Substrate Self-Assisted Secondary Bond Activation of Allylic Alcohol in

Subscriber access provided by Bibliothèque de l'Université Paris-Sud

Note

Substrate Self-Assisted Secondary Bond Activation of Allylic Alcohol in Tsuji–Trost Reaction Revealed by NMR Methods Xiantao Ma, Jing Yu, Qiuju Zhou, Ran Yan, Lingyun Zheng, and Lingling Wang J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 15 May 2019 Downloaded from http://pubs.acs.org on May 15, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Organic Chemistry

Substrate Self-Assisted Secondary Bond Activation of Allylic Alcohol in Tsuji–Trost Reaction Revealed by NMR Methods Xiantao Ma, †,* Jing Yu,† Qiuju Zhou‡,* Ran Yan,† Lingyun Zheng,‡ Lingling Wang‡ †College

of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang, Henan 464000, China. & Testing Center, Xinyang Normal University, Xinyang, Henan 464000, China. Supporting Information Placeholder ‡Analysis

Variable-Temperature 1H NMR DOSY The Job's method and 1H NMR Titration 2 D NOESY Evidences for Hydrogen Bond Evidences for P---O non-Covalent Bond Six-Membered Ring Model Practical and Specific Experimental and Detailed

ABSTRACT: The first experimental evidences for palladium-catalyzed secondary bond activation of allylic alcohols in Tsuji–Trost reaction were provided by NMR methods, such as variable-temperature 1H NMR, Diffusion-Ordered SpectroscopY (DOSY), Job’s method, 1H NMR titration, and Nuclear Overhauser Enhancement SpectroscopY (NOESY). The experimental results revealed that the substrate self-assisted activation of allylic alcohols is probably performed via a 1:1 binding six-membered-ring complex, which are formed by the formation of the secondary bonds, hydrogen bond and P…O non-covalent bond between allylic alcohol and phosphonium ylide.

The Tsuji–Trost reaction is a powerful tool to construct C-C and C-X (X = O, N, S, P etc.) bonds. The reactive allylic halides and allylic alcohol derivatives such as allylic ethers or esters, were traditionally employed as the allylic partners.1-4 In recent decades, the direct use of the cheap and easily-available allylic alcohols as the alkylating reagents to develop a much atomeconomic and environmentally-friendly Tsuji–Trost reaction has received much attention, since the reactions with allylic alcohols usually give water as the sole by-product.5-8 However, owing to the poor leaving character of the hydroxy group, stoichiometric or catalytic amount of an acid activator such as As2O3, B2O3, BEt3, or Ti(O-iPr)4 is generally required.6-8 Therefore, it is still highly desired to develop an activator-free Tsuji–Trost reaction of allylic alcohol. Ozawa reported the first activator-free Tsuji–Trost reactions of allylic alcohols for the waste-free synthesis of

A) Palladium hydride intermediate supported by both theoretical calculations and experimental approaches. OH L

OTf

Pd H L

PdL2

B) Secondary bonds activation supported by theoretical calculations H O

(H-bonds donor)

PdL2

PdL2

C) This work: Substrate self-assisted secondary bond activation supported by NMR techniques

O R

1

H

L2Pd O PPh3

R2

PdL2 R2

Scheme 1. Mechanism study methods for activator-free Tsuji– Trost reactions of allylic alcohols allylic amines,9 in which the activation of allylic alcohol involving a palladium hydride intermediate which was well documented by both theoretical calculations and experimental

ACS Paragon Plus Environment

The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

approaches (Scheme 1A).10-13 Afterwards, the reaction mechanisms involved secondary bonds activation such as hydrogen bond, supported by theoretical calculations,14-18 were proposed in some activator-free Tsuji–Trost reactions of allylic alcohols (Scheme 1B).19-25 However, probably owing to the elusory character of secondary bond, experimental evidences are still rare.26 Very recently, we developed an extra activator-free Tsuji– Trost reaction of allylic alcohols with stabilized phosphonium ylides in water media (Table 1, run 1).27 Control experiments using Diffusion-Ordered SpectroscopY (DOSY) NMR and ESI-HRMS techniques indicated that hydrogen bond is probably formed between water and allylic alcohols and therefore leads to the activation of allylic alcohols. Hence, one may hypothesize that aprotic solvents may hinder the reaction. However, to our surprise, the reaction of cinnamyl alcohol 1a and stabilized phosphonium ylide 2a heated at 60 oC in cyclohexane, a typical nonpolar and aprotic solvent, could still afford the desired product 3a in 65% isolated yield (run 2). Likewise, the reaction in toluene and CHCl3 could also give the desired 3a in moderate to low yields (runs 3-4). Thus, a new activation mechanism may be involved. Table 1. Solvent effects of the reaction [a]

O Ph

1a

OH + Ph 2a

1) [Pd(allyl)Cl]2 (2.5 mol%) dppf (5 mol%) O solvent (0.5 mL) o Ph PPh3 60 C, N2, 10 h 2) HCHO (3.0 equiv.) - Ph3PO, H2O

formation of intermolecular hydrogen bond. The signals of hydroxy group in cinnamyl alcohol 1a were carefully examined. The results showed that the chemical shift of OH group moves upfield from 4.88 (293 K), to 4.71 (333 K) and to 4.38 (393 K), when the test temperature was increased, revealing the possible formation of intermolecular hydrogen bond between cinnamyl alcohol 1a and stabilized phosphonium ylide 2a (Figure 1).

Ph

OH 293 K

Ph

OH 333 K

Ph Ph

OH 393 K

3a

run

solvent

Yield/%[b]

1 2 3 4

H2O cyclohexane toluene CHCl3

92 65 60 10

Unless otherwise noted, the mixture of 1a (0.36 mmol), 2a (0.3 mmol), [Pd(ally)Cl]2 (2.5 mol%), dppf (5 mol%) in a solvent (0.5 mL) was sealed under N2 in a Schlenk tube, heated at 60 oC for 10 h, then HCHO (37% w/w in water, 3 equiv.) was added and stirred at rt for another 6 h and monitored by TLC and/or GC-MS. [b] Isolated yield based on 2a. dppf: 1,1'Bis(diphenylphosphino)ferrocene With our continuous interest in alkylation with alcohols as the synthons and NMR studies,28-33 herein, we investigated the activation mechanism of allylic alcohols with stabilized phosphonium ylides by using NMR techniques. According to our results, we put forward a new mechanism (Scheme 1C), in which a substrate self-assisted activation of allylic alcohols is achieved via a binding six-membered ring complex, which are formed by the formation of the secondary bonds, hydrogen bond and P…O non-covalent bond between allylic alcohol and phosphonium ylide. Variable-temperature 1H NMR, DOSY, the Job’s method, 1H NMR titration experiments, and two-dimensional Nuclear Overhauser Enhancement SpectroscopY (NOESY) were conducted to investigate the possible activation mechanism in the activator-free Tsuji–Trost reaction of allylic alcohol with stabilized phosphonium ylide.34 Variable-temperature 1H NMR experiments35-36 for the mixture of cinnamyl alcohol 1a and stabilized phosphonium ylide 2a were initially carried out to investigate the possible [a]

Page 2 of 6

Figure 1. Variable-temperature NMR analysis The possible intermolecular hydrogen bond between cinnamyl alcohol 1a and stabilized phosphonium ylide 2a was then investigated by DOSY NMR techniques.37-38 The equation (1) indicates that the self-diffusion coefficient (D) of a given molecular complex under controlled conditions has a negative relation with its hydrodynamic radius (RH).37 As shown in figure 2, the diffusion coefficient of cinnamyl alcohol 1a in CDCl3 is 1.98×10-9 (sample 1, see spectra highlighted in red ), while it significantly decreased to 1.61 × 10-9 m2/s, when phosphonium ylide 2a was added (sample 2, see spectra highlighted in green). These results suggested that a much bigger complex might be formed by binding cinnamyl alcohol 1a with phosphonium ylide 2a and that hydrogen bond might be formed between cinnamyl alcohol 1a and phosphonium ylide 2a.


(1)

Page 3 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Organic Chemistry Sample 1: D(1a) = 1.98 * 10-9 m2/s

D(1a) = 0.37 * 10-9 m2/s

Sample 2: D(1a) = 1.61 * 10-9 m2/s

Figure 2. DOSY NMR analysis More detailed host-guest binding interactions of cinnamyl alcohol 1a and stabilized phosphonium ylide 2a were further investigated by Job’s method and 1H NMR titration experiments.39-43 The Job's method of continuous variation to the NMR results for the binding complex in rapid exchange was employed to confirm the expected 1:1 binding stoichiometry for cinnamyl alcohol 1a and stabilized phosphonium ylide 2a. According to the Job’s method, the total concentration, [1a] + [2a], is constant in all solutions, therefore, the concentration of the possible 1:1 binding complex will reach a maximum value when [1a] = [2a]. As shown in figure 3, the maximum in the curve for phosphonium ylide 2a is at XH = 0.5, indicating that the stoichiometry between cinnamyl alcohol 1a and stabilized phosphonium ylide 2a is 1:1 as expected.44 Moreover, the theoretical fitting of the 1H NMR titration experimental results gave an association constant of Ka=153±6 M-1 with 0.93±0.01 binding ratio at 298 K in CDCl3,44 which further indicating the possible 1:1 binding complex (Figure 4). These experiment results suggested that a substrate self-assisted secondary bond activation of allylic alcohol via a 1:1 binding six-memberedring complex might be present (Figure 5). The rigid sixmembered-ring complex is possibly formed by the formation of hydrogen bond and P…O non-covalent bond between cinnamyl alcohol 1a and stabilized phosphonium ylide 2a (Figure 5).

Figure 4. 1H NMR titration experiments

hydrogen bond O Ph

H

O

Ph

PPh3

P-O non-covalent bond

Figure 5. The possible 1:1 binding six-membered-ring complex Finally, the two-dimensional NOESY method, which could provide detailed information of internuclear spatial proximity,45-46 was employed to further confirm the possible formation of P…O non-covalent bond between allylic alcohol and stabilized phosphonium ylide (Figure 5).47 In order to obtain a clear and unambiguous result, the mixture of 2methylprop-2-en-1-ol (1b) and stabilized phosphonium ylide (2b) was selected as the test sample (Figure 6). As shown in figure 7, the key cross-peaks (H1/H2, δ: 1.72/3.75, marked with triangle; H1/H3, δ: 1.72/7.60, marked with rectangle) revealed that the dipolar couplings between allylic alcohol 1b and stabilized phosphonium ylide 2b may be present. These results suggested that the formation of P…O non-covalent bond brings these nuclei close enough and therefore they can interact to give rise to the NOE effect among them. According to the dependence between longer range NOEs and internuclear separation, it could be inferred that the internuclear separation among these protons (H1, H2 and H3) is within ca. 0.5 nm.46 Hence, a six-membered ring is probably formed by the formation of the secondary bonds, hydrogen bond and P…O non-covalent bond (Figure 6). H1 O PPh3

OH

Figure 3. The Job’s method

O

1 1H H O H 3 H

C 1b

2b

Figure 6. Test sample: 1b and 2b


H2

P


In conclusion, variable-temperature 1H NMR, DOSY, the Job’s method and 1H NMR titration and 2D NOESY experiments were employed to investigate the activation mechanism of allylic alcohols with stabilized phosphonium ylides in Tsuji–Trost reaction and the results revealed that a substrate self-assisted activation of allylic alcohols probably performed via the 1:1 binding six-membered ring complex. Notably, to our best knowledge, it is the first time to investigate the palladium-catalyzed secondary bond activation of allylic alcohols by using NMR techniques and it may provide a practical experimental approach to investigate the secondary bond in mechanism studies so as to scientifically design and explore new reactions.

H1/H2

H1/H3

H1/H2

H1/H3

EXPERIMENTAL SECTION Figure 7. 2D NOESY spectrum of the mixture of 1b and 2b ne xa he clo b cy th pa

O R2

PPh3

[Pd] H

O

R1

O PPh3

R2

OH (2)

5

2

OH (H2O)m

pa R1

OH

H 2O

th a

[Pd] (H2O)m R1

OH

4

1 [Pd] [Pd] (0)

R1

[Pd(ally)Cl]2 + dppf

6 O R2

O R1

R2 PPh3 8

R

[Pd]

2

R1 PPh3 7

O 2

O

H 2O

- Ph3PO HCHO

R

PPh3 2

R

OH (H2O)m or OH (2)

1

CH2 3

Scheme 2. Possible activation model of cinnamyl alcohol under extra activator-free conditions Based on these control experiments and the literature reports,5-8,14-18,27 a possible reaction mechanism was depicted in scheme 2. As to this novel extra activator-free Tsuji–Trost reaction of allylic alcohols 1 with stabilized phosphonium ylides 2, two activation paths might be involved in the activation of allylic alcohols 1 (Scheme 2). When the reaction is carried out in water media, allylic alcohols 1 may be mainly activated by water via hydrogen bond (path a), followed by the cleavage of C-O bond gives π-allyl palladium intermediate 6. When the reaction is carried out in nonpolar aprotic solvent such as cyclohexane, the substrate self-assisted activation of allylic alcohols via six-membered ring complex 4 may be the main path (path b), thus giving π-allyl palladium intermediate 6. Then a nucleophilic attack of π-allyl palladium intermediate 6 by stabilized phosphonium ylides 2, followed by a proton transfer of phosphonium salt intermediate 7, gives a new stabilized phosphonium ylide 8, liberating Pd (0) to continue the catalytic cycle and a molecule of water. Finally, a one-pot Wittig reaction of phosphonium ylide 8 with formaldehyde gives the desired product 3.

General Information. The 1H NMR, DOSY, the Job’s method and NOE spectra were recorded on a JNM-ECZ600R/S3 (Jeol, Japan) (600 MHz) using tetramethylsilane as an internal reference. Chemical shifts (δ) and coupling constants (J) were expressed in ppm and Hz, respectively. The following abbreviations are used in reporting NMR data s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. Mass spectra were measured on an Agilent GC-MS-5890A/5975C Plus spectrometer (EI). All air-sensitive manipulations were conducted under a nitrogen atmosphere by standard Schlenk techniques. Phosphonium ylides, were prepared from α-halo carbonyl compounds according to known procedures.48 Chemicals were purchased from the Energy and Tansoole Chemical Reagent Co., and used as received. Typical Procedure for activator-free Tsuji–Trost reaction of cinnamyl alcohol 1a and Stabilized Phosphonium Ylides 2a. A mixture of cinnamyl alcohol 1a (0.36 mmol, 48.2 mg), phosphonium ylide 2a (0.30 mmol, 114.0 mg), [Pd(allyl)Cl]2 (2.8 mg, 2.5 mol%), and dppf (8.3 mg, 5 mol%) in cyclohexane (0.50 mL) was heated under nitrogen at 60 oC for 10 h. After cooling down to room temperature, formalin (37% in water, w/w, 0.068 mL, 0.90 mmol) was added, and the resulting mixture was stirred for 6 h. Then the solvent was evaporated and the residue was purified by silica gel chromatography, eluting with ethyl acetate/petroleum ether (0/100~1/20), to give compound 3a in 65% yield. (E)-2-methylene-1,5-diphenylpent-4-en-1-one (3a).27 colorless oil (48.4 mg, 65% yield); 1H NMR (600 MHz, CDCl3) δ 7.79– 7.75 (m, 2H), 7.58–7.52 (m, 1H), 7.44 (t, J = 7.8 Hz, 2H), 7.36 (d, J = 7.2 Hz, 2H), 7.30 (t, J = 7.2 Hz, 2H), 7.21 (t, J = 7.2 Hz, 1H), 6.51 (d, J = 15.6 Hz, 1H), 6.30 (dt, J = 15.6, 7.2 Hz, 1H), 5.94 (s, 1H), 5.71 (s, 1H), 3.38 (d, J = 7.2 Hz, 2H); 13C {1H} NMR (150 MHz, CDCl3) δ 197.8, 146.6, 137.8, 137.4, 132.6, 132.3, 129.6, 128.6, 128.3, 127.4, 126.9, 126.7, 126.3, 35.5; MS (EI): m/z 248, 233, 219, 215, 203, 190, 178, 169, 152, 143, 128, 115, 105, 91, 77. Materials and methods for the Variable-temperature NMR analysis. A mixture of cinnamyl alcohol 1a (0.0156 mmol, 2.1 mg), stabilized phosphonium ylide 2a (0.010 mmol, 3.8 mg) and DMSO-d6 (0.50 mL) was prepared as the test sample. Then variable-temperature NMR experiments (293, 333 and 393 K) were conducted. Materials and methods for the DOSY NMR analysis. Two samples are prepared: a mixture of cinnamyl alcohol 1a (0.0075 mmol, 1.0 mg) and CDCl3 (0.50 mL) (Sample 1), a mixture of cinnamyl alcohol 1a (0.0075 mmol, 1.0 mg), stabilized phosphonium ylide 2a (0.0079 mmol, 3.0 mg) and CDCl3 (0.50 mL) (Sample 2). Then the DOSY NMR spectra were recorded


Page 4 of 6

Page 5 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Organic Chemistry by using a simple Carr-Purcell spin-echo sequence (diffusion time = 0.08 s, FG pulse width = 0.002 s, relaxation time = 1 s, points =16, BASE = 2, and scans = 8) at 298K. Materials and methods for the investigation on the hostguest binding interactions by the Job’s method. A stock solvent of cinnamyl alcohol 1a (0.026 mmol, 3.5 mg) in 2.2 mL CDCl3 was prepared and the concentration of cinnamyl alcohol 1a is 0.012 mmol/mL. A stock solvent of stabilized phosphonium ylide 2a (0.026 mmol, 9.9 mg) in 2.2 mL CDCl3 was prepared and the concentration of stabilized phosphonium ylide 2a is 0.012 mmol/mL. The solutions of the cinnamyl alcohol 1a (Host) and stabilized phosphonium ylide 2a (Guest) were mixed to NMR tubes according to certain proportions. The CH2 chemical shift of free host is 4.337. Then the host-guest binding interactions was studied by the Job’s method at 293 K. Materials and methods for the 1H NMR titration. Cinnamyl alcohol 1a (0.0186mmol, 2.5 mg) was dissolved in 0.55 mL CDCl3 and the concentration is 0.034 mmol / mL. Certain amount of phosphonium ylide 2a was added to the above solution. All 1H NMR titration experiments were performed at 293 K. Materials and methods for the 2D NOESY analysis. A mixture of allylic alcohol 1b (0.060 mmol, 4.3 mg), stabilized phosphonium ylide 2b (0.013 mmol, 4.7 mg) was dissolved CDCl3 (0.50 mL) for 24 h. Then 2D NOESY spectrum was recorded with a spectral width of 15 ppm, 1 K data points in the t2 time domain, and 256 t1 increments, a relaxation delay of 1.5 second, and a mixing time of 2.5 second.

ASSOCIATED CONTENT Supporting Information Details of the control experiments for mechanistic studies are supplied as Supporting Information (i.e., PDF) and this material is available free of charge via the Internet at http://pubs.acs.org.”

AUTHOR INFORMATION Corresponding Author * [email protected] * [email protected]

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT We thank the Foundation of Key Scientific and Technological Project of Henan Province (192102310031，182400410166)，the Key Research Programs in Universities of Henan Province (19B150018, 18A150049), and the Nanhu Scholars Program for Young Scholars of XYNU and Young Core Instructor Program of XYNU (2018GGJS—05).

REFERENCES 1. Trost, B. M.; Van Vranken, D. L., Asymmetric transition metalcatalyzed allylic alkylations, Chem. Rev. 1996, 96, 395-422. 2. Trost, B. M.; Crawley, M. L., Asymmetric transition-metalcatalyzed allylic alkylations: applications in total synthesis, Chem. Rev. 2003, 103, 2921-2944. 3. Fu, J.; Huo, X.; Li, B.; Zhang, W., Cooperative bimetallic catalysis in asymmetric allylic substitution, Org. Biomol. Chem. 2017, 15, 97479759. 4. Cheng, Q.; Tu, H.-F.; Zheng, C.; Qu, J.-P.; Helmchen, G.; You, S.L., Iridium-catalyzed asymmetric allylic substitution reactions, Chem. Rev. 2019, 119, 1855-1969.

5. Bandini, M., Allylic alcohols: sustainable sources for catalytic enantioselective alkylation reactions, Angew. Chem. Int. Ed. 2011, 50, 994-995. 6. Sundararaju, B.; Achard, M.; Bruneau, C., Transition metal catalyzed nucleophilic allylic substitution: activation of allylic alcohols via π-allylic species, Chem. Soc. Rev. 2012, 41, 4467-4483. 7. Butta, N. A.; Zhang, W., Transition metal-catalyzed allylic substitution reactions with unactivated allylic substrates, Chem. Soc. Rev. 2015, 44, 7929-7967. 8. Ferraccioli, R.; Pignataro, L., Tsuji-Trost type functionalization of allylic substrates with challenging leaving groups: recent developments, Curr. Org. Chem. 2015, 19, 106-120. 9. Ozawa, F.; Okamoto, H.; Kawagishi, S.; Yamamoto, S.; Minami, T.; Yoshifuji, M., (π-Allyl) palladium complexes bearing diphosphinidenecyclobutene ligands (DPCB): highly active catalysts for direct conversion of allylic alcohols, J. Am. Chem. Soc. 2002, 124, 10968-10969. 10. Ozawa, F.; Ishiyama, T.; Yamamoto, S.; Kawagishi, S.; Murakami, H., Catalytic C-O bond cleavage of allylic alcohols using diphosphinidenecyclobutene-coordinated palladium complexes: a mechanistic study, Organometallics 2004, 23, 1698-1707. 11. Piechaczyk, O.; Thoumazet, C.; Jean, Y.; le Floch, P., DFT study on the palladium-catalyzed allylation of primary amines by allylic alcohol, J. Am. Chem. Soc. 2006, 128, 14306-4317. 12. Sawadjoon, S.; Sjçberg, P. J. R.; Orthaber, A.; Matsson, O.; Samec, J. S. M., Mechanistic insights into the Pd-catalyzed direct amination of allyl alcohols: evidence for an outer-sphere mechanism involving a palladium hydride intermediate, Chem. Eur. J. 2014, 20, 1520-1524. 13. Xie, J.; Xue, S.; Escudero-Adán, E. C.; Kleij, A. W., Domino synthesis of α,β-unsaturated γ-lactams by stereoselective amination of α‐tertiary allylic alcohols, Angew. Chem. Int. Ed. 2018, 57, 1672716731. 14. Kinoshita, H.; Shinokubo, H.; Oshima, K., Water enables direct use of allyl alcohol for Tsuji-Trost reaction without activators, Org. Lett. 2004, 6, 4085-4088. 15. Hikawa, H.; Yokoyama, Y., Palladium-catalyzed mono-Nallylation of unprotected anthranilic acids with allylic alcohols in aqueous media, J. Org. Chem. 2011, 76, 8433-8439. 16. Huo, X.; Yang, G.; Liu, D.; Liu, Y.; Gridnev, I. D.; Zhang, W., Palladium-catalyzed allylic alkylation of simple ketones with allylic alcohols and its mechanistic study, Angew. Chem. Int. Ed. 2014, 53, 6776-6780. 17. Jing, J.; Huo, X.; Shen, J.; Fu, J.; Meng, Q.; Zhang, W., Direct use of allylic alcohols and allylic amines in palladium-catalyzed allylic amination, Chem. Commun. 2017, 53, 5151-5154. 18. Haruki, H.; Yasuda, S.; Nagao, K.; Ohmiya, H., Dehydrative allylation between aldehydes and allylic alcohols through synergistic N-heterocyclic carbene/palladium catalysis, Chem. Eur. J. 2019, 25, 724-727. 19. Ghosh, R.; Sarkar, A., Palladium-catalyzed amination of allyl alcohols, J. Org. Chem. 2011, 76, 8508-8512. 20. Banerjee, D.; Jagadeesh, R.V.; Junge, K.; Junge, H.; Beller, M., Efficient and convenient palladium-catalyzed amination of allylic alcohols with N-heterocycles, Angew. Chem. Int. Ed. 2012, 51, 1155611560. 21. Zhou, H.; Yang, H.; Yin, H.; Liu, M.; Xia, C.; Jiang, G., Palladium catalyzed direct allylation of azlactones with simple allylic alcohols in the absence of any activators, RSC Adv. 2014, 4, 25596-25599. 22. Kita, Y.; Kavthe, R. D.; Oda, H.; Mashima, K., Asymmetric allylic alkylation of β-ketoesters with allylic alcohols by a nickel/diphosphine catalyst, Angew. Chem. Int. Ed. 2016, 55, 1098-1101. 23. Lauwick, H.; Sun, Y.; Akdas-Kilig, H.; Derien, S.; Achard, M., Access to 3-oxindoles from allylic alcohols and indoles, Chem. Eur. J. 2018, 24, 7964-7969. 24. Sweeney, J. B.; Ball, A. K.; Smith, L. J., Catalytic C-C bond formation using a simple nickel precatalyst system: base- and activatorfree direct C-allylation by alcohols and amines, Chem. Eur. J. 2018, 24, 7354-7357. 25. Shimizu, A.; Hirata, G.; Onodera, G.; Kimura, M., Direct allylation of active methylene compounds with allylic alcohols by use of



palladium/phosphine-borane catalyst system, Adv. Synth. Catal. 2018, 360, 1954-1960. 26. To our best knowledge, only in Ohshima and Mashima’s platinumcatalyzed direct amination of allylic alcohols, 1H and 31P{1H} NMR techniques were used to investigate the generation of active Pt(0) species, for details, see: Ohshima, T.; Miyamoto, Y.; Ipposhi, J.; Nakahara, Y.; Utsunomiya, M.; Mashima, K., Platinum-catalyzed direct amination of allylic alcohols under mild conditions: Ligand and microwave effects, Substrate scope, and mechanistic study, J. Am. Chem. Soc. 2009, 131, 14317-14328. 27. Ma, X.; Yu, J.; Han, C.; Zhou, Q.; Ren, M.; Li, L.; Tang, L., Dehydrative synthesis of functionalized skipped dienes from stabilized phosphonium ylides and allylic alcohols in water, Adv. Synth. Catal. 2019, 361, 1023-1027. 28. Ma, X.; Yu, J.; Ma, R.; Yan, R.; Zhang, Z., Palladium-catalyzed dehydrative cross couplings of stabilized phosphorus ylides with allylic alcohols, Chin. J. Org. Chem. 2019, 39, 830-835. 29. Ma, X.-T.; Dai, R.-H.; Zhang, J.; Gu, Y.; Tian, S.-K., Catalytic stereospecific substitution of enantioenriched allylic alcohols with sodium sulfinates, Adv. Synth. Catal. 2014, 356, 2984-2988. 30. Ma, X.; Yu. L.; Su. C.; Yang, Y.; Li. H.; Xu. Q., Efficient generation of C–S bonds via a by-product-promoted selective coupling of alcohols, organic halides, and thiourea, Adv. Synth. Catal. 2017, 359, 1649-1655. 31. Ma, X.; Xu, Q.; Li, H.; Su, C.; Yu, L.; Zhang, X.; Cao, H.; Han, L.B., Alcohol-based Michaelis–Arbuzov reaction: an efficient and environmentally-benign method for C–P (O) bond formation, Green Chem. 2018, 20, 3408-3413. 32. Ma, X.; Su, C.; Xu, Q., N-Alkylation by hydrogen autotransfer reactions in Hydrogen transfer reactions: reductions and beyond (Eds.: Guillena, G.; Ramón, D. J.), Top. Curr. Chem. 2016, 374, 27. 33. Zhou, Q.; Li, L.; Xiang, J.; Tang, Y.; Zhang, H.; Yang, S.; Li, Q.; Yang, Q.; Xu, G., Screening potential antitumor agents from natural plant extracts by G-quadruplex recognition and NMR methods, Angew Chem. Int. Ed. 2008, 47, 5590-5592. 34. Since stabilized phosphonium ylide 2a is almost insoluble in nonpolar cyclohexane and toluene, all NMR studies were carried out in CDCl3 except the Variable-temperature NMR analysis in DMSO-d6. 35. Cao, X.; Zhao, N.; Li, R.; Lv, H.; Zhang, Z.; Gao, A.; Yi, T., Steric structure dependent gel formation, hierarchical structures, rheological behaviour and surface wettability, Chem. - Asian J. 2016, 11, 31963204. 36. Cao, X.; Zhao, N.; Zou, G.; Gao, A.; Ding, Q.; Zeng, G.; Wu, Y., Dual response organogel based on iridium complex and Eu （Ⅲ）

hybrid for volatile acid and organic amine vapors, Soft Matter, 2017, 13, 3802-3811. 37. Li, D.; Keresztes, I.; Hopson, R.; Williard, P. G., Characterization of reactive intermediates by multinuclear diffusion-ordered NMR spectroscopy (DOSY), Acc. Chem. Res. 2009, 42, 270–280. 38. Cohen, Y.; Avram, L.; Frish, L., Diffusion NMR spectroscopy in supramolecular and combinatorial chemistry: an old parameter—new insights, Angew Chem. Int. Ed. 2005, 44, 520-554. 39. Blanda, M. T.; Horner, J. H.; Newcomb, M., Macrocycles containing tin. preparation of macrobicyclic lewis acidic hosts containing two tin atoms and 119Sn NMR studies of their chloride and bromide binding properties in solution, J. Org. Chem. 1989, 54, 46264636. 40. Cauble, D. F.; Lynch, V.; Krische M. J., Studies on the enantioselective catalysis of photochemically promoted transformations: “sensitizing receptors” as chiral catalysts, J. Org. Chem. 2003, 68, 15-21. 41. Du, L.; Cao, P.; Xing, J.; Lou, Y.; Jiang, L.; Li, L.; Liao, J., Hydrogen-bond-promoted palladium catalysis: allylic alkylation of indoles with unsymmetrical 1,3-disubstituted allyl acetates using chiral bis(sulfoxide) phosphine ligands, Angew. Chem. Int. Ed. 2013, 52, 4207-4211. 42. Du, L.; Cao, P.; Liao, J., Bifunctional ligand promoted Pdcatalyzed asymmetric allylic etherification/amination, Acta Chim. Sinica 2013, 71, 1239—1242. 43. Thordarson, P. Determining association constants from titration experiments in supramolecular chemistry, Chem. Soc. Rev. 2011, 40, 1305-1323. 44. See supporting information for details. 45. Neuhaus, D.; Williamson, M. P., The nuclear overhauser effect in structural and conformational analysis, 2nd Ed., Wiley-VCH, Weinheim, 2000. 46. Claridge, T. D. W., Chapter 8: Correlations through space: The nuclear Overhauser effect in High-resolution NMR techniques in organic chemistry. 2nd edition, Elsevier Science, 2009, pp: 247-302. 47. The 1H-13C and 1H-31P HMBC techniques were employed to get more supported evidences, but no useful informations could be obtained by these methods. 48. Fang, F.; Li, Y.; Tian, S.-K., Stereoselective olefination of Nsulfonyl imines with stabilized phosphonium ylides for the synthesis of electron-deficient alkenes, Eur. J. Org. Chem. 2011, 1084.


Page 6 of 6

Substrate Self-Assisted Secondary Bond Activation of Allylic Alcohol in

Recommend Documents