Photochemical synthesis of 3-alkynals from 1-alkynoxy-9,10-anthraquinones

Article abstract of DOI:10.1021/jo900298y

(Chemical Equation Presented) Photolysis of 1-(3-alkynoxy)-9,10- anthraquinones in deoxygenated methanol leads to moderate yields (35-45%) of 3-alkynals along with the unexpected formation of diacetals. Reaction of these 3-alkynals with Grignard and Witti

Full text of DOI:10.1021/jo900298y

Photochemical Synthesis of 3-Alkynals from
-Alkynoxy-9,10-anthraquinones
SCHEME 1. Photochemical Synthesis of Aldehydes
1
Ronald L. Blankespoor,* Peter J. Boldenow, Eric C. Hansen,
Jeffrey M. Kallemeyn, Andrew G. Lohse, David M. Rubush,
and Derek Vrieze
Department of Chemistry and Biochemistry, CalVin College,
1
726 Knollcrest Circle SE,
Grand Rapids, Michigan 49546-4403
blan@calVin.edu
ReceiVed February 18, 2009
been prepared in fairly high purity by using a mild chemo-
Photolysis of 1-(3-alkynoxy)-9,10-anthraquinones in deoxy-
7
enzymaticoxidation-hydrocyanationprotocol andtheDess-Martin
8
genated methanol leads to moderate yields (35-45%) of
oxidation.
3-alkynals along with the unexpected formation of diacetals.
Since alkanals can be prepared in isolated yields of 60-80%
in the absence of strong acids and strong oxidants by using a
photochemistry process developed in our laboratory (Scheme
Reaction of these 3-alkynals with Grignard and Wittig
reagents occurs nearly quantitatively without rearrangement
to their 2,3-dienal isomers.
9
1), we were confident that this method could provide another
entry into 3-alkynals without significant rearrangement to their
corresponding 2,3-dienals. In this work we describe the synthesis
of 3-alkynals using this photochemical method, which is
believed to occur through biradical and zwitterion inter-
3
-Alkynals have the potential to play an important role in
synthesis by selective reaction of their isolated functional groups.
They possess a triple bond, for example, that would be expected
to undergo cyclization reactions, and a carbonyl that would be
expected to react with a variety of nucleophiles including Wittig
reagents and enolates. Early attempts to prepare 3-alkynals
9
d
mediates. Oxidation of the anthrahydroquinone photoproduct
and hydrolysis of its acetal occur during the workup upon
1
9
d
exposure to oxygen.
2
3
Beginning with 1-hydroxy-2-butyl-9,10-anthraquinone (1),
4
5
by the hydrolysis of vinyl ethers and acetals, and the periodate
oxidation of glycols, were only marginally successful because
which can be made from commercially available 1-hydroxy-
6
10
9,10-anthraquinone by using the Marshalk reaction, and readily
the target compounds were often contaminated by their conju-
gated 2,3-dienal isomers, presumably formed by rearrangement
under the reaction conditions. More recently, 3-alkynals have
available 3-alkyn-1-ols, anthraquinones 2a and 2b were obtained
in isolated yields of 65% and 63%, respectively, using the
11
Mitsunobu reaction. (Scheme 2). Irradiation of 2 in the absence
of oxygen with 300-370 nm light gave anthraquinone 1, the
target 3-alkynals 3, and diacetals 4 in isolated yields of 50-55%,
(
1) (a) Wang, K. K. Chem. ReV. 1996, 96, 207–222. (b) Ojima, I.;
Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. ReV. 1996, 96, 635–662. (c)
Mikami, K.; Shimizu, M. Chem. ReV. 1992, 92, 1021–1050. (d) Marshall, J. A.;
Andersen, M. W. J. Org. Chem. 1992, 57, 2766–2768. (e) Marshall, J. A.; DuBay,
W. J. J. Org. Chem. 1994, 59, 1703–1708.
(7) Vugts, D. J.; Veum, L.; al-Mafraji, K.; Lemmens, R.; Schmitz, R. F.; de
Kanter, F. J. J.; Groen, M. B.; Hanefeld, U.; Orru, R. V. A. Eur. J. Org. Chem.
2006, 7, 1672–1677.
(
(
2) Journet, M.; Malacria, M. J. Org. Chem. 1992, 57, 3085–3093.
3) (a) Mukai, C.; Kataoka, O.; Hanaoka, M. Tetrahedron Lett. 1991, 32,
(8) Wavrin, L.; Viala, J. Synthesis 2002, 326–330.
7
553–7556. (b) Mukai, C.; Kataoka, O.; Hanaoka, M. J. Chem. Soc., Perkin
(9) (a) Blankespoor, R. L.; Smart, R. P.; Batts, E. D.; Kiste, A. A.; Lew,
R. E.; Vander Vliet, M. E. J. Org. Chem. 1995, 60, 6852–6859. (b) Smart, R. P.;
Peelen, T. J.; Blankespoor, R. L.; Ward, D. L. J. Am. Chem. Soc. 1997, 119,
461–465. (c) Blankespoor, R. L.; DeVries, T.; Hansen, E.; Kallemeyn, J. M.;
Klooster, A. M.; Mulder, J. A.; Smart, R. P.; Vander Griend, D. A. J. Org.
Chem. 2002, 67, 2677–2681. (d) Blankespoor, R. L.; De Jong, R. L.; Dykstra,
R.; Hamstra, D. A.; Rozema, D. B.; VanMeurs, D. P.; Vink, P. J. Am. Chem.
Soc. 1991, 113, 3507–3513.
Trans. 1 1993, 563–571.
4) (a) Herbertz, T. Chem. Ber. 1952, 85, 475–482. (b) Herbertz, T. Chem.
Ber. 1959, 92, 541–550. (c) Winter, M. HelV. Chim. Acta 1963, 46, 1754–60.
d) Durand, M. H.; Piaux, L. C. R. Hebd. Seances Acad. Sci. 1958, 246, 1055–
057.
5) (a) Barbot, F.; Miginiac, P. Synthesis 1983, 651–654. (b) Roush, W. R.
(
(
1
(
Tetrahedron Lett. 1991, 32, 6285–6288. (c) de Sousa, P. T., Jr.; Taylor, R. J. K.
J. Braz. Chem. Soc. 1993, 4, 109–112.
(10) Marschalk, C.; Koenig, F.; Oursoussoff, N. Bull. Soc. Chim. Fr. 1936,
3, 1545-1575.
(11) Mitsunobu, O. Synthesis 1981, 1–28.
(
6) (a) Winter, M. HelV. Chim. Acta 1963, 46, 1749–1754. (b) Corey, E. J.;
Wright, S. W. J. Org. Chem. 1990, 55, 1670–1673.
1
0.1021/jo900298y CCC: $40.75  2009 American Chemical Society
J. Org. Chem. 2009, 74, 3933–3935 3933
Published on Web 04/17/2009

SCHEME 2. Synthesis of 3-Alkynal Precursors
SCHEME 4. Photolysis of Anthraquinone 5 in
12
Deoxygenated Methanol
SCHEME 3. Photolysis of Anthraquinones 2 in
Deoxygenated Methanol
SCHEME 5. Reaction of 3-Alkynals with Grignard and
Wittig Reagents
3
5-45%, and 30-35%, respectively (Scheme 3). Only trace
amounts of 2,3-dienals were formed as shown in the proton
NMR spectrum of 3-decynal in Figure 1 (left spectrum), which
displays a very weak doublet (J ) 7.24 Hz) for the aldehydic
proton of 2,3-decadienal at 9.53 ppm with an integration of less
than 2% relative to the triplet at 9.60 ppm.
The lower than expected yields of 3-alkynals 3 can be
attributed to the formation of significant amounts of diacetals
using flash chromatography. In an attempt to increase the yields
of 3-alkynals by preventing the formation of their corresponding
diacetals, the photolysis of 2b was conducted in 90% aqueous
THF. Unfortunately, the yield of 3-decynal did not increase
significantly in this medium.
4
. In our earlier work using this photochemistry alkanals were
obtained in isolated yields of 60-80% without the formation
9a
of significant amounts of the corresponding diacetals. Interest-
ingly, Jones and Brinson obtained similar yields of R,ꢀ-
unsaturated aldehyde 6 and diacetal 7 when anthraquinone 5
was irradiated at wavelengths above 350 nm in degassed
Not surprisingly, 3-alkynals rearrange in the presence of silica
gel to their corresponding 2,3-dienals as shown in Figure 1 for
1
2
methanol (Scheme 4). It is not clear what role the triple and
double bonds are playing that leads to these diacetal byproducts.
Unlike diacetal 7, though, diacetal 4 does not form more
3-decynal. Therefore, ether solutions of 3, which were obtained
by vacuum distillation from their reaction mixtures, but were
not further purified, were reacted with methylmagnesium
bromide to give the corresponding 4-alkyn-2-ols 8 in overall
yields of 35-40% from 2 without significant amounts of 3,4-
alkadien-2-ols. Similar results were obtained when alkynals 3
were reacted with methyl (triphenylphosphoranylidene)acetate
to form their corresponding methyl 2-alken-5-ynoate esters 9
with trans:cis ratios of ca. 7:1. One may conclude then that
strong nucleophiles undergo carbonyl addition to 3 in high yield
without prior rearrangement of these 3-alkynals to their 2,3-
dienal isomers (Scheme 5).
1
3
aldehyde when irradiated at shorter wavelengths.
Since diacetals 4 only slowly hydrolyzed on a silica gel
column, it was possible to obtain them in fairly high purity by
In conclusion, 3-alkynals with only trace amounts of their
2
,3-dienal isomers can be prepared in moderate yield by using
a photochemical process that employs a 1-alkynoxy-9,10-
anthraquinone template. Comparable yields of diacetal byprod-
ucts are also obtained. Reaction of these 3-alkynals with
Grignard and Wittig reagents occurred almost quantitatively
without prior rearrangement to their 2,3-dienals.
Experimental Section
-Heptynal: 1H NMR (400 MHz; CDCl
.9 Hz), 3.22 (dt, 2H, J ) 1.9, 2.5 Hz), 2.16 (tt, 2H, J ) 2.5, 7.0
4d
) δ 9.59 (t, 1H, J )
3
3
1
FIGURE 1. 1H NMR spectra of the aldehydic proton of 3-decynal
before (left) and after (right) a solution of the compound was stirred
for 10 min in the presence of silica gel. The appearance of the doublet
in the spectrum to the right shows that extensive rearrangement to 2,3-
decadienal has occurred.
(
(
12) Brinson, R. G.; Jones, P. B. Org. Lett. 2004, 6, 3767–3770.
13) Diacetal 4b was irradiated with 280-370 nm light using a quartz
container for 24 h without appreciable reaction. Brinson and Jones found that
diacetal 7 rapidly produces 6 and 1-hydroxy-2-propyl-9,10-anthraquinone when
irradiated in methanol at 366 nm.
3
934 J. Org. Chem. Vol. 74, No. 10, 2009

Hz), 1.51 (sext, 2H, J ) 7.3 Hz), 0.97 (t, 3H, J ) 6.8 Hz) ppm;
(1 H, dt, J ) 15.4, 2.0 Hz), 3.74 (3 H, s), 3.10 (2 H, m), 2.19 (2
H, tt, J ) 7.0, 2.4 Hz), 1.51 (2 H, pent, J ) 7.3 Hz), 1.42-1.26 (6
1
3
C NMR (100 MHz, CDCl
4.4 ppm.
3
) δ 196.4, 86.4, 70.3, 34.8, 22.6, 21.7,
13
1
3
H, m), 0.89 (3 H, t, J ) 6.8 Hz) ppm; C NMR (100 MHz; CDCl )
5
b
3
-Decynal: 1H NMR (400 MHz; CDCl
3
) δ 9.60 (t, 1H, J )
δ 166.8, 143.7, 122.1, 84.4, 74.3, 51.5, 31.3, 28.9, 28.6, 22.5, 22.0,
+
1
.9 Hz), 3.23 (dt, 2H, J ) 1.9, 2.5 Hz), 2.20 (tt, 2H, J ) 2.5, 7.0
18.7, 14.0 ppm; HRMS [EI ] found 208.1461, C13
208.1463.
20 2
H O requires
Hz), 1.50 (br pent, 2H, J ) 7.3 Hz), 1.42-1.26 (m, 6H), 0.89 (t,
1
3
3
H, J ) 6.9 Hz) ppm; C NMR (100 MHz, CDCl
0.2, 34.9, 31.5, 28.9, 28.7, 22.7, 19.0, 14.2 ppm.
-(3-Heptynoxy)-2-butyl-9,10-anthraquinone (2a). To 35 mL
of dry THF in a 50 mL round-bottomed flask was added 2-butyl-
-hydroxy-9,10-anthraquinone (0.187 g, 6.68 mmol), Ph P (2.75
g, 10.4 mmol), and 3-heptyn-1-ol (1.39 g, 12.4 mmol). To the
resulting solution cooled in a bath at -10 °C under N was added
3
) δ 196.1, 86.3,
Diacetal 4a: off-white solid; IR (neat) ν 3072, 2956, 2252, 1728,
7
1675, 1591, 1440, 1260, 1122, 1058, 1039, 1016, 900, 772, 710
11
-1 1
1
3
cm ; H NMR (400 MHz; CDCl ) δ 8.13 (1 H, br d, J ) 7.6 Hz),
7.85 (1 H, br d, J ) 7.5 Hz), 7.59 (1 H, br t, J ) 7.6 Hz), 7.57 (1
H, d, J ) 7.8 Hz), 7.51 (1 H, br t, J ) 7.5 Hz), 7.23 (1 H, d, J )
7.8 Hz), 5.83 (1 H, br t, J ) 5.5 Hz), 3.06 (3 H, s), 2.95-2.91 (2
H, m), 2.65 (2 H, br t, J ) 7.6 Hz), 2.21 (2 H, tt, J ) 6.8, 2.4 Hz),
1.62-1.52 (4 H, m), 1.36 (2 H, sext, J ) 7.4 Hz), 1.03 (3 H, t, J
1
3
2
diisoproyl azodicarboxylate (2.50 g, 12.4 mmol) dropwise over 30
min. The bath was removed and the reaction mixture was stirred
at room temperature for 48 h. The bulk of the THF was removed
in a rotary evaporation under reduced pressure and the residue was
combined with 50 mL of boiling hexane. The solid residue,
1
3
) 7.4 Hz), 0.93 (3 H, t, J ) 7.4 Hz) ppm; C NMR (100 MHz,
CDCl
3
) δ 184.6, 148.7, 137.4, 136.0, 133.1, 131.4, 130.4, 129.9,
129.2, 127.7, 125.0, 123.2, 119.6, 92.4, 91.9, 82.8, 73.7, 49.1, 31.5,
+
29.4, 25.5, 22.4, 22.3, 20.8, 13.9, 13.4 ppm; HRMS [EI ] found
consisting of the hydrazine and Ph
3
PO byproducts, was removed
28 4
404.1992, C26H O requires 404.1988.
by hot filtration. The solvent in the filtrate was removed in the rotary
evaporator under reduced pressure giving a viscous red liquid, which
was dissolved in 15 mL of hot methanol. On cooling the desired
product was obtained as yellow crystals (1.63 g, 65%): mp 92-93
Diacetal 4b: off-white solid; IR (neat) ν 3073, 2954, 2927, 2857,
2249, 1728, 1677, 1591, 1441, 1258, 1059, 1040, 1016, 944, 798,
-
1 1
707 cm ; H NMR (400 MHz; CDCl ) δ 8.13 (1 H, dd, J ) 7.6,
3
1.2 Hz), 7.85 (1 H, dd, J ) 7.6, 1.2 Hz), 7.59 (1 H, dt, J ) 7.6, 1.6
Hz), 7.57 (1 H, d, J ) 7.6 Hz), 7.51 (1 H, dt, J ) 7.6, 1.2 Hz),
7.23 (1 H, br d, J ) 7.6 Hz), 5.83 (1 H, dd, J ) 6.0, 4.8 Hz), 3.06
(3 H, s), 2.94-2.91 (2 H, m), 2.65 (2 H, t, J ) 7.6 Hz), 2.23 (2 H,
tt, J ) 6.8, 2.4 Hz), 1.62-1.50 (4 H, m), 1.46-1.26 (8 H, m), 0.93
°
C; IR (KBr) 2957, 2930, 2873, 1671, 1582, 1566, 1468, 1326,
-1 1
1
283, 1255, 1239, 1045, 1030, 979, 715 cm ; H NMR (400 MHz;
) δ 8.26-8.20 (m, 2H), 8.06 (d, 1H, J ) 7.9 Hz), 7.78-7.71
m, 2H), 7.61 (d, 1H, J ) 7.9 Hz), 4.06 (t, 2H, J ) 7.0 Hz), 2.86
m, 4H), 2.13 (tt, 2H, J ) 2.2, 7.0 Hz), 1.65 (quintet, 2H, J ) 7.7
CDCl
3
(
(
1
3
(3 H, t, J ) 7.4 Hz), 0.89 (3 H, t, J ) 7.2 Hz) ppm; C NMR (100
MHz; CDCl
Hz), 1.51 (sextet, 2H, J ) 7.1 Hz), 1.42 (sextet, 2H, J ) 7.2 Hz),
3
) δ 184.6, 148.7, 137.4, 136.0, 133.1, 131.4, 130.4,
1
3
0
1
1
2
7
.96 (t, 6H, J ) 7.3 Hz) ppm; C NMR (100 MHz, CDCl
3
) δ
129.9, 129.2, 127.7, 125.0, 123.2, 119.6, 92.4, 91.9, 82.9, 73.5,
82.9, 182.5, 157.3, 145.5, 135.4, 134.8, 133.9, 133.6, 133.3, 132.6,
27.1, 126.5, 125.5, 123.4, 81.7, 76.3, 72.9, 32.3, 30.0, 22.6, 22.3,
49.0, 31.5, 31.4, 29.4, 28.9, 28.6, 25.5, 22.6, 22.4, 18.7, 14.0, 13.9
+
ppm; HRMS [EI ] found 446.2461, C29
H
34
O
4
requires 446.2457.
) δ 3.91
1
0.7, 20.6, 13.9, 13.4 ppm. Anal. Calcd for C25
.00. Found: C, 80.45; H, 6.77.
H
26
O
3
: C, 80.19; H,
4-Octyn-2-ol: colorless oil; H NMR (400 MHz; CDCl
3
(1 H, br s), 2.38 (1 H, ddt, J ) 16.4, 4.8, 2.5 Hz), 2.28 (1 H, ddt,
J ) 16.4, 6.8, 2.4 Hz), 2.16 (2 H, tt, J ) 7.2, 2.4 Hz), 2.02 (1 H,
br d, J ) 2.8 Hz), 1.52 (2 H, sext, J ) 7.3 Hz), 1.24 (3 H, d, J )
1
1
1
-(3-Decynoxy)-2-butyl-9,10-anthraquinone (2b). The pro-
cedure for preparing anthraquinone 2a was used giving an-
thraquinone 2b as yellow crystals (63%): mp 64-65 °C; IR (KBr)
1
3
6.4 Hz), 0.98 (3 H, t, J ) 7.4 Hz) ppm; C NMR (100 MHz;
CDCl ) δ 83.1, 76.2, 66.5, 29.4, 22.4, 22.1, 20.7, 13.5 ppm.
4-Undecyn-2-ol: colorless oil; H NMR (400 MHz; CDCl ) δ
2
1
958, 2934, 2872, 2859, 1673, 1580, 1567, 1466, 1326, 1281, 1254,
3
-
1
1
1
192, 1045, 1028, 978, 865, 795, 716 cm ; H NMR (400 MHz;
) δ 8.26-8.20 (m, 2H), 8.06 (d, 1H, J ) 7.9 Hz), 7.78-7.70
3
CDCl
3
3.99 (1 H, br sext, J ) 6.0 Hz), 2.37 (1 H, ddt, J ) 16.4, 4.9, 2.4
Hz), 2.27 (1 H, ddt, J ) 16.4, 6.7, 2.4 Hz), 2.17 (2 H, tt, J ) 7.2,
2.4 Hz), 2.03 (1 H, br s), 1.49 (2 H, pent, J ) 7.1 Hz), 1.41-1.27
(
2
2
)
1
1
1
m, 2H), 7.61 (d, 1H, J ) 7.9 Hz), 4.06 (t, 2H, J ) 7.0 Hz),
.86-2.81 (m, 4H), 2.14 (tt, 2H, J ) 2.3, 7.1 Hz), 1.69-1.61 (m,
H), 1.51-1.21 (m, 10H), 0.96 (t, 3H, J ) 7.3 Hz), 0.87 (t, 3H, J
(6 H, m), 1.24(3 H, d, J ) 6.4 Hz), 0.89 (3 H, t, J ) 7.0 Hz) ppm;
6.9 Hz) ppm; 13C NMR (100 MHz, CDCl
13
3
) δ 182.9, 182.6, 157.3,
3
C NMR (100 MHz; CDCl ) δ 83.3, 76.0, 66.5, 31.3, 29.4, 28.9,
2
8.5, 22.5, 22.1, 18.7, 14.0 ppm.
45.4, 135.4, 134.8, 133.9, 133.6, 133.3, 132.6, 127.1, 126.4, 125.5,
23.4, 81.9, 76.1, 73.0, 32.3, 31.3, 30.0, 28.9, 28.5, 22.6, 22.4, 20.6,
8.7, 14.0, 13.9 ppm. Anal. Calcd for C28H O : C, 80.74; H, 7.74.
32 3
Acknowledgment. We gratefully acknowledge the donors
of the Petroleum Research Fund, administered by the American
Chemical Society, for partial support of this research. R.L.B.
acknowledges the support of the Brummel Chair at Calvin
College. HRMS were obtained at the Michigan State University
Mass Spectrometry Facility.
Found: C, 80.64; H, 7.59.
Methyl trans-2-nonen-5-ynoate: colorless oil; IR (neat) ν 2963,
-
1
2
931, 2876, 2213, 1731, 1661, 1436, 1276, 1170, 1039, 984 cm ;
1
H NMR (400 MHz; CDCl
6
3
) δ 6.94 (1 H, dt, J ) 15.2, 5.00 Hz),
.16 (1 H, dt, J ) 15.2, 2.1 Hz), 3.75 (3 H, s), 3.12-3.09 (2 H,
m), 2.18 (2 H, tt, J ) 7.0, 2.4 Hz), 1.54 (2 H, sext, J ) 7.2 Hz),
1
3
0
.99 (3 H, t, J ) 7.2) ppm; C NMR (100 MHz; CDCl
3
) δ 166.8,
Supporting Information Available: General procedures;
proton and carbon NMR spectra of reported compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
43.8, 122.1, 84.2, 74.5, 51.4, 22.3, 22.0, 20.7, 13.4 ppm; HRMS
+
[
EI ] found 166.0994, C10
H
14
O
2
requires 166.0994.
Methyl trans-2-dodecen-5-ynoate: colorless oil; IR (neat) ν
1
1
2
960, 2928, 2857, 2230, 1729, 1661, 1274, 1168, 984 cm- ; H
NMR (400 MHz; CDCl
3
) δ 6.93 (1 H, dt, J ) 15.4, 5.04 Hz), 6.15
JO900298Y
J. Org. Chem. Vol. 74, No. 10, 2009 3935