New regiospecific synthesis of tri- and tetra-substituted furans

Article abstract of DOI:10.1021/jo9003986

β-Acyloxy α,β-unsaturated acetylenic ketones have been shown to react with organocuprate reagents and undergo cyclization followed by dehydration to give substituted furans as the final products. The transformation appeared to be versatile, and tri- and t

Full text of DOI:10.1021/jo9003986

New Regiospecific Synthesis of Tri- and Tetra-Substituted Furans
Leiv K. Sydnes,*,† Bjarte Holmelid,† Myagmarsuren Sengee,†,‡ and Miriam Hanstein†,§
Department of Chemistry, UniVersity of Bergen, Alle´gt 41, NO-5007 Bergen, Norway, Department of Organic
Chemistry, National UniVersity of Mongolia, P.O. Box 46, Post Office 46, Ulaanbaatar 210646, Mongolia, and
Fakulta¨t fu¨r Chemie and Bioanorganische Chemie, Technische UniVersita¨t Dortmund, Otto-Hahn-Strausse 6,
DE-44227 Dortmund, Germany
leiV.sydnes@kj.uib.no
ReceiVed February 27, 2009
ꢀ-Acyloxy R,ꢀ-unsaturated acetylenic ketones have been shown to react with organocuprate reagents
and undergo cyclization followed by dehydration to give substituted furans as the final products. The
transformation appeared to be versatile, and tri- and tetra-substituted furans were obtained with
regiochemical control in moderate to good yields. The best yields were generally obtained when the
reactions were performed around -60 °C with substrates and cuprates containing sterically demanding
substituents. The proposed mechanism for furan formation has been supported by experiments.
SCHEME 1. Synthesis of Ketoesters 4 from TEB (1)
Introduction
We have reported a simple and efficient synthesis of 3,3,4,4-
tetraethoxybutyne (TEB) (1), using ethyl vinyl ether as starting
material and taking advantage of the serendipitous discovery
that 1,1,2-trihalocyclopropanes undergo ring-opening under
phase-transfer conditions in the presence of ethanol.1 Easy access
to TEB has made the preparation of 1-substituted 4,4,5,5-
tetraethoxypent-2-yn-1-ols (2) straightforward (Scheme 1).2-4
These alcohols are highly functionalized, and by selectively
exploiting their reactive moieties, syntheses of a range of
interesting compounds can be envisaged and are being
investigated.
Among the compounds easily obtained from TEB in good
yields are 1-alkyl- and 1-aryl-4,4,5,5-tetraethoxy-pent-2-yn-1-
† University of Bergen.
‡ National University of Mongolia.
yl esters (3), which, like 1, appear to be labile under acidic,
aqueous conditions and undergo deketalization to give the
corresponding ketoesters (4) (Scheme 1 and Experimental
Section). These ketoesters contain an electron-deficient, activated
triple bond which should be prone to react with nucleophilic
reagents, but due to the presence of other electrophilic functional
groups the outcome of the reactions is not necessarily obvious.
That appears in fact to be the case; with some nucleophiles,
very complex reaction mixtures are obtained whereas in other
cases clean reactions are observed.5
§ Technische Universita¨t Dortmund.
(1) (a) Sydnes, L. K.; Bakstad, E. Acta Chem. Scand. 1996, 50, 446. (b)
Sydnes, L. K.; Bakstad, E. Acta Chem. Scand. 1997, 51, 1132. (c) Bakstad, E.;
Sydnes, L. K. Acta Chem. Scand. 1998, 52, 1029. (d) Bakstad, E.; Olsen, A. S.;
Sandberg, M.; Sydnes, L. K. Acta Chem. Scand. 1999, 53, 465. (e) Sydnes,
L. K. Eur. J. Org. Chem. 2000, 3511. (f) Kvernenes, O. H.; Sydnes, L. K. Org.
Synth. 2005, 83, 184. (g) Sydnes, L. K.; Holmelid, B.; Kvernenes, O. H.;
Sandberg, M.; Hodne, M.; Bakstad, E. Tetrahedron 2007, 63, 4144. (h) Holmelid,
B.; Kvernenes, O. H.; Hodne, M.; Sydnes, L. K. ARKIVOC 2008, (vi), 26–41.
(2) Sydnes, L. K.; Kvernenes, O. H.; Valdersnes, S. Pure Appl. Chem. 2005,
77, 119.
(3) Some results were presented at the Petra International Chemistry
Conference in Petra, Jordan, June 2007; see: Sydnes, L. K.; Holmelid, B.;
Valdersnes, S.; Sengee, M.; Boman, K. Jordanian J. Chem. 2007, 2, 105.
(4) Sydnes, L. K.; Holmelid, B.; Kvernenes, O. H.; Valdersnes, S.; Hodne,
M.; Boman, K. ARKIVOC 2008, xiV, 242.
(5) Sydnes, L. K.; Sengee, M. To be published.
3430 J. Org. Chem. 2009, 74, 3430–3443
10.1021/jo9003986 CCC: $40.75 2009 American Chemical Society
Published on Web 04/03/2009

Synthesis of Tri- and Tetra-Substituted Furans
Exploratory experiments with lithium dimethylcuprate,6 which
is well-known to react with conjugated, unsaturated ketones,7-9
revealed that several ketoesters consistently gave fairly simple
product mixtures when treated with this reagent and afforded
substituted furans in variable yields. This observation is quite
interesting considering the growing attention this class of
compounds has received in recent years. Not only are furans
important structural motifs in natural products and pharmaceuti-
cal substances,10,11 such heterocycles have also turned out to
be quite valuable intermediates in organic synthesis.12 As a result
development of syntheses of highly functionalized furans has
emerged as an increasingly active field of research.13 In this
paper, we describe our successful regiospecific synthesis of tri-
and tetra-substituted furans.
TABLE 1. Isolated Yields of Alcohols 2, Esters 3, and Ketoesters
4, Synthesized from TEB (1) as Summarized in Scheme 1a
stepwise results; compound/yield (%)
total yield of
R1
R2
S1
S2
S3
4 from 1 (%)
H
H
H
CH3
i-Pr
Ph
CH3
i-Pr
Ph
CH3
i-Pr
Ph
CH3
i-Pr
Ph
2a/94
3a/95
3b/87
3c/76
3d/96
3e/82
3f/85
3g/90
3h/84
3i/84
3j/90
3k/80
3l/82
3m/81
3n/80
3o/75
3p/90
3q/84
3r/85
4a/90
4b/95
4c/90
4d/91
4e/88
4f/91
4g/95
4h/92
4i/92
4j/89
4k/88
4l/85
4m/94
4n/98
4o/95
4p/92
4q/90
4r/91
80
78
64
80
66
71
67
60
60
44
39
38
53
55
50
72
66
67
CH3
CH3
CH3
i-Pr
i-Pr
i-Pr
t-Bu
t-Bu
t-Bu
Ph
2b/92
2c/78
2d/55b
2e/70b
2f/87
Results and Discussion
CH3
i-Pr
Ph
Ph
Ph
The ketoesters 4 used in this study were prepared from TEB
by the three-step synthesis outlined in Scheme 1. The yield in
each step was in most cases very good, and the total yield was
in almost every case well above 50% (Table 1) whether the
reactions were performed on a small or a large scale.
C6H13 CH3
C6H13 i-Pr
C6H13 Ph
a Stepwise yields are for compounds 2, 3, and 4 obtained in steps
1-3 (S1 - S3), respectively. b Isolated yield after reductive workup as
described in ref.4
(6) Gilman, H.; Jones, R. G.; Woods, L. A. J. Org. Chem. 1952, 17, 1630.
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Exploratory experiments using some ketones and Me2CuLi
(prepared as described by Gilman et al.6) showed that 4 reacted
at room temperature and below to give essentially two products,
a 2-alkenone and a substituted furan. The yield of the former
was low and temperature sensitive in the sense that it dropped
when the reaction temperature approached 0 °C; the furan
formation, on the other hand, became gradually more important
as the temperature dropped, and when it reached -50 °C this
transformation was completely predominant.
In order to uncover the scope of the reaction acetylenic
ketoesters 4a - 4r were treated with one molar equivalent of
Me2CuLi at temperatures ranging from room temperature to -78
°C. The ketoesters were completely consumed and, as the results
compiled in Table 2 show, all substrates gave a 3-(2,2-
diethoxyacetyl)-4-methyl-2-R2-5-R1-furan (5) in fair to good
yield with a predictable substitution pattern. In accordance with
the results from the exploratory experiments the yield was
sensitive to the temperature prevailing during the reaction; the
yield increased significantly, in the best cases more than 2.5
times (e.g., entries 1, 11 and 16), when the temperature was
lowered from 0 °C to the -60 °C and below. However, running
the reactions below -60 °C did not really improve the outcome;
on the contrary, in some cases the yield even dropped, e.g.
entries 7 and 16. It is also noteworthy that the yield dropped
somewhat when cyanocuprate Me2Cu(CN)Li2 was applied.14
Conjugated alkenones were formed from some substrates when
reactions were run at and above 0 °C, but the yields were so
low that isolation was not worthwhile.
(10) (a) Keay, B. A.; Dibble, P. W. In ComprehensiVe Heterocyclic Chemistry
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J. Org. Chem. Vol. 74, No. 9, 2009 3431

Sydnes et al.
SCHEME 3. Synthesis of Congested Furans from
TABLE 2. Isolated Yields of Furans 5 Synthesized by Treating
Ketoesters 4 with Me2CuLi between rt and -78 °C
Ketoesters 4g and 4h
isolated yield (%)
entry
4
furan
-78 °C
-60 °C
0 °C
rt
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
50
45
40
48
50
53
81a
75
47
70
68
52
52
60
53
70
69
50
10
45
25
20
26
40
70
51
45
30
25
46
47
74
56
only partly. Thus, a drop in the yield of 5 was observed for
several ketoesters as the hydrocarbon part of the acyloxy moiety,
that is, R2, became sterically more demanding whereas the 5,5-
diethoxy-1-R1-pent-2-ynyl group remained the same; compare,
for example, entries 7 (R2 ) Me; 81%), 8 (R2 ) i-Pr; 75%),
and 9 (R2 ) Ph; 47%) for reactions run at -60 °C. For some
other series, on the other hand, the yield increased instead
(compare entries 4 (R2 ) Me; 48%), 5 (R2 ) i-Pr; 50%), and
6 (R2 ) Ph; 53%) for reactions run at -60 °C). However, when
different esters of the same acid were reacted, the furan yield
generally increased as the steric crowding increased. Particu-
larly noteworthy is the series of substrates comprised of
isobutyrates 4b, 4e, 4h, and 4k which at -60 °C gave the
corresponding furans in 45, 50, 75, and 68% yield, respectively,
as R1 changes from H via Me and i-Pr to t-Bu (see Table 2,
entries 2, 5, 8, and 11, respectively). This trend is further
underlined when ketoesters 4g and 4h are treated with the butyl
and t-butyl equivalents of the Gilman cuprate and furnish the
expected and sterically quite congested furans 6 and 7,
respectively, in quite acceptable yields (Scheme 3).
9
10
11
12
13
14
15
16
17
18
72
68
24
41
35
18
28
32
50
67
26
a Yield was 74% when a higher-order cuprate was used.
SCHEME 2. Suggested Reaction Mechanism for Cuprate
Addition to 4a
It is known that cuprate addition to acyclic R,ꢀ-unsaturated
ketones in general gives acyclic products, also when other
functional groups are present.8b,17 The course of reaction
reported here therefore raises the question as to why cyclization
occurs when 4 reacts.18 One plausible explanation is based on
the fact that copper is known to form complexes with oxygen-
containing ligands,19 including conjugated enones and eno-
lates.20 As outlined in Scheme 2, cuprate addition to 4 affords
(15) (a) Kluender, H.; Bradley, C. H.; Sih, C. J.; Fawcett, P.; Abraham, E. P.
J. Am. Chem. Soc. 1973, 95, 6149. (b) House, H. O.; Wilkins, J. M. J. Org.
Chem. 1976, 41, 4031. (c) Obayashi, M.; Utimoto, K.; Nozaki, H. Tetrahedron
Lett. 1977, 1807. (d) Newton, R. F.; Roberts, S. M. Tetrahedron 1980, 36, 2163.
(e) Roush, W. R.; Peseckis, S. M. J. Am. Chem. Soc. 1981, 103, 6696. (f) Marino,
J. P.; Linderman, R. J. J. Org. Chem. 1981, 46, 3696. (g) Fleming, I.; Perry,
D. A. Tetrahedron. 1981, 37, 4027. (h) Vellekoop, A. S.; Smith, R. A. J. J. Am.
Chem. Soc. 1994, 116, 2902, and references cited therein. (i) Nilsson, K.;
Andersson, T.; Ullenius, C.; Gerold, A.; Krause, N. Chem.-Eur. J. 1998, 4,
2051, and references cited therein. (j) Mori, S.; Nakamura, E.; Morokuma, K.
Organometallics 2004, 23, 1081.
(16) Henze, W.; Vyater, A.; Krause, N.; Gschwind, R. M. J. Am. Chem.
Soc. 2005, 127, 17335, and references cited therein.
(17) When the distance between an enolate and an alkoxycarbonyl moiety
is larger, however, cyclization takes place; a relevant example is found in: Olsson,
T.; Rahman, M. T.; Ullenius, C. Tetrahedron Lett. 1977, 75.
(18) An interesting analogy is published by Stirling and co-workers; see: (a)
Batty, J. W.; Howes, P. D.; Stirling, C. J. M. J. Chem. Soc., Perkin Trans. I
1973, 65. (b) Ellis, B. S.; Griffiths, G.; Howes, P. D.; Stirling, C. J. M.; Fishwick,
B. R. J. Chem. Soc., Perkin Trans. I 1977, 286.
(19) Hathaway, B. J. In ComprehensiVe Coordination Chemistry; Wilkinson,
G., Gillard, R. D., McCleverty, J. A., Eds.; Pergamon Press: Oxford, England,
1987; Vol. 5, chapter 53, pp 533-774.
(20) (a) Krauss, S. R.; Smith, S. G. J. Am. Chem. Soc. 1981, 103, 141. (b)
Corey, E. J.; Boaz, N. W. Tetrahedron Lett. 1985, 26, 6015. (c) Hallnemo, G.;
Olsson, T.; Ullenius, C. J. Organomet. Chem. 1984, 265, C22; 1985, 282, 133.
a M+denotes an unknown cationic species, formed from Li+, CuR3, and
one or several cuprate species.16
A conceivable reaction mechanism for furan formation is
outlined in Scheme 2. The initial step is attack of the electron-
deficient conjugated carbon-carbon triple bond in a 1,4-fashion
(conjugate addition) or a 1,2-fashion (carbocupration), two
reactions with solid literature precedence.15 In all the cases
studied, the carbon atom attacked by the alkyl group in the
copper reagent is directly attached to a sp3-hybridized carbon
atom. The bulkiness of this substituent varies quite a bit among
the ketoesters, so it was expected that the outcome of the
addition reaction would vary to a significant extent and be most
successful for the ketoesters with the sterically least demanding
group attached to C-ꢀ. Based on the furan yields, which reflect
how successful the first step is, this was indeed the case, albeit
3432 J. Org. Chem. Vol. 74, No. 9, 2009

Synthesis of Tri- and Tetra-Substituted Furans
SCHEME 4
SCHEME 5
an allenoate (8) which, along with the carboxyl group and the
acetal moiety, can act as a ligand to the copper species formed.
If such complexation takes place the distance between the
allenoate moiety and the carboxyl group is reduced enough to
make cyclization feasible. This line of reasoning is supported
by the outcome of reactions between similar ketoesters and other
Michael donors under copper-free conditions; conjugate addition
occurs but in no case was there any trace of furan whatsoever.21,22
But copper complexation is not the only reason; another factor
must be the steric bulk of R1 and R3 since furans with sterically
demanding substituents are formed in higher yields than furans
with small substituents. When the size of R1 and R3 increases,
the central carbon atom of the allenoate moiety will be pushed
closer to the carboxyl carbon atom which will favor enolate
attack and cyclization. This rationale is in keeping with what
happens when γ-acyloxybutynoates are exposed to triarylphos-
phines under copper-free conditions and form intermediates,
which undergo reductive condensation to give furans.23
addition took place and furnished the corresponding and
expected ꢀ-methylated R,ꢀ-unsaturated alkenone after standard
hydrolytic workup. In all the reactions carried out under these
conditions the yield was excellent as illustrated by the results
obtained when 5,5-diethoxy-4-oxo-1-phenylpent-2-ynyl acetate
(4m) was treated with lithium dimethylcuprate under standard
conditions at -78 °C; hydrolysis furnished a 1:1 mixture of
(E)- and (Z)-5,5-diethoxy-2-methyl-4-oxo-1-phenylpent-2-enyl
acetate (12E and 12Z, respectively) in 84% yield when aqueous
ammonium chloride was used and the 3-deuterated analogue
3-deuterio-5,5-diethoxy-2-methyl-4-oxo-1-phenylpent-2-enyl ac-
etate (13) when deuterium oxide was applied (Scheme 5).
A third consequence of the proposed reaction mechanism
is that if the alkynyl group in ketoester 4 comes from a
tertiary propargylic alcohol, no furan can be formed because
dehydration becomes impossible. In order to check out this
corollary 5,5,6,6-tetraethoxy-2-methylhex-3-yn-2-ol (14) was
prepared and converted to 5,5-diethoxy-1,1-dimethyl-4-
oxopent-2-ynyl acetate (16), which was treated with the
Gilman reagent under the same conditions that led to furan
formation (Scheme 6). Notably, one product only was
obtained, viz. 2,2-diethoxy-1-(2,5-dihydro-2-hydroxy-2,4,5,5-
tetramethylfuran-3-yl)ethanone (17), which is exactly the
compound expected from the mechanism in Scheme 2.
In summary, we have developed a new method for the
synthesis of tri- and tetra-substituted furans. Under the best
conditions (around -60 °C) the cyclization proceeds in 40-80%
yield. The highest yields were generally obtained with substrates
containing the more bulky substituents. The ease with which
our starting materials, acylated γ-hydroxy R,ꢀ-unsaturated
acetylenic ketones, can be prepared makes the method a good
On the basis of the mechanism depicted in Scheme 2 it is
posssible to draw at least three obvious conculsions that can be
tested experimentally. First, by replacing the acyloxy moiety
in 4 with a silyloxy group no cyclization should occur, and that
change was indeed observed. Thus, treatment of 5-{(tert-
butyl)diphenylsiloxy}-1,1-diethoxyundec-3-yn-2-one (10), pre-
pared from 1,1,2,2-tetraethoxyundec-3-yn-5-ol (2f) via (tert-
butyl)(4,4,5,5-tetraethoxy-1-hexyl-2-pentynoxy) diphenylsilane
(9) as shown in Scheme 4, with the Gilman reagent under
standard conditions gave two acyclic compounds as the only
products, viz. the (E) and the (Z) isomers of 5-{(t-butyl)diphe-
nylsiloxy}-1,1-diethoxy-4-methylundec-3-en-2-one (11).
Second, cyclization would also be prevented if allenoate 8
could be trapped before it attacks the acyloxy moiety. In order
to try to achieve this cuprate addition was carried out in the
presence of trimethylsilyl chloride (TMSCl), which is known
to be both compatible with and capable of trapping enolates
under the conditions prevailing when R,ꢀ-unsaturated ketones
are reacted with cuprate reagents.24 To our satisfaction it
appeared that the allenoate attack of the acyloxy group was
completely intercepted under these conditions; instead, conjugate
(21) (a) Jung, M. E. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press: Oxford, England, 1991;
Vol. 4, chapter 1.1, pp 1-67. (b) Gaunt, M. J.; Sneddon, H. F.; Hewitt, P. R.;
Orsini, P.; Hook, D. F.; Ley, S. V. Org. Biomol. Chem. 2003, 1, 15.
(22) Sydnes, L. K.; Valdersnes, S.; Sengee, M.; Apeland, I. M. To be
published.
(23) (a) Jung, C.-K.; Wang, J.-C.; Krische, M. J. J. Am. Chem. Soc. 2004,
126, 4118. (b) Guo, C.; Lu, X. J. Chem. Soc., Chem. Commun. 1993, 394. (c)
Kuroda, H.; Hanaki, E.; Kawakami, M. Tetrahedron Lett. 1999, 40, 3753.
(24) (a) Corey, E. J.; Boaz, N. W. Tetrahedron Lett. 1985, 26, 6019. (b)
Alexakis, A.; Berlan, J.; Besace, Y. Tetrahedron Lett. 1986, 27, 1047. (c)
Horiguchi, Y.; Matsuzawa, S.; Nakamura, E.; Kuwajima, I. Tetrahedron Lett.
1986, 27, 4025. (d) Nakamura, E.; Matsuzawa, S.; Horiguchi, Y.; Kuwajima, I.
Tetrahedron Lett. 1986, 27, 4029. (e) Johnson, C. R.; Marren, T. J. Tetrahedron
Lett. 1987, 28, 27.
J. Org. Chem. Vol. 74, No. 9, 2009 3433

Sydnes et al.
SCHEME 6
acetate, 80:20) and gave 2c (1.41 g, 78%) as a clear liquid. IR
(film) 3443 (s), 2976 (s), 2931 (s), 2897 (s), 2875 (s), 2240 (w),
1469 (m), 1458 (m), 1444 (m), 1388 (m), 1370 (m), 1329 (m),
1293 (w), 1245 (m), 1117 (s), 1077 (s), 919 (w), 878 (m), 805 (w),
1
759 (w), 702 (w) cm-1; H NMR (200 MHz, CDCl3) δ 4.38 (s,
1H), 4.28-4.24 (m, 1H), 3.79-3.70 (m, 8H), 2.03-1.85 (m, 1H),
1.78 (bs, 1H), 1.27-1.18 (m, 12H), 1.05-0.99 (m, 6H); 13C NMR
(50 MHz, CDCl3) δ 103.9, 98.6, 86.7, 80.1, 67.7, 64.5, 59.6, 34.3,
17.9, 17.4, 15.3, 15.2; MS (ESI) m/z 285 (100), 257 (50), 246 (20),
211 (10); HRMS Calcd for C14H25O4 [M+· - EtO·] 257.1753,
+
found 257.1732.
Synthesis of Propargylic Esters (3) from 2; General
Procedure. Carboxylic anhydride (3.0 mol equiv), triethylamine
(TEA) (2.0 mol equiv.), and 4-(N,N-dimethylamino)pyridine (DMAP)
(0.15 mol equiv) were added to a stirred solution of propargylic
alcohol 2 in CHCl3 (for volume see the description for the individual
esters below) and left stirring at room temperature until all the
starting material was consumed (TLC). The reaction mixture was
cooled to 0 °C and hydrolyzed with saturated aqueous NaHCO3
(equal the volume of CHCl3). The resulting mixture was stirred
for 15 min, the phases were separated, and the aqueous layer was
extracted with DCM (3 × the volume of the NaHCO3 solution).
The combined organic layers were dried over MgSO4 (anhd.) and
then concentrated under vacuum on a rotary evaporator to give a
crude product, which was purified by flash chromatography.
4,4,5,5-Tetraethoxypent-2-ynyl Acetate (3a). Acetic anhydride
(0.92 g, 9.0 mmol), TEA (0.61 g, 6.0 mmol), and DMAP (0.037 g,
0.30 mmol) were added to a solution of 2a (0.78 g, 3.0 mmol) in
CHCl3 (10 mL) and reacted for 15 min to give the title compound
(0.86 g, 95%) as a colorless liquid after isolation by flash
chromatography using hexanes-ethyl acetate (90:10). IR (film)
2980 (s), 2932 (s), 2894 (s), 2250 (w), 1750 (s), 1481 (w), 1443
(m), 1378 (s), 1333 (m), 1225 (s), 1184 (s), 1117 (s), 1078 (s),
alternative to other syntheses used to prepare the same sort of
compounds,forinstancebasedonconjugatedallenylketones.13a,d,25
The reaction is somewhat similar to the phosphine-mediated
synthesis of furans by reductive condensation of γ-acyloxy
butynoates,23 but a major difference is apparent: whereas the
phosphine-based method can only give di- and trisubstituted
furans, our method furnishes tri- and tetra-substituted furans.
Experimental Section
General. IR spectra were run on a Nicolet Impact 410 infrared
spectrophotometer or a Spectrum One FT-IR ATR spectrometer.
NMR spectra were recorded on a Bruker Spectrospin AC 200 F or
a Bruker Spectrospin DPX-400 MHz spectrometer. Chemical shifts
are reported in ppm downfield from TMS. TLC analyses of the
reaction mixtures were performed with Silica gel (60 F254) on
aluminum sheets with mixtures of hexanes (a commercial mixture
of isomeric hexanes) and ethyl acetate as the mobile phase. Flash
chromatography was carried out with Silica gel (230-400 mesh)
as the stationary phase and mixtures of ethyl acetate and hexanes
(a commercial mixture of isomeric hexanes) as the mobile phase.
The eluent composition is given in each case. Mass spectra were
obtained on a VG 7070 Micromass spectrometer, an Autospec
Ultima spectrometer, a three-sector instrument with EBE geometry
from Micromass, and a JEOL AccuTOF T100GC spectrometer.
The instruments were operated in the EI mode at 70 eV or the
DART/ESI+ mode.
Synthesis of Propargylic Alcohols (2) from TEB (1). 4,4,5,5-
Tetraethoxypent-2-yn-1-ol (2a), 5,5,6,6-tetraethoxyhex-3-yn-2-ol
(2b), 6,6,7,7-tetraethoxy-2,2-dimethylhept-4-yn-3-ol (2d), 4,4,5,5-
tetraethoxy-1-phenylpent-2-yn-1-ol (2e), and 1,1,2,2-tetraethoxy-
undec-3-yn-5-ol (2f) were synthesized as described in the literature4
whereas 6,6,7,7-tetraethoxy-2-methylhept-4-yn-3-ol (2c) was pre-
pared as follows.
An EtMgBr solution in Et2O (2.1 mL, 3.0 M, 6.3 mmol) was
added dropwise through a septum to a stirred solution of TEB (1.38
g, 6.0 mmol) in dry THF (9.0 mL) kept under nitrogen atmosphere
at room temperature. The resulting mixture was refluxed for 80
min before it was cooled to room temperature. Isobutyraldehyde
(0.45 g, 6.3 mmol) was then added dropwise and the resulting
solution was stirred and refluxed for 3 h. The reaction mixture was
cooled to room temperature, quenched with saturated aqueous
NH4Cl (15 mL), and extracted with DCM (3 × 20 mL). The
combined organic extracts were dried over MgSO4 (anhd.) and then
concentrated under vacuum on a rotary evaporator. The crude
product was purified by flash chromatography (hexanes-ethyl
1
1033 (s), 961 (m), 913 (w), 881 (w), 827 (w), 754 (w) cm-1; H
NMR (200 MHz, CDCl3) δ 4.76 (s, 2H), 4.39 (s, 1H), 3.84-3.62
(m, 8H), 2.08 (s, 3H), 1.23 (q, J ) 7.0 Hz, 12H); 13C NMR (50
MHz, CDCl3) δ 169.9, 103.6, 98.4, 81.1, 80.5, 64.7, 59.4, 52.1,
20.4, 15.0; MS (EI) m/z 257 (85), 229 (40), 212 (45), 200 (55),
199 (65), 187 (35), 172 (85), 170 (35), 169 (75), 155 (85), 143
(15), 142 (48), 141 (65), 140 (80), 129 (55), 126 (70), 125 (40),
124 (35), 114 (45), 112 (80), 111 (75), 104 (70), 97 (80), 85 (70),
84 (100), 83 (80), 76 (70); HRMS Calcd for C13H21O5 [M+·
-
+
EtO·] 257.1389, found 257.1384.
4,4,5,5-Tetraethoxypent-2-ynyl Isobutyrate (3b). Isobutyric
anhydride (2.46 g, 15.6 mmol), TEA (1.05 g, 10.4 mmol) and
DMAP (0.097 g, 0.8 mmol) were added to a solution of 2a in CHCl3
(10 mL) and reacted for 30 min to give the title compound (1.50
g, 87%) as a colorless liquid after isolation by flash chromatography
using hexanes-ethyl acetate (90:10). IR (film) 2976 (s), 2932 (s),
2891 (s), 2737 (w), 2628 (w), 2255 (w), 1929 (w), 1744 (s), 1471
(m), 1445 (m), 1389 (m), 1372 (m), 1339 (m), 1295 (w), 1245
(m), 1185 (s), 1144 (s), 1118 (s), 1079 (s), 1022 (s), 966 (m), 920
(w), 888 (m), 815 (w), 752 (m), 665 (w) cm-1; 1H NMR (200 MHz,
CDCl3) δ 4.76 (s, 2H), 4.38 (s, 1H), 3.84-3.62 (m, 8H), 2.58 (se,
J ) 7.0 Hz, 1H), 1.28-1.15 (m, 18H); 13C NMR (50 MHz, CDCl3)
δ 176.1, 103.7, 98.5, 81.0 (2C), 64.7, 59.6 (2CH2), 52.0 (2CH2),
33.6, 18.7 (2CH3), 15.2 (2CH3), 15.1 (2CH3); MS (ESI) m/z 285
+
(100), 257 (10), 239 (5), 211 (12); HRMS Calcd for C15H25O5
[M+· - EtO·] 285.1702, found 285.1724.
4,4,5,5-Tetraethoxypent-2-ynyl Benzoate (3c). Benzoic anhy-
dride (3.53 g, 15.6 mmol), TEA (1.05 g, 10.4 mmol) and DMAP
(0.097 g, 0.8 mmol) were added to a solution of 2a (1.36 g, 5.2
mmol) in CHCl3 (10 mL) and reacted for 15 min to give the title
compound (1.45 g, 76%) as a colorless liquid after isolation by
flash chromatography using hexanes-ethyl acetate (95:5). IR (film)
3063 (w), 3034 (w), 2976 (s), 2929 (s), 2898 (s), 2874 (s), 2737
(w), 2250 (w), 1970 (w), 1913 (w), 1729 (s), 1601 (m), 1585 (w),
1452 (m), 1371 (m), 1315 (m), 1268 (s), 1177 (s), 1113 (s), 1097
(s), 1079 (s), 1027 (s), 947 (m), 877 (w), 805 (w), 751 (w), 713
(25) (a) Sromek, A. W.; Kel’in, A. V.; Gevorgyan, V. Angew. Chem., Int.
Ed. 2004, 43, 2280. (b) Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem.
Soc. 2005, 127, 10500. (c) Schwier, T.; Sromek, A. W.; Yap, D. M. L.; Chernyak,
D.; Gevorgyan, V. J. Am. Chem. Soc. 2007, 129, 9868. (d) Dudnik, A. S.; Sromek,
A. W.; Rubina, M.; Kim, J. T.; Kel’in, A. V.; Gevorgyan, V. J. Am. Chem. Soc.
2008, 130, 1440, and references cited therein.
3434 J. Org. Chem. Vol. 74, No. 9, 2009

Synthesis of Tri- and Tetra-Substituted Furans
(s), 687 (m), 665 (m) cm-1 1H NMR (200 MHz, CDCl3) δ
;
1H NMR (200 MHz, CDCl3) δ 5.33 (d, J ) 5.4 Hz, 1H), 4.39 (s,
1H), 3.79-3.67 (m, 8H), 2.30-2.15 (m, 1H), 2.07 (s, 3H),
1.26-1.17 (m, 12H), 1.02 (t, J ) 6.2 Hz 6H); 13C NMR (50 MHz,
CDCl3) δ 169.7, 103.8, 98.5, 83.0, 80.7, 68.7, 64.3 (2CH2), 59.8
(2CH2), 32,3, 20.8, 18.0, 17.3, 15.2 (2CH3), 15.1 (2CH3); MS (EI)
m/z 299 (6), 257 (12), 241 (28), 182 (19), 167 (17), 153 (23), 139
(14), 125 (19), 103 (48), 75 (51); HRMS Calcd for C16H27O5+ [M+·
- EtO·] 299.1858, found 299.1852.
8.07-8.03 (d, 2H), 7.62-7.41 (m, 3H), 5.01 (s, 2H), 4.40 (s, 1H),
3.88-3.63 (m, 8H), 1.28-1.18 (m, 12H); 13C NMR (50 MHz,
CDCl3) δ 165.6, 133.1, 129.7, 129.5 (2C), 128.3 (2C), 103.7, 98.5,
81.5, 80.7, 64.8 (2CH2), 59.6 (2CH2), 52.7, 15.2 (2CH3), 15.1
(2CH3); MS (ESI) m/z 319 (100), 291 (10), 273 (5), 245 (10);
HRMS Calcd for C18H23O5 [M+· - EtO·] 319.1545, found
+
319.1558.
4,4,5,5-Tetraethoxy-1-methylpent-2-ynyl Acetate (3d). Acetic
anhydride (0.92 g, 9.0 mmol), TEA (0.61 g, 6.0 mmol) and DMAP
(0.037 g, 0.3 mmol) were added to a solution of 2b (0.82 g, 3.0
mmol) in CHCl3 (10 mL) and reacted for 45 min to give the title
compound (0.91 g, 96%) as a colorless liquid after isolation by
flash chromatography using hexanes-ethyl acetate (90:10). IR (film)
2977 (s), 2933 (s), 2892 (s), 1746 (s), 1281 (w), 1445 (m), 1389
(s), 1372 (s), 1338 (m), 1306 (w), 1232 (s), 1184 (s), 1117 (s),
4,4,5,5-Tetraethoxy-1-isopropylpent-2-ynyl Isobutyrate (3h).
Isobutyric anhydride (2.37 g, 15.0 mmol), TEA (1.01 g, 10.0 mmol)
and DMAP (0.10 g, 0.8 mmol) were added to a solution of 2c (1.51
g, 5.0 mmol) in CHCl3 (15 mL) was added and reacted for 30 min
to give the title compound (1.56 g, 84%) as a colorless liquid after
isolation by flash chromatography using hexanes-ethyl acetate (90:
10). IR (film) 2975 (s), 2933 (s), 2898 (s), 2878 (s), 2737 (w),
2255 (w), 1743 (s), 1470 (m), 1455 (m), 1388 (m), 1370 (m), 1349
(m), 1331 (m), 1246 (m), 1188 (s), 1080 (s), 1020 (m), 986 (m),
1
1081 (s), 1022 (s), 959 (m), 918 (w), 875 (w), 730 (w) cm-1; H
1
914 (w), 873 (w), 811 (w), 754 (w) cm-1; H NMR (200 MHz,
NMR (200 MHz, CDCl3) δ 5.53 (q, J ) 6.7 Hz, 1H), 4.39 (s, 1H),
3.88-3.65 (m, 8H), 2.04 (s, 1H), 1.51 (d, J ) 6.7 Hz, 3H),
1.32-1.18 (m, 12H); 13C NMR (50 MHz, CDCl3) δ 169.2, 103.5,
98.1, 84.8, 79.3, 64.3, 59.8, 59.3, 20.8, 20.6, 15.0, 14.9; MS (EI)
m/z 316 (2), 273 (50), 272 (40), 257 (45), 243 (50), 228 (20), 226
(25), 214 (90), 201 (90), 184 (55), 171 (60), 155 (60), 139 (80),
CDCl3) δ 5.29 (d, J ) 6.9 Hz, 1H), 4.38 (s, 1H), 3.86-3.60 (m,
8H), 2.57 (septet, J ) 7.0 Hz, 1H), 2.11-1.95 (m, 1H), 1.32-1.15
(m, 18H), 1.05-1.00 (m, 6H); 13C NMR (50 MHz, CDCl3) δ 175.7,
103.9, 98.5, 83.5, 80.5, 68.4, 64.2 (2CH2), 59.9 (2CH2), 33.9, 32.4,
18.8, 18.7, 18.0, 17.4, 15.3 (2CH3), 15.2 (2CH3); MS (ESI) m/z
327 (100), 316 (35), 299 (82), 257 (4), 229 (5); HRMS Calcd for
137 (80), 127 (60), 111 (100), 109 (55), 104 (50), 97 (50), 89 (30),
83 (70), 76 (65), 69 (50); HRMS Calcd for C16H28O6 [M+·
EtO·] 316.1886, found 316.1888.
-
C18H31O5 [M+· - EtO·] 327.2171, found 327.2159.
+
+
4,4,5,5-Tetraethoxy-1-isopropylpent-2-ynyl Benzoate (3i). Ben-
zoic anhydride (3.46 g, 15.3 mmol), TEA (1.03 g, 10.2 mmol) and
DMAP (0.10 g, 0.8 mmol) were added to a solution of 2c (1.54 g,
5.1 mmol) in CHCl3 (20 mL) and reacted for 45 min to give the
title compound (1.74 g, 84%) as a colorless liquid after isolation
by flash chromatography using hexanes-ethyl acetate (95:5). IR
(film) 3090 (w), 3063 (w), 3034 (w), 2975 (s), 2931 (s), 2898 (s),
2877 (s), 2736 (w), 2623 (w), 2250 (w), 1976 (w), 1919 (w), 1820
(w), 1727 (s), 1601 (m), 1585 (m), 1469 (m), 1452 (s), 1389 (s),
1370 (s), 1335 (s), 1315 (s), 1264 (s), 1176 (s), 1094 (s), 1026 (s),
978 (s), 959 (m), 937 (m), 916 (m), 877 (m), 804 (w), 760 (w),
4,4,5,5-Tetraethoxy-1-methylpent-2-ynyl Isobutyrate (3e). Isobu-
tyric anhydride (1.42 g, 9.0 mmol), TEA (0.61 g, 6.0 mmol) and
DMAP (0.037 g, 0.3 mmol) were added to a solution of 2b (0.82
g, 3.0 mmol) in CHCl3 (10 mL) and reacted for 30 min to give the
title compound (0.85 g, 82%) as a colorless liquid after isolation
by flash chromatography using hexanes-ethyl acetate (90:10). IR
(film) 2977 (s), 2933 (m), 2897 (m), 2250 (w), 1742 (s), 1470 (w),
1457 (w), 1446 (w), 1388 (m), 1372 (m), 1333 (m), 1249 (m), 1188
(m), 1148 (s), 1118 (s), 1081 (s), 1021 (m), 950 (m), 907 (w), 850
(w), 754 (w) cm-1; 1H NMR (200 MHz, CDCl3) δ 5.55 (q, J ) 6.0
Hz, 1H), 4.39 (s, 1H), 3.87-3.63 (m, 8H), 2.54 (septet, J ) 7.0
Hz, 1H), 1.50 (d, J ) 6.0 Hz, 3H), 1.29-1.15 (m, 18H); 13C NMR
(50 MHz, CDCl3) δ 175.6, 103.7, 98.3, 85.3, 79.3, 64.5, 64.4, 59.8,
1
713 (s), 687 (m), 673 (m) cm-1; H NMR (200 MHz, CDCl3) δ
8.08-8.04 (m, 2H), 7.62-7.41 (m, 3H), 5.58 (d, J ) 6.5 Hz, 1H),
4.40 (s, 1H), 3.93-3.63 (m, 8H), 2.24-2.14 (m, 1H), 1.27-1.09
(m, 18H); 13C NMR (50 MHz, CDCl3) δ 165.2, 132.9, 130.0, 129.6
(2CH), 128.2 (2CH), 103.8, 98.5, 83.1, 81.1, 69.2, 64.3 (2CH2),
59.9 (2CH2), 32.6, 18.1, 17.5, 15.3 (2CH3), 15.1 (2CH3); MS (ESI)
m/z 361 (100); HRMS Calcd for C21H29O5+ [M+· - EtO·] 361.2015,
found 361.1999.
59.6, 33.7, 20.9, 18.7, 18.6, 15.2, 15.1; MS (EI) m/z 299 (100),
273 (30), 201 (5), 103 (5); HRMS Calcd for C16H27O5 [M+·
-
+
EtO·] 299.18585, found 299.18608.
4,4,5,5-Tetraethoxy-1-methylpent-2-ynyl Benzoate (3f). Ben-
zoic anhydride (1.49 g, 6.6 mmol), TEA (0.44 g, 4.4 mmol) and
DMAP (0.04 g, 0.3 mmol) were added to a solution of 2b (0.60 g,
2.2 mmol) in CHCl3 (20 mL) and reacted for 45 min to give the
title compound (0.70 g, 85%) as a colorless liquid after isolation
by flash chromatography using hexanes-ethyl acetate (90:10). IR
(film) 3063 (w), 3035 (s), 2977 (s), 2931 (s), 2896 (s), 2250 (w),
1971 (w), 1913 (w), 1725 (s), 1602 (m), 1586 (m), 1481 (m), 1452
(m), 1390 (m), 1372 (m), 1338 (m), 1315 (s), 1267 (s), 1176 (s),
1109 (s), 1097 (s), 1079 (s), 1026 (s), 946 (m), 922 (w), 872 (w),
1-(t-Butyl)-4,4,5,5-tetraethoxypent-2-ynyl Acetate (3j). Acetic
anhydride (0.92 g, 9.0 mmol), TEA (0.61 g, 6.0 mmol) and DMAP
(0.037 g, 0.3 mmol) were added to a solution of 2d (0.95 g, 3.0
mmol) in CHCl3 (10 mL) and reacted for 45 min to give the title
compound (0.97 g, 90%) as a colorless liquid after isolation by
flash chromatography using hexanes-ethyl acetate (90:10). IR (film)
2975 (s), 2932 (m), 2899 (m), 2873 (m), 1746 (s), 1481 (w), 1444
(w), 1391 (m), 1370 (s), 1235 (s), 1182 (m), 1235 (s), 1182 (m),
1118 (s), 1081 (s), 1019 (s), 980 (m), 909 (w) cm-1; 1H NMR (200
MHz, CDCl3) δ 5.21 (s, 1H), 4.38 (s, 1H), 3.85-3.62 (m, 8H),
2.10 (s, 3H), 1.23 (t, J ) 7.1 Hz, 6H), 1.22 (t, J ) 7.1 Hz, 6H),
1.03 (s, 9H); 13C NMR (50 MHz, CDCl3) δ 170.1, 103.8, 83.2,
80.5, 71.4, 64.1, 59.8, 35.2, 25.3, 20.6, 15.2; MS (EI) m/z 358 (M+,
2), 313 (45), 272 (20), 271 (50), 256 (60), 255 (70), 225 (55), 200
(40), 197 (60), 196 (65), 182 (45), 181 (70), 168 (70), 153 (70),
127 (35), 125 (70), 111 (90), 103 (100), 95 (70), 93 (60), 83 (58),
1
853 (w), 806 (w), 714 (s), 688 (m), 665 (m) cm-1; H NMR (200
MHz, CDCl3) δ 8.07-8.03 (m, 2H), 7.61-7.40 (m, 3H), 5.80 (q,
J ) 6.7 Hz, 1H), 4.40 (s, 1H), 3.87-3.61 (m, 8H), 1.65 (d, J )
6.7 Hz, 3H), 1.26-1.17 (m, 12H); 13C NMR (50 MHz, CDCl3) δ
165.5, 133.0, 130.1, 129.6 (2C), 128.2 (2C), 103.7, 98.4, 85.1, 79.9,
64.6, 64.5, 60.8, 59.7, 59.6, 21.2, 15. (2CH3), 15.1 (2CH3); MS
(ESI) m/z 333 (100), 305 (7); HRMS Calcd for C19H25O5+ [M+·
-
EtO·] 333.1702, found 333.1706.
75 (98), 67 (60); HRMS Calcd for C17H29O5 [M+· - EtO·]
+
4,4,5,5-Tetraethoxy-1-isopropylpent-2-ynyl Acetate (3g). Ace-
tic anhydride (1.22 g, 12.0 mmol), TEA (0.81 g, 8.0 mmol) and
DMAP (0.07 g, 0.6 mmol) were added to a solution of 2c (1.21 g,
4.0 mmol) in CHCl3 (15 mL) and reacted for 30 min to give the
title compound (1.24 g, 90%) as a colorless liquid after isolation
by flash chromatography using hexanes-ethyl acetate (85:15). IR
(film) 2976 (s), 2931 (s), 2898 (s), 2877 (s), 2737 (w), 2250 (w),
1747 (s), 1444 (s), 1389 (s), 1371 (s), 1357 (s), 1331 (m), 1228
313.2015, found 313.2023.
1-(t-Butyl)-4,4,5,5-tetraethoxypent-2-ynyl Isobutyrate (3k).
Isobutyric anhydride (1.42 g, 9.0 mmol), TEA (0.61 g, 6.0 mmol)
and DMAP (0.037 g, 0.3 mmol) were added to a solution of 2d
(0.95 g, 3.0 mmol) in CHCl3 (10 mL) and reacted for 200 min to
give the title compound (0.93 g, 80%) as a colorless liquid after
isolation by flash chromatography using hexanes--ethyl acetate (90:
10). IR (film) 2976 (s), 2933 (m), 2900 (s), 2896 (s), 1743 (s),
(s), 1117 (s), 1078 (s), 1021 (s), 984 (s), 902 (m), 604 (m) cm-1
;
J. Org. Chem. Vol. 74, No. 9, 2009 3435

Sydnes et al.
1480 (m), 1471 (m), 1445 (m), 1388 (m), 1368 (m), 1329 (m),
1247 (m), 1186 (s), 1150 (s), 1118 (s), 1082 (s), 1020 (m), 977
chromatography using hexanes-ethyl acetate (95:5). IR (film) 3090
(m), 3065 (m), 3035 (m), 2976 (s), 2929 (s), 2896 (s), 2735 (w),
2255 (w), 1965 (w), 1913 (w), 1725 (s), 1601 (m), 1585 (m), 1495
(m), 1481 (m), 1453 (s), 1390 (m), 1371 (m), 1317 (s), 1259 (s),
1176 (s), 1093 (s), 1026 (s), 941 (m), 913 (m), 803 (m), 759 (m),
1
(m), 919 (w), 907 (w) cm-1; H NMR (200 MHz, CDCl3) δ 5.20
(s, 1H), 4.38 (s, 1H), 3.81-3.62 (m, 8H), 2.59 (septet, J ) 7.0 Hz,
1H), 1.27 (t, J ) 7.1 Hz, 6H), 1.24 (t, J ) 7.1 Hz, 6H), 1.03 (s,
9H); 13C NMR (50 MHz, CDCl3) δ 175.6, 103.9, 98.5, 83.6, 80.4,
71.2, 64.1, 60.0, 35.3, 34.0, 25.4, 18.9, 18.6, 15.3, 15.2; MS (ESI)
1
713 (s), 698 (s) cm-1; H NMR (200 MHz, CDCl3) δ 8.08-8.03
(m, 2H), 7.67-7.36 (m, 8H), 6.83 (s, 1H), 4.44 (s, 1H), 3.85-3.60
(m, 8H), 1.26-1.16 (m, 12H); 13C NMR (50 MHz, CDCl3) δ 165.1,
136.7, 133.1, 129.8 (2CH), 129.7, 128.8, 128.4 (2CH), 128.2 (2CH),
127.9 (2CH), 103.8, 98.6, 83.1, 82.7, 65.9, 64.3 (2CH2), 59.9
(2CH2), 15.3 (2CH3), 15.1 (2CH3); MS (ESI) m/z 395 (100); HRMS
Calcd for C24H27O5 [M+· - EtO·] 395.1858, found 395.1875.
4,4,5,5-Tetraethoxy-1-hexylpent-2-ynyl Acetate (3p). Acetic
anhydride (0.92 g, 9.0 mmol), TEA (0.61 g, 6.0 mmol) and DMAP
(0.037 g, 0.3 mmol) were added to a solution of 2f (1.03 g, 3.0
mmol) in CHCl3 (10 mL) and reacted for 15 min to give the title
compound (1.04 g, 90%) as a colorless liquid after isolation by
flash chromatography using hexanes-ethyl acetate (90:10). IR (film)
2977 (s), 2932 (m), 2895 (m), 1747 (s), 1481 (w), 1445 (w), 1389
(s), 1372 (s), 1337 (m), 1306 (w), 1233 (s), 1184 (m), 1117 (s),
m/z 386 (M+, 45), 341 (80), 103 (100); HRMS: calcd for C19H33O5
+
[M+· - EtO·] 341.2335, found 341.2341.
1-(t-Butyl)-4,4,5,5-tetraethoxypent-2-ynyl Benzoate (3l). Ben-
zoic anhydride (2.04 g, 9.0 mmol), TEA (0.61 g, 6.0 mmol), and
DMAP (0.037 g, 0.3 mmol) were added to a solution of 2d (0.95
g, 3.0 mmol) in CHCl3 (10 mL) and reacted for 5 h to give the
title compound (1.03 g, 82%) as a colorless liquid after isolation
by flash chromatography using hexanes-ethyl acetate (90:10). IR
(film) 3090 (w), 3063 (w), 3033 (w), 2975 (s), 2932 (s), 2898 (s),
2873 (s), 2250 (w), 1727 (s), 1601 (m), 1585 (w), 1480 (m), 1452
(s), 1395 (m), 1367 (s), 1337 (s), 1315 (s), 1267 (s), 1177 (s), 1106
(s), 1082 (s), 1026 (s), 964 (s), 937 (m), 914 (w), 878 (w), 805
(w), 767 (w), 713 (s), 687 (w), 671 (w) cm-1; 1H NMR (200 MHz,
CDCl3) δ 8.10-8.03 (m, 2H), 7.62-7.40 (m, 3H), 5.45 (s, 1H),
4.39 (s, 1H), 3.87-3.61 (m, 8H), 1.19 (t, J ) 7.0 Hz, 3H), 1.17 (t,
J ) 7.0 Hz, 3H), 1.13 (s, 9H); 13C NMR (50 MHz, CDCl3) δ 165.2,
132.9, 130.0, 129.6, 128.2, 103.9, 98.5, 83.3, 80.9, 72.1, 64.1, 60.0,
35.6, 25.6, 15.3, 15.1; MS (ESI) m/z 375 (100), 161 (25); HRMS
1
1080 (s), 1021 (s), 960 (m), 909 (w), 876 (w), 754 (w) cm-1; H
NMR (200 MHz, CDCl3) δ 5.43 (s, 1H), 4.36 (s, 1H), 3.83-3.58
(m, 8H), 2.04 (s, 3H), 1.81-1.15 (m, 22H), 0.86 (t, J ) 6.1 Hz,
1H); 13C NMR (50 MHz, CDCl3) δ 170.0, 103.7, 98.6, 84.4, 80.1,
64.5, 63.9, 59.7, 34.5, 31.6, 28.7, 24.9, 22.5, 21.0, 15.3, 15.1, 14.0;
MS (EI) m/z 341 (60), 327 (15), 300 (40), 299 (65), 284 (60), 283
(70), 269 (15), 252 (20), 253 (55), 241 (5), 229 (5), 225 (55), 214
(40), 197 (50), 196 (65), 182 (30), 179 (70), 167 (60), 153 (55),
149 (55), 139 (50), 125 (35), 125 (60), 107 (55), 103 (95), 97 (80),
95 (65), 93 (60), 83 (40), 81 (100), 75 (90); HRMS Calcd for
C19H33O5 [M+· - EtO·] 341.2328, found 341.2323.
Calcd for C22H31O5 [M+· - EtO·] 375.21715, found 375.21690.
+
4,4,5,5-Tetraethoxy-1-phenylpent-2-ynyl Acetate (3m). Acetic
anhydride (1.38 g, 13.5 mmol), TEA (0.91 g, 9.0 mmol) and DMAP
(0.09 g, 0.7 mmol) were added to a solution of 2e (1.50 g, 4.5
mmol) in CHCl3 (10 mL) and reacted for 30 min to give the title
compound (1.36 g, 81%) as a colorless liquid after isolation by
flash chromatography using hexanes-ethyl acetate (90:10). IR (film)
3090 (w), 3065 (m), 3035 (m), 2976 (s), 2930 (s), 2897 (s), 2245
(w), 1744 (s), 1600 (w), 1570 (w), 1496 (m), 1481 (m), 1456 (s),
1445 (m), 1370 (s), 1342 (m), 1274 (m), 1224 (s), 1178 (s), 1117
(s), 1078 (s), 1019 (s), 955 (s), 902 (m), 832 (w), 757 (m), 698 (s),
604 (m) cm-1; 1H NMR (200 MHz, CDCl3) δ 7.60-7.51 (m, 2H),
7.44-7.30 (m, 3H), 6.57 (s, 1H), 4.43 (s, 1H), 3.87-3.60 (m, 8H),
2.08 (s, 3H), 1.26-1.17 (m, 12H); 13C NMR (50 MHz, CDCl3) δ
170.6, 137.5, 129.6, 129.2 (2CH), 128.7 (2CH), 104.4, 99.1, 83.6,
82.8, 65.7, 64.8 (2CH2), 60.1 (2CH2), 21.0, 15.2 (2CH3), 15.1
(2CH3); MS (EI) m/z 333 (5), 291 (24), 275 (25), 217 (25), 216
(100), 187 (14), 160 (15), 143 (13), 131 (12), 115 (47), 103 (86),
75 (39); HRMS Calcd for C19H25O5 [M+· - EtO·] 333.1702, found
333.1717.
4,4,5,5-Tetraethoxy-1-hexylpent-2-ynyl Isobutyrate (3q). Isobu-
tyric anhydride (1.42 g, 9.0 mmol), TEA (0.61 g, 6.0 mmol) and
DMAP (0.037 g, 0.3 mmol) were added 2f (1.03 g, 3.0 mmol) in
CHCl3 (10 mL) and reacted for 45 min to give the title compound
(1.04 g, 84%) as a colorless liquid after isolation by flash
chromatography using hexanes-ethyl acetate (90:10). IR (film)
2976 (s), 2931 (s), 2897 (s), 2250 (w), 1742 (s), 1470 (m), 1459
(m), 1445 (m), 1388 (m), 1370 (m), 1333 (m), 1246 (m), 1187 (s),
1152 (s), 1118 (s), 1081 (s), 1021 (m), 970 (m), 910 (w) cm-1; 1H
NMR (200 MHz, CDCl3) δ 5.46 (t, J ) 6.5 Hz, 1H), 4.38 (s, 1H),
3.87-3.60 (m, 8H), 2.55 (septet, J ) 6.9 Hz, 1H), 1.48-1.10 (m,
22H), 0.90 (t, J ) 6.9 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ
175.7, 103.8, 98.4, 84.6, 79.9, 71.2, 64.3, 63.5, 59.8, 34.4, 33.8,
31.5, 28.6, 24.7, 22.3, 18.7, 18.6, 15.2, 15.1, 13.9; MS (ESI) m/z)
414 (M+, 5), 369 (60), 312 (10), 299 (20), 103 (100); HRMS: calcd
4,4,5,5-Tetraethoxy-1-phenylpent-2-ynyl Isobutyrate (3n). Isobu-
tyric anhydride (1.71 g, 10.8 mmol), TEA (0.73 g, 7.2 mmol) and
DMAP (0.07 g, 0.7 mmol) were added to a solution of 2e (1.20 g,
3.6 mmol) in CHCl3 (10 mL) and reacted for 30 min to give the
title compound (1.17 g, 80%) as a colorless liquid after isolation
by flash chromatography using hexanes-ethyl acetate (95:5). IR
(film) 3090 (w), 3065 (m), 3035 (m), 2976 (s), 2932 (s), 2896 (s),
2737 (w), 2623 (w), 2255 (w), 1955 (w), 1740 (s), 1603 (w), 1587
(w), 1496 (m), 1473 (m), 1456 (s), 1388 (s), 1370 (m), 1345 (m),
1295 (m), 1274 (m), 1242 (m), 1183 (s), 1143 (s), 1116 (s), 1081
(s), 1028 (s), 946 (m), 908 (m), 876 (m), 815 (w), 757 (m), 698
for C21H37O5 [M+· - EtO·] 369.2641, found 369.255.
+
4,4,5,5-Tetraethoxy-1-hexylpent-2-ynyl Benzoate (3r). Benzoic
anhydride (2.71 g, 12.0 mmol), TEA (0.81 g, 8.0 mmol) and DMAP
(0.07 g, 0.6 mmol) were added 2f (1.40 g, 4.0 mmol) in CHCl3
(20 mL) and reacted for 45 min to give the title compound (1.53
g, 85%) as a colorless liquid after isolation by flash chromatography
using hexanes-ethyl acetate (90:10). IR (film) 3062 (m), 2975 (s),
2956 (s), 2930 (s), 2871 (s), 2250 (w), 1971 (w), 1913 (w), 1725
(s), 1603 (m), 1586 (m), 1452 (s), 1395 (m), 1371 (m), 1342 (m),
1267 (s), 1176 (s), 1105 (s), 1070 (s), 1026 (s), 969 (m), 938 (m),
1
880 (m), 806 (w), 713 (s), 669 (m), 642 (m) cm-1; H NMR (200
1
(s), 675 (w) cm-1; H NMR (200 MHz, CDCl3) δ 7.57-7.51 (m,
MHz, CDCl3) δ 8.14-8.03 (m, 2H), 7.62-7.40 (m, 3H), 5.72 (t,
J ) 6.5 Hz, 1H), 4.40 (s, 1H), 3.86-3.63 (m, 8H), 1.99-1.87 (m,
2H), 1.30-1.17 (m, 20H), 0.88 (t, J ) 6.5 Hz, 3H); 13C NMR (50
MHz, CDCl3) δ 165.2, 132.9, 130.1, 129.6 (2CH), 128.2 (2CH),
103.8, 98.5, 84.4, 80.5, 64.5, 64.4 (2CH2), 59.8 (2CH2), 34.6, 31.5,
28.7, 24.8, 22.4, 15.2 (2CH3), 15.1 (2CH3), 13.9; MS (ESI) m/z
2H), 7.42-7.26 (m, 3H), 6.56 (s, 1H), 4.42 (s, 1H), 3.86-3.60
(m, 8H), 2.58 (septet, J ) 7.0 Hz, 1H), 1.28-1.10 (m, 18H); 13C
NMR (50 MHz, CDCl3) δ 175.5, 136.8, 128.6, 128.3 (2CH), 127.7
(2CH), 103.8, 98.6, 83.4, 82.2, 65.1, 64.3 (2CH2), 59.9 (2CH2),
33.8, 18.6 (2CH3), 15.2 (2CH3), 15.1 (2CH3); MS (ESI) m/z 361
(85), 333 (100), 319 (12), 291 (10), 263 (30), 216 (13); HRMS
403 (100), 375 (30); HRMS Calcd for C24H35O5 [M+· - EtO·]
+
Calcd for C21H29O5 [M+· - EtO·] 361.2015, found 361.2018.
+
403.2485, found 403.2490.
4,4,5,5-Tetraethoxy-1-phenylpent-2-ynyl Benzoate (3o). Ben-
zoic anhydride (3.80 g, 16.8 mmol), TEA (1.13 g, 11.2 mmol) and
DMAP (0.10 g, 0.8 mmol) were added to 2e (1.88 g, 5.6 mmol) in
CHCl3 (25 mL) and reacted for 45 min to give the title compound
(1.85 g, 75%) as a colorless liquid after isolation by flash
Synthesis of Propargylic Ketoesters 4 from Ketals 3; General
Procedure. Ester 3 was dissolved in a mixture of acetone and water
(2:1/v:v) containing some p-TsOH and refluxed for 3-8 h. The
reaction mixture was then cooled to room temperature before DCM
3436 J. Org. Chem. Vol. 74, No. 9, 2009

Synthesis of Tri- and Tetra-Substituted Furans
(volume equal to that of the reaction mixture) and H2O (volume
equal to that of the reaction mixture) were added. The phases were
separated and the aqueous layer was extracted with DCM (3 ×
volume of the aqueous layer). The organic phases were combined,
washed with an equal volume of a saturated aqueous NaHCO3
solution, and dried over MgSO4 (anhd.). Filtration and concentration
on a rotary evaporator in Vacuo gave ketoester 4, which, if not
pure enough for subsequent reactions, was purified by flash
chromatography.
5,5-Diethoxy1-1-methyl-4-oxopent-2-ynyl Isobutyrate (4e).
4,4,5,5-Tetraethoxy-1-methylpent-3-ynyl isobutyrate (3e) (0.69 g,
2.0 mmol) and p-TsOH (0.038 g, 0.2 mmol) in a mixture of acetone
and water (20 mL) were refluxed for 2 h and gave the title
compound (0.48 g, 88%) as a yellowish liquid. IR (film) 2979 (s),
2938 (m), 2880 (m), 2222 (m), 1742 (s), 1697 (s), 1471 (m), 1447
(m), 1388 (m), 1373 (m), 1331 (m), 1300 (m), 1244 (s), 1187 (s),
1151 (s), 1134 (s), 1106 (s), 1067 (s), 956 (w), 910 (w), 846 (w),
1
822 (w), 753 (w) cm-1; H NMR (200 MHz, CDCl3) δ 5.61 (q, J
5,5-Diethoxy-4-oxopent-2-ynyl Acetate (4a). 4,4,5,5-Tetra-
ethoxypent-2-ynyl acetate (3a) (0.60 g, 2.0 mmol) and p-TsOH
(0.038 g, 0.2 mmol) in a mixture of acetone and water (20 mL)
were refluxed for 2 h and gave the title compound (0.41 g, 90%)
as a colorless liquid. IR (film) 2980 (m), 2934 (m), 2888 (m), 2220
(m), 1754 (s), 1692 (s), 1560 (m), 1444 (m), 1376 (m), 1319 (w),
1221 (s), 1168 (m), 1117 (s), 1065 (s), 964 (w), 906 (w), 828 (w)
) 6.8 Hz, 1H), 4.75 (s, 1H), 3.73-3.59 (m, 4H), 2.57 (septet, J )
7.0 Hz, 1H), 1.56 (d, J ) 6.8 Hz, 3H), 1.26 (t, J ) 7.0 Hz, 6H),
1.18 (d, J ) 7.0 Hz, 6H); 13C NMR (50 MHz, CDCl3) δ 182.3,
175.4, 101.2, 93.1, 81.3, 62.9, 59.2, 33.6, 20.1, 18.7, 14.9; MS (EI)
m/z 270 (M+, 10), 225 (70), 199 (40), 183 (55), 167 (30), 155 (30),
103 (100); HRMS Calcd for C14H22O5 [M+] 270.14672, found
+
270.14659.
1
cm-1; H NMR (200 MHz, CDCl3) δ 4.89 (s, 2H), 4.74 (s, 1H),
5,5-Diethoxy1-1-methyl-4-oxopent-2-ynyl Benzoate (4f). 4,4,5,5-
Tetraethoxy-1-methylpent-3-ynyl benzoate (3f) (0.70 g, 1.8 mmol)
and p-TsOH (0.10 g, 0.5 mmol) in a mixture of acetone and water
(20 mL) were refluxed for 3 h and gave the title compound (0.51
g, 91%) as a yellowish liquid after purification by flash chroma-
tography (hexanes-ethyl acetate, 90:10). IR (film) 3064 (m), 3034
(m), 2979 (s), 2936 (s), 2896 (s), 2223 (s), 1970 (w), 1913 (w),
1727 (s), 1694 (s), 1602 (m), 1585 (m), 1492 (m), 1480 (m), 1452
(s), 1393 (m), 1337 (s), 1315 (s), 1304 (s), 1265 (s), 1176 (s), 1135
(s), 1106 (s), 1097 (s), 1070 (s), 1026 (s), 948 (m), 907 (m), 866
(m), 850 (m), 805 (m), 713 (s), 688 (m) cm-1; 1H NMR (200 MHz,
CDCl3) δ 8.09-8.03 (m, 2H), 7.63-7.42 (m, 3H), 5.86 (q, J )
6.8 Hz, 1H), 4.76 (s, 1H), 3.79-3.54 (m, 4H), 1.70 (d, J ) 6.8 Hz,
3H), 1.25 (t, J ) 7.0 Hz, 6H); 13C NMR (50 MHz, CDCl3) δ 182.4,
165.0, 133.3, 129.7 (2CH), 129.2, 128.3 (2CH), 101.2, 93.0, 81.7,
63.0 (2CH2), 60.1, 20.3, 14.9 (2CH3); MS (ESI) m/z 305 (100),
259 (84); HRMS Calcd for C17H21O5 [M + H]+ 305.1389, found
305.1390.
5,5-Diethoxy-1-isopropyl-4-oxopent-2-ynyl Acetate (4g). 4,4,5,5-
Tetraethoxy-1-isopropylpent-2-ynyl acetate (3g) (1.17 g, 3.4 mmol)
and p-TsOH (0.15 g, 0.8 mmol) in a mixture of acetone and water
(25 mL) were refluxed for 3 h and gave the title compound (0.87
g, 95%) as a yellowish liquid after purification by flash chroma-
tography (hexanes-ethyl acetate, 90:10). IR (film) 2976 (s), 2933
(s), 2879 (s), 2217 (m), 1747 (s), 1694 (s), 1618 (w), 1467 (m),
1447 (m), 1373 (s), 1326 (m), 1228 (s), 1112 (s), 1070 (s), 1025
(s), 991 (m), 903 (m), 720 (m), 602 (m) cm-1; 1H NMR (200 MHz,
CDCl3) δ 5.37 (d, J ) 5.8 Hz, 1H), 4.75 (s, 1H), 3.76-3.55 (m,
4H), 2.16-2.02 (m, 1H), 2.11 (s, 3H), 1.26 (t, J ) 7.0 Hz, 6H),
1.08-0.97 (m, 6H); 13C NMR (50 MHz, CDCl3) δ 188.4, 169.5,
101.3, 91.7, 82.8, 68.2, 62.9 (2CH2), 32.2, 20.6, 18.0, 17.4, 15.0
(2CH3); MS (EI) m/z 225 (3), 183 (13), 182 (17), 167 (10), 141
(9), 140 (90), 139 (25), 137 (20), 125 (12), 112 (20), 107 (31), 104
(64), 103 (75), 47 (85), 43 (100); HRMS Calcd for C12H17O4+ [M+·
- EtO·] 225.1127, found 225.1120.
3.81-3.56 (m, 4H), 2.12 (s, 3H), 1.25 (t, J ) 7.0 Hz, 6H); 13C
NMR (50 MHz, CDCl3) δ 181.9, 169.5, 101.2, 88.9, 83.0, 63.0,
51.2, 20.2, 15.0, 14.8; MS (EI) m/z 183 (24), 156 (5), 155 (18),
141 (25), 140 (18), 125 (20), 113 (52), 104 (50), 103 (90), 83 (15),
+
76 (20), 75 (100), 67 (58), 66 (80); HRMS Calcd for C9H11O4
[M+· - EtO·] 183.0657, found 183.0660.
5,5-Diethoxy-4-oxopent-2-ynyl Isobutyrate (4b). 4,4,5,5-Tet-
raethoxypent-2-ynyl isobutyrate (3b) (1.04 g, 3.1 mmol) and
p-TsOH (0.15 g, 0.8 mmol) in a mixture of acetone and water (25
mL) were refluxed for 3 h and gave the title compound (0.99 g,
95%) as a yellowish liquid after purification by flash chromatog-
raphy (hexanes-ethyl acetate, 90:10). IR (film) 2979 (s), 2937 (s),
2881 (s), 2220 (m), 1747 (s), 1697 (s), 1621 (w), 1471 (s), 1446
(m), 1428 (m), 1389 (s), 1372 (m), 1339 (s), 1246 (s), 1186 (s),
1145 (s), 1119 (s), 1069 (s), 969 (m), 909 (m), 837 (w), 815 (m),
1
754 (m) cm-1; H NMR (200 MHz, CDCl3) δ 4.87 (s, 2H), 4.74
(s, 1H), 3.77-3.56 (m, 4H), 2.62 (se, J ) 7.0 Hz, 1H), 1.31-1.18
(m, 12H); 13C NMR (50 MHz, CDCl3) δ 182.1, 175.8, 101.3, 89.3,
83.1, 63.1 (2CH2), 51.3, 33.6, 18.7 (2CH3), 15.0 (2CH3); MS (ESI)
m/z 256 (M+·, 6), 211 (100); HRMS Calcd for C11H15O4+ [M+·
-
EtO·] 211.0970, found 211.0954.
5,5-Diethoxy-4-oxopent-2-ynyl Benzoate (4c). 4,4,5,5-Tetra-
ethoxypent-2-ynyl benzoate (3c) (1.35 g, 3.7 mmol) and p-TsOH
(0.17 g, 0.9 mmol) in a mixture of acetone and water (25 mL)
were refluxed for 4 h and gave the title compound (0.97 g, 90%)
as a yellowish liquid after purification by flash chromatography
(hexanes-ethyl acetate, 95:5). IR (film) 3074 (w), 2979 (s), 2954
(m), 2904 (m), 2897 (m), 2221 (m), 1730 (s), 1693 (s), 1601 (m),
1452 (s), 1425 (m), 1370 (s), 1316 (s), 1267 (s), 1177 (s), 1107
(s), 1096 (s), 1070 (s), 1027 (s), 956 (w), 902 (w), 806 (w), 712
1
(s), 687 (m) cm-1; H NMR (200 MHz, CDCl3) δ 8.10-8.04 (m,
2H), 7.64-7.42 (m, 3H), 5.12 (s, 2H), 4.76 (s, 1H), 3.78-3.59
(m, 4H), 1.31-1.22 (t, J ) 7.0 Hz, 6H); 13C NMR (50 MHz,
CDCl3) δ 182.1, 165.4, 133.5, 130.1, 129.8 (2CH), 128.4 (2CH),
101.4, 89.1, 83.5, 63.2 (2CH2), 52.0, 15.0 (2CH3); MS (ESI) m/z
291 (28), 245 (100); HRMS Calcd for C16H19O5 [M + H]+
+
5,5-Diethoxy-1-isopropyl-4-oxopent-2-ynyl Isobutyrate (4h).
4,4,5,5-Tetraethoxy-1-isopropylpent-2-ynyl isobutyrate (3h) (1.46
g, 3.9 mmol) and p-TsOH (0.19 g, 1.0 mmol) in a mixture of
acetone and water (25 mL) were refluxed for 3 h and gave the title
compound (1.07 g, 92%) as a yellowish liquid after purification by
flash chromatography (hexanes-ethyl acetate, 90:10). IR (film)
2976 (s), 2935 (s), 2899 (s), 2878 (s), 2218 (s), 1744 (s), 1693 (s),
1618 (w), 1470 (s), 1389 (s), 1371 (s), 1350 (m), 1322 (m), 1297
(m), 1244 (s), 1186 (s), 1151 (s), 1112 (s), 1066 (s), 993 (s), 962
(m), 930 (m), 911 (m), 839 (w), 800 (w), 752 (m) cm-1; 1H NMR
(200 MHz, CDCl3) δ 5.38 (d, J ) 5.8 Hz, 1H), 4.75 (s, 1H),
3.79-3.55 (m, 4H), 2.60 (septet, J ) 6.6 Hz, 1H), 2.19-1.95 (m,
1H), 1.35-1.18 (m, 12H), 1.08-1.03 (m, 6H); 13C NMR (50 MHz,
CDCl3) δ 182.4, 175.5, 101.2, 91.9, 82.6, 67.9, 62.8 (2CH2), 33.8,
32.3, 18.8, 18.6, 18.0, 17.5, 15.0 (2CH3); MS (ESI) m/z 299 (93),
283 (20), 271 (25), 253 (100), 225 (10), 211 (5), 183 (5); HRMS
291.1232, found 291.1241.
5,5-Diethoxyl-1-methyl-4-oxopent-2-ynyl Acetate (4d). 4,4,5,5-
Tetraethoxy-1-methylpent-3-ynyl acetate (3d) (0.63 g, 2.0 mmol)
and p-TsOH (0.038 g, 0.2 mmol) in a mixture of acetone and water
(20 mL) were refluxed for 2 h and gave the title compound (0.44
g, 91%) as a colorless liquid. IR (film) 2980 (s), 2937 (m), 2898
(m), 2222 (m), 1758 (s), 1693 (s), 1619 (m), 1447 (m), 1372 (s),
1336 (m), 1300 (m), 1229 (s), 1194 (s), 1167 (s), 1135 (s), 1106
(s), 1071 (s), 1042 (s), 962 (m), 906 (m), 828 (w), 757 (m) cm-1
;
1H NMR (200 MHz, CDCl3) δ 5.59 (q, J ) 6.9 Hz, 1H), 4.75 (s,
1H), 3.77-3.55 (m, 4H), 2.11 (s, 3H), 1.57 (d, J ) 6.9 Hz, 3H),
1.30-1.24 (m, 6H); 13C NMR (50 MHz, CDCl3) δ 182.2, 169.3,
101.2, 92.8, 81.4, 62.9, 59.4, 20.6, 20.1, 14.9; MS (EI) m/z 242
(M+, 5), 197 (50), 183 (10), 171 (60), 155 (100), 139 (75), 127
(90), 75 (50); HRMS Calcd for C12H18O5 [M+] 242.1154, found
+
Calcd for C16H27O5 [M + H]+ 299.1858, found 299.1856.
+
242.1151.
J. Org. Chem. Vol. 74, No. 9, 2009 3437

Sydnes et al.
5,5-Diethoxy-1-isopropyl-4-oxopent-2-ynyl Benzoate (4i). 4,4,5,5-
Tetraethoxy-1-isopropylpent-2-ynyl benzoate (3i) (1.70 g, 4.2
mmol) and p-TsOH (0.19 g, 1.0 mmol) in a mixture of acetone
and water (25 mL) were refluxed for 5 h and gave the title
compound (1.28 g, 92%) as a yellowish liquid after purification by
flash chromatography (hexanes-ethyl acetate, 95:5). IR (film) 3062
(w), 2976 (s), 2932 (s), 2898 (m), 2878 (s), 2217 (m), 1727 (s),
1693 (s), 1602 (m), 1586 (w), 1452 (s), 1371 (m), 1333 (m), 1315
(s), 1274 (s), 1261 (s), 1177 (s), 1163 (s), 1106 (s), 1095 (s), 1069
(s), 1026 (s), 984 (s), 911 (w), 843 (w), 806 (w), 712 (s) cm-1; 1H
NMR (200 MHz, CDCl3) δ 8.10-8.05 (m, 2H), 7.64-7.42 (m,
3H), 5.63 (d, J ) 5.7 Hz, 1H), 4.76 (s, 1H), 3.79-3.54 (m, 4H),
2.34-2.18 (m, 1H), 1.28-1.02 (m, 12H); 13C NMR (50 MHz,
CDCl3) δ 182.4, 165.1, 133.3, 129.7 (2CH), 129.3, 128.4 (2CH),
101.2, 91.7, 83.0, 68.7, 62.9 (2CH2), 32.5, 18.1, 17.6, 15.0 (2CH3);
MS (ESI) m/z 333 (100), 305 (12), 287 (65), 259 (50); HRMS Calcd
(20 mL) were refluxed for 3 h and gave the title compound (0.83
g, 94%) as a yellowish liquid after purification by flash chroma-
tography (hexanes-ethyl acetate, 90:10). IR (film) 3064 (w), 2979
(s), 2933 (s), 2890 (s), 2219 (s), 1961 (w), 1898 (w), 1746 (s),
1694 (s), 1601 (m), 1492 (m), 1372 (s), 1319 (m), 1222 (s), 1113
(s), 1071 (s), 1023 (s), 962 (m), 906 (m), 835 (m), 757 (m), 700
(m), 648 (w), 603 (w) cm-1 1H NMR (200 MHz, CDCl3) δ
;
7.56-7.36 (m, 5H), 6.62 (s, 1H), 4.77 (s, 1H), 3.80-3.54 (m, 4H),
2.13 (s, 3H), 1.26 (t, J ) 7.0 Hz, 6H); 13C NMR (50 MHz, CDCl3)
δ 182.2, 169.2, 134.8, 129.2, 128.6 (2CH), 127.6 (2CH), 101.1,
90.7, 83.2, 64.7, 62.9 (2CH2), 20.6, 14.8 (2CH3); MS (EI) m/z 304
(M+, 1), 291 (24), 275 (25), 217 (25), 216 (100), 187 (14), 160
(15), 143 (13), 131 (12), 115 (47), 103 (86), 75 (39); HRMS Calcd
for C17H20O5 [M+] 304.1311, found 304.1291.
+
5,5-Diethoxy-4-oxo-1-phenylpent-2-ynylIsobutyrate(4n).4,4,5,5-
Tetraethoxy-1-phenylpent-2-ynyl isobutyrate (3n) (1.15 g, 2.8
mmol) and p-TsOH (0.13 g, 0.7 mmol) in a mixture of acetone
and water (20 mL) were refluxed for 3 h and gave the title
compound (0.92 g, 98%) as a yellowish liquid. IR (film) 3066 (w),
3035 (w), 2978 (s), 2934 (s), 2879 (s), 2220 (m), 1744 (s), 1695
(s), 1603 (w), 1496 (m), 1470 (m), 1456 (s), 1388 (m), 1370 (m),
1352 (m), 1272 (m), 1240 (s), 1184 (s), 1142 (s), 1112 (s), 1066
(s), 953 (m), 909 (m), 877 (w), 842 (w), 811 (w), 758 (m), 698 (s),
665 (m) cm-1; 1H NMR (200 MHz, CDCl3) δ 7.54-7.26 (m, 5H),
6.62 (s, 1H), 4.77 (s, 1H), 3.79-3.55 (m, 4H), 2.62 (septet, J )
7.0 Hz, 1H), 1.30-1.13 (m, 12H); 13C NMR (50 MHz, CDCl3) δ
182.3, 175.3, 135.2, 129.2, 128.7 (2CH), 127.4 (2CH), 101.2, 91.1,
83.3, 64.6, 62.9 (2CH2), 33.7, 18.6 (2CH3), 14.9 (2CH3); MS (ESI)
m/z 333 (100), 305 (20), 287 (12), 263 (15), 245 (40), 217 (9);
HRMS Calcd for C19H25O5+ [M + H]+ 333.1702, found 333.1709.
5,5-Diethoxy-1-phenyl-4-oxopent-2-ynyl Benzoate (4o). 4,4,5,5-
Tetraethoxy-1-phenylpent-2-ynyl benzoate (3o) (1.60 g, 3.6 mmol)
and p-TsOH (0.15 g, 0.8 mmol) in a mixture of acetone and water
(25 mL) were refluxed for 3 h and gave the title compound (1.23
g, 95%) as a yellowish liquid after purification by flash chroma-
tography (hexanes-ethyl acetate, 95:5). IR (film) 3063 (m), 3033
(m), 2980 (s), 2932 (s), 2897 (s), 2220 (s), 1727 (s), 1693 (s), 1601
(m), 1585 (m), 1495 (m), 1452 (s), 1392 (m), 1316 (s), 1250 (s),
1176 (s), 1091 (s), 1068 (s), 916 (m), 838 (w), 803 (w), 760 (m),
for C19H25O5 [M + H]+ 333.1702, found 333.1689.
+
1-(t-Butyl)-5,5-diethoxy-4-oxopent-2-ynyl Acetate (4j). 1-(t-
Butyl)-4,4,5,5-tetraethoxypent-2-ynyl acetate (3j) (0.72 g, 2.0 mmol)
and p-TsOH (0.038 g, 0.2 mmol) in a mixture of acetone and water
(20 mL) were refluxed for 5 h and gave the title compound (0.51
g, 89%) as a yellowish liquid. IR (film) 2976 (s), 2935 (m), 2904
(m), 2875 (m), 2216 (m), 1746 (s), 1694 (s), 1481 (w), 1445 (w),
1445 (w), 1398 (w), 1371 (s), 1332 (w), 1233 (s), 1223 (s), 1166
(m), 1118 (s), 1067 (s), 1020 (s), 985 (m), 910 (w), 840 (w) cm-1
;
1H NMR (200 MHz, CDCl3) δ 5.28 (s, 1H), 4.75 (s, 1H), 3.76-3.38
(m, 4H), 2.12 (s, 3H), 1.25 (t, J ) 7.1 Hz, 6H), 1.05 (s, 9H); 13C
NMR (50 MHz, CDCl3) δ 182.4, 169.7, 101.2, 92.0, 82.6, 71.0,
62.7, 35.4, 25.4, 20.5, 14.9; MS (EI) m/z 239 (10), 228 (15), 223
(20), 211 (20), 197 (30), 182 (60), 168 (50), 153 (60), 140 (80),
139 (60), 125 (55), 121 (55), 112 (75), 111 (100), 103 (95), 95
(60), 89 (50), 83 (75), 75 (90), 67 (60); HRMS Calcd for C13H19O4
[M+· - EtO·] 239.1283 found, 239.1283.
1-(t-Butyl)-5,5-diethoxy-4-oxopent-2-ynyl Isobutyrate (4k).
1-(t-Butyl)-4,4,5,5-tetraethoxypent-2-ynyl isobutyrate (3k) (0.77 g,
2.0 mmol) and p-TsOH (0.038 g, 0.2 mmol) in a mixture of acetone
and water (20 mL) were refluxed for 6 h and gave the title
compound (0.55 g, 88%) as a yellowish liquid. IR (film) 2976 (m),
2936 (m), 2877 (m), 2216 (m), 1743 (s), 1694 (s), 1480 (m), 1470
(m), 1448 (m), 1418 (w), 1397 (w), 1369 (m), 1327 (m), 1241 (m),
1185 (s) 1147 (s), 1116 (s), 1065 (s), 983 (m), 937 (w), 919 (m),
1
712 (s), 698 (s), 665 (m) cm-1; H NMR (200 MHz, CDCl3) δ
8.10-8.05 (m, 2H), 7.64-7.26 (m, 8H), 6.87 (s, 1H), 4.78 (s, 1H),
3.75-3.58 (m, 4H), 1.27-1.17 (m, 6H); 13C NMR (50 MHz,
CDCl3) δ 182.3, 164.9, 135.1, 133.4, 129.8 (2CH), 129.3, 129.0,
128.8 (2CH), 128.4 (2CH), 127.7 (2CH), 101.3, 90.9, 83.6, 65.4,
63.0 (2CH2), 14.9 (2CH3); MS (ESI) m/z 367 (100), 321 (8), 245
1
838 (w), 752 (w) cm-1; H NMR (200 MHz, CDCl3) δ 5.28 (s,
1H), 4.74 (s, 1H), 3.70-3.58 (m, 4H), 2.62 (septet, J ) 6.9 Hz,
1H), 1.23 (d, J ) 6.9 Hz, 6H), 1.21 (t, J ) 7.0 Hz, 3H), 1.19 (t, J
) 7.0 Hz, 3H), 1.06 (s, 9H); 13C NMR (50 MHz, CDCl3) δ 182.5,
175.5, 101.2, 92.2, 82.6, 70.7, 62.7, 35.6, 33.9, 25.5, 18.9, 18.6,
15.0; MS (ESI) m/z 312 (M+, 90), 267 (75), 209 (25), 179 (15);
(25); HRMS Calcd for C22H23O5 [M + H]+ 367.1545, found
+
367.1556.
HRMS Calcd for C15H23O4 [M+· - EtO·] 267.15963, found
+
5,5-Diethoxy-1-hexyl-4-oxopent-2-ynyl acetate (4p). 4,4,5,5-
Tetraethoxy-1-hexylpent-2-ynyl acetate (3p) (0.77 g, 2.0 mmol) and
p-TsOH (0.038 g, 0.2 mmol) in a mixture of acetone and water
(20 mL) was refluxed for 3 h and gave the title compound (0.57 g,
92%) as a yellowish liquid. IR (film) 2975 (m), 2938 (m), 2907
(m), 2875 (m), 2217 (m), 1746 (s), 1698 (s), 1481 (m), 1466 (w),
1446 (w), 1398 (w), 1372 (s), 1332 (m), 1299 (m), 1234 (s), 1117
(s), 1067 (s), 1022 (s), 986 (m), 910 (w), 837 (w) cm-1; 1H NMR
(200 MHz, CDCl3) δ 5.50 (t, J ) 6.9 Hz, 1H), 4.73 (s, 1H),
3.78-3.54 (m, 4H), 2.08 (s, 3H), 1.88-1.21 (m, 22H), 0.88 (t, J
) 6.6 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ 182.4, 170.5, 102.2,
93.7, 89.8, 64.3, 64.0, 34.7, 32.4, 29.5, 25.6, 23.3, 21.6, 15.8, 14.8;
MS (EI) m/z 267 (5), 253 (10), 225 (25), 209 (25), 197 (15), 179
(20), 149 (30), 135 (20), 125 (30), 122 (40), 112 (30), 103 (100),
95 (40), 93 (40), 81 (75), 75 (95), 67 (60), 61 (40), 55 (70); HRMS
Calcd for C15H23O4 [M+· - EtO·] 267.1596, found 267.1592.
5,5-Diethoxy-1-hexyl-4-oxopent-2-ynyl Isobutyrate (4q). 4,4,5,5-
Tetraethoxy-1-hexyl-pent-2-ynyl isobutyrate (3q) (0.83 g, 2.0 mmol)
and p-TsOH (0.038 g, 0.2 mmol) in a mixture of acetone and water
(20 mL) were refluxed for 6 h and gave the title compound (0.61
g, 90%) as a yellowish liquid. IR (film) 2977 (s), 2957 (s), 2932
(m), 2874 (m), 2862 (m), 2218 (m), 1744 (s), 1696 (s), 1469 (m),
267.16214.
1-(t-Butyl)-5,5-diethoxy-4-oxopent-2-ynyl Benzoate (4l). 1-(t-
Butyl)-4,4,5,5-tetraethoxypent-2-ynyl benzoate (3l) (0.84 g, 2.0
mmol) and p-TsOH (0.038 g, 0.2 mmol) in a mixture of acetone
and water (20 mL) was refluxed for 8 h and gave the title compound
(0.59 g, 85%) as a yellowish liquid. IR (film) 3066 (w), 3034 (w),
2975 (s), 2934 (m), 2875 (m), 2899 (m), 2217 (m), 1727 (s), 1694
(s), 1601 (w), 1585 (w), 1480 (w), 1452 (m), 1397 (m), 1369 (m),
1335 (m), 1315 (m), 1303 (m), 1264 (s), 1176 (m), 1097 (s), 1069
(s), 1026 (m), 970 (m), 937 (w), 907 (w), 838 (w), 767 (w), 713
(s), 687 (w), 672 (w) cm-1; 1H NMR (200 MHz, CDCl3) δ 8.09 (t,
J ) 1.5 Hz, 1H), 8.05 (d, J ) 1.5 Hz, 1H), 7.64-7.42 (m, 3H),
5.54 (s, 1H), 4.75 (s, 1H), 3.78-3.53 (m, 4H), 1.23 (t, J ) 7.0 Hz,
3H), 1.22 (t, J ) 7.0 Hz, 3H), 1.16 (s, 9H); 13C NMR (50 MHz,
CDCl3) δ 182.4, 165.1, 133.3, 129.7, 129.3, 128.4, 101.2, 91.9,
82.9, 71.6, 64.1, 35.9, 25.6, 15.1; MS (EI) m/z 347 (85), 301 (50),
+
273 (50), 225 (25), 179 (10) 103 (5); HRMS Calcd for C20H27O5
[M + H]+ 347.18585, found 347.18245.
5,5-Diethoxy-4-oxo-1-phenylpent-2-ynyl Acetate (4m). 4,4,5,5-
Tetraethoxy-1-phenylpent-2-ynyl acetate (3m) (1.10 g, 2.91 mmol)
and p-TsOH (0.13 g, 0.7 mmol) in a mixture of acetone and water
3438 J. Org. Chem. Vol. 74, No. 9, 2009

Synthesis of Tri- and Tetra-Substituted Furans
1388 (m), 1372 (m), 1337 (m), 1296 (w), 1243 (m), 1186 (s) 1149
acetate (97.5:2.5). IR (film) 2975 (s), 2930 (s), 2874 (m), 1680 (s),
1662 (s), 1555 (m), 1467 (m), 1458 (m), 1448 (m), 1409 (m), 1374
(m), 1289 (m), 1264 (w), 1186 (m), 1137 (m), 1114 (m), 1067 (s),
966 (w), 927 (m), 913 (m), 892 (w), 833 (w), 733 (w), 683 (w)
(s), 1113 (s), 1065 (s), 985 (m), 916 (w), 842 (w), 752 (w) cm-1
;
1H NMR (200 MHz, CDCl3) δ 5.52 (t, J ) 6.8 Hz, 1H), 4.74 (s,
1H), 3.80-3.55 (m, 4H), 2.58 (septet, J ) 6.8 Hz, 1H), 1.90-1.17
(m, 17H), 0.89 (t, J ) 7.1 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ
181.7, 174.9, 100.6, 92.2, 81.4, 62.3, 62.2, 33.2, 33.1, 30.8, 27.9,
24.0, 21.7, 18.1, 17.9, 14.3, 13.2; MS (ESI) m/z 340 (M+·, 90),
295 (100), 267 (85), 253 (55), 225 (15); HRMS Calcd for C17H27O4+
[M+· - EtO·] 295.19093, found 295.19072.
1
cm-1; H NMR (200 MHz, CDCl3) δ 7.04 (s, 1H), 5.07 (s, 1H),
3.71-3.60 (m, 5H), 2.16 (s, 3H), 1.26 (t, J ) 7.0 Hz, 3H), 1.25 (d,
J ) 6.8 Hz, 6H), 1.24 (t, J ) 7.0 Hz, 3H); 13C NMR (50 MHz,
CDCl3) δ 191.9, 168.6, 138.0, 120.1, 117.6, 101.4, 62.5 (2CH2),
28.0, 20.8 (2 CH3), 15.2 (2 CH3), 10.6; MS (ESI) m/z 255 (40),
216 (8), 169 (13), 139 (22), 117 (75), 85 (9), 59 (100); HRMS
5,5-Diethoxy-1-hexyl-4-oxopent-2-ynyl Benzoate (4r). 4,4,5,5-
Tetraethoxy-1-hexyl-pent-2-ynyl benzoate (3r) (1.55 g, 3.5 mmol)
and p-TsOH (0.15 g, 0.8 mmol) in a mixture of acetone and water
(25 mL) were refluxed for 4 h and gave the title compound (1.17
g, 91%) as a yellowish liquid after purification by flash chroma-
tography (hexanes-ethyl acetate, 90:10). IR (film) 3063 (m), 2977
(s), 2955 (s), 2930 (s), 2860 (s), 2218 (s), 1970 (w), 1919 (w),
1727 (s), 1694 (s), 1602 (m), 1587 (m), 1452 (s), 1372 (m), 1340
(s), 1316 (s), 1265 (s), 1177 (s), 1105 (s), 1095 (s), 1069 (s), 1026
(s), 1002 (m), 976 (m), 909 (m), 842 (w), 805 (w), 713 (s), 687
(m), 671 (m) cm-1; 1H NMR (200 MHz, CDCl3) δ 8.08-8.04 (m,
2H), 7.64-7.42 (m, 3H), 5.78 (t, J ) 6.6 Hz, 1H), 4.75 (s, 1H),
3.79-3.54 (m, 4H), 2.04-1.93 (m, 2H), 1.37-1.14 (m, 14H), 0.88
(t, J ) 6.4 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ 182.4, 165.1,
133.3, 129.7 (2CH), 129.3, 128.3 (2CH), 101.2, 92.6, 82.4, 63.8,
62.9 (2CH2), 34.0, 31.4, 28.6, 24.8, 22.4, 14.9 (2CH3), 13.9; MS
(ESI) m/z 375 (100), 347 (15), 329 (92), 301 (35), 279 (19), 253
Calcd for C14H23O4 [M + H]+ 255.15885, found 255.15963.
+
2,2-Diethoxy-1-(4-methyl-2-phenylfuran-3-yl)ethanone (5c).
5,5-Diethoxy-4-oxopent-2-ynyl benzoate (4c) (0.29 g) was reacted
at -60 °C and gave the title compound (0.11 g, 40%) as a colorless
liquid after purification by flash chromatography (hexanes-ethyl
acetate, 97.5:2.5). IR (film) 3062 (m), 3039 (m), 2977 (s), 2930
(s), 2896 (s), 1775 (s), 1686 (s), 1595 (m), 1547 (m), 1485 (s),
1446 (s), 1372 (s), 1339 (m), 1269 (s), 1177 (s), 1159 (s), 1118
(s), 1067 (s), 966 (m), 917 (m), 839 (m), 771 (s), 698 (s), 600 (m)
cm-1 1H NMR (200 MHz, CDCl3) δ 7.58-7.53 (m, 2H),
;
7.46-7.41 (m, 3H), 7.27 (s, 1H), 4.97 (s, 1H), 3.59-3.31 (m, 4H),
2.16 (s, 3H), 1,12 (t, J ) 7.0 Hz, 6H); 13C NMR (50 MHz, CDCl3)
δ 193.8, 156.8, 139.4, 130.7, 129.2, 128.4 (2CH), 128.0 (2CH),
122.1, 121.0, 99.2, 62.0 (2CH2), 14.9 (2CH3), 9.3; MS (ESI) m/z
289 (33), 243 (100), 197 (30), 117 (38); HRMS Calcd for C17H21O4+
[M + H]+ 289.1440, found 289.1436.
(25), 225 (13); HRMS Calcd for C22H31O5 [M + H]+ 375.2171,
+
2,2-Diethoxy-1-(2,4,5-trimethylfuran-3-yl)ethanone (5d). 5,5-
Diethoxy1-1-methyl-4-oxopent-2-ynyl acetate (4d) (0.24 g) was
reacted at -60 °C and gave the title compound (0.12 g, 48%) as a
colorless liquid after purification by flash chromatograph using
hexanes-ethyl acetate (97.5:2.5). IR (film) 2976 (s), 2929 (s), 2873
(m), 1664 (s), 1612 (m), 1594 (w), 1454 (w), 1444 (w), 1405 (m),
1386 (w), 1371 (w), 1368 (m), 1280 (m), 1232 (s), 1188 (m), 1174
(s), 1099 (s), 1017 (s), 965 (m), 944 (w), 837 (w), 709 (m), 703
(w) cm-1; 1H NMR (200 MHz, CDCl3) δ 5.04 (s, 1H), 3.72-3.54
(m, 4H), 2.58 (s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 1.23 (t, J ) 7.0
Hz, 3H), 1.22 (t, J ) 7.0 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ
192.1, 160.6, 137.8, 121.0, 118.2, 101.2, 62.4 (2CH2), 15.5 (2CH3),
10.7, 10.4, 10.2; MS (ESI) m/z 241 (10), 240 (M+, 5), 195 (70),
found 375.2172.
Synthesis of Furans 5 from Ketoesters 4; General Procedure.
CuI (0.19 g, 1.0 mmol) [CuCN (0.090 g, 1.0 mmol) when the
higher-order cyanocuprate Me2Cu(CN)Li2 was made14] was dis-
persed in dried THF (10 mL) [distilled from sodium-benzophenone
ketyl prior to use] and cooled to -30 °C. MeLi (1.25 mL, 1.6 M,
2.0 mmol) was added dropwise during 15 min (BuLi and ButLi
were used instead of MeLi in syntheses of 6 and 7 respectively).
When the addition was complete the reaction mixture was allowed
to stir at -30 °C for 30 min before it was cooled to either -78 or
-60 °C or heated to 0 °C or room temperature (see Table 2 and
subsequent descriptions). Ketoester 4 (1.0 mmol), dissolved in dried
THF (2 mL), was then added dropwise during 15 min at the selected
temperature, and the resulting mixture was stirred for an additional
60 min at the same temperature before a saturated aqueous solution
of NH4Cl (10 mL) was added in one portion, also at the same
temperature. The hydrolysate was allowed to reach room temper-
ature, the phases were separated, and the water phase was extracted
with diethyl ether (3 × 10 mL). The combined organic extracts
were washed with an equal volume of a saturated aqueous NaCl
solution, dried over MgSO4 (anhd.), and then concentrated under
vacuum on a rotary evaporator to give a crude product, which was
purified by flash chromatography.
103 (100); HRMS Calcd for C13H20O4 [M+] 240.13616, found
+
240.13583.
2,2-Diethoxy-1-(2-isopropyl-4,5-dimethylfuran-3-yl)etha-
none (5e). 5,5-Diethoxy1-1-methyl-4-oxopent-2-ynyl isobutyrate
(4e) (0.27 g) was reacted at -60 °C and gave the title compound
(0.13 g, 50%) as a colorless liquid after purification by flash
chromatograph using hexanes-ethyl acetate (97.5:2.5). IR (film)
2975 (s), 2930 (s), 2874 (m), 1681 (s), 1662 (s), 1555 (s), 1467
(m), 1448 (m), 1409 (m), 1389 (m), 1374 (m), 1322 (m), 1289
(m), 1264 (w), 1188 (m), 1114 (m), 1068 (s), 1014 (m), 966 (m),
948 (w), 912 (m), 833 (w), 732 (w), 683 (m) cm-1; 1H NMR (200
MHz, CDCl3) δ 5.07 (s, 1H), 3.71-3.60 (m, 5H), 2.17 (s, 3H),
2.07 (s, 3H), 1.25 (d, J ) 6.8 Hz, 6H), 1.24 (t, J ) 7.0 Hz, 3H),
1.23 (t, J ) 7.0 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ 191.9,
165.7, 145.8, 118.2, 113.8, 101.1, 62.1 (2CH2), 27.9, 20.9 (2CH3),
15.0 (2CH3), 10.8, 10.2; MS (EI) m/z 268 (M+, 20), 223 (50), 165
2,2-Diethoxy-1-(2,4-dimethylfuran-3-yl)ethanone (5a). 5,5-
Diethoxy-4-oxopent-2-ynyl acetate (4a) (0.23 g) was reacted at -60
°C and gave the title compound (0.11 g, 50%) as a colorless liquid
after purification by flash chromatograph using hexanes-ethyl
acetate (97.5:2.5). IR (film) 2978 (s), 2931 (s), 2875 (m), 1665 (s),
1617 (m), 1594 (m), 1551 (m), 1457 (m), 1445 (w), 1405 (m),
1386 (w), 1368 (m), 1311 (m), 1282 (m), 1232 (s), 1188 (m), 1101
+
(20), 131 (30), 103 (100) 75 (60); HRMS Calcd for C15H24O4
[M+] 268.16745, found 268.16740.
(s), 1055 (s), 1017 (s), 965 (m), 941 (w), 837 (w), 709 (m) cm-1
;
2,2-Diethoxy-1-(4,5-dimethyl-2-phenylfuran-3-yl)ethanone (5f).
5,5-Diethoxy1-1-methyl-4-oxopent-2-ynyl benzoate (4f) (0.30 g)
was reacted at -60 °C and gave the title compound (0.16 g, 53%)
as a colorless liquid after purification by flash chromatography
(hexanes-ethyl acetate, 95:5). IR (film) 3059 (m), 3032 (m), 2976
(s), 2926 (s), 2898 (s), 2359 (w), 2338 (w), 1960 (w), 1893 (w),
1686 (s), 1633 (m), 1604 (m), 1556 (s), 1487 (s), 1446 (s), 1389
(s), 1370 (s), 1304 (s), 1285 (m), 1247 (w), 1096 (s), 1073 (s), 969
(s), 921 (s), 840 (s), 769 (s), 698 (s), 656 (m) cm-1; 1H NMR (200
MHz, CDCl3) δ 7.55-7.36 (m, 5H), 4.96 (s, 1H), 3.61-3.27 (m,
4H), 2.27 (s, 3H), 2.07 (s, 3H), 1.12 (t, J ) 7.1 Hz, 6H); 13C NMR
(50 MHz, CDCl3) δ 194.0, 154.3, 148.1, 130.8, 128.9, 128.4 (2CH),
1H NMR (200 MHz, CDCl3) δ 7.02 (s, 1H), 5.06 (s, 1H), 3.75-3.53
(m, 4H), 2.58 (s, 3H), 2.18 (s, 3H), 1.24 (t, J ) 7.0 Hz, 3H), 1.23
(t, J ) 7.0 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ 192.4, 160.8,
137.8, 121.1, 119.4, 101.3, 62.4 (2CH2), 29.6, 15.5, 15.0, 10.4; MS
(EI) m/z 226 (M+, 3), 181 (20), 153 (30), 131 (5), 123 (80), 103
+
(95), 95 (5), 75 (90), 65 (30), 47 (100); HRMS Calcd for C12H18O4
[M+] 226.1205, found 226.1196.
2,2-Diethoxy-1-(2-isopropyl-4-methylfuran-3-yl)ethanone (5b).
5,5-Diethoxy-4-oxopent-2-ynyl isobutyrate (4b) (0.25 g) was reacted
at -60 °C and gave the title compound (0.11 g, 45%) as a colorless
liquid after purification by flash chromatograph using hexanes-ethyl
J. Org. Chem. Vol. 74, No. 9, 2009 3439

Sydnes et al.
127.8 (2CH), 125.1, 116.0, 99.0, 61.9 (2CH2), 15.0 (2CH3), 11.1,
compound (0.21 g, 68%) as a colorless liquid after purification by
flash chromatograph using hexanes-ethyl acetate (97.5:2.5). IR
(film) 2975 (s), 2932 (s), 2874 (m), 1676 (s), 1661 (s), 1598 (w),
1554 (m), 1466 (m), 1394 (w), 1375 (m), 1365 (m), 1323 (m),
1272 (w), 1220 (w), 1128 (s), 1065 (s), 958 (w), 821 (w), 832 (w),
+
9.2; MS (ESI) m/z 303 (100), 257 (35); HRMS Calcd for C18H23O4
[M + H]+ 303.1596, found 303.1601.
2,2-Diethoxy-1-(5-isopropyl-2,4-dimethylfuran-3-yl)etha-
none (5 g). 5,5-Diethoxy-1-isopropyl-4-oxopent-2-ynyl acetate (4g)
(0.27 g) was reacted at -60 °C and gave the title compound (0.21
g, 81% when Me2CuLi was used; 0.19 g, 74% when Me2Cu(CN)Li2
was applied) as a colorless liquid after purification by flash
chromatography (hexanes-ethyl acetate, 90:10). IR (film) 2973 (s),
2930 (s), 2874 (s), 1681 (s), 1663 (s), 1561 (m), 1447 (m), 1411
(m), 1380 (m), 1266 (m), 1124 (m), 1057 (s), 950 (w), 885 (w),
1
702 (w), 676 (w) cm-1; H NMR (200 MHz, CDCl3) δ 5.05 (s,
1H), 3.73-3.50 (m, 5H), 2.20 (s, 3H), 1.31 (s, 9H), 1.24 (d, J )
6.6 Hz, 6H), 1.23 (2 almost overlapping t, J ) 7.0 Hz for each, 3H
for each); 13C NMR (50 MHz, CDCl3) δ 192.8, 163.4, 155.2, 119.1,
112.3, 101.6, 62.4 (2CH2), 33.7, 29.4 (3CH3), 28.1, 21.2 (2CH3),
15.2 (2CH3), 10.6; MS (EI) m/z 310 (M+, 20), 265 (40), 207 (30),
103 (100); HRMS Calcd for C18H30O4 [M+ ] 310.21440, found
+
1
800 (w), 670 (w) cm-1; H NMR (200 MHz, CDCl3) δ 5.06 (s,
310.21446.
1H), 3.77-3.54 (m, 4H), 2.97 (septet, J ) 7.0 Hz, 1H), 2.55 (s,
3H), 2.10 (s, 3H), 1.28-1.18 (m, 12H); 13C NMR (50 MHz, CDCl3)
δ 192.0, 154.2, 152.9, 120.0, 112.7, 101.3, 62.3 (2CH2), 25.3, 21.1
(2CH3), 15.4, 15.0 (2CH3), 9.9; MS (EI) m/z 268 (M+,1), 195 (5),
1-(5-tert-Butyl-4-methyl-2-phenylfuran-3-yl)-2,2-diethoxyeth-
anone (5 L). 7,7-Dieth-oxy-2,2-dimethyl-6-oxohept-4-yn-3-yl ben-
zoate (4l) (0.35 g) was reacted at -60 °C and gave the title
compound (0.18 g, 52%) as a colorless liquid after purification by
flash chromatograph using hexanes-ethyl acetate (95:5). IR (film)
3059 (w), 3028 (w), 2975 (s), 2931 (s), 2905 (m), 2875, 1686 (s),
1611 (w), 1597 (w), 1578 (w), 1556 (m), 1487 (m), 1461 (m), 1446
(m), 1392 (m), 1366 (m), 1342 (w), 1317 (w), 1306 (w), 1268 (w),
1224 (w), 1202 (w), 1132 (m), 1117 (s), 1071 (s), 1006 (m), 967
165 (19), 103 (100), 75 (82); HRMS Calcd for C15H24O4 [M+]
+
268.1675, found 268.1684.
2,2-Diethoxy-1-(2,5-diisopropyl-4-methylfuran-3-yl)etha-
none (5 h). 5,5-Diethoxy-1-isopropyl-4-oxopent-2-ynyl isobutyrate
(4h) (0.30 g) was reacted at -60 °C and gave the title compound
(0.22 g, 75%) as a colorless liquid after purification by flash
chromatography (hexanes-ethyl acetate, 95:5). IR (film) 2971 (s),
2932 (s), 2874 (s), 2756 (m), 2618 (w), 2360 (m), 1732 (m), 1681
(s), 1660 (s), 1619 (m), 1556 (s), 1468 (s), 1409 (m), 1377 (s),
1364 (m), 1322 (s), 1267 (s), 1157 (s), 1122 (s), 1073 (s), 1013
(s), 955 (m), 912 (m), 892 (m), 832 (m), 793 (m), 765 (m), 730
(m), 960 (m), 923 (m), 843 (m), 824 (w), 770 (m), 698 (s) cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.50-7.37 (m, 5H), 4.94 (s, 1H),
3.57-3.51 (m, 2H), 3.42-3.36 (m, 2H), 2.17 (s, 3H), 1.38 (s, 9H),
1.12 (t, J ) 7.0 Hz, 6H); 13C NMR (50 MHz, CDCl3) δ 194.7,
157.5, 152.0, 130.7, 128.6, 128.3 (2CH), 127.4 (2CH), 122.6, 114.1,
99.1, 61.9 (2CH2), 33.8, 29.3 (2CH3), 14.9 (2CH3), 9.6; MS (ESI)
m/z 299 (100), 253 (35); HRMS Calcd for C19H23O3+ [M+· - EtO·]
299.16472, found 299.16648.
1
(m), 701 (m), 679 (m) cm-1; H NMR (200 MHz, CDCl3) δ 5.07
(s, 1H), 3.72-3.54 (m, 5H), 2.98 (septet, J ) 7.0 Hz, 1H), 2.09 (s,
3H), 1.27-1.19 (m, 18H); 13C NMR (50 MHz, CDCl3) δ 192.0,
165.3, 153.8, 118.1, 111.8, 101.2, 62.2 (2CH2), 28.0, 25.5, 21.0
(2CH3), 20.8 (2CH3), 15.0 (2CH3), 9.9; MS (ESI) m/z 297 (100),
223 (10), 119 (5); HRMS Calcd for C17H29O4+ [M + H]+ 297.2066,
found 297.2075.
2,2-Diethoxy-1-(2,4-dimethyl-5-phenylfuran-3-yl)ethanone (5m).
5,5-Diethoxy-4-oxo-1-phenylpent-2-ynyl acetate (4m) (0.30 g) was
reacted at -60 °C and gave the title compound (0.15 g, 52%) as a
colorless liquid after purification by flash chromatography (hex-
anes-ethyl acetate, 90:10). IR (film) 3054 (w), 2977 (s), 2928 (s),
2879 (s), 1681 (s), 1666 (s), 1614 (m), 1575 (w), 1553 (m), 1494
(m), 1444 (m), 1494 (m), 1409 (m), 1376 (m), 1322 (m), 1303
(m), 1252 (w), 1157 (m), 1117 (s), 1062 (s), 1016 (s), 969 (w),
2,2-Diethoxy-1-(5-isopropyl-4-methyl-2-phenylfuran-3-yl)-
ethanone (5i). 5,5-Diethoxy-1-isopropyl-4-oxopent-2-ynyl ben-
zoate (4i) (0.33 g) was reacted at -60 °C and gave the title
compound (0.15 g, 47%) as a colorless liquid after purification by
flash chromatography (hexanes-ethyl acetate, 95:5). IR (film) 3062
(m), 3030 (m), 2972 (s), 2930 (s), 2899 (s), 2873 (s), 1960 (w),
1815 (w), 1686 (s), 1603 (m), 1556 (m), 1485 (s), 1459 (m), 1446
(m), 1381 (m), 1371 (m), 1315 (w), 1295 (m), 1265 (m), 1161
(m), 1119 (s), 1073 (s), 1058 (s), 1051 (s), 1007 (m), 960 (m), 922
(m), 909 (m), 840 (m), 832 (m), 769 (s), 698 (s), 669 (w), 647 (w),
625 (m) cm-1; 1H NMR (200 MHz, CDCl3) δ 7.55-7.33 (m, 5H),
4.97 (s, 1H), 3.63-3.29 (m, 4H), 3.13-2.99 (m, 1H), 2.08 (s, 3H),
1.28 (d, J ) 7.0 Hz, 6H), 1.12 (t, J ) 7.0 Hz, 6H); 13C NMR (50
MHz, CDCl3) δ 194.1, 156.1, 153.7, 130.9, 128.8, 128.3 (2CH),
127.7 (2CH), 121.6, 114.0, 98.9, 61.8 (2CH2), 25.8, 21.0 (2CH3),
14.9 (2CH3), 8.8; MS (ESI) m/z 331 (50), 285 (100); HRMS Calcd
1
911 (w), 765 (s), 696 (s), 665 (m) cm-1; H NMR (200 MHz,
CDCl3) δ 7.59-7.56 (m, 2H), 7.46-7.20 (m, 3H), 5.09 (s, 1H),
3.82-3.55 (m, 4H), 2.65 (s, 3H), 2.39 (s, 3H), 1.26 (t, J ) 7.0 Hz,
6H); 13C NMR (50 MHz, CDCl3) δ 192.0, 158.7, 147.9, 130.4,
129.2 (2CH), 128.0, 127.1 (2CH), 121.6, 117.7, 102.2, 62.6 (2CH2),
15.1, 15.0 (2CH3), 11.2; MS (EI) m/z 302 (M+, 33), 257 (10), 229
(45), 201 (14), 200 (35), 199 (52), 171 (95), 143 (18), 130 (18),
129 (55), 128 (71), 127 (28), 115 (15), 105 (96), 104 (64), 103
(50), 77 (100), 75 (53); HRMS Calcd for C18H22O4 [M+
302.1518, found 302.1522.
]
+
2,2-Diethoxy-1-(2-isopropyl-4-methyl-5-phenylfuran-3-yl)-
ethanone (5n). 5,5-Diethoxy-4-oxo-1-phenylpent-2-ynyl isobu-
tyrate (4n) (0.33 g) was reacted at -60 °C and gave the title
compound (0.20 g, 60%) as a colorless liquid after purification by
flash chromatography (hexanes-ethyl acetate, 95:5). IR (film) 3083
(w), 3055 (m), 2975 (s), 2931 (s), 2874 (s), 1714 (m), 1688 (s),
1664 (s), 1611 (m), 1549 (m), 1493 (m), 1466 (m), 1445 (m), 1376
(m), 1316 (m), 1259 (w), 1222 (m), 1113 (s), 1063 (s), 1013 (s),
955 (m), 911 (m), 831 (w), 766 (s), 728 (w), 696 (s) 666 (m), 655
for C20H27O4 [M + H]+ 331.1909, found 331.1911.
+
1-(5-tert-Butyl-2,4-dimethylfuran-3-yl)-2,2-diethoxyetha-
none (5j). 7,7-Diethoxy-2,2-dimethyl-6-oxohept-4-yn-3-yl acetate
(4j) (0.28 g) was reacted at -78 °C and gave the title compound
(0.21 g, 72%) as a colorless liquid after purification by flash
chromatograph using hexanes-ethyl acetate (97.5:2.5). IR (film)
2963 (s), 2930 (s), 2872 (s), 1680 (s), 1660 (s), 1622 (w), 1552
(m), 1466 (m), 1409 (m), 1377 (m), 1322 (m), 1283 (m), 1175 (s),
1118 (s), 1071 (s), 954 (w), 913 (m), 891 (w), 832 (w), 770 (w),
1
(m) cm-1; H NMR (200 MHz, CDCl3) δ 7.60-7.56 (m, 2H),
7.46-7.26 (m, 3H), 5.10 (s, 1H), 3.81-3.56 (m, 5H), 2.37 (s, 3H),
1.34-1.18 (m, 12H); 13C NMR (50 MHz, CDCl3) δ 192.4, 166.1,
147.5, 130.9, 128.4 (2CH), 127.2, 126.3 (2CH), 119.7, 116.2, 101.6,
62.5 (2CH2), 28.0, 21.0 (2CH3), 15.0 (2 CH3), 11.2; MS (ESI) m/z
331 (100), 317 (8), 285 (10), 257 (7), 186 (10); HRMS Calcd for
1
732 (w), 680 (m) cm-1; H NMR (200 MHz, CDCl3) δ 5.05 (s,
1H), 3.80-3.54 (m, 4H), 2.52 (s, 3H), 2.22 (s, 3H), 1.32 (s, 9H),
1.24 (t, J ) 7.0 Hz, 3H), 1.23 (t, J ) 7.0 Hz, 3H); 13C NMR (50
MHz, CDCl3) δ 192.1, 158.8, 136.3, 120.4, 113.3, 101.3, 62.4
(2CH2), 29.4 (3CH3), 26.1, 15.2 (2CH3), 14.2, 10.6; MS (EI) m/z
282 (M+, 5), 237 (5), 179 (25), 103 (100), 75 (90); HRMS Calcd
C20H27O4 [M + H]+ 331.1909, found 331.1906.
+
2,2-Diethoxy-1-(4-methyl-2,5-diphenylfuran-3-yl)ethanone (5o).
5,5-Diethoxy-1-phenyl-4-oxopent-2-ynyl benzoate (4o) (0.37 g) was
reacted at -60 °C and gave the title compound (0.19 g, 53%) as a
colorless liquid after purification by flash chromatography (hex-
anes-ethyl acetate, 95:5). IR (film) 3057 (w), 3031 (w), 2975 (s),
for C16H26O4 [M+ ] 282.1831, found 282.1833.
+
1-(5-tert-Butyl-2-isopropyl-4-methylfuran-3-yl)-2,2-diethoxy-
ethanone (5k). 7,7-Diethoxy-2,2-dimethyl-6-oxohept-4-yn-3-yl isobu-
tyrate (4k) (0.31 g) was reacted at -60 °C and gave the title
3440 J. Org. Chem. Vol. 74, No. 9, 2009

Synthesis of Tri- and Tetra-Substituted Furans
2956 (s), 2926 (s), 2871 (m), 2856 (m), 1688 (s), 1613 (m), 1595
(m), 1555 (m), 1486 (m), 1445 (m), 1381 (m), 1316 (m), 1265
(w), 1158 (m), 1112 (s), 1070 (s), 965 (m), 912 (m), 839 (m), 766
191.4, 157.1, 154.3, 119.1, 118.3, 101.0, 62.2 (2CH2), 33.1, 25.3,
23.7, 22.6, 21.4 (2CH3), 15.6, 15.0 (2CH3), 13.9; MS (ESI) m/z
311 (70), 309 (100), 281 (48), 263 (10), 235 (7), 117 (34); HRMS
(s), 695 (s), 667 (m) cm-1
;
1H NMR (200 MHz, CDCl3) δ
Calcd for C18H31O4 [M + H]+ 311.2222, found 311.2218.
+
7.71-7.59 (m, 4H), 7.49-7.29 (m, 6H), 5.00 (s, 1H), 3.66-3.32
(m, 4H), 2.36 (s, 3H), 1.11 (t, J ) 7.0 Hz, 6H); 13C NMR (50
MHz, CDCl3) δ 194.5, 154.3, 149.3, 130.6, 130.4, 129.2, 128.5
(4CH), 127.8 (2CH), 127.5, 126.1 (2CH), 123.1, 117.9, 99.3, 62.2
(2CH2), 14.9 (2CH3), 10.3; MS (ESI) m/z 364 (M+, 40), 335 (20),
319 (42), 293 (30), 279 (20), 215 (20), 187 (100), 158 (10); HRMS
1-(4-tert-Butyl-2,5-diisopropylfuran-3-yl)-2,2-diethoxyetha-
none (7). 5,5-Diethoxy-1-isopropyl-4-oxopent-2-ynyl isobutyrate
(4h) (0.30 g, 1.0 mmol) and in situ formed But2CuLi (1.0 mmol)
were reacted at -60 °C and gave the title compound (0.19 g, 55%)
as a colorless liquid after purification by flash chromatography
(hexanes-ethyl acetate, 95:5). IR (film) 2970 (s), 2932 (s), 2873
(s), 1699 (s), 1600 (w), 1560 (m), 1483 (m), 1468 (s), 1394 (m),
1364 (s), 1276 (m), 1261 (m), 1205 (m), 1157 (s), 1111 (s), 1080
(s), 1064 (s), 1011 (s), 929 (m), 845 (w), 762 (w) cm-1; 1H NMR
(200 MHz, CDCl3) δ 4.96 (s, 1H), 3.85-3.54 (m, 4H), 3.23 (septet,
J ) 6.9 Hz, 1H), 2.93 (septet, J ) 6.9 Hz, 1H), 1.29-1.13 (m,
27H); 13C NMR (50 MHz, CDCl3) δ 199.1, 156.0, 153.1, 124.8,
118.9, 101.8, 63.0 (2CH2), 31.9 (3CH3), 27.9, 27.3, 22.3, 21.6
(2CH2), 21.3 (2CH3), 15.0 (2CH3); MS (ESI) m/z 339 (70), 338
(20), 337 (100), 293 (28), 271 (15) 213 (21), 143 (10), 59 (17);
HRMS Calcd for C20H35O4+ [M + H]+ 339.2535, found 339.2526.
(tert-Butyl)(4,4,5,5-tetraethoxy-1-hexyl-2-pentynoxy)diphenyl-
silane (9). 1,1,2,2-Tetraethoxyundec-3-yn-5-ol (0.69 g, 2.0 mmol)
was dissolved in CHCl3 (20 mL) under N2 at 20 °C. After addition
of Et3N (0.40 g, 4.0 mmol) and DMAP (0.037 g, 0.3 mmol) (t-
butyl)(chloro)-diphenylsilane (0.60 g, 2.2 mmol) was added drop-
wise during 5 min. The reaction mixture was allowed to stir for an
additional 30 min before the reaction was quenched by a saturated
aqueous solution of NaHCO3 (20 mL). The phases were separated,
the aqueous phase was extracted with DCM (3 × 20 mL), and the
organic extracts were combined and dried over MgSO4 (anhd.).
Filtration and evaporation of the solvent followed by isolation by
flash chromatography using hexanes-ethyl acetate (95:5) as eluent,
gave the title compound (0.98 g, 84%) as a clear liquid. IR (film)
3071 (m), 3049 (w), 3028 (w), 3014 (w), 2961 (s), 2930 (s), 2894
(s), 2858 (s), 1587 (w), 1473 (m), 1463 (m), 1448 (s), 1427 (m),
1390 (w), 1332 (w), 1258 (w), 1186 (m), 1113 (s), 1082 (s), 1020
(m), 1010 (m), 998 (w), 963 (w), 938 (w), 854 (m), 823 (m), 741
Calcd for C23H24O4 [M+] 364.1675, found 364.1662.
+
2,2-Diethoxy-1-(5-hexyl-2,4-dimethylfuran-3-yl)ethanone (5p).
5,5-Diethoxy-1-hexyl-4-oxopent-2-ynyl acetate (4p) (0.31 g) was
reacted at -60 °C and gave the title compound (0.22 g, 70%) as a
colorless liquid after purification by flash chromatograph using
hexanes-ethyl acetate (90:10). IR (film) 2972 (s), 2930 (s), 2873
(s), 1681 (s), 1663 (s), 1560 (m), 1457 (m), 1447 (m), 1414 (m),
1380 (m), 1323 (w), 1295 (w), 1271 (m), 1259 (m), 1159 (m), 1124
(m), 1061 (s), 968 (m), 914 (w), 785 (w), 699 (m) cm-1; 1H NMR
(200 MHz, CDCl3) δ 5.06 (s, 1H), 3.76-3.59 (m, 4H), 2.54 (s,
3H), 2.10 (s, 3H), 1.64-1.59 (m, 10H), 1.31-1.22 (m, 6H), 0.88
(t, J ) 7.0 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ 191.5, 158.0,
150.1, 119.9, 114.3, 101.1, 62.3 (2 CH2), 31.5, 29.7, 28.8, 28.4,
25.3, 22.5, 15.4 (2 CH3), 14.0, 10.3; MS (EI) m/z 310 (M+, 10),
265 (10), 237 (40), 207 (70), 137 (20), 103 (100), 75 (90), 43 (80);
HRMS Calcd for C18H30O4 [M+] 310.2144, found 310.2141.
+
2,2-Diethoxy-1-(5-hexyl-2-isopropyl-4-methylfuran-3-yl)etha-
none (5q). 5,5-Dieth-oxy-1-hexyl-4-oxopent-2-ynyl isobutyrate (4q)
(0.34 g) was reacted at -60 °C and gave the title compound (0.23
g, 69%) as a colorless liquid after purification by flash chromato-
graph using hexanes-ethyl acetate (90:10). IR (film) 2963 (s), 2930
(s), 2872 (m), 2860 (s), 1742 (w), 1681 (s), 1660 (s), 1623 (m),
1555 (s), 1467 (s), 1409 (m), 1377 (m), 1361 (m), 1339 (m), 1322
(m), 1283 (m), 1175 (m), 1118 (s), 1071 (s), 1013 (m), 954 (m),
927 (m), 891 (w), 832 (w), 732 (w), 680 (w) cm-1; 1H NMR (200
MHz, CDCl3) δ 5.08 (s, 1H), 3.72-3.56 (m, 4H), 2.49 (se, J )
7.0 Hz, 1H), 2.04 (s, 3H), 1.56-1.21 (m, 22H), 0.90 (t, J ) 6.6
Hz, 3H); 13C NMR (50 MHz, CDCl3) δ 191.8, 165.6, 150.0, 118.1,
113.5, 101.1, 62.2 (2 CH2), 31.4, 28.6, 28.1, 27.9, 27.8, 25.2, 22.4,
20.9 (2 CH3), 15.8 (2 CH3), 10.1; MS (ESI) m/z 339 (100), 310
1
(m), 709 (s) cm-1; H NMR (400 MHz, CDCl3) δ 7.70-7.65 (m,
4H), 7.41-7.33 (m, 6H), 4.43 (t, J ) 6.6 Hz, 1H), 4.35 (s, 1H),
3.66-3.52 (m, 8H), 1.72-1.55 (m, 10H), 1.23 (t, J ) 7.0 Hz, 6H),
1.21 (t, J ) 7.0 Hz, 6H), 1.19 (s, 9H), 0.88 (t, J ) 6.9 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 135.7, 135.5, 133.1, 132.8, 129.8,
129.7, 127.6, 127.5, 101.1, 95.8, 83.6, 63.9, 62.6, 37.4, 31.7, 28.8,
26.7, 24.4, 22.4, 15.0, 14.9, 13.9; MS (ESI) m/z 537 (45), 479 (20),
327 (50), 255 (20), 103 (100); HRMS Calcd for C33H49O4Si+ [M+·
- EtO·] 537.3400, found 537.3402.
(40), 293 (60); HRMS Calcd for C18H29O3 [M+· - EtO·]
+
293.21167, found 293.21172.
2,2-Diethoxy-1-(5-hexyl-4-methyl-2-phenylfuran-3-yl)etha-
none (5r). 5,5-Diethoxy-1-hexyl-4-oxopent-2-ynyl benzoate (4r)
(0.37 g) was reacted at -60 °C and gave the title compound (0.19
g, 50%) as a colorless liquid after purification by flash chroma-
tography (hexane-ethyl acetate, 90:10). IR (film) 3064 (w), 3034
(w), 2956 (s), 2925 (s), 2871 (s), 2855 (s), 1686 (s), 1605 (m),
1584 (w), 1559 (m), 1459 (s), 1378 (m), 1265 (s), 1176 (m), 1098
(s), 1070 (s), 1027 (m), 964 (w), 917 (w), 768 (m), 711 (m), 666
5-{(tert-Butyl)diphenylsiloxy}-1,1-diethoxyundec-3-yn-2-one
(10). A mixture of silane 9 (0.58 g, 1.0 mmol) and p-TsOH (0.058
g, 0.3 mmol) in a 70:30 mixture of THF and H2O (10 mL) was
refluxed for 4 h. Most of the THF was then evaporated, leaving a
residue which was mixed with CH2Cl2 (20 mL) and H2O (10 mL).
The phases were separated, the aqueous phase was extracted with
DCM (3 × 20 mL), and the organic phases were combined and
dried over MgSO4 (anhd.). Filtration and evaporation of the solvent
followed by isolation by flash chromatography using hexanes-ethyl
acetate (95:5) as eluent, gave the title compound (0.45 g, 89%) as
a clear oil. IR (film) 3072 (m), 3050 (w), 3013 (w), 2956 (s), 2931
(s), 2897 (s), 2859 (s), 2213 (s), 1690 (s), 1589 (w), 1472 (m),
1464 (m), 1428 (s), 1391 (w), 1318 (w), 1245 (w), 1187 (w), 1158
(m), 1113 (s), 1085 (s), 1008 (s), 999 (w), 932 (w), 823 (m), 741
(s) cm-1 1H NMR (200 MHz, CDCl3) δ 7.55-7.50 (m, 2H),
;
7.43-7.37 (m, 3H), 4.97 (s, 1H), 3.59-3.32 (m, 4H), 2.61 (t, J )
7.0 Hz, 2H), 2.04 (s, 3H), 1.43-0.98 (m, 17H); 13C NMR (50 MHz,
CDCl3) δ 194.1, 154.0, 152.2, 130.9, 128.8, 128.4 (2CH), 127.8
(2CH), 121.8, 115.8, 99.0, 61.9 (2CH2), 31.5, 29.3, 28.7, 26.8, 22.6,
14.9, 14.0 (2CH3), 9.1; MS (ESI) m/z 373 (100), 359 (6); HRMS
Calcd for C23H33O4 [M + H]+ 373.2379, found 373.2373.
1-(4-Butyl-5-isopropyl-2-methylfuran-3-yl)-2,2-diethoxyetha-
none (6). 5,5-Diethoxy-1-isopropyl-4-oxopent-2-ynyl acetate (4g)
(0.27 g, 1.0 mmol) and in situ formed Bu2CuLi (1.0 mmol) were
reacted at -60 °C and gave the title compound (0.28 g, 90%) as a
colorless liquid after purification by flash chromatography (hex-
anes-ethyl acetate, 95:5). IR (film) 2968 (s), 2931 (s), 2873 (s),
1685 (s), 1661 (s), 1560 (s), 1466 (m), 1410 (m), 1381 (m), 1323
(m), 1300 (w), 1259 (m), 1159 (m), 1125 (s), 1054 (s), 968 (m),
911 (m), 841 (w), 798 (w), 691 (m), 666 (m) cm-1; 1H NMR (200
MHz, CDCl3) δ 5.07 (s, 1H), 3.77-3.53 (m, 4H), 2.95 (septet, J
) 7.0 Hz, 1H), 2.56 (s, 3H), 2.51 (t, J ) 7.4 Hz, 2H), 1.40-1.18
(m, 16H), 0.90 (t, J ) 6.9 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ
1
(m), 702 (s) cm-1; H NMR (400 MHz, CDCl3) δ 7.71-7.66 (m,
4 H), 7.43-7.35 (m, 6H), 4.62 (s, 1H), 4.47 (t, J ) 6.6 Hz, 1H),
3.66-3.52 (m, 4H), 1.72-1.55 (m, 10H), 1.23 (t, J ) 7.0 Hz, 3H),
1.21 (t, J ) 7.0 Hz, 3H), 1.19 (s, 9H), 0.88 (t, J ) 6.9 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 182.4, 135.9, 135.7, 133.0, 132.9,
129.8, 129.7, 127.6, 127.5, 101.1, 96.8, 82.1, 63.9, 62.6, 37.4, 31.7,
28.8, 26.7, 24.4, 22.4, 14.9, 13.9; MS (ESI) m/z 465 (20), 464 (50),
463 (100), 269 (10), 239 (10); HRMS Calcd for C29H39O3Si+ [M+·
- EtO·] 463.26711, found 463.26295.
J. Org. Chem. Vol. 74, No. 9, 2009 3441

Sydnes et al.
5-{(tert-Butyl)diphenylsiloxy}-1,1-diethoxy-4-methylundec-3-
en-2-one (11). CuI (0.051 g, 0.27 mmol) was dispersed in
anhydrous THF (3 mL) and cooled to -30 °C. MeLi (0.33 mL,
1.6 M, 0.54 mmol) was added dropwise during 10 min. When the
addition was complete the reaction mixture was allowed to stir at
-30 °C for 30 min before it was cooled to -78 °C. Silyloxyketone
10 (0.136 g, 0.27 mmol), dissolved in anhydrous THF (2 mL), was
then added dropwise during 2 min, and the resulting mixture was
stirred for an additional 60 min at -78 °C before a saturated
aqueous solution of NH4Cl (5 mL) was added in one portion, also
at -78 °C. The hydrolysate was allowed to reach room temperature,
the phases were separated, and the aqueous phase was extracted
with diethyl ether (3 × 10 mL). The combined organic extracts
were washed with an equal volume of a saturated aqueous NaCl
solution, dried over MgSO4 (anhd.), and then concentrated under
vacuum on a rotary evaporator to give a crude product, from which
the products 11E (0.062 g, 44%) and 11Z (0.059 g, 42%) were
isolated as clear liquids by flash chromatography using hexanes-ethyl
acetate (97.5:2.5) as eluent. (E)-11: IR (film) 3071 (w), 3049 (w),
3013 (w), 2956 (s), 2931 (s), 2897 (s), 2858 (s), 1693 (m), 1615
(m), 1591 (w), 1472 (m), 1462 (m), 1428 (m), 1390 (m), 1372
(w), 1318 (w), 1311 (m), 1261 (w), 1158 (m), 1106 (s), 1065 (s),
1028 (m), 999 (m), 937 (w), 908 (w), 894 (w), 838 (m), 739 (m),
702 (s), 611 (m) cm-1; 1H NMR (400 MHz, CDCl3) δ 7.68-7.58
(m, 4H), 7.43-7.30 (m, 6H), 6.51 (s, 1H), 4.58 (s, 1H), 4.12 (t, J
) 5.6 Hz, 1H), 3.64-3.51 (m, 4H), 2.05 (s, 3H), 1.46-1.26 (m,
10H), 1.22 (t, J ) 7.0 Hz, 3H), 1.21 (t, J ) 7.0 Hz, 3H), 1.08 (s,
9H), 0.89 (t, J ) 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
195.4, 162.1, 135.8, 134.0, 133.4, 129.6, 127.5, 118.3, 102.4, 78.0,
62.5, 35.2, 31.5, 29.0, 26.9, 24.0, 22.4, 19.2, 15.7, 15.0, 13.9; MS
(ESI) m/z 481 (20), 480 (45), 479 (100), 421 (10), 269 (10); HRMS
Calcd for C30H43O3Si+ [M+· - EtO·] 479.29805, found 479.30529.
(Z)-11: IR (film) 3071 (w), 3049 (w), 3012 (w), 2957 (s), 2931 (s),
2858 (s), 2897 (s), 1695 (m), 1621 (m), 1590 (w), 1472 (m), 1460
(m), 1428 (m), 1390 (m), 1372 (w), 1318 (w), 1311 (m), 1261 (w),
1158 (m), 1106 (s), 1065 (s), 1028 (m), 999 (m), 937 (w), 908
1H, E and Z in a 1:1 ratio), 4.68 and 4.67 (2s, 1H, E and Z in a 1:1
ratio), 3.74-3.55 (m, 4H), 2.15 (s, 3H), 2.04 and 1.90 (2s, 3H, E
and Z in a 1:1 ratio), 1.27 (t, J ) 7.0 Hz, 3H), 1.25 (t, J ) 7.0 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 195.4, 194.0, 169.5, 156.3,
137.9, 136.8, 128.6, 128.2, 127.7, 127.6, 126.1, 121.5, 117.7, 102.6,
102.3, 78.6, 72.7, 63.0, 62.8, 62.8, 62.7, 21.0, 20.8, 19.0, 16.5, 15.0;
+
MS (ESI) m/z 275 (10), 261 (100); HRMS Calc. for C16H21O3
[M+· - AcO·] 261.14907, found 261.15154.
3-Deuterio-5,5-diethoxy-2-methyl-4-oxo-1-phenylpent-2-
enyl Acetate (13). When the reaction with 0.304 g (1.0 mmol) of
4m was repeated exactly as described under preparation of 12 except
that the hydrolysis was performed with D2O (5 mL) at -78 °C,
1
0.27 g (84%) of a 1:1 mixture (based on H NMR-spectroscopy)
of the (E) and the (Z) isomers of 13 was obtained. IR (film) 3082
(w), 3061 (w), 3031 (w), 2979 (s), 2931 (s), 2883 (m), 1744 (s),
1697 (s), 1624 (s), 1493 (w), 1452 (m), 1372 (s), 1319 (s), 1231
(s), 1180 (m), 1160 (m), 1112 (s), 1062 (s), 1025 (s), 982 (w), 912
(w), 891 (w), 822 (w), 751 (m), 700 (s) cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.55-7.30 (m, 5H), 7.28 and 6.54 (2s, 1H, E and Z in a
1:1 ratio), 4.68 and 4.67 (2s, 1H, E and Z in a 1:1 ratio), 3.74-3.55
(m, 4H), 2.14 (s, 3H), 2.04 and 1.92 (2s, 3H, E and Z in a 1:1
ratio), 1.27 (t, J ) 7.0 Hz, 3H), 1.25 (t, J ) 7.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 195.2, 194.1, 169.3, 156.3, 137.8, 136.6,
128.6, 128.1, 127.7, 127.6, 126.1, 121.5, 117.7, 102.5, 102.3, 78.5,
72.4, 63.0, 62.8, 62.8, 62.7, 21.0, 20.8, 19.0, 16.5, 15.1; MS (ESI)
+
m/z 276 (10), 262 (100), 218 (30); HRMS Calcd. for C16H20DO3
[M+· - AcO·] 262.15689, found 262.15712.
5,5,6,6-Tetraethoxy-2-methylhex-3-yn-2-ol (14). The compound
was synthesized from TEB, using BuLi or EtMgBr as base and
acetone as electrophile, following literature procedures.4 The
product was isolated as a pale yellow liquid employing silica gel
flash chromatography (hexane-ethyl acetate, 70:30) and was
obtained in 80 and 90% yield, respectively. IR (film) 3431 (m),
2978 (s), 2931 (s), 2896 (s), 2244 (w), 1480 (w), 1445 (m), 1388
(m), 1373 (m), 1336 (m), 1243 (m), 1169 (s), 1116 (s), 1017 (m),
1
969 (m), 933 (m), 879 (w), 808 (w), 760 (w), 736 (w) cm-1; H
1
(w), 894 (w), 838 (m), 739 (m), 702 (s), 611 (m) cm-1; H NMR
NMR (200 MHz, CDCl3) δ 4.38 (s, 1H), 3.88-3.62 (m, 8H), 3.34
(bs, 1H), 1.54 (s, 6H), 1.24 (t, J ) 7.0 Hz, 6H), 1.23 (t, J ) 7.0
Hz, 6H); 13C NMR (50 MHz, CDCl3) δ 103.6, 98.2, 91.5, 76.3,
64.4, 64.3, 59.2, 30.9, 15.0, 14.9; MS (EI) m/z 243 (9), 215 (2),
185 (21), 169 (5), 141 (4), 139 (4), 123 (6), 111 (9), 104 (4), 103
(400 MHz, CDCl3) δ 7.64-7.56 (m, 4H), 7.41-7.28 (m, 6H), 5.72
(t, J ) 6.2 Hz, 1H), 4.45 (s, 1H), 3.63-3.42 (m, 4H), 1.97 (s, 3H),
1.52-1.26 (m, 10H), 1.21 (t, J ) 7.0 Hz, 6H), 1.06 (s, 9H), 0.83
(t, J ) 6.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 193.4, 165.5,
135.8, 134.3, 134.0, 129.5, 127.4, 118.4, 102.7, 71.3, 62.6, 62.5,
36.8, 31.6, 29.2, 26.9, 24.9, 22.5, 19.9, 15.0, 13.9; MS (ESI) m/z
481 (20), 480 (50), 479 (100), 269 (20); HRMS Calcd for
C30H43O3Si+ [M+· - EtO·] 479.29805, found 479.30041.
(100), 95 (19), 83 (5), 75 (59); HRMS Calcd for C13H23O4 [M+·
+
- EtO·] 243.1596, found 243.1592.
1,1-Diethoxy-5-hydroxy-5-methylhex-3-yn-2-one (15). Alcohol
14 (1.73 g, 6.0 mmol) was refluxed for 3 h in a THF-H2O mixture
(6:4) (60 mL) containing p-TsOH (0.11 g, 0.6 mmol, 0.1 equiv).
Most of the THF was then evaporated on a rotary evaporator, and
the residue was mixed with DCM (20 mL). The phases were
separated, the aqueous phase was extracted with DCM (3 × 20
mL), and the combined organic phases were dried over MgSO4
(anhd.). Filtration followed by concentration under vacuum on a
rotary evaporator furnished a crude product, from which 15 (1.22
g, 95%) was isolated as a colorless liquid by flash chromatography
using hexanes-ethyl acetate (85:15) as eluent. IR (film) 3433 (m),
2982 (s), 2934 (m), 2896 (m), 2215 (s), 1690 (s), 1446 (m), 1372
(m), 1322 (m), 1292 (w), 1254 (s), 1233 (s), 1173 (s), 1105 (s),
5,5-Diethoxy-2-methyl-4-oxo-1-phenylpent-2-enyl Acetate (12).
CuI (0.190 g, 1.0 mmol) was dispersed in anhydrous THF (10 mL)
and cooled to -30 °C. MeLi (1.25 mL, 1.6 M, 2.0 mmol) was
added dropwise during 10 min. When the addition was complete
the reaction mixture was allowed to stir at -30 °C for 30 min before
it was cooled to -78 °C. A solution of 4m (0.304 g, 1.0 mmol)
and trimethylsilyl chloride (0.130 g, 1.2 mmol) in anhydrous THF
(5 mL) was then added dropwise to the reaction mixture during 5
min and the reaction was stirred for an additional 60 min at -78
°C before a saturated aqueous solution of NH4Cl (5 mL) was added
in one portion, also at -78 °C. The hydrolysate was allowed to
reach room temperature, the phases were separated, and the aqueous
phase was extracted with diethyl ether (3 × 10 mL). The combined
organic extracts were dried over MgSO4 (anhd.), filtered and then
concentrated under vacuum on a rotary evaporator to give a crude
product, from which was isolated, by flash chromatography with
silica gel and hexane-ethyl acetate (95:5), 0.27 g (84%) of a 1:1
1
1068 (s), 968 (m), 933 (m), 900 (m), 840 (w), 754 (w) cm-1; H
NMR (200 MHz, CDCl3) δ 4.76 (s, 1H), 3.81-3.56 (m, 4H), 3.18
(bs, 1H), 1.59 (s, 6H), 1.28 (t, J ) 7.0 Hz, 6H); 13C NMR (50
MHz, CDCl3) δ 182.6, 101.2, 99.6, 81.7, 79.2, 64.8, 62.9, 30.3,
14.9; MS (ESI) m/z 197 (10), 169 (60), 155 (10), 111 (65), 103
(40); HRMS Calcd for C19H13O3 [M+· - EtO·] 169.0865, found
+
1
mixture (based on H NMR-spectroscopy) of the (E) and the (Z)
169.0865.
isomers of 12. IR (film) 3083 (w), 3063 (w), 3032 (w), 2978 (s),
2932 (m), 2883 (m), 1745 (s), 1698 (s), 1624 (s), 1495 (w), 1450
(m), 1371 (s), 1317 (m), 1231 (s), 1181 (m), 1160 (m), 1112 (s),
1062 (s), 1027 (s), 982 (w), 912 (w), 894 (w), 822 (w), 751 (m),
5,5-Diethoxy-1,1-dimethyl-4-oxopent-2-ynyl Acetate (16). Hy-
droxyketone 15 (0.21 g, 1.0 mmol) was dissolved in CHCl3 (10
mL) and added dropwise to a stirred solution of acetic anhydride
(1.01 g, 10.0 mmol), pyridine (0.24 g, 3.0 mmol) and DMAP (0.018
g, 0.15 mmol) in CHCl3 (3 mL) kept at rt. The reaction mixture
was stirred at this temperature for 14 h and a saturated aqueous
1
700 (s) cm-1; H NMR (400 MHz, CDCl3) δ 7.55-7.30 (m, 5H),
7.29 and 6.54 (2s, 1H, E and Z in a 1:1 ratio), 6.83 and 6.19 (2s,
3442 J. Org. Chem. Vol. 74, No. 9, 2009

Synthesis of Tri- and Tetra-Substituted Furans
solution of NaHCO3 (20 mL) was then added. The phases were
separated, the aqueous phase was extracted with DCM (3 × 20
mL), and the combined organic extracts were dried over MgSO4
(anhd.). Filtration followed by concentration under vacuum on a
rotary evaporator furnished a crude product, from which 16 (0.23
g, 89%) was isolated as a colorless liquid by flash chromatography
using hexanes-ethyl acetate (95:5) as eluent. IR (film) 2980 (m),
2936 (m), 2916 (s), 2895 (s), 2222 (m), 1747 (s), 1698 (s), 1444
(w), 1370 (s), 1259 (m), 1239 (s), 1188 (m), 1138 (s), 1086 (s),
86%) was isolated as a colorless liquid by flash chromatography
using hexanes-ethyl acetate (80:20) as eluent. IR (film) 3466 (m),
2977 (s), 2931 (m), 2899 (m), 2877 (m), 1662 (s), 1583 (s), 1445
(m), 1444 (m), 1393 (m), 1374 (m), 1324 (m), 1284 (s), 1170 (m),
1122 (s), 1090 (s), 1064 (s), 982 (m), 929 (w), 865 (w), 822 (w),
1
751 (m), 702 (m) cm-1; H NMR (400 MHz, CDCl3) δ 5.05 (s,
1H), 4.57 (s, 1H), 3.71-3.58 (m, 4H), 1.96 (s, 3H), 1.62 (s, 3H),
1.33 (s, 6H), 1.23 (t, J ) 7.0 Hz, 3H), 1.22 (t, J ) 7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 190.9, 152.4, 134.2, 101.0, 98.9,
89.7, 62.2, 28.2, 17.2, 15.1, 11.2; MS (ESI) m/z 273 (25), 255 (100),
1
1079 (s), 1017 (m), 969 (w), 912 (w), 871 (w), 840 (w) cm-1; H
227 (45); HRMS Calcd for C14H23O4 [M+· - HO·] 255.15963
+
NMR (400 MHz, CDCl3) δ 4.78 (s, 1H), 3.75-3.60 (m, 4H), 2.04
(s, 3H), 1.71 (s, 6H), 1.27 (t, J ) 7.1 Hz, 3H), 1.25 (t, J ) 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 182.7, 169.0, 101.3, 96.1,
81.9, 70.8, 63.0, 28.1, 21.6, 15.0; MS (ESI) m/z 257 (25), 211 (55),
found, 255.16275.
Acknowledgment. Liberal financial support (to L.K.S.) from
Research Council of Norway is highly appreciated. Thanks are
also due to the Norwegian Centre for International Studies and
the Erasmus Programme for scholarships (to M.S. and M.H.,
respectively). Recording of mass spectra by Dr. Dag Egeberg
at Norwegian University of Environmental and Biological
Sciences and by Terje Lygre and Egil Nodland at University
of Bergen is highly appreciated. Institut fu¨r Organische Chemie,
Universita¨t Wien, Austria and Professor Udo H. Brinker are
gratefully acknowledged for excellent working conditions during
a recent sabbatical stay. Finally, valuable comments and
suggestions from the referees are highly appreciated.
197 (100), 153 (35). HRMS Calcd for C13H21O5 [M + H]+
+
257.13890, found 257.14186.
2,2-Diethoxy-1-(2,5-dihydro-2-hydroxy-2,4,5,5-tetramethylfu-
ran-3-yl)ethanone (17). CuI (0.040 g, 0.21 mmol) was dispersed
in anhydrous THF (3 mL) and cooled to -30 °C. MeLi (0.28 mL,
1.6 M, 0.44 mmol) was added dropwise in 5 min. When the addition
was complete the reaction mixture was allowed to stir at -30 °C
for 30 min before it was cooled to -78 °C. A solution of 16 (0.054
g, 0.21 mmol) in anhydrous THF (1 mL) was then added dropwise
to the reaction mixture in 3 min and the mixture was stirred for
additional 60 min at -78 °C before a saturated aqueous solution
of NH4Cl (5 mL) was added in one portion, also at -78 °C. The
hydrolysate was allowed to reach room temperature, the phases
were separated, and the aqueous phase was extracted with diethyl
ether (3 × 10 mL). The combined organic extracts were dried over
MgSO4 (anhd.), filtered and then concentrated under vacuum on a
rotary evaporator to give a crude product, from which 17 (0.049 g,
Supporting Information Available: 1H NMR and 13C NMR
spectra for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO9003986
J. Org. Chem. Vol. 74, No. 9, 2009 3443