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. 2021 Feb 22;40(4):539-556.
doi: 10.1021/acs.organomet.0c00787. Epub 2021 Jan 29.

Sequential Insertion of Alkynes, Alkenes, and CO into the Pd-C Bond of ortho-Palladated Primary Phenethylamines: from η3-Allyl Complexes and Enlarged Palladacycles to Functionalized Arylalkylamines

José-Antonio García-López  1 , María-José Oliva-Madrid  1 , Delia Bautista  2 , José Vicente  1 , Isabel Saura-Llamas  1
Affiliations

Sequential Insertion of Alkynes, Alkenes, and CO into the Pd-C Bond of ortho-Palladated Primary Phenethylamines: from η3-Allyl Complexes and Enlarged Palladacycles to Functionalized Arylalkylamines

José-Antonio García-López et al. Organometallics. .

Abstract

The eight-membered metallacycles arising from the insertion of 1 equiv of alkyne into the Pd-C bond of ortho-metalated homoveratrylamine and phentermine can further react with alkenes to give two different types of mononuclear complexes depending on the nature of the olefin. When terminal alkenes (styrene and ethyl acrylate) are used, a mixture of the anti/syn η3-allyl Pd(II) complexes are isolated, which evolve slowly to the syn isomers by heating the mixtures appropriately. These η3-allyl Pd(II) complexes do not react with CO or weak bases, but when they are treated with a strong base, such as KOtBu, they afford Pd(0) and the functionalized starting phenethylamines containing a 1,3-butadienyl substituent in an ortho position. When 2-norbornene was used instead of terminal alkenes, the strained olefin inserts into the alkenyl Pd(II) complex to afford a 10-membered norbornyl palladium(II) complex, in which the new C,N-chelate ligand is coordinated to the metal through an additional double bond, occupying three coordination positions. The reactivity of these norbornyl complexes depends on the substituents on the inserted alkenyl fragment, and thus they can further react with (1) KOtBu, to give Pd(0) and a tetrahydroisoquinoline nucleus containing a tricyclo[3.2.1]octyl ring, or (2) CO and TlOTf, to afford Pd(0) and amino acid derivatives or the corresponding lactones arising from an intramolecular Michael addition of the CO2H group to the α,β-unsaturated ester moiety. Crystal structures of every type of compound have been determined by X-ray diffraction studies.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Examples of Reactions Involving Sequential Migratory Insertion into Pd–C Bonds,
Scheme 2
Scheme 2. Synthesis of Benzazocinones through the Sequential Insertion of Alkynes and CO into the Pd–C Bond of Six-Membered Palladacycles
Chart 1
Chart 1. Previously Reported Eight-Membered Alkenyl Palladacycles Used as Starting Materials
Scheme 3
Scheme 3. Reactions of Eight-Membered Alkenyl Palladacycles with Terminal Alkenes
The ratios correspond to the isolated solids and were estimated by the integrals of the CH allylic signals of both isomers in the 1H NMR spectra of the mixtures.
Figure 1
Figure 1
1H NMR spectra (4.6–5.0 ppm) of complex 2a (CDCl3): (a) anti-enriched mixture of complex 2a at room temperature (300 MHz) and (b) after heating at 60 °C for 8 h (400 MHz), (c) 24 h (300 MHz) and (d) 48 h (300 MHz).
Scheme 4
Scheme 4. Formation of anti and syn Isomers of η3-Allyl Pd(II) Complexes
Figure 2
Figure 2
X-ray thermal ellipsoid plot (50% probability) of anti-1a along with the labeling scheme. The hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Pd(1)–Br(1) = 2.4959(3), Pd(1)–N(1) = 2.1124(15), Pd(1)–C(7) = 2.1295(15), Pd(1)–C(8) = 2.1047(15), Pd(1)–C(9) = 2.1181(16), C(7)–C(8) = 1.458(2), C(8)–C(9) = 1.427(2); Br(1)–Pd(1)–N(1) = 92.82(4), C(7)–C(8)–C(9) = 119.41(14), C(8)–C(9)–C(14) = 131.14(14).
Figure 3
Figure 3
X-ray thermal ellipsoid plot (50% probability) of syn-2b along with the labeling scheme. The hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Pd(1)–Cl(1) = 2.3864(5), Pd(1)–N(1) = 2.1257(18), Pd(1)–C(7) = 2.1198(19), Pd(1)–C(8) = 2.1400(19), Pd(1)–C(9) = 2.1167(19), C(7)–C(8) = 1.441(3), C(8)–C(9) = 1.421(3); Cl(1)–Pd(1)–N(1) = 89.81(5), C(7)–C(8)–C(9) = 117.38(18), C(8)–C(9)–C(14) = 122.49(18).
Scheme 5
Scheme 5. Reactions of η3-Allyl Complex 1b with p-Toluidine
Figure 4
Figure 4
1H NMR spectra (0.6–3.0 ppm) of complex 3b (400 MHz) in CDCl3 at 25 °C (bottom) and −40 °C (top). The asterisk indicates the signal corresponding to H2O. The blue and red circles correspond to the syn and anti isomers, respectively.
Figure 5
Figure 5
Thermal ellipsoid plot (50% probability) of the cation of one (A) of the two independent molecules of the complex syn-3b·CH2Cl2 showing the labeling scheme. The solvent molecule and the hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg) are given for both independent molecules (A and A′). For A: Pd(1)–N(1) = 2.131(2), Pd(1)–N(2) = 2.161(2), Pd(1)–C(7) = 2.100(2), Pd(1)–C(8) = 2.138(2), Pd(1)–C(9) = 2.165(2), C(7)–C(8) = 1.454(3), C(8)–C(9) = 1.408(3); N(1)–Pd(1)–N(2) = 90.26(9), C(7)–C(8)–C(9) = 116.9(2), C(8)–C(9)–C(14) = 124.9(2). For A′: Pd(1′)–N(1′) = 2.130(2), Pd(1′)–N(2′) = 2.163(2), Pd(1′)–C(7′) = 2.117(2), Pd(1′)–C(8′) = 2.134(2), Pd(1′)–C(9′) = 2.165(2), C(7′)–C(8′) = 1.452(3), C(8′)–C(9′) = 1.413(3); N(1′)–Pd(1′)–N(2′) = 88.94(8), C(7′)–C(8′)–C(9′) = 117.5(2), C(8)–C(9)–C(14) = 124.0(2).
Scheme 6
Scheme 6. Synthesis of Functionalized Phenethylamine Derivatives Containing 1,3-Butadienyl Substituents
Figure 6
Figure 6
Thermal ellipsoid plot (50% probability) of the cation of compound 5b·H2O along with the labeling scheme. The solvent molecule and the hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): C(1)–C(7) = 1.503(2), C(7)–C(8) = 1.359(2), C(8)–C(9) = 1.461(2), C(9)–C(14) = 1.341(2), C(14)–C(21) = 1.466(2), C(8)–C(31) = 1.496(2), C(7)–C(41) = 1.487(2); C(1)–C(7)–C(41) = 115.93(15), C(1)–C(7)–C(8) = 120.51(16), C(7)–C(8)–C(9) = 120.85(16), C(8)–C(9)–C(14) = 127.20(17), C(9)–C(8)–C(31) = 116.96(15).
Scheme 7
Scheme 7. Sequential Insertion of Alkyne/2-Norbornene into the Pd–C Bond of Six-Membered Palladacycle B
Figure 7
Figure 7
Thermal ellipsoid plot (50% probability) of the complex 7c·CHCl3 along with the labeling scheme. The solvent molecule and the hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Pd(1)–N(1) = 2.2185(19), Pd(1)–Cl(1) = 2.3589(5), Pd(1)–C(1) = 2.047(2), Pd(1)–C(3) = 2.159(2), Pd(1)–C(4) = 2.203(2), Pd(1)–X = 2.065, C(1)–C(2) = 1.553(3), C(2)–C(3) = 1.542(3), C(3)–C(4) = 1.403(3), C(4)–C(5) = 1.512(3); N(1)–Pd(1)–Cl(1) = 88.03(5), Cl(1)–Pd(1)–C(1) = 93.88(6), C(1)–Pd(1)–X = 76.7, X–Pd(1)–N(1) = 101.3, C(2)–C(3)–C(4) = 117.17(17), C(3)–C(4)–C(5) = 122.65(18). X represents the midpoint of the double bond C(3)–C(4).
Scheme 8
Scheme 8. Sequential Insertion of Norbornene/Alkynes into the Pd–C Bond of Palladacycle B
Scheme 9
Scheme 9. Sequential Insertion of Norbornene/DMAD into the Pd–C Bond of Palladacycle B
Scheme 10
Scheme 10. Reaction of Complex 7f with KOtBu
Figure 8
Figure 8
Thermal ellipsoid plot (50% probability) of the cation of compound 8f along with the labeling scheme. The hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): N(1)–C(8) = 1.5233(17), N(1)–C(9) = 1.5134(16), C(9)–C(10) = 1.5595(18), C(10)–C(13) = 1.5071(17), C(10)–C(18) = 1.5259(18), C(13)–C(18) = 1.5261(17); C(1)–C(9)–N(1) = 111.04(10), N(1)–C(9)–C(20) = 105.93(10), C(20)–C(9)–C(10) = 110.53(10), C(10)–C(18)–C(13) = 59.18(8), C(18)–C(13)–C(10) = 60.40(8), C(13)–C(10)–C(18) = 60.42(8).
Scheme 11
Scheme 11. Reactions of Complexes 7 with CO
Figure 9
Figure 9
Thermal ellipsoid plot (50% probability) of the cation of 9f·Et2O along with the labeling scheme. The solvent molecule and the hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): N(1)–C(8) = 1.5209(19), C(11)–C(12) = 1.522(2), C(11)–C(14) = 1.557(2), C(14)–O(4) = 1.4423(18), C(17)–O(3) = 1.2010(19), C(17)–O(4) = 1.3514(19), C(16)–C(17) = 1.499(2); C(1)–C(11)–C(12) = 107.19(12), C(11)–C(14)–O(4) = 109.88(12), C(14)–O(4)–C(17) = 111.86(11), O(4)–C(17)–C(16) = 111.77(13), C(17)–C(16)–C(15) = 104.53(12), C(16)–C(15)–C(14) = 104.02(12), C(15)–C(14)–O(4) = 106.07(11).
Figure 10
Figure 10
Thermal ellipsoid plot (50% probability) of the cation of 10c·H2O along with the labeling scheme. The solvent molecule and the hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): N(1)–C(8) = 1.518(2), C(1)–C(11) = 1.504(3), C(11)–C(14) = 1.342(3), C(14)–C(15) = 1.532(2), C(15)–C(16) = 1.582(2), C(16)–C(17) = 1.506(3), C(17)–O(1) = 1.218(2), C(17)–O(2) = 1.328(2); N(1)–C(8)–C(7) = 104.46(14), C(1)–(11)–C(14) = 121.73(17), C(11)–C(14)–C(15) = 121.56(17), C(14)–C(15)–C(16) = 118.26(15), C(15)–C(16)–C(17) = 116.58(15), C(16)–C(17)–O(1) = 126.22(17), C(16)–C(17)–O(2) = 111.65(16).
Chart 2
Chart 2. Numbering Schemes for the New Palladium(II) Complexes and the Organic Derivatives
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References

    1. Zeni G.; Larock R. C. Synthesis of Heterocycles via Palladium-Catalyzed Oxidative Addition. Chem. Rev. 2006, 106, 4644–4680. 10.1021/cr0683966. - DOI - PubMed
    2. He J.; Wasa M.; Chan K. S. L.; Shao Q.; Yu J.-Q. Palladium-Catalyzed Transformations of Alkyl C-H Bonds. Chem. Rev. 2017, 117, 8754–8786. 10.1021/acs.chemrev.6b00622. - DOI - PMC - PubMed
    3. Biffis A.; Centomo P.; Del Zotto A.; Zecca M. Pd Metal Catalysts for Cross-Couplings and Related Reactions in the 21st Century: A Critical Review. Chem. Rev. 2018, 118, 2249–2295. 10.1021/acs.chemrev.7b00443. - DOI - PubMed
    4. Devendar P.; Qu R.-Y.; Kang W.-M.; He B.; Yang G.-F. Palladium-Catalyzed Cross-Coupling Reactions: A Powerful Tool for the Synthesis of Agrochemicals. J. Agric. Food Chem. 2018, 66, 8914–8934. 10.1021/acs.jafc.8b03792. - DOI - PubMed
    5. Wang D.; Weinstein A. B.; White P. B.; Stahl S. S. Ligand-Promoted Palladium-Catalyzed Aerobic Oxidation Reactions. Chem. Rev. 2018, 118, 2636–2679. 10.1021/acs.chemrev.7b00334. - DOI - PubMed
    6. Dondas H. A.; Retamosa M. d. G.; Sansano J. M. Recent Development in Palladium-Catalyzed Domino Reactions: Access to Materials and Biologically Important Carbo- and Heterocycles. Organometallics 2019, 38, 1828–1867. 10.1021/acs.organomet.9b00110. - DOI
    1. Della Ca’ N.; Fontana M.; Motti E.; Catellani M. Pd/Norbornene: A Winning Combination for Selective Aromatic Functionalization via C-H Bond Activation. Acc. Chem. Res. 2016, 49, 1389–1400. 10.1021/acs.accounts.6b00165. - DOI - PubMed
    1. Beller M.; Seayad J.; Tillack A.; Jiao H. Catalytic Markovnikov and anti-Markovnikov Functionalization of Alkenes and Alkynes: Recent Developments and Trends. Angew. Chem., Int. Ed. 2004, 43, 3368–3398. 10.1002/anie.200300616. - DOI - PubMed
    1. Vlaar T.; Ruijter E.; Maes B. U. W.; Orru R. V. A. Palladium-Catalyzed Migratory Insertion of Isocyanides: An Emergin Platform in Cross-Coupling Chemistry. Angew. Chem., Int. Ed. 2013, 52, 7084–7097. 10.1002/anie.201300942. - DOI - PubMed
    2. Mehta V. P.; García-López J.-A. σ-Alkyl-PdII Species for Remote C-H Functionalization. ChemCatChem 2017, 9, 1149–1156. 10.1002/cctc.201601624. - DOI
    3. Xia Y.; Qiu D.; Wang J. Transition-Metal-Catalyzed Cross-Couplings through Carbene Migratory Insertion. Chem. Rev. 2017, 117, 13810–13889. 10.1021/acs.chemrev.7b00382. - DOI - PubMed
    4. Zeidan N.; Lautens M. Migratory Insertion Strategies for Dearomatization. Synthesis 2019, 51, 4137–4146. 10.1055/s-0037-1611918. - DOI
    1. Blouin S.; Blond G.; Donnard M.; Gulea M.; Suffert J. Cyclocarbopalladation as a Key Step in Cascade Reactions: Recent Developments. Synthesis 2017, 49, 1767–1784. 10.1055/s-0036-1588708. - DOI

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