Iron-Catalyzed Grignard Cross-Couplings with Allylic Methyl Ethers or Allylic Trimethylsilyl Ethers

Abstract

We have found that cross-coupling between aryl Grignard reagents and allylic methyl ethers proceeded well in the presence of a catalytic amounts of Fe(acac)₃ to afford the corresponding allylic substitution products in good yields. Under the same conditions, allylic trimethylsilyl ethers also reacted with Grignard reagents to give the corresponding cross-coupling products.

Key words

iron catalysis - Grignard reagents - cross-coupling - allylic substitution - allylic ethers

• References and Notes

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For reviews on iron-catalyzed cross-coupling reactions, see:
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• 8 When we carried out the reaction of 1a with 2a under Li’s conditions (DCE–NMP, –13 °C, 1 h) (see Ref. 5), we observed the formation of 3aa in 19% yield (75% of 1a was recovered).
• 9 The cross-coupling product 3ab (Table 2, entry 2) contained a small amount of an inseparable double-bond regioisomer, whereas the sample product 3ab prepared from the corresponding silyl ether (Scheme 6) did not contain this regioisomer (see Supporting Information). From these observations, we assume that an isomerization pathway from the normal coupling product to its double-bond regioisomer exists in the reaction system of the allylic methyl ether. A plausible mechanism is as follows. Oxidative addition of R–OMe to the low-valent iron species gives R–[Fe]–OMe. β-Hydrogen elimination from the methyl group results in the formation of an iron hydride species R–[Fe]–H. Insertion of olefin 3ab into the iron–hydride bond, followed by β-hydrogen elimination, affords the corresponding double-bond regioisomer.
• 10 We also attempted to react 1a with Me(CH₂)₇MgBr (2i) under Li’s conditions (DCE–NMP, –15 °C, 1 h; Ref. 5), but the yield of 3ai was only 5% (76% of 1a was recovered.). With our catalyst system (Table 2, entry 9), 1a was fully consumed, and large amounts of (1E)-prop-1-en-1-ylbenzene were formed.
• 11 The isolated mixture of (E)- and (Z)-3aa contained small amounts of the reductive homocoupling product PhCH=CH(CH₂)₂CH=CHPh (molar ratio: E/Z/homo = 84:13:3). This homocoupling product was inseparable from (Z)-3aa. See Supporting Information.
• 12 The formation of the branched isomer b-3ba from the hexyl-substituted substrates 1b and 1b′ might be due to a decrease in steric repulsion.
• 13 Similar results have been reported in nickel- or palladium-catalyzed allylic substitutions with Grignard reagents, although no detailed discussion has been reported on the difference between linear and branched substrates [see Refs. 7 (a) and 7 (b)].
• 14 The formation of an Fe(I) species by the reaction of FeX₃ with aryl Grignard reagents has been suggested; see: Hedström A. Lindstedt E. Norrby P.-O. J. Organomet. Chem. 2013; 748: 51

A similar discussion has been reported in the literature dealing with the nickel-catalyzed cross-coupling of allylic alcohols with Grignard reagents; see:
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• 16 The use of two equivalents of Grignard reagent resulted in a 69% yield of 3aa with an 8% yield of the reductive homocoupling product. In the case of the reaction with four equivalents of 2a (Scheme 5), the yield of the homocoupling product was 6%.
• 17 We have previously reported an iron-catalyzed chemoselective cross-coupling with a bifunctional substrate possessing both aryl triflate and alkyl bromide moieties: see Ref. 6(a).
• 18 Iron-Catalyzed Allylic Substitutions with Grignard Reagent; General Procedure To a solution of Fe(acac)₃ (9.0 mg, 0.025 mmol, 5 mol%) in THF (1 mL) was added the appropriate allylic ether (0.5 mmol) and additional THF (4 mL). A ~1 M solution of the appropriate Grignard reagent in THF (1.0 mmol) was added, and the mixture was stirred for 4 h at rt. The reaction was quenched by the addition of 1 N aq HCl, and the resulting mixture was extracted with CH₂Cl₂. The combined organic layers were dried (MgSO₄), filtered, and concentrated. The residue was purified by flash column chromatography or TLC on silica gel. 1,1′-(1E)-Prop-1-ene-1,3-diyldibenzene [(E)-3aa] Colorless oil; yield: 154 mg (79%). ¹H NMR (500 MHz, CDCl₃): δ = 7.36–7.28 (m, 10 H), 6.46 (d, J = 15.5 Hz, 1 H), 6.36 (dt, J = 15.5, 7.0 Hz, 1 H), 3.55 (d, J = 7.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 140.1, 137.4, 131.0, 129.2, 128.6, 128.5 (overlap), 127.1, 126.1, 126.1, 39.3. These NMR data are in agreement with those previously reported: see Ref. 7 (i).