Addition, Substitution, and Ring-Contraction Reactions of Quinones

Herein, we report a study of the reactivity of three common NHCs, 1,3-bis(2 .... Reaction of NHC 1a and 4-tert-butyl-o-benzoquinone (2f) did not affor...
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Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX

Addition, Substitution, and Ring-Contraction Reactions of Quinones with N‑Heterocyclic Carbenes Lucy Ping, JungMin Bak, Youngmee Kim, and Jean Bouffard* Department of Chemistry and Nano Science (BK 21 Plus), Ewha Womans University, 03760 Seoul, Korea

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S Supporting Information *

ABSTRACT: Despite the common use of quinones as oxidizing agents in N-heterocyclic carbene (NHC)-based organocatalysis and transition-metal catalysis, the direct reactivity of quinones with NHCs remains underexplored. In this paper, we report the reactivity of NHCs with common p- and o-quinones, uncovering three unreported reactions involving contractions of the quinone ring that lead to push−pull furanolactone chromophores, NHC fulvalenes, and α-acylimidazolium cyclopentenone derivatives. These experiments also provide a rationale for the superior compatibility of tetra-tert-alkylated diphenoquinones in NHC-based oxidative transformations.

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Scheme 1. Four Classes of Products 3−10 Obtained by Reacting Common NHCs with Common p- and o-Quinones

INTRODUCTION N-Heterocyclic carbenes (NHCs) and their transition-metal complexes1−6 are, by comparison to their phosphine counterparts, kinetically reluctant to undergo oxidative degradation reactions.7−12 As a result of this endowment, they have proven their utility in a growing number of either organocatalytic13−15 or transition-metal-catalyzed11,12,16 oxidative transformations, including the esterification and amidation of aldehydes, the aerobic oxidation of alcohols, and Wacker-type cyclizations. In a wide range of such oxidative transformations, quinones are employed either as terminal stoichiometric oxidizing agents or as intermediary redox mediators.1−21 However, despite the wealth of knowledge assembled on the reactivity of phosphines and other P- or N-centered nucleophiles with quinones,22−25 only rare reports have documented the reaction of an NHC with a quinone. In 2011, the Stahl group reported the isolation of an arylimidazolium salt resulting from the 1,4-addition of an imidazolylidene onto p-benzoquinone (Scheme 1).26 Moreover, the screening of quinone oxidants in organocatalytic NHC reactions has highlighted their general incompatibility.27 One notable exception, the Kharasch oxidant (3,3′,5,5′-tetra-tertbutyldiphenoquinone),28 was introduced to the field of oxidative NHC organocatalysis by Studer et al. in 2010.29,30 In view of the high nucleophilicity of NHCs (N = 20−24)31,32 and electrophilicity of quinones (E = −16 to −4)33,34 according to the Mayr scale,35−38 their cross-reactivity is ensured. Nevertheless, reports detailing the study of reactions between NHCs and quinones, the structure of their products, and likely mechanisms have yet to appear in the literature. Herein, we report a study of the reactivity of three common NHCs, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr, 1a), 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes, 1b), and 1,3-bis(2,6-diisopropylphenyl)imidazolin-2ylidene (SIPr, 1c), with a number of readily available quinones, © XXXX American Chemical Society

including p-benzoquinone (2a), p-naphthoquinone (2b), 2,3dichloro-p-naphthoquinone (2c), p-chloranil (2d), o-chloranil Received: May 14, 2018

A

DOI: 10.1021/acs.joc.8b01236 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry (2e), 4-tert-butyl-o-benzoquinone (2f), 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ, 2g), 2,3-dicyano-p-naphthoquinone (2h), 2,3,5,6-tetramethyl-p-benzoquinone (duroquinone, 2i), the aforementioned 3,3′,5,5′-tetra-tert-butyldiphenoquinone (2j), and 3,3′,5,5′-tetraisopropyldiphenoquinone (2k).39 Our results demonstrate that NHCs not only replicate the known reactivity patterns of phosphines with quinones, but also participate in previously unreported ring-contraction reactions leading to the formation of NHC-derived fulvalenes 7 with o-chloranil 2e, of cyclopentenone derivatives 8 with 4-tert-butylo-benzoquinone 2f, and of π-conjugated push−pull dichlorofuranone dyes 9 and 10 with dicyanoquinones 2g and 2h (Scheme 2).

(2a, E = −16.2).34 However, the products obtained under these conditions were dissimilar to those reported by Stahl et al.26 where the reaction occurred in the presence of benzoic acid. Instead, further oxidation by quinones or air and hydrolysis during the workup led to the isolation of triones 3a (10%), 3b (4%), 4a (2%), and 4b (19%) as the prominent constituents from complex reaction mixtures. Halogenated p-Quinones. NHCs 1a and 1b also react with 2,3-dichloro-p-naphthoquinone (2c) to give the same products 4a (63%) and 4b (69%) as with p-naphthoquinone (2b), albeit in far better yields due to an addition−elimination mechanism enabled by the presence of chloride leaving groups (Scheme 3). The related triones 5a (52%), 5b (23%), and 5c

Scheme 2. Isolated Yields of Products 3−10 Obtained from 1 equiv of Quinones 2a−k and ≤1.3 equiv of NHCs 1a−c39

Scheme 3. Proposed Mechanisms for the Formation of 3−5a

In the case of 2a and 2b, the elimination of Y/Y′− represents a formal oxidation via hydride loss. a

(27%) are similarly obtained from the reaction between NHCs 1a−c and p-chloranil (2d). An X-ray diffraction study confirmed the structure of 5a,40 indicating that, upon workup, hydrolysis of the postulated trichlorinated intermediate via addition−elimination occurs preferentially at the C−Cl position adjacent to the imidazolium ring (Figure 1). Similar regioselectivity has previously been observed upon subsequent hydrolysis for the addition− elimination of Et2PPh onto p-chloranil (2d).41−43 The X-ray structure shows that the imidazolium and quinonederived rings are connected by a long C−C bond (1.46 Å) and rotated by 64° from coplanarity. Furthermore, the cyclic trione features a delocalized 1,3-ketoenolate fragment (C−C, 1.42 Å; C−O, 1.22 Å) joined by long C−C bonds (1.52−1.54 Å) to the dichloroenone fragment. In view of the X-ray diffraction data, the charge-separated resonance forms 3′−5′ are more significant contributors than forms 3−5.44 o-Chloranil. Reactions between NHCs 1a−c and o-chloranil (2e) followed more complex pathways, because of the high electrophilicity of 2e both at C1 (E = −8.77) and at C4 (E = −12.02).32 Products 6a (17%), 6b (38%), and 6c (48%) likely derive from the nucleophilic attack of the NHC at C4, followed by hydrolysis upon workup as observed for other halogenated quinones. Surprisingly, regioselectivity during the hydrolytic step is dependent on the structure of the NHC. For the intermediate formed by NHC 1b, hydrolysis occurs at C6 to yield product 6b featuring a delocalized 1,5-ketodienolate fragment, as evidenced by the higher symmetry of its 13C NMR spectrum. By contrast, unsymmetrical products were obtained upon hydrolysis

a

4a and 4b were isolated from the reactions of both 2b (2% and 19%) and 2c (63% and 69%). bTwo isomers were isolated, α,β-8a (34%) and β,γ-8a (10%). cFrom NHCs 1a and 1b and quinone 2i.

The mechanisms of these transformations provide insight into the selection of quinones for oxidative transformations catalyzed by NHCs or their transition complexes and new synthetic opportunities for the development of π-conjugated molecules.

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RESULTS AND DISCUSSION A general synthetic procedure was adopted for the reactions of the NHCs 1a−c with the quinones 2a−k. Under standard airfree conditions, a slight excess of NHC (≤1.3 equiv) was allowed to react with the respective quinone in anhydrous toluene from −78 °C to room temperature. The products 3−10 (Scheme 2) were isolated after removal of the volatiles in vacuo and purification by column chromatography. Parent p-Quinones. NHCs 1a and 1b attack the parent 1,4-quinones 2a and 2b at the more electrophilic ortho-position B

DOI: 10.1021/acs.joc.8b01236 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry

Figure 1. Solid-state structures (ORTEP views) with 50% probability ellipsoids of compounds 5a, 7a, α,β-8a, and 9b. Hydrogen atoms are omitted for clarity.

an electrocyclic ring opening, then leads to the formation of a seven-membered lactone intermediate.50,54−57 A disrotatory 6π-electrocyclization of the pentadienyl fragment would then result in a fused β-lactone, and subsequent decarboxylation would provide the NHC fulvalenes 7. Although decarboxylation of fused β-lactones to afford cyclopentenes has been described as a concerted process,58,59 a stepwise ionic process could be feasible here given the charge stabilization of the imidazolium carboxylate intermediate. Preliminary DFT calculations at the M06 level of theory suggest that each of these postulated intermediates may be viable, lying in energy at least 17 kcal/mol lower than the starting NHC and quinone 2e reactants (see the Supporting Information for details). 4-tert-Butyl-o-benzoquinone. Reaction of NHC 1a and 4-tert-butyl-o-benzoquinone (2f) did not afford the corresponding fulvalene. Instead, two unexpected isomeric cyclopentenones, α,β-8a (34%) and β,γ-8a (10%), were isolated. An X-ray diffraction experiment confirmed the structure of α,β-8a (Figure 1)40 and 2D NMR analysis that of the prototropic isomer β,γ-8a (see the Supporting Information for details).60,61 In the solid state, the former features a long acyl−imidazolium bond (1.52 Å) connecting the orthogonal NHC to an exocyclic (E)-enolate (1.37 Å), as previously observed in analogous structures.60 Delocalization over the 1,3-ketoenolate fragment appears limited in view of the longer adjacent α,β-C−C bond (1.44 Å), but weak intermolecular hydrogen bonding of the enolate oxygen to a neighboring imidazolium ring (CH···O, 2.31 Å) may contribute to the polarization of the 1,3-ketoenolate in the solid state. In this case, we propose a ring-contraction mechanism beginning with the nucleophilic addition of the NHC at the C1 carbonyl (Scheme 5). 6π-Electrocyclic ring opening of this adduct would result first in a ketene enolate and then in the fivemembered dienolate through an intramolecular aldol-type addition. Proton transfer finally affords a mixture of the two isomeric (E)-enolates α,β-8a and β,γ-8a. Dicyano-p-quinones. The reaction of NHCs 1a and 1b with DDQ (2g) also gave rise to unanticipated products, the dichlorofuranone derivatives 9a (11%) and 9b (18%), isolated as major products following chromatographic separation. X-ray diffraction analysis of 9b confirmed the structure,40 which features a shorter C−C bond (1.43 Å) connecting the NHC fragment, rotated out of full conjugation by 35°, to a nearly coplanar π-system with limited bond length alternation (1.35− 1.44 Å C−C bond lengths along the chromophore’s π-system), and an s-cis conformation of the adjacent nitrile groups (Figure 1). The strong shielding of the cyanovinylene carbon62 connected to the NHC fragment in 13C NMR (δ = 51.2 ppm for 9a) is nonetheless indicative of the ylidic character of that exocyclic double bond (cf. 9 vs 9′). Dichlorofuranone derivatives have previously been obtained by the thermolysis or solvolysis of adducts formed between DDQ and dipyrromethenes63−65 or alkynes.66−69

at C3, following substitution of the C4 chloride by NHCs for products 6a and 6c. In addition to the products 6a−c, the unexpected and airstable NHC tetrachlorofulvalenes 7a (40%), 7b (8%), and 7c (11%) were also isolated from the same reaction mixtures. The structure of 7a, which was confirmed by X-ray crystallography (Figure 1),40 features a long C−C bond (1.44 Å) joining the two rings with a dihedral angle of ca. 58° and limited bond length alternation within the cyclopentadiene ring (C1(NHC)−C2(Cl), 1.41 Å; C2(Cl)−C3(Cl), 1.37 Å; C3(Cl)−C4(Cl), 1.39 Å). These characteristics are indicative of a high degree of charge separation and ylidic character of this fulvalene (cf. 7′ vs 7). NHC-derived fulvalenes and related donor-substituted fulvenes have previously been reported.45−49 However, their synthesis has so far relied on alternate routesmost commonly through the addition−elimination of cyclopentadienides onto imidazolium salts substituted with a leaving group at the 2-position. Instead, we propose a mechanism that begins with the nucleophilic addition of the NHC at the more electrophilic C1 position (Scheme 4). 1,2-Acyl migration,50−53 which could proceed through epoxide formation followed by ring expansion or through Scheme 4. Proposed Mechanism for the Formation of 7

a

Calculated relative energies of the intermediates (M06; kcal/mol) are shown in blue. b[1a + 2e]. cMinimization directly leads to the seven-membered lactone. d[7 + CO2]. C

DOI: 10.1021/acs.joc.8b01236 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry Scheme 5. Proposed Mechanism for the Formation of α,β-8a and β,γ-8a

Scheme 7. Reactions between NHCs and Alkylated p-Quinones

a Under standard conditions, in anhydrous PhMe at −78 °C. For 2i, both NHCs 1a (45%) and 1b (38%) afforded 11. No NHC adducts were found for the reactions of 2j (R = tBu) or 2k (R = iPr) with NHCs 1a,b.

a

Calculated relative energies of truncated intermediates (R = Me; M06; kcal/mol) are shown in blue. b[1a + 2f].

In the case of NHCs, we propose that the formation of 9a and 9b begins with the nucleophilic addition of the NHC at the most electrophilic 5-position (E = −3.7)33 of DDQ (2g) (Scheme 6).

3,3′,5,5′-tetra-tert-butyldiphenoquinone (2j), which lacks acidic protons. For instance, the unreacted 2j could be recovered in quantitative yield from its reaction with 1a and in nearly quantitative yield (92%) from its reaction with 1b, alongside trace amounts of the reduced congener 2jR. These observations are consistent with the privileged status of 2j among quinones for NHC-mediated oxidative organocatalytic transformations.13−15,29 3,3′,5,5′-Tetraisopropyldiphenoquinone (2k) is less robust in the presence of 1b, giving rise to greater amounts of the reduced 2kR with the recovered unreacted 2k.

Scheme 6. Proposed Mechanism for the Formation of 9

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CONCLUSION The reaction pathways of NHCs with quinones are far more diverse than the classical addition or addition−elimination reactions of quinones with N- or P-centered nucleophiles. In particular, three quinone ring-contraction reactions were uncovered, respectively leading to NHC fulvalenes 7 with o-chloranil, cyclopentenones 8 with 4-tert-butyl-o-benzoquinone, and furanone-derived push−pull chromophores 9 and 10 with dicyano p-quinones. These three ring-contraction reactions may involve electrocyclic ring openings of the initial NHC−quinone adducts as shared mechanistic underpinnings. Although the reported procedures are currently of limited preparative value, they provide a rationale for the superior properties of the NHC-resistant Kharasch diphenoquinone in organocatalysis and highlight possible pitfalls in the selection of quinones as redox mediators for oxidative transformations catalyzed by the transition-metal complexes of NHCs.

a

Calculated relative energies of the intermediates (M06; kcal/mol) are shown in blue. b[1a + 2g].

Although the possibility of an electrocyclic ring opening of the resulting adduct (path b) to provide a ketene intermediate may not entirely be ruled out, preliminary calculations (M06) suggest this is an unrealistically uphill process (ΔE = +30.8 kcal/mol). Instead, we postulate that a secondary nucleophile, such as adventitious water during the workup, attacks the carbonyl group adjacent to the imidazolium group (path a).63−65,67,68 Elimination of the carbanion that is doubly stabilized by the nitrile and imidazolium groups, followed by lactonization, would then afford the dichlorofuranone derivatives 9. 2,3-Dicyano-p-naphthoquinone (2h) reacted similarly with NHC 1b to furnish the conjugated benzofuranone derivative 10b (14%). Due to the extended conjugation of these furanones, the purple to pink 9a,b and 10b behave as push−pull dyes,70,71 with strong absorption bands in the visible range (λmax = 509−543 nm; ε = 8400−18400). Alkylated p-Quinones: Duroquinone and Diphenoquinones. The more sterically hindered duroquinone, 2i, does not react as an electrophile with the NHCs 1a and 1b. Instead, the NHCs act as Brønsted bases to initiate the dimerization of 2i into the previously reported diduroquinone (11)72 in moderate yields (with 1a, 45%; with 1b, 38%; Scheme 7). By contrast, no reaction was observed between NHC 1a or 1b and Kharasch’s

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EXPERIMENTAL SECTION

General Information. All reactions were carried out under standard air-free techniques, but workups and purification steps were performed in air. The following reagents were synthesized according to literature procedures: 1a−1c,73−75 2g,76 and 2h.77,78 A 230−400 mesh silica gel (Silicycle) was used for column chromatography. HRMS data were obtained by electrospray ionization mass spectroscopy using a quadrupole/time-of-flight mass spectrometer at the Organic Chemistry Research Center at Sogang University, Seoul, Korea. General Procedure. An appropriate reaction vessel (Schlenk flask or sealable test tube) was charged under an Ar atmosphere with a magnetic stir bar, the quinone (2a−2k, 1 equiv), and the NHC (1a, 1b, or 1c, 1.0−1.3 equiv). The contents were cooled to −78 °C in an acetone−dry ice bath before careful layering (no stirring) of anhydrous PhMe (10−20 mL) over the solids. After 10−15 min at −78 °C, to allow for the solvent to reach the bath temperature, the reaction mixture D

DOI: 10.1021/acs.joc.8b01236 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry was finally stirred for a minimum of 30 min at −78 °C, before removal of the cooling bath to allow the reaction mixture to warm to room temperature. With stirring for a minimum of 1 h at rt, and removal of the volatiles in vacuo, the crude mixture was purified by column chromatography on silica gel to yield the pure products 3−11. 3-(1,3-Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol2-ylidene)cyclohex-5-ene-1,2,4-trione (3a).

(td, J = 7.4, 1.4 Hz, 1H), 7.51 (td, J = 7.4, 1.4 Hz, 1H), 7.41 (t, J = 7.7 Hz, 2H), 7.27 (d, J = 7.7 Hz, 4H), 2.92 (m, 2H), 2.81 (m, 2H), 1.21−1.06 (m, 24H). 13C NMR (75 MHz, DMSO-d6): δ 183.2, 176.0, 179.9, 149.4, 145.64, 145.59, 134.6, 134.1, 131.7, 131.0, 130.3, 130.3, 125.6, 125.3, 124.6, 123.9, 99.1, 28.1, 25.7, 22.8, 22.7. HRMS (ESI): m/z [M + Na]+ calcd for C37H41N2O3 561.3118; found 561.3112. 3-(1,3-Dimesityl-1,3-dihydro-2H-imidazol-2-ylidene)naphthalene-1,2,4(3H)-trione (4b).

3a was obtained following the standard procedure with 1a (300 mg, 0.77 mmol, 1.04 equiv) and 2a (80 mg, 0.74 mmol, 1 equiv) in anhyd PhMe (12 mL). Reaction time (−78 °C/rt): 1.5 h/1 h. Eluent: 30% EtOAc/hexanes. 3a (orange solid, 38 mg, 10%). Mp: 217 °C dec. 1 H NMR (300 MHz, acetone-d6): δ 7.93 (s, 2H), 7.43 (t, J = 7.7 Hz, 2H), 7.31 (d, J = 7.7 Hz, 4H), 6.26 (d, J = 10.3 Hz, 1H), 6.20 (d, J = 10.3 Hz, 1H), 2.98−2.90 (m, 4H), 1.28 (dd, J = 9.7, 6.7 Hz, 12H), 1.14 (dd, J = 6.7, 3.2 Hz, 12H). 13C NMR (75 MHz, acetone-d6): δ 185.1, 179.7, 170.3, 146.9, 146.8, 142.8, 133.11, 133.07, 131.2 (2), 124.9, 124.84, 124.80, 98.4, 29.6, 26.1, 23.2, 23.1. HRMS (ESI): m/z [M + Na]+ calcd for C33H38N2O3Na 533.2780; found 533.2776. 3-(1,3-Dimesityl-1,3-dihydro-2H-imidazol-2-ylidene)cyclohex-5-ene-1,2,4-trione (3b).

Method A: 4b was obtained following the standard procedure with 1b (135 mg, 0.44 mmol, 1.06 equiv) and 2b (66 mg, 0.42 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 50% EtOAc/hexanes. 4b (yellow solid 37 mg, 19%). Method B: 4b was obtained following the standard procedure with 1b (111 mg, 0.36 mmol, 1.09 equiv) and 2c (75 mg, 0.33 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 50% EtOAc/ hexanes. 4b (light orange solid 108 mg, 69%). Mp: 245 °C dec. 1H NMR (300 MHz, CDCl3): δ 7.89 (m, 2H), 7.52 (td, J = 7.5, 1.4 Hz, 1H), 7.42 (td, J = 7.5, 1.4 Hz, 1H), 7.28 (s, 2H), 6.88 (s, 4H), 2.26 (s, 6H), 2.24 (d, J = 3.3 Hz, 12H) 13C NMR (75 MHz, CDCl3): δ 183.0, 176.7, 170.6, 1547.8, 138.8, 135.2, 135.1, 134.6, 134.1, 132.1, 131.3, 131.0, 129.0, 128.9, 125.8, 125.7, 123.7, 99.3, 20.5, 17.5 (2). HRMS (ESI): m/z [M + Na]+ calcd for C31H28N2O3Na 499.1998; found 499.1994. 3-(1,3-Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol2-ylidene)-5,6-dichlorocyclohex-5-ene-1,2,4-trione (5a).

3b was obtained following the standard procedure with 1b (160 mg, 0.53 mmol, 1.09 equiv) and 2a (53 mg, 0.48 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 60% EtOAc/hexanes. 3b (orange solid, 8 mg, 4%). Mp: 101 °C dec. 1 H NMR (300 MHz, CD3OD): δ 7.79 (s, 2H), 6.98 (s, 4H), 6.34 (s, 2H), 2.29 (s, 6H), 2.19 (s, 12H). 13C NMR (75 MHz, CD3OD): δ 185.2, 182.7, 171.9, 142.4, 141.2, 136.7, 136.5, 133.9, 133.3, 130.5, 130.3, 124.9, 99.34, 21.1, 18.2, 18.1. HRMS (ESI): m/z [M + Na]+ calcd for C27H26N2O3Na 449.1836; found 449.1836. 3-(1,3-Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol2-ylidene)naphthalene-1,2,4(3H)-trione (4a).

5a was obtained following the standard procedure with 1a (300 mg, 0.77 mmol, 1.05 equiv) and 2d (180 mg, 0.73 mmol, 1 equiv) in anhyd PhMe (16 mL). Reaction time (−78 °C/rt): 1.5 h/1 h. Eluent: 30% EtOAc/hexanes. 5a (orange-red solid, 243 mg, 52%). Orange square platelike crystals were obtained by vapor diffusion of hexane into a CHCl3 solution of 5a for X-ray diffraction analysis. Mp: >250 °C. 1H NMR (300 MHz, DMSO-d6): δ 8.24 (s, 2H), 7.46 (t, J = 7.4 Hz, 2H), 7.32 (d, J = 7.4 Hz, 4H), 2.70 (m, 4H), 1.21−1.08 (m, 24H). 13C NMR (125 MHz, CDCl3): δ 175.4, 170.4, 168.6, 149.8, 146.3, 146.01, 145.97, 136.0, 131.3, 131.2, 124.6, 124.5, 123.5, 95.1, 28.8, 28.6, 26.32, 26.27, 23.13, 23.06. HRMS (ESI): m/z [M + Na]+ calcd for C33H36Cl2N2O3Na 601.2001; found 601.1996. 5,6-Dichloro-3-(1,3-dimesityl-1,3-dihydro-2H-imidazol-2ylidene)cyclohex-5-ene-1,2,4-trione (5b).

Method A: 4a was obtained following the standard procedure with 1a (130 mg, 0.33 mmol, 1.06 equiv) and 2b (50 mg, 0.32 mmol, 1 equiv) in anhyd PhMe (12 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 25% EtOAc/hexanes. 4a (yellow solid, 4 mg, 2%). Method B: 4a was obtained following the standard procedure with 1b (113 mg, 0.29 mmol, 1.1 equiv) and 2c (60 mg, 0.26 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 25% EtOAc/hexanes. 4a (yellow solid, 97 mg, 63%). Mp: >250 °C. 1H NMR (300 MHz, DMSO-d6): δ 8.20 (s, 2H), 7.70 (td, J = 7.4, 1.4 Hz, 2H), 7.56 E

DOI: 10.1021/acs.joc.8b01236 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry

124.6, 123.1, 102.5, 29.3, 27.8, 26.2, 26.1, 23.5, 22.5. HRMS (ESI): m/z [M + Na]+ calcd for C33H36Cl2N2O3Na 601.2001; found 601.1996. 1,3-Dimesityl-2-(perchlorocyclopenta-2,4-dien-1-ylidene)2,3-dihydro-1H-imidazole (7b) and 2,4-Dichloro-3-(1,3-dimesityl-1H-imidazolium-2-yl)-5,6-dioxocyclohexa-1,3-dien-1olate (6b).

5b was obtained following the standard procedure with 1b (102 mg, 0.34 mmol, 1.10 equiv) and 2d (75 mg, 0.31 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 30% EtOAc/hexanes. 5b (pale red solid, 34 mg, 23%). Mp: 212 °C dec. 1 H NMR (300 MHz, CDCl3): δ 7.28 (s, 2H), 6.94 (s, 4H), 2.30 (s, 6H), 2.20 (s, 12H). 13C NMR (125 MHz, CDCl3): δ 175.2, 171.0, 169.2, 148.2, 146.1, 140.2, 136.0, 135.5, 135.1, 131.6, 129.9, 129.5, 122.9, 95.2, 21.1, 17.99, 17.97. HRMS (ESI): m/z [M + Na]+ calcd for C27H24Cl2 N2O3Na 517.1062; found 517.1057. 3-(1,3-Bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene)5,6-dichlorocyclohex-5-ene-1,2,4-trione 5 (5c).

5c was obtained following the standard procedure with 1c (208 mg, 0.53 mmol, 1.09 equiv) and 2d (120 mg, 0.49 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 30% EtOAc/hexanes. 5c (orange solid, 76 mg, 27%). Mp: >250 °C. 1 H NMR (300 MHz, CDCl3): δ 7.31 (t, J = 7.7 Hz, 2H), 7.17 (d, J = 7.7 Hz, 4H), 4.25 (s, 4H), 3.29−3.20 (m, 4H), 1.32 (d, J = 6.7 Hz, 12H), 1.25 (d, J = 6.7 Hz, 12H). 13C NMR (75 MHz, CDCl3): δ 174.8, 170.2, 169.1, 167.5, 146.5, 146.4, 146.3, 136.0, 132.6, 130.0, 124.7, 124.6, 97.0, 53.6, 28.8, 26.5, 23.9, 23.6. HRMS (ESI): m/z [M + Na]+ calcd for C33H38Cl2N2O3Na 603.2157; found 603.2154. 1,3-Bis(2,6-diisopropylphenyl)-2-(perchlorocyclopenta-2,4dien-1-ylidene)-2,3-dihydro-1H-imidazole (7a) and 6-(1,3-Bis(2,6-diisopropylphenyl)-1H-imidazol-2(3H)-ylidene)-4,5-dichlorocyclohex-4-ene-1,2,3-trione (6a).

7b and 6b were obtained following the standard procedure with 1b (113 mg, 0.37 mmol, 1.10 equiv) and 2e (83 mg, 0.34 mmol, 1 equiv) in anhyd PhMe (10 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: hexanes (7b) → 50% EtOAc/hexanes (6b). 7b (white solid, 13 mg, 8%) and 6b (yellow solid, 64 mg, 38%). Characterization for 7b. Mp: >250 °C. 1H NMR (300 MHz, acetone-d6): δ 7.88 (s, 2H), 6.99 (s, 4H), 2.29 (s, 6H), 2.14 (s, 12H). 13C NMR (125 MHz, acetone-d6, 40 °C): δ 140.5, 135.7, 133.2, 130.5 (2), 124.4, 104.6, 102.7, 92.2, 21.0, 18.9. HRMS (ESI): m/z [M + Na]+ calcd for C26H24Cl4N2Na 527.0591; found 527.0583. Characterization for 6b. Mp: >250 °C. 1H NMR (300 MHz, CDCl3): δ 7.24 (s, 2H), 6.90 (s, 4H), 2.31 (s, 6H), 2.27−2.22 (m, 12H). 13 C NMR (75 MHz, CDCl3): δ 160.6, 146.6, 141.1, 136.2, 135.1, 130.5, 129.9 (2), 122.5, 102.1, 21.2, 18.2. HRMS (ESI): m/z [M + Na]+ calcd for C27H24Cl2N2O3Na 517.1056; found 517.1058. 1,3-Bis(2,6-diisopropylphenyl)-2-(perchlorocyclopenta-2,4dien-1-ylidene)imidazolidine (7c) and 6-(1,3-Bis(2,6diisopropylphenyl)imidazolidin-2-ylidene)-4,5-dichlorocyclohex-4-ene-1,2,3-trione (6c).

7a and 6a were obtained following the standard procedure with 1a (111 mg, 0.29 mmol, 1.06 equiv) and 2e (66 mg, 0.27 mmol, 1 equiv) in anhyd PhMe (10 mL). Reaction time (−78 °C/rt): 2 h/12 h. Eluent: hexanes (7a) → 50% EtOAc/hexanes (6a). 7a (off-white solid, 64 mg, 40%) and 6a (yellow solid, 26 mg, 17%). A small portion of 7a was recrystallized from hot methanol to give small colorless blocks for X-ray diffraction crystallography. Characterization for 7a. Mp: >250 °C. 1H NMR (300 MHz, CDCl3): δ 7.46 (t, J = 7.8 Hz, 2H), 7.29 (m, 4H), 7.26 (s, 2H), 2.82−2.68 (sept, J = 6.6 Hz, 4H), 1.19 (d, J = 6.6 Hz, 12H), 1.12 (d, J = 6.6 Hz, 12H). 13C NMR (75 MHz, CDCl3): δ 147.9, 145.3, 131.9, 130.8, 124.9, 122.7, 105.1. 102.3, 91.5, 29.2, 26.5, 22.7. HRMS (ESI): m/z [M + Na]+ calcd for C32H36Cl4N2Na+ 611.1530; found 611.1502. Characterization for 6a. Mp: >250 °C. 1H NMR (300 MHz, CDCl3): δ 7.47 (t, J = 7.8 Hz, 2H), 7.31−7.25 (m, 6H), 3.29−3.24 (m, 2H), 2.69− 2.64 (m, 2H), 1.39 (d, J = 6.6 Hz, 6H), 1.23 (d, J = 6.8 Hz, 6H), 1.10 (d, J = 6.6 Hz, 6H), 1.03 (d, J = 6.8 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ 183.6, 181.7, 160.1, 147.5, 146.7, 146.5, 140.3, 137.4, 131.9, 130.0, 125.2,

7c and 6c were obtained following the standard procedure with 1c (168 mg, 0.43 mmol, 1.03 equiv) and 2e (103 mg, 0.42 mmol, 1 equiv) in anhyd PhMe (10 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 20% EtOAc/hexanes (7c) → 40% EtOAc/hexanes (6b). 7c (white solid, 27 mg, 11%) and 6c (yellow solid, 85 mg, 48%). Characterization for 7c. Mp: >250 °C. 1H NMR (300 MHz, CDCl3): δ 7.34−7.29 (t, J = 7.7 Hz, 2H), 7.17 (d, J = 7.7 Hz, 4H), 4.15 (s, 4H), 3.11−3.02 (m, 4H), F

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The Journal of Organic Chemistry 1.57 (d, J = 6.7 Hz, 12H), 1.10 (d, J = 6.7 Hz, 12H). 13C NMR (75 MHz, CDCl3): δ 164.0, 145.8, 135.3, 129.3, 124.9, 109.9, 105.3, 95.3, 53.0, 29.5, 26.8, 23.2. HRMS (ESI): m/z [M + Na]+ calcd for C32H38Cl4N2Na 617.1687; found 617.1683. Characterization for 6c. Mp: >250 °C. 1H NMR (300 MHz, CDCl3): δ 7.38 (t, J = 8.0 Hz, 2H), 7.20 (t, J = 8.0 Hz, 4H), 4.52 (m, 2H), 4.17 (m, 2H), 3.60−3.51 (m, 2H), 3.45−3.36 (m, 2H), 1.49 (d, J = 6.8 Hz, 6H), 1.25 (m, 12H), 1.08 (d, J = 6.8 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ 183.7, 181.6, 165.0, 161.5, 148.3, 147.2, 140.1, 137.5, 131.2, 130.0, 125.4, 125.2, 100.6, 53.0, 29.6, 27.8, 26.5, 26.0, 24.0, 23.4. HRMS (ESI): m/z [M + Na]+ calcd for C33H38Cl2N2O3Na 603.2157; found 603.2153. (E)-(1,3-Bis(2,6-diisopropylphenyl)-1H-imidazolium-2-yl)(4(tert-butyl)-2-oxocyclopent-3-en-1-ylidene)methanolate (α,β8a) and (E)-(1,3-Bis(2,6-diisopropylphenyl)-1H-imidazolium-2yl)(3-(tert-butyl)-5-oxocyclopent-2-en-1-ylidene)methanolate (β,γ-8a).79

9a was obtained following the standard procedure with 1a (296 mg, 0.76 mmol, 1.04 equiv) and 2g (166 mg, 0.73 mmol, 1 equiv) in anhyd PhMe (20 mL). Reaction time (−78 °C/rt): 1 h/1 h. Eluent: 25% EtOAc/hexanes. 9a (dark purple solid, 48 mg, 11%). Mp: 212 °C dec. 1 H NMR (300 MHz, CDCl3): δ 7.51 (t, J = 7.7 Hz, 2H), 7.34 (d, J = 7.7 Hz, 4H), 7.19 (s, 2H), 2.78 (sept, J = 6.8 Hz, 4H), 1.33 (d, J = 6.8 Hz, 12H), 1.17 (d, J = 6.8 Hz, 12H). 13C NMR (75 MHz, CDCl3): δ 160.3, 149.5, 145.8, 138.4, 137.2, 131.7, 130.7, 125.3, 122.8, 118.0, 114.9, 113.9, 101.0, 51.2, 29.1, 26.3, 22.7. HRMS (ESI): m/z [M + Na]+ calcd for C35H36Cl2N4O2Na 637.2113; found 637.2108. UV−vis (CH2Cl2): λmax, nm (ε) 536 (18800). (E)-2-(3,4-Dichloro-5-oxofuran-2(5H)-ylidene)-3-(1,3-dimesityl-1,3-dihydro-2H-imidazol-2-ylidene)succinonitrile (9b).

9b was obtained following the standard procedure with 1b (120 mg, 0.39 mmol, 1.24 equiv) and 2g (72 mg, 0.32 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 30% EtOAc/hexanes. 9b (purple solid, 30 mg, 18%). Mp: 216 °C dec. 1 H NMR (300 MHz, DMSO-d6): δ 8.00 (s, 2H), 7.10 (d, J = 0.3 Hz, 4H), 2.31 (s, 6H), 2.12 (s, 12H). 13C NMR (125 MHz, DMSO-d6): δ 159.9, 144.5, 139.9, 136.3, 136.1, 134.4, 130.6, 129.7, 123.1, 117.7, 113.7, 112.6, 99.6, 94.4, 52.8, 20.6, 17.8. HRMS (ESI): m/z [M + Na]+ calcd for C29H24Cl2N4O2Na 553.1174; found 553.1171. UV−vis (CH2Cl2): λmax, nm (ε) 543 (15800). (E)-2-(1,3-Dimesityl-1,3-dihydro-2H-imidazol-2-ylidene)-3(3-oxoisobenzofuran-1(3H)-ylidene)succinonitrile (10b).

α,β-8a and β,γ-8a were obtained following the standard procedure with 1a (503 mg, 1.29 mmol, 1.06 equiv) and 2f (200 mg, 1.22 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/1 h. Eluent: 20% EtOAc/hexanes (β,γ-8a) → 40% EtOAc/hexanes (α,β-8a). β,γ-8a (yellow powder, 65 mg, 10%) and α,β-8a (off-white powder, 230 mg, 34%). Characterization for β,γ-8a. Mp: 220−222 °C dec. 1H NMR (300 MHz, acetone-d6): δ 7.80 (s, 2H, HB), 7.47 (t, J = 7.7 Hz, 2H, HF and HL), 7.31 (t, J = 7.7 Hz, 4H, HE and HK), 5.58 (t, J = 1.5 Hz, 1H,), 3.73 (hept, J = 6.8 Hz, 2H, HG), 2.94 (p, J = 6.8 Hz, 2H, HM), 2.73 (d, J = 1.5 Hz, 2H, HS), 1.38 (d, J = 6.8 Hz, 6H, HN′), 1.17 (d, J = 6.8 Hz, 6HH′), 1.07 (d, J = 6.8 Hz, 12H, HH and HN), 1.00 (s, 9H, HV). 13C NMR (75 MHz, CDCl3): δ 201.0 (CT), 153.0 (CO), 151.4 (CA), 147.2 (CJ/D), 147.0 (CJ/D), 139.0 (CR), 131.2 (CR), 131.1 (CR), 124.9 (CE/K), 124.3 (CE/K), 122.6 (CQ), 122.52 (CB), 122.47 (CB), 116.8 (CP), 43.4 (CS), 32.9 (CU), 29.4 (CV), 29.1 (2) (CM), 27.8 (CG), 27.7 (CG), 26.1 (CN), 26.0 (CH′), 23.7 (CH), 22.7 (CN’). HRMS (ESI): m/z [M + H]+ calcd for C37H49N2O2 553.3789; found 553.3790. Characterization for α,β-8a. Mp: 239−241 °C dec. 1H NMR (300 MHz, CDCl3): δ 7.44 (t, J = 7.9 Hz, 2H, HF and HL), 7.26 (t, J = 7.9 Hz, 4H, HE and HK), 7.12 (s, 2H, HB), 5.66 (s, 1H, HS), 3.66 (sept, J = 6.8 Hz, 2H, HG), 2.93 (s, 2H, HQ), 2.84 (sept, J = 6.8 Hz, 2H, HM), 1.41 (d, J = 6.7 Hz, 6H, HN′), 1.20 (d, J = 6.7 Hz, 6H, HH′), 1.11 (d, J = 6.7 Hz, 6H, HH), 1.05 (d, J = 6.7 Hz, 6H, HN), 1.02 (s, 9H, HV). 13C NMR (75 MHz, CDCl3): δ 192.2 (CT), 173.9 (CR), 154.1 (CO), 151.7 (CA), 147.5 (CD), 147.0 (CJ), 131.3 (CC and CI), 130.9 (CF and CL), 128.6 (CS), 124.8 (CK), 124.1 (CE), 122.4 (CB), 110.8 (CP), 33.9 (CU), 32.6 (CQ), 29.5 (CV), 29.1 (CM), 27.6 (CG), 26.1 (CH′), 25.9 (CN), 23.7 (CH), 22.7 (CN′). HRMS (ESI): m/z [M + H]+ calcd for C37H49N2O2 553.3789; found 553.3796. (E)-2-(1,3-Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene)-3-(3,4-dichloro-5-oxofuran-2(5H)-ylidene)succinonitrile (9a).

10b was obtained following the standard procedure with 1b (174 mg, 0.57 mmol, 1.08 equiv) and 2h (110 mg, 0.53 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. Eluent: 20% EtOAc/hexanes. 10b (pink powder, 34 mg, 13%). Mp: 238 °C dec. 1 H NMR (300 MHz, CDCl3): δ 7.90 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.60 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 6.84 (s, 4H), 6.73 (s, 2H), 2.26 (s, 12H), 2.11 (s, 6H). 13C NMR (75 MHz, CDCl3): δ 164.5, 149.6, 148.5, 140.0, 136.4, 135.7, 134.8, 131.8, 130.3, 129.7, 125.5, 123.9, 122.7, 119.5, 119.1, 116.9, 90.6, 42.5, 21.0, 18.3. HRMS (ESI): m/z [M + Na]+ calcd for C33H28N4O2Na 535.2105; found 535.2104. UV−vis (CH2Cl2): λmax, nm (ε) 509 (8400). 7-Hydroxy-2,3,4a,5,6,8,9a-heptamethyl-9,9a-dihydro-1Hxanthene-1,4(4aH)-dione (Diduroquinone, 11).

Method A: 11 was obtained following the standard procedure with 1a (300 mg, 0.77 mmol, 1.06 equiv) and 2i (120 mg, 0.73 mmol, 1 equiv) in anhyd PhMe (16 mL). Reaction time (−78 °C/rt): 1.5 h/1 h. Eluent: 30% EtOAc/hexanes. 11 (yellow solid, 108 mg, 45%). Method B: 11 was obtained following the standard procedure with 1b (101 mg, 0.33 mmol, 1.09 equiv) and 2i (50 mg, 0.30 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 0.5 h/12 h. Eluent: 30% EtOAc/hexanes. 11 (yellow solid, 38 mg, 38%). Proton NMR spectra of G

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The Journal of Organic Chemistry

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the purified product from both reactions are consistent with that of the recrystallized product synthesized by literature procedures.72 Mp: 187−189 °C. 1H NMR (300 MHz, acetone-d6): δ 6.64 (s, 1H), 3.05 (d, J = 17.0 Hz, 1H), 2.47 (d, J = 17.0 Hz, 1H), 2.07 (m, 15H), 1.41 (s, 3H), 1.23 (s, 3H). 13C NMR (75 MHz, DMSO-d6): δ 200.6, 197.7, 146.6, 143.4, 142.9, 141.8, 123.6, 121.4, 120.7, 114.9, 82.4, 50.9, 32.9, 20.2, 18.0, 13.5, 13.2 (2), 12.3, 12.15. Reactions of NHCs with Diphenoquinones. With 2j. The products were obtained following the standard procedure with 1a (102 mg, 0.26 mmol, 1.07 equiv) and 2j (100 mg, 0.25 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. 2j was recovered by column chromatography on silica gel (eluent 5% EtOAc/ hexanes; 100 mg, 100%). The products were confirmed by comparison with the literature 1H NMR data.80 With 2k. The products were obtained following the standard procedure with 1b (89.6 mg, 0.28 mmol, 1.04 equiv) and 2k (100 mg, 0.28 mmol, 1 equiv) in anhyd PhMe (15 mL). Reaction time (−78 °C/rt): 1 h/12 h. 2k (40 mg, 40%) and its reduced biphenol 2kR (23 mg, 23%) were recovered by column chromatography on silica gel (eluent 5% EtOAc/hexanes). The products were confirmed by comparison with the literature 1H NMR data.81,82

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b01236. NMR spectra, UV−vis data, X-ray crystallographic data, and computational details (PDF) X-ray crystallographic data for 5a (CIF) X-ray crystallographic data for 7a (CIF) X-ray crystallographic data for α,β-8a (CIF) X-ray crystallographic data for 9b (CIF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: bouff[email protected] ORCID

Lucy Ping: 0000-0003-1865-0629 Jean Bouffard: 0000-0003-2281-2088 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant 2015R1D1A1A01059383). We thank Dr. Hea Kyoung Lee of the Organic Chemistry Research Center at Sogang University for ESI-MS analyses.

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REFERENCES

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DOI: 10.1021/acs.joc.8b01236 J. Org. Chem. XXXX, XXX, XXX−XXX

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DOI: 10.1021/acs.joc.8b01236 J. Org. Chem. XXXX, XXX, XXX−XXX