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Synlett 2023; 34(18): 2227-2231
DOI: 10.1055/a-2150-2912
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Modern Boron Chemistry: 60 Years of the Matteson Reaction

Conjugate Addition of Organoboron Compounds to α,β-Unsaturated Ketones Catalyzed by Nickelacycles

Kazuhiko Semba∗
,
Kotaro Nagase
,
Yoshiaki Nakao∗

This study was supported by JSPS KAKENHI Grant Number JP18K14213 and ISHIZUE 2021 of Kyoto University Research Development Program.
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Abstract

The catalytic activity of nickelacycles in the conjugate addition of arylboronates to α,β-unsaturated ketones was investigated. Nickelacycles afforded β-arylated ketones in moderate to high yields, whereas an analogous palladacycle did not catalyze the reaction. Studies on the time course of the reaction confirmed that the nickelacycles act as active species in the conjugate addition reaction.


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Key words

nickelacycles - nickel catalysis - organoboron compounds - enones - conjugate addition

Nickelacycles bearing an anionic four-electron donor ligand have been known since the seminal work of Kleiman and Dubeck, who isolated a nickelacycle derived from azobenzene and bis(cyclopentadienyl)nickel.[1] Nickelacycles are often suggested as reaction intermediates in various Ni-catalyzed reactions.[2] However, their use as catalysts has been elusive, whereas analogous palladacycles have served as catalysts in various reactions,[3] including conjugate additions of organoboronic acids[4] and phosphines,[5] C–H arylations of pyridine N-oxides,[6] rearrangements of allylic alcohol derivatives,[7] and the ring-opening reactions of oxabicyclic alkenes.[8]

The conjugate addition reaction of organoboronic acids and esters is a versatile and useful method for constructing carbon–carbon bonds with a broad functional-group compatibility, thanks to the bench-stability and commercial availability of organoboronic acids and esters. Several complexes of 4d transition metals such as rhodium[9] or palladium[10] have been employed as catalysts for the transformation. In contrast with the remarkable advances in catalysis by these complexes, complexes of 3d transition metals such as cobalt,[11] nickel,[12] or copper[13] have been less well explored, despite their sustainability.

In the case of nickel catalysis, the group of Shirakawa and Hayashi reported the first example of a Ni-catalyzed conjugate addition of organoboronic acids to α,β-unsaturated carbonyls.[12a] Although several nickel-catalyzed conjugate addition reactions have been reported, they compete with undesired side-reactions, including an oxidative Heck reaction through β-hydride elimination from alkylnickel intermediates (III to V) or the protodeboration of arylboronic acids (II to I), and they often require excess amounts of starting materials (Scheme [1], dashed lines).[12b]

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Scheme 1 A plausible catalytic cycle

Here we report a nickelacycle-catalyzed conjugate addition of arylboronates to α,β-unsaturated ketones (Scheme [1]). We expected that (a) the β-hydride elimination could be retarded due to the strong σ-donicity of the anionic carbonaceous ligand, which can shift the equilibrium between III and IV toward IV,[14] and (b) the Ar group of II would be more nucleophilic compared with the corresponding palladacycles, due to the lower electronegativity of Ni.[15]

According to the synthesis of phosphanickelacycles reported by Muller and co-workers,[16] a nickelacycle complex based on (2-chlorobenzyl)(diphenyl)phosphine was prepared (not shown). However, this gradually decomposed in toluene solution at room temperature to form black precipitates. We then focused on nickelacycles containing a more-electron-donating dialkylphosphino group. Ni(cod)2 (cod = 1,5-cyclooctadiene) was treated with one equivalent of the phosphine-tethered aryl chloride 1 to afford the corresponding nickelacycle Ni1 in 80% yield (Scheme [2a]); Ni1 was sufficiently stable, even in solution at ambient temperatures. In addition, nickelacycle Ni2, bearing a nitrogen-donor moiety, was prepared in a good yield by a similar method using imine 2 (Scheme [2b]).

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Scheme 2 Preparation of nickelacycles Ni1 and Ni2

Complexes Ni1 and Ni2 were characterized by means of NMR spectroscopy and HRMS. Furthermore, the crystal structures of Ni1 and Ni2 were determined by X-ray diffraction analysis (Figure [1]).[17] In the crystal structures, the sums of the angles around Ni were 360.6° (Ni1) and 362.5° (Ni2), which are consistent with a square-planar geometry around the Ni centers.

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Figure 1 Crystal structures of (a) Ni1 and (b) Ni2 with thermal ellipsoids at 30% probability. H atoms and solvent molecules are omitted for clarity.

The catalytic activities of nickelacycles Ni1 and Ni2 were evaluated in the conjugate addition of phenylboronic acid neopentyl glycol ester (4a) with chalcone (3a) (Scheme [3]). The reaction of 3a (0.20 mmol) with 4a (0.20 mmol) and i-PrOH (0.40 mmol) was performed in the presence of the appropriate nickelacycle (2.0 mol%) and t-BuONa (10 mol%) in THF at 60 °C for five hours. Although both nickelacycles afforded the conjugate addition product 5a, Ni2 showed a higher activity, giving 5a in 42% yield.

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Scheme 3 Effect of catalysts Ni1 and Ni2 in the reaction of 3a with 4a

The scope of the reaction of electron-deficient alkenes 3a–e with arylboronates 4a–g under slightly modified conditions using Ni2 was investigated on a 0.50 mmol scale (Scheme [4]).[18] Chalcone derivatives 3b and 3c bearing a methoxy and a fluoro group, respectively, at the para-position of the β-phenyl group reacted with arylboronate 4b, affording the corresponding products in high yields. trans-Benzalacetone (3d) also afforded the corresponding hydroarylation product in a good yield, whereas cyclohex-2-en-1-one (3e) afforded the corresponding product in a low yield.[19] With respect to the scope of the boron nucleophile 4 with chalcone (3a), (p-cyanophenyl)boronate 4b gave the corresponding product in a high yield, whereas the (p-chlorophenyl)boronate 4c and (p-methoxyphenyl)boronate 4d gave low yields of the corresponding products. In these cases, the conversions of the starting materials were moderate, although the corresponding oxidative Heck reaction products were not observed. The sterically demanding arylboronate 4e was accommodated under the optimized conditions, giving a high yield of the corresponding product. The arylboronic acid pinacol ester 4f also gave the corresponding product in a high yield, whereas the arylboronic acid 4g was not an effective substrate under the optimized conditions.

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Scheme 4 Scope of substrates under the optimized conditions; nep = OCH2CMe2CH2O. a t-BuONa (10 mol%). b Yield estimated by 1H NMR spectroscopy.

To confirm that Ni2 served as an active species and not as a precursor for other catalytically active species, the time course of the reaction of 3a with 4b in the presence of Ni2 or NiCl2(dme)/6/pyridine (dme = 1,2-dimethoxyethane) was monitored by gas chromatography (Figure [2]; orange and green lines, respectively). The reaction rate using Ni2 as a catalyst was higher than that with NiCl2(dme)/6/pyridine. In addition, an induction period was observed in the case of NiCl2(dme)/6/pyridine. These results support the view that nickelacycle Ni2 is an active species in the conjugate addition. Finally, the catalytic activity of nickelacycle Ni2 was compared with that of palladacycle Pd1 (blue line in Figure [2]). Ni2 was found to be superior to palladacycle Pd1, possibly due to the higher nucleophilicity of the arylnickel intermediate compared with that of the arylpalladium species.

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Figure 2 Time course of the conjugate addition of 3a with 4b in the presence of various catalysts

To gain insights into the deactivation pathways of the catalyst, nickelacycle Ni2 was mixed with 3a, 4a/t-BuONa, or MeOH at 60 °C. 3a and MeOH appeared to show no reaction with Ni2,[20] whereas 4a with t-BuONa afforded the cross-coupling product 7 in 55% yield (Scheme [5]). Product 7 was also observed after the reaction of 3a with 4a under the standard conditions. It could be argued that Ni2 might be a precursor that generates an active species through reaction with 4a with t-BuONa.

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Scheme 5 Formation of a cross-coupling product from Ni2 and 4a

The time course of the conjugate addition of phenylboronate 4a with chalcone (3a) was monitored under various conditions (Figure [3]). The initial rate with Ni2 (orange line) was higher than that observed with premixed Ni2, 4a, and t-BuONa (blue line). Additionally, Ni2 exhibited a higher activity than that of the catalysts generated in situ from Ni(cod)2, 7, and pyridine (green line) or NiCl2(dme), 7, and pyridine (purple line), even though Ni(cod)2, 7, and pyridine afforded the product with moderate efficiency. This result suggests that complexes generated from Ni(0) and 7 are also active in the conjugate addition; complexes of this type are probably generated when Ni2 is premixed with 4a and t-BuONa.[12a] The results mentioned above support the role of Ni2 as an active species in the conjugate addition, despite its decomposition during the reaction to form other active species.

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Figure 3 Time course of the conjugate addition of 3a with 4a in the presence of various catalysts

In conclusion, we have synthesized two different nickelacycles and have demonstrated their catalytic activity in the conjugate addition of arylboronates with electron-deficient alkenes. We also showed that the catalytic activity of the nickelacycle in the conjugate addition is superior to that of the corresponding palladacycle.


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Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2150-2912.
  • Supporting Information

Corresponding Authors

Kazuhiko Semba
Department of Material Chemistry, Graduate School of Engineering, Kyoto University
Katsura, Kyoto, 615-8510
Japan   

Yoshiaki Nakao
Department of Material Chemistry, Graduate School of Engineering, Kyoto University
Katsura, Kyoto, 615-8510
Japan   

Publication History

Received: 19 June 2023

Accepted after revision: 08 August 2023

Accepted Manuscript online:
08 August 2023

Article published online:
21 September 2023

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Zoom Image
Scheme 1 A plausible catalytic cycle
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Scheme 2 Preparation of nickelacycles Ni1 and Ni2
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Figure 1 Crystal structures of (a) Ni1 and (b) Ni2 with thermal ellipsoids at 30% probability. H atoms and solvent molecules are omitted for clarity.
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Scheme 3 Effect of catalysts Ni1 and Ni2 in the reaction of 3a with 4a
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Scheme 4 Scope of substrates under the optimized conditions; nep = OCH2CMe2CH2O. a t-BuONa (10 mol%). b Yield estimated by 1H NMR spectroscopy.
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Figure 2 Time course of the conjugate addition of 3a with 4b in the presence of various catalysts
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Scheme 5 Formation of a cross-coupling product from Ni2 and 4a
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Figure 3 Time course of the conjugate addition of 3a with 4a in the presence of various catalysts