Total synthesis of coronafacic acid through 6-endo-trig mode intramolecular cyclization of an enone-aldehyde to a hydrindanone using samarium(II) iodide

Article abstract of DOI:10.1016/S0040-4039(00)00786-3

Coronafacic acid has been synthesized from a hydrindanone prepared by a 6-endo-trig mode cyclization reaction of the enone-aldehyde with samarium(II) iodide. The stereochemistry of the hydrindanone was controlled by the coordinated samarium species resulting in cis in respect of the hydroxyl group at C-4 and the juncture proton at C-3a. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00786-3

Tetrahedron Letters 41 (2000) 5115±5118
Total synthesis of coronafacic acid through 6-endo-trig mode
intramolecular cyclization of an enone-aldehyde to a
hydrindanone using samarium(II) iodide
Masakazu Sono, Atsuko Hashimoto, Katsuyuki Nakashima and Motoo Tori*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro cho, Tokushima 770-8514, Japan
Received 17 April 2000; revised 10 May 2000; accepted 12 May 2000
Abstract
Coronafacic acid has been synthesized from a hydrindanone prepared by a 6-endo-trig mode cyclization
reaction of the enone-aldehyde with samarium(II) iodide. The stereochemistry of the hydrindanone was
controlled by the coordinated samarium species resulting in cis in respect of the hydroxyl group at C-4 and
the juncture proton at C-3a. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: biologically active compounds; carboxylic acids and derivatives; esters; indanes/hydrindanes.
We have previously reported an intramolecular cyclization reaction of an aldehyde and a,b-
unsaturated ketone using samarium(II) iodide.1 6 The reaction depends on the following conditions:
with or without a proton source and/or HMPA resulting in formation of hydridanones with trans
or cis selectivity in respect of the hydroxyl group at C-4 and the juncture proton at C-3a.1,2 We
have now successfully applied this reaction to the synthesis of coronafacic acid.7
Coronafacic acid (1) is itself a natural product isolated from the culture broth of Pseudomonas
syringae by Ichihara and his group in 1977.7 It has a cis-fused hydrindanone moiety (H-3a and H-
7a) with an ethyl group at C-6 and a trisubstituted double bond (Á4,5).7 The synthesis of this
compound has been reported by several groups.8 21 The cyclization of the cyclopentenone derivative
3 to ketol 2 is the key step of this synthesis. The stereochemical problem is to adjust the stereo-
chemistry at both the C-3a and C-7a positions relative to the ethyl group. However, this inversion
may be feasible by the base-catalyzed equilibration (Scheme 1).
The precursor for the cyclization was prepared starting from 4-ethylcyclohexanol (4) (Scheme 2).
Jones oxidation, Baeyer±Villiger oxidation, methanolysis, protection with the THP ether, and
LiAlH4 reduction a€orded alcohol 5 in 57% yield (®ve steps). Swern oxidation and the Grignard
reaction with the C3 unit, followed by deprotection of the TBDMS ether, yielded diol 6 in 60%
* Corresponding author. Tel: +81-88-622-9611; fax: +81-88-655-3051; e-mail: tori@ph.bunri-u.ac.jp
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00786-3

5116
Scheme 1. Synthetic plan
yield (three steps). Swern oxidation into keto-aldehyde, KOH-catalyzed intramolecular aldol
cyclization, and deprotection of the THP ether gave alcohol 7 in 47% yield (two steps). Swern
oxidation of 7 a€orded the desired enone-aldehyde 3 in 72% yield.
Scheme 2. (a) Jones' oxidation; (b) mCPBA, CH2Cl2, re¯ux, 4 h; (c) NaOMe, MeOH, rt, 2 h; (d) DHP, PPTS, CH2Cl2,
rt, 10 h; (e) LAH, ether, rt, 10 h (®ve steps 75%); (f) Swern oxidation; (g) BrMgCH2CH2CH2OTBDMS, THF, rt, 10 h;
(h) TBAF, THF, rt, 2 h (three steps 66%); (i) Swern oxidation; (j) 5% KOH, MeOH, rt, 10 h; then 1 M HCl (two steps
47%); (k) Swern oxidation (72%)
The enone-aldehyde 3 was treated with SmI2 in anhydrous THF at 0ꢀC to yield a mixture of
four stereoisomers of hydrindanones, the composition of which was determined by GC±MS
(Scheme 3).22 Separation of this mixture a€orded alcohol 2 as a major product.22 Treatment of 2
Scheme 3. (a) Sml2 (3 equiv.), 0ꢀC, THF (61%); (b) HOCH2CH2OH, TsOH, PhH (56%); (c) PDC, CH2Cl2, rt, 5 h
(quant.); (d) K2CO3, MeOH, re¯ux, 10 h (50%); (e) LDA, Cl-Py-N(Tf)2, THF, ^78ꢀC (70%); (f) CO, Pd(OAc)2, PPh3,
Et3N, MeOH, DMF (58%); (g) 3 M HCl (80%)

5117
with ethyleneglycol in the presence of TsOH a€orded epimerized ketal 8, stereochemistry of
which was determined by the NOESY spectrum.23 After oxidation of 8, the resulting ketone 9
was subjected to base-catalyzed equilibration (KOH±MeOH) to give cis-hydrindanone 10 along
with the starting ketone 9 in the ratio of 10:9=50:27. The ketone 10 was treated with LDA fol-
lowed by chloropyridine tri¯ate24 at ^78ꢀC to provide a tri-substituted enol tri¯ate in 70% yield.
The palladium chemistry of carboxylation under standard conditions25 a€orded the correspond-
ing methyl ester in 58% yield, which was hydrolyzed with 1 M aqueous HCl under re¯ux to yield
coronafacic acid (1) in 80% yield.7 The spectral data and mp (121±124ꢀC) [lit. 125±128ꢀC]7 were
identical with those of the natural product.
Herein we have demonstrated a new route to the hydrindanones by a 6-endo-trig mode of intra-
molecular cyclization using SmI2 and its successful application to the total synthesis of coronafacic
acid (1).
Acknowledgements
We thank Dr. Hiroaki Toshima, Hokkaido University, for sending us copies of NMR and IR
spectra and also an authentic sample of coronafacic acid. We are also grateful to Dr. M. Tanaka
and Miss Y. Okamoto, this university, for measurements of 600 MHz NMR and MS spectra,
respectively.
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