Synlett 2010(1): 81-84  
DOI: 10.1055/s-0029-1218528
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Pd(0)-Catalyzed Hiyama Cross-Coupling Reactions at Dihalo-Substituted Heterocycles

Stefan A. Schweizera,b, Thorsten Bach*a
a Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
b WACKER-Institut für Siliciumchemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913315; e-Mail: thorsten.bach@ch.tum.de;
Further Information

Publication History

Received 29 September 2009
Publication Date:
01 December 2009 (online)

Abstract

The regioselectivity of the Hiyama cross-coupling reaction at various dihalo-substituted heterocycles has been studied. Methyl 2,3-dibromo-5-furancarboxylate and n-octyltrifluorosilane were employed to find optimum reaction conditions [CsF; Pd2dba3/P(2-furyl)3 as catalyst, 80-150 ˚C in toluene or benzene] for the desired transformation. Subsequent experiments with the title compounds and with different primary alkyltrifluorosilanes illustrate the generality of this regiochemical process.

    References and Notes

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10

Activating reagents were screened in the reaction of substrate 3 with n-octyltrifluorosilane in THF at 100 ˚C, employing Pd2dba3/P(2-furyl)3 as the catalyst. Almost no conversion was achieved with the given activating reagents, while anhydrous CsF delivered a significant conversion after 18 h (26% 4a, 34% 5).

12

Other ligands that have been tested include tri-tert-butyl-phosphonium tetrafluoroborate (PtBu3˙HBF4), tricyclo-hexylphosphane (PCy3), 1,2-bis(diphenylphosphino)ethane (dppe), 1,2-bis(di-2-furylphosphino)ethane (dfpe), and 1,4-bis(diphenylphosphino)butane (dppb).

14

Typical procedure: A flame-dried Schlenk tube was charged with Pd2dba3 (9.2 mg, 0.01 mmol), P(2-furyl)3 (18.6 mg, 0.08 mmol) and benzene (2 mL) under an atmosphere of argon. The solution was stirred at r.t. for 15 min then n-octyltrifluorosilane (74 µL, 0.40 mmol) and CsF (122 mg, 0.80 mmol, which was stored and weighed in a glove box) were added, followed by dibromofuran 3 (56.8 mg, 0.20 mmol). The tube was closed with a Teflon screw plug, situated behind an explosion shield (CAUTION!), heated to 80 ˚C and stirred for 15 h. The reaction mixture was cooled to room temperature and diluted with EtOAc (5 mL) and H2O (5 mL). After separation of the layers, the aqueous phase was extracted with EtOAc (3 × 5 mL) and the combined organic layers were dried over Na2SO4 and concentrated in vacuo. Purification of the crude product by flash column chromatography (silica gel; pentane-Et2O, 99:1) yielded compound 4a (45.6 mg, 0.14 mmol, 72%) as a colorless liquid. ¹H NMR (500 MHz, CDCl3): δ = 0.88 (t, ³ J = 7.0 Hz, 3 H), 1.20-1.36 (m, 10 H), 1.68 (quint, ³ J = 7.5 Hz, 2 H), 2.70 (t, ³ J = 7.5 Hz, 2 H), 3.88 (s, 3 H), 7.11 (s, 1 H); ¹³C NMR (90.6 MHz, CDCl3): δ = 14.1, 22.6, 26.5, 27.5, 29.0, 29.1, 29.1, 31.8, 52.0, 97.9, 121.2, 142.6, 158.3, 158.5; HRMS: m/z calcd for C14H21BrO3: 316.0674; found: 316.0673.