Skip to main content
NCBI home page
ACS AuthorChoice logoLink to ACS AuthorChoice
. 2025 Jan 22;27(4):1078–1083. doi: 10.1021/acs.orglett.5c00050

Chiral Bis-8-Aryl-isoquinoline Bis-alkylamine Iron Catalysts for Asymmetric Oxidation Reactions

Tomer Mintz †, Lei Liu ‡, Doron Pappo †,*
PMCID: PMC11791880  PMID: 39841035

Abstract

graphic file with name ol5c00050_0007.jpg

A novel class of bis-8-aryl-isoquinoline (AriQ) bis-alkylamine iron complexes, FeII(AriQ2dp)(OTf)2 and FeII(AriQ2mc)(OTf)2 (dp = dipyrrolidinyl or mc = N,N′-dimethylcyclohexyl-diamine), for asymmetric oxidation reactions is reported. The scalable divergent synthesis of 8-aryl-3-formylisoquinolines (8), the key intermediates in preparing these ligands, enables precise structural and electronic tuning around the metal center. The enantioselective epoxidation and hydroxy carbonylation of conjugated alkenes, mediated by the FeII(3,5-di-CF3iQ2dp) catalyst with H2O2 as the oxidant, demonstrates the potential of these redox FeII[N4] catalysts in inducing face selection in oxygen transfer transformations.

Chiral iron and manganese complexes with well-defined first coordination sphere tetradentate ligands (N4) are privileged catalysts for various oxidation reactions.1 In recent years, these highly efficient catalysts were applied in water oxidation,2 oxidative coupling,3 stereoselective hydroxylation of strong and remote C–H bonds,4 and the enantioselective epoxidation and cis-dihydroxylation of both electron-deficient and electron-rich olefins.5 To further enhance oxidation reactions for preparing optically pure compounds from simple achiral substrates, there is an emerging need to develop innovative N4-type ligands that impart distinctive structural and electronic properties to the metal.

Que,6 Ménage,7 White,8 Costas,5a and others demonstrated that Fe and Mn complexes with aminopyridine ligands (Py2N2, e.g., 1a–1c; Figure 1A-i) serve as highly effective catalysts in oxygen transfer reactions.1d,6b The Py2N2 ligands are arranged around the metal in a cis-α topological configuration, with the two pyridine units positioned trans to each other, forming complexes that are resilient to oxidative degradation and demetalation.9 The M[Py2N2] complexes (M = Fe or Mn) facilitate the heterolytic cleavage of H2O2, resulting in the formation of reactive M[N2Py2][S]=O species (S = solvent, acid additive, or substrate; Figure 1A-ii) that transfer oxygen atom(s) or accept a hydrogen atom from substrates that are positioned within the active site, near the pyridine rings.1d,10 Therefore, the primary approach to regulating the enantioselectivity in these oxidation reactions involves structural modification of the pyridine moieties. A systematic study by the Costas group demonstrated that introducing substituents at the γ-pyridine position significantly alters the electronic configuration of the catalysts, thereby impacting their reactivity and selectivity.11 On the other hand, the α-pyridine site that should be most suitable to project the chirality to the incoming substrate is limited to H and Me substituents, as larger substituents tend to destabilize the complex.12 As a result, the chiral environment surrounding the metal center is typically regulated from the β-pyridine site.8a,13 From the perspective of catalyst design, this presents a constraint given that the orientation of the substituents (e.g., aryl groups) at the β position is directed away from the metal center, thereby rendering the catalytic site relatively exposed (Figure 1B).

Figure 1.

Figure 1

Open in a new tab

Selected examples of chiral tetradentate M[Py2N2]2+ catalysts and general mechanism of the asymmetric oxidation reaction catalyzed by them.

An additional developing approach to enhance the selectivity of redox M[N4] catalysts involves replacing the pyridine unit with alternative heterocycles. Utilizing this methodology, tetradentate iron and manganese complexes incorporating N-methylbenzimidazole,14 quinoline,15 and isoquinoline (iQ)16 moieties have been synthesized and effectively employed in a variety of oxidation reactions. The bis-isoquinoline bis-alkylamine iron complex [Fe(iQ2N2)] (Figure 1B; Ar = H) displayed similar reactivity and selectivity to the [Fe(Py2N2)] complex in olefin epoxidation and C–H hydroxylation reactions. These promising results inspired us to examine the idea of introducing a bulky group at the remote C-8 position of the isoquinoline units instead of the β-pyridine sites in the Py2N2 ligands. We hypothesized that the 8-isoquinoline position could be strategically employed to modulate the electronic characteristics of the metal while simultaneously generating a confined metal active site deeply buried within a highly demanding chiral environment (Figure 1B). To make this hypothesis possible, the tetradentate AriQ2N2 [AriQ = 8-arylisoquinoline and N2 = dp (dipyrrolidinyl) or mc (N,N′-dimethylcyclohexyl-diamine] ligands along with their corresponding metal complexes had to be prepared (Figure 1B).

Synthetically, 8-OTf-3-(diethoxymethyl)-isoquinoline product 6, which can be diversified by Suzuki–Miyaura coupling to different 8-aryl-3-formyl-isoquinoline products 8, was targeted (Figure 1B). Preparing the AriQ2dp and AriQ2mc ligands from compound 8 and chiral diamines allows further library expansion for structure–activity–selectivity relationship studies. However, a database search revealed no established synthetic pathway existed to prepare 8-substituted-3-formyl-isoquinolines 8. As a result, a new synthesis had to be developed.

Here within, this section, we describe the synthesis and catalytic activity of a new class of tetradentate Fe(AriQ2dp)(OTf)2 and Fe(AriQ2mc)(OTf)2 complexes with tunable electronic and steric properties. The potential of these chiral Earth-abundant metal complexes to promote enantioselective oxygen-transfer reactions is demonstrated for the enantioselective epoxidation and hydroxy carbonylation of conjugated alkenes.

The study began by developing a reliable and scalable synthesis of 8-OTf-3-formyl-isoquinoline 6 starting from 2-bromo-6-benzyloxybenzaldehyde 2 (Scheme 1). We employed the Larock isoquinoline synthesis, which enables the conversion of 2-ethynylbenzaldehydes into isoquinolines in the presence of an amine source, as the key step in our design.16a,17 This copper-catalyzed transformation has mainly been utilized for 2-ethynylbenzaldehydes with remote substitutions at the C-4 and C-5 positions. Applying the method for substrates with neighboring C-6 substituents,18 such as compound 4 (Scheme 1), is relatively uncommon.

Scheme 1. Synthesis of 8-Triflate-3-diethoxymethyl-isoquinoline 6.

Scheme 1

Open in a new tab

See the Supporting Information for the exact conditions.

Therefore, to synthesize compound 4, Sonogashira coupling between 2-benzyloxy-6-bromobenzaldehyde (2a), which was prepared by benzylation of 2-hydroxybenzaldehyde, and 3,3-diethoxyprop-1-yne (3) [1.3 equiv, Pd(PPh3)Cl2 (5 mol %), triethanolamine (TEA), 70 °C, 4 h; Scheme 1] was carried out. This reaction afforded 6-benzyloxy-2-ethynylbenzaldehyde 4 in moderate yields ranging between 50 and 78%. To address the inconsistency of the process, a bromide-to-iodine atom-exchange step by aromatic Finkelstein substitution (NaI, CuI, 1,3-diaminopropane, dioxane, 89% yield)19 was introduced before the cross-coupling. This tactic turned out to be successful, and the Sonogashira coupling of 2-(benzyloxy)-6-iodobenzaldehyde (2b) with alkyne 3 proceeded under milder reaction conditions [Pd(PPh3)Cl2 (2 mol %), TEA, 50 °C, 1 h], yielding product 4 with an improved 85% yield. The annulation of 2-ethynylbenzaldehyde 4 was best performed when we first ensured the formation of the N-tert-butyl-phenylmethanimine intermediate [t-BuNH2, 1,2-dichloroethane (DCE)] before proceeding to the annulation step [CuI, N,N-dimethylformamide (DMF)]. Under these conditions, the desired product 8-benzyloxy-3-(diethoxymethyl)-isoquinoline 5 was isolated in 75% yield. Selective hydrogenolysis of the benzyl-protecting group (H2, Pd/C, 88% yield) and triflation of the 8-OH group (Tf2O, pyridine, 94% yield) afforded the key 8-triflate-3-diethoxymethyl-isoquinoline 6 in excellent yields. This robust short synthesis was performed on a practical scale, delivering up to 9 g of compound 6 in a single campaign.

Isoquinoline 6, which is a stable solid that can be safely stored for a long period in a refrigerator, is an excellent partner in Suzuki–Miyaura cross-coupling reactions. Its reaction with different aryl boronic acids [1.2 equiv, Pd(PPh3)4 (5 mol %), ethanol, 90 °C, 4 h] affords, after acetal hydrolysis workup (aqueous HCl, dioxane), the target 8-aryl-3-formylisoquinolines 8a–8d and 8f–8h in good to excellent yields (Scheme 2A). Alternatively, isoquinoline 6 can be converted to 8-Bpin-3-(diethoxymethyl)-isoquinoline 7 through the Miyaura borylation method [bis(pinacolato)diboron (B2pin2, 3 equiv), Pd(dppf)2Cl2 (3 mol %), KOAc (3 equiv), 1,4-dioxane, 90 °C, 3 h, 84%]20 before subjected to coupling with aryl halides. For example, the coupling of compound 7 with 5-bromo-1,3-(bis-trimethylsilane)phenylene and 9-bromoanthracene afforded after acetal hydrolysis isoquinolines 8e and 8i in 58 and 74% yields, respectively. The 8-aryl-3-formyl-isoquinoline products 8a–8i highlight the versatility of this synthesis, allowing for the introduction of aryl groups with customizable electronic and steric characteristics.

Scheme 2. Synthesis of 8-Aryl-3-formylisoquinolines 8a–8i and the AriQ2mc and AriQ2dp Ligands.

Scheme 2

Open in a new tab

See the Supporting Information for the exact conditions.

Next, the tetradentate AriQ2mc and AriQ2dp ligands were prepared from 8-aryl-3-formylisoquinolines 8 and either (1S,2S)-cyclohexane-1,2-diamine or (2S,2′S)-2,2′-bipyrrolidine by employing established methodologies (Scheme 2B). Mixing these strong chelators with freshly prepared Fe(OTf)2(CH3CN)2 in tetrahydrofuran (THF) led to the formation of orange precipitates of FeII(AriQ2mc)(OTf)2 or FeII(AriQ2dp)(OTf)2 complexes (Figure 2). The structure of the novel complexes was determined by 1H nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS) analysis and confirmed by securing the crystal structures of Fe(3,5-di-CF3iQ2dp) and Fe(2,4,6-tri-iPriQ2dp) complexes (Figure 2).

Figure 2.

Figure 2

Open in a new tab

Fe(AriQ2mc)(OTf)2 and Fe(AriQ2dp)(OTf)2 complexes and the X-ray structure of Fe(2,4,6-tri-iPriQ2dp) (CCDC number 2361551), Fe(3,5-di-CF3iQ2dp) (CCDC number 2390794), and Fe(2,6-di-CF3pdp) (1a).4jaThe hydrogen atoms and outer sphere triflate anions were omitted for clarity. bThe hydrogen atoms and outer sphere SbF6 anions were removed for clarity.

To evaluate the reactivity and selectivity of the new complexes, we examined their catalytic activity for the enantioselective epoxidation of alkyl cinnamates (10a–10i; Table 1 and Scheme 3A,B). This transformation poses significant challenges for Fe(N4) complexes. For example, catalysts 1b and 1c (Figure 1A) facilitated the epoxidation of electron-deficient olefin 10a to produce methyl (2R,3S)-3-phenyloxirane-2-carboxylate 11a with a high degree of enantioselectivity yet with moderate yields (entries 1 and 2 in Table 1).21 First, we implemented the epoxidation conditions reported by Costas for catalyst 1b.5d,10b,11,16b,21 Under these conditions, the Fe(3,5-di-CF3iQ2dp) complex [2 mol %, 2-ethyl-hexanoic acid (EHA, 5 mol %) H2O2 (1.5 equiv), acetonitrile, −40 °C] mediated the formation of the desired epoxide 11a in a 20% conversion and with 73% enantiomeric excess (ee) (see Table S1 of the Supporting Information). After a short optimization phase, we identified that the use of benzoic acid (50 mol %) as the additive in a mixture of acetonitrile and 2,2,2-trifluoroethanol (TFE) at −40 °C leads to a significant improvement in the results, affording epoxide 11a in 99% yield and 95% ee (entry 3 in Table 1).

Table 1. Asymmetric Epoxidation of Methyl Cinnamate 10aa.

graphic file with name ol5c00050_0006.jpg

entry catalyst yield (%)c ee (%)d
1e 1b 66 91
2f 1c 48 95
3 Fe(3,5-diCF3iQ2dp) 99 (98)g 95
4 Fe(iQ2dp) 37 57
5 Fe(3,5-diCF3iQ2mc) 32 55
6 Fe(3,5-di-t-BuiQ2dp) 85 69
7 Fe(3,4,5-tri-FiQ2dp) 50 60
8 Fe(2,4,6-tri-iPriQ2dp) 0  
9 Fe(2,4,6-tri-iPriQ2mc) 0  
Open in a new tab
a

Reaction conditions: H2O2 (1.5 equiv) in acetonitrile (0.5 M) is added over 30 min to a TFE (0.25 M) solution of alkyl cinnamate (1 equiv), catalyst (2 mol %), and benzoic acid (0.5 equiv) at −40 °C.

b

The absolute configuration of the product was assigned as (−)-(2R,3S)-11.

c

High-performance liquid chromatography (HPLC) yield using chlorobenzene as internal standard.

d

Enantiomeric excess, determined by HPLC with a chiral stationary phase.

e

From ref (11).

f

From ref (21).

g

Isolated yield.

Scheme 3. Asymmetric Oxidation of Alkenes.

Scheme 3

Open in a new tab

The cone angle and cone of possible approach trajectories22 of the latter complexes and the White catalyst 1a (Figure 2) suggest that the C-8 substitution has a substantial impact on the environment surrounding the iron and, therefore, should lead to a notable effect on its catalytic performance. Indeed, the Fe(iQ2dp) complex, which lacks the C-8 aryl group, yielded epoxide 11a in 37% yield and 57% ee (entry 4), while Fe(3,5-diCF3iQ2mc), Fe(3,5-di-t-BuiQ2dp) and Fe(3,4,5-tri-FiQ2dp) complexes exhibited diminished effectiveness (entries 5–7). The inferior performance of Fe(3,5-di-t-BuiQ2dp) compared to Fe(3,5-di-CF3iQ2dp) (entries 3 and 6) may also be attributed to differences in the ligand electronic properties. The highly sterically demanding Fe(2,4,6-tri-iPriQ2dp) and Fe(2,4,6-tri-iPriQ2mc) complexes left the substrates untouched (entries 8 and 9).

The epoxidation of electron-deficient olefins 10b–10f using the Fe(3,5-di-CF3iQ2dp) complex further underscores the sensitivity of the reaction to steric changes (compare compounds 11a, 11b, and 11c as well as conjugated ketones 11d and 11e to chalcone 11f; Scheme 3A). Methyl cinnamates with a 4-methyl or 4-bromide substituent afforded the corresponding epoxides 11g (95% yield, 93% ee) and 11h (47% yield, 76% ee; Scheme 3A). On the other hand, methyl 4-methoxycinnamate underwent hydroxy carboxylation with the acid additive, affording monoprotected diols 12ia (benzoic acid, 46%, 37.5% ee), 12ib (pivalic acid, 62%, 82% ee), and 12ic [(S)-ibuprofen, 46%, 81% diastereomeric excess (de); Scheme 3B].23 Previous studies have proposed the involvement of a Fe(V)[N4][OC(O)R]=O intermediate, which facilitates the transfer of hydroxyl and carboxylate groups to olefin within the active site.24 The hydroxy lactonization of acid (E)-5-phenylpent-4-enoic acid (10j) by Fe(2,4,6-tri-iPriQ2dp) or Fe(3,4,5-tri-FiQ2dp) catalysts to afford lactone 12j (26% yield and 78% ee or 95% yield and 50% ee, respectively) further supports the role of such a chiral intermediate (Scheme 3C).

In conclusion, a new class of FeII(AriQ2dp)(OTf)2 and FeII(AriQ2mc)(OTf)2 catalysts for asymmetric oxidation reactions was designed and prepared. The divergent synthetic route to 8-aryl-3-formyl-isoquinolines offers an opportunity to explore metal catalysts characterized by a diverse range of structural and electronic attributes. The potential of these tetradentate iron catalysts to promote oxidation reactions is demonstrated for the highly enantioselective epoxidation and hydroxy carbonylation of conjugated alkenes. We intend to further explore the potential of these ligands in Fe- and Mn-catalyzed asymmetric oxidation and oxidative coupling reactions.

Acknowledgments

This research was supported by the Israel Science Foundation (ISF)–National Natural Science Foundation of China (NSFC) Joint Research Program (Grant 3507/21).

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.5c00050.

  • Experimental procedures, characterization data, and NMR spectra (PDF)

The authors declare no competing financial interest.

Supplementary Material

ol5c00050_si_001.pdf (8.3MB, pdf)

References

  1. a Nam W. High-Valent Iron(IV)–Oxo Complexes of Heme and Non-Heme Ligands in Oxygenation Reactions. Acc. Chem. Res. 2007, 40 (7), 522–531. 10.1021/ar700027f. [DOI] [PubMed] [Google Scholar]; b Company A.; Gómez L.; Güell M.; Ribas X.; Luis J. M.; Que L.; Costas M. Alkane Hydroxylation by a Nonheme Iron Catalyst that Challenges the Heme Paradigm for Oxygenase Action. J. Am. Chem. Soc. 2007, 129 (51), 15766–15767. 10.1021/ja077761n. [DOI] [PubMed] [Google Scholar]; c Doiuchi D.; Uchida T. Recent Strategies in Non-Heme-Type Metal Complex-Catalyzed Site-, Chemo-, and Enantioselective C–H Oxygenations. Synthesis 2021, 53 (18), 3235–3246. 10.1055/a-1525-4335. [DOI] [Google Scholar]; d Olivo G.; Cussó O.; Costas M. Biologically Inspired C–H and C = C Oxidations with Hydrogen Peroxide Catalyzed by Iron Coordination Complexes. Chem. - Asian J. 2016, 11 (22), 3148–3158. 10.1002/asia.201601170. [DOI] [PubMed] [Google Scholar]
  2. a D’Agostini S.; Kottrup K. G.; Casadevall C.; Gamba I.; Dantignana V.; Bucci A.; Costas M.; Lloret-Fillol J.; Hetterscheid D. G. H. Electrocatalytic Water Oxidation with α-[Fe(mcp)(OTf)2] and Analogues. ACS Catal. 2021, 11 (5), 2583–2595. 10.1021/acscatal.0c05439. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Fillol J. L.; Codolà Z.; Garcia-Bosch I.; Gómez L.; Pla J. J.; Costas M. Efficient water oxidation catalysts based on readily available iron coordination complexes. Nature Chem. 2011, 3 (10), 807–813. 10.1038/nchem.1140. [DOI] [PubMed] [Google Scholar]
  3. Vershinin V.; Feruz L.-n.; Forkosh H.; Kertzman L.; Libman A.; Burés J.; Pappo D. Aerobic Oxidative Coupling of 2-Aminonaphthalenes by Homogenous Nonheme Iron Catalysts. ACS Catal. 2024, 14 (11), 8261–8269. 10.1021/acscatal.4c01839. [DOI] [Google Scholar]
  4. a Call A.; Capocasa G.; Palone A.; Vicens L.; Aparicio E.; Choukairi Afailal N.; Siakavaras N.; López Saló M. E.; Bietti M.; Costas M. Highly Enantioselective Catalytic Lactonization at Nonactivated Primary and Secondary γ-C–H Bonds. J. Am. Chem. Soc. 2023, 145 (32), 18094–18103. 10.1021/jacs.3c06231. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Call A.; Cianfanelli M.; Besalú-Sala P.; Olivo G.; Palone A.; Vicens L.; Ribas X.; Luis J. M.; Bietti M.; Costas M. Carboxylic Acid Directed γ-Lactonization of Unactivated Primary C–H Bonds Catalyzed by Mn Complexes: Application to Stereoselective Natural Product Diversification. J. Am. Chem. Soc. 2022, 144 (42), 19542–19558. 10.1021/jacs.2c08620. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Costas M. Site and Enantioselective Aliphatic C–H Oxidation with Bioinspired Chiral Complexes. Chem. Rec. 2021, 21 (12), 4000–4014. 10.1002/tcr.202100227. [DOI] [PubMed] [Google Scholar]; d Cianfanelli M.; Olivo G.; Milan M.; Klein Gebbink R. J. M.; Ribas X.; Bietti M.; Costas M. Enantioselective C–H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids. J. Am. Chem. Soc. 2020, 142 (3), 1584–1593. 10.1021/jacs.9b12239. [DOI] [PubMed] [Google Scholar]; e Milan M.; Salamone M.; Costas M.; Bietti M. The Quest for Selectivity in Hydrogen Atom Transfer Based Aliphatic C–H Bond Oxygenation. Acc. Chem. Res. 2018, 51 (9), 1984–1995. 10.1021/acs.accounts.8b00231. [DOI] [PubMed] [Google Scholar]; f White M. C.; Zhao J. Aliphatic C–H Oxidations for Late-Stage Functionalization. J. Am. Chem. Soc. 2018, 140 (43), 13988–14009. 10.1021/jacs.8b05195. [DOI] [PMC free article] [PubMed] [Google Scholar]; g Milan M.; Bietti M.; Costas M. Enantioselective aliphatic C–H bond oxidation catalyzed by bioinspired complexes. Chem. Commun. 2018, 54 (69), 9559–9570. 10.1039/C8CC03165G. [DOI] [PubMed] [Google Scholar]; h Ottenbacher R. V.; Talsi E. P.; Rybalova T. V.; Bryliakov K. P. Enantioselective Benzylic Hydroxylation of Arylalkanes with H2O2 in Fluorinated Alcohols in the Presence of Chiral Mn Aminopyridine Complexes. ChemCatChem. 2018, 10 (22), 5323–5330. 10.1002/cctc.201801476. [DOI] [Google Scholar]; i Qiu B.; Xu D.; Sun Q.; Miao C.; Lee Y.-M.; Li X.-X.; Nam W.; Sun W. Highly Enantioselective Oxidation of Spirocyclic Hydrocarbons by Bioinspired Manganese Catalysts and Hydrogen Peroxide. ACS Catal. 2018, 8 (3), 2479–2487. 10.1021/acscatal.7b03601. [DOI] [Google Scholar]; j Gormisky P. E.; White M. C. Catalyst-Controlled Aliphatic C–H Oxidations with a Predictive Model for Site-Selectivity. J. Am. Chem. Soc. 2013, 135, 14052–14055. 10.1021/ja407388y. [DOI] [PubMed] [Google Scholar]; k Bigi M. A.; Reed S. A.; White M. C. Directed Metal (Oxo) Aliphatic C–H Hydroxylations: Overriding Substrate Bias. J. Am. Chem. Soc. 2012, 134, 9721–9726. 10.1021/ja301685r. [DOI] [PubMed] [Google Scholar]; l White M. C. Adding aliphatic C–H bond oxidations to synthesis. Science 2012, 335 (6700), 807–809. 10.1126/science.1207661. [DOI] [PubMed] [Google Scholar]
  5. a Vicens L.; Olivo G.; Costas M. Rational Design of Bioinspired Catalysts for Selective Oxidations. ACS Catal. 2020, 10 (15), 8611–8631. 10.1021/acscatal.0c02073. [DOI] [Google Scholar]; b Wei J.; Cao B.; Tse C.-W.; Chang X.-Y.; Zhou C.-Y.; Che C.-M. Chiral cis-iron(II) complexes with metal- and ligand-centered chirality for highly regio- and enantioselective alkylation of N-heteroaromatics. Chem. Sci. 2020, 11 (3), 684–693. 10.1039/C9SC04858H. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Cussó O.; Garcia-Bosch I.; Font D.; Ribas X.; Lloret-Fillol J.; Costas M. Highly Stereoselective Epoxidation with H2O2 Catalyzed by Electron-Rich Aminopyridine Manganese Catalysts. Org. Lett. 2013, 15 (24), 6158–6161. 10.1021/ol403018x. [DOI] [PubMed] [Google Scholar]; d Nishikawa Y.; Yamamoto H. Iron-Catalyzed Asymmetric Epoxidation of β,β-Disubstituted Enones. J. Am. Chem. Soc. 2011, 133 (22), 8432–8435. 10.1021/ja201873d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. a Chen K.; Costas M.; Kim J.; Tipton A. K.; Que L. Olefin cis-dihydroxylation versus epoxidation by non-heme iron catalysts: Two faces of an FeIII– OOH coin. J. Am. Chem. Soc. 2002, 124 (12), 3026–3035. 10.1021/ja0120025. [DOI] [PubMed] [Google Scholar]; b Chen K.; Que L. Stereospecific Alkane Hydroxylation by Non-Heme Iron Catalysts: Mechanistic Evidence for an FeVO Active Species. J. Am. Chem. Soc. 2001, 123 (26), 6327–6337. 10.1021/ja010310x. [DOI] [PubMed] [Google Scholar]
  7. Mekmouche Y.; Ménage S.; Toia-Duboc C.; Fontecave M.; Galey J. B.; Lebrun C.; Pécaut J. H2O2-Dependent Fe-Catalyzed Oxidations: Control of the Active Species. Angew. Chem., Int. Ed. 2001, 40 (5), 949–952. . [DOI] [PubMed] [Google Scholar]
  8. a Zhao J.; Nanjo T.; de Lucca E. C.; White M. C. Chemoselective methylene oxidation in aromatic molecules. Nature chem 2019, 11 (3), 213–221. 10.1038/s41557-018-0175-8. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Gormisky P. E.; White M. C. Catalyst-Controlled Aliphatic C–H Oxidations with a Predictive Model for Site-Selectivity. J. Am. Chem. Soc. 2013, 135 (38), 14052–14055. 10.1021/ja407388y. [DOI] [PubMed] [Google Scholar]
  9. England J.; Davies C. R.; Banaru M.; White A. J. P.; Britovsek G. J. P. Catalyst Stability Determines the Catalytic Activity of Non-Heme Iron Catalysts in the Oxidation of Alkanes. Adv. Synth. Catal. 2008, 350 (6), 883–897. 10.1002/adsc.200700462. [DOI] [Google Scholar]
  10. a Oloo W. N.; Que L. Jr. Bioinspired Nonheme Iron Catalysts for C–H and C=C Bond Oxidation: Insights into the Nature of the Metal-Based Oxidants. Acc. Chem. Res. 2015, 48 (9), 2612–2621. 10.1021/acs.accounts.5b00053. [DOI] [PubMed] [Google Scholar]; b Lyakin O. Y.; Ottenbacher R. V.; Bryliakov K. P.; Talsi E. P. Asymmetric Epoxidations with H2O2 on Fe and Mn Aminopyridine Catalysts: Probing the Nature of Active Species by Combined Electron Paramagnetic Resonance and Enantioselectivity Study. ACS Catal. 2012, 2 (6), 1196–1202. 10.1021/cs300205n. [DOI] [Google Scholar]
  11. Cussó O.; Garcia-Bosch I.; Ribas X.; Lloret-Fillol J.; Costas M. Asymmetric Epoxidation with H2O2 by Manipulating the Electronic Properties of Non-heme Iron Catalysts. J. Am. Chem. Soc. 2013, 135 (39), 14871–14878. 10.1021/ja4078446. [DOI] [PubMed] [Google Scholar]
  12. a Chen K.; Costas M.; Que L. Jr. Spin state tuning of non-heme iron-catalyzed hydrocarbon oxidations: Participation of FeIII–OOH and FeV=O intermediates. J. Chem. Soc., Dalton Trans. 2002, (5), 672–679. 10.1039/b108629d. [DOI] [Google Scholar]; b Zang Y.; Kim J.; Dong Y.; Wilkinson E. C.; Appelman E. H.; Que L. Models for nonheme iron intermediates: Structural basis for tuning the spin states of Fe (TPA) complexes. J. Am. Chem. Soc. 1997, 119 (18), 4197–4205. 10.1021/ja9638521. [DOI] [Google Scholar]
  13. a Chambers R. K.; Zhao J.; Delaney C. P.; White M. C. Chemoselective tertiary C– H hydroxylation for late-stage functionalization with Mn (PDP)/chloroacetic acid catalysis. Adv. Syn. Catal. 2020, 362 (2), 417–423. 10.1002/adsc.201901472. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Font D.; Canta M.; Milan M.; Cussó O.; Ribas X.; Klein Gebbink R. J.; Costas M. Readily accessible bulky iron catalysts exhibiting site selectivity in the oxidation of steroidal substrates. Angew. Chem., Int. Ed. 2016, 55 (19), 5776–5779. 10.1002/anie.201600785. [DOI] [PubMed] [Google Scholar]
  14. Wang X.; Miao C.; Wang S.; Xia C.; Sun W. Bioinspired Manganese and Iron Complexes with Tetradentate N Ligands for the Asymmetric Epoxidation of Olefins. ChemCatChem. 2013, 5 (8), 2489–2494. 10.1002/cctc.201300102. [DOI] [Google Scholar]
  15. Zang C.; Liu Y.; Xu Z. J.; Tse C. W.; Guan X.; Wei J.; Huang J. S.; Che C. M. Highly enantioselective iron-catalyzed cis-dihydroxylation of alkenes with hydrogen peroxide oxidant via an FeIII-OOH reactive intermediate. Angew. Chem., Int. Ed. 2016, 55 (35), 10253–10257. 10.1002/anie.201603410. [DOI] [PubMed] [Google Scholar]
  16. a Chen J.; Klein Gebbink R. J. M. Deuterated N2Py2 Ligands: Building More Robust Non-Heme Iron Oxidation Catalysts. ACS Catal. 2019, 9 (4), 3564–3575. 10.1021/acscatal.8b04463. [DOI] [Google Scholar]; b Cusso O.; Cianfanelli M.; Ribas X.; Klein Gebbink R. J.; Costas M. Iron catalyzed highly enantioselective epoxidation of cyclic aliphatic enones with aqueous H2O2. J. Am. Chem. Soc. 2016, 138 (8), 2732–2738. 10.1021/jacs.5b12681. [DOI] [PubMed] [Google Scholar]
  17. a Roesch K. R.; Larock R. C. Synthesis of Isoquinolines and Pyridines by the Palladium/Copper-Catalyzed Coupling and Cyclization of Terminal Acetylenes and Unsaturated Imines: The Total Synthesis of Decumbenine B. J. Org. Chem. 2002, 67 (1), 86–94. 10.1021/jo010579z. [DOI] [PubMed] [Google Scholar]; b Sakamoto T.; Numata A.; Kondo Y. The Cyclization Reaction of Ortho-Ethynylbenzalddehyde Derivatives into Isoquinoline Derivatives. Chem. Pharm. Bull. 2000, 48 (5), 669–672. 10.1248/cpb.48.669. [DOI] [PubMed] [Google Scholar]; c Roesch K. R.; Larock R. C. Synthesis of isoquinolines and pyridines by the palladium-and copper-catalyzed coupling and cyclization of terminal acetylenes. Org. Lett. 1999, 1 (4), 553–556. 10.1021/ol990067v. [DOI] [Google Scholar]
  18. a Haidar A. K.; Kjeldsen N. D.; Troelsen N. S.; Previtali V.; Lundquist K. P.; Larsen T. O.; Clausen M. H. A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B. Molecules 2022, 27 (2), 521. 10.3390/molecules27020521. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Cikotiene I.; Kairys V.; Buksnaitiene R.; Morkunas M.; Rudys S.; Brukstus A.; Fernandes M. X. Study on the cyclization of 6-arylethynylpyrimidine-5-carbaldehydes with tert-butylamine: Microwave versus thermal preparation of pyrido[4,3-d]pyrimidines. Tetrahedron 2009, 65 (29), 5752–5759. 10.1016/j.tet.2009.05.015. [DOI] [Google Scholar]
  19. a Murafuji T.; Hafizur Rahman A. F. M.; Magarifuchi D.; Narita M.; Miyakawa I.; Ishiguro K.; Kamijo S. One-Pot Synthesis of Hypervalent Diaryl (iodo) bismuthanes from o-Carbonyl Iodoarenes by Zincation. Heteroat. Chem. 2019, 2019 (1), 2385064. 10.1155/2019/2385064. [DOI] [Google Scholar]; b Klapars A.; Buchwald S. L. Copper-catalyzed halogen exchange in aryl halides: An aromatic Finkelstein reaction. J. Am. Chem. Soc. 2002, 124 (50), 14844–14845. 10.1021/ja028865v. [DOI] [PubMed] [Google Scholar]
  20. Ishiyama T.; Murata M.; Miyaura N. Palladium (0)-catalyzed cross-coupling reaction of alkoxydiboron with haloarenes: A direct procedure for arylboronic esters. J. Org. Chem. 1995, 60 (23), 7508–7510. 10.1021/jo00128a024. [DOI] [Google Scholar]
  21. Miao C.; Wang B.; Wang Y.; Xia C.; Lee Y.-M.; Nam W.; Sun W. Proton-promoted and anion-enhanced epoxidation of olefins by hydrogen peroxide in the presence of nonheme manganese catalysts. J. Am. Chem. Soc. 2016, 138 (3), 936–943. 10.1021/jacs.5b11579. [DOI] [PubMed] [Google Scholar]
  22. Goddard T. D.; Huang C. C.; Meng E. C.; Pettersen E. F.; Couch G. S.; Morris J. H.; Ferrin T. E. UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Sci. 2018, 27 (1), 14–25. 10.1002/pro.3235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sherstyuk V. A.; Ottenbacher R. V.; Talsi E. P.; Bryliakov K. P. Asymmetric Epoxidation vs syn-Hydroxy-Acyloxylation of Olefins in the Presence of Sterically Demanding Nonheme Manganese Complexes. ACS Catal. 2024, 14 (1), 498–507. 10.1021/acscatal.3c04832. [DOI] [Google Scholar]
  24. a Mas-Balleste R.; Fujita M.; Que L. Jr. High-valent iron-mediated cis-hydroxyacetoxylation of olefins. Dalton Trans. 2008, (14), 1828–1830. 10.1039/b802587h. [DOI] [PubMed] [Google Scholar]; b Serrano-Plana J.; Oloo W. N.; Acosta-Rueda L.; Meier K. K.; Verdejo B.; García-España E.; Basallote M. G.; Münck E.; Que L. Jr.; Company A.; Costas M. Trapping a Highly Reactive Nonheme Iron Intermediate That Oxygenates Strong C—H Bonds with Stereoretention. J. Am. Chem. Soc. 2015, 137 (50), 15833–15842. 10.1021/jacs.5b09904. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ol5c00050_si_001.pdf (8.3MB, pdf)

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Articles from Organic Letters are provided here courtesy of American Chemical Society

RESOURCES