Catalytic asymmetric dienylation of achiral aldehydes using buta-2,3-dienylstannane in the presence of chiral Lewis acid and synergetic reagent

Article abstract of DOI:10.1039/a908119d

Efficientcatalytic asymmetric dienylation of achiral aldehydes with buta-2,3-dienyltributylstannane promoted by a BINOL-Ti^IV complex is achieved with high enantio-selectivity by the utilization of Et₂BSPr¹ The Royal Society of Chemistry 1999.

Full text of DOI:10.1039/a908119d

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Catalytic asymmetric dienylation of achiral aldehydes using
buta-2,3-dienylstannane in the presence of chiral Lewis acid
and synergetic reagent
Chan-Mo Yu,* Seung-Joo Lee and Miyoo Jeon
Department of Chemistry and Institute of Basic Sciences, Sungkyunkwan University,
Suwon 440-746, Korea. E-mail: cmyu@chem.skku.ac.kr
Received (in Cambridge, UK) 11th October 1999, Accepted 4th November 1999
Efficient catalytic asymmetric dienylation of achiral
aldehydes with buta-2,3-dienyltributylstannane promoted
by a BINOL-TiIV complex is achieved with high enantio-
selectivity by the utilization of Et2BSPri.
The development of catalytic asymmetric methods for carbonyl
addition reactions is an important research area of current
organic chemistry.1 Recent efforts by several research groups
to activate chiral catalysts to reach maximum selectivity and
reactivity through the use of additives and cocatalysts have led
to impressive advances in carbonyl addition reactions.2 Recent
reports from this laboratory have shown that the utilization
of molecular synergetic reagents can provide highly enantio-
selective versions of allylic transfer reactions3 of achiral alde-
Scheme 2 Reagents and conditions: i) a. NaH, 0 ЊC, THF; b. p-TsCl,
THF, 0 ЊC; c. Bu3SnLi, Ϫ78 ЊC. ii) NaH, p-TsCl, Ϫ78 to Ϫ20 ЊC, THF.
iii) Bu3SnLi, Ϫ78 ЊC, 1 h.
hydes including allylation, propargylation and allenylation.4
More recently, we demonstrated the enantioselective synthesis
of dienyl alcohols by a two step sequence employing (4-
trimethylsilylbut-2-ynyl)tributylstannane (1) as an allylic trans-
fer reagent as depicted in Scheme 1.5 The efficiency of this
the next operation without isolation; ii) subsequent treatment
of tosylate 8 with Bu3SnLi at Ϫ78 ЊC for 1 h and then work up
(quenching with pH 7 buffer solution followed by extraction
with hexanes) afforded the crude product. After removal of
base line impurities by filtration through Et3N-pretreated silica
gel with hexanes, final purification was effected by bulb to bulb
distillation (0.1 mmHg, 150 ЊC, 54% yield).8 The stage was thus
set for the dienylation of 2 with aldehydes promoted by a chiral
Lewis acid catalyst.
Initial experiments on the dienylation of 2 with hydro-
cinnamaldehyde promoted by BINOL-TiIV complex indicated
that the tin reagent 2 turned out to be less reactive than other
allylic transfer reagents such as allyl-, propargyl- and allenyl-
stannanes. After surveying numerous conditions, several key
findings emerged: i) control experiment revealed that the reac-
tion proceeded only marginally in the absence of synergetic
reagent (10 mol% catalyst, Ϫ20 ЊC, 30 h, <5% yield); ii)
Et2BSPri exhibited moderate efficiency for the catalytic process
in increasing reaction rate; iii) a 2:1 mixture of the BINOL
and Ti(OPri)4 complex in the presence of 4 Å molecular sieves
proved to be the most efficient catalyst; iv) the reaction per-
formed at Ϫ20 ЊC in PhCF3 resulted in optimal chemical yields
and enantioselectivities in comparison with other solvents such
as CH2Cl2 and toluene.9 Under optimal conditions, the allylic
transfer reaction was conducted by the dropwise addition of
Et2BSPri (1.2 equiv) in PhCF3 at Ϫ20 ЊC to a mixture of 2 and
hydrocinnamaldehyde in the presence of (S)-BINOL-TiIV
(10 mol%)10 in PhCF3. After 8 h at Ϫ20 ЊC, the mixture was
quenched by the addition of a saturated aqueous NaHCO3.
Work up and chromatography on triethylamine treated silica
gel gave 4 (R = PhCH2CH2) in 74% yield with 97% ee. Addi-
tional experiments with various aldehydes were carried out
and representative results are summarized in Table 1. It can be
seen from Table 1 that the catalytic process is effective for a
variety of aldehydes. It is noteworthy that the protocol using
reagent 2 turned out to be more efficient than the two
step operation employing reagent 1 in terms of enantio-
selectivities and chemical yields. The absolute configuration of
Scheme 1 Catalytic asymmetric dienylation routes.
protocol in terms of enantioselectivity and catalytic ability has
encouraged us to develop a direct method for the catalytic
asymmetric dienylation process which would expand the utility
and practicability of allylic transfer reactions.6
The starting point of this investigation was the availability of
the reagent 2 in a regiochemically pure form. Initial attempts on
the synthesis of 2 using allenyl alcohol 57 afforded discouraging
results since the products were formed as a mixture of regio-
isomers. We were surprised to find that the reaction performed
under conditions i as described in Scheme 2 gave repeatedly 6 as
a major component (ca. 6:7:2 = 2:0.1:1). The formation of
but-2-ynylstannane 6 from 5 was attributed to basic media in
the reaction mixture. As a consequence, we speculated that the
formation of 6 could be avoided by small changes in the reac-
tion conditions to minimize basic media in the reaction mixture.
Indeed we were delighted to find that the tin reagent 2, a crucial
compound for this investigation, can be prepared by the follow-
ing sequence: i) addition of allenyl alcohol 5 to a mixture of
p-TsCl and NaH in THF at Ϫ78 ЊC for 1 h then Ϫ20 ЊC for 1 h
resulted in the formation of the tosylate 8 which was used for
J. Chem. Soc., Perkin Trans. 1, 1999, 3557–3558
This journal is © The Royal Society of Chemistry 1999
3557

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Table 1 Dienylation reactions of 2 with achiral aldehydesa,b
81%) as a colorless liquid: TLC, Rf 0.29 (9:1 hexane–EtOAc);
[α]D20 = Ϫ93.2 (c 1.34 in CHCl3); νmax (neat)/cmϪ1 3386, 3088,
3030, 1594, 1452, 992, 736, 664; Found: C, 82.33; H, 7.69. Calc.
for C11H12O: C, 82.46; H, 7.55; O, 9.99%; δH(500 MHz; CDCl3;
Me4Si) 2.01 (1H, d, J 3.40, OH), 5.05 (1H, d, J 11.34,
HC᎐CHHc), 5.22 (1H, d, J 17.85, HC᎐CHHt), 5.34 (1H, s,
᎐
᎐
C᎐CHH), 5.41 (1H, s, C᎐CHH), 5.48 (1H, d, J 3.40, CHOH),
᎐
᎐
6.31 (1H, dd, J 11.34 and 17.85, HC᎐CH ), 7.25–7.40 (5H, m,
PhH); δC(50 MHz; CDCl3; Me4Si) 74.03, 115.44, 115.61,
᎐
2
Entry
RCHO
t/h
Yield (%)c
Ee (%)d
126.85, 127.79, 128.46, 135.80, 141.97, 147.68.
1
2
3
4
5
PhCH2CH2
C6H13
Ph
8
8
8
16
16
74
72
81
53
61
97
94
98
91
93
Acknowledgements
PhCH᎐CH
᎐
᎐
This research was supported by the Korea Science & Engineer-
ing Foundation (KOSEF 97-0501-02-01-3) and the Center for
Molecular Design and Synthesis (CMDS) at KAIST sponsored
by KOSEF through the Science Research Center program.
PhC᎐C
᎐
a All reactions were carried out at Ϫ20 ЊC in PhCF3. b BINOL:Ti-
(OPri)4 = 2:1 (10 mol%). c Yields refer to isolated and purified products.
d Enantiomeric excesses were determined by preparation of (ϩ)-MTPA
ester derivatives, analysis by 500 MHz 1H NMR spectroscopy, and
comparison with corresponding diastereomers which were prepared
from (R)-BINOL-TiIV
.
References
1 General discussions on chiral Lewis acids: R. Noyori, Asymmetric
Catalysis in Organic Synthesis, Wiley, New York, 1994, pp. 255–297;
K. Maruoka and H. Yamamoto, in Catalytic Asymmetric Synthesis,
ed. I. Ojima, VCH, New York, 1993, pp. 413–440; K. Mikami,
in Advances in Catalytic Process, ed. M. P. Doyle, JAI Press,
Greenwich, 1995, pp. 1–44.
2 Review: E. M. Vogl, H. Groger and M. Shibasaki, Angew. Chem.,
Int. Ed., 1999, 38, 1571 and also see T. Mukaiyama, Aldrichimica
Acta, 1996, 29, 59; H. Ishitani, M. Ueno and S. Kobayashi, J. Am.
Chem. Soc., 1997, 119, 7153; K. Ding, A. Ishii and K. Mikami,
Angew. Chem., Int. Ed., 1999, 38, 497.
3 For comprehensive discussions on the allylic transfer reactions, see:
Y. Yamamoto and N. Asao, Chem. Rev., 1993, 93, 2207; D. Hoppe,
W. R. Roush and E. J. Thomas, in Stereoselective Synthesis, vol. 3,
eds. G. Helmchen, R. W. Hoffmann, J. Mulzer and E. Schaumann,
Thieme, Stuttgart, 1996, pp. 1357–1602; J. A. Marshall, Chem. Rev.,
1996, 96, 31; M. Santell and J.-M. Pons, Lewis Acids and Selectivity
in Organic Chemistry, CRC Press, New York, 1996, pp. 91–184.
4 C.-M. Yu, H.-S. Choi, W.-H. Jung and S.-S. Lee, Tetrahedron Lett.,
1996, 37, 7095; C.-M. Yu, H.-S. Choi, W.-H. Jung, H.-J. Kim and
J. Shin, Chem. Commun., 1997, 761; C.-M. Yu, S.-K. Yoon,
H.-S. Choi and K. Baek, Chem. Commun., 1997, 763; C.-M. Yu,
H.-S. Choi, S.-K. Yoon and W.-H. Jung, Synlett, 1997, 889; C.-M.
Yu, S.-K. Yoon, K. Baek and J.-Y. Lee, Angew. Chem., Int. Ed.,
1998, 37, 2392.
the predominating enantiomer of the adducts 4 was unambigu-
ously established by comparison of their specific rotations with
that of known alcohols.5,6
In summary, an efficient method for the catalytic enantio-
selective addition of buta-2,3-dienyltributylstannane to alde-
hydes is described which employs
a synergetic reagent,
Et2BSPri, and BINOL-TiIV complex, furnishing dienyl alcohols
in good yields with high levels of enantioselectivity. Studies are
in progress to enlarge the scope of this protocol with more
highly functionalized tin reagents, which will provide a better
understanding of this chemical phenomenon.
Experimental
Typical procedure for the catalytic dienylation (entry 3 of Table
1): a flame-dried flask containing (S)-BINOL (57.3 mg, 0.2
mmol) and activated powdered 4 Å molecular sieves (0.7 g) was
evacuated and carefully purged with nitrogen three times and
then charged with dry PhCF3 (2 mL) followed by freshly dis-
tilled Ti(OPri)4 (freshly prepared 0.5 M in PhCF3, 0.2 mL, 0.1
mmol). The mixture was allowed to proceed at 25 ЊC for 3 h.
The red-brown mixture was cooled to Ϫ20 ЊC in a dry ice–CCl4
bath, and benzaldehyde (1, R1 = Ph, 0.11 g, 1.0 mmol) in PhCF3
(0.5 mL) was added. To this mixture was added dropwise
buta-2,3-dienyltributylstannane (2, 0.41 g, 1.2 mmol) in PhCF3
(1 mL) followed by Et2BSPri (0.18 g, 1.25 mmol) in PhCF3
(1 mL) with a gas-tight syringe via a syringe pump over 1 h
along the wall of the flask while keeping the temperature below
Ϫ20 ЊC. After stirring for 8 h at Ϫ20 ЊC, aqueous NaHCO3
(5 mL) was added to the reaction mixture, and then diluted with
CH2Cl2 (10 mL). The molecular sieves were removed by filtra-
tion, and the aqueous layer was extracted with CH2Cl2 (ca. 20
mL). After drying the combined organic solution over
anhydrous Na2SO4, the solvents were removed under reduced
pressure. Flash column chromatography (Et3N pretreated SiO2,
10% EtOAc in hexanes) afforded 4 (R = Ph; 0.130 g, 0.81 mmol,
5 C.-M. Yu, S.-K. Yoon, S.-J. Lee, J.-Y. Lee and S. S. Kim, Chem.
Commun., 1998, 2749.
6 For the enantioselective synthesis of dienyl alcohols using stoichio-
metric chiral reagents, see: R. Soundararajan, G. Li and H. C.
Brown, J. Org. Chem., 1996, 61, 100; S. Hatakeyama, K. Sugawara
and S. Takano, J. Chem. Soc., Chem. Commun., 1991, 1533.
7 E. A. Adegoke, T. A. Emolpae and H. Ephraim-Bassey, J. Hetero-
cycl. Chem., 1986, 23, 1195.
8 M. Luo, Iwabuechi and S. Hatakeyama, Chem. Commun., 1999, 267.
9 A. Ogawa and D. P. Curran, J. Org. Chem., 1997, 62, 450.
10 G. E. Keck, K. H. Tarbet and L. S. Geraci, J. Am. Chem. Soc., 1993,
115, 8467; G. E. Keck and D. Krishnamurthy, J. Am. Chem. Soc.,
1995, 117, 2363; G. E. Keck and D. Krishnamurthy, Org. Synth.,
1997, 75, 12.
Communication 9/08119D
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J. Chem. Soc., Perkin Trans. 1, 1999, 3557–3558