Noncascade Tandem Transformations Involving Allylic Silanes. 1. Pericyclic and Ionic Reactions Combined into "One-Pot" Sequences

Full text of DOI:10.1021/jo962025f

J . Org. Chem. 1997, 62, 1881-1885
1881
maintain the silicon moiety in earlier steps because the
metal component is stable and can tolerate a range of
reaction conditions before it is activated selectively.8 We
have combined pericyclic and electrophilic substitution
reactions involving allylsilanes that can be promoted with
one catalyst in one reaction flask.
Reaction of dienes 1a and 1b (Scheme 1) with a variety
of dienophile partners and Lewis acids has been inves-
tigated to probe aspects of regioselectivity, catalyst
reactivity, and silane stability during cycloaddition. The
data are summarized in Table 1.9
Non ca sca d e Ta n d em Tr a n sfor m a tion s
In volvin g Allylic Sila n es. 1. P er icyclic a n d
Ion ic Rea ction s Com bin ed in to “On e-P ot”
Sequ en ces
Michael G. Organ* and Derick D. Winkle
Department of Chemistry, Indiana University-Purdue
University, 402 North Blackford Street,
Indianapolis, Indiana 46202
Received October 29, 1996
Electrophilic substitutions have been conducted on the
resultant intermediate allylsilane cycloaddition products
3 (see Scheme 2 and Table 2).10 Unless stated otherwise,
1.1 equiv of 5 was used relative to 3 for comparison sake
between runs.
The reactions were then combined tandemly (Scheme
3), and the data are summarized in Table 3. Like the
independent runs, the ratios of 1, 2, and 5 are 1:1:1.1
unless stated otherwise. When the Diels-Alder reaction
was judged complete by TLC analysis, the electrophile
was added followed by the catalyst solution.
Tandem reaction methodology is a powerful approach
to rapid buildup of molecular complexity from potentially
simple starting materials. Noncascade tandem reactions
are those operations that involve sequential addition of
reagents to some starting material, and these reagents
become incorporated into the final product.1 The devel-
opment of sequences that combine transformations of
differing fundamental mechanism broadens the scope of
such procedures in synthetic chemistry. We have focused
on silicon moieties as central functionalities in this
chemistry because silicon can support a range of reactions
including those of anionic,2,3 cationic,2,4 and radical
reaction mechanism.2,5
Both 1- and 2-[(trialkylsilyl)methyl)] 1,3-dienes are
known to undergo Diels-Alder cycloaddition with a range
of electron-deficient olefins.6 The same electrophiles
react with the corresponding stannane to give the prod-
ucts of electrophilic substitution.7 This has been at-
tributed to the increased ionic character and, therefore,
heightened reactivity of the tin-carbon bond relative to
the silane.7,8 Therefore, 2-[(trialkylsilyl)methyl)] 1,3-
dienes can be used in multireaction sequences that
A series of 1H NMR spectroscopic experiments on
reaction mixtures has provided insight into the different
yields seen in these reactions. Protodesilylation of 3 is
the principal cause for reduced yields in both reactions.
Purified adducts 3 were protodesilylated to provide 4 in
the presence of 20% TiCl4 in CD2Cl2 over a 4-5 day
period. Diels-Alder experiments with stoichiometric or
catalytic TiCl4 reveal that very little protodesilylation
occurs on the time scale (10 min to 1 h) during which 3
is formed. However, quenching of these NMR study
reactions with saturated NH4Cl resulted in over 50%
conversion of 3 to 4. These results suggest that even a
trace amount of acid in the presence of TiCl4 is very
detrimental to product recovery. Experiments using Me2-
AlCl (Table 1, entries 2 and 6-8), which can only be a
Lewis acid and never a Brønsted acid,11 provided high
yields of cycloadduct with no protodesilylation.
(1) For recent reviews on tandem chemistry, see: Ho, T.-L. Tandem
Organic Reactions; Wiley: New York, 1992. Bunce, R. A. Tetrahedron
1995, 51, 13103-13159. Tietze, L. F. Chem. Rev. 1995, 95, 115-136.
Parsons, P. J .; Penkett, C. S.; Shell, A. J . Chem. Rev. 1995, 95, 195-
206.
(2) For general reviews concerning the use of allylsilanes in organic
synthesis, see: Fleming, I. Chem. Soc. Rev. 1981, 10, 83-111. Parnes,
Z. N.; Bolestova, G. I. Synthesis 1984, 991-1008. Blumenkopf, T. A.;
Overman, L. E. Chem. Rev. 1986, 86, 857-873. Schinzer, D. Synthesis
1988, 263-273. Chan, T. H.; Wang, D.; Pellon, P.; Lamothe, S.; Wie,
Z. Y.; Li, L. H.; Chen, L. M. Enantioselective synthesis using silicon
compounds. In Frontiers of Organosilicon Chemistry; The Royal Society
of Chemistry: London, 1991; pp 344-355. Colvin, E. W.; Loreto, M.
A.; Montieth, M.; Tommasini, I. Frontiers of Organosilicon Chemistry;
The Royal Society of Chemistry: London, 1991; p 356. Fleming, I.;
Dunogues, J .; Smithers, R. Org. React. 1989, 31, 57-575.
(3) For uses of allylsilanes in anion-mediated transformations, see:
Yamamoto, Y.; Saito, Y.; Naruyam, K. J . Org. Chem. 1980, 45, 195-
196. Tsai, D. J . S.; Matteson, D. S. Tetrahedron Lett. 1981, 22, 2751-
2752. Tamao, K.; Nakajo, E.; Ito, Y. Tetrahedron 1988, 44, 3997-4007.
Chan, T. H.; Pellon, P. J . Am. Chem. Soc. 1989, 111, 8737-8738. Chan,
T. H.; Horvath, R. F. J . Org. Chem. 1989, 54, 317-327.
(4) For discussions regarding the â-effect, see: Wierschke, S. G.;
Chandrasekhar, J .; J orgensen, W. L. J . Am. Chem. Soc. 1985, 107,
1496-1500. Lambert, J . B. Tetrahedron 1990, 46, 2677-2689. Fleming,
I. Frontier Orbitals and Organic Chemical Reactions; Wiley: London,
1976; p 81. Eaborn, C. J . Chem. Soc., Chem. Commun. 1972, 1255.
Hanstein, W.; Berwin, H. J .; Traylor, T. G. J . Am. Chem. Soc. 1970,
92, 829-836.
(5) For discussion related to the use of silyl-stabilized radicals in
synthesis, see: Wilt, J . W.; Lusztyk, J .; Peeran, M.; Ingold, K. U. J .
Am. Chem. Soc. 1988, 110, 281-287. Auner, N.; Walsh, R.; Westrup,
J . J . Chem. Soc., Chem. Commun. 1986, 207-208.
(6) Hosomi, A.; Sakata, Y.; Sakurai, H. Tetrahedron Lett. 1985, 26,
5175-5178. Hosomi, A.; Saito, M.; Sakurai, H. Tetrahedron Lett. 1979,
429-432. Hosomi, A.; Otaka, K.; Sakurai, H. Tetrahedron Lett. 1986,
27, 2881-2884. Sakurai, H.; Hosomi, A.; Saito, M.; Sasaki, K.; Iguchi,
H.; Sasaki, J -i.; Araki, Y. Tetrahedron 1983, 39, 883-894.
(7) Naruta, Y.; Nagai, N.; Arita, Y.; Maruyama, K. Chem. Lett. 1983,
1683-1686. Naruta, Y.; Kashiwagi, M.; Nishigaichi, Y.; Uno, H.;
Maruyama, K. Chem. Lett. 1983, 1687-1690.
1
More useful information regarding yield came from H
NMR spectroscopic analysis of the reactions in Schemes
2 and 3. Diels-Alder runs using Me2AlCl catalysis are
almost quantitative (see Table 1, entries 6-8), but the
electrophilic substitutions on the resultant cycloadducts
using TiCl4 catalysis, i.e., method A, were of moderate
yield (see Table 2). Inspection of entries 7, 11, and 6 in
Tables 1-3, respectively, reveals that the overall yield
of the reactions performed independently is 53%, whereas
the tandem yield is 75%. This same trend is seen in
tandem runs with other diene, dienophile, and electro-
phile reaction partners. The only difference should be
the presence of Me2AlCl, which is in the tandem run, but
not in the independent electrophilic substitution. Sub-
stitution reactions containing Me2AlCl, i.e., method B,
(8) Walsh, R. Acc. Chem. Res. 1981, 14, 246-252. Giordan, J . C. J .
Am. Chem. Soc. 1983, 105, 6544-6546. Reynolds, W. F.; Hamer, G.
K.; Bassindale, A. R. J . Chem. Soc., Perkin Trans. 2 1977, 971-974.
Au-Yeung, B. W.; Fleming, I. J . Chem. Soc, Chem. Commun. 1977,
79, 81.
(9) All compounds in this study have been fully characterized by
1H NMR, 13C NMR, infrared, and mass spectroscopy. Each compound
has been checked for accurate mass and/or elemental analysis.
(10) The structure of the cis and trans isomers from the electrophilic
substitution reaction, i.e., 6 and 7, has been determined by a combina-
tion of X-ray structural data and chemical derivatization. The details
of structural determination will be revealed in due course.
(11) Snider, B. B.; Rodini, D. J . Tetrahedron Lett. 1980, 21, 1815-
1818. Schinzer, D. Angew. Chem., Int. Ed. Engl. 1984, 23, 308-309.
S0022-3263(96)02025-7 CCC: $14.00 © 1997 American Chemical Society

1882 J . Org. Chem., Vol. 62, No. 6, 1997
Ta ble 1. Diels-Ald er Cycloa d d ition betw een 1 a n d Va r iou s Dien op h iles
Notes
entry
product
R
R1
R2
catalysta
T (°C)
solvent
yieldb (%)
1
2
3
4
5
6
7
8
3a
3a
3a
3a
3a
3b
3c
3d
-CH3
-CH3
-CH3
-CH3
-CH3
-Ph
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-COCH3
H
H
H
H
H
H
H
AlCl3
40
40
40
40
40
40
rt
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
38c
88
52
15
38d
84
97
95
Me2AlCl
EtAlCl2
BF3‚OEt2
TiCl4
Me2AlCl
Me2AlCl
Me2AlCl
-Ph
-Ph
-COCH2CH3
-CH3
rt
a
b
20% catalyst was used relative to 1. All reported yields are based on purified material following silica gel chromatography. c 35% of
d
4 was also formed. 36% of 4 was also formed.
Sch em e 1
Sch em e 2
and 1,2,4,5-tetrasubstituted cyclohexane structures. Were
the diene 2,3-disubstituted to begin, the regioselectivity
in the cycloaddition would not have been as controllable.
When the substitution step was performed with excess
aldehyde relative to the control experiments (see Table
2, entries 7 vs 8, and Table 3, entries 2 vs 3), substantial
improvement in yield was observed, indicating that these
sequences are synthetically useful.
are significantly higher yielding. This can be seen in
entries 6 vs 7, 9 vs 10, 12 vs 13, and 14 vs 15 in Table 2.
This is seen again in the tandem run without Me2AlCl
(Table 3, entry 4) where the yield is 59%, compared to
66% (Table 3, entry 5) with the cocatalyst. TiCl4 is
extremely difficult to obtain “proton free”, but it can be
cleaned in situ, and we believe that Me2AlCl is serving
as a proton sponge in these reactions.11 Therefore, our
reactions do not require the second catalyst per se, only
a proton-free catalyst source. We are continuing to
pursue other means of purifying TiCl4 to alleviate the
acid problem.
In each parallel study, the tandem reaction provided
a higher yield of the final product than the nontandem
sequence. These results demonstrate that reaction work-
ups and purifications can substantially reduce yield and
lower synthetic efficiency. In one net process, three new
bonds have been formed, leading to the formation of one
ring with good diastereoselectivity, providing useful, well-
functionalized synthetic intermediates. We have reason
to believe that 6, the products of axial addition,12 are
formed almost exclusively during the electrophilic sub-
stitution reaction. TiCl4-catalyzed isomerization at the
position on the ring adjacent to the carbonyl group
following substitution results in formation of the diequa-
torial isomer 7.10 This has been confirmed by electro-
philic substitution studies on cycloadducts possessing a
group at the same position as 3c, but lacking the carbonyl
moiety. In these cases, only the axial substitution
product (i.e., trans) is isolated. We are continuing to
examine the cause of this epimerization and how to
prevent it from occurring. Further, this sequence has
allowed for the regiospecific formation of a 1,2,4-tri-
An “ideal” mechanistically-diverse tandem sequence
would be one where all reagents can simply be combined
and all reactions take place in the desired order with no
side products being formed. Such selectivity would be
based on the kinetic reactivities of the transformations
themselves. To this end we attempted such a sequence
by adding together propionaldehyde, a highly reactive
electrophile, methyl vinyl ketone, 1b, and Me2AlCl. This
diene possesses an allylsilane moiety and has itself been
used in allylic substitution reactions under nearly the
same reaction conditions.6 The desired Diels-Alder
reaction proceeded uneventfully, and when it was judged
complete by TLC analysis, TiCl4 was added and the
desired electrophilic substitution with 3c took place,
providing 6d and 7d in 40% combined yield. Although
this result is not optimized, it further demonstrates the
reliability of allylsilanes as partners in such tandem
reactions.
In summary, there is an improvement in overall yield
for tandem sequences involving allylsilanes in Diels-
Alder cycloaddition and allylic substitution reactions
compared to performing these transformations sepa-
rately. There is no loss in regio- or stereoselectivity in
these tandem sequences. Product handling and time
have been reduced significantly and waste generated
from the overall sequence of reactions has been cut in
half by combining the steps tandemly. Thus, the meth-
odology represents an efficient route to the production
of polysubstituted cyclohexane derivatives. The use of
chiral auxiliaries or chiral catalysts during the Diels-
Alder reaction offers the ability to produce optically
enhanced products from the overall sequence.13 Further,
we are currently developing this methodology toward the
synthesis of pyran-, pyridine-, and piperidine-based
heterocycles. This methodology may have direct ap-
(12) For detailed discussions regarding the origin of axial vs
equatorial selectivity, see: Allinger, N. L.; Riew, C. K. Tetrahedron
Lett. 1966, 1269-1272. Chamberlain, P.; Whitman, G. H. J . Chem.
Soc., Perkin Trans 2 1972, 130-135. Garbisch, E. W.; Schildcrout, S.;
Patterson, D. B.; Specher, C. M. J . Am. Chem. Soc. 1965, 87, 2932-
2944.
(13) Evans, D. A.; Chapman, K. T.; Bisaha, J . J . Am. Chem. Soc.
1988, 110, 1238-1256. Evans, D. A.; Miller, S. J .; Lectka, T. J . Am.
Chem. Soc. 1993, 115, 6460-6461.

Notes
J . Org. Chem., Vol. 62, No. 6, 1997 1883
Ta ble 2. Electr op h ilic Su bstitu tion Rea ction s w ith 3
entry
products
R
R1
R2
R3
catalysta
yieldd (%)/6:7
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
6a and 7a
6a and 7a
6a and 7a
6a and 7a
6a and 7a
6b and 7b
6b and 7b
6b and 7b
6c and 7c
6c and 7c
6d and 7d
6e and 7e
6e and 7e
6f and 7f
6f and 7f
6g and 7g
6h and 7h
-CH3
-CH3
-CH3
-CH3
-Ph
-Ph
-Ph
-Ph
-Ph
-Ph
-Ph
-Ph
-Ph
-Ph
-Ph
-Ph
-Ph
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-COCH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
-CH2CH3
AlCl3
Me2AlCl
40c/4:1
-CH2CH3
no reaction
trace
-CH2CH3
BF3‚OEt2
-CH2CH3
TiCl4
TiCl4
TiCl4
60e/4.4:1
61e/4.3:1
60e/1.1:1
70/1.3:1
82f/2:1
b
b
-CH2CH3
b
-CH(CH3)2
-CH(CH3)2
-CH(CH3)2
-CH2CH2Ph
-CH2CH2Ph
-CH2CH3
c
c
Me2AlCl/TiCl4
Me2AlCl/TiCl4
TiCl4
54e/5.8:1
76/7.4:1
55e/3:1
b
c
c
Me2AlCl/TiCl4
b
TiCl4
TiCl4
b
-COCH3
-CH2CH2Ph
-CH2CH2Ph
-CH(CH3)2
-CH(CH3)2
-CH2CH3
53e/4.4:1
62/4.4:1
54/2.3:1
69/1.8:1
65/4.6:1
53/trans only
-COCH3
Me2AlCl/TiCl4
b
-COCH3
TiCl4
c
c
c
-COCH3
Me2AlCl/TiCl4
Me2AlCl/TiCl4
Me2AlCl/TiCl4
-COCH2CH3
-COCH2CH3
-CH3
-CH3
-CH(CH3)2
a
b
One full equivalent of active catalyst is used in these reactions. Method A: solution of aldehyde and 3 in CH2Cl2 is cooled to -60
°C and TiCl4 is added dropwise. c Method B: A solution of dimethylaluminum chloride (0.2 equiv) and TiCl4 (1.0 equiv) in CH2Cl2 is
d
cooled to -60 °C and then added to a second flask containing 3, the aldehyde, and 0.2 equiv of Me2AlCl, also at -60 °C. All reported
yields are based on purified material following silica gel chromatography. e Up to 20% of the desilylated compound 4 is obtained in addition
to the substitution products 6 and 7. f Two equivalents of the aldehyde was used.
Sch em e 3
Ta ble 3. Ta n d em Diels-Ald er Cycloa d d ition /Electr op h ilic Su bstitu tion Sequ en ce
entry
product
R1
R2
Diels-Alder temp (°C)
R
yielda (%)/6:7
1
2
3
4
5
6
7
8
9
6a and 7a
6b and 7b
6b and 7b
6c and 7c
6c and 7c
6d and 7d
6e and 7e
6f and 7f
6f and 7f
6g and 7g
6h and 7h
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-CO2CH3
-COCH3
H
H
H
H
H
H
H
H
H
40
40
40
40
40
rt
rt
rt
rt
rt
-CH2CH3
-CH(CH3)2
-CH(CH3)2
-(CH2)2Ph
-(CH2)2Ph
-CH2CH3
-(CH2)2Ph
-CH(CH3)2
-CH(CH3)2
-CH2CH3
-CH(CH3)2
73/4.3:1
41/2:1
66b/2:1
59c/7:1
66/7:1
75/3:1
56/4.2:1
51/2.1:1
57b/3.1:1
64/2.8:1
40/trans only
-COCH3
-COCH3
-COCH3
-COCH2CH3
-COCH2CH3
10
11
-CH3
-CH3
rt
a
b
All reported yields are based on purified material following silica gel chromatography. Two equiv of the aldehyde was used in the
second step of the sequence. c One equiv of TiCl4 was used in the first step with no Me2AlCl followed by addition of the aldehyde upon
complete formation of 3b.
In a separate flame-dried flask equipped with a stir bar was
added 7.2 g of 2-chloro-1,3-butadiene (81.2 mmol), 1.1 g of [1,3-
bis(diphenylphosphino)propane]dichloronickel (2.0 mmol), and
40 mL of dry ether. This orange solution was then cooled to 0
°C. The Grignard solution was cooled to 0 °C, added dropwise
by cannula to the 2-chloro-1,3-butadiene solution, and refluxed
for 5 h. The yellow slurry was cooled to rt, quenched slowly
with saturated NaHCO3, extracted with ether, and washed with
water, and the organic layer was dried with MgSO4. Following
solvent removal in vacuo, the product was purified by flash
chromatography (hexanes), providing 10.6 g of diene 1b as a
clear, colorless liquid (97%): IR (thin film) 3089, 3070 cm-1; 1H
NMR (CDCl3, 300 MHz): δ 7.54-7.49 (m, 2 H), 7.38-7.31 (m, 3
H), 6.35 (dd, J ) 17.6, 11.0 Hz, 1 H), 5.07 (d, J ) 17.7 Hz, 1 H),
5.00 (d, J ) 11.0 Hz, 1 H), 4.90 (s, 1 H), 4.75 (s, 1 H), 1.93 (s, 2
H), 0.26 (s, 6 H); 13C NMR (CDCl3, 75 MHz, APT pulse
sequencesevens up (+), odds down (-)) δ 143.5 (+), 139.8 (-),
139.1 (+), 133.6 (-), 128.9 (-), 127.7 (-), 114.9 (+), 113.8 (+),
20.3 (+), -2.8(-); HRMS calcd for C13H18Si (M+ + H) 203.1257,
found 203.1251.
plicability to combinatorial synthesis of medicinally
important molecules.
Exp er im en ta l Section
Gen er a l P r oced u r e. All reactions were carried out under
a positive atmosphere of dry argon. Solvents were distilled prior
to use: Et2O was distilled from sodium benzophenone ketyl; CH2-
Cl2 was distilled from CaH2. Melting points are uncorrected.
1H NMR spectra were recorded in CDCl3 at 300 MHz. 13C NMR
spectra were recorded at 75 MHz in CDCl3. Chemical shifts are
listed relative to CHCl3 (δ 7.24) for 1H NMR and (δ 77.00) for
13C NMR. Diene 1a was prepared using literature procedures.6
Spectral data for allylsilane 3a correspond to that previously
published.6
2-[(Dim eth ylp h en ylsilyl)m eth yl]-1,3-bu ta d ien e (1b). To
a flask was added 1.45 g of magnesium turnings (59.5 mmol)
and a stir bar. The flask was flame dried under vacuum and
purged with argon. Five mL of dry ether was added along with
dropwise addition of 10.0 g of (chloromethyl)dimethylphenylsi-
lane (54.1 mmol). Upon initiation of the reaction, the flask was
cooled in an ice bath, and additional ether was added (40 mL
total). Following complete addition of the (chloromethyl)-
dimethylphenylsilane, the solution was heated to reflux for 4 h.
Meth yl 4-[(Dim eth ylp h en ylsilyl)m eth yl]-3-cycloh exen -
eca r boxyla te (3b). To a flame-dried flask equipped with a stir
bar was added 7 mL of dry CH2Cl2, 197 mg of 1b (0.97 mmol),
and 168 mg of methyl acrylate (1.95 mmol), and this was

1884 J . Org. Chem., Vol. 62, No. 6, 1997
Notes
followed by dropwise addition of dimethylaluminum chloride
(195 µL of a 1 M solution, 0.20 mmol). The mixture was heated
to reflux for 4.5 h, cooled to rt, and quenched with saturated
NaHCO3. The mixture was extracted with ether and washed
with water, and the organic layer was dried over MgSO4.
Following solvent removal in vacuo, the product was purified
by flash chromatography (5% ether in hexanes), providing 235
mg of allylsilane 3b as a clear colorless liquid (84%). IR (thin
(-), 51.7 (-), 46.3 (-), 42.2 (-), 35.0 (+), 30.0 (+), 28.7 (+), 27.6
(+), 10.6 (-). Anal. Calcd for C12H20O3: C, 67.89; H, 9.50.
Found: C, 67.83; H, 9.30.
6a : clear colorless oil; IR (thin film) 3447, 3071, 1733 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 4.73 (s, 1 H), 4.71 (s, 1 H), 3.70-
3.63 (m, 1 H), 3.65 (s, 3 H), 2.68 (tt, J ) 11.7, 3.5 Hz, 1 H), 2.36-
1.95 (m, 5 H), 1.80 (br s, 1 H), 1.67-1.54 (m, 3 H), 1.30-1.20
(m, 1 H), 0.94 (t, J ) 7.4 Hz, 3 H); 13C NMR (CDCl3, 75 MHz) δ
176.2, 148.0, 110.3, 71.2, 51.6, 48.5, 38.1, 31.4, 30.22, 30.15, 28.0,
film): 3070, 3001, 1737 cm-1 1H NMR (CDCl3, 300 MHz): δ
;
9.9; HRMS calcd for
213.1492.
C
12H20O3 (M+ + H) 213.1491, found
7.54-7.47 (m, 2 H), 7.38-7.32 (m, 3 H), 5.21 (br s, 1 H), 3.67 (s,
3 H), 2.51-2.40 (m, 1 H), 2.27-2.20 (m, 2 H), 1.94-1.78 (m, 3
H), 1.66 (s, 2 H), 1.71-1.57 (m, 1 H), 0.30 (s, 3 H), 0.29 (s, 3
H); 13C NMR (CDCl3, 75 MHz, APT pulse sequencesevens up
(+), odds down (-)) δ 176.5 (+), 139.2 (+), 134.6 (+), 133.5 (-),
128.9 (-), 127.7 (-), 117.6 (-), 51.6 (-), 39.2 (-), 30.2 (+), 27.8
(+), 26.7 (+), 25.6 (+), -2.8 (-); HRMS calcd for C17H24O2Si
288.1546, found 288.1553.
Meth od B. Meth yl 3-(1-Hyd r oxy-2-m eth ylp r op yl)-4-m e-
th ylen ecycloh exa n e ca r boxyla te (6b a n d 7b). To a flame-
dried flask equipped with a stir bar was added 0.75 mL of dry
CH2Cl2, 50 mg of 3a (0.17 mmol), and 14 mg of isobutyraldehyde
(0.19 mmol). After the mixture was cooled to -60 °C, dimethyl-
aluminum chloride (35 µL of a 1.0 M solution, 0.035 mmol) was
added dropwise. In a separate flame-dried flask equipped with
a stir bar was added 0.5 mL of dry CH2Cl2, dimethylaluminum
chloride (35 µL of a 1 M solution, 0.35 mmol), and 36 mg of TiCl4
(0.19 mmol). This yellow solution was stirred for 20 min at rt,
cooled to -60 °C, and added by cannula to the allylsilane,
generating an orange solution. The resultant orange mixture
was stirred cold for 1 h and then allowed to warm gradually to
-10 °C, quenched with saturated NaHCO3, and extracted with
ether, and the organic layer was dried over MgSO4. Following
solvent removal in vacuo, the product was purified by flash
chromatography (35% ether in hexanes), providing 27 mg of
product (1.3:1 6b:7b, 70%).
1-Acet yl-4-[(d im et h ylp h en ylsilyl)m et h yl]-3-cycloh ex-
en e (3c). To a flame-dried flask equipped with a stir bar was
added 5 mL of dry CH2Cl2, 100 mg of 1b (0.49 mmol), 35 mg of
methyl vinyl ketone (0.49 mmol), and dimethylaluminum chlo-
ride (100 µL of a 1 M solution, 0.10 mmol, added dropwise). The
mixture was stirred at rt for 3 h, quenched with saturated
NaHCO3, extracted with ether, and washed with water, and the
organic layer was dried over MgSO4. Following solvent removal
in vacuo, the product was purified by flash chromatography (7%
ether in hexanes), providing 131 mg of allylsilane 3c as a clear
colorless liquid (97%): IR (thin film) 3069, 3001, 1713 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 7.51-7.45 (m, 2 H), 7.36-7.30 (m, 3
H), 5.20 (br s, 1 H), 2.50-2.39 (m, 1 H), 2.17-2.10 (m, 2 H),
2.13 (s, 3 H), 1.90-1.78 (m, 3 H), 1.64 (s, 2 H), 1.56-1.41 (m, 1
H), 0.28 (s, 3 H), 0.27 (s, 3 H); 13C NMR (CDCl3, 75 MHz, APT
pulse sequencesevens up (+), odds down (-)) δ 211.5 (+), 138.9
(+), 134.5 (+), 133.4 (-), 128.8 (-), 127.5 (-), 117.5 (-), 47.0
(-), 30.3 (+), 27.8 (-), 27.1 (+), 26.5 (+), 24.8 (+), -2.9 (-) (2
coincident); HRMS calcd for C17H24OSi 272.1597, found 272.1595.
tr a n s-4-[(Dim et h ylp h en ylsilyl)m et h yl]-2-m et h yl-1-(1-
oxop r op yl)-4-cycloh exen e (3d ). To a flame-dried flask
equipped with a stir bar was added 4 mL of dry CH2Cl2, 100 mg
of 1b (0.49 mmol), and 48 mg of 4-hexen-3-one (0.49 mmol),
followed by dropwise addition of dimethylaluminum chloride
(100 µL of a 1 M solution, 0.10 mmol). The mixture was stirred
at rt for 3 h, and neutral alumina was added directly and the
solvent removed in vacuo. The alumina was loaded to a
prepacked silica gel column, and following flash chromatography
(1.5% ether in hexanes), 140 mg of allylsilane 3d was obtained
as a clear colorless oil (95%). Quenching with NH4Cl caused
substantial epimerization to the cis product: IR (thin film) 3070,
3049, 1713 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.52-7.45 (m, 2
H), 7.36-7.30 (m, 3 H), 5.16 (br s, 1 H), 2.53-2.34 (m, 2 H),
2.32-2.21 (m, 1 H), 2.13-2.05 (m, 2 H), 1.93-1.74 (m, 2 H),
1.67-1.46 (m, 1 H), 1.62 (s, 2 H), 1.03 (t, J ) 7.4 Hz, 3 H), 0.78
(d, J ) 5.9 Hz, 3 H), 0.28 (s, 3 H), 0.27 (s, 3 H); 13C NMR (CDCl3,
75 MHz, APT pulse sequencesevens up (+), odds down (-)) δ
215.6 (+), 139.1 (+), 134.3 (+), 128.9 (-), 127.6 (-), 117.3 (-),
53.2 (-), 39.3 (+), 36.0 (+), 30.8 (-), 28.9 (+), 26.4 (+), 19.7 (-),
7.6 (-), -2.9 (-), -2.8 (-); HRMS calcd for C19H28OSi 300.1910,
found 300.1925.
7b: clear colorless oil; IR (thin film) 3515, 3080, 1733 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 4.85 (br s, 1 H), 4.75 (br s, 1 H),
3.66 (s, 3 H), 3.55 (dd, J ) 7.4, 3.7 Hz, 1 H), 2.50 (tt, J ) 11.0,
3.7 Hz, 1 H), 2.37 (dt, J ) 13.2, 4.4 Hz, 1 H), 2.28-2.19 (m, 1
H), 2.13-1.51 (m, 7 H), 0.98 (d, J ) 6.6 Hz, 3 H), 0.87 (d, J )
6.6 Hz, 3 H); 13C NMR (CDCl3, 75 MHz, APT pulse se-
quencesevens up (+), odds down (-)) δ 175.9 (+), 148.8 (+),
107.3 (+), 75.9 (-), 51.7 (-), 43.5 (-), 42.3 (-), 35.1 (+), 30.1
(-), 30.0 (+), 28.5 (+), 19.5 (-), 18.5 (-); HRMS calcd for
C
13H22O3 (M+ + H) 227.1648, found 227.1648.
6b: clear colorless oil; IR (thin film) 3460, 3070, 1738 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 4.77-4.72 (m, 2 H), 3.67-3.60 (m,
1 H), 3.65 (s, 3 H), 2.71 (tt, J ) 11.8, 3.7, Hz, 1 H), 2.46-2.38
(m, 1 H), 2.34-1.92 (m, 4 H), 1.80-1.37 (m, 4 H), 0.95 (d, J )
6.6 Hz, 3 H), 0.84 (d, J ) 6.6 Hz, 3 H); 13C NMR (CDCl3, 75
MHz, APT pulse sequencesevens up (+), odds down (-)) δ 176.0
(+), 148.4 (+), 110.0 (+), 74.3 (-), 51.5 (-), 45.7 (-), 38.2 (-),
31.6 (+), 30.4 (+), 30.3 (+), 29.6 (-), 20.6 (-), 14.2 (-); HRMS
calcd for C13H22O3 (M+ + H) 227.1648, found 227.1646.
Gen er a l P r oced u r e for Ta n d em Rea ction Usin g a n
Ald eh yd e in th e Secon d Step . Meth yl 3-(1-Hyd r oxy-3-
p h en ylp r op yl)-4-m et h ylen ecycloh exa n e ca r b oxyla t e (6c
a n d 7c). To a flame-dried flask equipped with a stir bar was
added 3.0 mL of dry CH2Cl2, 100 mg of 1b (0.49 mmol), and 43
mg of methyl acrylate (0.49 mmol), and this was followed by
dropwise addition of dimethylaluminum chloride (100 µL of a 1
M solution, 0.10 mmol). The mixture was heated to reflux for 4
h, at which time the cycloaddition was judged complete and the
solution was cooled to -60 °C. Seventy-two mg of hydrocinna-
maldehyde (0.54 mmol) was added, followed by 102 mg of TiCl4
(0.54 mmol), producing a red mixture. After being stirred for 1
h, the mixture was allowed to warm to -10 °C, quenched with
saturated NaHCO3, extracted with ether, and washed with
water, and the organic layer was dried over MgSO4. Following
solvent removal in vacuo, the product was purified by flash
chromatography (35% ether in hexanes), providing 93 mg of
product (6.8:1 6c:7c, 66%).
Gen er a l P r oced u r e for Ad d ition of Ald eh yd e to Diels-
Ald er a d d u ct. Meth od A. Meth yl 3-(1-Hyd r oxyp r op yl)-4-
m eth ylen ecycloh exa n eca r boxyla te (6a a n d 7a ). To a flame-
dried flask equipped with a stir bar was added 3.0 mL of dry
CH2Cl2, 100 mg of 3a (0.35 mmol), and 24 mg of propionaldehyde
(0.39 mmol). After the solution was cooled to -60 °C, 66 mg of
TiCl4 (0.35 mmol) was added dropwise, producing an orange
solution. The mixture was stirred cold for 1 h and then allowed
to warm gradually to -10 °C, quenched with saturated NaHCO3,
and extracted with ether, and the organic layer was dried over
MgSO4. Following solvent removal in vacuo, the product was
purified by flash chromatography (45% ether in hexanes),
providing 45 mg of product (4.3:1 6a :7a , 61%).
7c: clear colorless oil; IR (thin film) 3503, 3026, 1733 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 7.30-7.23 (m, 2 H), 7.21-7.13 (m,
3 H), 4.81 (s, 1H), 4.67 (s, 1 H), 3.84 (q, J ) 6.6 Hz, 1 H), 3.65
(s, 3 H), 2.91-2.79 (m, 1 H), 2.72-2.60 (m, 1 H), 2.55-2.44 (m,
1 H), 2.26 (dt, J ) 13.2, 4.4 Hz, 1 H), 2.10-1.52 (m, 9 H); 13C
NMR (CDCl3, 75 MHz, APT pulse sequencesevens up (+), odds
down (-)) δ 176.0 (+), 148.5 (+), 142.1 (+), 128.4 (-), 128.3 (-),
125.8 (-), 107.8 (+), 69.9 (-), 51.8 (-), 47.3 (-), 41.7 (-), 36.6
(+), 34.4 (+), 32.5 (+), 29.9 (+), 28.9 (+); HRMS calcd for
7a : white solid, recrystallized from hexanes; mp 54.9-58.0
1
°C; IR (thin film) 3455, 3082, 1736 cm-1; H NMR (CDCl3, 300
MHz) δ 4.84 (s, 1 H), 4.74 (s, 1 H), 3.86-3.77 (m, 1 H), 3.66 (s,
3 H), 2.51 (tt, J ) 11.0, 3.7 Hz, 1 H), 2.35 (dt, J ) 13.2, 4.4 Hz,
1 H), 2.11-1.91 (m, 4 H), 1.75-1.47 (m, 5 H), 0.96 (t, J ) 7.4
Hz, 3 H); 13C NMR (CDCl3, 75 MHz, APT pulse sequencesevens
up (+), odds down (-)) δ 176.0 (+), 148.7 (+), 107.4 (+), 72.3
C
18H24O3 (M+ + H) 289.1805, found 289.1814.
6c: clear colorless oil; IR (thin film) 3450, 3065, 3026, 1717
cm-1; H NMR (CDCl3, 300 MHz) δ 7.30-7.23 (m, 2 H), 7.21-
1

Notes
J . Org. Chem., Vol. 62, No. 6, 1997 1885
7.13 (m, 3 H), 4.75 (s, 1 H), 4.73 (s, 1 H), 3.75 (td, J ) 9.8, 2.9
Hz, 1 H), 3.65 (s, 3 H), 2.92-2.80 (m, 1 H), 2.71-2.57 (m, 2 H),
29.66, 29.91, 27.77, 19.52, 18.43; HRMS calcd for C13H22O2 (M+
+ H) 211.1699, found 211.1690.
2.40-2.26 (m, 2 H), 2.24-1.83 (m, 5 H), 1.71-1.48 (m, 3 H); 13
C
6f: white crystals, recrystallized from pentane; mp 75.1-75.6
°C; IR (CCl4) 3460, 3073, 1713 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 4.73-4.70 (m, 2 H), 3.63 (dd, J ) 9.6, 2.2 Hz, 1 H), 2.73 (tt, J
) 11.8, 3.7 Hz, 1 H), 2.46-2.39 (m, 1 H), 2.34-2.26 (m, 1 H),
2.19 (dt, J ) 14.0, 3.7 Hz, 1 H), 2.12 (s, 3 H), 2.05 (dd, J ) 13.2,
4.4 Hz, 1 H), 2.01-1.88 (m, 1 H), 1.74 (m, 1 H), 1.56 (br s, 1 H),
1.52-1.40 (m, 2 H), 0.95 (d, J ) 6.6 Hz, 3 H), 0.81 (d, J ) 7.4 Hz,
3 H); 13C NMR (CDCl3, 75 MHz, APT pulse sequencesevens up
(+), odds down (-)) δ 211.6 (+), 148.2 (+), 110.2 (+), 74.0 (-),
46.0 (-), 45.9 (-), 31.4 (+), 30.0 (+), 29.8 (+), 29.4 (-), 28.0 (-),
20.7 (-), 13.6 (-); HRMS calcd for C13H23O2 (M+ + H) 211.1699,
found 211.1700.
NMR (CDCl3, 75 MHz, APT pulse sequencesevens up (+), odds
down (-)) δ 176.1 (+), 147.7 (+), 142.0 (+), 128.3 (-) (2
coincident), 125.7 (-), 110.7 (+), 69.0 (-), 51.6 (-), 49.0 (-), 38.0
(-), 36.9 (+), 31.9 (+), 31.3 (+), 30.22 (+), 30.16 (+); HRMS calcd
for C18H24O3 (M+ + H) 289.1805, found 289.1801.
1-Ace t yl-3-(1-h yd r oxyp r op yl)-4-m e t h yle n e cycloh e x-
a n e (6d a n d 7d ). Following the protocol for the preparation of
6c and 7c, 80 mg of 1b (0.40 mmol), 28 mg of methyl vinyl ketone
(0.40 mmol), dimethylaluminum chloride (80 µL of a 1 M
solution, 0.08 mmol), 26 mg of propionaldehyde (0.44 mmol), and
83 mg of TiCl4 (0.44 mmol) in 4 mL of dry CH2Cl2 gave, after
flash chromatography (50% ether in hexanes), 59 mg of product
(3.2:1 6d :7d , 75%).
7d : white needles, recrystallized from pentane; mp 67.0-67.7
°C; IR (CCl4): 3535, 3078, 1713 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 4.84 (s, 1 H), 4.74 (s, 1 H), 3.87-3.79 (m, 1 H), 2.51 (tt, J )
11.0, 3.7 Hz, 1 H), 2.37 (dt, J ) 13.2, 3.7 Hz, 1 H), 2.15 (s, 3 H),
2.18-1.90 (m, 4 H), 1.69-1.42 (m, 5 H), 0.96 (t, J ) 7.4 Hz, 3
H); 13C NMR (CDCl3, 75 MHz, APT pulse sequencesevens up
(+), odds down (-)) δ 211.6 (+), 148.7 (+), 107.4 (+), 72.4 (-),
50.7 (-), 46.3 (-), 35.3 (+), 29.7 (+), 28.1 (+), 27.8 (-), 27.6 (+),
3-(1-Hyd r oxyp r op yl)-5-m eth yl-4-m eth ylen e-1-(1-oxop r o-
p yl)cycloh exa n e (6g a n d 7g). Following the protocol for the
preparation of 6c and 7c, 100 mg of 1b (0.49 mmol), 48 mg of
4-hexen-3-one (0.49 mmol), dimethylaluminum chloride (100 µL
of a 1 M solution, 0.10 mmol), 31 mg of propionaldehyde (0.54
mmol), and 102 mg of TiCl4 (0.54 mmol) in 4 mL of dry CH2Cl2
gave, after flash chromatography (30% ether in hexanes), 71 mg
of product (2.8:1 6g:7g, 64%).
7g: white crystals, recrystallized from pentane; mp 106.2-
106.9 °C; IR (KBr pellet) 3340, 3082, 1701 cm-1; 1H NMR (CDCl3,
300 MHz) δ 4.84 (s, 1 H), 4.72 (s, 1 H), 3.87 (td, J ) 6.6, 3.7 Hz,
1 H), 2.59-2.21 (m, 4 H), 2.05-1.71 (m, 4 H), 1.60-1.31 (m, 4
H), 1.02 (t, J ) 6.6 Hz, 3 H), 0.96 (t, J ) 7.4 Hz, 3 H), 0.83 (d,
10.7 (-). Anal. Calcd for
C12H20O2: C, 73.43; H, 10.27.
Found: C, 73.40; H, 10.25.
6d : clear colorless oil; IR (thin film) 3413, 3070, 1702 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 4.71 (s, 1 H), 4.68 (s, 1 H), 3.64
(td, J ) 8.8, 2.9 Hz, 1 H), 2.69 (tt, J ) 11.8, 3.7 Hz, 1 H), 2.12
(s, 3 H), 2.36-1.87 (m, 5 H), 1.67-1.53 (m, 2 H), 1.51-1.35 (m,
2 H), 1.22 (m, 1 H), 0.93 (t, J ) 7.4 Hz, 3 H); 13C NMR (CDCl3,
75 MHz, APT pulse sequencesevens up (+), odds down (-)) δ
212.1 (+), 148.0 (+), 110.5 (+), 71.2 (-), 48.9 (-), 46.0 (-), 31.3
(+), 29.8 (+), 29.6 (+), 28.1 (+), 28.0 (-), 9.9 (-); HRMS calcd
for C12H20O2 (M+ + H) 197.1542, found 197.1542.
J
) 5.9 Hz, 3 H); 13C NMR (CDCl3, 75 MHz, APT pulse
sequencesevens up (+), odds down (-)) δ 214.3 (+), 148.5 (+),
106.9 (+), 72.5 (-), 57.6 (-), 46.2 (-), 44.4 (+), 35.5 (-), 35.1
(-), 29.3 (+), 27.9 (+), 20.1 (-), 10.6 (-), 7.6 (-). Anal. Calcd
for C14H24O2: C, 74.95; H, 10.78. Found: C, 74.53; H, 10.53.
6g: clear colorless oil; IR (thin film) 3422, 3070, 1702 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 4.74-4.68 (m, 2 H), 3.63 (td, J )
8.8, 2.9 Hz, 1 H), 2.62-2.11 (m, 6 H), 1.90-1.13 (m, 6 H), 1.03
(t, J ) 6.6 Hz, 3 H), 0.95 (t, J ) 7.4 Hz, 3 H), 0.83 (d, J ) 5.9
Hz, 3 H); 13C NMR (CDCl3, 75 MHz, APT pulse sequencesevens
up (+), odds down (-)) δ 215.0 (+), 147.7 (+), 110.6 (+), 71.1
(-), 52.4 (-), 49.1 (-), 39.8 (+), 35.6 (+), 35.5 (-), 30.9 (+), 28.2
1-Acet yl-3-(1-h yd r oxy-3-p h en ylp r op yl)-4-m et h ylen ecy-
cloh exa n e (6e a n d 7e). Following the protocol for the prepara-
tion of 6c and 7c, 100 mg of 1b (0.49 mmol), 35 mg of methyl
vinyl ketone (0.49 mmol), dimethylaluminum chloride (100 µL
of a 1 M solution, 0.10 mmol), 72 mg of hydrocinnamaldehyde
(0.54 mmol), and 102 mg of TiCl4 (0.54 mmol) in 4 mL of dry
CH2Cl2 gave, after flash chromatography (45:55 ether:hexanes),
75 mg of product (4.2:1 6e:7e, 56%).
(+), 20.4 (-), 9.8 (-), 7,6 (-); HRMS calcd for C14H24O2 (M+
H) 225.1856, found 225.1867.
+
3-(1-Hyd r oxy-2-m eth ylp r op yl)-5-m eth yl-4-m eth ylen e-1-
(1-oxop r op yl)cycloh exa n e (6h ). Following the protocol for the
preparation of 6c and 7c, 100 mg of 1b (0.49 mmol), 48 mg of
4-hexen-3-one (0.49 mmol), dimethylaluminum chloride (100 µL
of a 1 M solution, 0.10 mmol), 39 mg of isobutyraldehyde (0.54
mmol), and 102 mg of TiCl4 (0.54 mmol) in 4 mL of dry CH2Cl2
gave, after flash chromatography (25% ether in hexanes), 47 mg
of a single diastereomer 6h (40%): clear colorless oil; IR (thin
film) 3479, 3070, 1702 cm-1; 1H NMR (CDCl3, 300 MHz) δ 4.71
(br s, 2 H), 3.61 (d, J ) 10.3 Hz, 1 H), 2.61-2.06 (m, 6 H), 1.88-
1.48 (m, 4 H), 1.40 (td, J ) 13.2, 4.4 Hz, 1 H), 1.01 (t, J ) 7.4
7e: white needles, recrystallized from hexanes; mp 83.5-84.4
°C; IR (thin film) 3465, 3062, 3026, 1705 cm-1; 1H NMR (CDCl3,
300 MHz) δ 7.30-7.13 (m, 5 H), 4.82 (s, 1 H), 4.66 (s, 1 H), 3.93-
3.86 (m, 1 H), 2.92-2.60 (m, 2 H), 2.49 (tt, J ) 11.0, 3.7 Hz, 1
H), 2.31 (dt, J ) 13.2, 4.4 Hz, 1 H), 2.23-1.45 (m, 9 H), 2.15 (s,
3 H); 13C NMR (CDCl3, 75 MHz, APT pulse sequencesevens up
(+), odds down (-)) δ 211.6 (+), 148.5 (+), 142.1 (+), 128.5 (-),
128.4 (-), 125.8 (-), 107.6 (+), 70.3 (-), 50.4 (-), 47.1 (-), 36.8
(+), 35.0 (+), 32.6 (+), 29.7 (+), 28.3 (+), 27.9 (-); HRMS calcd
for C18H25O2 (M+ + H) 273.1856, found 273.1848.
6e: clear colorless oil; IR (thin film) 3424, 3065, 3026, 1698
Hz, 3 H), 0.95 (d, J ) 6.6 Hz, 3 H), 0.81 (t, J ) 6.6 Hz, 6 H); 13
C
1
cm-1; H NMR (CDCl3, 300 MHz) δ 7.30-7.23 (m, 2 H), 7.21-
NMR (CDCl3, 75 MHz, APT pulse sequencesevens up (+), odds
down (-)) δ 214.9 (+), 147.9 (+), 110.3 (+), 73.7 (-), 53.3 (-),
46.3 (-), 39.8 (+), 35.7 (-), 35.6 (+), 31.1 (+), 29.3 (-), 20.8 (-),
20.4 (-), 13.3 (-), 7.6 (-); HRMS calcd for C15H26O2 (M+ + H)
239.2012, found 239.2008.
7.13 (m, 3 H), 4.74 (s, 1 H), 4.72 (s, 1 H), 3.75 (td, J ) 9.6, 2.2
Hz, 1 H), 2.92-2.80 (m, 1 H), 2.72-2.58 (m, 2 H), 2.39-1.85
(m, 10 H), 1.64-1.35 (m, 3 H); 13C NMR (CDCl3, 75 MHz, APT
pulse sequencesevens up (+), odds down (-)) δ 211.7 (+), 147.8
(+), 141.9 (+), 128.43 (-), 128.38 (-), 125.9 (-), 110.9 (+), 69.4
(-), 49.3 (-), 45.9 (-), 37.1 (+), 31.9 (+), 31.3 (+), 29.7 (+), 29.6
(+), 28.0 (-); HRMS calcd for C18H25O2 (M+ + H) 273.1856, found
273.1853.
Ack n ow led gm en t. Support for this work has been
provided by Eli Lilly and Company in the form of a
research grant. D.D.W. acknowledges the School of
Science at IUPUI for financial support in the form of a
R.I.F. Fellowship. The authors are indebted to Dr. Ian
Fleming for useful insight regarding the potential role
of Me2AlCl in these studies.
1-Acetyl-3-(1-h yd r oxy-2-m eth ylp r op yl)-4-m eth ylen ecy-
cloh exa n e (6f a n d 7f). Following the protocol for the prepara-
tion of 6c and 7c, 100 mg of 1b (0.49 mmol), 35 mg of methyl
vinyl ketone (0.49 mmol), dimethylaluminum chloride (100 µL
of a 1 M solution, 0.10 mmol), 39 mg of isobutyraldehyde (0.54
mmol), and 102 mg of TiCl4 (0.54 mmol) in 4 mL of dry CH2Cl2
gave, after flash chromatography (45% ether:hexanes), 53 mg
of product (1.1:1 6f:7f, 51%).
Su p p or tin g In for m a tion Ava ila ble: 1H or 13C NMR
spectra for 1b, 3b-d , 6a -h , and 7b,c,e,f (16 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.
7f: clear colorless oil; IR (thin film) 3489, 3081, 1702 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 4.84 (s, 1 H), 4.73 (s, 1 H), 3.55
(dd, J ) 7.4, 3.7 Hz, 1 H), 2.50 (tt, J ) 11.0, 3.7 Hz, 1 H), 2.38
(dt, J ) 13.2, 3.7 Hz, 1 H), 2.14 (s, 3 H), 2.26-1.89 (m, 4 H),
1.81 (m, 1 H), 1.71 (br s, 1 H), 1.55-1.39 (m, 2 H), 0.97 (d, J )
6.6 Hz, 3 H), 0.86 (d, J ) 6.6 Hz, 3 H); 13C NMR (CDCl3, 75
MHz) δ 211.49, 148.84, 107.29, 75.97, 50.78, 43.51, 35.44, 30.14,
J O962025F