Concise synthesis of anolignan A

Article abstract of DOI:10.1016/S0040-4039(00)00604-3

An efficient synthesis of anolignan A has been achieved in eight steps in 30% overall yield from piperonal employing TiCl₄-mediated addition of a 1-trimethylsilyl-2,3-butadiene to an aldehyde as the key step. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00604-3

Tetrahedron Letters 41 (2000) 4401±4402
Concise synthesis of anolignan A
Meiming Luo, Akiko Matsui, Tomoyuki Esumi, Yoshiharu Iwabuchi and
Susumi Hatakeyama*
Faculty of Pharmaceutical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
Received 21 March 2000; revised 6 April 2000; accepted 7 April 2000
Abstract
An ecient synthesis of anolignan A has been achieved in eight steps in 30% overall yield from piperonal
employing TiCl4-mediated addition of a 1-trimethylsilyl-2,3-butadiene to an aldehyde as the key step.
# 2000 Elsevier Science Ltd. All rights reserved.
Keywords: lignans; silicon compounds; 1-trimethylsilyl-2,3-butadienes; addition reactions.
Anolignan A was isolated from Anogeissus acuminata as an active HIV-1 reverse transcriptase
inhibitory constituent by bioassay-guided fractionation.1 Recently, we have developed an ecient
method for the preparation of substituted 1,3-butadienes employing 1-trimethylsilyl-2,3-butadienes.2,3
The characteristic unsymmetrical 2,3-disubstituted 1,3-butadiene structure as well as its interesting
biological activity prompted us to investigate a total synthesis of anolignan A based on this
methodology. We report herein the ®rst synthesis of anolignan A.
Piperonal 1 was ®rst converted into propargyl alcohol 3 via acetate 2 by a three-step sequence
involving propargylation using tetrahydro-2-(2-propynyloxy)-2H-pyran, acetylation, and removal
of the benzylic acetoxy group with TFA±Et3SiH in 65% overall yield. Several attempts to obtain
3 by direct alkylation of tetrahydro-2-(2-propynyloxy)-2H-pyran with piperonyl chloride failed.
After tosylation of 3, reaction3 of tosylate 4 with trimethylsilylmethylmagnesium chloride in the
presence of CuCN and LiCl produced 1-trimethylsilyl-2,3-butadiene 5 selectively in good yield.
TiCl4-mediated addition of 5 to 2,4-diacetoxybenzaldehyde in the presence of acetonitrile
(1 equiv.) proceeded smoothly with concomitant acyl migration to give 1,3-butadiene 6. In this
particular case, addition of acetonitrile was found to be of critical importance for this successful
transformation, because compound 6 was not obtained in the absence of acetonitrile.y Possibly
the Lewis acidity of TiCl4 was appropriately attenuated by complexation with acetonitrile so that
* Corresponding author. Tel: +81 95 847 1111; fax: +81 95 848 4286; e-mail: susumi@net.nagasaki-u.ac.jp
y
Reaction of benzaldehyde with 1-trimethylsilyl-2,3-butadiene was found to be unsuccessful when TiCl4 was used as
the catalyst alone, see: Hatakeyama, S.; Sugawara, K.; Kawamura, M.; Takano, S. Tetrahedron Lett. 1991, 32, 4509±
4512.
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00604-3

4402
the resulting acid-labile 6 was obtained without decomposition. Upon treatment of 6 with
HCO2H±Et3N in the presence of PdCl2(PPh3)2 (3 mol%) in boiling dioxane,4 the reductive
removal of the benzylic acetoxy group took place with complete regioselectivity to give 7 exclusively.
Finally, saponi®cation of 7 furnished anolignan A as colorless needles, mp 97±98ꢀC (CH2Cl2),{
which exhibited spectral properties (1H and 13C NMR, IR, MS) in accord with those1 reported
(Scheme 1).
Scheme 1. Reactions and conditions: (a) tetrahydro-2-(2-propynyloxy)-2H-pyran, n-BuLi, THF, ^78ꢀC; (b) Ac2O,
Et3N, DMAP, CH2Cl2; (c) Et3SiH, TFA, CH2Cl2, ^20ꢀC; (d) n-BuLi, TsCl, THF, ^40ꢀC; (e) Me3SiCH2MgCl (3
equiv.), CuCN (3 equiv.), LiCl (6 equiv.), THF, ^40ꢀC; (f) 2,4-diacetoxybenzaldehyde, TiCl4 (1 equiv.), CH3CN (1
equiv.), CH2Cl2, ^78ꢀC; (g) HCOOH (10 equiv.), Et3N (10 equiv.), PdCl2(PPh3)2 (3 mol%), dioxane, re¯ux; (h) 5%
NaOH, MeOH
In conclusion, the present work illustrates a new methodology for the synthesis of dibenzyl-
butadiene lignans as well as the synthetic utility of 1-trimethylsilyl-2,3-butadienes.
Acknowledgements
This work was supported by a JSPS postdoctoral fellowship for M.L.
References
1. Rimando, A. M.; Pezzuto, J. M.; Fransworth, N. R. J. Nat. Prod. 1994, 57, 896±904.
2. Hatakeyama, S. J. Synth. Org. Chem. Jpn. 1997, 55, 793±802.
3. Nishiyama, T.; Esumi, T.; Iwabuchi, Y.; Irie, H.; Hatakeyama, S. Tetrahedron Lett. 1998, 39, 43±46.
4. Tsuji, J.; Minami, I.; Shimizu, I. Synthesis 1986, 623±627.
{
The melting point was not reported in the literature.