Gold(III) chloride catalyzed synthesis of chiral substituted 3-formyl furans from carbohydrates: Application in the synthesis of 1,5-dicarbonyl derivatives and furo[3,2-c]pyridine

Article abstract of DOI:10.1002/chem.201402286

This report describes a gold(III)-catalyzed efficient general route to densely substituted chiral 3-formyl furans under extremely mild conditions from suitably protected 5-(1-alkynyl)-2,3-dihydropyran-4-one using H₂O as a nucleophile. The react

Full text of DOI:10.1002/chem.201402286

DOI: 10.1002/chem.201402286
Full Paper
&
Chiral Furans
Gold(III) Chloride Catalyzed Synthesis of Chiral Substituted 3-
Formyl Furans from Carbohydrates: Application in the Synthesis
of 1,5-Dicarbonyl Derivatives and Furo[3,2-c]pyridine
Kanchan Mal, Abhinandan Sharma, and Indrajit Das*[a]
Abstract: This report describes a gold(III)-catalyzed efficient
general route to densely substituted chiral 3-formyl furans
under extremely mild conditions from suitably protected 5-
(1-alkynyl)-2,3-dihydropyran-4-one using H2O as a nucleo-
phile. The reaction proceeds through the initial formation of
an activated alkyne–gold(III) complex intermediate, followed
by either a domino nucleophilic attack/anti-endo-dig cycliza-
tion, or the formation of a cyclic oxonium ion with subse-
quent attack by H2O. To confirm the proposed mechanistic
pathway, we employed MeOH as a nucleophile instead of
H2O to result in a substituted furo[3,2-c]pyran derivative, as
anticipated. The similar furo[3,2-c]pyran skeleton with
a hybrid carbohydrate–furan derivative has also been ach-
ieved through pyridinium dichromate (PDC) oxidation of
a substituted chiral 3-formyl furan. The corresponding pro-
tected 5-(1-alkynyl)-2,3-dihydropyran-4-one can be synthe-
sized from the monosaccharides (both hexoses and pentose)
following oxidation, iodination, and Sonogashira coupling
sequences. Furthermore, to demonstrate the potentiality of
chiral 3-formyl furan derivatives, a TiBr4-catalyzed reaction of
these derivatives has been shown to offer efficient access to
1,5-dicarbonyl compounds, which on treatment with
NH4OAc in slightly acidic conditions afforded substituted
furo[3,2-c]pyridine.
Introduction
metalated furans with the carbonyl group or various other
electrophiles,[6] a Grignard-type addition reaction of furan car-
baldehyde with a variety of nucleophiles,[7] and Lewis acid cat-
alyzed Friedel–Crafts-type reactions of various carbonyl com-
pounds with furan derivatives are more common.[8] Chiral
products may be accessed by the use of chiral pool precursors
such as carbohydrates,[9] by enzymatic resolution of racemic
mixtures,[10] or by kinetic resolution of starting materials.[11] In
addition to the Garcia Gonzalez reaction,[12] addition/oxidative
rearrangement of 3-furfurals with N-bromosuccinimide (NBS)[13]
and tandem Suzuki–Miyaura coupling followed by acid-cata-
lyzed cyclization[14] also offer new ways to obtain polyhydroxyl-
ated furans.
Diversely substituted furans form an important structural motif
prevalent in a biologically indispensable natural products, sev-
eral pharmaceuticals, agrochemicals, as well as flavoring and
aroma compounds.[1] They are also useful building blocks
found in synthetic organic chemistry, materials chemistry, and
self-healing macromolecular materials.[2] Moreover, the func-
tionalized furan core has attracted tremendous attention for
the design of numerous intermediates and as versatile starting
materials for the synthesis of heterocyclic as well as acyclic
compounds.[2a,3] Importantly, substituted chiral furans find
widespread applications as versatile synthetic intermediates
and are commonly found in many bioactive natural products
(Figure 1).[2f,4]
Furthermore, substituted 3-formyl furan derivatives have
found widespread applications as synthetic intermediates for
the synthesis of bioactive natural products.[15] However, there
is a lack of general methods to synthesize them;[16] the few
methods available mainly involve the metalation of furan rings
Despite the development of numerous methods for the syn-
thesis of highly substituted furans in the past few years, includ-
ing transition-metal-mediated cyclization and cycloisomeriza-
tion methods,[2–5] devising efficient access to substituted chiral
furans from common precursors remains a challenging task.
Among the many methods developed so far, the reaction of
[a] K. Mal, A. Sharma, Dr. I. Das
Chemistry Division
CSIR-Indian Institute of Chemical Biology
4, Raja S. C. Mullick Road
Jadavpur, Kolkata 700032 (India)
Fax: (+91)33-2473-5197
E-mail: id@csiriicb.in
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402286.
Figure 1. Examples of bioactive chiral furan-containing natural products.
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followed by formylation.[6b,17] This approach is somewhat re-
stricted, because after metalation the addition of electrophiles
to furan rings occurs preferentially at the C-2 and C-5 posi-
tions, and there is always a great deal of difficulty separating
them from the unwanted regioisomers. The corresponding
chiral products are also potentially important synthetic inter-
mediates; however, their utility is very much underexplored
owing to the lack of general methods to synthesize them.[13]
As a consequence, establishing more efficient routes to highly
substituted chiral 3-formyl furans from easily accessible starting
materials continues to captivate synthetic chemists.
steps by following a well-documented literature procedure
(see the Supporting Information for details).[18] To obtain the
carbohydrate congeners, we used different hexoses such as d-
glucose, d-galactose, l-rhamnose, and l-fucose as well as the
pentose sugar d-xylose.[18,19] Common protecting groups such
as ꢀCOCH3 (acetyl), ꢀCH2Ph (benzyl), and ꢀTBDMS (tert-butyldi-
methylsilyl) were used for hydroxyl-group protection in mono-
saccharides. 2-Alkynylated sugars (3a–p) were synthesized by
the [Pd(PPh3)2Cl2]/CuI-catalyzed standard Sonogashira coupling
reaction (Scheme 2).[16c,20]
Herein, we report a gold(III)-catalyzed efficient route to
highly substituted chiral 3-formyl furans under extremely mild
conditions using H2O as a nucleophile from a suitably protect-
ed 5-(1-alkynyl)-2,3-dihydropyran-4-one. The latter can be pre-
pared from the corresponding appropriately functionalized
monosaccharides or commercially available glycals in a few
steps following oxidation, iodination, and Sonogashira cou-
pling sequences. To confirm the proposed mechanistic path-
way in the gold-catalyzed reaction, we employ MeOH as a nu-
cleophile instead of H2O to result in a substituted furo[3,2-
c]pyran derivative. The synthesis of a similar skeleton with
a hybrid carbohydrate–furan derivative was also carried out
with pyridinium dichromate (PDC) oxidation of chiral 3-formyl
furan. Furthermore, the substituted 3-formyl furans could then
be smoothly subjected to a TiBr4-catalyzed process to produce
1,5-dicarbonyl compounds, which on treatment with NH4OAc
under slightly acidic conditions afforded furo[3,2-c]pyridine.
Results and Discussion
A detailed retrosynthetic strategy towards substituted chiral
furans from suitably substituted 2-iodoglycals as starting mate-
rial is depicted in Scheme 1. 2-Iodoglycals (2) can easily be syn-
thesized from the corresponding appropriately functionalized
monosaccharides or commercially available glycals in a few
Scheme 2. Synthesis of 5-(1-alkynyl)-2,3-dihydropyran-4-ones from substitut-
ed 2-iodoglycals by Sonogashira coupling.
We used a variety of different aromatic, aliphatic, and TMS-
protected commercially available terminal alkynes as coupling
partners. It was found that the alkynes with electron-neutral
(3a–e) or electron-donating substituents (3 f–j) on the aromat-
ic ring resulted in 2-alkynylated carbohydrates in good to ex-
cellent yields (57–90%; Scheme 2). However, the yields were
moderate (40–58%; Scheme 2) when substrates with electron-
withdrawing substituents (3k–n) on the aromatic ring were
employed.
Importantly, trimethylsilyl acetylene was also found to be
amenable to the reaction conditions that afforded the corre-
sponding 2-alkynylated products (3o–p, Scheme 2) in greater
than 70% yields. However, the coupling reaction with alkylace-
Scheme 1. Retrosynthetic analysis and synthetic applications of polyhydrox-
ylated chiral substituted 3-formyl furans from monosaccharides (both hexo-
ses and pentoses). PG=protecting group.
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tylene did not produce the desired product by following the
general procedure (Scheme 2). After several attempts, the cou-
pling reaction with alkylacetylenes was successfully achieved
with [Pd(PPh3)2Cl2]/CuI/Et3N in moderate yields (3q–s, 52–56%;
Scheme 2) by following the literature procedure.[20b,c]
essary to conduct the reaction for a longer reaction time
(Table 1, entry 11; 20 h, 89%). Inspired by these cationic AuI
catalyst results, we also explored the scope of this cyclization
reaction with Ph3PAuCl+AgBF4. We observed that 10 mol% of
this catalyst was not as effective as other gold(I) catalysts
(Table 1, entry 12; 87%). Interestingly, a catalytic amount of
AuCl3 (0.5, 0.7, and 1 mol%) was also found to be equally ef-
fective (Table 1, entries 14–16; 90–91% yield), but once again
longer reaction times were necessary. The use of 5 mol% AuCl3
accelerated the transformation (Table 1, entry 17), and the reac-
tion proceeded to completion within 10 min (Table 1). The
yield was improved further with 10 mol% of AuCl3 (Table 1,
entry 18; 96% yield). AuBr3 was also found to be almost equal-
ly effective (Table 1, entry 19). However, the use of other sol-
vents (CH3CN and CH2Cl2) failed to improve the yield (Table 1,
entries 20 and 21). Thus, we concluded that the use of
10 mol% AuCl3 in THF at room temperature constitutes the
optimized reaction conditions.
During our initial investigations, we occasionally found that
a solution of 3a in EtOAc showed a marked propensity to un-
dergo cyclization upon exposure to open air to result in 4a in
50% yield after 48 h. A systematic study of this transformation
(to shorten the time period and to achieve higher yields)
showed that treating 3a in THF with H2O (0.2 mL) as a nucleo-
phile at room temperature furnished 4a in 55% yield (Table 1,
entry 1). Interestingly, treatment with Brønsted acids such as
methanesulfonic acid (MeSO3H), HCl, and HBr failed to improve
the yield (32–51%) even after 12–26 h (Table 1, entries 2–4).
Other metal catalysts such as CuI, CuBr, AgNO3, PPh3AuCl, and
AuCl also catalyzed this transformation, but resulted in moder-
ate to lower yields (Table 1, entries 5–9). However, the more re-
active cationic AuI catalysts Ph3PAuNTf2 and PPh3AuCl+AgOTf
(10 mol%) accelerated the transformations with excellent
yields, and the reaction proceeded to completion within 10 to
15 min (Table 1, entries 10 and 13; 90%); whereas 1 mol% of
Ph3PAuNTf2 also catalyzed this transformation, but it was nec-
Having established the optimized protocol, we next investi-
gated the substrate scope and generality for this transforma-
tion with H2O as a nucleophile. Scheme 3 summarizes the re-
sults. In general, the reaction is tolerant to variation in substi-
tution/protection at both the alkyne and the 4- and 6-positions
of the hexopyranose ring. It is interesting to note that the elec-
tronic nature of the aromatic substituents on the alkyne
moiety and the substitution/protection in carbohydrate conge-
ners played a significant role in the yield of the reaction. With
benzyl as a protecting group for the hexopyranose OH groups,
substrates that contain electron-neutral (4a,b,d,e) or electron-
donating (4 f,g,i,j) substituents on the terminal alkyne resulted
in chiral substituted 3-formyl furans in moderate to excellent
yields (Scheme 3; 43–96%). However, substrates that contain
electron-withdrawing substituents delivered the corresponding
chiral furans (4k,l,n) only in moderate yields (Scheme 3; 42–
67%). Furthermore, replacement of the aryl group with an
alkyl group in the terminal alkyne was also found to be com-
patible under the reaction conditions and delivered the corre-
sponding chiral furans (4q–s) in moderate to good yields
(Scheme 3; 52–82%).
Table 1. Reaction optimization for substituted chiral 3-formyl furans from
3-benzyloxy-2-benzyloxymethyl-5-phenylethynyl-2,3-dihydropyran-4-
one.[a]
Entry
Catalyst
Mol [%]
t
Yield[b] [%]
1
2
3
4
no catalyst
MeSO3H
HCl
HBr/AcOH
CuI
CuBr
AgNO3
PPh3AuCl
AuCl
PPh3AuNTf2
PPh3AuNTf2
PPh3AuCl+AgBF4
PPh3AuCl+AgOTf
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
–
20
10
10
10
10
10
10
10
10
1
10
10
1
0.7
0.5
5
48 h
12 h
24 h
26 h
12 h
10 h
12 h
12 h
10 min
10 min
20 h
15 h
15 min
5 h
55
32
51
50
52
42
73
65
71
90
89
87
90
91
90
90
92
96
90
42
77
5
6[c]
7
When we replaced the benzyl protection for OH groups with
a TBDMS group, it lowered the yield dramatically (4c,h,m,
Scheme 3; 21–49%). This might be attributed to the acid hy-
drolysis of the primary TBDMS group during the course of the
reaction, which results from the mild acidic property of AuCl3
in H2O, as it is well-documented in the literature that a secon-
dary benzylic hydroxyl group protected by TBDMS substitution
is stable under gold catalysis.[21] However, the purported prod-
ucts remained to be isolated by silica-gel column chromatogra-
phy. Thus, the possibility of competing intermolecular Reppe-
type vinylation that results from the C-4 hydroxyl group of the
hexopyranose ring might play an important role in the low
yields with the TBDMS group.[21b,22a]
8
9
10
11
12
13
14
15
16
17
18
19
20[d]
21[e]
18 h
26 h
10 min
10 min
10 min
10 min
10 min
10
10
10
10
AuBr3
AuCl3
AuCl3
[a] By stirring a mixture of 3a (0.03 g, 0.071 mmol, 1.0 equiv) and catalyst
(mol%) in dry THF (2 mL) under an Ar atmosphere at room temperature
(20–258C), employing time as noted, followed by quenching with H2O.
[b] Yields are of isolated products. [c] Reaction was performed at 508C.
[d] Reaction was carried out in acetonitrile. [e] Reaction was carried out in
dichloromethane; Tf=trifluoromethane sulfonyl.
To achieve higher yields for the entries with lower than 50%
yields (Scheme 3), the more reactive cationic gold(I) catalyst
was examined.[22b,c] To our surprise, when we treated 3c with
Ph3PAuNTf2 (10 mol%)/THF/H2O at room temperature, the cor-
responding 4c was isolated in 81% yield, and the reaction pro-
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cation or storing them for a long time. The structures of 3-
formyl furan products were assigned by 2D NMR spectroscopy
(see the Supporting Information).
The probable mechanism of the reaction may be explained
on the basis of that proposed for the chromones system.[23]
After the initial formation of an activated alkyne–gold inter-
mediate in the presence of AuCl3, it would undergo either
a domino nucleophilic attack by H2O followed by anti-endo-dig
cyclization (Scheme 4, path A) or the formation of a cyclic oxo-
nium ion with subsequent attack by H2O (Scheme 4, path B).
Scheme 4. A plausible mechanism for the formation of chiral substituted
furan.
Scheme 3. AuCl3- and Ph3PAuNTf2-catalyzed synthesis of substituted chiral 3-
formyl furans from protected 5-(1-alkynyl)-2,3-dihydropyran-4-ones.
Inspired by the above findings, and to further exploit the
potential of AuCl3 as a catalyst for chiral substituted furan syn-
thesis, the TMS-protected 2-alkynylated glycal derivatives (3o
and 3p) were treated under the standard reaction condition-
s.[23a] The results are shown in Scheme 5. To our delight, 3o
also underwent AuCl3-catalyzed cyclization, and the corre-
sponding furan derivative 4o was obtained in only 9% yield.
In addition, products 4oa and 4ob were also isolated in 11
and 16% yields, respectively (Scheme 5). Formation of 4ob
could be explained on the basis of removal of the TMS group
either prior to or soon after cyclization under slightly acidic re-
action conditions (AuCl3/H2O), whereas 4oa resulted from
a 1,2-Si migration from C-5 to the carbenoid center generated
at C-4.
ceeded to completion within 20 min. However, we observed
that use of 0.5 mol% Ph3PAuNTf2 was not effective to catalyze
this transformation (46% yields), even after 44 h. Similarly,
under these remarkably mild reaction conditions, the other 2-
alknylated glycals (3d and 3h) were converted to their respec-
tive furans (4d and 4h) in moderate to good yields relative to
the AuCl3-catalyzed reaction (Scheme 3). Unfortunately, 3k and
3m did not produce the corresponding 4k and 4m in satisfac-
tory yields under the same conditions, ostensibly owing to the
presence of a strong electron-withdrawing (ꢀNO2) group on
the aromatic ring (Scheme 3).
All the above reactions in Scheme 3 proceeded to full con-
version to the product irrespective of the starting materials
used, as monitored by TLC. For some of the entries, the drop
in yield was due to the inherent reactivity of these systems as
well as degradation of some of the products during column
chromatography (with both silica gel and neutral or basic alu-
mina). Otherwise, most of the substituted chiral furan alde-
hydes were stable, and we did not find any difficulty in purifi-
This unique 1,2-Si migration is particularly attractive as it
allows the synthesis of hitherto inaccessible unsymmetrical 2,3-
disubstituted C-4 silylated chiral furans.[16a] Further work is in
progress to increase the yield of the desired product. A perusal
of the literature also revealed that the 1,2-Si migration is kineti-
cally favored over 1,2-H migration in the case of an Auꢀcar-
bene intermediate.[2a,24] Switching to the galacto substrate 3p
also revealed the same situation (furan derivative 4p, 35%,
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furo[3,2-c]pyran-4-one (5b) could be possible upon PDC oxida-
tion of chiral substituted furan 4a (Scheme 6; 40%).[26]
To demonstrate the potential utility of the highly substituted
polyhydroxylated furan derivatives, we undertook a synthesis
of
2-phenyl-substituted
furo[3,2-c]pyridine.
Substituted
furo[3,2-c]pyridines form a key structural unit in drugs and bio-
logically active natural products and exhibit a wide range of
pharmaceutical activities.[27] Owing to their potential applica-
tions, a number of synthetically useful routes have been devel-
oped for their synthesis.[28] Furthermore, a literature survey re-
vealed that treatment of a,b-unsaturated 1,5-dicarbonyl deriva-
tives with NH4OAc under mild acidic conditions delivered the
corresponding substituted pyridine in good to excellent
yield.[29]
We therefore became interested in the synthesis of the key
intermediate a,b-unsaturated 1,5-dicarbonyl derivatives from
our synthesized furan products. When we treated 4a or 4b
with TiBr4 (2 equiv) in toluene under reflux conditions, the cor-
responding 1,5-dicarbonyl derivative 6 was isolated in 43%
yield (Scheme 7).
Scheme 5. Scope for the gold-catalyzed synthesis of polyhydroxylated chiral
furans from TMS-protected 2-alkynylated glycals.
and desilylated product 4pb, 30%), except that the 1,2-Si mi-
gration product 4pa was isolated only in trace amount
(Scheme 5). To achieve higher yields for the unsymmetrical 2,3-
disubstituted C-4 silylated chiral furans, the more reactive cat-
ionic gold(I) catalysts were examined. To our great disappoint-
ment, when we treated 3p with 10 mol% Ph3PAuNTf2 and
PPh3AuCl+AgOTf, respectively, only the corresponding 4pb
(Scheme 5; 30–32%) was isolated, devoid of any 4p and 4pa.
In addition, product 4pc, which resulted from the desilylation
of 3p before cyclization, was also obtained in 34 and 18%
yields, respectively (see the Supporting Information). Subse-
quently, we successfully performed the PPh3AuNTf2-catalyzed
cyclization reaction of 4pc to yield 4pb (Scheme 5; 48%).
Interestingly, when MeOH was used as a nucleophile instead
of H2O in the AuCl3-catalyzed cyclization, the corresponding
Scheme 7. Synthesis of substituted 2-phenylfuro[3,2-c]pyridine through 1,5-
dicarbonyl derivative.
substituted
4-methoxy-2-phenyl-6,7-dihydro-4H-furo[3,2-
c]pyran 5a was isolated from 3c in moderate yield (Scheme 6;
55%),[25] which might be considered a hybrid carbohydrate–
furan derivative, and also confirmed the mechanistic pathway
described in Scheme 4. The stereochemistry of MeOH addition
was assigned on the basis of NOESY experiments (see the Sup-
porting Information). Furthermore, synthesis of substituted
The mechanism of the reaction might be explained on the
basis of generation of the oxonium cationic species (II) through
TiBr4-mediated formation of complex (I) with secondary ꢀOBn
group, as described in Scheme 7.[30] Rearomatization of the fur-
anoid ring and subsequent tautomerization afforded a,b-unsa-
turated 1,5-dicarbonyl derivative 6. With the a,b-unsaturated
1,5-dicarbonyl precursor in hand, we next turned our attention
to the synthesis of substituted furo[3,2-c]pyridine following the
literature procedure.[29] The treatment of 6 with EtOH/NH4OAc
under mild acidic conditions at 408C indeed delivered the cor-
responding 2-phenyl-substituted furo[3,2-c]pyridine 7 in 60%
yield (Scheme 7).
Conclusion
In conclusion, we have successfully developed an efficient gen-
eral route to densely functionalized chiral 3-formyl furans from
suitably protected 5-(1-alkynyl)-2,3-dihydropyran-4-ones using
catalytic AuCl3 and water as a nucleophile. The reactions pro-
Scheme 6. Synthesis of substituted furo[3,2-c]pyran derivatives.
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product was extracted with EtOAc. The combined organic layers
were dried over anhydrous Na2SO4 and filtered, and the filtrate was
concentrated under reduced pressure to obtain a residue. The
crude residue was purified by using silica gel column chromatogra-
phy (230–400 mesh particle size; eluent: ethyl acetate/n-hexane) to
obtain 3q–s.
ceeded under mild conditions and resulted in moderate to ex-
cellent yields. The protected 5-(1-alkynyl)-2,3-dihydropyran-4-
ones have been prepared from the corresponding monosac-
charides following oxidation, iodination, and Sonogashira cou-
pling sequences. The potential of this approach has been de-
scribed by the preparation of a substituted furo[3,2-c]pyridine
derivative by following two-step reaction sequences: a TiBr4-
catalyzed reaction of the 3-formyl furan derivatives resulted in
the 1,5-dicarbonyl compound, which on treatment with
NH4OAc under slightly acidic conditions afforded substituted
furo[3,2-c]pyridine. The scope and limitations of these new
densely functionalized chiral furans towards synthesis of bio-
logically active heterocycles are currently under study in our
laboratory.
3-Benzyloxy-2-benzyloxymethyl-5-phenylethynyl-2,3-dihy-
dropyran-4-one (3a)
Compound 2a (0.1 g, 0.222 mmol) was converted to 3a (0.08 g,
85%) by following general procedure A: eluent, EtOAc/n-hexane
(8%); ½aꢁ2D0 = +147 (c=0.1 in MeOH); yellow gum. 1H NMR
(300 MHz, CDCl3): d=7.74 (s, 1H), 7.47–7.50 (m, 2H), 7.30–7.38 (m,
13H), 5.08 (d, J=11.1 Hz, 1H), 4.62 (d, J=10.8 Hz, 1H), 4.51–4.64
(m, 3H), 4.29 (d, J=10.8 Hz, 1H), 3.82 ppm (d, J=3.0 Hz, 2H);
13C NMR (75 MHz, CDCl3): d=190.3, 165.3, 137.3, 137.1, 131.6
(2CH), 128.5 (4CH), 128.4 (2CH), 128.2 (3CH), 128.1, 127.9, 127.8
(2CH), 122.9, 103.7, 92.3, 81.6, 79.3, 74.5 (CH2), 73.7, 73.6 (CH2),
67.7 ppm (CH2); IR (KBr): n˜max =2217, 1694, 1604, 1588, 1247, 1149,
Experimental Section
General information
1102 cmꢀ1
;
HRMS (ESI): m/z calcd for C28H24O4Na [M+Na]+:
447.1573; found: 447.1943.
Melting points were determined in open-end capillary tubes and
are uncorrected. TLC was performed on silica gel plates (Merck
silica gel 60, f254), and the spots were visualized with UV light (254
and 365 nm) or by charring the plate dipped in 5% H2SO4/MeOH
3-Benzyloxy-2-benzyloxymethyl-5-phenylethynyl-2,3-dihy-
dropyran-4-one (3b)
1
or 5% H2SO4/vanillin/EtOH solution. H (300 and 600 MHz) and 13C
Compound 2b (0.1 g, 0.222 mmol) was converted to 3b (0.085 g,
90%) by following general procedure A: eluent, EtOAc/n-hexane
(10%); ½aꢁ2D0 = +66 (c=0.1 in MeOH); yellow gum. 1H NMR
(300 MHz, CDCl3): d=7.79 (s, 1H), 7.48–7.51 (m, 2H), 7.30–7.37 (m,
13H), 4.75 (d, J=11.7 Hz, 1H), 4.47–4.60 (m, 4H), 3.93 (dd, J=6.9,
10.2 Hz, 1H), 3.82 (d, J=2.1 Hz, 1H), 3.78 ppm (dd, J=5.4, 10.2 Hz,
1H); 13C NMR (75 MHz, CDCl3): d=186.4, 165.7, 137.2, 136.6, 131.5
(2CH), 128.4 (2CH), 128.4 (2CH), 128.3 (2CH), 128.2, 128.2 (2CH),
128.0, 127.9, 127.7 (2CH), 122.9, 103.5, 92.4, 81.1, 79.8, 73.6 (CH2),
73.4, 72.0 (CH2), 67.2 ppm (CH2); IR (neat): n˜max =2218, 1683, 1588,
1367, 1256 cmꢀ1; HRMS (ESI): m/z calcd for C28H24O4Na [M+Na]+:
447.1573; found: 447.3194.
(75 and 150 MHz) NMR spectra were recorded in CDCl3 solvent
using TMS as the internal standard. HRMS (m/z) was measured
using EI and ESI techniques. Infrared (IR) spectra were recorded
using Fourier transform infrared spectroscopy; only intense peaks
are reported. Optical rotations were recorded at 589 nm.
A. General procedure for the synthesis of 3a–p
Corresponding iodo compounds (2a–g, 1.0 equiv) in dry THF
(10 mLmmolꢀ1) were placed separately into a flame-dried, two-
necked, round-bottomed flask equipped with a magnetic stir bar
and rubber septa. [PdCl2(PPh3)2] (0.05 equiv), terminal alkyne
(2.0 equiv), and CuI (0.1 equiv) were added into the flask at 08C
and then N,N-diisopropylethylamine (DIPEA; 3.0 equiv) was added
dropwise to the resulting mixtures and allowed to stir at room
temperature for the required times. After completion of the reac-
tion (TLC), saturated NH4Cl solution was added, and the product
was extracted with EtOAc. The combined organic layers were dried
over anhydrous Na2SO4 and filtered, and the filtrate was concen-
trated under reduced pressure to obtain a residue. The crude resi-
due was purified by using silica gel column chromatography (230–
400 mesh particle size; eluent: ethyl acetate/n-hexane) to obtain
3a–p. These compounds should not be either stored in solution or
exposed to open air for a long time, as they showed a marked pro-
pensity to undergo cyclization to result in mixtures of 3a–p and
4a–p. Owing to this tendency for cyclization, HRMS for some of
these derivatives were not matched exactly.
2-(tert-Butyldimethylsilanyloxymethyl)-3-hydroxy-5-phenyle-
thynyl-2,3-dihydropyran-4-one (3c)
Compound 2c (0.1 g, 0.26 mmol) was converted to 3c (0.079 g,
85%) by following general procedure A: eluent, EtOAc/n-hexane
(10%); ½aꢁ2D0 = +89 (c=0.1 in MeOH); brown gum. 1H NMR
(600 MHz, CDCl3): d=7.68 (s, 1H), 7.44–7.46 (m, 2H), 7.29–7.31 (m,
3H), 4.73–4.76 (m, 1H), 4.61 (d, J=6.6 Hz, 1H), 4.09 (dd, J=3.6,
11.4 Hz, 1H), 3.95 (dd, J=2.4, 11.4 Hz, 1H), 3.66 (brs, 1H), 0.87 (s,
9H), 0.05 ppm (d, J=9.0 Hz, 6H); 13C NMR (150 MHz, CDCl3): d=
189.6, 165.9, 131.6 (2CH), 128.2 (2CH), 128.2, 123.1, 102.1, 92.0,
82.5, 79.2, 68.5, 61.3 (CH2), 25.7 (3CH3), 18.2, ꢀ5.7, ꢀ5.8 ppm; IR
(KBr): n˜max =2214, 1691, 1602, 1588, 1253, 1140 cmꢀ1; HRMS (ESI):
m/z calcd for C20H26O4SiNa [M+Na]+: 381.1498; found: 381.1515.
3-Benzyloxy-2-methyl-5-phenylethynyl-2,3-dihydropyran-4-
one (3d)
B. General procedure for the synthesis of 3q–s
Corresponding iodo compounds (2a,b, 1.0 equiv) and the respec-
tive aliphatic terminal alkyne (2.0 equiv) were dissolved separately
in NEt3 (30 mLmmolꢀ1) in a flame-dried, two-necked, round-bot-
tomed flask equipped with a magnetic stir bar and rubber septa.
[PdCl2(PPh3)2] (5 mol%) and CuI (10 mol%) were subsequently
added into the flask, and the resulting mixtures were allowed to
stir at room temperature for the required times. After completion
of the reaction (TLC), saturated NH4Cl solution was added, and the
Compound 2d (0.1 g, 0.29 mmol) was converted to 3d (0.077 g,
84%) by following general procedure A: eluent, EtOAc/n-hexane
(8%); ½aꢁ2D0 =ꢀ159 (c=0.1 in MeOH); brown solid; m.p. 908C.
1H NMR (300 MHz, CDCl3): d=7.78 (s, 1H), 7.47–7.52 (m, 2H), 7.30–
7.41 (m, 8H), 4.81 (d, J=12.0 Hz, 1H), 4.52–4.56 (m, 2H), 3.62 (d,
J=2.4 Hz, 1H), 1.50 ppm (d, J=6.6 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=187.5, 166.3, 136.9, 131.6 (2CH), 128.4 (2CH), 128.4
&
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(2CH), 128.2 (3CH), 128.1, 123.0, 102.9, 92.3, 80.0, 79.0, 75.8, 71.9
(CH2), 15.0 ppm; IR (KBr): n˜max =2220, 1674, 1581, 1255 cmꢀ1; HRMS
(ESI): m/z calcd for C21H18O3Na [M+Na]+: 341.1154; found:
341.2915.
(75 MHz, CDCl3): d=192.3, 167.0, 159.7, 133.1 (2CH), 114.8, 113.9
(2CH), 102.3, 92.2, 83.9, 77.2, 67.0, 61.6 (CH2), 55.3, 25.8 (3CH3),
18.4, ꢀ5.3, ꢀ5.4 ppm; IR (KBr): n˜max =2207, 1677, 1607, 1512, 1251,
1240, 1140 cmꢀ1
;
HRMS (EI): m/z calcd for C21H28O5Si [M]+:
388.1706; found: 388.1704.
3-Benzyloxy-2-methyl-5-phenylethynyl-2,3-dihydropyran-4-
one (3e)
3-Benzyloxy-2-methyl-5-p-tolylethynyl-2,3-dihydropyran-4-
one (3i)
Compound 2e (0.1 g, 0.29 mmol) was converted to 3e (0.082 g,
89%) by following general procedure A: eluent, EtOAc/n-hexane
(5%); ½aꢁ2D0 =ꢀ186 (c=0.1 in MeOH); brown solid; m.p. 968C.
1H NMR (600 MHz, CDCl3): d=7.69 (s, 1H), 7.48–7.49 (m, 2H), 7.29–
7.40 (m, 8H), 5.03 (d, J=11.4 Hz, 1H), 4.67 (d, J=12.0 Hz, 1H), 4.60
(dq, J=6.6, 9.0 Hz, 1H), 3.78 (d, J=9.0 Hz, 1H), 1.45 ppm (d, J=
7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3): d=189.7, 165.2, 137.0,
131.6 (2CH), 128.5 (2CH), 128.5 (2CH), 128.2 (3CH), 128.1, 123.0,
Compound 2e (0.1 g, 0.29 mmol) was converted to 3i (0.085 g,
88%) by following general procedure A: eluent, EtOAc/n-hexane
(5%); ½aꢁ2D0 =ꢀ164 (c=0.1 in MeOH); white solid; m.p. 548C.
1H NMR (300 MHz, CDCl3): d=7.68 (s, 1H), 7.29–7.39 (m, 7H), 7.11
(d, J=7.8 Hz, 2H), 5.03 (d, J=11.4 Hz, 1H), 4.66 (d, J=11.7 Hz, 1H),
4.58 (dd, J=6.6, 9.3 Hz, 1H), 3.77 (d, J=9.3 Hz, 1H), 2.34 (s, 3H),
1.45 ppm (d, J=6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=189.8,
165.0, 138.3, 137.0, 131.4 (2CH), 129.0 (2CH), 128.5 (2CH), 128.4
(2CH), 128.1, 119.9, 103.6, 92.4, 79.3, 78.7, 77.9, 73.7 (CH2), 21.5,
17.0 ppm; IR (KBr): n˜max =2216, 1689, 1593, 1246, 1148 cmꢀ1; HRMS
(ESI): m/z calcd for C22H21O3 [M+H]+: 333.1490; found: 333.1439.
103.4, 92.2, 79.5, 79.4, 77.9, 73.7 (CH2), 17.0 ppm; IR (KBr): n˜max
=
2217, 1688, 1604, 1588, 1252, 1143 cmꢀ1; HRMS (ESI): m/z calcd for
C21H18O3Na [M+Na]+: 341.1154; found: 341.1152.
3-Benzyloxy-2-benzyloxymethyl-5-(4-methoxyphenylethyn-
yl)-2,3-dihydropyran-4-one (3 f)
3-Benzyloxy-5-(4-methoxyphenylethynyl)-2-methyl-2,3-dihy-
dropyran-4-one (3j)
Compound 2a (0.1 g, 0.222 mmol) was converted to 3 f (0.089 g,
89%) by following general procedure A: eluent, EtOAc/n-hexane
(15%); ½aꢁ2D0 = +146 (c=0.1 in MeOH); yellow gum. 1H NMR
(600 MHz, CDCl3): d=7.72 (s, 1H), 7.42–7.44 (m, 2H), 7.29–7.37 (m,
10H), 6.83–6.86 (m, 2H), 5.08 (d, J=11.4 Hz, 1H), 4.63 (d, J=
10.8 Hz, 1H), 4.59 (d, J=12.0 Hz, 1H), 4.51–4.55 (m, 2H), 4.29 (d,
J=11.4 Hz, 1H), 3.82 (m, 2H), 3.82 ppm (s, 3H); 13C NMR (150 MHz,
CDCl3): d=190.5, 164.9, 159.6, 137.3, 137.2, 133.1 (2CH), 128.5
(4CH), 128.4 (2CH), 128.1, 128.0, 127.8 (2CH), 115.1, 113.9 (2CH),
104.0, 92.3, 81.5, 77.8, 74.5 (CH2), 73.7, 73.6 (CH2), 67.7 (CH2),
55.3 ppm; IR (KBr): n˜max =2183, 1607, 1509, 1248 cmꢀ1; HRMS (ESI):
m/z calcd for C29H27O5 [M+H]+: 455.1858; found: 455.1334.
Compound 2e (0.1 g, 0.29 mmol) was converted to 3j (0.077 g,
76%) by following general procedure A: eluent, EtOAc/n-hexane
(15%); ½aꢁ2D0 =ꢀ194 (c=0.1 in MeOH); yellow gum. 1H NMR
(600 MHz, CDCl3): d=7.67 (s, 1H), 7.31–7.44 (m, 7H), 6.83–6.86 (m,
2H), 5.04 (d, J=11.4 Hz, 1H), 4.67 (d, J=11.4 Hz, 1H), 4.57–4.61 (m,
1H), 3.82 (s, 3H), 3.78 (d, J=9.6 Hz, 1H), 1.45 ppm (d, J=6.6 Hz,
3H); 13C NMR (150 MHz, CDCl3): d=189.9, 164.9, 159.6, 137.1, 133.1
(2CH), 128.5 (2CH), 128.5 (2CH), 128.1, 115.1, 113.9 (2CH), 103.7,
92.2, 79.3, 78.0, 77.9, 73.7 (CH2), 55.3, 17.0 ppm; IR (KBr): n˜max
=
1694, 1609, 1594, 1509, 1245 cmꢀ1; HRMS (ESI): m/z calcd for
C22H22O5Na [M+Na+H2O]+: 389.1366; found: 389.1379.
3-Benzyloxy-2-benzyloxymethyl-5-(4-methoxyphenylethyn-
yl)-2,3-dihydropyran-4-one (3g)
3-Benzyloxy-2-benzyloxymethyl-5-(4-nitrophenylethynyl)-
2,3-dihydropyran-4-one (3k)
Compound 2b (0.1 g, 0.222 mmol) was converted to 3g (0.063 g,
62%) by following general procedure A: eluent, EtOAc/n-hexane
(15%); ½aꢁ2D0 = +39 (c=0.1 in MeOH); brown solid; m.p. 848C.
1H NMR (600 MHz, CDCl3): d=7.76 (s, 1H), 7.43 (dt, J=2.4, 9.6 Hz,
2H), 7.28–7.37 (m, 10H), 6.84 (dt, J=2.4, 9.6 Hz, 2H), 4.74 (d, J=
11.4 Hz, 1H), 4.57 (d, J=11.4 Hz, 1H), 4.53–4.55 (m, 1H), 4.49 (dd,
J=6.6, 12.0 Hz, 2H), 3.93 (dd, J=6.6, 9.6 Hz, 1H), 3.81 (s, 3H), 3.80–
3.81 (m, 1H), 3.77 ppm (dd, J=6.0, 10.2 Hz, 1H); 13C NMR
(150 MHz, CDCl3): d=186.6, 165.4, 159.6, 137.3, 136.7, 133.1 (2CH),
128.5 (2CH), 128.4 (2CH), 128.4, 128.3, 128.1, 128.0, 127.8 (2CH),
115.0, 113.8 (2CH), 103.8, 92.4, 81.1, 78.3, 73.7 (CH2), 73.5, 72.0
(CH2), 67.3 (CH2), 55.2 ppm; IR (KBr): n˜max =2212, 1699, 1605, 1510,
1259, 1099 cmꢀ1; HRMS (ESI): m/z calcd for C29H26O5Na [M+Na]+:
477.1678; found: 477.2356.
Compound 2a (0.1 g, 0.222 mmol) was converted to 3k (0.06 g,
58%) by following general procedure A: eluent, EtOAc/n-hexane
(15%); ½aꢁ2D0 = +197 (c=0.1 in MeOH); yellow solid; m.p. 708C.
1H NMR (300 MHz, CDCl3): d=8.18 (d, J=8.7 Hz, 2H), 7.80 (s, 1H),
7.61 (d, J=8.7 Hz, 2H), 7.31–7.38 (m, 10H), 5.06 (d, J=11.1 Hz, 1H),
4.62 (d, J=11.1 Hz, 1H), 4.51–4.59 (m, 3H), 4.31 (d, J=10.8 Hz, 1H),
3.83 ppm (d, J=3.0 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=189.8,
166.3, 146.9, 137.2, 137.0, 132.1 (2CH), 130.0, 128.5 (4CH), 128.5,
128.2, 128.0, 127.8 (2CH), 123.6 (3CH), 103.0, 90.8, 85.3, 82.0, 74.5
(CH2), 73.7 (CH2), 73.6, 67.6 ppm (CH2); IR (KBr): n˜max 2213, 1681,
1594, 1581, 1522, 1345, 1252 cmꢀ1; HRMS (ESI): m/z calcd for
C28H23NO6Na [M+Na]+ 492.1423; found: 492.1452.
3-Benzyloxy-2-benzyloxymethyl-5-(4-nitrophenylethynyl)-
2,3-dihydropyran-4-one (3l)
2-(tert-Butyldimethylsilanyloxymethyl)-3-hydroxy-5-(4-me-
thoxyphenylethynyl)-2,3-dihydropyran-4-one (3h)
Compound 2b (0.1 g, 0.222 mmol) was converted to 3l (0.052 g,
50%) by following general procedure A: eluent, EtOAc/n-hexane
1
Compound 2 f (0.1 g, 0.26 mmol) was converted to 3h (0.058 g,
57%) by following general procedure A: eluent, EtOAc/n-hexane
(15%); ½aꢁ2D0 = +171 (c=0.1 in MeOH); white solid; m.p. 1048C.
1H NMR (300 MHz, CDCl3): d=7.82 (s, 1H), 7.43 (d, J=8.4 Hz, 2H),
6.86 (d, J=8.4 Hz, 2H), 4.46 (d, J=12.9 Hz, 1H), 4.22 (d, J=13.5 Hz,
1H), 4.13 (dd, J=3.6, 12.0 Hz, 1H), 4.05 (dd, J=3.6, 12.0 Hz, 1H),
3.83 (s, 3H), 3.56 (brs, 1H), 0.95 (s, 9H), 0.14 ppm (s, 6H); 13C NMR
(15%); ½aꢁ2D0 = +116 (c=0.2 in MeOH); red gum. H NMR (300 MHz,
CDCl3): d=8.19 (d, J=8.7 Hz, 2H), 7.84 (s, 1H), 7.63 (d, J=8.7 Hz,
2H), 7.28–7.38 (m, 10H), 4.71–4.77 (m, 1H), 4.48–4.60 (m, 4H), 3.95
(dd, J=6.9, 10.2 Hz, 1H), 3.85 (d, J=2.4 Hz, 1H), 3.78 ppm (dd, J=
5.4, 10.2 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=186.0, 166.7, 146.9,
137.2, 136.5, 132.1 (2CH), 129.9, 128.5 (2CH), 128.5 (2CH), 128.3
(2CH), 128.2, 128.0, 127.8 (2CH), 123.5 (2CH), 102.8, 90.9, 85.6,
Chem. Eur. J. 2014, 20, 1 – 15
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81.5, 73.7 (CH2), 73.3, 72.1 (CH2), 67.2 ppm (CH2); IR (KBr): n˜max
2216, 1582, 1516, 1341 cmꢀ1
HRMS (ESI): m/z calcd for
C28H23NO6Na [M+Na]+ 492.1423; found: 492.1390.
=
(CH2), ꢀ0.04 ppm (3CH3); IR (KBr): n˜max =2158, 1687, 1589, 1250,
1203, 1104 cmꢀ1; HRMS (ESI): m/z calcd for C25H29O4Si [M+H]+:
421.1835; found: 421.2083.
;
2-(tert-Butyldimethylsilanyloxymethyl)-3-hydroxy-5-(4-nitro-
phenylethynyl)-2,3-dihydropyran-4-one (3m)
3-Benzyloxy-2-benzyloxymethyl-5-hex-1-ynyl-2,3-dihydro-
pyran-4-one (3q)
Compound 2 f (0.1 g, 0.26 mmol) was converted to 3m (0.042 g,
40%) by following general procedure A: eluent, EtOAc/n-hexane
(15%); ½aꢁ2D0 = +135 (c=0.1 in MeOH); yellow solid; m.p. 1288C.
1H NMR (300 MHz, CDCl3): d=8.21 (d, J=8.7 Hz, 2H), 7.91 (s, 1H),
7.63 (d, J=8.7 Hz, 2H), 4.50 (d, J=13.2 Hz, 1H), 4.28 (d, J=13.2 Hz,
1H), 4.15 (dd, J=3.3, 12.0 Hz, 1H), 4.06 (dd, J=3.3, 12.0 Hz, 1H),
3.53 (brs, 1H), 0.95 (s, 9H), 0.15 ppm (s, 6H); 13C NMR (75 MHz,
CDCl3): d=191.8, 168.3, 147.0, 132.2 (2CH), 129.7, 123.6 (2CH),
101.4, 90.7, 84.4, 84.2, 67.0, 61.4 (CH2), 25.8 (3CH3), 18.4, ꢀ5.4 ppm
Compound 2b (0.1 g, 0.222 mmol) was converted to 3q (0.0467 g,
52%) by following general procedure B: eluent, EtOAc/n-hexane
(6%); ½aꢁ2D0 = +50 (c=0.1 in MeOH); yellow solid; m.p. 558C.
1H NMR (300 MHz, CDCl3): d=7.63 (s, 1H), 7.29–7.37 (m, 10H), 4.71
(d, J=12.0 Hz, 1H), 4.56 (d, J=11.7 Hz, 1H), 4.44–4.50 (m, 3H), 3.90
(dd, J=6.9, 9.9 Hz, 1H), 3.72–3.77 (m, 2H), 2.38 (t, J=6.9 Hz, 2H),
1.51–1.58 (m, 2H), 1.39–1.47 (m, 2H), 0.92 ppm (t, J=7.5 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=187.1, 165.2, 137.4, 136.8, 128.5
(2CH), 128.4 (2CH), 128.4 (2CH), 128.1, 128.0, 127.8 (2CH), 103.9,
93.6, 81.0, 73.7 (CH2), 73.5, 72.0 (CH2), 70.4, 67.4 (CH2), 30.8 (CH2),
22.0 (CH2), 19.2 (CH2), 13.6 ppm (CH3); IR (KBr): n˜max =2363, 1673,
1583, 1221 cmꢀ1; HRMS (ESI): m/z calcd for C26H28O4 [M+Na]+:
427.1886; found: 427.2039; HRMS (ESI): m/z calcd for C26H28O4
[M+Na+H2O]+: 445.1992; found: 445.1985.
(2CH3); IR (KBr): n˜max =2213, 1676, 1583, 1517, 1340, 1250 cmꢀ1
;
HRMS (ESI): m/z calcd for C20H25NO6SiNa [M+Na]+: 426.1349;
found: 426.1346.
3-Benzyloxy-2-benzyloxymethyl-5-(4-bromophenylethynyl)-
2,3-dihydropyran-4-one (3n)
3-Benzyloxy-2-benzyloxymethyl-5-hex-1-ynyl-2,3-dihydro-
pyran-4-one (3r)
Compound 2b (0.1 g, 0.222 mmol) was converted to 3n (0.056 g,
50%) by following general procedure A: eluent, EtOAc/n-hexane
(10%); ½aꢁ2D0 = +88 (c=0.1 in MeOH); white solid; m.p. 808C.
1H NMR (600 MHz, CDCl3): d=7.79 (s, 1H), 7.44–7.46 (m, 2H), 7.29–
7.37 (m, 12H), 4.75 (d, J=12.0 Hz, 1H), 4.56–4.59 (m, 2H), 4.50 (dd,
J=8.4, 11.4 Hz, 2H), 3.94 (dd, J=7.2, 10.2 Hz, 1H), 3.82 (d, J=
3.0 Hz, 1H), 3.78 ppm (dd, J=5.4, 10.2 Hz, 1H); 13C NMR (150 MHz,
CDCl3): d=186.3, 165.9, 137.3, 136.6, 133.0 (2CH), 131.5 (2CH),
128.5 (2CH), 128.5 (2CH), 128.4 (2CH), 128.2, 128.0, 127.8 (2CH),
122.5, 121.9, 103.3, 91.5, 81.3, 81.0, 73.7 (CH2), 73.4, 72.1 (CH2),
67.3 ppm (CH2); IR (KBr): n˜max =2220, 1684, 1595, 1580, 1485, 1368,
Compound 2a (0.1 g, 0.222 mmol) was converted to 3r (0.05 g,
56%) by following general procedure B: eluent, EtOAc/n-hexane
(6%); ½aꢁ2D0 = +114 (c=0.1 in MeOH); yellow gum. 1H NMR
(600 MHz, CDCl3): d=7.58 (s, 1H), 7.28–7.34 (m, 10H), 5.06 (d, J=
10.8 Hz, 1H), 4.59 (d, J=10.8 Hz, 1H), 4.49–4.57 (m, 2H), 4.45 (dt,
J=3.0, 11.4 Hz, 1H), 4.23 (d, J=10.8 Hz, 1H), 3.78 (d, J=3.0 Hz,
2H), 2.37 (t, J=7.2 Hz, 2H), 1.52–1.57 (m, 2H), 1.40–1.47 (m, 2H),
0.92 ppm (t, J=7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3): d=192.0,
165.7, 138.4, 138.2, 129.5 (4CH), 129.4 (2CH), 129.1, 128.9, 128.8
(2CH), 105.1, 94.5, 82.3, 75.4 (CH2), 74.6 (CH2), 74.6, 70.9, 68.7 (CH2),
1261, 1171, 1101, 1070 cmꢀ1
;
HRMS (ESI): m/z calcd for
C28H23BrO4Na [M+Na]+: 525.0678; found: 525.1106.
31.8 (CH2), 23.0 (CH2), 20.2 (CH2), 14.6 ppm (CH3); IR (neat): n˜max
=
2363, 1695, 1598, 1207 cmꢀ1; HRMS (ESI): m/z calcd for C26H28O4
[M+Na+H2O]+: 445.1992; found: 445.1560.
3-Benzyloxy-5-trimethylsilanylethynyl-2,3-dihydropyran-4-
one (3o)
3-Benzyloxy-2-benzyloxymethyl-5-cyclopentylethynyl-2,3-di-
hydropyran-4-one (3s)
Compound 2g (0.1 g, 0.30 mmol) was converted to 3o (0.068 g,
75%) by following general procedure A: eluent, EtOAc/n-hexane
(15%); ½aꢁ2D0 =ꢀ24 (c=0.1 in MeOH); yellowish white solid; m.p.
Compound 2a (0.1 g, 0.222 mmol) was converted to 3s (0.048 g,
52%) by following general procedure B: eluent, EtOAc/n-hexane
(7.5%); ½aꢁ2D0 = +25 (c=0.1 in MeOH); yellow gum. 1H NMR
(600 MHz, CDCl3): d=7.58 (s, 1H), 7.27–7.36 (m, 10H), 5.06 (d, J=
11.4 Hz, 1H), 4.59 (d, J=10.8 Hz, 1H), 4.50–4.57 (m, 2H), 4.44 (dt,
J=3.0, 11.4 Hz, 1H), 4.23 (d, J=11.4 Hz, 1H), 3.78 (d, J=3.0 Hz,
2H), 2.78 (quin, J=7.2 Hz, 1H), 1.94–1.99 (m, 2H), 1.71–1.77 (m,
2H), 1.63–1.68 (m, 2H), 1.53–1.60 ppm (m, 2H); 13C NMR (150 MHz,
CDCl3): d=192.0, 165.6, 138.4, 138.2, 129.5 (4CH), 129.4 (2CH),
129.1, 128.9, 128.8 (2CH), 105.1, 98.6, 82.3, 75.4 (CH2), 74.7, 74.6
(CH2), 70.4, 68.7 (CH2), 34.8 (2CH2), 31.8, 26.0 ppm (2CH2); IR (neat):
n˜max =2363, 1694, 1598, 1210 cmꢀ1; HRMS (ESI): m/z calcd for
C27H28O4 [M+Na+H2O]+: 457.1992; found: 457.1516.
1
708C. H NMR (300 MHz, CDCl3): d=7.72 (s, 1H), 7.31–7.37 (m, 5H),
4.85 (d, J=11.7 Hz, 1H), 4.60 (d, J=11.7 Hz, 1H), 4.55 (dd, J=5.7,
12.6 Hz, 1H), 4.40 (dd, J=3.6, 12.6 Hz, 1H), 3.83–3.86 (m, 1H),
0.23 ppm (s, 9H); 13C NMR (75 MHz, CDCl3): d=187.1, 167.0, 136.8,
128.5 (2CH), 128.2 (2CH), 128.1, 103.8, 97.7, 95.0, 72.7, 72.4 (CH2),
71.9 (CH2), ꢀ0.08 ppm (3CH3); IR (KBr): n˜max =2158, 1676, 1587,
1192 cmꢀ1 HRMS (ESI): m/z calcd for C17H20O3SiNa [M+Na]+:
;
323.1080; found: 322.6480.
3-Benzyloxy-2-benzyloxymethyl-5-trimethylsilanylethynyl-
2,3-dihydropyran-4-one (3p)
Compound 2b (0.1 g, 0.222 mmol) was converted to 3p (0.067 g,
72%) by following general procedure A: eluent, EtOAc/n-hexane
(8%); ½aꢁ2D0 = +70 (c=0.1 in MeOH); yellow gum. 1H NMR
(600 MHz, CDCl3): d=7.73 (s, 1H), 7.26–7.37 (m, 10H), 4.73 (d, J=
12.0 Hz, 1H), 4.56 (d, J=11.4 Hz, 1H), 4.46–4.50 (m, 3H), 3.90 (dd,
J=6.6, 9.6 Hz, 1H), 3.77 (d, J=2.4 Hz, 1H), 3.75 (dd, J=5.4, 10.2 Hz,
1H), 0.23 ppm (s, 9H); 13C NMR (150 MHz, CDCl3): d=186.4, 166.7,
137.3, 136.7, 128.5 (2CH), 128.4 (2CH), 128.3 (2CH), 128.1, 128.0,
127.8 (2CH), 103.6, 97.9, 95.2, 81.2, 73.7 (CH2), 73.3, 72.0 (CH2), 67.3
General procedure for the synthesis of 4a–s
In
a 25 mL flame-dried, two-necked, round-bottomed flask
equipped with a magnetic stir bar the corresponding substituted
ethynyl-2,3-dihydro-pyran-4-one (3a–s) was dissolved in dry THF
(2.5 mL) at room temperature under an argon atmosphere. AuCl3
[mol%] or PPh3AuNTf2 [mol%] or PPh3AuCl+AgOTf [mol%] was
added to the reaction mixtures and stirred for the required times.
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Full Paper
The resulting reaction mixtures were quenched with H2O, saturated
NH4Cl solution was added, and the product was extracted with
EtOAc. The combined organic layers were dried over anhydrous
Na2SO4 and filtered, and the filtrate was concentrated under re-
duced pressure to get a residue. The crude residue was purified by
using silica gel column chromatography (230–400; EtOAc/n-
hexane) to afford 4a–s.
(300 MHz, CDCl3): d=10.05 (s, 1H), 7.68–7.71 (m, 2H), 7.30–7.46
(m, 8H), 6.98 (s, 1H), 4.66 (d, J=11.4 Hz, 1H), 4.62 (d, J=7.8 Hz,
1H), 4.51 (d, J=11.4 Hz, 1H), 4.21–4.25 (m, 1H), 2.89 (m, 1H),
1.11 ppm (d, J=6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=184.8,
159.0, 155.1, 136.6, 129.1, 128.9 (2CH), 128.7, 128.7 (2CH), 128.3,
128.1 (2CH), 127.9, 124.3 (2CH), 102.7, 79.3, 72.1 (CH2), 69.8,
18.0 ppm; IR (KBr): n˜max =1679 cmꢀ1; HRMS (ESI): m/z calcd for
C21H20O4Na [M+Na]+: 359.1260; found: 359.1257.
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-phenylfuran-3-car-
baldehyde (4a)
2-(1-Benzyloxy-2-hydroxypropyl)-5-phenylfuran-3-carbalde-
hyde (4e)
Compound 3a (0.05 g, 0.117 mmol) was converted to 4a (0.05 g,
96%) by following the general procedure: eluent, EtOAc/n-hexane
(25%); ½aꢁ2D0 = +59 (c=0.1 in MeOH); yellow gum. 1H NMR
(600 MHz, CDCl3): d=10.01 (s, 1H), 7.68–7.69 (m, 2H), 7.40–7.43
(m, 2H), 7.29–7.36 (m, 9H), 7.23–7.24 (m, 2H), 6.99 (s, 1H), 4.93 (d,
J=7.8 Hz, 1H), 4.61 (d, J=11.4 Hz, 1H), 4.56 (d, J=12.0 Hz, 1H),
4.52 (d, J=11.4 Hz, 1H), 4.43 (d, J=12.0 Hz, 1H), 4.31 (dt, J=4.2,
7.2 Hz, 1H), 3.74 (dd, J=4.8, 9.6 Hz, 1H), 3.70 (dd, J=3.6, 9.0 Hz,
1H), 2.57 ppm (brs, 1H); 13C NMR (150 MHz, CDCl3): d=185.2 (d,
1C), 159.5, 154.9, 137.6, 136.8, 129.3, 128.8 (2CH), 128.5 (2CH),
128.5, 128.5 (2CH), 128.3, 128.2, 128.1 (2CH), 127.9, 127.8 (2CH),
124.3 (2CH), 102.6, 73.8, 73.6 (CH2), 71.8 (CH2), 71.7, 70.2 ppm
(CH2); IR (KBr): n˜max =1678 cmꢀ1; HRMS (EI): m/z calcd for C28H26O5
[M]+: 442.1780; found: 442.1777.
Compound 3e (0.05 g, 0.157 mmol) was converted to compound
4e (0.034 g, 64%) by following the general procedure: eluent,
EtOAc/n-hexane (20%); ½aꢁD20 =ꢀ3 (c=0.1 in MeOH); yellow gum.
1H NMR (600 MHz, CDCl3): d=10.06 (s, 1H), 7.69 (d, J=7.2 Hz, 2H),
7.43 (t, J=7.8 Hz, 2H), 7.29–7.36 (m, 6H), 7.01 (s, 1H), 4.75 (d, J=
4.8 Hz, 1H), 4.69 (d, J=12.0 Hz, 1H), 4.49 (d, J=11.4 Hz, 1H), 4.27–
4.31 (m, 1H), 2.20 (brs, 1H), 1.24 ppm (d, J=6.0 Hz, 3H); 13C NMR
(150 MHz, CDCl3): d=185.7, 159.0, 154.9, 136.8, 129.3, 128.9 (2CH),
128.6 (2CH), 128.6, 128.3, 128.2, 128.1 (2CH), 124.2 (2CH), 102.8,
78.4, 72.0 (CH2), 69.3, 18.7 ppm (CH3); IR (KBr): n˜max =1678 cmꢀ1
HRMS (ESI): m/z calcd for C21H20O4Na [M+Na]+: 359.1260; found:
;
359.1257.
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-phenylfuran-3-car-
baldehyde (4b)
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-(4-methoxyphe-
nyl)furan-3-carbaldehyde (4 f)
Compound 3b (0.05 g, 0.117 mmol) was converted to 4b (0.033 g,
63%) by following the general procedure: eluent, EtOAc/n-hexane
(25%); ½aꢁ2D0 =ꢀ2 (c=0.1 in MeOH); yellow gum. H NMR (300 MHz,
1
Compound 3 f (0.05 g, 0.11 mmol) was converted to 4 f (0.044 g,
84%) by following the general procedure: eluent, EtOAc/n-hexane
(30%); ½aꢁ2D0 = +75 (c=0.1 in MeOH); colorless gum. 1H NMR
(600 MHz, CDCl3): d=9.99 (s, 1H), 7.61–7.62 (m, 2H), 7.28–7.36 (m,
8H), 7.23–7.24 (m, 2H), 6.93–6.95 (m, 2H), 6.85 (s, 1H), 4.92 (d, J=
7.2 Hz, 1H), 4.61 (d, J=11.4 Hz, 1H), 4.56 (d, J=12.0 Hz, 1H), 4.52
(d, J=11.4 Hz, 1H), 4.42 (d, J=11.4 Hz, 1H), 4.31 (m, 1H), 3.85 (s,
3H), 3.74 (dd, J=4.8, 9.6 Hz, 1H), 3.70 (dd, J=4.2, 9.6 Hz, 1H),
2.55 ppm (brs, 1H); 13C NMR (150 MHz, CDCl3): d=185.2 (d, 1C),
159.9, 158.9, 155.1, 137.6, 136.9, 128.5 (2CH), 128.5 (2CH), 128.5,
128.2, 128.1 (2CH), 127.9, 127.9 (2CH), 125.8 (2CH), 122.3, 114.2
(2CH), 100.9, 73.8, 73.6 (CH2), 71.7, 71.7 (CH2), 70.2 (CH2), 55.4 ppm;
IR (KBr): n˜max =1677, 1502 cmꢀ1; HRMS (EI): m/z calcd for C29H28O6
[M]+: 472.1886; found: 472.1895.
CDCl3): d=10.0 (s, 1H), 7.65–7.68 (m, 2H), 7.19–7.45 (m, 13H), 6.95
(s, 1H), 5.03 (d, J=6.9 Hz, 1H), 4.66 (d, J=11.4 Hz, 1H), 4.51 (d, J=
11.7 Hz, 1H), 4.44–4.45 (m, 2H), 4.24–4.27 (m, 1H), 3.60 (dd, J=3.9,
10.2 Hz, 1H), 3.36 (dd, J=4.8, 10.2 Hz, 1H), 2.89 ppm (d, J=3.6 Hz,
1H); 13C NMR (75 MHz, CDCl3): d=185.0, 158.7, 155.0, 137.4, 136.7,
129.1, 128.8 (2CH), 128.6 (2CH), 128.6 (2CH), 128.3 (2CH), 128.2
(2CH), 128.1 (2CH), 127.9, 127.8, 124.2 (2CH), 102.5, 74.7, 73.6
(CH2), 72.5, 72.1 (CH2), 69.9 ppm (CH2); IR (neat): n˜max =1678 cmꢀ1
HRMS (ESI): m/z calcd for C28H26O5Na [M+Na]+: 465.1678; found:
;
465.1669.
2-[3-(tert-Butyldimethylsilanyloxy)-1,2-dihydroxypropyl]-5-
phenylfuran-3-carbaldehyde (4c)
Compound 3c (0.05 g, 0.14 mmol) was converted to 4c (0.026 g,
49%) by following the general procedure: eluent, EtOAc/n-hexane
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-(4-methoxyphe-
nyl)furan-3-carbaldehyde (4g)
1
(25%); ½aꢁ2D0 =ꢀ1 (c=0.1 in MeOH); brown gum. H NMR (300 MHz,
CDCl3): d=10.14 (s, 1H), 7.65–7.68 (m, 2H), 7.29–7.44 (m, 3H), 6.99
(s, 1H), 5.16–5.19 (m, 1H), 4.03–4.05 (m, 2H), 3.82 (dd, J=4.2,
10.5 Hz, 1H), 3.73 (dd, J=4.5, 10.5 Hz, 1H), 2.82 (d, J=5.4 Hz, 1H),
0.91 (s, 9H), 0.09 ppm (s, 6H); 13C NMR (75 MHz, CDCl3): d=186.7,
160.7, 154.2, 129.2, 128.8 (2CH), 128.5, 126.4, 124.2 (2CH), 103.5,
73.2, 69.5, 64.0 (CH2), 25.8 (3CH3), 18.2, ꢀ5.5 ppm (2CH3); IR (KBr):
n˜max =1673, 1121 cmꢀ1; HRMS (ESI): m/z calcd for C20H28O5SiNa
[M+Na]+: 399.1604; found: 399.1870.
Compound 3g (0.05 g, 0.11 mmol) was converted to 4g (0.040 g,
77%) by following the general procedure: eluent, EtOAc/n-hexane
(25%); ½aꢁ2D0 =ꢀ89 (c=0.1 in MeOH); yellow gum. 1H NMR
(300 MHz, CDCl3): d=9.98 (s, 1H), 7.59 (d, J=8.7 Hz, 2H), 7.20–7.31
(m, 10H), 6.95 (d, J=8.7 Hz, 2H), 6.81 (s, 1H), 5.01 (d, J=6.9 Hz,
1H), 4.66 (d, J=11.4 Hz, 1H), 4.51 (d, J=11.4 Hz, 1H), 4.40–4.45 (m,
2H), 4.24–4.28 (m, 1H), 3.86 (s, 3H), 3.59 (dd, J=3.6, 9.9 Hz, 1H),
3.36 (dd, J=4.5, 10.2 Hz, 1H), 2.87 ppm (brs, 1H); 13C NMR
(75 MHz, CDCl3): d=185.0, 160.0, 158.1, 155.2, 137.4, 136.7, 128.6
(2CH), 128.4 (2CH), 128.3 (2CH), 128.2 (2CH), 128.1, 127.8 ( 2CH),
125.8 (2CH), 122.1, 114.3 (2CH), 100.8, 74.6, 73.6 (CH2), 72.6, 72.1
2-(1-Benzyloxy-2-hydroxypropyl)-5-phenylfuran-3-carbalde-
hyde (4d)
Compound 3d (0.05 g, 0.157 mmol) was converted to 4d (0.023 g,
43%) by following the general procedure: eluent, EtOAc/n-hexane
(25%); ½aꢁ2D0 = +27 (c=0.1 in MeOH); yellow gum. 1H NMR
(CH2), 69.9 (CH2), 55.4 ppm; IR (KBr): n˜max =1676, 1501, 1252 cmꢀ1
;
HRMS (ESI): m/z calcd for C29H28O6Na [M+Na]+: 495.1784; found:
495.1786.
Chem. Eur. J. 2014, 20, 1 – 15
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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(CH2); IR (KBr): n˜max 1680, 1602, 1516, 1343 cmꢀ1; HRMS (ESI): m/z
calcd for C28H25NO7Na [M+Na]+: 510.1529; found: 510.1526.
2-[3-(tert-Butyldimethylsilanyloxy)-1,2-dihydroxypropyl]-5-
(4-methoxyphenyl)-furan-3-carbaldehyde (4h)
Compound 3h (0.05 g, 0.128 mmol) was converted to 4h (0.018 g,
33%) by following the general procedure: eluent, EtOAc/n-hexane
(30%); ½aꢁ2D0 =ꢀ0.1 (c=0.05 in MeOH); colorless gum. 1H NMR
(600 MHz, CDCl3): d=10.04 (s, 1H), 7.58 (d, J=8.4 Hz, 2H), 6.93 (d,
J=9.0 Hz, 2H), 6.84 (s, 1H), 5.06 (m, 1H), 4.17 (d, J=6.6 Hz, 1H),
4.00 (brs, 1H), 3.89 (dd, J=4.2, 10.2 Hz, 1H), 3.84 (s, 3H), 3.82 (dd,
J=4.2, 10.2 Hz, 1H), 2.74 (brs, 1H), 0.90 (s, 9H), 0.09 ppm (s, 6H);
13C NMR (150 MHz, CDCl3): d=187.0 (d, 1C), 160.9, 159.9, 154.3,
125.7 (2CH), 125.7, 122.1, 114.2 (2CH), 102.2, 72.7, 69.8, 63.8 (CH2),
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-(4-nitrophenyl)fur-
an-3-carbaldehyde (4l)
Compound 3l (0.05 g, 0.106 mmol) was converted to 4l (0.027 g,
53%) following the general procedure: eluent, EtOAc/n-hexane
(25%); ½aꢁ2D0 =ꢀ1 (c=0.1 in MeOH); yellow gum. H NMR (300 MHz,
1
CDCl3): d=10.02 (s, 1H), 8.28 (d, J=8.7 Hz, 2H), 7.77 (d, J=9.0 Hz,
2H), 7.19–7.36 (m, 10H), 7.14 (s, 1H), 5.04 (d, J=6.3 Hz, 1H), 4.67
(d, J=11.4 Hz, 1H), 4.55 (d, J=11.4 Hz, 1H), 4.45 (m, 2H), 4.22–4.24
(m, 1H), 3.62 (dd, J=4.5, 10.2 Hz, 1H), 3.42 ppm (dd, J=4.5,
10.2 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=184.7, 160.5, 152.4,
147.3, 137.3, 136.5, 134.8, 128.7 (2CH), 128.4 (2CH), 128.2 (2CH),
128.0, 127.9 (2CH), 127.8 (2CH), 124.6 (2CH), 124.4 (2CH), 106.4,
55.3, 25.8 (3CH3), 18.2, ꢀ5.5 ppm (2CH3); IR (KBr): n˜max =1671 cmꢀ1
;
HRMS (ESI): m/z calcd for C21H30O6SiNa [M+Na]+: 429.1710; found:
429.0250.
74.9, 73.7 (CH2), 72.6 (CH2), 72.4, 69.9 ppm (CH2); IR (KBr): n˜max
=
2-(1-Benzyloxy-2-hydroxypropyl)-5-p-tolylfuran-3-carbalde-
hyde (4i)
1598, 1516, 1339 cmꢀ1; HRMS (ESI): m/z calcd for C28H25NO7Na
[M+Na]+: 510.1529; found: 510.1527.
Compound 3i (0.05 g, 0.15 mmol) was converted to 4i (0.037 g,
72%) by following the general procedure: eluent, EtOAc/n-hexane
(25%); ½aꢁ2D0 =ꢀ124 (c=0.1 in MeOH); colorless gum. 1H NMR
(300 MHz, CDCl3): d=10.05 (s, 1H), 7.57 (d, J=8.1 Hz, 2H), 7.21–
7.38 (m, 7H), 6.94 (s, 1H), 4.74 (d, J=5.1 Hz, 1H), 4.68 (d, J=
11.7 Hz, 1H), 4.48 (d, J=11.7 Hz, 1H), 4.25–4.30 (m, 1H), 2.38 (s,
3H), 2.19 (d, J=4.8 Hz, 1H), 1.24 ppm (d, J=6.6 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=185.8, 158.9, 155.1, 138.6, 136.9, 129.5 (2CH),
128.6 (2CH), 128.2 (2CH), 128.1 (2CH), 126.6, 124.2 (2CH), 102.0,
2-[3-(tert-Butyldimethylsilanyloxy)-1,2-dihydroxypropyl]-5-
(4-nitrophenyl)furan-3-carbaldehyde (4m)
Compound 3m (0.05 g, 0.124 mmol) was converted to 4m
(0.011 g, 21%) by following the general procedure: eluent, EtOAc/
n-hexane (25%); ½aꢁ2D0 =ꢀ60 (c=0.1 in MeOH); reddish solid; m.p.
728C. 1H NMR (600 MHz, CDCl3): d=10.09 (s, 1H), 8.29 (d, J=
9.0 Hz, 2H), 7.82 (d, J=8.4 Hz, 2H), 7.23 (s, 1H), 5.09 (d, J=6.6 Hz,
1H), 4.14 (brs, 1H), 4.01–4.03 (m, 1H), 3.91 (dd, J=3.6, 10.2 Hz,
1H), 3.84 (dd, J=4.2, 10.8 Hz, 1H), 2.74 (brs, 1H), 0.92 (s, 9H),
0.11 ppm (d, J=1.2 Hz, 6H); 13C NMR (150 MHz, CDCl3): d=186.5
(d, 1C), 163.3, 151.7, 147.2, 134.9, 125.9, 124.5 (2CH), 124.4 (2CH),
107.8, 72.6, 69.8, 63.6 (CH2), 25.8 (3CH3), 18.2, ꢀ5.5 ppm (2CH3); IR
˜
78.4, 71.9 (CH2), 69.2, 21.3, 18.8 ppm (CH3); IR (KBr): n˜max
1676 cmꢀ1 HRMS (ESI): m/z calcd for C22H22O4Na [M+Na]+:
373.1416; found: 373.1413.
=
;
2-(1-Benzyloxy-2-hydroxypropyl)-5-(4-methoxyphenyl)furan-
3-carbaldehyde (4j)
(KBr): nmax =1685, 1673, 1524, 1345 cmꢀ1; HRMS (ESI): m/z calcd for
C20H27NO7SiNa [M+Na]+: 444.1455; found: 444.1710.
Compound 3j (0.05 g, 0.143 mmol) was converted to 4j (0.035 g,
67%) by following the general procedure: eluent, EtOAc/n-hexane
(30%); ½aꢁ2D0 =ꢀ120 (c=0.1 in MeOH); colorless gum. 1H NMR
(300 MHz, CDCl3): d=10.04 (s, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.31–
7.37 (m, 5H), 6.95 (d, J=8.7 Hz, 2H), 6.87 (s, 1H), 4.73 (d, J=4.8 Hz,
1H), 4.68 (d, J=11.7 Hz, 1H), 4.48 (d, J=11.7 Hz, 1H), 4.27–4.29 (m,
1H), 3.85 (s, 3H), 2.17 (d, J=4.8 Hz, 1H), 1.24 ppm (d, J=6.3 Hz,
3H); 13C NMR (75 MHz, CDCl3): d=185.7, 159.9, 158.5, 155.0, 136.9,
128.6 (2CH), 128.3, 128.2, 128.1 (2CH), 125.8 (2CH), 122.2, 114.3
(2CH), 101.1, 78.3, 71.9 (CH2), 69.3, 55.4, 18.8 ppm (CH3); IR (KBr):
n˜max =1676, 1502, 1252 cmꢀ1; HRMS (EI): m/z calcd for C22H22O5
[M]+: 366.1467; found: 366.1466.
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-(4-bromophenyl)-
furan-3-carbaldehyde (4n)
Compound 3n (0.05 g, 0.099 mmol) was converted to 4n (0.034 g,
67%) by following the general procedure: eluent, EtOAc/n-hexane
(25%); ½aꢁ2D0 =ꢀ30 (c=0.1 in MeOH); white solid; m.p. 958C.
1H NMR (600 MHz, CDCl3): d=10.0 (s, 1H), 7.50–7.56 (m, 4H), 7.20–
7.34 (m, 10H), 6.94 (s, 1H), 5.02 (d, J=7.2 Hz, 1H), 4.65 (d, J=
11.4 Hz, 1H), 4.52 (d, J=11.4 Hz, 1H), 4.46 (d, J=12.0, Hz, 1H), 4.43
(d, J=11.4 Hz, 1H), 4.23 (dt, J=4.2, 6.6 Hz, 1H), 3.60 (dd, J=4.2,
10.2 Hz, 1H), 3.38 (dd, J=4.2, 10.2 Hz, 1H), 2.83 ppm (brs, 1H);
13C NMR (150 MHz, CDCl3): d=184.9 (d, 1C), 159.0, 153.9, 137.4,
136.6, 132.1 (2CH), 128.6 (2CH), 128.4 (2CH), 128.3, 128.2 (2CH),
128.1, 127.9, 127.8, 127.8 (2CH), 125.7 (2CH), 122.6, 103.1, 74.7,
73.6 (CH2), 72.5, 72.3 (CH2), 69.8 ppm (CH2); IR (KBr): n˜max =1642,
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-(4-nitrophenyl)fur-
an-3-carbaldehyde (4k)
1546, 1496, 1478, 1452 cmꢀ1
; HRMS (ESI): m/z calcd for
C28H25O5BrNa [M+Na]+: 543.0783; found: 543.0782.
Compound 3k (0.05 g, 0.106 mmol) was converted to 4k (0.022 g,
42%) by following the general procedure: eluent, EtOAc/n-hexane
(30%); ½aꢁ2D0 =ꢀ40 (c=0.05 in MeOH); reddish gum. 1H NMR
(600 MHz, CDCl3): d=10.02 (s, 1H), 8.28 (d, J=9.0 Hz, 2H), 7.81 (d,
J=9.0 Hz, 2H), 7.29–7.37 (m, 8H), 7.22 (d, J=6.6 Hz, 2H), 7.19 (s,
1H), 4.95 (d, J=7.2 Hz, 1H), 4.60 (d, J=11.4 Hz, 1H), 4.57 (d, J=
11.4, 1H), 4.53 (d, J=11.4 Hz, 1H), 4.46 (d, J=11.4 Hz, 1H), 4.27–
4.30 (m, 1H), 3.76 (dd, J=4.8, 9.6 Hz, 1H), 3.70 (dd, J=4.2, 9.6 Hz,
1H), 2.56 ppm (brs, 1H); 13C NMR (150 MHz, CDCl3): d=184.8 (d,
1C), 161.3, 152.4, 147.2, 137.4, 136.6, 135.0, 128.6 (2CH), 128.5
(2CH), 128.4, 128.3, 128.1 (2CH), 128.0, 127.9 (2CH), 124.6 (2CH),
124.4 ( 2CH), 106.5, 73.9, 73.6 (CH2), 72.1 (CH2), 71.7, 70.0 ppm
2-(1-Benzyloxy-2-hydroxyethyl)-5-trimethylsilanylfuran-3-
carbaldehyde (4o), 2-(1-benzyloxy-2-hydroxyethyl)-4-trime-
thylsilanylfuran-3-carbaldehyde (4oa), and 2-(1-benzyloxy-2-
hydroxyethyl)furan-3-carbaldehyde (4ob)
Compound 3o (0.05 g, 0.166 mmol) was converted to 4o (0.005 g,
9%), 4oa (0.006 g, 11%), and 4ob (0.0065 g, 16%) by following
the general procedure. Compound 4o: eluent, EtOAc/n-hexane
(20%); ½aꢁ2D0 =ꢀ1 (c=0.11 in MeOH); colorless gum. 1H NMR
(600 MHz, CDCl3): d=10.06 (s, 1H), 7.27–7.35 (m, 5H), 6.95 (s, 1H),
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4.97 (dd, J=4.2, 7.8 Hz, 1H), 4.62 (d, J=12.0 Hz, 1H), 4.49 (d, J=
11.4 Hz, 1H), 3.99 (dd, J=7.8, 12.0 Hz, 1H), 3.86 (dd, J=4.2,
12.0 Hz, 1H), 2.24 (brs, 1H), 0.29 ppm (s, 9H); 13C NMR (150 MHz,
CDCl3): d=185.4 (d, 1C), 163.4, 162.5, 136.9, 128.6 (2CH), 128.2,
128.1 (2CH), 125.9, 117.9, 75.5, 72.0 (CH2), 64.7 (CH2), ꢀ1.9 ppm
(3CH3); IR (KBr): n˜max =1678, 1251 cmꢀ1; HRMS (ESI): m/z calcd for
C17H22O4SiNa [M+Na]+: 341.1185; found: 341.1183. Compound
4oa: eluent, EtOAc/n-hexane (20%); ½aꢁ2D0 = +24 (c=0.1 in MeOH);
colorless gum. 1H NMR (600 MHz, CDCl3): d=10.07 (s, 1H), 7.25–
7.35 (m, 6H), 4.96 (dd, J=3.6, 7.2 Hz, 1H), 4.62 (d, J=12.0 Hz, 1H),
4.48 (d, J=11.4 Hz, 1H), 3.99 (dd, J=7.8, 12.0 Hz, 1H), 3.84 (dd, J=
4.2, 12.0 Hz, 1H), 2.20 (brs, 1H), 0.26 ppm (s, 9H); 13C NMR
(150 MHz, CDCl3): d=185.4 (d, 1C), 161.4, 148.6, 136.8, 129.1, 128.6
(2CH), 128.2, 128.0 (2CH), 119.0, 74.7, 71.9 (CH2), 64.6 (CH2),
ꢀ1.1 ppm (3CH3); IR (KBr): n˜max =1679 cmꢀ1; HRMS (ESI): m/z calcd
for C17H22O4SiNa [M+Na]+: 341.1185; found: 341.1182. Compound
4ob: eluent, EtOAc/n-hexane (30%); ½aꢁ2D0 = +35.2 (c=0.5 in
MeOH); yellow gum. 1H NMR (600 MHz, CDCl3): d=10.05 (s, 1H),
7.43 (d, J=1.8 Hz, 1H), 7.28–7.36 (m, 5H), 6.78 (d, J=1.8 Hz, 1H),
4.96 (dd, J=4.2, 7.2 Hz, 1H), 4.63 (d, J=11.4 Hz, 1H), 4.48 (d, J=
11.4 Hz, 1H), 3.99 (dd, J=7.2, 11.4 Hz, 1H), 3.86 (dd, J=4.2,
12.0 Hz, 1H), 2.20 ppm (brs, 1H); 13C NMR (150 MHz, CDCl3): d=
185.1 (d, 1C), 159.5, 143.6, 136.7, 128.7 (2CH), 128.3, 128.1 (2CH),
sistent with the experimental details discussed above. Compound
4pc: eluent, EtOAc/n-hexane (12%); ½aꢁ2D0 = +14 (c=0.1 in MeOH);
1
white solid; m.p. 1328C. H NMR (600 MHz, CDCl3): d=7.75 (s, 1H),
7.27–7.36 (m, 10H), 4.71 (d, J=12.0 Hz, 1H), 4.56 (d, J=11.4 Hz,
1H), 4.52–4.54 (m, 1H), 4.49 (d, J=11.4 Hz, 1H), 4.46 (d, J=12.0 Hz,
1H), 3.91 (dd, J=6.6, 10.2 Hz, 1H), 3.79 (d, J=1.8 Hz, 1H), 3.76 (dd,
J=5.4, 10.2 Hz, 1H), 3.07 ppm (s, 1H); 13C NMR (75 MHz, CDCl3):
d=186.5, 166.8, 137.3, 136.6, 128.5 (3CH), 128.4 (2CH), 128.4,
128.1, 128.0, 127.8 (2CH), 102.4, 81.3, 80.7, 74.4, 73.7 (CH2), 73.3,
72.1 (CH2), 67.2 ppm (CH2); IR (KBr): n˜max =3265, 1693, 1586, 1198,
1102 cmꢀ1
;
HRMS (ESI): m/z calcd for C22H20O4Na [M+Na]+:
371.1260; found: 371.1254.
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)furan-3-carbaldehyde
(4pb)
Compound 4pc (0.05 g, 0.143 mmol) was converted to 4pb
(0.025 g, 48%) by following the general procedure with
PPh3AuNTf2 as catalyst. The analytical data of 4pb were consistent
with the experimental details discussed above: eluent, EtOAc/n-
hexane (30%).
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-butylfuran-3-car-
baldehyde (4q)
125.8, 108.5, 74.8, 71.9 (CH2), 64.5 ppm (CH2); IR (KBr): n˜max
=
1679 cmꢀ1 HRMS (ESI): m/z calcd for C14H14O4Na [M+Na]+:
;
269.0790; found: 269.0792.
Compound 3q (0.05 g, 0.124 mmol) was converted to 4q (0.027 g,
52%) by following the general procedure: eluent, EtOAc/n-hexane
(20%); ½aꢁ2D0 =ꢀ22 (c=0.1 in MeOH); colorless gum. 1H NMR
(600 MHz, CDCl3): d=9.91 (s, 1H), 7.21–7.34 (m, 10H), 6.33 (s, 1H),
4.91 (d, J=7.2 Hz, 1H), 4.59 (d, J=12.0 Hz, 1H), 4.41–4.46 (m, 3H),
4.17–4.18 (m, 1H), 3.53 (dd, J=3.6, 10.2 Hz, 1H), 3.28 (dd, J=4.2,
9.6 Hz, 1H), 2.85 (brs, 1H), 2.58–2.61 (m, 2H), 1.58–1.62 (m, 2H),
1.32–1.39 (m, 2H), 0.93 ppm (t, J=7.8 Hz, 3H); 13C NMR (150 MHz,
CDCl3): d=185.0, 158.3, 157.9, 137.5, 136.8, 128.6 (2CH), 128.4
(2CH), 128.2, 128.1 (2CH), 127.8 (2CH), 127.8, 127.1, 102.9, 74.3,
73.6 (CH2), 72.5, 71.9 (CH2), 69.8 (CH2), 29.5 (CH2), 27.3 (CH2), 22.1
(CH2), 13.7 ppm (CH3); IR (KBr): n˜max =1677 cmꢀ1; HRMS (ESI): m/z
calcd for C26H30O5Na [M+Na]+: 445.1991; found: 445.1991.
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-trimethylsilanylfuran-
3-carbaldehyde (4p) and 2-(1,3-bis(benzyloxy)-2-hydroxypro-
pyl)furan-3-carbaldehyde (4pb)
Compound 3p (0.05 g, 0.118 mmol) was converted to 4p (0.018 g,
35%) and 4pb (0.013 g, 30%) by following the general procedure
with AuCl3 as catalyst. Compound 4p: eluent, EtOAc/n-hexane
(20%); ½aꢁ2D0 =ꢀ1 (c=0.1 in MeOH); colorless gum. 1H NMR
(300 MHz, CDCl3): d=10.0 (s, 1H), 7.24–7.30 (m, 10H), 6.92 (s, 1H),
4.97 (d, J=6.6 Hz, 1H), 4.58 (d, J=11.4 Hz, 1H), 4.43–4.48 (m, 3H),
4.18–4.19 (m, 1H), 3.54 (dd, J=4.2, 10.2 Hz, 1H), 3.27 (dd, J=4.8,
10.2 Hz, 1H), 2.82 (d, J=3.6 Hz, 1H), 0.26 ppm (s, 9H); 13C NMR
(75 MHz, CDCl3): d=185.3, 163.4, 162.5, 137.5, 136.8, 128.6 (2CH),
128.4 (2CH), 128.2 (2CH), 128.1 (2CH), 127.8 (2CH), 126.3, 117.7,
75.1, 73.6 (CH2), 72.6, 72.2 (CH2), 69.9 (CH2), ꢀ1.9 ppm (3CH3); IR
(neat): n˜max =1680 cmꢀ1; HRMS (ESI): m/z calcd for C25H30O5SiNa
[M+Na]+: 461.1761; found: 461.1762. Compound 4pb: eluent,
EtOAc/n-hexane (30%); ½aꢁ2D0 =ꢀ116 (c=0.1 in MeOH); yellow
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-butylfuran-3-car-
baldehyde (4r)
Compound 3r (0.05 g, 0.124 mmol) was converted to 4r (0.027 g,
52%) by following the general procedure: eluent, EtOAc/n-hexane
(20%); ½aꢁ2D0 = +1 (c=0.1 in MeOH); colorless gum. 1H NMR
(600 MHz, CDCl3): d=9.91 (s, 1H), 7.21–7.36 (m, 10H), 6.36 (s, 1H),
4.82 (d, J=7.2 Hz, 1H), 4.49–4.55 (m, 3H), 4.36 (d, J=12.0 Hz, 1H),
4.19–4.23 (m, 1H), 3.69 (dd, J=5.4, 9.6 Hz, 1H), 3.65 (dd, J=3.6,
9.6 Hz, 1H), 2.63 (t, J=7.8 Hz, 2H), 2.47 (d, J=6.0 Hz, 1H), 1.60–
1.65 (m, 2H), 1.36–1.39 (m, 2H), 0.93 ppm (t, J=7.2 Hz, 3H);
13C NMR (150 MHz, CDCl3): d=186.2 (d, 1C), 159.7, 159.2, 138.6,
137.9, 129.5 (2CH), 129.5 (2CH), 129.1, 129.0 (2CH), 128.9, 128.8
(2CH), 128.5, 104.0, 74.5 (CH2), 74.4 (CH2), 72.6, 72.5 (CH2), 71.3
(CH2), 30.6 (CH2), 28.4 (CH2), 23.1 (CH2), 14.8 ppm (CH3); IR (KBr):
n˜max =1675 cmꢀ1; HRMS (ESI): m/z calcd for C26H30O5Na [M+Na]+:
445.1991; found: 445.1987.
1
gum. H NMR (600 MHz, CDCl3): d=9.98 (s, 1H), 7.40 (d, J=1.8 Hz,
1H), 7.22–7.34 (m, 10H), 6.75 (d, J=2.4 Hz, 1H), 4.99 (d, J=6.6 Hz,
1H), 4.60 (d, J=12.0 Hz, 1H), 4.44–4.47 (m, 2H), 4.42 (d, J=11.4 Hz,
1H), 4.18 (dt, J=4.2, 7.2 Hz, 1H), 3.54 (dd, J=4.2, 10.2 Hz, 1H), 3.29
(dd, J=4.8, 10.8 Hz, 1H), 2.83 ppm (brs, 1H); 13C NMR (150 MHz,
CDCl3): d=184.9 (d, 1C), 159.5, 143.6, 137.4, 136.7, 128.6 (2CH),
128.4 (2CH), 128.3, 128.1 (2CH), 127.9 (2CH), 127.8, 126.2, 108.2,
74.4, 73.6 (CH2), 72.5, 72.1 (CH2), 69.8 ppm (CH2); IR (KBr): n˜max
1680 cmꢀ1 HRMS (ESI): m/z calcd for C22H22O5Na [M+Na]+:
389.1365; found: 389.1364.
=
;
3-Benzyloxy-2-benzyloxymethyl-5-ethynyl-2,3-dihydropyran-
4-one (4pc)
2-(1,3-Bis(benzyloxy)-2-hydroxypropyl)-5-cyclopentylfuran-3-
carbaldehyde (4s)
Compound 3p (0.05 g, 0.118 mmol) was converted to 4pb
(0.013 g, 30%) and 4pc (0.014 g, 34%) by following the general
procedure with PPh3AuNTf2 as catalyst. Similarly, 3p (0.05 g,
0.118 mmol) was converted to 4pb (0.014 g, 32%) and 4pc
(0.0075 g, 18%) by following the general procedure with
PPh3AuCl+AgOTf as catalyst. The analytical data of 4pb were con-
Compound 3s (0.05 g, 0.120 mmol) was converted to 4s (0.043 g,
82%) by following the general procedure: eluent, EtOAc/n-hexane
(20%); ½aꢁ2D0 = +66 (c=0.1 in MeOH); colorless gum. 1H NMR
(300 MHz, CDCl3): d=9.91 (s, 1H), 7.20–7.37 (m, 10H), 6.36 (s, 1H),
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4.82 (d, J=7.2 Hz, 1H), 4.48–4.56 (m, 3H), 4.37 (d, J=11.7 Hz, 1H),
4.22 (m, 1H), 3.62–3.71 (m, 2H), 3.08 (quin, J=7.2 Hz, 1H), 2.50 (d,
J=4.5 Hz, 1H), 2.00–2.50 (m, 2H), 1.50–1.74 ppm (m, 6H); 13C NMR
(75 MHz, CDCl3): d=185.3, 161.6, 158.7, 137.6, 137.0, 128.5 (2CH),
128.5 (2CH), 128.1 (2CH), 128.0, 127.9, 127.8 (2CH), 127.3, 101.6,
73.7, 73.5 (CH2), 71.6 (CH2), 71.6, 70.3 (CH2), 38.3, 31.6 (CH2), 31.5
(CH2), 25.1 ppm (2CH2); IR (KBr): n˜max =1676 cmꢀ1; HRMS (ESI): m/z
calcd for C27H30O5Na [M+Na]+: 457.1991; found: 457.2024.
trated under reduced pressure to get a crude residue. The residue
was purified by using silica gel column chromatography to obtain
6 (0.016 g, 43%): eluent: EtOAc/n-hexane (15–20%); yellow gum.
1H NMR (600 MHz, CDCl3): d=9.91 (s, 1H), 7.64 (d, J=7.2 Hz, 2H),
7.31–7.42 (m, 8H), 6.96 (s, 1H), 4.64 (s, 2H), 4.26 (s, 2H), 4.22 ppm
(s, 2H); 13C NMR (150 MHz, CDCl3): d=202.1, 185.2 (d, 1C), 154.8,
154.7, 136.7, 129.3, 128.8 (2CH), 128.6 (2CH), 128.4, 128.2, 128.0
(2CH), 125.7, 124.1 (2CH), 103.4, 74.9 (CH2), 73.7 (CH2), 38.4 ppm
(CH2); IR (KBr): n˜max =1681, 1735 cmꢀ1; HRMS (ESI): m/z calcd for
C21H18O4Na [M+Na]+: 357.1103; found: 357.1106.
6-(tert-Butyldimethylsilanyloxymethyl)-4-methoxy-2-phenyl-
6,7-dihydro-4H-furo[3,2-c]pyran-7-ol (5a)
6-Benzyloxymethyl-2-phenylfuro[3,2-c]pyridine (7)
AuCl3 (0.0127 g, 10 mol%) and then methanol (0.034 mL, 2 equiv)
were added to a well-stirred solution of 3c (0.150 g, 0.418 mmol)
in dry THF (2.5 mL) under an argon atmosphere. The resulting reac-
tion mixture was stirred at room temperature for 20 min. After
completion of the reaction (TLC), the solvent was removed under
reduced pressure, and the residue was purified by flash chroma-
tography on silica gel (230–400) to obtain compound 5a (0.089 g,
55%): eluent: EtOAc/n-hexane (7.5%); white solid; m.p. 1208C.
1H NMR (300 MHz, CDCl3): d=7.67 (d, J=7.2 Hz, 2H), 7.35–7.40 (m,
2H), 7.26–7.30 (m, 1H), 6.60 (s, 1H), 5.53 (s, 1H), 4.65 (dd, J=1.5,
6.9 Hz, 1H), 4.20–4.25 (m, 1H), 3.97–4.04 (m, 2H), 3.54 (s, 3H), 2.42
(d, J=7.5 Hz, 1H), 0.93 (s, 9H), 0.13 ppm (d, J=2.4 Hz, 6H);
13C NMR (150 MHz, CDCl3): d=154.8, 150.3, 130.3, 128.7 (2CH),
127.9, 124.1 (2CH), 121.4, 102.5, 95.9, 71.7, 62.4 (CH2), 61.8, 55.7,
25.9 (3CH3), 18.2, ꢀ5.4 ppm (2CH3); HRMS (ESI): m/z calcd for
C21H30O5SiNa [M+Na]+: 413.1761; found: 413.1755.
1,5-Dicarbonyl derivative 6 (0.022 g, 0.066 mmol) was dissolved in
a solution of NH4OAc (50.7 mg, 0.66 mmol, 10 equiv) and acetic
acid (0.04 mL, 0.66 mmol, 10 equiv) in ethanol (0.01m with respect
to 6). The resulting mixture was heated at 408C for 12 h. After
completion of reaction (TLC), the reaction mixture was cooled to
room temperature and diluted with ethyl acetate, washed with
aqueous saturated NaHCO3 solution, followed by brine solution.
The combined organic layers were dried over anhydrous Na2SO4
and filtered, and the filtrate was concentrated under reduced pres-
sure to get a crude residue. The crude residue was purified by
using silica gel column chromatography to obtain 7 (0.012 g,
60%); eluent: EtOAc/n-hexane (35%); light yellow solid; m.p. 888C.
1H NMR (600 MHz, CDCl3): d=8.84 (s, 1H), 7.86–7.87 (m, 2H), 7.68
(s, 1H), 7.47 (t, J=7.2 Hz, 2H), 7.36–7.43 (m, 5H), 7.30–7.32 (m,
1H), 7.05 (s, 1H), 4.83 (s, 2H), 4.70 ppm (s, 2H); 13C NMR (150 MHz,
CDCl3): d=160.3, 157.1, 153.9, 142.7, 138.0, 129.5, 129.3, 128.9
(2CH), 128.4 (2CH), 127.8 (2CH), 127.7, 125.5, 125.2 (2CH), 104.6,
99.0, 73.0 (CH2), 72.9 ppm (CH2); HRMS (ESI): m/z calcd for
C21H18NO2 [M+H]+: 316.1337; found: 316.1104.
7-Benzyloxy-6-benzyloxymethyl-2-phenyl-6,7-dihydrofuro-
[3,2-c]pyran-4-one (5b)
PDC (0.127 g, 0.339 mmol, 3 equiv) was added to a well-stirred so-
lution of 4a (0.05 g, 0.113 mmol) in dry dichloromethane (5 mL)
under an argon atmosphere. The resulting reaction mixture was
stirred at room temperature for 48 h. After completion of reaction
(TLC), saturated NaHCO3 solution was added, and the product was
extracted with CH2Cl2. The combined organic layers were dried
over anhydrous Na2SO4 and filtered, and the filtrate was concen-
trated under reduced pressure to get a crude residue. The residue
was purified by using silica gel column chromatography to obtain
5b (0.020 g, 40%): eluent: EtOAc/n-hexane (20%); ½aꢁ2D0 = +48 (c=
0.1 in MeOH); white solid; m.p. 748C. 1H NMR (600 MHz, CDCl3):
d=7.67–7.68 (m, 2H), 7.43–7.45 (m, 2H), 7.25–7.38 (m, 9H), 7.21–
7.22 (m, 2H), 6.94 (s, 1H), 5.00 (d, J=4.2 Hz, 1H), 4.85–4.87 (m,
2H), 4.73 (d, J=11.4 Hz, 1H), 4.52 (d, J=11.4 Hz, 1H), 4.48 (d, J=
12.0 Hz, 1H), 3.77 (dd, J=4.2, 10.2 Hz, 1H), 3.63 ppm (dd, J=6.0,
10.8 Hz, 1H); 13C NMR (150 MHz, CDCl3): d=160.8, 158.1, 156.4,
137.3, 136.9, 129.1, 128.9 (2CH), 128.8, 128.6 (2CH), 128.4 (2CH),
128.2, 128.1 (2CH), 127.9, 127.6 (2CH), 124.3 (2CH), 114.9, 102.5,
Acknowledgements
I.D. thanks DST-SERB (no. SB/FT/CS-105/2012) for financial sup-
port, and Drs. Basudeb Achari and Ramalingam Natarajan for
valuable discussions. K.M. thanks the CSIR, India for a fellow-
ship. A.S. thanks NIPER-Kolkata for a fellowship. We thank the
reviewers for their valuable comments and suggestions, which
helped significantly to improve the quality of the manuscript.
Keywords: carbohydrates
homogeneous catalysis
·
chirality
·
furans
·
gold
·
[1] a) A. Boto, L. Alvarez in Heterocycles in Natural Product Synthesis (Eds.:
K. C. Majumdar, S. K. Chattopadhyay), Wiley-VCH, Weinheim, Germany,
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sive Heterocyclic Chemistry, Vol. 3 (Eds.: A. R. Katritzky, C. A. Ramsden,
E. F. V. Scriven, R. J. K. Taylor), Elsevier, Oxford, 2008, pp. 408–496;
c) X. L. Hou, Z. Yang, H. N. C. Wong in Progress in Heterocyclic Chemistry,
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pp. 167–205; d) H. Heaney, J. S. Ahn in Comprehensive Heterocyclic
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[2] For selected references, see: a) A. V. Gulevich, A. S. Dudnik, N. Chernyak,
V. Gevorgyan, Chem. Rev. 2013, 113, 3084–3213; b) E. B. Murphy, F.
Wudl, Prog. Polym. Sci. 2010, 35, 223–251; c) A. Gandini, A. J. D. Silves-
tre, C. P. Neto, A. F. Sousa, M. N. Gomes, Polym. Chem. 2009, 47, 295–
298; d) H.-C. Lin, W.-Y. Lin, H.-T. Bai, J.-H. Chen, B.-Y. Jin, T.-Y. Luh, Angew.
Chem. 2007, 119, 915–918; Angew. Chem. Int. Ed. 2007, 46, 897–900;
e) R. C. D. Brown, Angew. Chem. 2005, 117, 872–874; Angew. Chem. Int.
81.5, 73.5 (CH2), 72.2 (CH2), 68.5 (CH2), 67.0 ppm; IR (KBr): n˜max
=
1745 cmꢀ1 HRMS (ESI): m/z calcd for C28H24O5Na [M+Na]+:
;
463.1522; found: 463.1192.
2-(3-Benzyloxy-2-oxopropyl)-5-phenylfuran-3-carbaldehyde
(6)
TiBr4 (0.083 g, 0.226 mmol, 2 equiv) was added to a well-stirred so-
lution of 4a or 4b (0.05 g, 0.113 mmol) in dry toluene (2.5 mL)
under an argon atmosphere. The resulting reaction mixture was
heated under reflux conditions for 8 h. After completion of reac-
tion (TLC), saturated NH4Cl solution was added, and the product
was extracted with EtOAc. The combined organic layers were dried
over anhydrous Na2SO4 and filtered, and the filtrate was concen-
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Received: February 21, 2014
Published online on && &&, 0000
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FULL PAPER
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Chiral Furans
K. Mal, A. Sharma, I. Das*
&& – &&
Gold(III) Chloride Catalyzed Synthesis
of Chiral Substituted 3-Formyl Furans
from Carbohydrates: Application in
the Synthesis of 1,5-Dicarbonyl
Golden energy! An efficient gold(III)-
catalyzed route to substituted chiral 3-
formyl furans under extremely mild con-
ditions from suitably protected 5-(1-al-
kynyl)-2,3-dihydropyran-4-ones and H2O
as a nucleophile is described (see
scheme, TBS=tert-butyldimethylsilyl).
The latter can easily be synthesized
from appropriately functionalized mon-
osaccharides or commercially available
glycals in a few steps.
Derivatives and Furo[3,2-c]pyridine
Chem. Eur. J. 2014, 20, 1 – 15
www.chemeurj.org
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