Asymmetric Conversion of Arenechromium Complexes to Functionalized Cyclohexenones: Progress toward Defining an Optimum Chiral Auxiliary

Article abstract of DOI:10.1021/jo971676o

An investigation into the asymmetric synthesis of 5-substituted cyclohexenones via nucleophile addition to (alkoxyarene)chromium tricarbonyl complexes is described. Diastereoselectivity during the nucleophile addition step was achieved using alkoxy substituents derived from terpenoid substrates as chiral auxiliaries. Selectivities as high as 24:1 were obtained when 2-phenylisoborneol was used as the chiral auxiliary and as high as 17:1 using 3,3-(ethylenedioxy)isoborneol. The absolute stereochemistry of the major products was assigned by Mosher's method, after their conversion to the corresponding cyclohexenol. A study of the temperature dependence of the nucleophile addition to alkoxytoluene complexes revealed a thermodynamic preference for addition ortho to the ether substituent.

Full text of DOI:10.1021/jo971676o

152
J . Org. Chem. 1998, 63, 152-162
Asym m etr ic Con ver sion of Ar en ech r om iu m Com p lexes to
F u n ction a lized Cycloh exen on es: P r ogr ess tow a r d Defin in g a n
Op tim u m Ch ir a l Au xilia r y
Anthony J . Pearson* and Alexander V. Gontcharov
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106
Received September 9, 1997X
An investigation into the asymmetric synthesis of 5-substituted cyclohexenones via nucleophile
addition to (alkoxyarene)chromium tricarbonyl complexes is described. Diastereoselectivity during
the nucleophile addition step was achieved using alkoxy substituents derived from terpenoid
substrates as chiral auxiliaries. Selectivities as high as 24:1 were obtained when 2-phenylisoborneol
was used as the chiral auxiliary and as high as 17:1 using 3,3-(ethylenedioxy)isoborneol. The
absolute stereochemistry of the major products was assigned by Mosher’s method, after their
conversion to the corresponding cyclohexenol. A study of the temperature dependence of the
nucleophile addition to alkoxytoluene complexes revealed a thermodynamic preference for addition
ortho to the ether substituent.
In tr od u ction
Dearomatization by means of nucleophile addition to
arenes provides useful methodolgy for organic synthesis.
The nucleophile addition itself requires activation of the
normally inert aromatic ring, and transition metals, such
as chromium,1 iron,2 and manganese,3 are quite effica-
cious in this regard. Early work on nucleophile additions
to arenechromium tricarbonyl complexes led to the
development of methodology for the conversion of alkyl-
benzene derivatives to substituted cyclohexadienes and
of anisole derivatives to substituted cyclohexenones
(Figure 1, R* ) Me).4 Recent work from Ku¨ndig’s
laboratory showed that substituted cyclohexadienes could
be obtained with asymmetric induction via nucleophile
addition to arene-Cr(CO)3 complexes bearing an ortho
directing chiral auxiliary.5 We recognized that a similar
approach using alkoxyarenes could also afford 5-substi-
tuted cyclohexenones in optically enriched form, provided
an appropriate chiral auxiliary could be defined that
would lead to practical levels of asymmetric induction
(Figure 1).6
F igu r e 1. Schematic for asymmetric conversion of (alkoxy-
benzene)-Cr(CO)3 complexes to substituted cyclohexenones.
of the stereocontrol, we have proceeded to modify the
structures of the chiral alcohols aiming at more efficient
stereodifferentiation. Our progress is described in this
article. More recently, Ku¨ndig has developed an ap-
proach based on nucleophile additions to nonracemic
planar chiral complexes, which were prepared by asym-
metric deprotonation of anisolechromium tricarbonyl
systems, followed by silylation of the derived anion.7
Resu lts a n d Discu ssion
Figure 2 presents a collection of the chiral alcohols that
were chosen for our initial studies. All of them are
commercially available in optically pure form except for
isoborneol, which is prepared by L-Selectride (Aldrich)
reduction of (+)-camphor.8
We began our search for an efficient chiral auxiliary
(Figure 1, R*) with a number of readily available chiral
alcohols. Then, making some assumptions on the mode
Asymmetric nucleophile additions to two series of
alkoxy-substituted chromium complexes were studied:
with and without a methyl substituent in the position
para to the chiral auxiliary. The desired complexes were
prepared from fluorobenzene or (p-fluorotoluene)chro-
mium tricarbonyl by nucleophilic substitution of fluoride
with the corresponding potassium alkoxides (eq 1). These
reactions are easily monitored by TLC and were complete
within minutes after mixing the reagents.
X Abstract published in Advance ACS Abstracts, December 15, 1997.
(1) (a) Semmelhack, M. F. Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4. p 517. (b)
Semmelhack, M. F.; Clark, G. R.; Garcia, J . L.; Harrison, J . J .;
Thebtaranonth, Y.; Wulff, W.; Yamashita, A. Tetrahedron 1981, 37,
3957. (c) Ku¨ndig, E. P. Pure Appl. Chem. 1985, 57, 1855. (d) Semmel-
hack, M. F.; Yamashita, A. J . Am. Chem. Soc. 1980, 102, 5924. (e)
Semmelhack, M. F.; Thebtaranonth, Y.; Keller, L. J . Am. Chem. Soc.
1977, 99, 959. (f) Widdowson, D. A. Phil. Trans. R. Soc. London A 1988,
326, 595.
(2) Mandon, D.; Astruc, D. J . Organomet. Chem. 1989, 369, 383.
(3) Pike, R. D.; Sweigart, D. A. Synlett 1990, 565.
(4) (a) Ku¨ndig, E. P.; Cunningham, J ., A. F.; Paglia, P.; Simmons,
D. P.; Bernardinelli, G. Helv. Chim. Acta 1990, 73, 386. (b) Ku¨ndig, E.
P.; Ripa, A.; Liu, R.; Bernardinelli, G. J . Org. Chem. 1994, 59, 4773.
(c) Semmelhack, M. F.; Harrison, J . J .; Thebtaranonth, Y. J . Org.
Chem. 1979, 44, 3275.
(5) Ku¨ndig, E. P.; Ripa, A.; Bernadinelli, G. Angew. Chem., Int. Ed.
Engl. 1992, 31, 1071.
(7) (a) Quattropani, A.; Anderson, G.; Bernardinelli, G.; Ku¨ndig, E.
P. J . Am. Chem. Soc. 1997, 119, 4773. (b) Ku¨ndig, E. P.; Quattropani,
A. Tetrahedron Lett 1994, 35, 3497. See also: (c) Price, D. A.; Simpkins,
N. S.; MacLeod, A. M.; Watt, A. P. J . Org. Chem. 1994, 59, 1961. (d)
Price, D. A.; Simpkins, N. S.; MacLeod, A. M.; Watt, A. P. Tetrahedron
Lett. 1994, 35, 6159.
(6) Pearson, A. J .; Gontcharov, A. V.; Woodgate, P. D. Tetrahedron
Lett. 1996, 37, 3087.
(8) Brown, H. C.; Krishnamurthy, S. J . Am. Chem. Soc. 1972, 94,
7159.
S0022-3263(97)01676-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/09/1998

Asymmetric Conversion of Arenechromium Complexes
J . Org. Chem., Vol. 63, No. 1, 1998 153
Ta ble 1. Dia ster eom er Ra tios a n d Yield s of
Cycloh exa d ien ol Eth er s
ratios of
starting
complex
diastereomersa
combined
yield, %
product
A:B
1
2
3
4
5
6
7
8
9
11
12
13
14
15
16
17
18
19
20
1.2:1b
1:1
1:1
80
74
77
80
90
67
76
50
60
82
2.3:1
2.7:1
3.5:1
7.5:1
1:1
1:1.4b
b
10
1:1.8
a
b
Absolute stereochemistry assignment: see text. Absolute
stereochemistry not assigned.
sufficiently separated to allow for accurate integration.
In some cases, for example, with isopinocampheoxy-
substituted cyclohexadienes 15, use of an NMR shift
reagent was advantageous for signal separation.
In all cases the NMR patterns for the cyclohexadienes
were very consistent, presenting no doubts in assigning
the signals, even when some side products were present
in the crude reaction mixtures. The diastereomer ratios
of cyclohexadienol ethers 11-20 and their yields are
presented in Table 1.
F igu r e 2. Some mono- and bicyclic chiral alcohols readily
available in optically pure form.
A fairly high degree of asymmetric induction can be
achieved with some of these chiral auxiliaries. Thus,
fenchyl alcohol as auxiliary afforded 76% de with p-
methyl substituted complex 7. No stereoselectivity was
observed with monocyclic alcohols as chiral auxiliaries
(complexes 1-3) probably due to more facile rotation
about the two ether bonds in these complexes.
The presence of a methyl group in the para position
does not create a serious problem with regioselectivity
of nucleophilic addition, but noticeable amounts (ca. 10%)
of cyclohexadienes that result from ortho addition of the
nucleophile were detected by NMR or GC. We will
consider the problem of regioselectivity in more detail
later, when we discuss the temperature dependence of
the selectivities.
The increase in diastereoselectivity when a methyl
substituent is present in the position para to the chiral
auxiliary is fairly significant. We made a similar obser-
vation with arenemanganese complexes and explained
it by suggesting a nucleophile approach trajectory shift-
ing closer to the chiral auxiliary due to steric repulsion
between the nucleophile and the methyl group.9 On the
basis of this observation, one could speculate that a
further increase in steric hindrance at the para position
(e.g., by replacing the methyl group by trimethylsilyl)
would increase the diastereoselectivity of nucleophilic
addition. Moreover, a trimethylsilyl substituent is known
to activate the arene toward the nucleophilic attack at
positions ortho and para to itself, which should help to
control the regioselectivity of the additions.
Lithioisobutyronitrile has been shown before to be a
nucleophile of optimum reactivity for addition to meth-
oxy-substituted arene-chromium complexes, giving high
yields of addition products.1,4 Therefore, we used it in
our studies of asymmetric nucleophilic addition. The
whole sequence of transformations outlined in eq 2 is
conducted in one pot and leads to the formation of
mixtures of diastereomeric dienol ethers. The crude
[p-(Trimethylsilyl)(fenchyloxy)benzene]chromium tri-
carbonyl (24) was prepared as outlined in Scheme 1.
Direct complexation of arenes with chromium hexacar-
bonyl requires fairly harsh reaction conditions (prolonged
reflux at 140 °C), which arene 21 cannot withstand,
probably because of lability of the TMS group. This
prompted us to use a milder method, Cr(CO)3 transfer
mixtures were analyzed by NMR spectroscopy, and the
ratios of diastereomers were estimated by integrating the
NMR signals most conveniently separated in the spectra.
For example, Figure 3 shows the proton NMR spectrum
of the diastereomer mixture of dienol ethers 17A and 17B
obtained from [(fenchyloxy)toluene]chromium complex.
In this case, CHO protons of the fenchyl fragment are
(9) Pearson, A. J .; Gontcharov, A. V.; Zhu, P. Y. Tetrahedron 1997,
53, 3849.

154 J . Org. Chem., Vol. 63, No. 1, 1998
Pearson and Gontcharov
F igu r e 3. Proton NMR spectrum of crude diastereomer mixture of 17; (400 MHz, CDCl3/TMS, the spectrum was processed with
resolution enhancement).
Sch em e 1
from the naphthalene ligand of 22 to the arene, developed
Ta ble 2. Attem p ted Nu cleop h ilic Ad d ition s to
[p-(Tr im eth ylsilyl)(fen ch yloxy)ben zen e]ch r om iu m
by Ku¨ndig and co-workers.10 Arene 21 was prepared by
the literature procedure.11
Tr ica r bon yl 24
Our studies on nucleophilic addition to complex 24
nucleophile
reaction condns
reaction outcome
indicated that the trimethylsilyl group is too sterically
demanding for the isobutyronitrile anion addition to
occur (Table 2). Various methods for activation of the
nucleophile were attempted, but no cyclohexadienes were
detected after the starting complex was carried through
the sequence of transformations. Interestingly, the less
sterically demanding acetonitrile anion added easily meta
to the alkoxy substituent; however, the diastereoselec-
tivity of the addition was very low. This result empha-
sizes the importance of the steric requirements of the
nucleophile in determining diastereoselectivity during its
addition.
LiCMe2CN THF/HMPA, -78 °C, 2 h
LiCMe2CN DME, -78 °C, 2 h
no reaction
no reaction
LiCMe2CN THF/TMEDA, -78 °C, 2 h no reaction
LiCMe2CN THF, -78 °C, 5 days
extensive
decomplexationa
LiCH2CN
THF, -78 °C, 2 h
25 (1.4:1 diast. ratio,
66% yield)b
a
Mixture of products was recovered with p-FenOC6H4-TMS as
b
major. Absolute stereochemistry has not been assigned.
by Semmelhack,1,4 hydrolysis in THF/HCl (5 M aqueous)
at 100 °C leads to the formation of the thermodynamic
product, 2-cyclohexenone 26. However, our experiments
showed that under these conditions THF is not very
stable, and a significant amount of 4-chloro-n-butanol is
formed as a result of THF reaction with HCl, which
creates serious difficulties during isolation of the prod-
ucts. We found that methanol can be used instead of
THF without any change in the outcome of cyclohexadi-
Dienol ethers 11-20 are readily hydrolyzed to the
corresponding cyclohexenones (Scheme 2). As reported
(10) (a) Desobry, V.; Ku¨ndig, E. P. Helv. Chim. Acta 1981, 64, 1288-
1297. (b) Ku¨ndig, E. P.; Perret, C.; Spichiger, S.; Bernardinelli, G. J .
Organomet. Chem. 1985, 286, 183.
(11) Moerlein, S. M. J . Organomet. Chem. 1987, 319, 29.

Asymmetric Conversion of Arenechromium Complexes
J . Org. Chem., Vol. 63, No. 1, 1998 155
Sch em e 2
Ta ble 3. Resu lts of LiCMe2CN Ad d ition to
Ar en ech r om iu m Com p lexes w ith Ter tia r y Alcoh ols a s
Ch ir a l Au xilia r ies
Sch em e 3
diastereomer
starting
complex
ratios
A:B
combined
yield, %
product
34
35
36
37
38
39
40
41
42
43
1:1.8
1:9.5
ca. 4:1
24:1
89
81
95
63
91
1:1
Having thus established that chiral alcohols can be
used as chiral auxiliaries in the asymmetric conversion
of arene-chromium complexes to functionalized cyclohex-
enones, we turned our attention to modifications of the
auxiliary so as to increase the diastereoselectivity of the
nucleophilic addition.
Ca m p h or -Der ived Alcoh ols a s Ch ir a l Au xilia r ies.
As far as the synthetic chiral auxiliaries are concerned,
we considered one of their major requirements to be the
simplicity of their synthesis (besides, of course, high
stereoselectivities) because the chiral auxiliary in our
transformation is used stoichiometrically. The known
alcohols 31-33 were prepared by addition of the corre-
sponding Grignard reagent to a preformed complex of the
ketone with cerium(III) chloride.14 Addition of PhMgX
to fenchone gives an inseparable mixture of endo- and
exo-alcohols, so we elected not to study the fenchyl
analogue of 32.
enol ether hydrolysis. The corresponding chiral alcohols
formed in the hydrolysis can also be isolated, so the chiral
auxiliary is (partially) recoverable.
Hydrolysis of 4-methyl-substituted cyclohexadienes
(15, 17, 19, 20) under these conditions led to formation
of an approximately 1:1 mixture of cyclohexenones epimer-
ic at C(4). Mild hydrolysis in this case (5% HCl/THF,
rt) afforded the single kinetic hydrolysis product, 3-cy-
clohexenone 28.
Deter m in a tion of th e Absolu te Ster eoch em istr y
of Cycloh exen on e 26. Reduction of cyclohexenone 26,
obtained by the hydrolysis of cyclohexadiene 14 (with IPC
as a chiral auxiliary), with sodium borohydride in the
presence of cerium(III) chloride provided exclusively
equatorial alcohol 29 (Scheme 3). No traces of the
epimeric alcohol or of the 1,4-reduction product were
detected. The absolute stereochemistry of 29 was deter-
mined by the method developed by Mosher:12 conver-
sion into an R-methoxy-R-(trifluoromethyl)phenylacetate
(MTPA) ester 30, which was analyzed by NMR spectros-
copy.
After our preliminary report,6 an alternative method
for assignment of absolute stereochemistry of cyclohex-
enone 26 was carried out by Semmelhack.13 Hydrogena-
tion of 26 gave the corresponding cyclohexanone, the
stereochemistry of which was established from its CD
spectrum based on the “octant rule”. We were pleased
to find that Semmelhack’s and our assignments were in
agreement.
The absolute stereochemistries of cyclohexenones from
the remaining complexes were assigned on the basis of
comparison of their optical rotations. Also, we made an
assumption that no selectivity reversal occurs when the
methyl group is introduced into the position para to the
chiral auxiliary, thereby establishing the absolute ster-
eochemistry of methyl-substituted derivatives.
The results of addition of isobutyronitrile anion to
complexes 34-38 are presented in Table 3. Generally,
the increase in steric hindrance at the 2-position of
isoborneol leads to enhancement of the diastereoselec-
tivity of nucleophilic addition, which reaches a very high
level (24:1, 92% de) with phenylisoborneol (PIB) as a
chiral auxiliary (Scheme 4).
An interesting observation comes from comparing the
selectivities obtained with chiral auxiliaries having the
norbornane skeleton. Thus, neither borneol nor isoborneol
promoted any significant diastereoselectivity. Introduc-
(12) (a) Dale, J . A.; Mosher, H. S.J . Am. Chem. Soc. 1973, 95, 512.
(b) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969, 34, 2543.
(13) Semmelhack, M. F.; Schmalz, H.-G. Tetrahedron Lett. 1996, 37,
3089.
(14) Dimitrov, V.; Bratovanov, S.; Simova, S.; Kostova, K. Tetrahe-
dron Lett. 1994, 35, 6713.

156 J . Org. Chem., Vol. 63, No. 1, 1998
Pearson and Gontcharov
Sch em e 4
Sch em e 5
ing some substituents at either the 3-position (as in
fenchyl alcohol) or at the 2-position (as with the tertiary
alcohols discussed above) led to a substantial increase
in the effectiveness of the chiral auxiliary. The same
major diastereomer was formed with all these chiral
auxiliaries except one, 2-methylisoborneol. Substitution
at both the 2- and 3-positions (as in methylfenchyl ether
38) leads to complete loss of diastereoselectivity. It
appears that these observations correlate with an intui-
tive picture of conformational behavior of the arene
complexes and steric approach control of the diastereo-
selectivity.
parameters. We noted that the minimization process
often drives the tricarbonylmetal unit into the opposite
eclipsed or some staggered conformation. We do not
know the energetic cost of this conformational change,
but it would not be surprising if it could account for the
energy difference we seek.
The lowest box in the Figure 4 illustrates a similar
analysis of the conformational preference for (3-substi-
tuted isobornyloxy)arene complexes that predicts the
diastereoselectivity of nucleophilic addition to be opposite
to that observed with the fenchyloxy auxiliary. It was
encouraging to find that experimental results with such
chiral auxiliaries are consistent with this analysis. Below
we describe the synthesis of these complexes and the
results of nucleophilic addition to them.
One of the easiest ways to introduce functionality at
C-3 of camphor is its mild oxidation with selenium
dioxide, which leads to camphorquinone 44 in high yield
(Scheme 5).17 Reaction of 44 with ethylene glycol gave a
mixture of two monodioxolane derivatives and the cor-
responding bis-dioxolane, from which ketone 45 was
easily separated by crystallization, whereas the two other
products can be recycled by converting them back into
camphorquinone.18 Reduction of 45 with L-Selectride
gave a high yield of 3,3-(ethylenedioxy)isoborneol (DOIB-
OH) 46. Nucleophilic addition to the complexes derived
from 46 (see Scheme 4 for general structures: 47, R* )
DOIB, R ) H; 48, R* ) DOIB, R ) Me) afforded
diastereomer ratios A:B of 1:7.3 and 1:17, respectively
(dienes 49 and 50 analogous to Scheme 4). The latter is
a remarkable and synthetically useful level of asym-
metric induction and the absolute stereochemistry of the
major diastereomer agrees with our prediction.
Molecular mechanics calculations on the (fenchyloxy)-
arene and (isobornyloxy)arene complexes indicate that
there are two important conformations of approximately
the same energy, with the barrier between them of 3 kcal/
mol, and which differ from each other by 180° rotation
about the arene-oxygen bond.15 Projections of these two
conformations for chiral auxiliaries with variously sub-
stituted norbornane skeleta are shown in Figure 4. One
can speculate that introduction of substituents at C-2 or
C-3 of the chiral auxiliary should lead to an energy
difference between the conformers due to the steric
repulsion between that substituent and the chromium
tricarbonyl fragment. An assumption that addition of the
nucleophile to the complex occurs in the thermodynami-
cally preferred conformation would explain the experi-
mentally observed diastereoselectivity for the complexes
with bornyl, isobornyl, fenchyl, and phenylisobornyl as
chiral auxiliary. The only case that falls out of the trend
is [(methylisobornyl)oxy]arene complexes (34, 35), for
which we could not find any plausible explanation.
Interestingly, complex 34 showed a unique temperature
dependence of the selectivity, which we shall discuss
later. Also, it is difficult to predict the conformational
behavior of (methylfenchyl)oxy-substituted complex 38,
and with substituents present at both 2- and 3-positions,
the energy of the two conformers may again have become
equal.
We attempted to calculate the energy differences
between these conformers for complexes 34-38 by car-
rying out MMX calculations for arene complexes with a
series of chiral auxiliaries. However, we discovered some
grounds to doubt the reliability of the MMX force field
for this kind of calculation because it does not take into
account several steric and electronic factors inherent in
arene transition metal complexes. One of them is the
preference for chromium tricarbonyl to adopt the confor-
mation where one of the carbonyls is eclipsed with the
alkoxy substituent,16 which is not reflected in the MMX
(16) (a) Albright, T. A.; Carpenter, B. K. Inorg. Chem. 1980, 19, 3092.
(b) Semmelhack, M. F.; Garcia, J . L.; Cortes, D.; Farina, R.; Hong, R.;
Carpenter, B. K. Organometallics 1983, 2, 467. (c) Semmelhack, M.
F.; Clark, G. R.; Farina, R.; Saeman, M. J . Am. Chem. Soc. 1979, 101,
217.
(17) von Rupe, H.; di Vignano, T. A. Helv. Chim. Acta 1937, 20, 1078.
(18) (a) Fleming, I.; Woodward, R. B. J . Chem Soc. C 1968, 1289.
(b) Oppolzer, W.; Chapuis, C.; Dupuis, D.; Guo, M. Helv. Chim. Acta
1985, 68, 2100.
(15) Gontcharov, A. V. Ph.D. Dissertation, Case Western Reserve
University, 1997.

Asymmetric Conversion of Arenechromium Complexes
J . Org. Chem., Vol. 63, No. 1, 1998 157
F igu r e 4. Analysis of preferred conformations of arenechromium complexes with various chiral auxiliaries.
Sch em e 6
Ta ble 4. Dia ster eoselectivity of LiCMe2CN Ad d ition to
A related chiral auxiliary 53 was prepared by a
procedure developed by Oppolzer19 (Scheme 6). Alkyla-
tion of the enolsilane 51 afforded 52, reduction of which
afforded 3-exo-diphenylmethylisoborneol (DPMIB-OH,
53). Addition of LiCMe2CN to the corresponding chro-
mium complex 54 (R ) Me, R* ) DPMIB) proceeded with
83% de (11:1 diastereomer ratio). The results with
3-substituted isoborneols are collected in Table 4.
Ar en ech r om iu m Com p lexes 47, 48, a n d 54
diastereomer
starting yield of the
complex complex, %
ratios
A:B
combined
yield, %
R*
R
47
48
54
76
71
91
DOIB
DOIB
DPMIB Me
H
Me
1:7.6
1:17
1:11
86
65
76
corresponding R-hydroxy ketone, while DPMIB-OH does
not undergo any changes during the hydrolysis. There
may be two solutions to this chiral auxiliary recovery
problem. A mild hydrolysis (as in Scheme 2) could be
carried out first, which would lead to the nonconjugated
3-cyclohexenone and the chiral auxiliary, which would
be unchanged under these conditions. After separation,
the 3-cyclohexenone could be rearranged to the thermo-
dynamically more stable 2-cyclohexenone. The above
There is, however, a problem with most of the modified
chiral auxiliaries we studied: hydrolysis of the dienol
ethers under harsh conditions does not return the chiral
auxiliary unchanged. With tertiary alcohols, water
elimination usually occurs leading to the corresponding
alkenes. DOIB-OH (46) is easily hydrolyzed to the
(19) Oppolzer, W.; Kurth, M.; Reichlin, D.; Chapuis, C.; Mohnhaupt,
M.; Moffatt, F. Helv. Chim. Acta 1981, 64, 2802.

158 J . Org. Chem., Vol. 63, No. 1, 1998
Pearson and Gontcharov
Ta ble 5. Tem p er a tu r e Dep en d en ce of th e Selectivity in
Nu cleop h ilic Ad d ition to (Alk oxyben zen e)ch r om iu m
Com p lexes
Ta ble 6. Tem p er a tu r e Dep en d en ce of th e Selectivity in
Nu cleop h ilic Ad d ition s to (Alk oxytolu en e)ch r om iu m
Com p lexesa
transformation has been shown to work for [(methyl-
isobornyl)oxy]cyclohexadiene (39). Alternatively, the
products of the chiral auxiliary transformation during the
hydrolysis could be converted back into the chiral alcohol.
Thus, 3-oxoisoborneol, a product of DOIB-OH hydrolysis,
can be reoxidized to camphorquinone, from which a two-
step procedure affords the chiral auxiliary DOIB-OH as
described above. Another problem with all the chiral
auxiliaries studied so far is that the mixtures of diaster-
eomeric dienol ethers have proven to be impossible to
separate. The products are usually oils, fairly nonpolar,
and have very similar retention factors on silica gel.
Future work will focus on identifying systems that
provide a solution to this problem.
Sch em e 7. Or th o- vs Meta -Ad d ition to
(Alk oxytolu en e)ch r om iu m Com p lexes
Tem p er a tu r e Effects in Asym m etr ic Nu cleop h ile
Ad d ition s to Ar en ech r om iu m Com p lexes
Although the level of asymmetric induction Semmel-
hack and Schmaltz achieved was appreciably lower than
ours,13 they showed that thermodynamically controlled
nucleophilic addition gives a significantly higher level of
asymmetric induction than the kinetically controlled
reaction. Thus, in one case, the selectivity increased from
14% ee to 48% ee when the temperature of the reaction
was raised from -78 to 0 °C. With these rather unex-
pected results in mind, we decided to study the temper-
ature dependence of diastereoselectivity of nucleophilic
additions to some of our complexes.
The results of our studies are presented in Tables 5
(for alkoxybenzene complexes) and 6 (for alkoxytoluene
complexes). Interestingly, in none of the cases we studied
did raising the temperature of the reaction lead to an
increase of the diastereoselectivity of nucleophilic addi-
tion. Apparently, none of our chiral auxiliaries can create
a difference in the product diastereomer stabilities suf-
ficient to give any significant improvement in diastereo-
mer distribution at higher temperatures (in fact, the
opposite trend is observed).
The temperature dependence experiments with alkoxy-
toluene complexes allowed us to make an interesting
observation of regioselectivity change when the reaction
control switches from kinetic to thermodynamic. Ortho-
addition becomes dominant at higher temperatures,
although significant amounts of meta-addition products
are also formed (Table 6, Scheme 7). Despite the fact
that regioselectivity of nucleophilic addition to ani-
solechromium complexes has been extensively studied
over the years, this observation is the first report of
kinetic regioselectivity being different from thermody-
namic. The selectivity we observed with alkoxytoluene
complexes at low temperatures is consistent with the
known strong meta-directing effect of the alkoxy sub-
stituent during these reactions. In the absence of the
para-substituent, the combination of electronic and steric
effects probably makes the corresponding meta cyclo-
hexadienyl product also thermodynamically more stable.
It is possible that the introduction of the methyl sub-
stituent para to the alkoxy inverts the relative stabilities
of the two addition products. It seems improbable that
the electronic effect of the methyl group would be strong
enough to outweigh the electronic effect of alkoxy group,
so one would expect only a slight weakening of the
preference for the meta addition if the electron donating
effect of the methyl group is taken into consideration.
The only other obvious effect of the methyl group is steric,
and it has to be compared with the steric effect of
alkoxide. From the Newman projections of the C6-C1
bond of cyclohexadienyl ligand (Figure 5) one can see that
the added nucleophile (at C6 position) is involved in a
close to gauche interaction with the substituent at C1 (Me
in the case of meta-addition and alkoxide in the case of
ortho-addition). By its order of magnitude, gauche
interaction might be sufficient to account for the observed
ortho/meta selectivity (e.g., 0.8 kcal/mol in butane,20
whereas about 0.4 kcal/mol energy difference between the
isomers is required to produce 2:1 isomer distribution).
(20) Carey, F. A.; Sundberg, R. J . Advanced Organic Chemistry;
Plenum Press: New York, 1984; pp 104-105.

Asymmetric Conversion of Arenechromium Complexes
J . Org. Chem., Vol. 63, No. 1, 1998 159
carbonyl: yield 94% as yellow crystals; mp 75.5-77 °C; 1H
NMR (300 MHz, CDCl3) δ 5.57-5.51 (m, 2H), 5.14-5.07 (m,
2H), 4.87-4.81 (m, 1H), 4.31 (m, 1H), 1.00 (d, 3H, J ) 6.6 Hz),
0.92 (d, 3H, J ) 6.0 Hz), 0.90 (d, 3H, J ) 6.3 Hz), 1.95-0.84
(m, remaining H’s); FTIR (CH2Cl2) 1965, 1882 cm-1
.
η6-[[[(1S,2S,5R)-2-Isopropyl-5-methylcyclohex-2-yl]oxy]ben-
zene]chromium tricarbonyl (3) was prepared from (1S,2S,5R)-
(+)-neomenthol (Aldrich) and (fluorobenzene)chromium tri-
1
carbonyl: yield 71% as yellow crystals; H NMR (300 MHz,
CDCl3) δ 5.54-5.49 (m, 2H), 5.21-5.14 (m, 2H), 4.89-4.84 (m,
1H), 4.47 (m, 1H), 2.18-2.09 (m, 1H), 0.98 (d, 3H, J ) 6.6 Hz),
0.87 (d, 3H, J ) 6.6 Hz), 0.83 (d, 3H, J ) 6.6 Hz), 1.08-1.33,
1.06-1.83 (m’s, remaining H’s); FTIR (CH2Cl2) 1965, 1880
cm-1
.
F igu r e 5. Steric interactions of the substituents in cyclo-
hexadienylchromium complexes.
η6-[[[(1S,2S,3S)-2,6,6-Trimethylbicyclo[3.1.1]hept-3-yl]oxy]-
benzene]chromium tricarbonyl (4) was prepared from (+)-
isopinocampheol (Aldrich) and (fluorobenzene)chromium tri-
carbonyl: yield 96% as yellow crystals; mp 122-126 °C; EI
HRMS m/z 366.0926, calcd for C19H22O4Cr 366.0923; 1H NMR
(300 MHz, CDCl3) δ 5.59-5.49 (m, 2H), 5.18-5.12 (m, 1H),
5.08-5.03 (m, 1H), 4.89-4.83 (m, 1H), 4.27 (ddd, 1H, J ) 0.5,
5.0, 8.0 Hz), 2.59-2.48 (m, 1H), 2.42-2.32 (m, 1H), 2.31-2.19
(m, 1H), 2.02-1.94 (m, 1H), 1.93-1.83 (m, 2H), 1.25 (s, 3H),
1.19 (d, 3H, J ) 7.4 Hz)1.10 (d, 1H, J ) 9.9 Hz), 0.96 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 233.4, 142.4, 95.3, 94.5, 85.2, 80.4,
78.7 (2C), 47.2, 44.2, 41.1, 38.1, 35.7, 32.6, 27.2, 23.9, 20.6;
Con clu sion s
Terpenoid chiral alcohols and some of their simple
derivatives can serve as efficient chiral auxiliaries during
nucleophilic addition to arenechromium complexes. These
alcohols can be easily attached to the arene by nucleo-
philic substitution of fluoride in (fluoroarene)chromium
complexes with the corresponding potassium alkoxides.
Addition of nucleophiles to the resulting chiral complexes
occurs with high diastereoselectivity (up to 92% de), and
after protonation of the addition product, subsequent
demetalation, and hydrolysis, 5-substituted cyclohex-
enones of high enantiomeric purity are produced. Steric
approach control appears to be the dominant factor in
determining the stereochemical outcome of nucleophilic
addition.
FTIR (CH2Cl2) 1965, 1883 cm-1
.
η6-[4-[[(1S,2S,3S)-2,6,6-Trimethylbicyclo[3.1.1]hept-3-yl]oxy]-
toluene]chromium tricarbonyl (5) was prepared from isopi-
nocampheol (Aldrich) and (p-fluorotoluene)chromium tricar-
bonyl: yield 67% as yellow crystals; mp 123-124 °C; EI HRMS
1
m/z 380.1061 [M+], calcd for C20H24O4Cr 380.1080; H NMR
(300 MHz, CDCl3) δ 5.43-5.36 (m, 2H), 5.20-5.15 (m, 1H)
5.10-5.06 (m, 1H), 4.23-4.16 (m, 1H), 2.58-1.91 (m, 1H),
2.41-2.31 (m, 1H), 2.66-2.15 (m, 1H), 2.07 (s, 3H), 2.01-1.94
(m, 1H), 1.91-1.81 (m, 2H), 1.24 (s, 3H), 1.16 (d, 3H, J ) 7.2
Hz), 1.09 (d, 1H, J ) 10.1 Hz), 0.96 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 233.9, 140.2, 101.7, 95.6, 94.9, 81.2, 79.6, 78.8, 47.1,
44.2, 41.1, 38.1, 35.7, 32.7, 27.2, 23.9, 20.6, 19.8; FTIR (CH2Cl2)
Exp er im en ta l Section
General procedures and characterization methods are as
described elsewhere.9
1961, 1878 cm-1
.
η6-(Fluorobenzene)- and η6-(4-fluorotoluene)chromium tri-
carbonyls were synthesized by refluxing fluorobenzene or
fluorotoluene with chromium hexacarbonyl in dibutyl ether
according to the reported procedures.21 Yields were 50% and
56%, respectively.
η6-[[[(1R,2R)-1,3,3-Trimethylbicyclo[2.2.1]hept-2-yl]oxy]ben-
zene]chromium tricarbonyl (6) was prepared from (1R)-endo-
(+)-fenchyl alcohol (Aldrich) and (fluorobenzene)chromium
tricarbonyl: yield 90% as yellow crystals; mp 103-105 °C; EI
HRMS m/z 366.0892, calcd for C19H22O4Cr 366.0923; 1H NMR
(200 MHz, CDCl3) δ 5.56-5.47 (m, 2H), 5.23-5.18 (m, 1H),
5.11-5.06 (m, 1H), 4.88-4.82 (m, 1H), 3.68 (s, 1H), 1.87-1.37
(m, 5H), 1.24 (d, 1H, J ) 5.8 Hz), 1.18 (s, 6H), 1.13-1.02 (m,
1H), 0.85 (s, 3H); 13C NMR (50 MHz, CDCl3) δ 233.3, 144.0,
94.9, 94.0, 91.0, 85.4, 80.9, 79.0, 49.6, 48.9, 41.4, 40.2, 29.7,
Gen er a l P r oced u r e for Syn th esis of η6-(P h en yl a lk yl
eth er )ch r om iu m Tr ica r bon yl Com p lexes. A solution of
the alcohol (3 mmol) in 4 mL of dry diethyl ether was added
to a stirred suspension of potassium hydride (3 mmol) in 6
mL of ether cooled to 0 °C. After gas evolution had stopped,
the mixture was allowed to stir for 30 min at room tempera-
ture, and then a solution of (PhF)Cr(CO)3 (2.9 mmol) in 10
mL of ether was added dropwise. The progress of the reaction
was monitored by TLC. It was usually complete within
minutes. The reaction was worked up with 3 mL of a
saturated aqueous solution of NH4Cl. The layers were sepa-
rated. The water layer was extracted with ether, and the
combined organic phases were dried with MgSO4. Evaporation
of solvent gave the crude product, which was either crystallized
from CH2Cl2-hexanes or purified by flash chromatography on
silica gel (hexanes-CH2Cl2 as eluent).
26.3, 25.6, 20.4, 20.1; FTIR (CH2Cl2) 1965, 1883 cm-1
.
η6-{4-[[(1R,2R)-1,3,3-Trimethylbicyclo[2.2.1]hept-2-yl]oxy]-
toluene}chromium tricarbonyl (7) was prepared from fenchyl
alcohol (Aldrich) and (p-fluorotoluene)chromium tricarbonyl:
yield 89% as yellow crystals; mp 104-105 °C; EI HRMS m/z
1
380.1066 [M+], calcd for C20H24O4Cr 380.1080; H NMR (300
MHz, CDCl3) δ 5.39-5.31 (m, 2H), 5.28-5.23 (m, 1H), 5.13-
5.08 (m, 1H), 3.59 (d, 1H, J ) 1.6 Hz), 2.07 (s, 3H), 1.86-1.37
(m, 5H), 1.23-1.16 (m, 1H), 1.17 (s, 3H), 1.15 (s, 3H), 1.12-
1.00 (m, 1H), 0.85 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 233.9,
141.8, 102.1, 95.2, 94.2, 91.2, 82.1, 80.0, 49.6, 48.9, 41.3, 40.0,
η6-[[[(1R,2S,5R)-2-Isopropyl-5-methylcyclohex-2-yl]oxy]ben-
zene]chromium tricarbonyl (1) was prepared from (1R,2S,5R)-
(-)-menthol (Aldrich) and (fluorobenzene)chromium tricar-
bonyl: yield 83% as yellow crystals; 1H NMR (300 MHz,
CDCl3) δ 5.51 (2H), 5.18-5.13 (m, 2H), 4.86 (1H), 3.86 (dt, 1H,
J ) 4.2, 10.6 Hz), 2.26-2.18 (m, 1H), 2.18-2.07 (m, 1H), 1.76-
1.67 (m, 2H), 1.50-1.37 (m, 2H), 1.11-0.98 (m, 2H), 0.96 (d,
3H, J ) 6.6 Hz), 0.91 (d, 3H, J ) 7.2 Hz), 0.78 (d, 3H, J ) 6.9
30.4, 26.3, 25.6, 20.3, 20.0, 19.8; FTIR (CHCl3) 1965, 1886 cm-1
.
η6-{[[(1S,2R)-1,7,7-Trimethylbicyclo[2.2.1]hept-2-yl]oxy]ben-
zene}chromium tricarbonyl (8) was prepared from [(1S)-endo]-
(-)-borneol (Aldrich) and (fluorobenzene)chromium tricarbon-
yl: yield 90% as yellow crystals; mp 128-130 °C; 1H NMR
(300 MHz, CDCl3) δ 5.58-5.45 (m, 2H), 5.15-5.10 (m, 1H),
4.99-4.94 (m, 1H), 4.88-4.82 (m, 1H), 4.12 (ddd, 1H, J ) 1.7,
3.2, 9.3 Hz), 2.34-2.23 (m, 1H), 2.07-1.96 (m, 1H), 1.82-1.68
(m, 2H), 1.28 (s, 3H), 1.2 (d, 3H), 0.9 (s, 3H); 13C NMR, DEPT
(75 MHz, CDCl3) δ C: 233.4, 143.0, 49.6, 47.6, CH: 95.4, 94.8,
85.0, 84.3, 80.3, 78.4, 45.0, CH2: 36.3, 27.6, 36.3, CH3: 19.6,
Hz); FTIR (KBr pellet) 1954 (vs), 1887 (vs), 1862 (vs) cm-1
.
η6-[[[(1S,2R,5R)-2-Isopropyl-5-methylcyclohex-2-yl]oxy]ben-
zene]chromium tricarbonyl (2) was prepared from (1S,2R,5R)-
(+)-isomenthol (Aldrich) and (fluorobenzene)chromium tri-
18.9, 13.6; FTIR (CH2Cl2) 1963, 1881 cm-1
.
η6-{4-[[(1S,2R)-1,7,7-Trimethylbicyclo[2.2.1]hept-2-yl]oxy]-
toluene}chromium tricarbonyl (9) was prepared from [(1S)-
(21) Mahaffy, C. A. L.; Pauson, P. L. Inorg. Synth. 1979, 19, 154.

160 J . Org. Chem., Vol. 63, No. 1, 1998
Pearson and Gontcharov
endo]-(-)-borneol (Aldrich) and (p-fluorotoluene)chromium
tricarbonyl: yield 93% as yellow crystals; mp 146-148 °C dec;
1H NMR (300 MHz, CDCl3) δ 5.44-5.36 (m, 2H), 5.17-5.13
(m, 1H) 5.01-4.97 (m, 1H), 4.05 (m, 1H), 2.27 (m, 1H), 2.06
(s, 3H), 2.04-1.94 (m, 1H), 1.81-1.67 (m, 2H), 1.37-1.14 (m,
3H), 0.91 (s, 6H), 0.89 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
233.9, 141.0, 101.4, 95.8, 95.2, 84.4, 81.0, 79.2, 49.6, 47.5, 45.0,
36.3, 27.6, 26.6, 19.8, 19.5, 18.9, 13.5; FTIR (CH2Cl2) 1961,
(1R,2S)-2-phenyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (vide
infra) and (fluorobenzene) chromium tricarbonyl: yield 59%
as yellow crystals; mp 136-140 °C dec; EI HRMS m/z
442.123 01 (M+), calcd for C25H26O4Cr 442.123 61; 1H NMR
(200 MHz, CDCl3) δ 7.46-7.30 (m, 5H), 5.29-5.16 (m, 2H),
4.90-4.77 (m, 3H), 2.50 (ddd, 1H, J ) 2.3, 4.3, 14.2 Hz), 2.29
(d, 1H, J ) 14.2 Hz), 1.98 (t, 1H, J ) 4.3 Hz), 1.77 (m, 1H),
1.35-1.19 (m, 2H), 1.17 (s, 3H), 0.99 (s, 3H), 0.96 (s, 3H), 0.94-
0.73 (m, 1H); 13C NMR (50 MHz, CDCl3) δ 233.6,139.6, 137.9,
128.5 (2C), 127.76, 127.81, 125.1, 93.1, 93.2, 92.5, 87.4, 84.8,
83.6, 55.4, 50.4, 45.6, 39.6, 30.4, 26.2, 21.6, 21.1, 9.83; FTIR
1881 cm-1
.
η6-{4-[[(1R,2R)-1,7,7-Trimethylbicyclo[2.2.1]hept-2-yl]oxy]-
toluene}chromium tricarbonyl (10) was prepared from isoborneol
(synthesized by L-Selectride reduction of (+)-camphor (Acros)
as described in the literature) and (p-fluorotoluene)chromium
tricarbonyl: yield 74% as yellow crystals; mp 147-150 °C dec;
EI HRMS m/z 380.1089 (M+), calcd for C20H24O4Cr 380.1080;
1H NMR (200 MHz, CDCl3) δ 5.43-5.36 (m, 2H), 5.16-5.12
(m, 1H), 5.05-5.01 (m, 1H), 3.76 (dd, 1H, J ) 2.4, 4.9 Hz),
2.06 (s, 3H), 1.96-1.51 (m, 4H), 1.18-0.85 (m, 3H), 0.96 (s,
3H), 0.94 (s, 3H), 0.85 (s, 3H); 13C NMR (50 MHz, CDCl3) δ
233.9, 140.2, 101.4, 95.9, 95.3, 86.2, 80.9, 79.1, 49.4, 47.0, 45.3,
39.3, 33.9, 27.2, 20.1, 19.9, 19.8, 11.5; FTIR (CH2Cl2) 1962,
(CH2Cl2) 1964, 1876 cm-1
.
η6-4-{[[(1R,2S)-2-Phenyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-
yl]oxy]toluene}chromium tricarbonyl (37) was prepared from
(1R,2S)-2-phenyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (vide
infra) and (p-fluorotoluene)chromium tricarbonyl: yield 89%
as yellow crystals; mp 132-134 °C dec; EI HRMS m/z
456.139 74 (M+), calcd for C26H28O4Cr 456.139 27; 1H NMR
(200 MHz, CDCl3) δ 7.46-7.28 (m, 5H), 5.10-4.80 (m, 4H),
2.52 (ddd, 1H, J ) 3.1, 4.2, 14.2 Hz), 2.26 (d, 1H, J ) 14.2
Hz), 1.99 (s, 3H), 1.99 (t, 1H, J ) 4.9 Hz), 1.89-1.66 (m, 1H),
1.36-1.17 (m, 2H), 1.15 (s, 3H), 0.97 (s, 3H), 0.95 (s, 3H), 0.90-
0.73 (m, 1H); 13C NMR (50 MHz, CDCl3) δ 234.1, 139.6, 134.8,
128.5, 128.4, 127.8, 127.7, 125.2, 117.8, 103.9, 93.2, 92.8, 85.7,
84.5, 55.3, 50.4, 45.6, 39.3, 30.4, 26.2, 21.2, 21.0, 19.7, 9.8; FTIR
1878 cm-1
.
η6-[4-Flu or o(tr im eth ylsilyl)ben zen e]ch r om iu m Tr ica r -
bon yl (23). (Naph-thalene)chromium tricarbonyl (1.2 mmol),
p-fluoro(trimethylsilyl)benzene (1.5 mL), dry THF (1.5 mL),
and dry ether (10 mL) were placed into a 50 mL high-pressure
tube, which was then filled with nitrogen by freeze-pump-thaw
cycle and sealed under atmospheric pressure. The reaction
mixture was heated at 70 °C for 2 days (the color changes from
red to yellow). The product was isolated by column chroma-
tography on flash silica gel with hexanes-ether 10:1 as eluent:
yield 72% as yellow crystals; mp 97-98 °C; 1H NMR (300 MHz,
CDCl3) δ 5.49 (m, 2H), 5.26 (m, 2H), 0.25 (s, 9H); 13C NMR δ
232.0, 147.7 (d, J CF ) 267 Hz), 98.2 (d, J ) 6.4 Hz), 95.0, 78.7
(CH2Cl2) 1959, 1875 cm-1
.
η6-4-{[[(1R,2S)-1,2,3,3-Tetramethylbicyclo[2.2.1]hept-2-yl]-
oxy]toluene}chromium tricarbonyl (38) was prepared from
(1R,2S)-1,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-ol (vide in-
fra) and (p-fluorotoluene)chromium tricarbonyl: yield 72%; mp
158-160 °C dec; EI HRMS m/z 394.124 17 (M+), calcd for
1
C25H26O4Cr 394.123 62; H NMR (200 MHz, CDCl3) δ 5.37-
5.07 (m, 4H), 2.30-2.11 (m, 1H), 2.07 (s, 3H), 1.86-1.34 (m,
3H), 1.26 (s, 3H), 1.19-1.08 (m, 2H), 1.05 (s, 3H), 1.04 (s, 3H),
1.03 (s, 3H), 1.03-0.92 (m, 1H); 13C NMR (50 MHz, CDCl3) δ
234.0, 138.3, 102.5, 94.9, 94.3, 92.2, 87.4, 85.4, 54.1, 49.7, 43.8,
40.8, 29.0, 27.2, 25.8, 24.2, 19.8, 19.0, 17.2; FTIR (CH2Cl2)
(d, J ) 90 Hz), -1.1; FTIR (CH2Cl2) 1976, 1900 cm-1
.
η6-[4-[[(1R,2R)-1,3,3-Tr im eth ylbicyclo[2.2.1]h ep t-2-yl]-
oxy](tr im eth ylsilyl)ben zen e]ch r om iu m Tr ica r bon yl (24).
The complex was synthesized from η6-[p-fluoro(trimethylsilyl)-
benzene]chromium tricarbonyl and fenchyl alcohol (Aldrich)
according to the procedure used for other chromium complexes
reported above: yield 98% as yellow crystals; mp 96-98 °C;
EI HRMS m/z 438.1315 [M+], calcd for C22H30O4CrSi 438.1318;
1H NMR (300 MHz, CDCl3) δ 5.54 (m, 2H), 5.15 (m, 1H), 5.05
(m, 1H), 3.74 (s, 1H), 1.90-1.40 (m, 5H), 1.25-1.2 (1H)1.19
(s, 6H), 1.09 (m, 1H), 0.87 (s, 3H), 0.27 (s, 9H); 13C NMR (75
MHz, CDCl3) δ 233.6, 145.5, 100.3, 99.4, 92.9, 90.5, 80.4, 78.5,
49.6, 48.9, 41.5, 40.3, 30.3, 26.3, 25.6, 20.5, 20.2, -1.1; FTIR
1961, 1878 cm-1
.
η6-{[[Spiro[(1R,2S)-1,7,7-trimethylbicyclo[2.2.1]heptane-3,2′-
[1,3]dioxolan]-2-yl]oxy]benzene}chromium tricarbonyl (47) was
prepared from spiro[(1R,2S)-1,7,7-trimethylbicyclo[2.2.1]hep-
tane-3,2′-[1,3]dioxolan]-2-ol (vide infra) and (fluorobenzene)chro-
mium tricarbonyl: yield 70% as a yellow amorphous solid
slowly crystallizing at low temperature; mp 109-111 °C; EI
HRMS m/z 424.0989 (M+), calcd for C21H24O6Cr 424.0978; 1H
NMR (200 MHz, C6D6) δ 4.96-4.89 (m, 1H), 4.76-4.60 (m, 3H),
3.98-3.89 (m, 1H), 3.83 (s, 1H), 3.40-3.29 (m, 1H), 3.26-3.09
(m, 3H), 1.71-1.60 (m, 1H), 1.44-1.14 (m, 4H), 1.27 (s, 3H),
1.06 (s, 3H), 0.72 (s, 3H); 13C NMR (50 MHz, C6D6) δ 233.9,
143.5, 115.0, 95.4, 94.0, 90.1, 84.7, 81.1, 78.3, 64.4, 63.7, 52.2,
49.9, 48.2, 34.0, 21.1, 21.1, 20.5, 11.3; FTIR (CHCl3) 1966, 1888
(CH2Cl2) 1962, 1881 cm-1
.
η6-{[[(1R,2R)-1,2,7,7-Tetramethylbicyclo[2.2.1]hept-2-yl]oxy]-
benzene}chromium tricarbonyl (34) was prepared from (1R,2R)-
1,2,7,7-tetramethylbicyclo[2.2.1]heptan-2-ol (vide infra) and
(fluorobenzene)chromium tricarbonyl: yield 68% as yellow
crystals; mp 148-149 °C dec; EI HRMS m/z 380.107 34 (M+),
cm-1
.
η6-{4-[[Spiro[(1R,2S)-1,7,7-trimethylbicyclo[2.2.1]heptane-
3,2′-[1,3]dioxolan]-2-yl]oxy]toluene}chromium tricarbonyl (48)
was prepared from spiro[(1R,2S)-1,7,7-trimethylbicyclo[2.2.1]-
heptane-3,2′-[1,3]dioxolan]-2-ol (vide infra) and (p-fluorotolu-
ene)chromium tricarbonyl: yield 71% as yellow amorphous
solid; EI HRMS m/z 438.1133, calcd for C22H26O6Cr 438.1135;
1H NMR (200 MHz, CDCl3) δ 5.43-5.17 (m, 4H), 4.06-3.76
(m, 4H), 3.73 (s, 1H), 2.05 (s, 3H), 1.72-1.48 (m, 3H), 1.40-
1.24 (m, 2H), 1.10 (s, 3H), 0.95 (s, 3H), 0.85 (s, 3H); 13C (50
MHz, CDCl3) δ 234.0, 141.5, 114.9, 101.3, 96.2, 94.9, 90.2, 82.4,
79.1, 64.5, 63.9, 51.9, 49.7, 48.0, 33.9, 21.1, 20.7, 20.2, 19.8,
1
calcd for C25H26O4Cr 380.107 97; H NMR (400 MHz, CDCl3)
δ 5.52 (m, 2H), 5.05 (m, 2H), 4.85 (m, 1H), 2.47 (ddd, 1H, J )
3.0, 4.4, 13.1 Hz), 1.78 (t, 1H, J ) 4.7 Hz), 1.72 (m, 1H), 1.51-
1.41 (m, 3H), 1.06 (m, 1H), 1.51 (s, 3H), 0.95 (s, 3H), 0.90 (s,
6H); 13C NMR (50 MHz, CDCl3) δ 233.6, 139.1, 95.5, 94.5, 90.2,
85.0, 82.6, 81.6, 54.3, 48.7, 45.7, 43.8, 30.5, 26.3, 21.0, 20.8,
20.4, 10.1; FTIR (CH2Cl2) 1965, 1881 cm-1
.
η6-{4-[[(1R,2R)-1,2,7,7-Tetramethylbicyclo[2.2.1]hept-2-yl]-
oxy]toluene}chromium tricarbonyl (35) was prepared from
(1R,2R)-1,2,7,7-tetramethylbicyclo[2.2.1]heptan-2-ol (vide in-
fra) and (p-fluorotoluene)chromium tricarbonyl: yield 60% as
yellow crystals; decomp. ca. 135 °C without melting; EI HRMS
m/z 394.120 89 (M+), calcd for C21H26O4Cr 394.123 62; 1H NMR
(200 MHz, CDCl3) δ 5.36 (m, 2H), 5.12 (m, 1H), 5.04 (m, 2H),
2.49 (m, 1H), 2.06 (s, 3H), 1.78 (m, 1H), 1.67 (m, 1H), 1.54-
1.36 (m, 3H), 1.47 (s, 3H), 1.13-0.97 (m, 1H), 0.92 (s, 3H), 0.90
(s, 3H), 0.89 (s, 3H); 13C NMR (50 MHz, CDCl3) δ 234.1, 136.7,
101.6, 95.9, 94.6, 89.9, 83.7, 82.3, 54.3, 48.8, 45.8, 43.7, 30.6,
26.3, 21.0, 20.9, 20.1, 19.8, 10.2; FTIR (CH2Cl2) 1962, 1884
11.1; FTIR (CH2Cl2) 1960, 1876 cm-1
.
η6-{4-[[(1R,2R,3S)-3-Benzhydryl-1,7,7-trimethylbicyclo[2.2.1]-
hept-2-yl]oxy]toluene}chromium tricarbonyl (54) was prepared
from (1R,2R,3S)-3-benzhydryl-1,7,7-trimethylbicyclo[2.2.1]-
heptan-2-ol and (p-fluorotoluene)chromium tricarbonyl: yield
91% as yellow crystals; dec g 190 °C without melting; EI
HRMS m/z 546.1858 (M+), calcd for C33H34O4Cr 546.1862; 1H
NMR (200 MHz, C6D6) δ 7.20-6.65 (m, 10H), 4.40-4.18 (m,
5H), 3.79 (d, J ) 7.8, 1H), 2.62 (dd, J ) 7.8, 12.9, 1H), 1.55 (s,
3H), 1.47-1.38 (m, 3H), 1.37 (s, 3H), 1.12 (s, 3H), 1.16-0.84
(m, 2H), 0.61 (s, 3H); 13C NMR (50 MHz, C6D6) δ 234.7, 146.0,
145.2, 140.6, 129-125 (11 carbon signals, overlapped with the
cm-1
.
η6-{[[(1R,2S)-2-Phenyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]-
oxy]benzene}chromium tricarbonyl (36) was prepared from

Asymmetric Conversion of Arenechromium Complexes
J . Org. Chem., Vol. 63, No. 1, 1998 161
solvent signal), 103.3, 93.0, 91.7, 90.1, 84.4, 80.1, 54.9, 52.4,
51.3, 48.4, 47.6, 33.3, 30.2, 21.9, 19.3, 12.8; FTIR (CH2Cl2)
4H), 1.83 (s, 3H), 1.82-1.75 (m, 2H), 1.53-1.60 (m, 2H), 1.22-
1.12 (m, 1H), 1.11 (s, 3H), 1.09 (s, 6H), 1.07(d, 3H, J ) 7.5
Hz), 0.79(s, 3H); minor diastereomer (partial data) 4.70 (dd,
1H, J ) 2.4, 6.0 Hz), 1.82 (s, 3H), 0.77 (s, 3H), 1.14-1.05 (m,
remaining H’s).
(5R a n d 5S)-5-(1-Cya n o-1-m et h ylet h yl)-1-[[(1R,2R)-
1,3,3-tr im eth ylbicyclo[2.2.1]h ep t-2-yl]oxy]cycloh exa -1,3-
d ien es (16). Mixture of diastereomers (3.5:1); total yield 67%
as a colorless oil; 1H NMR (300 MHz, C6D6) δ major diastereo-
mer 5.94 (ddd, 1H, J ) 1.5, 6.3, 10.1 Hz), 5.19 (dd, 1H, J )
3.4, 9.5 Hz), 4.88 (d, 1H, J ) 6.3 Hz), 3.60 (d, 1H, J ) 1.9 Hz),
2.48-2.20 (m, 2H), 2.05-1.93 (m, 1H), 1.76-1.64 (m, 1H),
1.57-1.52 (m, 1H), 1.42-1.29 (m, 2H), 1.19-0.80 (m, 3H), 1.09,
0.98, 0.92, 0.87, 0.83 (5 s’s, 3H each); minor diastereomer
(partial data) 5.95 (m, 1H), 5.21 (dd, 1H, J ) 3.3, 9.6 Hz), 4.87
(d, 1H, J ) 6.3 Hz), 3.54 (d, 1H, J ) 2.0 Hz), 1.09, 1.04, 0.99,
0.91, 0.86 (5s’s, 3H each).
1957, 1873 cm-1
.
Gen er a l P r oced u r e for Nu cleop h ilic Ad d ition s of
Isob u t yr on it r ile Ca r b a n ion t o Ar ylch r om iu m Com -
p lexes w ith Su bsequ en t in Situ Con ver sion to th e
Cor r esp on d in g Cycloh exa d ien es. A THF solution of isobu-
tyronitrilelithium was prepared by adding 1 mmol of isobu-
tyronitrile to a solution of 1 mmol of LDA in 2 mL of THF
(prepared from diisopropylamine and butyllithium according
to the standard procedure22) at -78 °C and stirring the
resulting mixture at that temperature for 30 min. A solution
of the (arene)chromium tricarbonyl complex (0.2 mmol) in 2
mL of THF was added dropwise. The reaction mixture was
stirred for 2 h. Then 400 µL of trifluoroacetic acid was added
(this caused immediate color change to red), and stirring was
continued for another hour, the temperature still being
maintained at -78 °C. Decomplexation of the cyclohexadiene
chromium complex was accomplished by treating the reaction
mixture with a concentrated aqueous solution of NH3 for
approximately 2 h at room temperature. The organic products
(together with chromium containing products (most likely
[Cr(CO)3(NH3)3]) were extracted with diethyl ether. The ether
solution was washed with water, dried with MgSO4, and
evaporated. A mixture of diastereomeric cyclohexadienes was
isolated by TLC on a silica gel plate with hexanes-ether 10:1
as eluent.
(5R a n d 5S)-5-(1-Cya n o-1-m et h ylet h yl)-4-m et h yl-1-
[[(1R,2R)-1,3,3-t r im et h ylb icyclo[2.2.1]h ep t -2-yl]oxy]cy-
cloh exa -1,3-d ien es (17). Mixture of diastereomers (7.5:1):
1
total yield 76% as a colorless oil; H NMR (400 MHz, C6D6) δ
major diastereomer 5.75 (ddq, 1H, J ) 6.1, 0.7, 1.6 Hz), 4.77
(ddq, 1H, J ) 6.1, 2.4, 0.5 Hz), 3.46 (d, 1H, J ) 1.9 Hz), 2.54
(dddt, 1H, J ) 17.8, 9.6, 2.5, 0.5 Hz), 2.35 (dd, 1H, J ) 1.6,
17.8 Hz), 1.98 (dddd, 1H, J ) 2.2, 5.8, 9.0, 12.5 Hz), 1.88 (qdd,
1H, J ) 0.5, 1.6, 9.6 Hz), 1.82 (dq, 3H, 1.6, 0.5 Hz), 1.74-1.66
(m, 1H), 1.60-1.54 (m, 1H), 1.39-1.30 (m, 2H), 1.12-0.91 (m,
2H), 1.11, 1.09, 1.04, 0.98, 0.90 (5 s’s, 3H each); minor
diastereomer (partial data) 4.74 (ddq, 1H, J ) 6.1, 2.5, 0.6 Hz),
3.52 (d, 1H, J ) 1.9 Hz).
(5R a n d 5S)-5-(1-Cya n o-1-m eth yleth yl)-1-[[(1R,2S,5R)-
2-isop r op yl-5-m eth ylcycloh ex-2-yl]oxy]cycloh exa -1,3-d i-
en es (11). Mixture of diastereomers (1:1.2): combined yield
80% as a colorless oil; 1H NMR (300 MHz, C6D6) δ major
diastereomer: 5.98 (ddd, 1H, J ) 9.4, 6.5, 2.3 Hz), 5.21 (dd,
1H, J ) 9.6, 3.7 Hz), 4.83 (d, 1H, J ) 6.3 Hz), 3.82-3.69 (m,
1H), 2.50-2.08 (m, 7H), 2.58-2.36 (m, 4H), 1.25-1.07 (m, 1H),
0.93-0.76 (remaining H’s); minor diastereomer (partial
data): 5.23 (dd, 1H, J ) 9.4, 3.3 Hz).
(5R an d 5S)-5-(1-Cyan o-1-m eth yleth yl)-1-[[(1S,2R)-1,7,7-
t r im et h ylb icyclo[2.2.1]h ep t -2-yl]oxy]cycloh exa -1,3-d i-
en e (18). Mixture of diastereomers (1:1). combined yield 50%
as a colorless oil; 1H NMR (300 MHz, C6D6) δ 5.97 (ddd,1H +
1H, J ) 2.1, 6.0, 9.6 Hz), 5.26 (dd, 1H, J ) 3.1, 9.6 Hz), 5.23
(dd, 1H, 3.4, 9.6 Hz), 4.72 (d, 1H, J ) 6.0 Hz), 4.69 (d, 1H, J
) 6.0 Hz), 4.09 (ddd, 1H, J ) 1.8, 3.3, 9.3 Hz), 4.02 (ddd, 1H,
J ) 1.9, 3.4, 9.3 Hz), 2.47-1.99 (m, 4H + 4H), 1.73-1.50 (m,
2H + 2H), 1.34-1.14 (m, 2H + 2H), 1.13-0.94 (m, 2H + 2H),
0.91, 0.90, 0.89, 0.88, 0.86, 0.85 (6 × s’s, 3H each), 0.77, 0.73
(2 × s’s, 6H each).
(5R a n d 5S)-5-(1-Cya n o-1-m eth yleth yl)-1-[[(1S,2R,5R)-
2-isop r op yl-5-m eth ylcycloh ex-2-yl]oxy]cycloh exa -1,3-d i-
en es (12). Mixture of diastereomers (1:1): total yield 68%
1
as a colorless oil; H NMR (300 MHz, CDCl3) δ 5.98 (ddd, 1H
+ 1H, J ) 2.2, 6.1, 9.6 Hz), 5.21 (dd, 1H, J ) 2.6, 9.6 Hz), 5.20
(dd, 1H, 3.5, 9.6 Hz), 4.91 (d, 1H, J ) 6.5 Hz), 4.89 (d, 1H, J
) 6.6 Hz), 4.23 (m, 1H + 1H), 2.50-2.20 (m, 3H + 3H), 1.95-
0.98 (m, 9H + 9H), 0.93-0.78 (4s’s and 6 d’s).
(5R a n d 5S)-1-[[(1R,2R)-1,7,7-Tr im eth ylbicyclo[2.2.1]-
h ep t-2-yl]oxy]-4-m eth yl-5-(1-cya n o-1-m eth yleth yl)cyclo-
h exa -1,3-d ien es (20). Mixture of diastereomers (1:1.8): total
yield 82% as a colorless oil; 1H NMR (300 MHz, CDCl3) δ 5.87-
5.81 (m, 1H + 1H), 4.69 (dd, 1H, J ) 2.3, 5.9 Hz), 4.67 (major,
dd, 1H, J ) 2.3, 5.1 Hz), 3.73-3.65 (m, 1H + 1H), 2.78-2.61
(m, 1H + 1H), 2.28-2.15 (m, 2H + 2H), 1.91 (s, 3H + 3H),
1.75-1.48 (m, 4H + 4H), 1.26-1.21 (m, 1H + 1H), 1.10-0.99
(m, 2H + 2H), 1.34, 1.34, 1.33, 1.33, 0.97, 0.93, 0.90, 0.87, 0.81,
0.81 (10 s’s, 3H each).
(5R a n d 5S)-5-(1-Cya n o-1-m eth yleth yl)-1-[[(1S,2S,5R)-
2-isop r op yl-5-m eth ylcycloh ex-2-yl]oxy]cycloh exa -1,3-d i-
en es (13). Mixture of diastereomers (1:1): total yield 77%
as a colorless oil; 1H NMR (300 MHz, C6D6) δ 5.97 (ddd, 1H, J
) 2.2, 6.1, 9.7 Hz), 5.97 (ddd, 1H, J ) 1.9, 5.9, 9.8 Hz), 5.19
(dd, 1H, J ) 3.6, 9.7 Hz), 5.19 (dd, 1H, J ) 3.8, 9.5 Hz), 4.77
(d, 1H + 1H, J ) 5.4 Hz), 4.26-4.23 (m, 1H + 1H), 2.54-1.98
(m, 4H + 4H), 1.75-1.40 (m, 5H + 5H), 0.92-0.63 (m,
remaining H’s).
(5R a n d 5S)-5-(1-Cya n o-1-m eth yleth yl)-1-[[(1S,2S,3S)-
2,6,6-tr im eth ylbicyclo[3.1.1]h ep t-3-yl]oxy]cycloh exa -1,3-
d ien es (14). Mixture of diastereomers (2.3:1): total yield 40%
as a colorless oil; 1H NMR (300 MHz, CDCl3) δ major
diastereomer 6.00 (ddd, 1H, J ) 2.0, 6.1, 9.6 Hz), 5.25 (dd,
1H, J ) 3.6, 9.6 Hz), 4.78 (d, 1H, J ) 6.1 Hz), 4.22 (dt, 1H, J
) 8.7, 4.3 Hz), 2.50-2.18 (m, 6H), 1.88-1.65 (m, 3H), 1.22-
1.13 (m, 1H), 1.12 (s, 3H), 1.10 (d, 3H, J ) 7.7 Hz), 0.90, 0.86
(2 s’s, 3H each), 0.79 (s, 3H); minor diastereomer (partial data)
5.99 (m, 1H), 5.26 (dd, 1H, J ) 3.3, 9.6 Hz), 4.80 (d, 1H, J )
6.0 Hz), 4.17 (dt, 1H, J ) 8.6, 4.3 Hz), 1.7 (d, 1H, J ) 8.0 Hz),
0.91, 0.87 (2 s’s, 3H each).
(6R an d 6S)-6-(Cyan om eth yl)-1-[[(1R,2R)-1,3,3-tr im eth yl-
bicyclo[2.2.1]h ep t-2-yl]oxy]-4-(tr im eth ylsilyl)cycloh exa -
1,3-d ien es (25). Mixture of diastereomers (1.4:1): yield 66%
1
as a colorless oil; H NMR (400 MHz, CDCl3) δ 6.23 (dd, 1H,
J ) 1.2, 6.0 Hz), 5.07 (dd, 1H, J ) 2.0, 6.0 Hz), 3.63 (d, 1H, J
) 1.7 Hz), 2.69-2.61 (m, 1H), 2.60-2.52 (m, 1H), 2.44-2.33
(m, 2H), 2.19-2.10 (m, 1H), 1.90-1.80 (m, 1H), 1.74-1.63 (m,
1H), 1.55-1.49 (m, 1H), 1.47-1.37 (m, 1H), 1.19-1.15 (m, 1H),
1.07-0.99 (m, 1H), 1.11, 1.00, 0.85 (3 s’s, 3H each), 0.08 (s,
9H); minor diastereomer (partial data) 6.21 (dd, 1H, J ) 1.2,
6.0 Hz), 5.05 (dd, 1H, J ) 2.0, 6.0 Hz), 3.68 (d, 1H, J ) 1.7
Hz), 1.10, 1.06, 0.78 (3 s’s, 3H each), 0.08 (s, 9H).
(5R a n d 5S)-5-(1-Cya n o-1-m et h ylet h yl)-1-[[(1R,2R)-
1,2,7,7-tetr a m eth ylbicyclo[2.2.1]h ep t-2-yl]oxy]cycloh exa -
1,3-d ien es (39). Mixture of diastereomers (1:1.8): total yield
89% as a colorless oil; 1H NMR (400 MHz, C6D6) δ major
diastereomer 6.00-5.94 (m, 1H), 5.21 (dd, 1H, J ) 3.2, 9.6 Hz),
4.75 (d, 1H, J ) 6.0 Hz), 2.60-2.46 (m, 1H), 2.35-2.15 (m,
2H), 1.66-1.52 (m, 2H), 1.28, 0.98, 0.96, 0.91, 0.85, 0.81 (6
s’s, 3H each), 1.38-1.78 (m, remaining H’s); minor diastereo-
mer (partial data) 5.20 (m, 1H), 4.71 (d, 1H, J ) 6.1 Hz), 1.20,
1.01, 0.99, 0.94, 0.87, 0.82 (6 s’s, 3H each).
(5R a n d 5S)-5-(1-Cya n o-1-m et h ylet h yl)-4-m et h yl-1-
[[(1S,2S,3S)-2,6,6-tr im eth ylbicyclo[3.1.1]h ep t-3-yl]oxy]cy-
cloh exa -1,3-d ien es (15). Mixture of diastereomers (2.7:1):
1
total yield 80% as a colorless oil; H NMR (400 MHz, C6D6) δ
major diastereomer 5.86-5.81 (m, 1H), 4.73 (dd, 1H, J ) 2.4,
6.0 Hz), 4.19-4.11 (m, 1H), 2.68-2.55 (m, 1H), 2.41-2.17 (m,
(5R a n d 5S)-5-(1-Cya n o-1-m et h ylet h yl)-4-m et h yl-1-
[[(1R,2R)-1,2,7,7-tetr a m eth ylbicyclo[2.2.1]h ep t-2-yl]oxy]-
(22) Wakefield, B. J . Organolithium Methods; Academic Press
London, 1988; p 189.

162 J . Org. Chem., Vol. 63, No. 1, 1998
Pearson and Gontcharov
cycloh exa -1,3-d ien es (40). Mixture of diastereomers (1:9.5):
yield 81% as a colorless oil; H NMR (400 MHz, C6D6) δ 5.81
Hz), 2.74 (dd, 1H, J ) 12.9, 8.2 Hz), 2.0-0.7 (m, remaining
protons); minor diastereomer (partial data) 4.66 (dd, 1H, J )
6.4, 2.3 Hz).
1
(dq, 1H, J ) 6.1, 0.6 Hz), 4.68 (dd, 1H, J ) 2.6, 6.1 Hz), 2.62
(ddd, 1H, J ) 3.0, 4.5, 13.4 Hz), 2.49 (dddt, 1H, J ) 0.7, 2.5,
9.3, 17.6 Hz), 2.20 (dd, 1H, J ) 1.5, 17.6 Hz), 1.81 (dd, 3H, J
) 0.6, 1.5 Hz), 1.75 (ddd, 0.7, 1.5, 9.4 Hz), 1.64-1.52 (m, 2H),
1.38-1.23 (m, 3H), 1.22, 1.15, 1.12, 1.10, 0.96, 0.83 (6 s’s, 3H
each); minor diastereomer (partial data) 5.79 (m, 1H), 4.57 (dd,
1H, J ) 2.5, 6.1 Hz), 2.11 (dd, 1H, J ) 1.4, 17.4 Hz), 1.84 (dd,
3H, 0.5, 1.5 Hz), 1.23, 1.09, 1.08, 1.06, 0.93, 0.82 (6 s’s, 3H
each).
1-Met h oxy-4-m et h yl-6-(1-cya n o-1-m et h ylet h yl)cyclo-
h exa -1,3-d ien e (56, R* ) R ) Me) was isolated by TLC from
the product mixture of addition of LiCMe2CN to (methoxy-
toluene)chromium tricarbonyl at -5 °C: yield 33% as a
colorless oil; 1H NMR (300 MHz, CDCl3) δ 5.52 (ddq, 1H, J )
6.1, 3.0, 1.7 Hz), 5.11 (d, 1H, J ) 6.1 Hz), 3.57 (s, 3H), 2.69
(dd, 1H, J ) 18.5, 10.0 Hz), 2.37-2.28 (m, 2H), 1.77 (t, 3H, J
) 1.7 Hz), 1.36 (s, 3H), 1.32 (s, 3H).
(5R a n d 5S)-5-(1-Cya n o-1-m eth yleth yl)-1-[[(1R,2S)-2-
p h en yl-1,7,7-tr im eth ylbicyclo[2.2.1]h ep t-2-yl]oxy]cyclo-
h exa -1,3-d ien es (41). Mixture of diastereomers (4:1): total
yield 95% as a colorless oil; 1H NMR (300 MHz, CDCl3) δ major
diastereomer 7.55-7.95 (m, 5H, Ph), 5.58 (ddd, 1H, J ) 1.8,
6.2, 9.6 Hz), 4.98 (dd, 1H, J ) 3.6, 9.6 Hz), 4.22 (d, 1H, J )
6.2 Hz), 2.53-1.51 (m, 7H), 1.18, 0.98, 0.91, 0.86, 0.85 (5 s’s,
remaining H’s); minor diastereomer (partial data) 5.63 (ddd,
1H, J ) 1.9, 6.2, 9.6 Hz), 4.99 (dd, 1H, J ) 9.6 Hz), 4.27 (d,
1H, J ) 6.2 Hz).
5-(1-Cya n o-1-m et h ylet h yl)-4-m et h yl-2-cycloh exen -1-
on e (26). The cyclohexadienol ethers 11-14, 16, or 18 (0.05
mmol) and 2 mL of a 1:1 volume MeOH-HCl (5 M aqueous)
mixture were sealed in a glass ampule and heated at 100 °C
for 20 h. The resulting solution was diluted with water and
extracted with ether. The product was isolated by TLC or flash
chromatography on silica gel (hexanes-EtOAc as eluent).
Yields of 26 from different batches of dienol ethers ranged from
75 to 87%.
5-(1-Cya n o-1-m et h ylet h yl)-4-m et h yl-3-cycloh exen -1-
on e (28). Cyclohexadienol ether 17 (0.1 mmol) was treated
with 1 mL of 1:1 volume mixture of THF and 5% aqueous HCl
at room temperature overnight. Cyclohexenone 28 and the
corresponding alcohol were separated by column chromatog-
raphy (silica gel, hexanes-ethyl acetate 4:1as eluent): yield
of 28 46%; Rf 0.35 (3:1 hexane/ethyl acetate); 1H NMR (400
MHz, CDCl3) δ 5.84 (ddq, J ) 2.8, 4.6, 1.6 Hz, 1H), 2.94 (ddq,
J ) 23.3, 2.8, 2.6 Hz, 1H), 2.87 (ddq, J ) 23.3, 4.7, 1.6 Hz,
1H), 2.73 (dd, J ) 14.7, 1.3 Hz, 1H), 2.64 (d (broad lines), J )
7.0 Hz, 1H), 2.58 (dd, J ) 14.7, 7.0 Hz, 1H), 2.04 (dt, J ) 2.6,
1.6 Hz, 3H), 1.40 (s, 3H), 1.32 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 209.2, 134.0, 124.8, 124.4, 48.2, 41.5, 39.5, 36.5, 25.5,
25.0, 24.7.
(1R, 5R)- a n d (1S, 5S)-5-(1-Cya n o-1-m eth yleth yl)-2-
cycloh exen -1-ol (29). The enone 26 (0.05 mmol) and an
equimolar amount of CeCl3‚7H2O were dissolved in 2 mL of
methanol, and the resulting solution was cooled to 0 °C.
Sodium borohydride (6 mg) was added, and the reaction
mixture was stirred at room temperature for 30 min, after
which it was quenched with 1 mL of 1 N aqueous HCl. The
product was extracted with chloroform. The organic layer was
washed with saturated NaHCO3 solution and water and then
dried with Na2SO4. Evaporation of the solvents in vacuum
gave 95% of fairly pure 29. 1H NMR (400 MHz, CDCl3) δ 5.78
(ddt, 1H, J ) 10.0 Hz, 4,8, 1.0 Hz), 5.72 (d, 1H, J ) 10.0 Hz),
4.34 (m, 1H), 2.28 (m, 1H), 2.19 (m, 1H), 1.98 (m, 1H), 1.73
(dddd, 1H, J ) 2.3, 5.2, 11.1, 13.1 Hz), 1.38 (s, 3H), 1.35 (s,
3H), 1.33 (m, 1H).
Syn th esis of Mosh er ’s ester 30 was performed according
to the known procedure.12 A mixture of alcohol 29 (0.05 mmol),
30 mg of (+)-S-R-methoxy-R-(trifluoromethyl)phenylacetyl chlo-
ride (MTPA-Cl), 10 drops of dry pyridine, and 10 drops of CCl4
was stirred at room temperature for 2 days. After that ca. 1
mL of water was added. The resulting solution was extracted
with ether. The extract was washed thoroughly with 1 N HCl,
water and a saturated solution of NaHCO3 and dried with
Na2SO4. The solvent was evaporated in vacuum. The result-
ing mixture of diastereomeric esters was used directly for NMR
analysis (see discussion in text).
(5R a n d 5S)-5-(1-Cya n o-1-m et h ylet h yl)-4-m et h yl-1-
[[(1R,2S)-2-p h en yl-1,7,7-t r im et h ylb icyclo[2.2.1]h ep t -2-
yl]oxy]cycloh exa -1,3-d ien es (42). Mixture of diastereomers
1
(24:1): total yield 63% as a colorless oil; H NMR (400 MHz,
CDCl3) δ major diastereomer 7.39-7.19 (m, 5H), 5.57 (ddq,
1H, J ) 0.5, 6.2, 1.5 Hz), 3.96 (dd, 1H, J ) 6.2, 2.6 Hz), 2.68
(ddd, 1H, J ) 2.6, 9.8, 17.9 Hz), 2.38 (ddd, 1H, J ) 3.2, 4.4,
14.3 Hz), 2.35 (dd, J ) 1.2, 17.9 Hz), 2.27 (dd, 1H, J ) 1.2, 9.8
Hz), 2.13 (d, 1H, J ) 14.3 Hz), 1.80 (d, 3H, J ) 1.5 Hz), 1.70
(m, 1H), 1.26-1.08 (m, 3H), 1.27, 1.26, 1.05, 0.94, 0.89 (5 s’s,
3H each), 0.79 (ddd, 1H, J ) 4.0, 9.3, 13.5 Hz); minor (partial
data) 4.01 (dd, J ) 2.6, 6.2 Hz).
(5R a n d 5S)-5-(1-Cya n o-1-m et h ylet h yl)-4-m et h yl-1-
[[(1R,2R)-1,2,3,3-tetr a m eth ylbicyclo[2.2.1]h ep t-2-yl]oxy]-
cycloh exa -1,3-d ien es (43). Mixture of diastereomers (1:1):
total yield 91% as a colorless oil; 1H NMR (300 MHz, C6D6) δ
5.76-5.70 (m, 1H + 1H), 4.72 (dd, 1H, J ) 2.4, 6.2 Hz), 4.67
(dd, 1H, J ) 2.3, 6.1 Hz), 2.62-2.12 (m, 4H + 4H), 1.83 (s,
3H), 1.81 (s, 3H), 1.94-1.72 (m, 2H + 2H), 1.50-1.21 (m, 3H
+ 3H), 1.20 (s, 3H), 1.13 (s, 3H), 1.11 (s, 3H), 1.09 (s, 3H),
1.08 (s, 3H), 1.05 (s, 9H), 1.00 (s, 3H), 0.96 (s, 3H), 0.87 (s,
3H), 0.84 (s, 3H), 1.13-0.91 (m, remaining H).
(5R a n d 5S)-5-(1-Cya n o-1-m eth yleth yl)-1-[[sp ir o-2,3′-
[1,3]dioxolan ]-[(1R,2S)-1,7,7-tr im eth ylbicyclo[2.2.1]h eptan -
2-yl]oxy]cycloh exa -1,3-d ien es (49). Mixture of diastereo-
mers (1:7.6): yield 86% as a colorless oil; 1H NMR (400 MHz,
C6D6) δ major diastereomer 5.96 (ddd, 1H, J ) 2.1, 6.1, 9.5
Hz), 5.24 (dd, 1H, J ) 3.7, 9.5 Hz), 5.04 (dd, 1H, J ) 6.1 Hz),
3.90 (s, 1H), 3.50-3.25 (m, 4H), 2.49-2.33 (m, 2H), 2.26-2.19
(m, 1H), 1.40, 0.93, 0.91, 0.86, 0.77 (5 s’s, 3H each), 1.56-1.12
(m, remaining protons); minor diastereomer (partial data) 5.09
(d, 1H, J ) 6.1 Hz), 3.86 (s, 1H).
(5R a n d 5S)-5-(1-Cya n o-1-m et h ylet h yl)-4-m et h yl-1-
[[sp ir o-2,3′-[1,3]d ioxola n ]-[(1R,2S)-1,7,7-tr im eth ylbicyclo-
[2.2.1]h ep ta n -2-yl]oxy]cycloh exa -1,3-d ien es (50). Mixture
of diastereomers (1:17): total yield 65% as white crystals; 1H
NMR (300 MHz, C6D6) δ major diastereomer 5.79 (dqd, 1H, J
) 0.5, 1.6, 6.1 Hz), 4.93 (dd, 1H, J ) 2.4, 6.1 Hz), 3.80 (s, 1H),
3.55-3.20 (m, 4H), 2.56 (ddd, 1H, J ) 2.4, 9.5, 17.6 Hz), 2.31
(dd, 1H, J ) 1.0, 17.6 Hz), 1.87 (ddd, 1H, J ) 1.0, 9.5, 0.5 Hz),
1.88 (d, 3H, J ) 1.6 Hz), 1.54-1.51 (m, 1H), 1.48-1.42 (m,
2H), 1.26-1.17 (m, 1H), 1.06-0.93 (m, 1H), 1.38, 1.16, 1.11,
0.90, 0.76 (5 s’s, 3H each); minor diastereomer (partial data)
4.86 (dd, 1H, J ) 2.2, 6.0 Hz), 4.11 (s, 1H).
Ack n ow led gm en t. We are grateful to the U.S.
Public Health Service, National Institutes of Health, for
financial support (GM 36925).
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR
spectra for new compounds (38 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.
(5R a n d 5S)-1-[[(1R,2R,3S)-3-Ben zh yd r yl-1,7,7-tr im eth -
ylbicyclo-[2.2.1]h ep t-2-yl]oxy]-4-m eth yl-5-(1-cya n oeth yl-
1-m eth yl)cycloh exa -1,3-d ien es (55). Mixture of diastere-
omers from complex 54: yield 76% as a colorless oil; 1H NMR
(300 MHz, CDCl3) δ major diastereomer (partial data) 7.45-
6.96 (m, 10H), 5.59 (dq, 1H, J ) 6.2, 1.7 Hz), 4.59 (dd, 1H, J
) 6.2, 2.5 Hz), 4.34 (d, 1H, J ) 12.9 Hz), 4.18 (d, 1H, J ) 8.2
J O971676O