A Widely Applicable Chiral Auxiliary, cis-2-Amino-3,3-dimethyl-1-indanol: Conversion to a Novel Phosphorus-Containing Oxazoline and Its Application as a Highly Efficient Ligand for the Palladium-Catalyzed Enantioselective Allylic Amination Reaction

Article abstract of DOI:10.1021/jo970359e

A chiral amino alcohol, cis-2-amino-3,3-dimethyl-1-indanol (2), was converted into the corresponding enantiomerically pure phosphorus-containing oxazoline 4. Oxazoline 4 was found to be an efficient ligand for palladium-catalyzed enantioselective allylic amination reactions: In the amination reaction of (E)-1,3-diphenyl-2-propen-1-yl acetate (7a), 4 was found to be more efficient than the similar ligands 1a-c, derived from valinol, tert-leucinol, etc. Other 1,3-bis(p-substituted aryl)-2-propen-1-y] acetates were also converted to the corresponding amines in a similar manner and with excellent enantioselectivity. In the amination reaction of 1-alkyl-3,3-diphenyl-2-propen-1-yl acetates 11, the correponding amines 12 were obtained with excellent enantioselectivity when acetic acid was added to the reaction system.

Full text of DOI:10.1021/jo970359e

5508
J . Org. Chem. 1997, 62, 5508-5513
A Wid ely Ap p lica ble Ch ir a l Au xilia r y,
cis-2-Am in o-3,3-d im eth yl-1-in d a n ol: Con ver sion to a Novel
P h osp h or u s-Con ta in in g Oxa zolin e a n d Its Ap p lica tion a s a High ly
Efficien t Liga n d for th e P a lla d iu m -Ca ta lyzed En a n tioselective
Allylic Am in a tion Rea ction
Atsushi Sudo and Kazuhiko Saigo*
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113, J apan
Received February 25, 1997X
A chiral amino alcohol, cis-2-amino-3,3-dimethyl-1-indanol (2), was converted into the corresponding
enantiomerically pure phosphorus-containing oxazoline 4. Oxazoline 4 was found to be an efficient
ligand for palladium-catalyzed enantioselective allylic amination reactions: In the amination
reaction of (E)-1,3-diphenyl-2-propen-1-yl acetate (7a ), 4 was found to be more efficient than the
similar ligands 1a -c, derived from valinol, tert-leucinol, etc. Other 1,3-bis(p-substituted aryl)-2-
propen-1-yl acetates were also converted to the corresponding amines in a similar manner and
with excellent enantioselectivity. In the amination reaction of 1-alkyl-3,3-diphenyl-2-propen-1-yl
acetates 11, the correponding amines 12 were obtained with excellent enantioselectivity when acetic
acid was added to the reaction system.
Sch em e 1
In tr od u ction
The palladium-catalyzed allylic amination reaction is
a useful synthetic transformation as the resulting amines
can be converted into various kinds of chiral compounds
including R-amino acid derivatives.1 Recently, phosphorus-
containing oxazolines, 2-[2-(diphenylphosphino)phenyl]-
oxazolines 1,2-4 which are at present widely used for
various kinds of transition metal-catalyzed enantio-
selective reactions, have been reported also to be ap-
plicable to palladium-catalyzed allylic amination reac-
tions (Scheme 1).5 These studies showed that the effi-
ciency of chiral induction by 1 depends greatly on the
substituent at the 4-position of the oxazoline moiety.
Therefore, it is important to develop amino alcohols
allowing the construction of oxazolines having suitable
Sch em e 2
*To whom correspondence should be addressed. FAX: +81-3-5802-
3348. E-mail: saigo@chiral.t.u-tokyo.ac.jp.
X Abstract published in Advance ACS Abstracts, J uly 15, 1997.
(1) (a) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishikawa, E.; Miura,
H.; Yanagi, K. J . Am. Chem. Soc. 1989, 111, 6301. (b) Hayashi, T.;
Kishi, K.; Yamamoto, A.; Ito, Y. Tetrahedron Lett. 1990, 31, 1743. (c)
Yamazaki, A.; Achiwa, K. Tetrahedron: Asymmetry 1995, 6, 51. (d)
Togni, A.; Burckhardt, U.; Gramlich, V.; Pregosin, P. S.; Salzmann, R.
J . Am. Chem. Soc. 1996, 118, 1031. (e) Trost, B. M.; Kruger, A. C.;
Bunt, R. C.; Zambrano, J . J . Am. Chem. Soc. 1996, 118, 6520. (f) Trost,
B. M.; Vranken, D. L. V. Chem. Rev. 1996, 96, 395.
(2) For their preparations, see: (a) Allen, J . V.; Dauson, G. J .; Frost,
C. G.; Williams, J . M. J . Tetrahedron 1994, 50, 799. (b) Peer, M.; J ong,
J . C.; Kieter, M.; Langer, T.; Rieck, H.; Schell, H.; Sennhenn, P.; Sprinz,
J .; Steinhagen, H.; Wiese, B.; Helmchen, G. Tetrahedron 1996, 52,
7547. For a review, see: (c) Williams, J . M. J . Synlett 1996, 705.
(3) For allylic substitution reactions, see: (a) Matt, P. V.; Pfalz, A.
Angew. Chem., Int. Ed. Engl. 1993, 32, 566. (b) Sprinz, J .; Helmchen,
G. Tetrahedron Lett. 1993, 34, 1769. (c) Rieck, H.; Helmchen, G.
Angew. Chem., Int. Ed. Engl. 1995, 34, 2687. (d) Eichelmann, H.; Gais,
H. J . Tetrahedron: Asymmetry 1995, 6, 643. (e) Evans, P. A.; Branolt,
T. A. Tetrahedron Lett. 1996, 37, 9143.
(4) For hydrosilylations, see: (a) Newman, L. M.; Williams, J . M.
J .; McCague, R.; Potter, G. A. Tetrahedron: Asymmetry 1996, 7, 1597.
(b) Langer, T.; J anssen, J .; Helmchen, G. Tetrahedron: Asymmetry
1996, 7, 1599. (c) Nishibayashi, Y.; Segawa, K.; Ohe, K.; Uemura, S.
Organometallics 1995, 14, 5486. For the Heck reaction, see: (d)
Loiseleur, O.; Meier, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1996,
35, 200.
(5) (a) Matt, P. V.; Loiseleur, O.; Kock, G.; Pfaltz, A. Tetrahedron:
Asymmetry 1994, 5, 573. (b) J umnah, R.; Williams, A. C; Williams, J .
M. J . Synlett 1995, 821.
substituents in this position in order to achieve higher
selectivity in the palladium-catalyzed allylic amination
reaction.
In the course of our continuing investigations on the
consecutive design, synthesis, and resolution of non-
natural chiral auxiliaries,6 we have recently developed
a chiral amino alcohol, cis-2-amino-3,3-dimethyl-1-in-
danol (2),7 and found that a chiral oxazolidinone derived
from 2 is an efficient auxiliary for various kinds of
diastereoselective reaction of the corresponding imide
enolates 3 with electrophiles (Scheme 2).7a The success
of these reactions is thought to arise from the structural
characteristics of 2; the two conformationally-fixed meth-
yl substituents shield one side of the diastereofaces of 3
very effectively. These observations prompted us to
(6) (a) Hashimoto, Y.; Takaoki, K.; Sudo, A.; Ogasawara, T.; Saigo,
K. Chem. Lett. 1995, 235. (b) Hashimoto, Y.; Kobayashi, N.; Kai, A.;
Saigo, K. Synlett 1995, 961. (c) Hashimoto, Y.; Kai, A.; Saigo, K.
Tetrahedron Lett. 1995, 36, 8821. (d) Sudo, A.; Matsumoto, M.;
Hashimoto, Y.; Saigo, K. Tetrahedron: Asymmetry 1995, 6, 1853.
(7) (a) Sudo, A.; Saigo, K. Tetrahedron: Asymmetry 1996, 7, 2939.
(b) Sudo, A.; Saigo, K. Chem. Lett. 1997, 97.
S0022-3263(97)00359-9 CCC: $14.00 © 1997 American Chemical Society

cis-2-Amino-3,3-dimethyl-1-indanol
J . Org. Chem., Vol. 62, No. 16, 1997 5509
Sch em e 3
Sch em e 5
Sch em e 4
Ta ble 1. Asym m etr ic Am in a tion of 7a
T
(°C)
reaction
time/h product
yield/
%
%
eeb
entry
7
R
Nu
1
7a Ph
NHBn rt
24
(R)-8a
(S)-8a
(R)-9a
(R)-8b
(R)-9b
(R)-8c
(R)-9c
(S)-8d
89
92
88
94
81
97
96
99
95
98
2c
3
NPhth 50
11
21
13
24
10
8
4
5
6
7
8f
7b p-Cl-C6H4 NHBn rt
NPhth 50
7c p-Br-C6H4 NHBn rt
NPhth 50
66d 99
36e 97
80g 20h
7d Me
NHBn reflux
a
(+)-4, 3.6 mol %; [Pd(allyl)Cl]2, 1.5 mol %; BnNH2 or K-
b
phthalimide, 2 equiv; solvent, THF. Determined by chiral HPLC
analysis (Daicel Chiralcel OD). c (-)-4 was used instead of (+)-4.
7c was recovered in 22% yield. e 7c was recovered in 54% yield.
d
convert 2 to 2-[2-(diphenylphosphino)phenyl]oxazoline 4
in the expectation that this would be an efficient enan-
tiomerically-pure ligand for transition metal-catalyzed
reactions, since the two methyl substituents should
strongly influence the chiral environment around the
stereogenic center adjacent to the nitrogen atom of the
corresponding transition metal complex 5 (Scheme 3).
Amino alcohol 2 has the great advantage as a chiral
auxiliary that both its enantiomers can be obtained easily
via resolution. Consequently, both enantiomers of 4 are
available, with use of the appropriate one leading to the
synthesis of target compounds of the desired absolute
configuration.
f 5 mol % [Pd(allyl)Cl]2 and 12 mol % (+)-4 were used. E:Z ratio
g
of the product was determined to be 96:4 by 270 MHz 1H-NMR
analysis. Ee of the (E)-isomer was determined by 270 MHz 1H-
h
NMR analysis of the corresponding MTPA amide.
using (-)-4 as a ligand gave (S)-8a with excellent
selectivity (Table 1, entry 2). Excellent selectivities were
also observed in the amination reactions of 7b and 7c,
which contain para-substituted phenyl groups (Table 1,
entries 4-7). These results indicate that enantiomeri-
cally pure 4 is an excellent ligand for the palladium-
catalyzed asymmetric allylic amination.
However, the reactions of 7c to give (R)-8c and (R)-9c
were incomplete; the reason for this unsatisfactory result
is not clear at present, since no significant byproducts,
for example, such as might be formed via oxidative
addition of the palladium complex to the C-Br bond of
the substrate, were detected. Moreover, the reaction of
3-penten-2-yl acetate (7d ) with benzylamine required a
higher temperature and a larger amount of the catalyst
and resulted in disappointingly low enantioselectivity,
presumably due to the high reaction temperature (Table
1, entry 8).
In this paper, we describe the synthesis of the new
phosphorus-containing oxazoline 4 and its application as
a ligand for the enantioselective palladium-catalyzed
allylic amination reaction.
Resu lts a n d Discu ssion
The enantiomerically pure ligand (+)-4 was synthe-
sized from (1R,2S)-2 in two steps according to the
procedure reported for the preparation of 1 (Scheme 4).2
Condensation of (1R,2S)-2 with 2-fluorobenzonitrile in
the presence of a catalytic amount of ZnCl2 gave 2-(2-
fluorophenyl)oxazoline (+)-6, which was treated with
Ph2PK to give (+)-4. The enantiomer, (-)-4, was simi-
larly synthesized from (1S,2R)-2.
The palladium-catalyzed allylic amination reaction was
carried out in THF using a catalyst prepared in situ by
mixing 1.5 mol % of [Pd(allyl)Cl]2 and 3.6 mol % of (+)-4
(Scheme 5, Table 1). As nitrogen nucleophiles, benzyl-
amine and potassium phthalimide (2 equiv to the sub-
strate) were selected.
The reactions of (E)-1,3-diphenyl-2-propen-1-yl acetate
(7a ) with benzylamine and with potassium phthalimide
using (+)-4 as a ligand gave the corresponding aminated
products (R)-8a and (R)-9a , respectively, with excellent
selectivities (Table 1, entries 1 and 3), superior to the
results obtained by using 1 as a ligand;5 the reaction of
7a with benzylamine using 1b and that with potassium
phthalimide using 1a gave 8a of 89% ee and 9a of 96%
ee, respectively. The reaction of 7a with benzylamine
The absolute configurations of 8a and 8d were con-
firmed to be R and S, respectively, by comparison of the
signs of their optical rotations with those in the litera-
ture.1,5 The absolute configurations of the other products
were also deduced to be R by correlation of the signs of
their optical rotations (the signs of all the products are
minus) and of their the elution orders in HPLC analyses
with those of 8a .
As was observed in the reaction of 7d , with a few
exceptions1b,e,f achievement of excellent enantioselectivity
in the allylic substitution of 1,3-dialkyl-2-propen-1-ol
derivatives is known to be difficult. Thus, we chose the
3,3-diphenyl-2-propen-1-ol derivatives 10 and 11, which
can be regarded as synthetic equivalents of 7, as sub-
strates, because the product 12 gives the same amino acid
derivative on oxidative cleavage of the CdC bond as does
8 (Scheme 6), and carried out the reactions of carbonate
10 and acetate 11 with benzylamine in the presence of
the (+)-4-palladium complex as a catalyst.

5510 J . Org. Chem., Vol. 62, No. 16, 1997
Sudo and Saigo
Sch em e 6
Sch em e 8
Sch em e 7
reaction system, the amount of benzylamine was also
increased from 2 to 5 equiv, and this led to great
improvement in the chemical yield with no deterioration
in the enantiomeric excess of the product (Table 2, entry
5). Further increasing the amounts of benzylamine and
acetic acid allowed lowering of the reaction temperature
(Table 2, entry 6).
Ta ble 2. Effect of Ad d ition of Acetic Acid in Asym m etr ic
Am in a tion of 11a
Under the conditions used in entry 6 of Table 2, the
amination reaction of 1,1-diphenyl-1-hepten-3-yl acetate
(11b) was also carried out (Table 2, entry 7). Unfortu-
nately, the reaction did not go to completion even after
10 h, and 12% of acetate 11b was recovered. Further-
more, the yield of the product 12b was low (30%), and a
significant amount of the corresponding diene 13b was
obtained (58%), due to the high tendency of 11b to
eliminate. However, the enantiomeric excess of amine
12b obtained was excellent (94% ee). These results
clearly demonstrate that (+)-4 is a highly effective ligand
for the palladium-catalyzed asymmetric allylic amination;
Bosnich et al. reported that the reaction of the acetate
11a with benzylamine was catalyzed by a complex of
palladium with a chiral diphosphine to give the corre-
sponding amine regioselectively with moderate enantio-
selectivity (up to 76% ee using NORPHOS as a ligand),8
while Williams et al. reported that the reactions of
1-substituted 3,3-diphenyl-2-propen-1-yl acetates with
potassium phthalimide using the 1a -palladium complex
as a catalyst did not proceed at all.9
Amine 12a was converted to methyl (S)-2-(N-benzyl-
N-mesylamino)propionate according to the reported pro-
cedure,8 showing that the absolute configuration of 12a
is S. The absolute configuration of 12b is considered to
be S from correlation of the sign of its optical rotation
with that of 12a .
The excellent R selectivity in the reactions of 7 using
(+)-4 can be explained as follows. On the basis of
detailed NMR and X-ray crystallographic studies con-
cerning the structure of a π-allylpalladium complex with
1a ,10a (+)-4 is considered to coordinate with palladium
sub- amt of amt of reaction yield
yield
% ee
entry strate BnNH2 AcOH time/h of 12/% of 13/% of 12b
1
2
3
4
10a
11a
2
0
6
8
4
5
2
14c
38
48
43
79
82
30f
71
54
49
36d
20
13
58
85
92
98
>99
98
2
5
5
5
10
6e
7
10
3
10
98
11b
94g
a
(+)-4, 12 mol %; [Pd(allyl)Cl]2, 5 mol %; solvent, THF; reflux.
Determined by chiral HPLC analysis (Daicel Chiralcel OJ ). c A
b
d
trace amount of 14a was obtained. 11a was recovered in 21%
yield. e The reaction was carried out at 60 °C. f 11b was recovered
g
in 12% yield.
Chiralcel OD).
Determined by chiral HPLC analysis (Daicel
The reaction of the carbonate 10a with benzylamine
gave the corresponding amine 12a with good enantio-
selectivity (Scheme 7, Table 2, entry 1). However, the
chemical yield of 12a was low, and a significant amount
of 1,1-diphenyl-1,3-butadiene (13a ) and a trace amount
of N-benzyl-[(E)-1,1-diphenyl-2-butenyl]amine (14a ) were
obtained. Utilization of acetate 11a as a substrate
slightly improved both the chemical yield and the enan-
tiomeric excess of 12a , although 13a was also obtained
as a major product (Table 2, entry 2). These results
indicate that elimination reactions must be depressed if
the yield of the desired product is to be improved. To
this end, we examined addition of acetic acid to the
reaction of 11a with benzylamine.
When acetic acid (2 equiv versus 11a ) was added, the
reaction proceeded faster than in the absence of acid, and
not only the chemical yield, as expected, but also the
enantiomeric excess of 12a were improved (Table 2,
entries 2 vs. 3). However, addition of 5 equiv of acetic
acid inhibited complete conversion of 11a , probably due
to decomposition of the ligand under the acidic conditions
(Table 2, entry 4). In order to control the acidity of the
(8) Auburn, P. R.; Mackenzie, P. B.; Bosnich, B. J . Am. Chem. Soc.
1985, 107, 2033.
(9) Dowson, G. J . ; Williams, J . M. J .; Coote, S. J . Tetrahedron:
Asymmetry 1995, 6, 2535.

cis-2-Amino-3,3-dimethyl-1-indanol
J . Org. Chem., Vol. 62, No. 16, 1997 5511
Sch em e 9
using both phosphorus and nitrogen atoms, and the
conformation of the diphenylphosphino group of (+)-4 is
presumed to be as shown in 15 and 16 (Scheme 8). Since
the nucleophilic attack of benzylamine on a π-allyl-
palladium intermediate occurs regioselectively at the
carbon atom trans to phosphorus,1d,10 the enantioselec-
tivity of the product is strongly affected by the ratio of
these two intermediates. Of the two, 15 should be
preferred to 16, since the steric repulsion between the
Ar of the π-allyl moiety and the equatorial phenyl group
(PhE) on the phosphorus atom in 16 is serious. Here, the
conformationally-fixed methyl substituents of the ligand
(+)-4 are considered to have more effective bulk than the
tert-butyl substituent of 1b, and hence, in the (+)-4-
palladium complex, the π-allyl moiety is positioned closer
to the PhE in order to avoid steric repulsion between the
two methyl substituents of (+)-4 and the π-allyl moiety.
This causes the steric repulsion between the allylic
substituent and PhE in 16 to become more serious, and
consequently, its formation is strongly disfavored. Ben-
zylamine selectively reacts with 15 at the carbon atom
trans to the phosphorus of favored intermediate 15 to give
the product with excellent selectivity.
rus to afford the product with the observed regio- and
stereoselectivities. In contrast, in the case of 20 the
formation of (R)-12 requires reaction at the carbon atom
trans to the nitrogen; the reaction is unfavorable, even
though it is not negligible when the concentration of 20
is high. Since 18 and 20 are formed from (S)-11 and (R)-
11, respectively, a rapid interconversion between 18 and
20 is essential for the selective conversion of the both
enantiomers of 11 into (S)-12 (Scheme 9). The σ-allyl-
palladiums 21 and 22 would be the intermediates in such
an interconversion. Diene 13 is thought to be formed by
the â-elimination of palladium hydride from 22. There-
fore, the formation of a sufficient amount of 21 and 22,
along with the suppression of the â-elimination of pal-
ladium hydride from 22, is necessary to obtain (S)-12 in
high yield with excellent selectivity.
Such desirable reaction conditions can be achieved by
adding acetic acid to the reaction system; the role of this
is thought to be as follows. Since acetate anions are able
to strongly coordinate12 and fulfill the vacant sites of
palladium(II), the σ-allylpalladiums would be consider-
ably stabilized. Furthermore, the migration of â-hydride
to palladium(II) can be prevented by such coordination.
The explanation is strongly supported by the fact that
addition of 1-adamantylcarboxylic acid, which is unable
to coordinate to palladium because of its bulkiness, in
the place of acetic acid resulted in no improvement in
the chemical yield of the product (16% yield, 90% ee). It
might also be possible that the diene 13 is converted to
12 by palladium-catalyzed addition of benzylamine.
In the reaction of 11, there are four possible π-allyl-
palladium intermediates 17-20 as shown in Scheme 9.9,11
Of these, 18 and 20 would be more favorable than 17
and 19, respectively, as discussed above. Complex 18
reacts with benzylamine at the carbon trans to phospho-
(10) For detailed structural investigations of the π-allypalladium
complex of a phosphorus-containing oxazoline, see: (a) Sprinz, J .;
Kiefer, M.; Helmchen, G.; Reggelin, M.; Huttner, G.; Walter, O.;
Zsolnai, L. Tetrahedron Lett. 1994, 35, 1523. For detailed structural
investigations of the π-allypalladium complexes of other P,N ligands,
see: (b) Broun, J . M.; Hulues, D. I.; Guiry, P. J . Tetrahedron 1994,
50, 4493. (c) Blo¨chl, P. E.; Togni, A. Organometallics 1996, 15, 4125.
(11) Mackenzie, P. B.; Whelan, J .; Bosnich, B. J . Am. Chem. Soc.
1985, 107, 2046.
(12) A significant effect of the counteranion of palladium in an allylic
amination has recently been reported: Burckhardt, U.; Baumann, M.;
Togni, A. Tetrahedron: Asymmetry 1997, 8, 155.
(13) Armbruster, R. W.; Morgan, M. M.; Schmidt, J . L.; Lau, C. M.;
Riley, R. M.; Zabrowski, D. L.; Dieck, H. A. Organometallics 1986, 5,
234.

5512 J . Org. Chem., Vol. 62, No. 16, 1997
Sudo and Saigo
amorphous mass (881 mg, 3.13 mmol, 30%), which was used
for the following reaction without further purification.
An analytical sample was recrystallized from hexane to give
However, this mechanism can be excluded, since 13 was
inert under the reaction conditions used in entry 5 of
Table 2.
colorless prisms: [R]22 ) -118 (c 0.875, CHCl3). Other
D
physical data were identical with those of (+)-6.
Con clu sion s
(3a R,8bS)-2-[2-(Dip h en ylp h osp h in o)p h en yl]-3a ,8b-d i-
h yd r o-4,4-d im eth yl-4H-in d en o[1,2-d ]oxa zole ((+)-4). To
potassium diphenylphosphide17 (34 mL, 9.2 mmol; 0.27 M
solution in THF/dioxane (4/6)) was added a solution of (+)-6
(1.30 g, 4.62 mmol) in THF (5 mL) at 0 °C, and the resulting
solution was stirred for 1 h at rt. The reaction was quenched
by adding water (30 mL), and the mixture was extracted with
ether (3 × 20 mL). After usual workup, purification by column
chromatography (hexane/ethyl acetate (19/1)) gave (+)-4 as a
A chiral amino alcohol, cis-2-amino-3,3-dimethyl-1-
indanol (2), of which both enantiomers can be easily
obtained via its resolution, was converted into the cor-
responding enantiomerically pure phosphorus-containing
oxazoline 4. Oxazoline 4 was found to be an efficient
ligand for palladium-catalyzed enantioselective allylic
amination reactions: In the amination reaction of (E)-
1,3-diphenyl-2-propen-1-yl acetate (7a ), 4 was found to
be more efficient than the similar ligands 1, which were
derived from valinol, tert-leucinol, etc. Other 1,3-bis(p-
substituted aryl)-2-propen-1-yl acetates were also con-
verted to the corresponding amines with excellent enan-
tioselectivity. In the amination reaction of 1-alkyl-3,3-
diphenyl-2-propen-1-yl acetates 11, the corresponding
amines 12 were obtained with excellent enantioselectivity
when acetic acid was added to the reaction system.
colorless amorphous mass (1.43 g, 3.19 mmol, 65%): [R]22
)
D
1
+95 (c 2.99, CHCl3); IR (KBr) 1642; H-NMR (CDCl3) δ 1.08
(3H, s), 1.21 (3H, s), 4.50 (1H, d, J ) 7.6), 5.84 (1H, d, J )
7.6), 6.8-6.9 (1H, m), 7.1-7.4 (16H, m), 7.8-7.9 (1H, m);
HRMS(EI) calcd for C30H26NOP 447.1752, found 447.1737.
(3a S,8bR)-2-[2-(Dip h en ylp h osp h in o)p h en yl]-3a ,8b-d i-
h yd r o-4,4-d im eth yl-4H-in d en o[1,2-d ]oxa zole ((-)-4). Ac-
cording to the procedure given for the preparation of (+)-4,
(-)-4 was obtained from (-)-6 (800 mg, 2.84 mmol) as a
colorless amorphous mass (364 mg, 0.812 mmol, 29%): [R]22
D
) -96 (c 2.82, CHCl3). Other physical data were identical with
those of (+)-4.
(E)-1,3-Bis(2-ch lor op h en yl)-2-p r op en yl Aceta te (7b).
Sodium borohydride (0.10 g, 2.9 mmol) was added in several
portions to a suspension of (E)-1,3-bis(2-chlorophenyl)-1-oxo-
2-propene (0.80 g, 2.9 mmol) and cerium chloride heptahydrate
(1.1 g, 2.9 mmol) in methanol (20 mL) at 0 °C. After the
reaction mixture had been stirred at the same temperature
for 10 min, the reaction was quenched by adding water (20
mL), and the mixture was extracted with ether (3 × 30 mL).
Usual workup gave a viscous oil ((E)-1,3-bis(2-chlorophenyl)-
2-propen-1-ol), which was used for the following reaction
without further purification. To an ethereal solution (4 mL)
of this alcohol, pyridine (1 mL), and a catalytic amount of
4-(dimethylamino)pyridine was added acetyl chloride (0.50 mL,
7.0 mmol) dropwise at 0 °C. After the mixture had been stirred
for 12 h, the reaction was quenched by adding water (10 mL),
and the mixture was extracted with ether (3 × 20 mL). The
combined extracts were successively washed with 10% HCl (aq)
(3 × 20 mL), saturated aqueous NaHCO3 (30 mL), and brine
(30 mL). After usual workup, purification by column chro-
matography (hexane/ethyl acetate (9/1)) gave 7b as a colorless
oil (0.93 g, 2.9 mmol, quant): IR (NaCl) 1740, 1230; 1H-NMR
(CDCl3) δ 2.13 (3H, s), 6.27 (1H, dd, J ) 6.6, 16), 6.38 (1H, d,
J ) 6.6), 6.56 (1H, d, J ) 16), 7.2-7.4 (8H, m); HRMS(EI)
calcd for C17H14Cl2O2 320.0371, found 320.0360.
(E)-1,3-Bis(2-br om op h en yl)-2-p r op en yl Aceta te (7c).
According to the procedure given for the preparation of 7b,
7c (2.6 g, 6.3 mmol, 93%) was obtained from (E)-1,3-bis(2-
bromophenyl)-1-oxo-2-propene (2.50 g, 6.8 mmol) as a colorless
oil: IR (NaCl) 1740, 1230; 1H-NMR (CDCl3) δ 2.13 (3H, s), 6.30
(1H, d, J ) 22), 6.30 (1H, dd, J ) 16, 22), 6.54 (1H, dd, J )
16), 7.22 (2H, d, J ) 8.6), 7.27 (2H, d, J ) 8.6), 7.42 (2H, d, J
) 8.6), 7.50 (2H, d, J ) 8.6); HRMS(EI) calcd for C17H14Br2O2
407.9360, found 407.9374.
1,1-Dip h en yl-1-h ep ten -3-yl Aceta te (11b). To a solution
of 3,3-diphenylpropenal (1.00 g, 4.80 mmol) in THF (20 mL)
was added butyllithium (3.2 mL, 5.2 mmol; 1.63 M solution
in hexane) at -78 °C, and the mixture was stirred for 1 h at
0 °C. The reaction was quenched by adding saturated NH4Cl
(aq) (15 mL), and was extracted with ether (3 × 20 mL). Usual
workup gave a viscous oil, 1,1-diphenyl-1-hepten-3-ol, which
was used for the following reaction without further purifica-
tion. To an ethereal solution (15 mL) of this alcohol, pyridine
(1 mL), and a catalytic amount of 4-(dimethylamino)pyridine
was added acetyl chloride (1.0 mL, 14 mmol) dropwise at 0
°C, and this mixture was stirred for 12 h. The reaction was
quenched by adding water (10 mL), and the mixture was
extracted with ether (3 × 20 mL). The combined extracts were
Exp er im en ta l Section
Gen er a l. The starting materials and reagents, purchased
from commercial suppliers, were used after standard purifica-
tion. cis-2-Amino-3,3-dimethyl-1-indanol was synthesized and
resolved according to the procedure previously reported by us.6
(E)-1,3-Bis(2-chlorophenyl)-1-oxo-2-propene,14 (E)-1,3-bis(2-bro-
mophenyl)-1-oxo-2-propene,15 and 3,3-diphenylpropenal16 were
synthesized according to the reported procedures. All of the
solvents were dried over sodium wire or molecular sieves and
were distilled before use. Reaction flasks were flame-dried
under a stream of Ar. All moisture- and oxygen-sensitive
reactions were conducted under an Ar atomosphere. Flash
chromatography was carried out using silica gel 60 (70-230
mesh). Preparative TLC (PTLC) was carried out with Wakogel
B-5F. “Usual workup” represents the sequence of drying the
combined extracts over Na2SO4, filtering off Na2SO4, and
concentrating the filtrate under reduced pressure.
The melting points are uncorrected. HPLC analysis was
performed with detection by UV light. 1H-NMR (270 MHz)
spectra were measured with Me4Si as an internal standard;
the δ and J values are given in ppm and Hz, respectively. IR
spectral data are recorded in units of cm-1
.
(3a R ,8b S )-2-(2-F lu or op h e n yl)-3a ,8b -d ih yd r o-4,4-d i-
m eth yl-4H-in d en o[1,2-d ]oxa zole ((+)-6). To a suspension
of ZnCl2 (30 mg) and (1R,2S)-2-amino-3,3-dimethyl-1-indanol
((1R,2S)-2) (556 mg, 3.14 mmol) in chlorobenzene (7 mL) was
added 2-fluorobenzonitrile (0.38 g, 3.2 mmol), and the mixture
was stirred for 48 h under reflux. After the mixture was
concentrated under reduced pressure, purification by column
chromatography (hexane/ethyl acetate (20/1)) gave (+)-6 as a
greenish amorphous mass (420 mg, 1.49 mmol, 48%), which
was used for the following reaction without further purifica-
tion.
An analytical sample was recrystallized from hexane to give
colorless prisms: mp 115-160 °C; [R]22 ) +120 (c 1.71,
D
1
CHCl3); IR (KBr) 1640, 1495, 1150; H-NMR (CDCl3) δ 1.06
(3H, s), 1.21 (3H, s), 4.41 (1H, d, J ) 7.6), 5.74 (1H, d, J )
7.6), 7.0-7.9 (8H, m). Anal. Calcd for C18H16FNO: C, 76.85;
H, 5.73; N, 4.98. Found: C, 76.63; H, 5.70; N, 4.94.
(3a S ,8b R )-2-(2-F lu or op h e n yl)-3a ,8b -d ih yd r o-4,4-d i-
m eth yl-4H-in d en o[1,2-d ]oxa zole ((-)-6). According to the
procedure given for the preparation of (+)-6, (-)-6 was
obtained from (1S,2R)-2 (1.85 g, 10.4 mmol) as a greenish
(14) Meisenheimer, S. V. H. J . Chem. Ber. 1909, 42, 1804.
(15) Applequist, D. E.; Gdanski, R. D. J . Org. Chem. 1981, 46, 2502.
(16) Meyers, A. I.; Tomioka, K.; Fleming, M. P. J . Org. Chem. 1978,
43, 3788.
(17) Issleib, K.; Tzschach, A. Chem. Ber. 1959, 92, 1118.

cis-2-Amino-3,3-dimethyl-1-indanol
J . Org. Chem., Vol. 62, No. 16, 1997 5513
successively washed with 10% HCl (aq) (3 × 10 mL), saturated
aqueous NaHCO3 (10 mL), and brine (10 mL). After usual
workup, purification by column chromatography (hexane/ethyl
acetate (19/1)) gave 11b as a colorless oil (1.16 g, 3.76 mmol,
78%): IR (NaCl) 1738, 1240; 1H-NMR (CDCl3) δ 0.8-0.9 (3H,
br t), 1.1-1.3 (4H, br m), 1.5-1.8 (2H, m), 2.00 (3H, s), 5.34
(1H, dt, J ) 6.6, 9.2), 6.00 (1H, d, J ) 9.2), 7.2-7.4 (10H, m);
HRMS(EI) calcd for C21H24O2 308.1776, found 308.1772.
Gen er a l P r oced u r e for Am in a tion of 7 w ith Ben zyl-
a m in e. To a solution of [Pd(allyl)Cl]2 (3.5 mg, 0.0096 mmol)
and ligand (+)-4 (10.6 mg, 0.0237 mmol) in THF (1.0 mL),
which had been prestirred for 20 min, were added in succession
a solution of allylic acetate 7 (0.634 mmol) in THF (1.0 mL)
and a solution of benzylamine (175 mg, 1.63 mmol) in THF
(1.0 mL), and the resulting mixture was stirred for 19-24 h
at rt. After the mixture had been concentrated under reduced
pressure, the resulting residue was purified by PTLC (hexane/
ethyl acetate (9/1-19/1)) to give the corresponding amine as
colorless oil. Chiral HPLC analysis of the product was
performed in order to determine the enantioselectivity (an
authentic sample was prepared by the reaction of 7 with
benzylamine in the presence of Pd2(dba)3‚CHCl3/dppf (1/1)).
(R)-N-Ben zyl-[(E)-1,3-d ip h en yl-2-p r op en yl]a m in e ((R)-
8a ).1,5a The ee was determined to be 97% by chiral HPLC
analysis (Daicel Chiralcel OD, hexane/i-PrOH (199/1), R 1.13,
shorter retention time for the R isomer): [R]26D ) -26 (c 1.68,
for C23H17NO2 339.1259, found 339.1261. Anal. Calcd for
C23H17NO2: C, 81.40; H, 5.05; N, 4.13. Found: C, 81.05; H,
5.21; N, 4.26.
(R)-N-[(E)-1,3-Bis(2-ch olor oph en yl)-2-pr op en yl]p h th a l-
im id e ((R)-9b). The ee was determined to be 95% by chiral
HPLC analysis (Daicel Chiralcel OD, hexane/i-PrOH (599/1),
R 1.48, longer retention time for the R isomer): mp 144-145
°C; [R]26 ) -14 (c 2.07, CHCl3); IR (KBr) 1710, 1490, 1380;
D
1H-NMR (CDCl3) δ 6.07 (1H, d, J ) 8.6), 6.64 (1H, d, J ) 16),
6.97 (1H, dd, J ) 8.6, 16), 7.3-7.5 (8H, m), 7.7-7.9 (4H, m);
HRMS(EI) calcd for C23H15Cl2NO2 407.0479, found 407.0486.
Anal. Calcd for C23H15Cl2NO2: C, 67.66; H, 3.70; N, 3.43.
Found: C, 67.43; H, 3.77; N, 3.40.
(R)-N-[(E)-1,3-Bis(2-br om op h en yl)-2-p r op en yl]p h th a l-
im id e ((R)-9c). The ee was determined to be 97% by chiral
HPLC analysis (Daicel Chiralcel OD, hexane/i-PrOH (199/1),
R 1.19, longer retention time for the R isomer): mp 89-90
°C; [R]26 ) -11 (c 1.20, CHCl3); IR (KBr) 1710, 1490, 1380;
D
1H-NMR (CDCl3) δ 6.05 (1H, d, J ) 8.3), 6.63 (1H, d, J ) 16),
6.98 (1H, dd, J ) 8.3, 16), 7.2-7.5 (8H, m), 7.7-7.9 (4H, m);
HRMS(EI) calcd for C23H15Br2NO2 496.9419, found 496.9411.
(S )-N -B e n zy l-(3,3-d ip h e n y l-1-m e t h y l-2-p r o p e n y l)-
a m in e (12a ).8 To a solution of [Pd(allyl)Cl]2 (5.8 mg, 0.0159
mmol) and ligand (+)-2 (17.8 mg, 0.0398 mmol) in THF (0.75
mL), which had been prestirred for 20 min, was added a
solution of acetate 11a (83.6 mg, 0.314 mmol) and benzylamine
(0.35 g, 3.3 mmol) in THF (1.0 mL), and then AcOH (0.19 g,
3.2 mmol) was added. The mixture was stirred for 3 h at 60
°C. After being cooled to 0 °C, the reaction mixture was
treated with 1 M NaOH (aq) (5 mL), and this mixture was
extracted with CH2Cl2 (3 × 10 mL). After usual workup and
removal of the highly polar byproducts by short column
chromatography (hexane/ethyl acetate (1/1)), the mixture was
purified by PTLC (hexane/ethyl acetate (3/1)) to give 1,1-
diphenyl-1,3-butadiene (13a ) (8.6 mg, 0.042 mmol, 13%) and
CHCl3) (lit. [R]20 -25 (c 1.4, CHCl3) for the R isomer).1a
D
(S)-N-Ben zyl-[(E)-1,3-d ip h en yl-2-p r op en yl]a m in e ((S)-
8a ). The ee was determined to be 96% by chiral HPLC
analysis (Daicel Chiralcel OD, hexane/i-PrOH (199/1)): [R]26
) +25 (c 1.76, CHCl3).
D
(R )-N -B e n z y l-[(E )-1,3-b is (2-c h lo r o p h e n y l)-2-p r o -
p en yl]a m in e ((R)-8b). The ee was determined to be 95% by
chiral HPLC analysis (Daicel Chiralcel OD, hexane/i-PrOH
(99/1), R 1.50, shorter retention time for the R isomer): [R]21
D
) -7.3 (c 1.31, CHCl3); IR (NaCl) 1490, 1190; 1H-NMR (CDCl3)
δ 1.72 (1H, s), 3.74 (2H, s), 4.36 (1H, d, J ) 7.3), 6.22 (1H, dd,
J ) 7.3, 16), 6.50 (1H, d, J ) 16), 7.2-7.4 (13H, m); HRMS(EI)
calcd for C22H19Cl2N 367.0895, found 367.0885.
12a (80.3 mg, 0.256 mmol, 82%) as colorless oils. 12a : [R]22
) -92 (c 4.02, CHCl3).
D
The ee of 12a was determined to be 98% by chiral HPLC
analysis (Daicel Chiralcel OJ , hexane/i-PrOH ) 9:1), R 1.56,
shorter retention time for the S isomer) (an authentic sample
was prepared similarly by the reaction of 11a using racemic
2 instead of (+)-2).
(R )-N -B e n z y l-[(E )-1,3-b i s (2-b r o m o p h e n y l)-2-p r o -
p en yl]a m in e ((R)-8c). The ee was determined to be 97% by
chiral HPLC analysis (Daicel Chiralcel OD, hexane/i-PrOH
(99/1), R 1.40, shorter retention time for the R isomer): [R]26
D
(S)-N-Ben zyl-(3,3-d ip h en yl-1-bu tyl-2-p r op en yl)a m in e
(12b). A similar reaction of 11b (96.4 mg, 0.313 mmol),
followed by purification by PTLC (hexane/ethyl acetate (5/1)),
gave unreacted 11b (9.4 mg, 0.030 mmol, 9.8%), 1,1-diphenyl-
1,3-heptadiene (13b) (43.3 mg, 0.178 nnol, 56%), and 12b (36.7
) -1.5 (c 8.44, CHCl3); IR (NaCl) 1490; 1H-NMR (CDCl3) δ
1.65 (1H, br s), 3.74 (2H, s), 4.34 (1H, d, J ) 7.3), 6.23 (1H,
dd, J ) 7.3, 16), 6.49 (1H, d, J ) 16), 7.2-7.6 (13H, m);
HRMS(EI) calcd for C22H19Br2N 456.9863, found 456.9847.
Gen er a l P r oced u r e for Am in a tion of 7 w ith P ota ssiu m
P h th a lim id e. To a suspension of [Pd(allyl)Cl]2 (3.5 mg,
0.0096 mmol), ligand (+)-4 (10.6 mg, 0.0237 mmol), and
potassium phthalimide (0.35 g, 1.9 mmol) in THF (2.0 mL),
which had been prestirred for 20 min, was added a solution of
allylic acetate 7 (0.636 mmol) in THF (1.0 mL), and the
mixture was stirred for 12 h at 50 °C. After being allowed to
cool to rt, the reaction was quenched by adding water (3 mL),
and this mixture was extracted with ether (3 × 10 mL). After
usual workup and removal of the highly polar byproducts by
short column chromatography (hexane/ethyl acetate (1/1)), the
mixture was purified by PTLC (hexane/ethyl acetate (9/1-19/
1) to give the corresponding N-allylphthalimide as colorless
crystals. Chiral HPLC analysis of the product was performed
in order to determine the enantioselectivity (an authentic
sample was prepared by the reaction of 7 with potassium
phthalimide in the presence of Pd2(dba)3‚CHCl3/dppf (1/1)).
(R)-N-[(E)-1,3-Dip h en yl-2-p r op en yl]p h th a lim id e ((R)-
9a ). The ee was determined to be 99% by chiral HPLC
analysis (Daicel Chiralcel OD, hexane/i-PrOH (99/1), R 1.29,
mg, 0.103 mmol, 33%) as colorless oils. 12b: [R]22 ) -33 (c
D
1
1.84, CHCl3); H-NMR (CDCl3) δ 0.8-0.9 (3H, br t), 1.2-1.7
(7H, m), 3.28 (1H, dt, J ) 7.3, 9.9), 3.54 (1H, d, J ) 13), 3.82
(1H, d, J ) 13), 5.95 (1H, d, J ) 9.9), 7.1-7.4 (15H, m);
HRMS(EI) calcd for C26H29N 355.2300, found 355.2316.
The ee of 12b was determined to be 94% by chiral HPLC
analysis (Daicel Chiralcel OD, hexane/i-PrOH ) 199:1), R 1.20,
shorter retention time for the S isomer) (an authentic sample
was prepared similarly by the reaction of 11b using racemic
4 instead of (+)-4).
Ack n ow led gm en t. This work was financially sup-
ported by a Grant-in-Aid for Scientific Research (No.
08245215) from the Ministry of Education, Science,
Sports and Culture of J apan.
Su p p or tin g In for m a tion Ava ila ble: 1H-NMR spectra of
all new compounds (10 pages). This material is contained in
libraries on microfiche, immediately follows the article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
longer retention time for the R isomer): mp 119-120 °C; [R]26
D
) -17 (c 1.70, CHCl3); IR (KBr) 1710, 1385; 1H-NMR (CDCl3)
δ 6.17 (1H, d, J ) 8.3), 6.73 (1H, d, J ) 16), 7.07 (1H, dd, J )
8.3, 16), 7.2-7.5 (10H, m), 7.6-7.9 (4H, m); HRMS(EI) calcd
J O970359E