Expeditious procedure to synthesize ethers and esters of tri- and tetrahydroxy[6]helicenebisquinones from the dye-intermediates disodium 4-hydroxy- and 4,5-dihydroxynaphthalene-2,7-disulfonates

Article abstract of DOI:10.1021/jo001356w

A procedure is described for synthesizing appreciable quantities of both the tetradodecyloxy[6]helicenebisquinone 1 (R = dodecyl), which exhibits unique optical properties but previously was difficult to prepare, and a variety of analogues. The synthesis starts from disodium 4,5-dihydroxynaphthalene-2,7-disulforiate, the commercially available dye-intermediate known as chromotropic acid. It gives enantiopure 1, with R = (i-Pr)₃Si, whose silyl groups can be replaced by dodecyl and hexanoyl groups. The same procedure applied to disodium 4-hydroxynaphthalene-2,7-disulfonate, also an inexpensive, commercially available chemical, works equally well to produce the corresponding molecules that have one fewer side chain. Key steps are the use of tosyl groups to protect phenols and of a method described seven years ago by Satoh, Itoh, Miura, and Nomura to transform the sulfonic acid functions to iodides. The structure of tetra-(1S)-camphanate 20, the ester of the reduction product of (-)-1 [R = (i-Pr)₃Si], was analyzed by X-ray diffraction. It shows the absolute configurations and supports the presumed basis for the rule that the (1S)-camphanates of (P)-helicen-1-ols are more polar than their (M)-diastereomers.

Full text of DOI:10.1021/jo001356w

8774
J . Org. Chem. 2000, 65, 8774-8782
Exp ed itiou s P r oced u r e To Syn th esize Eth er s a n d Ester s of Tr i-
a n d Tetr a h yd r oxy[6]h elicen ebisqu in on es fr om th e
Dye-In ter m ed ia tes Disod iu m 4-Hyd r oxy- a n d
4,5-Dih yd r oxyn a p h th a len e-2,7-d isu lfon a tes†
Kamil Paruch,‡ Libor Vyklicky´,‡ Thomas J . Katz,*,‡ Christopher D. Incarvito,§ and
Arnold L. Rheingold§
Department of Chemistry, Columbia University, New York, New York 10027, and Department of
Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716
tjk1@columbia.edu
Received September 13, 2000
A procedure is described for synthesizing appreciable quantities of both the tetradodecyloxy[6]-
helicenebisquinone 1 (R ) dodecyl), which exhibits unique optical properties but previously was
difficult to prepare, and a variety of analogues. The synthesis starts from disodium 4,5-
dihydroxynaphthalene-2,7-disulfonate, the commercially available dye-intermediate known as
chromotropic acid. It gives enantiopure 1, with R ) (i-Pr)3Si, whose silyl groups can be replaced by
dodecyl and hexanoyl groups. The same procedure applied to disodium 4-hydroxynaphthalene-2,7-
disulfonate, also an inexpensive, commercially available chemical, works equally well to produce
the corresponding molecules that have one fewer side chain. Key steps are the use of tosyl groups
to protect phenols and of a method described seven years ago by Satoh, Itoh, Miura, and Nomura
to transform the sulfonic acid functions to iodides. The structure of tetra-(1S)-camphanate 20, the
ester of the reduction product of (-)-1 [R ) (i-Pr)3Si], was analyzed by X-ray diffraction. It shows
the absolute configurations and supports the presumed basis for the rule that the (1S)-camphanates
of (P)-helicen-1-ols are more polar than their (M)-diastereomers.
Sch em e 1
In tr od u ction
It is unfortunate that of all the helicenes, molecule 1
(R ) dodecyl) was found to exhibit the previously
unknown properties of self-assembly into helical colum-
nar stacks as well as a high second-order nonlinear
optical response owing to the chirality of the assembly.1
It is unfortunate because 1 is much harder to synthesize1a,b
than related structures such as 2 and 3 (R ) dodecyl).2,3
methyl ketone with 1,4-benzoquinone.1b,4 That reaction
works well for all three of these molecules. The problem
is that, as outlined in Scheme 1, 10 steps are required
from a commercially available material (dehydroacetic
acid) to synthesize the precursor of 1, structure 4.
There is a second difficulty. After the helicene skeleton
is constructed, it has been impossible to alter the alkyl
groups that were incorporated from 4. Attempts to
overcome the problem by replacing them with protecting
groups were only partially successful. When the protect-
ing groups were pivalates, the yield of the transformation
that led to the helicene was very poor.1a,b
The problem is not the key step that builds the helicene
skeleton, the reaction of an enol ether of an aryl bis-
Only few known naphthalenes have the required
substitution pattern. 2,7-Dimethyl-4,5-dihydroxynaph-
thalene is available in three steps from dehydroacetic
acid.5 Naphthalic anhydride derivatives 5 (X ) NO2 and
† Dedicated to Dr. Alfred P. Bader in appreciation of his support
for Czech students.
‡ Columbia University.
§ University of Delaware.
(1) (a) Nuckolls, C.; Katz, T. J .: Castellanos, L. J . Am. Chem. Soc.
1996, 118, 3767. (b) Nuckolls, C.; Katz, T. J .; Katz, G.; Collings, P. J .;
Castellanos, L. J . Am. Chem. Soc. 1999, 121, 79. (c) Lovinger, A. J .;
Nuckolls, C.; Katz, T. J . J . Am. Chem. Soc. 1998, 120, 264. (d) Nuckolls,
C.; Katz, T. J .; Verbiest, T.; Van Elshocht, S.; Kuball, H.-G.; Kiese-
walter, S.; Lovinger, A. J .; Persoons, A. J . Am. Chem. Soc. 1998, 120,
8656. (e) Verbiest, T.; Van Elshocht, S.; Kauranen, M.; Hellemans, L.;
Snauwaert, J .; Nuckolls, C.; Katz, T. J .; Persoons, A. Science (Wash-
ington, DC) 1998, 282, 913. (f) Busson, B.; Kauranen, M.; Nuckolls,
C.; Katz, T. J .; Persoons, A. Phys. Rev. Lett. 2000, 84, 79.
(2) Dreher, S. D.; Paruch, K.; Katz, T. J . J . Org. Chem. 2000, 65,
806.
(3) (a) Paruch, K.; Katz, T. J .; Incarvito, C.; Lam, K.-C.; Rhatigan,
B.; Rheingold, A. L. J . Org. Chem. 2000, 65, 7602. (b) Fox, J . M.;
Goldberg, N. R.; Katz, T. J . J . Org. Chem. 1998, 63, 7456.
(4) (a) Katz, T. J .; Liu, L.; Willmore, N. D.; Fox, J . M.; Rheingold,
A. L.; Shi, S.; Nuckolls, C.; Rickman, B. H. J . Am. Chem. Soc. 1997,
119, 10054. (b) Dreher, S. D.; Weix, D. J .; Katz, T. J . J . Org. Chem.
1999, 64, 3671. (c) Dreher, S. D.; Katz, T. J .; Lam, K.-C.; Rheingold,
A. L. J . Org. Chem., 2000, 65, 815.
(5) Overeem, J . C.; van der Kerk, G. J . M. Recl.: J . R. Neth. Chem.
Soc. 1964, 83, 1005.
10.1021/jo001356w CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/21/2000

Synthesis of Tri- and Tetrahydroxy[6]helicenebisquinones
J . Org. Chem., Vol. 65, No. 25, 2000 8775
SO3H) are obtained by nitrating6 and sulfonating7 1,8-
naphthalic anhydride and can be transformed into de-
rivatives such as 5 (X ) OH and Cl).7 The structurally
related 5 (X ) CO2H) has been prepared from mesity-
lene.8 1,3,6,8-Tetrahydroxynaphthalene has been made
from methyl 3,5-dihydroxybenzoate as well as from
chromotropic acid (see below).9 And chromotropic acid (6)
can be made by hydrolyzing 1-aminonaphthalene-3,6,8-
trisulfonic acid (“Koch-acid” in the dye industry).10 The
first of these was used previously to prepare 4, but the
last looked like an attractive alternative because to
install the required functional groups seemed easy and
because chromotropic acid is commercially available and
inexpensive. However, although this acid has the correct
substitution pattern, with oxygens correctly positioned,
the only transformations it is known to undergo are two
O-diacylations,11 two O-monoalkylations,12 alkali fusion
to give 1,3,6,8-tetrahydroxynaphthalene,9b and a number
of electrophilic substitutions, mainly diazo-couplings
ortho to the hydroxyls. None of these appear useful in
advancing the structure toward the goal.
Sch em e 2
Sch em e 3a
a
Reaction conditions and yields: (a) Ac2O, NaOH, H2O (40%);
(b) (t-Bu)2SiCl2, 1-hydroxybenzotriazole, Et3N, DMF (53%); (c)
TsCl, Na2CO3, H2O (55%); (d) SOCl2, DMF (small amount), reflux
(89-92%); (e) ZnI2, LiCl, Ti(O-i-Pr)4, PdCl2(PhCN)2 (2.6 mol %),
diglyme, 155 °C (yield of 10b, 31%; of 10c, 52%).
vinyl groups,15 or iodine16sor without, this last giving the
aryl chlorides.17 Of these transformations, those produc-
ing the aryl halides are particularly attractive because
if applied to chromotropic acid (6), further transformation
of the halogen substituents into acetyl groups would
complete the synthesis (Scheme 2).
However, before the sulfonic acid can be converted into
its acid chloride, the hydroxyl groups must be protected.
But no diethers of chromotropic acid are known, and a
number of attempts to prepare them failed.12 Among the
reagents we tried were the following: Me2SO418 and MeI
in the presence of KOH or K2CO3; Ph2CCl2, TIPSOTf, and
Ph2SiCl2 in the presence of triethylamine; Et3OSbCl6;19
and methanolic HCl.2,4c Experiments that did succeed
(Scheme 3) gave the following: the diacetate (8a , in 40%
yield) when chromotropic acid was treated with Ac2O in
aqueous NaOH;11b the cyclic silyl ether (8b, in 53% yield)
when the acid was treated with (t-Bu)2SiCl2, triethyl-
amine, and 1-hydroxybenzotriazole in DMF; and the di-
tosylate (8c, in 55% yield) when the acid was treated with
tosyl chloride in aqueous sodium carbonate. All of these
were converted into their sulfonyl chlorides, 9a -c.
Accordingly (Scheme 3), 9a -c were subjected to the
conditions of desulfonylative iodination reported by Sa-
toh, Itoh, Miura, and Nomura.16 Compound 9c was found
to undergo the transformation in the highest yield (52%).
Siloxane 9b gave a 31% yield, while diacetate 9a gave
no recognizable products. Because the yield is higher and
the cost less, the tosylate was used for the synthesis in
preference to the silyl ether.
In this paper, we describe a way to convert chromo-
tropic acid into 4, R ) TIPS, and then into enantiopure
1, R ) TIPS. The transformations are efficient, and the
product has the flexibility to act as the precursor for
derivatives of 1 that are substituted by a variety of alkyl
and ester groups. Similar procedures convert disulfonic
acid 7, also an inexpensive, commercially available
chemical, into the corresponding [6]helicenebisquinones
that have three substituents in place of the four in 1.
Resu lts
The essential step to convert chromotropic acid (6) into
4 is to replace the sulfonic acid functions with acetyl
groups. Although it is known that related transforma-
tions, in which aryl-sulfur bonds are replaced by aryl-
carbon bonds, can be brought about directly by fusing
the salts of arylsulfonic acids with KCN, the yields are
low.13 However, with the aid of noble metal catalysts, the
chlorides of arylsulfonic acids can be desulfonated, either
with incorporation of other groupsscarbon monoxide,14
(6) Bell, F. J . Chem. Soc. 1952, 1952 and references therein.
(7) (a) Dziewoski, K.; Majewicz, T.; Schimmer, L. Bull. Intern. Acad.
Polon. Sci., Classe Sci. Math. Nat. 1936A, 43. (b) Tse, B.; Kishi, Y. J .
Org. Chem. 1994, 59, 7807.
(8) (a) Canonne, P.; Holm, P.; Leitch, L. C. Can. J . Chem. 1967, 45,
2151. (b) Canonne, P.; Leitch, L. C. Can. J . Chem. 1967, 45, 1761.
(9) (a) Ichinose, K.; Ebizuka, Y.; Sankawa, U. Chem. Pharm. Bull.
1989, 37, 2873. (b) Tanaka, H.; Ohne, Y.; Ogawa, N.; Tamura, T. Agr.
Biol. Chem. 1963, 27, 48.
As summarized in Scheme 4, KOH in refluxing EtOH
removes the tosyl groups from 10c, and subsequent
treatment with TIPSOTf and Et3N in refluxing dichloro-
(14) (a) Satoh, T.; Itoh, K.; Miura, M.; Nomura, M. J . Mol. Catal.
1993, 83, 125. (b) Itoh, K.; Hashimoto, H.; Miura, M.; Nomura, M. J .
Mol. Catal. 1990, 59, 325.
(10) (a)Venkataraman, K. The Chemistry of Synthetic Dyes; Aca-
demic Press: New York, 1952; pp 167, 171, and 190-191. (b) Rathi,
A. K. A.; Puranik, S. A. Chem. Eng. World 1995, 30, 91.
(11) (a) Mohan, P.; Singh, R.; Baba, M. Drug. Des. Discovery 1991,
8, 69. (b) Georghiou, P. E.; Ho, C. K.; J ablonski, C. R. Can. J . Chem.
1991, 69, 1207.
(12) Ethylation with EtOSO3Na and benzylation with PhCH2Cl:
Farbenfabriken Bayer & Co. Patent DE 73741, issued 15 February
1894.
(15) (a) Miura, M.; Hashimoto, H.; Itoh, K.; Nomura, M. J . Chem.
Soc., Perkin Trans. 1 1990, 2207. (b) Kasahara, A.; Izumi, T.; Kudou,
N.; Azani, H.; Yamamoto, S. Chem. Ind. (London) 1988, 51.
(16) Satoh, T.; Itoh, K.; Miura, M.; Nomura, M. Bull. Chem. Soc.
J pn. 1993, 66, 2121.
(17) (a) Blum, J . Tetrahedron Lett. 1966, 3041. (b) Blum, J .; Scharf,
G. J . Org. Chem. 1970, 35, 1895.
(18) For the methylation of 7, see: Blangley, L.; Fierz-David, H. E.;
Ulrich, J . C.; Bretscher, K. Helv. Chim. Acta 1951, 34, 501.
(19) Meerwein, H. In Methoden der Organischen Chemie (Houben-
Weyl); Muller, E., Ed.; Georg Thieme Verlag: Stuttgart, 1965; Vol 6/3,
p 342.
(13) Friedrich, K.; Wallenfels, K. In The Chemistry of the Cyano
Group; Rappoport, Z., Ed.; Interscience Publishers: New York, 1970;
p 84.

8776 J . Org. Chem., Vol. 65, No. 25, 2000
Paruch et al.
Sch em e 4a
Sch em e 6a
a
Reaction conditions and yields: (a) (i) KOH, EtOH, reflux; (ii)
TIPSOTf, Et3N, (CH2Cl)2, reflux (80%); (b) n-BuLi, then N-
methoxy-N-methylacetamide, Et2O, -100 °C to +25 °C (66%); (c)
TIPSOTf, Et3N, CH2Cl2 (100%); (d) 1,4-benzoquinone, PhCH3, 90
°C (40%).
a
Sch em e 5a
Reaction conditions and yields: (a) Zn, (1S)-camphanoyl
chloride, DMAP, Et3N, CH2Cl2 [79% of (P)-20, 75% of (M)-20; 67%
of (P)-21, 74% of (M)-21]; (b) (i) MeLi, Et2O, -78 °C to +25 °C,
then aqueous NH4Cl; (ii) chloranil [87% of (P)-1, 88% of (M)-1;
61% of (P)-19, 73% of (M)-19]; (c) C12H25I, CsF, DMF, 60 °C [58%
of 1, 61% of 19]; (d) C5H11COCl, CsF, DMAP, DMF, 25 °C [68% of
1, 71% of 19].
lithium removes the camphanates from the individual
diastereomers and chloranil oxidizes the resulting hyd-
roquinones, enantiopure 1 and 19 (R ) TIPS) can be
prepared in gram quantities.
As Scheme 6 also shows, replacing the TIPS groups in
1 by dodecyl groups gives the tetraether, identical with
that synthesized previously,1a,b and replacing the TIPS
groups in 19 gives a new triether analogue. The reagents
are dodecyl iodide and CsF in DMF,22 a combination used
previously for related transformations.3 The yields are
58 and 61%, respectively. Similarly, when the reagents
are hexanoyl chloride, CsF, and DMAP in DMF, hexanoyl
groups replace the four TIPS groups of 1 and the three
of 19. The yields are 68-71%.
a
Reaction conditions and yields: (a) TsCl, Na2CO3, H2O (55%);
(b) SOCl2, DMF (72%); (c) ZnI2, LiCl, Ti(Oi-Pr)4, PdCl2(PhCN)2 (3
mol %), diglyme, 160 °C (46%); (d) (i) KOH, EtOH, reflux; (ii)
TIPSOTf, Et3N, CH2Cl2 (77%); (e) n-BuLi, then N-methoxy-N-
methylacetamide, Et2O, -100 °C to +25 °C (52%); (f) TIPSOTf,
Et3N, CH2Cl2 (100%); (g) 1,4-benzoquinone, PhCH3, 90 °C (38%).
A crystal suitable for X-ray diffraction analysis was
grown of the less polar of the diastereomeric tetracam-
phanates 20. The analysis shows, on the basis of the
known absolute configurations of the camphanate moi-
eties,23 that this diastereomer has the (M)-configuration.
The absolute structure parameter confirms this assign-
ment. The X-ray analysis also shows the conformations
of the camphanate groups with respect to the helicene
skeletons, providing support for a hypothesis relating
these conformations, the relative polarities of diastere-
omeric helicenol camphanates, and the absolute configu-
rations of the diastereomers.3a,21 There are two molecules
in the crystal’s unit cell. Table 1 summarizes two angles
that define the conformations of both the inner and outer
camphanates with respect to the ring system in the two
independent molecules. In keeping with the usage in the
previous study of camphanate conformations,21 the two
angles are called c (the dihedral angle O1dC2-C3-O4)
and a [the dihedral angle (H)C-C-O-C(dO)]. The
structures of the two molecules, with values of the angles
c, are displayed in Figure 1.
ethane puts TIPS groups in their place. Weinreb’s
procedure20 then converts the iodides in the resulting 11
(R ) TIPS) into aryl methyl ketones. The yield of 4
(R ) TIPS) is 66%. Like other diacetylarenes,1a,b,2-4
4
when combined with TIPSOTf and Et3N in CH2Cl2 and
then with 1,4-benzoquinone in PhCH3 produces the
corresponding helicene, 1 (R ) TIPS). The yield is 40%.
When the sequence of reactions was carried out start-
ing with technical grade chromotropic acid, 200 g of 6
gave 185 g of 8c and 120 g of 8c gave 14.7 g of 1 (R )
TIPS). Thus, appreciable amounts can be made easily at
moderate cost. Similarly, disodium 4-hydroxynaphtha-
lene-2,7-disulfonate (7), which is an even cheaper chemi-
cal than chromotropic acid, was transformed into [6]-
helicenebisquinone 19 (Scheme 5). Starting from 100 g
of technical grade 7, 79 g of 13 was obtained, and this
was converted into 5.9 g of 19.
The method used to resolve the enantiomers of 1 and
19 (R ) TIPS, Scheme 6) was that used previously to
resolve the enantiomers of a [6]helicenebisquinone having
only two TIPSO side chains21 and is related to the
original procedure used to resolve the enantiomers of 1
(R ) dodecyl).1b In the case of both 1 and 19, reduction
with Zn followed by esterification with (1S)-camphanoyl
chloride and Et3N in CH2Cl2 gave diastereomeric tetra-
camphanates 20 and 21. If DMAP is added to the reaction
mixtures, the yields improve and the reaction times are
shortened. In the case of both 20 and 21, chromatography
on silica gel separates the diastereomers. Since methyl-
Discu ssion
The method of synthesis described provides a way to
prepare a helicene, 1 (R ) C12H25), whose properties are
(22) Good yields could be obtained in some of these experiments only
when the CsF was ground to a fine powder by shaking it, by means of
a Wig-L-Bug, with a glass bead.
(20) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 39, 3815.
(21) Thongpanchang, T.; Paruch, K.; Katz, T. J .; Rheingold, A. L.;
Lam, K.-C.; Liable-Sands, L. J . Org. Chem. 2000, 65, 1850.
(23) Buckingham, J .; Hill, R. A. Atlas of Stereochemistry, Absolute
Configurations of Organic Molecules, 2nd ed.; Supplement; Chapman
and Hall: New York, 1986; p 62.

Synthesis of Tri- and Tetrahydroxy[6]helicenebisquinones
J . Org. Chem., Vol. 65, No. 25, 2000 8777
Ta ble 1. Dih ed r a l An gles OdC-C-O (a n gle c) a n d
(H)C-C-O-C(dO) (a n gle a ) Defin in g, in P a r t, th e
Con for m a tion s of th e Ca m p h a n a tes w ith Resp ect to th e
Helicen e Rin g System in (M)-(-)-20a
The key step is the application of the procedure of
Satoh, Itoh, Miura, and Nomura to replace the sulfonyl
chloride groups with iodines.16 This procedure appears
not to have been applied during the 7 years since its
discovery, but in the case of the two syntheses reported
here, it certainly works well and on scales up to 30 times
those reported in the original paper.
inside
outside
c
a
c
a
-140.5
-163.7
-129.0
-29.8
106.0
104.7
94.9
151.0
150.7
-154.9
172.4
86.2
59.8
-60.0
88.0
The method described for the preparations of 1 and
19 (R ) C12H25 and C5H11CO) should also allow the TIPS
groups on the helicene structures to be replaced by other
alkyl and acyl groups.22,24 For these preparations, struc-
ture 19 should be particularly useful because such
replacements seem to take place much more easily on it
than on the more sterically hindered structure 1.
The structure displayed in Figure 1 for the two
independent molecules in the crystal’s unit cell proves
the absolute configuration of (M)-(-)-20. The structure
therefore confirms the rule that the (1S)-(-)-camphan-
ates of (P)-helicen-1-ols are always more polar than their
diastereomers.3a,21 [In the case of both 20 and 21, as in
nineteen other cases,3a,21 the (M)-helicen-1-ol’s (1S)-
camphanate has the higher Rf on silica gel.] The struc-
tures in Figure 1 also confirm the hypothesis that when
a helix has the (M)-configuration, the lactone functions
of the camphanates attached to the inside oxygens point
toward the other parts of the helicene structure, whereas
in (P)-helicene derivatives, they point outward, away
from the helicene skeleton.3a,21 The basis for the hypoth-
esis is that the favored conformations keep the methyl
groups on the camphanates’ bridges away from other
parts of the molecule.21 The camphanate moieties in all
previously analyzed (M)-helicen-1-ol (1S)-camphanates
and for three of the four in Figure 1 on the insides of the
ring structures achieve this by adopting that one of two
favored conformations in which the OdC-C-O angle
(angle c) is close to 180° and the external carbonyl group
(C2dO1 in Figure 1) points away from the helicene
skeleton.25 However, in the molecule pictured on the
bottom in Figure 1, one of these angles has the other
favored value, close to zero (in this case -29.8°).25 Yet
the conformation still has the lactone pointing toward
the inside of the molecule. The reason is that the external
carbonyl group has the alternative conformation favored
for aryl esters:25 it points into the helicene skeleton. Table
1 also makes this clear. The Figure shows that this
change is correlated with a change in the conformation
of the opposing outside camphanate. In Table 1 this is
seen as a change in the angle a from the usual ca. 90° to
-60°.
-23.0
a
The angles are listed for the camphanates attached to the
oxygens on the inside and outside of the helicene, and the first
two lines refer to one of the two independent molecules in the unit
cell, the last two to the other. Angles are in degrees.
The demonstration by the X-ray diffraction analysis
that (-)-20 has the (M)-configuration also shows that
(-)-1 (R ) TIPS, dodecyl, and hexanoyl) have the (M)-
configuration, for the chemical transformations that
produce the latter structures from (M)-(-)-20 cannot
change the stereochemistry of the ring system. In addi-
tion, the similarity (displayed in the Supporting Informa-
tion), between the CD spectra of (-)-1 (R ) TIPS) and of
(-)-19 (R ) TIPS) implies that the latter and its deriva-
tives, (-)-19 with R ) TIPS, dodecyl, and hexanoyl, also
have this absolute stereochemistry. Above, we applied
this conclusion in assigning the (M)-configuration to the
diastereomer of 21 that has the higher Rf.
F igu r e 1. Structure of (M)-(-)-20 according to X-ray diffrac-
tion analysis. The two independent molecules in the unit cell
are both displayed. The OdC-C-O dihedral angles are shown
with dark arrows for the inner camphanate groups and dotted
arrows for the outer camphanate groups. Oxygen atoms are
shown in black, carbons in white. Hydrogens and the TIPSO
groups have been omitted for clarity.
interesting. Because it gives the structure with TIPS
groups in place of dodecyls, the method also provides the
flexibility required to easily prepare derivatives that have
other side chains, and because it is much shorter than
those reported before, the synthesis provides a way to
make these materials in much larger amounts than were
previously practical. In addition, the method is suf-
ficiently general that it can be used to prepare the related
helicenes 19, which have only three side chains.
(24) Related replacements of TIPS-groups by alkyls are reported in
ref 3a,b and by acyls in ref 3a.
(25) See ref 21 and references therein.

8778 J . Org. Chem., Vol. 65, No. 25, 2000
Paruch et al.
overnight in a vacuum at 150 °C. The yield of pale rose-colored
Con clu sion s. The dye intermediate disodium 4,5-
dihydroxynaphthalene-2,7-disulfonate (chromotropic acid)
can easily be converted into an enantiopure helicene
whose properties are unique and significant, but whose
synthesis was previously difficult. Because the synthesis
gives the TIPSO-substituted helicene skeleton, it provides
the flexibility to yield numerous derivatives in which the
TIPS groups are replaced. When applied to the related
dye intermediate disodium 4-hydroxynaphthalene-2,7-
disulfonate, the procedure gives the related enantiopure
helicenes that have one fewer side chain. The X-ray
diffraction analysis of a helicene tetracamphanate identi-
fies the absolute stereochemistries and supports a hy-
pothesis relating the conformations of helicenol cam-
phanes and the relative polarities and absolute configura-
tions of their diastereomers.
solid (mp > 250 °C) was 185 g (55%): IR (KBr) 1598, 1337,
1
1250, 1177, 1047 cm-1; H NMR (DMSO-d6, 400 MHz) δ 8.13
(d, 1.4 Hz, 2H), 7.55 (d, 8.3 Hz, 4H), 7.40 (d, 1.4 Hz, 2H), 7.36
(d, 8.3 Hz, 4H), 2.36 ppm (s, 6H); 13C NMR (DMSO-d6, 75 MHz)
146.4, 145.7, 142.2, 135.0, 131.3, 129.9, 128.4, 124.2, 119.9,
119.8, 21.2 ppm; UV-vis (MeOH, c ) 6.71 × 10-5 M) λmax (log
ꢀ) 239 (3.16), 287 (3.74), 329 nm (3.16); HRMS (FAB) m/z calcd
for C24H19Na2O12S4 [M + H]+ 672.9555, found 672.9553.
Disod iu m 4-Tosyloxyn a p h th a len e-2,7-d isu lfon a te (13).
The procedure in the preceding paragraph, when applied to
disodium 4-hydroxynaphthalene-2,7-disulfonate hydrate (100
g, 0.29 mol), Na2CO3 (32 g, 0.3 0 mol), and TsCl (60 g, 0.32
mol) in 500 mL of H2O, gave 79 g (55%) of slightly pink solid
1
13: mp >250 °C; IR (KBr) 1628, 1596, 1192, 1038 cm-1; H
NMR (DMSO-d6, 400 MHz) δ 8.20 (s, 1H), 8.13 (s, 1H), 7.84
(d, 8.3 Hz, 2H), 7.78 (d, 8.8 Hz, 1H), 7.74 (dd, 8.8 and 1.4 Hz,
1H), 7.57 (d, 1.4 Hz, 1H), 7.46 (d, 8.3 Hz, 2H), 2.40 ppm (s,
3H); 13C NMR (DMSO-d6, 75 MHz) 147.6, 146.9, 146.7, 145.2,
133.6, 132.5, 131.2, 129.0, 126.8, 126.5, 125.5, 124.7, 121.8,
117.6, 22.1 ppm; UV-vis (MeOH, c ) 8.2 × 10-5 M) λmax (log
ꢀ) 227 (4.57), 231 (4.58), 235 (4.57), 274 nm (3.59); HRMS
(FAB) m/z calcd for C17H12Na3O9S3 [M + Na]+ 524.9336, found
524.9316.
Exp er im en ta l Section
Diglyme, Et2O, and PhCH3 were distilled from Na/Ph2CO,
CH2Cl2, 1,2-dichloroethane, and triethylamine from CaH2.
DMF (anhydrous), ZnI2 (98%), Zn (dust, <10 µm, 98%),
1-iodododecane (98%), and 4,5-dihydroxynaphthalene-2,7-dis-
ulfonic acid, disodium salt dihydrate (technical grade) were
purchased from Aldrich. 4-Hydroxynaphthalene-2,7-disulfonic
acid, disodium salt hydrate (technical grade), TsCl (99%), Ti-
(O-i-Pr)4 (98%), hexanoyl chloride (87%), and CsF (99%) were
purchased from Acros, TIPSOTf from GSF Chemicals, and
PdCl2(PhCN)2 from Strem Chemicals. 1,4-Benzoquinone (98%,
Aldrich) was purified by slurrying it in CH2Cl2 with two times
its weight of basic alumina, filtering it through Celite, and
drying it under a vacuum. N-Methoxy-N-methylacetamide20
and (1S)-(-)-camphanoyl chloride26 were synthesized. Chro-
matography refers to flash chromatography on silica gel.27
Disod iu m 4,5-[Di(ter t-bu tyl)silyloxy]-2,7-n a p h th a len e
Disu lfon a te (8b). Di(tert-butyl)dichlorosilane (0.13 mL, 0.6
mmol) was added to a mixture of technical-grade chromotropic
acid (200 mg, ca. 0.5 mmol), 1-hydroxybenzotriazole (HOBt,
13 mg, 0.10 mmol), Et3N (0.2 mL), and DMF (1 mL) under a
nitrogen atmosphere, and the solution was then stirred for 1
h at 25 °C. After water (ca. 15 mL) had been added and
impurities had been extracted with CH2Cl2 (2 × 10 mL), EtOH
(10 mL) and enough K2CO3 were added to form two distinct
layers. The extraction with EtOH was repeated, and the
solvent was evaporated from the combined alcoholic solutions.
The residue, after it had been dried overnight in a vacuum,
weighed 194 mg, a 60% yield of the product assuming (in
accord with the NMR spectrum) that it is a complex with two
molecules of DMF. Pure material could be obtained by shaking
this material with EtOAc, filtering, and drying at 130 °C for
4,5-Diacetoxy-2,7-n aph th alen edisu lfon yl Ch lor ide (9a).
Disodium 4,5-diacetoxy-2,7-naphthalenedisulfonate11b (155 mg,
0.35 mmol), SOCl2 (1 mL), and DMF (0.1 mL) were refluxed
for 2 h. Cold water (15 mL) was added, the mixture was
extracted with CH2Cl2 (4 × 15 mL), and the combined organic
extracts were dried over Na2SO4. A quick filtration through a
pad of silica gel, evaporation, and vacuum-drying gave 75 mg
(49%) of yellow solid. Attempts to purify it failed: 1H NMR
(CDCl3, 300 MHz) 8.69 (d, 1.8 Hz, 2H), 7.90 (d, 1.8 Hz, 2H),
2.49 ppm (s, 6H); IR (KBr) 1780, 1377, 1174 cm-1
.
4,5-[Di(ter t-b u t yl)siloxy]-2,7-n a p h t h a len ed isu lfon yl
Ch lor id e (9b). A mixture of 8b (60 mg, 0.12 mmol), SOCl2 (1
mL), and DMF (1 drop) was refluxed for 1 h. After water (10
mL) had been added and the product extracted into CH2Cl2 (2
× 10 mL), the combined organic solutions were washed with
water and dried over MgSO4, and the solvent was evaporated.
After it had been dried in a vacuum, the resulting acid chloride
(36 mg, 61% yield) was only slightly impure and was used
directly in the next step: 1H NMR (CDCl3, 400 MHz) δ 8.28
(d, 1.7 Hz, 2H), 7.62 (d, 1.7 Hz, 2H), 1.14 ppm (s, 18H); IR
(KBr) 1591, 1383, 1172, 1106 cm-1
.
4,5-[Di(ter t-bu tyl)siloxy]-2,7-d iiod on a p h th a len e (10b).
Anhydrous diglyme (1.5 mL) was added to a mixture of 9b
(33 mg, 0.044 mmol), ZnI2 (100 mg, 0.31 mmol), LiCl (3 mg,
0.05 mmol), Ti(O-i-Pr)4 (15 µL, 0.05 mmol), and PdCl2(PPh3)2
(3 mg, 4 µmol) under nitrogen. The mixture was refluxed for
24 h, poured into water, and extracted twice with petroleum
ether. The combined organic solutions were washed with water
and dried (Na2SO4), and the solvent was stripped. Preparative
TLC on silica gel (eluent: petroleum ether) gave 11 mg (31%)
of a solid, 10b: 1H NMR (CDCl3, 300 MHz) δ 7.64 (d, 1.4 Hz,
2H), 7.22 (d, 1.4 Hz, 2H) 1.11 ppm (s, 18H).
4,5-Ditosyloxyn aph th alen e-2,7-disu lfon yl Ch lor ide (9c).
DMF (3.0 mL) was added to 8c (120 g, 0.18 mol) and SOCl2
(400 mL, 5.48 mol), and in a fume hood the mixture was stirred
and refluxed for 2 h under a drying tube. The mixture was
poured carefully onto crushed ice (3 L) and filtered. The solid
was washed with cold H2O (1 L), and mixed with CH2Cl2 (2
L). The aqueous layer was extracted further with CH2Cl2 (500
mL and 300 mL), and the combined CH2Cl2 extracts were dried
over MgSO4 and filtered. The solvent was evaporated. Drying
in a vacuum at 100 °C afforded 106 g (89%) of a pale yellow
solid that was used directly in the next step.
1
2 h: mp >250 °C; H NMR (DMSO-d6, 400 MHz) δ 7.66 (d,
1.3 Hz, 2H), 7.07 (d, 1.3 Hz, 2H), 1.06 ppm (s, 18H).
Disod iu m 4,5-Ditosyloxyn a p h th a len e-2,7-d isu lfon a te
(8c). Na2CO3 (106 g, 1.00 mol) was added in portions to a
stirred solution of technical-grade chromotropic acid (200 g,
ca. 0.5 mol) in H2O (1 L) in a 5 L round-bottomed flask. The
mixture was stirred for 10 min, and TsCl (191 g, 1.00 mol)
was added in portions. The mixture was stirred for 15 h and
filtered, and the solvent was evaporated. After the residue had
been suspended in MeOH (100 mL), toluene (100 mL) was
added, and the solvents were evaporated. This treatment was
repeated two more times. The resulting solid was dried in a
vacuum at 60 °C, pulverized, shaken for 5 min with MeOH (1
L), and filtered. The solid was extracted with MeOH (2 × 1
L), and the solvent was evaporated. The resulting solid was
dried in a vacuum at 100 °C, pulverized, boiled in anhydrous
EtOH (2 L) for 30 min, and filtered. After two more extractions
with boiling EtOH (2 and 0.5 L), the insoluble solid was dried
For characterization and analysis, a sample was recrystal-
lized from 1:2 EtOAc/(CH2Cl)2. This gave a white solid: mp
219-221 °C; IR (KBr) 3074, 1590, 1382, 1344, 1193, 1179,
1
1053, 1038, 911 cm-1; H NMR (CDCl3, 400 MHz) δ 8.66 (d,
1.8 Hz, 2H), 7.73 (d, 8.4 Hz, 4H), 7.70 (d, 1.8 Hz, 2H), 7.36 (d,
8.4 Hz, 4H), 2.48 ppm (s, 6H); 13C NMR (CDCl3, 75 MHz) 146.8,
145.5, 143.1, 133.8, 130.9, 130.1, 129.1, 128.5, 128.0, 121.0,
21.0 ppm; UV-vis (CH3CN, c ) 3.84 × 10-5 M) λmax (log ꢀ)
(26) Gerlach, H.; Kappes, D.; Boeckman, R. K.; Maw, G. N. Org.
Synth. 1993, 71, 48.
(27) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

Synthesis of Tri- and Tetrahydroxy[6]helicenebisquinones
J . Org. Chem., Vol. 65, No. 25, 2000 8779
228 (4.69), 246 (4.68), 292 (3.73), 327 (3.53), 342 nm (3.58).
Anal. Calcd for C24H18Cl2O10S4: C, 43.31; H, 2.73. Found: C,
43.22; H, 2.81.
with EtOAc (1 L, 2 × 200 mL), washed with 2:1 H2O/brine (2
× 1 L) and brine (100 mL), dried over Na2SO4, and filtered.
Evaporation of the solvent and drying in a vacuum at 25 °C
gave 28.6 g (100%) of crude 4,5-dihydroxy-2,7-diiodonaphtha-
lene, which was used directly in the next step. A pure sample
was prepared similarly in quantitative yield from analytically
pure 10c: mp 184-186 °C; IR (CCl4) 3584, 3477, 1615, 1594,
4-Tosyloxyn a p h t h a len e-2,7-d isu lfon yl Ch lor id e (14).
Following the procedure described for 9c, 13 (78.5 g, 156
mmol), 340 mL of SOCl2 (4.7 mol), and 5 mL of DMF gave
55.5 g (72%) of a pale yellow solid. A quick chromatographic
purification on neutral alumina (eluent: CH2Cl2) gave an
analytically pure sample (a white solid, mp 156-158 °C): IR
(KBr) 3078, 1588, 1376, 1175 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 8.76 (d, 1.9 Hz, 1H), 8.66 (d, 1.5 Hz, 1H), 8.39 (d, 9.1 Hz,
1H), 8.23 (dd, 9.1 and 1.9 Hz, 1H), 7.81 (d, 8.4 Hz, 2H), 7.69
(d, 1.8 Hz, 1H), 7.39 (d, 8.5 Hz, 2H), 2.48 (s, 3H); 13C NMR
(CDCl3, 75 MHz) 147.6, 147.4, 144.6, 143.2, 133.3, 132.2, 131.4,
130.9, 130.4, 129.1, 128.9, 126.7, 126.2, 118.6, 22.3; UV-vis
(CH3CN, c ) 4.80 × 10-5 M) λmax (log ꢀ) 222 (4.52), 225 (4.53),
228 (4.55), 232 (4.56), 237 (4.57), 240 (4.59), 244 (4.61), 251
nm (4.59); HRMS (FAB) m/z calcd for C17H12Cl2O7S3 493.9122,
found 493.9149.
1
1358, 1261 cm-1; H NMR (acetone-d6, 400 MHz) δ 10.34 (s,
2H), 7.68 (d, 1.4 Hz, 2H), 7.09 ppm (d, 1.4 Hz, 2H); 13C NMR
(acetone-d6, 75 MHz) 155.5, 139.5, 127.9, 118.7, 113.8, 93.2
ppm.
The solid from the previous step was mixed under N2 with
1,2-dichloroethane (200 mL) and Et3N (50 mL), and TIPSOTf
(44.8 mL, 0.167 mol) was added to the stirring mixture. After
the mixture had stirred and refluxed for 24 h, it was poured
onto saturated aqueous NaHCO3 (1 L) and extracted with
hexane (1 L, 2 × 150 mL). The combined extracts were dried
over Na2SO4, filtered, and concentrated to ca. 100 mL. The
oily material was loaded onto silica gel (5 in d × 4 in h), and
the product was eluted with hexane. Evaporation of the solvent
and drying in a vacuum gave 38.1 g (80%) of pure 11 (a white
solid, mp 106-107 °C): IR (CCl4) 2948, 2869, 1589, 1553, 1466,
4,5-Ditosyloxy-2,7-d iiod on a p h th a len e (10c). A dry 2 L
round-bottomed flask fitted with a reflux condenser and
containing 9c (100.0 g, 0.150 mol), ZnI2 (120.0 g, 0.376 mol),
LiCl (6.0 g, 0.140 mol), and PdCl2(PhCN)2 (1.5 g, 3.9 mmol)
was evacuated three times and flushed with N2. Diglyme (1
L) and Ti(Oi-Pr)4 (20.0 mL, 0.068 mol) were added through a
septum, and the mixture was stirred and heated in an oil bath
at 155 °C for 14 h. The reaction mixture was poured into 0.05
M HCl (10 L) and filtered through a wad of Celite. The filter
cake was mixed with CH2Cl2 (0.75 L, then 3 × 0.3 L), and each
time the mixture was filtered. The filtrate was dried over
MgSO4, filtered, and concentrated to ca. 500 mL. The solution
was poured onto silica gel (4 in d × 2 in h), and the product
was eluted with CH2Cl2 (3 × 300 mL). The brown solid left
when the solvent was evaporated was loaded onto silica gel (4
in d × 2 in h) that had been topped with sand, and the product
was eluted with CH2Cl2. Evaporation of the solvent and drying
in a vacuum gave an orange-yellow solid that was boiled for
10 min in EtOAc (250 mL). Anhydrous EtOH (250 mL) was
added, and after the mixture had been allowed to stand
overnight at 4 °C, the precipitated solid was filtered and
washed in the filter funnel with EtOH (200 mL). Drying in a
vacuum yielded 56 g (52%) of a pale yellow solid that was used
for the next step. Analytically pure 10c (a white solid mp 220-
222 °C) was obtained by column chromatography (silica gel,
5:1 CH2Cl2/hexane): IR (KBr) 3096, 1604, 1570, 1379, 1357,
1
1360, 1260, 1092, 885, 840 cm-1; H NMR (CDCl3, 400 MHz)
δ 7.58 (d, 1.5 Hz, 2H), 7.09 (d, 1.5 Hz, 2H), 1.32 (m, 6H), 1.04
ppm (d, 7.5 Hz, 36H); 13C NMR (CDCl3, 75 MHz) 153.9, 139.1,
128.5, 124.0, 120.4, 91.3, 17.9, 13.1 ppm; UV-vis (CH3CN, c
) 5.23 × 10-5 M) λmax (log ꢀ) 230 (sh, 4.39), 253 (4.66), 302
(3.72), 316 (3.76), 330 (3.76), 343 nm (3.75). Anal. Calcd for
C
28H46I2O2Si2: C, 46.41; H, 6.40. Found: C, 46.39; H, 6.40.
4-Tr iisop r op ylsiloxy-2,7-d iiod on a p h th a len e (16). When
the procedure described above for the preparation of 11 was
applied to 25 g (45.4 mmol) of 15, 12.7 g (227 mmol) of KOH,
and 230 mL of EtOH, it gave 16.8 g (a 93% yield) of crude
4-hydroxy-2,7-diiodonaphthalene, which was used directly in
the next step. An analytically pure sample (a white solid, mp
156-159 °C) was obtained by chromatography on silica gel
(eluent: 85:15 hexane/EtOAc): IR (KBr) 3297, 1570, 829 cm-1
;
1H NMR (acetone-d6, 400 MHz) δ 9.60 (broad s, 1H), 8.23 (d,
1.7 Hz, 1H), 7.96 (d, 8.8 Hz, 1H), 7.79 (s, 1H), 7.76 (dd, 8.8
and 1.7 Hz, 1H), 7.25 ppm (d, 1.5 Hz, 1H); 13C NMR (CDCl3,
75 MHz) 154.8, 138.2, 135.8, 134.7, 127.7, 125.1, 123.7, 118.2,
93.8, 92.8 ppm; UV-vis (CH3CN, c ) 4.20 × 10-5 M) λmax (log
ꢀ) 218 (4.36), 252 nm (4.73); HRMS (FAB) m/z calcd for
C
10H6I2O1 395.8508, found 395.8497.
TIPSOTf (12.5 mL, 46 mmol) was added at 0 °C to a stirred
1
1329, 1239, 1190, 1174, 1032 cm-1; H NMR (DMSO-d6, 400
mixture under N2 of crude 4-hydroxy-2,7-diiodonaphthalene
(16.6 g, 42 mmol), CH2Cl2 (170 mL), and Et3N (30 mL, 210
mmol). The mixture was stirred at 25 °C for 2 h, poured into
saturated aqueous NaHCO3, and extracted with CH2Cl2. The
extract was dried over Na2SO4 and filtered, and the solvent
was evaporated. The residue, dissolved in hexane, was poured
onto a short column of silica gel, and the product was eluted
with hexane. Evaporation of the solvent and drying in a
vacuum gave 17.9 g (77%) of a slightly yellow oil: IR (NaCl
MHz) δ 8.38 (d, 1.5 Hz, 2H), 7.57 (d, 8.3 Hz, 4H), 7.40 (d, 8.1
Hz, 4H), 7.17 (d, 1.5 Hz, 2H), 2.39 ppm (s, 6H); 13C NMR
(CDCl3, 75 MHz) 145.8, 143.1, 137.9, 134.8, 131.6, 130.6, 129.5,
129.0, 119.9, 90.8, 21.7 ppm; UV-vis (CH3CN, c ) 3.81 × 10-5
M) λmax (log ꢀ) 230 (4.67), 258 (4.70), 290 (sh, 3.87), 300 (sh,
3.80), 315 nm (sh, 3.59). Anal. Calcd for C24H18I2O6S2: C, 40.02;
H, 2.52. Found: C, 40.07; H, 2.46.
4-Tosyloxy-2,7-d iiod on a p h th a len e (15). Following the
procedure in the previous paragraph, 14 (50 g, 100 mmol), ZnI2
(80 g, 250 mmol), LiCl (2.1 g, 50 mmol), Ti(O-i-Pr)4 (14.8 mL,
50 mmol), and PdCl2(PhCN)2 (1.1 g, 3 mmol) in diglyme (1.6
L) gave 25 g (46%) of a white solid after chromatography on a
small amount of silica gel (eluent: 2:1 hexane/CH2Cl2): mp
1
window) 2945, 2867, 1604, 1563 cm-1; H NMR (CDCl3, 400
MHz) δ 8.04 (d, 1.5 Hz, 1H), 7.90 (d, 8.9 Hz, 1H), 7.70 (m, 2H),
7.13 (d, 1.3 Hz, 1H), 1.40 (m, 7.5 Hz, 3H), 1.15 ppm (d, 7.5 Hz,
18H); 13C NMR (CDCl3, 75 MHz) 152.7, 137.3, 135.0, 134.3,
128.3, 125.6, 124.7, 121.4, 93.4, 91.8, 18.1, 13.0 ppm; UV-vis
(CH3CN, c ) 4.64 × 10-5 M) λmax (log ꢀ) 221 (4.37), 243 (4.55),
247 (4.61), 251 (4.60), 254 nm (4.58); HRMS (FAB) m/z calcd
for C19H26I2O1Si 551.9842, found 551.9819.
4,5-Bis-(tr iisopr opylsiloxy)-2,7-diacetyln aph th alen e (4,
R ) TIP S). n-BuLi (2.5 M in hexanes, 91.6 mL, 230 mmol)
was added slowly under N2 at -100 °C to a stirred solution of
11 (37.5 g, 54.5 mmol) in dry Et2O (260 mL). The mixture was
stirred for 5 min at -100 °C, and then N-methoxy-N-methy-
lacetamide (17.5 mL, 164 mmol) was added during 5 min. The
solution was stirred at -100 °C for 15 min and then at 25 °C
for 1 h. Hexane (0.5 L) was added, and the solution was washed
with saturated aqueous NH4Cl (300 mL) and H2O (2 × 1 L),
dried over Na2SO4, and filtered. The solvent was evaporated,
and the residue was chromatographed on silica gel (5 in d ×
4 in h). Impurities were eluted with 1:1 hexane/CH2Cl2, the
product with CH2Cl2. Evaporation of the solvent and drying
1
153-155 °C; IR (KBr) 1604, 1565, 1379, 1355, 1174 cm-1; H
NMR (CDCl3, 400 MHz) δ 8.09 (d, 1.5 Hz, 1H), 8.0 (s, 1H),
7.77 (d, 8.3 Hz, 2H), 7.67 (dd, 8.9 and 1.6 Hz, 1H), 7.56 (d, 8.9
Hz, 1H), 7.43 (d, 1.5 Hz, 1H), 7.33 (d, 8.2 Hz, 2H), 2.46 ppm
(s, 3H); 13C NMR (CDCl3, 75 MHz) 146.1, 145.7, 137.0, 135.9,
135.2, 134.7, 132.2, 130.1, 128.6, 127.8, 125.4, 123.7, 94.0, 89.8,
21.9 ppm; UV-vis (CH3CN, c ) 5.24 × 10-5 M) λmax (log ꢀ)
227 (4.55), 230 (4.56), 234 (4.56), 245 (4.61), 253 nm (4.64).
Anal. Calcd for C17H12I2O3S: C, 37.11; H, 2.20. Found: C,
37.21; H, 2.17.
4,5-Bis(tr iisop r op ylsiloxy)-2,7-d iiod on a p h th a len e (11).
A solution of KOH (38.9 g, 695 mmol) in anhydrous EtOH (750
mL) was added under N2 to 10c (50.0 g, 69.5 mmol). The
mixture was stirred and refluxed for 150 min, cooled to
ambient temperature, and while still under N2, quenched with
5 M HCl (200 mL). It was poured into H2O (2 L), extracted

8780 J . Org. Chem., Vol. 65, No. 25, 2000
Paruch et al.
in a vacuum gave 19.9 g (66%) of a white solid: mp 116-117
°C (recrystallized from MeOH); IR (CCl4) 2948, 2869, 1686,
1574, 1379, 1354, 1216, 1108, 884 cm-1; 1H NMR (CDCl3, 400
MHz) δ 8.09 (d, 1.5 Hz, 2H), 7.51 (d, 1.5 Hz, 2H), 2.69 (s, 6H),
1.37 (m, 6H), 1.05 ppm (d, 7.5 Hz, 36H); 13C NMR (CDCl3, 75
MHz) 197.2, 154.0, 136.1, 135.2, 126.4, 124.6, 114.5, 26.5, 17.9,
13.1 ppm; UV-vis (CH3CN, c ) 6.65 × 10-5 M) λmax (log ꢀ)
233 (sh, 4.36), 264 (4.56), 366 (3.85), 385 nm (3.96); HRMS
(FAB) m/z calcd for C32H53O4Si2 [M + H]+ 557.3482, found
557.3471.
18.0, 17.7, 13.4, 13.2 ppm. Anal. Calcd for C62H92O8Si4: C,
69.10; H, 8.60. Found: C, 69.22; H, 8.84.
Tr is(tr iisop r op ylsiloxy)[6]h elicen ebisqu in on e 19, R )
TIP S. The same procedure was applied to 18 (11.9 g, 17 mmol)
and 1,4-benzoquinone (27.5 g, 255 mmol) in 70 mL of PhCH3.
Workup and chromatography (eluent 9:1 hexane/ethyl acetate)
gave crude product, which was purified by chromatography
on neutral alumina (2 in d × 1.5 in h, eluent: CH2Cl2). The
yield of red solid 19 was 5.9 g (38%): mp 119-125 °C; IR (KBr)
2946, 2868, 1664, 1506, 1226 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 8.43 (s, 2H), 7.73 (s, 1H), 7.52 (s, 1H), 7.48 (s, 1H), 6.75 (d,
10.1 Hz, 1H), 6.73 (d, 10.1 Hz, 1H), 6.63 (d, 10.1 Hz, 1H), 6.60
(d, 10.1 Hz, 1H) 1.58-1.50 (m, 9H), 1.23 ppm (m, 54H); 13C
NMR (CDCl3, 75 MHz) 185.5, 185.2, 156.6, 155.4, 152.6, 140.6,
140.2, 135.8, 135.6, 133.5, 131.9, 131.6, 131.0, 130.0, 129.3,
128.8, 128.0, 127.8, 127.5, 123.2, 122.3, 109.2, 106.1, 18.3, 18.2,
13.5, 13.4, 13.2 ppm. Anal. Calcd for C53H72O7Si3: C, 70.31;
H, 8.02. Found: C, 70.02; H, 7.92.
(M)-(-)- a n d (P )-(+)-20. CH2Cl2 (200 mL) and Et3N (20 mL)
were added under N2 to a mixture of 1 (R ) OTIPS, 5.00 g,
4.63 mmol), Zn (15.2 g, 233 mmol), (1S)-camphanoyl chloride
(10.0 g, 46 mmol), and DMAP (255 mg, 2.09 mmol), and the
mixture was stirred vigorously for 24 h. Hexane (800 mL) was
added, and the mixture was filtered through a wad of Celite.
The filtrate was washed with saturated aqueous NaHCO3 (3
× 200 mL), dried over Na2SO4, and filtered. After the solvent
had been evaporated, the residual solid was dissolved in a
minimal amount of 1:3 CH2Cl2/hexane and loaded onto a
column of silica gel that had been soaked with 3:1 hexane/
EtOAc. Impurities were eluted with 3:1 hexane/EtOAc, crude
(M)-(-)-20 with 2:1 hexane/EtOAc, and pure (P)-(+)-20 with
3:2 hexane/EtOAc. (M)-(-)-20 was rechromatographed with 5:1
PhCH3/EtOAc. The yield of (P)-(+)-20 was 3.28 g (79%), and
the yield of (M)-(-)-20 was 3.15 g (75%).
4-Tr iisopr opylsiloxy-2,7-diacetyln aph th alen e (17). When
the procedure in the previous paragraph was applied to 16
(17.9 g, 32.4 mmol), n-BuLi (2.5 M in hexanes, 61 mL, 152
mmol), and N-methoxy-N-methylacetamide (15 g, 146 mmol)
in 200 mL of Et2O, it afforded, after chromatography on silica
gel (eluent 90:10 hexane/ethyl acetate), 6.5 g (52%) of white
1
solid 17: mp 94-95 °C; IR (KBr) 2946, 2868, 1683 cm-1; H
NMR (CDCl3, 400 MHz) δ 8.53 (d, 1.6 Hz, 1H), 8.33 (d, 8.8
Hz, 1H), 8.17 (s, 1H), 8.12 (dd, 8.8 and 1.7 Hz, 1H) 7.54 (d, 1.4
Hz, 1H) 2.73 (s, 3H), 2.70 (s, 3H), 1.44 (m, 3H), 1.15 ppm (d,
7.5 Hz, 18H); 13C NMR (CDCl3, 75 MHz) 197.8, 197.4, 152.6,
135.9, 135.6, 133.4, 132.2, 131.3, 125.9, 124.6, 123.6, 111.6,
26.9, 26.7, 18.2, 13.1 ppm; UV-vis (CH3CN, c ) 4.00 × 10-5
M) λmax (log ꢀ) 264 nm (4.68). Anal. Calcd for C23H32O3Si1: C,
71.83; H, 8.39. Found: C, 71.85; H, 8.28.
4,5-Bis(t r iisop r op ylsiloxy)-2,7-b is-[1-(t r iisop r op yl-
siloxy)eth en yl]n a p h th a len e (12, R ) TIP S). TIPSOTf
(19.25 mL, 71.6 mmol) was added at 0 °C under N2 to a stirred
solution of 4 (19.0 g, 34.1 mmol) and Et3N (38 mL) in CH2Cl2
(150 mL). The solution was stirred for 15 min at 0 °C and then
for 2 h at 25 °C. Hexane (600 mL) was added. The solution
was washed with 10% aqueous Na2CO3 (3 × 300 mL), dried
over K2CO3, and filtered. Evaporation of the solvent and drying
in a vacuum at 90 °C gave 29.7 g (100%) of 12, a slightly orange
oil: IR (CCl4) 2946, 2868, 1562, 1464, 1384, 1285, 1017, 884
(M)-(-)-20: mp >240 °C; [R]D -281 (c ) 0.033, CH3CN); IR
1
cm-1; H NMR (CDCl3, 400 MHz) δ 7.68 (d, 1.5 Hz, 2H), 7.04
(CCl4) 2946, 2868, 1797, 1754, 1588, 1464, 1375, 1312, 1262,
(d, 1.5 Hz, 2H), 4.87 (d, 1.7 Hz, 2H), 4.47 (d, 1.7 Hz, 2H), 1.36-
1.30 (m, 12H), 1.15 (d, 7.3 Hz, 36 H), 1.04 ppm (d, 7.5 Hz, 36H);
13C NMR (CDCl3, 75 MHz) 155.9, 152.7, 137.0, 135.1, 121.8,
118.8, 112.5, 90.6, 18.1, 18.0, 13.3, 12.9 ppm.
1
1166, 1095, 1047 cm-1; H NMR (CDCl3, 400 MHz) δ 7.80 (s,
2H), 7.39 (s, 2H), 6.95 (d, 8.5 Hz, 2H), 6.44 (d, 8.5 Hz, 2H),
2.76 (m, 2H), 2.39 (m, 2H), 2.07 (m, 2H), 1.84 (m, 2H), 1.59-
1.05 (m, 92H), 0.89 (s, 6H), 0.84 (d, 7.5 Hz, 18H), 0.52 (s, 6H),
0.34 ppm (s, 6H); 13C NMR (CDCl3, 75 MHz) 178.0, 177.7,
165.9, 163.9, 152.0, 149.9, 143.5, 142.5, 129.6, 127.7, 125.9,
121.4, 121.2, 121.1, 117.3, 114.4, 109.9, 105.2, 91.1, 89.6, 55.0,
54.5, 53.9, 30.9, 29.1, 28.9, 28.6, 18.2, 18.0, 17.7, 17.0, 16.9,
16.1, 13.4, 13.3, 9.8, 9.5 ppm; UV-vis (CH3CN, c ) 3.31 ×
10-5 M) λmax (log ꢀ) 208 (4.71), 268 (sh, 4.73), 279 (4.76), 302
(sh, 4.42), 341 (4.39), 358 nm (sh, 4.31); CD (c ) 3.31 × 10-5
M, CH3CN), nm (∆ꢀ) 216 (-93), 267 (146), 302 (-39), 328 (10),
341 (sh, -8), 360 (-78). Anal. Calcd for C102H144O20Si4: C,
67.96; H, 8.05. Found: C, 67.88; H, 8.08.
4-Tr iisop r op ylsiloxy-2,7-bis-(1-(tr iisop r op ylsiloxy)eth -
en yl)n a p h th a len e (18). When the procedure in the previous
paragraph was applied to 6.5 g (17 mmol) of 17, 12 mL (85
mmol) of Et3N, and 10 mL (37 mmol) of TIPSOTf in CH2Cl2,
it afforded 12 g (101%) of 18, a colorless oil, which was used
directly in the next step. An analytical sample was obtained
by quickly chromatographing a sample on a short column of
neutral alumina (eluent: hexane): IR (CCl4) 2946, 2868, 1609,
1464, 1286, 1016, 883 cm-1; 1H NMR (CDCl3, 400 MHz) δ 8.12
(d, 8.8 Hz, 1H), 8.10 (s, 1H),7.75 (s, 1H), 7.68 (dd, 8.8 and 1.7
Hz, 1H), 7.11 (d, 1.3 Hz, 1H), 5.00 (d, 1.7 Hz, 1H), 4.89 (d, 1.6
Hz, 1H), 4.51 (d, 1.7 Hz, 1H), 4.48 (d, 1.6 Hz, 1H), 1.43-1.30
(m, 9H), 1.16 ppm (d, 7.5 Hz, 54 H); 13C NMR (CDCl3, 75 MHz)
156.3, 156.0, 151.6, 135.8, 135.5, 134.4, 127.3, 124.8, 122.9,
122.3, 118.2, 109.9, 90.6, 90.7, 18.1, 13.1, 12.9, 12.5 ppm.
Tetr a k is(tr iisop r op ylsiloxy)[6]h elicen ebisqu in on e 1,
R ) TIP S. A solution under N2 of 12 (29.7 g, 34.1 mmol) and
1,4-benzoquinone (55.3 g, 512 mmol) in PhCH3 (136 mL) was
stirred at 90 °C for 6.5 d. After it had cooled to 25 °C and
hexane (1 L) had been added, the mixture was filtered through
a wad of Celite. The Celite was then washed with hexane (ca.
200 mL) until the filtrate was no longer red. The solvent was
evaporated, and residual 1,4-benzoquinone was sublimed at
100 °C into a vacuum. The residue, dissolved in a minimal
amount of CH2Cl2, was loaded onto a short column of silica
gel (4 in d × 3 in h), and the red product was eluted with CH2-
Cl2. Chromatography on silica gel (4.5 in d × 8 in h) with 10:1
hexane/EtOAc yielded 14.7 g (40%) of a dark red solid: mp
123-125 °C; IR (CCl4) 2948, 2870, 1664, 1597, 1580, 1494,
1346, 1248, 1226, 1083, 1003 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 7.65 (s, 2H), 7.43 (s, 2H), 6.68 (d, 10.2 Hz, 2H), 6.52 (d, 10.2
Hz, 2H), 1.53-1.43 (m, 12H), 1.23 (d, 7.5 Hz, 18H), 1.20 (d,
7.5 Hz, 18H), 1.11 (d, 7.5 Hz, 18H), 1.05 ppm (d, 7.5 Hz, 18H);
13C NMR (CDCl3, 75 MHz) 185.1, 184.8, 154.7, 154.3, 140.0,
135.7, 133.5, 131.8, 130.2, 128.0, 127.4, 124.5, 109.1, 108.7,
(P)-(+)-20: mp >240 °C; [R]D +188 (c ) 0.036, CH3CN); IR
(CCl4) 2947, 2869, 1801, 1777, 1760, 1585, 1464, 1375, 1258,
1204, 1167, 1094, 1042 cm-1 1H NMR (CDCl3, 400 MHz) δ
;
7.73 (s, 2H), 7.17 (s, 2H), 6.83 (d, 8.3 Hz, 2H), 6.24 (d, 8.3 Hz,
2H), 2.70 (m, 2H), 2.31 (m, 2H), 2.10 (m, 2H), 1.89 (m, 2H),
1.70 (m, 2H), 1.53-0.79 (m, 120H), 0.56 ppm (s, 6H); 13C NMR
(CDCl3, 75 MHz) 177.6, 177.4, 166.1, 164.5, 153.1, 150.8, 143.6,
142.6, 130.6, 128.0, 125.0, 123.0, 122.4, 120.6, 118.1, 116.2,
110.1, 104.6, 90.8, 90.3, 54.8, 54.3, 54.2, 31.0, 29.0, 27.8, 18.1,
17.9, 17.8, 17.6, 17.1, 16.9 (2 peaks), 16.6, 13.5, 13.2, 9.7, 9.6
ppm; UV-vis (CH3CN, c ) 4.05 × 10-5 M) λmax (log ꢀ) 206
(4.66), 269 (sh, 4.73), 278 (4.74), 301 (sh, 4.43), 314 (sh, 4.37),
363 nm (sh, 4.15); CD (c ) 4.05 × 10-5 M, CH3CN), nm (∆ꢀ)
207 (sh, 90), 217 (141), 269 (-147), 302 (30), 327 (-9), 362
(58); HRMS (FAB) m/z calcd for C102H144O20Si4 1801.9357,
found 1801.9325.
X-r a y Diffr a ction An a lysis of (M)-(-)- 20.28 Crystals of
(M)-(-)-20 for X-ray diffraction analysis were obtained by
allowing the solvent to evaporate from an ethanol solution.
Crystal data: triclinic, P1, a ) 14.3608(5) Å, b ) 18.0032(5)
Å, c ) 21.0751(7) Å, R ) 95.441(2)°, â ) 94.484(2)°, γ )
(28) The data will be submitted to the Cambridge Crystallographic
Data Base (CCDC).

Synthesis of Tri- and Tetrahydroxy[6]helicenebisquinones
J . Org. Chem., Vol. 65, No. 25, 2000 8781
107.384(2)°, V ) 5143.8(3) Å3, Z ) 2, T ) 173 K. Of 34 359
reflections collected, 25 383 were independent. The unit cell
contains two crystallographically different, but chemically
similar molecules. The Flack parameter, which refined to a
value of 0.02(14), is in accord with the absolute configuration
displayed. R(F) ) 9.19%, wR(F2) ) 22.62%.
(M)-(-)- a n d (P )-(+)-21. CH2Cl2 (120 mL) and Et3N (12.5
mL) were added under N2 to a mixture of 19 (R ) TIPS, 2.7 g,
3 mmol), Zn (9.8 g, 150 mmol), (1S)-camphanoyl chloride (6.3
g, 29 mmol), and DMAP (146 mg, 1.20 mmol). The mixture
was stirred and refluxed for 2 h and then worked up as in the
experiment above. The yield of the higher Rf isomer, (P)-(+)-
21, was 1.60 g (67%). The yield of the lower Rf isomer, (M)-
(-)-21, after it had been obtained pure by rechromatography
(eluting with 10:1 toluene/EtOAc), was 1.77 g (74%).
(M)-(-)-21: mp >200 °C; [R]D -390 (c ) 0.011, CH3CN); IR
(KBr) 2947, 2869, 1799, 1752, 1261, 1093, 1044 cm-1; 1H NMR
(CDCl3, 400 MHz) δ 8.54 (d, 8.7 Hz, 1H), 8.46 (d, 8.7 Hz, 1H),
7.80 (s, 1H), 7.42 (s, H), 7.40 (s, 1H), 7.00 (d, 8.4 Hz, 1H), 6.95
(d, 8.4 Hz, 1H). 6.45 (d, 8.4 Hz, 1H), 6.42 (d, 8.4 Hz, 1H) 2.75
(m, 2H), 2.39 (m, 2H), 2.06 (m, 2H), 1.85 (m, 2H), 1.59-1.03
(m, 89H), 0.88 (s, 6H), 0.49 (s, 3H), 0.48 (s, 3H) 0.24 (s, 3H),
0.18 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz) 178.2, 177.7,
166.2, 164.5, 151.3, 150.8, 142.8, 142.7, 127.4, 121.5, 120.9,
118.5, 117.5, 155.0, 106.1, 105.6, 105.5, 91.3, 89.9, 55.1, 54.6,
54.4, 54.2, 31.1, 29.2, 29.0, 28.8, 18.3, 18.2, 17.2, 17.1, 16.3,
16.0, 15.9, 13.6, 13.2, 10.0, 9.7 ppm; UV-vis (CH3CN, c ) 6.74
× 10-5 M) λmax (log ꢀ) 206 (4.51), 275 (4.57), 339 nm (4.38); CD
(c ) 6.74 × 10-5 M, CH3CN), nm (∆ꢀ) 210 (-67), 230 (-41),
250 (117), 260 (sh, 108), 281 (-13), 302 (-49), 322 (10), 355
(-70); HRMS (FAB) m/z calcd for C93H124NaO19Si3 [M + Na]+
1651.7942, found 1651.8013.
(-)-19 (R ) TIPS): mp 126-130 °C; [R]D -1591 (c ) 0.0093,
CH3CN); UV-vis (CH3CN, c ) 1.026 × 10-4 M) λmax (log ꢀ)
252 (4.38), 308 (4.37), 449 nm (3.62); CD (c ) 1.026 × 10-4 M,
CH3CN), nm (∆ꢀ) 215 (-24), 228 (13), 237 (-5), 245 (-8), 259
(-20), 305 (51), 363 (-53), 440 (-15). Its IR and 1H and 13C
NMR spectra were identical to those of the racemic compound.
Similarly, 84 mg (61%) of (P)-(+)-19 (R ) TIPS) was
obtained from 250 mg (0.153 mmol) of (P)-(+)-21, 2.8 mL (4.5
mmol) of 1.6 M MeLi in Et2O, and 12 mL of THF: [R]D +1607
(c ) 0.7586, CH3CN); CD (c ) 8.30 × 10-5 M, CH3CN), nm
(∆ꢀ) 215 (24), 229 (-15), 238 (5), 245 (sh, 12), 259 (24), 305
(-53), 364 (55), 440 (15).
(()-1 (R ) Dod ecyl). 1-Iodododecane (1.95 mL, 7.90 mmol)
and DMF (2 mL) were added under N2 to a mixture of (()-1
(R ) TIPS, 170 mg, 0.158 mmol) and CsF (192 mg, 1.26 mmol).
The mixture was stirred at 60 °C for 24 h and poured into
H2O (50 mL). Brine (15 mL) was added, and the mixture was
extracted with PhCH3 (25 mL). The extract was dried over Na2-
SO4 and poured onto silica gel (1 in d × 1 in h). Residual
1-iodododecane was eluted with PhCH3 (ca. 30 mL) and the
crude product with 3:1 EtOAc/CH2Cl2. The solvent was evapo-
rated, and the residue was rechromatographed, eluting with
50:1 PhCH3/EtOAc. The yield of pure (()-1 (R ) dodecyl),
whose 1H and 13C NMR spectra were identical to those
published,1a was 121 mg (68%).
(M)-(-)-1 (R ) Dod ecyl). 1-Iodododecane (500 µL, 2.27
mmol) and DMF (3 mL) were added under N2 to a mixture of
(-)-1 (R ) TIPS, 100 mg, 0.09 mmol) and CsF (previously
ground finely by shaking with a glass bead in a Wig-L-Bug,
140 mg, 0.9 mmol). The mixture was stirred at 80 °C for 25 h.
The reaction mixture was diluted with EtOAc (20 mL) and
washed twice with H2O. The extract was dried over Na2SO4
and chromatographed on silica gel. Residual 1-iodododecane
eluted with hexane and the crude product with 90:10 hexane/
EtOAc. The solvent was evaporated and the residue was
chromatographed on basic alumina with 98:2 PhCH3/THF.
After the solvent had been evaporated, the product was
dissolved in less than 1 mL of CH2Cl2, precipitated with ca.
40 mL of MeOH, filtered with Celite, and washed from the
filter with CH2Cl2. The yield of pure product was 60 mg (58%).
Its 1H and 13C NMR spectra were identical to those published,1a
and its CD spectrum in CH2Cl2 (see the Supporting Informa-
tion) was the mirror image of that of a sample of (+)-1 (R )
dodecyl) prepared by Nuckolls et al.1a
(P )-(+)-19 (R ) Dod ecyl). 1-Iodododecane (250 µL, 1 mmol)
and DMF (0.75 mL) were added under N2 to a mixture of (P)-
(+)-19 (R ) TIPS, 30 mg, 33 µmol) and CsF (40 mg, 0.265
mmol). The mixture was stirred at 50 °C for 2 h, poured into
H2O (10 mL), and extracted with a mixture of EtOAc (15 mL)
and a small amount of CH2Cl2. The extract was dried over Na2-
SO4 and filtered. The solvent was evaporated, and the residue
was chromatographed. Residual 1-iodododecane was eluted
with hexane, colored impurities with 95:5 hexane/EtOAc, and
the red product with 90:10 hexane/EtOAc. After it had been
dried in a vacuum, the red solid product weighed 19 mg (a
61% yield): mp 218-219 °C; [R]D +1435 (c ) 0.0027, dode-
cane); IR (KBr) 2923, 2852, 1658, 1223 cm-1; 1H NMR (CDCl3,
400 MHz) δ 8.44 (s, 2H), 7.62 (s, 1H), 7.48 (s, 1H), 7.46 (s,
1H), 6.75 (m, 2H), 6.60 (2d, 10.1 Hz, 2H), 4.33 (m, 6H), 2.01
(m, 6H), 1.61 (m, 6H), 1.46-1.28 (m, 48H), 0.88 ppm (m, 9H);
13C NMR (CDCl3, 75 MHz) 185.7, 185.4, 185.3, 158.8, 157.7,
155.3, 140.4, 140.0, 135.9, 135.7, 133.8, 131.8, 131.1, 129.1,
128.2, 128.0, 127.7, 127.3, 126.8, 122.7, 121.8, 102.4, 102.0,
98.7, 69.5 (2 peaks), 68.9, 32.1, 29.8, 29.6, 29.5, 29.2, 26.5, 26.4,
22.9, 14.3 ppm; UV-vis (dodecane, c ) 2.1 × 10-5 M) λmax (log
ꢀ) 240 (4.71), 306 (4.52), 375 (sh, 3.77), 452 nm (3.71); CD (c )
2.1 × 10-5 M, dodecane), nm (∆ꢀ) 216 (24), 228 (-33), 25 (26),
266 (24), 302 (-59), 359 (62), 433 (19), 449 (18); HRMS (FAB)
m/z calcd for C62H85O7 [M + H]+ 940.6217, found 940.6233.
(P )-(+)-1 [R ) CO(CH2)4CH3]. Hexanoyl chloride (0.56 mL,
4.0 mmol) and DMF (3 mL) were added under N2 to a mixture
of (P)-1 (R ) TIPS, 108 mg, 0.10 mmol), CsF (123 mg, 0.80
mmol), and DMAP (49 mg, 0.40 mmol). The mixture was
stirred for 48 h, poured into 1 M HCl (50 mL), and extracted
with EtOAc (30 mL). The organic layer was washed with
(P)-(+)-21: mp >220 °C; [R]D +400 (c ) 0.0099, CH3CN);
1
IR (KBr) 2947, 2869, 1799, 1041 cm-1; H NMR (CDCl3, 400
MHz) δ 8.55 (d, 8.7 Hz, 1H), 8.40 (d, 8.7 Hz, 1H), 7.74 (s, 1H),
7.21 (s, 1H), 7.18 (s, 1H), 6.89 (d, 8.3 Hz, 1H), 6.84 (d, 8.3 Hz,
1H), 6.27 (2d, 8.3 Hz, 2H), 2.71 (m, 2H), 2.32 (m, 2H), 2.10
(m, 2H), 1.89 (m, 2H), 1.70 (m, 2H), 1.60-1.38 (m, 15H), 1.27-
1.17 (m, 72H), 0.95 (s, 3H), 0.94 (s, 3H), 0.81 (s, 3H), 0.78 (s,
3H), 0.55 (s, 3H), 0.49 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz)
177.7, 177.3, 177.2, 166.2, 164.9, 164.8, 152.1, 151.5, 144.7,
144.1, 142.8, 142.7, 129.8, 129.4, 127.4, 126.7, 126.4, 125.5,
125.4, 122.6, 122.5, 121.2, 120.4, 119.1, 118.0, 116.2, 116.0,
105.9, 104.3, 91.0, 90.6 (2 peaks), 55.0, 54.6, 54.4, 31.2, 29.2,
18.4, 18.2, 17.2, 17.1, 17.0, 16.9, 16.7, 16.6, 13.7, 13.5, 13.3,
9.9, 9.7 ppm; UV-vis (CH3CN, c ) 6.07 × 10-5 M) λmax (log ꢀ)
206 (4.55), 272 (4.61), 339 nm (4.33); CD (c ) 6.07 × 10-5 M,
CH3CN), nm (∆ꢀ) 210 (91), 230 (70), 252 (sh, -121), 262 (-125),
280 (8), 306 (43), 315 (-14), 357 (63); HRMS (FAB) m/z calcd
for C93H124O19Si3 1628.8045, found 1628.8115.
Non r a cem ic 1 (R ) TIP S). MeLi (1.4 M in Et2O, 35.5 mL,
50 mmol) was added under N2 at -78 °C to a stirred solution
of (M)-(-)-20 (3.00 g, 1.67 mmol) in Et2O (90 mL). The mixture
was stirred at -78 °C for 15 min and then at 25 °C for 1 h,
and it was then carefully quenched with saturated aqueous
NH4Cl (50 mL). The mixture was poured into H2O (300 mL)
and extracted with EtOAc (100 mL). The organic layer was
dried over Na2SO4 and filtered. Chloranil (2.00 g, 8.1 mmol)
was added. The mixture was stirred for 5 min and filtered.
The solvent was evaporated, and the residue was mixed with
hexane (50 mL) and filtered. The solvent was evaporated, and
the residue was chromatographed, eluting with 80:1 PhCH3/
EtOAc. The yield of (M)-(-)-1 (R ) TIPS) was 1.58 g (88%):
mp 115-117 °C; [R]D -1321 (c ) 0.0094, CH3CN); CD (c )
2.42 × 10-5 M, CH3CN), nm (∆ꢀ) 220 (-49), 232 (23), 258
1
(-144), 314 (146), 386 (-103). H and 13C NMR spectra were
identical to those of the racemic compound.
Similarly, 3.00 g of (P)-(+)-20 gave 1.56 g (87%) of (P)-(+)-1
(R ) TIPS): [R]D +1334 (c ) 0.0086, CH3CN); UV-vis (CH3-
CN, c ) 1.84 × 10-5 M) λmax (log ꢀ) 245 (4.77), 316 (4.55), 487
nm (3.76); CD (c ) 1.84 × 10-5 M, CH3CN), nm (∆ꢀ) 220 (54),
231 (-21), 257 (155), 315 (-154), 387 (108).
Non r a cem ic 19 (R ) TIP S). The same procedure, using
320 mg (0.196 mmol) of (M)-(-)-21, 4 mL (6.3 mmol) of 1.6 M
MeLi in Et2O, and 15 mL of THF, gave 130 mg (73%) of (M)-

8782 J . Org. Chem., Vol. 65, No. 25, 2000
Paruch et al.
saturated aqueous NaHCO3 (4 × 40 mL) and 1 M HCl (40 mL),
dried over Na2SO4, and filtered. The solvent was evaporated,
and the residue was chromatographed, eluting with 10:1
PhCH3/EtOAc. The yield of orange waxy solid (P)-(+)-1, R )
CO(CH2)4CH3, was 58 mg (68%): mp 77-79 °C; [R]D +1275 (c
) 0.017, CH3CN); IR (CCl4) 2959, 2931, 1776, 1669, 1612, 1504,
1349, 1288, 1196, 1135, 1090 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 8.06 (s, 2H), 7.76 (s, 2H), 6.85 (d, 10.2 Hz, 2H), 6.70 (d, 10.2
Hz, 2H), 2.73 (m, 8H), 1.86 (m, 8H), 1.45 (m, 16H), 0.96 ppm
(m, 12H); 13C NMR (CDCl3, 75 MHz) 184.7, 183.6, 171.7, 170.8,
149.4, 146.3, 139.6, 136.3, 132.7, 131.0, 129.5, 128.8, 122.8,
116.4, 115.0, 34.3 (2 peaks), 31.3, 31.2, 24.5 (2 peaks), 22.3 (2
peaks), 13.9 ppm (2 peaks); UV-vis (CH3CN, c ) 1.50 × 10-5
M) λmax (log ꢀ) 234 (4.76), 262 (sh, 4.55), 293 (4.59), 354 nm
(sh, 4.04); CD (c ) 1.50 × 10-5 M, CH3CN), nm (∆ꢀ) 234 (sh,
62), 217 (167), 261 (85), 292 (-264), 353 (250), 421 (46). Anal.
Calcd for C50H52O12: C, 71.07; H, 6.20. Found: C, 70.93; H,
6.21.
0.99 ppm (m, 9H); 13C NMR (CDCl3, 75 MHz) 185.3, 184.0,
171.5, 171.4, 171.2, 150.4, 150.1, 147.4, 140.0, 139.9, 136.4 (2
peaks), 131.4 (3 peaks), 129.4, 129.2, 128.2, 127.8, 123.0, 122.3,
116.3, 113.0, 34.7, 34.6, 31.5, 24.8, 22.5, 14.1 ppm; UV-vis
(CH3CN, c ) 7.8 × 10-5 M) λmax (log ꢀ) 246 (4.49), 292 (4.48),
351 (4.03), 408 (3.67); CD (c ) 7.8 × 10-5 M, CH3CN), nm (∆ꢀ)
216 (-44), 245 (1), 259 (-23), 291 (84), 352 (-85), 437 (-7).
Anal. Calcd for C50H52O12: C, 72.31; H, 5.79. Found: C, 71.97;
H, 5.82.
Ack n ow led gm en t. We thank the NSF for grant
support (CHE98-02316), Dr. Alfred Bader for Bader
Fellowships to K.P. and L.V., and Dr. Colin Nuckolls
for first suggesting that chromotropic acid might be used
to synthesize the ring system of 1.
Su p p or tin g In for m a tion Ava ila ble: 1H, 13C NMR, IR,
and UV spectra of 1 (R ) TIPS), (P)-(+)-1 (R ) CO(CH2)4CH3),
4 (R ) TIPS), 8c, 9c, 10, 11, 12 (R ) TIPS), 13, 14, 15, 16, 17
(R ) TIPS), 18, 19 (R ) TIPS), (P)-(+)-19 (R ) dodecyl), (M)-
(-)-19 [R ) CO(CH2)4CH3], (P)-(+)-20, (M)-(-)-20, (P)-(+)-21,
(M)-(-)-21, and 4-hydroxy-2,7-diiodonaphthalene. 1H, 13C NMR,
and IR spectra of 4,5-dihydroxy-2,7-diiodonaphthalene. CD
spectra of (P)-(+)-1 and (M)-(-)-1 (R ) TIPS), 1 (R ) dodecyl)
in CH2Cl2 [the (M)-(-)-enantiomer synthesized here and the
(P)-(+)-enantiomer synthesized according to ref 1b], (P)-(+)-1
[R ) CO(CH2)4CH3], (P)-(+)-19 and (M)-(-)-19 (R ) TIPS), (P)-
(+)-19 (R ) dodecyl), (M)-(-)-19 [R ) CO(CH2)4CH3], (P)-(+)-
20, (M)-(-)-20, (P)-(+)-21, and (M)-(-)-21. X-ray diffraction
data for (M)-(-)-20. This material is available free of charge
via the Internet at http://pubs.acs.org.
(M)-(-)-19 [R ) CO(CH2)4CH3]. Hexanoyl chloride (100
µL, 0.72 mmol) and DMF (0.5 mL) were added under N2 to a
mixture of (M)-19 (R ) TIPS, 20 mg, 0.022 mmol), CsF (28
mg, 0.18 mmol), and DMAP (8 mg, 0.7 mmol). The mixture
was stirred and heated at 50 °C for 2 h. Aqueous HCl (1 M,
10 mL) was added, and the mixture was extracted twice with
EtOAc (10 mL). The combined extracts were washed with H2O,
dried over Na2SO4, and filtered. After the solvent had been
evaporated, the residue was chromatographed, eluting with
20:1 toluene/EtOAc. Drying in a vacuum gave 11.3 mg (71%)
of orange solid (M)-(-)-19, R ) CO(CH2)4CH3: mp 81-82 °C;
[R]D -1450 (c ) 0.0057, CH3CN); IR (KBr) 2930, 1769, 1665,
1
1090 cm-1; H NMR (CDCl3, 400 MHz) δ 8.14 (2s, 2H), 8.06
(s, 1H), 8.05 (s, 1H), 8.01 (s, 1H), 6.86 (2d, 10.1 Hz, 2H), 6.69
(2d, 10.1 Hz, 2H), 2.81 (m, 6H), 21.91 (m, 6H), 1.48 (m, 12H),
J O001356W