[1,2]-Wittig rearrangement of acetals. Part 1: Investigation about structural requirements

Article abstract of DOI:10.1016/S0957-4166(99)00562-5

Acetals of different alcohols with (+)-camphor derived enantiomerically pure 7,8,8-trimethyl-4,7-methanobenzofuran-2-ol were prepared and subjected to conditions favorable for a [1,2]-Wittig rearrangement. Results with regard to conversion, yield and stereochemical course depending on the structure of the starting material are discussed. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(99)00562-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 10 (1999) 4811–4830
[1,2]-Wittig rearrangement of acetals. Part 1: Investigation about
structural requirements
Peter Gärtner,a,∗ Martin F. Letschnig,a Max Knollmüller a and Horst Völlenkle b
aInstitute of Organic Chemistry, Vienna University of Technology, Getreidemarkt 9, A-1060 Vienna, Austria
bInstitute of Mineralogy, Crystallography and Structural Chemistry, Vienna University of Technology, Getreidemarkt 9,
A-1060 Vienna, Austria
Received 10 November 1999; accepted 6 December 1999
Abstract
Acetals of different alcohols with (+)-camphor derived enantiomerically pure 7,8,8-trimethyl-4,7-methano-
benzofuran-2-ol were prepared and subjected to conditions favorable for a [1,2]-Wittig rearrangement. Results
with regard to conversion, yield and stereochemical course depending on the structure of the starting material are
discussed. © 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
The [1,2]-Wittig rearrangement1 is a classic class of carbanion rearrangement which has been
reviewed2 extensively, and most recently on the occasion of Wittig0s 100th birthday anniversary.3
Although this lithium base induced rearrangement has been known for more than 50 years only the
[2,3]-Wittig sigmatropic version of allyl ethers enjoys wide synthetic application.2c,4 The synthetic
utilization of the [1,2]-shift usually suffers from low yields and a limited range of substrates.5 However,
from a stereochemical point of view the reaction is quite interesting, because, despite the fact that it
is nowadays recognized that the reaction proceeds via a radical dissociation–recombination process,1–3
the stereogenicities of the two proradical centers are retained to an appreciable extent, i.e. retention of
configuration at the migrating carbon and inversion at the lithium bearing terminus under non-chelation
or retention under chelation controlled conditions.2,3,6 With regard to structure–reactivity relationships
it has been established that at either the carbanion terminus or the migrating group a radical-stabilizing
factor is required.6f Thus, it was envisaged that acetal systems such as O-glycosides would easily undergo
the [1,2]-Wittig rearrangement,7 providing an easy access to C-glycosides.
∗
Corresponding author. Fax: +43-1-58801-154-92; e-mail: pgaertne@mail.zserv.tuwien.ac.at
0957-4166/99/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00562-5
tetasy 3196

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During our own investigations on the application of acetals as chiral ligands for organometallics we
had observed such rearrangements.8 Being interested in the compounds produced by this reaction as
new ligands and because at this time little was known about acetals in [1,2]-Wittig rearrangements — in
the meantime some excellent work2d,3,9 by other groups has been performed as well — we started to
investigate this reaction in more detail. This first part deals with the influence of the structure of the
acetal on the conversion, yield and stereochemical course.
2. Results and discussion
The acetals 15–27 which were selected as starting materials for the [1,2]-Wittig rearrangement were
synthesized from anhydrolactol 1 and either alcohols 2–13 or thiol 14 following the standard acid
catalyzed procedure (Scheme 1, Table 1).10
Scheme 1. Synthesis and [1,2]-Wittig rearrangement of the acetals 15–27
The selection of 2–14 was based on considerations aimed at achieving a high divergence in the aglycon
part of the molecule. Thus, with compounds 15–22 we wanted to see what happens if the space required
by one of the ligands at the lithium bearing terminus increases and how this is modified by a second aryl-
ligand 21, with compounds 23–26 we wanted to check what the influence of the electronic properties of
the aryl-ligand itself is, acetals 22–25 should give us some insight into the effect of additional centers
for complex formation, and finally with 27 we wanted to look whether the rearrangement can be carried
out with O,S-acetals as well. For compounds 16–20 and 22 which were formed as a mixture of two
diastereomers in a ratio of about 2:1 according to the expected ‘enantiomer-selectivity’11 the mixtures
obtained after chromatography were used in this study. The configuration of the major diastereoisomer
1
was determined from characteristic shift differences in the H NMR spectra compared with the minor
isomer according to the b-pl-H rule.11,12 Results on the influence of the absolute configuration of the
aglycon part will be published soon.
For the sake of comparability the [1,2]-Wittig rearrangement of all acetals 15–27 was carried out
under standardized conditions which have turned out to be the best in most of the cases. A systematic
investigation with regard to different reaction conditions will be the main task of the next paper in this
series. Thus, a solution of each of the acetals 15–27 in tetrahydrofuran was treated with n-butyllithium
(3 equiv.) at room temperature for 3 h to give the rearranged benzylalcohols 28–35 as a mixture
of two diastereomers (de=12–65%). Diastereomeric ratios were determined by chromatography or by
comparison of integrals in the 1H NMR spectra. With the other acetals 19, 20, 22, 26, 27 no rearranged
product could be isolated, but for different reasons. The highly hindered acetals 19 and 20 did not
react at all, probably due to steric congestions in the course of the rearrangement. However, the starting
material was recovered quantitatively. The β-pyrrolidinyl substituted acetal 22 did not give the expected
β-pyrrolidinyl substituted benzylalcohol but instead furnished alcohol 37 which bore an alkyl group
as the sole substituent. This was rationalized by the pathway outlined in Scheme 2 where acetal 22
was deprotonated and rearranged as usual. However, in the following reaction cascade the alkoxide

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Table 1
Summary of the [1,2]-Wittig rearrangement of the acetals 15–27

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replaced the pyrrolidine in a nucleophilic substitution to afford an epoxide and eventually, this epoxide
was attacked by butyllithium to yield the lithium salt of 37.
Scheme 2. Reaction pathway for the rearrangement of the acetal 22
Compound 26 in which the benzylic protons should be more acidic due to the nitro group on the
aromatic ring was converted completely. In the complex reaction mixture we were not able to detect any
trace of the anticipated rearrangement product. With thioacetal 27, 70% of the starting material was not
recovered after treatment with butyllithium. However, the only reaction product which could be isolated
was a small amount of enol ether 36. This observation may be attributed to the fact that the desulfurizative
lithiation6c is faster than the Wittig rearrangement which was already found to be retarded when thio
ethers were used as starting materials.4a
As far as the stereochemistry of the former acetal center is concerned, it is assumed that the reaction
proceeds as usual with retention of configuration2d,3,9 although there was one example9 reported recently
which violates this principle. This was confirmed in our study by analyzing 13C NMR data for those
carbons of the methanobenzofuran system which should be influenced most, i.e. C-3a and C-7a (Table
2).
The interpretation of this data is not easy, because in the region where one would expect the signal for
C-3a there appears a further doublet which belongs to C-4. Thus, data for this carbon were also included
in the analysis. Anyway, as can be seen from Table 2 the data is consistent to a large extent, especially
for the rearranged products bearing an additional alkyl- or aryl-ligand at the newly formed alcohol center
(29–32, 37) and it is therefore highly probable that all rearranged products have the same configuration at
C-2. With compounds 28, 33–35 the shifts for C-3a and C-7a of isomer A are in satisfactory agreement,
but for the diastereomer B these signals are shifted upfield near to the range in which they were usually
observed for the starting acetals. This may be due to the fact that the hydrogen which is bound to the
alcohol carbon in these compounds allows conformations which are not populated if there is an alkyl- or
aryl-ligand located in this position.
The relative configuration of the newly formed alcohol center of the major diastereomer was deter-
1
mined by comparing coupling constants in the H NMR spectra and by characteristic shift differences
in the 13C NMR spectra which should be a result of the γ-effect. It is well known13 that in β-alkoxy
alcohols in which no additional functional group for hydrogen bond formation exists the vicinal coupling
constant between the hydrogen at the alcohol carbon and the hydrogen at the alkoxy center is bigger in

P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
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Table 2
Comparison of 13C NMR data for C-3a and C-7a of the methanobenzofuran system of the rearranged
products 28–35, 37 (2 stereoisomeric alcohols A and B) with the corresponding data of the starting
materials 15–27 (for acetals of secondary alcohols 2 stereoisomers)
the syn- than in the corresponding anti-isomer. Thus, we analyzed this coupling constant for the syn- and
anti-isomers of 28, 33–35 (Fig. 1, Table 3).
Fig. 1. syn- and anti-configuration of rearranged products 28, 33–35
As can be seen in Table 3 differences in coupling constants were significant and therefore, we deduced
the relative configurations given. To our surprise in one case 34 the major isomer had a bigger coupling
constant which would indicate that this is of the syn-form 34A. For all other products this coupling
constant was smaller and thus, the compound should have predominantly anti-configuration. However,
since some of the rearranged products had no hydrogen at the newly formed asymmetric carbon, we
proceeded to analyze the 13C NMR data. In analogy to the former products the configuration of these
compounds 29–31, 37 was assigned with like (R,R or S,S) and unlike (R,S or S,R) as shown in Fig. 2. The
chemical shift data for the carbons which should be influenced most by the relative configuration at the
alcohol center due to the anticipated γ-effect are summarized in Table 4. Thus, the δ-values for C-3 of
the methanobenzofuran system, C-1 of the aryl-ligand and the alkyl carbon which is directly connected
with the alcohol center are listed and shift differences are calculated. To indicate the significance of the
reported data the chemical shift for C-6 of the methanobenzofuran system is also given. This carbon has

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Table 3
Coupling constants between the hydrogens at the former acetal carbon and the newly generated alcohol
center
its signal near to C-3 and therefore perhaps it may be exchanged for it. However, since this part of the
molecules is very rigid only small shift differences for C-6 should be observed.
Fig. 2. Like- and unlike-configuration of rearranged products 29–31
With the exception of 33 which bears a pyridine ring instead of a phenyl ring, C-1 of the aryl-ligand
is shifted upfield (0.5–1.3 ppm) in all stereoisomers A compared with B. For compounds 28, 33–35
which are secondary alcohols C-3 is more shielded in B than in A (0.9–1.7 ppm) whereas for the tertiary
alcohols 29–32, 37 the shift of C-3 in B is bigger than in A (0.5–0.9 ppm). For the latter a significant
upfield shift of the first carbon of the aliphatic side chain is also observed for A in comparison to B
(4.0–5.1 (5.2) ppm). These results are in good accordance with previous investigations13a,14 on β-alkoxy
alcohols in which it was observed that the carbons in question (C-3, C*-Caliph) were more shielded in
the isomer which has a higher probability for gauche orientations of the bulky ligands at the neighboring
carbons.
From careful examination of the Newman projections shown in Fig. 3 it becomes quite clear that this
should be the case for compounds A rather than for B if R is an alkyl group. First of all A-1 should
be highly favored over A-2 due to strong steric repulsion of the big alkyl-ligand being placed under the
furan ring. For conformation B-2, this holds true only to a limited extent because steric requirements
of an aryl-ligand are far beyond those of an alkyl substituent. Thus, for B both conformations should
be equally populated. For the rearranged products 28, 33–35, the interpretation of the 13C NMR data is
even more complicated because steric interactions should be far smaller with these molecules. Therefore,
both conformations for A and B shown in Fig. 3 (R=H) should be considered as being represented in
the equilibrium of rotamers. However, since the chemical shift of C-1 of the aryl substituent is shifted in

P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
4817
Table 4
13C shifts and shift differences for C-3 and the ipso-C of the aryl substituent of the corresponding
isomers
the same direction for these molecules as it was for the former products we assume that in general the
conformations should be very similar. Since steric reasons cannot explain why A-2 should be less stable
we rationalized that A-1 should be favored due to a general stereoelectronic interaction between the σ-
orbital of a C–H bond and the σ*-orbital of a neighboring C–O bond. As a result of these considerations
one would estimate from Fig. 3 that C-3 should be more shielded now in B than in A which corresponds
exactly with the experimental data. The anomaly of C-1 of the pyridyl substituent in 33 with regard to the
direction of shift differences may be attributed to the fact that this aryl-ligand has a nitrogen which can
also be engaged in a hydrogen bond. Thus, it is likely that the distribution between possible conformations
is different from the former products.
Eventually, we were able to confirm the structure of 28B by X-ray crystallography. While alcohol
28 could not be separated by chromatography to give the pure diastereomers this operation was
easily performed with acetals 38 and 39 which were obtained by acid-catalyzed reaction of 28 with
anhydrolactol 1. Treatment of 38 and 39 with methanol and p-toluenesulfonic acid yielded 28A and
crystalline 28B (Scheme 3).

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Fig. 3. Newman-projection of C* on C-2 for conformations of the rearranged products 28–35 in which a hydrogen bond can be
established between the alcohol and the endocyclic oxygen
Scheme 3. Separation of alcohols 28A and 28B via acetals 38 and 39
After crystallization from petroleum ether an X-ray structure determination of 28B was carried
out.15 The compound crystallizes in the orthorhombic space group P212121 with two crystallograph-
ically independent molecules in the unit cell linked via O-H···O hydrogen bonds into chains par-
allel to the x-axis. Molecule 1 donates a hydrogen bond from its OH group to the OH oxygen of
molecule 2 (O···O=2.79 Å), whereas molecule 2 donates a hydrogen bond to furyl oxygen O1 of

P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
4819
molecule 1 (O···O=2.77 Å). Both molecules are very similar in bond lengths and conformation, but
differ somewhat in the orientations of their OH and phenyl groups: O1–C2–C12–O2=72.2(9)/67.9(9)°,
O1–C2–C12–C13=−164.2(7)/−167.8(7)° for molecule 1/molecule 2; these values correspond to relative
positional differences of 0.30 Å for C16 and C17 of both molecules if their camphor moieties are fitted
to coincide.16
A view of the molecular structure of 28B is shown in Fig. 4 which confirms the proposed configuration.
Although no intramolecular hydrogen bond was found in the crystalline state the conformation fits well
to B-1 given in Fig. 3 for this compound. Thus, we conclude that the assignment of configuration based
on NMR data is also correct for the other products 29–35, 37.
Fig. 4. Molecular structure of 28B in crystalline state. Only one of the two independent molecules is shown. Selected
geometric data [Å, °]: O1–C2=1.441(8), O1–C7A=1.425(8), C2–C12=1.517(9), C12–O2=1.420(8), O1–C2–C12–O2=72.2(9),
O1–C2–C12–C13=−164.2(7), C2–C12–O2–H2H=−137
Having secured the configuration of the obtained alcohols we tried to rationalize the results with
regard to the stereoselectivity in the formation of the new alcohol center. As noted previously2d,3,7 the
principle of ‘inversion of configuration at the lithium bearing terminus’ does not hold for the present
[1,2]-Wittig variants which involve configurationally labile α-oxybenzyllithium and thus, so far, there
are no rules for the prediction of the configuration at this center. Considering the proposed transition
state models2,3 wherein the two radical fragments are tightly held together through coordination with the
lithium counterion we may take our conformations, shown in Fig. 3, as a first rough estimation for the
recognition process. At this point it should be mentioned that this is only true for substrates which do not
bear additional elements for coordination or at least they are not able to interact due to steric reasons.
As already outlined above in connection with the interpretation of the 13C NMR data for alcohols
29–31 steric congestion should be more pronounced in diastereomer A than in B. Additionally, stereo-
electronic stabilization due to interactions between the σ-orbital of the C–H bond and the σ*-orbitals
of the C–O bond or the C–aryl bond which are possible in A-1, B-1 and B-2 should be considered.
Eventually, this has no influence, because both statements argue in the same direction, i.e. that the
preferentially formed product should be the one with unlike-configuration. For the secondary alcohols 28,
33–35 we argued that steric interactions should be less pronounced. In this case, if there is any influence
at all the formation of A should be favored. However, in conformation A-1 of these compounds there
are two stereoelectronic interactions between a C–H-σ- and a C–O-σ*-orbital possible now. In B-1 we
still have one as we had already with alcohols 29–32, but in B-2, in addition to the orbital interaction
possible in 29–32, a stabilization by overlapping of the C–H-σ-orbital with the C–O-σ*-orbital should

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P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
be considered. Thus, from experimental data we must assume that stereoelectronic effects, which would
preferentially yield the anti-isomer, override steric arguments. Compound 34 in which the lithium bearing
radical can be coordinated by the 2-methoxy substituent of the phenyl ring to form a stable six-membered
ring chelate violates the premise that coordination is only possible to the endo-oxygen of the former
acetal. Thus, in addition to the transition states derived from the conformations A-1, A-2, B-1, B-2,
further ones (A-3, B-3) in which no coordination to the other radical fragment is possible have to be
considered (Fig. 5).
Fig. 5. Additional transition states A-3 and B-3 in which no coordination occurs to the endocyclic oxygen of the other radical
fragment
While B-3 exhibits less steric hindrance, which probably has not so much influence but cannot be
stabilized stereoelectronically, A-3 has the possibility of stereoelectronic stabilization. This may explain
why the stereoselectivity is inverted for 24 as starting material.
3. Conclusion
In summary, we have shown that the above benzylacetals react in a [1,2]-Wittig rearrangement as
long as the other ligands at the lithium bearing terminus are not too sterically demanding which results
in low yields or prohibits the reaction. Electron donating groups on the aromatic ligand seem to be
an advantageous influence with regard to yield whereas electron withdrawing groups are better with
regard to stereoselectivity. Neither an O,S-benzylacetal nor 4-nitrobenzylacetal yields the anticipated
products. The retention of configuration at the former acetal center was confirmed. In substrates where
no additional coordination position is available the relative configuration at the formed alcohol center
in the major diastereomer is of the anti- or unlike-configuration. A rationale for this observation was
developed based on stereoelectronic effects. Further general investigations on this reaction type are in
progress in our laboratories.
4. Experimental
4.1. General
Melting points are uncorrected. NMR: Bruker AC 200 (200 and 50 MHz, for 1H and 13C, respectively).
1
For H NMR CHCl3 at δH 7.24 as internal standard; for 13C NMR CDCl3 at δC 77.0 as internal
standard. Optical rotations were measured with a Perkin–Elmer 241 polarimeter in a 10 cm cell. TLC
was performed with Merck silica gel 60 F254; with visualisation of the spots with molybdato phosphoric
acid (5% in ethanol) and heating. Column chromatography and vacuum flash chromatography (VFC)

P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
4821
was carried out with Merck silica gel 60 (230–400 mesh). Abbreviations used: PE=petroleum ether. Gas
chromatography was performed with a Carlo Erba HRGC 5300 Mega Series (Integration: Mega Series
Integrator). The data was processed with Labnet 2 (Spectra Physics). Carbowax 57 CB capillary column
(Chrompack) and helium (5.0) as carrier gas (preliminary pressure 50 kPa) were used. Detector: FID;
sample concentration: 10–20 mg/ml (crude product). Temperatures: injection: 260°C; detection: 260°C;
oven: 230°C/240°C (isotherm).
The content of n-butyllithium in n-hexane was determined by titration with t-butanol using 1,10-
phenantroline as indicator.
For the synthesis of the compounds 16, 20, 24 and 34 see Ref. 10 and Ref. 8e, respectively.
4.2. General procedure (GP-1) for the synthesis of the acetals 15–27
A solution of (2S,20S,-(2α,20α,3aα,3a0α,4β,40β,7β,70β,7aα,7a0α))-2,20-oxybis[octahydro-7,8,8-
trimethyl-4,7-methanobenzofuran] ((MBE)2O, 1) (1 equiv.), the corresponding alcohol or thiol (2–14;
4 equiv.) and 4-methylbenzenesulfonic acid monohydrate (0.1 equiv.) in anhydrous dichloromethane
was stirred for 30 min at room temperature. Sodium sulfate was added and the solution was stirred for a
further 90 min. The reaction mixture was washed with a saturated sodium hydrogen carbonate solution.
The aqueous phase was extracted twice with dichloromethane and the combined organic layers were
dried with sodium sulfate, filtered and the solvent was evaporated. The crude product was purified by
VFC or SC.
4.2.1. [2R-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-2-(phenylmethoxy)-4,7-methanobenzo-
furan 15
Following GP-1, 15 was prepared from 8.23 g (23.8 mmol) of 1, 10.3 g (92.2 mmol) of benzyl alcohol
2 and 0.4 g (2.1 mmol) of 4-methylbenzenesulfonic acid monohydrate in 100 ml of dichloromethane. The
crude product was purified by VFC (300 g silica gel, PE:Et2O, 10:1) and Kugelrohr distillation. Yield:
12.2 g (89%) of a colorless oil. Bp=90°C/0.01 torr (Kugelrohr), Rf (PE:Et2O, 8:1)=0.5, [α]D20=−104 (c
1.0, CH2Cl2); C19H26O2 (286.42): calculated: C 79.68, H 9.15; found: C 79.63, H 9.43; 1H NMR (200
MHz; CDCl3): δH=0.8–2.45 (m, 17H, aliphatic-H, therein: 0.80, 0.98, and 1.01 (3s, 9H, 3CH3)), 3.97
(d, 1H, J=6.6 Hz; 7a-H), 4.45 (d, 1H, Ph-CH2), 4.72 (d, 1H, Ph-CH2), 5.23 (dd, 1H, 2-H), 7.18–7.4 (m,
5H, aromatic-H); 13C NMR (50 MHz; CDCl3): δC=11.66/20.50/22.90 (3q, 3CH3), 28.91 (t, C-5), 32.47
(t, C-6), 38.61 (t, C-3), 45.96 (d, C-3a), 47.0 (s, C-8), 47.61 (s, C-7), 48.44 (d, C-4), 68.28 (t, Ph-CH2),
91.21 (d, C-7a), 104.32 (d, C-2), 127.35 (d, para-C), 127.77 (d, 2C, ortho-C), 128.28 (d, 2C, meta-C),
138.53 (s, ipso-C).
4.2.2. [2R-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-2-(1-phenylpropoxy)-4,7-methanobenzo-
furan 17
Following GP-1, 17 was prepared from 4 g (10.7 mmol) of 1, 5.82 g (42.7 mmol) (±)-1-phenyl-
1-propanol (4) and 0.2 g (1.05 mmol) of 4-methylbenzenesulfonic acid monohydrate in 55 ml of
dichloromethane. The crude product was purified by VFC (200 g silica gel, PE:Et2O, 30:1) and Kugelrohr
distillation. Yield: 6.1 g (91%, de=37% (S)) of a colorless oil. Bp=90°C/0.01 torr (Kugelrohr), Rf
(PE:Et2O, 4:1)=0.64; C21H30O2 (314.47): calculated: C 80.21, H 9.62; found: C 80.15, H 9.51; 1H NMR
(200 MHz; CDCl3): δH=0.72–2.46 (m, 44H, aliphatic-H (R,S)), 3.48 (d, 1H, 7a-H (R)), 3.97 (d, 1H,
7a-H (S)), 4.43 (dd, 1H, C*-H (R)), 4.54 (dd, 1H, C*-H (S)), 4.97 (d, 1H, 2-H (S)), 5.31 (d, 1H, 2-H
(R)), 7.15–7.39 (m, 10H, aromatic-H (R,S)); 13C NMR (50 MHz; CDCl3): δC=9.89/10.55 (2q, C*-CH2-
CH3 (R,S)), 11.40/11.71/20.48/22.86/22.90 (6q, 6MBE-CH3 (R,S)), 28.84 (t, C-5 (R)), 28.95 (t, C-5

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P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
(S)), 29.51 (t, C*-CH2 (R)), 31.35 (t, C*-CH2 (S)), 32.35 (t, C-6 (R)), 32.54 (t, C-6 (S)), 38.51 (t, C-3
(S)), 38.63 (t, C-3 (R)), 45.90 (d, C-3a (R)), 46.08 (d, C-3a (S)), 46.92 (2s, C-8 (R,S)), 47.29 (s, C-7
(R)), 47.56 (s, C-7 (S)), 48.43 (2d, C-4 (R,S)), 77.97 (d, C* (S)), 79.28 (d, C* (R)), 90.99 (d, C-7a (R)),
91.09 (d, C-7a (S)), 101.97 (d, C-2 (S)), 104.24 (d, C-2 (R)), 126.50 (2d, ortho-C (R)), 126.68 (d, para-C
(R)), 126.93 (2d, ortho-C (S)), 127.11 (d, para-C (S)), 127.84 (2d, meta-C (R)), 128.12 (2d, meta-C (S)),
142.85 (s, ipso-C (S)), 143.70 (s, ipso-C (R)).
4.2.3. [2R-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-2-(1-phenylpentoxy)-4,7-methanobenzo-
furan 18
Following GP-1, 18 was prepared from 4.23 g (11.3 mmol) of 1, 8 g (48.7 mmol) of (±)-1-
phenyl-1-pentanol 5 and 0.2 g (1.05 mmol) of 4-methylbenzenesulfonic acid monohydrate in 55 ml
of dichloromethane. The crude product was purified by VFC (220 g silica gel, PE:Et2O, 100:1) and
Kugelrohr distillation. Yield: 3.2 g (41%, de=67% (S)) of a colorless oil. Bp=90°C/0.01 torr (Kugelrohr),
Rf (PE:Et2O, 10:1)=0.53; C23H34O2 (342.52): calculated: C 80.65, H 10.01; found: C 80.65, H 9.82; 1H
NMR (200 MHz; CDCl3): δH=0.72–2.45 (m, 52H, aliphatic-H (R,S)), 3.46 (d, 1H, 7a-H (R)), 3.97 (d,
1H, 7a-H (S)), 4.45 (dd, 1H, C*-H (R)), 4.60 (dd, 1H, C*-H (S)), 4.93 (d, 1H, 2-H (S)), 5.29 (d, 1H, 2-H
(R)), 7.16–7.43 (m, 10H, aromatic-H (R,S)); 13C NMR (50 MHz; CDCl3): δC=11.43/11.71/20.48/22.92
(6q, 6CH3 (R,S)), 14.03 (2q, butyl-CH3 (R,S)), 22.43 (t, butyl-CH2 (S)), 22.68 (t, butyl-CH2 (R)), 27.76
(t, butyl-CH2 (R)), 28.07 (t, butyl-CH2 (S)), 28.81 (t, C-5 (R)), 28.97 (t, C-5 (S)), 32.43 (t, C-6 (R)), 32.59
(t, C-6 (S)), 38.20 (t, C*–CH2 (R,S)), 38.51 (t, C-3 (S)), 38.66 (t, C-3 (R)), 45.91 (d, C-3a (R)), 46.08 (d,
C-3a (S)), 46.94 (2s, C-8 (R,S)), 47.42 (s, C-7 (R)), 47.57 (s, C-7 (S)), 48.26 (2d, C-4 (R,S)), 76.50 (d,
C* (S)), 78.32 (d, C* (R)), 91.00 (d, C-7a (R)), 91.14 (d, C-7a (S)), 101.97 (d, C-2 (S)), 104.40 (d, C-2
(R)), 126.47 (2d, ortho-C (R)), 126.68 (d, para-C (R)), 126.88 (2d, ortho-C (S)), 127.09 (d, para-C (S)),
127.87 (2d, meta-C (R)), 128.16 (2d, meta-C (S)), 143.21 (s, ipso-C (S)), 144.06 (s, ipso-C (R)).
4.2.4. [2S-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-2-(2-methyl-1-phenylpropoxy)-4,7-
methanobenzofuran 19
Following GP-1, 19 was prepared from 4.33 g (11.6 mmol) of 1, 7.68 g (49.8 mmol) of (±)-2-
methyl-1-phenyl-1-propanol 6 and 0.2 g (1.05 mmol) of 4-methylbenzenesulfonic acid monohydrate
in 55 ml of dichloromethane. The crude product was purified by VFC (220 g silica gel, PE:Et2O,
100:1) and Kugelrohr distillation. Yield: 4.52 g (60%, de=67% (S)) of a colorless oil. Bp=90°C/0.01
torr (Kugelrohr), Rf (PE:Et2O, 20:1)=0.60; C22H32O2 (328.49): calculated: C 80.44, H 9.82; found: C
1
80.14, H 9.52; H NMR (200 MHz; CDCl3): δH=0.65–2.45 (m, 48H, aliphatic-H (R,S)), 3.32 (d, 1H,
7a-H (R)), 3.96 (d, 1H, 7a-H (S)), 4.08 (d, 1H, C*-H (R)), 4.27 (d, 1H, C*-H (S)), 4.89 (d, 1H, 2-
H (S)), 5.23 (d, 1H, 2-H (R)), 7.15–7.40 (m, 10H, aromatic-H (R,S)); 13C NMR (50 MHz; CDCl3):
δC=11.33/11.73/20.50/22.92 (6q, 6MBE–CH3 (R,S)), 18.84/18.93/19.24 (4q, C*-(CH3)2 (R,S)), 28.84
(t, C-5 (R)), 28.96 (t, C-5 (S)), 32.35 (t, C-6 (R)), 32.57 (t, C-6 (S)), 34.36 (d, C*-CH-(CH3)2 (R)), 34.65
(d, C*-CH-(CH3)2 (S)), 38.48 (t, C-3 (R,S)), 45.88 (d, C-3a (R)), 46.13 (d, C-3a (S)), 46.91 (2s, C-8
(R,S)), 47.20 (s, C-7 (R)), 47.56 (s, C-7 (S)), 48.43 (2d, C-4 (R,S)), 81.77 (d, C* (S)), 84.45 (d, C* (R)),
90.96 (d, C-7a(R)), 91.11 (d, C-7a (S)), 101.73 (d, C-2 (S)), 105.49 (d, C-2 (R)), 126.54 (d, para-C (R)),
127.06 (d, para-C (S)), 127.11/127.55 (2×2d, ortho-C (R), meta-C (S)), 127.77/127.87 (2×2d, ortho-C
(S), meta-C (R)), 141.68 (s, ipso-C (S)), 143.44 (s, ipso-C (R)).

P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
4823
4.2.5. [2R-(2α,3aα,4β,7β,7aα)]-2-(Diphenylmethoxy)-octahydro-7,8,8-trimethyl-4,7-methanobenzo-
furan 21
Following GP-1, 21 was prepared from 3.5 g (9.34 mmol) of 1, 10.32 g (56.04 mmol) of diphenyl-
methanol 8 and 0.2 g (1.05 mmol) of 4-methylbenzenesulfonic acid monohydrate in 50 ml of dichloro-
methane. The crude product was purified by VFC (200 g silica gel, PE:Et2O, 30:1) and the resulting
mixture of 21 and 1,10-oxybis[diphenylmethane] was treated with PE:Et2O, 100:1. The insoluble 1,10-
oxybis[diphenylmethane] was filtered off and the solvent was evaporated to furnish 21. Yield: 4.68 g
(69%) of a colorless oil. Rf (PE:Et2O, 8:1)=0.54, [α]D20=−118 (c 1.1, CH2Cl2); C25H30O2 (362.51): cal-
culated: C 82.83, H 8.34; found: C 82.93, H 8.27; 1H NMR (200 MHz; CDCl3): δH=0.75–2.48 (m, 17H,
aliphatic-H, therein: 0.80, 0.93, and 1.00 (3s, 9H, 3CH3)), 3.93 (d, 1H, 7a-H), 5.17 (dd, 1H, 2-H), 5.78
(s, 1H, (Ph)2-CH), 7.16-7.45 (m, 10H, aromatic-H); 13C NMR (50 MHz; CDCl3): δC=11.65/20.53/22.90
(3q, 3CH3), 28.91 (t, C-5), 32.45 (t, C-6), 38.58 (t, C-3), 46.01 (d, C-3a), 47.02 (s, C-8), 47.59 (s, C-
7), 48.46 (d, C-4), 77.80 (d, Ph2CH-), 91.28 (d, C-7a), 102.41 (d, C-2), 126.94/127.40 (2d, 2×para-C),
127.03/127.71/128.08/128.33 (4d, 2×2ortho-C, 2×2meta-C), 141.69/143.15 (2s, 2×para-C).
4.2.6. [2S-(2α,3aα,4β,7β,7aα)]-1-[[2-[Octahydro-7,8,8-trimethyl-(4,7-methanobenzofuran-2-yl)-
oxy]2-phenyl]ethyl]pyrrolidine 22
Following GP-1, 22 was prepared from 2.4 g (6.4 mmol) of 1, 2.1 g (12.97 mmol) of (±)-α-phenyl-
1-pyrrolidineethanol 9 and 2.6 g (13.65 mmol) of 4-methylbenzenesulfonic acid monohydrate in 55 ml
of dichloromethane. Sodium sulfate was added after 60 min and the reaction mixture was stirred for 3
h 30 min. The aqueous layer was extracted six times with dichloromethane and the crude product (4.4
g) was purified by VFC (100 g silica gel, gradient of PE:Et2O, 1:1 to diethyl ether). Yield: 0.63g (13%,
de=16% (R)) of a colorless oil. Rf (PE:Et2O, 1:1)=0.11; C24H35NO2 (314.47 g/mol): calculated: C 78.00,
H 9.55, N 3.79; found: C 77.78, H 9.68, N 3.98; 1H NMR (200 MHz; CDCl3): δH=0.63–2.92 (m, 54H,
aliphatic-H (R,S), therein: 0.72, 0.90, and 0.98 (3s, 9H, 3CH3 (S)), and 0.79, 0.88, and 0.98 (3s, 9H,
3CH3 (R))), 3.34 (d, 1H, 7a-H (S)), 4.01 (d, 1H, 7a-H (R)), 4.68 (dd, 1H, C*-H (S)), 4.87 (dd, 1H, C*-H
(R)), 4.93 (d, 1H, 2-H (R)), 5.36 (d, 1H, 2-H (S)), 7.14–7.43 (m, 10H, aromatic-H (R,S)); 13C NMR (50
MHz; CDCl3): δC=11.29/11.64/20.42/20.48/22.82/22.96 (6q, 6CH3 (R,S)), 23.49 (4t, 2×2N-CH2-CH2
(R,S)), 28.80 (t, C-5 (S)), 28.90 (t, C-5 (R)), 32.31 (t, C-6 (S)), 32.54 (t, C-6 (R)), 38.42 (t, C-3 (R)),
38.76 (t, C-3 (S)), 45.85 (d, C-3a (S)), 45.96 (d, C-3a (R)), 46.84 (s, C-8 (S)), 46.94 (s, C-8 (R)), 47.20
(s, C-7 (S)), 47.52 (s, C-7 (R)), 48.44 (2d, C-4 (R,S)), 54.42 (2t, 2×N-CH2 (R)), 54.82 (2t, 2×N-CH2
(R)), 62.97 (2t, C*-CH2 (R,S)), 75.87 (d, C* (R)), 77.95 (d, C* (S)), 91.03 (d, C-7a (S)), 91.20 (d, C-7a
(R)), 101.92 (d, C-2 (R)), 105.24 (d, C-2 (S)), 126.47 (2d, ortho-C (S)), 126.86 (d, para-C (S)), 127.09
(2d, ortho-C (R)), 127.38 (d, para-C (R)), 127.84 (2d, meta-C (S)), 128.18 (2d, meta-C (R)), 141.51 (s,
ipso-C (R)), 143.05 (s, ipso-C (S)).
4.2.7. [2R-(2α,3aα,4β,7β,7aα)]-2-[[(Octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl)oxy]-
methyl]pyridine 2
Following GP-1, 23 was prepared from 4.12 g (11.84 mmol) of 1, 2.58 g (23.68 mmol) of pyridine-
2-methanol 10 and 4.76 g (25 mmol) of 4-methylbenzenesulfonic acid monohydrate in 30 ml of
dichloromethane. In deviation of GP-1 the solution was stirred for 5 h at room temperature, and the
aqueous phase was extracted four times with dichloromethane. The crude product was purified by VFC
(100 g silica gel, PE:Et2O, 1:2). Compound 1 and the alcohol 10 were recovered, and the reaction
was repeated with these substrates. The combined fractions containing the product (2.19 g) were again
purified by column chromatography (80 g silica gel, gradient of PE:Et2O, 2:1 to PE:Et2O, 1:2) and after
this by Kugelrohr distillation. Yield: 1.05 g (38%) of a colorless oil. Bp=90°C/0.005 torr (Kugelrohr), Rf

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P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
(Et2O:PE, 2:1)=0.40, [α]D20=−99.4 (c 1.0, CH2Cl2); C18H25NO2 (287.4): calculated: C 75.22, H 8.77, N
4.87; found: C 75.29, H 8.82, N 4.83; 1H NMR (200 MHz; CDCl3): δH=0.78–2.45 (m, 17H, aliphatic-H,
therein: 0.80, and 1.00 (2s, 9H, 3CH3)), 3.95 (d, 1H, 7a-H), 4.58 (d, 1H, O-CH2), 4.81 (d, 1H, O-CH2),
5.29 (dd, 1H, 2-H), 7.18 (dd, 1H, 50-H), 7.40 (d, 1H, 30-H), 7.68 (dd, 1H, 40-H), 8.57 (d, 1H, 60-H); 13
C
NMR (50 MHz; CDCl3): δC=11.18/20.08/22.47 (3q, 3CH3), 28.49 (t, C-5), 32.01 (t, C-6), 38.27 (t, C-3),
45.51 (d, C-3a), 46.60 (s, C-8), 47.23 (s, C-7), 48.06 (d, C-4), 68.87 (t, O-CH2), 90.97 (d, C-7a), 104.53
(d, C-2), 121.20/121.78 (2d, C-30/C-50), 136.19 (d, C-40), 148.56 (d, C-60), 158.26 (s, C-20).
4.2.8. [2R-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-2-[(3,4,5-trimethoxyphenyl)methoxy]-
4,7-methanobenzofuran 2
Following GP-1, 25 was prepared from 4.16 g (11.96 mmol) of 1, 4.7 g (23.92 mmol) of 3,4,5-
trimethoxybenzyl alcohol 12 and 0.2 g (1.05 mmol) of 4-methylbenzenesulfonic acid monohydrate in
50 ml of dichloromethane. The crude product (8.64 g) was purified by VFC (160 g silica gel, PE:Et2O,
1:1). Yield: 7.18 g (80%) of colorless crystals. Mp=75–77°C, Rf (Et2O:PE, 2:1)=0.5, [α]D20=−70 (c 1.0,
CH2Cl2); C22H32O5 (376.49): calculated: C 70.19, H 8.57; found: C 70.43, H 8.57; 1H NMR (200 MHz;
CDCl3): δH=0.78–2.45 (m, 17H, aliphatic-H, therein: 0.81, 0.98, and 1.00 (3s, 9H, 3CH3)), 3.82 (s, 3H,
para-O-CH3), 3.87 (s, 6H, 2meta-O-CH3), 3.97 (d, 1H, 7a-H), 4.37 (d, 1H, O-CH2), 4.61 (d, 1H, O-CH2),
5.23 (dd, 1H, 2-H), 6.57 (s; 2H, aromatic-H); 13C NMR (50 MHz; CDCl3): δC=11.66/20.48/22.88 (3q,
3CH3), 28.90 (t, C-5), 32.47 (t, C-6), 38.63 (t, C-3), 45.97 (d, C-3a), 47.01 (s, C-8), 47.64 (s, C-7), 48.46
(d, C-4), 56.07 (2q, meta-O-CH3), 60.78 (q, para-O-CH3), 68.70 (t, O-CH2), 91.33 (d, C-7a), 104.48 (d,
C-2), 104.96 (2d, ortho-C), 134.12/137.2 (2s, para-C/ipso-C), 153.19 (2s, meta-C).
4.2.9. [2R-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-2-[(4-nitrophenyl)methoxy]-4,7-methano-
benzofuran 26
Following GP-1, 26 was prepared from 6.12 g (16.3 mmol) of 1, 10 g (65.3 mmol) of 4-nitrobenzyl
alcohol (13) and 0.5 g (2.6 mmol) of 4-methylbenzenesulfonic acid monohydrate in 75 ml of dichloro-
methane. The crude product (12.5 g) was purified by VFC (240 g silica gel, gradient of PE:Et2O, 20:1 to
5:1). Yield: 8.82 g (82%) of slightly yellow crystals. Mp=56–57°C, Rf (PE:Et2O, 10:1)=0.31; C19H25NO4
1
(331.41): calculated: C 68.86, H 7.60, N 4.23; found: C 69.02, H 7.68, N 4.24; H NMR (200 MHz;
CDCl3): δH=0.75–2.45 (m, 17H, aliphatic-H; therein: 0.81, 0.97, and 0.99 (3s, 9H, 3CH3)), 3.92 (d, 1H,
7a-H), 4.53 (d, 1H, O-CH2), 4.78 (d, 1H, O-CH2), 5.22 (dd, 1H, 2-H), 7.48 (d, 2H, aromatic-H (meta)),
8.18 (d, 2H, aromatic-H (ortho)); 13C NMR (50 MHz; CDCl3): δC=11.53/20.39/22.81 (3q, 3CH3), 28.80
(t, C-5), 32.33 (t, C-6), 38.60 (t, C-3), 45.81 (d, C-3a), 46.94 (s, C-8), 47.61 (s, C-7), 48.38 (d, C-4), 67.03
(t, O-CH2), 91.47 (d, C-7a), 104.73 (d, C-2), 123.44 (2d, ortho-C), 127.74 (2d, meta-C), 146.30/147.14
(2s, para-C/ipso-C).
4.2.10. [2S-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-2-[(phenylmethyl)thio]-4,7-methano-
benzofuran 27
Following GP-1, 27 was prepared from 3 g (8.0 mmol) of 1, 4.02 g (32.4 mmol) of benzyl thiol 14
and 0.2 g (1.05 mmol) of 4-methylbenzenesulfonic acid monohydrate in 55 ml of dichloromethane. In
deviation to GP-1 the solution was stirred for 20 h at room temperature, 2N sodium hydroxide solution
was added to the reaction mixture and the crude product (5.5 g) was purified by VFC (130 g silica gel,
PE:Et2O, 40:1). The combined fractions containing the product (3 g of 4.8 g) were further purified by
column chromatography (200 g silica gel, PE:Et2O, 40:1). Yield: 2.35 g (78% based on 3 g of purified
product) of a colorless oil. Rf (PE:Et2O, 30:1)=0.33, [α]D20=−365 (c 1.06, CHCl3); C19H26OS (302.48):
1
calculated: C 75.45, H 8.66; found: C 75.30, H 8.63; H NMR (200 MHz; CDCl3): δH=0.78–2.42 (m,

P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
4825
17H, aliphatic-H, therein: 0.83, 0.99, and 1.03 (3s, 9H, 3CH3)), 3.72 (d, 1H, S-CH2), 3.88 (d, 1H, S-
CH2), 4.02 (d, 1H, 7a-H), 5.42 (dd, 1H, 2-H), 7.17–7.41 (m, 5H, aromatic-H); 13C NMR (50 MHz;
CDCl3): δC=11.59/20.65/22.80 (3q, 3CH3), 28.79 (t, C-5), 32.27 (t, C-6), 34.61 (t, S-CH2), 38.52 (t, C-
3), 46.95 (d, C-3a), 47.09 (s, C-8), 47.53 (s, C-7), 48.40 (d, C-4), 84.16 (d, C-7a), 90.66 (d, C-2), 126.58
(d, para-C), 128.32/128.87 (2×2d, meta-C/ortho-C), 138.98 (s, ipso-C).
4.3. General procedure (GP-2) for the rearrangements of the acetals 15–27
The acetals 15–27 were dissolved in anhydrous THF under a nitrogen atmosphere. n-Butyllithium in
n-hexane was added dropwise to this solution at room temperature. The reaction mixture was stirred for
3 h at this temperature and then quenched with water. The mixture was concentrated and diethyl ether
was added. The aqueous phase was extracted twice with diethyl ether. The combined organic layers were
dried with sodium sulfate, filtered and the solvent was evaporated. The crude products were purified by
VFC or column chromatography.
4.3.1. Rearrangement of 15
Following GP-2, 2.2 ml (5.24 mmol) of n-butyllithium was added to a solution of 0.5 g (1.75 mmol)
of 15 in 6.3 ml of anhydrous THF. The crude product was purified by VFC (10 g silica gel, gradient of
PE:Et2O, 30:1 to 4:1). Yield: 0.277 g (55%) of a slightly yellow oil (diastereomeric mixture, 28A:28B,
1:1.63 (GC)). The diastereomers were separated by formation of the two acetals 38 and 39 and subsequent
column chromatography.
4.3.1.1. [2R-[2α(R*,(2S*,3aR*,4R*,7S*,7aR*)),3aα,4β,7β,7aα]]-Octahydro-2-[[(octahydro-7,8,8-
trimethyl-4,7-methanobenzofuran-2-yl)oxy]phenylmethyl]-7,8,8-trimethyl-4,7-methanobenzofuran 38,
and [2R-[2α(S*,(2S*,3aR*,4R*,7S*7aR*)),3aα,4β,7β,7aα]]-octahydro-2-[[(octahydro-7,8,8-tri-
methyl-4,7-methanobenzofuran-2-yl)oxy]phenylmethyl]-7,8,8-trimethyl-4,7-methanobenzofuran
39.
Following GP-1, 38 and 39 were prepared from 5.408 g (15.4 mmol) of 1, 4.408 g (15.4 mmol) of
a mixture of 28A and 28B and 0.3 g (1.575 mmol) of 4-methylbenzenesulfonic acid monohydrate
in 50 ml of dichloromethane. The crude product (9.47 g) was purified by MPLC (1000 g silica gel,
PE:Et2O, 30:1). Compound 38: yield: 1.622 g (23%) of a colorless rigid foam. Rf (PE:Et2O, 8:1)=0.44,
[α]D20=−143 (c 1, CH2Cl2); C31H44O3 (464.69): calculated: C 80.13, H 9.54; found: C 80.25, H
1
9.28; H NMR (200 MHz; CDCl3): δH=0.75–2.5 (m, 34H, aliphatic-H, therein: 0.78, 0.80, 0.92,
0.98, 1.00, and 1.02 (6s, 18H, 6CH3)), 3.98 (d, 1H, 7a-H (1)), 4.12 (d, 1H, 7a-H (2)), 4.15–4.27 (m,
1H, 2-H (1)), 4.45 (d, 1H, C*-H), 4.95 (d, 1H, 2-H (2)), 7.18–7.38 (m, 5H, aromatic-H); 13C NMR
(50 MHz; CDCl3): δC=11.48/11.54/20.06/20.28/22.42/22.48 (6q, 6CH3) 28.53 (2t, C-5 (1), C-5 (2)),
32.03/32.19/32.70/37.94 (4t, C-3 (1), C-3 (2), C-6 (1), C-6 (2)), 46.44/46.70/47.05/47.57 (4s, C-7 (1),
C-7 (2), C-8 (1), C-8 (2)), 45.44/47.32/48.10/48.36 (4d, C-4 (1), C-4 (2), C-3a (1), C-3a (2)), 77.31 (d,
C*), 82.10 (d, C-2 (1)), 90.41/90.91 (2d, C-7a (1), C-7a (2)), 101.85 (d, C-2 (2)), 127.19 (d, para-C),
127.70 (2d, ortho-C), 127.89 (2d, meta-C), 139.62 (s, ipso-C). Compound 39: yield: 2.06 g (29%) of
a colorless rigid foam. Rf (PE:Et2O, 8:1)=0.33, [α]D20=−37.6 (c 1.25, CH2Cl2); C31H44O3 (464.69):
1
calculated: C 80.13, H 9.54; found: C 80.36, H 9.61; H NMR (200 MHz; CDCl3): δH=0.73–2.4 (m,
34H, aliphatic-H, therein: 0.76, 0.78, 0.79, 0.92, 0.94, and 0.98 (6s, 18H, 6CH3)), 3.88 (d, 1H, 7a-H
(1)), 4.12 (d, 1H, 7a-H (2)), 4.17–4.28 (m, 1H, 2-H (1)), 4.65 (d, 1H, C*-H), 5.29 (d, 1H, 2-H (2)),
7.14–7.34 (m, 5H, aromatic-H); 13C NMR (50 MHz; CDCl3): δC=11.41/11.68/20.25/20.48/22.77/22.87
(6q, 6CH3) 28.81/28.91 (2t, C-5 (1), C-5 (2)), 31.39/32.40/32.48/38.90 (4t, C-3 (1), C-3 (2), C-6 (1), C-6
(2)), 46.49/46.88/47.43/48.26 (4s, C-7 (1), C-7 (2), C-8 (1), C-8 (2)), 46.09/48.51/48.92/49.07 (4d, C-4

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P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
(1), C-4 (2), C-3a (1), C-3a (2)), 81.74 (d, C*), 84.59 (d, C-2 (1)), 91.40/93.78 (2d, C-7a (1), C-7a (2)),
106.10 (d, C-2 (2)), 126.33 (2d, ortho-C), 126.68 (d, para-C), 127.83 (2d, meta-C), 140.95 (s, ipso-C).
4.3.1.2. [2R-(2α(R*),3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-α-phenyl-4,7-methanobenzofuran-
2-methanol 28A. Compound 38 (1.622 g, 3.49 mmol) was dissolved in 35 ml of methanol and 10 ml of
dichloromethane and 4-methylbenzenesulfonic acid monohydrate was added. This mixture was stirred
for 3 h at room temperature. Sodium hydrogen carbonate was added and the mixture was stirred again for
10 min. After extraction with water the aqueous phase was extracted twice with dichloromethane. The
combined organic layers were dried with sodium sulfate, filtered and the solvent was evaporated. The
crude product was purified by VFC (40 g silica gel, PE:Et2O, 10:1). Yield: 0.952 g (95%) of a slightly
yellow oil. Rf (PE:Et2O, 1:1)=0.47, [α]D20=−34.1 (c 1, CH2Cl2); C19H26O2 (286.42): calculated: C
79.68, H 9.15; found: C 79.97, H 9.33; 1H NMR (200 MHz; CDCl3): δH=0.78–1.9 (m, 16H, aliphatic-H,
therein: 0.80, 0.99, and 1.03 (3s, 9H, CH3)), 2.16–2.38 (m, 1H, 3a-H), 3.26 (s, 1H, OH), 3.94 (d, 1H,
7a-H), 4.03–4.16 (m, 1H, 2-H), 4.30 (d, 1H, C*-H), 7.23–7.42 (m, 5H, aromatic-H); 13C NMR (50 MHz;
CDCl3): δC=11.21/20.00/22.32 (3q, 3CH3), 28.37 (t, C-5), 31.85 (t, C-3), 32.20 (t, C-6), 46.36/47.86
(2s, C-7, C-8), 47.25/48.51 (2d, C-4, C-3a), 74.90 (d, C*), 84.24 (d, C-2), 90.82 (d, C-7a), 127.16 (2d,
ortho-C), 127.61 (d, para-C), 127.97 (2d, meta-C), 139.89 (s, ipso-C).
4.3.1.3. [2R-(2α(S*),3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-α-phenyl-4,7-methanobenzofuran-
2-methanol 28B. Following the above procedure (Section 4.3.1.2), 2.058 g (4.44 mmol) of 39 was
dissolved in 35 ml of methanol and 10 ml of dichloromethane and 4-methylbenzenesulfonic acid
monohydrate was added. The crude product was purified by VFC (40 g silica gel, PE:Et2O, 10:1).
Yield: 0.954 g (75%) of colorless crystals. Mp=119–123°C, Rf (PE:Et2O, 1:1)=0.47, [α]D20=−7.8 (c
1
1, CH2Cl2); C19H26O2 (286.42): calculated: C 79.68, H 9.15; found: C 79.98, H 9.01; H NMR (200
MHz; CDCl3): δH=0.78–2.28 (m, 17H, aliphatic-H, therein: 0.80, 0.96, and 0.99 (3s, 9H, CH3)), 3.97
(d, 1H, 7a-H), 4.29–4.40 (m, 1H, 2-H), 4.89 (d, 1H, C*-H), 7.15–7.40 (m, 5H, aromatic-H); 13C NMR
(50 MHz; CDCl3): δC=11.63/20.11/22.70 (3q, 3CH3), 28.66 (t, C-5), 31.02 (t, C-3), 32.30 (t, C-6),
46.41/48.51 (2s, C-7, C-8), 48.57/49.24 (2d, C-4, C-3a), 77.05 (d, C*), 84.72 (d, C-2), 94.20 (d, C-7a),
126.01 (2d, ortho-C), 127.27 (d, para-C), 128.22 (2d, meta-C), 141.06 (s, ipso-C).
4.3.2. Rearrangement of 16
Following GP-2, 2.1 ml (4.99 mmol) of n-butyllithium was added to a solution of 0.5 g (1.66 mmol)
of 16 in 6.3 ml of anhydrous THF. The crude product was purified by VFC (10 g silica gel, gradient
of PE:Et2O, 30:1 to 4:1). Yield: 0.13 g (26%) of a colorless oil (diastereomeric mixture, 29A:29B, 1:3
(GC)). The diastereomers 29A and 29B were separated by column chromatography (10 g silica gel,
PE:Et2O, 5:1).
4.3.2.1. [2R-(2α(R*),3aα,4β,7β,7aα)]-Octahydro-α,7,8,8-trimethyl-α-phenyl-4,7-methanobenzo-
furan2-methanol 29A. Rf (PE:Et2O, 3:1)=0.35, [α]D20=−39.1 (c 1.12, CH2Cl2); C20H28O2 (300.44):
1
calculated: C 79.96, H 9.39; found: C 79.86, H 9.48; H NMR (200 MHz; CDCl3): δH=0.75–2.35 (m,
20H, aliphatic-H, therein: 0.78, 0.92, and 0.99 (3s, 9H, CH3) and 1.51 (s, 3H, C*-CH3)), 2.90 (s, 1H,
OH), 3.94 (d, 1H, 7a-H), 4.19 (dd, 1H, 2-H), 7.18–7.55 (m, 5H, aromatic-H); 13C NMR (50 MHz;
CDCl3): δC=11.17/19.46/22.20/22.27 (4q, 3CH3, and C*-CH3), 28.12 (t, C-5), 31.87/31.99 (2t, C-3,
C-6), 45.91/48.33 (2s, C-7, C-8), 48.08/48.96 (2d, C-4, C-3a), 76.70 (s, C*), 88.21 (d, C-2), 94.05 (d,
C-7a), 125.92 (2d, ortho-C), 126.67 (d, para-C), 127.61 (2d, meta-C), 143.90 (s, ipso-C).

P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
4827
4.3.2.2. [2R-(2α(S*),3aα,4β,7β,7aα)]-Octahydro-α,7,8,8-tetramethyl-α-phenyl-4,7-methanobenzo-
furan2-methanol 29B. Rf (PE:Et2O, 3:1)=0.45, [α]D20=−18.7 (c 1, CH2Cl2); C20H28O2 (300.44):
1
calculated: C 79.96, H 9.39; found: C 79.83, H 9.26; H NMR (200 MHz; CDCl3): δH=0.75–2.15
(m, 20H, aliphatic-H, therein: 0.78, 0.97, and 0.99 (3s, 9H, CH3) and 1.59 (s, 3H, C*-CH3)), 2.62 (s,
1H, OH), 3.85 (d, 1H, 7a-H), 4.29 (dd, 1H, 2-H), 7.18–7.60 (m, 5H, aromatic-H); 13C NMR (50 MHz;
CDCl3): δC=11.65/20.03/22.70 (3q, 3CH3), 27.43 (q, C*-CH3), 28.59 (t, C-5), 32.32 (t, C-6), 32.62 (t,
C-3), 46.28/48.61 (2s, C-7, C-8), 48.61/49.26 (2d, C-4, C-3a), 77.64 (s, C*), 87.50 (d, C-2), 94.65 (d,
C-7a), 125.41 (2d, ortho-C), 126.53 (d, para-C), 128.00 (2d, meta-C), 145.23 (s, ipso-C).
4.3.3. Rearrangement of 17
Following GP-2, 3.7 ml (9.54 mmol) of n-butyllithium was added to a solution of 1 g (3.18 mmol) of
17 in 13 ml of anhydrous THF. The crude product was purified by SC (100 g silica gel, PE:Et2O, 10:1).
4.3.3.1. [2R-(2α(R*),3aα,4β,7β,7aα)]-α-Ethyl-octahydro-7,8,8-trimethyl-α-phenyl-4,7-methano-
benzofuran-2-methanol 30A. Yield: 0.027 g (2.7%) of a colorless oil. Rf (PE:Et2O, 4:1)=0.30,
[α]D20=−21.3 (c 0.54, CHCl3); C21H30O2 (314.47): calculated: C 80.21, H 9.62; found: C 80.13, H 9.84;
1H NMR (200 MHz; CDCl3): δH=0.64–2.20 (m, 22H, aliphatic-H, therein: 0.78, 0.93, and 0.97 (3s, 9H,
CH3) and 0.83 (s, 3H, C*-CH2-CH3)), 2.55 (s, 1H, OH), 3.84 (d, 1H, 7a-H), 4.14 (dd, 1H, 2-H), 7.18–7.52
(m, 5H, aromatic-H); 13C NMR (50 MHz; CDCl3): δC=7.52 (q, 3H, C*-CH2-CH3), 11.54/19.84/22.68
(3q, 3CH3), 27.46 (t, C*-CH2), 28.57 (t, C-5), 31.87 (t, C-3), 32.29 (t, C-6), 46.26/48.70 (2s, C-7, C-8),
48.44/49.35 (2d, C-4, C-3a), 79.70 (s, C*), 88.67 (d, C-2), 94.52 (d, C-7a), 126.71 (d, para-C), 126.93
(2d, ortho-C), 127.93 (2d, meta-C), 142.00 (s, ipso-C).
4.3.3.2. [2R-(2α(S*),3aα,4β,7β,7aα)]-α-Ethyl-octahydro-7,8,8-trimethyl-α-phenyl-4,7-methano-
benzofuran-2-methanol 30B. Yield: 0.034 g (3.4%) of a colorless oil. Rf (PE:Et2O, 4:1)=0.43,
[α]D20=−9.56 (c 0.68, CHCl3); C21H30O2 (314.47): calculated: C 80.21, H 9.62; found: C 80.36, H
1
9.80; H NMR (200 MHz; CDCl3): δH=0.64–2.20 (m, 22H, aliphatic-H, therein: 0.78, 0.95, and 0.98
(3s, 9H, CH3) and 0.71 (s, 3H, C*-CH2-CH3)), 3.84 (d, 1H, 7a-H), 4.32 (dd, 1H, 2-H), 7.15–7.40
(m, 5H, aromatic-H); 13C NMR (50 MHz; CDCl3): δC=7.47 (q, 3H, C*-CH2-CH3), 11.66/20.04/22.71
(3q, 3CH3), 28.63 (t, C-5), 31.89/32.35 (2t, C*-CH2, C-6), 32.83 (t, C-3), 46.25/48.66 (2s, C-7, C-8),
48.66/49.31 (2d, C-4, C-3a), 80.66 (s, C*), 87.43 (d, C-2), 94.74 (d, C-7a), 125.92 (2d, ortho-C), 126.34
(d, para-C), 127.96 (2d, meta-C), 143.03 (s, ipso-C).
4.3.4. Rearrangement of 18
Following GP-2, 3.38 ml (8.76 mmol) of n-butyllithium was added to a solution of 1 g (2.92 mmol) of
18 in 13 ml of anhydrous THF. The crude product was purified by SC (100 g silica gel, PE:Et2O, 10:1).
4.3.4.1. [2R-(2α(R*),3aα,4β,7β,7aα)]-α-Butyl-octahydro-7,8,8-trimethyl-α-phenyl-4,7-methano-
benzofuran-2-methanol 31A. Yield: 0.015 g (1.5%) of a colorless oil. Rf (PE:Et2O, 4:1)=0.35,
[α]D20=−20.7 (c 1.5, CHCl3); C23H34O2 (342.52): calculated: C 80.65, H 10.01; found: C 80.93, H 9.81;
1H NMR (200 MHz; CDCl3): δH=0.75–2.30 (m, 26H, aliphatic-H, therein: 0.77, 0.92, and 0.96 (3s, 9H,
CH3)), 2.55 (s, 1H, OH), 3.83 (d, 1H, 7a-H), 4.13 (dd, 1H, 2-H), 7.16–7.53 (m, 5H, aromatic-H); 13C
NMR (50 MHz; CDCl3): δC=11.57/14.11/19.84/22.69 (4q, 4CH3), 23.43/25.49 (2t, C*-CH2-CH2-CH2),
28.56 (t, C-5), 31.90 (t, C-3), 32.29 (t, C-6), 34.98 (t, C*-CH2), 46.24/48.73 (2s, C-7, C-8), 48.44/49.39

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P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
(2d, C-4, C-3a), 79.48 (s, C*), 88.80 (d, C-2), 94.54 (d, C-7a), 126.68 (d, para-C), 126.83 (2d, ortho-C),
127.90 (2d, meta-C), 142.49 (s, ipso-C).
4.3.4.2. [2R-(2α(S*),3aα,4β,7β,7aα)]-α-Butyl-octahydro-7,8,8-trimethyl-α-phenyl-4,7-methano-
benzofuran-2-methanol 31B. Yield: 0.022 g (2.2%) of a colorless oil. Rf (PE:Et2O, 4:1)=0.50,
[α]D20=−13.3 (c 2.2, CHCl3); C23H34O2 (342.52): calculated: C 80.65, H 10.01; found: C 80.43, H
10.30; 1H NMR (200 MHz; CDCl3): δH=0.72–2.20 (m, 26H, aliphatic-H, therein: 0.77, 0.93, and 0.97
(3s, 9H, CH3)), 3.84 (d, 1H, 7a-H), 4.28 (dd, 1H, 2-H), 7.11–7.41 (m, 5H, aromatic-H); 13C NMR (50
MHz; CDCl3): δC=11.67/14.04/20.03/22.70 (4q, 4CH3), 23.09/25.39 (2t, C*-CH2-CH2-CH2), 28.62 (t,
C-5), 32.35 (t, C-6), 32.74 (t, C-3), 39.06 (t, C*-CH2), 46.26/48.64 (2s, C-7, C-8), 48.64/49.30 (2d, C-4,
C-3a), 80.41 (s, C*), 87.65 (d, C-2), 94.75 (d, C-7a), 125.80 (2d, ortho-C), 126.30 (d, para-C), 127.96
(2d, meta-C), 143.43 (s, ipso-C).
4.3.5. Rearrangement of 21
Following GP-2, 0.46 ml (1.18 mmol) of n-butyllithium was added to a solution of 0.14 g (0.46 mmol)
of 21 in 2 ml of anhydrous THF. The crude product was purified by VFC (5 g silica gel, PE:Et2O, 30:1).
4.3.5.1. [2R-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-α,α-diphenyl-4,7-methanobenzofuran-
2-methanol 32. Yield: 0.068 g (41%) of a colorless oil. Rf (PE:Et2O, 8:1)=0.21, [α]D20=+36.5 (c 1.2,
CHCl3); C25H30O2 (362.51): calculated: C 82.83, H 8.34; found: C 82.56, H 8.25; 1H NMR (200 MHz;
CDCl3): δH=0.75–2.23 (m, 17H, aliphatic-H, therein: 0.81, 0.97, and 1.07 (3s, 9H, CH3)), 2.62 (s, 1H,
OH), 3.90 (d, 1H, 7a-H), 5.15 (dd, 1H, 2-H), 7.13–7.54 (m, 10H, aromatic-H); 13C NMR (50 MHz;
CDCl3): δC=11.51/19.96/22.73 (3q, 3CH3), 28.59 (t, C-5), 32.20 (t, C-6), 33.33 (t, C-3), 46.03/48.84 (2s,
C-7, C-8), 48.73/49.43 (2d, C-4, C-3a), 81.40 (s, C-OH), 85.07 (d, C-2), 95.04 (d, C-7a), 126.49/126.87
(2d, 2×para-C), 126.21/127.59/127.90 (8d, 4×ortho-C, 4×meta-C), 144.95/146.04 (2s, 2×ipso-C).
4.3.6. Rearrangement of 22
Following GP-2, 0.84 ml (2.17 mmol) of n-butyllithium was added to a solution of 0.267 g (0.72
mmol) of 22 in 3.5 ml of anhydrous THF. The crude product (complex mixture) was purified by SC (27
g silica gel, gradient of PE:Et2O, 30:1 to Et2O to Et2O:MeOH, 8:1 to MeOH). Compounds 37A and 37B
were isolated instead of the expected products.
4.3.6.1. [2R-(2α(R*),3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-α-pentyl-α-phenyl-4,7-methano-
benzofuran-2-methanol 37A. Yield: 0.026 g (10%) of a slightly yellow oil. Rf (PE:Et2O, 10:1)=0.29,
[α]D20=−12.3 (c 1.22, CHCl3); C24H36O2 (356.55): calculated: C 80.85, H 10.18; found: C 80.79, H
10.37; 1H NMR (200 MHz; CDCl3): δH=0.72–2.24 (m, 28H, aliphatic-H, therein: 0.76, 0.90, and 0.96
(3s, 9H, CH3)), 3.83 (d, 1H, 7a-H), 4.12 (dd, 1H, 2-H), 7.13–7.52 (m, 5H, aromatic-H); 13C NMR
(50 MHz; CDCl3): δC=11.57/14.07/19.84/22.69 (4q, 4CH3), 22.65/22.98 (2t, C*-CH2-CH2-CH2-CH2),
28.56 (t, C-5), 31.90 (t, C-3), 32.29 (t, C-6), 32.64 (t, C*-CH2-CH2), 35.15 (t, C*-CH2), 46.25/48.73 (2s,
C-7, C-8), 48.39/49.39 (2d, C-4, C-3a), 79.51 (s, C*), 88.83 (d, C-2), 94.54 (d, C-7a), 126.68 (d, para-C),
126.83 (2d, ortho-C), 127.91 (2d, meta-C), 142.48 (s, ipso-C).
4.3.6.2. [2R-(2α(S*),3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-α-pentyl-α-phenyl-4,7-methano-
benzofuran-2-methanol 37B. Yield: 0.026 g (10%) of a slightly yellow oil. Rf (PE:Et2O, 10:1)=0.44,
[α]D20=−8.57 (c 0.98, CHCl3); C24H36O2 (356.55): calculated: C 80.85, H 10.18; found: C 80.57, H

P. Gärtner et al. / Tetrahedron: Asymmetry 10 (1999) 4811–4830
4829
10.28; 1H NMR (200 MHz; CDCl3): δH=0.75–2.30 (m, 28H, aliphatic-H, therein: 0.76, 0.93, and 0.97
(3s, 9H, CH3)), 3.83 (d, 1H, 7a-H), 4.29 (dd, 1H, 2-H), 7.12–7.40 (m, 5H, aromatic-H); 13C NMR
(50 MHz; CDCl3): δC=11.67/14.01/20.02/22.70 (4q, 4CH3), 22.54/22.84 (2t, C*-CH2-CH2-CH2-CH2),
28.61 (t, C-5), 32.23 (t, C-6), 32.35 (t, C-3), 32.73 (t, C*-CH2-CH2), 39.24 (t, C*-CH2), 46.25/48.64
(2s, C-7, C-8), 48.64/49.30 (2d, C-4, C-3a), 80.43 (s, C*), 87.65 (d, C-2), 94.73 (d, C-7a), 125.79 (2d,
ortho-C), 126.30 (d, para-C), 127.95 (2d, meta-C), 143.42 (s, ipso-C).
4.3.7. Rearrangement of 23
Following GP-2, 1.76 ml (3.13 mmol) of n-butyllithium was added to a solution of 0.3 g (1.04 mmol)
of 23 in 3.8 ml of anhydrous THF. The crude product was purified by SC (80 g silica gel, gradient of
PE:Et2O, 2:1 to Et2O to MeOH).
4.3.7.1. [2R-(2α,3aα,4β,7β,7aα)]-α-(Octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl)-
pyridin-2-methanol 33A, 33B. Yield: 0.035 g (12%) of colorless crystals (diastereomeric mixture,
33A:33B, 1:4.71 (1H NMR)). Rf (Et2O:PE, 2:1)=0.23; C18H25NO2·0.25 H2O (291.91): calculated: C
1
74.06, H 8.81, N 4.80; found: C 74.07, H 8.83, N 4.64; H NMR (200 MHz; CDCl3): δH=0.78–2.40
(m, 34H, aliphatic-H, therein: 0.80, 0.96, and 0.98 (6s, 18H, CH3)), 3.85 (d, 1H, 7a-H (A)), 4.07 (d,
1H, 7a-H (B)), 4.14–4.29 (m, 2H, 2-H (A,B)), 4.51 (d, 1H, C*–H (A)), 4.77 (d, 1H, C*–H (B)), 7.20
(2dd, 2H, 50-H (A,B)), 7.27 (d, 1H, 30-H (B)), 7.42 (d, 1H, 30-H (A)), 7.66 (2dd, 2H, 40-H (A,B)), 8.53
(2d, 2H, 60-H (A,B)); 13C NMR (50 MHz; CDCl3): δC=11.57/20.28/22.67 (6q, 6CH3), 28.63 (2t, C-5
(A,B)), 31.66 (t, C-3 (B)), 32.21 (2t, C-6 (A,B)), 32.63 (t, C-3(A)), 46.58/48.24 (4s, C-7, C-8 (A,B)),
47.73/48.90 (2d, C-4, C-3a (A)), 48.38/49.03 (2d, C-4, C-3a (B)), 74.87 (d, C* (B)), 75.67 (d, C* (A)),
83.85 (d, C-2 (A)), 84.04 (d, C-2 (B)), 92.16 (d, C-7a (A)), 93.29 (d, C-7a (B)), 121.61/122.40 (2d, C-
30/C-50 (B)), 121.68/122.54 (2d, C-30/C-50 (A)), 136.44 (d, C-40 (B)), 136.57 (d, C-40 (A)), 147.79 (d,
C-60 (B)), 148.23 (d, C-60 (A)), 158.79 (s, C-20 (B)), 159.92 (s, C-20 (A)).
4.3.8. Rearrangement of 25
Following GP-2, 2.24 ml (3.98 mmol) of n-butyllithium was added to a solution of 0.5 g (1.33 mmol)
of 25 in 6.3 ml of anhydrous THF. The crude product was purified by SC (50 g silica gel, gradient of
PE:Et2O, 1:1 to MeOH).
4.3.8.1. [2R-(2α,3aα,4β,7β,7aα)]-Octahydro-7,8,8-trimethyl-α-(3,4,5-trimethoxyphenyl)-
4,7-methanobenzofuran-2-methanol 35A, 35B. Yield: 0.210 g (42%) of a colorless oil (diastereomeric
mixture, 35A:35B, 1:1.78 (1H NMR)). Rf (Et2O:PE, 2:1)=0.28; C22H32O5 (376.49): calculated: C 70.19,
1
H 8.57; found: C 70.42, H 8.58; H NMR (200 MHz; CDCl3): δH=0.70–2.36 (m, 34H, aliphatic-H
(A,B)), 3.65–4.32 (m, 23H, C*-H (A), 2-H (A,B), 7a-H (A,B)), 4.78 (d, 1H, C*-H (B)), 6.54 (s, 4H,
aromatic-H); 13C NMR (50 MHz; CDCl3): δC=11.55/20.36/22.54 (3q, 3CH3 (A)), 11.61/20.10/22.66
(3q, 3CH3 (B)), 28.63 (t, C-5 (B)), 28.71 (t, C-5 (A)), 31.09/32.29 (2t, C-3, C-6 (B)), 32.18/32.78 (2t,
C-6, C-3 (A)), 46.70/48.22 (2s, C-7, C-8 (A)), 46.39/48.43 (2s, C-7, C-8 (B)), 47.58/48.86 (2d, C-3a,
C-4 (A)), 48.57/49.18 (2d, C-4, C-3a (B)), 56.03 (4q, O-CH3 (A,B)), 60.74 (2q, O-CH3 (A,B)), 75.46 (d,
C*-OH (A)), 76.93 (d, C*-OH (B)), 84.50 (d, C-2 (A)), 84.72 (d, C-2 (B)), 91.19 (d, C-7a (A)), 94.06 (d,
C-7a (B)), 102.81 (2d, ortho-C (B)), 104.39 (2d, ortho-C (A)), 135.88/136.92/137.67 (4s, para-C, ipso-C
(A,B)), 153.14/153.06 (4s, meta-C (A,B)).

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15. Crystal data: C18H26O2; M=286.40, orthorhombic, space group P212121, a=7.090(2), b=20.182(6), c=23.354(8) Å,
α=β=γ=90°, U=3342(2) Å3, Z=8, Dc 1.139 Mg/m3, T=297(2) K, µ=0.072 mm−1, F(000)=1248, colorless prism
(0.07×0.07×0.56 mm). Data were collected on a Philips PW1100 four-circle diffractometer (sealed X-ray tube, graphite
monochromator, Mo-Kα radiation, λ=0.71073 Å, ω-scans). Structure solution by direct methods, refinement by full-matrix
least squares on F2 (Sheldrick, G. M.; SHELX-97, A System of Computer Programs for Crystal Structure Determination;
University of Göttingen, 1997.) Data/restraints/parameters=2366/69/382; final R1=0.073 (observed data), wR2=0.147 (all
data).
16. Further details on the crystal structure determination have been deposited with the Cambridge Structural Database.