Cobalt-catalyzed aerobic oxidation of (E)- and (Z)-bishomoallylic alcohols

Article abstract of DOI:10.1016/j.tetlet.2008.12.040

Stereoselectivity for (5-phenyltetrahydrofur-2-yl)alkan-1-ol formation (cis:trans < 1:99) from 5-methyl- and 5-phenyl-substituted 1-phenylpent-4-en-1-ols via cobalt-catalyzed aerobic oxidation was independent of the olefinic π-bond configuration of the su

Full text of DOI:10.1016/j.tetlet.2008.12.040

Tetrahedron Letters 50 (2009) 960–962
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Tetrahedron Letters
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Cobalt-catalyzed aerobic oxidation of (E)- and (Z)-bishomoallylic alcohols
*
Bárbara Menéndez Pérez, Jens Hartung
Fachbereich Chemie, Organische Chemie, Technische Universität Kaiserslautern, Erwin-Schrödinger-Straße, D-67663 Kaiserslautern, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Stereoselectivity for (5-phenyltetrahydrofur-2-yl)alkan-1-ol formation (cis:trans < 1:99) from 5-methyl-
and 5-phenyl-substituted 1-phenylpent-4-en-1-ols via cobalt-catalyzed aerobic oxidation was indepen-
dent of the olefinic p-bond configuration of the substrates.
Received 5 October 2008
Revised 5 December 2008
Accepted 9 December 2008
Available online 16 December 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Dioxygen
Cobalt(II) Complex
Tetrahydrofuran
Aerobic oxidation
Radicals
Stereoselective synthesis
Acceptor-substituted cobalt(II) chelates are valuable reagents
for 3O2 activation1–3 to serve as powerful but selective oxidants
for tetrahydrofuran formation from substituted pent-4-en-1-ols
(bishomoallylic alcohols).4–7 The oxidative ring closure occurs with
a notable degree of diastereoselection to afford 2,3-trans- (ꢀ99%
de), 2,4-cis- (ꢀ70% de), and 2,5-trans-configured (>99% de) tetra-
hydrofur-2-yl-methanols in ꢀ70–80% yield.8–10 If methyl groups
are substituted for terminal hydrogen atoms, or tertiary alkenols
are used instead of primary or secondary substrates, the cobalt
method surprisingly failed to provide a similar degree of product-
and diastereoselectivity.9,11 One of the most striking results in an
earlier series of experiments related to this topic originated from
an attempt to selectively oxidize an (E)-alkenol with O2 in the pres-
ence of a cobalt(II) complex. The stereochemical information orig-
stances to a symmetric intermediate, and hence to a sequential
mechanism for formation of the two new C,O bonds.
4-[3,5-Bis(trifluoromethyl)phenyl]-4-hydroxy-but-3-en-2-one-
derived cobalt(II) complex 1a was discovered in this laboratory in
the course of a reactivity survey associated with the search for
strong and selective aerobic oxidation catalysts. The compound
(yellow crystalline solid)24,25 was prepared from Co(OAc)2 Â 4H2O
and 2 equiv of auxiliary 2a in EtOH, in extension to a method re-
ported for the synthesis of camphor derivative 1b from 2b (Scheme
1).12
Bishomoallylic alcohols (E)/(Z)-3/4 were inert toward oxygen
[>95% (v/v), 1 bar], if stirred for ꢀ4 h in iPrOH at 60 °C. Addition
of cobalt(II) reagent 1a (10 mol %) to a likewise prepared solution
of (E)-1-phenylhex-4-en-1-ol (E)-(3)13 [(E):(Z) > 99:1; GC, 1H
NMR] furnished 63% of trans-2,5-disubstituted tetrahydrofuran
inating from the olefinic p-bond was lost in the course of oxidative
cyclization although the customary 2,5-trans selectivity for tetra-
hydrofuran formation was retained.9 If this selectivity posed a gen-
eral feature of the cobalt method, it would provide strong
mechanistic evidence for stepwise tetrahydrofurylmethanol for-
mation from open chain substrates. The advent of a more reactive
cobalt catalyst (vide infra) has enabled us to address the issue of
selectivity in oxidative cyclizations of (E)- and (Z)-alkenols more
systematically. The most important results from this investigation
showed that the 2,5-trans diastereoselectivity (>99% de) was en-
+ 2 HLn
CoLn
2
Co(OAc)2 × 4 H2O
EtOH / 20 °C
2a/2b
1a (n = a, 94 %)
1b (n = b, quant.)
CF3
CF3
O
tirely independent of the
p-bond configuration. A consistent
HLa =
HLb =
ꢀ35/65 distribution of stereoisomers with respect to the newly
F3C
formed stereocenter in the alkanol side chain pointed in all in-
O
H
2b
O
O
H
2a
* Corresponding author. Tel.: +49 0631 205 2431; fax: +49 0631 205 3921.
E-mail address: hartung@chemie.uni-kl.de (J. Hartung).
Scheme 1. Preparation of cobalt(II) complexes 1a–b.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.12.040

B. Menéndez Pérez, J. Hartung / Tetrahedron Letters 50 (2009) 960–962
961
Table 1
Synthesis of 2,5-disubstituted tetrahydrofurans 5/6 via aerobic cobalt-catalyzed oxidation of alkenols (E)-3/4
OH
n
H
H
H
H
Ph
OH
O2 / CoL2
O
O
Ph
Ph
RE
RE
+
β
RE
solvent / 60 °C
5
5/6
7/8
1.5–4 h
(E)-3/4
cis/trans < 1/99
cis/trans < 1/99
Entry
3/4
RE
Solvent
CoLn/mol %
Convn.
5/6 /% (dr)a,b
7/8/%a
7: 17c
1
2
3
4
5
6
(E)-3
(E)-3
(E)-3
(E)-4
(E)-4
(E)-4
CH3
CH3
CH3
C6H5
C6H5
C6H5
iPrOH
iPrOH
C6H6/CHD
iPrOH
iPrOH
1a/10
1b/20
1a/10
1a/10
1b/20
1a/10
97
66
Quant.
97
82
5: 63 (33:67)
5: 34 (56:44)
5: 8 (39:61)
6: 53 (13:87)
6: 22 (57:43)
6: 37 (38:62)
d
7: —
7: 86
e
d,f
8: —
8: —d
C6H6/CHD
Quant.
8: 15g
a
cis-5–8 were not detected (GC, NMR).
b
c
d
e
f
Diastereomeric ratio with respect to configuration at Cb (GC).
Additional products: 2-acetyl-5-phenyltetrahydrofuran (6%), (E)-1-phenylhex-4-en-1-one (7%).15
Not detected.
Additional product: 2-acetyl-5-phenyltetrahydrofuran (1%).
Additional products: 5-phenyltetrahydrofuran-2-ol (3%),16 5-phenyltetrahydrofuran-2-one (3%),17 1,5-diphenyl pentane-1,5-diol (7%),19,20 1,5-diphenyl-5-hydroxypen-
tane-1-one (4%),19 4-phenyl-4-oxobutanal (2%),18 benzaldehyde (4%).
g
Additional products: 5-phenyltetrahydrofuran-2-one (2%),17 benzaldehyde (2%).
59 (cis:trans < 1:99; Table 1, entry 1).26 Reaction parameters (tem-
perature, cobalt concentration, and molar catalyst/substrate ratio)
were independently varied (not shown), but finally corresponded
to those reported previously for related reactions.9,11 Oxidation of
(E)-1,5-diphenylpent-4-en-1-ol (E)-(4)13 [(E):(Z) > 99:1; GC, 1H
NMR] under such conditions afforded tetrahydrofuran 614 (cis:-
trans < 1:99) as the major product (53%, Table 1, entry 4). A similar
efficiency for tetrahydrofuran formation was not attainable, if pre-
viously established reagent 1b served as the catalyst (Table 1, en-
tries 2 and 5). Mass balances were in all instances supplemented in
combined GC–MS and NMR investigations using purified samples
from larger batches, and data from independently prepared
authentic samples15–20 [e.g., 96% mass balance for the oxidation
of (E)-3 and 79% mass balance for transformation of (E)-4; Table
1, entries 1 and 4).
combined yields of tetrahydrofurans 5/7 and 6/8 remained below
ꢀ80%. Product diversity in oxidations of (Z)-4 (RZ = C6H5) was lar-
ger than in transformations of (Z)-3 (RZ = CH3). The use of CHD/
C6H6 as the solvent instead of iPrOH furnished notable yields of tet-
rahydrofurans 7/8 from alkenols (Z)-3/4 (Table 2, entries 2 and 5).
The current investigation on cobalt(II)-catalyzed aerobic oxida-
tions of (E)- and (Z)-bishomoallylic alcohols provided four distinc-
tive results:
(i) Catalytic activity of bis{4-[3,5-bis(trifluoromethyl)phenyl]-
2-(oxo-
j
O)-but-3-en-4-olatojO}cobalt(II) (1a) for synthesis
of (2-phenyltetrahydrofur-2-yl)alkan-1-ols from d,
e-unsatu-
rated alcohols notably exceeded that of established reagent
1b.
(ii) Solvent variation from iPrOH to CHD/C6H6 was associated
with a change in product selectivity from oxidative cycli-
zation (formation of substituted tetrahydrofur-2-ylmetha-
nols 5/6) toward alkenol cyclization (synthesis of
substituted 2-alkyltetrahydrofurans 7/8). Given mild and
pH neutral conditions and the high degree of diastereose-
lection, the reductive tetrahydrofuran synthesis is
expected to offer important prospect for future heterocy-
cle synthesis.5,22,23
Diastereoselectivity for construction of the stereocenter at Cb in
the alkanol side chain of 5 and 6 ranged from 57/43 to 13/87. It was
dependent on the nature of the terminal substituent (i.e., CH3 or
C6H5), solvent, and applied cobalt reagent. An assignment of ster-
eoisomers was not attainable on the basis of available spectro-
scopic data. This issue is subject to ongoing investigations.
A change in solvent from iPrOH to a 50/50-mixture of C6H6/
cyclohexa-1,4-diene (CHD) significantly favored formation of
trans-2-phenyl-5-ethyltetrahydrofuran trans-7 from (E)-3 (Table
1, entries 1 and 3). No such marked variation in product selectivity
was observed in the oxidation of (E)-4 (Table 1, entries 4 and 6).
Aerobic oxidations of alkenols (Z)-313 and (Z)-413 [both
(E):(Z) < 1:99; GC, 1H NMR] in iPrOH solution of cobalt(II) reagent
1a (60 °C) afforded 2,5-trans-configured (5-phenyltetrahydrofur-
2-yl)alkan-1-ols 5 and 6 as major components, and derivatives 7/
8 as side products (Table 2, entries 1 and 3).9,14,16 Configuration
at newly formed stereocenters in alkanol side chains of heterocy-
cles 5 and 6 again showed a ꢀ35/65 distribution of stereoisomers,
with major components being equivalent to those from aerobic
oxidations of substrates (E)-3/4 (Table 1). Extended product analy-
sis clarified that autoxidation (formation of 2-acetyl-5-phen-
yltetrahydrofuran; Table 2, entries 1 and 2), olefin hydration
(formation of 1,5-diphenyl pentane-1,5-diol; Table 2, entry
3),19,20 C,C-bond cleavage (formation of 5-phenyltetrahydrofuran-
2-one; Table 2, entry 3),17 and reduction (formation of 1,5-diphe-
nyl pentan-1-ol, Table 2, entries 3–5)21 accounted for the fact that
(iii) The customary 2,5-trans selectivity (cis/trans < 1/99, GC) in
aerobic cobalt-catalyzed oxidations of substrates 3/4 was
retained. It was independent from olefinic p-bond configura-
tion, similar to isomer distribution with respect to the newly
formed stereocenter in the alkanol side chain.
(iv) Alkenols having a phenyl substituent attached at terminal
position of the olefinic
p-bond are prone to undergo C,C-
cleavage. The effect was more pronounced for (E)-b-alkyl
styrene derivative (E)-4 than for its (Z)-congener.
The most important implication from the presented data relates
to evidence for sequential C,O bond formation in this type of oxida-
tive alkenol ring closure. In combination with the selectivity effect
exerted by co-solvent CHD, this finding suggests that the reaction
is likely to be terminated via carbon radical trapping. This would
imply that groups other than the H-atom should be transferable
in the final step of the synthesis, which is being pursued at the mo-
ment in this laboratory.

962
B. Menéndez Pérez, J. Hartung / Tetrahedron Letters 50 (2009) 960–962
Table 2
Formation of 2,5-disubstituted tetrahydrofurans 5/6 via aerobic cobalt-catalyzed oxidation of (Z)-configurated bishomoallylic alcohols (Z)-3/4
OH
n
H
H
H
H
Ph
OH
O2 / CoL2
O
O
Ph
Ph
RZ
RZ
+
β
solvent / 60 °C
RZ
3–4 h
5/6
7/8
(Z)-3/4
cis/trans < 1/99
cis/trans < 1/99
Entry
3/4
RE
Solvent
CoLn/mol %
Convn.
5/6/% (dr)a,b
7/8/%a
1
2
3
4
5
(Z)-3
(Z)-3
(Z)-4
(Z)-4
(Z)-4
CH3
CH3
C6H5
C6H5
C6H5
iPrOH
C6H6/CHD
iPrOH
iPrOH
C6H6/CHD
1a/10
1a/10
1a/10
1b/20
1a/10
Quant.
96
98
44
89
5: 61 (39:61)
5: 9 (38:62)
6: 17 (35:65)
6: 9 (67:33)
6: 16 (31:69)
7: 8c
7: 71d
8: 1e
8: –f,g
8: 47h
a
cis-5–8 were not detected (GC, NMR).
b
c
Diastereomeric ratio with respect to configuration at Cb (GC).
Additional product: 2-acetyl-5-phenyltetrahydrofuran (8%).
Additional product: 2-acetyl-5-phenyltetrahydrofuran (5%).
d
e
Additional products: 5-phenyltetrahydrofuran-2-one (3%),17 1,5-diphenyl pentan-1-ol (23%),21 1,5-diphenyl pentane-1,5-diol (33%),19,20 (Z)-1,5-diphenyl pent-4-en-1-
one (3%),14 1,5-diphenyl pentan-5-ol-1-one (6%).18
f
Not detected.
g
Additional product: 1,5-diphenyl pentan-1-ol (19%).21
h
Additional products: 1,5-diphenyl pentan-1-ol (11%),21 (Z)-1,5-diphenyl pent-4-en-1-one (3%) 14.
17. Brown, H. C.; Kulkarni, S. V.; Racherla, U. S. J. Org. Chem. 1994, 59, 365–369.
Acknowledgments
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19. Zhang, H.-C.; Harris, B. D.; Costanzo, M. J.; Lawson, E. C.; Maryanoff, C. A.;
Maryanoff, B. E. J. Org. Chem. 1998, 63, 7964–7981.
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This work was supported by the Deutscher Akademischer Aust-
auschdienst (ISGS, TU Kaiserslautern; scholarschip for B.M.). Fur-
thermore, we wish to express our gratitude to Dr. Arne Ludwig
for providing samples of alkenols (E)-4, (Z)-3, and (Z)-4, and finally
to Dipl.-Chem. Dominik Schuch for helpful discussions.
23. Hartung, J.; Gottwald, T.; Špehar, K. Synthesis 2002, 1469–1498.
24. Satisfactory analytical data were obtained for all new compounds prepared in
the study.
25. UV/vis (iPrOH): kmax (lg
e
/m2 mÀo1lÀ1) = 231 (3.28), 326 (3.29), 429 nm
References and notes
~
(qualitative). IR (NaCl)
v
3434 cm
,
2925, 1624, 1590, 1516, 1375, 1280,
1178, 1136, 905, 682. 19F NMR (CDCl3/acetone 565 MHz): d À55.4. Anal. Calcd
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(0.10 equiv) in iPrOH (8 mL/mmol) was stirred at 60 °C for 2 h in a stationary
oxygen atmosphere. The reaction mixture is allowed to cool to 20 °C
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