Enantioselective acylation of 1,2- and 1,3-diols catalyzed by aminophosphinite derivatives of (1 S,2 R)-1-amino-2-indanol

Article abstract of DOI:10.1021/ol2033459

A phosphinite derivative that can be easily prepared in two steps from commercially available aminoindanol was found to be an effective catalyst for enantioselective acylation of diols. For the asymmetric desymmetrization of meso-1,2-diols, the correspond

Full text of DOI:10.1021/ol2033459

ORGANIC
LETTERS
2012
Vol. 14, No. 3
812–815
Enantioselective Acylation of 1,2- and
1,3-Diols Catalyzed by Aminophosphinite
Derivatives of (1S,2R)-1-Amino-2-indanol
Hiroyuki Aida,† Kouhei Mori,† Yasuyuki Yamaguchi,† Shinya Mizuta,†
Tomomi Moriyama,† Iwao Yamamoto,† and Tetsuya Fujimoto*,‡
Department of Functional Polymer Science and Interdisciplinary Graduate School of
Science and Technology, Shinshu University, Ueda, Nagano 386-8567, Japan
tfujimo@shinshu-u.ac.jp
Received December 15, 2011
ABSTRACT
A phosphinite derivative that can be easily prepared in two steps from commercially available aminoindanol was found to be an effective catalyst
for enantioselective acylation of diols. For the asymmetric desymmetrization of meso-1,2-diols, the corresponding monoester was obtained in up
to 95% ee from the reaction in the presence of 5 mol % catalyst.
Asymmetric desymmetrization of diols, which has a
plane of symmetry in the molecule, is an effective metho-
dology for obtaining chiral multifunctional organic com-
pounds.1 Enantioselective acylation of alcohols has been
frequently used as an effective transformation reaction for
both asymmetric desymmetrization and kinetic resolution
of racemic alcohols.2 To date, nonenzymatic enantio-
selective acylation of alcohols for asymmetric desymme-
trization has primarily been achieved by a strategy based
on activation of acylating reagents by nucleophilic
organocatalysts3 or molecular recognition of diols by chiral
metal complexes.4 In particular, for the organocatalytic
process, excellent catalysts in which a wide variety of
nucleophilic functional groups serve as reactive sites have
been reported.5 In addition, the asymmetric desymmetri-
zation of diols by silylation catalyzed by the nucleophilic
organocatalyst has also been achieved.6 Although these
catalysts produce the desired chiral alcohol derivatives
(5) For representative examples of asymmetric desymmetrization of
diols and kinetic resolution of monoprotected diols, see: (a) Iwahana, S.;
Iida, H.; Yashima, E. Chem.;Eur. J. 2011, 17, 8009. (b) Cao, J.-L.; Qu,
€
J. J. Org. Chem. 2010, 75, 3663. (c) Muller, C. E.; Zell, D.; Schreiner,
€
P. R. Chem.;Eur. J. 2009, 15, 9647. (d) Kundig, E. P.; Garcia, A. E.;
Lomberget, T.; Garcia, P. P.; Romanens, P. Chem. Commun. 2008, 3519.
(e) Lewis, C. A.; Gustafson, J. L.; Chiu, A.; Balsells, J.; Pollard, D.;
Murry, J.; Reamer, R. A.; Hansen, K. B.; Miller, S. J. J. Am. Chem. Soc.
2008, 130, 16358. (f) Kosugi, Y.; Akakura, M.; Ishihara, K. Tetrahedron
2007, 63, 6191. (g) Birman, V. B.; Jiang, H.; Li, X. Org. Lett. 2007, 9,
† Department of Functional Polymer Science.
‡ Interdisciplinary Graduate School of Science and Technology.
(1) Willis, M. C. J. Chem. Soc., Perkin Trans. 1 1999, 1765.
(2) For recent reviews on enantioselective acyl transfer reactions, see:
3237. (h) Yamada, S.; Misono, T.; Iwai, Y.; Masumizu, A.; Akiyama, Y.
ꢀ
ꢀ
J. Org. Chem. 2006, 71, 6872. (i) Dalaigh, C. O.; Hynes, S. J.; O’Brien,
J. E.; McCabe, T.; Maher, D. J.; Watson, G. W.; Connon, S. J. Org.
Biomol. Chem. 2006, 4, 2785. (j) Vedejs, E.; Daugulis, O.; Tuttle, N.
J. Org. Chem. 2004, 69, 1389. (k) Spivey, A. C.; Zhu, F.; Mitchell, M. B.;
Davey, S. G.; Jarvest, R. L. J. Org. Chem. 2003, 68, 7379. (l) Kawabata,
T.; Stragies, R.; Fukaya, T.; Nagaoka, Y.; Schedel, H.; Fuji, K.
Tetrahedron Lett. 2003, 44, 1545. (m) Priem, G.; Pelotier, B.; Macdonald,
S. J. F.; Anson, M. S.; Campbell, I. B. J. Org. Chem. 2003, 68, 3844.
(n) Oriyama, T.; Imai, K.; Sano, T.; Hosoya, T. Tetrahedron Lett. 1998,
39, 3529. (o) Ruble, J. C.; Tweddell, J.; Fu, G. C. J. Org. Chem. 1998, 63,
2794.
€
(a) Muller, C. E.; Schreiner, P. R. Angew. Chem., Int. Ed. 2011, 50, 6012.
(b) Spivey, A. C.; Arseniyadis, S. Top. Curr. Chem. 2010, 291, 233.
(3) For reviews, see: (a) Denmark, S. E.; Beutner, G. L. Angew.
Chem., Int. Ed. 2008, 47, 1560. (b) Wurz, R. P. Chem. Rev. 2007, 107,
5570. (c) France, S.; Guerin, D. J.; Miller, S. J.; Lectka, T. Chem. Rev.
2003, 103, 2985.
(4) (a) Arai, T.; Mizukami, T.; Yanagisawa, A. Org. Lett. 2007, 9,
1145. (b) Nakamura, D.; Kakiuchi, K.; Koga, K.; Shirai, R. Org. Lett.
€
2006, 8, 6139. (c) Mazet, C.; Kohler, V.; Pfaltz, A. Angew. Chem., Int. Ed.
2005, 44, 4888. (d) Matsumura, Y.; Maki, T.; Murakami, S.; Onomura,
O. J. Am. Chem. Soc. 2003, 125, 2052.
(6) Zhao, Y.; Rodrigo, J.; Hoveyda, A. H.; Snapper, M. L. Nature
2006, 443, 67.
r
10.1021/ol2033459
Published on Web 01/19/2012
2012 American Chemical Society

with a high level of enantioselectivity, multiple steps were
occasionally needed for the preparation of the catalysts,
and in some cases, only one of the enantiomers can be
synthesized because of limitations to the available chiral
reagent pool. We previously reported that phosphinite
derivatives of cinchona alkaloids, such as 1 and 2 (Figure 1),
are promising organocatalysts for asymmetric benzoyla-
tion of diols.7 These catalysts can be prepared by one-step
synthesis from cinchona alkaloids and effectively catalyze
acylation of 1,2-diaryl-1,2-diols, a reaction having limited
successful examples. For the acylation reaction, these
Scheme 1. Synthesis of Aminophosphinite 3a
at À78 °C in propionitrile (Table 1). As a result, the
corresponding ester was obtained with promising enan-
tioselectivity (84% ee, Table 1, entry 1). On the other hand,
similar aminophosphinite derivatives 3bÀd (Figure 1)
with various nitrogen substituents provided the product
Table 1. Asymmetric Acylation of Hydrobenzoin Catalyzed by
Aminophosphnites 3aÀd
Figure 1. Phosphinite derivatives as acylation catalysts.
entry
cat.
R
time(h)
yield (%)a
ee (%)b
catalysts were assumed to be a bifunctional catalyst in
which an amino and a phosphinite group cooperatively
1
2
3
4
5
3a
3b
3c
3d
3a
Ph
Ph
Ph
Ph
5
24
24
24
25
77
34
49
9
84
31
6
€
promote the reaction as a Bronsted and Lewis base,
35
93
respectively. However, more than 30 mol % of catalyst
loading was necessary for the reaction with many sub-
strates, and the catalysts needed to be used immediately
after their preparation because the tertiary phosphorus
group is susceptible to oxidation. Therefore, we attempted
to identify more reactive, tractable, and accessible small
molecule organocatalysts, maintaining the effectiveness of
the bifunctional catalyst.
Note that, after screening the available chiral aminoal-
cohols, N,N-dimethyl cis-aminoindanol phosphinite
derivative 3a (Figure 1), whose both enantiomers are
commercially available, was found to be a more reactive
and tractable aminophosphinite catalyst for enantioselec-
tive acylation of diols. Compound 3a was easily synthe-
sized in two steps from (1S,2R)-aminoindanol in high yield
(Scheme 1), and its relatively stable crystals can be purified
by standard column chromatography and stored under an
argon atmosphere in the refrigerator for more than three
months.
4-t-BuC6H4
50
a Isolated yield. b Determined by chiral HPLC analysis.
in lower yield and with lower enantioselectivity. In addi-
tion, when 4-tert-butylbenzoyl chloride replaced benzoyl
chloride as the acylating reagent for the reaction catalyzed
by 3a, the enantioselectivity of the product increased to
93% ee (Table 1, entry 5). The configuration of the major
product was assigned to be (1R,2S) on the basis of the
specific rotation of (R,R)-hydrobenzoin derived from the
product via a Mitsunobu reaction using benzoic acid
followed by hydrolysis (see Supporting Information).
Moreover, we evaluated other reaction solvents to
further improve the stereoselectivity of acylation, and
found that aromatic hydrocarbons were more effective
solvents for the present reaction. In particular, the reaction
using toluene as a solvent afforded the desired product in
97% yield and 95% ee even if the reaction was executed
under reduced catalyst loading (5 mol %) at 0 °C (Table 2,
entry 5). Benzene was also an effective solvent, and high
stereoselectivity was retained even for the reaction with
2.5 mol % catalyst (Table 2, entry 8). Other hydrocar-
bons, such as mesitylene, cyclohexane, and chloroben-
zene gave the product in lower yield as well as with low
Initially, the reaction of meso-hydrobenzoin with ben-
zoyl chloride in the presence of 20 mol % catalyst, diiso-
˚
propylethylamine, and 4 A molecularsieveswas conducted
(7) (a) Mizuta, S.; Tsuzuki, T.; Fujimoto, T.; Yamamoto, I. Org.
Lett. 2005, 7, 3633. (b) Mizuta, S.; Sadamori, M.; Fujimoto, T.;
Yamamoto, I. Angew. Chem., Int. Ed. 2003, 42, 3383.
Org. Lett., Vol. 14, No. 3, 2012
813

Table 2. Screening of Reaction Conditions
Table 3. Enantioselective Acylation of meso-1,2-Diols
entry
X
solvent
temp (°C) time (h) yield (%)a ee (%)b
1
2
3
4
5
6
7c
8
9
20 EtCN
20 EtCN
20 toluene
10 toluene
À78
0
25
12
12
12
12
24
48
24
48
45
45
50
82
93
98
97
62
4
93
74
95
94
95
90
69
93
81
68
78
0
0
5
toluene
2.5 toluene
toluene
0
rt
rt
rt
rt
rt
rt
5
2.5 benzene
71
16
19
54
2.5 mesitylene
10 2.5 cyclohexane
11 chlorobenzene
5
a Isolated yield. b Determined by chiral HPLC analysis. c Reaction in
˚
the absence of 4 A MS.
a Isolated yield. b Determined by chiral HPLC analysis. c Not
detected.
enantioselectivity (entries 9, 10, and 11, respectively). In
˚
the absence of 4 A molecular sieves and under the
optimized reaction conditions, drastic reduction in the
yield and enantioselectivity of the product was observed
(Table 2, entry 7). The effect of molecular sieves was
originally investigated by Oriyama et al. in enantioselec-
tive acylation of alcohols catalyzed by chiral diamines,
which were developed by his group.5n Similarly, molecu-
lar sieves were essential additives for the present reaction
catalyzed by aminophosphinite derivatives.
Enantioselective acylation of 1,2-diols catalyzed by 3a
could be realized for aliphatic diols (Table 3). For example,
the reaction of a 2,3-butandiol gave the corresponding
ester with 89% ee (Table 3, entry 2). Furthermore, cyclic
diol of 1,2-cyclohexanediol was converted to its ester with
high enantioselectivity (93% ee), whereas the stereoselectiv-
ity of the reaction using 1,2-cyclopentanediol was moderate.
Compared to 1,2-disubstituted-1,2-diols, fewer examples
of asymmetric desymmetrization of 2-substituted 1,3-pro-
panediols have been reported.8 This is possibly due to the
fact that the pro-chiral center locates at a carbon atom
adjacent to the carbinol groups and that primary hydroxyl
groups are more reactive than secondary ones. We also
previously attempted enantioselective acylation of 1,3-
propanediol derivatives catalyzed by cinchona alkaloid
phosphinite derivatives such as 1 and 2; however, asym-
metric induction was not observed in these reactions.7a For
exploring versatility of catalyst 3a, enantioselective acyla-
tion of 1,3-propanediol derivatives was attempted under
the optimized reaction conditions (Table 4). Although a
substantial amount of diester was generated along with the
desired monoester for all reactions, enantioselectivity for
the acylation reaction was observed. In particular, for the
reactions of aromatic or allyl 1,3-propanediol derivatives
(Table 4, entries 1, 2, and 4), the yield and enantioselec-
tivity of the products were maintained even though a
reduced amount of catalyst (2.5 mol %) was employed.
Meanwhile, the reaction of alkyl 1,3-propanediol or a
substrate containing a quaternary center gave the mono-
ester with lower enantioselectivity.
As described above, aminophosphinite derivatives were
€
designed as Bronsted-Lewis dibasic bifunctional organo-
catalysts. For the acylation reaction catalyzed by amino-
phosphinite derivatives, the phosphinite moiety and not
the amino group is assumed to serve as a Lewis base to
activate the acylating reagent. Although we have no direct
evidence for the reaction mechanism, aminoindanol deri-
vative 4, in which the phosphorus group is detached from
the original catalyst and the oxygen atom of aminoindanol
is acylated, was often isolated from the acylation reaction
of alcohols catalyzed by 3a. Derivative 4 was isolated as a
single stereoisomer, and its configuration was in accor-
dance with that of the original aminophosphinite deriva-
tive 3a. In fact, the reaction of 3a with 4-tert-butylbenzoyl
chloride in the absence of alcohols afforded 4 having the
same stereochemistry in 70% yield (Scheme 2). 1H NMR
and specific rotation of 4 was completely consistent with
that of the product obtained from the reaction of N,N-
dimethylaminoindanol with 4-tert-butylbenzoyl chloride
(8) (a) You, Z.; Hoveyda, A. H.; Snapper, M. L. Angew. Chem., Int.
Ed. 2009, 48, 547. (b) Trost, B. M.; Mino, T. J. Am. Chem. Soc. 2003, 125,
2410. (c) Oriyama, T.; Taguchi, H.; Terakado, D.; Sano, T. Chem. Lett.
2002, 26.
€
in the presence of Hunig’s base. The mechanism for the
814
Org. Lett., Vol. 14, No. 3, 2012

present, it is implied that the phosphinite moiety could
react with acyl chloride. On the other hand, the acylation
reaction of meso-hydrobenzoinusing 4 as a catalyst instead
of 3a gave only a trace amount of the racemate of the
corresponding ester. Therefore, 4 was not a catalyst for the
present acylation reaction.
Table 4. Enantioselective Acylation of 1,3-Diols
Scheme 2. Reaction of Acylating Reagent with Catalyst 3a
In summary, aminophosphinite derivative 3a was found
to be an effective organocatalyst for asymmetric acylation
of diols. In particular, the catalyst can be easily prepared
from cis-aminoindanol, whose both enantiomers are com-
mercially available, and can effectively catalyze asym-
metric desymmetrization of meso-1,2-diols. The kinetic
resolution of monoalcohols using the catalyst and studies
on the reaction mechanism including the mechanism for
the generation of 4 are in progress.
a Isolated yield. b Determined by chiral HPLC analysis. Symbols in
parentheses indicate the absolute configuration of the major products.
c Absolute configuration was not determined. d From chiral HPLC
analysis of the acetate derivative of the monoester.
Acknowledgment. This work was supported by JSPS
KAKENHI (Grant-in-Aid for Scientific Research (C),
21550102).
preparation of 4 cannot be clearly explained, but consider-
ing the retention of stereochemistry observed for 4, a
possible scenario would be ligand coupling9 via pentacoor-
dinated hypervalent phosphorus compound 5. Although
5 and chlorodiphenylphosphine, which should be extruded
from 5 through ligand coupling, could not be detected at
Supporting Information Available. Experimental pro-
cedure, compound characterization data, and NMR
spectra for catalysts 3aÀd and products. This material
is available free of charge via the Internet at http://pubs.
acs.org.
(9) For a review on ligand-coupling reactions, see:Oae, S.; Uchida, Y.
Acc. Chem. Res. 1991, 24, 202.
Org. Lett., Vol. 14, No. 3, 2012
815