Synthesis, resolution, and determination of absolute configuration of a vaulted 2,2′-binaphthol and a vaulted 3,3′-biphenanthrol (VAPOL)

Article abstract of DOI:10.1021/ja952018t

Two methods for the synthesis of vaulted biaryls were developed involving the reactions of carbene complexes with alkynes and the [2 + 2] cycloaddition of ketenes. The final step in the synthesis of 3,3′-diphenyl-[2,2′-binaphthalene]-1,1′-diol (39) and 2,2′-diphenyl-[3,3′-biphenanthrene]-4,4′-diol (47) (VAPOL) was phenol coupling of the 3-phenyl-1-naphthol (14) and the 2-phenyl-4-phenanthrol (28), respectively. The naphthol 14 could be prepared from the thermolysis of phenylacetyl chloride in the presence of phenylacetylene or from the benzannulation of the pentacarbonyl(phenylmethoxymethylene)chromium(0) (15) with phenylacetylene which upon an acetylative workup gives O-acetyl-4-methoxy-2-phenyl-1-naphthol (16). The reductive cleavage of the acetoxy group in 16 was unexpectedly affected by aluminum chloride and ethanethiol which were used to cleave the methyl ether. In a similar manner, the phenanthrol 28 could either be prepared from the 1-naphthylacetyl chloride (30) or pentacarbonyl-(1-naphthylmethoxymethylene)chromium(0) (21). A new procedure for the preparation of carbene complexes was developed utilizing dimethyl sulfate as methylating agent. Unlike the benzannulation of the phenyl complex 15, the benzannulation of the naphthylcarbene complex 21 with phenylacetylene gave a side product which resulted from the incorporation of 2 equiv of the alkyne. This side product could be minimized by the proper control of the concentration of the alkyne. The phenol coupling of the 3-phenyl-1-naphthol with ferric chloride gave 2,2′-diphenyl-[2,2′-binaphthalene]-4,4′-diol (38) and with air as oxidant gave the of 3,3′-diphenyl-[2,2′-binaphthalene]-1,1′-diol (39). Oxidative coupling of the 2-phenyl-4-phenanthrol (28) with air gave 2,2′-diphenyl-[3,3′-biphenanthrene]-4,4′-diol (47) (VAPOL), but the same coupling with 2-tert-butyl-4-phenanthrol (34) failed. The 2,2′-binaphthol 39 was resolved via its cyclic diester with phosphoric acid by salt formation with (-)-brucine, and the 3,3′-biphenanthrol 47 was resolved via its cyclic deiester with phosphoric acid (49) by salt formation with (-)-cinchonidine. The configuration of (-)-39 was shown to be S from an X-ray analysis of the brucine salt, and the configuration of (+)-47 was shown to be S from an X-ray analysis the amide (S,S)-54 derived from 49 and (S)-α-methylbenzylamine.

Full text of DOI:10.1021/ja952018t

3392
J. Am. Chem. Soc. 1996, 118, 3392-3405
Synthesis, Resolution, and Determination of Absolute
Configuration of a Vaulted 2,2′-Binaphthol and a Vaulted
3,3′-Biphenanthrol (VAPOL)
Jianming Bao,† William D. Wulff,*,† James B. Dominy,† Michael J. Fumo,†
Eugene B. Grant,† Alexander C. Rob,† Mark C. Whitcomb,† Siu-Man Yeung,†
Robert L. Ostrander,‡ and Arnold L. Rheingold‡
Contribution from the Searle Chemistry Laboratory, Department of Chemistry, UniVersity of
Chicago, Chicago, Illinois 60637, and Department of Chemistry, The UniVersity of Delaware,
Newark, Delaware 19716
ReceiVed June 21, 1995X
Abstract: Two methods for the synthesis of vaulted biaryls were developed involving the reactions of carbene
complexes with alkynes and the [2 + 2] cycloaddition of ketenes. The final step in the synthesis of 3,3′-diphenyl-
[2,2′-binaphthalene]-1,1′-diol (39) and 2,2′-diphenyl-[3,3′-biphenanthrene]-4,4′-diol (47) (VAPOL) was phenol coupling
of the 3-phenyl-1-naphthol (14) and the 2-phenyl-4-phenanthrol (28), respectively. The naphthol 14 could be prepared
from the thermolysis of phenylacetyl chloride in the presence of phenylacetylene or from the benzannulation of the
pentacarbonyl(phenylmethoxymethylene)chromium(0) (15) with phenylacetylene which upon an acetylative workup
gives O-acetyl-4-methoxy-2-phenyl-1-naphthol (16). The reductive cleavage of the acetoxy group in 16 was
unexpectedly affected by aluminum chloride and ethanethiol which were used to cleave the methyl ether. In a
similar manner, the phenanthrol 28 could either be prepared from the 1-naphthylacetyl chloride (30) or pentacarbonyl-
(1-naphthylmethoxymethylene)chromium(0) (21). A new procedure for the preparation of carbene complexes was
developed utilizing dimethyl sulfate as methylating agent. Unlike the benzannulation of the phenyl complex 15, the
benzannulation of the naphthylcarbene complex 21 with phenylacetylene gave a side product which resulted from
the incorporation of 2 equiv of the alkyne. This side product could be minimized by the proper control of the
concentration of the alkyne. The phenol coupling of the 3-phenyl-1-naphthol with ferric chloride gave 2,2′-diphenyl-
[2,2′-binaphthalene]-4,4′-diol (38) and with air as oxidant gave the of 3,3′-diphenyl-[2,2′-binaphthalene]-1,1′-diol
(39). Oxidative coupling of the 2-phenyl-4-phenanthrol (28) with air gave 2,2′-diphenyl-[3,3′-biphenanthrene]-4,4′-
diol (47) (VAPOL), but the same coupling with 2-tert-butyl-4-phenanthrol (34) failed. The 2,2′-binaphthol 39 was
resolved via its cyclic diester with phosphoric acid by salt formation with (-)-brucine, and the 3,3′-biphenanthrol 47
was resolved via its cyclic deiester with phosphoric acid (49) by salt formation with (-)-cinchonidine. The
configuration of (-)-39 was shown to be S from an X-ray analysis of the brucine salt, and the configuration of
(+)-47 was shown to be S from an X-ray analysis the amide (S,S)-54 derived from 49 and (S)-R-methylbenzylamine.
The enantiomeric atropisomers of 1,1′-binapth-2-ol are among
formylation,22 ring opening metathesis polymerization,23 group
transfer polymerization,24 alkene, diene, and alkyne polymeri-
zation,25 molecular recognition,26 nonlinear optical and other
materials,27 phase transition induction,28 and membrane bi-
layers.29
the most widely used ligands in asymmetric synthesis. The
binaphthol 1a (Chart 1) has been used as a ligand for both
stoichiometric and catalytic asymmetric reactions with success
achieved over a truly impressive range of reactions.1 The
current use of 1,1′-binaphthol is so pervasive that a compre-
hensive citation is not possible here. The range of applications
that have appeared since 1994 for 1,1′-binaphthol and its
derivatives2 includes Diels-Alder,4 aldol,5 Michael,6 Ene reac-
tions,7 carbonyl additions,8 carbonyl reductions,9 heteroatom
Diels-Alder,10 alkylations,11 π-allyl additions,12 [3 + 2]-cyclo-
additions,13 [2 + 2]-cycloadditions,14 Claisen rearrangements,15
reductive cyclization,16 olefin additions,17 epoxidation,18 epoxide
opening,19 asymmetric protonation,20 hydrosilylation,21 hydro-
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† University of Chicago.
‡ The University of Delaware.
X Abstract published in AdVance ACS Abstracts, February 15, 1996.
(1) (a) Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, D. Synthesis
1992, 503. (b) See citations given in ref 30a.
(2) With the exception of bis-phosphine derivatives,3 this includes C-2
symmetrical and C-2 nonsymmetrical derivatives in which one or both of
the oxygen atoms in 1 are replaced by other atoms.
(6) (a) Sasai, H.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc. 1994, 116,
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0002-7863/96/1518-3392$12.00/0 © 1996 American Chemical Society

Synthesis of Vaulted Biaryls
J. Am. Chem. Soc., Vol. 118, No. 14, 1996 3393
Chart 1
Chart 2
A few years ago we began work on a program to prepare
and evaluate a series of new biaryl ligands of the type 3 and 4
where the phenol functions were embedded within a chiral
pocket created by the walls of the biaryl unit. When this work
was initially conceived, a search of the literature revealed that
no examples of the vaulted biaryls 3 or 4 were known except
for the parent 2,2′-binaphthol (3) (R ) H).32 This included a
search for 3,3′-biphenanthrols in which all of the aryl sites were
left open. However, when all sites were left open in the search
for 2,2′-binaphthols the 6,6′-biphenanthrol (5) and gossypol (6)
were identified as well as a large number of derivatives of
gossypol (Chart 2). Gossypol is abundant in cotton seeds and
has received considerable attention for its male antifertility
activity.33 While neither gossypol or its derivatives have been
investigated as chiral ligands in catalysis, the biphenanthrol (5)
has received some such attention. This compound contains both
1,1′-binaphthol and 2,2′-binaphthol units, and the studies of this
compound as a chiral ligand have not revealed any significant
advantages over the 1,1′-binaphthol (1a).34 In contrast, we
recently reported that both of the vaulted biaryls 3 and 4 (R )
Ph) are superior to the linear biaryls 1a or 2 (R ) Ph3Si) as a
ligand in Lewis acid-catalyzed Diels-Alder reactions.30 We
report herein the preparation, resolution, and determination of
the absolute configuration of the vaulted 2,2′-binaphthol 3 (R
) Ph) and the vaulted 3,3′-biphenanthrol 4 (R ) Ph).
The two synthetic approaches to the vaulted biaryls 3 and 4
are outlined in Scheme 1 and have in common the last step
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3394 J. Am. Chem. Soc., Vol. 118, No. 14, 1996
Bao et al.
Scheme 1
which is an oxidative phenol coupling reaction.35 One approach
to the monomeric phenol intermediate 8 is a benzannulation
process that in the retrosynthetic analysis requires a [2 + 2]
cycloaddition of a terminal acetylene with an aryl ketene
generated from the corresponding acid chloride 10.36,37 The
second approach to be considered is the benzannulation of an
arylcarbene complex with an alkyne which would initially
produce the p-methoxyphenol intermediate 9.38 The use of 9
as a precursor of 8 would require the reduction of the phenol
function and a deprotection of the methyl aryl ether. Both of
these approaches have been evaluated for the synthesis of 3
and 4, and the relative merits of each will be discussed. Since
the resolution of 3 and 4 into atropisomers will require that the
substituent R be non-hydrogen and since it is desirable that the
enantiomers of 3 and 4 be robust with respect to racemization,
the synthetic approaches outlined in Scheme 1 will be evaluated
with R ) Ph and R ) t-Bu.
Both of the approaches outlined in Scheme 1 are viable for
the preparation of 3-phenyl-1-naphthol (14), the monomer
required for the preparation of 2,2′-binaphthol 39 (3, R ) Ph).
The preparation of 14 from phenylacetyl chloride 12 and
phenylacetylene has been previously reported and can be
obtained in 56% overall yield from 12.36 The reaction is thought
to involve the [2 + 2] cycloaddition of phenylketene and
phenylacetylene, electrocyclic ring opening, and finally an
electrocyclic ring closure of the â-phenylvinylketene species
18. The benzannulation reaction of the chromium carbene
complex 15 with phenylacetylene is carried out as indicated in
the presence of acetic anhydride and triethylamine to give the
acylated naphthol 16 in 93% yield. The last step in this process
is related mechanistically to that for the conversion of 12 to 13
and is thought to involve the cyclization of the metal-complexed
â-phenylvinylketene species 20.38,39 The naphthol formed from
the reaction of complex 15 and phenylacetylene was trapped
as its acetate by the method of Yamashita40 in preparation for
the cleavage of the methyl ether. The treatment of naphthol
derivative 16 with aluminum chloride and ethanethiol was
performed to cleave the methyl ether, but much to our surprise
this resulted in a reduction of the acetoxyl group as well.41 This
of course was a much welcomed result since, as outlined in
Scheme 1, the synthetic plan for the removal of this group
anticipated that at least two additional steps would be required
via procedures that involved the reduction of an aryl triflate.42
The demethylation occurs first since with insufficient reaction
times, varying amounts of the 4-acetoxyphenol 19 can be
isolated from the reaction. For the large scale synthesis of 14,
the route starting from phenylacetyl chloride is the most
desirable. It is necessary for the oxidative coupling step that
the naphthol 14 be quite pure, and on a large scale it was
possible to obtain sufficiently pure material without column
chromatography only from the crude mixture obtained from the
reaction of phenylacetyl chloride and phenylacetylene.
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The synthesis of a phenanthrol monomer of the type 8
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(43) Node, M.; Kishide, K.; Ohta, K.; Fujita, E. Tetrahedron Lett. 1982,
23, 689.

Synthesis of Vaulted Biaryls
J. Am. Chem. Soc., Vol. 118, No. 14, 1996 3395
Scheme 2
Scheme 3
complex was pursued with the unsubstituted 1-naphthylcarbene
complex 21. Complex 21 is a known compound,44 but we have
developed a new procedure for the synthesis of this complex
that involves the use of dimethyl sulfate as methylating agent.
This was developed in an effort to minimize cost and maximize
convenience for large-scale throughput. Dimethyl sulfate has
not been previously used as a methylation agent due to poor
yields and low reactivity.45 This has been overcome by
generating the more reactive potassium salt of the metal acylate
by washing the lithium acylate with aqueous HCl to generate a
solution of a hydroxycarbene complex and directly exposing
this solution to solid potassium carbonate and dimethyl sulfate.
The benzannulation of the naphthylcarbene complex 21 with
phenylacetylene produced an additional product which was not
observed in the reactions of the phenylcarbene complex 15. In
addition to the desired 1,2,4-trisubstituted phenanthrene 22, the
bis(naphthyl)ethylene 23 was also isolated from this reaction
as a single stereoisomer whose stereochemistry was determined
to be E as will be described below. This product results from
the incorporation of 2 equiv of phenylacetylene and a cyclization
with CO insertion onto the phenyl ring of the first phenyl-
acetylene unit that was incorporated. This type of product has
been seen previously, but significant formation of this type of
product has only been seen when the normal cyclization is not
possible.46
As indicated in Scheme 3, it was found that the stereochem-
istry of the olefin product 23 has the E-configuration. This was
confirmed when the product obtained from the reaction was
photolyzed in benzene to produce its olefin isomer which was
separated and characterized. The stereochemistry of these olefin
isomers was assigned on the basis of NOE studies which
revealed that only one of the isomers displayed an enhancement
at the vinyl hydrogen when the methoxyl group was irradiated.
Since the primary product 23 has the E-configuration, it must
have arisen from a vinylcarbene-complexed intermediate (24)
that has an E-configuration, the necessary stereochemistry for
cyclization to the phenanthrol product 22. The branchpoint in
the mechanism thus is the vinylcarbene complex 24, and the
product distribution is thus determined by the relative rates of
a unimolecular CO insertion to give the vinyl ketene complexed
intermediate 25 and a bimolecular reaction with phenylacetylene
to give homologated vinyl carbene complexed intermediate 26.
These mechanistic considerations lead to the prediction that
product distribution will be concentration dependent with lower
(44) Fischer, E. O.; Kreiter, C. G.; Kollmeier, H. J.; Muller, J.; Fischer,
R. D. J. Organomet. Chem. 1971, 28, 237.
(45) Hoye, T. R.; Chen, K.; Vyvyan, J. R. Organometallics 1993, 12,
2806.
(46) (a) Challener, C. A.; Wulff, W. D.; Anderson, B. A.; Chamberlin,
S.; Faron, K. L.; Kim, O. K.; Murray, C. K.; Xu, Y.-C.; Yang, D. C.;
Darling, S. D. J. Am. Chem. Soc. 1993, 115, 1359. (b) Dietz, R.; Do¨tz, K.
H.; Neugebauer, D. NouV. J. Chim. 1978, 2, 59. (c) Wulff, W. D.; Kaesler,
R. W.; Peterson, G. A.; Tang, P. C. J. Am. Chem. Soc. 1985, 107, 1060.

3396 J. Am. Chem. Soc., Vol. 118, No. 14, 1996
Bao et al.
Table 1. Benzannulation of Naphthylcarbene Complex 21 with
completion by heating in the presence of air since the latter
occurred under the reduction conditions. Treatment with
aluminum chloride and ethanethiol gave phenanthrol 28 in 69%
overall yield. The free vinylketene approach to the synthesis
of phenanthrol 28 was also successful, providing a 54% overall
yield of 28 from 2-naphthyl acetyl chloride (30). However, it
was not possible to purify 28 from the black tarry material
obtained from this reaction without careful column chromatog-
raphy. Thus, in this case it was found that for large-scale
preparation it was best to utilize the route from the carbene
complex.
Phenylacetylenea
The tert-butyl-substituted phenanthrol 34 was prepared as a
potential precursor to the 3,3′-biphenanthrol 4 (Chart 2, R )
tert-Bu) since the tert-butyl group, like a phenyl group, would
be expected to provide a high barrier to racemization. The
benzannulation of the naphthylcarbene complex with tert-
butylacetylene gave a 91% total yield of the phenanthrol 31
and the metal complex 32 (Scheme 5). Despite the presence
of the free phenol function on the benzene ring coordinated by
the chromium tricarbonyl group, complex 32 is surprisingly
stable to air and silica gel, presumably due to the steric bulk of
the tert-butyl group. The acetylization of this mixture occurred
with loss of the metal to give 33 in 54% overall yield from the
carbene complex 21. Demethylation and deacetoxylation with
ethanethiol and aluminum chloride occurred smoothly to provide
the phenanthrol 34 in 85% yield.
[21]
(M)
[alkyne]
(M)
yield of
22 (%)
yield of
23-E (%)
yield of
23-Z (%)
NDc
ND
ND
solvent
0.005b
0.03d
0.05
0.5
0.01
0.06
0.10
1.0
0.6
1.0
THF
THF
THF
THF
THF
benzene
CH3CN
79
65
66
38
74
36
22
<1.2
8
<13
32
ND
0.5e
0.5
0.5
8f
<0.5f
<1.7f
<2.8f
25
18
1.0
a Unless otherwise specified, all yields are isolated. b 0.1 equiv of
DMAP was included in the acetylation step. c Not determined. d Con-
current reaction: reagents for acetylation were added with the alkyne.
e The alkyne (1.2 equiv) was added via syringe pump over 6 h at 65
°C and then stirred for 1 h longer before acetylation. f Maximum yield
1
determined on crude reaction mixture by H NMR.
The 1,1′-binaphthol 1a is prepared by an oxidative coupling
of â-naphthol which was first reported by Pummerer in 1928
who used ferric chloride to give 1a in greater than 90% yield.47
Interestingly, the oxidative coupling of R-naphthol 35 was
reported approximately 50 years earlier by Dainin to give the
para,para-coupling product 36.32a Some 70 years later, Edwards
and Cashaw demonstrated that this reaction also produces the
ortho,ortho-coupling product 37 as a minor product in the
oxidative coupling; however, the ratio of the two products were
never reported.32c This precedent did not bode well for the
proposed oxidative coupling of the 3-phenyl-1-naphthol (14).
Even with the knowledge of this precedent, it was disappointing
to find that the coupling of 14 with ferric chloride gave the
para,para-coupled product 38 in 62% yield (Scheme 6). Two
minor products were observed in this reaction which remain
unidentified, but it was determined that neither was the desired
ortho,ortho-coupled product 39. One solution to this problem
would involve a slight adjustment of the target vaulted biaryl.
Retention of the oxygen substituent in the 4-position of the
product 9 (Scheme 1) makes para,para coupling impossible and
would produce vaulted biaryl 7 with an oxygen substituent in
the 4- and 4′-positions. While this might produce vaulted biaryl
derivatives with quite different electronic properties, it would
not solve the problem for the general case.
In their studies on the synthesis of gossypol, Edwards and
Cashaw found that the 3-methyl-1-naphthol derivative 40 gave
a low yield of the ortho,ortho-coupled product 41 when treated
with ferric chloride.48 However, they reported that a quantitative
yield of 41 could be obtained if the monomer 40 was oxidized
by air by simply placing 40 in a test tube and placing it in an
oil bath and heating until a melt was obtained and then after 20
min the product 41 resolidified in the test tube.48b Despite the
high selectivity of this reaction, it was not clear how this would
translate to the oxidative air coupling of 14. It would be
reasonable to argue that the oxidative coupling of 40 would be
Scheme 4
concentration favoring the phenanthrol product 22. The data
in Table 1 show that this is the case and that the distribution
drops from nearly an equal mixture at a starting carbene complex
concentration of 0.5 M with 2 equiv of alkyne to at least a 66:1
ratio in favor of the phenanthrol when the concentration is
lowered by a factor of 100. For the purposes of large-scale
preparation, the reaction can be run at high concentrations,
avoiding the need for large volumes of solvent, and without
the formation of an unduly large amount of the side product 23
if the phenyacetylene is added slowly to a refluxing solution of
the carbene complex (entry 5, Table 1).
The synthesis of 2-phenyl-4-phenanthrol (28) from the
benzannulation reaction of the naphthylcarbene complex 21 was
accomplished in 69% overall yield on a 73 g scale as indicated
in Scheme 4. While small-scale reactions gave the desired
phenanthrol acetate 22 that had been completely divested of
the metal, larger scale reactions gave varying amounts of the
metal complex 29 where the chromium tricarbonyl group had
migrated to the phenyl substituent. It was not necessary to
separate 22 and 29 and/or to drive the demetalation to
(47) Pummerer, R.; Prell, E.; Reiche, A. Ber. 1926, 59B, 2159.
(48) (a) Edwards, J. D., Jr. J. Am. Chem. Soc. 1958, 80, 3798. (b)
Edwards, J. D., Jr.; Cashaw, J. L. J. Am. Chem. Soc. 1957, 79, 2283. For
recent citations, see: (c) Ognyanov, V.; Petrov, O.; Tikholov, E.; Mollov,
N. HelV. Chim. Acta 1989, 72, 353.

Synthesis of Vaulted Biaryls
J. Am. Chem. Soc., Vol. 118, No. 14, 1996 3397
Scheme 5
Scheme 6
Scheme 7
purity that is greater than 99% ee as determined by HPLC on
a Pirkle D-phenylglycine column (retention times: (-)-39 tR )
7.80 min; (+)-39, tR ) 7.26 min) (Scheme 8). The (+)
enantiomer of 39 can be easily recovered from the filtrate that
produced salt 45. Without purification, the crude solution of
the soluble diastereomer of the brucine salt is treated with acid,
esterified, and then reduced to give the free (+)-binaphthol 39.
A single crystallization gives a 70% overall yield of (+)-39
from racemic 39 in greater than 99% ee as determined by HPLC.
The oxidative coupling of 28 with ferric chloride, unlike that
of 14, did not produce a predominate product but rather several
different products in more or less equal amounts, and as a result
the disposition of this reaction was not further pursued. The
oxidative coupling of the tert-butyl-substituted phenanthrol 34
in air was not clean and produced more than six compounds in
approximately equal amounts as judged by the number of bay
region doublets between 9 and 10 ppm in the 1H NMR spectrum
of the crude reaction mixture. The oxidative coupling of the
phenanthrol 28 in air, on the other hand, was quite clean, and
like the oxidation of 14, gave the ortho,ortho-product in high
yield. The phenanthrol 28 (mp ) 154-55 °C) is simply placed
in a beaker and then melted by placing the beaker in an oil
bath at 190 °C. The reaction mixture solidifies prior to
completion of the reaction due to the higher melting point of
the product (mp > 250 °C). For multigram preparations, this
can cause the reaction to slow down due to insufficient diffusion
of air into the mixture. Deliberate injection of air or oxygen
into the sample has deleterious effects on the yield which is
likely due to overoxidation. This can be overcome by the
expected to favor the ortho,ortho-coupled product 41 since the
formation of the para,para-coupled product would presumably
be strongly disfavored of the presence of the isopropyl groups
(Scheme 7).
In light of the uncertain prediction that arose from the
consideration discussed above, it was a delight to find that when
3-phenyl-1-naphthol (14) was melted at 190 °C in a test tube
in the presence of air the 2,2′-binaphthol 39 was obtained in
87% yield. Although the difference in regiochemistry between
oxidation with air and with iron(III) is not understood, it may
be due to the fact that a metal-free phenol radical is not
generated in the latter. The resolution of acid 44 was achieved
with (-)-brucine which led to the selective precipitation of a
single diastereomer of the brucine salt 45 which, with one
crystallization, was free of the other diastereomer as indicated
by 31P NMR. The levorotatory enantiomer of 39 was released
from the salt 45 by treatment with acid, conversion to the methyl
ester, and then reduction.49 This resolution procedure gave
(-)-39 in 67% overall yield from racemic 39 with an optical
(49) (a) Jacques, J.; Fouquey, C. Org. Synth. 1988, 67, 1. (b) Truesdale,
L. K. Org. Synth. 1968, 67, 13.

3398 J. Am. Chem. Soc., Vol. 118, No. 14, 1996
Bao et al.
Scheme 8
Scheme 9
Scheme 10
addition of glass beads and stirring the reaction mixture with a
large magnetic stir bar. With this technique, an 89% yield of
47 can be obtained on a 10 g scale.
The resolution of 47 can be accomplished in a manner similar
to that described above for 39 except that (-)-cinchonidine is
required to give crystalline salts with the cyclic phosphoric acid
derivative 49. Another difference is that in this case both
diastereomers of the salt are crystalline solids which can be
separated by fractional crystallization. The least soluble salt
gives rise to (+)-47 by the procedure outlined in Scheme 9 in
80% overall yield from racemic 47 in g99.8% ee. In a similar
manner, (-)-47 can be obtained from the second salt 51 in 72%
overall yield in g99.9% ee as determined by HPLC with a Pirkle
D-phenylglycine column. The biphenanthrol 47 apparently
strongly interacts with the D-phenylglycine residues on the Pirkle
column since the retention times for (-)-47 and (+)-47 are 12.1
and 19.8 min, respectively. As an indicator of how much more
inaccessible the hydroxy groups in 47 are than those in 39, it
was found that the H5 protons in 47 (δ ) 9.71 ppm) were
completely unaffected by even large excesses of Eu(hfc)3. The
corresponding protons H8 in 39 (Scheme 8) are readily shifted
by the same reagent and can be used in the analysis of
enantiomeric purity. The enantiomeric purity of 47 can be
determined by 1H NMR with (-)-1-phenylethylamine as chiral
solvating agent.50
The ease with which highly optically pure enantiomers of
47 can be obtained is a consequence of the large solubility
difference between the racemate and each pure enantiomer. The
pure enantiomers of 47 are freely soluble in hexane but the
reacemate is not. For example, if a scalemic sample of 150
mg of 47 of 84% ee is washed three times with 5 mL of hexane,
there remains 58 mg of undissolved 47 of 57% ee and the
hexane solution contains 90 mg of 47 that is ∼100% ee. Thus,
final purification to nearly complete optical purity can easily
be obtained by hexane extraction or by chromatography on silica
gel from which the racemate elutes much more slowly with
hexane than the pure enantiomers.
(50) Pirkle, W. H.; Hoekstra, M. S. J. Magn. Reson. 1975, 18, 396.

Synthesis of Vaulted Biaryls
J. Am. Chem. Soc., Vol. 118, No. 14, 1996 3399
Chart 3
The absolute configuration of the enantiomers of the bi-
phenanthrol 47 where determined by an X-ray structure of the
(S,S)-isomer of 54 which was prepared by the reaction of the
acid chloride 48 (obtained from (+)-47) with (S)-1-phenyl-
ethylamine (53).51 It is interesting to note that the acid chloride
48 is stable to silica gel and will not react with the lithium salt
of (+)-sec-phenylethyl alcohol. The amide 54 was only
obtained in 35% yield, (Scheme 10), but perhaps this could be
improved if the reaction was performed with the amide anion
generated from 53.52 Since 54 contains the S-configuration
about the biaryl axis, the dextrorotatory enantiomer of 47 must
also have the S-configuration as (S,S)-54 was prepared from
(+)-47. In contrast, the absolute configuration of the dextro-
rotatory enantiomer of 39 was found to have the R-configuration.
This was determined by an X-ray diffraction of the salt 45
prepared from the phosphoric acid derivative 44 and (-)-
brucine, and the details can be found in the supporting
information. The salt 45 contains an S-configuration about the
biaryl axis and thus so must the levorotatory enantiomer of the
vaulted biaryl 39.
both monomers is most efficient with air as oxidant, and the
resolution of the resulting vaulted biaryls 39 and 47 was realized
in each case by a classical resolution of their cyclic phosphoric
acid derivatives 44 and 49. In this manner the optically pure
2,2′-binaphthol 39 can be obtained in 36% overall yield from
bromobenzene which includes the four chemical steps for the
preparation of racemic 39 and the resolution via the acid 44.
Optically pure 3,3′-biphenanthrol (47) (VAPOL) can be obtained
in 40% overall yield from 1-bromonaphthalene which includes
the four chemical steps for the preparation of racemic 47 and
the resolution via the acid 49. Given the efficacy of catalysts
derived from the VAPOL ligand 47 in the Diels-Alder
reaction,30 the relatively straightforward procedure for the large
scale preparation of 47 described herein should be important in
providing quantities of 47 sufficient for the evaluation of its
use in other asymmetric catalytic reactions. The most cumber-
some aspect of the synthesis of the VAPOL ligand 47 is the
resolution and other methods of deriving optical pure 47 from
the racemate are currently being evaluated.
Experimental Section
The enantiomers of 39 and 47 are quite robust with respect
to thermal racemization. The thermal isomerization of the
atropisomers of 39 was examined. A sample of (-)-39 was
dissolved in octane and sealed in a tube and heated at 200 °C.
After 3 h, 10% racemization was observed, and after 15 h 30%
racemization was observed. Assuming an Arrhenius preexpo-
nential factor of 1013, this rate of racemization corresponds to
a rotation barrier of approximately 40 kcal/mol.53
As is illustrated in Chart 3, the R-enantiomer of 39 has the
same sign of optical rotation as the R-enantiomer of 1a, whereas
the R-enantiomer of 47 has the opposite sign of rotation as the
R-enantiomer of 1a. This is consistent with the fact that
catalysts derived from diethylaluminum chloride and the (+)-
enantiomers of 39 and 47 give opposite enantiomers of the
Diels-Alder adduct from the reaction of methacrolein and
cyclopentadiene.30a The fact that catalysts derived from bro-
moborane and the R-enantiomers of 1a and 39 give different
enantiomers of cycloadducts in the same Diels-Alder reaction
apparently has an alternate explanation.30b
We have described herein methods for the synthesis and
resolution of the first members of the vaulted biaryls of the
type 3 and 4. The monomer 14 for the preparation of the 2,2′-
binaphthol 39 is best prepared by a benzannulation reaction of
the acid chloride 12 with phenylacetylene. The monomer 28
for the preparation of the 3,3′-biphenanthrol (47) (VAPOL) is
best prepared by the benzannulation reaction of the carbene
complex 21 with phenylacetylene. The oxidative coupling of
All reagents were obtained from commercial suppliers and used
without further purification unless otherwise indicated. Tetrahydro-
furan, ether, and benzene were distilled from benzophenone ketyl under
nitrogen. Dichloromethane and hexane were distilled from calcium
hydride. Proton NMR data were obtained either on a University of
Chicago built DS-1000 500 MHz instrument or a QE-300 MHz
instrument. Carbon-13 spectral data were obtained on the QE-300
instrument at 75 MHz. Infrared spectra were taken on a Nicolet 20SX
FTIR. Low-resolution mass spectra were recorded on a Finnigan 1015
mass spectrometer. High-resolution mass spectra were recorded on a
VG 70-250 instrument or obtained from the Midwest center for Mass
Spectrometry in Lincoln, NE. Elemental analyses were done by
Galbraith Laboratories, Knoxville, TN. Optical rotations were obtained
on a Perkin-Elmer 141 polarimeter at 589 nm (sodium D line) using
1.0 dm cells. Specific rotations, [R]D, are reported in degrees per
decimeter at 25 °C, and the concentration (c) is given in grams per
100 mL.
The Preparation of Acetylated Naphthol 16. A 20 mL single-
necked flask equipped with a threaded high vacuum stopcock was
charged with (phenylmethoxy)chromium complex 1554 (1.44 g, 4.62
mmol) and phenylacetylene (1.01 mL, 9.21 mmol) and diluted with
THF until the solution was 0.5 M in 15 (9.3 mL). The red solution
was deoxygenated by the freeze-thaw method (three cycles) and the
flask backfilled with argon at room temperature and sealed. After the
flask was heated at 45 °C for 11.5 h, the flask was allowed to cool,
and acetic anhydride (0.87 mL, 9.2 mmol) and triethylamine (1.28 mL,
9.2 mmol) were added to the mixture under argon. The solution was
heated at 60 °C for an additional 4 h. After the removal of all volatiles,
the residue was loaded onto a silica gel column and eluted with a 1:9
mixture of EtOAc/hexane to give 1.25 g (4.28 mmol, 93% yield) of
(51) The details of the X-ray structure of (S,S)-54 have been published.30a
(52) (a) Toda, F.; Tanaka, K.; Mak, T. C. W. Chem. Lett. 1984, 2085.
(b) Toda, F.; Tanaka, K.; Nagamatsu, S. Tetrahedron Lett. 1984, 25, 4929.
(53) (a) Schwartz, L. H.; Koukotas, C.; Yu, C.-S. J. Am. Chem. Soc.
1977, 99, 7710. (b) Oki, M. Angew. Chem., Int. Ed. Engl. 1976, 15, 87.
(54) (a) Fischer, E. O.; Schubert, U.; Kleine, W.; Fischer, H. Inorg. Synth.
1979, 19, 164. (b) Fischer, E. O.; Heckl, B.; Dotz, K. H.; Muller, J.; Werner,
H. J. Organomet. Chem. 1969, 16, P29.

3400 J. Am. Chem. Soc., Vol. 118, No. 14, 1996
Bao et al.
acetylated naphthol 16 as a white solid. The same reaction in hexane
gave a 90% yield. A reaction in THF at 0.03 M was performed by the
addition of 15, phenylacetylene, acetic anhydride, and triethylamine at
the beginning of the reaction, and after 16 h at 60 °C a 72% yield of
16 was obtained. Spectral data for 16: Rf ) 0.35 (1:9 EtOAc:hexane);
1H NMR (CDCl3) δ 2.16 (s, 3 H), 3.97 (s, 3 H), 6.77 (s, 1 H), 7.32-
7.51 (m, 7 H), 7.72 (d, 1 H, J ) 8.2 Hz), 8.24 (d, 1 H, J ) 8.3 Hz);
13C NMR (CDCl3) δ 20.62, 55.68, 105.52, 121.19, 122.35, 125.61,
125.67, 127.36, 127.46, 127.83, 128.33, 128.97, 130.72, 136.61, 138.35,
153.41, 169.61; IR (neat) 3060 w, 2938 w, 2844 w, 1762 s, 1630 w,
1596 m, 1500 w, 1450 m, 1445 m, 1399 w, 1365 s, 1279 w, 1229 w,
1204 s, 1167 m, 1150 w, 1102 m, 1052 m, 984 w, 895 w, 760 s, 700
m cm-1; mass spectrum, m/z (rel intensity), 292 M+(7), 264 (3), 250
(100), 235 (46), 218 (8), 205 (6), 189 (7), 178 (16), 105 (32), 76 (14);
exact mass calcd for C19H16O3 m/z 292.1099, found m/z 292.1146.
by rotatory evaporator. Additional aqueous KOH was added and the
solution extracted with several portions of ether. The aqueous phase
was neutralized with 6 N HCl and extracted with ether again. At this
1
point H NMR revealed that the ether layer contained the product 14
and phenylacetic acid which was removed by extraction (four times)
with aqueous sodium bicarbonate. Removal of the ether gave the
naphthol 14 as a white solid in 52% yield (2 g scale) which was pure
1
by H NMR.
The Preparation of the 1-Naphthylchromium Carbene Complex
21.44 Trimethyloxonium as Methylating Agent.44 To a solution of
1-bromonaphthalene (49.30 g, 238 mmol) in 500 mL of freshly distilled
ether at -78 °C was added n-butyllithium (164 mL, 1.6 M in hexane,
262 mmol) under nitrogen. The mixture was stirred for 1.5 h from
-78 to +25 °C. Then the milklike pale-orange solution was transferred
into a flask containing chromium hexacarbonyl (52.5 g, 238 mmol) in
110 mL of freshly distilled ether at -78 °C via cannula. After 5 min,
the cold bath was removed, and the solution was allowed to stir for an
additional 2 h at 25 °C. The solution of the lithium acylate was stripped
of solvent by rotary evaporator, the residue was taken up in 500 mL of
water, and resulting solution was filtered through Celite to remove
unreacted chromium hexacarbonyl. To the filtrate was added 500 mL
of hexane and Meenwein salt (38.8 g, 264 mmol). This mixture was
either stirred or shaken (separatory funnel) for several minutes, and
then the layers were separated. The organic phase was extracted with
hexane until all of the carbene complex was removed, and the combined
organic layer was washed with water and brine. The organic phase
was concentrated to one third of its original volume, and red crystals
formed and were collected. This process was repeated to give 69.74
g (193 mmol, 81% yield) of carbene complex 21 from two crops. The
naphthyl complex 21 is much more stable than phenyl complex 15.
The spectral data obtained for complex 21 match those previously
reported for this compound.44
Methyl Triflate as Methylating Agent.55 The ether solution of
the lithium acylate (from 0.250 mmol of 1-bromonaphthalene) was
cooled in an ice bath, and methyl triflate (30 mL, 0.265 mol) was added
slowly. The solution was stirred at 0 °C for 15 min and then in a
water bath (25 °C) for 30 min. The reaction mixture was filtered
through Celite, washed with saturated aqueous NaHCO3, water, and
brine, and then dried over MgSO4. The product was filtered through
a short column of silica gel, and then the solvent was partially removed
by rotary evaporator until a red solid formed. The product was collected
by filtration and washed with small portions of cold hexane. This
process was repeated until no more solid appeared upon concentration.
The remainder of the product in the mother liquor was purified by
flash chromatography on silica gel with hexane as eluent to give a
60% combined yield (54.16 g, 0.15 mmol) of carbene complex 21. A
repeat of this reaction on a similar scale gave a 70% yield.
Methyl Iodide As Methylating Agent.45 The ether solution of the
lithium acylate (from 0.025 mmol of 1-bromonaphthalene) was stripped
of solvent under reduced pressure, and then the last trace of solvent
was removed under high vacuum. The greenish-brown residue was
dissolved in 50 mL of water in a 100 mL single-necked flask equipped
with a threaded high vacuum stopcock to give a yellow solution.
Tetrabutylammonium bromide (0.806 g, 2.5 mmol) was added followed
by methyl iodide (3.11 mL, 50 mmol). The flask was sealed and
immersed in a 70 °C oil bath and stirred for 2 h. The deep red lower
layer was separated, and the top layer was extracted with hexane. The
combined organic layer was dried over MgSO4. The solution was
filtered through a short column of silica gel, and the volatiles were
evaporated to give a red liquid which was loaded onto a silica gel
column. The product was flash eluted with hexane to give a 36% yield
(3.30g, 9.11 mmol) of carbene complex 21.
Methanol/Acetyl Bromide as Methylating Agents.56a The solution
of the lithium acylate (from 0.050 mmol of 1-bromonaphthalene) was
stripped of solvent under reduced pressure, and then the last trace of
solvent was removed under vacuum. The greenish brown residue was
dissolved in 200 mL of CH2Cl2, and the solution was cooled to -20
°C (in acetone/dry ice bath) under nitrogen in a flask equipped with a
mechanical stirrer. TMEDA56b (7.55 mL, 50 mmol, distilled from KOH
The Preparation of 3-Phenyl-1-naphthol (14) by the Reduction
of 16 with Ethanethiol and Aluminum Chloride. To a red-orange
solution of 0.275 g (0.94 mmol) of naphthol acetate 16 and 0.40 g (3.0
mmol) aluminum trichloride in 2 mL of methylene chloride at 0 °C
was added 1.0 mL (13.5 mmol) of ethanethiol via syringe. After 0.5
h, the solution was warmed to 25 °C and stirred for an additional 2 h.
The solution was then diluted with ether and washed with pH ) 7
buffer solution, aqueous sodium bicarbonate, and brine and then dried
with anhydrous MgSO4. Upon removal of solvents, the residue was
loaded on a silica gel column and eluted with a 1:1:4 mixture of ether/
CH2Cl2/hexane to give 0.150 g (0.68 mmol, 73% yield) of 3-phenyl-
1-naphthol (14) and 0.027 g (0.098 mmol, 10% yield) of 4-acetoxy-
3-phenyl-1-naphthol (19) as white solids. On a larger scale (11.4 mmol)
and with a reaction time of 3.5 h at 25 °C, a 78% yield of 14 was
obtained (1.96 g) and 19 was not detected. Spectral data for 14: white
solid; mp 96-97.5 °C; Rf ) 0.16 (1:1:8 ether:CH2Cl2:hexane); 1H NMR
(CDCl3) δ 5.32 (s, 1 H), 7.06 (s, 1 H), 7.34 (t, 1 H), 7.41-7.50 (m, 4
H), 7.62 (s, 1 H), 7.64 (d, 2 H), 7.82 (d, 1 H), 8.13 (d, 1 H); 13C NMR
(CDCl3) δ 108.41, 118.73, 121.39, 123.47, 125.34, 126.86, 127.20,
127.37, 127.99, 128.75, 134.85, 138.73, 140.67, 151.47; IR (neat) 3268
bs, 3058 w, 1597 m, 1497 m, 1399 m, 1284 m, 1082 m, 851 s, 762 vs,
689 s cm-1; mass spectrum, m/z (rel intensity), 220 M+ (100), 202 (2),
191 (38), 165 (14), 115 (6), 110 (7); exact mass calcd for C16H12O m/z
220.0888, found m/z 220.0879. Spectral data for 19: white solid; Rf
1
) 0.054 (1:1:8 ether:CH2Cl2:hexane); H NMR (CDCl3) δ 2.18 (s, 3
H), 5.28 (s, 1 H), 6.82 (s, 1 H), 7.25-7.74 (m, 7 H), 7.74 (d, 1 H, J )
8.4 Hz), 8.15 (d, 1 H, J ) 8.5 Hz); 13C NMR (CDCl3) δ 20.76, 110.15,
121.13, 122.27, 124.54, 125.52, 127.32, 127.47, 127.82, 128.31, 128.93,
130.81, 136.43, 137.68, 149.70, 170.55; IR (neat) 3401 s, 3055 m, 3021
w, 2922 w, 1757 s, 1634 w, 1598 s, 1499 m, 1446 w, 1397 m, 1367 s,
1313 w, 1223 s, 1168 s, 1071 s, 1050 s, 909 m, 817 w, 761 s, 739 w,
701 s cm-1; mass spectrum, m/z (rel intensity), 278 M+ (6), 250 (5),
236 (100), 220 (5), 207 (8), 178 (12), 105 (12); exact mass calcd for
C18H14O3 m/z 278.0943, found m/z 278.1030.
The Preparation of 3-Phenyl-1-naphthol (14) from Phenylacetyl
Chloride and Phenylacetylene.36 The following procedure is similar
to that described in the original preparation of this compound.36
A
100 mL recovery flask equipped with a condenser was charged with
phenylacetyl chloride (20 mL, 151 mmol) and phenylacetylene (10 mL,
91 mmol). The condenser was connected to a drying tube. The flask
was heated at 180 °C under nitrogen with an oil bath for 16 h. Upon
being cooled to 25 °C, the dark brown mixture containing the acylated
naphthol 13 was up in a solution prepared from 5 g (89 mmol) of
potassium hydroxide, 10 mL of water, and 200 mL of methanol. The
aqueous mixture was stirred for 12 h at 25 °C and then washed
repeatedly with ether to extract the phenoxide. The organic layer was
washed with 6 N aqueous HCl solution, pH ) 7 buffer, and brine. The
organic solution was dried with anhydrous magnesium sulfate and
filtered through Celite. The filtrate was treated with activated charcoal
and heated to reflux for 20 min. The mixture was filtered through
Celite and concentrated, but the color was not diminished. The residue
was loaded onto a silica gel column and eluted with a 1:1:8 mixture of
ether:CH2Cl2:hexane to give 9.36 g (42.5 mmol, 56% yield) of naphthol
14 as a colored solid.
The following alteration of this procedure avoided a chromatography
workup, could be scaled up to 100 g, and gave purer material. After
the mixture was stirred with KOH for 12 h, the methanol was removed
(55) Harvey, D. F.; Brown, M. F. Tetrahedron Lett. 1990, 31, 2529.
(56) (a) Connor, J. A.; Jones, E. M. J. Chem. Soc., A 1971, 3368. (b)
Do¨tz, K. H.; Leue, V. J. Organomet. Chem. 1991, 407, 337.

Synthesis of Vaulted Biaryls
J. Am. Chem. Soc., Vol. 118, No. 14, 1996 3401
pellets) was added, and the solution became dark brown after 10 min.
Freshly distilled and precooled (-20 °C) acetyl bromide (11.09 mL,
150 mmol) was added slowly via cannula. The dark reddish-brown
slurry was allowed to stir for 30 min. Freshly distilled (from
Mg(OMe)2) and precooled (-20 °C) methanol (20.25 mL, 0.5 mol)
was added, and the mixture was stirred at 0 °C for 1 h to produce a
deep orange solution. The solution was poured into a separatory funnel
containing saturated aqueous NaHCO3. The CH2Cl2 layer was separated
and stripped of volatiles, and then the residue was taken up in hexane.
The hexane solution was washed with water and brine, dried over
MgSO4, and filtered through a short column of silica gel. The solvent
was partially removed until a red solid formed which was collected.
This process was repeated until no more solid appeared upon
concentration. The remainder of the product in the mother liquor was
purified by flash chromatography on silica gel with hexane as eluent
to give a 52% total yield (9.44g, 26.5 mmol) of carbene complex 21.
mass calcd for C23H18O3 m/z 342.1256, found m/z 342.1253. Anal.
Calcd for C23H18O3: C, 80.68; H, 5.30. Found: C, 80.76, H, 5.42.
Initial Addition of Phenylacetylene. A 50 mL single-necked flask
equipped with a threaded high vacuum stopcock was charged with (1-
naphthylmethoxy)chromium complex 21 (3.04 g, 8.4 mmol), phenyl-
acetylene (1.84 mL, 16.7 mmol), and 16.7 mL of THF to make a
solution 0.5 M in 21. The solution was deoxygenated via the freeze-
thraw method (three cycles), although this was found not to be necessary
as indicated by the above procedure. The flask was sealed with the
threaded stopcock at 25 °C under argon and then heated at 60 °C in an
oil bath for 19 h. Acetic anhydride (1.59 mL, 168 mmol) and
triethylamine (2.34 mL, 168 mmol) were added, and the solution was
heated at 60 °C for 17 h. The crude reaction mixture was worked up
as described above, and after removal of volatiles the residue was loaded
onto a silica gel column and eluted with a 1:9 mixture of EtOAc:hexane
to give 1.08 g (3.16 mmol, 38% yield) of acetylated phenanthrol 22
and 1.20 g (2.70 mmol, 32% yield) of the bis(naphthyl)ethylene 23-E
as a white solid. The results from other runs at different concentrations
and in different solvents are tabulated in Table 1. Spectral data for
Dimethyl Sulfate as Methylating Agent. A solution of the lithium
acylate (from 121 mmol of 1-bromonaphthalene) was generated as
described above in 150 mL of THF, diluted with 200 mL of ether, and
washed with 5% aqueous HCl (2 × 100 mL). The red organic layer
was separated and stirred over solid potassium carbonate (35 g, 252
mmol, 2.0 equiv). Dimethyl sulfate (17 mL, 182 mmol, 1.5 equiv)
was added via syringe and the reaction mixture allowed to stir for 12
h at 25 °C. The reaction mixture was washed with water (3 × 100
mL), filtered through a plug of silica, and concentrated in Vacuo.
Purification by crystallization from hexanes (two crops) afforded
carbene complex 21 in 77% yield (34.0 g) as a red solid. A repeat of
the reaction on the same scale gave 21 in 65% yield (one crop) if the
reaction time with dimethyl sulfate was 2 h. On a 5 mmol scale a
73% yield of 21 was obtained with a 2 h reaction time. If either a
THF or ether solution of the lithium acylate (5 mmol scale) is directly
treated with dimethyl sulfate, an 18% yield of 21 is obtained with a 2
h reaction time and a 45% yield with a 12 h reaction time.
1
23-E: Rf ) 0.15 (1:9 EtOAc:hexane); mp ) 150-151 °C; H NMR
(CDCl3) δ 2.10 (s, 3 H), 4.01 (s, 3 H), 6.57 (s, 1 H), 6.58 (d, 2 H, J )
6.6 Hz), 6.75 (s, 1 H), 7.05-7.11 (m, 3 H), 7.20-7.23 (m, 2 H), 7.36-
7.40 (m, 2 H), 7.48-7.53 (m, 2 H), 7.71 (d, 1 H, J ) 7.8 Hz), 7.74-
7.81 (m, 1 H), 7.80 (d, 1 H, J ) 7.5 Hz), 7.99 (d, 1 H, J ) 8.1 Hz),
8.24 (d, 1 H, J ) 8.0 Hz); 1H NMR (C6D6) δ 1.79 (s, 3 H), 3.63 (s, 3
H), 6.56 (s, 1 H), 6.94-6.95 (m, 3 H), 7.06-7.30 (m, 7 H), 7.46-
7.54 (m, 3 H), 7.65 (d, 1 H, J ) 6.8 Hz), 8.01 (d, 1 H, J ) 8.0 Hz),
8.26 (d, 1 H, J ) 7.1 Hz), 8.39 (d, 1 H, J ) 8.1 Hz); 13C NMR (CDCl3)
δ 20.42, 55.47, 100.33, 121.80, 124.58, 125.25, 125.35, 125.72, 125.98,
126.31, 126.40, 126.85, 126.96, 127.79, 128.01, 128.43, 128.54, 128.69,
128.97, 129.68, 131.80, 131.87, 132.30, 133.44, 133.76, 137.40, 141.27,
158.39, 169.03; IR (neat) 3059 s, 3001 w, 2956 w, 2934 w, 1761 s,
1705 w, 1633 s, 1618 s, 1595 s, 1579 m, 1506 m, 1445 m, 1366 s,
1265 m, 1237 s, 1196 s, 1051 s, 1033 m, 902 s, 803 s, 779 s cm-1
;
The Preparation of the Acetylated Phenanthrol 22 from the
Reaction of the 1-Naphthylcarbene Complex 21 with Phenylacety-
lene. Slow Addition of Phenylacetylene. The naphthyl carbene
complex 21 (5 g, 13.8 mmol) was placed in a 250 mL round-bottom
flask equipped with a reflux condenser. The whole system was purged
with nitrogen for 5 min, and then 27.6 mL of dry THF was added
under nitrogen to make a solution 0.5 M in 21. The solution was heated
in an oil bath at 65 °C under nitrogen. Phenylacetylene (1.8 mL, 16.6
mmol) was added slowly by means of a syringe pump over 6 h, and
then reflux was maintained for an additional hour. Upon cooling and
examination by TLC to confirm that consumption of the carbene
complex was complete, triethylamine (6 mL, 41.4 mmol) and acetic
anhydride (4 mL, 41.4 mmol) were added and the resulting solution
was refluxed for 13 h under nitrogen. The THF was partially removed
by rotary evaporator, and then the solution was diluted with ether and
washed with water and brine. This solution was dried over MgSO4
and filtered through a short column of SiO2 to remove a green insoluble
material, and then the solvent was removed to give a brown residue.
The 1H NMR of the crude reaction mixture reveals the presence of 22
and 23-E in a 9:1 ratio and that the ratio of the E and Z isomers of 23
is g16:1. Ether (50 mL) was added to the residue to give a light brown
solution and a pale yellow material that did not dissolve which was
found to be pure 22. Addition of hexane (25 mL) caused precipitation
of additional 22. Collection of this solid gave 3.3 g of pure product.
Additional 22 (0.21 g) was obtained from the mother liquor by flash
chromatography (1:9 EtOAc:hexane) to give a total isolated yield of
3.51 g of 22 (74.3%). On a larger scale (30 g of 21), this reaction
gave a 65% yield of 22. Spectral data for 22: Rf ) 0.23 (1:9 EtOAc:
hexane); white solid; mp ) 160-161 °C; 1H NMR (CDCl3) δ 2.19 (s,
3 H), 4.14 (s, 3 H), 7.13 (s, 1 H), 7.36 (t, 1 H, J ) 7.3 Hz), 7.43 (t, 2
H, J ) 7.6 Hz), 7.53-7.63 (m, 4 H), 7.70 (d, 1 H, J ) 8.9 Hz), 7.78
(d, 1 H, J ) 9.0 Hz), 7.85 (d, 1 H, J ) 7.8 Hz), 9.62 (d, 1 H, J ) 8.8
Hz); 13C NMR (CDCl3) δ 20.74, 55.98, 109.56, 119.50, 120.95, 126.30,
126.89, 127.52, 127.63, 128.35, 128.43, 128.56, 129.06, 129.30, 130.09,
131.93, 132.47, 137.34, 138.02, 156.65, 169.70; IR (neat) 3056 w, 2929
w, 2844 w, 1762 s, 1598 w, 1498 w, 1451 w, 1367 m, 1213 m, 1196
mass spectrum, m/z (rel intensity), 444 (20) M+, 402 (100), 369 (14),
359 (12), 341 (13), 339 (12), 202 (13); exact mass calcd for C31H24O3
m/z 444.1726, found m/z 444.1733. Anal. Calcd for C31H24O3: C,
83.76; H, 5.44. Found: C, 83.81, H, 5.50.
Isomerization of Alkene 23 and Stereochemical Assignment of
the E- and Z-Isomers. A solution of alkene 23-E (0.08g) in 100 mL
of benzene was irradiated in a quartz tube for 18 h using a Rayonet
photochemical reactor. A mixture of alkenes was produced which were
separated on silica gel by flash column chromatography using a 1:9
mixture of EtOAc:hexanes as eluant. Spectral data for 23-Z: Rf )
1
0.23 (1:9 EtOAc:hexane); white gum; H NMR (CDCl3) δ 2.25 (s, 3
H), 3.44 (s, 3 H), 6.38 (s, 1 H), 7.37-7.56 (m, 8 H), 7.62 (d, 2 H, J )
7.3 Hz), 7.68 (d, 1 H, J ) 6.8 Hz), 7.86-7.92 (m, 3 H), 8.15 (d, 1 H,
J ) 8.1 Hz), 8.26 (s, 1 H), 8.30 (d, 1 H, J ) 7.6 Hz); 1H NMR (C6D6)
δ 1.92 (s, 3 H), 3.13 (s, 3 H), 6.54 (s, 1 H), 7.26-7.48 (m, 8 H), 7.60
(d, 1 H, J ) 6.9 Hz), 7.76 (d, 2 H, J ) 7.8 Hz), 7.81 (d, 2 H, J ) 7.5
Hz), 8.13-8.16 (m, 2 H), 8.52 (d, 1 H, J ) 8.3 Hz), 8.73 (s, 1 H); 13
C
NMR (CDCl3) δ 20.76, 56.88, 107.33, 121.88, 124.59, 125.28, 125.59,
126.13, 126.21, 126.38, 126.86, 127.35, 127.99, 128.32, 128.36, 128.75,
129.24, 129.36, 130.67, 130.93, 131.87, 132.12, 133.38, 134.14, 138.48,
141.87, 156.71, 169.35, 1 aryl C not assigned; IR (neat) 1764 s, 1365
s, 1201 s, 1176 s, 1051 s, 780 s, 762 s cm-1; mass spectrum, m/z (rel
intensity), 444 (30) M+, 403 (30), 402 (100), 387 (5), 369 (7), 357 (5),
341 (5).
The stereochemistry of the isomers of 23 was assigned by NOE
experiments. Samples of each isomer were dissolved in C6D6 in a 5
mm NMR tube, and the solutions were deoxygenated by means of the
freeze-thraw method (three cycles). E-Isomer: Irradiation at the
methoxy proton (δ ) 3.63) gave rise to a 20% enhancement of the
vinyl proton (δ ) 6.56). Irradiation at the vinyl proton at δ ) 6.56
gave rise to a 10% enhancement of the methoxy proton at δ ) 3.63 as
well as a 13% enhancement of the aromatic proton at δ ) 8.39.
Irradiation at the aromatic proton (δ ) 8.39) gave rise to an
enhancement of the vinyl proton (δ ) 6.56). Z-Isomer: Irradiation at
either the methoxy proton (δ ) 3.13), the vinyl proton (δ ) 6.54), or
the aromatic proton (δ ) 8.73) gave no observable enhancements for
any of the protons in the spectrum.
vs, 1174 m, 1157 m, 1100 w, 1049 m, 815 w, 745 w, 700 m cm-1
;
mass spectrum, m/z (rel intensity), 342 M+ (8), 300 (100), 285 (46),
268 (8), 255 (6), 239 (10), 226 (12), 191 (2), 155 (27), 126 (18); exact

3402 J. Am. Chem. Soc., Vol. 118, No. 14, 1996
Bao et al.
The Preparation of 3-Phenylphenanthrol (28) by Reduction of
Acetylated Phenanthrol 22 with Ethanethiol and Aluminum Chlo-
ride. To a solution of the acetylated phenanthrol 22 (0.3144 g, 0.92
mmol) and aluminum chloride (0.42 g, 3.1 mmol) in 2 mL of
dichloromethane was added 2 mL of ethanethiol. The solution was
stirred at 25 °C for 4.5 h and was then diluted with dichloromethane.
The reaction mixture was then washed with aqueous sodium bicarbonate
and brine and then dried with anhydrous MgSO4. After the removal
of solvent, the residue was loaded onto a silica gel column and eluted
with a 1:5 mixture of EtOAc:hexane to give 0.2386 g (0.88 mmol,
96% yield) of phenanthrol 28 and 0.0045 g (0.014 mmol, 1.5% yield)
of a compound that was tentatively identified as 4-acetoxy-3-phenyl-
phenanthrol (55), both as white solids. Spectral data for 55: 1H NMR
(CDCl3) δ 2.20 (s, 3 H), 5.82 (s, 1 H), 6.96 (s, 1 H), 7.34 (t, 1 H, J )
7.5 Hz), 7.40 (t, 2 H, J ) 7.1 Hz), 7.48 (d, 2 H, J ) 7.3 Hz), 7.55 (t,
1 H, J ) 7.4 Hz), 7.58 (t, 1 H, J ) 7.1 Hz), 7.67 (d, 1 H, J ) 9.0 Hz),
7.75 (d, 1 H, J ) 9.1 Hz), 7.83 (d, 1 H, J ) 7.7 Hz), 9.55 (d, 1 H, J
) 8.6 Hz). Spectral data for 28: Rf ) 0.33 (1:5 EtOAc:hexane); mp
) 154-155 °C; 1H NMR (CDCl3) δ 5.71 (s, 1 H), 7.18 (s, 1 H), 7.35
(t, 1 H, J ) 7.5 Hz), 7.45 (t, 2 H, J ) 7.6 Hz), 7.55 (t, 1 H, J ) 7.2
Hz), 7.72 (t, 1 H, J ) 7.4 Hz), 7.64-7.70 (m, 5 H), 7.84 (d, 1 H, J )
7.8 Hz), 9.58 (d, 1 H, J ) 8.5 Hz); 13C NMR (CDCl3) δ 112.20, 118.52,
119.86, 125.99, 126.65, 127.21 (two carbons), 127.62, 128.25, 128.42,
128.89, 130.13, 132.57, 135.27, 139.17, 140.09, 154.61 (one carbon
not located); IR (neat) 3521 s, 3061 w, 2028 w, 1604 w, 1564 m, 1524
w, 1411 w, 1391 s, 1331 m, 1278 m, 1225 s, 1178 m, 1125 w, 1019
m, 745 s cm-1; mass spectrum, m/z (rel intensity), 270 (100) M+, 241
(23), 165 (8), 135 (12), 120 (11), 84 (43); exact mass calcd for C20H14O
m/z 270.1045, found m/z 270.1074. Anal. Calcd for C20H14O: C,
88.86; H, 5.22. Found: C, 88.52, H, 5.31.
heated to reflux for 1 h, at which point all starting material had been
consumed as indicated by 1H NMR. All of the volatiles were removed
by high vacuum to leave a yellow solid which appeared to be a single
compound by 1H NMR. To this solid was added phenylacetylene (10.1
mL, 92.0 mmol), and the resulting mixture was heated at 185 °C for
16 h under nitrogen. The 1H NMR spectrum indicated that a substantial
amount of the acid chloride remained unreacted. More phenylacetylene
(10 mL, 91.1 mmol) was added, and the mixture was heated at 185 °C
for 20 h after which time the 1H NMR indicated that the reaction was
complete. To the reaction mixture (black oil) was added KOH (8.5 g,
152 mmol), 200 mL of water, and 400 mL of methanol. After being
stirred at room temperature for 20 h, the solution was concentrated by
rotary evaporator. Ether was added, and the organic layer was washed
with water and brine. After removal of the solvents, the product 28
could be purified from the residue by flash chromatography on a silica
gel column with a 1:9 mixture of EtOAc/hexane and then on a second
silica gel column with a 1:1:8 mixture of CH2Cl2/ether/hexane to give
11.09 g (41.1 mmol, 54%) of phenanthrol 28 as a brown solid.
Attempts to purify phenanthrol 28 by extraction from ether with aqueous
potassium hydroxide were not successful. The phenanthrol 28 purified
from this reaction by chromatography on silica gel was not suitable
for the oxidative coupling to 47.
The Reaction of 1-Naphthylcarbene Complex 21 with tert-
Butylacetylene. According to the procedure described above for the
reaction of 21 with phenylacetylene, the reaction of complex 21 (1.12
g, 3.1 mmol) with tert-butylacetylene (0.57 mL, 4.6 mmol) in 6.2 mL
of THF was carried out at 60 °C for 17 h. The crude mixture was
stirred in air for 0.5 h and then filtered through Celite. Upon removal
of solvent, the residue was loaded onto a silica gel column and eluted
with a 1:1:16 mixture of Et2O:CH2Cl2:hexane to give three com-
pounds: 31 (0.6784 g, 2.42 mmol, 78% yield), 32 (0.167g, 0.40 mmol,
13% yield, yellow solid), and an unidentified material (0.182 g).
Spectral data for 32: Rf ) 0.06 (1:1:16 Et2O:CH2Cl2:hexane); 1H NMR
(CDCl3) δ 1.56 (s, 9 H), 4.10 (s, 3 H), 5.01 (s, 1 H), 5.41 (t, 1 H, J )
6.9 Hz), 5.56 (t, 1 H, J ) 6.2 Hz), 5.96 (d, 1 H, J ) 6.2 Hz), 7.17 (s,
1 H), 7.29 (d, 1 H, J ) 9.1 Hz), 7.88 (d, 1 H, J ) 7.2 Hz), 7.96 (d, 1
H, J ) 9.0 Hz); IR (neat) 3583 w, 2969 w, 1951 s, 1874 s, 1440 w,
A Large Scale Preparation of 3-Phenylphenanthrol (28). A dry
5000 mL round-bottomed flask equipped with a reflux condensor was
charged with naphthylchromium complex 21 (73.10 g, 202 mmol),
phenylacetylene (26.6 mL, 243 mmol), and 4500 mL of THF (predis-
tilled from CaH2) under nitrogen. The solution was heated to reflux
for 17 h. Upon cooling, triethylamine (87.3 mL, 626 mmol) and acetic
anhydride (57.2 mL, 606 mmol) were added under nitrogen, and the
solution was heated to reflux for 24 h. The THF was removed by
rotary evaporator to give an oily residue. Upon addition of ether a
yellow solid precipitated which was collected to give 13.95 g (29.2
mmol, 14% yield) of a compound which was tentatively identified as
the arene chromium complex 29. Spectral data for 29: Rf ) 0.036
(1:9 EtOAc:hexane); 1H NMR (CDCl3) δ 2.32 (s, 3 H), 4.20 (s, 3 H),
5.28 (t, 2 H), 5.45 (t, 1 H), 5.76 (brd s, 2 H), 7.21 (s, 1 H), 7.58-7.67
(m, 3 H), 7.79 (d, 1 H), 7.86 (d, 1 H), 9.61 (d, 1 H); IR (neat) 1963 s,
1882 s, 1761 m, 1449 w, 1368 w, 1196 m, 1174 w, 1142 w, 1049 w,
817 w, 732 w, 701 w, 660 m cm-1. The mother liquor was washed
with aqueous saturated sodium bicarbonate and brine and then dried
with anhydrous MgSO4 and filtered through Celite. Upon concentra-
tion, crystals of the phenanthrol 22 began to separate, and collection
of two crops of these crystals gave 39.42 g (115 mmol, 57% yield) of
the acetylated phenanthrol 22. The acetylated phenanthrol 22 and the
arene complex 29 were combined and dissolved in 200 mL of
dichloromethane. To this solution was added aluminum trichloride (40
g, 300 mmol) and ethanethiol (200 mL, 2.7 mol), and the resulting
solution was stirred at 25 °C for 12 h under an inert atmosphere. The
crude reaction mixture was quenched with 1 N aqueous HCl (slowly
in a ice bath). The organic layer was washed with aqueous saturated
sodium bicarbonate and brine and then dried with anhydrous MgSO4.
After filtration through Celite and removal of solvent, the residue was
chromatographed on a 50 mm diameter silica gel column with a 1:9
mixture of EtOAc/hexane to remove base line impurities to give 37.74
g (140 mmol) of phenanthrol 28 as a white solid in 69% yield from
the carbene complex 21. Presumably, the amount of solvent for this
reaction could be reduced by at least a factor of 10 if slow addition of
phenylacetylene was employed as described above. Also, it has been
found phenanthrol 28 obtained by this reaction is pure enough to be
successfully employed in the synthesis of 47 without purification by
silica gel chromatography.
1362 w, 1228 w, 1055 w, 732 w, 713 w, 664 m cm-1
.
The three compounds were combined and dissolved in 20 mL of
THF. To this solution were added acetic anhydride (0.58 mL, 6.15
mmol) and triethylamine (0.86 mL, 6.17 mmol). The solution was
heated to reflux for 16 h. All volatiles were removed, and the residue
was dissolved in ether. The solution was washed with aqueous saturated
sodium bicarbonate, water, and brine. After drying with MgSO4 and
removal of solvent, the residue was loaded onto a silica gel column
and eluted with a 1:9 mixture of EtOAc:hexane to give 0.541 g (1.79
mmol, 54% from 21) of acetylated phenanthrol 33 as a light yellow
1
solid. Spectral data for 33: Rf ) 0.38 (1:9 EtOAc:hexane); H NMR
(CDCl3) δ 1.48 (s, 9 H), 2.49 (s, 3 H), 4.11 (s, 3 H), 7.17 (s, 1H), 7.45
(d, 1 H, J ) 9.2 Hz), 7.53 (t, 1 H, J ) 6.1 Hz), 7.58 (t, 1 H, J ) 6.4
Hz), 7.69 (d, 1 H, J ) 9.2 Hz), 7.80 (d, 1 H, J ) 7.3 Hz), 9.55 (d, 1
H, J ) 8.6 Hz); 13C NMR (CDCl3) δ 21.55, 21.87, 30.49, 34.85, 119.84,
120.88, 122.62, 126.01, 126.81, 127.05, 128.02, 128.69, 128.74, 132.40,
139.15, 143.00, 145.69, 169.38, 169.78; IR (neat) 3053 w, 2963 w,
2869 w, 1764 s, 1717 w, 1598 w, 1357 m, 1191 s, 1157 m, 1136 m,
1037 w, 1018 w, 912 w, 820 w, 732 w cm-1
.
The Preparation of the tert-Butylphenanthrol (34) by Reduction
of Acetylated Phenanthrol 33. To a solution of the acetylated
phenanthrol 33 (0.54 g, 1.68 mmol) and aluminum chloride (0.54 g,
4.05 mmol) in 3 mL of dichloromethane was added ethanethiol (5 mL,
72 mmol). The solution was stirred at 25 °C for 15 h, and then the
volatiles were removed under vacuum. The residue was diluted with
ether, and the solution was washed with aqueous sodium bicarbonate,
water, and brine. After drying with MgSO4 and removal of solvent,
the residue was loaded onto a silica gel column and eluted with a 1:1:
16 mixture of ether:CH2Cl2:hexane to give 0.36 g (1.44 mmol, 85%
yield) of phenanthrol 34 as a white solid. Spectral data for 34: Rf )
1
0.21 (1:9 EtOAc:hexane); H NMR (CDCl3) δ 1.44 (s, 9 H), 5.67 (s,
1 H), 7.01 (d, 1 H, J ) 1.5 Hz), 7.45 (s, 1 H), 7.54 (t, 1 H, J ) 7.1
Hz), 7.62 (t, 1 H, J ) 8.0 Hz), 7.63-7.70 (m, 2 H), 7.84 (d, 1 H, J )
8.5 Hz), 9.56 (d, 1 H, J ) 8.4 Hz); 13C NMR (CDCl3) δ 31.28, 34.54,
111.55, 117.30, 117.77, 125.56, 126.39, 127.29, 127.83, 128.10, 128.22,
The Preparation of 3-Phenylphenanthrol (28) from 2-Naphthyl-
acetic acid and Phenylacetylene. A mixture of 28.5 g (153 mmol)
of naphthylacetic acid and thionyl chloride (40 mL, 548 mmol) was

Synthesis of Vaulted Biaryls
J. Am. Chem. Soc., Vol. 118, No. 14, 1996 3403
130.17, 132.33, 134.71, 149.71, 153.92; IR (neat) 3508 s, 3057 w, 2953
s, 2893 m, 2866 m, 1627 w, 1599 w, 1570 m, 1460 m, 1420 m, 1397
s, 1345 m, 1283 m, 1239 s, 1229 s, 1179 s, 1110 m, 1050 w, 1015 m,
2 H), 7.49-7.51 (m, 4 H), 7.77 (d, 2 H, J ) 7.4 Hz), 8.46 (d, 2 H, J
) 7.3 Hz). The acid 44 was taken on directly to 46. To a potassium
hydroxide solution (4.0 g, 71.4 mmol, in 10 mL of water) was added
15 mL of ether. The two-phase mixture was cooled to 0 °C, and
N-nitroso-N-methylurea (1.4 g, 13.5 mmol) was added. The mixture
was stirred for 25 min, and the organic layer was separated and dried
over potassium hydroxide pellets. The organic phase was then added
to a solution of phosphoric acid 44 (0.2312 g, 0.46 mmol) in 20 mL of
methylene chloride at 25 °C. After 10 min, the reaction was quenched
with acetic acid until bubbling stopped. The mixture was diluted with
ether and washed with aqueous saturated sodium bicarbonate, water,
and brine. The solution was dried over anhydrous MgSO4 and filtered
through Celite. Upon removal of solvent, the residue was loaded onto
a silica gel column and eluted with a 1:3 mixture of EtOAc:hexane to
give 0.210 g (0.41 mmol, 88% yield) of phosphate ester 46 as a white
solid. Spectral data for 46: white solid; Rf ) 0.07 (1:1:4 CH2Cl2:
ether:hexane); 1H NMR (CDCl3) δ 4.04 (d, 3 H, J ) 11.5 Hz), 6.43 (t,
4 H, J ) 7.4 Hz), 6.89 (q, 4 H, J ) 7.2 Hz), 7.06 (q, 2 H, J ) 7.0 Hz),
7.47 (s, 2 H), 7.55-7.65 (m, 4 H), 7.80 (t, 2 H, J ) 8.6 Hz), 8.31 (d,
1 H, J ) 8.3 Hz), 8.38 (d, 1 H, J ) 8.3 Hz); 13C NMR (CDCl3) δ
56.19 (d, JP-C ) 5.7 Hz), 121.74, 122.29, 122.49, 122.51, 125.24,
125.28, 125.66, 125.70, 126.56, 126.64, 127.02, 127.06, 127.30, 127.34,
127.51, 127.60, 127.70, 127.78, 127.99, 128.94, 128.96, 134.12, 134.29,
139.69, 139.94, 140.17, 144.58, 144.69, 145.72, 145.87; IR (neat) 3053
w, 2948 w, 2848 w, 2244 w, 1582 w, 1566 w, 1488 m, 1451 w, 1383
m, 1337 w, 1303 s, 1291 s, 1263 w, 1110 w, 1093 w, 1056 s, 1043 s,
867 m, 851 s, 811 s, 746 s, 715 cm-1
.
The Preparation of 4,4′-Binaphthol 38 by Oxidative Coupling
of 3-Phenyl-1-naphthol (14) with Ferric Chloride. To 0.245 g (1.11
mmol) of 3-phenyl-1-naphthol (14) in 30 mL of acetonitrile was added
1.66 g (6.15 mmol) of FeCl3‚6H2O at 25 °C. The solution was stirred
at 25 °C for 16 h. The crude reaction mixture was diluted with ether,
and the solution was washed with water and dried over anhydrous
MgSO4. Upon removal of solvent, the residue was loaded onto a silica
gel column and eluted with a 1:1:4 mixture of ether:CH2Cl2:hexane to
give 0.1529 g (0.35 mmol, 62% yield) of 4,4′-binaphthol 38. Two
minor products were also observed which were not characterized but
whose properties were not consistent with those known for 2,2′-
binaphthol 39 (Vide infra). Spectral data for 38: white solid; mp )
240-241 °C; Rf ) 0.23 (1:1:4 ether:CH2Cl2:hexane); 1H NMR (CDCl3)
δ 5.35 (s, 2 H), 6.37 (d, 4 H, J ) 7.7 Hz), 6.66 (s, 2 H), 6.83 (t, 4 H,
J ) 7.6 Hz), 6.97 (t, 2 H, J ) 7.2 Hz), 7.30 (t, 2 H, J ) 7.2 Hz), 7.37
(d, 2 H, J ) 8.4 Hz), 7.45 (t, 2 H, J ) 7.3 Hz), 8.23 (d, 2 H, J ) 8.3
Hz); 13C NMR (CDCl3) δ 111.09, 121.74, 123.45, 124.76, 125.98,
126.68, 126.95, 127.01, 127.45, 128.94, 135.99, 141.10, 141.42, 151.09;
IR (neat) 3518 bs, 3058 w, 1621 w, 1596 s, 1513 w, 1497 m, 1444 w,
1380 s, 1357 m, 1288 w, 1230 s, 1146 w, 1064 s, 908 m, 859 w, 732
s, 702 s cm-1; Mass spectrum, m/z (rel intensity), 438 M+ (85), 322
(7), 247 (25), 220 (100), 205 (16), 191 (23), 97 (38), 84 (64), 71 (63);
exact mass calcd for C32H22O2 m/z 438.1620, found m/z 438.1632.
969 s, 944 m, 911 s, 875 m, 864 m, 795 w, 774 m, 761 s, 730 s cm-1
;
mass spectrum, m/z (rel intensity) 514 M+ (100), 436 (12), 420 (10),
389 (6), 33 (12), 218 (11); exact mass calcd for C33H23O4P m/z 514,
1334, found 514.1334. Anal. Calcd for C33H23O4P: C, 77.04; H, 4.51;
P, 6.02. Found: C, 76.52; H, 4.79; P, 6.31.
The Preparation of 2,2′-Binaphthol 39 by Oxidative Coupling
of 3-Phenyl-1-naphthol (14) with Air.48b 3-Phenyl-1-naphthol (14)
(0.98 g, 4.45 mmol) was introduced into an 18 × 150 mm culture tube
which was placed in an oil bath at 190 °C. After 16 h, TLC indicated
only 50% conversion, but after an additional 16 h at 200 °C the reaction
was complete. The crude reaction mixture was directly loaded onto a
silica gel column and eluted with a 1:15 mixture of EtOAc:hexane to
give 0.0474 g (0.11 mmol, 2.5%) of a product 56 which was tentatively
identified as the furan resulting from the dehydration of 39, 0.856 g
(1.95 mmol, 87% yield) of the 2,2′-bi-1-naphthol 39, and 0.0458 g of
an unknown compound. Spectral data for 56: Rf ) 0.70 (1:9 EtOAc:
The Resolution of 3,3′-Diphenyl-2,2′-binaphthalene-1,1′-diol (39).
Preparation of Salt 45 from Acid 44 and Brucine. A mixture of
the binaphthylphosphoric acid 44 (53.7 mmol), prepared from 23.51 g
of racemic binaphthol 39 as described above, and brucine (22.3 g, 51.8
mmol as dihydrate) in 1000 mL of ethanol was heated to a boil. A
white solid begin to separate even with slight cooling. Upon cooling
to room temperature, the white solid was collected and then redissolved
in a small amount of CH2Cl2, and then ethanol was added. Methylene
chloride was removed via gentle vacuum until the solution was saturated
at ambient temperature. After a few hours, the fine crystals of the salt
45 were collected, washed with ethanol, and dried under high vacuum
overnight to give 20.48 g (22.9 mmol, 85% yield). These crystals were
of X-ray quality. An X-ray diffraction analysis was performed, and
the details can be found in the supporting information. The X-ray
analysis revealed that the 2,2′-binaphthol chiral axis in salt 45 has an
S-configuration.
1
hexane); H NMR (CDCl3) δ 6.91-6.92 (m, 6 H), 7.18-7.21 (m, 4
H), 7.55 (t 2 H, J ) 7.4 Hz), 7.59 (s, 2 H), 7.65 (t, 2 H, J ) 7.4 Hz),
7.92 (d, 2 H, J ) 8.1 Hz), 8.64 (d, 2 H, J ) 8.1 Hz); 13C NMR (CDCl3,
75 MHz) δ 118.10, 120.30, 120.79, 125.79, 126.30, 126.47, 126.97,
128.00, 128.09, 128.47, 132.08, 135.99, 141.81, 152.85; Mass spectrum,
m/z (rel intensity), 420 M+ (100), 389 (8), 342 (7), 313 (5), 171 (15);
exact mass calcd for C32H20O m/z 420.1514, found m/z 420.1505.
Spectral data for 39: Rf ) 0.36 (1:9 EtOAc:hexane); white solid; mp
1
) 231-233 °C; H NMR (CDCl3) δ 5.83 (s, 2 H), 6.61 (d, 4 H, J )
7.2 Hz), 6.93 (t, 4 H, J ) 7.7 Hz), 7.03 (t, 2 H, J ) 7.3 Hz), 7.29 (s,
2 H), 7.50-7.54 (m, 4 H), 7.73-7.75 (m, 2 H), 8.30-8.32 (m, 2 H);
13C NMR (CDCl3, 75 MHz) δ 112.64, 122.00, 122.78, 122.86, 125.66,
126.59, 127.43, 127.51, 127.67, 128.86, 134.56, 140.12, 140.65, 150.33;
IR (neat) 3508 s, 3054 m, 3030 w, 1948 w, 1630 w, 1502 m, 1569 m,
1493 s, 1439 w, 1383 s, 1285 m, 1233 m, 1221 m, 1192 m, 1140 m,
Isolation of Resolved Acid (+)-44. The above crystals of salt 45
(δ ) 7.25 ppm) were determined by 31P NMR to be free of the soluble
diastereomer (δ ) 7.31). All of the above crystals of salt 45 were
slurried in 200 mL of boiling ethanol. Not all of the salt dissolved
even at the boiling point. Hydrochloric acid (200 mL, 6 N) was added
by dropping funnel, and at one point during the addition all of the
solid disappeared, but the solution became cloudy again upon further
addition of acid. After cooling to 25 °C, the white solid was collected
and washed with water. The filtrates were combined and concentrated.
A second crop of the resolved acid 44 was collected and washed. The
two crops were combined and dried under high vacuum to give 10.81
g (21.6 mmol, 81% yield) of (+)-44: [R]D ) 20.4 (CHCl3, c ) 1.5).
1062 m, 1020 w, 947 m, 908 s, 879 m, 853 w, 798 w, 759 s cm-1
;
mass spectrum, m/z (rel intensity), 438 M+ (2), 420 (15), 408 (2), 389
(2), 234 (5), 206 (30, 83 (100), 71 (9); exact mass calcd for C32H22O2
m/z 438.1620, exact m/z 438.1610. Anal. Calcd for C32H22O2: C,
87.65; H, 5.06. Found: C, 87.89; H, 5.10.
The Preparation of 2,2′-Binaphthylphosphoric Acid 44 and Its
Conversion to the 2,2′-Binaphthyl Methyl Phosphate 46. To a
solution of the 2,2′-binaphthol 39 (4.6 g, 10.5 mmol) in 30 mL of
pyridine was added phosphorus oxychloride (1.37 mL, 14.7 mmol) at
0 °C under argon. This solution was heated at 90 °C for 2.5 h. Upon
cooling, 0.5 mL of water was added and the solution was heated to 90
°C for 1.5 h. After the pyridine was removed under vacuum, the residue
was taken up in 150 mL of aqueous HCl (6 N, 900 mmol). This
solution was heated to reflux for 1.5 h, and after the solution was cooled
the acid 44 precipitated as a white solid. The product was collected,
washed with water, and dried under high vacuum overnight to give
5.3 g (10.6 mmol, 100%) of acid 44. Spectral data for 44: white solid;
The Liberation of Binaphthol (-)-39 from Acid (+)-44. The
resolved binaphthol phosphoric acid (+)-44 (10.81 g, 21.6 mmol) was
taken up in 100 mL of N,N-dimethylacetamide, and dimethyl sulfate
(4.08 mL, 43.2 mmol) was added. Sodium bicarbonate (4.0 g, 47.6
mmol) was then added, and the mixture was stirred for 12 h at 25 °C
1
at which point the reaction was complete as indicated by H NMR.
The solvent was removed by rotary evaporator at 55 °C, and the residue
was dissolved in dichloromethane. This solution was washed with water
and brine and then dried with anhydrous MgSO4 and filtered through
Celite. After removal of solvent, the residue was redissolved in 60
mL of toluene, and then 15 mL of Red-Al (3.4 M in toluene, 51 mmol)
was introduced dropwisely at room temperature. After the solution
was stirred for 12 h it was diluted with ethyl acetate. The reaction
1
mp ) 220 °C dec; H (CDCl3) δ 5.80 (brd s, 1 H), 6.45 (d, 4 H, J )
7.5 Hz), 6.88 (t, 4 H, J ) 7.4 Hz), 7.06 (t, 2 H, J ) 7.2 Hz), 7.47 (s,

3404 J. Am. Chem. Soc., Vol. 118, No. 14, 1996
Bao et al.
mixture was washed with 1 N hydrochloric acid, aqueous saturated
sodium bicarbonate, and water and then dried over anhydrous MgSO4.
Upon removal of solvent, the residue was loaded onto a silica gel
column and eluted with a 1:9 mixture of EtOAc:hexane to give 9.26 g
(21.1 mmol, 98%) of (-)-39 as a crystalline white solid: [R]D ) -372.3
(THF, c ) 1.0). It was found that resolved 39 was much more soluble
than the racemate, and thus resolved 39 can be easily loaded onto a
column with a small portion of ethyl acetate. The optical purity of
NMR (CDCl3) δ 115.77, 118.09, 123.23, 126.36, 126.81, 126.99,
127.03, 127.53, 128.44, 128.82, 129.29, 130.28, 132.80, 135.27, 139.70,
141.56, 153.41 (one carbon not located); IR (neat) 3473 s, 3049 m,
1611 w, 1590 w, 1555 w, 1372 m, 1330 m, 1246 w, 1210 w, 1175 m,
1027 w, 816 w, 774 m, 731 m, 665 m cm-1; mass spectrum, m/z (rel
intensity), 538 (18) M+, 520 (5), 370 (3), 270 (100), 241 (30), 215 (7),
165 (10); exact mass calcd for C40H26O2 m/z 538.1933, found m/z
538.1933. Anal. Calcd for C40H26O2: C, 89.19; H, 4.87. Found: C,
88.43, H, 5.29.
1
(-)-39 was determined to be greater than 98% by H NMR in CDCl3
with Eu(hfc)3. The optical purity of (-)-39 was determined to be
greater than 99% by HPLC on a Pirkle D-phenylglycine column with
a 30:70 mixture of 2-propanol and hexane (550 psi, 0.9 mL/min) under
which conditions the retention time of (-)-39 is 7.83 min and that for
(+)-39 is 7.26 min.
Racemization of Binaphthol (-)-39 in Octane. A 15 mL Kontes
flask was charged with (-)-39 (0.020 g, 0.046 mmol) and 5 mL of
octane. The solution was deoxygenated by the freeze-thaw method
(two cycles) and was sealed under argon at 25 °C. The solution was
heated to 150 °C for 2 h. After cooling and removal of solvent, the
residue was dissolved in CDCl3 and Eu(hfc)3 was added. The 1H NMR
spectrum showed that no detectable amount of racemization had
occurred. The same procedure was repeated as follows: 180 °C for 2
h, no racemization; 200 °C for 3 h, 10% racemization (95:5); 200 °C
for 15 h, 30% racemization (85:15).
The Preparation of 3,3′-Biphenanthrylphosphoric Acid 49 and
Its Conversion to the 3,3′-Biphenanthrol Methyl Phosphate 52. To
a solution of biphenanthrol 47 (15.93 g, 29.6 mmol) in 120 mL of
pyridine was added phosphorus oxychloride (3.9 mL, 41.8 mmol). After
this solution was stirred at room temperature for 2 h, it was heated to
90 °C for 1 h. Upon cooling to 25 °C, 25 mL of water was added
with a noticable heat release and then the solution was heated to 95 °C
for 1.5 h. The pyridine was removed under vacuum, and the residue
was taken up in 200 mL of aqueous 6 N HCl solution and then heated
to reflux for 2 h in a 140 °C oil bath. The solution was cooled to
room temperature and filtered. The solid that was collected was washed
with water and dried under high vacuum to give 18.06 g (30.1 mmol,
100% yield) of the phosphoric acid 49 as a white solid (mp > 275
°C). Spectral data for 49: 1H NMR (CDCl3) δ 1.95 (brd s, 1 H), 6.49
(d, 4 H, J ) 7.4 Hz), 6.87 (t, 4 H, J ) 7.6 Hz), 7.23 (t, 2 H, J ) 7.7
Hz), 7.39-7.43 (m, 4 H), 7.53-7.59 (m, 4 H), 7.66 (d, 2 H, J ) 8.8
Hz), 7.76 (d, 2 H, J ) 7.5 Hz), 9.87 (d, 2 H, J ) 8.5 Hz); IR (neat)
3054 w, 3022 w, 2612 bs, 2133 w, 1616 w, 1597 w, 1487 m, 1375 m,
The Recovery of Binaphthol (+)-39 from the Mother Liquor.
The mother liquor remaining after the removal of salt 45 was
concentrated, and 300 mL of 6 N hydrochloric acid was added. The
mixture was heated to boiling, and the remaining ethanol was
evaporated. Upon cooling, the white solid that formed was collected,
washed with water, and dried to give 13.0 g (26 mmol) of the nearly
resolved binaphthol phosphoric acid (-)-44. This material was
converted to (+)-39 by the procedure described above for (-)-39.
Purification of (+)-39 was accomplished by chromatography on silica
gel with a 1:9 mixture of EtOAc-hexane. As the fractions of 39 were
collected, a small amount of crystals came out of solution which were
1288 m, 1246 m, 1131 w, 1075 w, 1023 m, 900 m, 750 s, 697 s cm-1
.
A small portion of acid 49 (0.162 g, 0.27 mmol) was converted to
the methyl ester 52 with CH2N2 by the procedure described above for
the preparation of 46. The product was purified on a silica gel column
with a 1:5 mixture of EtOAc:hexane to give 0.1106 g (0.18 mmol,
67% yield) of the biphenanthrol methyl phosphate 52 as a white solid.
Spectral data for 52: Rf ) 0.12 (1:5 EtOAc:hexane); white solid mp
> 300 °C; 1H NMR (CDCl3) δ 3.76 (d, 3 H, JP-H ) 11.6 Hz), 6.46 (d,
2 H, J ) 7.4 Hz), 6.50 (d, 2 H, J ) 7.8 Hz), 6.91 (m, 4 H), 7.05 (m,
2 H), 7.539 (s, 1 H), 7.54 (s, 1 H), 7.63-7.79 (m, 8 H), 7.92 (d, 1 H,
J ) 7.8 Hz), 7.95 (d, 1 H, J ) 8.1 Hz), 9.51 (d, 1 H, J ) 8.6 Hz), 9.59
(d, 1 H, J ) 8.6 Hz); 13C NMR (CDCl3) δ 56.19 (d, JP-C ) 5.4 Hz),
121.19, 121.24, 121.76, 121.80, 125.54, 125.56, 125.65, 125.68, 126.63,
126.72, 126.78, 127.12, 127.19, 127.41, 127.48, 127.63, 127.66, 127.78,
127.92, 128.16, 128.65, 128.92, 128.97, 129.01, 129.17, 129.39, 133.31,
133.41, 134.50, 134.80, 139.31, 141.15, 141.32, 146.74, 147.64, 147.80;
IR (neat) 3056 m, 2957 w, 2851 w, 1611 w, 1590 w, 1442 m, 1379 m,
1298 s, 1231 m, 1125 w, 1045 s, 1021 s, 911 s, 895 m, 868 m, 813 m,
732 s, 697 s cm-1; mass spectrum, m/z) (rel intensity), 614 (100) M+,
520 (15), 443 (5), 268 (7), 221 (6); exact mass calcd for C41H27O4P
m/z 614.1647, found m/z 614.1619. Anal. Calcd for C41H27O4P: C,
80.12; H, 4.43; P, 5.04. Found: C, 80.03; H, 4.59; P, 4.88.
1
collected to give 0.45 g of material that by H NMR (CDCl3) in the
presence of the chiral shift reagent Eu(hfc)3 was determined to be a
mixture of (-)-39 and (+)-39. Removal of solvent from the filtrate
from all of the fractions and drying of the residue gave 8.27 g (18.9
mmol, 70% from racemic 39) of optically pure binaphthol (+)-39: [R]D
) 362.0 (c ) 1.0, THF). The optical purity of (+)-39 was determined
1
to be greater than 98% by H NMR in CDCl3 with Eu(hfc)3 ((-)-39
could not be detected). The optical purity of (+)-39 was determined
to be greater than 99% by HPLC under the conditions described for
(-)-39.
The Preparation of 3,3′-Biphenanthrol 47 by Oxidative Coupling
of Phenanthrol 28 with Air. A mixture of 28 (9.94 g, 36.8 mmol)
and glass beads (∼50 beads) in a beaker (800 mL) was stirred with a
large magnetic stirring bar until a uniform layer of 28 (∼2 mm thick)
had formed on each bead. The resulting mixture was heated to 190
°C in air with continuous stirring. After 18 h, the reaction mixture
was allowed to cool to 25 °C, and the resulting dark solid layer was
ground to break up the fused coated-bead particles and then suspended
in EtOAc (∼25 mL). The beaker was covered with a watch glass and
slowly lowered back into the 190 °C oil bath to prevent spattering as
the ethyl acetate was boiled off. The reaction was monitored while
being heated at 190 °C for 16 h to ensure that continuous stirring was
maintained. An 1H NMR analysis revealed complete consumption of
starting material. The resulting dark brown reaction mixture was
extracted with EtOAc (4 × 100 mL), and the combined EtOAc layer
was filtered through filter paper and stripped of solvent to afford bis-
(phenanthrol) 47 (8.78 g, 9.89 g theor, 89%) as a light-brown solid.
This material was pure by 1H NMR and was used directly in the
resolution with (-)-cinchonidine. Further purification could be
achieved by crystallization from EtOAc. If continuous stirring was
not maintained during the reaction or if enough surface area was not
The Resolution of 2,2′-Diphenyl-[3,3′-biphenanthrene]-4,4′-diol
(47). Preparation of Salts 50 and 51 from Acid 49 and (-)-
Cinchonidine. To a solution of acid 49 (17.8 g, 29.6 mmol) in 300
mL of ethanol was added (-)-cinchonidine (8.73 g, 29.6 mmol). The
solution was heated to the boiling point to ensure complete dissolution
of all solids and then allowed to cool on the benchtop for 12 h. Crystals
were collected and shown by 1H NMR to be salt 50. The mother
solution was concentrated on a rotary evaporator to the saturation point
and then allowed to sit at room temperature for a few hours. The
1
crystals that were collected were shown by H NMR to be salt 51. In
both cases, the enrichment was greater than 40:1. The filtrate was
concentrated again to give additional crystals of salt 50. This process
was repeated until there was 2.67 g of a mixture of salts left which by
1H NMR was shown to consist of 50 and 51 in a 1:4 ratio. Salt 50:
1H NMR (CDCl3) δ 0.85-0.95 (m, 1H), 1.25-1.30 (m, 1H), 1.50-
1.60 (m, 1H), 1.65-1.75 (m, 2H), 1.91-1.95 (m, 2H), 2.21-2.23 (m,
1H), 2.45-2.55 (m, 1H), 2.73-2.83 (m, 2H), 4.10 (m, 1H), 4.70 (d,
1H, J ) 17.1 Hz), 4.83 (d, 1H, J ) 10.3 Hz), 5.08-5.12 (m, 1H), 5.92
(br s, 1H), 6.37 (br s, 1H), 6.49 (d, 4H, J ) 7.8 Hz), 6.77 (t, 1H, J )
7.7 Hz), 6.85 (t, 4H, J ) 7.6 Hz), 7.01 (t, 2H, J ) 7.3 Hz), 7.15 Hz,
(t, 2H, J ) 7.4 Hz), 7.58 (s, 2H), 755-7.61 (m, 7H), 7.75 (d, 1H, J )
8.4 Hz), 8.67 (d, 1H, J ) 4.4 Hz), 10.03 (d, 2H, J ) 8.6 Hz). Salt 51:
1H NMR (CDCl3) δ 1.02-1.05 (m, 1H), 1.30-1.40 (m, 1H), 1.65-
1
provided, small amounts of side products could be observed by H
NMR. Spectral data for 47: white solid; mp > 250 °C; Rf ) 0.29
1
(1:9 EtOAc:hexane); H NMR (CDCl3) δ 6.59 (s, 2 H), 6.66 (d, 4 H,
J ) 7.7 Hz), 6.93 (t, 4 H, J ) 7.5 Hz), 7.04 (t, 2 H, J ) 7.4 Hz), 7.42
(s, 2 H), 7.61 (t, 2 H, J ) 7.3 Hz), 7.64-7.67 (m, 4 H), 7.79 (d, 2 H,
J ) 8.8 Hz), 7.91 (d, 2 H, J ) 7.7 Hz), 9.71 (d, 2 H, J ) 8.4 Hz); 13
C

Synthesis of Vaulted Biaryls
J. Am. Chem. Soc., Vol. 118, No. 14, 1996 3405
1.72 (m, 1H), 1.65-1.73 (m, 2H), 2.04-2.07 (m, 1H), 2.18-2.19 (m,
1H), 2.40-2.50 (m, 3H), 3.10-3.15 (m, 1H), 4.05-4.15 (m, 1H), 4.75
(d, 1H, J ) 17.2 Hz), 4.81 (d, 1H, J ) 10.4 Hz), 5.22-5.32 (m, 1H),
6.33 (s, 1H), 6.40 (br s, 1H), 6.55 (d, 4H, J ) 7.4 Hz), 6.89 (t, 4H, J
) 7.6 Hz), 6.98 (t, 2H, J ) 7.8 Hz), 7.04 (t, 2H, J ) 7.3 Hz), 7.36-
7.31 (m, 4H), 7.48 (s, 2H), 7.59-7.68 (m, 6H), 7.75 (d, 2H, J ) 7.8
Hz), 8.11 (d, 1H, J ) 7.7 Hz), 8.35 (d, 1H, J ) 7.9 Hz), 8.72 (d, 1H,
J ) 5.0 Hz), 9.94 (d, 2H, J ) 8.6 Hz).
methylbenzylamine was added. The solution was stirred for 24 h, and
then it was diluted with dichloromethane, was washed with water and
brine, and dried with anhydrous MgSO4. Upon removal of solvent,
the residue was loaded onto a silica gel column and eluted with a 1:4
mixture of EtOAc:hexane to give, in order of elution, 0.0385 g (0.062
mmol, 15%) of acid chloride 48, 0.1014 g (0.14 mmol, 35% yield) of
(S,S)-54, and 0.1146 g of an unidentified compound. Crystals were
grown from a solution of (S,S)-54 in CH2Cl2, and an X-ray crystal
structure was obtained which revealed that the chiral axis in this
compound has an S configuration and the details have been previously
published.30a Spectral data for 48: Rf ) 0.57 (1:2 EtOAc:hexane); 1H
NMR (CDCl3) δ 6.46 (d, 2 H, J ) 7.5 Hz), 6.49 (d, 2 H, J ) 7.5 Hz),
6.90 (t, 4 H, J ) 7.4 Hz), 7.05-7.09 (m, 2 H), 7.59 (d, 2 H, J ) 5.2
Hz), 7.65-7.84 (m, 8 H), 7.94 (t, 2 H, J ) 7.9 Hz), 9.49 (d, 1 H, J )
9.0 Hz), 9.51 (d, 1 H, J ) 8.8 Hz); 13C NMR (CDCl3) δ 126.45, 126.54,
126.97 (two carbons), 127.47, 127.59, 127.75 (two carbons), 127.80,
127.89, 127.96, 128.09, 128.49, 128.56, 128.76, 128.80, 128.91, 128.93,
129.06, 129.40 (two carbons), 129.46, 129.69, 129.83, 133.52, 134.81,
134.99, 139.00, 139.08, 141.28, 141.39, 141.42 (4 carbons not located);
IR (neat) 3076 w, 3048 m, 1613 w, 1597 w, 1384 w, 1319 m, 1302 s,
1230 m, 1119 m, 1051 w, 1017 m, 917 s, 910 s, 868 m, 825 m, 780 w,
748 m, 738 s, 697 s cm-1; mass spectrum, m/z (rel intensity), 618 (1)
M+, 490 (12), 467 (7), 415 (5), 372 (18), 121 (100), 105 (24). Spectral
Biphenanthrol (+)-47 from Salt 50. All crops of salt 50 were
combined and recrystalized from ethanol. The 1H NMR and 31P NMR
spectra of the salt 50 indicated that the purity was greater than 98%.
The salt 50 was then treated with 6 N aqueous HCl solution and heated
to reflux for 1 h. The white solid that formed was collected and dried
under high vacuum to give 7.08 g (11.8 mmol, 80% yield) of the
resolved acid 49. All of this acid was dissolved in 100 mL of N,N-
dimethylacetamide, and then sodium bicarbonate (1.97 g, 23.4 mmol)
and dimethyl sulfate (2.23 mL, 23.4 mmol) were added. The solution
was stirred at room temperature for 20 h, and then the solvent was
removed by rotary evaporator at 55 °C. The residue was dissolved in
dichloromethane and was washed wtih aqueous saturated sodium
bicarbonate, water, and brine. After it was dried over MgSO4 and
stripped of all volatiles, the ester was dissolved in 150 mL of toluene,
and then Red-Al (12.5 mL, 42.5 mmol as a 3.4 M solution in toluene)
was added. The solution was allowed to stir at room temperature for
10 h and then was diluted with ethyl acetate and quenched with 1 N
aqueous HCl. The organic layer was washed with aqueous saturated
sodium bicarbonate, water, and brine and then dried (MgSO4). After
removal of solvent, the residue was loaded onto a silica gel column
and eluted with a 1:5 mixture of EtOAc:hexane to give 6.36 g (11.8
mmol, 99% yield) of resolved bisphenanthrol (+)-47 as a white
crystalline solid: [R]D ) 124.96 (c ) 1.0, THF). The optical purity
of (+)-47 was determined to be greater than 98% by 1H NMR with an
excess of (S)-(-)-R-methylbenzylamine as chiral shift reagent (no
detectable amount of (-)-47 was present). The optical purity by HPLC
was found to be greater than 99.8% by using a Pirkle D-phenylglycine
colum with the following conditions: 254 nm, 148 psi, 1.5 mL/min,
60:40 mixture of 2-propanol and hexane (tR ) 19.8 min for (+)-47
and tR ) 12.1 min for (-)-47). The configuration of (+)-47 was
determined to be S by its conversion to the amide (S,S)-54 with (S)-
1-phenylethyl amine as described below. It was also noted that the
racemate of 47 and the pure enanatiomers of 47 eluted with different
rates on a silica gel column. The elution by flash chromatography on
silica gel with a 1:1 mixture of methylene chloride and hexanes of a
sample of 47 with an optical purity of 89.7% ee into four fractions
gave a distribution of optical purities which in order of elution where
95.6%, 90.7%, 88.8%, and 82.9%.
Enrichment of (S)-3,3′-Biphenanthrol (+)-47 by Hexane Extrac-
tion. The following experiment illustrates that essentially optically pure
47 can be obtained from a scalemate by simple washing with hexane.
A 150 mg sample of 47 that was enriched in (+)-47 to 83.8% ee was
washed with three 5 mL portions of hexane. The combined hexane
layer was filtered, the filtrate was found to contain 89.6 mg of (+)-47
of greater than 99.8% ee, and the remaining solid consisted of 57.5
mg of (+)-47 of 56.5% ee.
Biphenanthrol (-)-47 from Salt 51. All crops of salt 51 were
combined and recrystallized once from ethanol to give material that
1H NMR indicated was greater than 98% free of salt 50. The salt 51
was then converted to (-)-47 with the procedure described above for
(+)-47. The (-)-47 obtained was purified on silica gel (1:5 mixture
of EtOAc/hexane) to give 5.75 g (10.7 mmol, 72% from racemic 47)
of bis(phenanthrol) (-)-47 as a white solid: [R]D ) -123.37 (c )
1.0, THF). The optical purity of (-)-47 was determined to be greater
than 98% by 1H NMR with an excess of (S)-(-)-R-methylbenzylamine
as chiral shift reagent (no detectable amount of (+)-47 was present).
The optical purity by HPLC was found to be greater than 99.9%
utilizing the conditions described for the analysis of (+)-47.
1
data for (S,S)-54: Rf ) 0.38 (1:2 EtOAc:hexane); mp > 250 °C; H
NMR (CDCl3) δ 0.89 (d, 3 H, J ) 6.8 Hz), 3.11 (dd, 1 H, J ) 9.6,
11.6 Hz), 4.54-4.59 (m, 1 H), 6.46 (d, 2 H, J ) 7.4 Hz), 6.50 (d, 2 H,
J ) 7.4 Hz), 6.87-6.91 (m, 4 H), 7.03-7.09 (m, 4 H), 7.15-7.21 (m,
3 H), 7.39 (t, 1 H, J ) 8.3 Hz), 7.52 (d, 2 H, J ) 7.8 Hz), 7.57 (t, 1
H, J ) 7.5 Hz), 7.63-7.67 (m, 3 H), 7.75-7.79 (m, 3 H), 7.87 (d, 1
H, J ) 8.1 Hz), 7.90 (d, 1 H, J ) 8.2 Hz), 9.40 (d, 1 H, J ) 8.7 Hz),
9.75 (d, 1 H, J ) 8.6 Hz); 13C NMR (CDCl3) δ 24.43 (d, J ) 7.0 Hz),
52.24, 121.50, 121.54, 121.88, 121.92, 125.28, 125.56, 125.61, 126.30,
126.33, 126.61, 126.74, 126.90, 126.98, 127.13, 127.21, 127.55, 127.60,
127.65, 127.81, 128.25, 128.41, 128.77, 128.82, 129.01, 129.21, 129.24,
129.32, 129.39, 133.18, 133.31, 134.44, 134.46, 134.60, 134.61, 139.41,
139.48, 140.99, 141.01, 141.34, 141.35, 144.52, 144.56, 146.90, 147.02,
147.43, 147.57; IR (neat) 3366 w, 3175 w, 3057 m, 3031 w, 2968 w,
2925 m, 2855 w, 2246 w, 1616 w, 1598 w, 1557 w, 1494 w, 1487 w,
1450 w, 1423 w, 1375 m, 1330 w, 1283 s, 1232 s, 1206 w, 1120 m,
1075 m, 1053 s, 1024 s, 989 m, 902 s, 847 s, 813 m, 781 w, 731 s,
697 s, 645 m cm-1; mass spectrum, m/z (rel intensity), 703 (8) M+,
199 (100), 149 (25), 97 (40), 83 (43), 69 (69); exact mass calcd for
C48H34O3NP, m/z, 703.2276, found m/z 703.2269.
The same procedure was carried out on racemic 47 (0.38 mmol) to
provide a sample of (R,S)-54 (18%) and also an 11% yield of the less
polar (S,S)-54. Spectral data for (R,S)-54: Rf ) 0.26 (1:2 EtOAc:
hexane); 1H NMR (CDCl3) δ 0.73 (d, 3 H, J ) 7.0 Hz), 3.36 (dd, 1 H,
J ) 9.0, 12.0 Hz), 3.57-3.62 (m, 1 H), 6.44 (d, 2 H, J ) 7.5 Hz), 6.50
(d, 2 H, J ) 7.5 Hz), 6.82 (d, 2 H, J ) 7.1 Hz), 6.88-6.91 (m, 4 H),
7.03-7.11 (m, 6 H), 7.44-7.48 (m, 2 H), 7.55-7.77 (m, 6 H), 7.81
(d, 1 H, J ) 8.8 Hz), 7.84 (d, 1 H, J ) 7.5 Hz), 7.93 (d, 1 H, J ) 7.3
Hz), 8.95 (d, 1 H, J ) 8.6 Hz), 9.77 (d, 1 H, J ) 8.5 Hz).
Acknowledgment. This work was supported by the National
Institutes of Health (PHS-GM 45326) and by the National
Science Foundation (CHE-8821326). We thank Amoco for a
summer fellowship for J.B.D. and the NSF for summer
fellowships for M.C.W. and M.J.F. The NMR instruments used
were funded in part by the NSF Chemical Instrumentation
Program.
Supporting Information Available: X-ray data for com-
pound 45, including fractional coordinates, isotropic and aniso-
tropic thermal parameters, and bond distances and bond angles;
listing of observed and calculated structure factors (15 pages).
This material is contained in many 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.
The Preparation of Phosphoric Amide (S,S)-54 from the Resolved
Biphenanthrol (+)-47. To a solution of resolved bis(phenanthrol) (+)-
47 (0.220 g, 0.41 mmol) in 4 mL of methylene chloride at ambient
temperature were added triethylamine (0.137 mL, 0.98 mmol) and
phosphorus oxychloride (0.053 mL, 0.57 mmol). After the solution
was stirred for 1 h at 25 °C, it was cooled to 0 °C and (S)-R-
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