Palladium-catalyzed intramolecular C-O bond formation: An approach to the synthesis of chiral benzodioxocines

Article abstract of DOI:10.1002/ejoc.200700762

Palladium-catalyzed intramolecular aryl etherification using bulky binaphthylphosphane or bis(diphenylphosphanyl)ferrocene ligands is shown to be a convenient method for the synthesis of eight-membered oxygen heterocycles. Application of this methodology to a sugar derivative led to the synthesis of chiral benzodioxocine. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200700762

FULL PAPER
DOI: 10.1002/ejoc.200700762
Palladium-Catalyzed Intramolecular C–O Bond Formation: An Approach to
the Synthesis of Chiral Benzodioxocines
Arpita Neogi,[a] Tirtha P. Majhi,[a] Basudeb Achari,[a] and Partha Chattopadhyay*[a]
Keywords: Palladium / Catalysts / Dioxocine / Ligands / Etherification / Heterocycles
Palladium-catalyzed intramolecular aryl etherification using
bulky binaphthylphosphane or bis(diphenylphosphanyl)fer-
rocene ligands is shown to be a convenient method for the
synthesis of eight-membered oxygen heterocycles. Applica-
tion of this methodology to a sugar derivative led to the syn-
thesis of chiral benzodioxocine.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
examples of the application of this useful reaction in the
synthesis of eight-membered rings. Herein we report the re-
sults of this investigation and demonstrate the applicability
of this methodology to the synthesis of enantiopure
benzannulated dioxocine derivatives.
Introduction
Palladium-mediated amination of aryl halides has
emerged as a versatile and efficient method for the synthe-
sis[1] of nitrogen heterocycles. The analogous process for the
addition of alcohols to produce aromatic ethers has also
been successfully established.[2] The initial work in this field
by Buchwald and co-workers focused on the intramolecular
etherification of o-haloaryl-substituted alcohols to give
benzo-fused cyclic ethers having five- to seven-membered
rings.[3] However, to the best of our knowledge, eight-mem-
bered rings have not been generated using this method.
Reported approaches to the construction of eight-mem-
bered rings by intramolecular etherification include nucleo-
philic aromatic substitution of fluorine by the OH group of
substituted phenols,[4a] cyclization of bromoallenes bearing
nucleophilic oxygen functionalities in the presence of a pal-
ladium catalyst,[4b] and palladium-induced cyclization of
phenols substituted with a tethered alkyne functionality.[4c]
The above methodologies either require a lengthy se-
quence of reactions or furnish low yields of the reaction
products. As a part of our research exploring the synthesis
of medium-sized ring compounds,[5] we have now applied
the process of intramolecular palladium-induced aryl
etherification using various aliphatic alcohols to the synthe-
sis of benzo-fused dioxocine derivatives (Scheme 1), the
structural unit found in some natural products,[6a,6b] some
analogues of which have a high affinity for the M3 musca-
rinic receptor.[6c] These reactions appear to be the first
Scheme 1. Mechanism of intramolecular aryl etherification in the
synthesis of medium-sized rings.
Results and Discussion
Our initial studies concerned the reaction of [2-(2-bromo/
iodobenzyloxy)phenyl]methanols 1a,b and their analogue
1c, prepared from salicylaldehyde/o-hydroxyacetophenone
by thioacetalization using propanedithiol,[7] arylation with
2-bromo/iodobenzyl bromides,[8] and dethioacetalization in
the presence of MeI/aqu. MeCN.[9] Compounds 1a,b were
readily converted (Scheme 2, Table 1) into dibenzodioxoc-
ine 2 by Pd-catalyzed intramolecular etherification in the
presence of base and ligands (L1 and L2) (Figure 1).
[a] Department of Chemistry, Indian Institute of Chemical
Biology,
4 Raja S. C. Mullick Road, Kolkata 700032, India
Fax: +91-33-24735197
E-mail: partha@iicb.res.in
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
330
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 330–336

Palladium-Catalyzed Intramolecular C–O Bond Formation
This could be employed in several instances, for example,
in the cyclization of the model substrates 1a,b at Ն90 °C in
toluene with Pd2(dba)3 as the palladium source in the pres-
ence of K3PO4. The yield of dibenzodioxocine 2 was about
62%. Use of 1,1Ј-bis(diphenylphosphanyl)ferrocene
(DPPF) (L2) as the ligand to cyclize 1a furnished a similar
yield of 2 (Entry 3, Table 1). This method works satisfacto-
rily with primary alcohols, but fails to produce any re-
ductive elimination product when a secondary alcohol is
used (Entry 6, Table 1).
Scheme 2. Synthesis of dibenzodioxocines.
Table 1. Palladium-catalyzed synthesis of dibenzodioxocines.
We then explored the reaction of various aryl halides
tethered to a sugar nucleus to obtain ethereal products. In
this cyclization, sugar plays a double role (a) as a chiral
source involving a strategy that is based on the concept of
“chiral template” and generates “chirons” which are enan-
tiomerically pure synthons and (b) by bringing rigidity to
the substrate. The rigidity imposed on the precursor by the
aromatic and tetrahydrofuran rings may assist the cycliza-
tion.[11] The starting material, O-2-bromobenzylated
1,2:5,6-di-O-isopropylideneglucofuranoside 3a, its ana-
logues 3b–d,[8] and the epimeric allofuranoside 3e[8] were
converted into the nor-aldehydes by selective deketalization
and NaIO4 oxidation. Subsequent reduction of the crude
aldehydes with NaBH4 furnished the sugar alcohols 4a–e[12]
in good yields (Scheme 3, Table 2). The spectroscopic data
of the product alcohols are in excellent agreement with the
assigned structures.
Entry
Substrate
R
X
Product[a] % Yield
1
2
3
4
5
6
1a
1b
1a
1a
1b
1c
H
H
H
H
H
Br
I
Br
Br
I
2
2
2
2
2
–
62[b]
62[b]
61[c]
44[d]
45[e]
[b,f]
Me
Br
–
[a] β-Eliminated products (8–10%) were detected in all cases. [b]
Reaction conditions: 5 mol-% Pd2(dba)3, 7 mol-% L1, 2.0 equiv.
K3PO4, toluene (10 mL/mmol substrate), 90 °C, 16 h. [c] Reaction
conditions: 5 mol-% Pd2(dba)3, 7 mol-% L2, 2.0 equiv. K3PO4, tol-
uene (10 mL/mmol substrate), 90 °C, 16 h. [d] Reaction conditions:
4 mol-% Pd2(dba)3, 5 mol-% L1, 2.0 equiv. Cs2CO3, toluene
(10 mL/mmol substrate), 90 °C, 10 h. [e] Reaction conditions:
4 mol-% Pd2(dba)3, 5 mol-% L1, 2.0 equiv. NaOtBu, toluene
(10 mL/mmol substrate), 90 °C, 10 h. [f] No cyclized product de-
tected.
Table 2. Preparation of furano sugar alcohols.
Entry Substrate
C-6config.
R1
R2
X
Product % Yield
1
2
3
4
5
3a
3b
3c
3d
3e
S
S
S
S
R
H
H
H
H
H
Br
I
4a
4b
4c
4d
4e
80
75
85
82
77
OMe Br
–OCH2O– Br
Br
H
H
Figure 1. Ligands used in Pd-catalyzed C–O bond formation.
Pd-catalyzed intramolecular aryl etherification of 4a–e in
By screening a variety of bases, we found K3PO4 to be the presence of base and ligands afforded furobenzodioxoc-
the most effective for the intramolecular etherification reac- ine derivatives 5a,b (Scheme 4; no cyclization products were
tion. With respect to the product yield, K3PO4 is clearly detected with 4c,d). The reactions carried out in the pres-
superior[10] to other bases, including Cs2CO3, K2CO3, and ence of K3PO4 and ligands afforded the desired benzodiox-
NaOtBu, which are less effective for this reaction (Table 1). ocine-annulated furanose derivatives 5a,b in around 65%
The most versatile ligand was found to be (Ϯ)-BINAP (L1). yield. (Entries 1–3 and 8, Table 3). As in the previous case,
Scheme 3. Construction of O-bromo/iodobenzylated sugar alcohols.
Eur. J. Org. Chem. 2008, 330–336
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
331

A. Neogi, T. P. Majhi, B. Achari, P. Chattopadhyay
FULL PAPER
use of the ferrocene ligand (L2) gave a similar yield of the
reductive elimination product to that obtained with ligand
L1 (Entry 3, Table 3). The structures of the products 5a,b
1
were ascertained by H NMR spectroscopy as well as by
1
13C NMR, H–1H COSY and mass spectral analyses. As
expected from the studies of Buchwald and co-workers,[3c,13]
compounds bearing an electron-donating group (methoxy
or methylenedioxy) para to the halogen (Entries 6 and 7,
Table 3) proved difficult substrates for this type of cycliza-
tion reaction.
Scheme 5. Intramolecular aryl etherification of pyranose deriva-
tives.
Table 4. Optimization of the intramolecular aryl etherification of
pyranose derivatives.
Entry
Substrate
R
Product[a]
% Yield
1
2
3
4
6a
6a
6a
6b
H
H
H
7
7
7
–
50[b]
67[c]
65[d]
[e]
OMe
–
[a] Small amounts of β-eliminated products (nearly 4%) were de-
tected. [b] Reaction conditions: 3 mol-% Pd(OAc)2, 4 mol-% L1,
2.0 equiv. Cs2CO3, toluene (10 mL/mmol substrate), 90 °C, 10 h.
[c] Reaction conditions: 5 mol-% Pd(OAc)2, 7 mol-% L1, 2.0 equiv.
K3PO4, toluene (10 mL/mmol substrate), 90 °C, 18 h. [d] Reaction
conditions: 5 mol-% Pd2(dba)3, 7 mol-% L2, 2.0 equiv. K3PO4, tol-
uene (10 mL/mmol substrate), 90 °C, 18 h. [e] No cyclized product
detected.
Scheme 4. Intramolecular aryl etherification of furanose deriva-
tives.
The feasibility of synthesizing chiral benzodioxocines
from the annulated sugar derivatives could then be realized
by using 5a (Scheme 6). Thus, 5a was converted into the
functionalized benzodioxocine 8 in 60% overall yield by a
sequence of reactions involving the removal of the 1,2-O-
isopropylidene group, oxidative cleavage of the diol, re-
duction of the carbonyl group, and acetylation. The forma-
tion of 8 was deduced from the appearance of three methyl-
ene carbon signals at δ = 64.4, 72.7, and 75.5 in its 13C
NMR spectrum besides other corroborative evidence.
Table 3. Optimization of the intramolecular aryl etherification of
furanose derivatives.
Entry Substrate
C-6 config.
Product[a]
% Yield
1
2
3
4
5
6
7
8
9
4a
4b
4a
4a
4a
4c
4d
4e
4e
S
S
S
S
S
S
S
R
R
5a
5a
5a
5a
5a
–
–
5b
5b
65[b]
65[b]
64[c]
45[d]
46[e]
[b,f]
–
–
[b,f]
65[b]
45[e]
[a] β-Eliminated products (5–10%) were detected in all cases. [b]
Reaction conditions: 5 mol-% Pd2(dba)3, 7 mol-% L1, 2.0 equiv.
K3PO4, toluene (10 mL/mmol substrate), 90 °C, 18 h. [c] Reaction
conditions: 5 mol-% Pd2(dba)3, 7 mol-% L2, 2.0 equiv. K3PO4, tol-
uene (10 mL/mmol substrate), 90 °C, 18 h. [d] Reaction conditions:
3 mol-% Pd(OAc)2, 4 mol-% L1, 2.0 equiv. NaOtBu, toluene
(10 mL/mmol substrate), 90 °C, 16 h. [e] Reaction conditions:
4 mol-% Pd2(dba)3, 5 mol-% L1, 2.0 equiv. Cs2CO3, toluene
(10 mL/mmol substrate), 90 °C, 10 h. [f] No cyclized product de-
tected.
Scheme 6. Conversion of 5a to a benzodioxocine derivative.
Conclusions
The same reaction was then studied with the O-(2-
bromoaryl)mannopyranose derivatives 6a,b[14] (Scheme 5).
Evaluation of reagents and conditions showed that the opti-
mum conditions for this reaction were with Pd(OAc)2 as the
palladium source, (Ϯ)-BINAP (L1) as the ligand, K3PO4 as
the base, and toluene as the solvent. The yield of purified
pyranobenzodioxocine 7 was 67% (Entry 2, Table 4). The
structure of the product 7 was ascertained by 1H NMR
spectroscopy as well as by 13C NMR and mass spectral
analyses. As in the furanose system (Entries 6 and 7,
Table 3), an aryl bromide tethered substrate containing a
strongly electron-donating group para to the bromide was
not amenable to cyclization (Entry 4, Table 4).
In conclusion, we have developed a strategy for palla-
dium-catalyzed intramolecular C–O bond formation which
can be applied to the synthesis of benzodioxocines fused to
an aromatic or sugar template. The reaction is applicable to
a variety of aromatic- or hexose-tethered primary alcohols,
as shown in Tables 1, 2, 3, and 4, and can be used in the
synthesis of enantiopure functionalized benzodioxocines.
Experimental Section
1
General: Melting points are uncorrected. H (300 MHz, 600 MHz)
and 13C (75 MHz, 150 MHz) NMR spectra were recorded with
332
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 330–336

Palladium-Catalyzed Intramolecular C–O Bond Formation
Bruker DPX-300 and AVANCE-600 spectrometers using CDCl3 as
solvent and TMS as the internal standard. Mass spectra were re-
corded with a JEOL AX-500/Micromass Q-Tof microTM instru-
ment. Elemental analyses were carried out with a C,H,N analyzer.
Specific rotations were measured at 589 nm with a JASCO P-10
polarimeter. TLC was performed on precoated plates (0.25 nm, sil-
ica gel 60 F254). Organic extracts were dried with anhydrous sodium
sulfate. Solvents were distilled and dried immediately prior to use.
Column chromatography and flash chromatography were carried
out by using commercial grade silica gel (60–120 or 230–400 mesh).
PS and EA stand for petroleum spirit (boiling range 60–80 °C) and
ethyl acetate.
(20 mL) at 0 °C. The reaction mixture was stirred at room tempera-
ture for 12 h and extracted with CH2Cl2 (4ϫ25 mL). The com-
bined organic layers were washed with H2O (3ϫ25 mL), dried
(Na2SO4) and evaporated to afford a syrup, which, on column
chromatography over silica gel, yielded the corresponding bromo/
iodobenzyl derivatives 3a–e.
(3aR,5R,6S,6aR)-6-(2-Bromobenzyloxy)-5-(2,2-dimethyl-1,3-diox-
olan-4-yl)-2,2-dimethyltetrahydro-2H-furo[2,3-d][1,3]dioxole (3a):
Thick oil. Yield 300 mg (70%) (eluent: PS/EA, 13:1). [α]2D5 = –21.6
1
(c = 0.25, CHCl3). H NMR (CDCl3, 300 MHz): δ = 1.32 (s, 3 H,
CH3), 1.35 (s, 3 H, CH3), 1.42 (s, 3 H, CH3), 1.50 (s, 3 H, CH3),
4.00 (dd, J = 5.8, 8.4 Hz, 1 H, 5-H), 4.07–4.18 (m, 3 H), 4.39 (dd,
J = 13.6, 6.0 Hz, 1 H, 6-H), 4.65–4.69 (d-like, 2 H, 6a-H signal
overlapped by Ha of ArCH2O), 4.76 (d, J = 12.8 Hz, 1 H, Hb of
ArCH2O), 5.92 (d, J = 3.6 Hz, 1 H, 3a-H), 7.15–7.54 (m, 4 H,
ArH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 25.7, 26.6, 27.1, 27.2,
67.8, 70.0, 72.8, 81.7, 82.6, 82.9, 105.7, 109.4, 112.2, 123.0, 127.7,
General Procedure for Dethioacetalization: A solution of the
thioacetal/ketal (1 mmol) and CH3I (710 mg, 5.0 mmol) in 84%
aqueous CH3CN (20 mL) was stirred at 25 °C for 12 h. After com-
pletion of the reaction, as revealed by TLC, the reaction mixture
was evaporated under reduced pressure. The residue obtained was
extracted with CH2Cl2 (3ϫ20 mL), the combined organic layer was
washed successively with a saturated aqueous solution of Na2S2O3
and water, and then dried (Na2SO4). Without further purification,
the crude mass was dissolved in absolute ethanol (30 mL) at 0 °C
and treated with NaBH4 (113 mg, 3 mmol) in small portions over
a period of 1 h; the stirring was continued for another 2 h at room
temperature to complete the reaction. The solvent was evaporated
under reduced pressure and the residue was extracted with CH2Cl2
(4ϫ25 mL). The combined organic layers were washed with water
and dried (Na2SO4). Evaporation of solvent afforded the alcohol
as a crude oil, which, on column chromatography over silica gel,
furnished the pure alcohol derivatives 1a–c.
129.5, 129.6, 132.9, 137.4 ppm. IR (film): νmax = 2985, 1450, 1376,
˜
1215, 1078, 1024 cm–1. MS (ESI): m/z = 451, 453 [MNa]+ (for Br79,
Br81). C19H25BrO6 (429.30): calcd. C 53.16, H 5.87; found C 53.00,
H 5.75.
(3aR,5R,6S,6aR)-6-(2-Iodobenzyloxy)-5-(2,2-dimethyl-1,3-dioxolan-
4-yl)-2,2-dimethyltetrahydro-2H-furo[2,3-d][1,3]dioxole (3b): Thick
pale-yellow oil. Yield 333 mg (70%) (eluent: PS/EA, 13:1). [α]2D5
=
1
–21.2 (c = 1.0, CHCl3). H NMR (CDCl3, 300 MHz): δ = 1.33 (s,
3 H, CH3), 1.35 (s, 3 H, CH3), 1.43 (s, 3 H, CH3), 1.51 (s, 3 H,
CH3), 4.01 (dd-like, 1 H, 5-H), 4.09–4.18 (m, 3 H), 4.39 (dd, J =
12.8, 6.9 Hz, 1 H, 6-H), 4.58–4.74 (m, 3 H, 6a-H and ArCH2 pro-
tons), 5.92 (d, J = 3.2 Hz, 1 H, 3a-H), 6.97–7.83 (m, 4 H,
ArH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 25.4, 26.2, 26.7, 26.8,
67.3, 71.5, 72.4, 81.2, 82.0, 82.4, 97.5, 105.2, 108.9, 111.8, 128.1,
128.7, 129.1, 129.3, 139.8 ppm. MS (ESI): m/z = 499 [MNa]+.
C19H25IO6 (476.30): calcd. C 47.91, H 5.29; found C 47.67, H 5.30.
[2-(2-Bromobenzyloxy)phenyl]methanol (1a): White crystalline solid,
m.p. 77 °C. Yield 234 mg (80%) (eluent: PS/EA, 9:1). 1H NMR
(CDCl3, 300 MHz): δ = 1.88 (br. s, 1 H), 4.77 (s, 2 H), 5.18 (s, 2
H), 6.97 (dd-like, 2 H), 7.19–7.37 (m, 4 H), 7.51 (d, J = 7.3 Hz, 1
H), 7.61 (d, J = 7.8 Hz, 1 H) ppm. 13C NMR (CDCl3, 150 MHz):
δ = 62.1, 69.5, 111.5, 121.2, 122.6, 127.7, 128.9, 129.0, 129.4, 129.6,
133.0, 136.0, 156.2 ppm. MS (ESI): m/z = 315, 317 [MNa]+ (for
Br79, Br81). C14H13BrO2 (293.16): calcd. C 57.36, H 4.47; found C
57.10, H 4.62.
(3aR,5R,6S,6aR)-6-(2-Bromo-5-methoxybenzyloxy)-5-(2,2-dimethyl-
1,3-dioxolan-4-yl)-2,2-dimethyltetrahydro-2H-furo[2,3-d][1,3]dioxole
(3c): Thick oil. Yield 330 mg (72%) (eluent: PS/EA, 10:1). [α]2D5
=
–24.5 (c = 0.22, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 1.32 (s,
3 H, CH3), 1.35 (s, 3 H, CH3), 1.42 (s, 3 H, CH3), 1.50 (s, 3 H,
CH3), 3.79 (s, 3 H, OCH3), 4.00 (dd, J = 8.4, 5.8 Hz, 1 H, 5-H),
4.08–4.18 (m, 3 H), 4.41 (dd, J = 12.1, 5.9 Hz, 1 H, 6-H), 4.61–
4.66 (d-like, 2 H, 6a-H signal overlapped by Ha of ArCH2O), 4.72
(d, J = 13.1 Hz, 1 H, Hb of ArCH2O), 5.92 (d, J = 3.6 Hz, 1 H,
3a-H), 6.71 (dd, J = 8.6, 2.9 Hz, 1 H, ArH), 7.07 (d, J = 2.8 Hz, 1
H, ArH), 7.41 (d, J = 8.7 Hz, 1 H, ArH) ppm. 13C NMR (CDCl3,
75 MHz): δ = 25.3, 26.2, 26.7, 26.8, 55.4, 67.3, 71.4, 72.4, 81.2,
82.1, 82.4, 105.2, 109.0, 111.8, 112.5, 114.4, 114.9, 133.0, 137.9,
[2-(2-Iodobenzyloxy)phenyl]methanol (1b): White crystalline solid,
m.p. 79 °C. Yield 245 mg (72%) (eluent: PS/EA, 9:1). 1H NMR
(CDCl3, 300 MHz): δ = 2.25 (br. s, 1 H), 4.77 (s, 2 H), 5.09 (s, 2
H), 6.93–7.08 (m, 3 H), 7.22–7.62 (m, 4 H), 7.89 (d, J = 7.8 Hz, 1
H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 61.7, 73.7, 97.4, 111.4,
121.1, 127.6, 128.4, 128.5, 128.8, 129.0, 129.6, 138.7, 139.3,
156.0 ppm. IR (film): ν
= 3296, 2912, 2860, 1604, 1488, 1369,
˜
max
1237, 1044 cm–1. MS (ESI): m/z = 363 [MNa]+. C14H13IO2
(340.16): calcd. C 49.43, H 3.85; found C 49.16, H 3.70.
159.1 ppm. IR (film): ν
= 2986, 1577, 1473, 1375, 1215, 1079,
˜
max
1021 cm–1. MS (ESI): m/z = 481, 483 [MNa]+ (for Br79, Br81).
C20H27BrO7 (459.33): calcd. C 52.30, H 5.92; found: C 52.17, H
5.88.
1-[2-(2-Bromobenzyloxy)phenyl]ethanol (1c): White crystalline solid,
m.p. 82 °C. Yield 215 mg (70%) (eluent: PS/EA, 9:1). 1H NMR
(CDCl3, 300 MHz): δ = 1.54 (d, J = 6.5 Hz, 3 H), 2.51 (br. s, 1 H),
5.16–5.25 (m, 3 H), 6.93 (d, J = 8.2 Hz, 1 H), 7.00 (t-like, 1 H),
7.23 (dd-like, 2 H), 7.34–7.42 (m, 2 H), 7.51 (d, J = 7.5 Hz, 1 H),
7.60 (d, J = 7.9 Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
23.0, 65.6, 69.3, 111.4, 121.2, 122.3, 126.0, 127.5, 128.1, 128.7,
129.3, 132.6, 134.0, 136.0, 155.0 ppm. MS (ESI): m/z = 329, 331
[MNa]+ (for Br79, Br81). C15H15BrO2 (307.18): calcd. C 58.65, H
4.92; found C 58.57, H 4.74.
(3aR,5R,6S,6aR)-5-Bromo-6-{5-[2,2-dimethyl-1,3-dioxolan-4-yl]-
2,2-dimethyltetrahydro-2H-furo[2,3-d][1,3]dioxol-6-yloxymethyl}-
benzo[1,3]dioxole (3d): Thick oil. Yield 331 mg (70%). [α]2D7 = –29.3
1
(c = 0.71, CHCl3). H NMR (300 MHz, CDCl3): δ = 1.33 (s, 3 H,
CH3), 1.37 (s, 3 H, CH3), 1.43 (s, 3 H, CH3), 1.50 (s, 3 H, CH3),
3.99 (dd, J = 5.8, 8.5 Hz, 1 H, 5-H), 4.03 (d, J = 2.9 Hz, 1 H, 6-
H), 4.09–4.15 (m, 2 H), 4.37 (dd, J = 6.0, 13.9 Hz, 1 H), 4.58 (d, J
= 12.6 Hz, 1 H, Ha of ArCH2O), 4.64 (d, J = 3.7 Hz, 1 H, 6a-H),
4.67 (d, J = 12.6 Hz, 1 H, Hb of ArCH2O), 5.91 (d, J = 3.6 Hz, 1
H, 3a-H), 5.96 (s, 2 H, O-CH2-O), 6.99 (s, 1 H, ArH), 7.03 (s, 1 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 25.7, 26.7, 27.1, 27.2,
68.0, 71.8, 72.8, 81.7, 82.3, 82.9, 102.1, 105.7, 109.5, 109.8, 112.2,
General Procedure for the Synthesis of Bromo/iodobenzylfurano
Sugar Derivatives: Bu4NBr (50 mg) followed by aqueous NaOH
(50%, 20 mL) were added to a magnetically stirred solution of
1,2:5,6-di-O-isopropylidenegluco/allofuranoside (260 mg, 1 mmol)
and the appropriate 2-bromobenzyl bromide (1.2 mmol) in CH2Cl2
Eur. J. Org. Chem. 2008, 330–336
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
333

A. Neogi, T. P. Majhi, B. Achari, P. Chattopadhyay
FULL PAPER
113.0, 113.5, 130.6, 148.0, 148.2 ppm. MS (ESI): m/z (%) = 472,
474 (40) [M]+ (for Br79, Br81]. C20H25BrO8 (473.31): calcd. C 50.75,
H 5.32; found C 50.42, H 5.29.
8.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 26.2, 26.7,
60.7, 75.5, 80.3, 82.0, 83.0, 98.0, 105.0, 112.0, 128.3, 129.0, 129.3,
129.6, 139.2 ppm. IR (film) ν
= 3443, 2981, 2933, 1438, 1375,
˜
max
1252, 1014 cm–1. MS (ESI): m/z = 429 [MNa]+. C15H19IO5
(3aR,5R,6R,6aR)-6-(2-Bromobenzyloxy)-5-(2,2-dimethyl-1,3-diox-
olan-4-yl)-2,2-dimethyltetrahydro-2H-furo[2,3-d][1,3]dioxole (3e):
White solid. Yield 317 mg (74%) (eluent: PS/EA, 6:1). [α]2D5 = +99.1
(406.21): calcd. C 44.35, H 4.71; found C 44.62, H 4.49.
(3aR,5R,6S,6aR)-[6-(2-Bromo-5-methoxybenzyloxy)-2,2-dimethyl-
tetrahydro-2H-furo[2,3-d][1,3]dioxol-5-yl]methanol (4c): Thick oil.
Yield 660 mg (85%) (eluent: PS/EA, 4:1). [α]2D5 = –36.3 (c = 2.23,
1
(c = 1.07, CHCl3). H NMR (CDCl3, 300 MHz): δ = 1.36 (s, 9 H,
3ϫCH3), 1.59 (s, 3 H, CH3), 3.93 (dd, J = 8.5, 4.6 Hz, 1 H, 5-H),
4.00 (d, J = 7.0 Hz, 2 H), 4.16 (dd, J = 8.5, 3.4 Hz, 1 H, 6-H),
4.33–4.39 (m, 1 H), 4.68 (d, J = 12.8 Hz, 1 H, Ha of ArCH2O),
4.72 (d, J = 4.2 Hz, 1 H, 6a-H), 4.85 (d, J = 12.8 Hz, 1 H, Hb of
ArCH2O), 5.80 (d, J = 3.7 Hz, 1 H, 3a-H), 7.16 (dt-like, 1 H, ArH),
7.32 (dt-like, 1 H, ArH), 7.55 (dd-like, 2 H, ArH) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 25.2, 26.2, 26.7, 26.8, 65.2, 71.3, 74.9, 77.8,
78.2, 78.3, 104.0, 109.6, 113.0, 122.7, 127.4, 129.2, 129.6, 132.5,
1
CHCl3). H NMR (CDCl3, 300 MHz): δ = 1.35 (s, 3 H), 1.51 (s, 3
H), 2.14 (br. s, 1 H), 3.79 (s, 3 H), 3.90–4.02 (m, 2 H), 4.10 (d, J =
3.4 Hz, 1 H), 4.35 (d-like, 1 H), 4.53 (d, J = 12.6 Hz, 1 H), 4.71 (d-
like, 2 H), 6.00 (d, J = 3.8 Hz, 1 H), 6.74 (dd, J = 8.7, 3.0 Hz, 1
H), 6.96 (d, J = 3.0 Hz, 1 H), 7.43 (d, J = 8.7 Hz, 1 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 26.3, 26.8, 55.5, 61.0, 71.3, 80.1, 82.2,
83.3, 105.1, 112.0, 113.0, 115.0, 115.1, 133.3, 137.4, 159.1 ppm. IR
(film): ν
= 3493, 2985, 2936, 1475, 1454, 1375, 1240 cm–1. MS
˜
137.0 ppm. IR (film): ν
= 2985, 1450, 1376, 1215, 1078,
˜
max
max
(ESI): m/z = 411, 413 [MNa]+ (for Br79, Br81). C16H21BrO6
1024 cm–1. MS (ESI): m/z: 451, 453 [MNa]+ (for Br79, Br81].
C19H25BrO6 (429.30): calcd. C 53.16, H 5.87; found C 52.97, H
5.71.
(389.24): calcd. C 49.37, H 5.44; found C 49.10, H 5.17.
(3aR,5R,6S,6aR)-{6-[6-Bromobenzo[1,3]dioxol-5-ylmethoxy]-2,2-di-
methyltetrahydro-2H-furo[2,3-d][1,3]dioxol-5-yl}methanol (4d):
Thick oil. Yield 660 mg (82%) (eluent: PS/EA, 4:1). [α]2D5 = –26.7
General Procedure for the Synthesis of Sugar Alcohols 4a–e: The
appropriate bromo/iodobenzyl derivative 3a–e (2 mmol) was stirred
overnight with 70% aqueous HOAc (25 mL, v/v) at room tempera-
ture (monitored by TLC until disappearance of the starting mate-
rial). Removal of HOAc on a rotary evaporator under reduced
pressure (temp. 40 °C) by codistillation with dry toluene
(4ϫ25 mL) afforded the intermediate diol as a viscous syrup. A
solution of the diol in a minimum volume of methanol was cooled
to 0 °C and treated with aqueous NaIO4 (513 mg, 2.4 mmol, dis-
solved in 20 mL of water) dropwise with stirring (45 min). The re-
action mixture was evaporated under reduced pressure and the re-
sidual mass was extracted with CHCl3 (4ϫ25 mL). The combined
organic layer was washed with water (3 ϫ 25 mL) and dried
(Na2SO4). The solvent was evaporated to furnish the crude alde-
hyde. Without further purification, this was dissolved in absolute
ethanol (30 mL) at 0 °C and treated with NaBH4 (113 mg, 3 mmol)
in small portions over a period of 1 h. Stirring was continued for
another 2 h at room temperature. The solvent was evaporated un-
der reduced pressure and the residue was extracted with CH2Cl2
(4ϫ25 mL). The combined organic layer was washed with water
and dried (Na2SO4). Evaporation of the solvent afforded the
alcohol as a crude oil, which, on column chromatography over sil-
ica gel, furnished the pure alcohol derivatives 4a–e.
1
(c = 1.8, CHCl3). H NMR (CDCl3, 300 MHz): δ = 1.35 (s, 3 H),
1.51 (s, 3 H), 2.09–2.10 (br. s, 1 H), 3.84–4.00 (m, 2 H), 4.06 (d, J
= 3.2 Hz, 1 H), 4.32 (d-like, 1 H), 4.49 (d, J = 12.0 Hz, 1 H), 4.67
(d-like, 2 H), 5.99 (s, 3 H), 6.88 (s, 1 H), 7.02 (s, 1 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 26.3, 26.7, 61.0, 71.2, 80.2, 82.2, 83.0,
102.0, 105.0, 109.5, 112.0, 113.0, 114.0, 129.4, 147.4, 148.1 ppm.
IR (film): ν
= 3478, 2984, 2934, 1503, 1481, 1454, 1375,
˜
max
1238 cm–1. MS (ESI): m/z = 425, 427 [MNa]+ (for Br79, Br81).
C16H19BrO7 (403.22): calcd. C 47.66, H 4.75; found C 47.41, H
4.92.
(3aR,5R,6R,6aR)-[6-(2-Bromobenzyloxy)-2,2-dimethyltetrahydro-
2H-furo[2,3-d][1,3]dioxol-5-yl]methanol (4e): Thick oil. Yield
552 mg (77%) (eluent: PS/EA, 4:1). [α]2D5 = +84.6 (c = 1.5, CHCl3).
1H NMR (CDCl3, 300 MHz): δ = 1.38 (s, 3 H), 1.60 (s, 3 H), 3.70
(d, J = 11.0 Hz, 1 H), 3.89–3.97 (m, 2 H), 4.16 (d, J = 8.9 Hz, 1
H), 4.68 (d-like, 2 H), 4.83 (d, J = 12.7 Hz, 1 H), 5.79 (d, J =
3.4 Hz, 1 H), 7.17 (t-like, 1 H), 7.33 (t-like, 1 H), 7.53 (t-like, 2
H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 26.5, 27.0, 61.0, 71.5,
77.3, 77.5, 79.0, 104.2, 113.2, 123.0, 127.5, 129.3, 129.5, 132.6,
137.0 ppm. IR (film): ν
= 3538, 2966, 2935, 1408, 1375, 1210,
˜
max
1023, 1009 cm–1. MS (ESI): m/z = 381, 383 [MNa]+ (for Br79, Br81).
C15H19BrO5 (359.21): calcd. C 50.15, H 5.33; found C 50.21, H
5.11.
(3aR,5R,6S,6aR)-[6-(2-Bromobenzyloxy)-2,2-dimethyltetrahydro-
2H-furo[2,3-d][1,3]dioxol-5-yl]methanol (4a): Thick oil. Yield
574 mg (80%) (eluent: PS/EA, 17:3). [α]2D5 = –34.2 (c = 1.2, CHCl3).
1H NMR (CDCl3, 300 MHz): δ = 1.35 (s, 3 H), 1.51 (s, 3 H), 2.12
(br. s, 1 H), 3.90–3.97 (m, 2 H), 4.10 (d, J = 3.1 Hz, 1 H), 4.34 (d,
J = 4.0 Hz, 1 H), 4.58 (d, J = 12.3 Hz, 1 H), 4.72 (d, J = 3.6 Hz,
1 H), 4.76 (d, J = 12.4 Hz, 1 H), 6.01 (d, J = 3.5 Hz, 1 H), 7.17–
7.41 (m, 3 H), 7.57 (d, J = 7.9 Hz, 1 H) ppm. 13C NMR (CDCl3,
150 MHz): δ = 26.3, 26.8, 60.8, 71.4, 80.2, 82.2, 83.3, 105.1, 112.0,
General Procedure for the Deprotection of Silyl Ethers: A mixture
of the silyl ether[14] (1 mol-equiv.) and TBAF (tetrabutylammonium
fluoride) (1.2 molequiv.) in dry THF was refluxed under nitrogen
for 4 h. Excess THF was then removed from the reaction mixture
under reduced pressure. The residue was diluted with water and
extracted with CH2Cl2 (4ϫ25 mL). The combined organic extracts
were washed with water and dried (Na2SO4). The solvent was evap-
orated to furnish the crude product, which, on column chromatog-
raphy over silica gel, furnished the pure alcohol derivatives 6a,b.
123.0, 127.6, 129.5, 129.6, 133.0, 136.4 ppm. IR (film): νmax = 3476,
˜
2986, 2935, 1441, 1375, 1214, 1081 cm–1. MS (ESI): m/z = 381, 383
[MNa]+ (for Br79, Br81). C15H19BrO5 (359.21): calcd. C 50.15, H
5.33; found C 49.90, H 5.21.
(3aS,4S,6R,7R,7aS)-[7-(2-Bromobenzyloxy)-4-methoxy-2,2-dimeth-
yltetrahydro-2H,4H-[1,3]dioxolo[4,5-c]pyran-6-yl]methanol (6a):
Thick oil. Yield 282 mg (70%) (eluent: PS/EA, 5:1). [α]2D5 = +43.5
(3aR,5R,6S,6aR)-[6-(2-Iodobenzyloxy)-2,2-dimethyltetrahydro-2H-
furo[2,3-d][1,3]dioxol-5-yl]methanol (4b): Thick oil. Yield 608 mg
(75%) (eluent: PS/EA, 17:3). [α]2D5 = –15.4 (c = 2.4, CHCl3). 1H
NMR (CDCl3, 300 MHz): δ = 1.35 (s, 3 H), 1.51 (s, 3 H), 1.85 (br.
s, 1 H), 3.89–4.02 (m, 2 H), 4.10 (d, J = 3.4 Hz, 1 H), 4.34 (d-like,
1 H), 4.51 (d, J = 12.2 Hz, 1 H), 4.70 (d-like, 2 H), 6.00 (d, J =
1
(c = 0.5, CHCl3). H NMR (CDCl3, 300 MHz): δ = 1.38 (s, 3 H),
1.55 (s, 3 H), 1.95 (br. s, 1 H), 3.39 (s, 3 H), 3.56–3.68 (m, 2 H),
3.80 (dd-like, 1 H), 3.89 (dd, J = 11.7, 2.6 Hz, 1 H), 4.15 (d, J =
5.7 Hz, 1 H), 4.33 (t, J = 6.1 Hz, 1 H), 4.68 (d, J = 12.2 Hz, 1 H),
4.95 (d-like, 2 H), 7.15 (t-like, 1 H), 7.28 (t-like, 1 H), 7.46 (dd-like,
3.7 Hz, 1 H), 7.00–7.04 (m, 1 H), 7.32–7.36 (m, 2 H), 7.84 (d, J = 1 H), 7.56 (d, J = 7.9 Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz):
334
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 330–336

Palladium-Catalyzed Intramolecular C–O Bond Formation
δ = 26.2, 28.0, 55.0, 62.3, 68.4, 72.1, 75.6, 76.3, 78.4, 98.0, 109.3,
301 [MNa]+. C15H18O5 (278.30): calcd. C 64.74, H 6.52; found C
64.61, H 6.59.
123.0, 127.2, 129.0, 130.0, 132.5, 137.3 ppm. IR (film): νmax = 3267,
˜
2921, 1460, 1370, 1246, 1022 cm–1. MS (ESI): m/z = 425, 427
[MNa]+ (for Br79, Br81). C17H23BrO6 (403.26): calcd. C 50.63, H
5.75; found C 50.34, H 5.51.
(2S,3S,4S,4aR,12aR)-3,4-Isopropylidenedioxy-2-methoxy-
2,3,4,4a,12,12a-hexahydro-6H-1,5,11-trioxadibenzo[a,e]cyclooctene
(7): White crystalline solid, m.p. 124 °C. Yield 216 mg (67%) (elu-
ent: PS/EA, 9:1). [α]2D5 = +62.9 (c = 0.6, CHCl3). 1H NMR (CDCl3,
600 MHz): δ = 1.48 (s, 3 H), 1.59 (s, 3 H), 3.39 (s, 3 H), 3.68–3.72
(m, 1 H), 3.77–3.83 (m, 3 H), 3.89–3.96 (m, 2 H), 4.73 (d, J =
13.2 Hz, 1 H), 4.79 (d, J = 13.2 Hz, 1 H), 4.88 (d, J = 4.2 Hz, 1
H), 7.01–7.04 (m, 1 H), 7.13–7.17 (m, 2 H), 7.22–7.26 (m, 1
H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 19.1, 29.2, 55.2, 62.5,
63.3, 71.7, 72.9, 81.0, 83.0, 99.3, 99.8, 121.4, 123.8, 129.3, 129.5,
(3aS,4S,6R,7R,7aS)-[7-(2-Bromo-5-methoxybenzyloxy)-4-methoxy-
2,2-dimethyltetrahydro-2H,4H-[1,3]dioxolo[4,5-c]pyran-6-yl]meth-
anol (6b): White crystalline solid, m.p. 83 °C. Yield 294 mg (68%)
(eluent: PS/EA, 5:1). [α]2D5 = +23.1 (c = 0.3, CHCl3). 1H NMR
(CDCl3, 300 MHz): δ = 1.37 (s, 3 H), 1.54 (s, 3 H), 3.39 (s, 3 H),
3.56–3.65 (m, 2 H), 3.79 (s-like, 4 H), 3.80–3.87 (m, 1 H), 4.15 (d,
J = 6.3 Hz, 1 H), 4.33 (t, J = 6.1 Hz, 1 H), 4.65 (d, J = 12.5 Hz, 1
H), 4.90 (d-like, 2 H), 6.71 (dd, J = 8.7, 3.1 Hz, 1 H), 7.04 (d, J =
3.1 Hz, 1 H), 7.41 (d, J = 8.7 Hz, 1 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 26.3, 28.0, 55.0, 55.5, 62.5, 68.4, 72.2, 76.0, 76.6,
78.5, 98.3, 109.4, 113.2, 115.0, 115.4, 133.1, 138.4, 159.0 ppm. IR
132.3, 158.2 ppm. IR (film): ν
= 2993, 2918, 1487, 1372,
˜
max
1264 cm–1. MS (ESI): m/z = 345 [MNa]+. C17H22O6 (322.35): calcd.
C 63.34, H 6.88; found C 63.06, H 6.64.
(3R,4R)-4-Acetoxymethyl-3,4-dihydro-2H,6H-benzo[1,5]dioxocin-3-
yl Acetate (8): Compound 5a (1 mmol) was dissolved in CH3CN/
H2O (3:1) containing 4% H2SO4. The mixture was stirred at 0 °C
for 3 h and then at room temperature for 5 h. The acidic solution
was neutralized with solid NaHCO3 at 0 °C and filtered. The fil-
trate was evaporated in vacuo. The residue was extracted with ethyl
acetate (6ϫ25 mL) and the combined organic layers were dried
and concentrated under vacuum. The colorless residue was dis-
solved in a minimum volume of methanol and treated with aqueous
NaIO4 (256 mg, 1.2 mmol, dissolved in 3 mL of water) at 0 °C, then
stirred for 45 min at room temperature. Usual work up followed by
NaBH4 (1.5 mmol, 57 mg) reduction of the crude in dry methanol
(20 mL) afforded the diol. This was dissolved in dry pyridine
(5 mL), treated with Ac2O (0.5 mL), and stirred at room tempera-
ture for 12 h. Pyridine was evaporated from the reaction mixture
under reduced pressure and the product was extracted with CHCl3
(6ϫ25 mL). The combined organic layers were washed successively
with cold aqueous HCl (1% v/v, 2ϫ30 mL) and water (3ϫ50 mL)
and then dried. The solvent was evaporated under vacuum. The
crude mass was purified by silica gel flash chromatography to af-
ford the diacetate 8 as a colorless oil.
(film): ν
= 3283, 2910, 1573, 1472, 1370, 1297, 1096 cm–1. MS
˜
max
(ESI): m/z = 455, 457 [MNa]+ (for Br79, Br81). C18H25BrO7
(433.29): calcd. C 49.90, H 5.82; found C 49.63, H 5.54.
General Procedure for the Synthesis of Dioxocine Derivatives:
Pd2(dba)3 or Pd(OAc)2 (5 mol-%), (Ϯ)-BINAP or DPPF (7 mol-%)
and K3PO4 (2.0 equiv.) were added to a solution of the alcohol
(1 mmol) in dry toluene (10 mL/mmol substrate) and the reaction
mixture was heated at 90 °C for 16–18 h under argon. After com-
pletion of the reaction, the crude mixture was passed through a
bed of silica gel. The solvent was evaporated and the residue was
extracted with CH2Cl2 (4ϫ25 mL). The organic layer was washed
with water (4ϫ25 mL) and dried. The solvent was evaporated un-
der reduced pressure to give the crude product which was purified
by column chromatography over silica gel to furnish the pure cy-
clized product.
6H,12H-Dibenzo[b,f][1,5]dioxocine (2): White crystalline solid, m.p.
77 °C. Yield 131 mg (62 %) (eluent: PS/EA, 19:1). 1H NMR
(CDCl3, 300 MHz): δ = 5.12 (s, 4 H), 7.03–7.11 (m, 4 H), 7.23–
7.42 (m, 4 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 75.4, 122.0,
124.0, 130.0, 130.1, 131.0, 160.3 ppm. IR (film): νmax = 2950, 1600,
˜
1488, 1305, 1273, 1186 cm–1. MS (ESI): m/z = 235 [MNa]+.
Overall yield 176 mg (60%) (eluent: PS/EA, 17:3). [α]2D5 = –42.0 (c
= 1.1, CHCl3). 1H NMR (CDCl3, 600 MHz): δ = 1.93 (s, 3 H),
2.08 (s, 3 H), 4.03 (dd, J = 12.3, 5.4 Hz, 1 H), 4.09 (dd, J = 10.8,
5.4 Hz, 1 H), 4.22 (dd, J = 10.8, 7.2 Hz, 1 H), 4.26 (dt, J = 7.2,
1.8 Hz, 1 H), 4.38 (dd, J = 12.6, 4.8 Hz, 1 H), 4.73 (d, J = 13.2 Hz,
1 H), 4.90 (d, J = 13.2 Hz, 1 H), 5.15 (dt, J = 4.8, 1.8 Hz, 1 H),
7.09–7.31 (m, 4 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 20.6,
20.8, 64.4, 71.8, 72.7, 75.5, 78.1, 122.0, 124.7, 130.0, 130.1, 132.0,
C14H12O2 (212.24): calcd. C 79.22, H 5.70; found C 79.46, H 5.56.
(2R,3R,3aS,11aR)-2,3-Isopropylidenedioxy-3,3a,11,11a-tetrahydro-
2H,5H-1,4,10-trioxabenzo[a]cyclopenta[e]cyclooctene (5a): Pale yel-
low solid, m.p. 102 °C. Yield 181 mg (65%) (eluent: PS/EA, 9:1).
[α]2D5 = +24.0 (c = 2.1, CHCl3). H NMR (CDCl3, 300 MHz): δ =
1
1.34 (s, 3 H), 1.52 (s, 3 H), 3.78 (t, J = 10.5 Hz, 1 H), 4.45 (d, J =
3.3 Hz, 1 H), 4.55 (dd, J = 10.7, 5.5 Hz, 1 H), 4.63 (d, J = 14.2 Hz,
1 H), 4.66 (d, J = 5.4 Hz, 1 H), 4.71–4.75 (m, 1 H), 4.89 (d, J =
13.6 Hz, 1 H), 5.91 (d, J = 3.4 Hz, 1 H), 7.24–7.77 (m, 4 H) ppm.
13C NMR (CDCl3, 150 MHz): δ = 26.4, 27.1, 74.3, 76.2, 79.5, 85.4,
89.0, 105.2, 112.0, 122.3, 124.2, 129.8, 130.0, 131.5 161.0 ppm. IR
159.6, 170.3, 170.7 ppm. IR (film): ν
= 2935, 1744, 1491, 1454,
˜
max
1371, 1232 cm–1. MS (ESI): m/z = 317 [MNa]+. C15H18O6 (294.30):
calcd. C 61.22, H 6.16; found C 61.03, H 6.24.
Supporting Information (see also the footnote of the first page of
this article): Experimental details and 1H and 13C NMR spectra
for compounds 1a–c, 2, 4a–e, 5a,b, 6a,b, 7, 8.
(film): ν
= 2989, 2934, 1492, 1253, 1084 cm–1. MS (ESI): m/z =
˜
max
301 [MNa]+. C15H18O5 (278.30): calcd. C 64.74, H 6.52; found C
64.49, H 6.35.
(2R,3R,3aR,11aR)-2,3-Isopropylidenedioxy-3,3a,11,11a-tetrahydro-
2H,5H-1,4,10-trioxabenzo[a]cyclopenta[e]cyclooctene (5b): Pale-yel-
low sticky liquid. Yield 180 mg (65%) (eluent: PS/EA, 17:3). [α]2D5
Acknowledgments
We are grateful to Dr R. Mukherjee, Mr. E. Padmanaban and Mr.
K. Sarkar of our Department for recording 1D and 2D NMR and
LCMS spectra, and to the Council of Scientific and Industrial Re-
search for the awards of Senior Research Fellowships (A. N. and
T. M.) and Emeritus Scientist (B. A.).
1
= –28.3 (c = 1.1, CHCl3). H NMR (CDCl3, 300 MHz): δ = 1.33
(s, 3 H), 1.49 (s, 3 H), 3.78 (t, J = 11.3 Hz, 1 H), 4.06 (dd, J = 8.0,
4.8 Hz, 1 H), 4.19–4.24 (m, 1 H), 4.50 (dd, J = 11.4, 5.4 Hz, 1 H),
4.69 (t, J = 3.7 Hz, 1 H), 4.74 (d, J = 12.1 Hz, 1 H), 4.85 (d, J =
12.1 Hz, 1 H), 5.72 (d, J = 3.2 Hz, 1 H), 7.12–7.38 (m, 4 H) ppm.
13C NMR (CDCl3, 150 MHz): δ = 26.5, 27.0, 69.1, 75.1, 77.3, 80.8,
82.7, 103.6, 113.4, 121.5, 125.1, 130.8, 131.1, 131.7, 158.0 ppm. IR
[1] For reviews on palladium-catalyzed aminations, see: a) J. P.
(film): ν
= 2930, 1453, 1372, 1252, 1029 cm–1. MS (ESI): m/z =
Wolfe, S. Wagaw, J.-F. Marcoux, S. L. Buchwald, Acc. Chem.
˜
max
Eur. J. Org. Chem. 2008, 330–336
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
335

A. Neogi, T. P. Majhi, B. Achari, P. Chattopadhyay
FULL PAPER
Res. 1998, 31, 805–818; b) J. F. Hartwig, Angew. Chem. Int. Ed.
1998, 37, 2046–2067; c) B. H. Yang, S. L. Buchwald, J. Or-
ganomet. Chem. 1999, 576, 125–146; d) A. R. Muci, S. L. Buch-
wald, Practical Palladium Catalysts for C–N and C–O Bond
2377; b) H. Ohno, H. Hamaguchi, M. Ohata, S. Kosaka, T.
Tanaka, J. Am. Chem. Soc. 2004, 126, 8744–8754; c) Y. Davion,
G. Guillaumet, J.-M. Léger, C. Jarry, B. Lesur, J.-Y. Mérour,
Heterocycles 2003, 60, 1793–1804.
Formation in Cross-Coupling Reactions: A Practical Guide (Ed.: [5] T. P. Majhi, A. Neogi, S. Ghosh, A. K. Mukherjee, P. Chatto-
N. Miyaura), Topics in Current Chemistry, Series 219,
Springer, New York, 2002, pp. 131–209; e) J. Barluenga, C.
Valdés, Chem. Commun. 2005, 4891–4901.
padhyay, Tetrahedron 2006, 62, 12003–12010.
[6] a) T. Sassa, G. Niwa, H. Unno, M. Ikeda, Y. Miura, Tetrahe-
dron Lett. 1974, 15, 3941–3942; b) K. Suzuki, K. Nozawa, S.-
I. Udagawa, S. Kawai, K.-I. Nakajima, Phytochemistry 1991,
30, 2096–2098; c) S. Sonda, K. Katayma, M. Fujio, S. Sakshita,
K. Inaba, K. Asano, T. Akira, Bioorg. Med. Chem. Lett. 2007,
17, 925–931.
[7] H. Firouzabadi, N. Iranpoor, H. Hazarkhani, J. Org. Chem.
2001, 66, 7527–7529.
[8] A. Nandi, R. Mukhopadhyay, P. Chattopadhyay, J. Chem. Soc.
Perkin Trans. 1 2001, 3346–3351, and references cited therein.
[9] S. Takano, S. Hatakeyama, K. Ogasawara, J. Chem. Soc. Chem.
Commun. 1977, 68.
[10] K3PO4 was found to be a superior base during diaryl ether
formation from electron-deficient aryl halides, see: A. Aranyos,
D. W. Old, A. Kiyomori, J. P. Wolfe, J. P. Sadighi, S. L. Buch-
wald, J. Am. Chem. Soc. 1999, 121, 4369–4378.
[11] M. C. Elliott, J. Chem. Soc. Perkin Trans. 1 1998, 4175–4200.
[12] A. Neogi, T. P. Majhi, N. Ghoshal, P. Chattopadhyay, Tetrahe-
dron 2005, 61, 9368–9374.
[13] M. Wolter, G. Nordmann, G. E. Job, S. L. Buchwald, Org. Lett.
2002, 4, 973–976.
[14] A. Nandi, P. Chattopadhyay, Tetrahedron Lett. 2002, 43, 5977–
5980.
[2] For Pd-catalyzed intermolecular C–O bond formation, see a)
G. Mann, J. F. Hartwig, J. Am. Chem. Soc. 1996, 118, 13109–
13110; b) G. Mann, C. Incarvito, A. L. Rheingold, J. F. Hart-
wig, J. Am. Chem. Soc. 1999, 121, 3224–3225; c) M. Watanabe,
M. Nishiyama, Y. Koie, Tetrahedron Lett. 1999, 40, 8837–8840;
d) Q. Shelby, N. Kataoka, G. Mann, J. F. Hartwig, J. Am.
Chem. Soc. 2000, 122, 10718–10719; e) K. E. Torraca, X. Hu-
ang, C. A. Parrish, S. L. Buchwald, J. Am. Chem. Soc. 2001,
123, 10770–10771; f) C. A. Parrish, S. L. Buchwald, J. Org.
Chem. 2001, 66, 2498–2500; g) N. Kataoka, Q. Shelby, J. P.
Stambuli, J. F. Hartwig, J. Org. Chem. 2002, 67, 5553–5566; h)
A. V. Vorogushin, X. Huang, S. L. Buchwald, J. Am. Chem.
Soc. 2005, 127, 8146–8149; i) M. C. Willis, D. Taylor, A. T.
Gillmore, Tetrahedron 2006, 62, 11513–11520.
[3] For Pd-catalyzed intramolecular C–O bond formation, see a)
M. Palucki, J. P. Wolfe, S. L. Buchwald, J. Am. Chem. Soc.
1996, 118, 10333–10334; b) K. E. Torraca, S.-I. Kuwabe, S. L.
Buchwald, J. Am. Chem. Soc. 2000, 122, 12907–12908; c) S.-I.
Kuwabe, K. E. Torraca, S. L. Buchwald, J. Am. Chem. Soc.
2001, 123, 12202–12206.
[4] For intramolecular etherification leading to eight-membered
medium-ring heterocycles, see: a) X. Ouyang, Z. Chen, L. Liu,
C. Dominguez, A. S. Kiselyov, Tetrahedron 2000, 56, 2369–
Received: August 16, 2007
Published Online: October 23, 2007
336
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 330–336