Synthesis of homo- and heteroprotected furcated units for modular chemistry

Full text of DOI:10.1021/jo0101508

6480
J . Org. Chem. 2001, 66, 6480-6482
Sch em e 1
Syn th esis of Hom o- a n d Heter op r otected
F u r ca ted Un its for Mod u la r Ch em istr y
Adi Dahan and Moshe Portnoy*
School of Chemistry, Raymond and Beverly Sackler Faculty
of Exact Sciences, Tel-Aviv University,
Tel-Aviv 69978, Israel
Sch em e 2
portnoy@post.tau.ac.il
Received February 6, 2001
Furcated modular units of type AB2 or ABB′ are
possible monomers for the construction of branched
oligomers. One of the leading routes to dendrimer
synthesis is based on such building blocks.1 Moreover,
such furcated units are used as branching-inducing
templates in solid-phase synthesis.2
Sch em e 3
Numerous units of type AB2 are readily available
(commercially or via well-established procedures).1b How-
ever, specific requirements, in numerous cases, dictate
the design of novel dendrimer structures and, conse-
quently, the development of suitable building blocks for
modular chemistry. Recently, our attention has been
focused on flexible dendrimers, which are based on ether
linkage. Surprisingly, we could not find a concise proce-
dure for the preparation of flexible, aliphatic, partially
protected polyols. Herein, we report the synthesis of units
1, which are suitable for the construction of ether-linked
dendrimers through a divergent strategy.3
Sch em e 4
The synthetic strategy was based on malonic ester
synthesis4 using readily available bromopropanols 2,
protected under mildly basic or acidic conditions (Scheme
1). Numerous attempts to perform alkylation of diethyl
malonate with 2a or 2b in alcoholic solvents failed.
Finally, a successful dialkylation was accomplished in
THF using NaH as a base and Bu4NI as a promoter
(Scheme 2). Remarkably, with only 15% excess of 2
employed, solely the dialkylation products were formed,
accompanied by negligible traces of monoalkylated prod-
ucts.
4a (Scheme 3). However, the hydrolysis was not compat-
ible with the TBDMS ethers. Accordingly, the two steps
were successfully replaced by a single decarbethoxylation
step.5 Optimization of this process for compounds 3
demonstrated that the best results were achieved with
3 equiv of dry LiCl in rigorously dried DMSO containing
1 equiv of H2O. While the optimized yield of this step is
not very high, most of the unreacted starting material
can be recovered and recycled, leading to good overall
conversion to monoesters 5a and 5b (Scheme 3).
The remaining steps of the malonic ester synthesis, i.e.,
hydrolysis and decarboxylation, worked perfectly well
with the PMB protecting group, leading to carboxylic acid
Synthesis of the target compounds 1a and 1b was
accomplished by the reaction of esters 5a ,b or acid 4a
with a 1 M solution of LiAlH4 in THF at 0 °C. Preparation
of the heteroprotected unit 1c was based on stepwise
alkylation of diethyl malonate with 2d and 2c, in that
order (Scheme 4). We were able to easily perform
monoalkylation with both bromides when an excess of
malonate was used. However, the reverse course of
substitutions caused severe separation problems after the
* To whom correspondence should be addressed. Fax: +972-3-640-
9293.
(1) (a) Chow, H. F.; Mong, T. K. K.; Nongrum, M. F.; Wan, C. W.
Tetrahedron 1998, 54, 8543. (b) Tomalia, D. A.; Naylor, A. M.; Goddard,
W. A., III Angew. Chem., Int. Ed. 1990, 29, 138. (c) Frechet, J . M. J .
Science 1994, 263, 1710. (d) Newkome, G. R.; Moorefield, C. N.; Baker,
G. R. Aldrichimica Acta 1992, 25, 31. (e) Fischer, M.; Vo¨gtle, F. Angew.
Chem., Int. Ed. 1999, 38, 884.
(2) (a) Posnett, D. N.; McGrath, H.; Tam, J . P. J . Biol. Chem. 1988,
263, 1719. (b) Pattarawarapan, M.; Burgess, K. Angew. Chem., Int.
Ed. 2000, 39, 4299.
(3) See, for example: Padias, A. B.; Hall, H. K, J r.; Tomalia, D. A.;
McConnell, J . R. J . Org. Chem. 1987, 52, 5305.
(4) March, J . Advanced Organic Chemistry, 4th ed.; Wiley: New
York, 1992; p 465.
(5) Krapcho, A. P.; Weimaster, J . F.; Eldridge, J . M.; J ahngen, E.
G. E., J r.; Lovey, A. J .; Stephens, W. P. J . Org. Chem. 1978, 43, 138.
10.1021/jo0101508 CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/28/2001

Notes
J . Org. Chem., Vol. 66, No. 19, 2001 6481
1-Br om o-3-tr ip h en ylm eth yloxyp r op a n e (2c). Trityl bro-
mide (9.69 g, 30 mmol, 1.0 equiv), triethylamine (7.5 mL, 53.8
mmol, 1.8 equiv), and DMAP (291 mg, 1.5 mmol) were added to
a solution of 3-bromo-1-propanol (4.12 g, 2.71 mL, 30 mmol, 1.0
equiv) in dry DMF (50 mL) at room temperature. The reaction
mixture was stirred for 12 h. Ice-cold water (300 mL) was added
to the pink cloudy solution, and the resulting mixture was
extracted with DCM (4 × 100 mL). The combined organic layer
was washed with an aqueous ammonium chloride solution (2 ×
100 mL) and dried over sodium sulfate. After evaporation of the
solvent, the colorless solid was recrystallized from ethanol to
give 6.6 g (85%) of pure 2c. Mp ) 77 °C. 1H NMR (200 MHz,
CDCl3): δ 7.44 (m, 6H), 7.5 (m, 9H), 3.55 (t, J ) 6.8 Hz, 2H),
3.20 (t, J ) 5.7 Hz, 2H), 2.10 (quin, J ) 6.4 Hz, 2H). 13C NMR
(50 MHz, CDCl3): δ 144.3, 128.8, 127.9, 127.1, 86.8, 61.4, 39.0,
second alkylation. The diester product, 3c, was subjected
to the decarbethoxylation and reduction leading to 1c
(Scheme 3). The lower yield of 1c is explained by the
diminished stability of the trityl protecting group under
decarbethoxylation conditions. The chosen DMB and
trityl protecting groups can be independently removed,
enabling selective functionalization of each arm.6
In conclusion, we developed a fast route to branching
homo- and heteroprotected units 1 with a range of
protecting groups. These previously unknown units can
now be used in modular chemistry.
Exp er im en ta l Section
33.7, 30.8. Anal. Calcd for
Found: C, 69.59; H, 5.57.
C22H21BrO: C, 69.30; H, 5.55.
Gen er a l. All reactions were conducted under an atmosphere
of nitrogen in oven-dried glassware with magnetic stirring. THF,
ether, and hexanes were dried over, and distilled from, sodium
metal with benzophenone as the indicator. Dichloromethane
(DCM) and DMSO were dried over, and distilled from, CaH2.
NaH (60% suspension in oil) was washed with dry hexanes and
dried in vacuo before use. 1H NMR (200 MHz) and 13C NMR (50
MHz) spectra were recorded in CDCl3 using TMS (1H, 0 ppm),
residual CHCl3 (1H, 7.26 ppm), or solvent (13C, 77.16 ppm) as
internal standard. The IR spectra were measured in CHCl3 using
a FTIR. The Elemental Analysis Laboratory of the Hebrew
University of J erusalem performed the elemental analysis.
Column chromatography was performed using silica gel 60
(particle size 0.04-0.063 mm).
Gen er a l P r oced u r e for th e Dia lk yla tion of Eth yl Ma l-
on a te (3a , 3b). Diethyl malonate (0.527 g, 0.5 mL, 3.3 mmol,
1.0 equiv) was slowly added to a suspension of NaH (0.36 g, 9
mmol, 2.7 equiv) in dry THF (15 mL) cooled to 0 °C. The mixture
was stirred until the hydrogen evolution had ceased and the
solution was homogeneous (1 h at 0 °C and 2 h at room
temperature). The resultant reaction mixture was cooled to 0
°C, and tetrabutylammonium iodide (2.6 g, 7 mmol, 2.1 equiv)
was added. Alkyl bromide 2 (7.7 mmol, 2.3 equiv) was added,
and the reaction mixture was refluxed for 48 h. An aqueous
ammonium chloride solution (10 mL) was added, and the
resulting mixture was extracted with EtOAc (3 × 50 mL). The
combined organic extracts were washed with water (2 × 50 mL)
and dried over magnesium sulfate. After evaporation of the
solvent, the residue was chromatographed on a silica gel column
(EtOAc/hexanes) to give the pure product (3a , 3b) as a colorless
oil.
1-Br om o-3-ter t-bu tyld im eth ylsilyloxyp r op a n e (2b). The
compound 2b was prepared according to the literature proce-
dure.7 Bp 85-90 °C (12 Torr). 1H NMR (200 MHz, CDCl3): δ
3.73 (t, J ) 5.7 Hz, 2H), 3.63 (t, J ) 6.4 Hz, 2H), 1.93 (quin, J
) 6.0 Hz, 2H), 0.67 (s, 9H), 0.40 (s, 6H).
3a : 64% yield. 1H NMR (200 MHz, CDCl3): δ 7.24 (d, J ) 8.5
Hz, 4H), 6.85 (d, J ) 8.5 Hz, 4H), 4.40 (s, 4H), 4.14 (q, J ) 7.0
Hz, 4H), 3.79 (s, 6H), 3.41 (t, J ) 6.5 Hz, 4H), 1.95 (m, 4H), 1.49
(m, 4H), 1.25 (t, J ) 7.0 Hz, 6H). 13C NMR (50 MHz, CDCl3): δ
171.6, 159.1, 130.5, 129.1, 113.7, 77.8, 72.46, 69.9, 61.0, 57.0,
55.2, 29.1, 24.4, 14.1. IR (chloroform) (cm-1): ν 1723. Anal. Calcd
for C21H31O7: C, 67.42; H, 7.80. Found: C, 67.31; H, 7.81.
3b: 68% yield. 1H NMR (200 MHz, CDCl3): δ 4.17 (q, J ) 6.9
Hz, 4H), 3.58 (t, J ) 6.2 Hz, 4H), 1.9 (m, 4H), 1.4 (m, 4H), 1.32
(t, J ) 6.9 Hz, 6H), 0.86 (s, 18H), 0.23 (s, 12H). 13C NMR (50
MHz, CDCl3): δ 169.5, 62.8, 60.7, 56.7, 28.5, 27.2, 25.7, 18.1,
13.9, -5.4. IR (chloroform) (cm-1): ν 1733. Anal. Calcd for
C25H52O6Si2: C, 59.48; H, 10.38. Found: C, 59.78; H, 10.47.
2-(3-(3,4-Dim eth oxyben zyloxy)-1-p r op yl) Ma lon a te, Di-
eth yl Ester . For this monoalkylation, the dialkylation procedure
(vide supra) was adapted using appropriate amounts of the
reagents: diethyl malonate (5.98 g, 5.68 mL, 37.5 mmol, 2.5
equiv), NaH (0.6 g, 15 mmol, 1 equiv), THF (40 mL), Bu4NI (5.54
g, 15 mmol, 1 equiv), 2d (4.29 g, 15 mmol, 1 equiv). Chroma-
tography on a silica gel column (EtOAc/hexanes 1:10 to 1:2) gave
the pure product as a colorless oil; 66% yield. 1H NMR (200 MHz,
CDCl3): δ 6.81 (s, 1H), 6.77 (m, 2H), 4.34 (s, 2H), 4.08 (q, J )
7.1 Hz, 4H), 3.81 (s, 3H), 3.78 (s, 3H), 3.39 (t, J ) 6.4 Hz, 2H),
3.28 (t, J ) 7.6 Hz, 1H), 1.9 (m, 2H), 1.58 (m, 2H), 1.17 (t, J )
7.1 Hz, 6H). 13C NMR (50 MHz, CDCl3): δ 169.3, 149.2, 148.6,
131.2, 120.2, 111.2, 72.7, 69.4, 61.2, 56.0, 55.9, 51.8, 27.4, 25.7,
14.0. IR (chloroform) (cm-1): ν 1726. HRMS (CI): found (m/z),
368.1837; calcd for C19H28O7 (M), 368.1835.
2-(3-(3,4-Dim eth oxyben zyloxy)-1-p r op yl)-2-(3-tr ip h en yl-
m eth yloxy-1-p r op yl) Ma lon a te, Dieth yl Ester (3c). For this
alkylation, the dialkylation procedure (vide supra) was adapted
using appropriate amounts of the reagents: monoalkylated
malonate (3.5 g, 9.5 mmol, 1 equiv), NaH (0.57 g, 14.25 mmol,
1.5 equiv), THF (15 mL), KI (2.36 g, 14.25 mmol, 1.5 equiv), 2c
(3.72 g, 14.25 mmol, 1.5 equiv). Chromatography on a silica gel
column (EtOAc/hexanes 1:10 to 1:2) gave the pure product 3c
as a colorless oil; 47% yield. 1H NMR (200 MHz, CDCl3): δ 7.43
(m, 6H), 7.32 (m, 9H), 6.87 (s, 1H), 6.82 (m, 2H), 4.42 (s, 2H),
4.14 (q, J ) 7.2 Hz, 4H), 3.86 (s, 3H), 3.85 (s, 3H), 3.44 (t, J )
6.4 Hz, 2H), 3.04 (t, J ) 6.4 Hz, 2H), 1.94 (m, 4H), 1.49 (m, 4H),
1.22 (t, J ) 7.1 Hz, 6H). 13C NMR (50 MHz, CDCl3): δ 171.7,
149.3, 148.8, 144.5, 131.4, 128.8, 127.8, 127.0, 120.2, 111.3, 86.6,
72.8, 70.1, 63.7, 61.2, 57.3, 56.1, 56.0, 51.8, 29.4, 29.3, 25.0, 24.6,
Gen er a l P r oced u r e for th e P r otection of 3-Br om o-1-
p r op a n ol w ith Ben zylic P r otectin g Gr ou p s (2a , 2d ). A
solution of the appropriate benzyl alcohol (37.6 mmol, 1.5 equiv)
in dry ether (35 mL) was slowly added to a suspension of sodium
hydride (0.15 g, 60%, 3.8 mmol, 0.15 equiv) in dry ether (40 mL)
at room temperature. The reaction mixture was stirred for 30
min and then cooled to 0 °C. Trichloroacetonitrile (3.8 mL, 37.6
mmol, 1.5 equiv) was added, and the reaction mixture was
allowed to warm slowly to room temperature over 4 h. After
evaporation of the solvent, the residue was dissolved in petro-
leum ether (50 mL) containing methanol (0.16 mL). The suspen-
sion was filtered through Celite, and the filtrate was concen-
trated into a yellow oil. The crude imidate was dissolved in
cyclohexane (60 mL), and a solution of 3-bromo-1-propanol (4.9
g, 2.3 mL, 25 mmol, 1 equiv) in 30 mL of methylene chloride
was added. The resulting solution was cooled to 0 °C and treated
with a catalytic amount of 10-camphorsulfonic acid. The reaction
mixture was warmed to room temperature and stirred for 12 h,
while a white precipitate was formed. The solution was filtered
through Celite, and the solids were washed with 1:2 methylene
chloride/cyclohexane (2 x 25 mL). The filtrate was washed with
saturated aqueous sodium bicarbonate (50 mL), dried over
magnesium sulfate, and concentrated. The residue was purified
by flash chromatography (EtOAc/hexanes) to give the pure
product (2a , 2d ) as a colorless oil.
2a :8 60% yield. 1H NMR (200 MHz, CDCl3): δ 7.23 (d, J )
8.5 Hz, 2H), 6.85 (d, J ) 8.5 Hz, 2H), 4.39 (s, 2H), 3.74 (s, 3H),
3.54 (t, J ) 5.8 Hz, 2H), 3.49 (t, J ) 5.8 Hz, 2H), 2.06 (quin, J
) 6.1 Hz, 2H). 13C NMR (50 MHz, CDCl3): δ 159.2, 130.4, 129.3,
113.6, 72.7, 67.4, 5.2, 32.9, 30.7.
2d : 66% yield. 1H NMR (200 MHz, CDCl3): δ 6.88 (s, 1H),
6.86 (m, 2H), 4.45 (s, 2H), 3.89 (s, 3H), 3.87 (s, 3H), 3.58 (t, J )
5.8 Hz, 2H), 3.55 (t, J ) 5.8 Hz, 2H), 2.12 (quin, J ) 6.1 Hz,
2H). 13C NMR (50 MHz, CDCl3): δ 148.8, 148.3, 130.6, 119.8,
110.8, 72.5, 67.0, 55.5, 55.4, 32.5, 30.3. HRMS (CI): found (m/
z), 289.0439/291.0419; calcd for C12H18BrO3 (M + 1), 289.0433/
291.0376.
(6) Kocienski, P. J . Protecting groups; Thieme: Stuttgart, Germany,
1994; pp 2-11.
(7) Wilson, S. R.; Zucker, P. A. J . Org. Chem. 1988, 53, 4682.
(8) Clark, J . S.; Dossetter, A. G.; Whittingham, W. G. Tetrahedron
Lett. 1996, 37, 5605.

6482 J . Org. Chem., Vol. 66, No. 19, 2001
Notes
14.2. IR (chloroform) (cm-1): ν 1723. Anal. Calcd for C41H48O8:
4.13 (q, J ) 6.9 Hz, 2H), 3.79 (s, 6H), 3.41 (m, 4H), 2.34 (m,
1H), 1.50 (m, 8H), 1.24 (t, J ) 6.9 Hz, 3H). 13C NMR (50 MHz,
CDCl3): δ 176.2, 159.4, 130.9, 129.3, 114.0, 72.7, 69.9, 60.2, 55.4,
45.3, 29.2, 27.7, 14.5. IR (chloroform) (cm-1): ν 1722. HRMS
(CI): found (m/z), 323.1878; calcd for C18H27O5 (M - PMB),
323.1858.
C, 73.63; H, 7.23. Found: C, 73.93; H, 7.34.
2,2-Bis[3-(4-m eth oxyben zyloxy)-1-p r op yl]m a lon ic Acid .
Compound 3a (456 mg, 0.88 mmol) was dissolved in 9.26 mL of
ethanol/water (70:30, v/v) containing 2.3 g of KOH. The two-
phase mixture was stirred at 80 °C for 8 h, cooled to 0 °C, and
acidified with 20% H2SO4 (18.5 mL). Water (20 mL) was then
added, and the mixture was extracted with EtOAc (2 × 30 mL).
The extract was washed with water (2 × 20 mL) and brine (2 ×
10 mL) and then dried over magnesium sulfate. The dried
extract was concentrated under reduced pressure, and the yellow
solid residue was used without further purification (261 mg,
65%). 1H NMR (200 MHz, CDCl3): δ 7.24 (d, J ) 8.5 Hz, 4H),
6.88 (d, J ) 8.5 Hz, 4H), 4.43 (s, 4H), 3.78 (s, 6H), 3.44 (t, J )
6.5 Hz, 4H), 1.93 (m, 4H), 1.24 (m, 4H). 13C NMR (50 MHz,
CDCl3): δ 177.1, 159.4, 129.7, 114.0, 72.7, 69.7, 55.4, 33.8, 25.6.
5b: 55% yield (75% brsm).9 1H NMR (200 MHz, CDCl3): δ
4.13 (q, J ) 6.9 Hz, 4H), 3.58 (t, J ) 6.2 Hz, 4H), 2.34 (m, 1H),
1.50 (m, 8H), 1.24 (t, J ) 6.9 Hz, 6H), 0.86 (s, 18H), 0.31 (s,
12H). 13C NMR (50 MHz, CDCl3): δ 176.0, 63.0, 60.2, 45.2, 30.6,
28.8, 26.0, 18.4, 14.4, -5.1. IR (neat) (cm-1): ν 1735. Anal. Calcd
for C22H48O4Si2: C, 61.05; H, 11.18. Found: C, 61.33; H, 11.37.
5c: 13% yield (37% brsm).9 1H NMR (200 MHz, CDCl3): δ 7.40
(m, 6H), 7.20 (m, 9H), 6.83 (m, 3H), 4.41 (s, 2H), 4.11 (q, J ) 7.1
Hz, 2H), 3.40 (m, 4H), 2.32 (m, 1H), 1.60 (m, 8H), 1.23 (t, J )
7.1 Hz, 3H). 13C NMR (50 MHz, CDCl3): δ 176.1, 148.7, 144.5,
131.3, 128.7, 128.4, 127.8, 126.9, 120.2, 111.2, 86.5, 72.8, 69.9,
63.4, 60.1, 56.0, 55.9, 45.6, 45.3, 29.3, 29.0, 27.9, 27.6, 14.4. IR
(chloroform) (cm-1): ν 1722. Anal. Calcd for C38H44O6: C, 76.48;
H, 7.43. Found: C, 76.70; H, 7.03.
Gen er a l P r oced u r e for Ester Red u ction (1a , 1b, 1c). A
solution of the monoester 5 (0.462 mmol, 1 equiv) in dry THF (5
mL) was dropwise added to a suspension of LiAlH4 (0.36 mL,
0.36 mmol, 0.75 equiv, 1 M in THF) in dry THF (20 mL) at 0
°C. When TLC analysis indicated complete consumption of the
starting material (2 h), the solution was quenched using the
Fieser method (50 µL of H2O, 50 µL of 15% NaOH, 150 µL of
H2O).10 The solution was allowed to warm to room temperature
and filtered through a 1 cm pad of Celite, and the Celite pad
was washed with hot EtOAc (200 mL). The combined filtrates
were concentrated, and the residue was chromatographed on a
silica gel column (EtOAc/hexanes) to give the pure product (1)
as a colorless oil.
5-(4-Met h oxyb en zyloxy)-2-[3-(4-m et h oxyb en zyloxy)-1-
p r op yl]p en ta n oic Acid (4a ). A sample of 2,2-bis[3-(4-meth-
oxybenzyloxy)-1-propyl]malonic acid (56.5 mg) was placed in a
small dry flask with a minimal volume of 1,2-dichlorobenzene
and heated to 150 °C for 40 min. Evolution of CO2 was visible
during the first 30 min of heating. The solvent was then removed
under reduced pressure, and the residue was purified by column
chromatography (silica gel; CHCl3, followed by CHCl3/2% acetic
1
acid), yielding 4a as a yellow oil (43.2 mg, 85%). H NMR (200
MHz, CDCl3): δ 7.24 (d, J ) 8.5 Hz, 4H), 6.88 (d, J ) 8.5 Hz,
4H), 4.41 (s, 4H), 3.79 (s, 6H), 3.43 (m, 4H), 2.3 (m, 1H), 1.62
(m, 8H). 13C NMR (50 MHz, CDCl3): δ 181.5, 159.3, 130.6, 129.5,
113.9, 72.7, 69.8, 55.4, 45.0, 29.0, 27.5. HRMS (CI): found (m/
z), 295.1531; calcd for C16H23O5 (M - PMB), 295.1545.
Red u ction of 5-(4-Meth oxyben zyloxy)-2-[3-(4-m eth oxy-
ben zyloxy)-1-p r op yl]p en ta n oic Acid (1a ). A solution of 4a
(43 mg, 0.1 mmol, 1 equiv) in dry ether (2 mL) was dropwise
added to a suspension of LiAlH4 (16 mg, 0.42 mmol, 4.2 equiv)
in dry ether (10 mL) at room temperature. The mixture was
stirred overnight. After the mixture was cooled, water was added
cautiously followed by a 10% solution of sulfuric acid until
neutral pH was reached. The contents of the flask were washed
with brine followed by a saturated aqueous solution of NaHCO3
and dried over magnesium sulfate. The residue was evaporated
and chromatographed on a silica gel column (EtOAc/hexanes 1:2)
to give the pure product 1a as a colorless oil; 30% yield. 1H NMR
(200 MHz, CDCl3): δ 7.24 (d, J ) 8.6 Hz, 4H), 6.86 (d, J ) 8.6
Hz, 4H), 4.40 (s, 4H), 3.77 (s, 6H), 3.54 (d, J ) 4.8 Hz, 2H), 3.43
1a : 83% yield.
1
1b: 88% yield. H NMR (200 MHz, CDCl3): δ 3.57 (t, J ) 6.0
Hz, 4H), 3.50 (d, J ) 5.2 Hz, 2H), 2.33 (s, 1H), 1.47 (m, 2H),
1.47 (m, 1H), 1.34 (m, 4H), 0.86 (s, 18H), 0.18 (s, 12H). 13C NMR
(50 MHz, CDCl3): δ 65.6, 63.6, 40.1, 30.0, 27.1, 26.1, 18.4, -5.1.
IR (neat) (cm-1): ν 3356. Anal. Calcd for C20H46O3Si2: C, 61.48;
H, 11.87. Found: C, 61.69; H, 11.56.
1c: 80% yield. 1H NMR (200 MHz, CDCl3): δ 7.40 (m, 6H),
7.20 (m, 9H), 6.83 (m, 3H), 4.42 (s, 4H), 3.86 (s, 6H), 3.52 (m,
2H), 3.43 (t, J ) 6.5 Hz, 2H), 3.05 (t, J ) 6.5 Hz, 2H), 1.53 (m,
4H), 1.53 (m, 1H), 1.38 (m, 4H). 13C NMR (50 MHz, CDCl3): δ
149.3, 148.8, 144.6, 131.3, 128.8, 127.8, 127.0, 120.3, 111.3, 86.6,
73.0, 70.6, 65.5, 64.0, 63.3, 56.0, 40.3, 27.5, 27.0. IR (chloroform)
(cm-1): ν 3750, 3445. Anal. Calcd for C36H42O5: C, 76.48; H,
7.43. Found: C, 76.64; H, 7.56.
(t, J ) 6.5 Hz, 4H), 1.53 (m, 4H), 1.53 (m, 1H), 1.38 (m, 4H). 13
C
NMR (50 MHz, CDCl3): δ 159.2, 130.7, 129.2, 113.9, 72.6, 70.5,
65.2, 55.3, 40.2, 27.5, 27.0. IR (chloroform) (cm-1): ν 3628, 3445.
HRMS (CI): found (m/z), 281.1769; calcd for C16H25O4 (M -
PMB), 281.1753.
Ack n ow led gm en t. This research was partially sup-
ported by the Tel-Aviv University Research Fund.
Gen er a l P r oced u r e for th e Deca r beth oxyla tion (5a , 5b,
5c). The proper diester (0.99 mmol, 1 equiv) was added to a
solution of water (0.018 mL, 0.99 mmol, 1 equiv) and LiCl (126
mg, 2.97 mmol, 3 equiv) in dry DMSO (10 mL) at room
temperature. The mixture was stirred for 3 days in a wax bath
at 140 °C. Ice-cold water (30 mL) was added to the brown cloudy
solution, and the resulting mixture was extracted with hexanes
(4 × 50 mL) and dried over sodium sulfate. After evaporation of
the solvent, the residue was chromatographed on a silica gel
column (EtOAc/hexanes) to give the pure product (5) as a
colorless oil.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra.
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J O0101508
(9) To maximize the yield of 5, the reaction should be terminated
before the starting material 3 is fully consumed. Thus, part of 3 is
recovered upon purification and brsm (i.e., based on recovered starting
material) yields are included.
(10) Fieser, L. F.; Fieser, M. Reagents of Organic Synthesis; Wiley:
New York, 1967; Vol. 1, p 584.
5a : 38% yield (47% brsm).9 1H NMR (200 MHz, CDCl3): δ
7.24 (d, J ) 6.6 Hz, 4H), 6.86 (d, J ) 6.6 Hz, 4H), 4.40 (s, 4H),