A highly enantioselective indium-mediated allylation reaction of aldehydes

Article abstract of DOI:10.1021/ol990316f

(formula presented) The first highly enantioselective indium-mediated allylation of aldehydes was reported. In most cases, good chemical yields and moderate to high enantioselectivies (up to 90% ee) were obtained in the presence of external chiral ligands

Full text of DOI:10.1021/ol990316f

ORGANIC
LETTERS
1
999
Vol. 1, No. 11
855-1857
A Highly Enantioselective
Indium-Mediated Allylation Reaction of
Aldehydes
1
Teck-Peng Loh,* Jian-Rong Zhou, and Zheng Yin
Department of Chemistry, National UniVersity of Singapore, 10 Kent Ridge Crescent,
Singapore 119260
chemlohtp@nus.edu.sg
Received October 7, 1999
ABSTRACT
The first highly enantioselective indium-mediated allylation of aldehydes was reported. In most cases, good chemical yields and moderate to
high enantioselectivies (up to 90% ee) were obtained in the presence of external chiral ligands, (+)-cinchonine and (−)-cinchonidine.
In recent years, indium-mediated allylation of carbonyl
compounds has emerged as one of the most useful methods
for the preparation of synthetically useful homoallylic
Up to now, as far as we know, an enantioselective version
of this reaction is still unavailable. In this Letter, we showed
that a highly enantioselective indium-mediated allylation
3
1
alcohols. Its mild reaction condition and wide applicability
reaction of aldehydes can be achieved using (+)-cinchonine
4
to a variety of allylic bromides and carbonyl compounds have
made this reaction attractive for the construction of natural
1 and (-)-cinchonidine 2 as chiral ligands (Scheme 1).
2
and unnatural complex molecules. Although much attention
has been focused on the stereochemical studies of this
reaction, the development of a new method for the control
of absolute stereochemistry in this indium-mediated allylation
reaction continues to pose a challenge to organic chemists.
Scheme 1
(
1) For a review, see: (a) Li, C. J. Chem. ReV. 1993, 93, 2023-2035.
(
b) Chan, T. H.; Li, C. J.; Lee, M. C.; Wei, Z. Y. Can. J. Chem. 1994, 72,
1
181-1192. (c) Cintas, P. Synlett 1995, 1087. (d) For mechanistic studies,
see: Chan, T. H.; Yang, Y. J. Am. Chem. Soc. 1999, 121, 3228-3229. (e)
Araki, S.; Ito, H.; Butsugan, Y. J. Org. Chem. 1988, 53, 1831-1833. (f)
Paquette, L. A.; Lobben, P. C. J. Am. Chem. Soc. 1996, 118, 1917-1930.
(
1
g) Paquette, L. A.; Mitzel, T. M. J. Am. Chem. Soc. 1996, 118, 1931-
937. (h) Fujiwara, N.; Yamamoto, Y. J. Org. Chem. 1997, 62, 2318. (i)
Paquette, L. A.; Mitzel, T. M.; Isaac, M. B.; Crasto, C. F.; Schomer, W.
W. J. Org. Chem. 1997, 62, 4293-4301. (j) Hirashita, T.; Kamei, T.; Horie,
T.; Yamamura, H.; Kawai, M.; Araki, S. J. Org. Chem. 1999, 64, 172-
1
77. (k) Paquette, L. A.; Rothaar, R. R. J. Org. Chem. 1999, 64, 217-224.
(
2) (a) Chan, T. H.; Li, C. J. J. Chem. Soc., Chem. Commun. 1992, 747-
First, we investigated the indium-mediated allylation
reaction of allyl bromide with benzaldehyde using various
chiral promoters 1-5 (5, (-)-sparteine) under different
conditions (eq i). The results are shown in Table 1. The
following are the characteristic features of the reaction. In
all cases except for entries 2, 4, and 7, the reactions
7
7
48. (b) Gordon, D. M.; Whitesides, G. M. J. Org. Chem. 1993, 58, 7937-
938. (c) Paquette, L. A.; Stepanian, M.; Mallavadhani, U. V.; Cutarelli,
T. D.; Lowinger, T. B.; Klemeyer, H. J. J. Org. Chem. 1996, 61, 7492-
7
5
1
507. (d) Isaac, M. B.; Paquette, L. A. J. Org. Chem. 1997, 62, 5333-
338. (e) Loh, T. P.; Cao, G. Q.; J. Pei, Tetrahedron Lett. 1998, 39, 1453-
457. (f) Yi, X. H.; Meng, Y.; Li, C. J. Chem. Commun. 1998, 11, 1237;
(g) 1998, 4, 449-450.
1
0.1021/ol990316f CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/05/1999

enantioselectivity, demonstrating the importance of the
formation of a 1:1 indium-chiral promoter complex (entry
Table 1. Enantioselective Allylation of Benzaldehyde with
Allyl Bromide
8
). Interestingly, replacement of the ligand from 1 to its
“
pseudo-enantiomer” 2 not only afforded higher enantio-
selectivity (from 72% to 75%) but also reversed the chirality
of the homoallylic alcohol. It was also found that the ligands
facilitated the “insertion” of indium into allyl bromide. In
this aspect, 2 was much more effective than 1, as indicated
by the time required to form a clear solution from a
suspension of insoluble ligands in THF (1 h with 2 and 3 h
with 1). Moreover, the chiral promoters could be easily
recovered in high yield by routine acid-base workup (95%
recovery for 1 and 97% recovery for 2).
b
entry
chiral promoter
conditionsa
yield (%) ee (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
2
3
4
5
DMF/Hex 3:1
THF
THF/Hex 2:1
74
38
78
73
86
4
3(R)
26(S)
64(S)
72(S)
38(S)
44(S)
THF/Hex 3:1
THF/Hex 3:1c
THF/Hex 3:1d
The optimized reaction condition was extended to various
aldehydes with allyl bromide and prenyl bromide, and the
results are summarized in Table 2 and Table 3, respectively.
THF/Hex 3:1e
THF/Hex 3:1f
THF/Hex 3:1
THF/Hex 3:1
THF/Hex 3:1
THF/Hex 3:1
0
91
73
87
97
71
19(S)
75(R)
36(S)
9(R)
1
1
1
0
1
2
10(S)
Table 2. Enantioselective Indium-Mediated Addition of Allyl
Bromide to Aldehydes
a
For experimental, refer to the Typical Experimental Procedure (ref 10)
b
unless modification is indicated. Determined by HPLC analysis employing
a Daicel Chiracel OD column. Absolute configuration assignment by
comparison with literature value of optical rotation. All the reactants were
added together and stirred at 25 °C for 2 h. Immediately before the addition
of benzaldehyde, 0.5 mmol of water was added. Immediately before the
addition of benzaldehyde, 0.1 mL of water was added. 1 mmol of indium
was added.
1
2
c
yield, eea
entry
R
yield, ee
73, 75(R)5
90, 73(R)6
84, 73(R)5
89, 76(R)7
77, 62(R)c
92, 59(R)5
69, 57(S)8
d
e
1
2
3
4
5
6
7
Ph
73, 72(S)
67, 59(S)b
85, 38(S)
78, 84(S)
76, 56(S)
f
3-MeOC6H4
4-MeOC6H4
1-naphthyl
2-naphthyl
(E)-PhCHdCH
n-octyl
proceeded smoothly to afford the corresponding homoallylic
alcohols in good yields. It was noticed that in contrast to
normal indium-mediated allylation reactions, our reaction
was sensitive to water. The best result with (+)-cinchonidine
87, 56(S)
66, 30(R)d
a
Enantioselectivities determination by HPLC analysis employing a Daicel
Chiracel OD column. Absolute configuration assignment by comparison
with literature value of optical rotations. b Enantioselectivities determination
2
was obtained when a 3:1 THF/hexane mixed solvent was
c
by HPLC analysis employing a Daicel Chiracel OJ column. Absolute
employed (entry 9). In contrast, the use of other solvent
systems afforded the product in much lower enantioselec-
tivities. The use of catalytic or substoichiometric amounts
of the chiral promoter afforded the product in much lower
d
configuration assignment by analogy. Enantioselectivitydetermination by
optical rotation. [R]25 +3.2 (c 3.05 in CCl ) for the product obtained with
D
4
1
; [R]25D -6.0 (c 2.46 in CCl4) for the product obtained with 2.
(
3) For selected enantioselective allylation of aldehydes with allylzinc
Consistent with the result obtained with benzaldehyde, 2
generally gave better selectivities than 1. Another notable
trend is that prenyl bromide afforded better chemical yields
reagents, see: (a) Hong, B.-C.; Hong, J.-H.; Tsai, Y.-C. Angew. Chem. Int.
Ed. 1998, 37, 468-470; Angew. Chem. 1998, 110, 482-484. For enanti-
oselective reaction with allylsilanes, see: (b) Keck, G. E.; Tarbet, K. H.;
Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467-8468. (c) Ishihara, K.;
Mouri, M.; Gao, Q.; Maruyama, T.; Furuta, K.; Yamamoto, H. J. Am. Chem.
Soc. 1993, 115, 11490-11495. For enantioselective reaction with allyl-
stannanes, see: (d) Yanagisawa, A.; Nakashima, H.; Ishiba, A.; Yamamoto,
H. J. Am. Chem. Soc. 1996, 118, 4723-4724. (e) Nakajima, M.; Saito, M.;
Shiro, M.; Hashimoto, S.-I. J. Am. Chem. Soc. 1998, 120, 6419-6420. For
enantioselective reaction with allyltitanium reagents, see: (f) Hafner, A.;
Duthaler, R. O.; Marti, R.; Rihs, G.; Rothe-Streit, P.; Schwarzenbach, F. J.
Am. Chem. Soc. 1992, 114, 2321-2336. For enantioselective ene reaction,
see: (g) Mikami, K.; Terada, M.; Nakai, T. J. Am. Chem. Soc. 1990, 112,
Table 3. Enantioselective Indium-Mediated Addition of Prenyl
Bromide to Aldehydes
1
2
entry
R
yield, eea
yield, ee
3
949-3954. (h) For enantioselective reaction with allylboranes, see: Corey,
E. J.; Yu, C. M.; S. S. Kim, J. A. Chem. Soc. 1989, 111, 5495-5496.
4) The cinchona alkaloids have been applied to other enantioselective
1
2
3
4
5
6
7
Ph
98, 76(S)
96, 62(S)
98, 29(S)b
91, 41(S)
86, 29(S)
88, 72(S)
87, 27(R)b
99, 90(R)9
95, 77(R)c
3-MeOC6H4
4-MeOC6H4
1-naphthyl
2-naphthyl
(E)-PhCHdCH
n-octyl
(
97, 78 (R)c
organic transformations. (a) Reformatsky reactions: Johar, P. S.; Araki,
S.; Butsugan, Y. J. Chem. Soc., Perkin Trans. 1 1992, 711-713. (b) Michael
additions: Latvala, A.; Stanchev, S.; Linden, A.; Hesse, M. Tetrahedron:
Asymmetry 1993, 4, 173-176. (c) Dihydroxylation: Crispino, G. A.; Ho,
P. T.; Sharpless, K. B. Science, 1993, 259, 64-66 and references therein.
83, 64(R)c
95, 81(R)c
98, 56(R)c
89, 41(S)c
(
d) [1,3]-Proton shift reaction: Soloshonok, V. A.; Kirilenko, A. G.;
Galushko, S. V.; Kukhar, V. P. Tetrahedron Lett. 1994, 35, 5063-5064.
e) Acetylide addition to ketimines: Huffman, M. A.; Yasuda, N.; DeCamp,
a
(
Enantioselectivity determination by HPLC analysis employing a Daicel
Chiracel OD column. Absolute configuration assignment by comparison
with literature value of optical rotation. b Enantioselectivity determination
by HPLC analysis employing a Daicel Chiracel OD column of the
corresponding 3,5-dinitrobenzoate derivatives. c Assigned by analogy.
A. E.; Grabowski, E. J. J. J. Org. Chem. 1995, 60, 1590-1594. (f) Enolate
alkylation: Corey, E. J.; Xu, F.; Noe, M. N. J. Am. Chem. Soc. 1997, 119,
1
2414-12415 and references therein. (g) Hydrogenation: Kunkle, N.;
Szabo, A.; Schurch, M.; Wang, G.; Mallat, T.; Baiker, A. Chem. Commun.
999, 1377-1378 and referances cited therein.
1
1856
Org. Lett., Vol. 1, No. 11, 1999

and better enantioselectivities than allyl bromide. The best
result (99% yield, 90%(R) ee) was obtained when benz-
aldehyde was treated with prenyl bromide in the presence
of 2 (Table 3, entry 1). The allylation reaction of most
aromatic aldehydes gave good results, except for 4-meth-
oxybenzaldehyde in the presence of 1 (entry 3). However,
application of the protocol to an R,â-unsaturated aldehyde
such as (E)-cinnamaldehyde (entry 6) and an aliphatic
aldehyde such as nanyl aldehyde (entry 7) only led to
moderate selectivities. In the case of cinnamaldehyde, only
the 1,2-addition product was obtained without any detectable
hydes; (2) the chiral promoters can be easily obtainable
commercially at low cost and recoverable by simple ma-
nipulations; (3) in general, good yields and moderate to high
selectivities were obtained and both enantiomers of the
homoallylic alcohols can be easily obtained by changing the
chiral source. The identity of the allyl indium-chiral
promoter complexes and reaction mechanism still remains
obscure, and further work in this area is underway in our
laboratory.
Acknowledgment. This research was assisted financially
1
,4-addition byproduct.
by grants from the National University of Singapore.
This new method10 has several advantages due to the
following reasons: (1) its experimentation is practically
simple and applicable to various allyl bromides and alde-
Supporting Information Available: General procedure
of the indium-mediated addition of the allylic bromides to
1
13
aldehydes and H and C NMR and HPLC data of all of
the homoallylic alcohols. This material is available free of
charge via the Internet at http://pubs.acs.org.
(
5) Minowa, N.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1987, 60, 3697-
3
1
2
704.
(6) Denmark S. E., Coe, D. M.; Pratt, N. E.; Griedel, B. D. J. Org. Chem.
994, 59, 6161-6163.
(7) Sugimoto, K.; Aoyaji, S.; Kibayashi, C. J. Org. Chem. 1997, 62,
OL990316F
322-2323.
(
(
(
8) Wang, Z.; Wang, D.; Sui, X. Chem. Commun. 1996, 2261-2262.
9) Manabe, S. Chem. Commun. 1997, 737-738.
to room temperature, and finally quenched with 10 mL of a dilute HCl
solution. The aqueous layer was extracted with hexane (10 mL × 3). The
combined organic extracts were washed with brine, dried over anhydrous
sodium sulfate, concentrated under vacuum, and purified by flash silica
gel column chromatography to afford 73% of the homoallylic alcohol as a
10) Typical Experimental Procedure: To a 50 mL round-bottom flask
containing an egg-shaped stirring bar were added (-)-chinchonidine 2 (0.5
mmol) and indium powder (0.5 mmol, 57 mg). The solids were azeotro-
pically dried with 3 mL of dry THF twice and then treated with 3 mL of
dry THF and allyl bromide (1.5 mmol, 126 mL). The mixture was stirred
vigorously till it turned into a clear solution, to which was added dropwise
25
9
colorless oil (27 mg, 0.183 mmol); [R] D +49.5 (c 1.05, benzene). The
aqueous phase was neutralized with 1 M sodium bicarbonate solution and
extracted with ethyl acetate (10 mL × 5). The combined organic extracts
were dried with sodium sulfate and concentrated under vacuum to give
97% of 2 as a white solid (143 mg, 0.243 mmol).
1
mL of dry hexane. The resulting clear solution was cooled to -78 °C,
followed by introduction of benzaldehyde (0.25 mmol, 25 mL) dropwise.
The reaction mixture was stirred at -78 °C for 2 h, then allowed to warm
Org. Lett., Vol. 1, No. 11, 1999
1857