Regioselective Synthesis of Polyketide-Type Phenols by Formal [3+3]-Cyclocondensations of 1,3-Bis(silyloxy)-1,3-butadienes with 3-Oxoorthoesters

Abstract

A variety of 4-methoxysalicylates and related polyketide-type phenols are regioselectively prepared by the first formal [3+3]-cyclocondensations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-oxoorthoesters.

Key words

arenes - cyclizations - regioselectivity - silyl enol ethers

References and Notes

• 1a Staunton J. Weissman KJ. Nat. Prod. Rep.  2001,  18:  380 
• 1b Koskinen AMP. Karisalmi K. Chem. Soc. Rev.  2005,  34:  677 
• 1c Römpp-Lexikon Naturstoffe   Fugmann B. Georg Thieme Verlag; Stuttgart / New York: 1997. 
• For a review, see:
• 2a Harris TM. Harris CM. Tetrahedron  1977,  33:  2159 
• See also:
• 2b Murray TP. Harris TM. J. Am. Chem. Soc.  1972,  94:  8253 
• 2c Harris CM. Roberson JS. Harris TM. J. Am. Chem. Soc.  1976,  98:  5380 
• 2d Harris TM. Hay JV. J. Am. Chem. Soc.  1977,  99:  1631 
• 2e Hubbard JS. Harris TM. Tetrahedron Lett.  1978,  47:  4601 
• 2f Sandifer RM. Bhattacharya AK. Harris TM. J. Org. Chem.  1981,  46:  2260 
• 2g Gilbreath SG. Harris CM. Harris TM. J. Am. Chem. Soc.  1988,  110:  6172 
• 3 Chan T.-H. Brownbridge P. J. Am. Chem. Soc.  1980,  102:  3534 
• 4 For a review of 1,3-bis(silyl enol ethers), see: Langer P. Synthesis  2002,  441 
• 5 For a review of formal [3+3]-cyclizations of 1,3-bis(silyl enol ethers), see: Feist H. Langer P. Synthesis  2007,  327 
• 6a Chan T.-H. Stössel D. J. Org. Chem.  1988,  53:  4901 
• 6b Chan T.-H. Stössel D. J. Org. Chem.  1986,  51:  2423 
• 7 Sher M. Langer P. Synlett  2008,  1050 
• 8 The TiCl₄-mediated reaction of 5a (2 equiv) with trimethyl orthoacetate has been reported to give a homophthalate by 2:1 condensation and subsequent aldol reaction: Brownbridge P. Chan TH. Brook MA. Kang GJ. Can. J. Chem.  1983,  61:  688 
• 9a Wilson BD. Synthesis  1992,  283 
• 9b Heilbron I. Jones ERH. Julia M. J. Chem. Soc.  1949,  1434 
• 9c Searles S. Sanchez RA. Soulen RL. Kundinger DG. J. Org. Chem.  1967,  32:  2655 
• 9d Banville J. Brassard P. J. Chem. Soc., Perkin Trans. 1  1976,  1852 
• 9e Barker D. Brimble MA. Do P. Turner P. Tetrahedron  2003,  59:  2441 
• 10 Krägeloh K. Simchen G. Synthesis  1981,  30 

11

Typical Procedure for the Synthesis of Methyl 2-hydroxy-4-methoxy-6-( n -propyl)benzoate (6e): To a CH₂Cl₂ solution (2 mL) of 4c (0.191 g, 1.0 mmol) and 5a (0.521 g, 2.0 mmol) was added TiCl₄ (0.11 mL, 1.0 mmol) at -78 ˚C under an argon atmosphere. The temperature of the reaction mixture was allowed to rise to 20 ˚C during 14 h with stirring. To the mixture was added hydrochloric acid (10%, 10 mL). The organic and the aqueous layer were separated and the latter was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried (Na₂SO₄), filtered and the filtrate was concentrated in vacuo. After column chromatography (silica gel; heptanes-EtOAc, 1:1), 6e was obtained as a colorless oil (92 mg, 42%); R _f 0.88 (heptanes-EtOAc, 1:1). ^¹H NMR (250 MHz, CDCl₃): δ = 11.73 (s, 1 H, OH), 6.33 (s, 1 H, ArH), 6.30 (s, 1 H, ArH), 3.93 (s, 3 H, OMe), 3.38 (s, 3 H, OMe), 2.83 (t, ^³ J = 7.7 Hz, 2 H, ArCH₂), 1.49-1.63 (m, 2 H, CH ₂CH₃), 0.95 (t, ^³ J = 7.4 Hz, 3 H, Me). ^¹³C NMR (63 MHz, CDCl₃): δ = 172.0 (C=O), 165.5, 163.9 (CO), 147.7 (C), 110.7 (CH), 104.6 (C), 98.7 (CH), 55.3, 51.8 (OMe), 38.9 (ArCH₂), 24.9 (CH₂CH₃), 14.2 (Me). IR (ATR): 2956 (br m), 2871 (w), 2846 (w), 1649 (s), 1611 (s), 1575 (s) cm^-¹. MS (EI, 70 eV): m/z (%) = 224 (33) [M⁺], 192 (100), 164 (34), 135 (45). Anal. Calcd for C₁₂H₁₆O₄ (224.26): C, 64.27; H, 7.19. Found: C, 64.27; H, 7.39.

12

CCDC 690564 contains all crystallographic details of this publication and is available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the following address: Cambridge Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB21EZ; Fax: [phone]; or [e-mail].