A new approach to helical primary structures of four-membered rings: (P)- and (M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecane

Article abstract of DOI:10.1016/j.tet.2003.11.081

A new approach to helical primary structures of four-membered rings uses a cycloaddition of a trimethylenketeniminium salt to suitable tailored methylenecyclobutanes to assemble the desired carbon framework. The results are short and effective syntheses of (M)-trispiro[3.0.0.3.2.2]tridecane [(M)-5], and (P)- and (M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecane [(P)- and (M)-24]. Unlike helices of three-membered rings, the specific rotation decreases, as the length of the helix increases.

Full text of DOI:10.1016/j.tet.2003.11.081

Tetrahedron 60 (2004) 1205–1213
A new approach to helical primary structures of four-membered
rings: (P)- and (M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecaneq
*
Lutz Fitjer, Andreas Kanschik and Ralf Gerke
¨ ¨ ¨ ¨
Institut fur Organische Chemie der Universitat Gottingen, Tammannstrasse 2, D-37077 Gottingen, Germany
Received 2 September 2003; revised 10 November 2003; accepted 18 November 2003
Abstract—A new approach to helical primary structures of four-membered rings uses a cycloaddition of a trimethylenketeniminium salt
to suitable tailored methylenecyclobutanes to assemble the desired carbon framework. The results are short and effective syntheses
of (M)-trispiro[3.0.0.3.2.2]tridecane [(M)-5], and (P)- and (M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecane [(P)- and (M)-24]. Unlike helices of
three-membered rings, the specific rotation decreases, as the length of the helix increases.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
The interesting quest, whether and to what extent the
chiroptical properties of helical hydrocarbons of spiro-
annelated rings are governed by static parameters like the
identity period and the diameter and length of the helix,
and/or by dynamic phenomena like conformational changes
may best be answered experimentally in conjunction with an
appropriate theoretical treatment. Towards this end, helical
structures of rings of different size, and, for five-membered
and larger rings, with different location of the spiro-centers
should be considered. However, until now only three
examples exist,1,2 and methods with a general applicability
for a synthesis of such compounds are rare.3
We recently described the synthesis of (M)-trispiro-
[3.0.0.3.2.2]tridecane [(M)-5],1 the first helical hydrocarbon
of spiroannelated four-membered rings,4 via a substance-,
diastereo- and enantioselective enzymatic reduction of an
inseparable 2:1-mixture of the trispiroketones 2 and 3 [2/3–
(5S,10S)-4], itself obtained from bicyclobutylidene 1 by an
addition of dichloroketene and a reductive dehalogenation.
Oxidation with pyridinium chlorochromat followed by
Wolff–Kishner reduction then yielded (M)-5 (Scheme 1).
Scheme 1.
To improve the synthesis of 5, and to make it suitable for a
synthesis of higher analogues as well, we thought it
necessary to prevent the formation of regioisomers and to
establish the spiro[3.3]heptan-1-one subunit in 2 regio-
specifically in a single step. Towards this end, we envisaged
a cycloaddition of a trimethylenketeniminium salt 105 to
1-methylenespiro[3.3]heptane (8), readily obtained by
methylenation of 6. As will be shown below, this approach
proved successful, and therefore, a synthesis of the next
higher analogue via a homologization of 6, followed by the
q Polyspiranes, Part 28. For Part 27, see Ref. 1.
same set of reactions as used for the synthesis of 2 [6–7–9–
Keywords: Helicenes; Spiro compounds; Keteniminium salts;
11(12)] seemed feasible (Scheme 2). Stereochemically, a
Cyclobutanones; Resolution.
large preference for a formation of (5R p,6R p)-11 with the
desired helical carbon framework could be expected, and
*
Corresponding author. Tel.: þ49-551-395631; fax: þ49-551-395644;
e-mail address: lfitjer@gwdg.de
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.11.081

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L. Fitjer et al. / Tetrahedron 60 (2004) 1205–1213
2. Results
Due to the pioneering work of Ghosez and co-workers5 it is
well known that keteniminium salts 13 may conveniently
be generated by treatment of carboxylic acid amides 15
with trifluromethanesulfonic acid anhydride followed by
2,4,6-collidine, and that these salts effectively add to olefins
yielding cyclobutylidene ammonium salts 14, and, after
hydrolysis, cyclobutanones 16 (Scheme 3). However,
keteniminium salts derived from cycloalkanecarboxylic
acid amides, representing a promising source for a variety
of spiranes, have never been explored.
With this knowledge in mind, we reacted cyclobutane-
carboxylic acid chloride (17) with piperidine and treated a
solution of the resulting amide 188 in dichloromethane first
with trifluoromethanesulfonic acid anhydride, and then, in
the presence of an excess of 8, with 2,4,6-collidine. After
24 h of reflux and subsequent hydrolysis, the desired
trispiroketone 2 was isolated in 50% yield (Scheme 4).
This indicates that trimethylenketeniminium salts may offer
distinct advantages over trimethylenketene itself,9 at least in
[2þ2] cycloadditions with electron-poor olefins.
Having established a short and effective route to 2, we next
investigated its reduction with (2)-DIP-Cl. No reduction of
an a-tertiary cyclobutanone had been described before, but
spiro[4.4]nonan-1-one as an a-tertiary cyclopentanone had
been transformed to the corresponding S-configurated
alcohol within 12 h in 65% yield and 95% ee.6 In any
case, we were pleased to learn that (2)-DIP-Cl and 2
reacted almost instantaneously, and that the 1:1-mixture of
alcohols formed consisted of (5S,10S)-4 and a diastereo-
isomer, tentatively assigned as (5R,10S)-19 (Scheme 4).
Both alcohols were known from the reduction of 2 with
Scheme 2.
concerning its resolution, alternative possibilities to an
enzymatic reduction were available. Of these, a use of
(2)-diisopinocampheylchloroborane [(2)-DIP-Cl]6 as
S-selective reducing agent for a-tertiary cycloalkanones
and/or a use of (S)-(2)-2-hydrazino-2-oxo-N-(1-phenyl-
ethyl)-acetamide7 as ketone resolving reagent seemed most
promising. Research following these lines not only
shortened the synthesis of (M)-trispiro[3.0.0.3.2.2]tridecane
(5), but also enabled the first synthesis of (P)- and
(M)-tetraspiro[3.0.0.0.3.2.2.2]hexadecane 24 as next higher
analogues.
Scheme 3.
Scheme 4.

L. Fitjer et al. / Tetrahedron 60 (2004) 1205–1213
1207
bakers’ yeast,1 and both were enantiomerically pure (.99%
ee) according to capillary gas chromatography on a
g-cyclodextrin as chiral phase. As (5S,10S)-4 had already
been transformed to (M)-5 by oxidation with pyridinium
chlorochromate followed by Wolff–Kishner reduction1
(Scheme 1), no efforts were made to repeat these reactions
with (5R,10S)-19.
For the synthesis of tetraspiro[3.0.0.0.3.2.2.2]hexadecane
(24), we first explored two routes to ketone 7 as precursor of
olefin 9, itself needed for a cycloaddition to the keteni-
minium salt derived from 18: (a) an addition of 1-lithio-
cyclopropylphenyl sulphide to 6, and a subsequent
rearrangement with tetrafluoroboric acid [6–20–7(22)],10
and (b) a cyclopropylidenation of 6, and a subsequent
epoxidation and rearrangement with boron trifluoride
etherate [6–21–7(22)] (Scheme 5). In both cases, the
C3–C4 ring enlargement leading to 7 was accompanied by a
C4 –C5 ring enlargement followed by a C4 –C3 ring
contraction and another C4–C5 ring enlargement leading
to 22, yielding the two ketones in a ratio of 72:28 from 20,
and 80:20 from 21. Unfortunately, the two ketones were
inseparable on a preparative scale, and the same was true for
the two olefins 9 and 23 derived therefrom. However, no
complications were met during the next step.
Scheme 6.
ducts derived from 23 was achieved by column chroma-
tography, and Wolff–Kishner reduction then yielded
tetraspiro[3.0.0.0.3.2.2.2]hexadecane [rac-24] (Scheme 6).
As the number and multiplicities of the resonance lines in
the 13C NMR spectrum [15.74 (t), 26.43 (t), 26.51 (t), 30.70
(t), 31.31 (t), 32.37 (t), 49.21 (s), 52.34 (s)] could account
for both rac-24 (symmetry C2) and its achiral counterpart
derived from (5R p,6S p)-12 (symmetry Cs), a capillary gas
chromatographic analysis on a g-cyclodextrin as chiral
phase proved necessary. This analysis revealed that the
hydrocarbon in question was a racemic mixture of two
enantiomers, and hence rac-24.
As was to be expected, the cycloaddition of the ketenimi-
nium salt derived from 18 to 1-methylene-dispiro[3.0.3.2]-
decane (9) proceeded regio- and stereoselectively and
delivered the desired tetraspiroketone (5R p,6R p)-11 as
major product of a 92:8-mixture with (5R p,6S p)-12, in 30%
combined yield. Separation from (5R p,6S p)-12 and pro-
For the resolution of (5R p,6R p)-11, we first tried an
enantioselective reduction with (2)-DIP-Cl6 as already
applied to the resolution of (5R p)-2 (Scheme 4). Unfortu-
nately, this time the two diastereoisomeric alcohols formed
were not separable on a preparative scale, neither by column
nor by gas chromatography. We therefore investigated the
usefulness of (S)-(2)-2-hydrazino-2-oxo-N-(1-phenyl-
ethyl)-acetamide7 as ketone resolving reagent (Scheme 7).
Catalyzed by p-toluenesulfonic acid, this reagent yielded a
1:1-mixture of two diastereoisomeric hydrazones, which
could be separated by column chromatography on silica gel
in pentane/ether (1:1), albeit partial hydrolysis was
observed. As a consequence, both the first (Rf¼0.33) and
the second eluted hydrazone (Rf¼0.28) contained ketone
(Rf¼0.77): the former more (10%) than the latter (3%) (1H
NMR). As the second eluted hydrazone could only contain
ketone originating from itself, we hoped that its hydrolysis
would deliver an enantiomerically pure ketone. However,
due to an incomplete separation from the first eluted
hydrazone, the optical purity was slightly diminished (94%
ee, [a]2D0¼246.38, c¼1.09, acetone), as evidenced by
capillary gas chromatography of the corresponding hydro-
carbon obtained by Wolff–Kishner reduction (94% ee,
[a]2D0¼224.28, c¼1.17, CHCl3). The identity of the ketone
as (5S,6S)-11, the hydrocarbon as (M)-24 and the hydrazone
as (10S,5S,6S)-25 followed from the fact, that in the CD
Scheme 5.

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L. Fitjer et al. / Tetrahedron 60 (2004) 1205–1213
and trispiro[3.0.0.3.2.2]tridecane (5).1 The present contri-
bution describes the synthesis of tetraspiro[3.0.0.0.3.2.2.2]-
hexadecane (24) and thereby allows a first comparison of
two pairs of helical primary structures of spiroannelated
three and four-membered rings (Scheme 8).
As pointed out elsewhere,1 helical hydrocarbons of
spiroannelated three- and four-membered rings form regular
helices, but their identity periods differ: that of the former
comprises eight three-membered rings within two helical
turns, that of the latter five four-membered rings within one
helical turn. This means, that in 24 a helical turn is just
complete, while in 28 it goes about 508 beyond (Fig. 1). A
second difference concerns the fact, that helices of three-
membered rings form rigid structures, while those of four-
membered rings may adopt different conformations. Thus,
within 3 kcal above the global minimum, our conforma-
tional search routine HUNTER12 in connection with MM313
located seven additional minima for 5, and three for 24.
Only the global minimum conformations represent regular
helices (Fig. 1), while all other conformations contain
non-regular sections. We therefore believe, that the large
difference in the specific rotations of (M)-27 ([a]2D0¼
2192.78, c¼1.2, CHCl3)2 and (M)-5 ([a]D20¼263.38,
c¼1.09, CHCl3)1 is due to the conformational mobility of
Scheme 7.
spectrum of the ketone ([u]302¼þ1967, CH3OH) a net
positive Cotton effect11 was observed.
For the synthesis of (P)-24, we used the same set of
reactions as for (M)-24. This time, the starting hydrazone
(10S,5R,6R)-26 was contaminated with 10%0 ketone origi-
nating from both (10S,5S,6S)-25 and (1 S,5R,6R)-26.
Consequently, its hydrolysis to (5R,6R)-11 delivered a
product of lower optical purity (92% ee, [a]2D0¼þ45.98,
c¼1.09, acetone), which translated to (P)-24 (92% ee,
[a]2D0¼þ23.98, c¼1.18, CHCl3) through Wolff–Kishner
reduction.
3. Discussion
Until now, only three examples for hydrocarbons with a
helical primary structure were known: trispiro[2.0.0.2.1.1]-
nonane (27),2a,b tetraspiro[2.0.0.0.2.1.1.1]undecane (28)2b
Figure 1. Global minimum structures of (M)-27, (M)-28, (M)-5 and (M)-24:
views along the helical axis. The structure of (M)-28 was generated using
the crystal structure data of rac-28.2b The remaining structures were
determined by molecular mechanics using PC-model14 [(M)-27] and the
conformational search routine HUNTER12 in connection with MM313
[(M)-5, (M)-24], respectively. All carbon–hydrogen bonds within the inner
spheres have been omitted for clarity. For (M)-5 and (M)-24, the heats of
formation (in kcal/mol) of all minimum conformations up to 3 kcal/mol
above the global minimum (in bold) are given. For views of their structures,
see Ref. 1.
Scheme 8.

L. Fitjer et al. / Tetrahedron 60 (2004) 1205–1213
1209
(M)-5, not present in (M)-27, and to the fact, that (M)-5
describes a distinctly shorter section of a helix than (M)-27.
4.1.1. 1-Methylene-spiro[3.3]heptane (8). To a suspension
of methyltriphenylphosphonium bromide (46.4 g, 130 mmol)
in anhydrous ether (250 ml) was added under argon with
stirring potassium-t-butoxide (14.6 g, 130 mmol) and the
mixture heated to reflux. After 15 min, most of the ether was
distilled off (bath temperature up to 60 8C), 6 (12.1 g,
110 mmol) was added dropwise, and after additional 30 min
at 60 8C the reaction was complete according to GC [column
A, 120 8C; retention times (min): 1.03 (8), 4.63 (6)]. The
mixture was diluted with pentane (100 ml) and hydrolyzed
with water (11 ml). The organic layer was decanted, the
residue was extracted with pentane (2£70 ml), and the
combined organic phases were washed with water
(3£70 ml) and dried (MgSO4). The solvent was distilled
off through a 20 cm vigreux column (bath temperature up to
130 8C) and the remaining material fractionated to yield
10.7 g (90%) of 8 as colorless liquid, bp 116–118 8C (purity
97% GC). IR (neat): 1670 cm21 (CvC); 1H NMR
(600 MHz, CDCl3, CHCl3 int): d¼1.73–1.87 (m, 2H),
1.95 (t, J¼8 Hz, 2H), 1.95–2.03 (m, 2H), 2.10–2.17 (m,
2H), 2.51 (tt, J¼8, 2 Hz, 2H), 4.67 (t, J¼2 Hz, 1H), 4.88 (t,
J¼2 Hz, 1H); 13C NMR (150.8 MHz, CDCl3, CDCl3 int):
d¼16.15 (t), 27.30 (t), 32.01 (t), 34.41 (t), 50.80 (s), 101.40
(t), 159.10 (s); MS (EI): m/e¼108 (3, Mþ), 79 (100); C8H12
requires C, 88.82; H, 11.18. Found: C, 88.96; H, 10.98.
As mentioned above, the number of conformations within
3 kcal/mol above the global minimum is reduced from eight
in (M)-5 to four in (M)-24. This indicates that the
conformational mobility of a helix of four-membered rings
decreases, as the length of the helix increases. It was
therefore tempting to speculate,1 that the large difference
between the specific rotations of (M)-27 and (M)-5 for
(M)-28 ([a]2D0¼2381.28, c¼1.2, CHCl3)2 and (M)-24
([a]2D0¼224.28, c¼1.17, CHCl3) could diminish. However,
the contrary is true: while the specific rotation of (M)-27
doubles, the specific rotation of (M)-5 is cut in three. The
reason for this unexpected result is not yet clear, but ab
initio calculations on a sufficiently large set of potentially
low-lying conformers with subsequent calculation of
Boltzmann-averaged CD or ORD spectra should help to
clarify the matter.15
4. Experimental
4.1. General
IR-spectra were obtained with a Perkin–Elmer 298
spectrophotometer. 1H and 13C NMR spectra were recorded
on a Bruker AMX 300 or a Varian VXR 500 or VXR 600
spectrometer. For standards other than TMS the following
chemical shifts were used: dH (C2HDCl4)¼5.99, dH
(CHCl3)¼7.24, dH (C6D5H)¼7.15, dC (C2D2Cl4)¼73.71,
dC (CDCl3)¼77.00, dC (C6D6)¼128.00. 13C multiplicities
were studied by APT and/or DEPT measurements. Mass
spectra were obtained with a Varian CH 5 (CI) or a
Finnegan MAT 95 spectrometer (EI und HR-EI) operated at
70 eV. Optical rotations were measured on a Perkin–Elmer
241 digital polarimeter in a 1 dm cell. UV and CD spectra
were obtained with a JASCO J-710/720 spektropolarimeter.
Preparative GC was carried out on a Carlo-Erba GC 6000
Vega series 2 instrument employing a thermal conductivity
detector, and hydrogen as carrier gas. Analytical GC was
performed on a Carlo-Erba GC 6000 Vega series 2
instrument employing a split/splitless injector, a FID 40
detector, and hydrogen (0.6 bar) as carrier00 gas. The
following columns were used: (A): 3 m£1/4 all-glass
system, 15% FFAP on Chromosorb W AW/DMCS 60/80
mesh; (B) 25 m£0.25 mm i.d. deactivated fused-silica
capillary column coated with oktakis-(2,6-di-O-pentyl-3-
O-butyryl)-g-cyclodextrin (Lipodexw E); (C) 25 m£
0.25 mm i.d. deactivated fused-silica capillary column
coated with oktakis-(2,3-di-O-pentyl-6-O-methyl)-g-cyclo-
dextrin (Lipodexw G). Product ratios were not corrected for
relative response. Rf values are quoted for Macherey &
Nagel Polygram SIL G/UV254 plates. Colorless substances
were detected by oxidation with 3.5% alcoholic 12-molyb-
dophosphoric acid and subsequent warming. Melting points
were observed on a Reichert microhotstage and are not
corrected. Microanalytical determinations were done at the
Microanalytical Laboratory of the Institute of Organic
4.1.2. 1-(Cyclobutylcarbonyl)-piperidine (18). To a solu-
tion of piperidine (34.0 g, 0.40 mol) in dichloromethane
(150 ml) was added under argon with stirring cyclobutyryl
chloride (23.6 g, 0.20 mol) such that, the internal tempera-
ture did not exceed 25 8C. After the addition was complete,
the mixture was stirred for 30 min at room temperature and
then washed with water (80 ml), 2 N HCl (80 ml), saturated
sodium bicarbonate (80 ml) and dried (MgSO4). The solvent
was distilled off and the residue fractionated to yield 32.6 g
(97%) of 18 as colorless liquid, bp 147 8C/16 Torr (purity
99% GC) (lit.8 bp 89–91 8C/1 Torr). IR (neat): 1640 cm21
(CvO); 1H NMR (600 MHz, symm C2D2Cl4, C2DHCl4 int,
120 8C): d¼1.47–1.54 (m, 4H), 1.58–1.65 (m, 2H), 1.83–
1.98 (m, 2H), 2.09–2.17 (m, 2H), 2.28–2.37 (m, 2H), 3.18–
3.26 (m, 1H), 3.37 (br s, 4H); 13C NMR (150.8 MHz, symm
C2D2Cl4, C2D2Cl4 int, 120 8C): d¼17.70 (t), 24.28 (t), 24.92
(t), 25.74 (t), 37.11 (d), 44.10 (br t), 172.38 (s); MS (EI):
m/e¼167 (42, Mþ), 84 (100); C10H17NO requires C, 71.81;
H, 10.24; N, 8.55. Found: C, 71.75; H, 10.18; N, 8.60.
4.1.3. (5R p)-Trispiro[3.0.0.3.2.2]tridecan-10-one (2). To
a solution of 18 (1.68 g, 10 mmol) in 1,2-dichloroethane
(10 ml) was added at 215 8C under argon with stirring
trifluoromethanesulfonic acid anhydride (3.38 g, 12 mmol),
and, within 20 min, a solution of 2,4,6-collidine (1.46 g,
12 mmol) and 8 (2.16 g, 20 mmol). The mixture was heated
for 24 h to reflux and then concentrated on a rotary
evaporator (bath temperature 35 8C/15 Torr). The residual
black oil was extracted with anhydrous ether (3£20 ml), and
the remaining material hydrolyzed in a two-phase system of
dichloromethane (15 ml) and water (15 ml). After 2 h of
reflux, GC analysis [column A, 230 8C; retention times
(min): 2.58 (2), 4.49 (18)] indicated the presence of a 76:24-
mixture of 2 and 18. The organic phase was washed with
2 N H2SO4 (10 ml), dried (MgSO4/K2CO3) and concen-
¨
Chemistry, Gottingen. (S)-(2)-1-phenyl-ethylamine, 98%,
used for the preparation of (S)-(2)-2-hydrazino-2-oxo-N-
(1-phenyl-ethyl)-acetamide [(S)-(2)-9],7 was purchased
from Aldrich Chemical Company, Inc.
trated on
35 8C/15 Torr), and the residual brown oil (2.50 g)
a
rotary evaporator (bath temperature

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L. Fitjer et al. / Tetrahedron 60 (2004) 1205–1213
chromatographed on silica gel (0.05–0.20 mm) in pentane/
ether [8:2, Rf¼0.62 (2); column 75£5 cm] yielding 950 mg
(50%) of 2 as colorless liquid (purity 96% GC). The 1H and
13C NMR data reported1 are data from spectra of a
2:1-mixture with 3 in C6D6. The data for pure 2 in CDCl3
(t), 31.41 (t), 31.54 (s), 51.08 (s), 80.73 (s), 125.92 (d),
128.30 (d), 129.94 (d), 136.79 (s); MS (EI): m/e¼260 (85,
Mþ), 192 (100); C16H20SO requires C, 73.80; H, 7.74; S,
12.31. Found: C, 73.85; H, 7.87.
1
are as follows: H NMR (500 MHz, CDCl3, CHCl3 int):
4.1.6. 1-Cyclopropylidenspiro[3.3]heptane (21). To a
suspension of potassium-t-butoxide (44.8 g, 0.40 mol) in
dry benzene (700 ml) was added under argon with stirring
d¼1.65–1.82 (m, 5H), 1.82–1.92 (m, 1H), 1.95–2.15 (m,
7H), 2.15–2.30 (m, 4H), 2.60 (d, J¼17 Hz, 1H), 2.92 (d,
J¼17 Hz, 1H); 13C NMR (125.7 MHz, CDCl3, CDCl3 int):
d¼16.29 (t), 16.77 (t), 24.87 (t), 27.23 (t), 27.92 (t), 30.91
(t), 32.01 (t), 32.73 (t), 43.77 (s), 48.85 (s), 49.57 (t), 67.23
(s), 213.22 (s).
cyclopropyltriphenylphosphonium
bromide
(153 g,
0.40 mmol) and the mixture heated for 2 h to 55 8C. 6
(22.0 g, 0.20 mol) was added, and after additional 2 h at
70 8C the reaction was complete according to GC [column
A, 140 8C; retention times (min): 1.97 (21), 2.37 (6)]. The
mixture was diluted with pentane (700 ml) and hydrolyzed
with water (30 ml). The liquid phase was decanted and the
residue extracted with pentane (2£100 ml). The combined
organic phases were concentrated through a 40 cm vigreux
column (bath temperature up to 130 8C), and the residue was
diluted with pentane (600 ml), causing a heavy precipitate.
The mixture was filtered and the residue washed with
pentane (2£100 ml). The combined filtrates were concen-
trated through a 40 cm vigreux column (bath temperature up
to 135 8C) and the residue was fractionated through a
microdistillation apparatus to yield 23.8 g (89%) of 21 as
colorless liquid, bp 67–68 8C/15 Torr (purity 97% GC). IR
4.1.4. (5S,10S)-(1)-Trispiro[3.0.0.3.2.2]tridecan-10-ol
[(5S,10S)-4] and (5R,10S)-(2)-trispiro[3.0.0.3.2.2]tri-
decan-10-ol [(5R,10S)-19]. To (2)-diisopinocampheyl-
chloroborane [(2)-DIP-Cl] (642 mg, 2.00 mmol) was
added under argon with stirring (R p)-2 (380 mg,
2.00 mmol) via a syringe. A slightly exothermic reaction
was observed, and, within a few minutes, a clear solution
had formed. After 45 min at room temperature, the solution
was diluted with ether (4 ml), and diethanolamine (210 mg,
2.0 mmol) was added, causing a heavy precipitate. After 1 h
the mixture was filtrated and the residue washed with
pentane (2£4 ml). The combined organic phases were
washed with saturated sodium carbonate (4 ml) and water
(4 ml), and dried (MgSO4). The solvents were evaporated
and the residue chromatographed on silica gel (0.05–
0.20 mm) in pentane/ether[7:3; Rf¼0.32 (4/19); column
60£4.5 cm] to give 356 mg (93%) of a 1:1-mixture of 4 and
19. According to capillary gas chromatography on a chiral
phase [column B, 120 8C, retention times (min): 24.68 (4),
28.86 (19)] both alcohols were enantiomerically pure
(.99% ee). Analytically pure samples were obtained by
preparative GC [column A, 210 8C; retention times (min):
1
(neat): 1788 cm21 (CvC); H NMR (600 MHz, CDCl3,
CHCl3 int): d¼0.90–0.95 (m, 2H), 1.09–1.14 (m, 2H),
1.76–1.91 (m, 2H), 1.95–2.02 (m, 2H), 2.03 (t, J¼8 Hz,
2H), 2.20–2.27 (m, 2H), 2.58 (ttt, J¼8, 2.5, 2.5 Hz, 2H);
13C NMR (150.8 MHz, CDCl3, CDCl3 int): d¼0.04 (t),
1.04 (t), 16.51 (t), 26.38 (t), 32.46 (t), 34.03 (t), 50.83 (s),
107.99 (s), 136.37 (s); MS (EI): m/e¼134 (5, Mþ), 91 (100);
C10H14 requires C, 89.49; H, 10.51. Found: C, 89.51; H,
10.53.
1
9.75 (4), 10.65 (19)]. Their H NMR data were identical
with those of racemic samples.1
4.1.7. Dispiro[3.0.3.2]decan-1-one (7) and dispiro-
[2.0.3.3]decan-5-one (22). A. From 20. To a stirred solution
of 20 (26.0 g, 0.10 mol) in ether (300 ml) was added at
5–7 8C within 30 min 50% aqueous tetrafluoroboric acid
(60 ml). The mixture was allowed to warm to room
temperature and the reaction progress was monitored by
GC [column A, 245 8C; retention time (min): 18.8 (20)].
After 6 h, more tetrafluoroboric acid (10 ml) was added, and
after 22 h the reaction was complete. Sodium bicarbonate
(50 g, 0.60 mol) was added in portions, and the organic
phase was separated, washed with 5% aqueous potassium
hydroxide (2£150 ml), water (2£150 ml) and dried
(MgSO4). The solvent was distilled off and the residue
fractionated to yield 7.8 g (52%) of a 72:28-mixture of 7 and
22 as colorless liquid, bp 78–80 8C/13 Torr. Analytically
pure samples were obtained by preparative GC [3 m£1/400
all-glass system, 15% FFAP on Chromosorb W AW/DMCS
60/80 mesh, 180 8C; retention times (min): 3.11 (7), 3.44
(22)]. 7: IR (neat): 1770 cm21 (CvO); 1H NMR (600 MHz,
CDCl3, CHCl3 int): d¼1.65–1.74 (m, 1H), 1.74–1.90 (m,
6H), 1.90–1.98 (m, 1H), 1.99–2.06 (m, 1H), 2.13–2.23 (m,
3H), 2.83 (mc, 2H); 13C NMR (150.8 MHz, CDCl3, CDCl3
int): d¼16.05 (t), 19.82 (t), 25.23 (t), 30.87 (t), 31.04 (t),
31.16 (t), 43.28 (t), 48.23 (s), 70.80 (s), 213.42 (s); MS (EI):
m/e¼150 (17, Mþ), 79 (100); C10H14O requires C, 79.96; H,
9.39. Found: C, 80.10; H, 9.46. 22: IR (neat): 1765 cm21
(CvO); 1H NMR (600 MHz, CDCl3, CHCl3 int): d¼0.31–
0.37 (m, 1H), 0.43–0.56 (m, 3H), 1.52–1.60 (m, 1H),
4.1.5. 1-(1-Phenylsulfanyl-cyclopropyl)-spiro[3.3]hep-
tan-1-ol (20). To a stirred solution of cyclopropyl phenyl
sulphide (21.6 g, 144 mmol) in anhydrous tetrahydrofuran
(300 ml) under argon at 0 8C was added within 45 min a
1.60 M solution of n-butyllithium in hexane (90 ml,
144 mmol). After 1.5 h at 0 8C, a solution of 6 (13.2 g,
120 mmol) in tetrahydrofuran (40 ml) was added within
30 min and the temperature maintained for additional 1.5 h
at 0 8C. The mixture was hydrolyzed with saturated
ammonium chloride (15 ml), the liquid phase was decanted,
and the residue was extracted with ether (3£50 ml). The
organic phases were concentrated on a rotary evaporator
(bath temperature 50 8C/15 Torr), and the residual oil (36 g)
was chromatographed on silica gel (0.05–0.20 mm) first
using pentane (column 70£3 cm) to yield 5.0 g of unreacted
cyclopropyl phenyl sulphide, and then ether to yield 29.0 g
(93%) of 20 as slightly yellowish oil. IR (neat): 3600–
1
3300 cm21 (OHass); H NMR (600 MHz, symm C2D2Cl4,
C2DHCl4 int, 120 8C): d¼0.85–0.90 (m, 1H), 1.04–1.09
(m, 1H), 1.13–1.18 (m, 2H), 1.70–1.95 (m, 7H), 2.07–2.14
(m, 1H), 2.26 (br s, 1H), 2.45 (ddd, J¼10, 10, 10 Hz, 1H),
2.54 (ddd, J¼10, 10, 10 Hz, 1H), 7.21 (tt, J¼8, 1 Hz, 1H),
7.30 (dd, J¼8, 8 Hz, 2H), 7.56 (dd, J¼8, 1 Hz, 2H); 13C
NMR (150.8 MHz, symm C2D2Cl4, C2D2Cl4 int, 120 8C):
d¼10.79 (t), 14.67 (t), 14.88 (t), 27.16 (t), 29.87 (t), 29.90

L. Fitjer et al. / Tetrahedron 60 (2004) 1205–1213
1211
1.64–1.84 (m, 6H), 2.10–2.16 (m, 1H), 2.61 (mc, 1H), 2.85
(mc, 1H); 13C NMR (150.8 MHz, CDCl3, CDCl3 int):
d¼8.55 (t), 9.14 (t), 20.76 (t), 22.51 (t), 26.98 (s), 35.10 (t),
35.97 (t), 42.59 (t), 72.72 (s), 215.52 (s); MS (EI): m/e¼150
(6, Mþ), 79 (100); C10H14O requires C, 79.96; H, 9.39.
Found: C, 80.14; H, 9.55.
NMR (600 MHz, CDCl3, CHCl3 int): d¼0.27–0.34 (m,
2H), 0.40–0.48 (m, 1H), 0.48–0.56 (m, 1H), 1.52–1.60 (m,
1H), 1.62–1.82 (m, 8H), 1.87–1.94 (m, 1H), 2.29 (mc, 1H),
2.48 (mc, 1H), 4.67 (t, J¼2.5 Hz, 1H), 4.70 (t, J¼2.0 Hz,
1H); 13C NMR (150.8 MHz, CDCl3, CDCl3 int): d¼8.29 (t),
10.21 (t), 21.55 (t), 27.17 (t), 28.39 (t), 28.46 (s), 34.68 (t),
39.70 (t), 57.16 (s), 104.42 (t), 156.36 (s); MS (EI):
m/e¼148 (1, Mþ), 120 (100); C11H16 requires C, 89.12; H,
10.88. Found: C, 89.06; H, 10.86.
B. From 21. To a vigorously stirred solution of 21 (26.8 g,
200 mol) in dichloromethane (350 ml) was added a 0.7 M
aqueous solution of sodium bicarbonate (500 ml), and,
within 2.5 h at 5 8C, a solution of 3-chloro-peroxybenzoic
acid (54.3 g, 70% w/w, 220 mol) in dichloromethane
(500 ml). After 1 h, the reaction was complete according
to GC [column A, 160 8C; retention times (min): 1.45 (21),
3.00 (epoxide), 4.51 (7), 5.08 (22)]. The organic layer was
washed with 1 N NaOH (200 ml), dried (K2CO3/MgSO4),
and concentrated to approximately 500 ml by distillation
over a 40 cm vigreux column. Solid potassium carbonate
(1.0 g) was added to the remaining solution, until it was
cooled to 5 8C and borontrifluoride etherate (300 mg,
2.1 mmol) was added drop by drop, causing an exothermic
reaction, which with the last drops subsided. After the
addition was complete, the mixture was stirred for 30 min at
room temperature, until it was washed with 1 N NaOH
(50 ml), water (150 ml), and dried (K2CO3/MgSO4). The
solvent was distilled off over a 40 cm vigreux column and
the residue fractionated to yield 25.9 g (86%) of a 80:20-
mixture of 7 and 22 as colorless liquid, bp 85–88 8C/13 Torr
(purity 97% GC). Analytically pure samples were obtained
by preparative GC. Their NMR data were identical with
those of authentic samples.
4.1.9. (5R p,6R p)-Tetraspiro[3.0.0.0.3.2.2.2]hexadecan-
11-one [(5R p,6R p)-11] and (5R p,6S p)-tetraspiro-
[3.0.0.0.3.2.2.2]hexadecan-11-one [(5R p,6S p)-12]. To a
solution of 18 (8.40 g, 50 mmol) in dichloromethane
(50 ml) was added at 215 8C under argon with stirring
trifluoromethanesulfonic acid anhydride (16.9 g, 60 mmol),
and, within 20 min, a solution of 2,4,6-collidine (7.26 g,
60 mmol) in a 78:22-mixture of 9 and 23 (14.8 g,
100 mmol). The mixture was heated for 44 to reflux and
then concentrated on a rotary evaporator (bath temperature
35 8C/15 Torr). The residual black oil was extracted with
anhydrous ether (4£70 ml), and the remaining material
hydrolyzed in a two-phase system of dichloromethane
(70 ml) and water (70 ml). After 2 h of reflux, GC analysis
[column A, 230 8C; retention times (min): 4.48 (18), 5.76
(11/12)] indicated the presence of a 60:40-mixture of 11/12
and 18. The organic phase was washed with 2 N H2SO4
(60 ml), dried (MgSO4/K2CO3) and concentrated on a rotary
evaporator (bath temperature 35 8C/15 Torr). The residual
brown oil (21.5 g) was extracted with pentane/ether (1:1;
2£100 ml), the combined extracts were concentrated on a
rotary evaporator (bath temperature 35 8C/15 Torr), and the
remaining oil (10.7 g) was chromatographed first on silica
gel (0.05–0.20 mm) in pentane/ether [95:5, column
70£5 cm, Rf¼0.36–0.39 (11/12)] yielding 3.43 g (30%) of
a 92:8-mixture of 11 and 12 (1H NMR), and then on silica
gel (0.040–0.063 mm) in pentane/ether [97:3, column
70£5 cm, Rf¼0.21 (11), 0.19 (12)] yielding 2.42 g (21%)
of pure 11 and 0.50 g (4%) of a 2:1-mixture of 11 and 12 (1H
NMR) as colorless oils. 12 could not be obtained pure. 12:
1H NMR (600 MHz, CDCl3, CHCl3 int): only the protons
neighboring the carbonyl group could be assigned: d¼2.60
(J¼17 Hz, 1H), 2.88 (J¼17 Hz, 1H); 13C NMR
(150.8 MHz, CDCl3, CDCl3 int): all resonances could be
assigned: d¼15.33 (t), 16.28 (t), 25.46 (t), 27.14 (t), 27.80
(t), 28.27 (t), 28.96 (t), 31.21 (t), 31.21 (t), 31.94 (t), 46.60
(s), 47.42 (s), 50.64 (t), 54.28 (s), 66.13 (s) 213.17 (s). 11:
1H NMR (600 MHz, CDCl3, CHCl3 int): d¼1.55–1.90
(m, 10H), 1.95–2.25 (m, 9H), 2.36–2.43 (m, 1H), 2.71
(d, J¼17 Hz, 1H), 3.31 (d, J¼17 Hz, 1H); 13C NMR
(150.8 MHz, CDCl3, CDCl3 int): d¼15.46 (t), 16.56 (t),
26.26 (t), 26.60 (t), 26.90 (t), 26.97 (t), 27.09 (t), 30.48 (t),
31.34 (t), 32.08 (t), 43.81 (s), 48.91 (s), 50.61 (t), 52.57 (s),
67.76 (s), 213.17 (s); MS (EI): m/e¼230 (,1, Mþ), 120
(100); C16H22O requires C, 83.43; H, 9.63. Found: C, 83.55;
H, 9.67.
4.1.8. 1-Methylene-dispiro[3.0.3.2]decane (9) and
5-methylene-dispiro[2.0.3.3]decane (23). To a suspension
of methyltriphenylphosphonium bromide (78.5 g, 220 mmol)
in anhydrous ether (450 ml) was added under argon with
stirring potassium-t-butoxide (24.6 g, 220 mmol) and the
mixture heated to reflux. After 1 h, a 80:20-mixture of 7 and
22 (25.5 g, 170 mmol) was added dropwise, and after
additional 1 h of reflux the reaction was complete according
to GC [column A, 160 8C; retention times (min): 1.39 (9),
1.54 (23), 4.51 (7), 5.08 (22)]. The mixture was hydrolyzed
with saturated aqueous ammonium chloride (15 ml), the
liquid phase was decanted, the residue was extracted with
pentane (3£200 ml), and the combined organic phases were
filtrated, washed with water (3£200 ml) and dried (MgSO4).
Most of the solvents were distilled off over a 40 cm vigreux
column (bath temperature up to 70 8C), the residue was
diluted with pentane (200 ml), and, after filtration, first
concentrated by distillation over a 20 cm vigreux column
(bath temperature up to 135 8C) and then fractionated over a
microdistillation apparatus to yield 22.9 g (91%) of a 80:20-
mixture of 9 and 23 as colorless liquid, bp 95 8C/55 Torr.
Analytically pure samples were obtained by preparative GC.
9: IR (neat): 1669 cm21 (CvC); 1H NMR (600 MHz,
CDCl3, CHCl3 int): d¼1.61–1.69 (m, 1H), 1.69–1.85 (m,
7H), 1.91–1.97 (m, 1H), 2.05–2.14 (m, 3H), 2.41–2.53 (m,
2H), 4.73 (t, J¼2.5 Hz, 1H), 4.75 (t, J¼2.0 Hz, 1H); 13C
NMR (150.8 MHz, CDCl3, CDCl3 int): d¼15.48 (t), 26.42
(t), 27.92 (t), 29.28 (t), 30.35 (t), 30.36 (t), 31.37 (t), 49.02
(s), 56.02 (s), 103.29 (t), 155.55 (s); MS (EI): m/e¼148 (14,
Mþ), 79 (100); C11H16 requires C, 89.12; H, 10.88. Found:
4.1.10. rac-Tetraspiro[3.0.0.0.3.2.2.2]hexadecane [rac-24].
To a solution of hydrazine hydrate (300 mg, 6.0 mmol) and
powdered potassium hydroxide (450 mg, 8.0 mmol) in
diethylene glycol (4.0 ml) was added under argon with
stirring 11 (230 mg, 1.0 mmol). The mixture was heated for
2 h to 160 8C, until it was diluted with water (40 ml) and
1
C, 89.24; H, 10.88. 23: IR (neat): 1670 cm21 (CvC); H

1212
L. Fitjer et al. / Tetrahedron 60 (2004) 1205–1213
extracted with pentane (3£20 ml). The combined extracts
were washed with water (30 ml), dried (MgSO4), and
concentrated using a 20 cm vigreux column. Last traces of
solvent were evaporized under reduced pressure yielding
207 mg (96%) of rac-24 as colorless oil (purity 97% GC).
The enantiomers could be resolved by capillary gas
chromatography on a chiral phase [column C, 105 8C,
retention times (min): 40.32/41.49 (rac-24)]. An analytic-
ally pure sample was obtained by preparative GC [column
126.62 (d), 127.50 (d), 128.83 (d), 143.22 (s), 155.53 (s),
159.63 (s), 167.79 (s).
4.1.12. (5S,6S)-(2)-Tetraspiro[3.0.0.0.3.2.2.2]hexadecan-
11-one [(5S,6S)-11]. To a solution of (10S,5S,6S)-25
(356 mg, 0.85 mmol) in benzene (25 ml) was added 60%
H2SO4 (4.0 ml). The resulting two-phase system was
vigorously stirred at room temperature. According to TLC
[pentane/ether (1:1); Rf¼0.77 (11), 0.28 (25)], after 1 h the
hydrolysis was complete. The organic phase was decanted,
the heterogeneous residue was extracted with benzene
(10 ml), and the combined organic phases were washed with
water (10 ml) and dried (MgSO4). Evaporation of the
solvent (bath temperature 55 8C/15 Torr) yielded 190 mg
(97%) of crude (5S,6S)-11 (purity 97% GC). Preparative GC
[column A, 230 8C; retention time (min): 5.76 (11)] yielded
an analytically pure sample as colorless oil (94% ee;
[a]2D0¼246.3, c¼1.09, acetone). For the preparation of
1
A, 200 8C; retention time (min): 3.01 (rac-24)]. H NMR
(500 MHz, CDCl3, CHCl3 int): d¼1.45 (mc, 2H), 1.53–1.63
(m, 4H), 1.64–1.72 (m, 2H), 1.75–1.94 (m, 10H),
1.98–2.05 (m, 2H), 2.25 (mc, 2H), 2.35–2.44 (m, 2H);
13C NMR (125.7 MHz, CDCl3, CDCl3 int): d¼15.74 (t),
26.43 (t), 26.51 (t), 30.70 (t), 31.31 (t), 32.37 (t), 49.21 (s),
52.34 (s); MS (EI): m/e¼216 (,1, Mþ), 120 (96), 79 (100);
C16H24 requires C, 88.82; H, 11.18. Found: C, 88.71; H,
10.90.
1
(M)-24, the crude material was used. The H NMR data
4.1.11. (10S,5S,6S)-2-(N0-Tetraspiro[3.0.0.0.3.2.2.2]hexa-
dec-11-ylidene-hydrazino)-2-oxo-N-(1-phenyl-ethyl)-
acetamide [(10S,5R,6S)-25] and (10S,5R,6R)-2-(N0-tetra-
spiro[3.0.0.0.3.2.2.2]hexadec-11-ylidene-hydrazino)-2-
oxo-N-(1-phenyl-ethyl)-acetamide [(10S,5S,6R)-26]. To
a suspension of (S)-(2)-2-hydrazino-2-oxo-N-(1-phenyl-
ethyl)-acetamide7 (2.59 g, 12.5 mmol) in benzene (200 ml)
was added under argon with stirring 11 (1.15 g, 5.0 mmol)
and a 0.74 M solution of anhydrous p-toluenesulfonic acid
in benzene (10 ml, 7.4 mmol). The mixture was heated to
reflux and the reaction progress monitored by TLC in
pentane/ether [1:1; Rf¼0.77 (11), 0.33 (26), 0.28 (25)].
After 2 h more acetamide (0.52 g, 2.5 mmol) was added,
and after an additional hour the reaction was complete. The
mixture was filtrated, the residue was washed with ether
(2£50 ml), and the combined filtrates were washed with
saturated sodium carbonate (50 ml), water (100 ml), and
dried (MgSO4). The solvents were distilled off (bath
temperature 60 8C/15 Torr), and the remaining material
(2.70 g) was chromatographed on silica gel (0.05–
0.20 mm) in pentane/ether [1:1, column 100£6.5 cm;
Rf¼0.77 (11), 0.33 (26), 0.28 (25)] yielding 690 mg (33%)
of 26 as sticky oil, 290 mg (14%) of a 3:1-mixture of 25 and
26 as waxy solid, and 480 mg (23%) of 25 as amorphous
solid, mp 116–117 8C. 25: 1H NMR (300 MHz, C6D6,
C6D5H int): d¼1.08–1.18 (m, 1H), 1.13 (d, J¼7 Hz, 3H),
1.32–1.42 (m, 1H), 1.45–1.80 (m, 10H), 1.80–2.00
(m, 3H), 1.90 (d, J¼16 Hz, 1H), 2.04–2.32 (m, 5H), 2.66
(d, J¼16 Hz, 1H), 5.10 (dq, J¼9, 7 Hz, 1H), 6.96–7.14
(m, 5H), 8.10 (d, J¼9 Hz, 1H), 9.84 (s, 1H); 13C NMR
(150.8 MHz, C6D6, C6D6 int): d¼16.02 (t), 16.85 (t), 21.80
(q), 26.87 (t), 26.91 (t), 27.05 (t), 28.67 (t), 29.79 (t), 30.98
(t), 31.73 (t), 32.45 (t), 37.10 (t), 47.37 (s), 48.99 (s), 50.03
(d), 52.86 (s), 58.64 (s), 126.83 (d), 127.63 (d), 128.97 (d),
were identical with those of racemic 11. UV (CH3OH):
lmax¼292 nm, 1¼14; CD (CH3OH): [u]302¼þ1964.
4.1.13. (5R,6R)-(1)-Tetraspiro[3.0.0.0.3.2.2.2]hexa-
decan-11-one [(5R,6R)-11]. (10S,5R,6R)-26 0 (587 mg,
1.40 mmol) was hydrolyzed as described for (1 S,5S,6S)-
25 yielding 292 mg (90%) of crude (5R,6R)-11 (purity 97%
GC). Preparative GC [column A, 230 8C; retention time
(min): 5.76 (11)] yielded an analytically pure sample as
colorless oil (92% ee; [a]2D0¼þ45.98, c¼1.09, acetone).
For the preparation of (P)-24, the crude material was
used. The 1H NMR data were identical with those of
racemic 11.
4.1.14. (M)-(2)-Tetraspiro[3.0.0.0.3.2.2.2]hexadecane
[(M)-24]. To a solution of hydrazine hydrate (150 mg,
3.0 mmol) and powdered potassium hydroxide (224 mg,
4.0 mmol) in diethylene glycol (2 ml) was added under
argon with stirring (5S,6S)-11 (99 mg, 0.43 mmol) and the
mixture heated to 160 8C. After 1 h, the mixture was diluted
with water (20 ml) and extracted with pentane (3£15 ml).
The extracts were washed with water (20 ml), dried
(MgSO4) and concentrated on a rotary evaporator (bath
temperature 40 8C/15 Torr) to yield 87 mg (93%) of crude
(M)-24 (purity 97% GC). Preparative GC [column A,
200 8C; retention time (min): 3.01 (M)-24)] yielded 40 mg
of analytically pure (M)-24 as colorless oil ([a]2D0¼224.28,
c¼1.17, CHCl3). According to capillary chromatography on
a chiral phase [column C, 105 8C, retention times (min):
40.68 (M)-24, 41.13 (P)-24], the material contained 3%
1
(P)-24 (94% ee). The H NMR data were identical with
those of racemic 24.
4.1.15. (P)-(1)-Tetraspiro[3.0.0.0.3.2.2.2]hexadecane
[(P)-24]. (5R,6R)-11 (150 mg, 0.65 mmol) was reduced as
described for (5S,6S)-11 yielding 110 mg (79%) of crude
(P)-24 (purity 97% GC). Preparative GC [column A,
200 8C; retention time (min): 3.01 (M)-24)] yielded 56 mg
of analytically pure (P)-24 as colorless oil ([a]2D0¼þ23.98,
c¼1.18, CHCl3). According to capillary chromatography on
a chiral phase [column C, 105 8C, retention times (min):
39.70 (M)-24, 41.49 (P)-24], the material contained 4%
1
143.44 (s), 155.75 (s), 159.79 (s), 167.95 (s). 26: H NMR
(300 MHz, C6D6, C6D5H int): d¼1.12–1.20 (m, 1H), 1.20
(d, J¼7 Hz, 3H), 1.32–1.44 (m, 1H), 1.46–1.82 (m, 10H),
1.82–2.00 (m, 3H), 1.92 (d, J¼16 Hz, 1H), 2.00–2.30
(m, 5H), 2.69 (d, J¼16 Hz, 1H), 5.12 (dq, J¼9, 7 Hz, 1H),
6.98–7.12 (m, 3H), 7.16–7.22 (m, 2H), 8.34 (d, J¼9 Hz,
1H), 9.87 (s, 1H); 13C NMR (150.8 MHz, C6D6, C6D6 int):
d¼15.87 (t), 16.72 (t), 21.57 (q), 26.69 (t), 26.76 (t), 26.89
(t), 28.55 (t), 29.54 (t), 30.81 (t), 31.56 (t), 32.30 (t), 36.90
(t), 47.21 (s), 48.84 (s), 49.83 (d), 52.72 (s), 58.51 (s),
1
(M)-24 (92% ee). The H NMR data were identical with
those of racemic 24.

L. Fitjer et al. / Tetrahedron 60 (2004) 1205–1213
1213
7. Leonard, N. J.; Boyer, J. H. J. Org. Chem. 1950, 15, 42–45.
8. 18 has first been obtained by Hopkins et al.: Hopkins, T. R.;
Neighbors, R. P.; Phillips, L. V. J. Agric. Food Chem. 1967,
501–507. However, no spectroscopic data were given.
References and notes
1. Fitjer, L.; Gerke, R.; Weiser, J.; Bunkoczi, G.; Debreczeni,
J. E. Tetrahedron 2003, 59, 4443–4449.
2. (a) de Meijere, A.; Khlebnikov, A. F.; Kostikov, R. R.;
Kozhuskov, S. I.; Schreiner, P. R.; Wittkopp, A.; Yufit, D. S.
Angew. Chem. 1999, 111, 3682–3685, Angew. Chem., Int. Ed.
Engl. 1999, 38, 3474–3477. (b) de Meijere, A.; Khlebnikov,
A. F.; Kozhushkov, S. I.; Kostikov, R. R.; Schreiner, P. R.;
Wittkopp, A.; Rinderspacher, C.; Menzel, H.; Yufit, D. S.;
Howard, J. A. K. Chem. Eur. J. 2002, 828–842.
9. For a cycloaddition of trimethylenketene to an electron-rich
olefin, see: (a) Fitjer, L.; Quabeck, U. Angew. Chem. 1987, 99,
1054–1056, Angew. Chem., Int. Ed. Engl. 1987, 26, 1023–
¨
1025. (b) Fitjer, L.; Steeneck, C.; Gaini-Rahimi, S.; Schroder,
U.; Justus, K.; Puder, P.; Dittmer, M.; Haßler, C.; Weiser, J.;
Noltemeyer, M.; Teichert, M. J. Am. Chem. Soc. 1998, 120,
317–328.
3. For early reviews, see: (a) Krapcho, A. P. Synthesis 1974,
383–419. (b) Krapcho, A. P. Synthesis 1976, 425–444.
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