Highly enantioselective allylation of aldehydes catalyzed by indium(III) - PYBOX complex

Article abstract of DOI:10.1021/ol047711c

(Chemical Equation Presented) A chiral indium(III) - PYBOX complex prepared from indium triflate and chiral PYBOX has been discovered to effect high enantioselectivities in the addition of allyltributyl stannane to aldehydes. The allylation of a variety of aromatic, α,β-unsaturated, and aliphatic aldehydes resulted in good yields and high enantioselectivities (up to 94% ee).

Full text of DOI:10.1021/ol047711c

ORGANIC
LETTERS
2
005
Vol. 7, No. 1
59-161
Highly Enantioselective Allylation of
Aldehydes Catalyzed by
1
Indium(III)
−PYBOX Complex
Jun Lu,†,‡ Shun-Jun Ji,*,‡ Yong-Chua Teo, and Teck-Peng Loh*
†
,†,‡
Department of Chemistry, National UnViVersity of Singapore, 3 Science DriVe 3,
Singapore 117543, and Key Laboratory of Organic Synthesis of Jiangsu ProVince,
College of Chemistry and Chemical Engineering of Suzhou UniVersity,
Suzhou 215006, China
chmlohtp@nus.edu.sg
Received November 8, 2004
ABSTRACT
A chiral indium(III)−PYBOX complex prepared from indium triflate and chiral PYBOX has been discovered to effect high enantioselectivities
in the addition of allyltributyl stannane to aldehydes. The allylation of a variety of aromatic,
in good yields and high enantioselectivities (up to 94% ee).
r
,
â
-unsaturated, and aliphatic aldehydes resulted
3
The synthesis of enantiomerically enriched homoallylic
alcohols is an important goal in organic synthesis. This is
because homoallylic alcohols are versatile intermediates that
can be converted to a wide variety of synthetically useful
synthetic transformations. In this paper, we describe a
procedure for the synthesis of chiral homoallylic alcohols
by the reaction of aldehydes with allyltributylstannane
catalyzed by novel chiral In(OTf)
1).
4
3
-PYBOX complexes (eq
1
compounds. Therefore, there has been intense research
2
activity in this area in recent years,
leading to the
Our initial studies began with allyltributylstannane and
benzaldehyde in the catalytic amount of chiral In(III)-
PYBOX complex. The chiral complex was prepared by
3
development of a large and diverse array of chiral catalysts,
especially chiral Lewis acid catalyzed addition of the allyl
transfer reagents to carbonyl functionality. Most of them
consist of chiral ligands attached to metals such as Zn, Ti,
B, Cr, and Rh. However, enantioselective allylation using
chiral indium(III) catalyst has been relatively unexplored,
although indium(III) complexes have gained widespread
application as efficient Lewis acid catalysts for various
reacting In(OTf) (0.2 equiv) and (S)-i-PrPYBOX (1) (0.22
(
2) (a) Denmark, S. E.; Fu, J.-P. Chem. ReV. 2003, 103, 2763. For some
examples see: (b) Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem.
Soc. 1993, 115, 8467. (c) Cosata, A. L.; Piazza, M. G.; Tagliavini, E.;
Trombini, C.; Ronchi, A. U. J. Am. Chem. Soc. 1993, 115, 7001. (d)
Yanagisawa, A.; Nakashima, H.; Ishiba, A.; Yamamoto, H. J. Am. Chem.
Soc. 1996, 118, 4723. (e) Yanagisawa, A.; Ishiba, A.; Nakashima, H.;
Yamamoto, H. Synlett 1996, 88. (f) Yanagisawa, A.; Nakashima, H.;
Nakatsuka, Y.; Ishiba, A.; Yamamoto, H. Bull. Chem. Soc. Jpn. 2001, 74,
1129. (g) Hanawa, H.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2003,
125, 1708. (h) Cozzi, P. G.; Orioli, P.; Tagliavini, E.; Umani-Ronchi, A.
Tetrahedron Lett. 1997, 38, 145. (i) Loh, T.-P. In Science of Synthesis;
Yamamoto, H., Ed.; Georg Thieme Verlag Stuttgart: New York, 2004;
p 413.
†
National Unviversity of Singapore.
College of Chemistry and Chemical Engineering of Suzhou University.
‡
(
1) (a) Nicolaou, K. C.; Kim, D. W.; Baati. R. Angew. Chem., Int. Ed.
2
002, 41, 3701. (b) 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. (d) Yamamoto, Y. Acc. Chem. Res. 1987, 20, 243.
1
0.1021/ol047711c CCC: $30.25
© 2005 American Chemical Society
Published on Web 12/07/2004

ee; Table 1, entry 1) when the reaction was carried out at at
-
-
60 °C (78% ee at -10 °C, 84% ee at -40 °C, 81% ee at
78 °C).
We also screened other indium salts using identical
conditions and found that the products were obtained in lower
yields and enantioselectivities (Table 1, entries 3 and 4).
After optimizing these allylation reaction conditions,
several other chiral ligands were synthesized and screened
equiv) in solvent at room temperature in the presence of MS
Å. After 2 h of stirring, allyltributylstannane (1.2 equiv)
was added followed by benzaldehyde (1 equiv) with TMSCl
1.2 equiv). The homoallylic alcohol was then obtained by
aqueous workup and column chromatography. The results
are summarized in Table 1.
3
with In(OTf) , among which tetraphenyl-substituted (S)-i-
PrPYBOX (6) gave the best result (81% yield, 92% ee; Table
1, entry 9).
4
(
Through this screening process, the following points could
be established: (1) The use of tridentate bis(oxazolinyl)-
pyridine (PYBOX) (entries 1-4, 7-9, Table 1) gave the
homoallylic alcohols in good yields with high enantioselec-
tivities. (2) The yields and enantioselectivities of homoallylic
alcohols depends on the indium salt (Br < Cl , OTf) (Table
1, entries 1, 3, 4). (3) As a “promoter”, it was found that
TMSCl was more superior than TESCl, TBSCl, and TIPSCl.
Table 1. Evaluation of Various Chiral Indium(III) Complexes
for the Asymmetric Allylation Reactiona
(4) Of these complexes surveyed, the tetraphenyl-substituted
(S)-i-PrPYBOX (6)-derived complex provided superior levels
of asymmetric induction, affording the homoallylic alcohol
in 92% ee (Table 1, entry 9).
Having optimized the reaction conditions, we extended
the catalytic enantioselective allylation to a wide variety of
aldehydes in the presence of the tetraphenyl-substituted (S)-
i-PrPYBOX (6). The results obtained are shown in Table 2.
Table 2. In(OTf) -Pybox (6)-Catalyzed Allylation of
3
Aldehydea
entry
chiral ligand
indium salt
yield (%)b
ee (%)c
85
entry
R
yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
1
1
1
1
2
3
4
5
6
In(OTf)3
In(OTf)3
InBr3
80
81
12
84
0
d
d
1
2
3
4
5
6
7
8
9
Ph
Ph
81
85
92
91
94
90
94
84
86
91
85
22
e
31
40
0
2-naphthyl
4-ClC6H4
86
61
80
81
91
78
68
InCl3
In(OTf)3
In(OTf)3
In(OTf)3
In(OTf)3
In(OTf)3
5-Me-furyl
PhCH2CH2
PhCHdCH
BnO(CH2)3
n-C8H17
0
0
96
84
81
52
63
92
a
All reactions were carried out with benzaldehyde (1 equiv), TMSCl
1.2 equiv), and allyltributylstannane (1.2 equiv) using indium salt (0.2
a
(
All reactions were carried out with aldehyde (1 equiv), TMSCl (1.2
equiv) and chiral ligands (0.22 equiv) in the presence of activated MS 4Å
equiv), and allyltributylstannane (1.2 equiv) using In(OTf)3 (0.2 equiv) and
(S)-iPrPYBOX (6) (0.22 equiv) in the presence of activated MS 4Å in
anhydrous CH2Cl2. The reaction mixture was kept for 30 h at -60 °C.
in anhydrous CH2Cl2. The reaction mixture was kept for 30 h at -60 °C.
b
c
d
Isolated yield. Ee determined by HPLC. Without TMSCl.
b
Isolated yield. c ee determined by HPLC or 500 MHz H NMR of the
1
corresponding MTPA ester. For further details see Supporting Information.
d
8% of chiral ligand was recovered. e Recovered (S)-i-Pr PYBOX (6) was
8
First, the effects of solvent and temperature were surveyed.
used for the reaction.
The allylation reaction carried out at room temperature in
CH Cl afforded the product in 59% ee (only 12% ee without
TMSCl). The use of other solvents led to lower selectivities
42% ee in toluene, 54% ee in EtCN, 55% ee in 1:1 CH
Cl /toluene).
Next, the reaction was performed in CH
temperatures. The best result was obtained (80% yield, 85%
2
2
As shown in Table 2, all of the aldehydes, including
aromatic aldehydes, R,â-unsaturated, and aliphatic aldehydes,
furnished the products in high enantioselectivities (84-94%
ee) and good yields. Furthermore, (S)-i-PrPYBOX (6) could
be easily recovered in 88% yield without racemization and
(
2
-
2
2
2
Cl at different
160
Org. Lett., Vol. 7, No. 1, 2005

could be reused to afford the product in equal yield and
enantioselectivity (Table 2, entry 2). This makes the cost of
the chiral catalyst irrelevant.
Scheme 1. Application to the Steroid Side-Chain Synthesis
It is noteworthy that the chiral steroidal aldehyde 8 was
allylated to give 9 with high enantioselectivity (22S:22R )
96:4) (Scheme 1). Furthermore, the reaction was highly
chemoselective, reacting only with the aldehyde functionality.
No reaction was observed with the enone functionality in
the A ring. Interestingly, the use of (R)-i-PrPYBOX (6)
afforded the 22S-product as a single isomer (22S:22R )
100:0).
In conclusion, we have developed a highly catalytic
enantioselective allylation of aldehydes to give enantiomeri-
cally enriched homoallylic alcohols in good yields and
excellent enantiomeric excess in the presence of a catalytic
amount of In(OTf) -PYBOX complexes. Further work on
3
(
3) For reviews, see: (a) Chauhan, K. K.; Frost, C. G. J. Chem. Soc.,
redesigning high affinity chiral PYBOX applicable to the
allylation reaction as well as for other organic transformations
is in progress.
Perkin Trans. 1 2000, 3015. (b) Babu, G.; Perumal, P. T. Aldrichimica
Acta 2000, 33, 16. For recent examples, see: (c) Mukaiyama, T.; Ohno,
T.; Nishimura, T.; Han, J. S.; Kobayashi, S. Chem. Lett. 1990, 2239. (d)
Trost, B. M.; Sharma, S.; Schmidt, T. J. Am. Chem. Soc. 1992, 114, 7903.
(
1
2
e) Loh, T.-P.; Pei, J.; Cao, G.-Q. J. Chem. Soc., Chem. Commun. 1996,
819. (f) Loh, T.-P.; Pei, J.; Lin, M. J. Chem. Soc., Chem, Commun. 1996,
315. (g) Loh, T.-P.; Chua, G.-L.; Vittal, J. J.; Wong, M.-W. J. Chem.
Acknowledgment. We thank the National University of
Singapore and the National Natural Science Foundation of
China (no. 20472062) for providing the research funding.
We are also grateful to Medicinal Chemistry Program
(R-143-600-600-712) for financial support.
Soc., Chem. Commun. 1998, 861. (h) Loh, T.-P.; Wei, L.-L. Tetrahedron
Lett. 1998, 39, 323. (i) Loh, T.-P.; Huang, J.-M.; Goh, S.-H.; Vittal, J. J.
Org. Lett. 2000, 2, 1291. (j) Yang, J.; Li, C.-J. Synlett 1999, 717. (k)
Viswanathan, G.-S.; Yang, J.; Li, C.-J. Org. Lett. 1999, 1, 993. (l) Ranu,
B. C.; Jana, U. J. Org. Chem. 1998, 63, 8212. (m) Ranu, B. C.; Hajra, A.;
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C. G. Tetrahedron Lett. 1999, 40, 5621. (o) Chauhan, K. K.; Frost, C. G.;
Love, I.; Waite, D. Synlett 1999, 1743. (p) Tsuchimoto, T.; Maeda, T.;
Shirakawa, E.; Kawakami, Y. J. Chem. Soc., Chem. Commun. 2000, 1573.
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.
(
(
q) Gadhwal, S.; Sandhu, J. S. J. Chem. Soc., Perkin Trans. 1 2000, 2827.
r) Zhu, C.-J.; Yuan, F.; Gu, W.-J.; Pan, Y. J. Chem. Soc., Chem. Commun.
2
003, 692.
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1
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H.; Radinov, R.; Porter, N. A. J. Am. Chem. Soc. 1995, 117, 11029. (d)
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8
489.
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