Ring-opening of 2,3-epoxy-1-propanol with R3Al: Unprecedented regiochemical switching simply achieved by changing alkyl substituents of aluminium reagent

Article abstract of DOI:10.1016/j.jorganchem.2005.03.069

Several control experiments were designed to optimize the reaction of 2,3-epoxy-1-propanol with R₃Al (R = Me, Et or ⁱBu) and to probe for the nature of aluminium-bound alkyl groups that influence the reactivity and selectivity. The reported studies revealed that the Et ₃Al mediated reaction leads to the C-2 product in contrast to the well-known C-3 substitution promoted by Me₃Al.

Full text of DOI:10.1016/j.jorganchem.2005.03.069

Journal of Organometallic Chemistry 690 (2005) 3697–3699
www.elsevier.com/locate/jorganchem
Ring-opening of 2,3-epoxy-1-propanol with R3Al: Unprecedented
regiochemical switching simply achieved by changing
alkyl substituents of aluminium reagent
a,
a
a
Janusz Lewinski *, Paweł Horeglad , Ewa Tratkiewicz ,
´
Iwona Justyniak a,b, Zbigniew Ochal
a
a
Department of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland
Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
b
Received 23 February 2005; received in revised form 29 March 2005; accepted 29 March 2005
Available online 15 June 2005
Abstract
Several control experiments were designed to optimize the reaction of 2,3-epoxy-1-propanol with R3Al (R = Me, Et or iBu) and
to probe for the nature of aluminium-bound alkyl groups that influence the reactivity and selectivity. The reported studies revealed
that the Et3Al mediated reaction leads to the C-2 product in contrast to the well-known C-3 substitution promoted by Me3Al.
Ó 2005 Elsevier B.V. All rights reserved.
Keywords: Aluminum; Regioselectivity; Epoxides; Alkylation
Organoaluminium compounds have proven to be
very important reagents for the selective addition of car-
bon nucleophiles to 2,3-epoxy alcohols [1]. For example,
the reaction of 2,3-epoxy-1-alkanols mediated by Me3Al
can provide 1,2-diols regio- and stereoselectively [2,3],
e.g., the incorporation of the methyl group occurs regio-
selectively at the position 3 of epoxy alcohol, which is
usually accompanied by the inversion of configuration
at the C-3 atom. Similar selectivity have been observed
for the nucleophile addition to epoxy alcohols with
R2AlN3 [3a,3d,3e] or R2AlCN reagents [4]. Only re-
cently, a reversal of regioselectivity was revealed for
the alkylation of 2,3-epoxy alcohols with R3Al/BuLi sys-
tem, where R = Me or Et [5]. We have recently initiated
systematic studies on the selective alkyl addition to 2,3-
epoxy alcohols choosing the group 13 metal alkyls and
rac-2,3-epoxy-1-propanol (epol-H) as a simple model
system. For example, investigations involving the reac-
tion between epol-H and Me3Ga have succeeded in the
isolation and structure characterization of the first
example of group 13 metal–epoxide complex I [6], which
may mimic a potential intermediate complex in the ring-
opening transformations mediated by aluminium alkyls.
Moreover, our recent results also allow for better under-
standing of factors controlling the formation and redis-
tribution of products in the reaction involving hydroxy
organic compounds bearing Lewis base termini and
two or more equivalents of R3Al [7].
I
As a part of our investigations of the epoxides chem-
istry [6,8], here we report on reactions of epol-H with
i
R3Al (R = Me, Et or Bu) and demonstrate for the first
time that the regiochemical switching in the substitution
*
Corresponding author. Tel.: +48 22 660 7315/fax: +48 22 660 7279.
´
E-mail address: lewin@ch.pw.edu.pl (J. Lewinski).
0022-328X/$ - see front matter Ó 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.03.069

´
J. Lewinski et al. / Journal of Organometallic Chemistry 690 (2005) 3697–3699
3698
reaction may be achieved simply by changing the char-
acter of alkyl substituent of the aluminium reagent.
Initially, we have optimized the Me3Al-promoted
ring-opening of 2,3-epoxy-1-propanol (epol-H), and
studied the effect of excess Me3Al (Scheme 1, Table 1)
[9,10]. When only 2 equiv. of Me3Al were employed,
the low temperature (À78 °C) completely retarded the
epoxide ring cleavage (entry 1), however, the reaction
proceeded smoothly at higher temperature with high
regioselectivity (entries 2 and 3). Thus, we found surpris-
ingly that a lower amount of Me3Al may be applied
without loss of the regioselectivity in comparison with
the most commonly used reaction conditions following
the OshimaÕs pioneering studies (i.e., just 2 instead of
3 equiv., entry 4) [2a].
Interestingly, we have found that the reactivity and
regioselectivity of the epol-H/Et3Al and epol-H/iBu3Al
systems is dramatically different. Most strikingly, for
the Et3Al mediated reaction, the substitution occurred
highly selectively at the C-2 position, i.e., at the more
sterically hindered carbon atom, leading to 2-ethyl-1,3-
propanediol (Scheme 1 and Table 1, entries 5–8) [9,10].
The highest regioselectivity was observed when 3 equiv.
of Et3Al were added at À78 °C and then the reaction
was carried on at À40 °C (entries 6 and 7). The higher
reaction temperature was found to enhance the reaction
Scheme 2.
rate but lower the regioselectivity (entry 8). In addition,
the substitution reaction was not observed for the Et3Al/
epol-H ratio of 2:1 at temperatures up to 0 °C, (entry 5)
in contrast to the reaction mediated by Me3Al (entries 2
and 3).
In the case of iBu3Al, the ring-opening of epol-H pro-
i
ceeds with a lower selectivity. When 3 equiv. of Bu3Al
were used (0 °C, 5 h) the reaction affords a mixture of
C-2 (major isomer) and C-3 alkylated products as well
as a small amount of two regioisomers resulting from
the hydride transfer (Scheme 2).
In conclusion, the reported results represent a signif-
icant advance from synthetic point of view in the ring-
opening reaction of 2,3-epoxy-1-alkanols mediated by
aluminium alkyls. Current efforts are directed toward
determining both the scope and limitation, and mecha-
nistic aspects of the regiochemical switching in the
ring-opening of 2,3-epoxy-1-alkanols.
Acknowledgments
Financial support from the State Committee for Sci-
entific Research (Grant No. 3 T09A 08127) and Warsaw
University of Technology is gratefully acknowledged.
Scheme 1.
Table 1
The ring-opening reactions of epol-H mediated by R3Al (where R = Me or Et)
Entry
Ratioa
Temperature (°C)
Xb
Time
Conv.d (%)
Selectivity
C-3
Yc
C-2
R = Me
1
2
3
4
2:1
2:1
2:1
3:1
À78
À78
0
À78
5 h
0
>99
>99
>99
–
–
0
0
0
10 min
10 min
10 min
90.2
87.0
88.5
9.8
13.0
11.5
0
R = Et
5
6
7
8
2:1
3:1
3:1
3:1
0
À78
À78
0
0
À40
À40
0
30 min
3 h
5 h
0
97
–
–
6.5
5.0
15.0
93.5
95.0
85.0
98
>99
30 min
Reaction conditions: all reactions were carried out in CH2Cl2 and later hydrolyzed with an excess of KF and H2O. The organic products formed were
determined by GC and 1H NMR spectra analysis.
a
Ratio – R3Al/epol-H molar ratio.
X – temperature of reagents mixing.
b
c
Y – temperature of reaction.
Conv. – conversion.
d

´
J. Lewinski et al. / Journal of Organometallic Chemistry 690 (2005) 3697–3699
3699
or 4.5 mmol) in CH2Cl2 (3 mL) was added to vigorously mixing
solution of 2,3-epoxy-1-propanol (1.5 mmol) in CH2Cl2 (3 mL) at
the temperature indicated in Table 1 as ‘‘temperature of reagents
mixing’’ (the temperature of reagents mixing ranged from À78 to
0 °C depending on the entry) under nitrogen atmosphere. The
reaction was further mixed at the temperature indicated in Table 1
as ‘‘temperature of reaction’’ (the reaction temperature ranged
from À78 to 0 °C depending on the entry). The reaction time
varied from 10 min to 5 h (depending on the entry). Finally, the
solution was treated with KF (1.75 g, 30 mmol) and water (0.6 g,
33 mmol) at À78 °C to form white precipitate in each case.
Vigorous stirring of the resulting suspension was continued at
25 °C for 0.5 h. The organic products formed were extracted with
ethyl ether. The ether solution was dried with anhydrous MgSO4
and analyzed by GC and 1H NMR spectroscopy.
References
[1] (a) J.J. Eisch, in: G. Wilkinson, F.G.A. Stone, E.W. Abel (Eds.),
Comprehensive Organometallic Chemistry, vol. 1, Pergamon
Press, Oxford, 1991, Chapter 10;
(b) P.C.A. Pena, S.M. Roberts, Curr. Org. Chem. 7 (2003) 555.
[2] (a) T. Suzuki, H. Saimoto, H. Tomioka, K. Oshima, H. Nozaki,
Tetrahedron Lett. 23 (1982) 3597;
(b) W.R. Roush, M.A. Adam, S.M. Peseckis, Tetrahedron Lett.
24 (1983) 1377.
[3] For more recent examples involving organoaluminium reagents
promoted ring-openning reaction of 2,3-epoxy-1-ols see:
(a) C.E.M.Davis, J.L. Bailey, J.W. Lockner, R.M. CoatesJ. Org.
Chem. 68 (2003) 75;
(b) L. Carde, D.H. Davies, S.M.J. Roberts, Chem. Soc. Perk. T. 1
(2000) 2455;
[10] 1H NMR (CD3Cl, 20 °C) spectra of the obtained compounds were
consistent with the literature data.
(c) M. Inoue, M.W. Carson, A.J. Frontier, S.J. Danishefsky, J.
Am. Chem. Soc. 123 (2001) 1878;
(a) For 1,2-butanediol H.K. Chenault, M.J. Kim, A. Akiyama,
T. Miyazawa, E.S. Simon, G.M. Whitesides, J. Org. Chem. 52
(1987) 2608;
(d) K.C. Nicolaou, F.S. Baran, R. Jautelat, Y. He, K.C. Fong,
H.S. Choi, W.H. Yoon, Y.L. Zhong, Angew. Chem., Int. Ed.
Engl. 38 (1999) 549;
(b) For 2-methyl-1,3-propanediol M. Scheck, H. Waldmann,
Can. J. Chem. 80 (2002) 571;
(e) F. Benedetti, F. Berti, S. Norbedo, Tetrahedron Lett. 39
(1998) 7971.
(c) For 1,2-pentanediol R. Hayakawa, K. Nozawa, K. Kimura,
M. Shimizu, Tetrahedron 55 (1999) 7519;
[4] F. Benedetti, F. Berti, S. Norbedo, Tetrahedron Lett. 40 (1999)
1041.
[5] M. Sasaki, K. Tanino, M. Miyashita, Org. Lett. 3 (2001) 1765.
(d) For 2-ethyl-1,3-propanediol A. Gaucher, J. Ollivier, J.
Marguerite, R. Paugam, J. Salauen, Can. J. Chem. 72 (1994)
1312;
´
[6] J. Lewinski, J. Zachara, P. Horeglad, D. Glinka, J. Lipkowski, I.
Justyniak, Inorg. Chem. 40 (2001) 6086.
(e) For products obtained in the reaction between 2,3-epoxy-1-
i
propanol with Bu3Al see: Y. Landais, D. Planchenault, Tetra-
´
[7] J. Lewinski, I. Justyniak, P. Horeglad, E. Tratkiewicz, J. Zachara,
Z. Ochal, Organometallics 23 (2004) 4430.
hedron 53 (1997) 2855;
M.J. Burk, C.S. Kalberg, A. Pizzano, J. Am. Chem. Soc. 120
´
[8] J. Lewinski, Z. Ochal, E. Bojarski, E. Tratkiewicz, I. Justyniak, J.
(1998) 4345;
C.M. Pearce, J.K.M. Sanders, J. Chem. Soc., Perk. T. 1 (1994)
1119.
Lipkowski, Angew. Chem., Int. Ed. Engl. 42 (2003) 4643.
[9] General procedures of the alkylation of 2,3-epoxy-1-propanol
with R3Al: a solution of corresponding R3Al compound (3 mmol