Stereoselective 4-benzyloxybut-2-enylation of aldehydes via an allyl-transfer reaction using a chiral allyl donor

Article abstract of DOI:10.1021/ol050890t

(Chemical Equation Presented) A direct and highly stereoselective (E)-4-benzyloxybut-2-enylation of aldehydes was successfully carried out to give 5-benzyloxyhomoallylic alcohol (11) via an allyl-transfer reaction using a chiral allyl donor (10). The chir

Full text of DOI:10.1021/ol050890t

ORGANIC
LETTERS
2005
Vol. 7, No. 14
2957-2960
Stereoselective
4-Benzyloxybut-2-enylation of Aldehydes
via an Allyl-Transfer Reaction Using a
Chiral Allyl Donor
Siddiqi M. Shafi, Jingyu Chou, Kazuhide Kataoka, and Junzo Nokami*
Department of Applied Chemistry, Okayama UniVersity of Science, 1-1 Ridai-cho,
Okayama 700-0005, Japan
nogami@dac.ous.ac.jp
Received April 22, 2005
ABSTRACT
A direct and highly stereoselective (E)-4-benzyloxybut-2-enylation of aldehydes was successfully carried out to give 5-benzyloxyhomoallylic
alcohol (11) via an allyl-transfer reaction using a chiral allyl donor (10). The chiral allyl donor (10) was prepared by catalytic Sharpless asymmetric
epoxidation of 3-methylbut-2-en-1-ol, followed by a stereospecific vinyl Grignard reaction of the epoxide in the presence of CuBr and selective
benzylation of the primary alcohol of diol.
The reaction of an allylic nucleophile with an aldehyde (or
ketone) is one of the most attractive and practical carbon-
carbon bond formation reactions to give a homoallylic
alcohol. In this reaction, the product has both a chiral center
and a double bond, which serve as useful building blocks in
organic synthesis.1 There are many reports on the preparation
of highly optically active homoallyl(ic) alcohols, including
substituted homoallyl alcohols, via nucleophilic allylation of
an aldehyde using allyl(ic)metal reagents.2
homoallylic alcohol is obtained regioselectively with low
diastereoselectivity, although the corresponding allylic zinc
compound is not detected (eq 1).3a
However, there are few reports on the reaction of alde-
hydes with 4-alkoxyalk-2-enylmetallic compounds. One
exception is the Barbier-type reaction of an aldehyde with
1-bromo-4-benzyloxybut-2-ene 1 and zinc (under Luche’s
condition), in which the corresponding γ-adduct of the
Another exception is the reaction of (4-alkoxyalk-2-enyl)-
trialkylstannanes 4 with an aldehyde in the presence or
absence of tin(IV) chloride to give the corresponding
R-adduct 5 or γ-adduct 6 of the homoallylic alcohol (eqs 2
and 3) which is reported by Naruta3b and Thomas3c,d
independently.
(1) For reviews on reactions using allyl(ic) metals, see: (a) Yamamoto,
Y.; Asao, N. Chem. ReV. 1993, 93, 2207. (b) Marshall, J. A. In Lewis Acids
in Organic Synthesis; Yamamoto, H., Ed.; Wiley-VCH: New York. 2000;
Vol. 1. For reviews on asymmetric allylations and related reactions, see:
(c) Denmark, S. E.; Almstead, N. G. In Modern Carbonyl Chemistry; Otera,
J., Ed.; Wiley-VCH: New York, 2000. (d) Chemler, S. R.; Roush, W. R.
In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH: New York,
2000.
It is reasonable to expect that an elimination reaction will
take place by treatment of a 4-alkoxyalk-2-enyl halide with
metal, such as Mg and Zn, to give a diene. Therefore, the
10.1021/ol050890t CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/08/2005

transfer reaction using a stable and environmentally friendly
crotyl donor, such as 2,3-dimethylpent-4-en-2-ol, in the
presence of an acid catalyst as shown in Scheme 1.
Scheme 1. But-2-enylation of Aldehyde via Allyl-Transfer
Reaction
reaction does not give an allylic metal compound that is
stable enough to react with an aldehyde stereoselectively to
give the corresponding homoallylic alcohol, although (4-
alkoxyalk-2-enyl)trialkylstannanes 4 are stable enough as a
result of the high covalent character of the R3Sn-C (R )
alkyl) bond as shown above (eqs 2 and 3).
These facts prompted us to establish a convenient method
for enantioselective 4-benzyloxybut-2-enylation of an alde-
hyde via an allyl-transfer reaction.4 In the reaction, the alk-
2-enylation of the aldehyde is not a nucleophilic reaction.
Rather, it is a [3.3]-sigmatropic rearrangement, in which
C-C bond formation and cleavage take place concertedly
via a six-membered transition state. That is, direct but-2-
enylation of aldehydes 2 will take place to give the
corresponding R-adduct of homoallylic alcohols via allyl-
Therefore, we attempted to prepare a new chiral 4-ben-
zyloxybut-2-enyl donor 10 via a highly stereoselective
reaction of vinylmagnesium chloride with the optically active
epoxide 8 formed by Sharpless AE (asymmetric epoxidation)
of 3-methylbut-2-enol 7, as shown in Scheme 2.
Scheme 2. Preparation of Chiral 4-Benzyloxybut-2-enyl
Donor 10
(2) Asymmetric alk-2-enylation of aldehydes; for a review, see: (a)
Denmark, S. E.; Fu, J. Chem. ReV. 2003, 103, 2763. Original papers, for
example: catalytic asymmetric allylation with chiral catalyst, by allylsi-
lanes: (b) Wadamoto, M.; Ozasa, N.; Yanagisawa, A.; Yamamoto, H. J.
Org. Chem. 2003, 68, 5593 and references therein. (c) Malkov, A. V.; Orsini,
M.; Pernazza, D.; Muir, K. W.; Langer, V.; Meghani, P.; Kocovsky, P.
Org. Lett. 2002, 4, 1047. (d) Malkov, A. V.; Dufkova´, L.; Farrugia, L.;
Kocovsky, P. Angew. Chem., Int. Ed. 2003, 42, 3674. By allylboronate:
(e) Wada, R.; Oisaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2004,
126, 8910. Asymmetric allylation with stoichiometric chiral auxiliary, by
allylboronate: (f) Lachance, H.; Lu, X.; Gravel, M.; Hall, D. G. J. Am.
Chem. Soc. 2003, 125, 10160. (g) Rauniyar, V.; Hall, D. G. J. Am. Chem.
Soc. 2004, 126, 4518. By allylsilane: (h) Kubota, K.; Leighton, J. L. Angew.
Chem., Int. Ed. 2003, 42, 946.
(3) Barbier reactions of aldehydes (RCHO) with zinc dust and (Z)-4-
benzyloxy-1-bromobut-2-ene (BnOCH2CHdCHCH2Br) under Luche’s
condition to give the corresponding homoallylic alcohol γ-adducts [RCH-
(OH)CH(CH2OBn)CHdCH2] in low de: (a) Chattopadhyay, A.; Dhotare,
B.; Hassarajani, S. J. Org. Chem. 1999, 64, 6874. 4-Alkoxyalk-2-enyl-
stannanes (e.g., BnOCH2CHdCHCH2SnMe3) were prepared by a coupling
reaction of the corresponding bromide with Me3SnLi and treated with
benzaldehyde in the presence of SnCl4 to give unusual adducts [(Z)-PhCH-
(OH)CH2CHdCHCH2OBn] highly selectively, regardless of the stereo-
chemistry of allylstannane: (b) Naruta, Y.; Maruyama, K. J. Chem. Soc.,
Chem. Commun. 1983, 1264. 4-(tert-Butyldimethylsilyloxy)but-2-enylzir-
conium reagent (TBDMSOCH2CHdCHCH2ZrCp2OTBDMS) was prepared
via oxidative addition of “ZrCp2” with 1,4-bis(tert-butyldimethylsilyloxy)-
but-2-ene and was treated with aldehydes to give the corresponding
γ-adducts anti selectively [RCH(OH)CH(CH2OTBDMS)CHdCH2]: (c)
Clark, A. J.; Kasujee, I.; Peacock, J. L. Tetrahedron Lett. 1995, 36, 7137.
4-Benzyloxypent-2-enyltributylstannane was prepared from the correspond-
ing dithiocarbonate [CH3CH(OBn)CH(SCOSCH3)CHdCH2] with tributyltin
hydride in the presence of AIBN: (d) Mortlock, S. V.; Thomas, E. J.
Tetrahedron Lett. 1988, 29, 2479. Thomas et al. also discovered that the
reaction of the allylicstannane with aldehydes in the presence of SnCl4 gave
(Z)-5-benzyloxyhomoallylic alcohols [(Z)-RCH(OH)CH2CHdCHCH(OBn)-
CH3] highly selectively: (e) McNeill, A. H.; Thomas, E. J. Tetrahedron
Lett. 1990, 31, 6239; 1992, 33, 1369; Synthesis 1994, 322.
The Sharpless AE reaction of 3-methylbut-2-en-1-ol 7,
using tert-butylhydroperoxide (TBHP) with 12 mol % of (+)-
diethyl tartrate and titanium(IV) isopropoxide, followed by
benzoylation, gave 8 in 70% yield with >90% ee.5 To a
solution of 8 (2 mmol), dimethyl sulfide (0.6 mL), and CuBr‚
SMe2 (3.2 mmol) in ether (4 mL) was added vinylmagnesium
chloride (8 mL; 1 M THF solution) at -25 °C, and the
reaction mixture was stirred for 5 h at -25 °C and then
stirred overnight at room temperature under an argon
atmosphere.6 While protecting the hydroxyl group of the diol,
9 was converted to the corresponding benzyl ether 10 by
treatment with sodium hydride and benzyl bromide in THF.
(4) (a) Nokami, J.; Yoshizane, K.; Matsuura, H.; Sumida, S. J. Am. Chem.
Soc. 1998, 120, 6609. (b) Sumida, S.; M. Ohga, M.; Mitani, J.; Nokami, J.
J. Am. Chem. Soc. 2000, 122, 1310. (c) Nokami, J.; Anthony, L.; Sumida,
S. Chem. Eur. J. 2000, 6, 2909. (d) Nokami, J.; Ohga, M.; Nakamoto, H.;
Matsubara, T.; Hussain, I.; Kataoka, K. J. Am. Chem. Soc. 2001, 123, 9168.
(e) Hussain, I.; Komasaka, T.; Ohga, M.; Nokami, J. Synlett 2002, 640. (f)
Nokami, J.; Nomiyama, K.; Matsuda, S.; Imai, N.; Kataoka, K. Angew.
Chem., Int. Ed. 2003, 42, 1273. (g) Nokami, J.; Nomiyama, K.; Shafi, S.;
Kataoka, K. Org. Lett. 2004, 6, 1261. (h) Nokami, J. J. Synth. Org. Chem.
Jpn. 2003, 61, 992.
2958
Org. Lett., Vol. 7, No. 14, 2005

Table 1. Asymmetric 4-Benzyloxybut-2-enylation of Aldehydes via Allyl-Transfer Reaction by Chiral Allyl Donor 10a
RCHO 2
product 11
yield (%)d
(R)-10
entry
R
% eeb
catalystc
TfOH
TfOH
TfOH
% eee
E/Ze
1
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2c
2d
2d
2e
2e
2f
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
85
90
85
90
85
85
85
85
84
90
90
90
90
90
90
90
90
(S)-11a
(S)-11a
(S)-11a
(S)-11a
(S)-11a
(S)-11a
(S)-11a
(S)-11a
(R)-11a
(R)-11b
(R)-11b
(S)-11c
(S)-11d
(S)-11d
(S)-11e
(S)-11e
(R)-11f
80
82
80
80
75
40
66
92
79
76
82
86
77
77
78
80
60
86
90
85
90
86
86
85
86
83
90
90
90
90
90
90
90
90
18/1
21/1
12/1
11/1
35/1
58/1
12/1
12/1
12/1
10/1
10/1
26/1
35/1
21/1
29/1
22/1
20/1
2
3f
4f
TfOH
5f
Sn(OTf)2
p-TsOH‚H2O
SnCl4
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
6f
7f
8f,g
9f,h
10
11f
12
13
14f
15
16f
17
Ph(CH2)2
PhS(CH2)2
PhS(CH2)2
BnO(CH2)5
CH3(CH2)4
CH3(CH2)4
CH2dCH(CH2)7
CH2dCH(CH2)7
(CH3)3C
TfOH
TfOH
TfOH
a All reactions were performed with allyl donor (R)-10 (0.5 mmol), aldehydes 2 (0.5 mmol), and TfOH (20 mol %) in CH2Cl2 (2.5 mL) at 10 °C for 30
h unless otherwise stated. b Determined by HPLC analysis (CHIRALCEL AD-H), using hexane/PriOH (40/1) as eluent, flow rate 0.3 mL/min. c TfOH
(trifluoromethnesulfonic acid); Sn(OTf)2 (tintriflate); p-TsOH‚H2O (p-toluenesulfonic acid monohydrate). d Isolated yield of E and Z mixture. e % ee values
of E and E/Z ratio were determined by HPLC analysis (CHIRALCEL AD-H) using hexane/PriOH (20/1) as eluent, flow rate 0.3 mL/min. f Performed at 20
°C for 20 h. g Performed with 2.0 equiv of (R)-10 to aldehyde 2a. h Performed with allyl donor (S)-10 prepared via Sharpless AE using (-)-DET.
After stirring for 12 h at room temperature and the usual
workup of the reaction mixture, pure 10 was obtained by
column chromatography on silica gel. The optical purity was
determined to be 90% ee by HPLC using CHIRALCEL
AD-H (Daicel Co. Ltd.) with n-hexane/2-propanol (40/1).
4-Benzyloxybut-2-enylation of aldehydes via allyl-transfer
reaction using the allyl donor 10 thus obtained was carried
out in the presence of an acid catalyst to give the optically
active (2E)-1-benzyloxyalk-2-en-5-ols 11 in good yields with
high ee, which depended on that of the Sharpless AE (Table
1). Higher E selectivity was observed at 10 °C rather than
20 °C.
Scheme 3. 4-Benzyloxybut-2-enylation of Aldehyde via
Allyl-Transfer Reaction
It is noteworthy that tin tetrachloride (SnCl4) served as a
catalyst similar to trifluoromethansulfonic acid (TfOH) and
gave 11a from 10 in the same enantioselectivity (85% ee)
and E/Z selectivity (12/1) (entries 3 and 7 in Table 1).
The stereoselectivities (enantio- and E/Z selectivity) of the
product via this allyl-transfer reaction were dependent on
both the optical purity of the allyl donor 10 and the
conformational stability of the six-membered ring chairlike
(5) (a) Suga, T.; Ohta, S.; Ohmoto, T. J. Chem. Soc., Perkin Trans. 1
1987, 2845. Higher ee (>95% ee) will be obtained via recrystalization of
its p-nitrobenzoyl ester: (b) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko,
S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765.
(6) Highly stereoselective copper(I)-catalyzed C-C bond formation of
â,γ-epoxy alcohols with Grignard reagents: (a) Tius, M. A.; Fauq, A. H.
J. Org. Chem. 1983, 48, 4131. (b) Roush, W. R.; Adam, M. A.; Walts, A.
E. Harris, D. J. J. Am. Chem. Soc. 1986, 108, 3422. (c) Roush, W. R.;
Ando, K.; Powers, D. B.; Palkowitz, A. D.; Halterman, R. L. J. Am. Chem.
Soc. 1990, 112, 6339.
Org. Lett., Vol. 7, No. 14, 2005
2959

transition state (TS) formed from 10 and aldehydes. This
means that the proposed 4-benzyloxybut-2-enylation also
takes place in a stereospecific manner via a conformationally
more stable six-membered chairlike transition state TSE from
optically active γ-adducts of homoallylic alcohols 10 as well
as crotylation (Scheme 3).2 That is, any remarkable effect
of the benzyloxy group was observed in the stereochemistry
of the allyl-transfer reaction, even if it was catalyzed by tin
tetrachloride.
The configuration of the Z isomer was determined to be
opposite of that of the major product (E isomer) as follows:
hydrogenation of the allyl-transfer product (S)-11a (86% ee,
E/Z ) 18/1, entry 1 in Table 1) gave 7-benzyloxy-1-
phenylheptan-3-ol in 85% yield with 77% ee, showing that
the configuration of the major Z isomer of 11a should be R.
The amount of the minor Z isomer of 11a was too small for
it to be detected by HPLC analysis.
can obtain the desired enantiomer selectively by a choice of
(+)- or (-)-diethyltartrate in the Sharpless AE reaction of
3-methylbut-2-en-1-ol in the preparation of the allyl donor
(10).
Acknowledgment. This work was financially supported
by a Grant in Aid for Scientific Research from the Ministry
of Education, Science, Culture, and Sports, Japan (no.
15350063), the Okayama Science and Technology Founda-
tion, and a Grant for Cooperative Research Administered
by the Japan Private School Promotion Foundation.
Supporting Information Available: Experimental pro-
cedures and complete characterization (1H and 13C NMR,
IR, and elemental analysis or mass spectra) for compounds
10 and 11. This material is available free of charge via the
Internet at http://pubs.acs.org.
Selective deprotection of the benzyl group of 11 was easily
carried out by treatment with powdered Ca in liquid NH3.7
In conclusion, we propose a flexible, environmentally
friendly, and E-selective 4-benzyloxybut-2-enylation of al-
dehydes via an allyl-transfer reaction. In this reaction, we
OL050890T
(7) (a) Hwu, J. R.; Chua, V.; Schroder, J. E.; Barrans, R. E., Jr.;
Khoudary, K. P.; Wang, N.; Wetzel, J. M. J. Org. Chem. 1986, 51, 4731.
(b) Hwu, J. R.; Wein, Y. S.; Leu, Y.-J. J. Org. Chem. 1996, 61, 1493.
2960
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