Radical cyclization of N-aziridinylimines 4. Highly efficient synthesis of dl-pentalenene via consecutive carbon-carbon bond formation approach

Article abstract of DOI:10.1055/s-1998-1850

dl-Pentalenene, an angular triquinane, has been synthesized via tandem radical cyclization of N-aziridinylimine 10 involving the formation of consecutive carbon-carbon bonds.

Full text of DOI:10.1055/s-1998-1850

September 1998
SYNLETT
981
Radical Cyclization of N-Aziridinylimines 4. Highly Efficient Synthesis of dl-Pentalenene via
Consecutive Carbon-Carbon Bond Formation Approach
Sunggak Kim,* Jae Ho Cheong, and Jimmy Yoo
Department of Chemistry, Korea Advanced Institute of Science and Technology, Taejon 305-701, Korea
Fax: +82 42 8695820; e-mail: skim@sorak.kaist.ac.kr
Received 9 June 1998
Abstract: dl-Pentalenene, an angular triquinane, has been synthesized
via tandem radical cyclization of N-aziridinylimine 10 involving the
formation of consecutive carbon-carbon bonds.
The angularly fused triquinane pentalenene bearing tricyclo
4,8
[6.3.0.0 ]undec-2-ene ring system is the parent hydrocarbon of the
pentalenolactone family of fungal metabolites exhibiting antibiotic
1
activity. Intensive efforts have been directed toward the synthesis of
these structurally intriguing molecules and reported syntheses include
2
3
vinylcyclopropane-cyclopentene rearrangement, spiro-annulation, and
Pauson-Khand reaction strategies.
4,5
Furthermore, several promising
radical strategies utilizing tandem radical cyclizations for the synthesis
6
of angular triquinanes have been reported.
N-Aziridinylimines have been served as geminal radical acceptor and
donor equivalents in a single operation, thereby allowing the formation
7
of consecutive carbon-carbon bonds. This approach turned out to be
exceedingly effective for the construction of quaternary carbon centers.
Based on the consecutive carbon-carbon bond formation approach, we
8
previously reported very efficient synthesis of dl-modhephene and dl-
9
zizaene. Herein we report another successful utilization of the
consecutive carbon-carbon bond formation approach for a synthesis of
dl-pentalenene.
A pentalenene skeleton contains three cyclopentane rings and one
quaternary carbon center at the ring junction. Since the carbonyl carbon
would be converted into the quaternary carbon in the present approach,
two of four carbon-carbon bonds at the quaternary carbon center can be
formed by tandem radical cyclizations via consecutive carbon-carbon
bond formation approach. Thus, in retrosynthetic analysis (Figure 1),
two of four bonds at the quaternary carbon center can be disconnected
as indicated by dotted lines and any one of the three rings can be
selected as a central ring. In the synthetic scheme, the dotted lines also
indicate the formation of two carbon-carbon bonds by tandem radical
cyclizations. Approach a, b, and c seem to be unsuitable because the key
intermediates for radical cyclizations involve 8- and 11-membered rings
which would be very difficult to prepare. Approach d and e seem to be
attractive but the trans-stereocontrol of two substituents in the
cyclopentanone derivative would be requisite. Furthermore, the
isomerization of the carbon-carbon double bond should be facile in
approach d. Thus, we adopted approach f in which the key intermediate
1 could be readily accessible from the cyclopentanone derivative 2 and
phenylselenoalkyllithium 3.
The stereocontrol in the radical cyclization reactions would be the most
important factor for the success of this approach and the high
stereoselectivity could be anticipated as shown in Figure 2. The
stereoselectivity of the first cyclization reaction is crucial for the
successful construction of the tricyclic ring system since the undesired
isomeric product could not proceed further in the tandem cyclization
reaction. In the first cyclization, intermediate 4a would be favored over
intermediate 4b, in which the substituent bearing the alkenyl group
would be located below the cyclopentane ring, thereby causing strong
steric interaction between the substituent and the cyclopentane ring
bearing gem-dimethyl group. Furthermore, the stereooutcome of the
second cyclization could be anticipated. We envisioned that the

982
LETTERS
SYNLETT
easily synthesized from allylcyclopentanone 7 in overall approximately
13
30% yield by a 7-step sequence in a highly stereoselective manner.
Acknowledgment. We thank the Korea Science and Engineering
Foundation for financial support (95-0501-06-01-3).
References
1.
2.
3.
4.
5.
(a) Koe, B. K.; Sobin, B. A.; Celmer, W. D. Antibiot. Annu. 1956/
1957, 672. (b) Aizawa, S.; Akutsu, H.; Satomi, T.; Kawabata, S.;
Sasaki, K. J. Antibiot. 1978, 31, 729.
(a) Hudlicky, T.; Natchus, M. G.; Sinai-Zingde, G. J. Org. Chem.
1987, 52, 4641. (b) Hudlicky, T.; Sinai-Zingde, G.; Natchus, M.
G.; Rann, B. C.; Papadopolous, P. Tetrahedron 1987, 43, 5685.
(a) Wu, Y. J.; Burnell, D. J. J. Chem. Soc., Chem. Commun. 1991,
764. (b) Wu, Y. J.; Zhu, Y.-Y.; Burnell, D. J. J. Org. Chem. 1994,
59, 104.
(a) Schore, N. E.; Rowley, E. G. J. Am. Chem. Soc. 1988, 110,
5224. (b) Rowley, E. G.; Schore, N. E. J. Org. Chem. 1992, 57,
6853.
Other synthetic approaches, see : (a) Hua, D. H. J. Am. Chem. Soc.
1986, 108, 3835. (b) Imanishi, T.; Yamashita, M.; Ninbari, F.;
Tanaka, T.; Iwata, C. Chem. Pharm. Bull. 1988, 36, 1371. (c)
Agnel, G.; Negishi, E.-i. J. Am. Chem. Soc. 1991, 113, 7424. (d)
Franck-Neumann, M.; Miesch, M.; Gross, L. Tetrahedron Lett.
1992, 33, 3879. (e) Lange, G. L.; Gottardo, C. J. Org. Chem. 1995,
60, 2183.
6.
(a) Curran, D. P.; Kuo, S.-C. J. Am. Chem. Soc. 1986, 108, 1106.
(b) Schwartz, C. E.; Curran, D. P. J. Am. Chem. Soc. 1990, 112,
9272. (c) Enholm, E. J.; Jia, Z. Tetrahedron Lett. 1996, 37, 1177.
7.
8.
9.
(a) Kim, S.; Kee, I. S.; Lee, S. J. Am. Chem. Soc. 1991, 113, 9882.
(b) Kim, S.; Kee, I. S. Tetrahedron Lett. 1993, 34, 4213.
Lee, H.-Y.; Kim, D.-I.; Kim, S. J. Chem. Soc., Chem. Commun.
1996, 1539.
Kim, S.; Cheong, J. H. Synlett 1997, 947.
10. Treatment of methyl 4,4-dimethyl-2-oxocyclopentanecarboxylate
with allyl bromide and K2CO3 followed by addition of aqueous
KOH afforded 4,4-dimethyl-2-prop-2-enylcyclopentan-1-one (7)
in 70% yield.
stereochemistry of the methyl group would be controlled by steric
interaction between the alkenyl group and hydrogen at the ring junction.
Thus, intermediate 5a would be predominant over intermediate 5b,
yielding the desired stereoisomer as a major product. Furthermore, the
undesired isomer 6 could not undergo cyclization due to the unfavorable
strain form the trans-fused cyclized product.
11. The stereochemistry for hydrogen (2.91ppm) at C1 position of 14
was determined by NOE measurement. Significant NOE was
observed of about 3.07% for hydrogen (2.37ppm) at C8 position.
1H NMR (300 MHz, CDCl3, 14) : δ 5.77 (m, 1H), 4.98 (m, 2H),
2.91 (m, 1H), 2.63 (m, 2H), 2.37 (m, 1H), 2.20-2.01 (m, 3H), 1.95-
1.60 (m, 3H), 1.30-1.15 (m, 3H), 1.04 (s, 3H), 1.01 (s, 3H). 13C
NMR (75 MHz, CDCl3, 14) : δ 220.0, 138.3, 115.0, 51.7, 48.8,
45.1, 43.2, 42.5, 40.1, 35.8, 32.0, 30.2, 28.9, 25.2.
Our synthetic route to the target molecule is straightforward and is
10
shown in Scheme 1. The readily accessible allylcyclopentanone 7 was
12. (a) Piers, E.; Karunaratne, V. J. Chem. Soc., Chem. Commun. 1984,
959. (b) Piers, E.; Karunaratne, V. Can. J. Chem. 1989, 67, 160.
protected and ozonized to afford the aldehyde 8 in 83% yield. Treatment
of 8 with phenylselenoalkyllithium 3 followed by the addition of
aqueous HCl afforded the hydroxyketone 9 in 70% yield. Fortunately,
the formation of the hemiacetal in 9 was not observed. After the
conversion of 9 into N-aziridinylimine 10, when 10 was subjected to the
highly diluted cyclization conditions, an inseparable mixture of the
desired tricyclic compound 11 and the bicyclic compound 12 was
isolated in 84% yield, which existed approximately in a ratio of 6:1
13. A solution of 10 (108 mg, 0.22 mmol) in benzene (44 mL,
0.005M) and a solution of Bu3SnH (139 mg, 0.48 mmol) and
AIBN (11 mg, 0.3 equiv) in benzene (16 mL, 0.03 M) were
degassed for 30 min with nitrogen, respectively. The solution of
Bu3SnH and AIBN was dropwise added to the refluxing benzene
solution of 10 for 30 h by a syringe pump. After being stirred for
additional 2 h, the reaction mixture was concentrated under
reduced pressure and the crude product was subjected to silica gel
column chromatography to give 11 and 12 (38 mg, 6:1, 84%).
Treatment of 11 and 12 (38 mg) with PCC afforded 13 (29 mg,
1
according to H NMR. The stereoselectivity in the first cyclization
turned out to be slightly lower than that we anticipated. After PCC
oxidation of a mixture of 11 and 12, 14 was separated and the
stereochemistry of the substituent was determined by NOE
1
80%) and 14 (4 mg, 11%). H NMR (300 MHz, CDCl3, 13a) : δ
2.67 (m, 1H), 2.36 (m, 1H), 2.27 (d, J=8.6 Hz, 1H), 2.20 (m, 1H),
1.91-1.70 (m, 7H), 1.24 (m, 2H), 1.01 (s, 3H), 1.00 (s, 3H), 0.97
(d, J=7.0 Hz, 3H). 13C NMR (75 MHz, CDCl3, 13a) : δ 225.0,
62.0, 61.3, 56.5, 50.6, 46.5, 45.2, 39.0, 38.8, 34.7, 30.2, 30.1, 29.7,
14.4. IR (NaCl, cm-1) : 2946, 2867, 1737, 1461, 1116. HRMS
calcd. for C14H22O : 206.1671, found 206.1650.
11
experiment. As we anticipated, a 10:1 mixture of 13a and 13b was
1
determined by GC and H NMR analysis, indicating that the second
cyclization was somewhat more stereoselective than the first cyclization.
The conversion of intermediate 13a into the target molecule, dl-
4,12
pentalenene, was previously reported.
The key intermediate 13 was