Pseudohelical and helical primary structures of 1,2-spiroannelated four- and five-membered rings: Syntheses and chiroptical properties

Article abstract of DOI:10.1021/jo7017558

(Chemical Equation Presented) The pseudohelical hydrocarbons (R)-6, (S)-7, and (R)-8 and the helical hydrocarbon (P)-9, formally derived from the helical hydrocarbon (P)-4 by stepwise replacement of each of the four-membered rings by a five-membered ring,

Full text of DOI:10.1021/jo7017558

Pseudohelical and Helical Primary Structures of 1,2-Spiroannelated
Four- and Five-Membered Rings: Syntheses and Chiroptical
Properties†
Tien Widjaja,‡ Lutz Fitjer,*,‡ Aritra Pal,§ Hans-Georg Schmidt,§ Mathias Noltemeyer,§
Christian Diedrich, and Stefan Grimme*,
Institut fu¨r Organische und Biomolekulare Chemie, UniVersita¨t Go¨ttingen, Tammannstr. 2,
37077 Go¨ttingen, Germany, Institut fu¨r Anorganische Chemie, UniVersita¨t Go¨ttingen, Tammannstr. 4,
37077 Go¨ttingen, Germany, and Organisch Chemisches Institut (Abt. Theoretische Chemie),
UniVersita¨t Mu¨nster, Corrensstr. 40, 48149 Mu¨nster, Germany
lfitjer@gwdg.de; grimmes@uni-muenster.de
ReceiVed August 10, 2007
The pseudohelical hydrocarbons (R)-6, (S)-7, and (R)-8 and the helical hydrocarbon (P)-9, formally derived
from the helical hydrocarbon (P)-4 by stepwise replacement of each of the four-membered rings by a
five-membered ring, have been prepared. Their optical rotations vary systematically, both in magnitude
and sign. Of the extremes, (P)-4 represents the usual case of a right-handed dextrorotatory helix, while
(P)-9 represents the unusual case of a right-handed levorotatory helix. To rationalize these facts, DFT
calculations of the rotatory power of (P)-helices of three-, four-, and five-membered rings have been
performed. The results show a very good agreement with the experimental data for the rigid helices of
three-membered rings and always show the correct sign and order of magnitude for the flexible helices
of four- and five-membered rings for which Boltzmann-averaged optical rotations of up to six conformers
had to be used. Within the conformers of the latter, a set of large dihedral angles for the bonds of the
inner sphere correspond to a high specific rotation, and a set of small dihedral angles correspond to a
low specific rotation. As a consequence, the Boltzmann-averaged values markedly depend on the geometry
and weight of the conformers involved.
Introduction
membered rings are known, among them trispiro[2.0.0.2.1.1]-
nonane (1),3,4 tetraspiro[2.0.0.0.2.1.1.1]undecane (2),4 and
octaspiro[2.0.0.0.0.0.0.0.2.1.1.1.1.1.1.1]nonadecane (3).5,6 In
comparison, only two examples of helices of four-membered
Helical primary structures of spiroannelated rings are un-
known in nature but have been artificially produced, both in
racemic and enantiomerically pure form.2 However, it was only
in 19993 that the first enantiomerically pure helical hydrocarbon
was reported. Today, five examples3-6 for helices of three-
(3) de Meijere, A.; Khlebnikov, A. F.; Kostikov, R. R.; Kozhushkov, 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.
(4) 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.
(5) de Meijere, A.; Khlebnikov, A. F.; Kozhushkov, S. I.; Miyazawa,
K.; Frank, D.; Schreiner, P. R.; Rinderspacher, C.; Yufit, D. S.; Howard, J.
A. K. Angew. Chem. 2004, 116, 6715-6719; Angew. Chem. Int. Ed. 2004,
43, 6553-6557.
(6) de Meijere, A.; Khlebnikov, A. F.; Kozhushkov, S. I.; Yufit, D. S.;
Chetina, O. V.; Howard, J. A. K.; Kurahashi, T.; Mijazawa, K.; Frank, D.;
Schreiner, P. R.; Rinderspacher, B. C.; Fujisawa, M.; Yamamoto, C.;
Okamoto, Y. Chem. Eur. J. 2006, 5697-5721.
† Polyspiranes, Part 29. For Part 28, see ref 1.
‡ Institut fu¨r Organische und Biomolekulare Chemie der Universita¨t Go¨ttingen.
§ Institut fu¨r Anorganische Chemie der Universita¨t Go¨ttingen.
Organisch-Chemisches Institut der Universita¨t Mu¨nster.
(1) Fitjer, L.; Kanschik, A.; Gerke, R. Tetrahedron 2004, 60, 1205-
1213.
(2) (a) Gange, D.; Magnus, P.; Bass, L.; Arnold, E. V.; Clardy, J. J. Am.
Chem. Soc. 1980, 120, 317-328. (b) Trost, B. M.; Shi, Y. J. Am. Chem.
Soc. 1991, 113, 701-703. (c) Trost, B. M.; Shi, Y. J. Am. Chem. Soc.
1993, 115, 9421-9438. (d) Hormuth, S.; Schade, W.; Reiâig, H.-U. Liebigs
Ann. 1996, 2001-2006.
10.1021/jo7017558 CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/01/2007
9264
J. Org. Chem. 2007, 72, 9264-9277

Helical and Pseudohelical Hydrocarbon Syntheses
SCHEME 1
rings have been reported: trispiro[3.0.0.3.2.2]tridecane (4)7 and
tetraspiro[3.0.0.0.3.2.2.2]hexadecane (5).1 Of the systems
cited, 1-3 are rigid and exist as single minimum structures,3-6
while 4 and 5 are flexible and adopt different conformations.7
These peculiarities translate to a high specific rotation of (M)-1
([R]D20 ) -192.7, c ) 1.2, CHCl3),3,4 which doubles in (M)-2
([R]D20 ) -381.2, c ) 1.2, CHCl3)4 and again in (M)-3 ([R]20
D
) -890.5, c ) 1.01, CHCl3),5,6 and to a low specific rotation
of (M)-4 ([R]2D0 ) -63.3, c ) 1.1, CHCl3)7 which is further
diminished in (M)-5 ([R]2D0 ) -24.2, c ) 1.2, CHCl3).1 The
latter observation is especially surprising.
anhydride and 2,4,6-collidine,8 adds to 1-methylenespiro[3.3]-
heptane (12) to yield, after hydrolysis, ketone 13 as a direct
precursor of 4. Likewise, the keteniminium salt 14 could add
to 12 with the formation of ketone 15, and both 11 and 14 could
react with 1-methylenespiro[4.4]nonane (16) to yield the ketones
17 and 18, respectively. A final deoxygenation could then lead
from 15 and 17 to 6 and 7, respectively, and after ring
enlargement, from 15, 17, and 18 to 7, 8, and 9, respectively
(Scheme 1). With a successful resolution at the stage of the
ketones given, a synthesis of optically active samples seemed
feasible.
Synthesis of (R)-6 and (S)-7. The amide 20, needed for the
generation of 14, was obtained by reaction of the acid chloride
19 with piperidine, and the olefin 16, needed for cycloaddition
reactions, was obtained by cyclobutylidenation of cyclopen-
tanone (21), followed by an epoxidation, an oxaspirohexane to
cyclopentanone rearrangement,9 and a methylenation (21-22-
23-16) (Scheme 2). This sequence compares favorably with
the known syntheses of 2310 and 16.11
For the synthesis of trispiroketone 15, we followed the same
protocol1 as for the synthesis of 13: to a solution of 20 in
dichloromethane were added trifluoromethanesulfonic acid
anhydride and a solution of 2,4,6-collidine in 12, and, after 20
h of reflux, 15 was isolated in 21% yield (Scheme 3). This
compound was easily recognized by an AB system for the
protons neighboring the carbonyl group (δ ) 2.87, ∆νAB ) 300
Hz, JAB ) 16.5 Hz, 2H). To complete the synthesis of 6 and 7,
we subjected 15 both directly and after ring enlargement with
diazomethane12 to a Wolff-Kishner reduction. In the first case,
As pointed out elsewhere,7 striking differences in the overall
geometry (identity period, diameter, and length of the helix) of
helices of three- (1, 2, 3) and four-membered rings (4, 5) exist.
However, it is only with the rigid helices 1, 2, and 3 that a
single geometry determines the observed optical rotations. With
4 and 5, the observed optical rotations are Boltzmann averages
over different conformations. Experimentally, these conforma-
tions can neither be distinguished nor be weighted.
The same problem exists with the hitherto unknown pseudohe-
lical trispiranes 6, 7, and 8 and the helical trispirane 9, formally
derived from 4 by stepwise replacement of each of the four-
membered rings by a five-membered ring. Our objective in
studying their chiroptical properties was twofold: first, to
investigate whether the systematic variation of the structure
within the series 4, 6, 7, 8, and 9 would also provoke a
systematic variation of the specific rotations, and second, to
establish an understanding of the experimental data by means
of an adequate theoretical treatment. Accordingly, we developed
syntheses for the pseudo-P-helical trispiranes (R)-6, (S)-7, and
(R)-8 as well as for the helical trispirane (P)-9, determined their
optical rotations, and finally performed quantum chemical
calculations of structures, relative energies, and specific rota-
tions. As the number of potential low-energy conformations of
the pseudohelical trispiranes 6, 7, and 8 was found to be too
high as to allow an in-depth theoretical treatment, the calcula-
tions were restricted to the helical trispiranes (P)-4, (P)-5, and
(P)-9 but included the as yet unknown tetraspirane (P)-10 as a
higher analogue of (P)-9. In fact, the collective data show that
the specific rotations systematically depend on the conformations
involved.
(8) Schmit, C.; Falmagne, J. B.; Escudero, J. Vanlierde, H.; Ghosez, L.
Org. Synth. 1990, 69, 199-205.
(9) (a) Leriverend, M. L.; Leriverend, P. C. R. Acad. Sci. Ser. C 1975,
280, 791-792. (b) Trost, B. M.; Latimer, L. H. J. Org. Chem. 1978, 43,
1031-1040. (c) Halazy, S.; Krief, A. J. Chem. Soc., Chem. Commun. 1982,
1200-1201.
(10) (a) Mayer, R.; Wenschuh, G.; To¨pelmann, W. Chem. Ber. 1958,
91, 1616-1620. (b) Krieger, H.; Ruotsalainen, H.; Montin, J. Chem. Ber.
1966, 99, 3715-1717.
(11) (a) Christol, H.; Vanel, R. Bull. Soc. Chim. France 1968, 1398-
1402. (b) Rieke, R. D.; Xiong, H. J. Org. Chem. 1992, 57, 6560-6565.
(12) Review: Gutsche, C. D. Org. React. 1954, 8, 365-429.
Results
Synthetic Aspects. For the synthesis of the trispiranes 6-9,
we thought to benefit from the fact1 that the keteniminium salt
11, as generated from the corresponding carboxylic acid amide
by successive treatment with trifluoromethanesulfonic acid
(7) Fitjer, L.; Gerke, R.; Weiser, J.; Bunkoczi, G.; Debreczeni, J. E.
Tetrahedron 2003, 59, 4443-4449.
J. Org. Chem, Vol. 72, No. 24, 2007 9265

Widjaja et al.
SCHEME 2
SCHEME 4
SCHEME 3
11S)-27. The observed S-selective reduction had already been
met with 137 and is in accord with Prelog’s rule.15 The
assignment of the minor diastereoisomer as (5R,11S)-28 is
tentative and implies an S-selective reduction too.16
At this stage we had to decide whether to oxidize the 96:4
mixture of the alcohols (5S,11S)-27 and (5R,11S)-28 and to
accept a diminished optical purity of the ketone (5S)-15 or to
eliminate the minor enantiomer from the 83:17 mixture of (5R)-
and (5S)-15 of the recovered ketones by further reductions. In
view of the fact that the alcohols could not be separated on a
preparative scale, we subjected the recovered ketones to further
reductions. Four days of a second exposure to bakers’ yeast
resulted in 28% conversion to a 58:42 mixture of (5S,11S)-27
and (5R,11S)-28, and hence in a 99:1 mixture of (5R)- and (5S)-
15 as remaining ketones, and two days of a third exposure
resulted in 12% conversion to a 5:95 mixture of (5S,11S)-27
and (5R,11S)-28, and hence in enantiopure (5R)-15 (>99% ee,
[R]2D0 ) -0.6°, c ) 1.13, acetone).
The reactions which followed were identical to those applied
for the synthesis of racemic 6 and 7: direct Wolff-Kishner
reduction delivered (R)-trispiro[3.0.0.4.2.2]tetradecane [(R)-6]
(>99% ee, [R]2D0 ) -4.5°, c ) 1.13, CHCl3), and ring
enlargement with diazomethane followed by Wolff-Kishner
reduction (S)-trispiro[3.0.0.4.3.2]pentadecane [(S)-7] (>99% ee,
[R]2D0 ) -1.1°, c ) 1.09, CHCl3).
we obtained the trispirane 6, and in the second case, with
intermediate formation of a 55:45 mixture of the ketones 24
and 25, we obtained the trispirane 7.
For the resolution of the ketone 15, we hoped for a dia- and
enantioselective reduction with bakers’ yeast.7,13 Indeed, after
22 h of exposure, 42% conversion to a 96:4 mixture of two
diastereoisomeric alcohols was observed (Scheme 4). The major
alcohol was identical with the major alcohol formed by reduction
with lithium aluminum hydride and enantiomerically pure
according to capillary gas chromatography on a chiral phase.
Unfortunately, the enantiomers of the minor alcohol could not
be resolved. For the determination of the relative and absolute
configuration of the major alcohol formed by reduction with
bakers’ yeast, we reacted the 96:4 mixture of alcohols with (-)-
(1S)-camphanic acid chloride,14 eliminated the minor ester by
fractional crystallization, and subjected the major ester (mp
109-110 °C, yield 69%, [R]2D0 ) +29.5, c 1.28, acetone) to an
X-ray structure analysis. This disclosed its identity as (1S,5′S,-
11′S)-26 and hence that of the corresponding alcohol as (5S,-
Synthesis of (R)-8 and (P)-9. Much to our disappointment,
all efforts to achieve cycloadditions between the keteniminium
salts 11 and 14, respectively, and the olefin 16 failed. Occasion-
ally extensive polymerization was observed, but usually no
reaction occurred, neither in refluxing dichloromethane nor in
refluxing 1,2-dichloroethane.8 Therefore, other routes for a
synthesis of 8 and 9 had to be explored.
(13) For bakers’ yeast reductions of cyclobutanones in bicyclic systems,
see: (a) Newton, R. F.; Paton, J.; Reynolds, D. P.; Young, S.; Roberts, S.
M. J. Chem. Soc. Chem. Commun. 1979, 908-909. (b) Dawson, M. J.;
Lawrence, G. C.; Lilley, G.; Todd, M.; Noble, D.; Green, S. M.; Roberts,
S. M.; Wallace, T. W.; Newton, R. F.; Carter, M. C.; Hallet, P.; Paten, J.;
Reynolds, D. P.; Young, S. J. Chem. Soc. Perkin Trans. 1 1983, 2119-
2125. (c) Lowe, G.; Swain, S. J. Chem. Soc. Perkin Trans. 1 1985, 391-
398. (d) Kertesz, D. J.; Kluge, A. F. J. Org. Chem. 1988, 53, 4962-4968.
(14) (a) Gerlach, H.; HelV. Chim. Acta 1968, 51, 1587-1593. (b) Gerlach,
H.; Mu¨ller, W. HelV. Chim. Acta 1972, 55, 2277-2286. (c) Gerlach, H.;
Oertle, K.; Thalmann, A. HelV. Chim. Acta 1976, 59, 755-760. (d) Gerlach,
H. HelV. Chim. Acta 1978, 61, 2773-2776. (e) Gerlach, H. HelV. Chim.
Acta 1985, 68, 1815-1821.
At first glance, the spiroanellation of a four- and a five-
membered ring, respectively, to dispiroketone 32 seemed most
(15) Prelog, V. Pure Appl. Chem. 1964, 9, 119-130.
(16) Bakers’ yeast reductions of cyclobutanones are S-selective.7,13
Exceptions exist for fluorinated derivatives.
9266 J. Org. Chem., Vol. 72, No. 24, 2007

Helical and Pseudohelical Hydrocarbon Syntheses
SCHEME 5
SCHEME 6
promising.17 In contrast to the only existing synthesis,18 this
compound was prepared as follows: 4-nitrobenzenesulfonic acid
azide19 reacted with cyclobutylidene-cyclopentane (22) to yield
the sulfonimide 29,20,21 which was hydrolyzed to spiroketone
30,20 then spiroalkylated to dispiroketone 31,22 and finally
rearranged to dispiroketone 3223 by treatment with acid. Albeit
extensive polymerization during the last step occurred, multi-
gram quantities of 32 could be prepared. A cyclobutylidenation
of ketone 23 as requisite for an alternative synthesis via an
epoxidation and oxaspirohexane to cyclopentanone rearrange-
ment9 failed (Scheme 5).
It soon turned out that enolization and/or steric hindrance
were the main problems in reactions with 32. Thus, cyclopro-
pylidenetriphenylphosphorane,24 diphenylsulfoniumcyclopro-
pylide,25 and 1-lithio-cyclopropylphenylsulfide,26 which may act
as nucleophile and base, did not react at all. Therefore, we were
pleased to learn that, catalyzed by anhydrous cerium trichlo-
ride,27 1-ethoxyvinyllithium28 added to 32 yields a single allylic
alcohol 33 as the first intermediate of an annelation sequence
first described by Baldwin et al.29 The next two steps proceeded
smoothly: cyclopropanation using a modified Simmons-Smith
procedure30 yielded the ethoxycyclopropane 35,31 and acid
catalyzed rearrangement of 35 delivered a single cyclobutanone,
recognized as 36 by an X-ray structure analysis of its 2,4-
dinitrophenylhydrazone 34 (Scheme 6). Interestingly, the forma-
tion of 34 was extremely slow and took 7 days at room
temperature to go to completeness. This indicated that other
carbonyl reactions of 36 could also be difficult to achieve.
Indeed, the Wolff-Kishner reduction using a variant of Barton
et al.32 for sterically hindered ketones required 66 h at 180 °C
for the formation of the hydrazone and 72 h at 205 °C for the
liberation of trispirane 8.
Disappointingly, all attempts of a direct ring enlargement of
36 with diazomethane failed. Therefore, a sequential ring
enlargement via a high-temperature methylenation,33 an epoxi-
dation, and a lithium iodide-induced rearrangement9 proved
necessary. This sequence led to a single cyclopentanone 38 (36-
37-39-38), and a subsequent Wolff-Kishner reduction then
yielded the desired trispirane 9 (symmetry C2), easily recognized
by the appearance of only nine resonance lines in the 13C
NMR spectrum [δ ) 19.6 (t), 23.4 (t), 24.3 (t), 32.5 (t), 35.2
(t), 35.8 (t), 40.9 (t), 55.9 (s), 56.7 (s)]. However, in view
(17) For a compilation of methods, see: (a) Krapcho, A. P. Synthesis
1974, 383-419. (b) Krapcho, A. Synthesis 1976, 425-444. (c) Krapcho,
A. Synthesis 1978, 77-126.
(18) Kakiuchi, K.; Okada, H.; Kanehisa, N.; Kai, Y.; Kurosawa, H. J.
Org. Chem. 1996, 61, 2972-2979.
(19) Horner, L.; Christmann, A. Chem. Ber. 1963, 96, 388-398.
(20) Fitjer, L.; Rissom, B.; Kanschik, A.; Egert, E. Tetrahedron 1994,
50, 10879-10892.
(21) For other ring enlargements via ∆2-triazolines, see: (a) Wohl, R.
A. J. Org. Chem. 1973, 38, 3862-3864. (b) McManus, S. P.; Ortiz, M.;
Abramovitch, R. A. J. Org. Chem. 1981, 46, 336-342. (c) Fitjer, L. Chem.
Ber. 1982, 115, 1047-1060.
(22) For spiroalkylations of cycloalkanones, see: (a) Mousseron, M.;
Jacquier, R.; Christol, H. Bull. Soc. Chim. Fr. 1957, 346-356. (b) Brugidou,
J.; Christol, H. Bull. Soc. Chim. Fr. 1968, 1141-1144.
(23) An analogous rearrangement of 30 to 23 is known: Mundy, B. P.;
Otzenberger, R. D. J. Org. Chem. 1973, 38, 2109-2110.
(24) Utimoto, K.; Tamura, M.; Sisido, K. Tetrahedron 1973, 29, 1169-
1171.
(25) (a) Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973, 95,
5298-5307. (b) Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973,
95, 5321-5334. (c) Bogdanowicz, M. J.; Trost, B. M. Org. Synth. 1974,
54, 27-32.
(26) (a) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Rigby, J. H.;
Bogdanowicz, M. J. J. Am. Chem. Soc. 1977, 99, 3080-3087. (b) Trost,
B. M.; Keeley, D. E.; Arndt, H. C.; Bogdanowicz, M. J. J. Am. Chem. Soc.
1977, 99, 3088-3100.
(30) Denis, J. M.; Girard, C.; Conia, J. M. Synthesis 1972, 549-551.
(31) For an alternative approach via addition of 1-ethoxycyclopropyl-
lithium to carbonyl compounds, see: (a) Gadwood, R. C.; Rubino, M. R.;
Nagarajan, S. C.; Michel, S. T. J.Org. Chem. 1985, 50, 3255-3260. (b)
Gadwood, R. C.; Mallik, I. M.; De Winter, A. J. J. Org. Chem. 1987, 52,
774-782.
(27) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamija,
J. J. Am. Chem. Soc. 1989, 111, 4392-4398.
(28) Scho¨llkopf, U.; Ha¨nâle, P. Liebigs Ann. Chem. 1972, 763, 208-
210.
(29) Baldwin, J. E.; Ho¨fle, G. A.; Lever, O. W., Jr. J. Am. Chem. Soc.
1974, 96, 7125-7127.
(32) Barton, D. H. R.; Ives, D. A. J.; Thomas, B. R. J. Chem. Soc.
(London) 1955, 2056.
(33) Fitjer, L.; Quabeck, U. Synth. Commun. 1985, 15, 855-864.
J. Org. Chem, Vol. 72, No. 24, 2007 9267

Widjaja et al.
SCHEME 7
SCHEME 8
led to ring opening, tri-n-butyltin hydride led to ring enlarge-
ment, and only zinc in acetic acid provided the desired ketone
46. The subsequent Wolff-Kishner reduction in the variant of
Barton et al.32 proved even more difficult than that of 36. It
required 2 days at 180 °C for the formation of the hydrazone
and 10 days at 205 °C for the liberation of trispirane 9.
In contrast to that of 43, a reductive debromination of 45
with zinc in acetic acid failed. Therefore, an alternative approach
to 47 via a â-hydroxyselenide37 was envisaged. Accordingly,
we treated 41 with 1-lithio-1-methylselenocyclobutane,38 rear-
ranged the â-hydroxyselenide 48 obtained with a large excess
of 3-chloroperbenzoic acid, and deoxygenated the resulting
ketone 47 to trispirane 8 (Scheme 8).
Clearly, the syntheses of 8 and 9 from 21 via 41 were much
more effective than those from 21 via 32. Therefore, the
necessary resolution was performed with 41. Two methods were
employed: (a) an addition of (+)-(S)-N,S-dimethyl-S-phenyl-
sulfoximine with subsequent fragmentation,39 and (b) a reduction
with (-)-diisopinocampheyl chloroborane [(-)-DIP-Cl]40 with
subsequent oxidation (Scheme 9).
In the first case, two diastereoisomeric â-hydroxy-sulfox-
imines were formed. Their separation was achieved by column
chromatography and their identity disclosed as (SS,1R,4R)-50
(mp 61-63 °C; >99% ee, [R]2D0 ) +61.3, c 1.07, CHCl3) and
(SS,1S,4S)-52 (mp 70 °C; >99% ee, [R]2D0 ) +42.0, c 1.06,
CHCl3) by X-ray analyses. Subsequent thermal fragmentations
of an enantioselective synthesis, the need to combine a
sequential annelation with a sequential ring enlargement seemed
inconvenient. Therefore, a more direct approach to 8 and 9 was
searched for.
At this stage, we became aware of a study of a halogen cation-
induced rearrangement of allylic alcohols to â-haloketones,34
indicating that an addition of 1-lithiocyclobutene35 and 1-lithio-
cyclopentene,36 respectively, to the hitherto unknown dispiroke-
tone 41 could lead to the allylic alcohols 42 and 44, and hence
to two further potential precursors of 8 and 9 (Scheme 7). For
the experimental realization, we reacted spiroketone 23 with
cyclopropylidene-triphenylphosphorane,24 subjected the resulting
olefin 40 to an epoxidation and oxaspiropentane to cyclobu-
tanone rearrangement,9 and added the vinyllithium reagents,
catalyzed by anhydrous cerium trichloride,27 to the dispiroketone
41 formed. A single allylic alcohol resulted in both cases, and
a regio- and stereoselective rearrangement then yielded the
bromoketones 43 (42-43) and 45 (44-45), respectively. Of
these, the structure and relative configuration of 43 was secured
by an X-ray structure analysis.
delivered the enantiopure ketones (4R)-41 (>99% ee, [R]D20
)
+145, c 1.21, acetone) and (4S)-41 (>99% ee, [R]2D0 ) -145,
c 1.14, acetone), respectively. As could have been expected,41
(4R)-41 showed a strong positive Cotton effect (θ307 ) +6328,
CH3OH), and (4S)-41 showed a strong negative Cotton effect
(θ307 ) -6538, CH3OH).
In the second case, two diastereoisomeric alcohols resulted.
Upon oxidation with pyridinium chlorochromate,42 the major
alcohol ([R]2D0 ) +1.2, c 1.24, acetone) yielded (4S)-41 (
[R]2D0 ) -84.4, c 1.24, acetone) with diminished optical purity
(69% ee), but the minor alcohol ([R]2D0 ) +22.1, c 1.20,
(37) For ring enlargements of â-hydroxyselenides with insertion of a
cyclobutane ring, see: Fitjer, L.; Steeneck, C.; Gaini-Rahimi, S.; Schroeder,
U.; Justus, K.; Puder, P.; Dittmer, M.; Hassler, C.; Weiser, J.; Noltemeyer,
M.; Teichert, M. J. Am. Chem. Soc. 1998, 120, 317-328.
(38) Synthesis of selenoketals: (a) Krief, A.; Clarembeau, M.; Cravador,
A.; Dumont, W.; Hevesi, L.; Luchetti, J.; van Ende, D. Tetrahedron 1985,
41, 4793-4812. Reductive lithiations: (b) Krief, A. Tetrahedron 1980, 36,
2531-2540.
(39) (a) Johnson, C. R.; Zeller, J. R. J. Am. Chem. Soc. 1982, 104, 4021-
4023. (b) Johnson, C. R.; Zeller, J. R. Tetrahedron 1984, 40, 1225-1233.
(40) Brown, H. C.; Chandrasekharan, J.; Ramachandran, P. V. J. Org.
Chem. 1986, 51, 3394-3396.
(41) For a review on the chiroptical properties of carbonyl compounds,
see: Kirk, D. N. Tetrahedron 1986, 42, 777-818.
(42) Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 16, 2647-2650.
Nothing was known about the reductive debromination of
R-tertiary â-bromoketones. With 43, lithium aluminum hydride
(34) Wang, B. M.; Song, Z. L.; Fan, C. A.; Tu, Y. Q.; Chen, W. M.
Synlett 2003, 1497-1499.
(35) Synthesis of 1-bromo-cyclobutene: (a) Willsta¨tter, R.; von Schma¨del,
W. Ber. Dtsch. Chem. Ges. 1905, 38, 1992-1999. The reductive lithiation
was performed as described or 1-bromo-cyclopentene.36b
(36) Synthesis of 1-bromo-cyclopentene: (a) Abell, P. I.; Chiao, C. J.
Am. Chem. Soc. 1960, 82, 3610-3613. Reductive lithiation: (b) Neumann,
H.; Seebach, D. Chem. Ber. 1978, 111, 2785-2812.
9268 J. Org. Chem., Vol. 72, No. 24, 2007

Helical and Pseudohelical Hydrocarbon Syntheses
SCHEME 9
SCHEME 10
case of a right-handed, levorotatory helix. With respect to their
rotatory powers, all other cases fall in between.
As already pointed out, it is only with (P)-1 that a single
geometry determines the observed optical rotation. In all other
cases, the observed optical rotations should be interpreted as
Boltzmann averages over different conformations. Therefore,
the unusual but systematic changes in the specific rotations on
going from (P)-1 via (P)-4, (P)-5, (R)-6, (S)-7, and (R)-8 to
(P)-9 could only be explored computationally by a quantum
chemical study of all energetically low-lying conformers. Given
the fact that a preliminary conformational search using our
search routine HUNTER43 in connection with MM344 produced
by far more low-lying minima for the nonregular helices (R)-6,
(S)-7, and (R)-8 than for the regular helices (P)-4, (P)-5, and
(P)-9, we restricted our study to the latter but included (P)-1,
(P)-2, and (P)-3 as rigid helices and the as yet unknown (P)-10
as a higher analogue of (P)-9.
Calculations. All quantum chemical calculations were carried
out with the TURBOMOLE45 program package. The geometries
were optimized at the B97-D DFT level of theory45 using triple-ú
valence basis sets on all atoms [TZV(d,p)].46 This approach
includes intramolecular dispersion effects that are important in
larger, sterically overcrowded organic molecules. The optical
rotations were obtained from time-dependent density functional
theory (TDDFT47) calculations using the BH-LYP functional48
and a split valence basis set [SV(d,p)]49 augmented by a set of
acetone) yielded (4R)-41 ([R]2D0 ) +145, c 1.21, acetone)
optically pure (>99% ee). The minor alcohol was recognized
as (1S,4R)-51 by an X-ray analysis of its 3,5-dinitrobenzoate
(1S,4R)-49, and accordingly, the major alcohol was (1S,4S)-
53. For the syntheses of optically pure samples of 8 and 9, (4R)-
41 was used throughout.
For the syntheses of (5R)-8 and (P)-9, we applied the same
reactions as for the synthesis of the racemic specimen (Scheme
10). For the synthesis of (5R)-8, we reacted (4R)-41 with
1-lithio-1-methylselenocyclobutane, rearranged the â-hydroxy-
selenide (1R,4R)-48 obtained with 3-chloroperbenzoic acid, and
deoxygenated the resulting dispiroketone (5R)-47 (>99% ee,
[R]2D0 ) -12.7, c 1.23, acetone) to trispirane (5R)-8 (>99% ee,
[R]2D0 ) -30.7, c 1.15, CHCl3). For the synthesis of (P)-9, we
reacted (4R)-41 with 1-lithio-cyclopentene, rearranged the
resulting allyl alcohol (1S,4R)-42 (>99% ee, [R]2D0 ) -46.1, c
1.30, acetone) to the â-bromoketone (6R,7R,8S)-43 (>99% ee,
[R]2D0 ) -46.3, c 1.24, acetone), debrominated this compound
to (6R)-46 (>99% ee, [R]D20 ) -127, c 1.21, acetone), and
deoxygenated the latter to trispirane (P)-9 (>99% ee, [R]D20
)
-62.6, c 1.10, CHCl3). This completed the series of optically
pure nonregular [(R)-6, (S)-7, (R)-8)] and regular helices [(P)-
9] of spiroannelated four- and five-membered rings.
(43) Weiser, J.; Holthausen, M. C.; Fitjer, L. J. Comput. Chem. 1997,
18, 1264-1281.
Chiroptical Properties. As may be seen from the specific
rotations of (P)-1, (P)-4, (P)-5, (R)-6, (S)-7, (R)-8, and (P)-9,
interesting regularities exist (Table 1). On going from (P)-1 to
(P)-4, a distinct decrease of the specific rotation is observed,
which continues with (P)-5, (R)-6, and (S)-7, until with (R)-8
and (P)-9 the sign of rotation changes and the amount increases
again. Of the extremes, (P)-1 represents the usual case of a right-
handed, dextrorotatory helix, while (P)-9 represents the unusual
(44) Allinger, N. L.; Yuh, Y. H.; Lii, J.-H. J. Am. Chem. Soc. 1989,
111, 8551-8556.
(45) TURBOMOLE 5.6; Ahlrichs, R. et al., Universita¨t Karlsruhe, 2003.
See also: http://www.turbomole.com.
(46) (a) Grimme, S. J. Comput. Chem. 2004, 25, 1463-1476. (b)
Grimme, S. J. Comput. Chem. 2006, 27, 1787-1799.
(47) Scha¨fer, A.; Huber, C.; Ahlrichs, R. J. Chem. Phys. 1994, 100,
5829-5835.
(48) Casida, M. E. In Recent AdVances in Density Functional Methods;
Chong, D. P., Ed.; World Scientific: Singapore, 1995.
J. Org. Chem, Vol. 72, No. 24, 2007 9269

Widjaja et al.
TABLE 1. Experimental Optical Rotations (in CHCl3) of Pseudohelical and Helical Hydrocarbons of Three-, Four-, and Five-Membered
Rings
diffuse functions (s,p,d) taken from the Dunning’s aug-cc-pVDZ
basis set50 (hereafter called aug-SVP). For a general overview
about chiroptical calculations, see ref 51; for the particular
application of TDDFT methods for computations of optical
rotations, see ref 52; and for examples that include several
conformers, see ref 53. For 1 the basis set effect on the optical
rotation has been studied by comparing the aug-SVP derived
value with one obtained by an accordingly composed aug-TZV-
(p,d) basis set. The difference of about 8° (4%) is very small
compared to other sources of error inherent to the TDDFT
method. Similar differences were obtained in test calculations
employing optimized geometries from other sources (e. g. DFT-
B3LYP).54 Due to technical reasons, the TDDFT/BHLYP
calculations of the optical rotations could be performed only in
the coordinate origin-dependent dipole-length representation for
the rotatory strengths. Test calculations employing nonhybrid
density functionals and the origin-independent velocity gauge
representation show, however, that the differences between the
two forms with the aug-SVP basis set are only about 1%. Note
that our TDDFT/BHLYP results for 1 agree better with the
experiment than those reported recently using the B3LYP
functional55 (see below).
Except for 1, 2, and 3, the correct determination of the optical
rotation of the investigated compounds required a careful
analysis of their respective conformational flexibility. With 4
and 5, this analysis was done by systematically generating all
different combinations arising by ring flippings, and with 9 and
10 the analysis was done by using the GMMX routine as
implemented in PC-Model 7.0.56 Subsequent optimization at the
DFT-B-97-D/TZVP level yielded six relevant conformers each
for 4 and 5, four conformers for 9, and two conformers for 10.
For all compounds, the Boltzmann weighting for the calculation
of the total optical rotations was done on the basis of SCS-
MP2/TZVPP58 and, for the sake of comparison, also with DFT-
B-97-D/TZVPP relative energies. All conformers with popu-
lations above 3% at room temperature were taken into account.
Results and Discussion. A comparison of the computed and
experimental optical rotations for the (P)-helices of 1-5, 9, and
10 is given in Table 2, and a list of contributions of the
individual conformers of 4, 5, 9, and 10 together with views
along and perpendicular to their helical axis is given in Tables
3-5. Perusing Table 2, one finds in general a good agreement
between theory and experiment for the optical rotations, i.e., a
correct sign, and always the right order of magnitude. In
particular, the agreement for the rigid systems 1-3 is excellent.
For the flexible systems 4, 5, 9, and 10, the specific rotations
refer to Boltzmann-averaged values of different conformations.
(49) Becke, A. D. J. Chem. Phys. 1993, 98, 1372-1377.
(50) Scha¨fer, A.; Horn, H.; Ahlrichs, R. J. Chem. Phys. 1992, 97, 2571-
2577.
(51) (a) Polavarapu, P. L. Chirality 2002, 14, 768-781. (b) Crawford,
T. D. Theor. Chem. Acc. 2006, 115, 227-245.
(52) Kendall, R. A.; Dunning, T. H., Jr.; Harrison, R. J. J. Chem. Phys.
1992, 96, 6796-6806.
(53) (a) Cheeseman, J. R.; Frisch, M. J.; Devlin, F. J.; Stephens, P. J. J.
Phys. Chem. A 2000, 104, 1039-1046. (b) Grimme, S. Chem. Phys. Lett.
2001, 339, 380-388. (c) Stephens, P. J.; Devlin, F. J.; Cheeseman, J. R.;
Frisch, M. J. J. Phys. Chem. A 2001, 105, 5356-5371. (d) Autschbach, J.;
Patchkovskii, S.; Ziegler, T.; van Gisbergen, S.; Baerends, E. J. J. Chem.
Phys. 2002, 117, 581-592. (e) Ruud, K.; Helgaker, T. Chem. Phys. Lett.
2002, 352, 533-539. (f) Stephens, P. J.; McCann, D. M.; Cheeseman, J.
R.; Frisch, M. J. Chirality 2005, 17, 52-64.
(54) (a) Grimme, S.; Bahlmann, A.; Haufe, G. Chirality 2002, 14, 793-
797. (b) Pecul, M.; Ruud, K.; Rizzo, A.; Helgaker, T. J. Phys. Chem. A
2004, 108, 4269-4276. (c) Lattanzi, A.; Viglione, R. G.; Scettri, A.; Zanasi,
R. J. Phys. Chem. A 2004, 108, 10749-10753. (d) Marchesan, D.; Coriani,
S.; Forzato, C.; Nitti, P.; Pitacco, G.; Ruud, K. J. Phys. Chem. A 2005,
109, 1449-1453. (e) Wiberg, K. B.; Wang, Y. G.; Vaccaro, P. H.;
Cheeseman, J. R.; Luderer, M. R. J. Phys. Chem. A 2005, 109, 3405-
3410. (f) Giorgio, E.; Roje, M.; Tanaka, K.; Hamersak, Z.; Sunjic, V.;
Nakanishi, K.; Rosini, C.; Berova, N. J. Org. Chem. 2005, 70, 6557-6563.
(55) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652. (b) Stephens,
P. J.; Devlin, F. J.; Chablowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994,
98, 11623-11627.
(56) Crawford, T. D.; Owens, L. S.; Tam, M. C.; Schreiner, P. R.; Koch,
H. J. Am. Chem. Soc. 2005, 127, 1368-1369.
(57) PC-Model 7.0, Serena Software, Bloomington, IN 47405.
(58) Grimme, S. J. Chem. Phys. 2003, 118, 9095-9102.
9270 J. Org. Chem., Vol. 72, No. 24, 2007

Helical and Pseudohelical Hydrocarbon Syntheses
TABLE 2. Experimental and Computed Specific Rotations for
TABLE 4. Conformers of (P)-5: Views along and Perpendicular
to the Helical Axis, Dihedral Angles of the Bonds Forming the Inner
Helix, Relative Energies (in kcal/mol), Populations (at 298 K), and
Specific Rotations
(P)-Helices of Three-, Four-, and Five-Membered Rings
molecule
calc.a
exp.b
(P)-1
(P)-2
(P)-3
+184.1
+192.7c
+373.0d
+909.9e
+63.3g
+26.0h
-62.6
+388.3
+827.8
(P)-4f
(P)-5 f
(P)-9 f
(P)-10 f
+82.7 (+79.5)
+61.7 (+83.8)
-50.9 (-54.1)
-36.2 (-35.4)
a TDDFT/aug-SVP//B-97-D/TZVP level. b In CHCl3, c ) 0.96-1.20.
c Derived from (M)-1; see ref 4. d From ref 4. e From ref 6. f Boltzmann
weighted average of two (10), four (9), and six conformations (4, 5),
respectively, at 298 K based on SCS-MP2/TZVPP//B-97-D/TZVP relative
energies. Specific rotations based on B-97-D/TZVPP//B-97-D/TZVP relative
energies are given in parentheses. g Derived from (M)-4; see ref 7. h From
ref 1.
TABLE 3. Conformers of (P)-4: Views along and Perpendicular
to the Helical Axis, Dihedral Angles of the Bonds Forming the Inner
Helix, Relative Energies (in kcal/mol), Populations (at 298 K), and
Specific Rotations
of conformers of type A and B (>100) render the averaged
values extremely sensitive toward any change in the population
of individual conformers. This means that even small errors for
∆E in the order of 0.1 kcal/mol can lead to large errors in the
averaged specific rotations. It is therefore no surprise that both
the SCS-MP2 and DFT energy based Boltzmann-weighted
values for the specific rotation of (P)-4 and (P)-5 do not exactly
match the experimental values (Table 2). Especially for (P)-5,
the theoretical values are distinctly too high. This indicates that
at least in this case the contribution of conformers of type A
(5-2 and/or 5-4 and/or 5-6) is overestimated. Note, however,
that the theoretical data derived from the more sophisticated
quantum chemical model (i.e., SCS-MP2) agree in this critical
case better with experiment.
In (P)-9 and (P)-10, the number of relevant conformers is
reduced to four and two, respectively, and all conformers belong
to type B (Table 5). Consequently, only small, but, surprisingly,
positive rotations result. These vary to a considerably larger
extent than those of type B in (P)-4 and (P)-5. Tentatively, this
may be attributed to a greater conformational mobility of five-
as compared to four-membered rings, but no simple explanation
can be given for the sign change of the optical rotation in going
from (P)-4 to (P)-9 and from (P)-5 to (P)-10. In any case, the
calculated Boltzmann-averaged values for the specific rotation
of (P)-9 match the experimental value closely, while for the
still unknown (P)-10 these values remain to be verified.
Therefore, in these cases each conformer had to be analyzed
separately. In a search for a simple but reliable relation between
the geometry of a conformer and its specific rotation we found
that the dihedral angles of the bonds of the inner spheres and
the specific rotations correlated best.
In (P)-4 (Table 3) and (P)-5 (Table 4), three types of
conformers may be distinguished: in conformers of type A (4-
1, 4-4, 4-5, 5-2, 5-4, 5-6), a set of large dihedral angles
generates inner helices of five bonds within two helical turns;
in conformers of type B (4-3, 4-6, 5-1, 5-3), a set of small
dihedral angles generates inner helices of four bonds within one
helical turn; and in conformers of type C (4-2, 5-5), a
combination of large and small dihedral angles leads to cases
which fall in between. Within a given type, the calculated
specific rotations vary only slightly. They are consistently high
for conformers of type A, consistently low for conformers of
type B, and lie in between for conformers of type C. Especially
the large differences between the calculated specific rotations
An interesting quest concerns the relation between the specific
rotation and the length of a helix. In helices of three-membered
rings, the specific rotation increases as the length of the helix
increases. It is already high in (P)-1, and doubles in (P)-2, and
again in (P)-3. Obviously, the electronic structure of helices of
three-membered rings allows some conjugation, and, due to their
J. Org. Chem, Vol. 72, No. 24, 2007 9271

Widjaja et al.
TABLE 5. Conformers of (P)-9 and (P)-10: Views along and
Perpendicular to the Helical Axis, Dihedral Angles of the Bonds
Forming the Inner Helix, Relative Energies (in kcal/mol),
Populations (at 298 K), and Specific Rotations
functionals perform significantly worse. For example, a test
calculation for (P)-2 with TDDFT-B3-LYP/aug-SVP yielded
[R]D ) 436.1, corresponding to an error of ∼15%, which has
to be compared to the almost perfect agreement with the
experiment that is obtained at the TDDFT-BH-LYP/aug-SVP
level. To this end this work impressively confirms the suitability
of BH-LYP calculations to reproduce the optical rotations of
saturated systems. We therefore strongly recommend the use
of this functional for comparable applications in the future.
Conclusion
In conclusion, we developed syntheses for the pseudohelical
hydrocarbons 6-8 and the helical hydrocarbon 9, formally
derived from the helical hydrocarbon 4 by stepwise replacement
of each of the four-membered rings by a five-membered ring.
Optically active specimens were obtained via enzymatic [(R)-
6, (S)-7] or chemical resolution [(R)-8, (P)-9] of appropriate
precursor ketones. In going from (P)-1 via (P)-4, (P)-5, and
(R)-6 to (S)-7, a distinct decrease in the specific rotation is
observed, until, with (R)-8 and (P)-9, the sign of rotation changes
and the amount increases again. To account for this finding, a
quantum chemical study on the rotatory power of helical
hydrocarbons of three- [(P)-1, (P)-2, (P)-3], four- [(P)-4, (P)-
5], and five-membered rings [(P)-9, (P)-10] has been performed.
We have shown that for the rigid helices of three-membered
rings the agreement between theory and experiment is excellent,
while for the flexible helices of four- and five-membered rings
the results strongly depend on the geometry and weight of the
conformers involved. However, even in these cases, the sign
and the order of magnitude of the specific rotation were
reproduced correctly. With regard to the fact that up to six
conformers with very different specific rotations had to be
analyzed and weighted, this result is remarkable.
Experimental Section
rigid structures, an increase of the spatial dimension of their
chromophore with the length of the helix results.
(5R*)-Trispiro[3.0.0.4.2.2]tetradecan-11-one (15). To a solution
of 20 (15.1 g, 83.5 mmol) in dichloromethane (80 mL) was added
at -15 °C under argon with stirring trifluoromethanesulfonic acid
anhydride (28.3 g, 100 mmol). Then, within 15 min, a solution of
2,4,6-collidine (13.1 g, 108 mmol) in 1-methylenespiro[3.3]heptane
(12) was also added.1 The mixture was heated for 20 h to reflux
and then concentrated on a rotary evaporator (bath temperature 40
°C/20 Torr). The residue was extracted with anhydrous ether (6 ×
40 mL), and the remaining brown oil was hydrolyzed in a two-
phase system of dichloromethane (170 mL) and water (170 mL).
After 2 h of reflux the phases were separated, the aqueous phase
was extracted with dichloromethane (6 × 60 mL), and the combined
organic phases were washed with saturated ammonium chloride
(60 mL) and dried (K2CO3/MgSO4). The solvent was distilled off
(bath temperature 40 °C/20 Torr), the residue (26.1 g) was extracted
with pentane/ether (1:1, 3 × 50 mL), and the combined extracts
were washed with 2 N HCl (30 mL) and dried (MgSO4). The
solvent was evaporated (bath temperature 40 °C/20 Torr) and the
remaining material (9.4 g) chromatographed on silica gel (0.05-
0.20 mm) in pentane/ether [9:1, column 75 × 5 cm, Rf ) 0.45
(15)] to yield 3.63 g (21%) of 15 as a colorless liquid [purity 83%
GC, column A, 230 °C, retention time (min): 5.11 (15)]. For the
reduction with bakers’ yeast, the material was used as such. For
other preparations, the material was chromatographed twice (purity
95%). An analytically pure sample was obtained by preparative
In helices of four- and five-membered rings the situation is
different. In these cases several conformers exist, but only the
rotations of pairs with identical or closely related geometries
are meaningful and may be compared. Within helices of four-
membered rings, such pairs are 4-3 and 5-1, and 4-5 and
5-6, and in both cases the specific rotation increases as the
length of the helix increases. This means that no principal
differences between helices of three- and four-membered rings
exist, albeit the rotatory power of the latter is strongly
diminished.
Due to pronounced differences within the geometry of the
outer spheres, no closely related pairs of conformers could be
found for helices of five-membered rings. Therefore, in this case
no conclusive answer concerning a possible relation between
the specific rotation and the length of the helix can be given.
All in all, with the exception of 4-5 and 5-6, the conformers
of the flexible systems (P)-4, (P)-5, (P)-9, and (P)-10 seem to
behave more like a collection of mutually independent and
electronically isolated rings, which in the large system limit
could well lead to cryptochirality. However, this hypothesis
remains to be verified.
In summary, the optical rotations of the considered molecules
are very well reproduced by TDDFT-BH-LYP/aug-SV(d,p)
computations. Density functionals with a smaller fraction of
Hartree-Fock exchange (like, e.g., B3-LYP) or nonhybrid
1
GC. IR (neat): 1770 cm-1 (CdO). H NMR (600 MHz, CDCl3,
CHCl3 int): δ ) 1.54-1.78 (m, 9H), 1.78-1.93 (m, 5H), 1.97-
2.04 (m, 2H), 2.10 (mc, 1H), 2.28 (mc, 1H), 2.62 (d, J ) 16.5 Hz,
1H), 3.12 (d, J ) 16.5 Hz, 1H). 13C NMR (75.5 MHz, CDCl3,
9272 J. Org. Chem., Vol. 72, No. 24, 2007

Helical and Pseudohelical Hydrocarbon Syntheses
CDCl3 int): δ ) 15.4 (t), 25.2 (t), 26.0 (t), 26.3 (t), 30.0 (t), 31.0
(t), 31.3 (t), 32.5 (t), 44.6 (s), 48.7 (s), 51.7 (t), 71.8 (s), 214.1 (s).
MS (EI): m/e ) 204 (<1, M+), 134 (100). C14H22O requires C,
82.30; H, 9.87. Found: C, 81.99, H, 9.72.
and dried (MgSO4). The solvent was distilled off over a 20 cm
vigreux column and the remaining material chromatographed on
silica gel (0.05-0.20 mm) in pentane [column 45 × 3 cm, Rf )
0.77 (7)] yielding 187 mg (66%) of 7 as a colorless liquid (purity
87% GC). An analytically pure sample was obtained by prepara-
tive GC [column A, 180 °C, retention time (min): 6.64 (7)]. The
enantiomers of the racemic material could not be resolved [column
(5R*)-Trispiro[3.0.0.4.2.2]tetradecane (6). To a solution of
hydrazine hydrate (150 mg, 3.0 mmol) and powdered potassium
hydroxide (225 mg, 4.0 mmol) in diethylene glycol (2.0 mL) was
added under argon with stirring 15 (102 mg, 0.50 mmol). The
mixture was heated for 1.5 h to 160 °C, until it was diluted with
water (20 mL) and extracted with pentane (3 × 15 mL). The
combined extracts were washed with water (15 mL), dried (MgSO4),
and concentrated using a 20 cm vigreux column. The last traces of
solvent were evaporized under reduced pressure yielding 88 mg
(82%) of 6 as a colorless oil [purity 99% GC, column A, 180 °C,
retention time (min): 3.69]. The enantiomers could be resolved by
capillary gas chromatography on a chiral phase [column D, 90 °C,
retention times (min): 32.85/33.42]. An analytically pure sample
was obtained by preparative GC. 1H NMR (600 MHz, CDCl3,
CHCl3 int): δ ) 1.35-1.40 (m, 1H), 1.40-1.65 (m, 11H), 1.68-
1.87 (m, 6H), 1.93 (mc, 1H), 1.99 (mc, 1H), 2.09 (mc, 1H), 2.23-
2.30 (m, 1H). 13C NMR (75.5 MHz, CDCl3, CDCl3 int): δ ) 15.8
(t), 23.1 (t), 24.3 (t), 26.6 (t), 27.1 (t), 30.4 (t), 31.1 (t), 32.1 (t),
32.2 (t), 33.4 (t), 36.1 (t), 49.0 (s), 51.9 (s), 52.1 (s). MS (EI): m/e
) 190 (<1, M+), 162 (38, M+ - C2H4), 79 (100). C14H22 requires
C, 88.35; H, 11.65. Found: C, 88.01; H, 11.45.
1
E, 110 °C, retention time (min): 21.09 (5R)-7/(5S)-7]. H NMR
(600 MHz, CDCl3, CHCl3 int): δ ) 1.19-1.26 (m, 1H), 1.28-
1.37 (m, 2H), 1.39-1.64 (m, 13H), 1.67-1.81 (m, 4H), 1.88-
1.96 (m, 2H), 1.99 (mc, 1H), 2.28 (mc, 1H). 13C NMR (150.8 MHz,
CDCl3, CDCl3 int): δ ) 16.0 (t), 19.4 (t), 24.9 (t), 25.2 (t), 25.6
(t), 32.21 (t), 32.22 (t), 32.8 (t), 33.4 (t), 33.6 (t), 34.7 (t), 38.2 (t),
48.8 (s), 54.0 (s), 55.1 (s). MS (EI): m/e ) 204 (5, M+), 121 (100).
C15H24 requires C, 88.16; H, 11.84. Found: C, 88.02; H, 11.79.
Reduction of 15 with Lithium Aluminum Hydride: (5S*,
11S*)-Trispiro[3.0.0.4.2.2]tetradecan-11-ol (27) and (5R*,11S*)-
Trispiro[3.0.0.4.2.2]tetradecan-11-ol (28). To a suspension of
lithium aluminum hydride (114 mg, 3.0 mmol) in anhydrous ether
(8.0 mL) was added at room temperature under argon with stirring
a solution of 15 (204 mg, 1.0 mmol) in ether (1.5 mL). After 30
min the reduction was complete according to GC [column A,
230 °C, retention times (min): 5.11 (15), 7.22 (27), 7.62 (28)].
Water (114 µL), 15% aqueous potassium hydroxide (114 µL), and
water (442 µL) were added, the liquid phase was decanted, and
the residue was extracted with ether (3 × 10 mL). The combined
organic phases were dried (MgSO4) and concentrated on a rotary
evaporator (bath temperature 45 °C/20 Torr) to yield 200 mg of a
65:35 mixture of 27 and 28. Unfortunately, the two alcohols could
not be separated by preparative GC, but the enantiomers of 27 could
be resolved [column C, 130 °C, retention times (min): 27.02 (5R,-
11R)-27, 27.45 (5S,11S)-27, 30.07 (5R,11S)- and (5S,11R)-28]. All
assignments are based on the results of the reduction with bakers’
(5R*)-Trispiro[3.0.0.4.3.2]pentadecan-12-one (24) and (5R*)-
Trispiro[3.0.0.4.3.2]pentadecan-11-one (25). To a stirred solution
of powdered potassium hydroxide (1.94 g, 34.7 mmol) in methanol
(4.4 mL) and water (0.7 mL) containing 15 (592 mg, 2.90 mmol)
was added within 25 min N-methyl-N-nitroso-4-toluenesulfonic acid
amide (Diazald) (806 mg, 3.76 mmol) in small portions. Afterward,
the mixture was diluted with methanol (3.0 mL), and, after 45 min,
more Diazald (820 mg, 3.83 mmol) followed by more methanol
(3.0 mL) was added. After additional 1 h, GC analysis [column A,
230 °C, retention times (min): 4.88 (15), 7.86 (25), 10.13 (24)]
indicated the presence of a 55:45 mixture of 24 and 25. The
heterogeneous reaction mixture was diluted with water (8 mL) and
the resulting clear solution extracted with pentane (7 × 10 mL).
The extracts were washed with saturated ammonium chloride (15
mL) and water (15 mL) and were dried (MgSO4) until the solvent
was distilled off on a rotary evaporator (bath temperature 40 °C/
15 Torr) yielding 449 mg (71%) of a 55:45 mixture of 24 and 25
as a colorless liquid (purity 93% GC). This mixture was used for
the preparation of 7. Analytically pure samples of 24 and 25 were
obtained by preparative GC as colorless liquids. 24: IR (neat): 1750
cm-1 (CdO). 1H NMR (600 MHz, CDCl3, CHCl3 int): δ ) 1.35-
1.40 (m, 1H), 1.41-1.46 (m, 1H), 1.50-1.89 (m, 12H), 1.92-
2.08 (m, 3H), 1.95 (d, J ) 18 Hz, 1H), 2.16 (d, J ) 18 Hz, 1H),
2.18 (d, J ) 18 Hz, 1H), 2.31-2.38 (m, 1H), 2.37 (d, J ) 18 Hz,
1H). 13C NMR (150.8 MHz, CDCl3, CDCl3 int): δ ) 15.7 (t), 24.5
(t), 25.1 (t), 25.2 (t), 32.0 (t), 32.3 (t), 32.9 (t), 33.2 (t), 34.9 (t),
47.8 (t), 48.3 (s), 51.6 (s), 52.5 (t), 53.0 (s), 218.9 (s). MS (EI):
m/e ) 218 (29, M+), 122 (100). HRMS: m/e (M+) calcd 218.1671,
1
yeast (see below). The H and 13C NMR spectra of the mixture
were in accord with the spectra of the pure alcohols. The analysis
counts for the mixture. C14H22O requires C, 81.50; H, 10.75.
Found: C, 81.38; H, 10.81.
Reduction of 15 with Bakers Yeast: (5S,11S)-(+)-Trispiro-
[3.0.0.4.2.2]tetradecan-11-ol [(5S,11S)-(+)-27], (5R,11S)-(+)-
Trispiro[3.0.0.4.2.2]tetradecan-11-ol [(5R,11S)-(+)-28], and (5R)-
(-)-Trispiro[3.0.0.4.2.2]tetradecan-11-one [(5R)-(-)-15]. To a
stirred mixture of fresh bakers’ yeast (40 g), sucrose (40 g), and
water (400 mL), maintained at 37 °C, was added a solution of 15
(3.25 g, purity 83%, 13.3 mmol) in ethanol (13.5 mL). The reaction
progress was monitored by GC [column A, 230 °C, retention times
(min): 5.11 (15), 7.22 (27), 7.62 (28)], and, after 8 h, more yeast
(40 g), sucrose (40 g), and water (200 mL) were added. After 22
h, the mixture was diluted with water (4.5 l) and continuously
extracted with ether (1.0 L, 6 h, control by GC). The extract was
concentrated to 150 mL, washed with saturated sodium bicarbonate
(2 × 30 mL), dried (MgSO4), and evaporated to dryness (bath
temperature 50 °C/20 Torr). According to GC, the residual oil (3.46
g) contained 15, (5S,11S)-27, and (5R,11S)-28 in proportions of
58:40:2shence 15 as 83:17 mixture of (5R)- and (5S)-15. This
material was chromatographed on silica gel (0.05-0.20 mm) in
pentane/ether [7:3, column 80 × 5 cm, Rf ) 0.65 (15), 0.35 (27/
28)] yielding 1.44 g (53%) of 15 as a colorless oil (purity 90%)
and 919 mg (34%) of a 96:4 mixture of (5S,11S)-27 and (5R,11S)-
1
obsd 218.1671. 25: IR (neat): 1740 cm-1 (CdO). H NMR (600
MHz, CDCl3, CHCl3 int): δ ) 1.50-1.55 (m, 2H), 1.57-1.74 (m,
12H), 1.76-1.85 (m, 2H), 1.91-2.00 (m, 2H), 2.01-2.09 (m, 2H),
2.21 (pseudo t, J ) 7.5 Hz, 2H). 13C NMR (75.5 MHz, CDCl3,
CDCl3 int): δ ) 15.8 (t), 24.2 (t), 25.8 (t), 26.5 (t), 28.5 (t), 29.5
(t), 31.5 (t), 32.2 (t), 32.8 (t), 33.1 (t), 33.9 (t), 48.1 (s), 52.4 (s),
62.3 (s), 221.4 (s). MS (EI): m/e ) 218 (6, M+), 41 (100). C15H22O
requires C, 82.52; H, 10.16. Found: C, 82.42; H, 9.82.
(5R*)-Trispiro[3.0.0.4.3.2]pentadecane (7). To a solution of
hydrazine hydrate (446 mg, 8.9 mmol) and powdered potassium
hydroxide (670 mg, 11.9 mmol) in diethylene glycol (7.0 mL) was
added under argon with stirring a 55:45 mixture of 24 and 25 (325
mg, 1.49 mmol). The mixture was heated for 2 h to 120° and 5 h
to 195 °C, until it was diluted with water (10 mL) and extracted
with pentane (6 × 10 mL). The combined extracts were washed
with saturated ammonium chloride (15 mL) and water (15 mL)
28 as a colorless solid, mp 47-52 °C (purity 98%). R[R]D20
)
+33.6, c ) 1.13, acetone). According to GC on a chiral phase
[column C, 130 °C, retention times (min): 27.45] (5S,11S)-27 was
enantiomerically pure (>99% ee). The reduction of the 83:17
mixture of (5R)- and (5S)-15 (1.44 g, purity 90%, 6.35 mmol) in
a mixture of yeast (19 g), sucrose (19 g), and water (190 mL) was
performed analogously. After 7, 24, 31, 48, and 72 h more yeast
(19 g), sucrose (19 g), and water (95 mL) were added, and after 96
h the extract (1.26 g) contained 15, (5S,11S)-27, and (5R,11S)-28
in proportions of 78:16:12shence 15 as 99:1 mixture of (5R)- and
(5S)-15. A total of 810 mg (62%) of 15 was isolated by chroma-
J. Org. Chem, Vol. 72, No. 24, 2007 9273

Widjaja et al.
tography on silica gel. Of this, 786 mg (purity 92%, 3.54 mmol)
was subjected to a third reduction with yeast (11 g), sucrose (11
g), and water (110 mL). After 6, 23, and 30 h, more yeast (11 g),
sucrose (11 g), and water (55 mL) were added, and after 48 h the
extract (811 mg) contained 15, (5S,11S)-27, and (5R,11S)-28 in
proportions of 88:0.5:11.5shence 15 as enantiomerically pure (5R)-
15. Chromatography on silica gel yielded 564 mg (78%) of (5R)-
15 as a colorless liquid (purity 92%) and 73 mg (10%) of a 95:5
mixture of (5R,11S)-28 and (5S,11S)-27 as a colorless solid, mp
78-82 °C (purity 96%). Analytically pure samples of (5R)-15 (
[R]2D0 ) -0.5, c ) 1.13, acetone) and the 95:5 mixture of (5R,-
11S)-28 and (5S,11S)-27 ([R]2D0 ) +62.5, c ) 1.13, acetone) were
obtained by preparative GC. The 1H and 13C NMR data of (5R)-15
were identical with those of racemic 15. The spectral data for the
alcohols was as follows. (5S,11S)-27: 1H NMR (600 MHz, CDCl3,
CHCl3 int): δ ) 1.41-1.49 (m, 3H), 1.49-1.68 (m, 6 H), 1.68-
1,90 (m, 8H), 1.92-2.06 (m, 3H), 2.28 (mc, 1H), 3.74 (dd, J ) 8
Hz, 7 Hz, 1H). 13C NMR (150.8 MHz, CDCl3, CDCl3 int): δ )
15.5 (t), 24.2 (t), 24.8 (t), 26.1 (t), 27.1 (t), 30.1 (t), 30.5 (t), 32.5
(t), 35.9 (t), 38.0 (t), 44.9 (s), 48.4 (s), 57.6 (s), 72.1 (d). (5R,-
11S)-28: 1H NMR (600 MHz, CDCl3, CHCl3 int): δ ) 1.440-
1.46 (m, 2H), 1.47-1.59 (m, 6H), 1.59-1.65 (m, 1H), 1.59-1.65
(m, 2H), 1.65 - 1.72 (m., 1H), 1.74-1.88 (m, 6H), 2.07 (mc, 1H),
2.18 (mc, 1H), 2.34 (dd, J ) 9 Hz, 7.5 Hz, 1H), 3.85 (dd, J ) 7.5
Hz, 7.5 Hz, 1H). 13C NMR (150.8 MHz, CDCl3, CDCl3 int): δ )
16.0 (t), 24.4 (t), 25.1 (t), 25.3 (t), 28.1 (t), 32.0 (t), 32.2 (t), 32.2
(t), 34.3 (t), 37.7 (t), 46.8 (s), 49.3 (s), 57.8 (s), 72.8 (d).
was diluted with pentane (130 mL) and hydrolyzed with saturated
aqueous ammonium chloride (1.6 mL, 15 min stirring). The liquid
phase was decanted, and the residue was extracted with ether (3 ×
50 mL). The combined organic phases were washed with saturated
aqueous ammonium chloride (80 mL) and water (2 × 80 mL), dried
(MgSO4), and concentrated (bath temperature 50 °C/15 Torr) to
yield 2.65 g (69%%) of crude 35 as a slightly yellow liquid (purity
80% GC). This material was directly used in the next step. An
analytically pure sample was obtained by preparative GC. IR
(neat): 3600-3400 cm-1 (OHass.). 1H NMR (600 MHz, C6D6,
C6D5H int): δ ) 0.62-0.68 (m, 1H), 0.68-0.76 (m, 3H), 0.98
(dd, J ) 7, 7 Hz, 3H), 1.20-1.28 (m, 2H), 1.32 (mc, 1H), 1.42-
1.83 (m, 13H), 1.87 (ddd, J ) 12, 10, 5 Hz, 1H), 2.02-2.10 (m,
2H), 2.18-2.24 (m, 1H), 2.30 (ddd, J ) 13, 10, 7 Hz, 1H), 3.13
(dq, J ) 9, 7 Hz, 1H), 3.35 (dq, J ) 9, 7 Hz, 1H). 13C NMR (150.8
MHz, C6D6, C6D6 int): δ ) 8.9 (t), 10.4 (t), 16.1 (t), 20.2 (q), 20.7
(t), 24.3 (t), 25.3 (t), 34.6 (t), 35.6 (t), 36.4 (t), 38.3 (t), 39.1 (t),
40.3 (t), 56.7 (s), 61.4 (s), 63.4 (t), 65.2 (s), 87.0 (s). MS (EI): m/e
) 278 (8, M+), 108 (100). HRMS m/e (M+) calcd 278.2246, obsd
278.2246.
(4R*,5S*)-Trispiro[3.0.0.4.3.3]hexadecane-1-one [4R*,5S*)-
36]: A mixture of 35 (2.42 g, 8.68 mmol, purity 80%) and 8 M
aqueous tetrafluoroboric acid (4.40 mL, 35.2 mmol) in ether (85
mL) was stirred at room temperature. According to 1H NMR, after
2 h the reaction was complete. The mixture was treated with
saturated aqueous sodium bicarbonate (3 × 50 mL), then washed
with water (2 × 50 mL), and dried (MgSO4). The solvent was
evaporated (bath temperature (45 °C/15 Torr) and the residue (2.12
g) chromatographed on silica gel (0.05-0.20 mm) in pentane/ether
9:1 [column 75 × 5.5 cm, Rf ) 0.42 (36)] to yield 1.09 g (64%) of
35 as a colorless liquid. According to GC [column B, 210 °C;
retention time (min): 5.88 (36)], the material was 94% pure. IR
(1S*,5S*)-1-(1-Ethoxy-vinyl)-dispiro[4.0.4.3]tridecan-1-ol [(1S*,
5S*)-33]. To a solution of methyl-vinylether (7.22 g, 100 mmol)
in anhydrous THF (85 mL) was added within 50 min at -78 °C
under argon with stirring a 1.5 M solution of tert-butyllithium in
hexane (40 mL, 60 mmol). After an additional 15 min at -78 °C,
the mixture was allowed to warm to room temperature. The resulting
pale yellow solution of 1-ethoxy-vinyllithium was used in the next
step. A suspension of finely powdered dry CeCl3 (9.60 g, 39.0 mol)
in anhydrous THF (145 mL) was stirred at room temperature under
argon for 2 h. After addition of 32 (3.10 g, 16.1 mmol), stirring
was continued for 2 h until the mixture was cooled to 0 °C, and
the freshly prepared solution of 1-ethoxy-vinyllithium was added
within 45 min. After an additional 45 min at room temperature,
GC analysis [column B, 210 °C; retention times (min): 2.81 (32),
4.32 (33)] indicated no further rise in the concentration of 33 (89%).
The mixture was diluted with pentane (100 mL) and hydrolyzed
with saturated aqueous ammonium chloride (40 mL). The mixture
was suction filtered and the residue washed with pentane (4 × 50
mL). The combined filtrates were washed with water (2 × 250
mL), the phases were separated, the aqueous phase was extracted
with pentane (250 mL), and the combined organic phases were dried
(MgSO4) and concentrated (bath temperature 50 °C/15 Torr) to yield
3.88 g (94%) of crude 33 as a slightly yellow liquid (purity 81%
GC). This material was used in the next step. An analytically pure
sample was obtained by preparative GC. IR (neat): 3600-3300
1
(neat): 1770 cm-1 (CdO). H NMR (600 MHz, CDCl3, CHCl3
int): δ ) 1.20 (mc, 1H), 1.27 (mc, 1H), 1.35-1.80 (m, 16H), 1.86
(ddd, J ) 12.5, 9, 9 Hz, 1H), 1.95 (mc, 1H), 2.03 (ddd, J ) 10.5,
8, 4 Hz, 1H), 2.25 (ddd, J ) 10.5, 10, 7 Hz, 1H), 2.77 (ddd, J )
18, 10.5, 5.5 Hz, 1H), 2.88 (ddd, J ) 18, 10, 7 Hz, 1H). 13C NMR
(150.8 MHz, CDCl3, CDCl3 int): δ ) 19.9 (t), 20.7 (t), 21.4 (t),
22.7 (t), 23.8 (t), 34.7 (t), 34.8 (t), 35.4 (t), 35.6 (t), 38.8 (t), 38.9
(t), 40.4 (t), 55.9 (s), 59.0 (s), 76.1 (s), 216.4 (s). MS (EI): m/e )
232 (23, M+), 108 (100). C16H24O requires C, 82.70; H, 10.41.
Found: C, 82.54; H, 10.56.
(5S*)-Trispiro[3.0.0.4.3.3]hexadecane (5S*-8). To a solution
of sodium (276 mg, 12.0 mmol) in diethylene glycol (16 mL) were
added 36 (232 mg, 1.0 mmol) and anhydrous hydrazine (2.60 g,
81 mmol), and the mixture was heated under argon with stirring to
180 °C until GC analysis [column A, 230 °C; retention times
(min): 3.75 (8), 10.09 (36), 25.80 (hydrazone)] indicated that 36
had been consumed (66 h). Most of the surplus hydrazine and most
of the water formed were distilled off under a stream of argon while
the temperature was gradually raised to 200-205 °C. According
to GC, after additional 72 h at this temperature the reduction was
complete. The apparatus was rinsed with pentane (20 mL), and the
reaction mixture was poured into water (60 mL) and extracted with
pentane (2 × 60 mL). The combined organic phases were washed
with water (3 × 60 mL), dried (MgSO4), and concentrated (bath
temperature 35 °C/15 Torr), and the residue was filtered over a
short path of silica gel (0.05-0.20 mm, column 15 × 1 cm) and
eluted with pentane [Rf ) 0.77 (8)]. The solvent was evaporated
(bath temperature 50 °C/15 Torr) to yield 140 mg (58%) of crude
8 as a colorless liquid (purity 90% GC). An analytically pure sample
was obtained by preparative GC. 1H NMR (600 MHz, CDCl3,
CHCl3 int): δ ) 1.24-1.29 (m, 1H), 1.30-1.38 (m, 4H), 1.43-
1.74 (m, 16H), 1.78-1.90 (m, 2H), 1.93 (ddd, J ) 12, 8, 4 Hz,
1H), 2.25 (ddd, J ) 10, 10, 10 Hz, 1H), 2.31 (ddd, J ) 10, 10, 10
Hz, 1H). 13C NMR (150.8 MHz, CDCl3, CDCl3 int): δ ) 15.9 (t),
19.6 (t), 20.6 (t), 23.7 (t), 24.7 (t), 30.3 (t), 32.0 (t), 32.6 (t), 34.1
(t), 35.1 (t), 35.8 (t), 40.4 (t), 41.4 (t), 52.1 (s), 55.7 (s), 56.5 (s).
1
cm-1 (OHass.). H NMR (600 MHz, C6D6, C6D5H int): δ ) 0.97
(t, J ) 7 Hz, 3H), 1.39-1.86 (m, 16H), 1.92-1.99 (m, 1H), 2.13-
2.22 (m, 3H), 2.41 (mc, 1H), 3.32 (q, J ) 7 Hz, 2H), 3.93 (d, J )
2 Hz, 1H), 4.40 (d, J ) 2 Hz, 1H). 13C NMR (150.8 MHz, C6D6,
C6D6 int): δ ) 14.3 (q), 20.1 (t), 20.3 (t), 24.3 (t), 25.5 (t), 33.6
(t), 35.6 (t), 35.8 (t), 36.5 (t), 39.3 (t), 41.5 (t), 56.6 (s), 60.9 (s),
62.9 (t), 82.1 (t), 85.8 (s), 166.3 (s). MS (EI): m/e ) 264 (22,
M+), 97 (100). HRMS m/e (M+) calcd 264.2089, obsd 264.2089.
(1S*,5S*)-1-(1-Ethoxy-cyclopropyl)-dispiro[4.0.4.3]tridecane-
1-ol [(1S*,5S*)-35]. To a suspension of freshly prepared zinc/silver
couple30 (9.2 g) in anhydrous ether (50 mL) was added under argon
with stirring diiodomethane (20.7 g, 77.4 mmol) causing an
exothermic effect and a gentle to strong reflux. After 20 min, 33
(3.65 g, 13.8 mmol, purity 81%) was added, and after an additional
1.5 h of reflux, the reaction was complete according to GC [column
B, 210 °C; retention times (min): 4.32 (33), 6.41 (35)]. The mixture
9274 J. Org. Chem., Vol. 72, No. 24, 2007

Helical and Pseudohelical Hydrocarbon Syntheses
MS (EI): m/e ) 218 (1, M+), 79 (100). C16H26 requires C, 88.00;
H, 12.00. Found: C, 87.87; H, 11.83.
19.3 (t), 19.7 (t), 23.7 (t), 24.6 (t), 33.3 (t), 33.4 (t), 33.5 (t), 35.4
(t), 35.5 (t), 36.6 (t), 40.1 (t), 40.8 (t), 46.9 (t), 51.9 (s), 56.2 (s),
56.5 (s), 216.8 (s). MS (EI): m/e ) 246 (3, M+), 67 (100). C17H26O
requires C, 82.87; H, 10.64. Found: C, 82.67; H, 10.42.
(4R*,5S*)-1-Methylen-trispiro[3.0.0.4.3.3]hexadecane [(4R*,
5S*)-37]. To a suspension of methyltriphenylphosphonium bromide
(3.97 g, 11.1 mmol) in dry benzene (20 mL) was added under argon
with stirring potassium t-butoxide (1.12 g, 10.0 mmol), and the
mixture was heated to reflux. After 2.5 h, most of the benzene was
distilled off (bath temperature up to 120 °C) until 36 (700 mg, 2.92
mmol) was added. According to GC [column B, 200 °C; retention
times (min): 3.73 (37), 7.56 (36)] after 1.5 h at 120 °C the reaction
was complete. The mixture was diluted with pentane (40 mL) and
hydrolyzed with water (0.8 mL). The organic phase was decanted,
the residue was extracted with pentane (3 × 8 mL), and the
combined organic phases were concentrated over a 30 cm vigreux
column (bath temperature up to 90 °C). Precipitated triphenylphos-
phine oxide was filtered off, and the filtrate was chromatograped
on silica gel (0.05-0.20 mm) in pentane [column 30 × 2.5 cm, Rf
) 0.66 (37)] yielding 582 mg (87%) of 37 as a colorless glassy
solid, mp 27-33 °C (purity >99% GC). IR (neat): 1660 cm-1
rac-Trispiro[4.0.0.4.3.3]heptadecane (rac-9). To finely ground
potassium hydroxide (224 mg, 4.0 mmol) and hydrazine hydrate
(150 mg, 3.0 mmol) in diethylene glycol (2.5 mL) was added 38
(123 mg, 0.50 mmol), and the mixture was heated under argon
with stirring to 180 °C. After 2 h, GC analysis [column B, 200 °C;
retention times (min): 4.13 (9), 25.59 (38)] indicated that the
reaction was complete. The apparatus was rinsed with pentane (15
mL), and the reaction mixture was poured into water (8 mL) and
extracted with pentane (3 × 8 mL). The combined organic phases
were washed with water (2 × 8 mL), dried (MgSO4), and
concentrated over a 30 cm vigreux column (bath temperature
60 °C). The residue was chromatographed over a short path of silica
gel (0.05-0.20 mm, column 15 × 1 cm) and eluted with pentane
(Rf ) 0.74). The solvent was evaporated (bath temperature 40 °C/
1
15 Torr) to yield 94 mg (82%) of pure 9 as a colorless liquid. H
1
(CdC). H NMR (600 MHz, C6D6, C6D5H int): δ ) 1.30-1.42
NMR (600 MHz, CDCl3, CHCl3 int): δ ) 1.28-1.36 (m, 6H),
(m, 3H), 1.43-1.48 (m, 1H), 1.50-1.80 (m, 14H), 1.87 (mc, 1H),
1.96-2.01 (m, 1H), 2.15-2.26 (m, 2H), 2.46-2.56 (m, 2H), 4.83
1.45-1.67 (m, 18H), 1.67-1.73 (m, 2H), 1.82-1.88 (m, 2H). 13
C
NMR (150.8 MHz, CDCl3, CDCl3 int): δ ) 19.6 (t), 23.4 (t), 24.3
(t), 32.5 (t), 35.2 (t), 35.8 (t), 40.9 (t), 55.9 (s), 56.7 (s). MS (EI):
m/e ) 232 (14, M+), 43 (100). C17H28 requires C, 87.86; H, 12.14.
Found: C, 88.06; H 11.92.
(dd, J ) 2.25, 2.25 Hz, 1H), 4.85 (dd, J ) 2.75, 2.75 Hz, 1H). 13
C
NMR (150.8 MHz, C6D6, C6D6 int): δ ) 19.6 (t), 19.8 (t), 23.2
(t), 24.1 (t), 25.5 (t), 26.2 (t), 33.2 (t), 34.9 (t), 35.2 (t), 36.0 (t),
39.6 (t), 43.7 (t), 56.4 (s), 57.3 (s), 60.2 (s), 106.2 (t), 158.6 (s).
MS (EI): m/e ) 230 (28, M+), 121 (100). C17H26 requires C, 88.63;
H, 11.37. Found: C, 88.53; H, 11.09.
(1R*,4S*)-1-Cyclopent-1-enyl-dispiro[3.0.4.3]dodecan-1-ol [(1R*,
4S*)-42]. To a solution of 1-bromo-cyclopentene36a (10.6 g, 72
mmol) in anhydrous THF (240 mL) was added within 1 h at -78
°C under argon with stirring a 1.5 M solution of tert-butyllithium
in pentane (96 mL, 144 mmol). After an additional 45 min at -78
°C, the mixture was allowed to warm to 0 °C. The resulting 0.21
M solution of 1-lithio-cyclopentene (340 mL) was used in the next
step. A suspension of finely powdered dry CeCl3 (14.8 g, 60 mmol)
in anhydrous THF (220 mL) was stirred at room temperature under
argon for 2 h. After addition of 41 (5.34 g, 30 mmol, purity 87%),
stirring was continued for 2 h until the mixture was cooled to 0
°C, and 230 mL (48 mmol) of the 0.21 M solution of 1-lithio-
cyclopentene was added. Afterward, the mixture was stirred at room
temperature, and the reaction progress was monitored by GC
[column B, 200 °C; retention time (min): 2.56 (41), 5.90 (42)].
After 16 h, 28% of unreacted ketone was still present. Therefore,
the remaining 110 mL (23 mmol) of the 0.21 M solution of 1-lithio-
cyclopentene was added, and, after an additional 30 min, the
reaction was complete. The mixture was diluted with pentane (300
mL) and hydrolyzed with saturated aqueous ammonium chloride
(60 mL). The liquid phase was decanted, the residue was extracted
with pentane (2 × 150 mL), and the combined organic phases were
washed with water (2 × 300 mL) and dried (MgSO4). The solvents
were distilled off (bath temperature 40 °C/15 Torr), and the residual
brown liquid (8.8 g) was chromatographed on silica gel (0.05-
0.20 mm) in pentane/ether 9:1 [column 100 × 7 cm, Rf ) 0.46
(42)] yielding 5.49 g (82%) of 42 as a colorless liquid (purity 96%
(3S*,4R*,5S*)-1-Oxa-tetraspiro[2.0.0.0.4.3.3.2]octadecane [(3S*,
4R*,5S*)-39]. To a solution of 37 (582 mg, 2.53 mmol) in
dichloromethane (8.0 mL) was added 3-chloroperoxybenzoic acid
(940 mg, 70% w/w, 3.80 mmol), and the mixture was stirred at
room temperature. According to TLC [pentane/ether 9:1, Rf ) 0.72
(37), 0.30 (39)] after 1.5 h the reaction was complete. The mixture
was washed with 1 N KOH (6 mL), the aqueous phase was
extracted with dichloromethane (3 × 8 mL), and the combined
organic phases were washed with water (2 × 15 mL) and dried
(MgSO4). The solvent was distilled off (bath temperature 40 °C/
15 Torr) and the solid residue (650 mg) chromatographed on silica
gel (0.05-0.20 mm) in pentane/ether 9:1 (column 65 × 4.5 cm) to
yield 360 mg (58%) of pure 39 as a colorless glassy solid, mp 78
1
°C. H NMR (600 MHz, C6D6, C6D5H int): δ ) 1.20-1.82 (m,
20H), 1.90-1.99 (m, 1H), 2.08-2.19 (m, 2H), 2.43 (d, J ) 4.5
Hz, 1H), 2.54-2.68 (m, 1H), 2.83 (d, J ) 4.5 Hz, 1H). 13C NMR
(150.8 MHz, C6D6, C6D6 int): δ ) 20.3 (t), 21.3 (t), 22.9 (t), 23.7
(t), 23.9 (t), 26.1 (t), 33.8 (t), 35.2 (t), 36.7 (t), 37.17 (t), 37.19 (t),
40.8 (t), 54.0 (t), 55.3 (s), 58.1 (s), 58.7 (s), 65.5 (s). MS (EI): m/e
) 246 (3, M+), 108 (100). C17H26O requires C, 82.87; H, 10.64.
Found: C, 82.61; H, 10.48.
(5S*,6S*)-Trispiro[4.0.0.4.3.3]heptadecan-2-one [(5S*,6S*)-
38]. Lithium iodide (1.98 g, 14.8 mmol) was dried for 1.5 h at 120
°C/0.1 Torr and dissolved in anhydrous THF (14.8 mL, exothermic
effect) yielding a 1 M stock solution. A total of 0.98 mL (0.98
mmol) of this solution was added to a solution of 39 (242 mg,
0.98 mmol) in anhydrous THF. After 6 h at 60-70 °C, TLC
[pentane/ether 8:2, Rf ) 0.67 (39), 0.42 (38)] indicated that the
rearrangement was complete. The mixture was diluted with pentane
(4 mL) and washed with water (4 mL). The aqueous phase was
extracted with pentane (3 × 5 mL), and the combined organic
phases were washed with water (2 × 8 mL) and dried (MgSO4).
The solvents were evaporated (bath temperature 45 °C/15 Torr),
and the liquid residue was chromatographed on silica gel (0.05-
0.20 mm) in pentane/ether 8:2 (column 95 × 2.5 cm, Rf ) 0.42)
yielding 213 mg (88%) of 38 as a colorless liquid. According to
GC [column B, 230 °C; retention time (min): 9.58 (38)] the material
was >99% pure. IR (neat):1745 cm-1 (CdO). 1H NMR (600 MHz,
C6D6, C6D5H int): δ ) 1.08-1.13 (m, 1H), 1.15-1.27 (m, 4H),
1.28-1.58 (m, 16H), 1.80-1.94 (m, 2H), 1.94-2.01 (m, 2H), 2.17
(d, J ) 17 Hz, 1H). 13C NMR (150.8 MHz, C6D6, C6D6 int): δ )
1
GC). IR (neat): 3600 (OH), 3580-3350 cm-1 (OHass.). H NMR
(600 MHz, C6D6, C6D5H int): δ ) 0.94-0.97 (m, 1H), 1.32-
1.60 (m, 8H), 1.61-1.72 (m, 4H), 1.73-1.84 (m, 4H), 1.89-1.95
(m, 1H), 2.15 (mc, 1H), 2.22-2.28 (m, 3H), 2.31 (mc, 1H), 2.35-
2.45 (m, 2H), 5.43 (dddd, J ) 2, 2, 2, 2 Hz, 1H). 13C NMR (150.8
MHz, C6D6, C6D6 int): δ ) 19.5 (t), 24.4 (t), 25.1 (t), 25.6 (t),
26.7 (t), 31.9 (t), 32.6 (t), 33.4 (t), 34.2 (t), 35.5 (t), 36.3 (t), 38.9
(t), 55.2 (s), 58.2 (s), 81.2 (s), 125.4 (d), 149.4 (s). MS (EI): m/e
) 246 (1, M+), 110 (100). HRMS m/e (M+) calcd 246.1984, obsd
246.1984. C17H26O requires C, 82.87; H, 10.64. Found: C, 81.64:
H, 10.33.
(6S*,7S*,8R*)-8-Bromo-trispiro[4.0.0.4.3.3]heptadecan-12-
one [(6S*,7S*,8R*)-43]. To dry zinc bromide (1.08 g, 4.8 mmol)
in dry acetonitrile (22 mL) was added dry N-chloro-toluene-4-
sulfonamide (1.09 g, 4.8 mmol), and the mixture was stirred under
argon until a nearly clear yellow solution was formed (10 min).
This solution was added under argon with stirring to neat 42 (984
J. Org. Chem, Vol. 72, No. 24, 2007 9275

Widjaja et al.
mg, 4.0 mmol). A precipitate formed, and the mixture went
colorless. After 15 min, TLC [pentane/ether 8:2; Rf ) 0.62 (42),
0.45 (43)] indicated that the reaction was complete. The mixture
was filtered over a short path of silica gel (colum 8 × 4.5 cm) and
eluted with ether. The solvents were evaporated (bath temperature
40 °C/15 Torr), and the heterogeneous residue was extracted with
pentane (2 × 25 mL). The extracts were concentrated (bath
temperature 40 °C/15 Torr), and the residue (1.34 g) was chro-
matographed on silica gel (0.05-0.20 mm) in pentane/ether 8:2
(column 70 × 4.5 cm) to yield 1.07 g (82%) of pure 43 as a slightly
-78 °C continued until TLC [pentane/ether 9:1, Rf ) 0.52 (48),
0.43 (41)] indicated that no further reaction occurred (1 h). The
still cold mixture was hydrolyzed with saturated aqueous ammonium
chloride (5 mL), and the organic phase was separated and dried
(MgSO4). The solvents were evaporated (bath temperature 60 °C/
20 Torr), and the remaining liquid (3.60 g) was chromatographed
on silica gel (0.05-0.20 mm) in pentane/ether 9:1 (column 65 ×
4.5 cm) to yield 1.26 g (37%) of a 85:15 mixture of 48 and 41 as
a vile-smelling colorless liquid. This material was used in the next
step. 48: 1H NMR (600 MHz, CDCl3, CHCl3 int): δ ) 1.24-
1.35 (m, 3H), 1.36-1.48 (m, 4H), 1.49-1.69 (m, 6H), 1.77-1.99
(m, 4H), 2.02-2.18 (m, 3H), 2.12 (s, 3H), 2.21-2.34 (m, 3H),
2.47 (mc, 1H), 2.67-2.74 (m, 1H). 13C NMR (150.8 MHz, CDCl3,
CDCl3 int): δ ) 4.9 (q), 16.6 (t), 19.1 (t), 25.7 (t), 25.8 (t), 27.3
(t), 28.5 (t), 29.0 (t), 34.1 (t), 34.2 (t), 34.8 (t), 35.1 (t), 38.1 (t),
55.2 (s), 56.9 (s), 58.5 (s), 83.8 (s).
1
beige-colored solid, mp 76 °C. IR (KBr): 1730 cm-1 (CdO). H
NMR (600 MHz, C6D6, C6D5H int): δ ) 1.03-1.15 (m, 3H), 1.18-
1.27 (m, 2H), 1.30-1.51 (m, 10H), 1.52-1.67 (m, 3H), 1.85 (mc,
1H), 1.89-2.07 (m, 3H), 2.15 (ddd, J ) 18.5, 10, 10 Hz, 1H),
2.47-2.56 (m, 1H), 4.11 (ddd, J ) 8, 8, 2.5 Hz, 1H). 13C NMR
(150.8 MHz, C6D6, C6D6 int): δ ) 19.9 (t), 23.2 (t), 23.7 (t), 24.3
(t), 28.8 (t), 31.4 (t), 33.9 (t), 34.7 (t), 35.7 (t), 35.8 (t), 37.4 (t),
40.1 (t), 53.6 (d), 56.6 (s), 56.7 (s), 65.1 (s), 215.8 (s). MS (EI):
m/e ) 326, 324 (9, 9, M+), 108 (100). C17H25BrO requires C, 62.77;
H, 7.75. Found: C, 62.85; H, 7.64.
(6S*)-Trispiro[4.0.0.4.3.3]heptadecan-12-one [(6S*)-46]. A
mixture of 43 (976 mg, 3.00 mmol) and zinc powder (1.11 g, 17
mmol) in acetic acid (3.0 mL) was heated under argon with stirring
to 60 °C. According to GC [column B, 230 °C; retention times
(min): 6.63 (46), 11.89 (43)], after 1.5 h the reaction was complete.
The mixture was diluted with water (40 mL) and extracted with
pentane (40 mL). The aqueous phase was extracted with pentane
(3 × 30 mL), and the combined organic phases were washed with
saturated aqueous sodium bicarbonate (80 mL) and water (2 × 80
mL) and dried (MgSO4). The solvent was evaporated (bath
temperature 40 °C/15 Torr), and the remaining 46 (mp 61 °C, purity
94% GC) was used in the next step. Crystallization from acetone
by diffusion of water yielded an analytically pure sample of
colorless crystals, mp 67-68 °C. IR (KBr): 1730 cm-1 (CdO).
1H NMR (600 MHz, C6D6, C6D5H int): δ ) 1.10-1.16 (m, 1H),
1.20-1.35 (m, 5H), 1.37-1.63 (m, 14H), 1.64-1.74 (m, 2H),
1.89-1.99 (m, 2H), 2.02 (mc, 1H), 2.14 (ddd, J ) 19, 10, 2 Hz,
1H). 13C NMR (150.8 MHz, C6D6, C6D6 int): δ ) 20.3 (t), 23.3
(t), 24.0 (t), 25.2 (t), 25.5 (t), 28.7 (t), 29.7 (t), 31.1 (t), 32.8 (t),
33.1 (t), 34.7 (t), 36.4 (t), 40.1 (t), 55.0 (s), 56.1 (s), 63.3 (s), 219.0
(s). MS (EI): m/e ) 246 (100, M+). C17H26O requires C, 82.87;
H, 10.64. Found: C, 82.68; H, 10.65.
(5S*)-Trispiro[3.0.0.4.3.3]hexadecan-16-one [(5S*)-47]. To a
solution of 4-chloroperoxybenzoic acid (2.94 g, 70% w/w, 12.0
mmol) in dichloromethane (30 mL) was added under argon with
stirring 48 (556 mg, 1.70 mmol), causing a slightly exothermic
effect. After 45 min, the reaction was complete according to TLC
[pentane/ether 9:1, Rf ) 0.52 (48), 0.43 (41), 0.27 (47)]. The mixture
was washed with 1 N NaOH (3 × 20 mL) and water (30 mL) and
dried (MgSO4). The solvent was evaporated (bath temperature
30 °C/15 Torr) and the residue (520 mg) chromatographed on silica
gel in pentane/ether 9:1 (colum 45 × 2.5 cm) to yield 236 mg (70%)
of 47 as a colorless liquid. According to GC [column B, 230 °C;
retention time (min): 3.78 (47)], the material was >99% pure. IR
1
(neat): 1735 cm-1 (CdO). H NMR (600 MHz, CDCl3, CHCl3
int): δ ) 1.32-1.38 (m, 3H), 1.46-1.67 (m, 11H), 1.67-1.77 (m,
2H), 1.84-1.98 (m, 3H), 2.04 (mc, 1H), 2.17-2.25 (m, 3H), 2.29
(mc, 1H). 13C NMR (150.8 MHz, CDCl3, CDCl3 int): δ ) 14.8
(t), 19.7 (t), 22.6 (t), 23.3 (t), 25.5 (t), 28.2 (t), 28.3 (t), 33.05 (t),
33.09 (t), 33.4 (t), 35.1 (t), 38.4 (t), 54.2 (s), 56.4 (s), 58.4 (s),
221.1 (s). MS (EI): m/e ) 232 (30, M+), 123 (100). C16H24O
requires C, 82.70; H, 10.41. Found: C, 82.76; H, 10.12.
(5S*)-Trispiro[3.0.0.4.3.3]hexadecane [(5S*)-8]: The reduction
of 47 was performed as described for 36. A total of 116 mg (0.5
mmol) of 47 yielded 87 mg (78%) of (5S*)-8. According to GC
[column A, 230 °C; retention times (min): 3.86 (8), 13.54 (47),
34.31 (hydrazone)], the formation of the hydrazone occurred at 16
h at 180 °C, and the subsequent liberation of 8 occurred at 72 h at
200-205 °C. The 1H and 13C NMR data were identical with those
of an authentic sample.
(SS,1R,4R)-(+)-[(N-Methyl-S-phenylsulfonimidoyl)methyl]-
dispiro[3.0.4.3]dodecan-1-ol [(SS,1R,4R)-(+)-50] and (SS,1S,4S)-
(+)-[(N-Methyl-S-phenylsulfonimidoyl)methyl]-dispiro[3.0.4.3]-
dodecan-1-ol [(SS,1S,4S)-(+)-52]. To a solution of (S)-(+)-N,S-
dimethyl-S-phenylsulfonimid39 (8.80 g, 50 mmol) in anhydrous THF
(150 mL) was added at 0 °C under argon with stirring a 1.6 M
solution of n-butyllithium in hexane (31.2 mL, 50 mmol). The
mixture was stirred for 1 h at 0 °C and then used in the next step.
A suspension of finely powdered dry CeCl3 (4.94 g, 20 mmol) in
anhydrous THF (75 mL) was stirred at room temperature under
argon for 2 h. After addition of rac-41 (1.78 g, 10 mmol), stirring
was continued for 2 h until the mixture was cooled to -78 °C;
then the solution of the lithiated N,S-dimethyl-S-phenylsulfonimid
was added within 15 min. According to TLC (pentane/ether 7:3;
Rf ) 0.58 (41), 0.33 [(SS,1R,4R)-50], 0.25 [(SS,1S,4S)-52]), after
1 h at -78 °C and 1 h at room temperature, the reaction had ceased.
The mixture was diluted with ether (300 mL) and hydrolyzed with
water (10 mL). The liquid phase was decanted, the residue was
extracted with ether (100 mL), and the combined organic phases
were dried (MgSO4) and concentrated (20 °C/15 Torr). The residue
(6.10 g) was chromatographed on silica gel (0.05-0.20 mm) in
pentane/ether 7:3 (column 70 × 5 cm) to yield 0.26 g (15%) of
unreacted 41 as a colorless liquid, 1.28 g (37%) of (SS,1R,4R)-50
as a colorless solid, mp 61-63 °C, (purity 99% 1H NMR, 99% ee,
[R]2D0 ) +61.3, c ) 1.07, CHCl3), and 0.84 g (24%) of (SS,1S,4S)-
rac-Trispiro[4.0.0.4.3.3]heptadecane (rac-9): To a solution of
sodium (276 mg, 12.0 mmol) in diethylene glycol (16 mL) were
added 46 (246 mg, 1.0 mmol) and anhydrous hydrazine (2.60 g,
81 mmol), and the mixture was heated under argon with stirring to
180 °C until GC analysis [column A, 230 °C; retention times
(min): 2.06 (9), 5.93 (46), 51.85 (hydrazone)] indicated that 46
had been consumed (48 h). Most of the surplus hydrazine and of
the water formed was distilled off under a stream of argon while
the temperature was gradually raised to 200-205 °C. After 10 days
at this temperature the reduction was complete. The apparatus was
rinsed with pentane (20 mL), and the reaction mixture was poured
into water (50 mL) and extracted with pentane (2 × 50 mL). The
combined organic phases were washed with water (3 × 50 mL)
and dried (MgSO4). The solvent was evaporated (bath temperature
35 °C/15 Torr), and the residue (150 mg) was filtered over a short
path of silica gel (0.05-0.20 mm, column 18 × 1 cm) and eluted
with pentane [Rf ) 0.74 (rac-9)] to yield 119 mg (50%) of rac-9
1
as a colorless liquid (purity 96% GC). The H and 13C NMR data
were identical with those of an authentic sample prepared from
37.
(1S*,4S*)-1-[(1′-Methylselanyl)cyclobutyl)]dispiro[3.0.4.3]-
dodecan-1-ol [(1S*,4S*)-48]. To a solution of 1,1-bis(methylselanyl)-
cyclobutane38a (2.70 g, 11.0 mmol) in anhydrous ether (11 mL)
was added at -78 °C under argon with stirring a 1.5 M solution of
tert-butyllithium in pentane (7.9 mL, 11.8 mmol) such that the
internal temperature did not exceed 60 °C (1 h). After an additional
1 h at -78 °C, 41 (1.60 g, 9.0 mmol) was added, and stirring at
9276 J. Org. Chem., Vol. 72, No. 24, 2007

Helical and Pseudohelical Hydrocarbon Syntheses
1
52 as a colorless solid, mp 70 °C, (purity 99% H NMR, 99% ee,
CH3OH). The chemical purity was determined by GC [column A,
[R]2D0 ) +42.0, c ) 1.06, CHCl3). Both sulfonimides were
crystallized from ethanol by diffusion of water. (SS,1R,4R)-(+)-
1
230 °C; retention time (min): 3.71 (4R)-(+)-41]. The H and 13C
NMR data were identical with those of rac-41.
50: IR (KBr): 3600-3200 cm-1 (OHass.). H NMR (600 MHz,
1
(4S)-(-)-Dispiro[3.0.4.3]dodecan-1-one [(4S)-(-)-41]. (SS,1S,4S)-
(+)-52 (675 mg, 1.94 mmol) was thermolyzed and the reaction
mixture purified as described for (SS,1R,4R)-(+)-50, yielding 331
mg (96%) of (4S)-(-)-41 as a colorless liquid (purity 99%, >99%
ee, [R]2D0 ) -145, c ) 1.14, acetone; θ307 ) -6538, CH3OH). The
1H and 13C NMR data were identical with those of rac-41.
X-ray Analyses of 26, 34, 43, 49, 50, and 52. The data were
collected at 140 K on a Stoe IPDS 2 diffractometer with Mo KR
radiation (71.073 pm) (26, 34, 43) and at 100 K on a Bruker-Smart
6000 diffractometer with Cu KR radiation (154.178 pm) (49, 50,
52), respectively. The structures were solved by direct methods and
refined anisotropically against F2 using SHELXL-97.59 The crystal-
lographic data (excluding structure factors) have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
publications number CCDC 652397 (26), 652398 (34), 652399 (43),
652400 (49), 652401 (50), and 652402 (52). Copies of the data
can be obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, U.K. (fax: +44-1223-336033; e-
mail: deposit@ccdc.cam.ac.uk).
CD2Cl2, CDHCl2 int, -50 °C): δ ) 1.05-1.10 (br s, 1H), 1.13-
1.24 (m, 2H), 1.37-1.50 (m, 10H), 1.51-1.59 (m, 2H), 2.04 (mc,
1H), 2.14 (mc, 1H), 2.25-2.32 (m, 1H), 2.48 (s, 3H), 2.55 (mc,
1H), 3.22 (AB, ∆νAB ) 45 Hz, JAB ) 13 Hz, 2H), 7.58 (t, J ) 7.5
Hz, 2H), 7.64 (t, J ) 7.5 Hz, 1H), 7.84 (d, J ) 7.5 Hz, 2H). 13C
NMR (150.8 MHz, CDCl3, CDCl3 int): δ ) 18.60 (t), 24.75 (t),
24.91 (t), 27.77 (t), 28.69 (q), 31.34 (t), 33.75 (t), 34.68 (t), 34.72
(t), 38.02 (t), 54.72 (s), 58.26 (s), 62.32 (t), 78.52 (s), 128.95 (d),
129.65 (d), 133.29 (d), 138.38 (s). MS (EI): m/e ) 348 (<1, M+),
125 (100). C20H29NO2S requires C, 69.12; H, 8.41. Found: C,
68.99: H, 8.66. (SS,1S,4S)-(+)-52: IR (KBr): 3350-3100 cm-1
(OHass.). 1H NMR (600 MHz, CD2Cl2, CDHCl2 int, -50 °C): δ )
1.06-1.24 (m, 5H), 1.27-1.33 (m, 1H), 1.35-1.48 (m, 5H), 1.49-
1.61 (m, 5H), 1.96 (mc, 1H), 2.24 (mc, 2H), 2.63 (s, 3H), 3.33 (AB,
∆νAB ) 29 Hz, JAB ) 14 Hz, 2H), 7.55 (t, J ) 7.5 Hz, 2H), 7.63
(t, J ) 7.5 Hz, 1H), 7.78 (d, J ) 7.5 Hz, 2H). 13C NMR (150.8
MHz, CDCl3, CDCl3 int): δ ) 18.7 (t), 24.7 (t), 24.9 (t), 27.1 (t),
28.8 (q), 32.4 (t), 33.5 (t), 34.5 (t), 34.8 (t), 37.9 (t), 54.8 (s), 58.0
(s), 63.2 (t), 76.7 (s), 129.47 (d), 129.54 (d), 133.4 (d), 138.3 (s).
MS (EI): m/e ) 348 (1, M+), 211 (100). C20H29NO2S requires C,
69.12; H, 8.41. Found: C, 69.24; H, 8.50.
Supporting Information Available: Experimental procedures
for all compounds not covered in the Experimental Section, 1H and
13C NMR spectra, data of the X-ray analyses including ORTEP-
plots of 26, 34, 43, 49, 50, and 52, and computational data of the
(P)-helices of 1, 2, 3, 4, 5, 9, and 10. This material is available
free of charge via the Internet at http://pubs.acs.org.
(4R)-(+)-Dispiro[3.0.4.3]dodecan-1-one[(4R)-(+)-41].(SS,1R,4R)-
(+)-50 (1.10 g, 3.16 mmol) was heated under argon to 110 °C.
According to TLC (pentane/ether 7:3; Rf ) 0.52 [(4R)-(+)-41], 0.30
[(SS,1R,4R)-(+)-50]), after 14 h the reaction was complete. The
mixture was dissolved in ether, the solution was concentrated (20
°C/15 Torr), and the residue was chromatographed on silica gel
(0.05-0.20 mm) in pentane/ether 7:3 (column 45 × 2.5 cm)
yielding 495 mg (87%) of (4R)-(+)-41 as a colorless liquid (purity
99%, >99% ee, [R]2D0 ) +145, c ) 1.21, acetone; θ307 ) +6328,
JO7017558
(59) Sheldrick, G. M. SHELXL-97, a program for crystal structure
refinement; University of Go¨ttingen, 1997.
J. Org. Chem, Vol. 72, No. 24, 2007 9277