Enantiomerically pure poly(oxymethylene) helices: Correlating helicity with centrochirality

Article abstract of DOI:10.1002/hlca.200890062

A first series of enantiomerically pure helical oligo(formaldehyde)s (=oligo(oxymethylen)s) 16-20 was synthesized. To induce the chiral uniformity of the helices, we used (1S)-2,2-dimethyl-1-phenylpropan-1-ol (14) to generate the end groups at the α and ω

Full text of DOI:10.1002/hlca.200890062

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Enantiomerically Pure Poly(oxymethylene) Helices: Correlating Helicity with
Centrochirality
by Simon Eppachera), Gerald Giesterb), Jan W. Batsc), and Christian R. Noe*a)
a) Department of Medicinal Chemistry, University of Vienna, Althanstrasse 14, A-1090 Wien
(phone: þ 431427755103; fax þ 43142779551; e-mail: christian.noe@univie.ac.at)
b) Department of Mineralogy and Crystallography, University of Vienna, Althanstrasse 14, A-1090 Wien
c) Department of Organic Chemistry, University of Frankfurt, Max-von-Laue-Strasse 7, D-60438
Frankfurt am Main
A first series of enantiomerically pure helical oligo(formaldehyde)s (¼oligo(oxymethylen)s) 16 – 20
was synthesized. To induce the chiral uniformity of the helices, we used (1S)-2,2-dimethyl-1-phenyl-
propan-1-ol (14) to generate the end groups at the a and w terminus (Scheme 6). Propanol 14 was
accessible from its racemate by acetal formation with lactol 12 and separation of the diastereoisomers
(Scheme 5). The helicity of the oligomers was investigated by temperature-dependent CD, NMR, and
optical-rotation studies. In addition to qualitative considerations concerning the helicity of oligo(form-
aldehyde)s, we performed calculations of the dimer 17 and the pentamer 20 as well as X-ray structure
analyses of the dimer 17 and the tetramer 19 to establish the handedness of the helices and to correlate
their sense with the absolute configuration of the inducing stereogenic center. The results may be of
relevance with respect to induction and propagation of chirality in prebiotic chemistry.
Introduction. – Formaldehyde is one of the ꢀmost fundamental organic moleculesꢁ.
It is also a versatile building block in organic chemistry and found in several
modifications. In the gas phase, it exists as monomeric formaldehyde, in aqueous
solution, it forms a hydrate (formalin, formol), and in the solid state, it is composed of
either cyclic trimers (1,3,5-trioxane, metaformaldehyde), cyclic tetramers (1,3,5,7-
tetroxocane), or linear poly(oxymethylene) (paraformaldehyde), respectively [1 – 3].
Short oligomers of poly(oxymethylene) were found in the tail of the Halley comet [4].
It is well accepted that paraformaldehyde forms a helix as it was shown by theoretical
calculations [5], by IR spectroscopy [6], and by X-ray analysis [7 – 13] (see below).
During our investigation of stereoelectronic effects, we became interested in the
structure of oligomers of formaldehyde, i.e., of 1,13-diphenyl-2,4,6,8,10,12-hexaoxa-
tridecane [14] and its corresponding heptamer (¼1,17-diphenyl-2,4,6,8,10,12,14,16-
octaoxaheptadecane) [15], respectively. These oligomers crystallize as helices and may
serve as ꢀmost basic referenceꢁ for the investigation of stereoelectronic effects, the
anomeric effect (interaction of the n0 lone pair of the O-atom and the s* orbital of the
CÀO bond), in particular, since there are no other interacting effects [16].
To synthesize for the first time an enantiomerically pure oligo(formaldehyde)
(¼oligo(oxymethylene)) helix with predicted handedness, we decided to use a chiral
alcohol, (1S)-2,2-dimethyl-1-phenylpropan-1-ol (14), to generate both end groups (at
the a and w terminus) of the formaldehyde oligomer. We report the synthesis and
ꢂ 2008 Verlag Helvetica Chimica Acta AG, Zürich

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characterization of a first series of enantiomerically pure oligo(oxymethylene)s up to
pentamer 20, capped by 14. As evidence of the correct structure, we additionally
present the crystal structure of the dimer 17 and the tetramer 19.
Results and Discussion. – 1. Qualitative Considerations of the Helicity of
Poly(formaldehyde). The conformational analysis of the poly(formaldehyde) helix is
in line with the rules applied by Eschenmoser and Dobler for the conformational
analysis of homo-DNA [17] and p-RNA and which is also comprehensively discussed in
the book of Quinkert, Egert, and Griesinger [18].
If only the three idealized staggered conformations (þsc, À sc, and trans) are
considered, one needs two criteria to explain the helicity of poly(formaldehyde): a) the
anomeric effect (stereoelectronic rule), b) each electron pair should be involved only in
one anomeric effect. This is the generalized b(ulky), pl(anar), and H rule (b-pl-H rule)
[19] with one additional H instead of the b(ulky) group. Depending on whether one
starts from position a) or b) depicted in Fig. 1, one ends up with a right- or a left-handed
helix, respectively. Since benzyl alcohol, which was first used for the end groups at the a
and w terminus, is an achiral substrate, there is no preference to start from position a)
or b), and as a result, a racemic mixture of oligomers is formed [14][15]. To obtain a
first enantiomerically pure oligo(formaldehyde), we decided to use a chiral alcohol to
generate the end groups. By applying the b-pl-H rule [19], it can be predicted that helix
formation will be left-handed if both end groups will be derived from a ꢀBꢁ-configured
alcohol, and a right-handed helix will be formed if both end groups will be an ꢀAꢁ-
configured alcohol.
Fig. 1. Qualitative conformational analysis of an oligo(oxymethylene) strand
2. Synthesis of the Protected Enantiomerically Pure Oligo(oxymethylene)s. As a first
enantiomerically pure inducer for the oligomerization, we prepared (1S)-1-phenyl-
propan-1-ol (4), a ꢀBꢁ-type compound, from lactone 1 in three steps (Scheme 1). We
used lactol 2 [20][21], which is accessible from lactone 1 by reduction with
diisobutylaluminium hydride (DIBAL) in 90% yield, to resolve (Æ)-4. Acetal 3 was

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obtained with a diastereoselectivity of 4.5 :1 by reacting lactol 2 with an excess of (Æ)-4
in the presence of catalytic amounts of triphenylphosphonium bromide. The good
diastereoselectivity can be explained by a combination of anomeric, exo-anomeric, and
steric effects as described earlier [22 – 26] and will be discussed in detail in a
forthcoming publication. The diastereoisomer of acetal 3, formed in minor quantities,
could be removed by flash chromatography. The enantiomerically pure (1S)-1-
phenylpropan-1-ol (4) was liberated by treatment of acetal 3 with catalytic amounts of
TsOH in iPrOH/CH2Cl2. Propanol 4 could be separated from acetal 5 by bulb-to-bulb
distillation.
Scheme 1
a) DIBAL, toluene; 90%. b) (Æ)-4, cat. [HPPh3]Br, CH2Cl2; 49% of 3 and 31% of 3/diastereoisomer of
3. c) TsOH, iPrOH/CH2Cl2 3 :1; 47%.
Unfortunately, a trial experiment with racemic (Æ)-4, which we carried out to
investigate the oligomerization reaction under the same conditions as in the case of
benzyl alcohol (Scheme 2), had an unexpected outcome. Instead of the expected
oligomerization products, we found trans-5-methyl-4-phenyl-1,3-dioxolane (6). For its
formation, we propose the following reaction sequence: elimination of H2O from 1-
phenylpropan-1-ol, a Prins reaction, and a final cyclization with a second molecule of
formaldehyde [27].
To prevent the elimination reaction leading to the Prins reaction sequence, we
chose a 4-nitrophenyl group to destabilize the positive charge at the benzylic position,
which is generated in the elimination step. The 1-(4-nitrophenyl)ethanol (8) was
obtained by reduction of 4-nitroacetophenone (7) with NaBH4 in EtOH and was
treated under our standard oligomerization conditions (Scheme 3). As foreseen, the
elimination reaction was now suppressed and did no longer control the scene. However,
instead of the wanted longer oligomers we could only isolate the monomer 9 in
reasonable yields.
As the next b-pl-H-type chiral inducer, we tested lactol 2 (Scheme 4). But, as in the
case of (Æ)-4, we obtained the dioxolane derivative 10, which is probably built by the
same elimination, Prins reaction, and cyclization sequence as that leading to dioxolane
6.

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Scheme 2
a) Cat. H2SO4, paraformaldehyde, benzene; 81%.
Scheme 3
a) NaBH4, EtOH; 98%. b) Cat. H2SO4, paraformaldehyde, benzene; 83%.
Scheme 4
a) Cat. H2SO4, paraformaldehyde, benzene; 37%.
Finally, we decided to use (1S)-2,2-dimethyl-1-phenylpropan-1-ol (14) as chirality-
inducing unit (Scheme 5). To separate racemic 14, we used lactol 12, which is accessible
from lactone 11 by reduction with DIBAL. By using a fourfold excess of (Æ)-14, we
obtained acetal 13 with the good diastereoselectivity ratio of 5.4 :1, which could be
enriched to a 12 :1 ratio and to pure 13, depending on the conditions used for flash
chromatography. When lactol 2 was used instead of lactol 12, the corresponding acetal
was not separable from the excess of (Æ)-14. The enantiomerically enriched 14 was
released by treatment of acetal 13 with a catalytic amount of TsOH in MeOH/CH2Cl2
1:1 in 67% yield.
By using first (Æ)-14 for our standard oligomerization protocol (2 h in refluxing
benzene with catalytic amounts of H2SO4), we found a complex reaction mixture. By
optimizing the reaction conditions, we realized that the reaction was complete within
5 min in refluxing benzene/cat. H2SO4 and an excess of paraformaldehyde (Scheme 6).

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Scheme 5
a) DIBAL, toluene; 91%. b) (Æ)-14, cat. [HPPh3]Br, CH2Cl2; 38% of 13, and 49% of 13/diastereoisomer
of 13. c) TsOH, MeOH/CH2Cl2 1:1, 67%.
By immediate quenching of the reaction with NaHCO3, we could isolate our desired
oligomers up to a pentamer 20 in yields which where sufficient for most character-
izations.
Scheme 6
a) Cat. H2SO4, paraformaldehyde, benzene; 12% (16), 18% (17), 8% (18), 8% (19), and 1% (20).
1
3. Characterization of the Compounds. In the H-NMR spectrum of compound 3,
HÀC(2) is shifted downfield by 0.33 ppm compared to the corresponding signal in the
diastereoisomer of 3, and HÀC(7a) of 3 is shifted upfield by 0.15 ppm compared to
HÀC(7a) of the diastereoisomer of 3. As discussed in an earlier paper [28], this
indicates the (S)-configuration at C(1) of the 1-phenylpropoxy part of acetal 3, which
was established by the optical rotation of the liberated alcohol 4.
The structure of the dioxolane derivative 10 was established by its 1H- and
13C-NMR, HSQC, HMBC, COSY, and NOESY data. The relative configuration at
HÀC(4a) of 10 was ascertained by a cross-peak of the signal of one Me group with the
signal of HÀC(4a).
As in the case of acetal 3, the signal of HÀC(2) of 13 is shifted downfield by
0.30 ppm compared to that of its diastereoisomer, and HÀC(7a) of 13 is shifted upfield
by 0.65 ppm compared to HÀC(7a) of its diastereoisomer. Again, this shows the (S)-
configuration at C(1) in the 2,2-dimethyl-1-phenylpropoxy part of acetal 13, which was
again established by the optical rotation of the liberated alcohol 14 [29].

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Since the oligomers 16 – 20 all possess a twofold axis of symmetry, we observed only
one set of signals in the NMR spectra. For the monomer 16, we found a s at d(H) 4.41
due to the OCH2O group and a s at d(H) 4.36 due to HÀC(1,5)1). For the dimer 17,
however, we found two ds at d(H) 4.96 and 4.36 which are due to the two diastereotopic
H-atoms of the OCH2O groups. The Dd value can be explained by the fact that one of
the two H-atoms of the OCH2O groups is in close contact to the Ph group and therefore
shielded, whereas the other one is too far-off from the Ph group to be influenced. The
comparably small Jgem value of 7.1 Hz is typical for normal formaldehyde acetals. In the
13C-NMR spectrum of 17, we found (as expected) one t at d(C) 88.3 due to the two
equivalent OCH2O groups. For the trimer 18, we found, according to HSQC and
HMBC, a s at d(H) 4.88 that is correlated to the inner OCH2O group (CH2(5)1)) and
two ds for the outer OCH2O groups (HaÀC(3), HaÀC(7) and HbÀC(3), HbÀC(7),
resp.) at d(H) 4.78 and 4.37, respectively. This shift difference of the two pairs of H-
atoms can be explained as in the case of dimer 17, and also Jgem ¼ 7.0 Hz is almost the
same as for 17. In the 13C-NMR spectrum of 18, the inner C(5) gives raise to a t at d(C)
87.4, while the outer two C-atom signals (C(3) and C(7)) appear as one t at d(C) 89.0
which was again verified by HSQC and HMBC data. As expected, we observed a ca.
1:2 intensity ratio of the two ts, in accord with a C2 symmetry. For the tetramer 19, we
found, in addition to the coupling of the outer diastereotopic H-atoms (HaÀC(3),
HaÀC(9) and HbÀC(3), HbÀC(9), resp.1)) at d(H) 4.73 and 4.37, a coupling of the
inner H-atoms of the OCH2O groups (HaÀC(5), HaÀC(7) and HbÀC(5), HbÀC(7),
resp.) at d(H) 4.76 and 4.71, as shown again by HSQC and HMBC measurements. In
the 13C-NMR spectrum of 19, the inner two C-atoms (C(5) and C(7)) give raise to one t
at d(C) 88.1, while the outer two C-signals (C(3) and C(9)) resonate as one t at d(C)
89.5, which was again verified by HSQC and HMBC measurements. For the 1H-NMR
spectrum of the pentamer 20, we observed three sets of signals for the OCH2O groups.
One s corresponding to the innermost OCH2O group at d(H) 4.78, one pair of ds for the
second-outermost OCH2O groups (HaÀC(5), HaÀC(9) and HbÀC(5), HbÀC(9),
resp.1)) appearing at d(H) 4.86 and 4.80, and an other pair of ds for the outermost
OCH2O groups (HaÀC(3), HaÀC(11) and HbÀC(3), HbÀC(11), resp.) showing up at
d(H) 4.79 and 4.46. Again, the signals were correlated by a combination of HSQC and
HMBC measurements. In the 13C-NMR, we observed three ts for the corresponding
OCH2O C-atoms. As shown by the HSQC and HMBC plots, C(7) resonates at d(C)
88.7, C(3,11) at d(C) 89.7, and, finally C(5,9) at d(C) 88.3, the three ts exhibiting a ca.
1:2 :2 intensity ratio.
To get additional experimental proof for the helical properties of our oligomers 16 –
20, we investigated temperature-depending CD spectra. Unfortunately, we observed
only little effects in the oligomers 16 – 20, which we also observed for the monomer 14,
the latter being chosen as reference. For example, the pentamer 20 shows (as expected)
a 10% decrease of ellipticity at lmax 260 nm when the temperature was increased from
48 to 708. However, when we examined alcohol 14 as a reference, we also observed a
13% decrease of ellipticity by increasing the temperature from 48 to 708. Besides these
only minor changes in the ellipticity with temperature, it was also found that the
1
)
Arbitrary atom numbering of the heterochain (C(1) is Ph-substituted); for systematic names, see
Exper. Part.

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absolute ellipticity of the oligomers was in the same range as that of the reference
alcohol 14. In conclusion, no evidence was found by CD spectroscopy supporting the
occurrence of helix formation.
Next, we examined the temperature-dependence of the 1H-NMR (300 MHz)
signals of the three inner OCH2O units of pentamer 20 in relation to the signals of
HÀC(1,13)1) (Fig. 2). As can be seen from Fig. 2, the HaÀC(5,9) and HbÀC(5,9)
signals are shifted upfield by 0.018 and 0.009 ppm, respectively, while the CH2(7)
signals are shifted downfield by 0.013 ppm, when the temperature was increased from
288 to 888. In comparison to these changes, the signal of HÀC(1,13) remains within a
0.001 ppm range in this temperature interval. By cooling down the sample to the
starting temperature, we obtained the same spectra as at the beginning. This suggests a
conformational reversibility within the heating and cooling cycle. These results are a
clear indication for an ordered structure in the pentamer 20, which breaks down as the
temperature is raised.
Fig. 2. Temperature dependency of selected 1H-NMR signals of pentamer 20
As a next criterion for the structure attribution of our oligomers, we examined the
temperature dependency k of the optical rotation of the oligomers 16 – 20 at 589 and
436 nm. In contrast to the temperature-dependent CD spectra, we observed a clear
difference of the temperature dependency k of the optical rotation of the oligomers
16 – 20, in contrast to the monomer 14 (Fig. 3), which was measured at 589 nm. For
example, the pentamer 20 (n ¼ 4) shows the largest dependency of the optical rotation
with temperature (k ([a]D) ¼ 1.41/8), while the reference alcohol 14 exhibits a far
smaller ([a]D) value k (0.06/8). All oligomers and the reference alcohol 14 show a linear
dependency of the specific optical rotation within the measured temperature range
(20 – 508), with a linearity coefficient larger than 0.99.
In addition to this fact, also the absolute specific rotation varies significantly on
increasing the chain length (Fig. 4): We observed a large increase of [a]D for the
monomer 16 (n ¼ 0) compared to the small value for the reference alcohol 14, and a

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Fig. 3. Dependency of the temperature dependency k of the optical rotation k ([a]D)/8) with the chain
length n
further increase for the dimer 17. For the trimer 18, tetramer 19, and pentamer 20, the
value of the specific optical rotation remains approximately the same.
Fig. 4. Dependency of the optical rotation [a]D with the chain length
By measuring the dependency k of the optical rotation with the temperature at
436 nm, the same tendency as described above for the measurement at 589 nm was
observed, with approximately two times higher values (data not shown). All the
measurements were reversible within a range of 208 to 508. The strong temperature
dependency of the optical rotation of the oligomers 16 – 20 and the high optical
rotations of 16 – 20 in comparison to that of 14 are a clear evidence for the ordered
structure of the oxymethylene units in the oligomers 16 – 20.

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4. Molecular Modeling. To get a first idea about the way the conformation of our
helix would be initiated by (1S)-2,2-dimethyl-1-phenylpropan-1-ol (14), we performed
modeling calculations. First we calculated the right-handed conformation for the
oxymethylene units in dimer 17 (n ¼ 1). As starting conformation, we chose the b-pl-H
rule conformation around the C(1)ÀO(2) as for the O(6)ÀC(7) bond1), respectively
(corresponding to an anti-periplanar (ap) arrangement of the tert-butyl groups and
C(3) and C(5), resp.) and the þ sc conformation around the other bonds along the
helix. After the minimization, we examined the torsion angles along the chain. We
found a significant deviation of the ap conformation for the C(1)ÀO(2) bond of 238 as
well as a deviation from the sc conformation of 88 and 178 for the remaining bonds in
the helix chain. This calculation was repeated with the same starting conformation
around the C(1)ÀO(2) bond (and around the O(6)ÀC(7) bond) but with À sc
conformation around the other bonds along the helix. After the minimization, we found
here smaller deviations in the ap conformation for the C(1)ÀO(2) bond of 128 as well
as for the deviation from the À sc conformation of 58 and 108 for the remaining bonds
in the helix chain. Therefore, we concluded that if the helix is induced by 14, we should
end up with a left-handed conformation for the poly(oxymethylene) helix. These
calculations were compared with the results of the X-ray structure analysis of dimer 17
and tetramer 19.
Next, we performed the same calculations with pentamer 20. As in the case of dimer
17, we obtained, after the minimization of the right-handed case of the idealized
structure, considerable deviations of the torsion angles of the C(1)ÀO(2) bond (ca. 308)
and deviations for the other bond angles in the helix from the þ sc conformation (0 –
188). In the case of the left-handed helix, we got smaller aberrations for the torsion
angles of the C(1)ÀO(2) bond (ca. 108) as well as for the other bond angles in the helix
from the À sc conformation (2 – 58). Therefore, we concluded again that these results
give a clue about the preferred conformation of the helix in pentamer 20.
5. X-Ray Structure Analysis of Dimer 17 and Tetramer 19. From dimer 17 and
tetramer 19, we obtained suitable crystals by recrystallization from EtOH for an X-ray
analysis2).
For dimer 17, the absolute structure could not be determined reliably (see poorly
defined Flack parameter). However, since the absolute configuration of 14 is (S),
corresponding to a ꢀB-descriptorꢁ in the stereoelectronic-effect-based classification
[19], we find from the optical rotation the left-handed conformation for the
oxymethylene helix, as it was predicted by the calculations for dimer 17 (see Fig. 5).
As expected, the torsion angles C(5)ÀC(1)ÀO(1)ÀC(2) (Fig. 5, Table 1) and
C(3)ÀO(3)ÀC(4)ÀC(15) are 150.1(2) and 156.9(2)8, respectively, with a deviation
of 308 and 238, respectively, from the b-pl-H rule.
The remaining torsion angles in the poly(oxymethylene) helix of 17 are in the
expected range of À 698 to À 798 resulting in a deviation of 9 – 198 from the idealized
conformation according to the anomeric effect as shown by the calculations. The
2
)
CCDC-658327 (17) and CCDC-658328 (19) contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif (or
from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax:
þ 44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk).

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Fig. 5. Structure of 17 obtained by X-ray diffraction. Thermal ellipsoids at 50% level; H-atoms shown as
small spheres of arbitrary radii; drawings performed with ATOMS [30].
Table 1. Selected Bond Lengths, Bond Angles, and Torsion Angles of 17. See Fig.5 for atom numbering.
Length [Š]
Angle [8]
Torsion angle [8]
C(1)ÀO(1) 1.447(2)
C(1)ÀO(1)ÀC(2) 113.5(2) C(5)ÀC(1)ÀO(1)ÀC(2)
150.1(2)
O(1)ÀC(2) 1.399(3)
C(2)ÀO(2) 1.406(3)
O(2)ÀC(3) 1.412(3)
C(3)ÀO(3) 1.404(3)
O(3)ÀC(4) 1.439(3)
O(1)ÀC(2)ÀO(2) 112.9(2) C(1)ÀO(1)ÀC(2)ÀO(2) À 79.4(2)
C(2)ÀO(2)ÀC(3) 112.0(2) O(1)ÀC(2)ÀO(2)ÀC(3) À 69.4(2)
O(2)ÀC(3)ÀO(3) 112.0(2) C(2)ÀO(2)ÀC(3)ÀO(3) À 72.6(2)
C(3)ÀO(3)ÀC(4) 113.2(2) O(2)ÀC(3)ÀO(3)ÀC(4) À 76.4(2)
C(3)ÀO(3)ÀC(4)ÀC(15) 156.9(2)
CÀOÀC bond angles are almost constant and within the range 113.5(2) – 112.0(2)8.
The OÀCÀNO bond angles are also almost constant with 112.9(2) and 112.0(2)8. No
stereoelectronic effects are expected for the terminal CÀO bonds. Those bonds show a
length of 1.447(2) and 1.439(3) Š, and thus are significantly longer than the remaining
CÀO bonds which are in the range 1.399(3) – 1.412(3) Š. This shortening of ca. 0.038 Š
with respect to a standard CÀO bond indicates a clear operating anomeric effect and
indicates a C¼O bond character of ca. 28%.
For tetramer 19, we observed a similar picture as in the case of dimer 17 (Fig. 6,
Table 2). Similarly, the refinement of the tetramer 19 did not allow a reliable
determination of the absolute structure. But since the absolute configuration of 14 is
known from the specific rotation as mentioned above, we can define a left-handed
conformation for the poly(oxymethylene) helix of 19, as predicted by the calculations
and shown in Fig. 6. As for 17, no steric effect is operating for the teminal CÀO bonds.
These bonds show a length of 1.436(4) and 1.402(5) Š, and are again significantly
longer than the remaining CÀO bonds, which are within the range 1.370(5) – 1.416(5)
Š. This shortening of ca. 0.027 Š with respect to a standard CÀO bond indicates again
the operating anomeric effect. The torsion angles C(7)ÀC(1)ÀO(1)ÀC(2) and
C(5)ÀO(5)ÀC(6)ÀC(17) are 161.8(3) and 149.2(4)8, respectively, with a deviation

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of 188 and 318, respectively, according to the b-pl-H rule. The remaining torsion angles
in the poly(oxymethylene) helix lie within the expected range (À658 to À 908),
resulting in a deviation of up to 308 from the idealized conformation according to the
anomeric effect, as shown by the calculations. The CÀOÀC bond angles are almost
constant and in the range of 113 – 1158. The OÀCÀO bonds are also almost constant
within 1118 and 1158.
Fig. 6. Structure of 19 obtained by X-ray diffraction. Thermal ellipsoids at 50% level; H-atoms shown as
small spheres of arbitrary radii; drawings performed with ATOMS [30]. Arbitrary atom numbering.
Table 2. Selected Bond Lengths, Bond Angles, and Torsion Angles of 19. See Fig.6 for atom numbering.
Length [Š]
C(1)ÀO(1) 1.436(4)
Angle [8]
Torsion angle [8]
C(1)ÀO(1)ÀC(2) 113.1(3) C(7)ÀC(1)ÀO(1)ÀC(2)
161.8(3)
O(1)ÀC(2) 1.411(4)
C(2)ÀO(2) 1.388(5)
O(2)ÀC(3) 1.392(6)
C(3)ÀO(3) 1.416(5)
O(3)ÀC(4) 1.409(6)
C(4)ÀO(4) 1.370(5)
O(4)ÀC(5) 1.406(6)
C(5)ÀO(5) 1.414(5)
O(5)ÀC(6) 1.402(5)
O(1)ÀC(2)ÀO(2) 113.7(4) C(1)ÀO(1)ÀC(2)ÀO(2) À 67.1(5)
C(2)ÀO(2)ÀC(3) 114.1(4) O(1)ÀC(2)ÀO(2)ÀC(3) À 78.7(5)
O(2)ÀC(3)ÀO(3) 111.1(4) C(2)ÀO(2)ÀC(3)ÀO(3) À 80.1(5)
C(3)ÀO(3)ÀC(4) 112.7(4) O(2)ÀC(3)ÀO(3)ÀC(4) À 77.6(5)
O(3)ÀC(4)ÀO(4) 114.7(4) C(3)ÀO(3)ÀC(4)ÀO(4) À 74.1(6)
C(4)ÀO(4)ÀC(5) 113.4(4) O(3)ÀC(4)ÀO(4)ÀC(5) À 64.9(5)
O(4)ÀC(5)ÀO(5) 112.1(4) C(4)ÀO(4)ÀC(5)ÀO(5) À 71.2(5)
C(5)ÀO(5)ÀC(6) 114.5(4) O(4)ÀC(5)ÀO(5)ÀC(6) À 90.3(5)
C(5)ÀO(5)ÀC(6)ÀC(17) 149.2(4)
Conclusions. – We synthesized a set of enantiomerically pure poly(oxymethylene)
helices with predictable handedness, which are capped by moieties derived from (1S)-
2,2-dimethyl-1-phenylpropan-1-ol (14), up to a pentamer 20. By measuring the
1
temperature-dependent optical rotation and temperature-dependent H-NMR shifts,

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we found a reversibility of an ordered structure that breaks down as soon as the
temperature is increased, thus confirming the helical structure of the molecules in
solution. In the X-ray structure analysis of dimer 17 and tetramer 19, the helical
arrangement of the oxymethylene units induced by the anomeric effect could also be
found. Starting from 14 corresponding to a ꢀBꢁ-descriptor according to the b-pl-H rule,
we were able to establish the left-handedness of all the poly(oxymethylene) helices,
which we could isolate and investigate. The option to directly correlate a B-type center
of chirality to a left-handed helix may also be of importance in planning syntheses of
enantiomerically pure oligo- and poly(acetals). Last but not least, it should be
mentioned that in the case of an oxymethylene chain, helix chirality is introduced into
an organic molecule by conformational order caused by stereoelectronic effects.
Conditions for such an induction might easily be given by environmental circumstances,
such as the presence of chiral inorganic molecules. The direct association of the
handedness of a helix and the configuration of a chirality center bearing ligands, a
situation frequently found in biomolecules, would then unambiguously define the
direction of the propagation of this chirality.
Experimental Part
General. THF was distilled from Na/benzophenone, toluene from Na. Petroleum ether was of
b.p. 50 – 758. Reactions were run under Ar. Qual. TLC: precoated silica-gel plates (Merck silica gel 60
F254): detection by spraying with ꢀmostainꢁ (400 ml of 10% aq. H2SO4 soln., 20 g of (NH4)6Mo7O2 · H2O,
0.4 g of Ce(SO4)2) and heating. Flash chromatography (FC): silica gel Merck 60 (0.04 – 0.063 mm).
1
Optical rotations: 1-dm cell at 208 (unless otherwise given) and 589 nm. FT-IR: 1 – 2% KBr plates. H-
and 13C-NMR: at 200, 300, or 500 MHz and 50 or 125 MHz, resp. MS: Electron-spray ionization (ESI).
All molecular-modeling calculations were performed with the ProTM Plus program (version 6.2.2) of
ChemSW (Fairfield, CA 94534).
(2R,3aR,4R,7S,7aR)-Hexahydro-2-hydroxy-8,8-dimethyl-N,N-bis(phenylmethyl)-4,7-methanoben-
zofuran-7(4H)-methanesulfonamide (2). At À 788, a soln. of exo-lactone 1 (4 g, 8.83 mmol) in toluene
(60 ml) was treated dropwise with a soln. of 20% DIBAL in toluene (1.7 equiv., 15.0 mmol) in a way that
the temp. did not exceed À 408 and stirred for 2 h at À 608. The soln. was poured into ice (50 g) and 2n
HCl (60 g), and the aq. phase was extracted with CH2Cl2 (2Â). The combined org. phase was washed
with sat. aq. NaHCO3 soln. and H2O, dried (Na2SO4), and concentrated: 3.6 g (90%) of 2. Colorless
crystals. Rf (petroleum ether/Et2O 1:1) 0.39. M.p. 129 – 1308. IR: 3282m (br.), 2935m, 1453m, 1332s,
1
1143s, 1089m, 1042m, 1013m, 934m, 792m, 702m. H-NMR (200 MHz, CDCl3): 7.35 – 7.30 (m, 10 arom.
H); 5.40 (d, J ¼ 3.4, HÀC(2)); 4.60 (d, J ¼ 7.6, HÀC(7a)); 4.40 (d, J ¼ 15.1, PhCH2N); 4.29 (d, J ¼ 15.1,
PhCH2N); 3.26 (d, J ¼ 13.6, 1 H, SO2CH2C(7)); 2.67 (br. s, OH); 2.67 (d, J ¼ 13.5, 1 H, SO2CH2C(7));
2.52 – 2.38 (m, HÀC(3a)); 2.20 – 1.65 (m, HÀC(7a)); 2.20 – 1.65 (m, 1 HÀC(5), 1 HÀC(6), CH2(3),
HÀC(4)); 1.60 – 1.40 (m, 1 HÀC(5)); 1.20 – 1.00 (m, 1 HÀC(6)); 0.81, 0.71 (2s, Me2C). 13C-NMR
(50 MHz, CDCl3): 136.0 (s, C(1) of Ph); 129.1 (d, C(2,6) of Ph); 128.8 (d, C(3,5) of Ph); 128.0 (d, C(4) of
Ph); 99.8 (d, C(2)); 87.6 (d, C(7a)); 51.6 (t, SO2CH2ÀC(7)); 50.1 (t, PhCH2N); 49.4 (s, C(8)); 48.5 (s,
C(7)); 47.6 (d, C(4)); 46.1 (t, C(3)); 39.3 (d, C(3a)); 29.0 (t, C(5)); 28.6 (t, C(6)); 23.2, 20.4 (2q, Me2C).
ESI-MS (pos.-ion mode): 949 (20, [2M þ K]þ), 933 (100, [2M þ Na]þ), 494 (7, [M þ K]þ), 478 (15, [M þ
Na]þ). Anal. calc. for C26H33NO4S (455.61): C 68.54, H 7.30, N 3.07, S 7.04; found: C 68.44, H 7.53, N 3.16,
S 6.84.
(2R,3aR,4R,7S,7aR)-Hexahydro-8,8-dimethyl-N,N-bis(phenylmethyl)-2-[(1S)-1-phenylpropoxy]-
4,7-methanobenzofuran-7(4H)methanesulfonamide (3). A soln. of (Æ)-4 (4.31 ml, 31.5 mmol) and 2
(3.6 g, 7.9 mmol) in CH2Cl2 (25 ml) was treated with triphenylphosphonium bromide (343 mg, 1 mmol)
and stirred at 238 for 20 h. The mixture was washed with sat. aq. NaHCO3 soln. and brine, dried
(Na2SO4), and concentrated. FC (petroleum ether/tBuOMe 30 :1 ! 6 :1) gave 3 (2.11 g, 49%) and 3/

Helvetica Chimica Acta – Vol. 91 (2008)
593
diastereoisomer of 3 (1.35 g, 31.3%). Data of 3: Colorless oil. Rf (petroleum ether/Et2O 3 :1) 0.68.
1
[a]2D5 ¼ À84.5 (c ¼ 0.99, acetone). IR: 2903s, 1495m, 1456m, 1336s, 1148s, 1009m, 790m, 701s. H-NMR
(200 MHz, CDCl3): 7.60 – 7.20 (m, 15 arom. H); 4.97 (d, J ¼ 4.7, HÀC(2)); 4.58 (d, J ¼ 7.7, H ÀC(7a));
4.57 – 4.54 (m, HÀC(1’)); 4.58 (d, J ¼ 15.1, PhCH2N); 4.32 (d, J ¼ 15.1, PhCH2N); 3.26 (d, J ¼ 13.5, 1 H,
SO2CH2ÀC(7)); 2.62 (d, J ¼ 13.5, 1H, SO2CH2ÀC(7)); 2.55 – 2.28 (m, HÀC(3a)); 2.20 – 1.65 (m,
HÀC(7a)); 2.20 – 1.50 (m, CH2(5), CH2(6), CH2(3), HÀC(4), CH2(2’)); 0.92 (t, J ¼ 7.7, Me(3’)); 0.77,
0.73 (2s, Me2C). 13C-NMR (50 MHz, CDCl3): 142.0 (s, C(1) of Ph); 136.1 (s, C(1) of Bn); 129.2 (d, C(2,6)
of Bn); 128.8 (d, C(3,5) of Bn); 128.3 (d, C(2,6) of Ph); 128.1 (d, C(3,5) of Ph); 127.3 (d, C(4) of Ph);
127.2 (d, C(4) of Bn); 101.5 (d, C(2); 87.0 (d, C(7a)); 78.1 (d, C(1’); 51.8 (t, SO2CH2ÀC(7)); 50.0 (t,
PhCH2N); 49.4 (s, C(8)); 48.5 (s, C(7)); 47.7 (d, C(4)); 46.4 (t, C(3)); 38.8 (d, C(3a)); 31.5 (t, C(2’)); 29.1
(t, C(5)); 28.4 (t, C(6)); 23.2, 20.4 (2q, Me2C); 10.9 (q, C(3’).
(1S)-1-Phenylpropan-1-ol (4). A soln. of 3 (4.8 g, 8.8 mmol) in CH2Cl2 (6 ml) and iPrOH (18 ml) was
treated with TsOH · H2O (1 g, 5,3 mmol) and stirred at 238 for 100 h. The mixture was diluted with
AcOEt (50 ml), washed with sat. aq. NaHCO3 soln. and brine, dried (Na2SO4), and concentrated, and
the residue purified by bulb-to-bulb distillation: 4 (558 mg, 47%).
Data of 4: Colorless oil. Rf (petroleum ether/Et2O 15 :1) 0.20. [a]2D5 ¼ À30.1 (c ¼ 0.85, acetone). IR:
3370m (br.), 2964m, 2930m, 2860m, 1492m, 1453s, 1096m, 1013m, 775m, 763m, 700s. 1H-NMR (200 MHz,
CDCl3): 7.45 – 7.25 (m, 5 arom. H); 4.59 (t, J ¼ 6.7, HÀC(1)); 1.88 (quint., J ¼ 8.8, 1 HÀC(2)); 1.74 (quint.,
J ¼ 9.0, 1 HÀC(2)); 0.93 (t, J ¼ 7.3, Me(3)). 13C-NMR (50 MHz, CDCl3): 144.7 (s, C(1) of Ph); 128.5 (d,
C(2,6) of Ph); 127.6 (d, C(3,5) of Ph); 126.1 (d, C(4) of Ph); 76.1 (d, C(1)); 32.0 (t, C(2)); 10.3 (q, C(3)).
ESI-MS (pos.-ion mode): 159 (20, [M þ Na]þ).
Data of (2R,3aR,4R,7S,7aR)-Hexahydro-8,8-dimethyl-2-(1-methylethoxy)-N,N-bis(phenylmethyl)-
4,7-methanobenzofuran-7(4H)-methanesulfonamide (5): Colorless oil. Rf (petroleum ether/Et2O 15 :1)
0.36. 1H-NMR (200 MHz, CDCl3): 7.50 – 7.20 (m, 10 arom. H); 5.25 (d, J ¼ 3.5, HÀC(2)); 4.48 (d, J ¼ 7.6,
HÀC(7a)); 4.50 (d, J ¼ 15.2, PhCH2N); 4.37 (d, J ¼ 13.5, PhCH2N); 3.97 (sept., J ¼ 6.2, Me2CHÀC(2));
3.30 (d, J ¼ 13.5, 1 H, SO2CH2ÀC(7)); 2.63 (d, J ¼ 13.5, 1H, SO2CH2ÀC(7)); 2.50 – 2.30 (m, HÀC(3a));
2.20 – 1.65 (m, HÀC(7a)); 2.15 – 1.60 (m, 1 HÀC(5), 1 HÀC(6), CH2(3), HÀC(4)); 1.20 (d, J ¼ 7.7, 3 H,
Me2CHÀC(2)); 1.15 – 1.10 (m, 1 HÀC(5)); 1.10 (d, J ¼ 6.1, 3 H, Me2CHÀC(2)); 1.00 – 0.90 (m,
1 HÀC(6)); 0.87, 0.74 (2s, Me2C).
trans-5-Methyl-4-phenyl-1,3-dioxolane (6). A suspension of paraformaldehyde (12.0 g, 0.4 mol) and
(Æ)-4 (5.4 ml, 0.04 mol) in benzene (60 ml) was treated dropwise at 238 with H2SO4 (0.5 ml), stirred
under reflux for 2 h, cooled to 238, treated with solid NaHCO3 (2 g), and stirred for 30 min. The mixture
was filtered, the solid washed with tBuOMe, and the filtrate concentrated. FC (petroleum ether/tBuOMe
60 :1 ! 6 :1) gave 6 (5.74 g, 81%). Colorless oil. Rf (petroleum ether/Et2O 15 :1) 0.17. IR: 2959m, 2842m,
1494w, 1455m, 1402m, 1380m, 1175s, 1107m, 1072s, 1029s, 956m, 756m, 700s. 1H-NMR (500 MHz,
CDCl3): 7.40 – 7.25 (m, 5 arom. H); 5.20 (d, Jgem ¼ 6.2, 1 HÀC(2)); 4.82 (d, Jgem ¼ 6.3, 1 HÀC(2)); 4.12 (d,
3
J ¼ 10, HÀC(4)); 4.11 (d, J ¼ 11.1, HaÀC(6)); 3.40 (t, Jgem ꢀ J(6b,5) ¼ 11.1, HbÀC(6)); 2.18 – 2.05 (m,
HÀC(5)); 0.58 (d, J ¼ 8.8, MeÀC(5)). 13C-NMR (125 MHz, CDCl3): 139.4 (s, C(1) of Ph); 128.3 (d,
C(2,6) of Ph); 128.1 (d, C(4) of Ph); 127.2 (d, C(3,5) of Ph); 94.0 (t, C(2)); 86.1 (d, C(4)); 72.9 (t, C(6));
36.3 (d, C(5)); 12.4 (q, Me).
1-(4-Nitrophenyl)ethanol (8). At 08, a soln. of 4-nitroacetophenone (5 g, 30 mmol) in EtOH (30 ml)
was treated dropwise with a soln. of NaBH4 (0.34 g, 9.1 mmol) in EtOH (8 ml) and stirred for 1 h. The
mixture was then treated with sat. aq. NH4Cl soln. (15 ml), diluted with AcOEt (80 ml), washed with sat.
aq. NH4Cl soln. and brine, dried (Na2SO4), and concentrated: 8 (4.9 g, 98%). Rf (petroleum ether/Et2O
1:1) 0.28. IR (KBr): 3399m (br.), 2975w, 1605m, 1519s, 1347s, 1107m, 1090m, 1013w, 856m, 700m.
1H-NMR (200 MHz, CDCl3): 8.16 (d, J ¼ 6.2, HÀC(3’,5’); 7.52 (d, J ¼ 8.6, HÀC(2’,6’); 5.01 (q, J ¼ 6.6,
HÀC(1)); 2.20 (s, OH); 1.50 (d, J ¼ 6.6, Me(2)). 13C-NMR (125 MHz, CDCl3): 153.2 (s, C(4) of Ar);
146.0 (s, C(1) of Ar); 126.2 (d, C(2,6) of Ar); 123.8 (d, C(3,5) of Ar); 69.6 (d, C(1)); 25.6 (q, Me).
2,6-Bis(4-nitrophenyl)-3,5-dioxaheptane (¼1,1’-[Methylenebis(oxyethylidene)]bis[4-nitrobenzene];
9). A suspension of paraformaldehyde (3.6 g, 120 mmol) and (Æ)-8 (2 g, 12 mmol) in benzene (20 ml)
was treated dropwise at 238 with H2SO4 (0.13 ml), stirred under reflux for 2 h, cooled to 238, treated with
solid NaHCO3 (0.5 g), and stirred for 30 min. The mixture was filtered, the solid washed with tBuOMe,
and the filtrate evaporated. FC (petroleum ether/tBuOMe 10 :1 ! 1:1) gave 9 (1.70 g, 83%). Yellow

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Helvetica Chimica Acta – Vol. 91 (2008)
crystals. Rf (petroleum ether/Et2O 1:1) 0.28. M.p. 123 – 1268. IR (KBr): 3109w, 2979w, 1607m, 1520s,
1
1348s, 1105m, 1094m, 1024s, 1008m. H-NMR (200 MHz, CDCl3): 8.14 (d, J ¼ 8.6, HÀC(3’,5’)); 7.43 (d,
J ¼ 8.6, HÀC(2’,6’); 4.91 (q, J ¼ 6.6, HÀC(2,6)); 4.55 (s, OCH2O); 1.49 (d, J ¼ 6.6, 2 Me). 13C-NMR
(50 MHz, CDCl3): 150.8 (s, C(4) of Ar); 147.5 (s, C(1) of Ar); 127.2 (d, C(2,6) of Ar); 123.9 (d, C(3,5) of
Ar); 91.2 (t, OCH2O); 73.6 (d, C(1,5); 25.6 (q, Me). ESI-MS (pos.-ion mode): 369.1 (100, [M þ Na]þ).
Anal. calc. for C17H18N2O4 (346.12): C 58.96, H 5.24, N 8.09; found: C 59.21, H 5.31, N 7.98.
(4aR,4bS,5R,8S,8aR,9aS)-Hexahydro-10,10-dimethyl-N,N-bis(phenylmethyl)-5,8-methano-4H-1,3-
dioxino[4,5-b]benzofuran-8(5H)-methanesulfonamide (10). A suspension of paraformaldehyde (1.3 g,
40 mmol) and 2 (2 g, 4.4 mmol) in benzene (15 ml) was treated dropwise at 238 with.H2SO4 (0.05 ml),
stirred under reflux for 1 h, cooled to 238, treated with solid NaHCO3 (0.2 g), and stirred for 1 h. The
mixture was filtered, the solid washed with tBuOMe, and the filtrate evaporated. FC (petroleum ether/
tBuOMe 3 :1 ! 1:2) gave 10 (0.93 g, 37%). Yellow foam. [a]D25 ¼ 4 (c ¼ 1.0, acetone). Rf (petroleum
ether/Et2O 1:1) 0.16. IR: 2935m, 1494w, 1455w, 1334s, 1147s, 1111s, 1038m, 1014m, 918m, 892m, 791m,
704m. 1H-NMR (500 MHz, CDCl3): 7.36 – 7.25 (m, 10 arom. H); 5.25 (d, J ¼ 3.5, HÀC(9a)); 4.96 (d, J ¼
7.0, 1 H, HÀC(2)); 4.72 (d, J ¼ 7.6, HÀC(8a)); 4.63 (d, J ¼ 6.6, 1 H, HÀC(2)); 4.42 (d, J ¼ 15.2, PhCH2N);
4.32 (d, J ¼ 15.2, PhCH2N); 4.07 (d, J ¼ 12.3, 1 H, HÀC(4)); 3.90 (dd, J ¼ 12.0, 3.5, 1 H, HÀC(4)); 3.26 (d,
J ¼ 13.6, 1 H, SO2CH2ÀC(8)); 2.65 (d, J ¼ 13.6, 1 H, SO2CH2ÀC(8)); 2.40 (t, J ¼ 7.9, HÀC(4b)); 2.23 (dt,
J ¼ 3.2, 7.9, HÀC(4a)); 1.92 (td, J ¼ 3.8, 11.7, 1 H, HÀC(7)); 1.81 (tt, J ¼ 3.8, 12.0, 1 H, HÀC(6)); 1.75 (d,
J ¼ 4.1, HÀC(5)); 1.52 (td, J ¼ 4.5, 13.2, 1H, HÀC(7)); 1.16 (dt, J ¼ 3.8, 12.3, 1 H, HÀC(6)); 0.91, 0.79 (2s,
Me2C). 13C-NMR (125 MHz, CDCl3): 135.9 (s, C(1) of Ph); 129.0 (d, C(2,6) of Ph); 128.5 (d, C(3,5) of
Ph); 127.8 (d, C(4) of Ph); 99.8 (d, C(9a)); 90.3 (t, OCH2O); 89.2 (d, C(8a)); 66.9 (t, C(4)); 51.0 (t,
SO2CH2ÀC(8)); 49.9 (t, PhCH2N); 49.5 (s, C(10)); 49.2 (d, C(4b)); 48.3 (s, C(8)); 46.6 (d, C(5)); 45.0 (d,
C(4a)); 28.9 (t, C(6)); 28.2 (t, C(7)); 23.1, 20.8 (2q, Me2C). ESI-MS (pos.-ion mode): 536 (70, [M þ K]þ),
520 (100, [M þ Na]þ). Anal. calc. for C28H35NO5S (497.22): C 67.38, H 7.09, N 2.81; found: 67.65, H 7.16, N
2.67.
(2R,3aR,4R,7R,7aR)-Octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-ol (12) and (2S,3aR,
4R,7R,7aR)-Octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-ol (C(2)-anomer of 12). At À 788, a
soln. of exo-lactone 11 (5.83 g, 30 mmol) in toluene (100 ml) was treated dropwise with a soln. of 20%
DIBAL in toluene (35 ml, 1.7 equiv., 51 mmol) such that the temp. did not exceed À 408 and stirred for
3 h a À 608. The soln. was poured into ice (50 g) and 2n HCl (100 ml) and the aq. phase extracted with
AcOEt (2Â). The combined org. phase was washed with sat. aq. NaHCO3 soln. and brine, dried
(Na2SO4), and concentrated: 5.3 g (91%) of 12. Colorless crystals. Rf (petroleum ether/Et2O 1:1) 0.47.
1
M.p. 68 – 708. IR: 3404m (br.), 29515s, 1482m, 1450m, 1089s, 1020s, 946s. H-NMR (200 MHz, CDCl3);
mixture of 12 and anomer): 5.56 (t, J ¼ 2.0, HÀC(2)); 5.40 (d, J ¼ 3.9, HÀC(2) of anomer); 4.08 (d, J ¼
7.6, HÀC(7a)); 3.80 (d, J ¼ 3.8, HÀC(7a) of anomer); 2.39 – 1.30 (m, HÀC(3a), HÀC(3), HÀC(4),
CH2(5), CH2(6)); 0.96, 0.95 (s, Me2C); 0.82, 0.81 (2s, MeÀC(7)). 13C-NMR (50 MHz, CDCl3): 101.0 (d,
C(2)); 100.2 (d, C(2) of anomer); 91.9 (d, C(7a) of anomer); 91.6 (d, C(7a)); 48.5 C(s, C(8)); 48.0 (d,
C(4)); 47.4 (t, C(3)); 46.4 (s, C(7)); 46.1 (s, C(7) of anomer); 39.6 (d, C(3a)); 38.8 (d, C(3a) of anomer);
32.8 (t, C(5)); 29.3 (t, C(6)); 23.3, 20.94 (2q, Me2C), 12.1, 11.9 (2q, MeÀC(7)).
(2S,3aR,4R,7R,7aR)-2-[(1S)-2,2-Dimethyl-1-phenylpropoxy]octahydro-7,8,8-trimethyl-4,7-metha-
nobenzofuran (13). A soln. of (Æ)-14 (8.0 g, 48.7 mmol) and lactol 12 (2.39 g, 12.2 mmol) in CH2Cl2
(10 ml) was treated with triphenylphosphonium bromide (837 mg, 2.4 mmol) and stirred at 238 for 72 h.
The mixture was diluted with AcOEt (50 ml), washed with sat. aq. NaHCO3 soln. and brine, dried
(Na2SO4), and concentrated. FC (petroleum ether/tBuOMe 200 :1 ! 20 :1) gave 13 (1.58 g, 38%) and 13/
diastereoisomer of 13 (2.0, 49%). 13: Colorless oil. Rf (petroleum ether/Et2O 70 :1) 0.21. [a]2D5 ¼ À137
(c ¼ 0.33, acetone). IR (KBr): 2955s, 1480m, 1450m, 1362s, 1188m, 1069m, 1022s, 956m, 739m, 702m.
1H-NMR (200 MHz, CDCl3): 7.30 – 7.20 (m, 5 arom. H); 4.84 (d, J ¼ 4.9, HÀC(2)); 4.30 (s, HÀC(1’)); 3.94
(d, J ¼ 7.4, HÀC(7a)); 2.36 – 1.35 (m, HÀC(3a), HaÀC(5), HaÀC(6), CH2(3), HÀC(4)); 1.10 – 0.85 (m,
HbÀC(5), HbÀC(6)); 1.00 (s, 3 H, Me2C), 0.82 (s, Me3C); 0.81 (s, MeÀC(7)); 0.77 (s, 3 H, Me2C).
13C-NMR (50 MHz, CDCl3): 140.1 (s, C(1) of Ph); 129.0 (d, C(2,6) of Ph); 127.4 (d, C(3,5) of Ph); 127.0
(d, C(4) of Ph); 102.0 (d, C(2)); 91.3 (d, C(7a)); 83.7 (d, C(1’)); 48.6 (s, C(8)); 47.7 (d, C(4)); 47.1 (t,
C(3)); 46.3 (s, C(7)); 38.6 (d, C(3a)); 35.2 (s, C(2’)); 32.3 (t, C(6)); 29.1 (t, C(5)); 25.0 (t, C(3’)); 23.1, 20.6
(2q, Me2C); 11.9 (q, MeÀC(7)). Anal. calc. for C23H34O2 (342.51): C 80.65, H 10.01; found: 80.51, H 9.74.

Helvetica Chimica Acta – Vol. 91 (2008)
595
(1S)-2,2-Dimethyl-1-phenylpropan-1-ol (14). A soln. 13 (1.56 g, 4.6 mmol) in CH2Cl2 (4 ml) and
MeOH (4 ml) was treated with TsOH · H2O (35 mg, 0.2 mmol) and stirred at 238 for 20 h. The mixture
was diluted with AcOEt (50 ml), washed with sat. aq. NaHCO3 soln. and brine, dried (Na2SO4), and
concentrated. FC (petroleum ether/tBuOMe 75 :1 ! 2 :1) gave 14 (500 mg, 67%).
Data of 14: Colorless crystals. M.p. 55 – 568. Rf (petroleum ether/Et2O 15 :1) 0.23. [a]2D5 ¼ À22.7 (c ¼
0.75, acetone). IR (KBr): 3420s (br.), 2952m, 1479m, 1452m, 1304w, 1236w, 1179w, 1044m, 1003s, 737s,
1
701s. H-NMR (200 MHz, CDCl3): 7.35 – 7.15 (m, 5 arom. H); 4.35 (s, HÀC(1)); 1.90 (s, OH); 0.95 (s,
Me3C)). 13C-NMR (50 MHz, CDCl3): 142.3 (s, C(1) of Ph); 127.7 (d, C(2,6) of Ph); 127.6 (d, C(3,5) of
Ph); 127.41 (d, C(4) of Ph); 82.5 (d, C(1)); 35.7 (t, C(2)); 26.0 (q, C(3)). ESI-MS (pos.-ion mode): 187 (15,
[M þ Na]þ). Anal. calc. for C11H16O (164.24): C 80.44, H 9.82; found: 80.31, H 9.82.
Data of (2R,3aR,4R,7R,7aR)-Octahydro-2-methoxy-7,8,8-trimethyl-4,7-methanobenzofuran (15):
Colorless oil. Rf (petroleum ether/Et2O 1:1) 0.50. [a]2D5 ¼ À125.3 (c ¼ 0.70, acetone). IR (KBr): 2947s,
2825w, 1478m, 1447m, 1391m, 1347m, 1212m, 1108s, 1073m, 1034s, 955s, 886m. 1H-NMR (200 MHz,
CDCl3): 4.99 (t, J ¼ 2.4, HÀC(2)); 3.90 (d, J ¼ 7.4, HÀC(7a)); 3.29 (s, MeO); 2.28 (q, J ¼ 8.5, HÀC(3a));
2.05 (d, J ¼ 2.6, HaÀC(3)); 2.02 – 2.00 (m, HbÀC(3)); 1.80 – 1.60 (m, HaÀC(6), HÀC(4)); 1.42 (m,
HaÀC(5)); 1.03 – 0.88 (m, HbÀC(5), HbÀC(6)); 0.98, 0.96 (2s, Me2C); 0.79 (s, MeÀC(7)).
(1S,5S)-1,5-Di(tert-butyl)-1,5-diphenyl-2,4-dioxapentane (¼1,1’-{Methylenebis{oxy[(1S)-2,2-dimeth-
ylpropylidene]}}bis[benzene]; 16), (1S,7S)-1,7-Di(tert-butyl)-1,7-diphenyl-2,4,6-trioxaheptane (¼1,1’-
{Oxybis{methyleneoxy[(1S)-2,2-dimethylpropylidene]}}bis[benzene]; 17), (1S,9S)-1,9-Di(tert-butyl)-1,9-
diphenyl-2,4,6,8-tetraoxanonane (¼(3S,11S)-2,2,12,12-Tetramethyl-3,11-diphenyl-4,6,8,10-tetraoxatridec-
ane; 18), (1S,11S)-1,11-Di(tert-butyl)-1,11-diphenyl-2,4,6,8,10-pentaoxaundecane (¼(3S,13S)-2,2,14,14-
Tetramethyl-3,13-diphenyl-4,6,8,10,12-pentaoxapentadecane; 19), (1S,13S)-1,13-Di(tert-butyl)-1,13-di-
phenyl-2,4,6,8,10,12-hexaoxatridecane (¼(3S,15S)-2,2,16,16-Tetramethyl-3,15-diphenyl-4,6,8,10,12,14-
hexaoxaheptadecane; 20). A suspension of paraformaldehyde (0.89 g, 30 mmol) and 14 (489 mg,
3.0 mmol) in benzene (4 ml) was treated dropwise at 238 with H2SO4 (4 drops), stirred under reflux for
5 min, treated immediately with solid NaHCO3 (0.4 g), and stirred for 30 min. The mixture was filtered,
the solid washed with tBuOMe, and the filtrate evaporated. FC (petroleum ether/tBuOMe 200 :1 ! 0 :2)
and prep. TLC (petroleum ether/tBuOMe 15 :1 for 16, 17, and 18 and petroleum ether/tBuOMe
6 :1 for 20) gave 16 (61 mg, 12%), 17 (98 mg, 18%), 18 (46 mg, 7.7%), 19 (49 mg, 7.6%), and 20
(9 mg, 1.3%).
Data of 16: Colorless oil. Rf (petroleum ether/Et2O 15 :1) 0.77. [a]2D5 ¼ À134 (c ¼ 0.25, acetone). IR:
2956w, 1478w, 1451w, 1391w, 1360w, 1194w, 1155w, 1040s, 1020s, 740m, 703m. 1H-NMR (200 MHz,
CDCl3)1): 7.26 – 7.15 (m, 10 arom. H); 4.41 (s, OCH2O)); 4.36 (s, HÀC(1,5)); 0.92 (s, Me3CÀC(1,5)).
13C-NMR (50 MHz, CDCl3)1): 139.2 (s, C(1) of Ph); 129.1 (d, C(2,6) of Ph); 127.5 (d, C(3,5) of Ph); 127.3
(s, C(4) of Ph); 89.7 (t, OCH2O); 85.1 (d, C(1,5)); 26.7 (q, Me3C); signal of Me3C not found. ESI-MS
(pos.): 363 (15, [M þ Na]þ).
Data of 17: Colorless crystals. Rf (petroleum ether/Et2O 15 :1) 0.57. [a]2D5 ¼ À229 (c ¼ 0.52, acetone).
M.p. 123 – 1278. IR: 2970s, 2897m, 1480m, 1451w, 1393m, 1365m, 1200m, 1138m, 1095s, 969s, 938m, 775m,
705s. 1H-NMR (200 MHz, CDCl3)1): 7.32 – 7.17 (m, 10 arom. H); 4.96 (d, J ¼ 7.1, 2 Ha, OCH2O); 4.36 (d,
J ¼ 7.1, 2 Hb, OCH2O); 4.27 (s, HÀC(1,7)); 0.85 (s, Me3CÀC(1,7)). 13C-NMR (50 MHz, CDCl3)1): 139.2
(s, C(1) of Ph); 129.0 (d, C(2,6) of Ph); 127.6 (d, C(3,5) of Ph); 127.4 (s, C(4) of Ph); 88.3 (t, OCH2O); 85.6
(d, C(1,7)); 35.0 (s, Me3C); 26.7 (q, Me). ESI-MS (pos.): 393 (100, [M þ Na]þ).
Data of 18: Colorless crystals. Rf (petroleum ether/Et2O 15 :1) 0.30. M.p. 68 – 728. [a]2D5 ¼ À208 (c ¼
0.21, acetone). IR: 2956m, 1478m, 1451m, 1391m, 1360m, 1190w, 1140s, 1040s, 1020s, 740m, 703m.
1H-NMR (500 MHz, CDCl3)1): 7.31 – 7.20 (m, 10 arom. H); 4.88 (s, OCH2(5)O); 4.78 (d, J ¼ 7.0, 2 Ha,
OCH2(3,7)O); 4.37 (d, J ¼ 6.9, 2Hb, OCH2(3,7)O); 4.29 (s, HÀC(1,9)); 0.89 (s, Me3CÀC(1,9)).
13C-NMR (125 MHz, CDCl3)1): 139.0 (s, C(1) of Ph); 128.7 (d, C(2,6) of Ph); 127.5 (d, C(3,5) of Ph); 127.3
(s, C(4) of Ph); 89.0 (t, OCH2(3,7)O); 87.4 (t, OCH2(5)O); 85.7 (d, C(1,9)); 35.3 (s, Me3C); 26.7 (q,
Me3C). ESI-MS (pos.): 423 (100, [M þ Na]þ).
Data of 19: Colorless crystals. Rf (petroleum ether/Et2O 15 :1) 0.20. M.p. 61 – 668. [a]2D5 ¼ À193 (c ¼
0.20, acetone). IR: 2956m, 2904w, 1482m, 1452m, 1366m, 1119s, 1067m, 954s, 744m, 704m. 1H-NMR
(500 MHz, CDCl3)1): 7.28 – 7.11 (m, 10 arom. H); 4.76 (d, J ¼ 7.0, 2 Ha, OCH2(5,7)O); 4.73 (d, J ¼ 7.3,
2Ha, OCH2(3,9)O); 4.71 (d, J ¼ 6.9, 2 Hb, OCH2(5,7)O); 4.37 (d, J ¼ 7.0, 2 Hb, OCH2(3,9)O); 4.21 (s,

596
Helvetica Chimica Acta – Vol. 91 (2008)
HÀC(1,11)); 0.81 (s, Me3CÀC(1,11)). 13C-NMR (125 MHz, CDCl3)1): 139.0 (s, C(1) of Ph); 128.6 (d,
C(2,6) of Ph); 127.4 (d, C(3,5) of Ph); 127.3 (s, C(4) of Ph); 89.5 (t, OCH2(3,9)O); 88.1 (t, OCH2(5,7)O);
86.1 (d, C(1,11)); 35.3 (s, Me3C); 26.2 (q, Me). ESI-MS (pos.): 453 (100, [M þ Na]þ).
Data of 20: Colorless crystals. Rf (petroleum ether/Et2O 15 :1) 0.18. M.p. 86 – 918. [a]2D5 ¼ À199 (c ¼
0.21, acetone). 1H-NMR (500 MHz, CDCl3)1): 7.33 – 7.20 (m, 10 arom. H); 4.86 (d, J ¼ 6.7, 2 Ha,
OCH2(5,9)O); 4.80 (d, J ¼ 6.7, 2Hb, OC(5,9)O); 4.79 (d, J ¼ 6.3, 2 Ha, OCH2(3,11)O); 4.78 (s,
OCH2(7)O); 4.46 (d, J ¼ 7.0, 2 Hb, OCH2(3,11)O); 4.28 (s, HÀC(1,13)); 0.89 (s, Me). 13C-NMR
(125 MHz, CDCl3)1): 139.0 (s, C(1) of Ph); 128.6 (d, C(2,6) of Ph); 127.5 (d, C(3,5) of Ph); 127.3 (s, C(4) of
Ph); 89.7 (t, OCH2(3,11)O); 88.7 (t, OCH2(7)O); 88.3 (t, OCH2(5,9)O); 86.2 (d, C(1,13)); 35.3 (s, Me3C);
26.2 (q, Me3C). ESI-MS (pos.): 483 (100 , [M þ Na]þ).
Crystal Structure Determinations. Single-crystal X-ray diffraction data for 17 and 19 were measured
at 200 K on a Nonius-Kappa-CCD diffractometer (graphite monochromatized MoKa radiation)
equipped with a 0.3 mm monocapillary optics collimator. The extraction and correction of the intensity
data, including a pseudoabsorption correction by frame scaling and the refinement of lattice parameters,
were performed with the program package DENZO-SMN [31]. For structure solutions by direct
methods and the structure refinements, the programs SHELXS-97 [32] and SHELXL-97 [33] were used.
The structures were refined by full-matrix least-squares procedures on F2. All non-H-atoms were
refined with anisotropic displacement parameters. The H-atoms were localized from difference Fourier
maps. Finally, idealized groups were used to describe the positions of the H-atoms with UH-atom ¼ 1.2 ·
Uequiv. of the parent atom. Crystal parameters, details of data collection, and structure refinement are
summarized in Table 3. In the case of 19, a twin refinement was applied. Analysis of the final structure
model gave no hints for a higher symmetry.
Table 3. Crystallographic Data for 17 and 19
17
19
Empirical formula
C24H34O3
C26H38O5
Mr
370.52
430.58
Crystal system
orthorhombic
monoclinic
Space group
P212121
P21
Z
4
2
Unit cell parameters a [Š]
7.531(2)
6.007 (1)
b [Š]
10.945(2)
9.482 (2)
c [Š]
27.297(6)
22.145 (4)
a [8]
90
90
b [8]
90
90.02(3)
g [8]
V [Š3]
90
90
2250.1(8)
1261.4(4)
1 [g/cm3] (calc.)
1.094
0.07
808.0
1.134
0.08
468
m [mmÀ1
F (000)
]
2q max [8]
50
52
Lim. indices
À 8 ꢁ h ꢁ 8, 12 ꢁ k ꢁ 13,
À 7 ꢁ h ꢁ 7, À 11 ꢁ k ꢁ 11,
À 32 ꢁ l ꢁ 32
À 27 ꢁ l ꢁ 27
Indep. refl.
3946
4866
Obs. refl. (Io ꢂ 2s(I))
2636
245
2822
282
No. ref. param.
wR2 (all data)
0.098
0.113
R1 (Io ꢂ 2s(I))
0.046
1.046
À 0.12, 0.13
0.058
1.013
À 0.12, 0.22
Goodness of fit (on F2)
D1min, D1max [e/Š3]

Helvetica Chimica Acta – Vol. 91 (2008)
597
REFERENCES
[1] H. Staudinger, M. Luthy, Helv. Chim. Acta 1925, 8, 41.
[2] H. Staudinger, Helv. Chim. Acta 1925, 8, 67.
[3] H. Staudinger, M. Luthy, Helv. Chim. Acta 1925, 8, 65.
[4] W. F. Huebner, Science (Washington, DC, U.S.) 1987, 237, 628.
[5] R. M. Minyaev, Y. A. Zhdanov, I. I. Zakharov, V. I. Minkin, Vysokomol Soedin., Ser. B 1974, 16, 190.
[6] A. Novak, E. Whalley, Trans. Faraday Soc. 1959, 55, 1484.
[7] M. L. Huggins, J. Chem. Phys. 1945, 13, 37.
[8] G. Carazzolo, G. Putti, Chim. Ind. (Milan) 1963, 45, 771.
[9] G. Carazzolo, Gazz. Chim. Ital. 1962, 92, 1345.
[10] C. F. Hammer, T. A. Koch, J. F. Whitney, J. Appl. Polym. Sci. 1959, 1, 169.
[11] J. Hengstenberg, Ann. Phys. (Berlin) 1927, 389, 245.
[12] T. Uchida, H. Tadokoro, J. Polym. Sci., Polym. Phys. Ed. 1967, 5, 63.
[13] G. Carazzolo, M. Mammi, J. Polym. Sci., Part A 1963, 1, 965.
[14] C. R. Noe, C. Miculka, J. W. Bats, Angew. Chem. 1994, 106, 1559; Angew. Chem., Int. Ed. 1994, 33,
1476.
[15] J. W. Bats, C. Miculka, C. R. Noe, Acta Crystallogr., Sect. C 2007, 63, o190.
[16] P. Deslongchamps, ꢀStereoelectronic Effects in Organic Chemistryꢁ, Pergamon Press, Oxford – New
York – Beijing – Frankfurt – Sao Paulo – Sydney – Tokyo – Toronto, 1984.
[17] A. Eschenmoser, M. Dobler, Helv. Chim. Acta 1992, 75, 218.
[18] G. Quinkert, E. Egert, C. Griesinger, ꢀAspekte der Organischen Chemieꢁ, Verlag Helvetica Chimica
Acta and VCH, Weinheim – New York – Basel – Cambridge – Tokyo, 1995; G. Quinkert, E. Egert, C.
Griesinger, ꢀAspects of Organic Chemistryꢁ, Verlag Helvetica Chimica Acta and VCH, Weinheim –
New York – Basel – Cambridge – Tokyo, 1996.
[19] C. R. Noe, M. Knollmueller, G. Goestl, B. Oberhauser, H. Voellenkle, Angew. Chem. 1987, 99, 467;
Angew. Chem., Int. Ed. 1987, 26, 442.
[20] C. R. Noe, M. Knollmüller, E. Jangg, G. P. Gmeiner, Chirality 2007, submitted.
[21] K. Mehraban, Ph.D. Thesis, Technische Universität Wien, Vienna, 1993.
[22] C. R. Noe, Chem. Ber. 1982, 115, 1591.
[23] C. R. Noe, Chem. Ber. 1982, 115, 1576.
[24] C. R. Noe, M. Knollmueller, K. Dungler, C. Miculka, Chem. Ber. 1994, 127, 359.
[25] C. R. Noe, M. Knollmueller, C. Miculka, K. Dungler, E. Wagner, P. Ettmayer, Chem. Ber. 1994, 127,
887.
[26] C. R. Noe, M. Knollmueller, E. Wagner, H. Voellenkle, Chem. Ber. 1985, 118, 1733.
[27] T. Bach, J. Lobel, Synthesis 2002, 2521.
[28] C. R. Noe, M. Knollmueller, B. Oberhauser, G. Steinbauer, E. Wagner, Chem. Ber. 1986, 119, 729.
[29] S. Winstein, B. K. Morse, J. Am. Chem. Soc. 1952, 74, 1133.
[30] E. Dowty, ATOMS for Windows V6.3., a Program for Atomic-Structure Display, Shape Software,
Kingsport, TN, 2006.
[31] Z. Otwinowski, W. Minor, in ꢀMethods in Enzymology 276ꢁ, ꢀMacromolecular Crystallography, Part
Aꢁ, Eds. C. W. Carter Jr., and R. M. Sweet, Academic Press, 1997, pp. 307 – 326.
[32] G. M. Sheldrick, SHELXS-97, a Program for the Solution of Crystal Structures, Universität
Gçttingen, Gçttingen, 1997.
[33] G. M. Sheldrick, SHELXL-97, a Program for Crystal Structure Refinement, Universität Gçttingen,
Gçttingen, 1997.
Received September 3, 2007