDCl3) MHz δ
141.5, 134.4, 133.7, 133.6, 133.5, 133.3, 132.8, 132.4, 131.2,
130.8, 130.7, 130.1, 129.2, 128.9, 128.9, 128.8, 128.7, 128.7,
128.3, 128.1, 127.8, 127.3, 127.0, 126.7, 126.3, 126.0, 55.5, 49.2,
30.9 (d, J ) 33.0 Hz), 30.3 (d, J ) 30.5 Hz), 22.7 (d, J ) 25.5
Hz); 31P NMR (202 MHz, CDCl3) δ 47.2 (br).
1,3-Bis[(S)-4,5-d ih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]a ze-
p in o]p r op a n e (13).46 Compound 13 was prepared similarly
to 11 using 1,2-diaminopropane but was purified by column
chromatography on basic alumina (CH2Cl2/MeOH 9:1): yield
73% (pale yellow powder); mp 221-223 °C; [R]25 -172.6 (c
D
0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J ) 8.2 Hz,
8H), 7.58 (d, J ) 8.2 Hz, 4H), 7.52-7.45 (m, 8H), 7.29-7.25
(m 4H), 3.76 and 3.21 (AB, J ) 12.3 Hz, 8H), 2.68-2.62 (m,
2H), 2.51-2.44 (m, 2H), 2.03-1.96 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 135.0, 133.4, 133.1, 131.3, 128.29, 128.27, 127.8,
127.4, 125.7, 125.3, 55.3, 53.2, 26.9; MS (EI, direct inlet) 630
(M+), 308, 293, 266.
Dieth yl 2-[4,5-Dih yd r o-3H-d iben zo[c-e]a zep in o]eth -
ylp h osp h on a te (36). A solution of (2-aminoethyl)phosphonic
acid diethyl ester (21, 216 mg, 1.2 mmol) in THF (2.5 mL) was
added dropwise to a solution of 2,2′-di(bromomethyl)-1,1′-
diphenyl26 (35, 408 mg, 1.2 mmmol) and triethylamine (0.37
mL, 2.7 mmol) in THF (5 mL), and the mixture was stirred
for 8 h at 50 °C. The salt was filtered off and the filtrate
concentrated under reduced pressure to give, after purification
by flash chromatography on silica gel using CHCl3/MeOH (99:
1) as eluent, 36 (405 mg, 93%) as a yellow oil: 1H NMR (400
MHz, CDCl3) δ 7.55 (d, J ) 7.6 Hz, 2H), 7.41 (t, J ) 6.3 Hz,
2H), 7.37-7.32 (m, 4H), 4.18 (m, 4H), 3.46 (s, 4H), 2.92 (app.q,
J ) 8.3 Hz, 2H), 2.18 (m, 2H), 1.16 (t, J ) 7.0 Hz, 6H); 13C
NMR (100 MHz, CDCl3) δ 141.5, 134.7, 130.1, 128.3, 128.2,
128.0, 62.0 (d, J ) 5.7 Hz), 55.5, 48.9, 25.8 (d, J ) 138 Hz),
16.9 (d, J ) 6 Hz).
2-[4,5-Dih yd r o-3H -d ib e n zo[c-e ]a ze p in o]e t h ylp h os-
p h in e (37). Compound 37 was prepared by LAH reduction of
36 (130 mg, 0.36 mmol) in THF according to the procedure
used for the preparation of 29-BH3: yield 75% (white solid,
69 mg); 1H NMR (400 MHz, CDCl3) δ 7.41(d, J ) 7.6 Hz, 2H),
7.35 (td, J ) 6.8, 1.6 Hz, 2H), 7.30-7.23 (m, 4H), 3.32 (s, 4H),
2.64 (dd, J ) 14.4, 5.9 Hz, 2H), 2.61 (dt, J ) 195, 8.2 Hz, 2H),
1.73 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 141.5, 134.9, 130.1,
128.5, 128.14, 128.06, 58.5 (d, J ) 3.0 Hz), 55.5, 13.2 (d, J )
8.8 Hz).
2-[4,5-Dih yd r o-3H -d ib en zo[c-e]a zep in ob or a n e]et h -
ylp h osp h in e-Bor a n e (37-2BH3). Compound 37-2BH3 was
prepared from 37 (120 mg, 0.47 mmol) using a solution of BH3‚
Me2S (2M in THF): yield 89% (white solid, 117 mg); 1H NMR
(400 MHz, CDCl3) δ 7.52-7.48 (m, 4H), 7.42-7.35 (m, 4H),
4.62 (dsext, J ) 365, 7.1 Hz, 2H), 3.69 (d, J ) 12.4 Hz, 2H),
3.32 (br s, 2H), 2.99 (dd, J ) 16.3, 7.3 Hz, 2H), 2.53 (oct, J )
5.7 Hz, 2H), 1.0-0.6 (br, 3H), 0.6-0.1 (br, 3H); 13C NMR (100
MHz, CDCl3) δ 141.2, 132.4, 131.2, 130.2, 128.7, 128.6, 61.5
(br), 56.9, 12.6 (d, J ) 35 Hz).
1-[4,5-Dih yd r o-3H-d iben zo[c-e]a zep in obor a n e]-2-[(S)-
4,5-d ih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]p h osp h ep in obor a -
n e]eth a n e (14-2BH3). Compound 14-2BH3 was prepared in
analogy to 7 from 37-2BH3 (50 mg, 0.18 mmol) and (S)-2,2′-
di(bromomethyl)-1,1′-dinaphthyl ((S)-24, 79 mg, 0.18 mmol):
1-[(S)-4,5-Dih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]a zep in o-
b or a n e]-2-[4,5-d ih yd r o-3H -d ib en zo[c-e]p h osp h ep in o-
bor a n e]eth a n e (15-2BH3). Compound 15-2BH3 was pre-
pared by the method described for 14-BH3 using 38-2BH3
(55 mg, 0.14 mmol) and 2,2′-di(bromomethyl)-1,1′-diphenyl (35,
48 mg, 0.14 mmol): yield 53% (white solid, 42 mg): [R]20D +207
1
(c 0.5, CHCl3); H NMR (400 MHz, CDCl3) δ 8.09 (d, J ) 7.9
Hz, 0.5H), 8.05-7.96 (m, 3.5H), 7.78 (d, J ) 8.3 Hz, 0.5H),
7.71 (d, J ) 7.9 Hz, 0.5H), 7.62 (J ) 8.6 Hz, 0.5H), 7.59-7.27
(m, 14.5H), 4.02 (d, J ) 11.2 Hz, 0.5H), 3.92 (d, J ) 11.7 Hz,
0.5H), 3.81 (s, 1H), 3.73 (d, J ) 13.6 Hz, 0.5H), 3.64 (J ) 13.6
Hz, 0.5H), 3.26 (d, J ) 11.2 Hz, 0.5H), 3.21 (d, J ) 11.7 Hz,
0.5H), 3.10-2.60 (m, 6H), 2.17 (m, 2H), 1.75-1.45 (br, 3H),
0.8-0.1 (br, 3H); 31P NMR (202 MHz, CDCl3) δ 44.14 (br). Anal.
Calcd for C38H38B2NP: C, 81.31; H, 6.82; N, 2.50. Found: C,
81.09; H, 6.68; N, 2.42.
1-[(S)-4,5-Dih yd r o-3H-d in a p h th o[1,2-c:2′,1′-e]a zep in o]-
2-[4,5-d ih yd r o-3H -d ib e n zo[c-e ]p h osp h e p in ob or a n e ]-
eth a n e (15-BH3). Compound 15-BH3 was prepared by the
method employed for the preparation of 14-BH3 from 15-
2BH3 (40 mg, 0.071 mmol): yield 86% (white solid, 34 mg);
[R]20 +110.0 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ
D
7.82-7.74 (m, 4H), 7.39 (d, J ) 8.4 Hz, 1H), 7.34-7.06 (m,
14.5 H), 6.93 (d, J ) 7.8 Hz, 0.5H), 3.53 (d, J ) 12.4 Hz, 1H),
3.52 (d, J ) 12.2 Hz, 1H), 3.05 (d, J ) 12.4 Hz, 1H), 3.01 (d,
J ) 12.2 Hz, 1H), 2.81 (m, 1H), 2.73-2.44 (m, 5H), 1.81 (m,
1H), 1.61 (m, 1H), 0.8- -0.1 (br, 3H); 13C NMR (100 MHz,
CDCl3) δ 140.4, 139.7, 134.9, 133.2, 131.3, 130.4, 129.8, 129.2,
128.5 (2C), 128.2, 128.1, 128.0, 127.8 (2C), 127.5, 127.4, 125.8,
125.5, 55.1 (d, J ) 24 Hz), 48.8 (d, J ) 24 Hz), 29.7 (d, J ) 36
Hz), 29.1 (d, J ) 13 Hz), 22.6 (d, J ) 27.0 Hz), 22.2 (d, J )
29.0 Hz).
Typ ica l P r oced u r e for Ca ta lytic Asym m etr ic Allylic
Su bstitu tion Usin g P a lla d iu m Aceta te a s P a lla d iu m
Sou r ce. Ligand (S,S)-5-BH3 (5 mg, 0.0077 mmol) and rac-
1,3-diphenyl-2-propenyl acetate (78 mg, 0.31 mmol) were
mixed in degassed CH2Cl2 (0.7 mL) in a dry flask. Palladium
(46) This compound has previously been reported (electronic pub-
lication in J apanese): Nakada, M. Asahi Garasu Zaidan J osei Kenkyu
Seika Hokoku 1998; Chem. Abstr. 1998, 132, 193960.
J . Org. Chem, Vol. 68, No. 8, 2003 3269

Vasse et al.
acetate (1.73 mg, 0.0077 mmol) was added, and the solution
was degassed and stirred for 15 min at room temperature. A
solution of dimethyl malonate (91.8 mg, 0.69 mmol) and BSA
(189 mg, 0.93 mmol) in degassed CH2Cl2 (0.7 mL) was added
at -78 °C. Potassium acetate (a few crystals) was added, and
the solution was degassed and stirred at room temperature.
After complete reaction (monitored by HPLC), a saturated
solution of NH4Cl in water was added, and the aqueous layer
was extracted with Et2O. The organic phases were combined,
dried over Na2SO4, and concentrated under reduced pressure.
The residue was purified by flash chromatography on silica
gel with hexane/EtOAc (4:1) as eluent to give the product (95%,
98.5% ee (S)) as a white solid. The enantiomeric excess was
measured using HPLC (chiralcel OD-H, flow rate ) 0.5 mL/
min, hexane/2-propanol ) 99:1, tR ) 21.30 min, tS ) 22.85 min.
The same procedure was used for the dimethyl(3-cyclohex-
enyl)malonate, but the product was purified by flash chroma-
tography on silica gel with hexane/EtOAc (95:5) as eluent. The
enantiomeric excess was mesured using GC: Chrompack
Permethyl-â-CD.
the solution was degassed, allylpalladium chloride dimer (1.05
mg, 2.9 µmol) was added, and the solution was stirred at room
temperature for 20 min. rac-1,3-Diphenyl-2-propenyl acetate
(138.8 mg, 0.55 mmol) in degassed CH2Cl2 (0.6 mL) was added
at -78 °C, followed by a solution of dimethyl malonate (163
mg, 1.24 mmol) and BSA (335 mg, 1.65 mmol) in degassed CH2-
Cl2 (0.8 mL). Potassium acetate (a few crystals) was added,
and the solution was degassed and stirred at room tempera-
ture. After complete reaction, a saturated solution of NH4Cl
in water was added, and the aqueous layer was extracted with
diethyl ether. The organic phases were combined, dried over
Na2SO4, and concentrated under reduced pressure. The residue
was purified by flash chromatography on silica gel with
hexane/EtOAc (4:1) as eluent to give the product (93%, 98.4%
ee (S)) as a white solid.
Ack n ow led gm en t. This work was supported finan-
cially by the Go¨ran Gustafsson Foundation for Research
in Sciences and Medicine and by the Swedish Research
Council.
Typ ica l P r oced u r e for Ca ta lytic Asym m etr ic Allylic
Su bstitu tion Usin g Allylp a lla d iu m Ch lor id e Dim er a s
P a lla d iu m Sou r ce. To a degassed solution of (S,S)-1-BH3
(7.15 mg, 11 µmol) in toluene (0.3 mL) was added a degassed
solution of DABCO (2.5 mg, 22.1 µmol) in toluene (0.1 mL),
and the mixture was stirred for 8 h at 80 °C. The solvent was
removed under reduced pressure. CH2Cl2 (0.5 mL) was added,
Su p p or tin g In for m a tion Ava ila ble: NMR spectra for
obtained compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O026889E
3270 J . Org. Chem., Vol. 68, No. 8, 2003