Allyldimethyltritylsilane. Synthesis of Cyclopentanols, Oxetanes, and Tetrahydrofurans by Reaction with Electron Deficient Olefins

Article abstract of DOI:10.1021/jo9805652

Allyldimethyltritylsilane (ADTS, 1) has been employed to access a variety of cyclopentanols via Lewis acid mediated annulation to electron deficient olefins. The intermediate silylcyclopentanes were converted to their respective cyclopentanols under mild, nonepimerizing oxidative conditions. In addition, ADTS undergoes efficient annulation onto aldehydes to provide oxetanes and tetrahydrofurans. Some preliminary investigations of this annulation to chiral nonracemic bicyclic lactams are presented.

Full text of DOI:10.1021/jo9805652

J . Org. Chem. 1998, 63, 5517-5522
5517
Allyld im eth yltr itylsila n e. Syn th esis of Cyclop en ta n ols, Oxeta n es,
a n d Tetr a h yd r ofu r a n s by Rea ction w ith Electr on Deficien t Olefin s
Michael D. Groaning, Gregory P. Brengel, and A. I. Meyers*
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872
Received March 26, 1998
Allyldimethyltritylsilane (ADTS, 1) has been employed to access a variety of cyclopentanols via
Lewis acid mediated annulation to electron deficient olefins. The intermediate silylcyclopentanes
were converted to their respective cyclopentanols under mild, nonepimerizing oxidative conditions.
In addition, ADTS undergoes efficient annulation onto aldehydes to provide oxetanes and
tetrahydrofurans. Some preliminary investigations of this annulation to chiral nonracemic bicyclic
lactams are presented.
Sch em e 1
The Lewis acid mediated 1,2- and 1,4-additions of
allylsilanes to aldehydes and electron deficient olefins has
become a very powerful tool in synthesis since allylsilanes
are relatively stable compared to other allylmetalloid
species and they are easily accessible by conventional
synthetic methods.1-3 In addition to simple 1,2- and 1,4-
additions, allylsilanes have demonstrated that they may
be utilized to annulate olefins and carbonyls to a variety
of four- and five-membered rings ranging from car-
bocycles to tetrahydrofurans, oxetanes, azetidines, and
pyrrolidines.4,5 A notable feature of these annulations
is the high propensity for a trans configuration in the
cyclic product, 2 (Scheme 1). This stereoselectivity can
be attributed to the preference of the electron-withdraw-
ing group and the silicon to align themselves to produce
a syn-clinal transition state.6 Although there are four
possible syn-clinal transition states that can be written
for this reaction, the carbonyl group prefers to adopt an
endo (A) rather than the exo orientation with respect to
the silane moiety in order to minimize charge separation
in the dipolar transition state. Furthermore, the initial
adduct, B, can also close to a four-membered ring under
certain conditions, as previously reported.7 This annu-
lation process provides a potentially powerful tool for the
construction of carbo- and heterocycles with predictable
and highly selective stereocenters.
demonstrated that any silane containing a nucleofugal
group such as a halogen, oxygen, or nitrogen can be
oxidized to a hydroxyl group with retention of stereo-
chemistry at the silicon-bearing carbon. This, in combi-
nation with the allylsilane addition to electron deficient
olefins or carbonyls augers well for the development of
these reagents as valuable additions to current synthetic
methods. For example, allylmethyldiphenylsilane 1a has
been shown by Kno¨lker9 to undergo annulation (Table
1) with 1-acetylcyclohexene 3 followed by oxidative
conversion to the alcohol 5. This interesting and useful
transformation, however, suffered from a modest yield
(26-38%) in the annulation to 4, while the oxidative
removal via the Tamao10 method proceeded well (80%)
to give 5. We found that allyltriisopropylsilane 1b
underwent similar annulations with excellent yields but
we were unable to convert the silyl adduct to the carbinol,
4. On the other hand, allyltriphenylsilane 1c underwent
annulations to 3 with very poor yields but was converted
to the carbinol 5 quantitatively (Table 1).
Another important feature of allylsilanes is the ability
of silicon to act as a hydroxyl surrogate.8 It has been
(1) Majetich, G. Allylsilanes in Organic Synthesis in Organic
Synthesis: Theory and Applications, Vol. 1; Hudlicky, T., Ed., J AI
Press: Greenwich, CT, 1989.
(2) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063
and references therein.
(3) (a) Sarkar, T. K. Synthesis 1990, 969. (b) Sarkar, T. K. Synthesis
1990, 1101.
(4) Majetich, G.; Desmond, R.; Soria, J . J . Org. Chem. 1986, 51, 1753.
(5) (a) Brengel, G. P.; Meyers, A. I. J . Org. Chem. 1996, 61, 3230.
(b) Akiyama, T.; Yasusa, T.; Ishikawa, K.; Ozaki, S. Tetrahedron Lett.
1994, 35, 8401. (c) Panek, J .; J ain, N. J . Org. Chem. 1994, 59, 2674.
(d) Akiyama, T.; Yamanaka, M. Synlett 1996, 1095. (e) For another
method for stereoselective [3 + 2] cyclopentanone annulations using
a 3-(alkylthio)-2-siloxyallyl cationic species, see: Masuya, K.; Domon,
K.; Tanino, K.; Kuwajima, I. J . Am. Chem. Soc. 1998, 120, 1724.
(6) (a) Danheiser, R. L.; Takahashi, T.; Berto´k, B.; Dixon, B. R.
Tetrahedron Lett. 1993, 34, 3845. (b) Seebach, D.; Golinski, J . Helv.
Chim. Acta 1981, 64, 1413.
It is apparent that at least two alkyl groups on the
silicon atom are required to effect efficient addition-
(9) (a) Kno¨lker, H.; Wanzl, G. Synlett 1995, 378. (b) Kno¨lker, H.;
Foitzik, N.; Goesman, H.; Graf, R. Angew Chem., Int. Ed. Eng. 1993,
32, 1081.
(7) Brengel, G. P.; Rithner, C.: Meyers, A. I. J . Org. Chem. 1994,
59, 5144.
(8) For reviews on oxidative removal of silicon, see: (a) Fleming, I.
CHEMTRACTS-ORGANIC CHEMISTRY 1996, 9, 1. (b) J ones, G.;
Landais, Y. Tetrahedron 1996, 52, 7599.
(10) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organometallics
1983, 2, 1694. Tamao, K.; Ishida, N. J . Organomet. Chem. 1984, 269,
C37.
S0022-3263(98)00565-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/10/1998

5518 J . Org. Chem., Vol. 63, No. 16, 1998
Ta ble 1. Allyl Sila n e An n u la tion s-Oxid a tion to F u sed Cyclop en ta n ols
Groaning et al.
annulation and a readily F-labile group is necessary for
efficient oxidation. This delicate balance between reac-
tivity and oxidative silicon removal was fortunately
achieved by use of allyldimethyltritylsilane, 1d . We
recently reported our preliminary results on the use of
allyldimethyltritylsilane (ADTS) to annulate several
enone systems.5a When enone 3 was treated with ADTS
under Lewis acid conditions, the annulation occurred in
80% yield and more importantly, the oxidative disilyla-
tion proceeded in 67-70% yields. The large trityl group,
the necessary alkyl groups, and ease of oxidative removal
of the silicon all contributed to a successful solution to
the problem at hand. The further versatility of this
reagent in annulation and subsequent oxidative silicon
removal is the subject of this report.
hydrogen peroxide in THF. The examples depicted in
Table 2 demonstrate the advantages of ADTS when
compared to earlier allylsilanes utilized in annulations.
Syn th esis of 2,4-Disu bstitu ted Oxeta n es a n d Tet-
r a h yd r ofu r a n s. In addition to the carbocycle formation
seen above, ADTS was found to smoothly cycloadd to
aldehydes 19. There are two reaction pathways which
may occur and therefore offer the option to form oxetane
20 or tetrahydrofuran 21. For example, if the intermedi-
ate alkoxide A undergoes a 4-endo mode of attack (path
b), the oxetane is formed, whereas 5-exo attack (path a)
leads to the tetrahydrofuran.
Syn th esis of 3-Su bstitu ted , 3,3-Disu bstitu ted , a n d
3,4-Disu bstitu ted Cyclop en ta n ols. When 1.5 equiv of
allyldimethyltritylsilane (ADTS) 1d was added to a
premixed solution of the electron deficient olefin (Table
2) and titanium(IV) chloride in dichloromethane at -78
°C, the cyclopentyldimethyltritylsilanes were obtained in
moderate to high yield (40-85%). The various olefins
annulated in Table 2 exhibit the versatility of the silane
addition as well as the diastereoselectivity of the process.
In almost every case, except in entry f, we were unable
to observe any other stereoisomer. The silylcyclopen-
tanes were subsequently converted to their respective
cyclopentanol derivatives by a modified Tamao oxida-
tion.10 The tritylsilane was first converted to the meth-
oxysilane 18 by reaction with tetrabutylammonium
fluoride or cesium fluoride in a MeOH-THF solution.
In contrast to the carbocycle formation where temper-
ature dictates whether a four- or a five-membered ring
will form,7 changing the nature of the Lewis acid affects
ring size in the heterocycle formation. Thus, when
benzyloxyacetaldehyde 19b is added to a mixture of
ADTS and zirconium(IV) chloride at -20 °C, oxetane 20b
is obtained exclusively in 88% yield after 30 min. In
contrast, when benzyloxyacetaldehyde is added to a
solution of BF3‚OEt2 and ADTS at -78 °C, the tetrahy-
drofuran 21b is the only product obtained in 72% yield
after 12 h. The stereochemistry of 20b and 21b was
assigned on the basis of literature precedent for similar
annulations with other allylsilanes.
To demonstrate that ADTS may serve as a hydroxyl
equivalent, attempts were made to convert the silylmeth-
yl oxetanes 13a to the hydroxymethyl oxetanes 22.
However, after some effort no oxetane product was
obtained. This failure was attributed to the facile
â-cleavage of the oxetane during the Tamao oxidation.
In an attempt to determine which step in the oxidation
was causing the ring opening, an effort was made to
isolate the intermediate fluoro or methoxy silane from
20.
Treatment of the crude methoxysilane 18 with basic
hydrogen peroxide in a MeOH-THF solution furnished
the cyclopentanols in consistently good yields (67-93%)
(Table 2). It is noteworthy that little or no epimerization
occurred during the transformation of the silyl group to
the hydroxyl. The stereochemical assignments are based
on comparison to spectral data of known or analogous
compounds. It is also important to mention that the mild
oxidation conditions showed only a slight loss of the
diastereomeric integrity in only two cases (entries b and
c). In the cases where epimerization was not a concern,
Tamao oxidation could be achieved in one pot by a
combination of tetrabutylammonium hydroxide and

Allyldimethyltritylsilane
J . Org. Chem., Vol. 63, No. 16, 1998 5519
Ta ble 2. Ster eoselective Cyclop en ta n ol Syn th esis Usin g ADTS, 1d
An n u la tion s to r,â-Un sa tu r a ted Ch ir a l Bicyclic
La cta m s. To assess the versatility and scope of the
annulations above, a study to determine whether the
chiral bicyclic lactams 25, reported earlier7 to give either
four- or five-membered ring annulation, would respond
to the allyltritylsilane. These annulations were previ-
ously performed using triisopropylallyl silanes (TIPS),
but these products were obviously incapable of generating
the alcohols. When the bicyclic lactams 25 were treated
with TiCl4 in CH2Cl2 at -78 °C and the reaction mixture
was allowed to warm to 0 °C, a 50-75% yield the
cyclobutane adducts 26 and 27 was exclusively obtained
as a mixture of exo-endo silyl substituent. The major
products in each instance were the exo products 26a -c.
It is noteworthy that no cyclopentane products 32 were
observed as was previously observed7 when warming the
triisopropyl adducts to 0 °C in the presence of TiCl4.
Furthermore, the rates of reaction were qualitatively
slower with ADTS when compared to those exhibited by
A solution of the silylmethyl oxetane 20 was added to
a solution of tetrabutylammonium fluoride in THF at -20
°C. After 45 min the oxetane was completely converted
to the homoallylic alcohol 23. Solvolysis of 20 with
tetrabutylammonium hydroxide and protodesilylation
were both unsuccessful as well. However, in the case of
the silyl tetrahydrofurans 21, the ring cleavage should
not be a competing pathway, and their corresponding
hydroxytetrahydrofurans 24 were expected to form. In
the event, the conversion of the 4-silyltetrahydrofuran
20b to the 4-hydroxytetrahydrofuran 24b proceeded
cleanly in 86% yield.

5520 J . Org. Chem., Vol. 63, No. 16, 1998
Groaning et al.
cyclobutanes 26 with only tetrabutylammonium hydrox-
ide in the presence of hydrogen peroxide produced the
solvolyzed intermediate 28 which was readily oxidized
to the primary alcohols 29a and b in moderate yields.
In summary, allyldimethyltritylsilane (ADTS) has
proven to be a potentially useful and convenient reagent
for the construction of a variety of hydroxy carbo- and
heterocycles via annulation of simple enones and alde-
hydes. Annulations with this silyl reagent on chiral
nonracemic bicyclic lactams have also been demonstrated
and appear to show promise in their application toward
the synthesis of enantiopure carbo- and heterocycles.
Further studies in this area will be reported soon.
Exp er im en ta l12 Section
Allyld im eth yltr itylsila n e (ADTS) (1). To a solution of
bromodimethyl(triphenylmethyl)silane13 (6.06 g, 15.9 mmol)
in dry THF (110 mL) was added a solution of allylmagnesium
chloride (2.0 M in THF, 47.7 mmol, 24 mL). The resulting
mixture was brought to reflux and stirred for 12 h. After being
cooled to room temperature, the reaction mixture was slowly
poured into a separatory funnel containing cold saturated
aqueous NH4Cl and Et2O. The layers were separated, and the
aqueous layer was washed with Et2O. The organic layers were
combined, washed with brine, and dried over MgSO4. Filtra-
tion and rotary evaporation then gave a crude brown solid
which was purified via flash chromatography (elution with
hexane) to afford the allylsilane as a colorless solid (4.22 g,
77% yield), mp 86-89 °C: 1H NMR (CDCl3, 300 MHz) δ 0.14
(s, 6H), 1.58 (d, J ) 8.2 Hz, 2H), 4.74-4.83 (m, 2H), 5.58-
5.72 (m, 1H), 7.00-7.04 (m, 6H), 7.14-7.28 (m, 9H); 13C NMR
(CDCl3, 75 MHz) δ -0.7, 24.8, 53.9, 113.7, 125.5, 127.9, 130.1,
135.1, 146.3; IR (neat) 3052, 700 cm-1; HRMS (EI), (M+) calcd
for C24H26Si 342.1804, found 342.1806.
allyl TIPS additions, presumably due to slightly less
inductive stabilization by the methyl and trityl groups.
TiCl4-mediated rearrangement7 of the initially formed
cyclobutane from 25b to cyclopentane products 32 were
attempted by warming the reaction mixture to 20-25 °C,
but thermal decomposition of both the product and
starting materials became quite noticeable and the
cyclopentane was indeed formed in poor yield and with
loss of stereochemical integrity. Thus, 32a was obtained
in 33% yield, but with only a diastereomeric ratio of 78:
22, indicating that rearrangement took place with poor
stereoconservation. The details of this rearrangement
have already been discussed.7
Gen er a l Meth od for Cyclop en ta n n u la tion . To a solu-
tion of the electron deficient olefin (0.30 mmol) in CH2Cl2 (3
mL) at -78 °C was added titanium(IV) chloride (0.36 mmol,
1.0 M solution in dichloromethane) dropwise via syringe. After
5 min of vigorous stirring, allyltrityldimethylsilane (0.12 g,
0.36 mmol) was added dropwise as a solution in CH2Cl2. The
reaction temperature was slowly allowed to reach 0 °C
(approximately 4 h). The reaction was monitored via TLC (1:4
EtOAc/Hex) and quenched by the addition of saturated aque-
ous NH4Cl, resulting in a colorless mixture. The layers were
separated, and the aqueous layer was washed with CH2Cl2.
The organic layers were combined, dried over Na2SO4, filtered,
and concentrated via rotary evaporation to yield the crude
product which was purified via flash chromatography (9:1 Hex/
EtOAc) and analyzed as shown below.
Attempts to oxidize the silane 26 to the corresponding
carbinol using standard Tamao conditions10 resulted in
formation of the Sakurai product,11 31. This was con-
sidered to be a result of nucleophilic attack on the silicon
by the fluoride ion and subsequent elimination to the
alkene 30. If fluoride ion is indeed responsible for this
t r a n s-1-Ace t yl-8-(d im e t h ylt r it ylsilyl)b icyclo[4.3.0]-
n on a n e (4): colorless solid (0.11 g, 85% yield), mp 152-153
°C; 1H NMR (CDCl3, 300 MHz) δ 0.17 (s, 3H), 0.21 (s, 3H),
1.09-1.60 (m, 12H), 1.69-1.76 (m, 1H), 1.93 (s, 3H), 2.21-
2.29 (m, 1H), 7.01-7.27 (m, 15H); 13C NMR (CDCl3, 75 MHz)
δ -1.8, -0.7, 22.0, 23.3, 24.2, 25.3, 26.6, 31.4, 33.6, 38.6, 40.7,
54.1, 58.0, 125.5, 127.9, 130.2, 146.4, 212.9; IR (neat) 1698
cm-1; HRMS (FAB), (M+) calcd for C32H38OSi 466.2692, found
466.2676.
tr a n s-1-Acetyl-3-(d im eth yltr itylsilyl)cyclop en ta n e (6):
colorless oil (80 mg, 78% yield); 1H NMR (CDCl3, 300 MHz) δ
0.16 (s, 3H), 0.18 (s, 3H), 1.01-1.25 (m, 2H), 1.71-1.79 (m,
1H), 1.98 (s, 3H), 2.73-2.76 (m, 1H), 7.04-7.06 (m, 6H), 7.13-
7.26 (m, 9H); 13C NMR (CDCl3, 75 MHz) δ -1.7, -1.0, 27.1,
28.4, 29.4, 30.6, 31.7, 52.3, 54.1, 125.5, 127.9, 130.2, 146.4,
210.7; IR (neat) 1707 cm-1
.
2-Oxo-7-(d im eth yltr itylsilyl)bicyclo[3.3.0]octa n e (14):
colorless oil (70 mg, 46% yield); 1H NMR (CDCl3, 300 MHz) δ
fragmentation, then omitting it from the silyl-trityl
solvolysis should avoid the problem. Thus, treating the
(12) Combustion analyses were performed by Atlantic Microlabs
Inc., Norcross, GA. High-resolution mass spectra were obtained from
U.C.sRiverside.
(11) Hosomi, A.; Kobayashi, H.; Sakurai, H. Tetrahedron Lett. 1980,
21, 955.
(13) Ager, D. J .; Fleming, I. J . Chem. Res., Miniprint 1977, 136.

Allyldimethyltritylsilane
J . Org. Chem., Vol. 63, No. 16, 1998 5521
0.31 (s, 3H), 0.32 (s, 3H), 0.86-1.13 (m, 1H), 1.15-1.32 (m,
1H), 1.60-1.72 (m, 1H), 1.94 (app q, J ) 8.1 Hz, 1H), 2.09-
2.23 (m, 2H), 2.28-2.41 (m, 2H), 2.64 (app t, J ) 10.1 Hz, 1H),
2.85-2.88 (m, 1H), 7.17-7.48 (m, 15H); 13C NMR (CDCl3, 75
MHz) δ -1.8, -0.7, 25.6, 27.3, 34.3, 38.1, 39.5, 40.3, 52.0, 54.3,
stirred at room temperature for 4 h, then was partitioned
between water and CH2Cl2, the layers were separated, and
the aqueous layer was washed with CH2Cl2. The combined
organic layers were dried over Na2SO4, filtered, and concen-
trated in vacuo. The crude residue was dissolved in THF (2.5
mL) and MeOH (1.0 mL) and sequentially treated with KHCO3
(30 mg, 0.29 mmol), 30% H2O2 (9.79 M in H2O, 3.92 mmol,
0.40 mL), and tetrabutylammonium fluoride (1.0 M in THF,
0.25 mmol, 0.25 mL). The reaction mixture was vigorously
stirred at room temperature for 5 h and then partitioned
between water and CH2Cl2. The layers were separated, and
the aqueous layer was washed with CH2Cl2. The combined
organic layers were dried over Na2SO4, filtered, and concen-
trated in vacuo. The crude products were purified by flash
chromatography eluting with EtOAc/Hex (1:9).
125.5, 127.9, 130.2, 146.3, 223.1; IR (neat) 1651 cm-1
.
Sp ir o silyl k eton e 16: colorless oil (50 mg, 68% yield); 1H
NMR (CDCl3, 300 MHz) δ 0.31 (s, 3H), 0.32 (s, 3H), 0.86-
1.13 (m, 1H), 1.15-1.32 (m, 1H), 1.60-1.72 (m, 1H), 1.94 (app
q, J ) 8.1 Hz, 1H), 2.09-2.23 (m, 2H), 2.28-2.41 (m, 2H), 2.64
(app t J ) 10.1 Hz, 1H), 2.85-2.88 (m, 1H), 7.17-7.48 (m,
15H); 13C NMR (CDCl3, 75 MHz) δ -1.8, -0.7, 25.6, 27.3, 34.3,
38.1, 39.5, 40.3, 52.0, 54.3, 125.5, 127.9, 130.2, 146.3, 223.1;
IR (neat) 1651 cm-1; HRMS (EI), (M+) calcd for C35H36OSi
500.2535, found 500.2537.
tr a n s-1-Acetyl-8-h yd r oxybicyclo[4.3.0]n on a n e (5): col-
orless oil (30 mg, 67% yield): 1H NMR (CDCl3, 300 MHz) δ
1.15-1.23 (m, 1H), 1.33-1.77 (m, 8H), 1.82-1.89 (m, 1H),
1.98-2.16 (m, 2H), 2.09 (s, 3H), 2.31-2.36 (m, 1H), 4.29-4.37
(m, 1H); 13C NMR (CDCl3, 75 MHz) δ 21.7, 22.9, 25.4, 26.1,
Gen er a l P r oced u r e for An n u la tion to Ald eh yd es. To
a solution of aldehyde (0.18 mmol) and 1d (0.27 mmol) in
toluene (1.0 mL) was added zirconium(IV) chloride (0.19 mmol)
at -20 °C. After being stirred at -20 °C for 30 min, the
reaction mixture was treated with saturated aqueous NH4Cl.
The aqueous layer was extracted with CH2Cl2, and the
combined organic layers were washed with brine, dried over
Na2SO4, and concentrated in vacuo. The crude products were
purified via flash chromatography eluting with EtOAc/Hex (1:
9).
30.0, 38.2, 39.3, 44.4, 57.7, 71.2, 212.7; IR (neat) 3420 cm-1
;
HRMS (FAB), (M+) calcd for C11H18O2 183.1385, found 183.1387.
tr a n s-1-Acetyl-3-h yd r oxycyclop en ta n e (7): colorless oil
1
(34 mg, 69% yield); H NMR (CDCl3, 300 MHz) δ 1.57-2.10
(m, 6H), 2.15 (s, 3H), 3.16 (dddd, J ) 9.5, 7.0, 5.5, 4.2 Hz, 1H),
4.38 (dddd, J ) 8.5, 7.0, 3.5, 3.1 Hz, 1H); 13C NMR (CDCl3, 75
MHz) δ 26.1, 29.1, 34.9, 37.8, 49.8, 73.6, 210.7; IR (neat) 3390
cis-2-Cycloh e xyl-4-(d im e t h ylt r it ylsilyl)m e t h yloxe -
ta n e (20a ): colorless oil (110 mg, 55% yield); 1H NMR (CDCl3,
300 MHz) δ 0.39 (s, 3H), 0.41 (s, 3H), 1.18-2.1 (m, 13H), 3.58-
3.82 (m, 1H), 4.22-4.35 (m, 1H), 6.95-7.05 (d, J ) 9 Hz, 6H),
7.12 (m, 9H), 13C NMR (CDCl3, 75 MHz) δ -0.1, 1.3, 24.2, 25.1,
26.2, 27.8, 28.9, 29.2, 39.8, 46.5, 54.1, 59.8, 72.6, 125.6, 128.0,
cm-1
.
Hyd r oxy k eton e 15: colorless oil (71 mg, 93% yield); 1H
NMR (CDCl3, 300 MHz) δ 1.17-1.29 (m, 1H), 1.34-1.80 (m,
7H), 1.82-1.92 (m, 1H), 2.01-2.14 (m, 2H), 2.29-2.33 (m, 1H),
4.24-4.31 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 27.1, 31.3,
130.1, 146.3; IR (neat) 3051, 850 cm-1
.
39.2, 40.3, 44.4, 56.7, 73.2, 192.7; IR (neat) 3392 cm-1
.
cis-2-Ben zyloxym eth yl-4-(d im eth yltr itylsilyl)m eth yl-
oxeta n e (20b): colorless oil (220 mg, 88% yield); 1H NMR
(CDCl3, 300 MHz) δ 0.16 (s, 3H), 0.19 (s, 3H), 1.03-1.28 (m,
2H), 1.46-1.68 (m, 2H), 3.14-3.24 (m, 1H), 3.29-3.38 (m, 1H),
3.91-4.04 (m, 1H), 4.16-4.28 (m, 1H), 4.42 (app t, J ) 9 Hz,
2H), 6.86-6.91 (m, 6H), 7.02-7.28 (m, 14H); 13C NMR (CDCl3,
75 MHz) δ -0.1, 1.3, 29.2, 39.8, 42.5, 54.1, 59.8, 68.7, 72.6,
74.4, 125.6, 126.9, 128.0, 130.1, 137.5, 146.3; IR (neat) 3063,
845 cm-1; HRMS (CI), (MNH4+) calcd for C33H40O2NSi 510.2828,
found 510.2828.
Sp ir o h yd r oxy k eton e 17: colorless oil (61 mg, 78% yield);
1H NMR (CDCl3, 300 MHz) δ 1.15-1.32 (m, 1H), 1.60-1.72
(m, 1H), 1.94 (app q, J ) 8.1 Hz, 1H), 2.09-2.23 (m, 2H), 2.28-
2.41 (m, 2H), 2.64 (app t, J ) 10.1 Hz, 1H), 2.85-2.88 (m, 1H),
7.17-7.48 (m, 4H); 13C NMR (CDCl3, 75 MHz) δ 26.6, 29.7,
32.8, 34.9, 36.4, 44.0, 52.5, 74.1, 126.6, 128.1, 128.6, 131.3,
133.1, 143.7, 201.7; IR (neat) 3399 cm-1
14H16O2: C, 77.75; H, 7.46. Found: C, 77.83; H, 7.52.
Hyd r oxytetr a h yd r ofu r a n 24: colorless oil (81 mg, 86%
. Anal. Calcd for
C
yield). Spectral data were identical with those reported.15
Gen er a l Meth od for Cyclop en ta n n u la tion on to Bicy-
clic La cta m (25). To a solution of the bicyclic lactam 25 (1.2
mmol) in CH2Cl2 (10 mL) at -78 °C was added titanium(IV)
chloride (1.2 mmol, 1.0 M solution in CH2Cl2) dropwise via
syringe. After 5 min of vigorous stirring, allyltrityldimethyl-
silane (600 mg, 1.75 mmol) was added as a solution in CH2Cl2
dropwise. The reaction temperature was allowed to rise to 0
°C over 4 h. The reaction was monitored via TLC (4:1 Hex/
EtOAc) and then treated with saturated aqueous NH4Cl,
resulting in a colorless mixture. The layers were separated,
and the aqueous layer was washed with CH2Cl2. The organic
layers were combined, dried (Na2SO4), filtered, and concen-
trated under reduced pressure to afford the crude products
26a -c. The crude products were purified by flash chroma-
tography on SiO2 eluting with EtOAc/Hex (1:1).
cis-2-Ben zyloxym eth yl-4-(d im eth yltr itylsilyl)tetr a h y-
d r ofu r a n (21b). To a solution of aldehyde (0.18 mmol) and
allylsilane (0.27 mmol) in toluene (1.0 mL) was added BF3‚
OEt2 (0.19 mmol) at -78 °C. After being stirred at -78 °C
for 12 h, the reaction mixture was allowed to warm to room
temperature and was treated with saturated aqueous NH4Cl.
The aqueous layer was extracted with CH2Cl2. The combined
organic layers were washed with brine, dried over Na2SO4, and
concentrated in vacuo. The crude product was purified by
flash chromatography eluting with EtOAc/Hex (1:9) to afford
the oxetane as a colorless oil (200 mg, 83% yield): 1H NMR
(CDCl3, 300 MHz) δ 0.16 (s, 3H), 0.19 (s, 3H), 1.03-1.28 (m,
2H), 1.46-1.68 (m, 2H), 3.14-3.24 (m, 1H), 3.29-3.38 (m, 1H),
3.91-4.04 (m, 1H), 4.16-4.28 (m, 1H), 4.42 (app t, J ) 9 Hz,
2H), 6.86-6.91 (m, 6H), 7.02-7.28 (m, 14H); 13C NMR (CDCl3,
75 MHz) δ -0.1, 1.3, 25.2, 40.8, 43.5, 53.1, 60.8, 68.7, 72.6,
74.4, 125.6, 125.9, 128.0, 130.1, 137.5, 146.3; IR (neat) 3041,
863 cm-1; HRMS (CI), (MNH4+) calcd for C33H40O2NSi 510.2828,
found 510.2825.
Hom oa llylic Alcoh ol 23. Colorless oil (120 mg, 89% yield).
The spectral data were identical with those reported.14
Gen er a l P r oced u r e for Oxid a tive Rem ova l of Silicon .
A single-neck, round-bottomed flask, equipped with a Teflon
stirbar, was charged with cesium fluoride (0.13 g, 0.87 mmol),
and the flask was heated under vacuum with a heat gun. After
being cooled to room temperature, the flask was filled with
argon. Anhydrous MeOH (0.5 mL) and THF (2.5 mL) were
added to the flask, and the silyl adduct (0.17 mmol) was added
as a solution in THF (1.0 mL) via syringe. The reaction was
Bicyclic la cta m 26a : colorless solid (0.59 g, 68% yield), mp
1
240 °C (dec); H NMR (CDCl3, 300 MHz) δ 0.11 (s, 3H), 0.14
(s, 3H), 0.83 (app t, J ) 14.1 Hz, 1H), 1.10 (dd, J ) 13.9, 3.0,
Hz, 1H), 1.19 (s, 9H), 1.68 (ddd, J ) 12.6, 9.0, 3.5, Hz, 1H),
2.55-2.65 (m, 1H), 2.74-2.82 (m, 1H), 3.23 (dd, J ) 8.8, 7.3
Hz, 1H), 3.95 (app t, J ) 9.1 Hz, 1H), 4.73 (dd, J ) 8.8, 7.7
Hz, 1H), 5.12 (app t, J ) 8.3, 1H), 6.95-7.34 (m, 25H); 13C
NMR (CDCl3, 75 MHz) δ -0.4, 1.3, 19.9, 25.0, 27.8, 37.9, 44.5,
53.8, 59.5, 64.4, 75.2, 81.8, 100.1, 125.5, 127.2, 127.6, 128.0,
128.2, 128.4, 129.9, 138.0, 142.2, 165.8, 176.1; IR (neat) 1736,
1717 cm-1; [R]23 ) - 11.5 (c ) 0.80, CH2Cl2).
D
Bicyclic la cta m 26b: colorless solid (0.15 g, 75% yield), mp
1
140-143 °C; H NMR (CDCl3, 300 MHz) δ 0.13 (s, 6H), 0.81
(14) Takano, S.; Sekiguchi, Y.; Sato, N.; Ogasawara, K. Synthesis
1987, 139.
(15) Talekar, R. R.; Wightman, R. H. Nucleosides Nucleotides 1997,
16, 495.

5522 J . Org. Chem., Vol. 63, No. 16, 1998
Groaning et al.
(app t, J ) 14.2 Hz, 1H), 1.22-1.26 (m, 1H), 1.30 (s, 9H), 1.48
(s, 3H), 1.49-1.60 (m, 1 H), 2.28-2.38 (m, 1H), 2.64-2.71 (m,
1H), 3.23 (app t, J ) 8.2 Hz, 1H), 4.18 (dd, J ) 8.7, 7.8 Hz,
1H), 4.74 (app t, J ) 8.7 Hz, 1H), 5.13 (app t, J ) 7.8 Hz, 1H),
6.98-7.35 (m, 20H); 13C NMR (CDCl3, 75 MHz) δ -0.4, 1.5,
19.8, 24.0, 24.8, 28.0, 37.7, 43.5, 54.0, 57.6, 65.1, 75.2, 82.0,
98.1, 125.6, 125.7, 127.6, 128.1, 128.8, 130.0, 139.4, 146.3,
Na2SO4, filtered, and concentrated in vacuo to yield a crude
oil. The crude products were purified by flash chromoatogra-
phy eluting with EtOAc/Hex (1:1) to yield the hydroxymeth-
ylcyclobutane 29.
Bicyclic la cta m 29a : viscous oil/foam (50 mg, 63% yield);
1H NMR (CDCl3, D2O wash, 300 MHz) δ 1.40 (s, 9 H), 2.03
(ddd, J ) 13.2, 9.3, 4.1 Hz, 1H), 2.58 (ddd, J ) 12.9, 9.4, 6.8
Hz, 1H), 2.80 (m, 1H), 3.27 (dd, J ) 9.3, 6.9 Hz, 1H), 3.72 (dd,
J ) 12.1, 6.0 Hz, 1H), 3.85 (dd, J ) 12.0, 3.8 Hz, 1H), 3.96
(app t, J ) 9.0 Hz, 1H), 4.73 (br, s, HOD), 4.78 (dd, J ) 9.0,
7.8 Hz, 1H), 5.17 (app t, J ) 8.1 Hz, 1H), 7.09-7.41 (m, 10H);
13C NMR (CDCl3, 75 MHz) δ 19.8, 27.8, 41.7, 47.5, 59.1, 62.0,
63.0, 74.7, 83.3, 100.6, 125.8, 126.9, 127.6, 128.3, 128.5, 138.0,
141.9, 168.1, 176.6; IR (neat) 1731 cm-1; HRMS: (FAB); (M +
166.7, 174.5; IR (neat) 1735, 1712 cm-1; [R]23 ) +32.3 (c )
D
0.86, CH2Cl2). Anal. Calcd for C39H53NO4Si: C, 76.67, H, 7.20.
Found: C, 76.70, H, 7.24.
Bicyclic la cta m 26c: colorless solid (100 mg, 50% yield),
mp 82-85 °C; 1H NMR (CDCl3, 300 MHz) δ 0.11 (s, 3H), 0.14,
(s, 3H), 0.83 (app t, J ) 14.1 Hz, 1H), 1.30 (s, 9H), 1.40 (dd, J
) 14.2, 2.7 Hz, 1H), 2.00-2.18 (m, 2H), 2.74-2.83 (m, 1H),
3.18 (dd, J ) 9.9, 4.5 Hz, 1H), 3.78 (dd, J ) 8.6, 7.1 Hz, 1H),
4.47 (app t, J ) 8.3 Hz, 1H), 4.92 (s, 1H), 5.14 (app t, J ) 7.5
Hz, 1H), 6.96-7.36 (m, 20H); 13C NMR (CDCl3, 75 MHz) δ
-0.3, 1.2, 21.7, 28.0, 30.4 35.7, 40.6, 53.7, 58.9, 60.8, 73.0, 82.0,
96.1, 125.6, 126.1, 127.7, 128.0, 128.8, 129.9, 139.8, 146.1,
H) calcd for C26H29NO5 436.2124, found 436.2130; [R]23
+19.1 (c ) 0.68, CH2Cl2).
)
D
Bicyclic la cta m 29b: viscous oil/foam (33 mg, 53% yield);
1H NMR (CDCl3, D2O wash, 300 MHz) δ 1.48 (s, 3H), 1.51 (s,
9H), 1.80 (ddd, J ) 13.0, 9.3, 3.6 Hz, 1H), 2.33 (ddd, J ) 13.1,
9.5, 7.2 Hz, 1H), 2.70 (m, 1H), 3.20 (dd, J ) 9.2, 7.4 Hz, 1H),
3.78 (dd, J ) 11.8, 6.3 Hz, 1H), 3.88 (dd, J ) 11.7, 3.8 Hz,
1H), 4.22 (dd, J ) 8.8, 7.3 Hz, 1H), 4.76 (br s, HOD), 4.81 (app
t, J ) 8.7 Hz, 1H), 5.18 (app t, J ) 7.6 Hz, 1H), 7.20-7.35 (m,
5H); 13C NMR (CDCl3, 75 MHz) δ 19.0, 24.6, 28.0, 41.1, 46.6,
56.9, 62.5, 63.4, 75.3, 83.1, 98.4, 125.3, 127.5, 128.7, 168.6,
174.4; IR (film) 3478, 1734, 1710 cm-1; HRMS (FAB), (M +
166.4, 177.9; IR (neat) 1744, 1712 cm-1; [R]23 ) +90.6 (c )
D
0.64, CH2Cl2). Anal. Calcd for C41H45NO4Si: C, 76.48, H, 7.04.
Found: C, 76.30; H, 7.09.
Bicyclic la cta m 32: colorless oil (80 mg, 50% yield) as an
inseparable mixture of diastereomers. Major diastereomer: 1H
NMR (CDCl3, 300 MHz) δ 0.13 (s, 6H), 0.79-0.88 (m, 1H), 1.28
(s, 3H), 1.39-1.50 (m, 1H), 1.89 (dd, J ) 9.3 Hz, 1H), 2.28-
2.38 (m, 1H), 2.41-2.48 (m, 1H), 2.83 (d, J ) 8.2 Hz, 1H), 3.9
(dd, J ) 8.7, 7.8 Hz, 1H), 4.24 (app t, J ) 8.7 Hz, 1H), 4.73
(app t, J ) 7.8 Hz, 1H), 5.1 (s, 2H), 6.98-7.35 (m, 25H); 13C
NMR (CDCl3, 75 MHz) δ -0.4, 1.3, 19.9, 25.0, 27.8, 37.9, 44.5,
53.8, 59.5, 64.4, 75.2, 81.8, 100.1, 126.5, 127.2, 127.6, 128.0,
128.2, 128.4, 131.9, 138.0, 142.2, 165.8, 176.1; IR (neat) 1748,
H) Calcd for C21H27NO5 374.1967, found 374.1969; [R]23
+103.1 (c ) 1.3, CH2Cl2).
)
D
Ack n ow led gm en t. The authors are grateful to the
National Institutes of Health for financial support of
this work.
1716 cm-1
.
Gen er a l P r oced u r e for t h e Oxid a t ive R em ova l of
Silicon . To a solution of the silylcyclobutane 26 (0.47 mmol)
in 10 mL of THF at 0 °C was added tetrabutylammonium
hydroxide (0.94 mL, 1.0 M in MeOH). Hydrogen peroxide (1.40
mL, 30% solution in water) was added, and the reaction was
stirred vigorously for 24 h and then diluted with CH2Cl2 and
water. The layers were separated, and the aqueous layer was
washed with CH2Cl2. The combined layers were dried over
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for all products and characterization data for com-
pounds, 8-13 (36 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
J O9805652