First reference to the alkoxymetallation of diisobutylaluminium and bromomagnesium-2-vinyloxy ethoxide to the corresponding (1,3-dioxolan-2- yl)methyl organometallics

Article abstract of DOI:10.1055/s-2000-6480

Diisobutylaluminium and bromomagnesium-2-vinyloxy-ethoxide add at carbonyl compounds in the manner of (1,3-dioxolan-2-yl)methyl organometallics, giving the carbon-carbon addition products. It is assumed that the aluminium and magnesium compounds of 2-viny

Full text of DOI:10.1055/s-2000-6480

LETTER
257
First Reference to the Alkoxymetallation of Diisobutylaluminium and
Bromomagnesium-2-vinyloxy Ethoxide to the Corresponding (1,3-Dioxolan-
-yl)methyl Organometallics
2
Peter Maier, Hartmut Redlich*
Organisch-Chemisches Institut der Westfälischen Wilhelms-Universität Münster, Correnstraße 40, D-48149 Münster, Germany
Fax +49 251-833-9772; E-mail: redlich@uni-muenster.de
Received 17 September 1999
5
lent yields (Scheme 2, path A). The discrepancy in both
Abstract: Diisobutylaluminium and bromomagnesium-2-vinyl-
findings caused us to approach the problem from the op-
oxy-ethoxide add at carbonyl compounds in the manner of (1,3-di-
posite side. Bromomagnesium-2-vinyloxy-ethoxide (4a),
oxolan-2-yl)methyl organometallics, giving the carbon-carbon ad-
the product of β-elimination from (1,3-dioxolan-2-yl)-
dition products. It is assumed that the aluminium and magnesium
compounds of 2-vinyloxy-ethoxide are in equilibrium with the cor- methylmagnesium bromide, was generated at room tem-
responding (1,3-dioxolan-2-yl)methide.
perature (Scheme 2, path B), by addition of ethylmagne-
Key words: carbanion, intramolecular cyclization, metallation, or- sium bromide in tetrahydrofuran to a solution of 2-
ganometallic reagent, rearrangement
vinyloxy-ethanol (2a) in tetrahydrofuran. The mixture
was allowed to warm to room temperature and then a so-
lution of ulose 6 in tetrahydrofuran was added. After re-
fluxing for four hours the reaction was quenched.
Organometallic compounds, bearing a functional group at
the β-position, undergo facile β-elimination. This elimi-
1
nation is only prevented by generating the carbanion at
low temperature, with a very poor leaving group X at the
β-position, or in the case of a perpendicular arrangement
of lone electron pair and C-X bond. Earlier studies estab-
lished that the action of sodium on 2-bromomethyl-1,3-di-
oxolane (1) in ether proceeds according to Scheme 1.2
Similar results were obtained by Feugeas for the Grignard
reagent from 2-bromomethyl-2-methyl-1,3-dioxolane.
Refluxing in tetrahydrofuran yielded the corresponding β-
O
O
Br
MgBr
i
O
O
iii
O
O
1
path A
5a
O
O
O
HO
O
path B
O
iii
7
OH
O
OMgBr
ii
3
elimination compound as the sole reaction product. On
the other hand, there are a few examples in the literature
on the successful addition of the Grignard reagent of
O
2a
4a
Reagents and conditions: (i): Mg, 1.0 equiv, THF, r.t.; (ii): EtMgBr,
.0 equiv, THF, r.t.; (iii):1,2;5,6-Di-O-isopropyliden-α- D-ribo-hexo-
furanos-3-ulose (6), 0.2 equiv, 4h, 65 °C, NH Cl/H O; A:64%,
2
-bromomethyl-1,3-dioxolane (1) to carbonyl com-
1
pounds. Kibayashi et al. reported the generation of 3 by
addition of the organomagnesium compound of 1 to the
aldehyde group of a threo-configurated carbohydrate de-
4
2
B:67%.
Scheme 2
4
rivative.
O
i
OH
Br
ii
O
R1 R2
OH
O
i or
ii
OM
O
iii or
iv
1
2a
O
O
O
OMOM
R1
R2
R1
R2
Ph
O
R
R =
OBn
OMOM
OH
3
2
a-c
4a-c
8a-c
O
OH
M = MgBr,
i-Bu)2Al
(
Reagents and conditions: (i): Na, Et O, 35 °C, H O, 64%; (ii): Mg,
THF, r.t., RCHO, NH Cl/H O, 70% (100% de).
2
2
R1
R2
4
2
O
Ph
Scheme 1
O
a-c
O
9
In a preceding paper we described the preparation of the
Grignard reagent from (1) and magnesium and its reaction
with less reactive carbohydrate ketones in refluxing tet-
rahydrofuran. These uloses gave the corresponding
branched chain carbohydrate derivatives in good to excel-
Reagents and conditions: (i): EtMgBr, 1.1 equiv, 0 °C, THF; (ii):
DIBALH, 1.1 equiv, 0 °C, THF; (iii): PhCHO, 2.0 equiv, 160 h, r.t.;
NH Cl/H O; (iv): PhCHO, 2.0 equiv, 4 h, 65 °C; NH Cl/H O.
4
2
4
2
Scheme 3
Synlett 2000, No. 2, 257–259 ISSN 0936-5214 © Thieme Stuttgart · New York

2
58
P. Maier, H. Redlich
LETTER
Surprisingly, the magnesium alkoxide 4a gave the carbon-
carbon addition product of the Grignard reagent of 2-bro-
momethyl-1,3-dioxolane 5a in a comparable yield. This
unexpected result led to further examinations (Scheme 3),
concerning the nature of metal and substituents. These re-
actions were carried out with the highly reactive benzal-
dehyde instead of ulose 6. The data shown in the Table
indicate a strong enhancement of yield for the diisobutyl-
aluminium alkoxide. Furthermore, the reaction was ob-
served to be feasible even in the case of the substituted
alkoxides 4b-c.
2a-c
4a-c
OH
O
EtMgBr/
(i-Bu)2AlH
OM
O
R
R
M = MgBr,
(i-Bu) Al
R
THF
2
R
R = H, CH3
β-elimination alkoxymetallation
6
,7
R
R
R
R
5a-c
O
O
O
O
R'2C
O
OH
M
NH4Cl/H2O
R' R'
Mechanistic conception
Moreover, we observed the ketones 9a-c, generated by
mono addition of 4a-c to benzyl benzoate, as additional
products. A reasonable explanation for the generation of
the ester intermediate is given by the Tishenko reaction,
the alkoxide catalyzed disproportionation of aldehydes to
Scheme 4
8
esters. We also attempted, unsuccessfully, to detect the
References and Notes
C-C addition products of the lithium, sodium or potassium
derivative of 4a, generated by deprotonation of 2a with n-
butyllithium, sodium hydride and potassium hydride.
(1) Seebach, D.; Hungerbühler, E. Modern Synthetic Methods,
Vol 2, Otto Salle Verlag: Frankfurt a. Main, 1980.
2) Hill, H.S.; Potter, J.C. J. Am. Chem. Soc. 1929, 51, 1509.
3) Feugeas, C. Bull. Soc. Chim. Fr. 1963, 2568.
(
(
Table Influence of metal and substituents
(4) Iida, H.; Yamazaki, N.; Kibayashi, C. J. Org. Chem. 1986, 51,
245.
4
(
(
5) Schmeichel, M.; Redlich, H. Synthesis 1996, 8, 1002.
6) 2-Vinyloxy-ethanol (2a) was obtained from Aldrich. 2-(α-
propenyloxy)-ethanol (2b) and 2-methyl-(α-propenyloxy)-
ethanol (2c) were prepared by the literature method: Davis,
H.A.; Brown, R.K. Can. J. Chem. 1971, 49, 2563.
(
7) General Procedure for the reactions shown in the Table.
A 0.1-0.2 M solution of the alcohol (2a-c, typically 2.0-3.0
mmol) was cooled to 0 °C under an argon atmosphere and
with stirring, 1.1 molar equiv of DIBALH in THF was added
via syringe. The solution was allowed to warm to r.t. before
addition of 2.0 molar equiv of benzaldehyde. After stirring for
160 h at r.t., the reaction was quenched with 1-2 mL of sat. aq
NH Cl. The mixture was extracted with Et O, washed with
water, dried (Na SO ), filtered, evaporated and analysed by
2 4
GC. Quantitative GC analyses were obtained with response
corrected peak areas by using diphenylmethane as an internal
standard.
4
2
In consideration of the resemblance to the corresponding
carba-analogous carbometallations, these results can be
explained by the mechanism, shown in Scheme 4. This in-
tramolecular rearrangement of an unsaturated alkoxide to
a carbanion corresponds to an alkoxymetallation. As a
strong support for such a supposed anionic mechanism,
Alexakis et al. already mentioned the cyclization of
(
8) Zakharkin, L.I.; Sorokina, L.P. J. Gen. Chem. USSR 1967, 37,
525. (b) Saegusa, T.; Ueshima, T.; Kitagawa, S. Bull. Chem.
Soc. Jpn. 1969, 42, 248. (c) Ogata, Y.; Kawasaki, A.
Tetrahedron 1969, 25, 929.
9
alkoxyallene derivatives. Another description of these
(9) Alexakis, A.; Mangeney, P.; Normant, J.F. Bull. Soc. Chim.
Fr. 1992, 129, 171.
10) Drozd, V.N.; Ustynyuk, Y.A.; Tsel’eva, M.A.; Dimitriev,
findings is that the examined (1,3-dioxolan-2-yl)methyl
organometallics 5a-c are in equilibrium with their prod-
ucts of β-elimination (4a-c). From the mechanistic point
of view the assumed equilibrium may have some analo-
(
L.B. J. Gen. Chem. USSR 1968, 38, 2047; Zh. Obsch. Khim.
1968, 38, 2144. (b) Drozd, V.N.; Ustynyuk, Y.A.; Tsel’eva,
M.A.; Dimitriev, L.B. J. Gen. Chem. USSR 1969, 39, 1951;
Zh. Obsch. Khim. 1969, 39, 1991.
1
0-13
gies to the well-known 5-hexenyl system.
However,
due to the strong O-M bond in the open-chain compo-
nents, the equilibria are expected to be far on the side of
the alkoxide compounds.
(
11) (a) Richey, H.G., Jr.; Rees, T.C. Tetrahedron Lett. 1966,
4297. (b) Kossa, W.C., Jr.; Rees, T.C.; Richey, H.G., Jr.
Tetrahedron Lett. 1971, 3455. (c) Hill, E.A. J. Organomet.
Chem. 1975, 91, 123.
(
12) (a) Denis, J.; Dolzine, T.; Oliver, J.P. J. Am. Chem. Soc. 1972,
94, 8260. (b) Smart, J.B.; Hogan, R.; Scherr, P.A.; Emerson,
M.T.; Oliver, J.P. J. Organomet. Chem. 1974, 64, 1. (c) Denis,
J.; Oliver, J.P.; Dolzine, T.W.; Smart, J.B. J. Organomet.
Chem. 1974, 71, 315. (d) Dolzine, T.W.; Oliver, J.P. J.
Organomet. Chem. 1974, 78, 165.
Acknowledgement
We are grateful to the Deutsche Forschungsgemeinschaft [SFB
4
24], the Fonds der Chemischen Industrie and the Graduiertenför-
derung des Landes Nordrhein-Westfalen for providing financial
support.
(
13) (a) Bailey, W.F.; Ovaska, T.V Advances in Detailed Reaction
Mechanisms, Vol. 3, JAI Press Inc. 1994, 251. (b) Bailey,
Synlett 2000, No. 2, 257–259 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
First Reference to the Alkoxymetallation of 2-Vinyloxy Ethoxide
259
1
W.F.; Punzalan, E.R.; Zarcone, L.M.J. Heteroatom Chem.
992, 55. (c) Bailey, W.F.; Patricia, J.J.; DelGobbo, V.C.;
Jarret, R.M.; Okarma, P.J. J. Org. Chem. 1985, 50, 2000.
d) Bailey, W.F.; Zarcone, L.M.J. Tetrahedron Lett. 1991,
8b, anti; H NMR (300 MHz, C D , TMS): δ = 0.82 (3H, d,
6
6
1
J = 7.0 Hz, methyl-H), 2.20 (1H, ddq, J = 4.4 Hz, 7.0 Hz, 8.2
Hz, 2-H), 3.24, (2H, m, dixolane-H), 3.42 (2H, m, dioxolane-
H), 4.72 (1H, d, J = 8.2 Hz, 1-H), 4.81 (1H, d, J = 4.4 Hz,
dioxolane-H), 7.16 (3H, m, aryl-H), 7.33 (2H, m, aryl-H); C
NMR (75 MHz, CDCl , TMS): δ = 11.73 (CH , methyl-C),
(
1
3
4425.
1
(
14) All the compounds were characterized by H and 13C NMR.
3
3
Data for selected products are as follows.
7
43.27 (CH, 2-C), 64.77, 65.02 (2 x CH , dioxolane-C), 76.05
(CH, 1-C), 106.52 (CH, dioxolane-C), 126.88, 127.52, 128.21
2
; H NMR data is identical to literature data; 13C NMR (75
1
MHz, CDCl , TMS): δ = 25.73, 26.90, 27.14, 27.52 (4 x CH ,
(3 x CH, aryl-C), 142.59 (C, aryl-C).
3
3
1
C(CH ) ), 35.72 (CH , 2’-C), 64.80, 65.35 (2 x CH ,
8c; H NMR (300 MHz, CDCl , TMS): δ = 0.76 (3H, s,
3
2
2
2
3
dioxolane-C), 67.71 (CH , 6-C), 73.10 (CH, 5-C), 79.91 (C, 3-
C), 84.22 (CH, 4-C), 86.41 (CH, 2-C), 103.11 (CH, 1’-C),
methyl-H), 0.95 (3H, s, methyl-H), 2.80 (1H, s, -OH), 3.94
(4H, m, dioxolane-H), 4.70 (1H, s, 1-H), 4.74 (1H, s,
dioxolane-H), 7.31 (5H, m, aryl-H); C NMR (75 MHz,
2
1
3
1
05.25 (CH, 1-C), 109.46, 112.63 (2 x C, C(CH ) ).
3
2
1
8a; H NMR (300 MHz, CDCl , TMS): δ = 2.01 (1H, ddd,
CDCl , TMS): δ = 15.92, 20.67 (2 x CH , methyl-C), 64.89,
3
3
3
J = 3.8 Hz, 4.8 Hz, 14.4 Hz, 2a-H), 2.11 (1H, ddd, J = 4.8 Hz,
.2 Hz, 14.4 Hz, 2b-H), 3.75-3.99 (4H, m, dioxolane-H), 4.93
1H, dd, J = 3.8 Hz, 9.2 Hz, 1-H), 4.97 (1H, t, J = 4.8 Hz,
65.14 (2 x CH , dioxolane-C), 78.08 (CH, 1-C), 109.69 (CH,
dioxolane-C), 127.21, 127.46, 128.00 (3 x CH, aryl-C),
140.79 (C, aryl-C).
2
9
(
1
3
dioxolane-H), 7.17-7.36 (5H, m, aryl-H); C NMR (75 MHz,
C D , TMS): δ = 43.53 (CH , 2-C), 64.63, 64.80 (2 x CH ,
6
6
2
2
dioxolane-C), 70.53 (CH, 1-C), 103.35 (CH, 3-C), 126.09,
27.37, 127.71 (3 x CH, aryl-C), 145.10 (C, aryl-C).
Article Identifier:
1437-2096,E;2000,0,02,0257,0259,ftx,en;G23399ST.pdf
1
Synlett 2000, No. 2, 257–259 ISSN 0936-5214 © Thieme Stuttgart · New York