Regiochemistry in aryl radical cyclization onto methylenecycloalkanes

Article abstract of DOI:10.1021/jo001086h

Bu₃SnH-mediated aryl radical cyclization onto methylenecycloalkanes having a phenylthio, an ester, or a nitrile group at the terminus of the alkenic bond provides exclusively exo cyclization products. The results are in sharp contrast to those reported for nonsubstituted methylenecycloalkanes, which give exclusively endo cyclization products. Formation of endo cyclization products has been suggested to be a result of a consecutive 5-exo cyclization of an aryl radical and neophyl rearrangement. The exo-selective aryl radical cyclization offers a new method for synthesizing fused aromatic compounds containing a benzylic quaternary carbon atom.

Full text of DOI:10.1021/jo001086h

9022
J . Org. Chem. 2000, 65, 9022-9027
Regioch em istr y in Ar yl Ra d ica l Cycliza tion on to
Meth ylen ecycloa lk a n es
Hiroyuki Ishibashi,* Tetsuya Kobayashi, Sayaka Nakashima, and Osamu Tamura
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa 920-0934, J apan
isibasi@dbs.p.kanazawa-u.ac.jp
Received J uly 18, 2000
Bu3SnH-mediated aryl radical cyclization onto methylenecycloalkanes having a phenylthio, an ester,
or a nitrile group at the terminus of the alkenic bond provides exclusively exo cyclization products.
The results are in sharp contrast to those reported for nonsubstituted methylenecycloalkanes, which
give exclusively endo cyclization products. Formation of endo cyclization products has been suggested
to be a result of a consecutive 5-exo cyclization of an aryl radical and neophyl rearrangement. The
exo-selective aryl radical cyclization offers a new method for synthesizing fused aromatic compounds
containing a benzylic quaternary carbon atom.
In tr od u ction
Aryl radical cyclizations are now widely used in organic
synthesis for the construction of fused aromatic com-
pounds.1 It has been recognized that a 5-exo cyclization
is generally preferred over a 6-endo ring closure in those
systems having an alkenic bond at the 5-position relative
to the aryl radical center. For example, o-bromo(3-
butenyl)benzene and related compounds 1, upon treat-
ment with Bu3SnH in the presence of AIBN, gave almost
exclusively the 5-exo cyclization products 2.2-4 This was
also the case for the cyclizations of 3-methyl-3-butenyl
congeners 3, in which X ) O2a or NAc,4a giving predomi-
nantly or exclusively the 5-exo cyclization product 4,
respectively. However, when X ) CH2 in 3, the 6-endo
cyclization predominated to give mixtures of 5 and the
5-exo cyclization product 4 in a ratio of (1.3-1.8):1.5
Ghatak and co-workers reported that the aryl radical
cyclization onto methylenecyclohexane 6 gave exclusively
the 6-endo cyclization product 7.6 Formation of 7 from 6
was considered to be a result of the preferred attack of
an aryl radical at the least-substituted methylene center.
On the other hand, we recently reported that methyl-
enecyclohexane 9, having a phenylthio group at the
terminus of the alkene bond, affords exclusively the 5-exo
cyclization product 15.7 The difference between the modes
of cyclization of 6 and 9 led us to further investigate the
role of the substituents in determining the course of the
cyclization onto methylenecycloalkanes. Here, we present
full details of the results with a range of methylenecy-
cloalkanes, showing that a 5-exo cyclization is essentially
preferred over a 6-endo ring closure for the cyclization
onto methylenecycloalkanes and that the formation of
6-endo products is not a result of a direct 6-endo cycliza-
tion of aryl radicals but is explained in terms of a
consecutive 5-exo cyclization and neophyl rearrangement.
* To whom correspondence should be addressed. Fax: +81(76)-234-
4476.
(1) For reviews, see: (a) Giese, B. Radicals in Organic Synthesis:
Formation of Carbon- Carbon Bonds; Pergamon: New York, 1986. (b)
Fossey, J .; Lefort, D.; Sorba, J . Free Radicals in Organic Chemistry;
Wiley: New York, 1995. (c) Curran, D. P. Synthesis 1988, 417, 489.
(d) J asperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91,
1237.
(2) For X ) CH2, see: (a) Abeywickrema, A. N.; Beckwith, A. L. J .;
Gerba, S. J . Org. Chem. 1987, 52, 4072. See also: (b) Beckwith, A. L.
J .; Gara, W. B. J . Am. Chem. Soc. 1969, 91, 5691. (c) Beckwith, A. L.
J .; Gara, W. B. J . Chem. Soc., Perkin Trans. 2 1975, 593, 795. (d)
Beckwith, A. L. J .; O’Shea, D. M.; Roberts, D. H. J . Chem. Soc., Chem.
Commun. 1983, 1445. (e) Abeywickrema, A. N.; Beckwith, A. L. J . J .
Chem. Soc., Chem. Commun. 1986, 464. (f) Meijs, G. F.; Bunnet, J . F.;
Beckwith, A. L. J . J . Am. Chem. Soc. 1986, 108, 4899.
(3) For X ) O, see: (a) Chung, S.-K.; Chung, F. Tetrahedron Lett.
1979, 2473. See also: (b) Beckwith, A. L. J .; Meijs, G. F. J . Chem.
Soc., Chem. Commun. 1981, 136, 595. (c) Ueno, Y.; Chino, K.; Okawara,
M. Tetrahedron Lett. 1982, 23, 2575. (d) Shankaran, K.; Sloan, C. P.;
Snieckus, V. Tetrahedron Lett. 1985, 26, 6001. (e) Meijs, G. F.;
Beckwith, A. L. J . Am. Chem. Soc. 1986, 108, 5890. (f) Beckwith, A.
L. J .; Meijs, G. F. J . Org. Chem. 1987, 52, 1922. (g) Parker, K. A.;
Spero, D. M.; Epp, J . V. J . Org. Chem. 1988, 53, 4628. (h) Bhandal,
H.; Patel, V. F.; Pattenden, G.; Russell, J . J . J . Chem. Soc., Perkin
Trans. 1 1990, 2691. (i) Clark, A. J .; Davies, D. I.; J ones, K.; Millbanks,
C. J . Chem. Soc., Chem. Commun. 1994, 41. (j) Yorimitsu, H.;
Shinokubo, H.; Oshima, K. Chem. Lett. 2000, 104. See also refs 2a,c,e.
(4) For X ) NAc, see: (a) Dittami, J . P.; Ramanathan, H. Tetrahe-
dron Lett. 1988, 29, 45. (b) O¨ zlu¨, Y.; Cladingboel, D. E.; Parsons, P. J .
Tetrahedron 1994, 50, 2183. See also: Inanaga, J .; Ujikawa, O.;
Yamaguchi, M. Tetrahedron Lett. 1991, 32, 1737. See also ref 2c.
Resu lts a n d Discu ssion
The requisite radical precursors 9-14 were prepared
as follows. Reactions of ketone 88 with Ph2P(O)CH(Li)R
(5) (a) Miura, K.; Ichinose, Y.; Nozaki, K.; Fugami, K.; Oshima, K.;
Utimoto, K. Bull. Chem. Soc. J pn. 1989, 62, 143. (b) Rigollier, P.;
Young, J . R.; Fowley, L. A.; Stille, J . R. J . Am. Chem. Soc. 1990, 112,
9441.
(6) (a) Pal, S.; Mukherjee, M.; Podder, D.; Mukherjee, A. K.; Ghatak,
U. R. J . Chem. Soc., Chem. Commun. 1991, 1591. (b) Pal, S.;
Mukhopadhyaya, J . K.; Ghatak, U. R. J . Org. Chem. 1994, 59, 2687.
(7) Ishibashi, H.; Kobayashi, T.; Takamasu, D. Synlett 1999, 1286.
(8) Booth, S. E.; J enkins, P. R.; Swain, C. J .; Sweeney, J . B. J . Chem.
Soc., Perkin Trans. 1 1994, 3499.
10.1021/jo001086h CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/02/2000

Aryl Radical Cyclization onto Methylenecycloalkanes
J . Org. Chem., Vol. 65, No. 26, 2000 9023
Sch em e 1
(for R ) SPh, OMe) gave 9 (91%) and 12 (72%), and
reactions with (EtO)2P(O)CH(Li)R (for R ) CO2Et, CN)
gave 10 (76%) and 11 (86%), respectively. On the other
hand, reaction of 8 with Ph3PdCHR (for R ) Cl or Me)
gave 13 and 14 in 92% and 76% yields, respectively (see
Supporting Information). 1H NMR spectra of compounds
9, 12, and 14 showed them to be mixtures of two
stereoisomers with respect to the alkene bond in ratios
of 22:1, 5:4, and 8:1, respectively, and compounds 10, 11,
and 13 were shown to be single stereoisomers.
When a mixture of Bu3SnH (1.2 equiv) and a catalytic
amount of AIBN in benzene was added slowly to a
solution of ((phenylthio)methylene)cyclohexane 9 in boil-
ing benzene over a period of 1 h and the whole solution
was further heated at reflux for 3 h, the 5-exo cyclization
product 15 was obtained in 91% yield. The structure of
Sch em e 2
15 was readily confirmed by its 1H NMR spectrum, which
showed signals due to the methylene protons R to the
PhS group as two parts of an AB quartet at δ 3.13 and
3.16 (J ) 12.2 Hz). Desulfurization of 15 with Raney Ni
gave the known compound 18,9 thereby confirming the
cis stereochemistry of the ring juncture of 15. In addition,
the whole sequence of the reactions (18 from 9 via 15)
can be regarded in a formal sense as a 5-exo cyclization
of methylenecyclohexane 6.
The chloro-substituted congener 13 gave a mixture of
the 5-exo cyclization product 20 and the reduction product
22 in a ratio of ca. 2:1 and in 55% combined yield. The
1H NMR spectrum of the mixture showed that it also
contained a small quantity of 21.
The ester and nitrile congeners 10 and 11 also gave
the 5-exo cyclization products 16 and 17 in 87 and 81%
yields, respectively.
The methoxy-substituted congener 12 gave the 5-exo
cyclization product 19 (55% yield) along with hexahy-
droanthracene 2110 (15% yield). The NOE difference
Ethylidenecyclohexane 14 gave almost exclusively the
6-endo cyclization products 23a -c in 79% combined yield
as an inseparable mixture containing a trace amount of
the 5-exo cyclization product 24. The stereochemistries
of 23a -c were tentatively assigned as depicted in Scheme
1 by a comparison of the chemical shifts of their methyl
protons (δ 1.10 (J ) 7.3 Hz), 1.31 (J ) 6.9 Hz), and 1.32
(J ) 6.9 Hz)) with those reported for 23a (δ 1.08), 23b (δ
1.28), and 23c (δ 1.31), respectively.11 The structure of
24 was established by its independent synthesis from
ester 16 through LiAlH4 reduction, tosylation of the
resulting alcohol 25, and LiAlH4 reduction of tosylate 26.
The results by Ghatak and us showed that nonsubsti-
tuted and alkyl-substituted methylenecyclohexanes 6 and
14 gave almost exclusively the 6-endo cyclization prod-
ucts, whereas compounds 9-13 gave exclusively or
predominantly the 5-exo cyclization products. Formation
of the observed 5-exo and 6-endo cyclization products was
rationalized by an attack of Bu3SnH on the intermediate
radicals II and III formed from aryl radical I, respectively
(Scheme 2). Compound 21 from 12 or 13 might have
arisen due to elimination of a methoxyl radical or chlorine
spectroscopy showed the ring juncture of 19 to be a cis
relationship. 1H NMR spectral properties of 21 were
identical with the literature values.10
(9) Barrow, C. J .; Bright, S. T.; Coxon, J . M.; Steel, P. J . J . Org.
Chem. 1989, 54, 2542.
(10) Clive, D. L. J .; Zhang, C.; Murthy, K. S. K.; Hayward, W. D.;
Daigneault, S. J . Org. Chem. 1991, 56, 6447.
(11) Hagishita, S.; Kuriyama, K. Bull. Chem. Soc. J pn. 1982, 55,
3216.

9024 J . Org. Chem., Vol. 65, No. 26, 2000
Ishibashi et al.
atom from the intermediate radicals III. The obvious
question, however, is whether the intermediate radicals
III are formed directly by a 6-endo cyclization of aryl
radicals I (R ) H, Me) or by a consecutive 5-exo cycliza-
tion of I and neophyl rearrangement12 of the resulting
radicals II via the intermediates IV.13 We therefore
examined the cyclizations of 6 and 14 in more detail.
When compound 6 was treated with Bu3SnH at a
concentration of 0.1 M, which was much higher than that
(0.007-0.02 M) employed by Ghatak and co-workers,6 a
small quantity of the 5-exo cyclization product 18 was
obtained along with the 6-endo cyclization product 7 in
a ratio of ca. 1:7, along with small quantities of the
recovered 6 and the simple reduction product 27.
Several explanations can be offered for the effect of the
substituent (R) of radicals II on the tendency to undergo
a neophyl rearrangement. One possible explanation is
derived from the consideration of a steric factor of the
substituent. A sterically more demanding substituent
such as an OMe, Cl, SPh, or COOEt group prevents an
attack of a radical center on the aromatic ring, thereby
retarding the neophyl rearrangement. However, despite
its small size, a CN group did not bring out the neophyl
rearrangement. Another explanation involves the relative
stability of radicals II. The nonsubstituted or alkyl-
substituted radical II (R ) H, Me) might be less stable
than the others,14 so that these radicals immediately
attacked the neighboring aromatic ring to give relatively
stable cyclohexadienyl radicals IV, which then afforded
the much more stable tertiary radicals III. Although the
radical II (R ) OMe) is expected to be stabilized signifi-
cantly, the radical underwent the neophyl rearrangement
to some extent. Consequently, an additional possibility
may be derived from the consideration of the nucleophi-
licity of radicals. The radical adjacent to the OMe group
is given nucleophilicity by interacting with the lone pair
of electrons of the oxygen atom, and hence, the radical
has some tendency to attack on the aromatic ring, giving
IV.15
Formation of 18 from 6 suggested that radical I (R )
H) (Scheme 2) cyclized in a 5-exo manner and that the
resulting radical II (R ) H) was rapidly attacked by a
large quantity of Bu3SnH. It is assumed that when the
concentration of Bu3SnH is low (0.007-0.02 M), as
employed by Ghatak, radical II undergoes a neophyl
rearrangement before an attack by Bu3SnH resulting in
the formation of III. A more distinguishing result was
obtained by treating 14 with 1.2 equiv. of Bu3SnH (not
using the slow addition technique) in the presence of
triethylborane at room temperature for 12 h. This gave
predominantly the 5-exo cyclization product 24 together
with the recovered starting material 14 in a ratio of ca.
As noted above, vinyl sulfide 9 gave 15 and 18 (by
desulfurization of 15), and this method therefore provides
a new synthesis of fused aromatic compounds containing
a benzylic quaternary carbon atom.16 We then examined
an extended application of this method to the cyclization
of vinyl sulfides 30 and 31 having a methylenecyclopen-
tane or -cycloheptane ring.
Treatment of compounds 30 and 31 with Bu3SnH in
the presence of AIBN in boiling benzene gave the
expected 5-exo cyclization products 32 and 33 in 75 and
82% yields, respectively. Desulfurization of compounds
1
6:1. The H NMR spectrum of this mixture also showed
a negligibly small signal due to the methyl protons for
23a , and accordingly, it seemed reasonable to assume
that the reaction also provided small quantities of the
6-endo cyclization product 23a -c. This result strongly
suggests that the 5-exo cyclization of I (R ) Me) giving
II (R ) Me) (Scheme 2) is kinetically favored over the
6-endo cyclization and that the formation of the 6-endo
cyclization products 23a -c under the usual radical
reaction conditions (slow addition of Bu3SnH) is a result
of a consecutive 5-exo cyclization and neophyl rearrange-
ment.
32 and 33 with Raney Ni afforded 34 and 35, respec-
tively. The NOE difference spectra showed compound 34
to be a single cis isomer and compound 35 to be a mixture
of cis and trans isomers in a ratio of 4.3:1.
(14) (a) McMillen, D. F.; Golden, D. M. Annu. Rev. Phys. Chem. 1982,
33, 493. (b) Bordwell, F. G.; Zhang, X.-M. Acc. Chem. Res. 1993, 26,
510. (c) Leroy, G.; Sana, M.; Wilante, C. J . Mol. Struct. (THEOCHEM)
1989, 198, 159. See also ref 1b, pp 31-38.
(12) (a) Ruchardt, C.; Hecht, R. Chem. Ber. 1965, 98, 2471. (b)
Parker, K. A.; Spero, D. M.; Inman, K. C. Tetrahedron Lett. 1986, 27,
2833. (c) McNab, H. J . Chem. Soc., Chem. Commun. 1990, 543. (d)
Crich, D.; Yao, Q. J . Org. Chem. 1995, 60, 84. (e) Ishibashi, H.; Ohata,
K.; Niihara, M.; Sato, T.; Ikeda, M. J . Chem. Soc., Perkin Trans. 1
2000, 547. See also ref 2a.
(13) In Scheme 2, reverse processes of the radicals II and III to the
aryl radical I are not considered, since it is well-known that a primary
or a secondary radical is much more stable than is an aryl radical (bond
dissociation energies: Et-H, 101 kcal/mol; cyclo-C6H11-H, 99 kcal/
mol; Ph-H, 111 kcal/mol).1b For a similar discussion, see ref 2a.
(15) Kurz, M. E.; Baru, V.; Nguyen, P.-N. J . Org. Chem. 1984, 49,
1603. See also ref 1a, pp 4-35.
(16) For other sulfur-controlled exo selective radical cyclizations,
see: (a) Ishibashi, H.; Kameoka, C.; Iriyama, K.; Kodama, K.; Sato,
T.; Ikeda, M. J . Org. Chem. 1995, 60, 1276. (b) Ishibashi, H.; Kameoka,
C.; Kodama, K.; Ikeda, M. Tetrahedron 1996, 52, 489. (c) Ishibashi,
H.; Kawanami, H.; Nakagawa, H.; Ikeda, M. J . Chem. Soc., Perkin
Trans. 1 1997, 2291.

Aryl Radical Cyclization onto Methylenecycloalkanes
J . Org. Chem., Vol. 65, No. 26, 2000 9025
Ra d ica l Cycliza tion of 9 w ith Bu 3Sn H-AIBN in Boil-
in g Ben zen e. Gen er a l P r oced u r e. To a boiling solution of
9 (301 mg, 0.807 mmol) in benzene (75 mL) was added
dropwise a solution of Bu3SnH (282 mg, 0.969 mmol) and AIBN
(15.9 mg, 0.097 mmol) in benzene (38 mL) via a syringe over
1 h, and the mixture was further heated under reflux for 3 h.
After evaporation of the solvent, Et2O (50 mL) and an 8%
aqueous KF solution (50 mL) were added to the residue, and
the whole mixture was vigorously stirred at room temperature
for 16 h. The organic phase was separated, and the aqueous
phase was further extracted with Et2O. The combined organic
phase was washed with brine, dried (MgSO4), and concen-
trated. The residue was chromatographed on silica gel (hexane/
AcOEt, 50:1) to give cis-1,2,3,4,4a,9a-hexahydro-4a-((phenylthio)-
methyl)fluorene (15) (216 mg, 91%) as a colorless oil: 1H NMR
(500 MHz) δ 1.14-1.27 (2 H, m), 1.29-1.37 (1 H, m), 1.44-
1.55 (2 H, m), 1.65-1.72 (1 H, m), 1.78 (1 H, ddd, J ) 14.2,
10.3, 3.9 Hz), 1.95-2.01 (1 H, m), 2.46-2.52 (1 H, m), 2.53 (1
H, dd, J ) 15.1 4.4 Hz), 3.01 (1 H, dd, J ) 15.1 6.4 Hz), 3.13
(1 H, d, J ) 12.2 Hz), 3.16 (1 H, d, J ) 12.2 Hz), 7.09-7.26 (9
H, m); 13C NMR (125.7 MHz) δ 22.1, 23.5, 28.2, 32.2, 36.3, 42.8,
44.3, 50.5, 122.9, 125.5, 125.6, 126.1, 126.7, 128.7 (2C), 129.0
(2C), 138.2, 142.8, 148.1. Anal. Calcd for C20H22S: C, 81.58;
H, 7.53. Found: C, 81.27; H, 7.67.
Ghatak and co-workers reported that the homologous
system 36 cyclized also in an endo manner to give the
product 37.17,18 We found that vinyl sulfide 39 gave the
Ra d ica l Cycliza tion of 10. Following the general proce-
dure, compound 10 (111 mg, 0.33 mmol) was treated with Bu3-
SnH (122 mg, 0.42 mmol) in the presence of AIBN (6.6 mg,
0.042 mmol) in benzene (51 mL). After workup, the crude
material was chromatographed on silica gel (hexane/AcOEt,
20:1) to give ethyl cis-1,2,3,4,4a,9a-hexahydrofluorene-4a-
acetate (16) (75.9 mg, 87%) as a colorless oil: IR (CHCl3) ν
1720 cm-1 1H NMR (500 MHz) δ 1.15 (3 H, t, J ) 6.3 Hz),
;
exo cyclization product 40 in 40% yield along with small
amounts of 41 and the reduction product 42. The cis
stereochemistry of the ring juncture of 40 was established
by transforming it to the known compound 43.19 Forma-
tion of 41 may be rationalized in terms of an elimination
of the benzenethiyl radical from the intermediate radical
44 formed by a 7-endo cyclization of an aryl radical.
In conclusion, we revealed that aryl radical cyclization
onto methylenecycloalkanes occurred initially in a 5-exo
manner20 and that formation of endo cyclization products
was a result of a consecutive exo cyclization and neophyl
rearrangement. In adidition, the whole sequence of the
reactions for vinyl sulfides 9, 30, 31, and 39 can be
regarded in a formal sense as an exo cyclization of the
corresponding nonsusbtituted methylenecycloalkanes,
since the products could readily be desulfurized to give
18, 34, 35, and 43, respectively. Moreover, the exo
selective aryl radical cyclization herein described offers
a new method for synthesizing fused aromatic compounds
containing a benzylic quaternary carbon atom.
1.18-1.53 (5H, m), 1.66-1.73 (2 H, m), 1.95-2.01 (1 H, m),
2.39-2.45 (1 H, m), 2.47 (1 H, d, J ) 13.7 Hz), 2.53 (1 H, d, J
) 13.7 Hz), 2.55 (1 H, dd, J ) 15.6, 4.7 Hz), 3.11 (1 H, dd, J
) 15.0, 6.9 Hz), 4.03 (1 H, dq, J ) 15.6, 6.3 Hz), 4.04 (1 H, dq,
J ) 15.6, 6.3 Hz), 7.08-7.25 (4 H, m); 13C NMR (125.7 MHz)
δ 14.1, 21.9, 23.2, 27.8, 32.7, 37.0, 43.4, 43.5, 48.6, 59.9, 122.7,
125.5, 126.0, 126.4, 142.5, 148.4, 171.7. HRMS: calcd for
C
17H22O2, 258.1620; found, 258.1625.
Ra d ica l Cycliza tion of 11. Following the general proce-
dure, compound 11 (89.0 mg, 0.31 mmol) was treated with Bu3-
SnH (120 mg, 0.41 mmol) in the presence of AIBN (8.6 mg,
0.052 mmol) in benzene (47 mL). After workup, the crude
material was chromatographed on alumina (hexane/AcOEt, 20:
1) to give cis-1,2,3,4,4a,9a-hexahydrofluorene-4a-acetonitrile
(17) (52.5 mg, 81%) as a colorless oil: IR (CHCl3) ν 2250 cm-1
;
1H NMR (500 MHz) δ 1.16-1.45 (3 H, m), 1.45-1.59 (2 H, m),
1.67-1.80 (2 H, m), 2.05-2.12 (1 H, m), 2.26-2.33 (1 H, m),
2.48 (1 H, d, J ) 16.6 Hz), 2.52 (1 H, d, J ) 16.6 Hz), 2.59 (1
H, dd, J ) 15.6, 3.8 Hz), 3.02 (1 H, dd, J ) 15.6, 6.3 Hz), 7.15-
7.32 (4 H, m); 13C NMR (125.7 MHz) δ 21.7, 23.2, 27.9, 28.4,
32.0, 36.1, 43.9, 47.8, 118.3, 122.3, 125.8, 126.7, 127.4, 142.1,
146.2. Anal. Calcd for C15H17N: C, 85.26; H, 8.11; N, 6.63.
Found: C, 84.93; H, 8.24; N, 6.45.
cis-1,2,3,4,4a ,9a -Hexa h yd r o-4a -m eth ylflu or en e (18). To
a solution of 15 (105 mg, 0.357 mmol) in EtOH (10 mL) was
added Raney Ni, and the mixture was heated under reflux for
2 h. Raney Ni was filtered off, and the filtrate was concentrated
to give 189 (65.3 mg, 98%) as a colorless oil: 1H NMR (500
MHz) δ 1.23 (3 H, s), 1.23-1.50 (6 H, m), 1.60-1.74 (2 H, m),
2.08 (1 H, br quintet, J ) 6.4 Hz), 2.66 (1 H, dd, J ) 15.1, 7.3
Hz), 2.89 (1 H, dd, J ) 15.1, 7.3 Hz), 7.10 (1 H, br d, J ) 7.3
Hz), 7.12 (1 H, br t, J ) 7.3 Hz), 7.16 (1 H, br t, J ) 7.3 Hz),
7.22 (1 H, br d, J ) 7.3 Hz); 13C NMR (125.7 MHz) δ 22.2,
22.8, 25.7, 26.8, 35.4, 35.6, 45.3, 46.3, 121.6, 125.2, 125.9, 126.1,
142.4, 152.6.
Ra d ica l Cycliza tion of 12. Following the general proce-
dure, compound 12 (106 mg, 0.36 mmol) was treated with Bu3-
SnH (133 mg, 0.46 mmol) in the presence of AIBN (10.5 mg,
0.064 mmol) in benzene (54 mL). After workup, the crude
material was chromatographed on silica gel (hexane/AcOEt,
50:1). The first fraction gave 1,2,3,4,4a,10-hexahydroan-
thracene (21) (10.2 mg, 15%), which crystallized on standing:
mp 32-34 °C (lit.10 an oil); 1H NMR (500 MHz) δ 1.15-1.95 (5
Exp er im en ta l Section
Melting points are uncorrected. 1H and 13C NMR spectra
were measured for solutions in CDCl3. Column chromatogra-
phy was performed on silica gel 60 PF254 (Nacalai Tesque) or
alumina 90 (70-230 mesh) (E. Merck, No. 1097) under
pressure.
(17) (a) Ghosh, A. K.; Ghosh, K.; Pal, S.; Ghatak, U. R. J . Chem.
Soc., Chem. Commun. 1993, 809. (b) Ghosh, A. K.; Mukhopadhyaya,
J . K.; Ghatak, U. R. J . Chem. Soc., Perkin Trans. 1 1997, 2747.
(18) For analogous endo selective aryl radical cyclizations, see: (a)
Ghosh, K.; Ghosh, A. K.; Ghatak, U. R. J . Chem. Soc., Chem. Commun.
1994, 629. (b) Ghosh, K.; Ghatak, U. R. Tetrahedron Lett. 1995, 36,
4897.
(19) (a) Sinha, G.; Maji, S. K.; Ghatak, U. R.; Mukherjee, M.;
Mukherjee, A. K.; Chakravarty, A. K. J . Chem. Soc., Perkin Trans. 1
1983, 2519. (b) Campbell, A. L.; Leader, H. N.; Sierra, M. G.; Spencer,
C. L.; McChesney, J . D. J . Org. Chem. 1979, 44, 2755. (c) Barnes, R.
A.; Beachem, M. T. J . Am. Chem. Soc. 1955, 77, 5388.
(20) The exo selective aryl radical cyclizations onto the corresponding
oxime ethers have been reported.8

9026 J . Org. Chem., Vol. 65, No. 26, 2000
Ishibashi et al.
H, m), 1.95-2.25 (2 H, m), 2.35-2.55 (2 H, m), 2.56 (1 H, dd,
J ) 15.5, 12.2 Hz), 2.90 (1 H, dd, J ) 15.5, 7.3 Hz), 6.12 (1 H,
t, J ) 2.0 Hz), 6.93 (1 H, d, J ) 7.3 Hz), 7.00-7.30 (3 H, m).
The second fraction gave cis-1,2,3,4,4a,9a-hexahydro-4a-(meth-
oxymethyl)fluorene (19) (42.6 mg, 55%) as a colorless oil: 1H
NMR (500 MHz) δ 1.17-1.93 (8 H, m), 2.32-2.38 (1 H, m),
2.55 (1 H, dd, J ) 15.5, 4.6 Hz), 2.98 (1 H, dd, J ) 15.5, 6.8
Hz), 3.23 (1 H, d, J ) 9.3 Hz), 3.30 (3 H, s), 3.34 (1 H, d, J )
9.3 Hz), 7.10-7.25 (4 H, m); 13C NMR (125.7 MHz) δ 22.3, 23.6,
28.3, 30.2, 36.7, 40.7, 50.7, 59.6, 78.6, 123.2, 125.6, 126.3, 126.7,
143.5, 148.4. Anal. Calcd for C15H20O: C, 83.29; H, 9.32.
Found: C, 82.92; 9.49.
P r ep a r a tion of 24 fr om 16. LiAlH4 (19.0 mg, 0.500 mmol)
was added to a solution of 16 (64.6 mg, 0.250 mmol) in THF
(2 mL) at 0 °C, and the mixture was stirred at the same
temperature for 6 h. After completion of the reaction, Celite,
AcOEt (1 mL), EtOH (1 mL), and water (1 mL) were added
successively to the reaction mixture, and the mixture was
stirred for 1 h. The inorganic materials were filtered off, and
the filtrate was washed with brine, dried (MgSO4), and
concentrated. The residue was chromatographed on silica gel
(hexane/AcOEt, 2:1) to give cis-1,2,3,4,4a,9a-hexahydro-4a-(2-
hydroxyethyl)fluorene (25) (49.9 mg, 92%) as a colorless oil:
1
IR (CHCl3) ν 3620 cm-1; H NMR (500 MHz) δ 1.15 (1 H, br),
1.18-1.28 (2 H, m), 1.29-1.40 (1 H, m), 1.40-1.53 (3 H, m),
1.61-1.70 (1 H, m), 1.80 (1 H, ddd, J ) 13.9, 8.8, 5.9 Hz), 1.80-
1.89 (1 H, m), 1.98 (1 H, ddd, J ) 13.7, 8.8, 5.9 Hz), 2.20 (1 H,
br quintet, J ) 6.3 Hz), 2.56 (1 H, dd, J ) 15.3, 5.1 Hz), 2.99
(1 H, dd, J ) 15.3, 6.6 Hz), 3.56 (1 H, ddd, J ) 10.3, 8.8, 5.9
Hz), 3.65 (1 H, ddd, J ) 10.3, 8.8, 5.9 Hz), 7.07-7.18 (3 H, m),
7.22 (1 H, br d, J ) 6.4 Hz). This compound was used
immediately in the next step.
Ra d ica l Cycliza tion of 13. Following the general proce-
dure, compound 13 (57.0 mg, 0.19 mmol) was treated with Bu3-
SnH (76.9 mg, 0.26 mmol) in the presence of AIBN (5.2 mg,
0.032 mmol) in benzene (28 mL). After workup, the crude
material was chromatographed on alumina (hexane) to give a
ca. 2:1 mixture of cis-4a-(chloromethyl)-1,2,3,4,4a,9a-hexahy-
drofluorene (20) and 2-(phenylmethyl)-1-(chloromethylene)-
cyclohexane (22) (23.2 mg, 55%) as a colorless oil. A 1H NMR
spectrum of the mixture showed it to contain a trace amount
of 21.
Compound 25 (49.9 mg, 0.231 mmol) was dissolved in
pyridine (1 mL), p-toluenesulfonyl chloride (52.8 mg, 0.277
mmol) was added to the solution at room temperature, and
the mixture was stirred at the same temperature for 18 h. The
reaction mixture was diluted with AcOEt (30 mL), and the
whole mixture was washed successively with 1 N HCl (30 mL)
and brine, dried (MgSO4), and concentrated. The residue was
chromatographed on silica gel (hexane/AcOEt, 7:1) to give cis-
1,2,3,4,4a,9a-hexahydro-4a-[2-(p-toluenesulfonyloxy)ethyl]fluo-
rene (26) (52.4 mg, 61%) as a colorless oil: IR (CHCl3) ν 1360,
An analytical sample of 20 was prepared as follows. To a
solution of the above mixture (44.0 mg) in t-BuOH/H2O (5:4)
(1.8 mL) was added KMnO4 (31.5 mg), and the mixture was
stirred at room temperature for 2 h. After the inorganic
materials had been filtered off, the filtrate was diluted with
water (20 mL) and the whole mixture was extracted with
AcOEt. The extract was washed with aqueous Na2S2O3 solu-
tion (20 mL), dried (MgSO4), and concentrated. The crude
material was chromatographed on alumina (hexane) to give
20 (9.6 mg) as a colorless oil: 1H NMR (500 MHz) δ 1.10-
1.24 (2 H, m), 1.25-1.37 (1 H, m), 1.45-1.57 (2 H, m), 1.66-
1.74 (1 H, m), 1.85 (1 H, ddd, J ) 14.7, 10.7, 3.9 Hz), 1.93-
2.00 (1 H, m), 2.42-2.49 (1 H, m), 2.52 (1 H, dd, J ) 15.4, 3.7
Hz), 3.04 (1 H, dd, J ) 15.4, 6.6 Hz), 3.48 (1 H, d, J ) 11.0
Hz), 3.56 (1 H, d, J ) 11.0 Hz), 7.16-7.27 (4 H, m); 13C NMR
(125.7 MHz) δ 21.9, 23.6, 28.5, 30.0, 36.4, 41.4, 51.2, 52.3,
123.2, 125.9, 126.3, 127.2, 143.1, 146.2. HRMS: calcd for
1
1175 cm-1; H NMR (500 MHz) δ 1.13-1.35 (3 H, m), 1.38-
1.47 (3 H, m), 1.57-1.65 (1 H, m), 1.73-1.80 (1 H, m), 1.87 (1
H, ddd, J ) 15.1, 8.8, 6.3 Hz), 2.01 (1 H, ddd, J ) 15.1, 8.8,
5.8 Hz), 2.08 (1 H, br quintet, J ) 6.9 Hz), 2.44 (3 H, s), 2.53
(1 H, dd, J ) 15.6, 5.8 Hz), 2.87 (1 H, dd, J ) 15.6, 6.3 Hz),
3.93 (1 H, ddd, J ) 10.0, 9.4, 5.9 Hz), 4.03 (1 H, ddd, J ) 10.0,
9.4, 6.3 Hz), 6.91 (1 H, br d, J ) 6.9 Hz), 7.09 (1 H, br t, J )
6.9 Hz), 7.12 (1 H, td, J ) 6.9, 1.9 Hz), 7.19 (1 H, br d, J ) 6.9
Hz), 7.30 (2 H, d, J ) 7.8 Hz), 7.70 (1 H, d, J ) 7.8 Hz). This
compound was used immediately in the next step.
C
14H1735Cl, 220.1019; found, 220.1014.
The structure of 22 was confirmed by the following inde-
Compound 26 (52.4 mg, 0.141 mmol) was dissolved in THF
(2 mL), LiAlH4 (10.7 mg, 0.283 mmol) was added to the
solution at room temperature, and the mixture was heated
under reflux for 2 h. After workup as described above for the
preparation of 25, the crude material was chromatographed
on silica gel (hexane/AcOEt, 2:1) to give 24 (22.9 mg, 81%) as
a colorless oil: 1H NMR (500 MHz) δ 0.76 (3 H, t, J ) 7.4 Hz),
1.14-1.36 (3 H, m), 1.38-1.54 (2 H, m), 1.59-1.72 (2 H, m),
1.81-1.89 (1 H, m), 2.19 (1 H, quintet, J ) 6.6 Hz), 2.52 (1 H,
dd, J ) 15.1, 4.9 Hz), 2.98 (1 H, dd, J ) 15.1, 6.8 Hz), 7.06 (1
H, br d, J ) 6.4 Hz), 7.10-7.17 (4 H, m), 7.22 (1 H, br d, J )
6.4 Hz); 13C NMR (67.9 MHz) δ 8.7, 22.1, 23.5, 28.0, 30.9, 32.8,
36.3, 43.3, 49.4, 122.8, 125.5, 125.6, 125.9, 143.2, 149.2. Anal.
Calcd for C15H20: C, 89.94; H, 10.06. Found: C, 89.77; H, 10.29.
pendent synthesis. Using a procedure similar to that described
above for the preparation of 13, a suspension of (chloromethyl)-
triphenylphosphonium chloride (732 mg, 2.11 mmol) in Et2O
(3 mL) was treated with PhLi (0.88 M cyclohexane/diethyl
ether solution) (2.40 mL, 2.11 mmol) and then with 2-(phe-
nylmethyl)cyclohexanone21 (132 mg, 0.70 mmol). After workup,
the crude material was chromatographed on alumina (hexane)
to give 22 (146 mg, 94%) as a colorless oil: 1H NMR (500 MHz)
δ 1.32-1.40 (1 H, m), 1.40-1.50 (1 H, m), 1.50-1.76 (4 H, m),
2.29 (1 H, ddd, J ) 13.3, 7.5, 4.7 Hz), 2.38-2.45 (1 H, m), 2.51
(1 H, ddd, J ) 13.3, 8.0, 4.7 Hz), 2.61 (1 H, dd, J ) 13.2, 8.8
Hz), 2.89 (1 H, dd, J ) 13.2, 6.3 Hz), 5.70 (1 H, s), 7.11 (2 H,
br d, J ) 7.0 Hz), 7.19 (1 H, br t, J ) 7.0 Hz), 7.28 (2 H, br t,
J ) 7.0 Hz). HRMS: calcd for C14H1735Cl, 220.1019; found,
220.1018.
Ra d ica l Cycliza tion of 14. Following the general proce-
dure, compound 14 (123 mg, 0.44 mmol) was treated with Bu3-
SnH (194 mg, 0.67 mmol) in the presence of AIBN (10.4 mg,
0.063 mmol) in benzene (66 mL). After workup, the crude
material was chromatographed on alumina (hexane) to give a
mixture of (4aS*,9R*,9aR*)-23a ,11 (4aS*,9S*,9aR*)-23b,11 and
(4aR*,9S*,9aR*)-1,2,3,4,4a,9,9a,10-octahydro-9-methylan-
thracene (23c)11 (70.0 mg, 79%) as a colorless oil: 1H NMR
(270 MHz) δ 0.80-2.00 (m), 1.10 (d, J ) 7.3 Hz, Me for 23a ),
1.31 (d, J ) 6.9 Hz, Me for 23b), 1.32 (d, J ) 6.9 Hz, Me for
23c), 2.00-3.10 (m), 6.98-7.30 (4 H, m). The 1H NMR
spectrum of this mixture showed it to contain a trace amount
of cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrofluorene (24) (δ 0.76 (t,
J ) 7.4 Hz, MeCH2)), whose structure was confirmed by the
following independent synthesis.
Ra d ica l Cycliza tion of 6 w ith Bu 3Sn H a t a 0.1 M
Con cen tr a tion . To a solution of 66,22 (92.2 mg, 0.360 mmol)
in benzene (3.5 mL) were added Bu3SnH (115 mg, 0.396 mmol)
and AIBN (9.7 mg, 0.040 mmol), and the mixture was heated
under reflux for 9 h. After workup, the crude material was
chromatographed on silica gel (hexane). The first fraction gave
an oily mixture of 7,6,22 18, and the recovered 6 (52.1 mg) in a
ratio of ca. 7:1:2: 1H NMR (500 MHz) δ 1.00-1.10 (7/10 × 2 H,
m, for 7), 1.23 (1/10 × 3 H, s, for 18), 1.23-1.90 [(2/10 × 6 + 7/10
1
1
× 8 + /10 × 8) H, m], 2.05-2.13 [(2/10 + /10) H, m], 2.35 (2/10
H, dt, J ) 13.1, 3.8 Hz, for 6), 2.40-2.50 [(2/10 + /10) × 2 H,
7
m], 2.66 (1/10 H, dd, J ) 15.1, 7.3 Hz, for 18), 2.72 (2/10 H, dd,
J ) 14.1, 8.8 Hz, for 6), 2.78 (7/10 × 2 H, dd, J ) 15.5, 4.0 Hz,
for 7), 2.89 (1/10 H, dd, J ) 15.1, 7.3 Hz, for 18), 3.08 (2/10 H,
dd, J ) 14.1, 5.6 Hz, for 6), 4.60 (2/10 H, s, for 6), 4.70 (2/10 H,
s, for 6), 7.00-7.30 [(3 + 8/10) H, m], 7.53 (2/10 H, d, J ) 6.9 Hz,
for 6). The second fraction gave 1-methylene-2-(phenylmethyl)-
(21) (a) Stork, G.; Brizzolara, A.; Landesman, H.; Szmuszkovicz, J .;
Terrell, R. J . Am. Chem. Soc. 1963, 85, 207. (b) Yasuda, M.; Hayashi,
K.; Katoh, Y.; Shibata, I.; Baba, A. J . Am. Chem. Soc. 1998, 120, 715.
(22) Volk, T.; Bernicke, D.; Bats, J . W.; Schmalz, H.-G. Eur. J . Inorg.
Chem. 1998, 1883.

Aryl Radical Cyclization onto Methylenecycloalkanes
J . Org. Chem., Vol. 65, No. 26, 2000 9027
cyclohexane (27)23 (10.8 mg, 16%) as a colorless oil: 1H NMR
(500 MHz) δ 1.10-1.74 (7 H, m), 2.00-2.12 (1H, m), 2.25-
2.37 (1 H, m), 2.53 (1 H, dd, J ) 13.4, 9.3 Hz), 2.98 (1 H, dd,
J ) 13.4, 5.4 Hz), 4.60 (1 H, s), 4.68 (1 H, s), 7.16 (1 H, br d,
J ) 7.3 Hz), 7.18 (1 H, br t, J ) 7.3 Hz), 7.27 (1 H, br t, J )
7.3 Hz).
that described above for the preparation of 18 from 15,
compound 33 (204 mg, 0.661 mmol) was treated with Raney
Ni in EtOH (20 mL). Workup gave 35 (124 mg, 95%) as an
oily mixture of two stereoisomers in the ratio of ca. 4.3:1: 1H
NMR (500 MHz) δ 1.03 (10/53 × 3 H, s), 1.21 (43/53 × 3 H, s),
1.25-1.96 [(43/53 + 9) H, m], 2.15-2.23 (1 H, m), 2.35-2.45
(10/53 H, m), 2.60 (1 H, dd, J ) 16.1, 3.9 Hz), 2.80 (10/53 H, dd,
J ) 16.1, 8.3 Hz), 3.23 (43/53 H, dd, J ) 16.1, 8.3 Hz), 7.09-
7.23 (4 H, m); 13C NMR (125.7 MHz) δ 20.1 (trans), 24.2 (cis),
26.2 (trans), 26.6 (trans), 26.9 (trans), 27.8 (trans), 28.5 (cis),
30.0 (cis), 31.3 (cis), 32.8 (cis), 38.0 (trans), 39.0 (cis), 39.2 (cis),
40.6 (trans), 48.1 (cis), 49.0 (trans), 50.5 (trans), 50.9 (cis), 121.9
(trans), 122.8 (cis), 124.0 (trans), 124.2 (cis), 125.9 (trans), 126.1
(cis), 126.2 (trans), 126.3 (cis), 141.78 (cis), 141.84 (trans), 152.8
(cis), 155.0 (trans). HRMS: calcd for C15H20, 200.1565; found,
200.1566.
Ra d ica l Cycliza tion of 14 w ith Bu 3Sn H-Et3B a t Room
Tem p er a tu r e. A 1.06 M solution of Et3B in hexane (1.10 mL,
1.17 mmol) was added in one portion to a solution of 14 (81.6
mg, 0.29 mmol) and Bu3SnH (114 mg, 0.39 mmol) in benzene
(4 mL) at room temperature, and the mixture was stirred for
12 h under the same conditions. After workup, the crude
material was chromatographed on alumina (hexane) to give
an oily mixture of 24 and the recovered 14 (54.0 mg) in a ratio
of ca. 6:1: 1H NMR (270 MHz) δ 0.76 (6/7 × 3 H, t, J ) 7.4 Hz,
for 24), 1.10-2.15 (10 H, m, for 14 and 24), 2.19 (6/7 H, br
quintet, J ) 6.6 Hz, for 24), 2.25-2.45 (1/7 H, m, for 14), 2.52
(6/7 H, dd, J ) 15.1, 4.9 Hz, for 24), 2.75-3.15 (1/7 × 3 H, m,
for 14), 2.98 (6/7 H, dd, J ) 15.1, 6.8 Hz, for 24), 5.12 (1/7 H, q,
J ) 6.4 Hz, for 14), 6.97-7.30 [(6/7 × 4 + 1/7 × 3) H, m, for 14
Ra d ica l Cycliza tion of 39. Following the general proce-
dure, compound 39 (138 mg, 0.355 mmol) was treated with
Bu3SnH (310 mg, 1.06 mmol) and AIBN (17.5 mg, 0.106 mmol)
in benzene (52 mL). After workup, the crude material was
chromatographed on silica gel (hexane). The first fraction gave
an inseparable mixture of 1,3,4,10,11,11a-hexahydro-2H-
dibenzo[a,d]cycloheptene (41) and unknown compounds (total
12.7 mg). The mass spectrum of this mixture showed peaks
1
and 24], 7.49 (1/7 H, dd, J ) 7.8, 1.0 Hz, for 14). The H NMR
spectrum of this mixture also showed a negligibly small signal
due to the methyl protons for 23a [δ 1.10 (d, J ) 7.3 Hz)].
Ra d ica l Cycliza tion of 30. Following the general proce-
dure, compound 30 (250 mg, 0.696 mmol) was treated with
Bu3SnH (243 mg, 0.835 mmol) in the presence of AIBN (13.7
mg, 0.083 mmol) in benzene (105 mL). After workup, the crude
material was chromatographed on silica gel (hexane) to give
cis-1,2,3,3a,8,8a-hexahydro-3a-((phenylthio)methyl)cyclopenta-
[a]indene (32) (145 mg, 75%) as a colorless oil: 1H NMR (500
MHz) δ 1.37-1.50 (2 H, m), 1.60-1.70 (1 H, m), 1.91-2.07 (3
H, m), 2.65 (1 H, dd, J ) 16.6, 2.0 Hz), 2.74 (1 H, ddt, J )
14.1, 6.3, 2.0 Hz), 3.28 (1 H, d, J ) 12.0 Hz), 3.29 (1 H, dd, J
) 16.6, 8.8 Hz), 3.33 (1 H, d, J ) 12.0 Hz), 7.09-7.14 (1 H,
m), 7.15-7.29 (8 H, m); 13C NMR (125.7 MHz) δ 26.1, 35.6,
38.8, 39.6, 45.5, 47.3, 60.8, 123.7, 124.6, 125.5, 126.7, 127.0,
128.7 (2C), 128.8 (2C), 138.1, 143.4, 148.8. Anal. Calcd for
1
at m/z 310, 200, and 198 (for 41). H NMR for 41 (500 MHz):
δ 1.18-1.65 (5 H, m), 1.75-1.89 (2 H, m), 2.04 (1 H, dddd, J
) 14.9, 8.9, 6.6, 1.0 Hz), 2.13-2.23 (1 H, m), 2.33-2.43 (2 H,
m), 2.74 (1 H, ddd, J ) 14.9, 9.9, 0.5 Hz), 2.81 (1 H, ddd, J )
14.9, 8.9, 1.0 Hz), 6.24 (1 H, s), 7.00-7.05 (2 H, m), 7.09-7.14
(2 H, m). The second fraction gave 2-(2-phenylethyl)-1-((phen-
ylthio)methylene)cyclopentane (42) (5.5 mg, 5%) as a colorless
oil: 1H NMR (500 MHz) δ 1.45-1.87 (7 H, m), 1.93-2.04 (1
H, m), 2.23-2.34 (1 H, m), 2.40 (2 H, t, J ) 6.1 Hz), 2.62 (2 H,
t, J ) 8.1 Hz), 5.9 (16/17 H, s), 5.97 (1/17 H, s), 7.10-7.34 (5
H, m). Anal. Calcd for C21H24S: C, 81.77; H, 7.84. Found: C,
81.97; H, 8.10. The third fraction gave cis-1,2,3,4,4a,9,10,10a-
octahydro-4a-((phenylthio)methyl)phenanthrene (40) (44.1 mg,
40%) as a colorless oil: 1H NMR (500 MHz) δ 1.19-1.46 (3 H,
m), 1.48-1.70 (4 H, m), 1.80 (1 H, ddd, J ) 14.4, 11.5, 3.4
Hz), 1.96-2.05 (1 H, m), 2.13-2.27 (2 H, m), 2.79 (1 H, ddd, J
) 17.6, 6.8, 3.4 Hz), 2.88 (1 H, ddd, J ) 17.6, 10.3, 7.3 Hz),
3.12 (1 H, d, J ) 12.5 Hz), 3.30 (1 H, d, J ) 12.5 Hz), 7.06-
7.17 (4 H, m), 7.21 (2 H, br t, J ) 6.8 Hz), 7.29 (2 H, br d, J )
6.8 Hz), 7.32 (1 H, br d, J ) 6.8 Hz); 13C NMR (125.7 MHz) δ
22.5, 23.7, 25.3, 26.3, 27.8, 34.5, 36.6, 42.1, 47.9, 123.78, 123.80,
125.7, 125.92, 125.94, 126.2, 128.7, 129.4, 129.6, 136.5, 138.1,
141.2. Anal. Calcd for C21H24S: C, 81.77; H, 7.84. Found: C,
81.86; H, 7.94.
C
19H20S: C, 81.38; H, 7.19. Found: C, 81.30; H, 7.26.
Ra d ica l Cycliza tion of 31. Following the procedure,
compound 31 (260 mg, 0.67 mmol) was treated with Bu3SnH
(585 mg, 2.01 mmol) and AIBN (33.0 mg, 0.201 mmol) in
benzene (100 mL). After workup, the crude material was
chromatographed on silica gel (hexane) to give cis- and trans-
1,2,3,4,5,5a,10,10a-octahydro-5a-(phenylthiomethyl)cyclohep-
ta[a]indene (33) (168 mg, 82%) as an oily mixture of two
stereoisomers in a ratio of ca. 4:1: 1H NMR (270 MHz) δ 1.26-
1
2.16 [(4/5 × 9 + /5 × 10) H, m], 2.28 (4/5 H, dd, J ) 14.5, 8.9
Hz), 2.50-2.69 (2 H, m), 2.79-2.94 (1/5 H, m), 3.09 (1/5 H, d, J
) 11.8 Hz), 3.16 (4/5 H, d, J ) 12.0 Hz), 3.23 (4/5 H, d, J ) 12.0
Hz), 3.32 (4/5 H, dd, J ) 16.5, 8.9 Hz), 3.34 (1/5 H, d, J ) 11.8
Hz), 7.05-7.30 (9 H, m). HRMS: calcd for C21H24S, 308.1599;
found, 308.1600.
cis-1,2,3,4,4a ,9,10,10a -Oct a h yd r o-4a -m et h ylp h en a n -
th r en e (43). Using a procedure similar to that described above
for the preparation of 18 from 15, compound 40 (47.5 mg, 0.154
mmol) was treated with Raney Ni in EtOH (3 mL). Workup
gave 4319 (30.1 mg, 98%) as a colorless oil: 1H NMR (500 MHz)
δ 1.24 (3 H, s), 1.18-1.74 (9 H, m), 1.98-2.07 (1 H, m), 2.10-
2.20 (1 H, m), 2.76 (1 H, ddd, J ) 16.4, 6.4, 4.9 Hz), 2.86 (1 H,
ddd, J ) 16.4, 9.3, 6.4 Hz), 7.02-7.16 (3 H, m), 7.28 (1 H, d, J
) 7.8 Hz).
cis-1,2,3,3a ,8,8a -Ta t r a h yd r o-3a -m et h ylcyclop en t a [a ]-
in d en e (34). Using a procedure similar to that described above
for the preparation of 18 from 15, compound 32 (126 mg, 0.448
mmol) was treated with Raney Ni in EtOH (12 mL). Workup
gave 34 (77.9 mg, quant.) as a colorless oil: 1H NMR (500 MHz)
δ 1.32 (3 H, s), 1.35-1.47 (2H, m), 1.55-1.64 (1 H, m), 1.66-
1.74 (1 H, m), 1.86-2.00 (2 H, m), 2.38 (1 H, tdd, J ) 8.8, 4.7,
2.7 Hz), 2.61 (1 H, dd, J ) 16.1, 2.7 Hz), 3.22 (1 H, dd, J )
16.1, 8.8 Hz), 7.06-7.20 (4 H, m); 13C NMR (125.7 MHz) δ 26.2,
28.4, 35.2, 38.6, 41.9, 50.1, 56.5, 123.1, 124.4, 126.2, 126.6,
Ack n ow led gm en t. Financial support of this study
by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Science, Sports, and Culture of
J apan is gratefully acknowledged.
142.7, 152.1. HRMS: calcd for
172.1253.
cis- a n d tr a n s-1,2,3,4,5,5a ,10,10a -Octa h yd r o-5a -m eth -
ylcycloh ep ta [a ]in d en e (35). Using a procedure similar to
C13H16, 172.1252; found,
Su p p or tin g In for m a tion Ava ila ble: Text giving experi-
mental procedures for radical precusors 8-14, 28-31, 38, and
1
39 and figures giving H NMR spectra for 16, 20, 22, 33-35,
and 41 and a 13C NMR spectrum for 34. This material is
available free of charge via the Internet at http://pubs.acs.org.
(23) Destabel, C.; Kilburn, J . D.; Knight, J . Tetrahedron 1994, 50,
11267.
J O001086H