The regioselective mono-deprotection of 1,3-dioxa-2,2-(di-tert-butyl)-2-silacyclohexanes with BF3·SMe2

Article abstract of DOI:10.1021/jo025624x

The selective mono-deprotection of di-tert-butylsilylene ethers prepared from substituted 1,3-pentanediols and 2,4-hexanediols has been achieved with BF₃·SMe₂. The reaction conditions are compatible with esters, allyl ethers, and TIPS ethers. The resulting di-tert-butylfluorosilyl ethers are stable to various conditions including low pH aqueous solutions and silica gel chromatography; the di-tert-butylfluorosilyl ethers are readily cleaved with HF-pyridine. Substrate stereochemistry and conformation influences the efficiency of the deprotection, while the deprotection regiochemistry is consistent with coordination of boron to the sterically more accessible oxygen prior to intramolecular delivery of fluoride.

Full text of DOI:10.1021/jo025624x

J . Org. Chem. 2002, 67, 4553-4558
4553
Th e Regioselective Mon o-d ep r otection of
1,3-Dioxa -2,2-(d i-ter t-bu tyl)-2-sila cycloh exa n es w ith BF 3‚SMe2
Ming Yu and Brian L. Pagenkopf*
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712
pagenkopf@mail.utexas.edu
Received February 18, 2002
The selective mono-deprotection of di-tert-butylsilylene ethers prepared from substituted 1,3-
pentanediols and 2,4-hexanediols has been achieved with BF3‚SMe2. The reaction conditions are
compatible with esters, allyl ethers, and TIPS ethers. The resulting di-tert-butylfluorosilyl ethers
are stable to various conditions including low pH aqueous solutions and silica gel chromatography;
the di-tert-butylfluorosilyl ethers are readily cleaved with HF-pyridine. Substrate stereochemistry
and conformation influences the efficiency of the deprotection, while the deprotection regiochemistry
is consistent with coordination of boron to the sterically more accessible oxygen prior to
intramolecular delivery of fluoride.
Sch em e 1
In tr od u ction
The installation of protecting groups at the more
hindered hydroxyl of 1,3-diols is frequently required in
organic synthesis, but is not generally available by direct
methods.1 The task is often accomplished through mul-
tistep transformations, as with the hydridic cleavage of
benzylidene acetals. Silylation at the more hindered site
of a 1,3-diol is likewise complicated because standard
conditions result in preferential reaction at the less
hindered hydroxyl group.2 The increased reactivity at the
more accessible position normally permits selective depro-
tection at the less hindered site of a persilylated sub-
strate.3 A few reports have appeared regarding the ring
opening of di-tert-butyl-, dicyclohexyl-, and diphenylsi-
lylene ethers of 1,3- and 1,2-diols with Grignard or
alkyllithium reagents.4,5 Additionally, haloboranes are
known to deprotect silyl ethers,6,7 and have been used
for the regioselective desilylation of tert-butyldimethyl-
silyl ethers.8 We recently reported the highly regioselec-
tive mono-deprotection of the di-tert-butylsilylene ether
1 with BF3‚OEt2 (85 °C, toluene), which gave exclusively
the di-tert-butylfluoro silyl ether 2a (Scheme 1).9 In this
Paper we illuminate some of the structural and chemical
Sch em e 2
parameters that influence the mono-deprotection of tBu2-
Si(OR)2 ethers, describe the reactivity of the (F)tBu2Si
hydroxyl protecting group, and explore the compatibility
of the method with other functionality.
(1) (a) Green, W. P.; Wuts, P. G. M.; Protective Groups in Organic
Synthesis; Wiley: Toronto, 1999. (b) Kociensky, P. J . Protecting Groups;
Thieme: Stuttgart, 1994.
(2) Chaudhary, S. K.; Hernandez, O. Tetrahedron Lett. 1979, 20,
99-102.
Resu lts a n d Discu ssion
(3) (a) Boschelli, D.; Takemasa, Y.; Nishitani, Y.; Masamune, S.
Tetrahedron Lett. 1985, 26, 5239-5244. (b) Crimmins, M. T.; Lever,
J . G. Tetrahedron Lett. 1986, 27, 291-294.
The di-tert-butylsilylene ether 4,10 which like 1 was
prepared from a primary and a secondary 1,3-diol, was
selected as a model substrate to explore the generality
of the BF3‚OEt2-mediated deprotection (Scheme 2). Using
conditions similar to those utilized for 1,11 the reaction
with 4 provided the desired fluorosilane 5a along with a
(4) The 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl protecting group can
be regioselectively mono-deprotected at the less hindered site: (a) Zhu,
X. F.; Williams, H. J .; Scott, A. I. Tetrahedron Lett. 2000, 41, 9541-
9545. (b) Pankiewicz, K. W.; Watanabe, K. A.; Takayanagi, H.; Itoh,
T.; Ogura, H. J . Het. Chem. 1985, 22, 1703-1710.
(5) Tanino, K.; Shimizu, T.; Kuwahara, M.; Kuwajima, I. J . Org.
Chem. 1998, 63, 2422-2423.
(6) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
6190-6191.
(7) Kelly, D. R.; Roberts, S. M.; Newton, R. F. Synth. Commun. 1979,
9, 295-299.
(10) Corey, E. J .; Hopkins, P. B. Tetrahedron Lett. 1982, 23, 4871-
4874.
(11) The addition of allyl trimethylsilane to the reaction minimizes
the formation of side products during the first few seconds after the
addition of BF3 and is presumably serving as a kinetically fast trap
for HF.
(8) Yang, Y,-Y.; Yang, W.,-B.; Teo, C.-F.; Lin, C.-H. Synlett 2000,
1634-1636.
(9) Yu, M.; Lynch, V.; Pagenkopf, B. L. Org. Lett. 2001, 3, 2563-
2566.
10.1021/jo025624x CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/11/2002

4554 J . Org. Chem., Vol. 67, No. 13, 2002
Yu and Pagenkopf
Ta ble 1. Dep r otection of Di-ter t-bu tylsilylen e Eth er s in
Sch em e 3
th e P r esen ce of Oth er F u n ction a lity
entry
n
R
product
yield, %a
a
b
c
d
e
f
g
h
i
2
1
2
1
2
2
2
2
2
2
H
-
decomp
91b
87
CH3CO
CH3CO
PhCO
PhCO
Allyl
PhCH2
CH3
(iPr)3Si
(tBu)Me2Si
13b
13c
13d
13e
90
82
13f
78c
11g, 13g
11a , 13h
13i
57, 35
50, 43
78%
97%
j
11a
a
b
Isolated yields. 8% of the isomeric fluorosilane 12b was
detected in the crude 19F NMR. c 4% of 12f.
disappointing mixture of its regioisomer 5b, silanols 6a
and 6b, diol 3, and unreacted starting material. The
addition of 3 Å molecular sieves to the reaction prevented
the formation of silanols 6a and 6b, which were likely
due to interaction with adventitious water. The screening
of other commercially available BF3-Lewis base com-
plexes, including BF3‚THF, BF3‚tBuOMe, and BF3‚
MeOH, revealed that BF3‚SMe2 improved both the con-
version and selectivity of the reaction. However, the
formation of considerable amounts of diol 3 continued to
plague the process. The varying reactivity displayed by
different BF3 sources clearly demonstrated the impor-
tance of Lewis bases in the reaction, and a survey of
assorted adjuncts including esters, ethers, amines, and
salts showed that the addition of excess anhydrous
potassium acetate to the reaction greatly minimized
complete desilylation to diol 3.12 Replacing the toluene
solvent with chloroform or hexane further minimized
formation of diol 3. With these modifications, the regio-
selective deprotection of 4 with BF3‚SMe2 consistently
gave the fluorosilanes 5a :5b in a >15:1 ratio and 79-
85% isolated yields.13
easily cleaved to the diol 3 with HF‚pyridine (5a f 3,
96%).14
With the integrity of the di-tert-butylfluorosilane ether
amply demonstrated, substrate compatibility and avail-
ability of orthogonal protective functions was briefly
surveyed. As anticipated, the Lewis acidic nature of the
reaction media precluded the use of substrates with
Lewis acid sensitive functionality. For example, at its
current state of development, silylene ethers prepared
from tertiary or benzylic alcohols predominately undergo
elimination under the deprotection reaction conditions.
The model substrates 11a -j shown in Table 1 were used
to explore the functional group orthogonality between a
di-tert-butylsilylene ether and several common protective
groups. Acetate and benzoate esters are highly compat-
ible with the deprotection conditions (entries b-e), and
no diminution of regioselectivity at the silylene ether (i.e.,
12 vs 13) was observed,13 as might have occurred if
complicated by neighboring group participation of the
ester functionality. An allyl group easily survived the
reaction conditions, as did benzyl, but the reaction with
11g failed to go to completion. With 11h selectivity
between the methyl and silylene ethers was poor (entry
h). The bulky triisopropylsilyl ether was unaffected
during the deprotection with BF3‚SMe2, whereas cleavage
of the tert-butyl dimethylsilyl ether demarcates silicon
reactivity (entries i and j).
To ascertain whether deprotection could succeed se-
lectively when challenged with substrates presenting less
steric differentiation, silylene ethers derived from two
secondary alcohols were examined (Table 2). In entries
1 and 2 a methyl and tert-butyl group were compared,
and each reaction provided exclusively one isomeric
fluorosilane.13 The syn diastereomer (entry 2) required
nearly three times as long (2.5 h) for complete consump-
tion of starting material than did the anti diastereomer,
and a third of the starting material was fully desilylated.
Stopping the reaction in entry 2 prematurely before
significant amounts of diol formed increased the yield to
79%, based on recovered starting material. Analogous
results occurred with the anti and syn substrates shown
in entries 3 and 4. Again, reaction with the syn diaster-
eomer (entry 4) gave nearly 30% of unwanted diol when
allowed to proceed until complete consumption of starting
Although the selective deprotection of 4 under opti-
mized conditions was promising, for this new transfor-
mation to be of value the fluorosilane products must be
sufficiently robust to serve as viable protecting groups
in subsequent reactions. In this regard, the fluorosilane
2a survived several synthetic steps and flash chroma-
tography.9 Likewise, the fluorosilane 5a was stable to
aqueous acid for 15 h (THF, 10% aqueous HCl) and
neutral solutions (THF, saturated NaHCO3) (Scheme 3);
however, more strongly basic conditions resulted in
closure to the silylene ether 4 (THF, 10% aqueous NaOH,
15 min, 96%). Several transformations at the primary
alcohol of the fluorosilane 5a illustrate the stability of
the (F)tBu2Si group, including J ones oxidation, PCC
oxidation, and Finkelstein reaction. The silanol 6a was
also fairly stable, as demonstrated by its conversion to
10 in 81% yield. The di-tert-butylfluoro silane 5a can be
(12) The exact role of the KOAc is unclear, and related salts that
proved less effective include NaOAc, CsOAc, n-C15H31CO2K, PhCO2-
Na, PhCO2K, Na2CO3, K2CO3. Sodium 2-ethylhexanoate performed
similarly to KOAc.
(13) Regiochemistry was determined by oxidation to the ketone/
aldehyde or conversion of the alcohol to the iodide, cf., 8 and 9. See
Supporting Information.
(14) Trost, B. M.; Caldwell, C. G. Tetrahedron Lett. 1981, 22, 4999-
5002.

Regioselective Mono-deprotection
J . Org. Chem., Vol. 67, No. 13, 2002 4555
Ta ble 2. Dep r otection of Di-ter t-bu tylsilylen e Eth er s
P r ep a r ed fr om 2,4-Hexa n ed iols
F igu r e 1. Low energy reactive conformations.
key reaction intermediate. In an idealized chair confor-
mation the equatorial oxygen lone pair would be anti-
periplanar to the σSi-O bond of the other oxygen while
positioning fluoride sufficiently close to donate electron
density into an available orbital on silicon.16 For the anti
diastereomer in a chair conformation unfavorable 1,3-
diaxial interactions exist between the axial methyl and
a tert-butyl group on silicon, and molecular models
suggested a boat (26) for the lower energy conformation
where both the ring methyl and tert-butyl groups occupy
quasi-equatorial positions.17 In the boat conformation 26,
the boron can coordinate to the â or quasi-equatorial lone
pair without severe steric crowding. The higher temper-
atures necessary for the deprotection of 1 (85 °C) along
with the results in Table 2 suggest that conformational
freedom to permit favorable orbital alignment may be key
to efficient deprotection.
The initial difficulties encountered during the depro-
tection of 4 (Scheme 2) indicate the delicate balance
between the rate of the mono-deprotection and the rate
of the second desilylation leading to diol 3. We speculate
that the transition state corresponding to conformation
24 is higher in energy than for the anti diastereomer (26).
The longer reaction times necessary for consumption of
the syn diastereomers 16 and 20 allows the second
desilylation event to become competitive in these reac-
tions.
a
Ratio determined by 19F NMR of crude reaction mixtures, see
ref 13. Isolated yields, averaged from two runs. c 79% yield based
on recovered starting material.
b
In conclusion, parameters influencing the regioselec-
tive mono-desilylation of di-tert-butylsilylene ethers using
BF3‚SMe2 have been elucidated. The reaction can be
efficient, highly selective and provide access to 1,3-diols
silylated at the sterically more hindered position. This
new method is likely to see continued use in total
synthesis.
Sch em e 4
Exp er im en ta l Section
material. These experiments revealed that stereochem-
istry greatly influenced the efficiency of the desilylation
reaction.
All reactions were run under an atmosphere of argon unless
otherwise indicated. Reaction vessels were oven or flamed-
dried and allowed to cool in a drybox or desiccator prior to
use. Solvents and reagents were purified by standard meth-
ods.18 CHCl3 was purified by distillation from CaH2 and stored
While cleavage of silyl ethers with BCl3 is known,8 it
is interesting to note that selective mono-desilylation of
the di-tert-butylsilylene ether 4 and 11i occurred cleanly
with BCl3 (Scheme 4). However, the chlorosilanes had
to be characterized as their acetates 23, as the reactive
free alcohols 22 reverted back to starting material (with
up to 15% silanol formation) under acidic, neutral or basic
conditions, including simply standing in CDCl3 or metha-
nol. The instability displayed by the chlorosilanes dis-
couraged further investigation at this stage.
(16) For a discussion of the precise orbitals that might be involved
in this process the reader is referred to reviews on extracoordinate
silicon chemistry: Brook, M. A. Silicon in Organic, Organometallic,
and Polymer Chemistry; Wiley: New York, 2000, Chapter 2 and
Chapter 5. Nucleophilic displacement at silanes with endocyclic leaving
groups often occurs with retention. See: Bassindale, A. R.; Taylor, P.
G. Reaction Mechanisms of Nucleophilic Attack at Silicon. In The
Chemistry of Organosilicon Compounds; Patai, S.; Rappoport, Z.; Eds.,
Wiley: Chichester, UK, 1989; Vol. 1, Chapter 14. (b) Bassindale, A.
R.; Taylor, P. G. Reaction Mechanisms of Nucleophilic Attack at Silicon.
In The Chemistry of Organosilicon Compounds; Patai, S.; Rappoport,
Z.; Eds., Wiley: Chichester, UK, 1988; Vol. 2, Chapter 9.
(17) Molecular modeling with Spartan software predicted that the
ground state conformation for both the syn and anti diastereomers is
best described as a half chair given the small dihedral angles for the
CMe-O-Si-O bond in the syn (+9°, chair) and anti (-10°, boat)
diastereomers.
The regiochemistry observed in these selective depro-
tections was consistent with coordination of the boron to
the more sterically accessible oxygen prior to delivery of
fluoride.15 For the syn diastereomers coordination by
boron to the sterically more accessible R (equatorial) lone
pair of the oxygen (24, Figure 1) might be expected as a
(15) Denmark, S. E.; Willson, T. M.; Almstead, N. G. J . Am. Chem.
Soc. 1989, 111, 9258-9260.
(18) Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory
Chemicals, 4th ed.; Oxford: Butterworth Heinemann, 1996.

4556 J . Org. Chem., Vol. 67, No. 13, 2002
Yu and Pagenkopf
over Na2CO3 under an Ar atmosphere in the dark. BF3‚SMe2
(Alfa-Aesar) and BCl3 in heptane (Aldrich) were used as
received from commercial sources. Powdered KOAc was flame
dried as a melt under vacuum (0.1 mmHg). Thin-layer chro-
matography (TLC) was performed on EM 250 Kieselgel 60
F254 silica gel plates. The plates were visualized by staining
with I2 on silica, CAM,19 ninhydrin, or potassium permanga-
nate. Column chromatography was performed with silica gel
60 according to the method of Still.20
15:1 hexanes-EtOAc for elution provided the title compound
as a yellow oil (112 mg, 72%). Rf 0.34 (50% EtOAc/hexanes);
IR (thin film) ν 3110 (br), 1738 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.33-7.19 (m, 5H), 4.61 (dddd, J ) 5.9, 5.9, 5.9, 5.9
Hz, 1H), 2.78-2.63 (m, 4H), 2.03-1.95 (m, 2H), 1.07 (s, 18H);
13C NMR (75 MHz, CDCl3) δ 177.1, 141.9, 128.7, 128.6, 126.2,
70.7, 42.1, 39.1, 31.3, 27.25, 27.21, 20.5 (d, J ) 15.3 Hz), 20.4
(d, J ) 15.3 Hz); 19F NMR (300 MHz, CDCl3) δ -158.8; HRMS
m/z calcd for C19H31FO3Si [M + H]+ 355.2105, found: 355.2100.
2,2-Di-ter t-bu tyl-4-p h en eth yl-[1,3,2]-d ioxa silin a n e (4).
3-(Di-ter t-bu tyl-flu or o-silan yloxy)-5-ph en ylpen tan al (8).
To a room temperature suspension of pyridinium chlorochro-
mate (133 mg, 0.62 mmol) in CH2Cl2 (3.5 mL) was added a
solution of 5a (60 mg, 0.18 mmol) in CH2Cl2 (1.2 mL). After
2.5 h florisil and Et2O (5 mL) were added to the reaction
mixture, which was subsequently filtered through florisil. The
volatile components were removed under reduced pressure and
purification of the residue by flash chromatography on silica
gel (20:1 hexanes-EtOAc for elution) provided the title
compound as a colorless oil (109 mg, 82%). Rf 0.65 (25% EtOAc/
To a solution of diol 321 (2.59 g, 14.4 mmol) in THF:Me2NCHO
t
(2:1, 30 mL) cooled to -30 °C was added Bu2Si(OTf)2 (5.80
mL, 15.8 mmol) dropwise over 15 min. After 25 min the
reaction mixture was neutralized with pyridine (2.40 mL, 30.0
mmol), allowed to warm to room temperature, and diluted with
Et2O (150 mL). The reaction mixture was washed with
saturated NaHCO3 solution, H2O, and brine, dried (MgSO4),
and filtered through Celite. Volatiles were removed under
reduced pressure, and the residue was purified by flash
chromatography on silica gel using 20:1 hexanes-EtOAc for
elution to provide the title compound as a colorless oil (4.01 g,
87%). Rf 0.70 (5% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3)
δ 7.35-7.20 (m, 5H), 4.12-4.02 (m, 3H), 2.90-2.71 (m, 2H),
1.93-1.73 (m, 3H), 1.62 (dd, J ) 14.1, 1.5 Hz, 1H), 1.08 (d, J
) 1.2 Hz, 9H), 1.06 (d, J ) 1.2 Hz, 9H); 13C NMR (75 MHz,
CDCl3) δ 142.7, 128.8, 128.5, 125.9, 73.0, 64.5, 40.7, 36.8, 31.6,
27.7, 27.4, 22.9, 20.1; HRMS m/z calcd for C19H32O2Si [M +
H]+ 321.1150, found: 321.2248.
hexanes); IR (thin film) ν 1722 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 9.88 (dd, J ) 2.3, 2.3 Hz, 1H), 7.34-7.20 (m, 5H),
4.66 (dddd, J ) 5.8, 5.8, 5.8, 5.8 Hz, 1H), 2.78-2.69 (m, 4H),
2.00 (ddd, J ) 5.8, 2.9, 2.9 Hz, 2H), 1.07 (s, 18H); 13C NMR
(75 MHz, CDCl3) δ 201.5, 141.7, 128.7, 128.6, 126.3, 69.6, 50.7,
39.4, 31.5, 27.2, 20.6, 20.4; 19F NMR (300 MHz, CDCl3) δ
-159.1; HRMS m/z calcd for C19H3F1O2Si [M + H]+ 339.2156,
found: 339.2158.
Di-ter t-b u t yl-flu or o-(3-iod o-1-p h en et h yl-p r op oxy)si-
la n e (9). To a room temperature solution of 5a (160 mg, 0.47
mmol) and p-toluenesulfonyl chloride (106 mg, 0.59 mmol) in
CH2Cl2 (4.5 mL) was added pyridine (0.5 mL, 6.2 mmol) in
one portion. The resulting solution was stirred at room
temperature for 20 h, and then volatiles were removed under
reduced pressure. The resulting residue was dissolved in CH2-
Cl2, and the solution was washed with saturated NaHCO3
solution, H2O, and brine and dried (MgSO4). After filtration
through a pad of Celite, volatiles were removed under reduced
pressure, and the residue was dissolved in a mixture of acetone
(4.5 mL) and NaI (720 mg, 4.8 mmol, 10.0 equiv). After 30 h
at reflux, the cooled reaction mixture was treated with
saturated NaHCO3 solution, and the acetone was removed
under reduced pressure. The resulting mixture was extracted
with EtOAc, and the combined organic layers were washed
with H2O and brine and dried (MgSO4). After filtration through
a pad of Celite, volatiles were removed under reduced pressure.
Purification of the residual oil by flash chromatography on
silica gel with 15:1 hexanes-EtOAc for elution provided the
title compound as a pale yellow syrup (180 mg, 85%). Rf 0.57
(15% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3) δ 7.34-7.19
(m, 5H), 4.23 (dddd, J ) 6.5, 6.5, 6.5, 6.5 Hz, 1H), 3.30 (t, J )
7.2 Hz, 2H), 2.74-2.68 (m, 2H), 2.17 (ddd, J ) 7.2, 7.2, 7.2
Hz, 2H), 1.96-1.89 (m, 2H), 1.08 (s, 18H); 13C NMR (75 MHz,
CDCl3) δ 142.1 (C), 128.7 (CH), 128.6 (CH), 126.1 (CH), 74.0
(CH), 41.0 (CH2), 38.5 (CH2), 31.3 (CH2), 27.4 (CH3), 27.3 (CH3),
20.6 (C), 20.4 (C), 1.9 (CH2); 19F NMR (300 MHz, CDCl3) δ
-157.9; HRMS m/z calcd for C19H32FIOSi [M + H]+ 451.1330,
found: 451.1334.
3-(Di-ter t-bu tyl-flu or o-sila n yloxy)-5-p h en yl-p en ta n -1-
ol (5a ). To a 10-mL round-bottomed flask containing 4 (350
mg, 1.09 mmol) were added KOAc (300 mg, 3.0 mmol) and
freshly activated molecular sieves (3 Å, 250 mg). The flask was
sealed with a rubber septum, flushed with argon, and treated
sequentially with CHCl3 (2.5 mL), allyl trimethylsilane (35 µL,
0.20 mmol), and BF3‚Me2S (860 µL, 8.2 mmol, 7.5 equiv). After
5.5 h the mono-deprotection was complete (TLC), and the
reaction mixture was transferred into a vigorously stirred
saturated NaHCO3 solution (10 mL) with the aid of CH2Cl2.
The heterogeneous solution was filtered through a glass frit,
and the organic layer was separated and washed with H2O,
brine, and dried (MgSO4). After filtration through a small pad
of Celite, volatiles were removed under reduced pressure.
Purification of the residual oil by flash chromatography on
silica gel with 15:1 hexanes-EtOAc for elution afforded the
title compound as a colorless oil (301 mg, 81%). Rf 0.61 (33%
EtOAc/hexanes); IR (thin film) ν 3450 (br) cm-1; 1H NMR (300
MHz, CDCl3) δ 7.36-7.21 (m, 5H), 4.42-4.38 (dddd, J ) 5.3,
5.3, 5.3, 5.3 Hz, 1H), 3.92-3.79 (m, 2H), 2.77-2.72 (m, 2H),
2.36 (br s, 1H), 2.10-1.84 (m, 5H), 1.13 (s, 9H), 1.12 (s, 9H);
13C NMR (75 MHz, CDCl3) δ 142.4 (C), 128.7 (CH), 128.6 (CH),
126.1 (CH), 72.0 (CH), 59.7 (CH2), 39.1 (CH2), 38.9 (CH2), 31.5
(CH2), 27.4 (CH3), 20.7 (d, J ) 15.1 Hz, C), 20.4 (d, J ) 15.1
Hz, C); 19F NMR (300 MHz, CDCl3) δ -158.7; HRMS m/z calcd
for C19H33FO2Si [M + H]+ 341.2312, found: 341.2323.
3-(Di-ter t-b u t yl-flu or o-sila n yloxy)-5-p h en ylp en t a n o-
ic Acid (7). To a room temperature solution of 5a (150 mg,
0.44 mmol) in acetone (3.5 mL) was added J ones reagent22
dropwise until a brown color persisted. The resulting solution
was then treated with 2-propanol dropwise until the solution
became green-blue. To the reaction mixture was added H2O,
and the organic solvent was removed under reduced pressure.
The residue was redissolved in Et2O, and the solution was
washed with saturated NaHCO3 solution, H2O, and brine and
dried (MgSO4). The solution was filtered through Celite, and
volatiles were removed under reduced pressure. Purification
of the residual oil by flash chromatography on silica gel with
Acetic Acid 2,2-Di-ter t-bu tyl-[1,3,2]d ioxa silin a n -4-yl-
m eth yl Ester (11b). To a solution of (2,2-di-tert-butyl-[1,3,2]-
dioxasilinan-4-yl)methanol23 (2.52 g, 10.2 mmol) in CH2Cl2 (22
mL) was added pyridine (2.41 mL, 29.7 mmol) and Ac2O (4.33
mL, 45.9 mmol). After 15 h at room temperature, the mixture
was poured into a vigorously stirred saturated NaHCO3
solution (20 mL). The organic layer was separated and washed
with saturated NH4Cl solution, H2O, and brine, dried (MgSO4),
and filtered through Celite. Volatile components were removed
under reduced pressure, and the residual oil was purified by
flash chromatography on silica gel using 15:1 hexanes-EtOAc
for elution to provide the title compound as a pale yellow oil
(2.70 g, 92%). Rf 0.35 (15% EtOAc/hexanes); IR (thin film) ν
(19) See footnote 50 in: Gao, Y.; Hanson, R. M.; Klunder, J . M.; Ko,
S. Y.; Masamune, H.; Sharpless, K. B. J . Am. Chem. Soc. 1987, 109,
5765-5780.
(20) Still, W. C.; Kahn, M.; Mitra, A. A. J . Org. Chem. 1978, 43,
2923-2925.
1
1744 cm-1; H NMR (300 MHz, CDCl3) δ 4.31-4.27 (m, 1H),
(21) Kiyooka, S.; Kaneko, Y.; Komura, M.; Matsuo, H.; Nakano, M.
J . Org. Chem. 1991, 56, 2276-2278.
4.13-4.08 (m, 3H), 4.03 (ddd, J ) 11.0, 5.2, 1.0 Hz, 1H), 2.06
(22) Bowden, K.; Halsall, T. G.; J ones, E. R. H.; Weedon, B. C. L. J .
Chem. Soc. 1946, 39-45.
(23) See Supporting Information.

Regioselective Mono-deprotection
J . Org. Chem., Vol. 67, No. 13, 2002 4557
(s, 3H), 1.95-1.81 (m, 1H), 1.66 (ddd, J ) 14.1, 4.1, 1.5 Hz,
1H), 1.01 (s, 9H), 0.98 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
171.1, 71.9, 68.4, 63.9, 33.1, 27.5, 27.2, 22.8, 21.1, 20.1; HRMS
m/z calcd for C14H28O4Si [M + H]+ 289.1835, found: 289.1833.
68.0, 58.8, 37.0, 27.2, 27.1, 21.0, 20.5, 20.3; 19F NMR (300 MHz,
CDCl3) δ -160.0; HRMS m/z calcd for C14H29FO4Si [M + H]+
309.1897, found: 309.1894.
Acetic Acid 3-(Di-ter t-bu tyl-flu or o-sila n yloxy)-5-h y-
d r oxy-p en tyl Ester (13c). The title compound was prepared
from 11c according to the general procedure described for the
preparation 5a , except that 4.5 equiv of BF3‚Me2S was used
(colorless oil, 364 mg, 87%). Rf 0.55 (25% EtOAc/hexanes); IR
(thin film) ν 3450 (br), 1743 cm-1; 1H NMR (300 MHz, CDCl3)
δ 4.38 (dddd, J ) 6.0, 6.0, 6.0, 6.0 Hz, 1H), 4.15 (t, J ) 6.5 Hz,
2H), 3.78-3.74 (m, 2H), 2.01 (s, 3H), 2.00-1.73 (m, 5H), 1.01
(d, J ) 0.8 Hz, 9H), 1.00 (d, J ) 0.8 Hz, 9H); 13C NMR (75
MHz, CDCl3) δ 171.3, 69.4, 61.2, 59.4, 39.3, 36.0, 27.3, 27.2,
21.2, 20.5 (d, J ) 14.7 Hz), 20.4 (d, J ) 14.7 Hz); 19F NMR
(300 MHz, CDCl3) -159.1; HRMS m/z calcd for C15H31FO4Si
[M + H]+ 323.2054, found: 323.2054.
Ben zoic Acid 2-(Di-ter t-bu tyl-flu or o-sila n yloxy)-4-h y-
d r oxy-bu tyl Ester (13d ). The title compound was prepared
from 11d according to the general procedure described for the
preparation of 5a , except that 4.0 equiv of BF3‚Me2S was used
(colorless oil, 274 mg, 90%). Rf 0.69 (20% EtOAc/hexanes); IR
(thin film) ν 3460 (br), 1720 cm-1; 1H NMR (300 MHz, CDCl3)
δ 8.04 (d, J ) 7.3 Hz, 2H), 7.53-7.50 (m, 1H), 7.41 (dd, J )
7.3, 7.3 Hz, 2H), 4.57 (dddd, J ) 5.5, 5.5, 5.5, 5.5 Hz, 1H),
4.37 (d, J ) 4.8 Hz, 2H), 3.86-3.78 (m, 2H), 1.99-1.81 (m,
3H), 1.03 (s, 9H), 1.01 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
166.7, 133.3, 130.2, 129.9, 128.6, 70.0, 68.4, 59.2, 37.2, 27.2,
27.1, 20.5 (d, J ) 14.0 Hz), 20.3 (d, J ) 14.0 Hz); 19F NMR
(300 MHz, CDCl3) δ -160.0; HRMS m/z calcd for C19H31FO4Si
[M + H]+ 371.2054, found: 371.2049.
Ben zoic Acid 2,2-Di-ter t-bu tyl-[1,3,2]d ioxa silin a n -4-
ylm eth yl Ester (11d ). To a solution of(2,2-di-tert-butyl-[1,3,2]-
dioxasilinan-4-yl)methanol23 (1.76 g, 7.2 mmol) in CH2Cl2 (20
mL) was added pyridine (1.00 mL, 12.3 mmol) and benzoyl
chloride (2.51 mL, 21.6 mmol). After stirring for 13 h at room
temperature the mixture was worked up as described for 11b.
Purification of the residual oil by flash chromatography on
silica gel using 18:1 hexanes-EtOAc for elution provided the
title compound as a colorless oil (2.23 g, 89%). Rf 0.45 (20%
EtOAc/hexanes); IR (thin film) ν 1720 cm-1 1H NMR (300
;
MHz, CDCl3) δ 8.10-8.06 (m, 2H), 7.62-7.58 (m, 1H), 7.57-
7.44 (m, 2H), 4.49-4.38 (m, 2H), 4.33-4.26 (m, 1H), 4.18 (ddd,
J ) 7.8, 2.5, 2.5 Hz, 2H), 2.06-1.94 (m, 1H), 1.79 (ddd, J )
13.8, 2.5, 2.5 Hz, 1H), 1.06 (s, 9H), 1.03 (s, 9H); 13C NMR (75
MHz, CDCl3) δ 166.6, 133.2, 130.4, 129.8, 128.6, 72.0, 68.8,
64.0, 33.2, 27.6, 27.2, 22.9, 20.1; HRMS m/z calcd for C19H30O4-
Si [M + H]+ 351.1992, found: 351.1985.
4-(2-Allyloxy-et h yl-2,2-d i-ter t-b u t yl-[1,3,2]-d ioxa sili-
n a n e (11f). To a room temperature solution of 11a (1.22 g,
4.7 mmol) in CH2Cl2 (1.4 mL) and cyclohexane (2.8 mL) was
added allyl trichloroacetimidate24 (1.78 g, 8.9 mmol) and
catalytic trifluoromethanesulfonic acid (∼50 µL). After 3 h the
reaction mixture was filtered through florisil and concentrated
under reduced pressure. The residue was dissolved in CH2-
Cl2, washed with saturated NaHCO3 solution, H2O, and brine
and dried (MgSO4). After filtration through Celite, the volatile
components were removed under reduced pressure, and the
residual oil was purified by flash chromatography on silica gel
using 40:1 hexanes-EtOAc for elution to provide the title
compound as a colorless oil (1.14 g, 81%). Rf 0.68 (20% EtOAc/
hexanes); 1H NMR (300 MHz, CDCl3) δ 5.98-5.81 (m, 1H),
5.30-5.14 (m, 2H), 4.27-4.19 (m, 1H), 4.10-4.07 (m, 2H),
3.99-3.96 (m, 2H), 3.66-3.52 (m, 2H), 1.88-1.66 (m, 3H), 1.60
(dddd, J ) 14.1, 2.6, 2.6, 2.6 Hz, 1H), 1.02 (s, 9H), 0.98 (s,
9H); 13C NMR (75 MHz, CDCl3) δ 135.2, 117.0, 72.2, 71.1, 66.6,
64.6, 38.9, 36.9, 27.7, 27.3, 22.9, 20.0; HRMS m/z calcd for
Ben zoic Acid 3-(Di-ter t-bu tyl-flu or o-sila n yloxy)-5-h y-
d r oxy-p en tyl Ester (13e). The title compound was prepared
from 11e according to the general procedure described for the
preparation of 5a , except that 5.0 equiv of BF3‚Me2S was used
(colorless oil, 198 mg, 82%). Rf 0.67 (15% EtOAc/hexanes); IR
(thin film) ν 3420 (br), 1720 cm-1; 1H NMR (300 MHz, CDCl3)
δ 8.04 (d, J ) 7.5 Hz, 2H), 7.61-7.57 (m, 1H), 7.46 (dd, J )
7.5, 7.5 Hz, 2H), 4.48-4.42 (m, 3H), 3.91-3.77 (ddd, J ) 7.6,
6.4, 6.4 Hz, 2H), 2.11 (ddd, J ) 6.4, 6.4, 6.4 Hz, 2H), 1.97-
1.84 (m, 3H), 1.82 (br s, 1H), 1.08 (s, 9H), 1.07 (s, 9H); 13C
NMR (75 MHz, CDCl3) δ 166.8, 133.2, 130.5, 129.8, 128.6, 69.6,
61.7, 59.5, 39.3, 36.1, 27.6, 27.3, 20.5 (d, J ) 15.2 Hz), 20.4 (d,
J ) 15.2 Hz); 19F NMR (300 MHz, CDCl3) δ -159.1; HRMS
m/z calcd for C20H33FO4Si [M + H]+ 385.2210, found: 385.2210.
5-Allyloxy-3-(d i-ter t-bu tyl-flu or o-sila n yloxy)p en ta n -1-
ol (13f). The title compound was prepared from 11f according
to the general procedure described for the preparation of 5a ,
except that 6.5 equiv of BF3‚Me2S was used (colorless oil, 219
mg, 78%). Rf 0.59 (20% EtOAc/hexanes); IR (thin film) ν 3395
C
16H32O3Si [M + H]+ 301. 2199, found: 301.2201.
2,2-Di-t er t -b u t yl-4-(2-t r iisop r op ylsila n yloxy-e t h yl)-
[1,3,2]-d ioxa silin a n e (11i). To a room temperature solution
of 11a (1.97 g, 7.6 mmol) in CH2Cl2 (7.5 mL) were added
pyridine (1.22 mL, 15.0 mmol) and triisopropylsilyl chloride
(1.58 mL, 11.4 mmol). The reaction mixture was stirred at
room temperature for 20 h and then poured into a vigorously
stirred saturated NH4Cl solution (8 mL). The organic layer
was separated, and the aqueous layer was extracted with CH2-
Cl2. The combined organic layers were washed with H2O and
brine and dried (MgSO4). After filtration through Celite,
volatiles were removed under reduced pressure. Purification
of the residual oil by flash chromatography on silica gel using
30:1 hexanes-EtOAc for elution provided the title compound
as a colorless oil (1.91 g, 90%). Rf 0.69 (5% EtOAc/hexanes);
1H NMR (300 MHz, CDCl3) δ 4.29 (dddd, J ) 12.8, 6.2, 6.2,
2.6 Hz, 1H), 4.13-4.08 (m, 2H), 3.95-3.79 (m, 2H), 1.91-1.77
(m, 1H), 1.73-1.61 (m, 3H), 1.11-0.98 (m, 39H); 13C NMR (75
MHz, CDCl3) δ 70.9, 64.4, 59.7, 42.1, 37.0, 27.6, 27.4, 22.8,
20.0, 18.3, 12.2; HRMS m/z calcd for C22H48O3Si [M + H]+
417.3220, found: 417.3220.
Acetic Acid 2-(Di-ter t-bu tyl-flu or o-sila n yloxy)-4-h y-
d r oxy-bu tyl Ester (13b). The title compound was prepared
from 11b according to the general procedure described for the
preparation of 5a , except that 2.3 equiv of BF3‚Me2S was used
(colorless oil, 378 mg, 91%). Rf 0.48 (33% EtOAc/hexanes); IR
(thin film) ν 3450 (br), 1744 cm-1; 1H NMR (300 MHz, CDCl3)
δ 4.42 (dddd, J ) 4.2, 4.2, 4.2, 4.2 Hz, 1H), 4.09 (dddd, J )
11.2, 11.2, 11.2, 4.2 Hz, 2H), 3.94-3.71 (m, 2H), 2.39 (br s,
1H), 2.04 (s, 3H), 1.78 (ddd, J ) 11.2, 3.8, 3.8 Hz, 2H), 1.01 (s,
9H), 1.00 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 171.3, 68.7,
(br) cm-1 1H NMR (300 MHz, CDCl3) δ 5.98-5.85 (m, 1H),
;
5.31-5.16 (m, 2H), 4.44 (dddd, J ) 5.8, 5.8, 5.8, 5.8 Hz, 1H),
3.97 (ddd, J ) 5.5, 3.1, 1.6 Hz, 2H), 3.94-3.74 (m, 2H), 3.58-
3.52 (m, 2H), 2.15 (br s, 1H), 1.96-1.77 (m, 4H), 1.07 (d, J )
0.9 Hz, 9H), 1.06 (d, J ) 0.9 Hz, 9H); 13C NMR (75 MHz,
CDCl3) δ 135.0, 117.2, 72.2, 70.3, 66.7, 59.7, 39.3, 37.0, 27.3,
27.2, 20.5 (d, J ) 12.1 Hz), 20.3 (d, J ) 12.1 Hz); 19F NMR
(300 MHz, CDCl3) δ -159.3; HRMS m/z calcd for C16H33FO3Si
[M + H]+ 321.2261, found: 321.2252.
5-Ben zyloxy 3-(d i-ter t-bu tyl-flu or o-sila n yloxy)p en ta n -
1-ol (13g). The title compound was prepared from 11g
according to the general procedure described for the prepara-
tion of 5a , except that 6.5 equiv of BF3‚Me2S was used
(colorless oil, 65 mg, 35%). Rf 0.62 (15% EtOAc/hexanes); IR
(thin film) ν 3405 (br) cm-1; 1H NMR (300 MHz, CDCl3) δ 7.39-
7.28 (m, 5H), 4.60-4.45 (m, 3H), 3.84-3.77 (m, 2H), 3.61 (dd,
J ) 6.2, 6.2 Hz, 2H), 2.00-1.84 (m, 4H), 1.69 (br s, 1H), 1.07
(d, J ) 0.8 Hz, 9H), 1.05 (d, J ) 0.8 Hz, 9H); 19F NMR (300
MHz, CDCl3) δ -159.3; HRMS m/z calcd for C20H35FO3Si [M
+ H]+ 371.2418, found: 371.2419.
3-(Di-ter t-bu tyl-flu or o-sila n yloxy)-5-m eth oxy-p en ta n -
1-ol (13h ). The title compound was prepared from 11h
according to the general procedure described for the prepara-
tion of 5a , except that 3.5 equiv of BF3‚Me2S was used
(colorless oil, 31 mg, 43%). Rf 0.32 (33% EtOAc/hexanes); IR
(thin film) ν 3390 (br) cm-1; 1H NMR (300 MHz, CDCl3) δ 4.43
(24) Wessel, H. P.; Iverson T.; Bundle, D. R. J . Chem. Soc., Perkin
Trans. 1 1985, 2247-2249.

4558 J . Org. Chem., Vol. 67, No. 13, 2002
Yu and Pagenkopf
(dddd, J ) 6.1, 6.1, 6.1, 6.1 Hz, 1H), 3.85-3.72 (m, 2H), 3.53-
3.45 (m, 2H), 3.35 (s, 3H), 2.04 (br s, 1H), 1.97-1.79 (m, 4H),
1.07 (s, 9H), 1.06 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 70.3,
69.1, 59.7, 58.8, 39.3, 37.0, 27.3, 27.2, 20.6 (d, J ) 15.1 Hz),
20.5 (d, J ) 15.1 Hz); 19F NMR (300 MHz, CDCl3) δ -159.4;
HRMS m/z calcd for C20H36FO3Si [M + H]+ 371.2418, found:
371.2419.
CDCl3) δ 4.57-4.48 (m, 1H), 3.70 (ddd, J ) 9.3, 8.1, 2.7 Hz,
1H), 2.51 (br s, 1H), 1.67-1.47 (m, 3H), 1.29 (d, J ) 6.1 Hz,
3H), 1.03 (d, J ) 1.1 Hz, 9H), 1.01 (d, J ) 1.1 Hz, 9H), 0.89
(dd, J ) 6.7, 6.7 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 72.7,
68.7, 41.7, 33.9, 27.0, 26.9, 23.3, 20.4 (d, J ) 15.3 Hz), 19.8 (d,
J ) 15.3 Hz), 18.4, 17.6; 19F NMR (300 MHz, CDCl3) δ -162.0;
HRMS m/z calcd for C15H33FO2Si [M + H]+ 293.2312, found:
293.2319.
3-(Di-ter t-b u t yl-flu or o-sila n yloxy)-5-t r iisop r op ylsila -
n yloxy-p en tyl-1-ol (13i). The title compound was prepared
from 11i according to the general procedure described for the
preparation of 5a , except that 7.0 equiv of BF3‚Me2S was used
(colorless oil, 170 mg, 78%). Rf 0.48 (15% EtOAc/hexanes); IR
(thin film) ν 3380 (br) cm-1; 1H NMR (300 MHz, CDCl3) δ 4.48
(dddd, J ) 5.9, 5.9, 5.9, 5.9 Hz, 1H), 3.88-3.76 (m, 3H), 2.03-
1.91 (m, 2H), 1.89-1.77 (m, 1H), 1.63 (br s, 1H), 1.09-1.06
(m, 39H); 13C NMR (75 MHz, CDCl3) δ 70.6, 60.1, 59.9, 40.1,
39.0, 27.3, 20.6 (d, J ) 12.0 Hz), 20.3 (d, J ) 12.0 Hz), 18.2,
12.2; 19F NMR (300 MHz, CDCl3) δ -159.4; HRMS m/z calcd
for C22H49FO3Si2 [M + H]+ 437.3283, found: 437.3282.
4-(Di-ter t-bu tyl-flu or o-sila n yloxy)-5,5-d im eth yl-h exa n -
2-ol (15). The title compound was prepared from 14 according
to the general procedure described for the preparation of 5a ,
except that 3.0 equiv of BF3‚Me2S were used (colorless oil, 255
mg, 93%). Rf 0.44 (33% EtOAc/hexanes); IR (thin film) ν 3415
4-(Di-ter t-b u t yl-flu or o-sila n yloxy)-5-m et h yl-h exa n -2-
ol (21a ). The title compound was prepared from 20 according
to the general procedure described for the preparation of 5a ,
except that 2.5 equiv of BF3‚Me2S was used (colorless oil, 136
mg, 37%). Rf 0.48 (33% EtOAc/hexanes); IR (thin film) ν 3330
1
(br) cm-1; H NMR (300 MHz, CDCl3) δ 4.16 (dddd, J ) 4.2,
4.2, 4.2, 0.8 Hz, 1H), 3.92-3.86 (m, 1H), 2.39 (br s, 1H), 1.98
(qdd, J ) 6.8, 6.8, 6.8 Hz, 1H), 1.68-1.47 (m, 3H), 1.18 (d, J
) 6.1 Hz, 3H), 1.05 (d, J ) 0.8 Hz, 9H), 1.03 (d, J ) 0.8 Hz,
9H), 0.93 (d, J ) 6.8 Hz, 3H), 0.84 (d, J ) 6.8 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 79.1, 67.2, 40.5, 33.4, 27.5, 27.4, 24.1,
20.9, 18.1, 16.8; 19F NMR (300 MHz, CDCl3) δ -156.6; HRMS
m/z calcd for C15H33FO2Si [M + H]+ 293.2312, found: 293.2305.
Acetic Acid 3-(Di-ter t-bu tyl-ch lor o-sila n yloxy)-5-p h en -
yl-p en tyl Ester (23a ). To a room temperature solution of 4
(540 mg, 1.69 mmol) in CHCl3 (5.5 mL) was added BCl3 (2.1
mL, 1.0 M in heptane, 2.1 mmol). After 25 min TLC analysis
of an aliquot indicated the reaction was complete, and the
reaction mixture was transferred with the aid of CH2Cl2 into
a stirring saturated NaHCO3 solution (8 mL). The organic
layer was separated, washed with H2O and brine, and dried
(br) cm-1 1H NMR (300 MHz, CDCl3) δ 4.12 (qdd, J ) 6.2,
;
12.2, 2.3 Hz, 1H), 4.02 (dd, J ) 8.3, 1.8 Hz, 1H), 1.64-1.55
(m, 1H), 1.51 (br s, 1H), 1.45 (ddd, J ) 14.6, 8.3, 2.5 Hz, 1H),
1.27 (d, J ) 6.2 Hz, 3H), 1.05 (s, 9H), 1.04 (s, 9H), 0.91 (s,
9H); 13C NMR (75 MHz, CDCl3) δ 80.1, 64.6, 42.8, 35.8, 27.5,
27.3, 26.2, 24.9, 21.1 (d, J ) 16.0 Hz), 20.3 (d, J ) 16.0 Hz);
19F NMR (300 MHz, CDCl3) δ -152.0; HRMS m/z calcd for
(MgSO4). After filtration through
a small pad of Celite,
volatiles were removed under reduced pressure and the residue
was purified by flash chromatography on silica gel using 10:1
hexanes-EtOAc for elution to provide the alcohol 22a as a
C
16H35FO2Si [M + H]+ 307.2469, found: 307.2453.
4-(Di-ter t-bu tyl-flu or o-sila n yloxy)-5,5-d im eth yl-h exa n -
1
2-ol (17). The title compound was prepared from 16 according
to the general procedure described for the preparation 5a ,
except that 5.0 equiv of BF3‚Me2S was used (colorless oil, 178
mg, 64%). Rf 0.42 (40% EtOAc/hexanes); IR (thin film) ν 3365
colorless oil (534 mg, 89%). Rf 0.38 (33% EtOAc/hexanes); H
NMR (300 MHz, CDCl3) δ 7.35-7.20 (m, 5H), 4.36 (dddd, J )
5.7, 5.7, 5.7, 5.7 Hz, 1H), 3.95-3.88 (m, 1H), 3.84-3.76 (m,
1H), 2.75-2.68 (m, 2 H), 2.05-1.85 (m, 4H), 1.75 (br s, 1H),
1.14 (s, 9H), 1.13 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 142.3,
128.7, 128.6, 126.1, 72.3, 59.5, 38.3, 38.2, 31.3, 27.6, 27.5, 23.5,
23.3. The oil was immediately acylated according to the general
procedure described for the preparation of 11b to afford the
product as colorless oil (544 mg, 91%). Rf 0.67 (10% EtOAc/
(br) cm-1 1H NMR (300 MHz, CDCl3) δ 4.00-3.91 (m, 1H),
;
3.80 (ddd, J ) 6.1, 3.6, 1.5 Hz, 1H), 1.77 (ddd, J ) 14.8, 6.9,
3.6 Hz, 1H), 1.64-1.55 (m, 3H), 1.17 (d, J ) 6.1 Hz, 3H), 1.04
(d, J ) 1.0 Hz, 9H), 1.03 (d, J ) 1.0 Hz, 9H), 0.90 (s, 9H); 13
C
NMR (75 MHz, CDCl3) δ 80.7, 66.7, 44.2, 36.2, 27.4, 27.1, 25.9,
23.6, 21.1 (d, J ) 15.0 Hz), 21.0 (d, J ) 15.0 Hz); 19F NMR
(300 MHz, CDCl3) δ -153.2; HRMS m/z calcd for C16H35FO2Si
[M + H]+ 307.2469, found: 307.2461.
hexanes); IR (thin film) ν1739 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.35-7.18 (m, 5H), 4.32-4.20 (m, 3H), 2.72 (dddd, J
) 13.5, 7.8, 2.7, 2.7 Hz, 2H), 2.08 (s, 3H), 2.03-1.99 (m, 4H),
1.12 (s, 18H); 13C NMR (75 MHz, CDCl3) δ 171.3, 142.2, 128.7,
128.6, 126.1, 71.5, 61.3, 38.2, 34.7, 31.1, 27.6 23.4, 21.3; HRMS
m/z calcd for C21H35ClO3Si [M + H]+ 399.2122, found: 399.2115.
4-(Di-ter t-b u t yl-flu or o-sila n yloxy)-5-m et h yl-h exa n -2-
ol (19a ) a n d 5-(Di-ter t-bu tyl-flu or o-sila n yloxy)-2-m eth yl-
h exa n -3-ol (19b). The title compounds were prepared from
18 according to the general procedure described for the
preparation of 5a , except that 2.5 equiv of BF3‚Me2S was used.
Purification of the reaction mixture by flash chromatography
on silica gel using 10:1 hexanes-EtOAc for elution provided
the title compounds 19a and 19b as colorless oils. 19a : 138
mg, 76%; Rf 0.45 (33% EtOAc/ hexanes); IR (thin film) ν 3365
Ack n ow led gm en t. We thank the Robert A. Welch
Foundation, the Texas Advanced Research Program
003658-0455-2001 and the DOD Prostate Cancer Re-
search Program DAMD17-01-1-0109 for financial sup-
port.
1
(br) cm-1; H NMR (300 MHz, CDCl3) δ 4.13 (dddd, J ) 4.1,
4.1, 4.1, 4.1 Hz, 1H), 4.06-3.99 (m, 1H), 2.05-2.00 (br s, 1H),
1.92 (dddd, J ) 7.6, 4.1, 4.1, 0.4 Hz, 1H), 1.54-1.43 (m, 2H),
1.18 (d, J ) 6.3 Hz, 3H), 1.01 (s, 18H), 0.87 (dd, J ) 6.9, 6.9
Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 75.9, 64.3, 41.2, 33.6,
27.2, 24.4, 20.5, 20.3, 18.1, 16.8; 19F NMR (300 MHz, CDCl3)
δ -157.0; HRMS m/z calcd for C15H33FO2Si [M + H]+: 293.2312,
found: 293.2308. 19b: 23 mg, 13%; Rf 0.34 (33% EtOAc/
hexanes); IR (thin film) ν 3350 (br) cm-1; 1H NMR (300 MHz,
Su p p or tin g In for m a tion Ava ila ble: Preparation of start-
ing materials (11a , 11c, 11e, 11g, 11h , 11j, 14, 16, 18, 20),
regiochemical proofs for 6a , 13b, 13c, 13f, 13i, 15, 19a ,
characterization data for 5b, 6a , 6b, 23b, and copies of NMR
spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O025624X