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

Mathias Lubbe; Jörg-Peter Gütlein; Helmut Reinke; Peter Langer

doi:10.1055/s-0028-1083524

LETTER

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

Mathias Lubbe^a, Jörg-Peter Gütlein^a, Helmut Reinke^a, Peter Langer*^a,b
^a Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
^b Leibniz-Institut für Katalyse, Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
e-Mail: peter.langer@uni-rostock.de;

Abstract

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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

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References

References and Notes

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See also:

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<A NAME="RD20608ST-4">4</A> For a review of 1,3-bis(silyl enol ethers), see: Langer P. Synthesis 2002, 441

<A NAME="RD20608ST-5">5</A> For a review of formal [3+3]-cyclizations of 1,3-bis(silyl enol ethers), see: Feist H. Langer P. Synthesis 2007, 327

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<A NAME="RD20608ST-8">8</A> 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

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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.

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