8160
J . Org. Chem. 2001, 66, 8160-8164
A New On e-Step Str a tegy for th e Ster eoch em ica l Assign m en t of
Acyclic 2- a n d 3-Su lfa n yl-1-a lk a n ols Usin g th e CD Exciton
Ch ir a lity Meth od
Bernhard Weckerle, Peter Schreier, and Hans-Ulrich Humpf*,†
Lehrstuhl fu¨r Lebensmittelchemie, Universita¨t Wu¨rzburg, Am Hubland, D-97074 Wu¨rzburg, Germany
humpf@pzlc.uni-wuerzburg.de
Received J uly 30, 2001
A new one-step strategy is described for the stereochemical assignment of acyclic 2- and 3-sulfanyl-
1-alkanols using the CD exciton chirality method. Using the 9-anthroate chromophore for the
derivatization of both functional groups, the resulting bisignate CD curves unequivocally allow
the determination of the stereochemistry from a single CD measurement. The usefulness of the
new method is demonstrated using synthesized optically pure 3-sulfanyl-1-hexanols and 2-sulfanyl-
1-hexanols as model compounds. The developed microscale method is also useful for the stereo-
chemical assignment of 1,2- and 1,3-diols. To our knowledge this is the first application of the CD
exciton chirality method to acyclic 2- and 3-sulfanyl-1-alkanols.
The circular dichroism (CD) exciton chirality method
conformation. Nevertheless, the exciton chirality method
has been successfully applied to acyclic 1,2-/1,3-polyols5,6
and aminopolyols7 as well as acyclic R-hydroxy carboxylic
acids.8 However, to our knowledge the CD exciton chiral-
ity method has not been applied to acyclic 2- and
3-sulfanyl-1-alkanols to date.9 In the following we de-
scribe a simple one-step method for the configurational
assignment of 2- and 3-sulfanyl-1-alkanols and diols
using 3-sulfanyl-1-hexanol 6, 2-sulfanyl-1-hexanol 7, 1,3-
butandiol 8, and 1,2-propandiol 9 as model compounds.
is a versatile and sensitive procedure for determining the
absolute configuration and conformation of organic mol-
ecules containing two or more chromophores and has
been widely used in the field of natural products.1
Hydroxyl groups are converted into various p-substituted
benzoates or other chromophores, which may or may not
be identical. Exciton coupling is based on the through
space coupling of two or more chromophores in chiral
substrates, giving rise to bisignate or split CD curves,
the signs and shapes of which are defined nonempirically
by the spatial arrangement of the interacting chro-
mophores. If the orientation of the electric transition
moments is clockwise (looking from the chromophore in
front to the chromophore in back), defined as positive
chirality, the CD shows a positive first and a negative
second Cotton effect (CE) and vice versa.1 The amplitude2
of the CD curve is (i) inversely proportional to the square
of the interchromophoric distance, (ii) proportional to the
chromophoric absorption coefficient, and (iii) depending
on the chromophoric projection angle with a maximum
at approximately 70°. The exciton chirality method can
be extended to nondegenerate systems consisting of
different chromophores, as well as chromophores which
already preexist in the molecule, e.g., monoene3 and
diene4 moieties. Chromophores with UV maxima as far
apart as 100 nm still can couple. Since the exciton
chirality method depends on the conformation of the
molecules, the stereochemical assignment is most straight-
forward and unambiguous in rigid molecules with fixed
Resu lts a n d Discu ssion
Sulfur compounds play an important role as flavor
compounds because many of them have very low odor
thresholds and contribute considerably to the overall odor
impression even at low concentrations.10 Among this class
of compounds there are many optical active sulfur
compounds, e.g., 3-sulfanyl-1-hexanol11 and 3-sulfanyl-
2-methylpentanol.12 The odor properties of diastereomers
and enantiomers can differ tremendously and therefore
the determination of the absolute configuration is crucial.
(5) (a) Wiesler, W. T.; Nakanishi, K. J . Am. Chem. Soc. 1989, 111,
3446-3447. (b) Rele, D.; Zhao, N.; Nakanishi, K.; Berova, N. Tetra-
hedron 1996, 52, 2759-2776. (c) Akritopoulou-Zanze, I.; Nakanishi,
K.; Stepowska, H.; Grzeszczyk, B.; Zamojski, A.; Berova, N. Chirality
1997, 9, 699-712.
(6) (a) Harada, N.; Saito, A.; Ono, H.; Gawronski, J .; Gawronska,
K.; Sugioka, T.; Uda, H.; Kuriuki, T. J . Am. Chem. Soc. 1991, 113,
3842-3850. (b) Harada, N.; Saito, A.; Ono, H.; Murai, S.; Li, H.-Y.;
Gawronski, J .; Gawronska, K.; Sugioka, T.; Uda, H. Enantiomer 1996,
1, 119-138. (c) Uzawa, H.; Nishida, Y.; Ohrui, H.; Meguro, H. J . Org.
Chem. 1990, 55, 116-122.
† Phone: +49 931 8885483. Fax: +49 931 8885484.
(1) (a) Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopy-
Exciton Coupling in Organic Stereochemistry; University Science
Books: Mill Valley, CA, 1983. (b) Nakanishi, K.; Berova, N. In Circular
Dichroism Principles and Applications; Nakanishi, K., Berova, N.,
Woody, R. W., Eds; VCH Publishers Inc.: New York, 1994.
(2) The distance between the peak and trough of a split CD curve
is defined as the “amplitude” A, and either a positive or negative sign
is assigned to it depending whether the first CE is positive or negative.
(3) Humpf, H.-U.; Berova, N.; Nakanishi, K.; J arstfer, M. B.; Poulter,
C. D. J . Org. Chem. 1995, 60, 3539-3542.
(7) Zhou, P.; Berova, N.; Wiesler, W. T.; Nakanishi, K. Tetrahedron
1993, 49, 9343-9352.
(8) Ho¨r, K.; Gimple, O.; Schreier, P.; Humpf, H.-U. J . Org. Chem.
1998, 63, 322-325.
(9) There is only one application of the exciton chirality method to
a cyclic sulfanyl compound by Gawronski, J .; Gawronska, K.; Wynberg,
H. J . Chem. Soc., Chem. Commun. 1981, 307-308.
(10) Boelens, M. H.; van Gemert, L. J . Perfum. Flavor 1993, 18, 1-6.
(11) Weber, B.; Dietrich, A.; Maas, B.; Marx, A.; Olk, J .; Mosandl,
A. Z. Lebensm. Unters. Forsch. 1994, 199, 48-50.
(4) Schneider, C.; Schreier, P.; Humpf, H.-U. Chirality 1997, 9, 563-
567.
(12) Lu¨ntzel, C. S.; Widder, S.; Vo¨ssing, T.; Pickenhagen, W. J . Agric.
Food Chem. 2000, 48, 424-427.
10.1021/jo010768h CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/27/2001