Catalytic enantioselective allylation of ketones via a chiral indium(III) complex

Article abstract of DOI:10.1021/ol051018n

(Chemical Equation Presented) A chiral indium complex has been discovered to effect high enantioselectivities in the addition of allyltributylstannanes to ketones. The allylation of a variety of aromatic, α,β-unsaturated and aliphatic ketones resulted in

Full text of DOI:10.1021/ol051018n

ORGANIC
LETTERS
2
005
Vol. 7, No. 13
743-2745
Catalytic Enantioselective Allylation of
Ketones via a Chiral Indium(III) Complex
2
†
†
,‡
Yong-Chua Teo, Joshua-Daniel Goh, and Teck-Peng Loh*
DiVision of Chemistry and Biological Chemistry, Nanyang Technological UniVersity,
Singapore 637616, and Department of Chemistry, 3 Science DriVe, National UniVersity
of Singapore, Singapore 117543
teckpeng@ntu.edu.sg
Received May 4, 2005
ABSTRACT
A chiral indium complex has been discovered to effect high enantioselectivities in the addition of allyltributylstannanes to ketones. The
allylation of a variety of aromatic, -unsaturated and aliphatic ketones resulted in good yields and high enantioselectivities (up to 92% ee).
r,â
The utilization of indium(III) complexes as efficient Lewis
acid catalysts for organic synthesis, particularly to the ends
and pharmaceuticals.2 The development of asymmetric
catalytic processes for obtaining secondary homoallylic
1
3
of forming C-C bond(s), has been well established. How-
ever, efforts to develop an efficient chiral indium Lewis acid
for enantioselective organic transformations has been achieved
with limited success. Therefore, developing new chiral
indium complexes continues to pose a challenge to synthetic
chemists.
The enantioselective allylation of carbonyl functionality
to furnish homoallylic alcohols has acquired a major role
due to the versatility of the products, which are important
building blocks for the synthesis of many natural products
alcohols from aldehydes and allyltrialkylstannanes or al-
4
lyltrialkylsilanes greatly enhances the potential of this
synthetic tool. However, the catalytic asymmetric allylation
of ketones to generate enantiopure tertiary homoallylic
(
2) For reviews, see: (a) Roush, W. R. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon:
Oxford, 1991; Vol. 2, p 1. (b) Yamamoto Y.; Asao, N. Chem. ReV. 1993,
93, 2207. (c) Hoveyda, A. H.; Morken, J. P. Angew. Chem., Int. Ed. Engl.
1996, 35, 1262. (d) Nicolaou, K. C.; Kim, D. W.; Baati. R. Angew. Chem.,
Int. Ed. 2002, 41, 3701. (e) Hornberger, K. R.; Hamblet, C. L.; Leighton,
J. L. J. Am. Chem. Soc. 2000, 122, 12894. (c) Felpin, F. X.; Lebreton. J. J.
Org. Chem. 2002, 67, 9192.
†
National University of Singapore.
Nanyang Technological University.
(3) For reviews, see: (a) Denmark, S. C.; Fu, J.-P. Chem. Rew. 2003,
103, 2752 and references therein. For representative examples, see: (b)
Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini, C.; Umani-Ronchi,
A. J. Am. Chem. Soc. 1993, 115, 7001. (c) Keck, G. E.; Tarbet, K. H.;
Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467. (d) Bedeschi, P.; Casolari,
S.; Costa, A. L.; Tagliavini, E.; Umani-Ronchi, A. Tetrahedron Lett. 1995,
36, 7897. (e) Weigand, S.; Bruckner, R. Chem. Eur. J. 1996, 2, 1077. (f)
Yanagisawa, A.; Nakaahima, H.; Ishiba, A., Yamamoto, H. J. Am. Chem.
Soc. 1996, 118, 4723. (g) Casolari, S.; Cozzi, P. G.; Orioli, P.; Tagliavini,
E.; Umani-Ronchi, A. Chem. Commun. 1997, 2123. (h) Yu, C.-M.; Choi,
H.-S.; Jung, W.-H.; Kim, H.-J.; Shin, J. Chem. Commun. 1997, 761. (i)
Yu, C.-M.; Yoon. S.-K.; Choi, H.-S.; Back, K. Chem. Commun. 1997, 763.
(4) Ishiara, K.; Mouri, M.; Gao, Q.; Maruyama, T.; Furuta, K.; Yama-
moto, H. J. Am. Chem. Soc. 1993, 115, 11490. (b) Gauthier, D. R. J.;
Carreira, E. M. Angew. Chem., Int. Ed. Engl. 1996, 35, 2363.
‡
(1) For reviews, see: (a) Loh, T.-P. In Science of Synthesis; Yamamoto,
H., Ed.; Georg Thieme Verlag Stuttgart: New York, 2004; p 413. (b) Loh,
T.-P.; Chua, G.-L. Activation of Reactions by Lewis acid derived from
Ga, In, Sb and Bi. In AdV. Org. Synth.-Online, Atta-ur-Rahman, Ed. 2005,
1
1
, in press. (c) Chauhan, K. K.; Frost, C. G. J. Chem. Soc., Perkin Trans.
2000, 3015. (d) Babu, G.; Perumal, P. T. Aldrichim. Acta 2000, 33, 16.
For representative examples, see: (e) Viswanathan, G.-S.; Yang, J.; Li,
C.-J. Org. Lett. 1999, 1, 993. (f) Ranu, B. C.; Jana, U. J. Org. Chem. 1998,
6
3, 8212. (g) Ranu, B. C.; Hajra, A.; Jana, U. J. Org. Chem. 2000, 65,
6270. (h) Tsuchimoto, T.; Maeda, T.; Shirakawa, E.; Kawakami, Y. J. Chem.
Soc., Chem. Commun. 2000, 1573. (i) Gadhwal, S.; Sandhu, J. S. J. Chem.
Soc., Perkin Trans. 1 2000, 2827. (j) Loh, T.-P.; Hu, Q.-Y.; Ma, L.-T. J.
Am. Chem. Soc. 2001, 123, 2450.
1
0.1021/ol051018n CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/01/2005

alcohols has proven to be a more challenging transformation
owing to the significant difference in reactivity between
aldehydes and ketones. As is anticipated by the lesser
reactivity of ketones toward nucleophilic addition, the
number of methods for enantioselective construction of
the allylation reaction. The results from our efforts to
optimize the reaction are shown in Table 1. The reaction
carried out using 3 equiv of allyltributylstannanes leads to
an increase in conversion with retention of enantiomeric
excess (entry 2). To compensate for the reduced reactivity
5
tertiary alcohols by this approach is very limited. Moreover,
3
of ketones, we attempted to use InBr as the indium reagent
to the best of our knowledge, these methods require the
strong allylating reagent, tetraallylstannane, in the process
and possess limited substrate scope in some cases. In this
paper, we report the first efficient asymmetric allylation of
ketones using the less reactive allytributylstannane as the
allylating reagent catalyzed by a chiral (R)-BINOL-In(III)
complex.
for the catalyst preparation due to its higher Lewis acidity.
The reaction proceeded at ambient temperature, and the
homoallylic alcohol was isolated in 76% yield and 82%
enantioselective excess (entry 4). It is noteworthy that the
chiral ligand, (R)-BINOL, can be easily recovered by silica
gel chromatography in almost quantitative yield (94%).
Having optimized the reaction parameters for the allylation
process, we extended the catalytic enantioselective addition
of allyltributylstannane to a selection of ketones. The results
are shown in Table 2.
Recently, we have reported a practical catalytic asymmetric
allylation of aldehydes with allyltributylstannanes in the
presence of an indium(III) catalyst as a chiral Lewis acid
6
which has proven to be efficient and especially convenient.
The chiral indium(III) catalyst was prepared by simply
3 2 2
mixing (R)-BINOL with InCl in CH Cl at room temperature
Table 2. Enantioselective Allylations of Various Ketones
Catalyzed by Chiral (R)-BINOL-In(III) Complexa
for 2 h. However, the reaction of acetophenone with
allyltributylstannane using the optimum conditions previously
described for the corresponding allylstannane reaction af-
forded the homoallylic alcohol in low yield and good
enantiomeric excess (Table 1, entry 1). This result prompted
Table 1. Enantioselective Allylation of Acetophenone
Catalyzed by Chiral (R)-BINOL-In(III) Complexa
indium
reagent
allyl stannane
(equiv)
yieldb
(%)
eec
(%)
entry
T (°C)
1
2
3
4
InCl3
InCl3
InCl3
InBr3d
2.0
3.0
3.0
3.0
-78 to rt
-78 to rt
rt
rt
25
46
54
76
81
81
81
82
a
Unless otherwise specified, the reaction was carried out using the chiral
indium(III) catalyst prepared from (R)-BINOL (22 mol %) and InCl3 (20
mol %) in the presence of 15 mg of powdered activated 4 Å molecular
sieves in 1.0 mL of CH2Cl2. The reaction mixture was kept for 4 h at -78
b
c
°
C and then 72 h at rt. Isolated yield. Please refer to the Supporting
d
Information for enantiomeric excess determination. The reaction was
stirred at rt for 72 h.
us to utilize a stronger indium-based lewis acid in an attempt
to increase both the chemical yield and enantioselectivity of
a
Unless otherwise specified, the reaction was carried out with allyltributyl
stannane (1.5 mmol) and ketone (0.5 mmol) using the chiral indium(III)
catalyst prepared from (R)-BINOL (22 mol %) and InBr3 (20 mol %) in
the presence of 15 mg of powdered activated 4 Å molecular sieves in 1.0
(
5) For representative examples of enantioselective allylation of ketones,
see (a) Tieze, L. F.; Schiemann K.; Wegner C. J. Am. Chem. Soc. 1995,
17, 5851. (b) Tieze, L. F.; Schiemann, K.; Wegner, C.; Wulff, C. Chem.
1
b
mL of CH2Cl2. The reaction mixture was stirred at rt for 72 h. Isolated
Eur. J. 1998, 4, 1862. (c) Yasuda, M.; Kitahara, N.; Fujibayashi, T.; Baba,
A. Chem. Lett. 1998, 8, 743. (d) Casolari, S.; D’Addario, D.; Tagliavini, E.
Org. Lett. 1999, 1, 1061. (e) Yamasaki, S.; Fujii, K.; Wada, R.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 2002, 124, 6536. (f) Cunningham, A.;
Woodward, S. Synlett 2002, 43. (g) Waltz, K. M.; Gavenois, J.; Walsh, P.
J. Angew. Chem., Int. Ed. 2002, 41, 3697. (h) Satoshi, K.; Keiji, M. Chirality,
003, 15, 68. (i) Hanawa, H.; Kii, S.; Maruoka, K. AdV. Synth. Catal. 2001,
, 57. (j) Wada, R.; Oisaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem.
Soc. 2004, 125, 8910. (k) Kim, J.-K.; Waltz, K. M.; Garcia, L. F.;
Kwiatkowski, D.; Walsh, P. J. J. Am. Chem. Soc. 2004, 126, 12580.
yield. c Please refer to the Supporting Information for enantiomeric excess
determination.
In all cases, the homoallylic alcohols were obtained in
good enantioselectivities (up to 92% ee) not only with
aromatic ketones but also with aliphatic and cyclic aromatic
ketones. The allylation reaction of acetophenone and 4-meth-
2
1
(6) Teo, Y.-C.; Tan, K.-T.; Loh, T.-P. Chem. Commun. 2005, 1318.
2744
Org. Lett., Vol. 7, No. 13, 2005

ylacetophenone under the influence of the chiral indium
catalyst furnished the homoallylic alcohols with 82% and
tributylstannanes. As such, this facilitated the addition of the
allyl moiety to the re face of the ketone leading to the
enantiomers shown in Tables 1 and 2.
8
2
4% ee, respectively (Table 2, entries 1 and 2). Moreover,
′-acetonaphthone also underwent the allylation reaction
It is worthy to note that the catalytic allylation of ketones
for this chiral indium complex can be accomplished simply
by using allyltributylstannane unlike most other asymmetric
catalytic systems which require stronger allylation reagents
such as tetraallylstannanes. In fact, as far as we know, this
is the first example of catalytic enantioselective allylation
of ketones using allyltributylstannanes as the allylation
reagent.
affording the product in 80% yield and 84% ee.
Allylation of a representative conjugated enone gave
exclusively a 1,2-allylation product in good yield with high
enantioselectivity (entry 4). Interestingly, while trans-4-
phenyl-3-buten-2-one underwent allylation with 90% ee, the
saturated derivative reacted to give the homoallylic alcohol
with 80% ee (entry 5).
In conclusion, we have demonstrated the first highly
catalytic enantioselective allylation of ketones using a chiral
indium(III) complex prepared from (R)-BINOL and InBr3.
The main features of this reaction are as follows: (1) the
procedure is operationally simple and can furnish a wide
variety of homoallylic alcohols in good yields with high
levels of enantioselectivites; (2) the allylation can be
performed simply by using allyltributylstanannes and com-
mercially available chemicals; (3) the chiral ligand can be
recovered in high yield, thus making this method attractive
for scale-up preparation of homoallylic alcohols with high
enantioselectivities; Continuing investigations in this labora-
tory will attempt to elucidate the identity of the chiral
BINOL-In(III) species and further expand the scope of the
process.
The ketones, 1-indanone and 6-methyl-1-indanone, both
underwent the allylation reaction to afford the homoallylic
alcohols in 90% and 92% ee, respectively, though the yield
of the latter was only moderate (entries 6 and 7).
The absolute configuration of the tertiary homoallylic
alcohol (Table 1, entry 1) was determined by comparison of
5
d,7
the sign of the optical rotation with the literature value.
The re face of the ketone is attacked when the (R)-catalyst
is used, in agreement with the persistent preference shown
by BINOL-based catalysts. The stereochemical course of the
allylation process catalyzed by the chiral (R)-BINOL-In (III)
complex can be envisaged in terms of the catalyst-ketone
pre-transition state assembly depicted in Figure 1. In Figure
Acknowledgment. We thank the Nanyang Technological
University and National University of Singapore for their
generous financial support. Y.-C.T. is grateful to the Institute
of Chemical and Engineering Sciences Ltd. (ICES) for a
doctorate scholarship.
Supporting Information Available: Experimental de-
tails, characterization data, and stereochemical proofs. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 1. Proposed BINOL-In(III)-aldehyde pre-transition state.
OL051018N
1, the aromatic rings of the (R)-BINOL effectively screen
the si face of the complexed ketone from attack by allyl-
(7) Ishizaki, M.; Soai, K.; Yokoyama, S. Chem. Lett. 1987, 341.
Org. Lett., Vol. 7, No. 13, 2005
2745