The Claisen Rearrangement Followed by Phenol Oxidation: A Simple Route to Naturally Occurring Benzoquinones Including an Ansa-Bridged Derivative Related to the Ansamycin Antibiotics

Abstract

The naturally occurring benzoquinones primin 1 and pallasone B 2 were synthesised by a simple protocol involving microwave accelerated Claisen rearrangement of allyl ethers 4, followed by hydrogenation of the side chain alkene, and oxidation to the quinone; by incorporating a ring-closing metathesis step, the method was extended to the synthesis of the ansa-bridged benzoquinone 11, a structure related to the ansamycin antibiotics.

rearrangements - phenols - oxidations - quinones - natural products

References

1 Thomson RH. Naturally Occurring Quinones   4th ed.:  Blackie; London: 1997. 

2 Martin T. Moody CJ. J. Chem. Soc., Perkin Trans. 1  1988,  241 

3 Moody CJ. Swann E. J. Chem. Soc., Perkin Trans. 1  1993,  2561 

4 For the use of a Claisen rearrangement in the synthesis of the natural benzoquinone 4-methoxydalbergione, see: Barnes MF. Ollis WD. Sutherland IO. Gottlieb OR. Magalhaes MT. Tetrahedron  1965,  21:  2707 

5 Isolation: Bloch B. Karrer P. Vjschr. Naturforsch. Ges., Zürich  1927,  72:  1 

6 Isolation: Marini-Bettolo GB. Monache FD. daLima OG. Coelho SD. Gazz. Chim. Ital.  1971,  101:  41 

7 For a recent synthesis see: Mabic S. Vaysse L. Benezra C. Lepoittevin JP. Synthesis  1999,  1127 

8 Isolation: Seki K. Kaneko R. Chem. Ind. (London)  1975,  349 

9 Synthesis: Tao Z. Liu J. Zhongguo Yiyao Gongye Zazhi  1991,  22:  57 ; Chem. Abstr., 1991, 115, 8400

10 Capecchi T. de Koning CB. Michael JP. J. Chem. Soc., Perkin Trans. 1  2000,  2681 

11 Bagnell L. Cablewski T. Strauss CR. Trainor RW. J. Org. Chem.  1996,  61:  7355 

12 An JY. Bagnell L. Cablewski T. Strauss CR. Trainor RW. J. Org. Chem.  1997,  62:  2505 

13 Kumar HMS. Anjaneyulu S. Reddy BVS. Yadav JS. Synlett  2000,  1129 

14 Daskiewicz JB. Bayet C. Barron D. Tetrahedron Lett.  2001,  42:  7241 

15

General procedure. The allyl aryl ether 4 (0.200 g, 1.05 mmol) was dissolved in DMF (3 mL) in a sealed tube. The mixture was heated in a focused microwave reactor (300 W) at 180 °C for 25-30 min. The mixture was diluted with ethyl acetate (15 mL), washed with water (5 × 10 mL), brine (10 mL), dried (MgSO₄), filtered and evaporated. The crude product was purified by flash chromatography on silica, eluting with ethyl acetate and light petroleum (1:4).

16

Compound 1: mp 64.5-65.5 °C (lit. [6] mp 66-67 °C); compound 2: mp 97.5-98.5 °C (lit. [8] 90.5-91 °C.

17 For a total synthesis, see: Panek JS. Xu F. Rondon AC. J. Am. Chem. Soc.  1998,  120:  4113 

18 For a total synthesis, see: Nakata M. Osumi T. Ueno A. Kimura T. Tamai T. Tatsuta K. Bull. Chem. Soc. Jpn.  1992,  65:  2974 

19 For another RCM-based route to the ansamycins, see: Bach T. Lemarchand A. Synlett  2002,  1302 

20 Kato T. Nagae K. Hoshikawa M. Tetrahedron Lett.  1999,  40:  1941 

21

Compound 9 is formed as a 3:2 mixture of alkene isomers at the 4,5-double bond; ¹H NMR spectroscopic analysis does not allow the assignment of the major isomer.

22

The Claisen rearrangement of compounds similar to 9 has also been successfully carried out under microwave conditions (DMF, 150 °C).

23

Macrocycle 11 is formed as a mixture of all four possible geometric isomers at the two double bonds in the approximate ratio 12:10:6:3. Hydrogenation of 11 (H₂, Pd/C, EtOAc), followed by reoxidation of the hydroquinone, gives a single characterisable compound.