Synthesis of γ-Aryl Medium-Sized Cyclic Enones by a Domino 4π-Electrocyclic Reaction/Heck–Matsuda Arylation Sequence at Ambient Temperature

Abstract

Bicyclo[n.2.0]cyclobutenes were transformed into medium-sized cyclic γ-aryl enones by using a cationic aryl palladium(II) species generated from a diazonium salt. The reaction proceeded at ambient temperature by capturing the cis,trans-cycloalkadiene intermediate generated through a conrotatory 4π-electrocyclic ring-opening reaction, followed by a Heck–Matsuda arylation sequence. Optically pure γ-aryl enones were also synthesized by using a point-to-planar-to-point chirality-transfer process.

Cyclic α,β-unsaturated ketones are important frameworks found in many biologically active compounds, naturally occurring substances, and versatile intermediates used to synthesize these molecules.[2] Indeed, the syntheses of γ-functionalized α,β-unsaturated ketones have been extensively explored, with several approaches developed for introducing alkyl,[3] aryl,[4] or heteroatom-containing groups,[5] especially at the γ-positions of cyclic enones or 1-siloxy-1,3-dienes as their equivalents (Scheme [1]). Whereas the syntheses of γ-functionalized five-to-seven-membered cyclic enones have been broadly covered in the literature, synthetic methods for medium-sized ones (eight- to ten-membered rings) have rarely been reported, despite their potential utility.[6]

We recently reported a method for synthesizing medium-sized cyclic compounds from fused cyclobutenes through a 4π-electrocyclic reaction.[7] For example, the reaction of the bicyclo[4.2.0]octene 1 with various aryl iodides in the presence of a Pd(0) catalyst at 100 °C gave the corresponding 4-arylcyclooctadienes 3 (Scheme [2a]).[7a] The reaction proceeds via the cis,trans-cycloocta-1,3-dienes 2, formed as short-lived and highly reactive intermediates by a reversible conrotatory 4π-electrocyclic ring-opening reaction followed by a Pd-catalyzed Mizoroki–Heck reaction at the more-distorted trans-double bond. However, the high temperature required for this reaction is a drawback; moreover, the step requiring the high temperature (i.e., the 4π-electrocyclic or Heck step) has not been clarified.

Density functional theory calculations [B3LYP/6-31G(d,p) level] suggest that the electrocyclic ring opening of bicyclo[4.2.0]octenes 1 (R = CO₂Me, Si = TMS) might be feasible, even at 25 °C (ΔG^‡ = 22.6 kcal/mol).[8] [9] Given this case, we envisaged that arylated medium-sized cyclic compounds might be produced through a related domino reaction, even at ambient temperature, if the latter arylation, in which the distorted trans-double bond is captured by a more-reactive palladium species, proceeds fast enough. We therefore focused on the Heck–Matsuda reaction, which is generally faster than the conventional Mizoroki–Heck reaction due to the high reactivity of cationic arylpalladium(II) species derived from Pd(0) and aryldiazonium tetrafluoroborates.[10] Here, we report that such a domino reaction proceeds even at ambient temperature (Scheme [2b]). Notably, this reaction directly provides medium-sized γ-aryl cycloalkenones 5 as the final products without involving 3.

Preliminary experiments showed that Pd(OAc)₂ in MeCN is an appropriate combination for promoting the reaction of 1a with para-tolyldiazonium tetrafluoroborate (6a) to give the desired enone 5aa in 39% yield, along with 45% of the nonarylated byproduct 7 (Table [1], entry 1). The cis,cis-cyclooctadiene derivative 7 is formed through desilylation of 1a in the presence of tetrafluoroboric acid, liberated as a byproduct of the Heck–Matsuda reaction. The formation of 5aa clearly showed that the 4π-electrocyclic ring opening of 1a proceeded even at ambient temperature. Next, we investigated a suitable acid scavenger to suppress the side-production of 7.[10b] As a result, we found that 2,6-di-tert-butyl-4-methylpyridine (DTBMP), Na₂HPO₄, or Ag₂CO₃ afforded the desired product 5aa in a satisfactory yield (entries 2–4). We chose Ag₂CO₃ because it is easily separated by precipitation (Et₂O) and filtration (conditions A). Prolonging the reaction time from 24 to 38 hours resulted in a comparable 90% yield (entry 5), whereas the addition of pyridine or phosphine ligands resulted in a lower yield of 5aa, along with a complicated mixture of byproducts (entries 6 and 7). A competitive reaction between diazonium salt 6a and acetonitrile to give an acetanilide was sometimes observed under conditions A, although the desired reaction with 1 was much faster.[11] Further investigation revealed that the reaction with CaCO₃ as the base in 1,4-dioxane (conditions B) for 72 hours prevented the decomposition of 6a (as observed in entries 8–11), affording 5aa in 84% isolated yield (entry 12).

Table 1 Screening of Reaction Conditions^a

Entry	Solvent	Additivesb,c	Yieldd (%)
			5aa	7	1ae
1	MeCN	–	39	45	–
2	MeCN	DTBMP	89	–	trace
3	MeCN	Na2HPO4	82	–	16
4	MeCN	Ag2CO3	89	–	11
5f	MeCN	Ag2CO3	90g	–	0
6	MeCN	Ag2CO3, bpy	49	12	–
7	MeCN	Ag2CO3, PPh3	55	10	–
8	acetone	Ag2CO3	65	–	18
9	THF	Ag2CO3	68	–	21
10	1,4-dioxane	Ag2CO3	58	–	18
11	1,4-dioxane	CaCO3	74	trace	22
12h	1,4-dioxane	CaCO3	84g	–	–

^a Reaction conditions: Pd(OAc)₂ (5.0 mol%), 1a (0.27 mmol), 2a (1.5 equiv), 24 h, 25 °C.

^b Base (2.0 equiv): DTBMP, Na₂HPO₄, Ag₂CO₃, Ca₂CO₃.

^c Ligand (6.0 mol%): bpy, PPh₃.

^d Determined by ¹H NMR with 1,3-dinitro-5-(trifluoromethyl)benzene as internal standard.

^e Recovered starting material.

^f Reaction time: 38 h.

^g Isolated yield.

^h Reaction time: 72 h.

With the optimized conditions in hand, we next investigated the scope of the diazonium salt (Scheme [3]). The reaction of the ortho-tolyl diazonium salt 6c resulted in a lower yield than those of the para- and metaitolyl derivatives 6a and 6b under conditions A or B owing to steric hindrance associated with the substituent. An acetanilide byproduct was generated when 1a was reacted with 6c under conditions A. This domino reaction tolerates a halogen atom in the diazonium salt (i.e., 6d) to give 5ad in good yield under conditions B. The 1-naphthyl diazonium salt 6e, which is known to react with acetonitrile to yield a quinazoline,[11a] [12] also gave coupling product 5ae in moderate yield under conditions A. The poor solubility of 6e was reflected in its lower yield when the reaction was performed in 1,4-dioxane (conditions B). Diazonium 6f bearing an electron-withdrawing group afforded 5af only under conditions B; no product was formed under conditions A. Diazonium salt 6g bearing an electron-donating dioxolane group smoothly reacted under conditions A. Finally, we determined the structure of adduct 5ag by single-crystal X-ray crystallography.[13]

We next explored the scope of the fused cyclobutene substrate 1 (Scheme [4]). The corresponding cyclooctenone 5ba was obtained in excellent yield when bicyclo[4.2.0]octene 1b bearing two methoxycarbonyl functionalities on the cyclobutene ring reacted with 6a. In contrast, we note that none of the desired product was obtained in the 4π-electrocyclic ring-opening/Mizoroki–Heck arylation reaction (the previous method shown in Scheme [2]A),[7a] which suggests that a cationic palladium system is crucial. The reaction of azacycle 1c with 6a also proceeded in a domino manner to afford dihydroazocinone 5ca, albeit in low yield; substrate 1c was consumed very slowly in this reaction.

We next investigated how the size of the cis,trans-cycloalkadiene intermediate affects the reaction. Products 5da and 5ea were, respectively, formed more slowly and in a lower chemical yield than 5aa when bicyclo[5.2.0]nonenes 1d and 1e were subjected to the reaction conditions.[14] The lower reactivities of the bicyclo[5.2.0]nonenes compared with the [4.2.0]octenes are ascribable to the less-distorted trans-double bonds in the nine-membered diene intermediates compared with the eight-membered intermediates. The starting material was recovered after the attempted reaction of bicyclo[3.2.0]eptane 1f with 6a because the highly strained cis,trans-cycloheptadiene is almost impossible to form under these reaction conditions. Moreover, bicyclo[4.2.0]octene 1g, bearing a substituent at the ring junction, also failed to give the desired product.

We questioned whether the γ-aryl cycloalkenones 5 were formed via cyclooctadienes 3, which are the products under previously reported conditions[7a] (see, Scheme [2]A). We have reported chirality-transfer reactions of optically active cyclobutenes 1 through the short-lived planar chiral intermediates 2.[7a] [b] It would be expected that the point chirality of 1 would be transmitted to the γ-position in 5 if the reaction does not proceed via 3 as an achiral intermediate; therefore, we used optically active 1a as the starting material. To our delight, the chirality of (–)-1a (>99% ee) was perfectly transferred to (–)-5aa (>99% ee), which rules out the formation of diene 3aa (Scheme [5]). The chirality of (–)-5aa should be induced by the stereoselective insertion of an aryl palladium species into the distorted trans-double bond of optically active 2.

A plausible mechanism based on these results is proposed in Scheme [6]. First, fused cyclobutene 1 undergoes a reversible 4π-electrocyclic reaction to give a cis,trans-cycloalkadiene 2 as a short-lived intermediate. The cationic aryl palladium species generated from Pd(0) and diazonium 6 smoothly inserts into the more-reactive trans-double bond in 2 to give siloxyallylpalladium 4,[15] [16] which undergoes reductive elimination with the assistance of the siloxy group, followed by carbonate-ion-assisted desilylation, to provide the desired enone 5 and the Pd(0) species. Note that 4 preferentially undergoes reductive elimination rather than β-hydride elimination to give 3, although the reason for this preference is not yet clear.

In summary, we have developed a domino 4π-electrocyclic reaction/Heck–Matsuda arylation giving γ-aryl cyclooctenones or cyclononenones at ambient temperature.[17] Although inherent equilibration between the bicyclo[4.2.0]octene and the cis,trans-cyclooctadiene is unobservable, ligandless cationic palladium, which readily gives over a vacant site, smoothly traps the transiently generated cis,trans-cyclooctadiene intermediate to promote a Heck–Matsuda arylation, even at ambient temperature. The present reaction complements our previously reported arylation methods[6a] and successfully realizes the transfer of point chirality from the substrate to the product via a planar chiral intermediate.

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

T.I. expresses gratitude to JSPS for a research fellowship for young scientists (JP17J10201).

• References and Notes

• 1 Current address: School of Pharmacy, Hyogo University of Health Sciences, Kobe 650–8530, Japan.

For selected reviews, see:
• 2a Ishmuratov GY, Kharisov RY, Latypova ER, Talipov RF. Chem. Nat. Compd. 2006; 42: 367
  CrossrefSearch in Google Scholar
• 2b Conti M. Anticancer Drugs 2006; 17: 1017
  CrossrefPubMedSearch in Google Scholar
• 2c Das M, Manna K. Curr. Bioact. Compd. 2015; 11: 239
  CrossrefSearch in Google Scholar
• 2d Wang Z. Org. Chem. Front. 2020; 7: 3815
  CrossrefSearch in Google Scholar
• 3a Chen X, Liu X, Mohr JT. J. Am. Chem. Soc. 2016; 138: 6364
  CrossrefPubMedSearch in Google Scholar
• 3b Liu X, Chen X, Mohr JT. Org. Lett. 2016; 18: 3182
  CrossrefPubMedSearch in Google Scholar
• 3c Nambu H, Tamura T, Yakura T. J. Org. Chem. 2019; 84: 15990
  CrossrefPubMedSearch in Google Scholar
• 3d Christoffers J, Mann A. Eur. J. Org. Chem. 2000; 2000: 1977
  CrossrefSearch in Google Scholar
• 3e Hayashi Y, Suga Y, Umekubo N. Org. Lett. 2020; 22: 8603
  CrossrefPubMedSearch in Google Scholar
• 3f Yuan Q, Prater MB, Sigman MS. Adv. Synth. Catal. 2020; 362: 326
  CrossrefPubMedSearch in Google Scholar
• 4a Hyde AM, Buchwald SL. Angew. Chem. Int. Ed. 2008; 47: 177
  CrossrefPubMedSearch in Google Scholar
• 4b Huang DS, Hartwig JF. Angew. Chem. Int. Ed. 2010; 49: 5757
  CrossrefPubMedSearch in Google Scholar
• 4c Saini G, Mondal A, Kapur M. Org. Lett. 2019; 21: 9071
  CrossrefPubMedSearch in Google Scholar
• 5a Liu X, Chen X, Mohr JT. Org. Lett. 2015; 17: 3572
  CrossrefPubMedSearch in Google Scholar
• 5b Chen X, Liu X, Mohr JT. Org. Lett. 2016; 18: 716
  CrossrefPubMedSearch in Google Scholar
• 5c Szabó KF, Goliszewska K, Szurmak J, Rybicka-Jasińska K, Gryko D. Org. Lett. 2022; 24: 8120
  CrossrefPubMedSearch in Google Scholar
• 6a Molander GA. Acc. Chem. Res. 1998; 31: 603
  CrossrefSearch in Google Scholar
• 6b Reyes RL, Iwai T, Sawamura M. Chem. Rev. 2021; 121: 8926
  CrossrefPubMedSearch in Google Scholar
• 7a Arichi N, Yamada K.-i, Yamaoka Y, Takasu K. J. Am. Chem. Soc. 2015; 137: 9579
  CrossrefPubMedSearch in Google Scholar
• 7b Ito T, Tsutsumi M, Yamada K, Takikawa H, Yamaoka Y, Takasu K. Angew. Chem. Int. Ed. 2019; 58: 11836
  CrossrefPubMedSearch in Google Scholar
• 7c Takasu K, Tsustumi M, Ito T, Takikawa H, Yamaoka Y. Heterocycles 2020; 101: 423
  CrossrefSearch in Google Scholar
• 8 To the best of our knowledge, the 4π-electrocyclic reaction of bicyclo[4.2.0]octene at ambient temperature has not been reported except for one example; see: Reinhoudt DN, Verboom W, Visse GW, Trompenaars WP, Harkema S, Van Hummel GJ. J. Am. Chem. Soc. 1984; 106: 1341
  CrossrefPubMedSearch in Google Scholar

For attempts at 4π-electrocyclic reactions of bicyclo[4.2.0]octenes at higher temperatures, see:
• 9a McConaghy JS. Jr, Bloomfield JJ. Tetrahedron Lett. 1969; 10: 3719
  CrossrefSearch in Google Scholar
• 9b Clark RD, Untch KG. J. Org. Chem. 1979; 44: 248
  CrossrefSearch in Google Scholar
• 9c Wang X.-N, Krenske EH, Johnston RC, Houk KN, Hsung RP. J. Am. Chem. Soc. 2014; 136: 9802
  CrossrefPubMedSearch in Google Scholar
• 9d Ralph MJ, Harrowven DC, Gaulier S, Ng S, Booker-Milburn KI. Angew. Chem. Int. Ed. 2014; 54: 1527
  CrossrefPubMedSearch in Google Scholar
• 9e Murakami M, Matsuda T. In Comprehensive Organic Synthesis, 2nd ed., Vol. 5, Chap. 5.16. Knochel P. Elsevier; Amsterdam: 2014: 732
  Search in Google Scholar
• 10a Kikukawa K, Matsuda T. Chem. Lett. 1977; 6: 159
  CrossrefSearch in Google Scholar
• 10b Taylor JG, Moro AV, Correia CR. D. Eur. J. Org. Chem. 2011; 2011: 1403
  CrossrefSearch in Google Scholar
• 11a van Dijk T, Slootweg JC, Lammertsma K. Org. Biomol. Chem. 2017; 15: 10134
  CrossrefPubMedSearch in Google Scholar
• 11b Wang H, Xu Q, Shen S, Yu S. J. Org. Chem. 2017; 82: 770
  CrossrefPubMedSearch in Google Scholar
• 12 Petterson RC, Bennett JT, Lankin DC, Lin GW, Mykytka JP, Troendle TG. J. Org. Chem. 1974; 39: 1841
  CrossrefPubMedSearch in Google Scholar
• 13 CCDC 2234158 contains the supplementary crystallographic data for compound 5ag. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 14 Shea KJ, Kim J.-S. J. Am. Chem. Soc. 1992; 114: 3044
  CrossrefSearch in Google Scholar
• 15 A related transformation of an η³-1-hydroxyallylpalladium complex into an η²-enone has been reported; see: Ogoshi S, Morita M, Kurosawa H. J. Am. Chem. Soc. 2003; 125: 9020
  CrossrefPubMedSearch in Google Scholar
• 16 The generation of siloxyallylpalladium species from enones, which corresponds to the retro process of our proposed desilylative reductive elimination, has been reported; see: Ogoshi S, Tomiyasu S, Morita M, Kurosawa H. J. Am. Chem. Soc. 2002; 124: 11598
  CrossrefPubMedSearch in Google Scholar
• 17 γ-Arylcyclooctenones 5; General Procedure (Conditions A) A test tube was charged with Pd(OAc)₂ (0.014 mmol) together with the appropriate diazonium tetrafluoroborate 6 (0.41 mmol) and cyclobutene 1 (0.27 mmol). Ag₂CO₃ (0.54 mmol) and MeCN (0.20 M) were added to the mixture under argon, and the resulting slurry was vigorously stirred for 38 h. Et₂O was added to the mixture, which was then stirred for a further 15 min. The resulting slurry was filtered through Celite, and the filter cake was washed with Et₂O. The filtrate was concentrated under reduced pressure to remove the solvent and the residue was dissolved in Et₂O. Silica gel was added to the solution and the mixture was stirred for 30 min. The slurry was then filtered and the filter cake was washed with Et₂O. Concentration of the filtrate gave a crude product that was dissolved in CHCl₃ and purified by column chromatography (silica gel, hexane–EtOAc or hexane–EtOAc). Methyl 3-(4-Methylphenyl)-8-oxocyclooct-1-ene-1-carboxylate (5aa) Colorless oil; yield: 67 mg (90%). R_f = 0.38 (hexane–Et₂O, 4:1). IR (ATR): 2928, 2855, 1724, 1697, 1636, 1512, 1454, 1435, 1254, 1223, 1107, 1065 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.19 (d, J = 5.2 Hz, 1 H), 7.11 (d, J = 7.9 Hz, 2 H), 7.02 (d, J = 11.0 Hz, 2 H), 3.74 (s, 3 H), 3.49 (ddd, J = 10.7, 2.4, 2.4 Hz, 1 H), 2.67 (ddd, J = 16.0, 3.3, 3.3 Hz, 1 H), 2.58 (ddd, J = 14.0, 11.0, 3.0 Hz, 1 H), 2.31 (s, 3 H), 2.10–1.97 (m, 1 H), 1.97–1.86 (m, 2 H), 1.86–1.77 (m, 1 H), 1.77–1.62 (m, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 209.2, 164.4, 147.9, 139.4, 136.5, 130.5, 129.4, 127.5, 52.3, 46.9, 44.0, 30.7, 27.9, 22.1, 20.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₂₁O₃: 273.1485; found: 273.1484.

Corresponding Author

Publication History

Received: 09 January 2023

Accepted after revision: 01 February 2023

Accepted Manuscript online:
01 February 2023

Article published online:
02 March 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References and Notes

• 1 Current address: School of Pharmacy, Hyogo University of Health Sciences, Kobe 650–8530, Japan.

For selected reviews, see:
• 2a Ishmuratov GY, Kharisov RY, Latypova ER, Talipov RF. Chem. Nat. Compd. 2006; 42: 367
  CrossrefSearch in Google Scholar
• 2b Conti M. Anticancer Drugs 2006; 17: 1017
  CrossrefPubMedSearch in Google Scholar
• 2c Das M, Manna K. Curr. Bioact. Compd. 2015; 11: 239
  CrossrefSearch in Google Scholar
• 2d Wang Z. Org. Chem. Front. 2020; 7: 3815
  CrossrefSearch in Google Scholar
• 3a Chen X, Liu X, Mohr JT. J. Am. Chem. Soc. 2016; 138: 6364
  CrossrefPubMedSearch in Google Scholar
• 3b Liu X, Chen X, Mohr JT. Org. Lett. 2016; 18: 3182
  CrossrefPubMedSearch in Google Scholar
• 3c Nambu H, Tamura T, Yakura T. J. Org. Chem. 2019; 84: 15990
  CrossrefPubMedSearch in Google Scholar
• 3d Christoffers J, Mann A. Eur. J. Org. Chem. 2000; 2000: 1977
  CrossrefSearch in Google Scholar
• 3e Hayashi Y, Suga Y, Umekubo N. Org. Lett. 2020; 22: 8603
  CrossrefPubMedSearch in Google Scholar
• 3f Yuan Q, Prater MB, Sigman MS. Adv. Synth. Catal. 2020; 362: 326
  CrossrefPubMedSearch in Google Scholar
• 4a Hyde AM, Buchwald SL. Angew. Chem. Int. Ed. 2008; 47: 177
  CrossrefPubMedSearch in Google Scholar
• 4b Huang DS, Hartwig JF. Angew. Chem. Int. Ed. 2010; 49: 5757
  CrossrefPubMedSearch in Google Scholar
• 4c Saini G, Mondal A, Kapur M. Org. Lett. 2019; 21: 9071
  CrossrefPubMedSearch in Google Scholar
• 5a Liu X, Chen X, Mohr JT. Org. Lett. 2015; 17: 3572
  CrossrefPubMedSearch in Google Scholar
• 5b Chen X, Liu X, Mohr JT. Org. Lett. 2016; 18: 716
  CrossrefPubMedSearch in Google Scholar
• 5c Szabó KF, Goliszewska K, Szurmak J, Rybicka-Jasińska K, Gryko D. Org. Lett. 2022; 24: 8120
  CrossrefPubMedSearch in Google Scholar
• 6a Molander GA. Acc. Chem. Res. 1998; 31: 603
  CrossrefSearch in Google Scholar
• 6b Reyes RL, Iwai T, Sawamura M. Chem. Rev. 2021; 121: 8926
  CrossrefPubMedSearch in Google Scholar
• 7a Arichi N, Yamada K.-i, Yamaoka Y, Takasu K. J. Am. Chem. Soc. 2015; 137: 9579
  CrossrefPubMedSearch in Google Scholar
• 7b Ito T, Tsutsumi M, Yamada K, Takikawa H, Yamaoka Y, Takasu K. Angew. Chem. Int. Ed. 2019; 58: 11836
  CrossrefPubMedSearch in Google Scholar
• 7c Takasu K, Tsustumi M, Ito T, Takikawa H, Yamaoka Y. Heterocycles 2020; 101: 423
  CrossrefSearch in Google Scholar
• 8 To the best of our knowledge, the 4π-electrocyclic reaction of bicyclo[4.2.0]octene at ambient temperature has not been reported except for one example; see: Reinhoudt DN, Verboom W, Visse GW, Trompenaars WP, Harkema S, Van Hummel GJ. J. Am. Chem. Soc. 1984; 106: 1341
  CrossrefPubMedSearch in Google Scholar

For attempts at 4π-electrocyclic reactions of bicyclo[4.2.0]octenes at higher temperatures, see:
• 9a McConaghy JS. Jr, Bloomfield JJ. Tetrahedron Lett. 1969; 10: 3719
  CrossrefSearch in Google Scholar
• 9b Clark RD, Untch KG. J. Org. Chem. 1979; 44: 248
  CrossrefSearch in Google Scholar
• 9c Wang X.-N, Krenske EH, Johnston RC, Houk KN, Hsung RP. J. Am. Chem. Soc. 2014; 136: 9802
  CrossrefPubMedSearch in Google Scholar
• 9d Ralph MJ, Harrowven DC, Gaulier S, Ng S, Booker-Milburn KI. Angew. Chem. Int. Ed. 2014; 54: 1527
  CrossrefPubMedSearch in Google Scholar
• 9e Murakami M, Matsuda T. In Comprehensive Organic Synthesis, 2nd ed., Vol. 5, Chap. 5.16. Knochel P. Elsevier; Amsterdam: 2014: 732
  Search in Google Scholar
• 10a Kikukawa K, Matsuda T. Chem. Lett. 1977; 6: 159
  CrossrefSearch in Google Scholar
• 10b Taylor JG, Moro AV, Correia CR. D. Eur. J. Org. Chem. 2011; 2011: 1403
  CrossrefSearch in Google Scholar
• 11a van Dijk T, Slootweg JC, Lammertsma K. Org. Biomol. Chem. 2017; 15: 10134
  CrossrefPubMedSearch in Google Scholar
• 11b Wang H, Xu Q, Shen S, Yu S. J. Org. Chem. 2017; 82: 770
  CrossrefPubMedSearch in Google Scholar
• 12 Petterson RC, Bennett JT, Lankin DC, Lin GW, Mykytka JP, Troendle TG. J. Org. Chem. 1974; 39: 1841
  CrossrefPubMedSearch in Google Scholar
• 13 CCDC 2234158 contains the supplementary crystallographic data for compound 5ag. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 14 Shea KJ, Kim J.-S. J. Am. Chem. Soc. 1992; 114: 3044
  CrossrefSearch in Google Scholar
• 15 A related transformation of an η³-1-hydroxyallylpalladium complex into an η²-enone has been reported; see: Ogoshi S, Morita M, Kurosawa H. J. Am. Chem. Soc. 2003; 125: 9020
  CrossrefPubMedSearch in Google Scholar
• 16 The generation of siloxyallylpalladium species from enones, which corresponds to the retro process of our proposed desilylative reductive elimination, has been reported; see: Ogoshi S, Tomiyasu S, Morita M, Kurosawa H. J. Am. Chem. Soc. 2002; 124: 11598
  CrossrefPubMedSearch in Google Scholar
• 17 γ-Arylcyclooctenones 5; General Procedure (Conditions A) A test tube was charged with Pd(OAc)₂ (0.014 mmol) together with the appropriate diazonium tetrafluoroborate 6 (0.41 mmol) and cyclobutene 1 (0.27 mmol). Ag₂CO₃ (0.54 mmol) and MeCN (0.20 M) were added to the mixture under argon, and the resulting slurry was vigorously stirred for 38 h. Et₂O was added to the mixture, which was then stirred for a further 15 min. The resulting slurry was filtered through Celite, and the filter cake was washed with Et₂O. The filtrate was concentrated under reduced pressure to remove the solvent and the residue was dissolved in Et₂O. Silica gel was added to the solution and the mixture was stirred for 30 min. The slurry was then filtered and the filter cake was washed with Et₂O. Concentration of the filtrate gave a crude product that was dissolved in CHCl₃ and purified by column chromatography (silica gel, hexane–EtOAc or hexane–EtOAc). Methyl 3-(4-Methylphenyl)-8-oxocyclooct-1-ene-1-carboxylate (5aa) Colorless oil; yield: 67 mg (90%). R_f = 0.38 (hexane–Et₂O, 4:1). IR (ATR): 2928, 2855, 1724, 1697, 1636, 1512, 1454, 1435, 1254, 1223, 1107, 1065 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.19 (d, J = 5.2 Hz, 1 H), 7.11 (d, J = 7.9 Hz, 2 H), 7.02 (d, J = 11.0 Hz, 2 H), 3.74 (s, 3 H), 3.49 (ddd, J = 10.7, 2.4, 2.4 Hz, 1 H), 2.67 (ddd, J = 16.0, 3.3, 3.3 Hz, 1 H), 2.58 (ddd, J = 14.0, 11.0, 3.0 Hz, 1 H), 2.31 (s, 3 H), 2.10–1.97 (m, 1 H), 1.97–1.86 (m, 2 H), 1.86–1.77 (m, 1 H), 1.77–1.62 (m, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 209.2, 164.4, 147.9, 139.4, 136.5, 130.5, 129.4, 127.5, 52.3, 46.9, 44.0, 30.7, 27.9, 22.1, 20.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₂₁O₃: 273.1485; found: 273.1484.

• Supplementary Material