σ-π chelation-controlled chemoselective ring openings of epoxides

Article abstract of DOI:10.1016/S0040-4039(01)01669-0

The chemoselective ring opening of alkynyl epoxides in the co-existence of the corresponding alkyl epoxides is achieved in the Me₃Al mediated reaction with alkynyllithium reagents. The observed interesting chemoselectivity is most probably a reflection of bidentate complexation of the Lewis acid to an n-electron of an oxygen atom of the epoxide and π-electrons of the C-C triple bond.

Full text of DOI:10.1016/S0040-4039(01)01669-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7903–7905
s–p Chelation-controlled chemoselective ring openings of
epoxides
Naoki Asao, Taisuke Kasahara and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Received 16 July 2001; revised 29 August 2001; accepted 5 September 2001
Abstract—The chemoselective ring opening of alkynyl epoxides in the co-existence of the corresponding alkyl epoxides is achieved
in the Me3Al mediated reaction with alkynyllithium reagents. The observed interesting chemoselectivity is most probably a
reflection of bidentate complexation of the Lewis acid to an n-electron of an oxygen atom of the epoxide and p-electrons of the
CꢀC triple bond. © 2001 Elsevier Science Ltd. All rights reserved.
Lewis acid-mediated chelation control is one of the most
fundamental and efficient methodologies for effecting the
selective carbonꢀcarbon bond formation in modern
organic synthesis.1 It is well accepted that the chelation-
controlled reactions proceed through the coordination of
a lone pair of heteroatoms, such as an oxygen of an
aldehyde or a nitrogen atom of an imine, to a Lewis acid,
which is recognized as a s–s type chelation. Recently,
we reported that chemo- and regioselective reactions of
certain alkynyl and alkenyl aldehydes were accomplished
through a s–p chelation between a lone pair of the
carbonyl compounds and p-electrons of the CꢀC multiple
bond.2,3 Now, we report that the chemoselective ring
opening of alkynyl epoxides in the co-existence of the
corresponding alkyl epoxides is achieved in a Me3Al-
mediated reaction with alkynyl lithium reagents; this
interesting chemoselectivity is most probably a reflection
of bidentate complexation to an n-electron pair of the
oxygen atom of the epoxide and p-electrons of the CꢀC
triple bond (Eq. (1)).
ence of Lewis acids (1.2 equiv.) in toluene (Eq. (2)) and
the results are summarized in Table 1. The reaction of
phenyl-substituted epoxides 1a and 2a with lithium
phenylacetylide in the presence of BF3·OEt2 proceeded
smoothly and 4a was obtained predominantly over 3a
(3a:4a=23:77) (entry 1). However, the reverse chemosel-
ectivity was observed when we used Me3Al as a Lewis
acid; 3a was obtained in 77% yield along with recovered
1a (9% yield), and 4a was obtained only in 2% yield
together with recovered 2a (84% yield) (entry 2).4 The
selective alkynylation reaction of 1a was also observed
when the reaction was carried out using Et3Al instead of
Me3Al, though the selectivity slightly decreased (entry 3).
Other alkynyllithium reagents, such as hexyl- and
trimethylsilyl-substituted lithium acetylide, also reacted
chemoselectively with 1a in the presence of 2a (entries 4
and 5). Not only substrate 1a but also decyl- and
trimethylsilyl-substituted alkynyl epoxides, 1b and 1c,
underwent chemoselective ring opening reactions in the
presence of Me3Al (entries 6 and 7). In all the above
reactions, the material balance of substrates was high;
large amounts of 2 (49–90%) were recovered in entries
2–7, and small amounts (9–37%) of 1 were recovered in
The reactions of a 1:1 mixture of alkynyl epoxides 1 (1
equiv.) and their saturated analogues 2 (1 equiv.) with
alkynyllithiums (1.2 equiv.) were examined in the pres-
O
O
O
OH
O
Nu
M
Nu
M
+
+
(1 eq)
(1 eq)
(1)
(1 eq)
(1 eq)
σ-π chelation
Keywords: Lewis acids; chemoselectivity; coordination modes; alkynes; epoxides.
* Corresponding author. Tel.: +81-22-217-6581; fax: +81-22-217-6784; e-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01669-0

7904
N. Asao et al. / Tetrahedron Letters 42 (2001) 7903–7905
O
R2
(1.2 eq)
(2)
OH
R2
Li
R1
1 (1 eq)
R1
+
+
3
Lewis acid
(1.2 eq)
R1
R1
O
OH
R2
4
2 (1 eq)
Table 1. Lewis acid-mediated competitive ring opening reactions of 1 and 2 with alkynyllithiuma
Entry
Substrate
Alkynyl lithium
R2
Lewis acid
Yieldb
%
Yieldb
%
Ratio 3:4
R1
1
2
3
4
1
2
3
4
5
6
7
Ph
Ph
Ph
Ph
Ph
C10H23
Me3Si
1a
1a
1a
1a
1a
1b
1c
2a
2a
2a
2a
2a
2b
2c
Ph
Ph
Ph
C6H13
Me3Si
Ph
BF3·OEt2
Me3Al
Et3Al
Me3Al
Me3Al
Me3Al
Me3Al
3a
3a
3a
3b
3c
3d
3c
18
77
69
78
54
72
75
4a
4a
4a
4b
4c
4d
4e
59
2
6
8
5
23:77
97:3
92:8
91:9
92:8
92:8
87:13
6
11
Ph
a The reaction was performed in the following molar ratio at −78°C to rt; 1:2: alkynyl lithium:Lewis acid=1:1:1.2:1.2.
b Isolated yield.
9 derived from 1 rather than the monodentate coordi-
nation shown in 10 from 2 (Fig. 1).6–9
the case where the yields of 3 were not as high (for
example, entry 5).
Recently, we studied systematically the substituent
effect on the BF3·OEt2-mediated electrophilic reactions
of carbonyl compounds; for example, the allylation
reaction of aldehydes using allyltributylstannane, the
Diels–Alder reaction of aldehydes with cyclopentadi-
ene, and the reduction of aldehydes using Bu3SnH. We
found that aldehydes 5 bearing an electron-donating
group reacted with nucleophiles in the presence of
BF3·OEt2 much faster than aldehydes 6 having an
electron-withdrawing group (Eq. (3)).5 The above unex-
R1
R1
O
O
Al
Me3
AlMe3
9
1
0
Figure 1.
However, the above chemoselectivity might be
explained by a selective nucleophilic substitution of
epoxides by an aluminum ate complex formed from
Me3Al and alkynyllithium reagents, which might attack
1 rather than 2 selectively since the aluminum ate
complex would attack directly the more electrophilic
epoxide due to its nucleophilic character. In order to
clarify this issue, we examined the reactions using 1d
and 1e (Eq. (4)). The Me3Al-mediated reaction of 1d
with lithium phenylacetylide proceeded smoothly to
give the corresponding alcohol 3e in 67% yield. In
contrast, alcohol 3f was obtained only in 19% yield in
the reaction of 1e under the same reaction conditions.
If the nucleophilic character of the aluminum ate com-
plex is responsible to the chemoselectivity, 3f should
have been obtained in higher yield than 3e. Therefore,
the observed higher reactivity of 1d in comparison with
1e is due to the preferred formation of a s–p chelation
in the case of 1d rather than the formation of an
aluminum ate complex.
Nu
O
O
(1 eq)
+
BF3•OEt2
(1 eq)
EDG
H
EWG
EDG
H
5
6
OH
Nu
OH
Nu
+
(3)
EWG
7
8
major
minor
pected results are understandable if the coordination
ability of more electrophilic carbonyl compounds 6 to
Lewis acids is weaker than that of less electrophilic
analogues 5. This concept can explain clearly why the
selective reaction of 2a was observed in the competitive
reaction of 1a and 2a with phenylethynyllithium in the
presence of a monodentate BF3·OEt2 (entry 1). Com-
pound 1a having an electron-withdrawing alkynyl
group is less reactive to the nucleophile in the presence
of BF3·OEt2 than 2a having an electron-donating alkyl
group. On the other hand, the selective reaction of 1 in
the bidentate Me3Al-mediated reaction is ascribed most
probably to the preferred bidentate chelation shown in
Ph
Li
O
R1
Me3Al
1d: R1=p-MeC6H4
1e: R1=p-CF3C6H4
(4)
R1
OH
3e: R1=p-MeC6H4
3f: R1=p-CF3C6H4
Ph

N. Asao et al. / Tetrahedron Letters 42 (2001) 7903–7905
7905
It is now clear that the Lewis acid-mediated s–p chela-
tion between n- and p-electrons is operative not only in
the alkyne–aldehyde system2,3 but also in the alkyne–
epoxide analogue. Further studies on this new type of
chelation control are ongoing in our laboratory.
6. Trialkylaluminums and chlorodialkylaluminums are
known to act as bidentate Lewis acids, see: (a) Maruoka,
K.; Ooi, T. Chem. Eur. J. 1999, 5, 829–833; (b) Ooi, T.;
Kagoshima, N.; Ichikawa, H.; Maruoka, K. J. Am. Chem.
Soc. 1999, 121, 3328–3333; (c) Evans, D. A.; Allison, B.
D.; Yang, M. G. Tetrahedron Lett. 1999, 40, 4457–4460;
(d) Evans, D. A.; Chapman, K. T.; Bisaha, J. J. Am.
Chem. Soc. 1988, 110, 1238–1256.
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treated with lithium phenylacetylide in the absence of
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phenylacetylide under similar reaction conditions gave the
desired product 3a with similar chemoselectively (3a:4a=
97:3), the total yield of the products was lower (66%).
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