Preparation of an Arenylmethylzinc Reagent with Functional Groups by Chemoselective Cross-Coupling Reaction of Bis(iodo­zincio)methane with Iodoarenes

Abstract

Palladium-catalyzed cross-coupling reaction of bis(iodozincio)methane with iodoarenes carrying various functionalities such as ester, boryl, cyano, and halo groups proceeded chemoselectively to give the corresponding arenylmethylzinc species efficiently. The moderate reactivity of the gem-dizinc reagent imparted functional group tolerance to the process. The transformations from iodoheteroarenes were also performed; in the case of iodopyridine derivatives, the nickel-catalyzed reaction gave the corresponding organozinc species efficiently. The obtained arenylmethylzinc species underwent the copper-mediated coupling reaction with a range of organic halides.

Keywords

arenylmethylzinc - organozinc - cross-coupling - palladium - nickel

• References and Notes

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• 10 To perform the cross-coupling between the formed arenylmethylzinc iodide and iodoarene by Pd catalyst, we found that LiCl (1.0 equiv) plays a crucial role. As shown in Scheme 5, 4-methoxyphenylmethylzinc iodide, which was prepared from 4-methoxy-1-iodobenzene and bis(iodozincio)methane in the presence of Pd catalyst, was treated with p-tolyl iodide in the presence of a stoichiometric amount of LiCl and an additional Pd catalyst (PEPPSI-IPr) to afford 1-methoxy-4-(4-methylbenzyl)benzene in 81% yield. Without the addition of LiCl, no cross-coupling product was observed, see: Shimada, Y.; Matsubara, S.; Proceedings of the 95th CSJ Annual Meeting, Chiba, Japan, March 26–29, 2015; The Chemical Society of Japan: Tokyo, 2015; 2EA-46.
• 11 Preparation of 1-Phenyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethan-1-one (5ff) To a mixture of Pd₂dba₃ (0.015 mmol, 13.7 mg) and P(3,5-(CF₃)₂C₆H₃)₃ (0.12 mmol, 74.4 mg) in THF (2 mL), a solution of 2f (1.0 mmol, 330 mg) in THF (2.0 mL) was added. The mixture was stirred for 5 min at 25 °C, then a solution of bis(iodozincio)methane (0.36 M in THF, 1.0 mmol, 2.8 mL) was added. The resulting mixture was stirred for 1 h at the same temperature. The mixture was cooled to –30 °C, then a solution of CuCN·2 LiCl (1.0 M in THF, 1.0 mmol, 1.0 mL) was added and the resulting mixture was stirred for 15 min at the same temperature. A solution of benzoyl cyanide (0.9 mmol, 118 mg) in THF (0.5 mL) was added at the same temperature and the mixture was stirred for 10 h at 25 °C. Aqueous work-up (sat. aq NH₄Cl) followed by extraction with Et₂O gave the crude product. Purification by silica gel column chromatography (5 wt% boric acid) gave the title compound (168 mg, 52%). ¹H NMR (CDCl₃): δ = 8.00 (d, J = 8.0 Hz, 2 H), 7.78 (d, J = 8.0 Hz, 2 H), 7.54 (dd, J = 8.0, 8.0 Hz, 1 H), 7.44 (dd, J = 8.0, 8.0 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H), 4.30 (s, 2 H), 1.33 (s, 12 H). ¹³C NMR (CDCl₃): δ = 197.4, 137.7, 136.4, 135.1, 133.1, 130.1, 128.8, 128.6, 128.4, 83.7, 45.8, 24.8. HRMS (ESI): m/z [M + K]⁺ calcd for C₂₀H₂₃O₃B: 361.1372; found: 361.1359. 2-[4-(But-3-en-1-yl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxa­borolane (5fb): ¹H NMR (CDCl₃): δ = 7.78 (d, J = 8.5 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 2 H), 5.9–5.8 (m, 1 H), 5.06 (ddt, J = 17.0, 1.5, 1.0 Hz, 1 H), 5.00 (dd, J = 10, 1.5, 1.0 Hz, 1 H), 2.75 (t, J = 7.5 Hz, 2 H), 2.40 (dtt, J = 7.5, 7.5, 1.0 Hz, 2 H), 1.36 (s, 12 H). ¹³C NMR (CDCl₃): δ = 145.2, 137.9, 134.8, 127.9, 114.9, 83.6, 35.5, 35.3, 24.8. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₂₃O₂B: 281.1683; found: 281.1683. 2-[4-(Buta-2,3-dien-1-yl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5fe): ¹H NMR (CDCl₃): δ = 7.76 (d, J = 8.5 Hz, 2 H), 7.26 (d, J = 8.5 Hz, 2 H), 5.27 (dt, J = 7.0, 7.0 Hz, 1 H), 4.73 (dt, J = 7.0, 3.0 Hz, 2 H), 3.38 (dt, J = 7.0, 3.0 Hz, 2 H), 1.35 (s, 12 H). ¹³C NMR (CDCl₃): δ = 143.6, 135.2, 134.9, 128.0, 127.8, 89.2, 83.6, 75.2, 35.2, 24.8. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₂₁O₂B: 279.1527; found: 279.1515.