Ni-Catalyzed Carbocyclization of 1,6-Enynes Mediated by Dialkylzinc Reagents: Me₂Zn or Et₂Zn Makes a Difference

Abstract

Unactivated 1,6-enynes were firstly found to undergo different cyclization process under the catalysis of Ni⁰ species in situ generated from Ni^II complexes and dialkylzinc reagents. When stoichiometric Me₂Zn was used as the reducing agent, only the dimerization products {[2+2+2+2] or [2+2+2]} were obtained. On the other hand, reductive cyclization products were obtained solely when 0.6 equivalents of Et₂Zn were employed as the reductant under otherwise the same reaction conditions. In the former case, up to 1:7 selectivity in favor of the [2+2+2] products was also achieved with NiCl₂(PPh₃)₂/Me₂Zn.

Key words

organozinc reagents - enynes - cyclizations - nickel

References and Notes

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4

Dialkylzinc reagents, zinc powder, triethylsilane, triethylboranes, and DIBAL-H have been used as the reducing agent in this type of transformation.

9

For examples of Ni-catalyzed reductive cyclization pro-cesses with the methyl shift involving Me₂Zn, see ref. 5a and references cited therein.

13

CCDC 690610(3a) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data-request/cif. See the Supporting Information for a figure of its X-ray structure.

14

The [2+2+2+2] process has been found to be favored at a large loading amount of Ni catalyst for the dimerization of terminal 1,6-diynes, see ref. 10.

15

When 50 mol% or 20 mol% of Me₂Zn were used, the reaction failed to proceed.

17

CCDC 690609(2h) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data-request/cif. See the Supporting Information for a figure of its X-ray structure.

19

In ref. 7, the authors also proposed that oligomerization may be the possible reason for the decreased yield with 1j.

21

The addition of 5 mol% of Ph₃P, PCy₃ or (R)-BINAP did not improve the product selectivity significantly.

22

Typical Procedure for the Dimerization of 1 with Ni ^II /Me ₂ Zn Combination Under an atmosphere of argon, 3.2 mg (0.012 mmol) of Ni(acac)₂ were added to a Schlenk tube, and the system was purged with argon three times. Then enyne 1a (86 mg, 0.3 mmol) in 3.0 mL of freshly distilled THF was added via a syringe followed by the addition of Me₂Zn 0.3 mmol (1.2 M in toluene) in one portion [in the case of NiCl₂(PCy₃), Me₂Zn was added at reflux]. The reaction mixture was stirred for 1 h at r.t. before being quenched with sat. aq NH₄Cl soln. Then, the mixture was extracted with CH₂Cl₂ (3 × 3 mL), dried with anhyd Na₂SO₄. After removal of the solvent in vacuum, the residue was purified by column chromatography (silica gel, PE-Et₂O = 4:1) to provide the desired products 2a and 3a. (5 E ,10 E )-Tetramethyl-5,10-diphenyl-3a,4,8a,9-tetrahydropyrene-2,2,7,7(1 H ,3 H ,6 H ,8 H )-tetracarboxy-late (2a)
Colorless crystal; mp 193-194 ˚C (hexane-Et₂O). ^¹H NMR (300 MHz, CDCl₃): δ = 7.36-7.17 (m, 10 H), 3.67 (s, 6 H), 3.63 (s, 6 H), 3.05-2.70 (m, 10 H), 2.24 (d, J = 10.6 Hz, 2 H), 1.95-1.89 (dd, J = 13.1, 6.8 Hz, 2 H) ppm. ^¹³C NMR (75 MHz, CDCl₃): δ = 172.0, 171.7, 145.2, 144.2, 136.1, 128.3, 127.7, 126.3, 59.4, 52.60, 52.59, 46.2, 43.9, 43.0, 40.4 ppm. IR (KBr): 2952, 1734, 1434, 1250, 1205, 1070, 703 cm^-¹. MS (EI): m/z = 572 [M⁺], 167(base). HRMS (EI): m/z calcd for C₃₄H₃₆O₈: 572.2410; found: 572.2413. Dimethyl 6-[2,2-Bis(methoxycarbonyl)pent-4-enyl]-5,7-diphenyl-3a,4-dihydro-1 H -indene-2,2(3 H )-dicarboxy-late (3a)
Colorless crystal;^¹³ mp 87-89 ˚C (hexane-Et₂O). ^¹H NMR (300 MHz, CDCl₃): δ = 7.39-7.18 (m, 10 H), 4.86-4.74 (m, 1 H), 4.58-4.68 (m, 2 H), 3.77 (s, 3 H), 3.64 (s, 3 H), 3.46 (s, 3 H), 3.36 (s, 3 H), 3.32-3.22 (m, 1 H), 2.97-2.57 (m, 5 H), 2.28 (d, J = 6.9 Hz, 2 H), 2.14 (t, J = 17.4 Hz, 1 H), 2.02-1.95 (dd, J = 13.2, 8.8 Hz, 2 H) ppm. ^¹³C NMR (75 MHz, CDCl₃): δ = 172.2, 171.9, 171.1, 142.1, 141.4, 139.2, 133.7, 133.1, 130.1, 129.8, 129.6, 128.4, 128.0, 127.8, 127.0, 126.6, 117.7, 60.2, 59.0, 52.9, 52.7, 52.0, 39.6, 39.1, 38.5, 38.4, 37.8, 30.5 ppm. IR (KBr): 2953, 1732, 1491, 1435, 1380, 763, 735, 703 cm^-¹. MS (EI): m/z = 572 [M⁺], 279(base). HRMS (EI): m/z calcd for C₃₄H₃₆O₈Na⁺: 595.2316 ± 0.002; found: 595.2302.