One- And Two-Electron Reactions from the Rearrangement of α-Ketocyclopropanes by O-Stannyl Ketyls

Article abstract of DOI:10.1021/jo971287u

This work summarizes an investigation of the bifunctional reactions of tin(IV) enolates and radicals derived from the cleavage rearrangement of ketocyclopropanes with tributyltin hydride. The intermediates provide an unparalleled dual reactivity in synthe

Full text of DOI:10.1021/jo971287u

J . Org. Chem. 1997, 62, 9159-9164
9159
On e- a n d Tw o-Electr on Rea ction s fr om th e Rea r r a n gem en t of
r-Ketocyclop r op a n es by O-Sta n n yl Ketyls
Eric J . Enholm* and Zhaozhong J . J ia
Department of Chemistry, University of Florida, Gainesville Florida 32611
Received J uly 14, 1997X
Abstract: This work summarizes an investigation of the bifunctional reactions of tin(IV) enolates
and radicals derived from the cleavage rearrangement of ketocyclopropanes with tributyltin hydride.
The intermediates provide an unparalleled dual reactivity in synthesis, allowing for independent
transformations with both electrophiles and radicophiles. Reactions of the enolate with aldehydes
led to aldol products in diastereoselectivities up to 20:1 favoring the erythro product. Reactions
with alkyl halides were also successful, constructing new carbon-carbon bonds by a nucleophilic
displacement reaction. These reactions provide a neutral, mild, and novel alternative to the classical
methods of ketone enolate alkylation performed with hindered bases. Finally, the radical portion
of the cleaved intermediates, separated from the enolate by a methylene unit, was reacted with
allylstannanes to prepare new γ-carbon bonds to an allyl unit. Overall, these new trialkyltin-
associated radical anion intermediates allow entry into the rapidly developing manifold of one-
and two-electron reactions.
In tr od u ction
of the O-stannyl ketyl 2, followed by ring scission (3),
prepares the tin(IV) enolate 4 after transfer of the R
group. The enolates were reacted with aldehyde or alkyl
halide electrophiles (E+), as in the transformation of 4
f 5, to examine the scope and stereochemical conse-
quences of the two-electron reaction sequence. The one-
pot process provides a useful one-electron alternative to
the classical methods of ketone enolate alkylation per-
formed with hindered bases such as LDA. Radical
reactions with allyltributylstannane, as in the transfor-
mation of 3 f 4, were also examined.4 These transfor-
mations take advantage of the radical character in the
bifunctional intermediate 3.
R-Ketocyclopropanes are generally not recognized by
the synthetic community to be useful as a free radical
precursor. However, the reaction of tributyltin hydride
with this functionality led to a radical rearrangement
discovered by Peryere over 25 years ago.1,2 Although this
rearrangement was originally just a mechanistic curios-
ity, potentially useful intermediates involving a tin(IV)
enolate and a radical separated by a methylene unit can
be readily obtained. After those seminal studies, further
investigations of these promising intermediates have not
appeared. An obvious extension of this work would
involve two-electron reactions by quenching the tin(IV)
enolate with electrophilic partners which could form new
carbon-carbon bonds.3 Moreover, one-electron elabora-
tions with radicophiles such as allyltributylstannane also
seemed promising and appeared to have not been exam-
ined in any synthetic applications.4 The dualism in
reactions of bifunctional intermediates such as radical
anions has become an important goal in recent synthetic
organic chemistry, and it is hoped that this work will
further extend the utility of these species in one- and two-
electron transformations.5-7
Resu lts a n d Discu ssion
The first reactions to be studied involved simple
quenching of the tin(IV) enolate with aldehydes, as shown
in Scheme 2. This reaction was run with tin hydride and
a suitable cyclopropyl ketone under standard free radical
conditions, and after TLC indicated consumption of the
starting substrate, an aldehyde was added to the pot.
Three observations about this reaction were readily
apparent. First, if the cyclopropane ring is substituted
with a radical-stabilizing function, such as a phenyl
The reaction used to prepare the enolate and radical
reactive intermediates involves the tributyltin radical
cleavage of a cyclopropyl ketone, as shown in the syn-
thetic sequence of 1 f 4 (Scheme 1). Initial formation
(5) For reviews of ketyl radical anions, see: (a) Hirota, N. In Radical
Ions; Kaiser, E. T., Kevan, L., Eds.; Wiley-Interscience: New York,
1968; pp 35-85. (b) Russell, G. A. In Radical Ions Kaiser, E. T., Kevan,
L., Eds.; Wiley-Interscience: New York, 1968; pp 87-150. (c) Forrester,
A. R.; Hay, J . M.; Thompson, R. H. Organic Chemistry of Stable Free
Radicals; Academic Press: New York, 1968; pp 82-90.
(6) (a) Enholm, E. J .; Kinter, K. S. J . Am. Chem. Soc. 1991, 113,
7784. (b) Enholm, E. J .; Xie, Y.; Abboud, K. A. J . Org. Chem. 1995, 60,
1112. (c) Enholm, E. J .; Kinter, K. S. J . Org. Chem. 1995, 60, 4850. (d)
Enholm, E. J .; Whitley, P. E. Tetrahedron Lett. 1996, 37, 559. (e)
Enholm, E. J .; J ia, Z. J . Tetrahedron Lett. 1996, 37, 1177. (f) Enholm,
E. J .; J ia, Z. J . Tetrahedron Lett. 1995, 36, 6819. (g) Enholm, E. J .;
Whitley, P. E. Tetrahedron Lett. 1995, 36, 9157. (h) Enholm, E. J .;
J ia, Z. J . J . Chem. Soc., Chem. Commun. 1996, 1567. (i) Enholm, E.
J .; J ia, Z. J . J . Org. Chem. 1997, 62, 174. (j) Enholm, E. J .; Whitley, P.
E.; Xie, Y.-P. J . Org. Chem. 1996, 61, 5384.
X Abstract published in Advance ACS Abstracts, December 1, 1997.
(1) (a) Pereyre, M.; Godet, J . Y. Tetrahedron Lett. 1970, 11, 3653.
(b) Mariano, P. S.; Bay, E. J . Org. Chem. 1980, 45, 1763. (c) Davies,
A. G.; Godet, J .-Y.; Muggleton, B.; Pereyre, M. J . Chem. Soc., Chem.
Commun. 1976, 813, 814; (d) Castaing, M.; Pereyre, M.; Ratier, M.;
Blum, P. M.; Davies, A. G. J . Chem. Soc., Perkin Trans. II 1979, 589.
(e) Godet, J .-Y.; Pereyre, M. Acad. Sci. Paris 1971, 1183. (f) Godet,
J .-Y.; Pereyre, M. J . Orgmet. Chem. 1972, 40, C23. (g) Godet, J .-Y.;
Davies, A. G.; Muggleton, B.; Pereyre, M. J . Chem. Soc., Perkin Trans.
II 1976, 1719.
(2) Pereyre, M.; Quintard, J . P.; Rahm A. Tin in Organic Synthesis;
Butterworths: Boston, 1987.
(3) For a review, see: Shibata, I.; Baba, A. Org. Prep. Proc. Int. 1994,
26, 87.
(4) (a) Giese, B. Radicals in Organic Synthesis: Formation of
Carbon-Carbon Bonds; Pergamon Press: New York, 1986. (b) Ra-
maiah, M. Tetrahedron 1987, 43, 3541. (c) Curran, D. P. Synthesis
1988, 417, 489. (d) Hart, D. J . Science 1984, 223, 883. (e) Motherwell,
W. B.; Crich, D. Free Radical Chain Reactions in Organic Synthesis;
Academic Press: New York, 1992.
(7) For related work, see: (a) Kim, Y. H.; Lee, I. S. Heteroatom Chem.
1992, 3, 509. (b) Batey, R. A.; Motherwell, W. B. Tetrahedron Lett.
1991, 32, 6211. (c) Molander, G. A.; McKie, J . A. J . Org. Chem. 1991,
56, 4112. (d) Kirschberg, T.; Mattay, J . J . Org. Chem. 1996, 61, 8885.
(e) Kirschberg, T.; Mattay, J . Tetrahedron Lett. 1994, 35, 7217.
S0022-3263(97)01287-5 CCC: $14.00 © 1997 American Chemical Society

9160 J . Org. Chem., Vol. 62, No. 26, 1997
Enholm and J ia
Sch em e 1
product, the coupling constant between the carbinol
proton and the methine proton was ∼4-5 Hz; for the
minor product, the coupling constant was ∼7-8 Hz. This
assignment was further confirmed by 13C NMR spectra.
According to Heathcock’s earlier studies, the carbinol
resonance of erythro-â-hydroxycarbonyl compounds should
be at 71.6-78.1 ppm and that of threo-isomer should be
higher at 74.0-82.5 ppm.10 For example, in Table 1,
entry 2, the carbinol of the major erythro product 9
appeared at 73.8 ppm, while the carbinol of the minor
threo product 10 was at 75.6 ppm. The erythro assign-
ment for all major products was confirmed using these
complementary methods.
The tin(IV) enolate, formed by the fragmentation of the
R-ketocyclopropane, also was reacted with primary and
allylic alkyl iodides, as shown in Scheme 4. To facilitate
the reaction, 5 equiv of HMPA was added along with the
alkyl halide. Previous studies in our laboratories have
demonstrated that this is an optimum amount of HMPA
to use in tin(IV) enolate alkylations.6j A collection of
several results have been gathered in Table 2. All yields
were synthetically useful for this mild transformation.
In most cases overnight reflux was required. One limita-
tion to this method is that only reactive alkyl halides,
such as primary and activated allylic iodides, could be
used, due to the reduced nucleophilicity of the intermedi-
ate tin enolate.6j
Next, the radical portion of the fragmented intermedi-
ates was reacted with allylstannanes to prepare a new
carbon-carbon bond to an allyl unit. Related reactions
using allyltributyltin have been systematically studied
in some detail since Migita and Pereyre first reported
organohalides undergo this free radical transforma-
tion.11,12 Although numerous free radical reactions with
allyltributylstannanes have been examined using halide,
phenyl selenide, sulfide, and other precursors,13 we could
not find studies using ketocyclopropanes as starting
substrates.
Sch em e 2
group, then it should be possible to selectively favor
cleavage of one bond over the other. Second, two carbons
in the cyclopropane ring become an appendage on the
main backbone between the alcohol and the ketone.
Third, two adjacent stereocenters are present in the
products, affording the possibility of two diastereomers,
the erythro- and threo-aldols.
Several results have been collected in Table 1. The
aldol reaction appears to function well in the unconven-
tional benzene solvent. In most cases the yields are quite
good; however, the modest yield for the non-aryl ketocy-
clopropane 16 is not clear; the intermediate tin enolate
appears to have reduced reactivity toward benzaldehyde.
Ketocyclopropane 11 was utilized in an effort to study
the effects of selective bond scission. The phenyl-
stabilized radical intermediate formed from 11 was
clearly what led to products, while the other bond
cleavage was not observed even in minor products.
Also of interest was the major erythro-aldol formed in
the reaction. Because tin(IV) enolates do not likely react
in a cyclic chelated Zimmerman-Traxler transition state,
particularly at or above ambient temperature, an ex-
tended transition state is proposed for the aldol, shown
in Scheme 3.8a A related open transition state for aldol
reactions of tributyltin(IV) enolates leading to the erythro-
diastereomer has been proposed by Shibata.3 The Z-
isomer of the tin(IV) enolate bearing the aryl substituent
should be preferred.8b Transition state 21 places the
aldehyde R in a less-hindered environment when com-
pared with 23, leading to a predominance of the erythro-
aldol. Particularly noteworthy is the 20:1 ratio of 7 to 8.
The simple diastereoselectivity is synthetically useful in
several examples. Lower reaction temperatures were not
practical due to the freezing point of benzene.
It was hoped that the propagation steps in these
reactions would follow the sequence shown in Scheme 5.
Initiation with AIBN forms the tributyltin radical from
(10) Heathcock, C. H.; Pirrung, M. C.; Sohn, J . E. J . Org. Chem.
1979, 44, 4294.
(11) (a) Kosugi, M.; Kurino, K.; Takayama, K.; Migita, T. J .
Organomet. Chem. 1973, 56, C11. (b) Grignon, J .; Pereyre, M. J .
Organomet. Chem. 1973, 61, C33. (c) Grignon, J .; Servens, C.; Pereyre,
M. J . Organomet. Chem. 1975, 96, 225.
(12) (a) Keck, G. E.; Yates, J . B. J . Am. Chem. Soc. 1982, 104, 5829.
(b) Keck, G. E.; Enholm, E. J .; Yates, J . B.; Wiley, M. R. Tetrahedron,
1985, 41, 4079.
(13) (a) Webb, R. R., II; Danishefsky, S. Tetrahedron Lett. 1983, 24,
1357. (b) Migita, T.; Nagai, K.; Kosugi, M. Bull. Chem. Soc. J pn. 1983,
56, 2480. (c) Ono, N.; Zinsmeister, K.; Kaji, A. Bull. Chem. Soc. J pn.
1985, 58, 1069. (d) Russell, G. A.; Herold, L. L. J . Org. Chem. 1985,
50, 1037. (e) Keck, G. E.; Kachensky, D. F.; Enholm, E. J . J . Org. Chem.
1985, 50, 4317. (f) Hanessian, S.; Alpegiani, M. Tetrahedron Lett. 1986,
27, 4857. (g) Groninger, K. S.; J ager, K. F.; Giese, B. Liebigs Ann.
Chem. 1987, 731. (h) Kano, S.; Yokomatsu, T.; Shibuya, S. J . Org.
Chem. 1989, 54, 513. (i) Chu, C. K.; Doboszewski, B.; Schmidt, W.;
Ullas, G. V.; Roey, P. V. J . Org. Chem. 1989, 54, 2767. (j) Kelly, M. J .;
Newton, R. F.; Roberts, S. M.; Whitehead, J . F. J . Chem. Soc., Perkin
Trans. 1 1990, 2352. (k) Blaszczak, L. C.; Armour, H. K.; Halligan, N.
G. Tetrahedron Lett. 1990, 31, 5693. (l) Ferrier, R. J .; Lee, C.-K.; Wood,
T. A. J . Chem. Soc., Chem. Commun. 1991, 690. (m) Hamon, D. P. G.;
Massy-Westropp, R. A.; Razzino, P. J . Chem. Soc., Chem. Commun.
1991, 722. (n) Paulsen, H.; Matschulat, P. Liebigs Ann. Chem. 1991,
487. (o) Takuwa, A.; Nishigaichi, Y.; Iwamoto, H. Chem. Lett. 1991,
1013. (p) Hasegawa, E.; Ishiyama, K.; Horaguchi, T.; Shimizu, T.
Tetrahedron Lett. 1991, 32, 2029. (q) Yoshida, M.; Morinaga, Y.; Ueda,
M.; Kamigata, N.; Iyoda, M. Chem. Lett. 1992, 227. (r) Waglund, T.;
Claesson, A. Acta Chem. Scand. 1992, 46, 73. (s) Itoh, Y.; Haraguchi,
K.; Tanaka, H.; Matsumoto, K.; Nakamura, K. T.; Miyasaka, T.
Tetrahedron Lett. 1995, 36, 3867. (t) Roe, R. A.; Boojamra, C. G.;
Griggs, J . L.; Bertozzi, C. R. J . Org. Chem. 1996, 61, 6442.
The stereochemical assignments (erythro or threo) were
made by 1H NMR, examining related aldol products and
applying the J threo > J erythro relationship.9 For the major
(8) (a) Zimmerman, H. E.; Traxler, M. D. J . Am. Chem. Soc. 1957,
79, 1920. (b) For a discussion of tin enolate geometry in the aldol
reaction, see: Heathcock, C. H. In The Aldol Addition Reaction in
Asymmetric Synthesis; Morrison, J . D., Ed.; Academic Press: New York,
1984; Vol. 3, pp 136-144.
(9) (a) House, H. O.; Crumrine, D. S.; Teranishi, A. Y.; Olmstead,
H. D. J . Am. Chem. Soc. 1973, 95, 3310. (b) Noyori, R.; Nishida, I.;
Sakata, J . J . Am. Chem. Soc. 1981, 103, 2106.

Rearrangement of Ketocyclopropanes by Stannyl Ketyls
J . Org. Chem., Vol. 62, No. 26, 1997 9161
Ta ble 1. Ald ol Rea ction s of r-Ketocyclop r op a n es
a
b
A ) cyclohexanecarboxaldehyde, B ) benzaldehyde. Ratios determined by 1H NMR integration.
Sch em e 3
O-stannyl ketyl-promoted cyclopropane fragmentations,
allowing a combination of this work with allyltributyltin
chemistry.
Cyclopropyl ketone 6 was first used to examine the
fragmentation-allylation reaction. Refluxing with ben-
zene and allyltributyltin (2 equiv) for several hours
produced the desired product 32, isolated in 50% yield
based on recovered 6, as shown in Scheme 6. Although
the first example was only modestly successful, a second
example with tricyclic ketone 336i as a starting substrate
underwent excellent fragmentation-allylation, as shown
in Scheme 7. The desired allylation product 35 was
isolated as a single diastereomer (>50:1) in 94% yield.
The increase in yield in this case can probably be
attributed to the increase in release of strain energy
during the fragmentation.
Sch em e 4
Several interesting aspects of these reactions are worth
noting. First, selective cleavage of the cyclopropane bond
leading to the ester-stabilized radical center was observed
in Scheme 7, likely as a result of thermodynamic control.6f
Even though there is better orbital overlap with the ketyl
carbon, the kinetically controlled cleavage of the other
cyclopropane bond did not predominate and no allyl
transfer from this alternate mode of cyclopropane cleav-
age was observed. Moreover, the high diastereoselectiv-
ity in 35 might be rationalized by the steric differences
between the faces of the radical center in intermediate
34 for approaching the allyltributyltin molecule. The face
bearing the tin(IV) enolate is less hindered due to the
presence of two sp2 carbons. The stereochemistry of 34
was confirmed by NOE difference NMR. Finally this
interesting free radical method constructed a new carbon-
carbon bond at the γ-position, relative to the carbonyl.
allyltributyltin and sets the propagation process in
motion. The tin radical adds to the carbonyl of cyclo-
propyl ketone 1, giving O-stannyl ketyl species 2. The
cyclopropane fragments to afford enolate radical 3. Al-
lyltributyltin adds an allyl unit through an SH2′ substitu-
tion and regenerates tributyltin radical to continue the
chain reaction. Fragmentation-allylation product 31 is
thus produced. This reaction expands the scope of

9162 J . Org. Chem., Vol. 62, No. 26, 1997
Ta ble 2 Alk yla tion Rea ction s of r-Ketocyclop r op a n es
Enholm and J ia
Sch em e 5
Sch em e 7
erythro-diastereomer. The radical center also underwent
reactions with allyltributylstannane, with one example
giving a diastereoselectivity of 50:1. Overall, these new
trialkyltin-associated radical anion intermediates allow
entry into the rapidly developing manifold of one- and
two-electron reactions.
Sch em e 6
Exp er im en ta l Section
This type of bond construction using nonnucleophilic
methods with a cyclopropyl ketone is difficult to achieve.
Gen er a l. Melting points were determined on a capillary
melting point apparatus and are uncorrected. Infrared spectra
are reported in wavenumbers (cm-1). Chemical shifts for NMR
are reported in ppm downfield (δ) relative to tetramethylsilane
as an internal standard in chloroform. All product ratios were
determined by 1H NMR integration of the mixture of aldols.
Con clu sion
The fragmentation reaction of a cyclopropyl ketone
with tributyltin radical produces a tin(IV) enolate sepa-
rated from a carbon-centered radical by a methylene unit.
These distinct entities allow for reactions with both
electrophiles and radicophiles. Primary and activated
alkyl iodides readily react with the tin(IV) enolate,
affording a new method to form carbon-carbon bonds.
Aldehydes reacted with the enolate to produce aldol-type
products with stereoselectivities up to 20:1, favoring the
All reactions were run under an inert atmosphere of argon
using flame-dried apparatus. All reactions were monitored by
thin-layer chromatography (TLC) and judged complete when
starting material was no longer visible in the reaction mixture
as spotted on TLC. All yields reported refer to isolated
material judged to be homogeneous by thin-layer chromatog-

Rearrangement of Ketocyclopropanes by Stannyl Ketyls
J . Org. Chem., Vol. 62, No. 26, 1997 9163
raphy and NMR spectroscopy. Temperatures above and below
ambient temperature refer to bath temperatures unless oth-
erwise stated. Solvents and anhydrous reagents were dried
according to established procedures by distillation under
nitrogen from an appropriate drying agent: ether, benzene,
and THF from benzophenone ketyl; dichloromethane from
CaH2. Other solvents were used as received from the manu-
facturer. Analytical TLC was performed using precoated silica
gel plates (0.25 mm) using phosphomolybdic acid in ethanol
as an indicator. Column chromatography was performed using
flash silica gel (230-400 mesh). Compounds 6 and 16 were
commercially available.
Gen er a l P r oced u r e for Cyclop r op a n e F r a gm en ta -
tion -Ald ol Rea ction . A cyclopropyl ketone (1 equiv), tribu-
tyltin hydride (1.5 equiv), and AIBN (0.3 equiv) were dissolved
in benzene (0.3 M) and degassed for 20 min with a stream of
Ar. The reaction mixture was then refluxed until the ketone
was consumed by TLC (∼2 h). The reaction flask was cooled
to room temperature, and an aldehyde (3 equiv) was added.
The reaction was allowed to stir for 8 h. To the reaction
mixture were added DBU (1.8 equiv) and 2-3 drops of water.14
A solution of iodine in ethyl ether was added dropwise by a
pipet, until the iodine orange color permanently persisted. The
mixture was suctioned through a silica plug in a coarse fritted
funnel using copious amount of ether. The ether solution was
rotovapped, and the residue was subjected to column chroma-
tography to afford the aldol products.
Ald ols 12 a n d 13: Rf (1:2 ether/hexane) 0.38. For erythro-
12: 1H NMR δ 7.75 (d, J ) 7.5 Hz, 2H), 7.51 (t, J ) 7.5 Hz,
1H), 7.39-7.11 (m, 10H), 6.93 (d, J ) 6.3 Hz, 2H), 5.05 (d, J
) 2.7 Hz, 1H), 3.79 (m, 1H), 3.35 (d, J ) 2.4 Hz, 1H), 2.53-
2.28 (m, 2H), 2.22-2.03 (m, 2H); 13C NMR δ 204.8 (s), 141.8
(s), 141.3 (s), 136.9 (s), 133.4 (d), 128.6 (d, 2C), 128.3 (d, 8C),
127.5 (d), 126.1 (d, 2C), 125.9 (d), 73.7 (d), 52.0 (d), 33.6 (t),
28.4 (t). For threo-13: 1H NMR δ 5.00 (d, J ) 6.3 Hz) for the
carbinol proton; 13C NMR δ 75.8 for the carbinol. HRMS for
C23H22O2 M + H, calcd 331.1698, found 331.1694.
Ald ols 14 a n d 15: Rf (1:2 ether/hexane) 0.39. For erythro-
14: 1H NMR δ 7.76 (d, J ) 7 Hz, 2H), 7.56 (t, J ) 7.5 Hz, 1H),
7.41 (d, J ) 7.5 Hz, 2H), 7.30-7.12 (m, 5H), 3.72 (m, 1H), 3.53
(m, 1H), 2.73-2.62 (m, 1H), 2.58 (d, J ) 3 Hz, 1H), 2.49-2.25
(m, 2H), 2.02-1.92 (m, 2H), 1.78-1.36 (m, 10H); 13C NMR δ
204.9 (s), 141.6 (s), 137.0 (s), 133.3 (d), 128.7 (d, 2C), 128.4 (d,
2C), 128.3 (d, 2C), 128.2 (d, 2C), 125.9 (d), 76.0 (d), 46.6 (d),
40.7 (d), 33.7 (t), 29.2 (t), 29.0 (t), 27.6 (t), 26.2 (t), 26.0 (t),
25.8 (t). For threo-15: 13C NMR δ 77.0 for the carbinol. HRMS
for C23H28O2 M + H calcd 337.2168, found 337.2167.
Ald ols 17 a n d 18: Rf (1:1 ether/hexane) 0.37. For erythro-
17: 1H NMR δ 7.29 (m, 5H), 4.79 (d, J ) 6.3 Hz, 1H), 3.16 (s,
1H), 2.81 (m, 1H), 1.93 (s, 3H), 1.72 (m, 2H), 0.83 (t, J ) 7.5
Hz, 3H); 13C NMR δ 213.0 (s), 140.0 (s), 128.2 (d, 2C), 127.6
(d), 126.1 (d, 2C), 73.9 (d), 61.1 (d), 31.7 (q), 20.5 (t), 11.9 (q).
For threo-18: 1H NMR δ 4.72 (dd, J ) 7.8, 3.6 Hz) for the
carbinol proton; 13C NMR δ 75.4 for the carbinol. HRMS for
C12H16O2 M + H calcd 193.1229, found 193.1227.
Gen er a l P r oced u r e for Cyclop r op a n e F r a gm en ta -
tion -Alk yla tion Rea ction . A cyclopropyl ketone (1 equiv),
tributyltin hydride (1.5 equiv), and AIBN (0.3 equiv) were
dissolved in benzene (0.3 M) and degassed for 20 min with
Ar. The reaction mixture was then refluxed until the ketone
was consumed by TLC (∼2 h). The reaction flask was cooled
to room temperature, and HMPA (5.0 equiv) was added. The
mixture was stirred for 3-5 min, and an alkyl halide (4.0
equiv) was added. The mixture was refluxed for 8 h Workup
with DBU and iodine and chromatography identical with the
procedure above gave the desired alkylated products.14
P h en yl(tr a n s-2-p h en ylcyclop r op yl)m eth a n on e (11).15
Solid NaH (60% in oil, 231 mg, 5.77 mmol) was placed in a
3-necked flask, washed with n-pentane, and fully pumped to
dryness. Trimethyloxosulfonium iodide (1270 mg, 5.77 mmol)
was added, and DMSO (10 mL) was added dropwise to the
solid mixture through an addition funnel. After hydrogen
evolution, the milky solution turned clear and was stirred for
15 min. trans-Chalcone (1 mg, 4.81 mmol) was added. The
mixture was stirred for 20 h, and the reaction was quenched
with water. The mixture was extracted with ether, and the
organic layers were dried, rotovapped, and chromatographed
to give 11 (1080 mg, quantitative) as a white solid: Rf (1:3
1
Keton e 26: Rf (1:1 ether/hexane) 0.87; H NMR δ 7.87 (d,
J ) 9 Hz, 2H), 6.84 (d, J ) 9 Hz, 2H), 3.75 (s, 3H), 3.22 (m,
1H), 1.66 (m, 2H), 1.52-1.35 (m, 2H), 1.13 (m, 16H), 0.79-
0.74 (m, 6H); 13C NMR δ 202.9, 163.2, 130.8, 130.3 (2C), 113.5
(2C), 55.2, 47.1, 32.1, 31.8, 29.8, 29.5 (2C), 29.4, 29.2, 27.5,
25.5, 22.6, 14.0, 11.8; HRMS for C21H34O2 calcd 318.2559, found
318.2554.
Keton e 27: yield 86%; Rf (1:1 ether/hexane) 0.72; 1H NMR
δ 7.95 (d, J ) 9 Hz, 2H), 6.94 (d, J ) 7 Hz, 2H), 5.75 (m, 1H),
5.05-4.94 (m, 2H), 3.86 (s, 3H), 3.41 (m, 1H), 2.38 (m, 2H),
1.69 (m, 2H), 0.87 (t, J ) 7 Hz, 3H); 13C NMR δ 202.0, 163.3,
136.0, 130.4 (3C), 116.3, 113.7 (2C), 55.3, 46.8, 36.0, 25.0, 11.6;
HRMS for C14H18O2 calcd 218.1307, found 218.1304. Anal.
Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 76.92; H,
8.37.
Keton e 28: yield 67%; Rf (1:4 ether/hexane) 0.59; 1H NMR
δ 2.28 (m, 1H), 2.04 (s, 3H), 1.61-1.32 (m, 4H), 1.18 (m, 16H),
0.83-0.76 (m, 6H); 13C NMR δ 212.9 (s), 54.8 (d), 31.8 (t), 31.2
(t), 29.7 (t), 29.5 (t, 2C), 29.4 (t), 29.3 (t), 28.6 (q), 27.4 (t), 24.5
(t), 22.6 (t), 14.0 (q), 11.7 (q); HRMS for C15H30O M + H, calcd
227.2375, found 227.2382.
Keton e 29: yield 79%; Rf (1:4 ether/hexane) 0.69; 1H NMR
δ 7.78 (d, J ) 7.2 Hz, 2H), 7.43 (t, J ) 7 Hz, 1H), 7.32 (t, J )
7.5 Hz, 2H), 7.17-7.00 (m, 5H), 3.34 (m, 1H), 2.49 (m, 2H),
2.03 (m, 1H), 1.69 (m, 2H), 1.44 (m, 1H), 1.12 (m, 16H), 0.77
(t, J ) 7 Hz, 3H); 13C NMR δ 204.1 (s), 141.8 (s), 137.4 (s),
132.8 (d), 128.5 (d, 2C), 128.4 (d, 2C), 128.2 (d, 2C), 128.1 (d,
2C), 125.8 (d), 45.2 (d), 33.7 (t), 33.6 (t), 32.4 (t), 31.8 (t), 29.7
(t), 29.5 (t, 2C), 29.3 (t), 29.2 (t), 27.4 (t), 22.6 (t), 14.1 (q);
HRMS for C26H36O M + H, calcd 365.2844, found 365.2813.
Keton e 30: yield 97%; Rf (1:4 ether/hexane) 0.60; 1H NMR
δ 7.92 (d, J ) 7.2 Hz, 2H), 7.59 (t, J ) 7.2 Hz, 1H), 7.48 (t, J
) 7.5 Hz, 2H), 7.32-7.15 (m, 5H), 5.79 (m, 1H), 5.10-5.01 (m,
2H), 3.57 (m, 1H), 2.74-2.55 (m, 3H), 2.40-2.31 (m, 1H), 2.26-
2.13 (m, 1H), 1.96-1.84 (m, 1H); 13C NMR δ 203.1 (s), 141.6
(s), 137.1 (s), 135.4 (d), 132.9 (d), 128.6 (d, 2C), 128.4 (d, 2C),
128.3 (d, 2C), 128.2 (d, 2C), 125.9 (d), 116.8 (t), 44.9 (d), 36.3
(t), 33.3 (t), 33.2 (t); HRMS for C19H20O M + H, calcd 265.1592,
found 265.1592.
1-(4-Meth oxyp h en yl)h ep t-6-en on e (32). A mixture of
ketone 6 (200 mg, 1.14 mmol), allyltributyltin (1.7 mL, 5.68
mmol), and AIBN (186 mg, 1.14 mmol) in benzene (0.5 mL)
was degassed with a stream of Ar for 10 min and heated at 80
°C for 24 h. Then, AIBN (186 mg, 1.14 mmol) was added, and
the mixture was degassed again with Ar at room temperature
for 10 min. The mixture was again heated at 80 °C for 24 h.
The mixture was directly subjected to column chromatography
to give unreacted 6 (105 mg) and 32 (59 mg, 24%; 50% if
1
ether/hexane) 0.48; H NMR δ 8.01-7.98 (m, 2H), 7.59-7.56
(m, 1H), 7.49-7.43 (m, 2H), 7.35-7.29 (m, 2H), 7.25-7.22 (m,
1H), 7.21-7.17 (m, 2H), 2.91 (m, 1H), 2.70 (m, 1H), 1.93 (m,
1H), 1.56 (m, 1H); 13C NMR δ 198.5, 140.5, 137.8, 132.9, 128.5
(4C), 128.1 (2C), 126.6 (2C), 126.2, 30.0, 29.3, 19.2; HRMS for
C16H14O calcd 222.1045, found 222.1056.
Ald ols 7 a n d 8: Rf (1:1 ether/hexane) 0.36. For erythro-7:
1H NMR δ 7.96 (d, J ) 9 Hz, 2H), 6.96 (d, J ) 9 Hz, 2H), 3.87
(s, 3H), 3.65-3.55 (m, 2H), 2.02-1.87 (m, 2H), 1.82-1.66 (m,
4H), 1.53-0.84 (m, 11H); 13C NMR δ 204.1 (s), 163.7 (s), 130.6
(d, 2C), 130.3 (s), 113.8 (d, 2C), 76.0 (d), 55.3 (d), 48.0 (d), 40.6
(d), 29.4 (t), 28.8 (t), 26.2 (t), 26.0 (t), 25.8 (t), 19.7 (t), 12.3 (q).
For threo-8: 13C NMR δ 77.3 for the carbinol. HRMS for
C18H26O3 calcd 290.1882, found 290.1814.
Ald ols 9 a n d 10: Rf (1:1 ether/hexane) 0.24. For erythro-
9: 1H NMR δ 7.89 (d, J ) 9 Hz, 2H), 7.44-7.17 (m, 5H), 6.90
(d, J ) 9 Hz, 2H), 5.05 (d, J ) 4.5 Hz, 1H), 3.84 (s, 3H), 3.67
(m, 1H), 2.58 (s, 1H), 1.43-1.31 (m, 2H), 0.76 (t, J ) 7 Hz,
3H); 13C NMR δ 203.7, 163.8, 142.1, 130.6 (2C), 130.0, 128.1
(2C), 127.2, 126.1 (2C), 113.8 (2C), 73.8, 55.4, 53.5, 20.4, 12.1.
For threo-10: 1H NMR δ 4.99 (d, J ) 5.9 Hz) for the carbinol
proton; 13C NMR δ 75.6 for the carbinol. HRMS for C18H20O3
M + H calcd 285.1491, found 285.1463.
(14) Curran, D. P.; Chang, C.-T. J . Org. Chem. 1989, 54, 3140.
(15) Corey, E. J .; Chaykovsky, M. J . Am. Chem. Soc. 1965, 87, 1353.

9164 J . Org. Chem., Vol. 62, No. 26, 1997
Enholm and J ia
corrected with recovered 6): Rf (1:3 ether/hexane) 0.47; 1H
NMR δ 7.94 (d, J ) 9 Hz, 2H), 6.93 (d, J ) 9 Hz, 2H), 5.82 (m,
1H), 5.05-4.94 (m, 2H), 3.87 (s, 3H), 2.91 (q, J ) 7.5 Hz, 2H),
2.10 (q, J ) 7 Hz, 2H), 1.75 (m, 2H), 1.48 (m, 2H); 13C NMR δ
198.9, 163.3, 138.5, 130.3 (2C), 130.1, 114.5, 113.6 (2C), 55.4,
38.0, 33.6, 28.6, 24.0; HRMS for C14H18O2 calcd 218.1307, found
218.1304.
1.91-1.87 (m, 2H), 1.44 (m, 2H), 1.17 (t, J ) 7 Hz, 3H); 13C
NMR δ 212.0 (s), 173.8 (s), 133.0 (d), 118.0 (t), 60.4 (t), 58.5
(s), 47.6 (t, 2C), 39.3 (d, 2C), 27.2 (t, 3C), 14.3 (q); HRMS for
C14H20O3 M + H calcd 237.1491, found 237.1498.
Ack n ow led gm en t. We gratefully acknowledge sup-
port by the National Science Foundation (Grant CHE-
9708139) for this work.
8-Allyl-8-(eth oxycar bon yl)bicyclo[3.2.1]octan -3-on e (35).
A mixture of tricyclic ketone 546i (330 mg, 1.70 mmol),
allyltributyltin (1.3 mL, 4.25 mmol), and AIBN (139 mg, 0.851
mmol) in benzene (1.7 mL) was degassed with argon for 15
min and refluxed for 16 h. The mixture was directly chro-
matographed to give the allylation product 35 (376 mg, 94%)
Su p p or tin g In for m a tion Ava ila ble: Proton NMR spectra
for compounds 7-15, 17, 18, 26, 28-30, 32, and 35 (12 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
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1
as a clear oil: Rf (1:1 ether/hexane) 0.58; IR (KBr) 1720; H
NMR δ 5.70-5.57 (m, 1H), 4.99-4.97 (m, 1H), 4.97-4.91 (m,
1H), 4.09 (q, J ) 7 Hz, 2H), 2.65 (d, J ) 15 Hz, 2H), 2.37 (dd,
J ) 4.2 Hz, 2.7 Hz, 2H), 2.25 (d, J ) 7 Hz, 2H), 2.13 (m, 2H),
J O971287U