Bonded to Carbon or Nitrogen? This is a Question on the

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Bonded to the Carbon or Nitrogen? This is a Question on the Regioselectivity in Hyperconjugative Aromaticity Tingting Sun, Ping Guo, Qiong Xie, Liang Zhao, and Jun Zhu J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02996 • Publication Date (Web): 01 Mar 2019 Downloaded from http://pubs.acs.org on March 2, 2019

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The Journal of Organic Chemistry

Bonded to the Carbon or Nitrogen? This is a Question on the Regioselectivity in Hyperconjugative Aromaticity Tingting Sun,†, ║ Ping Guo, ‡,║ Qiong Xie, † Liang Zhao,* ,‡ Jun Zhu,*, † State Key Laboratory of Physical Chemistry of Solid Surfaces and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China †

Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. ‡

Hyperconjugative Aromaticity; Regioselectivity; Indolium; Transition Metals; Substituent Effect

ABSTRACT: In chemistry, regioselectivity is the preference of one direction of chemical bond making or breaking over all other possible directions. Although it has been extensively investigated in various reactions, the regioselectivity of hyperconjugative aromaticity on either main group systems or transition metal ones remains elusive due to the challenge of synthesizing the target products. Here we report a joint theoretical and experimental study on this issue. Theoretical calculations predicted that electron-withdrawing groups prefer an attachment to the sp3 hybridized carbon atom rather than the nitrogen atom in indoliums. For the electron-donating groups, the two isomers bonded to the sp3 hybridized carbon or nitrogen atom are almost isoenergetic. When both sp2 and sp3 hybridized carbon and nitrogen atoms in the fivemembered ring of indoliums are considered, the isomer with the polyaurated substituents bonded to the sp3 hybridized carbon atom is thermodynamically more stable than that with the polyaurated substituents bonded to the sp3 hybridized nitrogen atom. This prediction is reasonably verified by experimental observation. Bond dissociation energy is found to be more important than aromaticity in rationalizing such a preference. Our findings could help experimentalists to design and realize more novel hyperconjugative aromatics.

INTRODUCTION Aromaticity is one of the most important concepts in chemistry, which has received much attention from lots of experimentalists and theoreticians due to its many fascinating and ever-increasing manifestations.1-4 The concept of hyperconjugative aromaticity was proposed on the basis of hyperconjugation which is first proposed by Mulliken in 1939.5 In the work, the cyclopentadiene was reported to be aromatic because the “pseudo” 2π electrons from the saturated CH2 group could interact with the four olefinic π electrons in the five-membered ring. Thus, cyclopentadiene exhibits an enhanced diamagnetic susceptibility anisotropy. In 1999, Schleyer and Nyulászi confirmed the effective participation of the saturated CH2 group in cyclic electron delocalization of cyclopentadiene and examined the aromaticity in cyclopentadiene by energetic, geometric, and magnetic indices.6 They reported that if two hydrogen atoms on the saturated CH2 group are replaced by electropositive substituents (e.g., silyl, germyl, and stannyl), the aromaticity of cyclopentadiene will be enhanced by hyperconjugative effect. On the other hand, placing substituents on the saturated carbon by electronegative substituents (e.g., fluorine, chlorine) leads to an antiaromatic five-membered ring (5MR) system.

Later, nonatetraenes with electropositive substituents were also reported to exhibit 10π-electron aromaticity.7 Although there is a different voice against the concept of hyperconjugative aromaticity in cyclopentadiene,8 this concept, accepted by most computational and experimental chemists, has been extended to various systems including benzenium ions,9,10 cyclopropene, cyclopentadiene, cycloheptatriene, and cyclononatetraene derivatives.11 It is worth noting that the difference of the Diels-Alder reactivity could be also attributed to hyperconjugative aromaticity.12-14 In 2016, we examined and validated this concept in triplet-state aromaticity.15 However, most studies were limited to main group substituents and carbocyclic systems. In 2016, we extended the concept of hyperconjugative aromaticity to the heterocycles containing transition metal substituents.16 It is found that the aurated substituents can also serve as an electron donor through hyperconjugation and perform better than main group substituents. Very recently, we reported the hyperconjugative aromaticity caused by the transition metals (Ag and Cu) theoretically.17 In addition, it is well-known that regioselectivity plays an important role in chemistry, which has been extensively studied in various reactions.18-20 However, the regioselectivity in

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hyperconjugative aromaticity remains unclear possibly due to the challenge of synthesizing the target products. In general, the substituents could be possibly attached to the sp3 hybridized carbon atom in 3H-indoliums (Figure 1). How about the aromaticity and thermodynamic stability of substituted 3H-indolium in comparison with 1H-indolium? Here we report a joint theoretical and experimental study to address this issue (regioselectivity of hyperconjugative aromaticity). 1H-indoliums R1 R1 N

C

3

H3

H4

N 1.504 H5 1 1.4642 1.345 H6 N.H4 NICS(1)zz -3.6

F3 F4 N-H3: 92.9 1.4041.466 N 1.473 N-H4: 92.9 H5 C1-H5: 134.5 1 1.347 C2-H6: 132.0 1.476 2 Total: 452.3 H6

N-F3: 60.5 N-F4: 60.5 C1-H5: 138.5 C2-H6: 133.0 Total: 392.5

H 3 H4 C11.494 H5 N 2

1.312

H6

N-Sn3: 73.1 N-Sn4: 73.1 C1-H5: 135.8 C2-H6: 136.1 Total: 418.1

N.Sn2.H2 NICS(1)zz -17.9 0.0 (0.0)

0.0 (0.0)

-1.7 (-1.2)

-17.4 (-16.4)

1.513

4 SnH3 N 1.470 H5 1 1.359 1.450 2 H6

H Sn 1.414 3 1.467

N.F2.H2 NICS(1)zz 17.8

0.0 (0.0)

C.H4

C1-H3: C1-H4: C2-H5: N-H6: Total:

109.0 109.1 131.7 120.8 470.6

BDE

18.3

NICS(1)zz -7.3

R1 R1 R2

G(E) 1.403 1.500

1.425 1.409

3H-indoliums

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R2

3 4 H3Sn SnH 3 C1 1.444 H5 2 N 1.340

-92.8 (-94.5) F 3 F4

1.516

C1 1.540 H5 N 2 1.300 1.440 1.402 H6 C.F2.H2 NICS(1)zz 9.7

1.418 1.492

C1-F3: C1-F4: C2-H5: N-H6: Total:

118.2 118.3 133.2 119.5 489.2

BDE

96.7

1.406

H6

C.Sn2.H2

C1-Sn3: 81.8 C1-Sn4: 81.7 C2-H5: 134.9 N-H6: 126.5 Total: 424.9 BDE

6.8

NICS(1)zz -21.1

N R2 1

N.R .R

2

Figure 2. The calculated relative Gibbs energies at 298 K and electronic energies (in parentheses) (kcal mol-1), bond length (Å), NICS(1)zz values (ppm) of 5MRs and the selective bond dissociation energy and the BDE (kcal mol1) in substituted indoliums.

R2 1

C.R .R2

R1 = H, F, SnH3, AuPH3 R2 = H, AuPH3

Figure 1. The structures of substituted 1H-indoliums and 3H-indoliums.

RESULTS AND DISCUSSION We first examined the selectivity of hyperconjugative aromaticity of main group substituents in 1H-indolium and 3H-indolium by density functional theory (DFT) calculations. The calculated relative thermodynamic stabilities and aromaticity of different isomers are shown in Figure 2. The parent 1H-indolium (N.H4) is less stable than the 3H-indolium (C.H4) by 17.4 kcal mol-1. For the electronegative substituents fluorine, the complex C.F2.H2 is much more stable than 1,1-difluoroindoliums (N.F2.H2) by 92.8 kcal mol-1. In sharp contrast, 1H-indolium and 3Hindolium with stannyl substituents are almost isoenergetic and the difference is 1.7 kcal mol-1 only. At the beginning, we hypothesized that aromaticity might be one of the reasons for such a difference. The optimized bond lengths and nucleus-independent chemical shift (NICS),21-23 values of 5MRs in these isomers are given in Figure 2. Compared with other NICS indices, the NICS(1)zz value is chosen here as it can be easily computed and also highly effective in π aromaticity in both the S0 and T1 states13. Negative NICS values indicate aromatic rings, whereas antiaromatic rings are characterized by positive values. However, all these NICS values in the corresponding isomers are comparable to each other, indicating that the thermodynamic stability of these isomers does not correlate well with the aromaticity.

As the fact that isomer stability does not correlate with aromaticity have been reported24-26, we examined bond dissociation energies (BDEs), a useful method for computing the relative stability. 27-31 Note that the bond types are different between 1H-indoliums and 3Hindoliums. Four out-of-plane bonds in the 5MRs were chosen as they are easily computed and directly connected to the substituents. As shown in Figure 2, the higher thermodynamic stability of C.H4 over N.H4 could be mainly attributed to the larger difference (18.3 kcal mol-1) in BDEs (ΔBDE). Again, for the fluorine-substituted indoliums, the BDEs of the sp3 hybridized C-F bonds (118.2 kcal mol-1) in C.F2.H2 are almost doubled in comparison with the sp3 hybridized N-F bonds (60.5 kcal mol-1) in N.F2.H2, leading to an extremely large difference in their thermodynamic stabilities. Similarly, the C-Sn bonds in C.Sn2.H2 are stronger than the N-Sn bonds in N.Sn2.H2 by 17.3 kcal mol-1, the N-H6 bond in C.Sn2.H2 is weaker than the C2-H6 bond in N.Sn2.H2 by 9.6 kcal mol-1, resulting in a difference of 6.8 kcal mol-1 (ΔBDE) between two isomers. In addition, when one fluorine substituent was considered (Figure S1), the higher thermodynamic stability of C.HF.H2 over N.HF.H2 by 49.8 kcal mol-1 could be also attributed to the larger difference (50.4 kcal mol-1) in BDEs (ΔBDE). How about the selectivity of hyperconjugative aromaticity in transition metal substituents? As Ausubstituted 1H-indoliums were reported recently, we examined this issue by comparing it with Au-substituted 3H-indoliums. As previous studies have shown that the ligands on the transition metal have an ignorable effect on aromaticity,32-35 the simple ligand PH3 was used in this work. The calculated relative thermodynamic stabilities and aromaticity of different isomers with Au-substituents are shown in Figure 3. We first investigated the tetraaurated indoliums (N.Au4 and C.Au4). The results suggested that N.Au4 is less stable by 17.3 kcal mol-1 than C.Au4. Then we examined 1H-indolium and 3H-indolium with the substituents on sp3-hybridized N (N.Au2.H2) and


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The Journal of Organic Chemistry C (C.Au2.H2). Complex N.Au2.H2 is slightly less stable than C.Au2.H2. In addition, when the substituents on sp2hybridezed C atoms in 5MRs of 1H-indolium (N.H2.Au2) and sp2-hybridezed C and N atoms in 5MR of 3H-indolium (C.H2.Au2) are considered, complex C.H2.Au2 can be thermodynamically more stable than N.H2.Au2 by 32.1 kcal mol-1. [Au] = AuPH3 G(E) [Au] 3 [Au] 4 1.416 1.439

N 1.483 [Au] 1 1.383 5 1.458 2 [Au] 6 N.Au4

1.416

N-[Au]3: 98.3 N-[Au]4: 98.3 C1-[Au]5: 128.8 C2-[Au]6: 127.7 Total: 453.1

[Au] 4

N1.449

N-[Au]3: 93.2 H 5 N-[Au]4: 93.2 1 C1-H5: 139.0 1.448 2 1.362 C2-H6: 140.1 H6 Total: 465.5 N.Au2.H2 NICS(1)zz -18.0

NICS(1)zz -16.6

0.0 (0.0)

0.0 (0.0)

-17.3 (-17.9)

H3 1.403 H4 1.482 N 1.571

N1-H3: 100.4 N1-H4: 100.4 [Au] 5 C2-[Au]5: 127.2 N-[Au]6: 120.3 1.475 2 1.362 Total: 448.3 [Au] 6 1

N.H2.Au2 NICS(1)zz -2.9

0.0 (0.0)

-7.4 (-7.1) -32.1 (-31.6) C1-[Au]3: 106.1 H3 H C 11.425 C1-[Au]4: 106.1 4 H 5 C2-H5: 137.9 1.507 C1 1.520 N-H6: 122.5 N 2 1.401 1.355 Total: 472.6 2 [Au]5 1.419 N 1.327 H6 1.432 1.405 C.Au2.H2 [Au] 6 BDE 7.1 NICS(1)zz -20.3 C.H2.Au2 NICS(1)zz -4.9

[Au] 3 [Au] 4

[Au]3 [Au] 4 1.473

C1-[Au]3: 111.2 C 11.454 [Au] 5 C1-[Au]4: 111.2 C2-[Au]5: 126.8 N 21.363 1.408 N-[Au]6: 122.6 1.419 [Au] 6 Total: 471.8 C.Au4 NICS(1)zz -17.5

[Au] 3 1.447

BDE

18.7

1.477

C-H3: 119.6 C-H4: 119.6 C1-[Au]5: 122.5 C2-[Au]6: 120.7 Total: 482.4 BDE 34.1

Figure 3. The calculated relative Gibbs energies at 298 K and electronic energies (in parentheses) (kcal mol-1), bond length (Å), NICS(1)zz values (ppm), and selective bond dissociation energy (kcal mol-1) of Au-substituted 1H-indoliums and 3Hindoliums.

Note that all the Au-substituted 1H-indoliums have comparable NICS(1)zz values to the corresponding 3Hindoliums (Figure 3), indicating similar aromaticity. Thus, the higher thermodynamic stability of Au-substituted 3Hindoliums over the corresponding 3H-indoliums could not be explained by aromaticity. Again, we examined the effect of BDE on the relative stabilities between Au substituted 1H-indoliums and 3H-indolims (Figure 3). When the substituents on sp3 hybridized position are considered only, the sum of BDEs for the four calculated bonds in N.Au2.H2 (465.5 kcal mol-1) is very close to that of C.Au2.H2 (472.6 kcal mol-1). Again, the energy difference (32.1 kcal mol-1) between N.H2.Au2 and C.H2.Au2 is also in line with the ΔBDE (34.1 kcal mol-1). Although the sp2 C-Au bonds in N.H2.Au2 (127.2 and 120.3 kcal mol-1) are particularly close to the sp2 C-Au and N-Au bonds in C.H2.Au2 (122.5 and 120.7 kcal mol-1), the sp3 C-H bonds (119.6 kcal mol-1) in C.H2.Au2 are much stronger than the sp3 N-H bonds (100.4 kcal mol-1) in N.H2.Au2, leading to less stable 1H-indolium (N.H2.Au2). Furthermore the structures containing four Ausubstituted 1H-indolium and 3H-indolium in both sp3 and sp2 hybridized positions of the 5MRs have relatively small energy difference of 17.3 kcal mol-1. As shown in Figure 3, the BDE of C1-Au5 and C2-Au6 bond (128.8 and 127.7 kcal mol-1) in N.Au4 are similar to those of the C2-Au5 and NAu6 in C.Au4 (126.8 and 122.6 kcal mol-1), whereas there is a big difference between the N-Au bonds in N.Au4 (98.3 kcal mol-1) and C-Au bonds in C.Au4 (111.2 kcal mol-1), which indicates that the sp3 hybridized C-Au bond is stronger than the sp3 hybridized N-Au bond, leading to a 17.3 kcal mol-1 difference on Gibbs energies.

Note that the tetra-aurated indolium was previously synthesized and the structure was reported to be 1Hindolium.16 However, it is difficult to differentiate the carbon and nitrogen atoms by the X-ray crystallography.36 To examine the possibility of an existence of another isomer, 3H-indolium, we calculated the 13C-NMR of 5MRs in these two isomers (Figure S2). Considering the challenge in reproducing the absolute value of the experimental NMR data in organometallic complexes by DFT calculation,37-41 we choose a relative value, the difference between the largest and smallest chemical shifts (ΔC-NMR) for the carbon atoms in the 5MRs because some computational errors could be cancelled each other. Although the tetra-aurated 3H-indolium has higher thermodynamic stability by 17.3 kcal mol-1, the tetraaurated 1H-indolium has a closer ΔC-NMR to the experimental value and a smaller average absolute relative error based on the NMR data (Figure S2). As the C.Au4 is more stable than the isomer N.Au4, we next endeavor to synthesize related polyaurated compounds and discriminate the metalated regioselectivity by structural characterization. As shown in Figure 4a, we purposefully select the substrate 1 as a starting material in view of the structural characteristic of having a central carbon-carbon bond next to the amine group. Substrate 1 reacted with the Ph3PAuCl (2 equiv.) in the presence of KOH to give the -aurated complex 2. Treatment of complex 2 with oxotris((triphenylphosphine)gold)tetrafluoroborate ([(AuPPh3)3O(BF4)], 2 equiv.) led to a color change of the mixed solution from colorless to yellow. Diffusion of diethyl ether to the resulting yellow solution yielded yellow crystal of complex 1. Structural analysis by X-ray crystallography revealed that complex 3 has two C2-axis related tetra-aurated indolyl units (Figure 4b), which are connected by the central C7-C7A bond. With the C7-C7A bond as a positioning site, it is easy to differentiate the carbon and nitrogen atoms in the newly formed fivemembered ring. As shown in Figure 4, each of the nitrogen atom N1 and the carbon atom C1 is linearly coordinated to a gold atom via N1-Au1 = 2.037(6) Å and C1-Au2 = 2.032(8) Å. In contrast, the carbon atom C2 is bonded by two geminal gold atoms (C2-Au3 = 2.058(7) Å and C2-Au4 = 2.138(8) Å). Such two gold atoms together with C1 and C3 constitute a distorted tetrahedral bonding geometry for C2. The two gold atoms are held together by a strong aurophilic interaction42-44 with the Au···Au distance of 2.9055(4) Å. Aside from the biased positioning of carbon and nitrogen atoms relative to the C7-C7A bond, the bond distances in the formed five-membered ring also support the formation of the C.Au4 type structure. It is clear that the nitrogen-carbon bonds around N1 (N1-C8 = 1.372(9) Å and N1-C1 = 1.358(9) Å) are much shorter than the carboncarbon bonds around C2 (C2-C3 = 1.466(10) Å and C2-C1 = 1.418(10) Å). Particularly, the bond distance of C2-C3 is longer than the common carbon-carbon distances in an indole ring.



Figure 5. The calculated relative Gibbs free energies at 298 K (kcal mol-1), bond length (Å), NICS(1)zz values (ppm) of 3.N and 3.C.

CONCLUSIONS

Figure 4. Synthesis and crystal structure of the octa-aurated biindole complex 3. (a) Synthetic procedure for the octaaurated biindole compound 3. (b) Hydrogen atoms and tetrafluoroborate counter anions are omitted for clarity. The phenyl rings of PPh3 ligands are shown in pale pink color. Selected bond lengths and distances (Å): C1-C2 1.418(10), C2C3 1.466(10), C3-C8 1.419(10), N1-C1 1.358 (9), N1-C8 1.372(9), N1-Au1 2.037(6), C1-Au2 2.032(8), C2-Au3 2.058(7), C2-Au4 2.138(8), Au3Au4 2.906(1).

In order to evaluate the difference between the substituted sp3 hybridized C and N in the experimental structure, we investigated the aromaticity and stability of complexes 3.C and 3.N in simplified models as shown in Figure 5, in which the ligand PPh3 of compound 3 was replaced by PH3. It is understandable that complex 3.C is more stable than 3.N by 41.0 kcal mol-1 according to the energy difference (17.3 kcal mol-1) between N.Au4 and C.Au4. Again, the aromaticity of 5MRs in N.Au4 and C.Au4 is similar to each other, indicated by the comparable NICS(1)zz values (Figure 5). In order to further understand the energy difference of 41.0 kcal mol-1, we calculated the BDE of selected eight bonds on the 5MRs of 3.N and 3.C. The BDEs of Au-C and Au-N bonds are shown in Table S1 in detail. Similar to the previous results, the Au-Csp3 bonds in 3.C are stronger than the Au-N bonds in 3.N, resulting to the ΔBDE of 52.1 kcal mol-1, making the 3.C more stable, which could explain why the gold atoms prefer the C atom to the N atom. G(kcal/mol)

2 3.142 NICS(1)zz -16.1 1.413 [Au] [Au] N 2 [Au] 1.382 [Au] 2.914 1.459 [Au] NICS(1)zz -17.1 1.417 1.473 [Au] [Au] C 1.459 [Au] [Au] N N [Au] [Au] [Au] [Au] 3.153 N [Au] 3.N 0.0

[Au] [Au] 2.914 3.C -41.0

[Au] =AuPH3

The regioselectivity in hyperconjugative aromaticity is investigated by the combination of calculations with experiments. Calculations predicted that the electron withdrawing substituents prefer the sp3 hybridized C atoms to N atoms in indoliums through hyperconjugation. However, for the electron donating group, such a preference has been significantly reduced in substituted indoliums. In addition, when both the sp3 and sp2 hybridized positions are considered, the tetra-aurated 3Hindoliums are thermodynamically more stable than that of 1H-indoliums, which could be rationalized by the stronger Csp3-Au bonds in substituted 3H-indoliums over the N-Au bonds in substituted 1H-indoliums according to the BDE calculations. This prediction is reasonably verified by the experimental study via an isolation of an octa-aurated biindole compound, where the gold atoms are bonded to the sp3 carbon atoms rather than the nitrogen atoms. Our findings highlight that it is bond dissociation energy rather than aromaticity that can be used to rationalize the regioselectivity in hyperconjugative aromaticity, thus helping experimentalists to design and realize more novel hyperconjugative aromatics.

EXPERIMENTAL SECTION The All commercially available chemicals were used without further purification. The solvents used in this study were dried by standard procedures. 3,3’-Diiodo5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphthyl-2,2’-diamine45 and oxotris((triphenylphosphine)gold)tetrafluoroborate46 were synthesized according to the literature. Synthesis of 3,3'-bis((trimethylsilyl)ethynyl)5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyle-2,2'diamine. An oven-dried pressure tube containing 15 mL of dry Et3N was degassed for 30 min by bubbling N2. To this were added 3,3’-Diiodo-5,5’,6,6’,7,7’,8,8’-octahydro-1,1’binaphthyl-2,2’-diamine (108.8 mg, 0.2 mmol), trimethylsilylacetylene (196.0 mg, 2.0 mmol), Pd(PPh3)2Cl2 (56.0 mg, 0.08 mmol), and CuI (30.0 mg, 0.16 mmol) under nitrogen atmosphere. The pressure tube was tightly sealed and stirred at room temperature over 3 hours. At the end of this period, Et3N was removed in vacuo, and the reaction mixture was extracted with EtOAc/H2O. The organic layer was dried over anhydrous Na2SO4 and the solvent was removed in vacuo to obtain the crude product, which was purified by column chromatography. White solid, yield 74 mg (76%); 1H-NMR (400 MHz, CDCl3): δ 7.09 (s, 2H), 3.60 (s, 4H), 2.68-2.64 (m, 4H), 2.24-2.14 (m, 4H), 1.68–1.64 (m, 8H), 0.22 (s, 18H), 13C{1H}-NMR(100MHz, CDCl3): δ 143.5, 138.0, 132.1, 127.2, 120.4, 105.8, 102.5, 99.1, 29.1, 27.1, 23.3, 23.1, 0.3. FT-ICR-MS (ESI): calcd. for [M+H]+ (C30H41N2Si2) 485.2801, found 485.2803. Synthesis of 3,3'-diethynyl-5,5',6,6',7,7',8,8'octahydro-1,1'-binaphthyle-2,2'-diamine. Desilylation was carried out by adding n-Bu4NF (2.1 mL of a 1 M solution in THF) dropwise at room temperature to a solution of 3,3'-


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The Journal of Organic Chemistry bis((trimethylsilyl)ethynyl)-5,5',6,6',7,7',8,8'-octahydro1,1'-binaphthyle-2,2'-diamine (330.0 mg, 0.7 mmol) in 10 mL of dry THF under a nitrogen atmosphere. The reaction mixture was stirred for a further 5 h. The solvent was removed in vacuo, the reaction mixture was extracted with CH2Cl2/H2O. The organic layer was dried over anhydrous Na2SO4 and the solvent was removed in vacuo to obtain the crude product, which was purified by column chromatography. White solid, yield 116.4 mg (51%); 1HNMR (400 MHz, CDCl3): δ 7.12 (s, 2H), 3.89 (s, 4H), 3.36 (s, 2H), 2.69-2.66 (m, 4H), 2.28-2.14 (m, 4H), 1.69–1.56 (m, 8H), 13C{1H}-NMR (100MHz, CDCl ): δ 143.8, 138.3, 132.6, 127.3, 3 120.5, 104.6, 82.0, 81.2, 29.1, 27.1, 23.3, 23.1. FT-ICR-MS (ESI): calcd. for [M+H]+ (C24H25N2) 341.2013, found 341.2012. Synthesis of 2. 1 (20.0 mg, 0.06 mmol) and KOH (8.4 mg, 0.15 mmol) were dissolved in dry MeOH (2 ml). The reaction mixture was stirred for 0.5 h, then AuPPh3Cl (60.0 mg, 0.12 mmol ) was then added to the solution under stirring at room temperature for 12 hours. After being filtered through filter paper, the white solid which in the filter paper was washed with methanol and ether, and the pure product is obtained. Yield 65 mg (86%); 1H-NMR (400 MHz, CDCl3): δ 7.58-7.42 (m, 30H), 7.12 (s, 2H), 4.05 (s, 4H), 2.67-2.63 (m, 4H), 2.33-2.08 (m, 4H), 1.67–1.60 (m, 8H), 13C{1H}-NMR (100MHz, CDCl ): δ 143.8, 136.1, 134.5, 134.3, 3 132.1, 131.6, 130.2, 129.7, 129.2, 129.1, 126.3, 120.5, 107.6, 29.3, 27.0, 23.5, 23.4. 31P-NMR (162 MHz, CDCl3): δ 42.97. FTICR-MS (ESI): calcd. for [M+H]+ (C60H53Au2N2P2) 1257.3009, found 1257.3022. Synthesis of 3. 2 (6.3 mg, 0.005 mmol) and oxotris((triphenylphosphine)gold)tetrafluoroborate (14.8 mg, 0.01 mmol) were dissolved in CDCl3 (1.5 ml) with stirring at room temperature for 8h under the protection of nitrogen. Deep yellow plate crystals of 3 were acquired by diffusion of diethyl ether into the concentrated CDCl3 solution of 3. Yield 14 mg (67%); FT-ICR-MS (ESI): calcd. for [M–2BF4]2+ (C168H138Au8N2P8) 2003.8061, found 2003.8054. X-ray crystallographic analysis. Single-crystal X-ray data for 3 were collected at 173 K with Mo Ka radiation (λ = 0.71073 Å) on a Rigaku Saturn 724/724+ CCD diffractometer or Cu Kα radiation (λ = 1.54178 Å) on a Rigaku Oxford Diffraction SuperNova diffractometer. The selected crystal was mounted onto a nylon loop in polyisobutene and immersed in a low-temperature (173 K) stream of dry nitrogen gas during data collection. And the structure was solved by direct methods, and non-hydrogen atoms were located from difference Fourier maps. Nonhydrogen atoms were subjected to anisotropic refinement by full-matrix least-squares on F2 by using the SHELXTL program unless otherwise noticed. All figures were drawn by using X-seed program. Crystal data for 3 (CCDC1876273): C84H69Au4N1P4B1F4O0.5, M = 2098.96, orthorhombic, space group C2/c, a =21.8602(2) Å, b = 17.8588(2) Å, c = 39.6592(4) Å, α = 90°, β= 99.619(1)°, γ = 90°, V = 15265.1(3) Å3, Z = 8, T = 100 K, Dc = 1.827 g cm-3. The structure, refined on F2, converged for 13073 unique reflections (Rint = 0.0692) and

13714 observed reflections with I > 2σ(I) to give R1 = 0.0524 and wR2 = 0.1413 and a goodness-of-fit = 1.124.

COMPUTATIONAL DETAILS All structures were optimized at the TPSS level47 of density functional theory, and used “EmpiricalDispersion=GD3” 48 to describe the dispersion corrections. In addition, the frequency calculations were performed to confirm the characteristics of the calculated structures as minima. In the TPSS calculations, the fully relativistic effective core potentials (ECPs) with ECP46MDF49 basis set were used to describe the Sn atom ECP60MDF50 basis set for Au atom whereas the 6-31G(d) basis set51 for the C, N, P, F and H atoms were used for optimization and NICS calculation . All the optimizations were performed with the Gaussian 09 software package.52

ASSOCIATED CONTENT The Supporting Information is available free of charge on the ACS Publications website. HRESI-MS spectra, the 1H, 13CNMR and 31P spectra, and computational details (PDF). Crystallographic data for complex 3 (cif)

AUTHOR INFORMATION Corresponding Author * [email protected] * [email protected] ORCID Jun Zhu: 0000-0002-2099-3156 Author Contributions ║These authors contributed equally. Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT Financial support by Top-Notch Young Talents Program of China and NNSFC (21873079, 21573179, 21522206, 21772111 and 21661132006) is gratefully acknowledged.

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