Practical and efficient multigram preparation of a camphor-derived diol for the enantioselective Lewis acid catalyzed allylboration of aldehydes

Article abstract of DOI:10.1021/jo050207g

Chiral diols are important molecules with widespread use as chiral auxiliaries and ligands in enantioselective synthesis. Therefore, efficient and practical syntheses of highly dissymmetrical nonracemic diols are still a meaningful pursuit. Two new routes

Full text of DOI:10.1021/jo050207g

Practical and Efficient Multigram
Preparation of a Camphor-Derived Diol for
the Enantioselective Lewis Acid Catalyzed
Allylboration of Aldehydes
Hugo Lachance, Miguel St-Onge, and Dennis G. Hall*
Department of Chemistry, University of Alberta,
Edmonton, Alberta, Canada T6G 2G2
Recently, our group has reported the first examples of
enantioselective Lewis acid-catalyzed allylboration of
aldehydes (eq 1).8,9 This new catalytic allylboration
manifold affords excellent enantio- and diastereoselec-
tivities, along with moderate to good yields of products.
The camphor-derived allylboronates used in this method
tolerate a wide range of conditions, such as air, moisture,
and silica chromatography, thereby solving many of the
shortcomings of the previously mentioned methods. The
required camphordiol precursor, (-)-(1R,2R,3R,4S)-1,7,7-
trimethyl-2-phenylbicyclo[2.2.1]heptane-2,3-diol (1), was
originally synthesized3 in five steps (Scheme 1) from
dennis.hall@ualberta.ca
Received February 1, 2005
SCHEME 1. Original Synthesis of Diol 1
Chiral diols are important molecules with widespread use
as chiral auxiliaries and ligands in enantioselective synthe-
sis. Therefore, efficient and practical syntheses of highly
dissymmetrical nonracemic diols are still a meaningful
pursuit. Two new routes to access camphor-derived chiral
diol 1 have been developed. One route employs cam-
phorquinone (3) as the starting material, affording in only
two steps the desired diol in 55% overall yield. The second
route, from camphor (2), leads to the desired diol in an
efficient four-step synthesis, with an overall yield of 55%.
camphor (2) with a maximum overall yield of 25%. Four
of these steps each required a reaction time of over 18 h.
These limitations prompted us to look for a more
efficient route to access the Hoffmann camphor-derived
diol 1. The synthetic usefulness of this diol in the Lewis
acid-catalyzed allylboration reaction, as well as its po-
tential application to other reactions, made the develop-
ment of an improved synthetic route a worthwhile
endeavor. To be viable, the new route would have to be
short, quick, easy to execute, and amenable to multigram
preparation of diol 1.
The current synthesis of 1 begins with a selenium
dioxide oxidation10 of camphor (2). In our hands, in addi-
tion to the desired product, 4-10% of unreacted camphor
is recovered from the reaction. This residual camphor is
not easily removed from the product. Another drawback
For many years, the formation of new carbon-carbon
bonds has been the driving force behind many discoveries
in organic chemistry. In many stereocontrolled processes,
a chiral diol is used either as a chiral ligand or a chiral
auxiliary.1 Whereas the use of both natural and synthetic
C2-symmetric diols is widespread, the use of non-C2-
symmetric diols is not as common due to the limited
number of naturally occurring diols such as pinanediol.
In the domain of stereoselective carbon-carbon bond
formation, allylation of carbonyl compounds has attracted
a lot of attention.2 Among these methods, the allylbora-
tion of aldehydes stands out as a very successful meth-
odology. It allows formation of homoallylic alcohols
containing up to two stereogenic centers with high levels
of predictable diastereoselectivity (eq 1). Crotylboron
reagents, for example, allow access to the ubiquitous
propionate units found in a large number of coveted
biologically active natural products. The pioneering work
of Hoffmann,3 Brown,4 Corey,5 and Roush6 has produced
useful enantioselective versions with numerous applica-
tions in the synthesis of complex natural products.7
(3) Herold, T.; Schrott, U.; Hoffmann, R. W.; Schnelle, G.; Ladner,
W.; Steinbach, K. Chem. Ber. 1981, 114, 359-374.
(4) Brown, H. C.; Randad, R. S.; Bhat, K. S.; Zaidlewicz, M.;
Racherla, U. S. J. Am. Chem. Soc. 1990, 112, 2389-2392.
(5) Corey, E. J.; Yu, C. M.; Kim, S. S. J. Am. Chem. Soc. 1989, 111,
5495-5496.
(6) Roush, W. R.; Ando K.; Powers D. B.; Palkowitz A. D.; Halterman
R. L. J. Am. Chem. Soc. 1990, 112, 6339-6347.
(7) Chemler, S. R.; Roush, W. R. In Modern Carbonyl Chemistry;
Otera, T., Ed.; Wiley-VCH: Weinheim, 2001; pp 403-490.
(8) Lachance, H.; Gravel, M.; Lu, X.; Hall, D. G. J. Am. Chem. Soc.
2003, 125, 10160-10161.
(1) (a) Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem., Int. Ed.
2001, 40, 92-138. (b) Walsh, P. J.; Lurain, A. E.; Balsells, J. Chem.
Rev. 2003, 103, 3297-3344. (c) Walsh, P. J. Acc. Chem. Res. 2003, 36,
739-749.
(2) Denmark, S. E.; Almstead, N. G. In Modern Carbonyl Chemistry;
Otera, T., Ed.; Wiley-VCH: Weinheim, 2001; pp 299-401.
(9) Gravel, M.; Lachance, H.; Lu, X.; Hall, D. G. Synthesis 2004,
1290-1302.
(10) Meyer, W. L.; Lobo, A. P.; McCarty, R. N. J. Org. Chem. 1967,
32, 1754-1762.
10.1021/jo050207g CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/21/2005
4180
J. Org. Chem. 2005, 70, 4180-4183

TABLE 1. Optimization of Reduction Conditions for
Camphorquinone (3), Route Aa
SCHEME 2. Proposed Routes A and B to Diol 1
entry
hydride source [H-]
T (°C)
8a/8bb
yield (%)
1
2
DIBALH
0
0
1:1
d
c
Red-Al
c
3e
4f
5e
6
LiAlH(O-t-Bu)3
LiAlH(O-t-Bu)3
LiAlH(O-t-Bu)3
LiBH(Et)3
0
3:2
3:1
4:3
3:2
3:2
7:1
9:1h
5:1i
83
c
0
-40
0
51
49
c
7
LiBH(Et)3
-40
0
8
L-Selectride
L-Selectride
L-Selectride
g
of this synthetic route is the acetal formation step,11
which consistently gives rise to a 3:1 mixture in favor of
the desired product 4 over regioisomer 5, resulting in a
significant loss of material. Herein, two possible alterna-
tive routes to access diol 1 were envisaged. Route A
(Scheme 2), starting from compound 3, is an attempt to
circumvent the protection and deprotection steps of the
original synthesis by performing a selective reduction of
the least hindered ketone.12 The resulting reaction mix-
ture, containing the more hindered unreacted ketone,
would then be submitted to the addition of a phenylmetal
reagent to afford diol 1.
9
0
0
g
10
c
a Reactions were performed in THF with 1 equiv of hydride rea-
gent added over 10 min as their commercially available solution;
reactions were worked up using 1 M HCl (aq). b Ratio determined
by 1H NMR of the crude reaction mixture. c Product not isolated.
d Reduction of both carbonyls was observed. e LiAlH(O-t-Bu)3 was
added portionwise as a solid. f Hydride reagent was added as a
solution in THF. g Unpurified product was used directly for the
next step. h Hydride reagent was added over 40 min. i Ether used
as solvent.
TABLE 2. Optimization of Addition of
Phenylmagnesium Bromide to 8a, Route A
Route B (Scheme 2) makes use of camphor (2) as a sig-
nificantly cheaper raw material, which would be first
converted to its enol ether, then oxidized by dimethyl-
dioxirane (DMDO),13 followed by the addition of a phen-
ylmetal species. Like route A, this proposed route would
also circumvent the protection scheme of the original
synthesis of diol 1.
In the development of route A, we first investigated
the nature of the reducing agent, including common rea-
gents such as DIBALH and Red-Al as well as reagents
known to be more sensitive to steric bulk such as L-
Selectride, LiAlH(O-t-Bu)3, and LiBH(Et)3. The effects of
solvent and temperature were also investigated, as well
as the rate of addition. The results of these experiments
are summarized in Table 1. As seen in entries 1 and 2,
the most common reducing agents afforded no selectivity
at all, giving rise to low yields or unselective reduction
of the carbonyls. In the case of the more sterically sensi-
tive reagents, L-Selectride was found to be markedly
more selective than LiAlH(O-t-Bu)3 or LiBH(Et)3. The
importance of controlling the rate of addition is demon-
strated by entry 9, in which the ratio of desired product
rises from 7:1 to >9:1.
Following this study, we optimized the addition of the
phenylmetal reagent (Table 2), which proved to be more
challenging than expected. Phenylmagnesium bromide,
phenyllithium, as well as the lesser known phenyl cerium
dichloride were examined. To isolate the desired diol 1,
an oxidative workup was needed to break down the bor-
inate generated after the L-Selectride reduction. All at-
tempts to oxidize the borinate prior to the addition of the
phenylmetal reagent were unsuccessful. The optimal
results were achieved when the addition was performed
entry
solvent
T (°C)
conc (M)
equiv
yielda (%)
1
2
3
4
5
6
7
8
9
ether
THF
THF
THF
THF
THF
THF
THFc
THFd
-40
-78
-40
0
-78
-78
-40
-78
-78
0.4
0.4
0.4
0.4
0.2
0.2
0.2
0.5
0.2
2
b
20
4
2
2
2
4
1
6
2
b
2
b
1.1
1.1
b
55
a Crystallized from petroleum ether. b No product was isolated.
c Performed using PhLi. d Performed using PhCeCl2.
on the crude reaction mixture resulting from the acidic
workup following the L-Selectride reduction.
Phenylmagnesium bromide was the first reagent in-
vestigated. In most cases, none or very little product was
obtained with typical yields between 0 and 20%. Similar
results were obtained using phenyllithium. In all of these
cases, starting material was the main component of the
crude reaction mixture. The phenylcerium reagent,14
however, proved to be the most efficient reagent and
afforded the desired diol 1 in high yield. This was not
surprising, as cerium reagents are known to be less basic
than Grignard and organolithium reagents. The lack of
basicity of the cerium reagent makes it less prone to
remove the rigid axial hydrogen R to the carbonyl. When
this process happens, the starting material is regenerated
upon aqueous workup, which may explain the low
conversion observed with PhMgBr and PhLi. In all of
these cases, as also observed by Hoffmann,3 the reagent
adds from the least hindered face and none of the other
diastereoisomers were detected.
This new route A was found to be optimal (Scheme 3)
when the reduction of dicarbonyl 3 is performed by a slow
addition of L-Selectride at 0 °C, followed by an acidic
workup. The sequence is completed by the addition of
phenylcerium reagent to the crude hindered ketone, and
(11) Fleming, I.; Woodward, R. B. J. Chem. Soc. C 1968, 1289-1290.
(12) Kim, K. H.; Jimenez, L. S. Tetrahedron: Asymmetry 2001, 12,
999-1005.
(13) House, H. O.; Czuba, L. J.; Gall, M.; Olmstead, H. D. J. Org.
Chem. 1969, 34, 2324-2336.
(14) Adam, W.; Prechtl, F. Chem. Ber. 1991, 124, 2369-2372.
J. Org. Chem, Vol. 70, No. 10, 2005 4181

TABLE 3. Optimization of Oxidation of Silyl Enol
Ethers 9a or 9b, Route Ba
SCHEME 3. Optimal Route A from
Camphorquinonea
a Key: (a) L-Selectride, THF, 0 °C, 1 h; (b) PhMgBr, CeCl3, THF,
0 °C to rt, 3 h.
Oxone
(equiv)
NaHCO3
(equiv)
entry
conc (M)
10/11b
yield (%)
1
0.03
0.1
15
5
10:1
3:1
10:1
5:1
10:1
5:1
f
71
d
81
86
quant
86
d
2c
3
7.5
7.5
7.5
4.5
7.5
4.5
2.5
2.5
2.5
1.5
2.5
1.5
SCHEME 4. Formation of Enol Ethers of
(R)-(+)-Camphor (2), Route B
0.1
4
0.25
0.25
0.5
5
6
7e
0.5
a All reactions were performed with 9b at rt. b Ratio determined
by 1H NMR of the crude reaction mixture. c Done with 9a.
d Product not isolated. e Solvent was acetone/water 1:1. f Reaction
was incomplete.
TABLE 4. Optimization of Addition of Phenylmetal
Reagents to 10, Route Ba
the ensuing oxidative workup generates the desired diol
1 with an overall yield of 55% in just two steps from 3,
or 47% including the known oxidation of 2 to 3. This
improved sequence can be accomplished in less than 24
h and was easily performed on more than 5 g of 3 without
any purification steps.
The reaction sequence of route B begins with the
method reported in 1969 by House and co-workers15
(Scheme 4). Thus, (R)-(+)-camphor (2) is treated with
LDA, followed by a trialkylsilyl chloride and N,N,N′,N′-
tetramethylethylenediamine (TMEDA), and afforded the
desired silyl enol ethers 9a-c. In the case of 9a (R )
Me) and 9b (R ) Et), the product was obtained in
quantitative yield. When R ) i-Pr, no desired product
9c was observed due to steric bulk.
The crude trimethyl- or triethylsilyl enol ethers were
then oxidized using a procedure of Knight and Tcha-
banencko.16 This method has certain advantages such as
the in situ generation of DMDO, which avoids the
distillation of this explosive reagent. Moreover, the
reaction can be performed in an open flask. The large
volume of solvent needed for the reaction (0.03 M, 120
mL for 1 g), however, makes it inefficient. This procedure
also requires a large excess of the solid reagents, Oxone
and NaHCO3, which makes the agitation of the hetero-
geneous reaction mixture difficult. A variety of reaction
conditions were investigated and are reported in Table
3. The first conclusion that can be drawn from the results
is that the triethylsilyl enol ether 9b, made using
triethylsilyl chloride (TESCl), is more stable to the
oxidation conditions as shown by the 10:1 ratio of the
desired product 10 over the deprotected alcohol 11 (entry
2). The oxidation of the trimethylsilyl enol ether 9a,
under the same conditions, gave a ratio of 3:1 (entry 3).
The reaction efficiency was improved by increasing the
concentration from 0.03 to 0.25 M (1 g per 14 mL).
Reducing the number of equivalents of oxone and NaH-
CO3 did not affect the reaction (entry 5).
entry
metal
solvent
10/1b
yieldc (%)
1
2
3
4
5
6
Li
THF
ether
THF
ether
THF
THF
5:1
1:1
d
d
Li
Mg
Mg
Cef
Ceg
e
d
3:1
d
3:1
d
>10:1
55
a 1.1 equiv of PhM, 0 °C to rt. b Ratio determined by 1H NMR
of the crude reaction mixture. c Crystallized from petroleum ether.
d Product not isolated. e Mostly starting material obtained. f Made
using PhLi. g 1.1 equiv of PhMgBr, 1.15 equiv of anhydrous CeCl3,
0 °C to rt.
group to the carbonyl. The results of a representative set
of conditions tried are summarized in Table 4. The use
of either phenyllithium or the phenyl Grignard reagent
led to the recovery of a significant amount of starting
material (entries 1-4). As previously observed, the
phenylcerium reagent was significantly better and gave
a ratio of desired product to starting material over 10:1
(entry 5). It was also noted that the ratio of compounds
10 and 1 is greatly improved when the reaction is run
using PhCeCl2 made from PhMgBr instead of PhLi (entry
5). In all of these cases, as previously mentioned, none
of the other diastereoisomers were detected.
The final step requires the cleavage of the silyl ether.
This can be done efficiently with tetrabutylammonium
fluoride (TBAF), but on a large scale the cost of TBAF is
prohibitive. The procedure of Scheinmann and co-work-
ers17 was then tested for our sequence. It was found that
the silyl ether could be effectively removed by heating
compound 12 in a mixture of acetic acid, THF, and water
(6.5:3.5:1) at 45 °C for 3 h. The desired diol 1 was
obtained in a 55% yield comparable to that of the TBAF
procedure. As described in Scheme 5, the optimal route
to diol 1 is through the conversion of camphor 2 to its
triethylsilyl enol ether 9b followed by its oxidation to the
R-silyloxy ketone 10b. The sequence is completed by the
addition of the phenylcerium reagent and removal of the
TES group to afford, as demonstrated on a test sequence
with 10 g of camphor, diol 1 in an overall yield of 55%
without any purification steps.
With the desired alkoxyketone in hand, the following
step investigated was the introduction of the phenyl
(15) Paquette, L. A.; Gao, Z.; Ni, Z.; Smith, G. F. J. Am. Chem. Soc.
1998, 120, 2543-2552.
(16) Knight, J. G.; Tchabanencko, K. Tetrahedron 2003, 59, 281-
(17) Hart, T. W.; Metcalfe, D. A.; Scheinmann, F. J. Chem. Soc.,
Chem. Commun. 1979, 156-157.
286.
4182 J. Org. Chem., Vol. 70, No. 10, 2005

SCHEME 5. Optimal Route B from Camphora
mixture of 9b (10.0 g, 37.5 mmol) and NaHCO3 (14.2 g, 169
mmol) in acetone (100 mL) and water (50 mL) in open a flask.
The temperature was controlled with a water bath to keep it
below 30 °C. (Caution: DMDO is an explosive substance that
is generated in situ; the reaction should be run in a well-
ventilated fume hood using proper safety precautions.) The reac-
tion was left to stir for an additional 30 min at room temp-
erature. The reaction mixture was poured on water (500 mL)
and extracted three times with ethyl acetate. The combined
organic layers were washed once with a saturated aqueous solu-
tion of Na2S2O3, once with water, once with brine, dried over
anhydrous magnesium sulfate, and filtered, and the solvent was
evaporated to afford the triethylsilyl ether ketone 10b as a
yellow clear liquid. It was used without any further purification.
THF (100 mL) was added to a separate round-bottom flask
containing CeCl3‚7H2O (15.3 g, 43.4 mmol), which was dried for
18 h at 140 °C under high vacuum (<1 mmHg). The slurry was
stirred at 0 °C, and a 3 M THF solution of phenylmagnesium
bromide (13.9 mL, 41.7 mmol) was added slowly. The resulting
off-white to beige suspension was stirred for 30 min at 0 °C.
(Note: a darker solution indicates water is present.) The tri-
ethylsilyl ether ketone 10b (10.5 g, 37.8 mmol) in THF (20 mL)
was added slowly to the slurry. The resulting suspension was
stirred 30 min at 0 °C, warmed to room temperature, and
allowed to stir for 6 h. The reaction mixture was poured over a
saturated aqueous solution of ammonium chloride. The resulting
emulsion was filtered on a pad of Celite, the resulting clear
solution was extracted three times with diethyl ether, dried over
anhydrous magnesium sulfate, filtered, and the solvent was
evaporated. The resulting oil was then dissolved in a mixture
of acetic acid, water, and THF (65 mL, 35 mL, 10 mL) and heated
for 3 h at 45 °C. Water (100 mL) and ether (200 mL) were added
to the cooled reaction mixture, and solid NaOH was added until
the pH of the mixture was >7. The mixture was extracted three
times with ether; the combined organic layers were washed once
with brine, dried over anhydrous magnesium sulfate, filtered,
and the solvent was evaporated. The resulting oil was stirred
and heated to 100 °C under high vacuum (<1 mmHg) for 6 h to
remove the leftover triethylsilanol. The resulting sticky solid was
recrystallized from petroleum ether to afford, after four crops,
the desired diol 1 as a white crystalline powder (5.2 g, 55%
overall).
a Key: (a) LDA, TESCl, TMEDA, THF, -78 °C, 12 h; (b) Oxone,
NaHCO3, acetone, water, rt, 1 h; (c) CeCl3, PhMgBr, THF, -78
°C to rt, 6 h; (d) acetic acid, water, THF, 45 °C, 3 h.
In summary, we have developed and optimized two
new short syntheses of (-)-(1R,2R,3R,4S)-1,7,7-trimethyl-
2-phenylbicyclo[2.2.1]heptane-2,3-diol (1) that improve
upon the previous literature method of preparation.
Route A is performed in two steps from commercially
available camphorquinone (3) with an overall yield of
55%. Route B involves four steps from the cheap, com-
mercially available camphor (2) and gives an overall yield
of 55%. These two starting materials can be purchased
in both enantiomeric forms, which allow access to either
enantiomers of diol 1. Both of these syntheses are
efficient and practical and were successfully performed
without any purification steps on multigram scale.
Experimental Section
Method A. A 1 M THF solution of L-Selectride (30.1 mL, 30.1
mmol) was added to a solution of camphorquinone (3) (5.0 g,
30.1 mmol) in THF (100 mL) at 0 °C. The temperature was kept
below 5 °C throughout the addition. The mixture was stirred
for an additional 30 min. THF (100 mL) was added to a separate
flame dried round-bottom flask containing CeCl3‚7H2O (13.5 g,
36.1 mmol) dried for 18 h at 140 °C under high vacuum (<1
mmHg). The slurry was stirred at 0 °C, and a 3 M THF solution
of phenylmagnesium bromide (12.0 mL, 36.0 mmol) was added
slowly. The resulting off-white suspension was stirred for 30 min.
(Note: a darker solution indicates water is present.) The
reduction reaction mixture was then slowly cannulated to the
suspension using a double-ended needle. The resulting suspen-
sion was warmed to room temperature and allowed to stir for 3
h. The reaction mixture was poured slowly over a saturated
aqueous solution of ammonium chloride, extracted three times
with diethyl ether, dried over anhydrous magnesium sulfate,
filtered, and the solvent was evaporated. The resulting oil was
then dissolved in a mixture of THF (50 mL), water (25 mL), 1
M aqueous sodium hydroxide (50 mL), and 30% H2O2 (20 mL),
and the biphasic mixture was stirred at room temperature for 3
h. The mixture was extracted three times with diethyl ether;
the combined ether layers were washed once with water and
once with brine, dried over anhydrous magnesium sulfate,
filtered, and the solvent was evaporated. The resulting oil was
then left under vacuum (<1 mmHg) for 6 h. The resulting
product was recrystallized from petroleum ether to afford, after
three crops, the desired diol 1 as a white crystalline powder (4.0
g, 55% from (2)).
Method B. A 1.59 M hexane solution of n-BuLi (50.0 mL,
79.5 mmol) was added slowly to a solution of diisopropylamine
(10.6 mL, 75.7 mmol) in THF at -78 °C and stirred for 15 min.
A solution of (R)-(+)-camphor (2) (10.0 g, 65.8 mmol) in THF
(100 mL) was added slowly to this mixture at -78 °C and stirred
for 1 h. TMEDA (11.4 mL, 75.5 mmol) and TESCl (12.1 mL, 72.3
mmol) were added, and the mixture was kept at -78 °C for
another 1 h. The reaction mixture was then warmed to room
temperature and stirred for 12 h. The reaction mixture was
poured slowly on a saturated aqueous solution of ammonium
chloride and stirred for 15 min. The product was extracted three
times with ether; the combined layers were washed once with
water and once with brine, dried over anhydrous magnesium
sulfate, filtered, and the solvent was evaporated to afford the
triethylsilyl enol ether 9b as a yellow clear liquid. It was used
without any further purification. Oxone (34.6 g, 56.3 mmol) was
slowly added portionwise (over 45 min) to a heterogeneous
(-)-(1R,2R,3R,4S)-1,7,7-Trimethyl-2-phenylbicyclo[2.2.1]-
heptane-2,3-diol 1. White powder. Mp: 115-116 °C. [R]25
D
-26.34 (c ) 2.53, CHCl3). IR (CH2Cl2 cast, cm-1): 3286, 3055,
1
2951. H NMR (300 MHz, CDCl3): δ 7.56-7.48 (m, 2H), 7.37-
7.20 (m, 3H), 4.40 (s, 1H), 2.75 (br s, 2H), 1.90 (d, J ) 4.8 Hz,
1H), 1.83-1.69 (m, 1H), 1.30 (s, 3H), 1.20-1.10 (m, 2H), 1.05-
0.95 (m, 1H), 0.92 (s, 3H), 0.87 (s, 3H). 13C NMR (125 MHz,
CDCl3): δ 144.5, 127.6, 127.1, 126.6, 84.3, 80.5, 53.2, 51.9, 50.7,
30.4, 24.4, 23.1, 22.3, 9.9. HRMS (EI, m/z): calcd for C16H22O2
246.16215, found 246.16199. Anal. Calcd for C16H22O2: C, 78.01;
H, 9.00. Found: C, 77.78; H, 9.24.
Acknowledgment. This work was funded by the
Natural Sciences and Engineering Research Council
(NSERC) of Canada, and by an AstraZeneca Chemistry
Award to D.G.H. H.L. thanks NSERC and the Alberta
Ingenuity Fund for graduate scholarships. We thank Dr.
Jason Kennedy and Naheed Rajabali for providing
initial amounts of diols.
Supporting Information Available: Spectroscopic data
1
for intermediates 8a, 9a, and 12 and [R]25D, IR, H NMR, 13C
NMR, HRMS, and elemental analyses data for new compounds
9b and 10b. Spectral reproductions of 1, 8a, 9a,b, 10b, and
12. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO050207G
J. Org. Chem, Vol. 70, No. 10, 2005 4183