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DOI: 10.1055/a-1814-9853
Regiocontrol by Halogen Substituent on Arynes: Generation of 3-Haloarynes and Their Synthetic Reactions
Abstract
The use of arynes as highly reactive intermediates has attracted substantial attention in organic synthesis. To enhance the utility of arynes, the regiocontrol in the reactions of unsymmetrically substituted arynes is an important task. The introduction of halogen substituent at 3-position of arynes leads to sufficient regiocontrol for various synthetic reactions. This short review highlights the utility of 3-haloarynes in organic synthesis and discusses the distortion models used to explain regioselectivity, representative reactions of 3-haloarynes generated from polyhaloarenes, and the preparation and reactions of easily activatable aryne precursors.
1 Introduction
2 Distortion Models
3 Reaction of Precursors Activated by an Organometallic Reagent or Base
4 Preparation of Easily Activatable Precursors
5 Reactions of Easily Activatable Precursors
6 Concluding Remarks
# 1
Introduction
Since 2010, arynes have attracted increasing attention as highly reactive species for the construction of multisubstituted arenes with structural diversity and complexity.[1] The reactions of unsymmetrically substituted arynes are frequency constrained by low regioselectivity. To overcome these limitations, the introduction of a silyl[2] or boryl[3] group at the 3-position of the aryne has been studied. Furthermore, unsymmetrical arynes bearing a 3-alkoxy[4] or 3-triflyloxy[5] group as an inductive electron-withdrawing group are used to control regioselectivity. 3-Haloarynes are well known to react with a high degree of regioselectivity. This short review highlights regiocontrol by 3-haloarynes and discusses distortion models used to explain their regioselectivity, representative reactions of 3-haloarynes generated from polyhaloarenes, methods for preparing the easily activatable aryne precursors, and the representative reactions using these precursors.
# 2
Distortion Models
Regiocontrol can be achieved by 3-haloarynes 1a–d (Figure [1]).[6] The preferred attack of nucleophiles at C1 of 1a–d leads to the formation of meta-substituted arenes 2a–d rather than ortho-substituted arenes 3a–d. The groups of Garg and Houk proposed the distortion model to explain the regioselectivity of unsymmetrical arynes.[6] [7] The optimized structure of 3-fluoroaryne 1a shows significant distortion; its internal angles at C1 and C2 are 135° and 118°, respectively. The addition of nucleophiles is favored at the more linear C1, since the transition state distortion energy for attack at C1 is low. In contrast, the lower regioselectivity of 3-iodoaryne 1d can be explained by little unsymmetrical distortion. As described in Section 5, the degree of aryne distortion (F > Cl > Br > I) is consistent with the experimental results (Tables 1 and 2 in Section 5); thus, the effect of the halogen atom on directing the regioselectivity increases from 3-iodoaryne 1d to 3-fluoroaryne 1a.
The effect of the halogen atom on heterocyclic arynes was investigated.[8] [9] In general, the reaction of 3,4-pyridyne 4 shows a low degree of regioselectivity (Figure [2]).[8] In contrast, 5-bromo-3,4-pyridyne 7 reacts with sufficient regioselectivity to give C3-substituted pyridine 8 over the C4-substituted pyridine 9. In a DFT geometry optimization study, 5-bromo-3,4-pyridyne 7 displays significant aryne distortion, whereas 3,4-pyridyne 4 shows little distortion.
The introduction of a bromine atom into 4,5-indolyne led to a reversal in the regioselectivity (Figure [3]).[9] The addition of nucleophiles to 4,5-indolyne 10 is favored at C5, leading to the preferential formation of 5-substituted adduct 11.[7a] [b] In marked contrast, 6-bromo-4,5-indolyne 12 reacts preferentially with nucleophiles at C4 to give the 4-substituted adduct 13.[9] The reversed regioselectivity between 4,5-indolyne 10 and 6-bromo-4,5-indolyne 12 is also supported by the distortion model.
# 3
Reaction of Precursors Activated by an Organometallic Reagent or a Base
The generation of 3-haloarynes can be achieved by metal-halogen exchange or ortho-metalation of polyhaloarenes using organometallic reagents. Treatment of 1,3-dibromo-2-iodobenzene (14) with a phenyl Grignard reagent gave m-terphenyl (15) in 77% yield (Scheme [1]).[10a] This transformation proceeds through the domino generation of 3-bromoaryne from A and 3-phenylaryne from B; these arynes react regioselectively with the phenyl Grignard to give m-terphenyl (15) via the final protonation of C. Furthermore, the reaction of arynes generated from polyhaloarenes with alkenyl Grignard reagents was also reported.[10b]
3-Haloarynes can be prepared by ortho-lithiation of polyhaloarenes followed by elimination of LiX. The cycloaddition of furan to the 3-fluoroaryne generated from 1-chloro-2,4-difluorobenzene (16) proceeded to give benzo-fused 7-oxanorbornadiene 17 in 90% yield (Scheme [2]).[11] In this transformation, the selective lithiation of 16 and the subsequent elimination of LiF from aryllithium intermediate D gives the key 3-fluoroaryne. The competitive generation of 3-fluoroaryne and 3-chloroaryne by lithiation of 1-chloro-3-fluorobenzene (18) was largely dependent on solvent.[12] The reaction of 18 with t-BuLi was carried out in the presence of furan.[12b] When the reaction of 18 was performed in THF, 5-fluorobenzo-7-oxanorbornadiene 19a was predominantly obtained in 73% yield from 3-fluoroaryne, accompanied by a small amount of 5-chlorobenzo-7-oxanorbornadiene 19b from 3-chloroaryne. In marked contrast, the reaction in Et2O afforded 5-chlorobenzo-7-oxanorbornadiene 19b as the major product.
The generation of 3-haloarynes was also achieved through the regioselective zincation of dihaloarenes.[13] Effective aryne formation was observed using Me2Zn(TMP)Li (TMP = 2,2,6,6-tetramethylpiperidide) as the zinc reagent. Arenes 20a and 20b were treated with Me2Zn(TMP)Li in the presence of 1,3-diphenylisobenzofuran 21 in THF and gave adducts 22a and 22b, respectively, as a result of the cycloaddition between furan 21 and 3-haloarynes generated from arylzincates (Scheme [3]).
The borylzincation of arynes was studied using dialkylzinc, a diboron reagent, and a metal alkoxide.[14] The reaction of trihaloarenes 23a and 23b with bis(pinacolato)diboron (24) was performed in the presence of Me2Zn and Mg(O t Bu)2 in dioxane at 120 °C (Scheme [4]). Subsequent trapping of the arylzincates with allyl bromide gave the multifunctionalized arenes 25a and 25b. In this cascade reaction, the halogen-metal exchange of 23a and 23b with borylzincate, generated from bis(pinacolato)diboron (24) and Me2Zn, gives 3-haloarynes as key intermediates; arenes 25a and 25b are formed by reaction of 3-haloarynes with the borylzincate followed by trapping with allyl bromide.
The synthesis of biphenylene derivatives based on the cyclization of aryne intermediates, generated from polyhalobiaryls, was developed.[15] Treatment of 2′-bromo-4-chloro-2-fluorobiphenyl (26) with t-BuLi at low temperature gave 2-chlorobiphenylene (27) in 86% yield (Scheme [5]).[15] This transformation is initiated by the formation of a dilithiobiphenyl intermediate that undergoes elimination of LiF to give a 3-chloroaryne substituted by a lithiophenyl group. Subsequent cyclization of the aryne intermediate leads to biphenylene 27.
5-Arylthianthrenium perchlorates were utilized as an aryne precursor.[16] The reaction of 5-arylthianthrenium perchlorate 28 with t-BuOK in DMSO at room temperature gave 3-bromo-4-methoxy-2-(methylthio)phenol (29) in 73% yield together with 2-bromo-1,4-dimethoxy-3-(methylthio)benzene (30) in 3% yield (Scheme [6]). The formation of 29 and 30 can be explained by the generation of a 3-bromoaryne and subsequent trapping of this 3-bromoaryne with DMSO.
A one-pot, three-component coupling reaction was developed between allyltrimethylsilane (31), triflate 33, and O-benzoyl-N-hydroxypiperidine (34) (Scheme [7]).[17] Initially, lithium bis[3-(trimethylsilyl)prop-2-enyl]cuprate 32 was prepared by treatment of allyltrimethylsilane (31) with s-BuLi and CuI. Next, treatment of aryne precursor 33 with cuprate 32 induced the allylcupration of 3-fluoroaryne. Finally, trapping of the metalated arene E with O-benzoyl-N-hydroxypiperidine (34) as an electrophile gave the functionalized arene 35 by a one-pot procedure.
The regioselective reactions of the 3-fluoroaryne generated from 3-fluoro-2-iodophenyl triflate (36) were reported (Scheme [8]).[18a] Triflate 36 was efficiently activated by the silylmethyl Grignard reagent Me3SiCH2MgCl. The reaction of the 3-fluoroaryne with benzyl azide gave 1-benzyl-4-fluorobenzotriazole 37a as a single regioisomer. Similarly, the reaction of 36 with ketene silyl acetal or morpholine gave products 38 and 39, respectively. Furthermore, the selective and sequential generation of an aryne from bisaryne precursors bearing 2-iodo- and 2-silylaryl triflate moieties was studied.[18b] In the presence of 1-phenyl-1H-pyrrole, selective aryne generation from the 3-bromo-2-iodophenyl triflate moiety of 40 was triggered by Me3SiCH2MgCl to give the [2+4] cycloaddition product 41 containing a 2-silylaryl triflate moiety as the second aryne precursor. In 2021, a mild method for generating arynes from 2-iodophenyl triflates was developed.[18c] The generation of 3-fluoroaryne from 36 was achieved by treatment of 36 with triethylsilane and cesium fluoride in THF at 70 °C. The insertion reaction of 3-fluoroaryne into the C–C bond of 1,3-diketone 42 afforded the acylalkylation product 43 in 49% yield. In this method, the 3-fluoroaryne is generated through the activation of the C–I bond in 36 by silicate H–Si(F)Et3 formed from Et3SiH and CsF.
Aryne precursors with 4-chlorobenzenesulfonate (Ar = 4-ClC6H4) as a leaving group were developed (Scheme [9]).[19] Treatment of 2,6-diiodophenyl 4-chlorobenzenesulfonate 44 (Ar = 4-ClC6H4) with i-PrMgCl gave the corresponding aryne, which reacted with furan to give adduct 45 in 71% yield. The reaction of 3-fluoroaryne, generated from 3-fluoro-2-iodophenyl 4-chlorobenzenesulfonate 46 (Ar = 4-ClC6H4), with Me3Sn–PPh2 gave the regioisomers 47a and 47b in 6.8:1 ratio.[20a] However, the regioselectivity in the insertion of 3-chloroaryne, generated from 2-chloro-6-iodophenyl 4-chlorobenzenesulfonate 48, into the Sn–P bond was lower. Next, sulfonate 46 (Ar = 4-ClC6H4) was used in the formal [5+2] cycloaddition of 3-fluoroaryne with vinylaziridines 50a and 50b, leading to benzazepines 51a and 51b, respectively, with high degrees of regioselectivity.[20b] Furthermore, excellent regioselectivity was observed in the reaction of 3-chloroaryne, generated from 48, with stannylated imine 52 to provide o-stannylaniline 53 in 58% yield.[20c]
The generation of arynes can be achieved by ortho-deprotonation of diaryliodonium salts on treatment an alkoxide as a base (Scheme [10]).[21] [22] [23] Treatment of aryl(mesityl)iodonium tosylate salt 54 with NaO t Bu in tert-butyl methyl ether (TBME) at 50 °C generated an aryne that underwent cycloaddition with benzyl azide to give a 3.8:1 mixture of regioisomers 55a and 55b in 63% combined yield.[21a] The reaction of iodonium salt 56 with N-benzylbenzamide 57 in the presence of KO t Bu at room temperature gave two regioisomers 58a and 58b in a higher (>95:5) ratio.[21c] Using 3-halophenyl(mesityl)iodonium salts 59a–c and 1,3-dimethylimidazolidin-2-one (60) with NaO t Bu as the base resulted in the regioselective insertion reaction of the thus generated 3-haloarynes into 60 to give diazapinones 61a–c.[21e] Since the mesityl group of the aryl(Mes)iodoniums undergoes competitive aryl transfer by ipso-substitution, a method using aryl(TMP)iodonium tosylates (TMP = 2,4,6-trimethoxyphenyl) as an alternative precursor was developed.[22] The use of TMP as an auxiliary in the iodonium salts suppresses the competitive ipso-substitution pathways. The reaction of 3-chloroaryne, generated from 62, with N-tert-butyl-α-phenylnitrone (63) proceeded with excellent chemical efficiency to give adduct 64. Similarly, the reaction of 62 and 1-chloroazepane (65) gave the insertion product 66. Additionally, a further example of the generation of 3-haloarynes under basic conditions was reported in the coupling reaction of aryl halides with alkoxides.[23]
# 4
Preparation of Easily Activatable Precursors
It is well known that 3-chloroaryne can be obtained by treatment of 6-chloroanthranilic acid (67) with isoamyl nitrile under high temperature conditions (Figure [4]).[24] More recently, aryne-based reactions have made great advances in synthetic chemistry, particularly by the development of o-(trimethylsilyl)aryl triflates as an easily activatable aryne precursor.[1g] [i] [25] The generation of arynes can be achieved by treatment of o-(trimethylsilyl)aryl triflates with fluoride ion under mild reaction conditions. In recent years, several aryne precursors were developed for the generation of 3-haloarynes under mild reaction conditions. However, the preparation of these highly functionalized aryne precursors requires multistep syntheses. In this section, the methods for preparing these precursors are summarized.
Two methods for preparing 2-(trimethylsilyl)aryl triflates 68a–d have been developed.[6] [26] [27] These precursors can be synthesized by a route involving lithium-halogen exchange followed by migration of the trimethylsilyl group (Scheme [11]).[26] To prepare the O-trimethylsilylated intermediate F, 2-bromo-6-chlorophenol (75b) was initially reacted with hexamethyldisilazane (HMDS). Subsequent lithium-halogen exchange of intermediate F with BuLi induced TMS migration of G leading to C-trimethylsilylated phenoxide H. Finally, treatment of phenoxide H with Tf2O gave precursor 68b in 37% yield. As a modified procedure, precursors 68c and 68d were synthesized from phenols 75c and 75d by two steps involving the isolation of C-trimethylsilylated phenols 76c and 76d.
The groups of Garg and Houk developed an alternative method starting from the readily available phenols 77a and 77b (Scheme [12]).[6] [27] N-Isopropylcarbamates 78a and 78b were prepared by treatment of 77a and 77b with isopropyl isocyanate. Next, N-silylation and ortho-lithiation of carbamates 78a and 78b gave intermediates I that were quenched with TMSCl to provide silylcarbamates 79a and 79b. Finally, the aryne precursors 68a and 68b were obtained by the removal of the carbamate moiety using DBU and Et2NH followed by triflation using PhNTf2.
The 3-haloaryne precursors 69a–c were prepared from the readily available 3-halophenols 80a–c by a simple procedure involving O-trimethylsilylation and TMS-migration followed by triflation (Scheme [13]).[28] Employing Mg(TMP)2·2LiCl or LDA as the base gave the desired TMS-migration products 81a–c in reasonable chemical yields via intermediate J. The C-silylated phenols 81a–c were converted into precursors 69a–c by treatment with Tf2O in the presence of (i-Pr)2NEt.
The aryne precursors 70a and 70b were obtained in one step from commercially available starting materials 82a and 82b (Scheme [14]).[29] Lithium 2,2,6,6-tetramethylpiperidide (TMPLi) was used for the ortho-lithiation of aryl halides 82a and 82b; subsequent trapping of lithium intermediates with Me2SiHCl was performed at –110 °C with subsequent warming to give the silylaryl halides 70a and 70b.
The silylpyridyl triflate 71 was synthesized by the carbamation of 5-bromopyridin-3-ol (83) with isopropyl isocyanate (Scheme [15]).[8] The carbamate 84 was converted into silylcarbamate 85 by N-silylation with TBSOTf, ortho-lithiation with LDA, and C-silylation with TMSCl. Finally, removal of the carbamate moiety from 85 gave 86 which was treated with Tf2O to give aryne precursor 71.
The bromoindolyne precursor 72 was also synthesized by a method using an N-isopropylcarbamate (Scheme [16]).[9] Commercially available 5-(benzyloxy)-1H-indole (87) was converted into silylcarbamate 91 by a high-yielding multistep sequence. Next, bromination at C6 of 91 gave brominated intermediate 92, which was treated with DBU to remove the carbamate group, the hydroxy group was triflated with PhNTf2, and then the N-TIPS group was removed to give indolyne precursor 72.
As a 3-fluoroaryne precursor, 4-fluoro-1-mesitylbenziodoxaborole triflate 73 was prepared from 1-acetoxy-4-fluoro-1,2,3-benziodoxaborole 94 (Scheme [17]).[30] In the presence of trifluoromethanesulfonic acid (TfOH), the ligand exchange reaction between hypervalent iodine 94 and mesitylene proceeded effectively to give pseudocyclic iodonium triflate 73 in 95% yield.
Cyclic diaryl λ3-bromanes 74a and 74b were synthesized as aryne precursors (Scheme [18]).[31] Iodobenzene derivatives 95a and 95b were treated with trimethyl borate and i-PrMgBr to give boronic acids 96a and 96b that were converted into the diaryl compounds 97a and 97b by palladium-catalyzed cross-coupling with 2-iodoaniline. Finally, treatment of 97a and 97b with t-BuONO and MeSO3H gave diaryl λ3-bromanes 74a and 74b.
# 5
Reactions of Easily Activatable Precursors
The synthesis of triptycenes was studied by Diels–Alder reaction between anthracenes and arynes.[24] Treatment of 6-chloroanthranilic acid (67) with isoamyl nitrite in 1,2-dimethoxyethane (DME) under reflux gave a 3-chloroaryne that reacted with 1,8-dichloroanthracene (98) to give 1,8,16-trichlorotriptycenes syn-99 and anti-99 in 16% combined yield in 1:1.9 ratio (Scheme [19]).[24a]
The fluoride-promoted 1,2-elimination of o-(trimethylsilyl)aryl triflates leads to the generation of arynes under mild conditions. Regiocontrol by 3-haloarynes was studied by both experimental and computational methods.[6] The effects of the halogen atom on the regioselectivity were investigated using the reactions of precursors 68a–d with N-methylaniline (Table [1]). In the presence of CsF, 3-fluoroaryne, generated from precursor 68a, reacted with a high degree of regioselectivity to give the adduct 100a exclusively (entry 1). A sequential decrease in regioselectivity was observed for the reactions of precursors 68b–d (entries 2–4). The lowest regioselectivity was observed in the reaction of 3-iodoaryne generated from precursor 68d (entry 4). These results are consistent with the distortion model described in Section 2 (Figure [1]). Furthermore, ΔΔG ‡ values from transition state modeling using DFT calculations (B3LYP) indicate that the nucleophilic addition of N-methylaniline to 3-fluoroaryne should be highly regioselective (ΔΔG ‡ = 4.1 kcal/mol and >500:1 ratio, entry 1).
A similar regioselectivity trend was observed in the cycloaddition reaction of precursors 68a–d with benzyl azide (Table [2]).[6] The use of the 3-fluorinated precursor 68a resulted in highly controlled regioselectivity (entry 1). The regioselectivity decreased from 3-fluoroaryne to 3-iodoaryne (entries 1–4). These results were also supported by ΔΔG ‡ values of transition state modeling.
The precursors 68a–d were used in various aryne-based reactions.[32] [33] [34] [35] [36] [37] [38] As an example for regioselective insertion of 3-haloarynes into a σ bond, the fluorostannylation of arynes was reported (Scheme [20]).[32] Precursors 68b and 68c in the presence of KF and 18-crown-6 in DME at 0 °C generate 3-haloarynes that react with tributyltin fluoride to give 103b and 103c, the products of Ar–F and Ar–Sn bond-formation at adjacent positions in the aromatic ring. The reaction of 3-fluoro-, 3-chloro-, and 3-bromoarynes with sulfoxide 104 was investigated.[33a] Precursors 68a–c reacted with sulfoxide 104 in the presence of KF and 18-crown-6 in 1,4-dioxane at 80 °C to give the corresponding products 105a–c. This transformation involves the formation of C–O and C–S bonds followed by migratory O-arylation. The reaction of arynes with sulfoximines was also reported.[33b] Treatment of precursor 68b and S,S-di(p-tolyl)sulfoximine (106) with KF and 18-crown-6 in THF at 60 °C afforded o-sulfinylaniline derivative 107 in moderate yield. The proposed pathway involves the [2+2] cycloaddition between the aryne and the S=N bond of 106 followed by the migration of the aryl group. Furthermore, thioamination of arynes with sulfilimines was reported.[33c] The reaction of precursor 68c and sulfilimine 108 was promoted by KF and 18-crown-6 to give the thioamination product 109. The reaction of arynes with pyrazole N-oxides was studied.[34] Treatment of precursors 68a and 68b with 1-benzyl-1H-pyrazole 2-oxide 110 in the presence of CsF led to the regioselective formation of C3-hydroxyarylated pyrazoles 111a and 111b in 82% and 56% yields, respectively.
The annulation between precursor 68c and substrate 112 having a nucleophilic site and an alkene moiety was reported (Scheme [21]).[37] This cascade reaction proceeds by the sequential generation of two aryne species as key intermediates to give the cyclized product 113 via the ene reaction. Novel methodology for the synthesis of naphthalene derivatives was reported.[38] The reaction of precursor 68b with 2-oxocyclonon-8-enecarboxylate 114 in the presence of KF and 18-crown-6 gave the naphthyl carbocycle 115 in 64% yield. This cascade transformation involves the insertion of 3-chloroaryne into the C–C bond of 114 followed by a vinylogous aldol reaction.
A one-pot protocol for the insertion of arynes into nitrogen–halide bonds was investigated (Scheme [22]).[39] N-Chloromorpholine was prepared in situ from morpholine (116) and N-chlorosuccinimide. Subsequent treatment of N-chloromorpholine with 3-bromoaryne precursor 117 in the presence of CsF gave o-chloroaniline 118. The utility of 4-(pinacolatoboryl)-2-silylaryl triflates as a new class of building blocks was presented.[40] The reaction of 4-(pinacolatoboryl)-2-silylaryl triflate 119 with pyridine N-oxide in the presence of CsF and 18-crown-6 gave 3-substituted pyridine 120 exclusively via rearrangement. The synthesis of hetisine-type natural products was studied based on the synthetic strategy involving the acyl-alkylation of a 3-bromoaryne.[41] Treatment of a solution of β-keto ester 121 and precursor 122 in CH3CN with CsF at 70 °C gave tricycle 123 in 38–45% yield by the regioselective insertion of a 3-bromoaryne, generated from 122, into the C–C bond of 121.
When o-(trimethylsilyl)aryl triflates 68a–d are used as 3-haloaryne precursors, the thia-Fries rearrangement is frequently observed. Treatment of chloro-substituted precursor 68b with CsF gave phenoxathiin dioxide derivative 124b in 60% yield (Scheme [23]).[26a] Similarly, phenoxathiin dioxide derivative 124c was obtained from bromo-substituted precursor 68c. Initially, the fluoride-promoted C–Si bond cleavage of 68b and 68c gives anion K. Subsequent thia-Fries rearrangement of anion K gives phenolate L,[26a] [42] which reacts further with arynes. The cyclization of phenyl anion M onto the triflyl group gives 124b and 124c.
The reactions of 3-haloarynes, generated from precursors 68a–d, are plagued by the competitive thia-Fries rearrangement (Scheme [24]). Since the steric repulsion in anion K promotes thia-Fries rearrangement giving phenolate L, the competitive thia-Fries rearrangement could be suppressed by simply swapping the position of the triflate and TMS groups on the precursor. The use of precursors 69a–c suppressed the problematic thia-Fries rearrangement, leading to the selective generation of 3-haloarynes via anions N.[28]
The utility of precursor 69b was investigated by comparing it with precursor 68b (Scheme [25]).[28] Insertion reaction of precursor 68b with Bu3SnF gave the desired product 103b in 36% yield together with the competitive formation of the thia-Fries rearrangement product 125 in 14% yield. In marked contrast, using precursor 69b selectively gave the insertion product 103b in 92% yield. The advantage of precursor 69b over precursor 68b was also confirmed by the [3+2] cycloaddition with benzyl azide. Although Huisgen-type reaction of precursor 68b led to the competitive formation of the desired product 37b and thia-Fries rearrangement product 125, the reaction using precursor 69b gave the cyclic product 37b in 91% yield. A similar trend was observed in the three-component coupling reaction of diethyl malonate, N,N-dimethylformamide, and precursors 68b or 69a–c. The reaction using precursors 69a–c resulted in the selective formation of coumarin derivatives 126a–c in good yields.
The silylaryl bromides 70a and 70b were used for aryne generation under mild reaction conditions using the fluoride ion (Scheme [26]).[29] The arylation of 4-methoxy-N-tritylaniline (127) with aryne precursor 70a was performed in the presence of CsF in DME/toluene at 110 °C followed by treatment with TFA, to remove the trityl group, the arylated product 128 was isolated in 61% yield. Furthermore, treatment of precursor 70b and 1,3-dimethyl-3,4,5,6-tetrahydropyrimidin-2(1H)-one 129 with tetramethylammonium fluoride in Et2O at 0 °C afforded the desired product 130 in 51% yield.
The trend of regioselectivity using 3,4-pyridyne derivatives was investigated (Scheme [27]).[8] In general, 3,4-pyridyne is known to react with poor regioselectivity, which shows consistent with the distortion model described in Section 2 (Figure [2]). Indeed, the reactions of 3,4-pyridyne precursor 131 with morpholine in the presence of CsF afforded a 1.3:1 mixture of C4- and C3-substituted products 132 and 133 in 73% combined yield. As expected from the distortion model (Figure [2]), the use of bromopyridine precursor 71 resulted in a switch in the regioselectivity and the formation of C3-substituted product 134 was preferred over C4-substituted adduct 135 in a 2.9:1 ratio. Notably, the insertion reaction of 5-bromo-3,4-pyridyne, generated from 71, into 1,3-dimethylimidazolidin-2-one (60) gave the benzodiazepine derivative 136 in 79% yield without the formation of another regioisomer.
As expected from distortion models (Figure [3]), the reactions using 4,5-indolyne and 6-bromo-4,5-indolyne displayed reversals in regioselectivity (Scheme [28]).[9] For a representative example, the addition of 3-aminocyclohex-2-en-1-one (138) to 4,5-indolyne, generated from precursor 137, predominantly occurred at C5 to give the 5-alkylated indole 139 as the major isomer. In marked contrast, the reaction of 6-bromo-4,5-indolyne, generated from precursor 72, occurred at C4 with significant regioselectivity to give 4-alkylated indole 141 and 5-alkylated indole 142 in 20:1 ratio. Moreover, the regiocontrolled reaction of precursor 72 with peptide 143 was used for the total synthesis of indolactam V.
The simple treatment of aryliodonium salts, such as 1-mesitylbenziodoxaborole triflate 73, with water at room temperature generates arynes (Scheme [29]).[30] 4-Fluoro-1-mesitylbenziodoxaborole triflate 73 in CH2Cl2/water gave a 3-fluoroaryne that reacted with 9,10-dimethylanthracene (145) to give dimethyltriptycene 146 in 87% yield. The reaction of 73 with benzyl azide in CH2Cl2/water furnished triazole 37a in 78% yield. Furthermore, triflate 73 in CH2Cl2/ water acted as an arylating reagent toward 4-tert-butylphenol (147) giving the mono-ortho-arylated phenol 148 in 65% yield and the di-ortho-arylated phenol 149 in 30% yield.
In the presence of a weak base, cyclic diaryl λ3-bromanes 74a and 74b are a precursor to 3-haloarynes (Scheme [30]).[31] The reaction of 74a and 74b with furan in the presence of Cs2CO3 proceeded at room temperature to give the adducts 150a and 150b, respectively.[31b] The [2+2] reaction between 74a and 3,4-dihydro-2H-pyran 151 in the presence of Cs2CO3 proceeded with excellent efficiency to give adducts 152 and 153 in 1.7:1 ratio.[31b] Excellent regioselectivity was observed in the reaction of 74a with carboxylic acid 154 in the presence of Cs2CO3 to give the product 155 in 99% yield.[31a]
# 6
Concluding Remarks
Arynes are highly reactive and versatile intermediates that induce synthetically valuable chemical transformations. The use of unsymmetrically substituted arynes has become a subject of recent research in aryne-based synthetic chemistry. In recent years, effective regiocontrol was achieved by the introduction of a halogen substituent, or silyl, boryl, alkoxy and triflyloxy groups, at 3-position of the aryne. As discussed in this short review, 3-haloarynes can be generated by metal-halogen exchange or ortho-metalation of polyhaloarenes. More recently, the development of easily activatable aryne precursors revealed broader aspects of the utility of 3-haloarynes for the synthesis of highly functionalized aromatic compounds. This review will inspire the creativity of organic chemists.
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Conflict of Interest
The author declares no conflict of interest.
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- 1i Hazarika H, Gogoi P. Org. Biomol. Chem. 2021; 19: 8466
- 2a Matsumoto T, Sohma T, Hatazaki S, Suzuki K. Synlett 1993; 843
- 2b Heiss C, Cottet F, Schlosser M. Eur. J. Org. Chem. 2005; 5236
- 2c Akai S, Ikawa T, Takayanagi S, Morikawa Y, Mohri S, Tsubakiyama M, Egi M, Wada Y, Kita Y. Angew. Chem. Int. Ed. 2008; 47: 7673
- 2d Dai M, Wang Z, Danishefsky SJ. Tetrahedron Lett. 2008; 49: 6613
- 2e Ikawa T, Nishiyama T, Shigeta T, Mohri S, Morita S, Takayanagi S, Terauchi Y, Morikawa Y, Takagi A, Ishikawa Y, Fujii S, Kita Y, Akai S. Angew. Chem. Int. Ed. 2011; 50: 5674
- 2f Lv C, Wan C, Liu S, Lan Y, Li Y. Org. Lett. 2018; 20: 1919
- 2g Takikawa H, Nishii A, Takiguchi H, Yagishita H, Tanaka M, Hirano K, Uchiyama M, Ohmori K, Suzuki K. Angew. Chem. Int. Ed. 2020; 59: 12440
- 2h Shi J, Li L, Shan C, Wang J, Chen Z, Gu R, He J, Tan M, Lan Y, Li Y. J. Am. Chem. Soc. 2021; 143: 2178
- 2i Shi J, Li L, Shan C, Chen Z, Dai L, Tan M, Lan Y, Li Y. J. Am. Chem. Soc. 2021; 143: 10530
- 2j Tawatari T, Takasu K, Takikawa H. Chem. Commun. 2021; 57: 11863
- 3a Ikawa T, Takagi A, Kurita Y, Saito K, Azechi K, Egi M, Kakiguchi K, Kita Y, Akai S. Angew. Chem. Int. Ed. 2010; 49: 5563
- 3b Ikawa T, Takagi A, Goto M, Aoyama Y, Ishikawa Y, Itoh Y, Fujii S, Tokiwa H, Akai S. J. Org. Chem. 2013; 78: 2965
- 4a Hamura T, Ibusuki Y, Uekusa H, Matsumoto T, Suzuki K. J. Am. Chem. Soc. 2006; 128: 3534
- 4b Hamura T, Ibusuki Y, Uekusa H, Matsumoto T, Siegel JS, Baldridge KK, Suzuki K. J. Am. Chem. Soc. 2006; 128: 10032
- 4c Tadross PM, Gilmore CD, Bugga P, Virgil SC, Stoltz BM. Org. Lett. 2010; 12: 1224
- 4d Yoshida S, Yano T, Misawa Y, Sugimura Y, Igawa K, Shimizu S, Tomooka K, Hosoya T. J. Am. Chem. Soc. 2015; 137: 14071
- 4e Umezu S, dos Passos Gomes G, Yoshinaga T, Sakae M, Matsumoto K, Iwata T, Alabugin I, Shindo M. Angew. Chem. Int. Ed. 2017; 56: 1298
- 4f Wang J, Zhou Y, Xu X, Liu P, Dong G. J. Am. Chem. Soc. 2020; 142: 3050
- 4g Nakamura Y, Sakata Y, Hosoya T, Yoshida S. Org. Lett. 2020; 22: 8505
- 4h Nakajima H, Hazama Y, Sakata Y, Uchida K, Hosoya T, Yoshida S. Chem. Commun. 2021; 57: 2621
- 4i Scherübl M, Daniliuc CG, Studer A. Angew. Chem. Int. Ed. 2021; 60: 711
- 5a Yoshida S, Uchida K, Igawa K, Tomooka K, Hosoya T. Chem. Commun. 2014; 50: 15059
- 5b Shi J, Qiu D, Wang J, Xu H, Li Y. J. Am. Chem. Soc. 2015; 137: 5670
- 5c Ikawa T, Kaneko H, Masuda S, Ishitsubo E, Tokiwa H, Akai S. Org. Biomol. Chem. 2015; 13: 520
- 5d Qiu D, He J, Yue X, Shi J, Li Y. Org. Lett. 2016; 18: 3130
- 5e Shi J, Xu H, Qiu D, He J, Li Y. J. Am. Chem. Soc. 2017; 139: 623
- 5f Xiong W, Qi C, Cheng R, Zhang H, Wang L, Yan D, Jiang H. Chem. Commun. 2018; 54: 5835
- 5g He J, Qiu D, Li Y. Acc. Chem. Res. 2020; 53: 508
- 6a Medina JM, Mackey JL, Garg NK, Houk KN. J. Am. Chem. Soc. 2014; 136: 15798
- 6b Picazo E, Houk KN, Garg NK. Tetrahedron Lett. 2015; 56: 3511
- 7a Cheong PH.-Y, Paton RS, Bronner SM, Im G.-YJ, Garg NK, Houk KN. J. Am. Chem. Soc. 2010; 132: 1267
- 7b Im G.-YJ, Bronner SM, Goetz AE, Paton RS, Cheong PH.-Y, Houk KN, Garg NK. J. Am. Chem. Soc. 2010; 132: 17933
- 7c Bronner SM, Mackey JL, Houk KN, Garg NK. J. Am. Chem. Soc. 2012; 134: 13966
- 7d Lahm ME, Maynard RK, Turney JM, Weinhold F, Schaefer HF. III. J. Org. Chem. 2020; 85: 9905
- 9 Bronner SM, Goetz AE, Garg NK. J. Am. Chem. Soc. 2011; 133: 3832
- 10a Du C.-JF, Hart H, Ng K.-KD. J. Org. Chem. 1986; 51: 3162
- 10b Du C.-JF, Hart H. J. Org. Chem. 1987; 52: 4311
- 11 Caster KC, Keck CG, Walls RD. J. Org. Chem. 2001; 66: 2932
- 12a Ramírez A, Candler J, Bashore CG, Wirtz MC, Coe JW, Collum DB. J. Am. Chem. Soc. 2004; 126: 14700
- 12b Rao UN, Maguire J, Biehl E. ARKIVOC 2004; (i): 88
- 13a Uchiyama M, Miyoshi T, Kajihara Y, Sakamoto T, Otani Y, Ohwada T, Kondo Y. J. Am. Chem. Soc. 2002; 124: 8514
- 13b Uchiyama M, Kobayashi Y, Furuyama T, Nakamura S, Kajihara Y, Miyoshi T, Sakamoto T, Kondo Y, Morokuma K. J. Am. Chem. Soc. 2008; 130: 472
- 14 Nagashima Y, Takita R, Yoshida K, Hirano K, Uchiyama M. J. Am. Chem. Soc. 2013; 135: 18730
- 15 Wang S.-L, Pan M.-L, Su W.-S, Wu Y.-T. Angew. Chem. Int. Ed. 2017; 56: 14694
- 16 Kim KS, Ha SM, Kim JY, Kim K. J. Org. Chem. 1999; 64: 6483
- 17 Ganta A, Snowden TS. Org. Lett. 2008; 10: 5103
- 18a Yoshida S, Nagai A, Uchida K, Hosoya T. Chem. Lett. 2017; 46: 733
- 18b Kobayashi T, Hosoya T, Yoshida S. J. Org. Chem. 2020; 85: 4448
- 18c Minoshima M, Uchida K, Nakamura Y, Hosoya T, Yoshida S. Org. Lett. 2021; 23: 1868
- 19 Sapountzis I, Lin W, Fischer M, Knochel P. Angew. Chem. Int. Ed. 2004; 43: 4364
- 20a Li Y, Chakrabarty S, Mück-Lichtenfeld C, Studer A. Angew. Chem. Int. Ed. 2016; 55: 802
- 20b Kaldas SJ, Kran E, Mück-Lichtenfeld C, Yudin AK, Studer A. Chem. Eur. J. 2020; 26: 1501
- 20c Kran E, Mück-Lichtenfeld C, Daniliuc CG, Studer A. Chem. Eur. J. 2021; 27: 9281
- 21a Sundalam SK, Nilova A, Seidl TL, Stuart DR. Angew. Chem. Int. Ed. 2016; 55: 8431
- 21b Stuart DR. Synlett 2017; 28: 275
- 21c Wang M, Huang Z. Org. Biomol. Chem. 2016; 14: 10185
- 21d Chen H, Han J, Wang L. Beilstein J. Org. Chem. 2018; 14: 354
- 21e Nilova A, Sibbald PA, Valente EJ, González-Montiel GA, Richardson HC, Brown KS, Cheong PH.-Y, Stuart DR. Chem. Eur. J. 2021; 27: 7168
- 22 Nilova A, Metze B, Stuart DR. Org. Lett. 2021; 23: 4813
- 23 Dong Y, Lipschutz MI, Tilley TD. Org. Lett. 2016; 18: 1530
- 24a Mori I, Kadosaka T, Sakata Y, Misumi S. Bull. Chem. Soc. Jpn. 1971; 44: 1649
- 24b Rogers ME, Averill BA. J. Org. Chem. 1986; 51: 3308
- 24c Chmiel J, Heesemann I, Mix A, Neumann B, Stammler H.-G, Mitzel NW. Eur. J. Org. Chem. 2010; 3897
- 24d Lamm J.-H, Vishnevskiy YV, Ziemann E, Neumann B, Stammler H.-G, Mitzel NW. ChemistryOpen 2018; 7: 111
- 25 Himeshima Y, Sonoda T, Kobayashi H. Chem. Lett. 1983; 1211
- 26a Hall C, Henderson JL, Ernouf G, Greaney MF. Chem. Commun. 2013; 49: 7602
- 26b Peña D, Cobas A, Pérez D, Gutián E. Synthesis 2002; 1454
- 27 Bronner SM, Garg NK. J. Org. Chem. 2009; 74: 8842
- 28 Yoshioka E, Kakigi K, Miyoshi S, Kawasaki Y, Miyabe H. J. Org. Chem. 2020; 85: 13544
- 29 Mesgar M, Daugulis O. Org. Lett. 2016; 18: 3910
- 30 Yoshimura A, Fuchs JM, Middleton KR, Maskaev AV, Rohde GT, Saito A, Postnikov PS, Yusubov MS, Nemykin VN, Zhdankin VV. Chem. Eur. J. 2017; 23: 16738
- 31a Lanzi M, Dherbassy Q, Wencel-Delord J. Angew. Chem. Int. Ed. 2021; 60: 14852
- 31b Lanzi M, Abdine RA. A, De Abreu M, Wencel-Delord J. Org. Lett. 2021; 23: 9047
- 32 Yoshida H, Yoshida R, Takaki K. Angew. Chem. Int. Ed. 2013; 52: 8629
- 33a Matsuzawa T, Uchida K, Yoshida S, Hosoya T. Org. Lett. 2017; 19: 5521
- 33b Yoshida S, Nakajima H, Uchida K, Yano T, Kondo M, Matsushita T, Hosoya T. Chem. Lett. 2017; 46: 77
- 33c Matsuzawa T, Hosoya T, Yoshida S. Org. Lett. 2021; 23: 2347
- 34 O’Sullivan L, Patel KV, Rowley BC, Brownsey DK, Gorobets E, Gelfand BS, Van Humbeck JF, Derksen DJ. J. Org. Chem. 2022; 87: 846
- 35 Xie P, Yang S, Guo Y, Cai Z, Dai B, He L. J. Org. Chem. 2020; 85: 8872
- 36 Huang W.-B, Qiu L.-Q, Ren F.-Y, He L.-N. Chem. Commun. 2021; 57: 9578
- 37 Xu H, He J, Shi J, Tan L, Qiu D, Luo X, Li Y. J. Am. Chem. Soc. 2018; 140: 3555
- 38 Chaitanya NK, Rao YN. S, Choutipalli VS. K, Mainkar PS, Subramanian V, Chandrasekhar S. Chem. Commun. 2022; 58: 3178
- 39 Hendrick CE, Wang Q. J. Org. Chem. 2015; 80: 1059
- 40 Demory E, Devaraj K, Orthaber A, Gates PJ, Pilarski LT. Angew. Chem. Int. Ed. 2015; 54: 11765
- 41 Kou KG. M, Pflueger JJ, Kiho T, Morrill LC, Fisher EL, Clagg K, Lebold TP, Kisunzu JK, Sarpong R. J. Am. Chem. Soc. 2018; 140: 8105
- 42a Dyke AM, Gill DM, Harvey JN, Hester AJ, Lloyd-Jones GC, Muñoz MP, Shepperson IR. Angew. Chem. Int. Ed. 2008; 47: 5067
- 42b Cheng R, Xiong W, Qi C, Wang L, Ren Y, Jiang H. Chem. Commun. 2020; 56: 6495
- 42c Charmant JP. H, Dyke AM, Lloyd-Jones GC. Chem. Commun. 2003; 380
- 42d Korb M, Lang H. Chem. Soc. Rev. 2019; 48: 2829
For some reviews, see:
For examples of distortion model, See:
Corresponding Author
Publication History
Received: 16 March 2022
Accepted after revision: 01 April 2022
Accepted Manuscript online:
01 April 2022
Article published online:
17 May 2022
© 2022. Thieme. All rights reserved
Georg Thieme Verlag KG
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-
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- 4e Umezu S, dos Passos Gomes G, Yoshinaga T, Sakae M, Matsumoto K, Iwata T, Alabugin I, Shindo M. Angew. Chem. Int. Ed. 2017; 56: 1298
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- 5b Shi J, Qiu D, Wang J, Xu H, Li Y. J. Am. Chem. Soc. 2015; 137: 5670
- 5c Ikawa T, Kaneko H, Masuda S, Ishitsubo E, Tokiwa H, Akai S. Org. Biomol. Chem. 2015; 13: 520
- 5d Qiu D, He J, Yue X, Shi J, Li Y. Org. Lett. 2016; 18: 3130
- 5e Shi J, Xu H, Qiu D, He J, Li Y. J. Am. Chem. Soc. 2017; 139: 623
- 5f Xiong W, Qi C, Cheng R, Zhang H, Wang L, Yan D, Jiang H. Chem. Commun. 2018; 54: 5835
- 5g He J, Qiu D, Li Y. Acc. Chem. Res. 2020; 53: 508
- 6a Medina JM, Mackey JL, Garg NK, Houk KN. J. Am. Chem. Soc. 2014; 136: 15798
- 6b Picazo E, Houk KN, Garg NK. Tetrahedron Lett. 2015; 56: 3511
- 7a Cheong PH.-Y, Paton RS, Bronner SM, Im G.-YJ, Garg NK, Houk KN. J. Am. Chem. Soc. 2010; 132: 1267
- 7b Im G.-YJ, Bronner SM, Goetz AE, Paton RS, Cheong PH.-Y, Houk KN, Garg NK. J. Am. Chem. Soc. 2010; 132: 17933
- 7c Bronner SM, Mackey JL, Houk KN, Garg NK. J. Am. Chem. Soc. 2012; 134: 13966
- 7d Lahm ME, Maynard RK, Turney JM, Weinhold F, Schaefer HF. III. J. Org. Chem. 2020; 85: 9905
- 9 Bronner SM, Goetz AE, Garg NK. J. Am. Chem. Soc. 2011; 133: 3832
- 10a Du C.-JF, Hart H, Ng K.-KD. J. Org. Chem. 1986; 51: 3162
- 10b Du C.-JF, Hart H. J. Org. Chem. 1987; 52: 4311
- 11 Caster KC, Keck CG, Walls RD. J. Org. Chem. 2001; 66: 2932
- 12a Ramírez A, Candler J, Bashore CG, Wirtz MC, Coe JW, Collum DB. J. Am. Chem. Soc. 2004; 126: 14700
- 12b Rao UN, Maguire J, Biehl E. ARKIVOC 2004; (i): 88
- 13a Uchiyama M, Miyoshi T, Kajihara Y, Sakamoto T, Otani Y, Ohwada T, Kondo Y. J. Am. Chem. Soc. 2002; 124: 8514
- 13b Uchiyama M, Kobayashi Y, Furuyama T, Nakamura S, Kajihara Y, Miyoshi T, Sakamoto T, Kondo Y, Morokuma K. J. Am. Chem. Soc. 2008; 130: 472
- 14 Nagashima Y, Takita R, Yoshida K, Hirano K, Uchiyama M. J. Am. Chem. Soc. 2013; 135: 18730
- 15 Wang S.-L, Pan M.-L, Su W.-S, Wu Y.-T. Angew. Chem. Int. Ed. 2017; 56: 14694
- 16 Kim KS, Ha SM, Kim JY, Kim K. J. Org. Chem. 1999; 64: 6483
- 17 Ganta A, Snowden TS. Org. Lett. 2008; 10: 5103
- 18a Yoshida S, Nagai A, Uchida K, Hosoya T. Chem. Lett. 2017; 46: 733
- 18b Kobayashi T, Hosoya T, Yoshida S. J. Org. Chem. 2020; 85: 4448
- 18c Minoshima M, Uchida K, Nakamura Y, Hosoya T, Yoshida S. Org. Lett. 2021; 23: 1868
- 19 Sapountzis I, Lin W, Fischer M, Knochel P. Angew. Chem. Int. Ed. 2004; 43: 4364
- 20a Li Y, Chakrabarty S, Mück-Lichtenfeld C, Studer A. Angew. Chem. Int. Ed. 2016; 55: 802
- 20b Kaldas SJ, Kran E, Mück-Lichtenfeld C, Yudin AK, Studer A. Chem. Eur. J. 2020; 26: 1501
- 20c Kran E, Mück-Lichtenfeld C, Daniliuc CG, Studer A. Chem. Eur. J. 2021; 27: 9281
- 21a Sundalam SK, Nilova A, Seidl TL, Stuart DR. Angew. Chem. Int. Ed. 2016; 55: 8431
- 21b Stuart DR. Synlett 2017; 28: 275
- 21c Wang M, Huang Z. Org. Biomol. Chem. 2016; 14: 10185
- 21d Chen H, Han J, Wang L. Beilstein J. Org. Chem. 2018; 14: 354
- 21e Nilova A, Sibbald PA, Valente EJ, González-Montiel GA, Richardson HC, Brown KS, Cheong PH.-Y, Stuart DR. Chem. Eur. J. 2021; 27: 7168
- 22 Nilova A, Metze B, Stuart DR. Org. Lett. 2021; 23: 4813
- 23 Dong Y, Lipschutz MI, Tilley TD. Org. Lett. 2016; 18: 1530
- 24a Mori I, Kadosaka T, Sakata Y, Misumi S. Bull. Chem. Soc. Jpn. 1971; 44: 1649
- 24b Rogers ME, Averill BA. J. Org. Chem. 1986; 51: 3308
- 24c Chmiel J, Heesemann I, Mix A, Neumann B, Stammler H.-G, Mitzel NW. Eur. J. Org. Chem. 2010; 3897
- 24d Lamm J.-H, Vishnevskiy YV, Ziemann E, Neumann B, Stammler H.-G, Mitzel NW. ChemistryOpen 2018; 7: 111
- 25 Himeshima Y, Sonoda T, Kobayashi H. Chem. Lett. 1983; 1211
- 26a Hall C, Henderson JL, Ernouf G, Greaney MF. Chem. Commun. 2013; 49: 7602
- 26b Peña D, Cobas A, Pérez D, Gutián E. Synthesis 2002; 1454
- 27 Bronner SM, Garg NK. J. Org. Chem. 2009; 74: 8842
- 28 Yoshioka E, Kakigi K, Miyoshi S, Kawasaki Y, Miyabe H. J. Org. Chem. 2020; 85: 13544
- 29 Mesgar M, Daugulis O. Org. Lett. 2016; 18: 3910
- 30 Yoshimura A, Fuchs JM, Middleton KR, Maskaev AV, Rohde GT, Saito A, Postnikov PS, Yusubov MS, Nemykin VN, Zhdankin VV. Chem. Eur. J. 2017; 23: 16738
- 31a Lanzi M, Dherbassy Q, Wencel-Delord J. Angew. Chem. Int. Ed. 2021; 60: 14852
- 31b Lanzi M, Abdine RA. A, De Abreu M, Wencel-Delord J. Org. Lett. 2021; 23: 9047
- 32 Yoshida H, Yoshida R, Takaki K. Angew. Chem. Int. Ed. 2013; 52: 8629
- 33a Matsuzawa T, Uchida K, Yoshida S, Hosoya T. Org. Lett. 2017; 19: 5521
- 33b Yoshida S, Nakajima H, Uchida K, Yano T, Kondo M, Matsushita T, Hosoya T. Chem. Lett. 2017; 46: 77
- 33c Matsuzawa T, Hosoya T, Yoshida S. Org. Lett. 2021; 23: 2347
- 34 O’Sullivan L, Patel KV, Rowley BC, Brownsey DK, Gorobets E, Gelfand BS, Van Humbeck JF, Derksen DJ. J. Org. Chem. 2022; 87: 846
- 35 Xie P, Yang S, Guo Y, Cai Z, Dai B, He L. J. Org. Chem. 2020; 85: 8872
- 36 Huang W.-B, Qiu L.-Q, Ren F.-Y, He L.-N. Chem. Commun. 2021; 57: 9578
- 37 Xu H, He J, Shi J, Tan L, Qiu D, Luo X, Li Y. J. Am. Chem. Soc. 2018; 140: 3555
- 38 Chaitanya NK, Rao YN. S, Choutipalli VS. K, Mainkar PS, Subramanian V, Chandrasekhar S. Chem. Commun. 2022; 58: 3178
- 39 Hendrick CE, Wang Q. J. Org. Chem. 2015; 80: 1059
- 40 Demory E, Devaraj K, Orthaber A, Gates PJ, Pilarski LT. Angew. Chem. Int. Ed. 2015; 54: 11765
- 41 Kou KG. M, Pflueger JJ, Kiho T, Morrill LC, Fisher EL, Clagg K, Lebold TP, Kisunzu JK, Sarpong R. J. Am. Chem. Soc. 2018; 140: 8105
- 42a Dyke AM, Gill DM, Harvey JN, Hester AJ, Lloyd-Jones GC, Muñoz MP, Shepperson IR. Angew. Chem. Int. Ed. 2008; 47: 5067
- 42b Cheng R, Xiong W, Qi C, Wang L, Ren Y, Jiang H. Chem. Commun. 2020; 56: 6495
- 42c Charmant JP. H, Dyke AM, Lloyd-Jones GC. Chem. Commun. 2003; 380
- 42d Korb M, Lang H. Chem. Soc. Rev. 2019; 48: 2829
For some reviews, see:
For examples of distortion model, See:
