Conjugatively stabilized bridgehead olefins: Formation and reaction of remarkably stable homoadamant-3-enes substituted with phenyl and methoxycarbonyl groups

Article abstract of DOI:10.1021/ja953977q

Conjugatively stabilized double bonds were formed at the bridgehead of homoadamantane by way of the 1,2-carbon shift of adamantylcarbene (-carbenoid) intermediates generated from decomposition of the diazo precursors (1-adamantyl)diazophenylmethane (7) an

Full text of DOI:10.1021/ja953977q

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J. Am. Chem. Soc. 1996, 118, 7075-7082
7075
Conjugatively Stabilized Bridgehead Olefins: Formation and
Reaction of Remarkably Stable Homoadamant-3-enes
Substituted with Phenyl and Methoxycarbonyl Groups
Masatomi Ohno, Motohiro Itoh, Masami Umeda, Ryoji Furuta,
Kazumoto Kondo, and Shoji Eguchi*
Contribution from the Institute of Applied Organic Chemistry, Faculty of Engineering,
Nagoya UniVersity, Chikusa, Nagoya 464-01, Japan
ReceiVed NoVember 27, 1995X
Abstract: Conjugatively stabilized double bonds were formed at the bridgehead of homoadamantane by way of the
1,2-carbon shift of adamantylcarbene (-carbenoid) intermediates generated from decomposition of the diazo precursors
(1-adamantyl)diazophenylmethane (7) and methyl (1-adamantyl)diazoacetate (10). Decomposition to 4-phenyl- and
4-methoxycarbonyl-substituted homoadamant-3-enes 1 and 2 was much more efficient Via catalysis with Rh2(OAc)4
in dichloromethane than by photolysis or thermolysis (FVP; in the case of 7, indane-fused homoadamantane was
produced by a phenylcarbene rearrangement followed by insertion to a bridged methylene). In the Rh catalysis,
reactions of 7 and 10 in hexane and with Rh2(NHCOCH3)4 did not promote the formation of 1 and 2, suggesting that
the polarized structure of the Rh-carbene complex participated in the 1,2-carbon shift. The substituted bridgehead
olefins were considerably stable even at 0 °C to room temperature (more than half of 1 and 2 survived in solution
at room temperature after 12 and 1 h, respectively), while parent homoadamant-3-ene was recorded to be unstable
at -20 °C. Therefore, after decomposition of the diazo precursors was complete, reagents (electrophies for 1 and
nucleophiles for 2) were allowed to react at these temperatures to give 3,4-disubstituted homoadamantane derivatives,
including some cycloadducts. With atmospheric oxygen, addition and subsequent bond cleavage occurred smoothly
to give bicyclo[3.3.1]nonanones. The remarkable stability of 1 and 2 was considered to be the result of conjugation
with the substituents, along with some steric protection, which allowed the polarized structure to have a greater
effect in reducing the strain energy. This notion was verified by examining longer carbon-carbon double bonds
using spectroscopy and PM3 calculations.
Bridgehead olefins have attracted continuous attention since
and adamantene6 have been shown to be highly unstable.
Homoadamant-3-ene (3)7 is a bridged cycloheptene with an
olefin strain energy of 20 kcal/mol.3 This value suggests that
it can be observed only at very low temperature, which is in
fact the case.7e
The introduction of a substituent to such bridgehead olefins
is believed to alter their stability and reactivity. Schleyer
suggested that replacement of the vinyl hydrogen by bulky
groups or substituents which provide electronic stabilization
might result in observable species.3 In this regard, Jones
reported that 4-(1-adamantyl)homoadamant-3-ene (4) was amaz-
ingly stable and was unaffected by heating up to 185 °C.7g The
unusual stability of 4 has been attributed to steric protection.
Bredt first reported the prohibition of a double bond at a
bridgehead. Various studies have been performed to understand
the nature of such bonds, and the experimental and theoretical
results have been reviewed several times.1 The current under-
standing of the relative stability of bridgehead olefins can be
expressed by the rules suggested by Wiseman2 (who evaluated
the system as a trans-cycloalkene) and Schleyer3 (who consid-
ered olefin strain energy). In recent studies,4 noradamantene5
X Abstract published in AdVance ACS Abstracts, July 1, 1996.
(1) (a) Fawcett, F. S. Chem. ReV. 1950, 47, 219. (b) Koebrich, G. Angew.
Chem. 1973, 85, 494. (c) Keese, R. Angew. Chem., Int. Ed. Eng. 1975,
14, 528. (d) Buchanan, G. L. Chem. Soc. ReV. 1974, 3, 41. (e) Shea, K.
J. Tetrahedron 1980, 36, 1683. (f) Szeimies, G. ReactiVe Intermediate;
Abramovitch, R. A., Ed.; Plenum Press: New York, 1983; Vol. 3, p 299.
(g) Warner, P. M. Chem. ReV. 1989, 89, 1067. (h) Keese, R.; Luef, W.
Topics in Stereochemistry; Eliel, E. L., Wilen, S. H., Eds.; J. Wiley &
Sons: New York, 1991; Vol. 20, p 231.
(2) Wiseman, J. R.; Pletcher, W. A. J. Am. Chem. Soc. 1970, 92, 956.
(3) Maier, W. F.; Schleyer, P. R. J. Am. Chem. Soc. 1981, 103, 1891.
(4) For recent examples of the bridgehead olefin, see: (a) Shea, K. J.;
Cooper D. K.; England, W. P.; Ziller, J. W.; Lease, T. G. Tetrahedron
Lett. 1990, 31, 6843. (b) Chiang, Y.; Kresge, A. J.; Walsh, P. A. J. Org.
Chem. 1990, 55, 1309. (c) Trost, B. M.; Trost, M. K. J. Am. Chem. Soc.
1991, 113, 1850. (d) Detert, H.; Anthony-Mayer, C.; Meier, H. Angew
Chem., Int. Ed. Engl. 1992, 31, 791. (e) Wijsman, G. W.; Wolf, W. H.;
Bickelhaupt, F.; Kooijman, H.; Spek, A. J. Am. Chem. Soc. 1992, 114,
9191. (f) Lease, T. G.; Shea, K. J. J. Am. Chem. Soc. 1993, 115, 2248. (g)
Gudipati, M. S.; Radziszewski, J. G.; Kaszynski, P.; Michl, J. J. Org. Chem.
1993, 58, 3668. (h) Bunz, U.; Herpich, W.; Podlech, J.; Polborn, K.; Pratzel,
A.; Stephenson, D. S.; Szeimies, G. J. Am. Chem. Soc. 1994, 116, 7637.
(5) (a) Renzoni, G. E.; Yin, T.-K.; Borden, W. T. J. Am. Chem. Soc.
1986, 108, 7121. (b) Yin, T.-K.; Radziszewski, J. G.; Renzoni, G. E.;
Downing, J. W.; Michl, J.; Borden, W. T. J. Am. Chem. Soc. 1987, 109,
820. (c) Hrovat, D. A.; Borden, W. T. J. Am. Chem. Soc. 1988, 110, 4710.
(d) Radziszewski, J. G.; Yin, T.-K.; Renzoni, G. E.; Hrovat, D. A.; Borden,
W. T.; Michl, J. J. Am. Chem. Soc. 1993, 115, 1454.
(6) (a) Gano, J. E.; Eizenberg, L. J. Am. Chem. Soc. 1973, 95, 972. (b)
Alberts, A. H.; Strating, J.; Wynberg, H. Tetrahedron Lett. 1973, 3047. (c)
Burns, W.; Grant, G.; McKervey, M. A.; Step, G. J. Chem. Soc., Perkin
Trans. 1 1976, 234. (d) Martella, D. J.; Jones, M., Jr.; Schleyer, P. R. J.
Am. Chem. Soc. 1978, 100, 2896. (e) Cadgan, J. I. G.; Leardini, R. J. Chem.
Soc., Chem. Commun. 1979, 783. (f) Conlin, R. T.; Miller, R. D.; Michl,
J. J. Am. Chem. Soc. 1979, 101, 7637. (g) Gillespie, D. G.; Walker, B. J.
J. Chem. Soc., Perkin Trans. 1 1983, 1689. (h) Lenoir, D.; Kornrumpf,
W.; Fritz, H. P. Chem. Ber. 1983, 116, 2390. (i) Michl, J.; Radziszewski,
J. G.; Downing, J. W.; Kopecky, J.; Kaszynski, P.; Miller, R. D. Pure Appl.
Chem. 1987, 59, 1613. (j) Bian, N.; Jones, M., Jr. J. Am. Chem. Soc. 1995,
117, 8957.
(7) (a) Farcasiu, M.; Farcasiu, D.; Conlin, R. T.; Jones, M., Jr.; Schleyer,
P. R. J. Am. Chem. Soc. 1973, 95, 8207. (b) Adams, B. L.; Kovacic, P. J.
Am. Chem. Soc. 1973, 95, 8206. (c) Adams, B. L.; Kovacic, P. J. Org.
Chem. 1974, 39, 3090. (d) Adams, B. L.; Kovacic, P. J. Am. Chem. Soc.
1974, 96, 7014. (e) Martella, D. J.; Jones, M., Jr.; Schleyer, P. R.; Maier,
W. F. J. Am. Chem. Soc. 1979, 101, 7634. (f) Klebach, T. C.; Jones, M.,
Jr.; Kovacic, P. Tetrahedron Lett. 1977, 22, 497. (g) Sellers, S. F.; Klebach,
T. C.; Hollowood, F.; Jones, M., Jr. J. Am. Chem. Soc. 1982, 104, 5492.
(h) Myers, D. R.; Senthilnathan, V. P.; Platz, M. S.; Jones, M., Jr. J. Am.
Chem. Soc. 1986, 108, 4232. (i) Bly, R. S.; Bly, R. K.; Hossain, M. M.;
Lebioda, L.; Raja, M. J. Am. Chem. Soc. 1988, 110, 7723.
S0002-7863(95)03977-1 CCC: $12 00 © 1996 American Chemical Society

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7076 J. Am. Chem. Soc., Vol. 118, No. 30, 1996
Ohno et al.
Scheme 2
Figure 1.
Scheme 1
14. The formation of these products was explained by competi-
tive interaction of the carbene center with each ring. The
indane-fused adamatane 13 was produced as the result of
interaction with a phenyl ring Via tandem phenylcarbene
rearrangement11 and intramolecular C-H insertion. The dike-
tone 14 was produced as the result of interaction with an
adamantane ring. The desired route to 4-phenylhomoadamant-
3-ene (1), i.e., the 1,2-carbon shift of the carbene intermediate
was apparently followed by oxidative ring cleavage with
atmospheric oxygen. Strained bridgehead olefins are known
to undergo fragmentation to dicarbonyl compounds.12 On the
other hand, photolysis did not give a desired result. A hexane
solution of 7 was irradiated with a high-pressure Hg lamp
through a Pyrex filter, but the decomposition was sluggish (1 h
to complete the reaction) and only azine 15 (32%) and ketone
5 (32%) were produced. These results are summarized in
Scheme 2.
Catalytic decomposition was the most effective process for
generating 1 (Scheme 3). When a dichloromethane solution of
7 was treated with a catalytic amount of Rh2(OAc)4 under an
atmosphere of nitrogen, extrusion of nitrogen was complete
within 5 min at room temperature. Interestingly, 4-phenylho-
moadamant-4-ene (16) was obtained in 72% yield, even when
HCl was added to the resulting reaction mixture after decom-
position was complete. This result implies that the 1,2-carbon
shift took place more selectively under catalytic conditions and
the resulting bridgehead olefin could survive at room temper-
ature (if unstable at this temperature, the reaction could be
performed in the presence of a trapping reagent). The surviv-
ability of 1 was estimated by the decrease in the yield of the
product resulting from delayed addition of a reagent. When
Rh2(OAc)4-catalyzed decomposition at ambient temperature was
followed by addition of HCl after an appropriate interval, the
yield of 16 dropped from 71% (0 h) to 45% (after 12 h) and
0% (after 24 h).13 This suggests that more than half of the
bridgehead olefin 1 remained in solution14 at ambient temper-
ature after 12 h. The action of a weak acid such as acetic acid,
instead of HCl, also gave 16 in 53% yield. A catalyst/solvent
effect was observed in this rearrangement. Decomposition in
hexane proceeded more slowly to give the non-rearranged
coupling product, azine 15, in 40% yield. Furthermore, Rh2-
(NHCOCH3)4 did not promote the smooth decomposition of 7,
and only gave 15 as a separable product. On the other hand,
Rh2(OCOCF3)4 induced the 1,2-carbon shift more effectively
and increased the yield of 16 (73% yield after addition of acetic
acid).
We report here phenyl- and methoxycarbonyl-substituted ho-
moadamant-3-enes 1 and 2, which are remarkably stable mainly
due to a conjugative effect.
The conjugative bridgehead olefins 1 and 2 were formed using
the carbene method: i.e., 1,2-carbon shift of the carbene
intermediate. The corresponding diazo precursors were prepared
by oxidation of 1-adamantyl phenyl ketone hydrazone (6) with
BaMnO47g,8 and by formylation of methyl (1-adamantyl)acetate
(8) followed by diazo transfer with tosyl azide and butyllithium9
(Scheme 1). (1-Adamantyl)diazophenylmethane (7) was a wine-
colored solid, which was sufficiently pure for our purposes as
estimated from the isolated yield (80%) of the 1,3-dipolar
cycloadduct 11 with dimethyl acetylenedicarboxylate, and was
used without further purification. Methyl (1-adamantyl)diaz-
oacetate (10) was a yellow crystal, which could be purified by
silica gel chromatography, and which gave a similar 1,3-dipolar
cycloadduct 12 (88%). The obtained phenyl- and methoxycar-
bonyl-substituted diazo compounds were subjected to ther-
molytic, photolytic, and catalytic decompositions.
We first examined the case of a phenyl substituent. Ther-
molysis of 7 was carried out by means of spray flash vacuum
pyrolysis;10 a hexane solution of 7 was injected into a quartz
tube heated with an electric furnace and the products were
collected with a dry ice-cooled trap. After chromatographic
separation, two major products were obtained as an oil and a
crystal in yields (GLC) of 36% and 13% (400 °C), 37% and
23% (600 °C), and 14% and 24% (800 °C), respectively. Their
respective structures were characterized spectroscopically as
indano[1,2-1′,2′]adamantane (13) and 7-phenacylbicylo[3.3.1]-
nonan-3-one (14). The MS parent peaks at m/z 224 and 256
showed that they corresponded to 7-N2 and 7-N2+O2, respec-
tively. In the 13C-NMR spectra, the indane-fused form of 13
was suggested by a loss of symmetry, as indicated by the
presence of 10 signals due to all of the adamantane ring carbons
(DEPT analysis), and a Cs-symmetric bicyclic structure for 14
was supported by the presence of only 6 signals due to the 9
1
ring carbons. The H-NMR and IR spectra were compatible
with the assigned structures, as indicated by a methylene signal
with an ABC coupling pattern due to an indane ring in 13 and
by a doublet methylene signal due to a phenacyl group in 14,
together with carbonyl absorption at 1701 and 1688 cm-1 for
(11) McMahon, R. J.; Abelt, C. J.; Champman, O. L.; Johnson, J. W.;
Kreil, C. L.; LeRoux, J.-P.; Mooring, A. M.; West, P. R. J. Am. Chem.
Soc. 1987, 109, 2456.
(8) Oxidation was also attempted using MnO2. However, the yield of 7
was low, as estimated from the cycloadduct 11 (34% yield), and the long
reaction time (2 h) resulted in the formation of byproducts [e.g., R-(1-
adamantyl)benzyl alcohol].
(9) Regitz, M.; Maas, G. Diazo Compounds; Academic Press: Orlando,
1981; Chapter 13.
(12) (a) House, H. O.; Outcalt, R. J.; Haack, J. L.; VanDerveer, D. J.
Org. Chem. 1983, 48, 1654. (b) Bartlett, P. D.; Ganavali, R. J. J. Org.
Chem. 1991, 56, 6043. (c) Smith, J. M.; Hrovat, D. A.; Borden, W. T. J.
Am. Chem. Soc. 1993, 115, 3816.
(13) These yields were based on the relative intensity of 1H NMR signals
of the products (16: δ 6.21, 35: δ 3.49) to those of an internal standard
(benzyl ether: δ 4.56).
(10) Rubin, Y.; Lin, S. S.; Knobler, C. B.; Anthony, J.; Boldi, A. M.;
Diederich, F. J. Am. Chem. Soc. 1991, 113, 6943.
(14) Concentration of the solution: ca. 0.035 M.

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ConjugatiVely Stabilized Bridgehead Olefins
Scheme 3
J. Am. Chem. Soc., Vol. 118, No. 30, 1996 7077
Scheme 5
Scheme 4
Scheme 6
More evidently, the rearrangement aptitude of the Rh-
carbene complex intermediate was demonstrated under an
atmosphere of oxygen (Scheme 4). In this case, the Rh-carbene
complex reacts with oxygen before and after the 1,2-carbon shift.
Diketone 14 may be formed if facilitated by a ligand on Rh
and if not inhibited by the solvent. Otherwise, 5 is formed
without skeletal rearrangement. As a result, decomposition of
7 with Rh2(OAc)4 or Rh2(OCOCF3)4 in dichloromethane satur-
ated with oxygen gave 14 as the major product. In contrast, 5
was the major product under similar conditions in hexane with
Rh2(NHCOCH3)4. Thus, it is apparent that the more polar
solvent and electron-accepting ligand favored the 1,2-carbon
shift. Padwa recently demonstrated that ligands affected switch-
ing between competitive carbenoid transformations.15 When
the ligand is more electron accepting, the rhodium-carbene
complex becomes more polarized, and a reactive cation center
may therefore be involved in the carbenoid reaction. Davies
also reported a polarizing solvent effect in this polarization.16
A nonpolar solvent such as hexane disfavors the polarized
structure of the complex, leading to the formation of a product
different from that in dichloromethane. The above adamantyl-
carbene f homoadamant-3-ene rearrangement seems to be
closely related to the cationic adamantylmethyl f homoada-
mantyl rearrangement,17 and the polarized intermediate may
therefore participate prominently in the present reaction. This
is consistent with the observed solvent and ligand effects. A
similar result was obtained in the catalytic decomposition of
diazo ester 10 (Vide infra).
when a solution of 1 was exposed to air after Rh-catalyzed
decomposition. In this case, about half of 1 was destroyed
within 60 min (GLC measurement). While this result suggests
that this bond has a radical nature, a polar nature was indicated
in reactions with electrophiles. Reactions with proton acids were
as delineated above. The proton attacked the bridgehead carbon,
and subsequent deprotonation gave the isomeric homoadamant-
4-ene 16.7g The appreciable reactivity with acetic acid reflects
the nature of this strained olefin.18 In contrast, nucleophilic
addition of ethanol or aniline did not occur (Vide infra). In
this sense, while thiophenol was expected to be unreactive,
adduct 17 was obtained, albeit in a low yield. Presumably, it
was produced Via a radical pathway.19 Some cycloaddition
reactions were also successful, and the cycloadduct structures
were characterized by 13C NMR spectra coupled with DEPT
analysis and other spectral methods. Methyl R-cyanoacrylate
underwent formal [4 + 2 ] cycloaddition with 1 to give 18 after
oxidative rearomatization. Compound 18 might be formed Via
either a diradical or a zwitterionic intermediate.12a,20 The
reaction with dimethyl acetylenedicarboxylate was unusual, and
gave the [2 + 2 + 2] cycloadduct 19. These results are
summarized in Scheme 5. Scheme 6 illustrates two other
cycloaddition reactions involving a skeletal rearrangement.
Epoxidation with m-chloroperbenzoic acid gave rise to 3-phe-
nylhomoadamantan-4-one (21) as a result of homoadamantyl
f homoadamantyl rearrangement of the oxirane-fused ho-
moadamantane 20.2 1,3-Dipolar cycloaddition with tosyl azide
produced imine 23, which could be hydrolyzed to 5, Via ring
contraction of the triazoline-fused homoadamantane 22.21
In a related study on a cage compound, Eaton reported the
Bamford-Stevens reaction of tosylhydrazone 24 of cubyl phenyl
Although the stability of the bridgehead double bond was
enhanced with a phenyl group, it was still highly reactive. The
decomposition products found after allowing a solution of 1 to
stand under an atmosphere of nitrogen were not characterized,
since no low molecular weight products (e.g., a dimeric product)
could be separated on chromatography. Nevertheless, 1 reacted
with various reagents to give fragmentation, addition, and
rearrangement products. Diketone 14 was formed rapidly (59%)
(15) (a) Padwa, A.; Austin, D. J.; Price, A. T.; Semonnes, M. A.; Doyle,
M. P.; Protopopova, M. N.; Winchester, W. R.; Tran, A. J. Am. Chem.
Soc. 1993, 115, 8669. (b) Brown, D. S.; Eliott, M. C.; Moody, C. J.;
Mowlem, T. J.; Marino, J. P., Jr.; Padwa, A. J. Org. Chem. 1994, 59, 2447.
(c) Padwa, A.; Austin, D. J. Angew. Chem., Int. Ed. Engl. 1994, 33, 1797.
See also: (d) Cox, G. G.; Haigh, D.; Hindley, R. M.; Miller D. J.; Moody,
C. J. Tetrahedron Lett. 1994, 35, 3139. (e) Pirrung, M. C.; Morehead, A.
T., Jr. J. Am. Chem. Soc. 1994, 116, 8991.
(18) Similarly, the reaction with bromine gave a bromo-substituted
product which was reduced to 16 with Bu3SnH/AlBN. An analogous
electrophilic addition and elimination mechanism and formation of the
reduction product 16 may allow assignment of a tentative structure as
3-bromo-4-phenylhomoadamant-4-ene. The conclusive assignment awaits
further elaboration because 11 lines due to homoadamantene ring carbons
appeared in the 13C NMR spectrum despite Cs symmetry.
(16) (a) Davies, H. M. Tetrahedron 1993, 49, 5203. (b) Davies, H. M.;
Hu, B.; Saikali, E.; Bruzinski, P. R. J. Org. Chem. 1994, 59, 4535.
(17) Fort, R. C., Jr. Adamantane, The Chemistry of Diamond Molecules;
Marcel Dekker: New York, 1976: p 193.
(19) Mlinaric-Majerski, K.; Kaselj, M. J. Org. Chem. 1994, 59, 4362.
(20) Rasoul, H. A. A.; Hall, H. K., Jr. J. Org. Chem. 1982, 47, 2080.
(21) Lwowski, W. 1,3-Dipolar Cycloaddition Chemistry; Padwa A., Ed.;
J. Wiley & Sons: New York, 1984; Vol. 1, Chapter 5.

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7078 J. Am. Chem. Soc., Vol. 118, No. 30, 1996
Scheme 7
Ohno et al.
Scheme 9
had for 7 (Scheme 9). Decomposition occurred more slowly
in hexane (1 h at room temperature) to give azine 31.23 While
a slight increase in the yield of 29 was observed with
Rh2(OCOCF3)4, non-rearranged insertion product 30 was ob-
tained with Rh2(NHCOCH3)4. Consequently, the dipolar nature
of the Rh-carbene complex plays a significant role in promoting
the 1,2-carbon shift.
Scheme 8
The R,â-unsaturated ester at the bridgehead survived at 0 °C.
Therefore, the addition of 2 was successfully attempted after
completion of Rh-catalyzed decomposition. However, as with
1, identifiable decomposition products could not be obtained
after 2 was left without a reagent. After 10 was decomposed
with Rh2(OAc)4 in dichloromethane at 0 °C for 10 min, oxygen
was bubbled into the resulting solution to give the ring-cleaved
tricarbonyl compound 32 in 41% yield. This is similar to 1 f
14.12 While 1 did not react with a nucleophile, 2 underwent a
smooth addition reaction with an alcohol to give 3-alkoxyho-
moadamantane-4-carboxylates; as shown above, ethanol was
used to examine the efficiency of “lysis”. Likewise, adducts
33 and 34 were obtained with methanol and benzyl alcohol in
comparable yields, respectively. The formation of these adducts
indicates that the bridgehead unsaturated ester is highly reactive,
since unstrained methyl crotonate underwent no such addition
reaction under the same conditions. Other nucleophiles such
as aniline, benzylamine, and thiophenol gave adducts 35-37
in 42-80% yields. As shown above, the effective reaction with
aniline was employed as a survival test. Crowded nucleophiles
such as 2-propanol and diethylamine did not react because of
steric congestion at the bridgehead. The reaction with proton
acids such as hydrogen chloride and trifluoroacetic acid led to
the formation of 1,4-addition products 38 and 39 (78 and 53%
yields, respectively). The same product 38 was obtained with
the Lewis acid titanium tetrachloride. Reduction was achieved
with triethylsilane in the presence of trifluoromethanesulfonic
acid to yield methyl homoadamantane-4-carboxylate (40).
These addition products were characterized by spectroscopy and/
or independent synthesis. The rearranged structures were based
on 11 signals due to skeletal carbons in the 13C NMR spectra
coupled with DEPT analysis. In the 1H NMR spectra, however,
the coupling pattern of C4-H was not clearly resolved.24
Compound 40 was synthesized as a representative compound;
4-homoadamantanone (41) was converted into homoadaman-
tane-4-carboxaldehyde (43) (Ph3PdCOMe and then HClO425),
which was further oxidized to 44 (KMnO4) and esterified
(CH2N2) to authentic methyl homoadamantane-4-carboxylate.
This ester was consistent with the reduction product derived
from 2. The cycloaddition of 2 was performed by a simple
Diels-Alder reaction with butadiene to give 45 in 19%
yield.6c,d,g,h These results are summarized in Scheme 10.
ketone, which was accomplished with sodium ethoxide in
ethanol at reflux temperature to give the rearranged products
25 and 26 which had a homocubane structure.22 In contrast,
no such product was obtained from tosylhydrazone 27 or
adamantyl phenyl ketone (5) under identical conditions. Only
the insertion product 28, which retained an adamantane structure,
was obtained in good yield. This result can be explained by
the difference in the strain of each polycycle; unlike a cubyl
system, a strain-free adamantyl system need not rearrange to
the homolog in the absence of a catalyst or more energetic
conditions.
We next turn to the decomposition of diazo ester 10.
Thermolytic, photolytic, and catalytic decompositions were
carried out as for 7 (Scheme 8). In this case, the resulting
bridgehead olefin is an R,â-unsaturated ester, which is expected
to be trapped with an alcohol. Therefore, it was first character-
ized as the ethanol adduct. Spray flash vacuum pyrolysis (550
°C) gave a complex mixture after the pyrolysates were treated
with ethanol, from which only methyl 3-ethoxyhomoadaman-
tane-4-carboxylate (29) was isolated in 8% yield. Photolysis
(hexane solution including ethanol, room temperature, 7 h)
produced the rearranged product 29 and the direct insertion
product 30 in 28% and 31% yields, respectively. Alternatively,
catalytic decomposition with Rh2(OAc)4 was again most effec-
tive for the formation of the bridgehead olefin. When 10 was
treated in the presence of a catalytic amount of Rh2(OAc)4 in
dichloromethane including ethanol at room temperature, adduct
29 was obtained in 52% yield. Interestingly, even the successive
addition of ethanol after decomposition of 10 at 0 °C furnished
a comparable yield of 29 (56%). This result indicates that the
bridgehead R,â-unsaturated ester 2 is considerably stable around
0 °C. The survivability of 2 was estimated by the method that
was used for 1. In this case, aniline was used as a trapping
reagent and the yield of the product 35 (see below) after an
appropriate interval dropped from 80% (0 h) to 48% (after 1 h)
and 0% (after 2 h),13 indicating that more than half of 2 still
survived at ambient temperature after 1 h. The present case
and the aforementioned phenyl-substituted case confirm that the
bridgehead olefin is stabilized with a conjugative substituent.
In the above catalytic reaction including ethanol, a catalyst/
solvent effect controlled the mode of rearrangement of 10, as it
(23) Glaser, R.; Chen, G. S.; Barnes, C. L. J. Org. Chem. 1993, 58,
7446.
(24) Russian chemists previously reported compounds 38 and 40. In
their 1H NMR, the C4-H signal was described simply as a triplet. However,
it is split in a more complicated fashion and structures cannot be assigned
simply by referring to the data given therein: Krasutskii, P. A.; Semenova,
I. G.; Safronova, E. E.; Novikova, M. I.; Yurchenko, A. G. Zh. Org. Khim.
1989, 25, 2336.
(25) Danishefsky, S.; Nagasawa, K.; Wang, N. J. Org. Chem. 1975, 40,
1989.
(22) Eaton, P. E.; White, A. J. J. Org. Chem. 1990, 55, 1321.

+
+
ConjugatiVely Stabilized Bridgehead Olefins
J. Am. Chem. Soc., Vol. 118, No. 30, 1996 7079
Scheme 10
Figure 2.
Figure 3.
Finally, the enhanced stability of bridgehead olefins should
be addressed. As is well-known, parent homoadamant-3-ene 3
is unstable at ambient temperature and can be observed only at
much lower temperature. Indeed, Jones first characterized 1
spectroscopically at -196 °C.7e In contrast, 4-phenyl- and
4-methoxycarbonyl-substituted homoadamant-3-enes 1 and 2 are
considerably more stable at ambient temperature (Vide supra).
The stabilization by phenyl and methoxycarbonyl substituents
seems to be due essentially to their conjugative ability,26 while
kinetic stability due to steric protection, as in 4, may also play
a role. Resonance of the bridgehead olefin with these groups
promotes polarization of this bond to cause its single-bond
character to increase while the strain energy is reduced. An
informative X-ray analysis was recently reported by Shea,4a who
found that the carboxyl group-substituted bridgehead double
bond in bicyclic diene 46 was longer than the unsubstituted
bridgehead double bond. The optimized geometry according
to PM3 calculations27 suggests that the double bonds in 1 (1.363
Å) and 2 (1.362 Å) are longer than that in 3 (1.345 Å).28 In
comparison, 4-tert-butylhomoadamant-3-ene, which can be
considered a model kinetically stabilized compound, was
estimated to have a bond length of 1.356 Å. Thus, the
bridgehead double bonds with phenyl and methoxycarbonyl
groups were further lengthened as a result of conjugation. The
optimized geometry illustrated below showed some steric effect
compared with the parent homoadamant-3-ene 1, but a conjuga-
tive effect should be considered to play a significant role in the
observed stabilization.
Figure 4.
Here, the polarizability of 1 and 2 is essentially different.
As was seen in the reactions with HCl and nucleophiles,
protonation occurred at the bridgehead carbon of 1, leading to
16, and chlorination ocurred at that of 2, leading to 38, and
nucleophiles such as ethanol and aniline reacted with 2 but not
with 1. Thus, these compounds show an opposite polarization
of the C3-C4 bond (negative at C3 for 1 and positive at C3 for
2).
The spectroscopic features29 of the strained double bonds in
1 and 2 were compared with those of normal double bonds in
(1-cyclohexylidene)ethylbenzene (47) and methyl 2-cyclohexy-
lidenepropanoate (48)30 (which are formed by disconnections
at the C5-C6, C7-C8 and C1-C10 bonds of homoadamant-3-
ene).
In the IR spectra, weak absorption bands were observed at
1574 cm-1 for 1 and at 1570 cm-1 for 2, which are 69-79
cm-1 lower than those at 1653 cm-1 for 47 and at 1639 cm-1
for 48. Deviation from the standard is due to distortion6i and
is closely related to the 62-cm-1 shift from 3 (1610 cm-1) to
ethylidenecyclohexane (1672 cm-1). In the 13C NMR spectra,
olefinic signals were seen at δ 148.3 and 143.1 for 1 (olefinic
signals of 47 at δ 129.4 and 147.8) and at δ 170.5 and 128.8
for 2, together with a carbonyl signal at δ 171.9 (olefinic signals
for 48 at δ 148.2 and 119.7 with a carbonyl signal at δ 171.0).31
The lower shifts observed in 1 and 2 were compatible with a
more cationic nature at C4 and C3, respectively.
(26) A phenyl substituent (at C2) was previously reported to stabilize
the bicyclo[3.3.1]non-1-en-3-one system: see ref 12a.
(27) MOPAC Ver 5.00 (QCPE No. 445): Stewart J. J. P. QCPE Bull.
1989, 9, 10. Hirano, T. JCPE Newsletter 1989, 9(2), 36. Revised as Ver
5.01 by J. Toyoda for Apple Macintosh. HyperChem. 4.0 (Hypercube Inc.)
on an IBM compatible computer.
(28) The relative stability can be predicted by the “olefin strain” energy
(OS) defined by Schleyer. He noted that the OS-generalization for
trisubstituted olefins [the difference between the heat of formation (∆Hf°)
of an olefin and that of its parent alkane represents the heat of hydrogenation
(∆HH°); for most trisubstituted bridgehead olefins, OS and ∆HH° are related
by a constant difference, 26.1 kcal/mol] was not directly applicable to
tetrasubstituted analogs. Nevertheless, our PM3 calculations indicated that
the difference between the ∆Hf° of 1, 2 and 3 and the ∆Hf° of their parent
alkanes were 44.1, 46.2, and 49.0 kcal/mol, respectively. If changes in
∆HH° caused by substituting phenyl and methoxycarbonyl groups for a
hydrogen are assumed to be about -1 to -4 kcal/mol (cf. Jesen, J. L. Prog.
Phys. Org. Chem. 1976, 12, 189), the OS’s of 1 and 2 can be estimated to
be slightly lower than that of 3.
(29) These spectra were recorded at ambient temperature for IR and at
-80 °C for 13C NMR as soon as Rh-catalyzed decomposition was complete.
Although the sample used was a crude product, olefinic signals could be
distinguished from noisy signals due to contaminants.
(30) Compounds 47 and 48 were prepared from cyclohexanone and the
corresponding phosphonate reagents according to previously reported
proceduressfor 47: Shakak, I.; Almong, J.; Bergman, E. D. Isr. J. Chem.
1969, 9, 585. For 48: Courout, P.; Ghribi, A. Synthesis 1991, 790.
(31) The other 13C NMR signals were observed with DEPT analysis at
δ 27.5 (CH2), 27.7 (CH), 36.2 (CH2), 36.9 (CH), 42.9 (CH2), 48.8 (CH2),
124.9 (CH2), 126.5 (CH2), 127.7 (CH2), and 139.6 (quarternary C) for 1,
and at δ 27.8 (CH), 28.3 (CH2), 35.7 (CH), 35.8 (CH2), 41.3 (CH2), 41.7
(CH2), and 51.0 (CH3) for 2. The 1H NMR signals were observed at δ
1.41-2.52 (15 H, m) and 7.12-7.37 (5 H, m) for 1 and at δ 1.45-2.20
(15 H, m) and 3.70 (3 H, s) for 2.

+
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7080 J. Am. Chem. Soc., Vol. 118, No. 30, 1996
Ohno et al.
used without further purification for subsequent reactions. The sample
was dried over P2O5 under vacuum before use.
In summary, bridgehead olefins substituted with phenyl and
methoxycarbonyl groups were formed in a homoadamantane
system using the 1,2-carbon shift of the carbene (carbenoid)
intermediate. Among the methods used to decompose the diazo
precursors, catalysis with Rh2(OAc)4 was the most effective for
producing the desired 4-substituted homoadamant-3-enes, which
were more stable than unsubstituted homoadamant-3-ene. This
finding was explained by strain relief of the double bond as a
result of conjugation with the 4-substituent and to some extent
by steric protection. The survivability of this bond at 0 °C to
room temperature allowed the subsequent addition reaction with
nucleophiles or electrophiles after Rh-catalyzed decomposition
was complete, and a variety of 3,4-disubstituted homoadaman-
tane derivatives could be obtained. The 1,2-carbon shift of the
Rh-carbene complex was significantly affected by its polarized
structure.
Methyl 2-(1-Adamantyl)-3-oxopropanoate (9). To a solution of
LDA in THF (1 mL) prepared from BuLi (0.7 mL of 1.6 M hexane
solution, 1.1 mM) and diisopropylamine (114 mg, 1.1 mM) was added
a solution of 8 (208 mg, 1 mM) in THF (1 mL) at -78 °C under an
atmosphere of nitrogen, and stirring was continued for 35 min.
A
solution of ethyl formate (88 mg, 1.2 mM) in THF (1 mL) was added
and the mixture was stirred for an additional 2.5 h at the same
temperature. The reaction mixture was poured into ice-water, extracted
with ether, washed with water, and dried over Na2SO4. Evaporation
to dryness left a residue, which was chromatographed (H/A 25/1) to
give 9 (153 mg, 65%). Mp 52-54 °C. IR (KBr) 2920, 2860, 1745,
1
1720 cm-1; H NMR δ 1.60-2.10 (m, 15 H), 2.81 (d, J ) 4.8 Hz, 1
H) 3.76 (s, 3 H), 9.85 (d, J ) 4.8 Hz, 1 H); 13C NMR δ 28.58, 36.56,
38.09, 40.58, 51.91, 68.96, 169.66, 200.70; MS (EI) m/z (%) 236 (M,
3), 222 (6), 208 (100). Anal. Calcd for C14H20O3: C, 71.16; H, 8.53.
Found: C, 71.10; H, 8.66.
Methyl (1-Adamantyl)diazoacetate (10). To a solution of 9 (236
mg, 1 mM) in THF (2 mL) was added BuLi (0.62 mL of 1.6 M hexane
solution, 1 mM) at 0 °C under an atmosphere of nitrogen, and stirring
was continued for 30 min. A solution of tosyl azide (215 mg, 1.1
mM) and hexamethylphosphoramide (179 mg, 1 mM) in THF (1 mL)
was then added and stirring was continued for 1 h at 0 °C and for 4 h
at room temperature. Hexane (20 mL), 1 N aqueous NaOH (2 mL),
and water (20 mL) were added in succession, and the mixture was
shaken well. The organic layer was separated, washed with water, and
dried over Na2SO4. After evaporation of the solvent, the residue was
chromatographed (H/A 20/1) to give 10 (117 mg, 50%). Mp 85-87
Experimental Section
General. IR spectra were recorded on a JASCO FT/IR 5300
spectrophotometer. 1H and 13C NMR were obtained with a Varian
GEMINI-200 spectrometer at 200 and 50 MHz, respectively, for
samples in CDCl3 solution with SiMe4 as an internal standard. J values
are given in hertz. Mass spectra were recorded on a JEOL JMS-
AX505H spectrometer (EI at 70 eV). Microanalyses were performed
with a Perkin-Elmer 2400 elemental analyzer. Melting points were
determined on a Yanaco MP apparatus and are uncorrected. Unless a
melting point is given, the compound was obtained as an oil. Flash
chromatography was performed with a silica gel column (Fuji-Davison
BW-300) eluted with mixed solvents [hexane (H), ethyl acetate (A)].
THF was dried with Na-benzophenone and used after distillation.
Dichloromethane was dried and distilled over calcium chloride, kept
over molecular sieves, and bubbled with a nitrogen gas in an ultrasonic
bath before use. Rh2(OAc)4 was purchased from Aldrich, and Rh2-
(OCOCF3)4 and Rh2(NHCOCH3)4 were prepared by previously reported
methods.32,33
1
°C. IR (KBr) 2912, 2065, 1701 cm-1; H NMR δ 1.60-2.10 (m, 15
H), 3.73 (s, 3 H). 13C NMR δ 28.76, 31.04, 31.43, 36.53, 40.43, 51.37,
167.46; MS (EI) m/z (%) 234 (M, 12), 206 (100). Anal. Calcd for
C13H18N2O2: C, 66.64; H, 7.74; N, 11.96. Found: C, 66.56; H, 7.66;
N, 12.03.
In the above experiment, the yield of 10 dropped to 19% in the
absence of hexamethylphosphoramide. As with 7, 10 was treated with
1.5 equiv of dimethyl acetylenedicarboxylate at room temperature for
10 days to give 12 in 88% yield. Mp 125-128 °C. IR (KBr) 2912,
1-Adamantyl Phenyl Ketone Hydrazone (6). The starting ketone
5 was prepared in 84% yield from PhLi and 1-adamantanecarboxylic
acid, instead of the reported method using PhMgBr/CdCl2/1-adaman-
tanecarbonyl chloride (53%).34 A solution of 5 (4.8 g, 20 mM) and
hydrazine monohydrate (10 mL, 200 mM) in methanol (80 mL) was
refluxed for 8 h. The product was extracted with ether and recrystal-
lized from hexane to give 6 as a white crystal (3.36 g, 66%). Mp
143-145 °C. IR (KBr) 3377, 2901, 1628, 1577, 711 cm-1; 1H NMR
δ 1.50-2.05 (m, 15 H), 3.75 (br s, 2 H), 7.00-7.50 (m, 5 H); 13C
NMR δ 28.55, 36.70, 36.86, 40.05, 128.49, 128.78, 129.22, 133.78,
161.27. Anal. Calcd for C17H22N2: C, 80.27; H, 8.72; N, 11.01.
Found: C, 80.00; H, 8.80; N, 10.87.
1
1745, 1720 cm-1; H NMR δ 1.74-2.32 (m, 15 H), 3.86, 3.93 and
3.94 (s, each 3 H); MS (EI) m/z (%) 376 (M, 6), 361 (15), 345 (54),
330 (51), 135 (100). Anal. Calcd for C19H24N2O6: C, 60.63; H, 6.43;
N, 7.44. Found: C, 60.89; H, 6.60; N, 7.20
Thermolysis of 7. A solution of 7 in hexane (2 mL), starting from
127 mg (0.5 mM) of 6, was injected into an 8 mm × 50 cm quartz
tube fitted with a rubber septum at the top and a dry ice-cooled trap at
the bottom under vacuum (0.2 mmHg), while the center (30 cm) was
heated with an electric furnace at 400-800 °C. The collected products
were subjected to chromatography (hexane and then H/A 10/1) to give
13 as the first fraction and 14 as the second fraction. The yields of 7
and 13 based on 6 were determined by GLC: 13% and 37% at 400
°C, 23% and 36% at 600 °C, and 24% and 14% at 800 °C, respectively.
13: IR (neat) 2906, 1467, 752 cm-1; 1H NMR δ 1.25-2.32 (m, 14
H), 2.66 (dd, 1 H, J ) 4.8, 14.8 Hz), 2.91 (dd, 1 H, J ) 12.2, 14.8
Hz), 7.04-7.29 (m, 4 H); 13C NMR δ 28.42, 29.59, 30.66, 31.27, 33.48,
37.97, 39.68, 39.74, 40.84, 44.39, 53.72, 121.11, 125.83, 126.37, 126.47,
143.57, 153.71; MS (EI) m/z (%) 224 (M, 55), 167 (100), 130 (24).
Anal. Calcd for C17H20: C, 91.01; H, 8.99. Found: C, 91.10; H, 8.90.
(1-Adamantyl)diazophenylmethane (7). To a suspension of BaM-
nO4 (512 mg, 2 mM) and CaO (776 mg, 13.8 mM) in ether (6 mL)
was added a solution of 6 (127 mg, 0.5 mM) in ether (8 mL) under an
atmosphere of nitrogen, and the mixture was stirred at room temperature
for 15 min. Filtration of solids and evaporation of the solvent left a
wine-colored solid 7, which was characterized by IR absorption at 2033
cm-1 and MS signals at m/z (%) 252 (M, 5), 224 (66), 223 (100), 135
(61), and by the cycloadduct; 7 was dissolved in hexane (2 mL)/benzene
(1 mL), and the solution was mixed with dimethyl acetylenedicarboxy-
late (71 mg, 0.5 mM) and stirred at room temperature for 2 h. After
evaporation of the solvent, the product was chromatographed (H/A 10/
1) to give 11 (158 mg, 80%). Mp 155-156 °C. IR (KBr) 2925, 1750,
1730 cm-1; 1H NMR δ 1.50-2.15 (m, 15 H), 3.58 and 3.95 (s, each 3
H), 7.30-7.50 (m, 5 H). MS (EI) m/z (%) 394 (M, 29); 380 (32), 363
(100). Anal. Calcd for C22H26N2O4: C, 70.03; H, 6.64; N, 7.10.
Found: C, 70.03; H, 6.77; N, 7.03.
14: mp 50.0-51.5 °C; IR (CHCl3) 2930, 1701, 1688, 1597 cm-1
;
1H NMR δ 0.85-2.60 (m, 13 H), 2.77 (d, 1 H, J ) 6.6 Hz) 7.40-8.00
(m, 5 H); 13C NMR δ 24.99, 28.70, 28.89, 34.64, 45.44, 50.37, 128.44,
129.00, 133.46, 137.61, 200.19, 213.66; MS (EI) m/z (%) 256 (M, 3),
238 (10), 152 (100), 120 (90). Anal. Calcd for C17H20O2: C, 79.65;
H, 7.86. Found: C, 79.71; H, 7.89.
Photolysis of 7. A solution of 7 in hexane (4 mL), starting from
64 mg (0.25 mM) of 6, was irradiated with a high-pressure Hg lamp
through a Pyrex filter for 1 h under an atmosphere of nitrogen. White
precipitates were separated by filtration to give azine 15 (19 mg, 32%
based on 6). From the mother liquor, 19 mg (32%) of 5 was separated
by chromatography (H/A 50/1).
15: mp 231-234 °C; IR (CHCl3) 2925, 1605, 1495 cm-1; 1H NMR
δ 1.25-2.00 (m, 30 H), 6.94-7.40 (m, 10 H); 13C NMR δ 28.35, 36.70,
39.78, 40.48, 127.40, 127.74, 127.84, 136.79, 166.23; MS (EI) m/z (%)
Although attempts to purify 7 failed (for example, recrystallization
at -78 °C), the compound was sufficiently pure and was therefore
(32) Johnson, S. A.; Hunt, H. R.; Newmann H. M. Inorg. Chem. 1963,
2, 960.
(33) Doyle, M. P.; Bagheri, V.; Wandless, T. J.; Harn, N. K.; Brinker
D. A.; Eagle, C. T.; Loh, K.-L. J. Am. Chem. Soc. 1990, 112, 1906.
(34) Stetter, H.; Rauscher, E. Chem. Ber 1960, 93, 1161.

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ConjugatiVely Stabilized Bridgehead Olefins
J. Am. Chem. Soc., Vol. 118, No. 30, 1996 7081
476 (M, 83), 372 (100), 299 (60). Anal. Calcd for C34H40N2: C, 85.67;
H, 8.46; N, 5.88. Found: C, 85.82; H, 8.63; N, 5.75.
28.15, 31.90, 31.96, 33.63, 37.89, 43.52, 44.36, 51.82, 52.47, 52.54,
52.85, 62.66, 106.30, 116.72, 124.63, 127.81, 128.17, 129.01, 133.18,
145.37, 147.75, 161.80, 163.02, 164.86, 169.90; MS (EI) m/z (%) 508
(M, 1), 493 (3), 444 (31), 149 (47), 135 (39), 105 (100); HRMS calcd
for C29H32O8 508.2097, found 508.2082.
Catalysis of 7. A solution of 7 in dichloromethane (2 mL), starting
from 64 mg (0.25 mM) of 6, was mixed with a catalytic amount of
Rh2(OAc)4 in dichloromethane (1 mL) at room temperature under an
atmosphere of nitrogen, and nitrogen was evolved instantly. The
reaction mixture was stirred for 5 min and hydrogen chloride (0.75
mL of a 2 M dichloromethane solution, 1.5 mM) was added. After
being stirred overnight, the reaction mixture was poured into water
and extracted with dichloromethane. The extracts were washed with
water, dried over Na2SO4, and evaporated to dryness. The residue was
chromatographed (hexane) to give 16 (40 mg, 71% base on 6): IR
(neat) 2925, 1645, 1600, 1495 cm-1; 1H NMR δ 1.80-2.45 (m, 14 H),
6.21 (dd, 1 H, J ) 8.8, 1.8 Hz), 7.15-7.40 (m, 5 H); 13C NMR δ
29.58, 32.25, 34.09, 34.19, 36.75, 37.40, 125.86, 126.59, 128.46, 135.62,
145.19, 150.67; MS (EI) m/z (%) 224 (M, 100), 167 (21), 155 (45).
Anal. Calcd for C17H20: C, 91.01; H, 8.99. Found: C, 90.91; H, 9.09.
When the above catalysis was followed by the addition of acetic
acid (0.15 mL, 2.5 mM), 16 was obtained in 53% yield. 16 was
obtained at a yield of 73% when Rh2(OCOCF3)4 was used as a catalyst.
A similar procedure using Rh2(NHCOCH3)4 gave only 8 mg (13%) of
15 as a separable product. When a hexane solution of 7 was stirred in
the presence of Rh2(OAc)4 for 2 h to complete the reaction, 24 mg
(40%) of 15 was obtained.
Catalysis of 7 under an Atmosphere of Oxygen. Starting from
64 mg (0.25 mM) of 6, catalytic decomposition of 7 with Rh2(OAc)4
was carried out as described above under a stream of oxygen, and the
reaction mixture was stirred overnight while exposed to air. After
evaporation of the solvent, the residue was chromatographed (H/A 20/1
and then H/A 3/1) to give 18 mg (30% based on 6) of 5 as the first
fraction and 36 mg (56% based on 6) of 14 as the second fraction.
Likewise, reactions using Rh2(OCOCF3)4 and Rh2(NHCOCH3)4 as
catalysts gave 3 mg (5%) of 5 and 42 mg (66%) of 14, and 26 mg
(43%) of 5 and 9 mg (14%) of 14, respectively. When the Rh2(OAc)4-
catalyzed reaction was conducted using hexane as a solvent, 44 mg
(73%) of 5 was obtained.
With m-Chloroperbenzoic Acid. Addition of a solution of m-
chloroperbenzoic acid (130 mg, 0.75 mM) including NaHCO3 (63 mg,
0.75 mM) in THF (1 mL) and water (1 mL), workup b, and
chromatography (H/A 5/1) gave 21 (17 mg, 28%). Mp 75-79 °C. IR
1
(KBr) 2905, 1693, 1602, 1496 cm-1; H NMR δ 1.56-2.41 (m, 15
H), 2.78 (d, J ) 4.0 Hz, 2 H), 7.17-7.36 (m, 5 H); 13C NMR δ 26.07,
28.18, 35.18, 37.06, 39.14, 51.59, 55.02, 126.52, 126.59, 128.23, 148.29,
216.71; MS (EI) m/z (%) 240 (M, 65), 212 (14), 155 (100), 134 (29).
Anal. Calcd for C17H20O: C, 84.95; H, 8.39. Found: C, 84.82; H,
8.51.
With p-Toluenesulfonyl Azide. Addition of p-toluenesulfonyl azide
(30 mg, 0.28 mM), workup b, and chromatography (H/A 10/1) gave
23 (57 mg, 58%) as a 3/2 syn and anti mixture. Mp 133-143 °C. IR
(KBr) 2903, 1604, 1584, 1331, 1155 cm-1; 1H NMR δ 1.55-2.55 (m,
14 H), 2.32 and 2.40 (s, 2/3 × 3 H and 1/3 × 3 H), 3.51 (d, J ) 4.2
Hz, 1 H), 7.04-7.71 (m, 9 H); 13C NMR δ 21.61, 28.10, 36.29, 39.24,
44.83, 126.68, 127.57, 127.68, 129.12, 129.63, 135.29, 138.91, 143.55,
193.24 and the corresponding peaks due to the minor isomer; MS (EI)
m/z (%) 393 (M, 38), 238 (98), 135 (100). Anal. Calcd for C24H27-
NO2S: C, 73.24; H, 6.91; N, 3.56. Found: C, 73.20; H, 7.11; N, 3.50.
Imine 23 could be hydrolyzed to 5 by heating in wet ethanol with
sulfuric acid.
Bamford-Stevens Reaction of 27. The starting tosylhydrazone
27 was obtained in 76% yield by refluxing a solution of 5 (240 mg, 1
mM) and tosylhydrazide (186 mg, 1 mM) in methanol (2 mL) for 30
h. Sodium (80 mg) was dissolved in dry ethanol (3 mL) and to this
solution was added 27 (106 mg, 0.26 mM). The resulting solution
was refluxed for 6 h under an atmosphere of nitrogen. The reaction
mixture was poured into saturated aqueous NaHCO3 (30 mL) and
dichloromethane (30 mL). The organic layer was separated, washed
with water, and dried over Na2SO4. Evaporation to dryness and
chromatographic separation (hexane) of the residue gave 28 (53 mg,
83%).
Reaction of 1 after Catalysis of 7. This reaction was carried out
by adding an appropriate reagent soon after the catalytic decomposition
of 7 with Rh2(OAc)4 as described above. The reaction mixture of 1
formed in situ [starting from 64 mg (0.25 mM) of 6] and the reagent
in dichloromethane (3 mL) was stirred overnight at room temperature
under an atmosphere of nitrogen. Workup [(a) evaporation of the
solvent, or (b) evaporation after the reaction mixture was poured into
water, and the organic layer was extracted with dichloromethane and
dried over Na2SO4] and chromatography gave the product; the yields
given below are based on 6.
1
27: Mp 157-159 °C; IR (KBr) 3500, 2925, 1600, 1340 cm-1; H
NMR δ 1.50-2.02 (m, 15 H), 2.47 (s, 3 H), 6.70-8.30 (m, 10 H).
Anal. Calcd for C24H28N2O2S: C, 70.49; H, 6.85; N, 6.85. Found:
C, 70.38; H, 6.92; N, 6.80.
1
28: IR (neat) 2920, 1605, 1090 cm-1; H NMR δ 1.13 (t, J ) 7.0
Hz, 3 H), 1.35-2.00 (m, 15 H), 3.19 and 3.36 (dq, J ) 9.6, 7.0 Hz,
each 1 H) 3.70 (s, 1 H), 7.18-7.35 (m, 5 H); 13C NMR δ 15.28, 28.54,
37.15, 37.30, 38.65, 64.82, 90.65, 127.27, 127.60, 128.93, 139.93; MS
(EI) m/z (%) 270 (M, 9), 135 (100). Anal. Calcd for C19H26O: C,
84.39; H, 9.69. Found: C, 84.60; H, 9.65.
With Oxygen. Exposure to air, workup a, and chromatography (H/A
3/1) gave 14 (38 mg, 59%).
With Thiophenol. Addition of thiophenol (83 mg, 0.75 mM),
workup (b; the mixture was also washed with aqueous NaOH) and
preparative TLC (H/A 10/1) gave 17 (6 mg, 7%). IR (neat) 2901, 1581,
Thermolysis of 10. The diazo ester 10 (23 mg, 0.1 mM) dissolved
in hexane (1 mL) was thermolyzed at 550 °C as with 7. The hexane
solution collected in a cold trap was stirred with ethanol (1 mL) at
room temperature overnight. After evaporation of the solvent, the
residue was subjected to chromatography (H/A 20/1), but only 2 mg
(8%) of 29 was isolated from the complex mixture. 29: see below.
1
1491 cm-1; H NMR δ 1.04-2.52 (m, 16 H), 3.26 (t, J ) 9.8 Hz, 1
H), 7.20-7.46 (m, 10 H); 13C NMR δ 29.32, 29.51, 31.42, 34.03, 35.99,
38.37 41.10, 45.78, 48.93, 57.11, 77.45, 126.94, 128.00, 128.57, 128.83,
130.16, 134.26, 138.88, 145.97; MS (EI) m/z (%) 334 (M, 26), 225
(100), 135 (20). Anal. Calcd for C23H26S: C, 82.58; H, 7.84.
Found: C, 82.42; H, 8.01.
Photolysis of 10. A solution of 10 (23 mg, 0.1 mM) in hexane (1
mL) including ethanol (0.025 mL, 0.4 mM) was photolyzed (room
temperature, 7 h) as with 7. After evaporation of the solvent, the
products were chromatographed (H/A 20/1) to give 30 (8 mg, 31%) as
the first fraction and 29 (7 mg, 28%) as the second fraction.
With Methyl r-Cyanoacrylate. Addition of a solution of methyl
R-cyanoacrylate (28 mg, 0.25 mM) in dichloromethane (0.2 mL),
workup a, and chromatography (H/A 10/1) gave 18 (16 mg, 19%). IR
(neat) 2909, 2225, 1745, 1630, 1483 cm-1; 1H NMR δ 1.54-2.30 (m,
13 H), 2.15 and 2.42 (d, J ) 13.4 Hz, each 1 H), 3.87 (s, 3 H), 6.79
(d, J ) 9.4 Hz, 1 H), 7.01-7.63 (m, 4 H); 13C NMR δ 29.72, 29.84,
32.15, 33.13, 33.22, 35.85, 36.01, 36.74, 41.90, 42.23, 47.32, 49.46,
53.99, 119.95, 125.89, 127.40, 127.50, 129.58, 130.16, 136.82, 143.42,
169.41; MS (EI) m/z (%) 333 (M, 100), 292 (61), 274 (98). Anal.
Calcd for C22H23NO2: C, 79.25; H, 6.95; N, 4.20. Found: C, 79.10;
H, 6.97; N, 4.31.
1
29: mp 38-40 °C; IR (CHCl3) 2908, 1726, 1159, 1070 cm-1; H
NMR δ 1.06 (t, J ) 6.9 Hz, 3 H), 1.45-2.50 (m, 15 H), 3.16 (m, 1
H), 3.47 and 3.51 (dq, J ) 12.6, 6.9 Hz, each 1 H), 3.68 (s, 3 H); 13C
NMR δ 16.10, 27.24, 27.86, 31.29, 34.57, 34.62, 36.01, 37.79, 39.81,
44.95, 51.55, 52.92, 56.39, 77.33, 176.53; MS (EI) m/z (%) 252 (M,
3), 207 (34), 147 (48), 123 (100). Anal. Calcd for C15H24O3: C, 71.39;
H. 9.59. Found: C, 71.41; H, 9.58.
1
30: IR (CHCl3) 2909, 1736, 1107 cm-1; H NMR δ 1.20 (t, J )
With Dimethyl Acetylenedicarboxylate. Addition of dimethyl
acetylenedicarboxylate (355 mg, 2.5 mM), workup b, and chromatog-
raphy (H/A 10/1) gave 19 (33 mg, 26%): IR (CHCl3) 2906, 1724,
7.0 Hz, 3 H), 1.51-1.98 (m, 15 H), 3.32 and 3.56 (dq, J ) 9.4, 7.0
Hz, each 1 H), 3.37 (s, 1 H), 3.75 (s, 3 H); 13C NMR δ 15.01, 28.41,
36.53, 37.08, 38.52, 51.41, 66.68, 88.22, 172.95; MS (EI) m/z (%) 252
(M, 2), 193 (88), 135 (100). Anal. Calcd for C15H24O3: C, 71.39; H,
9.59 Found: C, 71.41; H, 9.58.
1
1595 cm-1; H NMR δ 1.55-2.65 (m, 15 H), 3.29, 3.76, 3.79 and
3.95 (s, each 3 H), 7.18-7.35 (m, 5 H); 13C NMR δ 27.58, 28.04,

+
+
7082 J. Am. Chem. Soc., Vol. 118, No. 30, 1996
Ohno et al.
Catalysis of 10 in the Presence of EtOH. A solution of 10 (23
mg, 0.1 mM) in dichloromethane (1 mL) including ethanol (0.025 mL,
0.4 mM) was mixed with a catalytic amount of Rh2(OAc)4 at room
temperature under an atmosphere of nitrogen, and the mixture was
stirred overnight. After evaporation of the solvent, the product was
chromatographed (H/A 20/1) to give 13 mg (52%) of 29. The same
experiments using Rh2(OCOCF3)4 and Rh2(NHCOCH3)4 as catalysts
gave 14 mg (56%) of 29 and 12 mg (48%) of 30, respectively. On the
other hand, the Rh2(OAc)4-catalyzed reaction conducted in hexane (2
mL) gave 31 (8 mg, 36%). Mp 55-58 °C. IR (CHCl3) 2901, 1736,
With Hydrogen Chloride. Addition of hydrogen chloride (2 mL
of a 0.5 M dichloromethane solution, 1 mM) and chromatography (H/A
10/1) gave 38 (19 mg, 78%). Mp 47-49 °C (lit. mp 50-51 °C).24 IR
1
(CHCl3) 2911, 1730, 1163 cm-1; H NMR δ 1.50-2.52 (m, 14 H),
3.09 (m, 1 H), 3.21 (m, 1 H), 3.71 (s, 3 H); 13C NMR δ 29.13, 29.42,
31.33, 34.13, 35.65, 36.77, 39.25, 42.59, 51.76, 53.10, 57.80, 73.76,
175.74; MS (EI) m/z (%) 242/244 (M, 1), 206 (100), 174 (48), 135
(93). Anal. Calcd for C13H19O2Cl: C, 64.33; H, 7.89. Found: C,
64.38, H, 7.83.
This compound was also obtained with TiCl4; addition of TiCl4 (0.2
mL of a 0.5 M dichloromethane solution, 0.1 mM) was followed by
stirring at 0 °C for 30 min. The rection mixture was poured into ice-
water, extracted with dichloromethane, washed with water, and dried
over Na2SO4. Evaporation to dryness left a residue, which was
chromatographed as above to give 38 (6 mg, 25%).
1628, 1153 cm-1; 1H NMR δ 1.59-2.02 (m, 30 H), 3.84 (s, 6 H); 13
C
NMR δ 28.06, 36.56, 38.18, 39.45, 51.12, 166.27, 171.96; MS (EI)
m/z (%) 440 (M, 6), 381 (100), 135 (76). Anal. Calcd for
C26H36N2O4: C, 70.88; H, 8.24; N, 6.36. Found C, 70.98; H, 8.25; N,
6.42.
Reaction of 2 after Catalysis of 10. An appropriate reagent was
added to 2 formed in situ, as soon as a mixture of 10 (23 mg, 0.1 mM)
and a catalytic amount of Rh2(OAc)4 in dichloromethane (2 mL) was
stirred at 0 °C for 10 min under an atmosphere of nitrogen. The reaction
mixture was then stirred overnight at room temperature. After
evaporation of the solvent, the residue was subjected to chromatography
to give the product.
With Oxygen. Treatment with oxygen (bubbling for 15 min) and
exposure to air overnight followed by chromatography (H/A 2/1) gave
32 (10 mg, 42%): IR (CHCl3) 2932, 1730, 1703, 1057 cm-1; 1H NMR
δ 1.56-2.53 (m, 13 H), 2.65 (d, J ) 7.0 Hz, 2 H), 3.87 (s, 3 H); 13C
NMR δ 24.44, 28.20, 28.71, 46.15, 50.49, 53.18, 161.91, 194.10,
213.16; MS (EI) m/z (%) 238 (M, 1) 206 (3), 179 (91), 151 (100).
Anal. Calcd for C13H18O4: C, 65.53, H, 7.61. Found: C, 65.41; H,
7.79.
With Methanol. Addition of methanol (1 mL) and chromatography
(H/A 20/1) gave 33 (14 mg, 59%): IR (CHCl3) 2908, 1726, 1197,
1076 cm-1; 1H NMR δ 1.46-2.47 (m, 15 H), 3.13 (m, 1 H), 3.23 and
3.69 (s, each 3 H); 13C NMR δ 27.14, 27.77, 31.27, 34.58, 34.74, 35.93,
36.98, 39.56, 43.82, 49.17, 51.62, 52.70, 79.34, 176.55; MS (EI) m/z
(%) 238 (M, 3), 207 (74), 146 (32), 135 (100). Anal. Calcd for
C14H22O3: C, 70.56; H, 9.31. Found: C, 70.55, H, 9.31.
With Ethanol. Addition of ethanol (1 mL) and chromatography
(H/A 20/1) gave 29 (14 mg, 56%).
With Trifluoroacetic Acid. Addition of trifluoroacetic acid (12
mg, 0.11 mM) and chromatography (H/A 5/1) gave 39 (17 mg, 53%):
1
IR (CHCl3) 2913, 1776, 1732, 1170 cm-1; H NMR δ 1.51-2.54 (m,
15 H), 2.70 (m, 1 H), 3.65 (s, 3 H), 3.82 (m, 1 H); 13C NMR δ 27.42,
31.11, 33.77, 35.05, 35.74, 37.80, 37.99, 44.11, 50.39, 52.04, 91.71,
114.72 (q, J ) 286 Hz), 156.16 (q, J ) 41 Hz), 175.05; MS (EI) m/z
(%) no molecular ion, 207 (100). Anal. Calcd for C15H18F3O4: C,
56.42; H, 5.68. Found: C, 56.23; H, 5.88.
With Triethylsilane and Trifluoromethanesulfonic Acid. Addi-
tion of a solution of triethylsilane (116 mg, 1 mM) and trifluo-
romethanesulfonic acid (15 mg, 0.1 mM) in dichloromethane (1 mL)
and chromatography (H/A 20/1) gave 40 (9 mg, 43%). IR (neat) 2903,
1
1734, 1165 cm-1; H NMR δ 1.47-2.40 (m, 15 H), 2.75 (m 1 H),
3.66 (s, 3 H); 13C NMR δ 27.13, 27.42, 31.10, 32.24, 34.50, 35.53,
36.34, 36.42, 40.15, 40.41, 49.91, 51.76, 178.13; MS (EI) m/z (%) 208
(M, 94), 176 (62), 148 (100). An authentic sample was obtained as
follows: Homoadamantanone (164 mg, 1 mM) was added to a Wittig
reagent prepared from (methoxymethyl)triphenylphosphonium chloride
(343 mg, 1.1 mM) and lithium diisopropylamide [diisopropylamine
(0.14 mL, 1 mM) + butyllithium (0.7 mL of 1.6 M hexane solution, 1
mM), 1 mM in THF (2 mL)] at -78 °C, and the mixture was stirred
for 4 h at this temperature and then for 4 h at room temperature. The
usual workup and chromatographic separation (hexane) gave 42 (40
1
mg, 22%) as a 1:5 stereoisomeric mixture: IR (neat) 1662 cm-1; H
With Benzyl Alcohol. Addition of benzyl alcohol (52 mg, 0.5 mM)
and chromatography (H/A 20/1) gave 34 (13 mg, 41%): IR (CHCl3)
2909, 1725, 1603, 1159 cm-1; 1H NMR δ 1.53-2.56 (m, 15 H), 3.24
(m, 1 H), 3.57 (s, each 3 H), 4.52 and 4.58 (dq, J ) 12.0 Hz, each 1
H), 7.18-7.72 (m, 5 H); 13C NMR δ 27.31, 27.85, 31.25, 34.63, 34.68,
35.96, 36.95, 39.74, 44.87, 51.57, 53.71, 63.23, 78.83, 127.25, 128.49,
128.77, 140.33, 176.49; MS (CI) m/z (%) 315 (M + H, 48), 207 (100).
Anal. Calcd for C20H26O3: C, 76.39; H, 8.33. Found: C, 76.27; H,
8.45.
With Aniline. Addition of aniline (93 mg, 1 mM) and chromatog-
raphy (H/A 10/1) gave 35 (24 mg, 80%). Mp 95-98 °C. IR (CHCl3)
3526, 2908, 1723, 1601, 1161 cm-1; 1H NMR δ 1.54-2.56 (m, 16 H),
3.25 (m, 1 H), 3.49 (s, 3 H), 6.72-7.71 (m, 5 H); 13C NMR δ 27.28,
27.89, 31.42, 35.48, 35.77, 35.90, 39.23, 40.08, 47.07, 51.42, 53.41,
58.82, 118.82, 119.23, 129.07, 146.30, 177.02; MS (EI) m/z (%) 299
(M, 100), 242 (37), 207 (60), 170 (94). Anal. Calcd for C19H25NO2:
C, 76.21; H, 8.42; N, 4.68. Found: C, 76.23; H, 8.45; N, 4.50.
With Benzylamine. Addition of benzylamine (54 mg, 0.5 mM)
and chromatography (H/A 10/1) gave 36 (13 mg, 42%): IR (CHCl3)
3549, 2909, 1723, 1604, 1152 cm-1; 1H NMR δ 1.46-2.42 (m, 16 H),
3.11 (m, 1 H), 3.66 (s, 3 H), 3.78 (s, 2 H), 7.19-7.30 (m, 5 H); 13C
NMR δ 27.36, 27.89, 31.59, 35.27, 36.06, 36.21, 39.41, 39.54, 46.02,
46.68, 51.49, 52.88, 57.19, 127.02, 128.49, 128.65, 144.86, 177.37;
MS (EI) m/z (%) 313 (M, 10), 256 (9), 207 (13), 184 (100). Anal.
Calcd for C20H27NO2: C, 76.64; H, 8.68; N, 4.47. Found: C, 76.62;
H, 8.72; N, 4.32.
NMR δ 1.45-2.44 (m, 15 H), 3.18 (m, 1 H), 3.53 and 3.56 (s, 3 H ×
5/6 and 3 H × 1/6), 5.66 and 5.85 (m, 1 H × 5/6 and 1 H × 1/6); 13
C
NMR (major isomer) δ 27.69, 30.21, 30.53, 36.43, 36.95, 37.72, 37.89,
38.58, 38.90, 59.44, 125.31, 140.61; MS (EI) m/z (%) 192 (M, 100),
135 (53). A solution of 42 (50 mg, 0.3 mM) in ether (6 mL) was
refluxed with 70% hydroperchloric acid (0.21 mL) for 15 min. The
usual workup and chromatographic separation (H/A 20/1) gave aldehyde
43 (40 mg, 75%): IR (neat) 1722 cm-1; 1H NMR δ 1.27-2.62 (m, 18
H), 9.68 (s, 1H); 13C NMR δ 26.93, 27.18, 30.73, 31.68, 32.42, 32.80,
35.93(2C), 39.78, 39.97, 57.28, 205.51: MS (EI) m/z (%) 178 (M, 18),
148 (100). Oxidation of 43 (18 mg, 0.1 mM) was performed by stirring
with KMnO4 (11 mg, 0.07 mM) in water (1 mL) and dichloromethane
(1 mL) including 0.1 mL of H2SO4 at 10 °C for 4 h to give acid 44 (15
1
mg, 69%): IR (KBr) 3500-2500, 1697 cm-1; H NMR δ 1.48-2.80
(m, 18 H), 13.02 (br s, 1H); 13C NMR δ 27.09, 27.38, 31.08, 32.28,
34.33, 35.51, 36.14, 36.34, 40.15, 40.36, 49.75, 183.60; MS (EI) m/z
(%) 194 (M, 100), 148 (40). Finally, esterification of 44 with
diazomethane gave the authentic sample (62% yield), which was
identical with the reduced product from 2.
With Butadiene. Addition of butadiene by bubbling (15 min) and
chromatography (H/A 10/1) gave 45 (5 mg, 19%): IR (neat) 2905,
1728, 1660 cm-1; 1H NMR δ 1.23-2.69 (m, 19 H), 3.63 (s, 3 H), 5.67
(m, 2 H); 13C NMR δ 28.33, 28.51, 32.89, 36.43, 37.68, 38.10, 38.23,
38.85, 41.17, 42.21, 44.40, 48.67, 51.62, 52.48, 126.14, 126.56, 179.11;
MS (EI) m/z (%) 260 (M, 18), 200 (100), 135 (54). Anal. Calcd for
C17H24O2: C, 78.42; H, 9.29. Found: C, 78.47; H, 9.22.
With Thiophenol. Addition of thiophenol (55 mg, 0.5 mM),
removal of the excess reagent under vacuum (3 mmHg at 100 °C),
and chromatography (H/A 5/1) gave 37 (19 mg, 60%): IR (CHCl3)
Acknowledgment. This study was supported in part by a
Grant-in-Aid for Developmental Scientific Research (No.
07555285) from the Ministry of Education, Science and Culture
of Japan. We are grateful to Professor Maitland Jones, Jr., of
Princeton University for providing helpful suggestions during
the preparation of this manuscript.
1
2907, 1725, 1157 cm-1; H NMR δ 1.36-2.84 (m, 15 H), 3.01 (m, 1
H), 3.77 (s, 3 H), 7.35-7.64 (m, 5 H); 13C NMR δ 28.54, 28.79, 31.94,
35.51, 35.79, 38.02, 38.38, 38.60, 48.38, 51.50, 53.55, 54.85, 128.82,
129.20, 132.24, 138.04, 176.73; MS (EI) m/z (%) 316 (M, 10), 207
(100), 147 (44). Anal. Calcd for C19H24O2S: C, 72.21; H, 7.64.
Found: C, 72.05; H, 7.68.
JA953977Q