The synthesis of BN-doped naphthalene derivatives with four different substituents

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1

Master's Thesis

The synthesis of BN-doped naphthalene derivatives with four different substituents

Hansol Kwon

Department of Chemistry

Graduate School of UNIST

2019

[UCI]I804:31001-200000223221 [UCI]I804:31001-200000223221

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The synthesis of BN-doped naphthalene derivatives with four different substituents

Hansol Kwon

Department of Chemistry

Graduate School of UNIST

3

The synthesis of BN-doped naphthalene derivatives with four different substituents

A thesis

submitted to the Graduate School of UNIST in partial fulfillment of the

requirements for the degree of Master of Science

Hansol Kwon

06/13/2019 of submission Approved by

_________________________

Advisor

Young S. Park

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The synthesis of BN-doped naphthalene derivatives with four different substituents

Hansol Kwon

This certifies that the thesis of Hansol Kwon is approved.

06/13/2019 of submission

___________________________

Advisor: Professor Young S. Park

___________________________

Professor BongSoo Kim

___________________________

Professor Han Yong Bae

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Abstract

Polycyclic aromatic hydrocarbons (PAHs) are molecules in which two or more fused benzenes are conjugated with each other. The unique properties of PAHs have led many scientists to pursue research in this area for more than 20 years. Currently, the application scope of PAHs in a wide range of fields, including organic synthesis, electronics, catalysts, and biological chemistry, is being investigated. We can tune the optical and electrochemical properties of PAHs by doping heteroatoms, such as oxygen, phosphorus, boron, and nitrogen. These heteroatom-doped compounds are called polycyclic heteroaromatics (PHAs). Their controlled properties may be used as the basis for optoelectronic devices such as organic light-emitting diodes (OLEDs), organic field-effect transistors (OFETs), and organic photovoltaics (OPVs).

Here, we initially explain the basic background related to our study. The definitions and properties of PAHs are described, in addition to those of PHAs. Among the heteroatoms, we select boron and nitrogen and study the properties of BN-doped PAH. We describe the methods of preparing BN-doped naphthalene, called 2,1-borazaronaphthalene. Furthermore, we present a strategy for incorporating different aryl groups at the desired positions of 2,1-borazaronaphthalene.

Using the bottom-up synthetic approach, we introduce the synthesis of several 2,1- borazaronaphthalene derivatives from a simple compound via sequential cross-coupling reactions and a borylative cyclization reaction. In addition, we compare the structural and optical properties of 2,1- borazaronaphthalene derivatives with the properties of the carbon analog. Finally, we discuss the synthetic efforts involved in preparing BN-doped PAHs with extended π-conjugation and the undesired products obtained during the intramolecular carbon-carbon bond formation.

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Contents

Introduction ... 12

Results and Discussion ... 18

Summary and Future Work ... 27

References ... 28

Experimental Data ... 31

General information and procedures ... 31

Detailed experimental protocols ... 32

Compiled NMR characterization data ... 40

Crystallographic data collection and structure refinement of compound 4a ... 74

HRMS spectra ... 82

References ... 91

Acknowledgements ... 92

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List of Figures

Figure 1. Examples of PAH compounds with two, three, four, and five fused benzene rings.

... 12 Figure 2. Examples of heteroatom-doped PAH compounds. ... 13

Figure 3. a. Isoelectronic relationship between CC and BN. b. Molecular consequences of BN/CC isosterism. ... 14 Figure 4. a. Structural diversity and synthesis of hexasubstituted benzenes. b.

Functionalization of pyridine derivatives. ... 15 Figure 5. Overall synthetic schemes designed through retrosynthetic analysis. ... 17

Figure 6. Superimposed ¹H NMR spectra of compounds 3a and 3b. ... 19 Figure 7. a. Molecular structure of compound 4a from single-crystal X-ray diffraction

(SCXRD). b. Molecular structure of 1,2,3,4-tetraphenylnaphthalene from single- crystal X-ray diffraction (SCXRD). ... 25 Figure 8. UV/Vis absorption spectroscopy of compounds 4a and 1,2,3,4-

tetraphenylnaphthalene in DCM. ... 26 Figure 9. UV/Vis absorption spectroscopy of 4b, 4c, 4d, 4e, and 4f in DCM. ... 26

List of Tables

Table 1. Failed intramolecular Heck cross-coupling reactions using compounds 4c, 4d, and 4e.

... 23 Table 2. Reaction conditions for the synthesis of compound 6. ... 24

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List of Schemes

Scheme 1. Synthetic methods for preparing 2,1-borazaronaphthalene. ... 16

Scheme 2. Overall synthetic schemes for preparing compound 4a. ... 18

Scheme 3. Proposed mechanism of the borylative cyclization reaction and synthesis of compounds 3a and 3b. ... 19

Scheme 4. Synthesis of compound 4b.... 20

Scheme 5. Overall synthetic schemes for preparing the 2,1-borazaronaphthalene derivative, 4f with four different aryls. ... 21

Scheme 6. Possible compounds from compound 4f. ... 21

Scheme 7. Overall synthetic schemes for compounds 4c, 4d, and 4e. ... 22

Scheme 8. Overall synthetic schemes for compound 3c. ... 24

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Abbreviations

B Boron

BCl3 Boron trichloride

BDE Bond-dissociation energy

n-Bu4NBr Tetra-n-butylammonium bromide

n-Bu4NI Tetra-n-butylammonium iodide

t-BuOK Potassium tert-butoxide

t-BuONa Sodium tert-butoxide

CDCl3 Chloroform-d

CH2Cl2 Dichloromethane

Cs2CO3 Cesium carbonate

Cu(OAc)2 Copper (II) acetate

Cu(OAc)2•H2O Copper (II) acetate monohydrate

CuI Copper (I) iodide

DBU 1,8-Diazabicyclo[5.4.0]undec-7-ene

DMA N,N-Dimethylacetamide

DMF N,N-Dimethylformamide

DPPF 1,1'-Bis(diphenylphosphino)ferrocene

ESI Electrospray ionization

Et2O Diethyl ether

Et3N Triethylamine

EtOAc Ethyl acetate

FeCl3 Iron (III) chloride

H2O Water

HCl Hydrogen chloride

HOMO Highest occupied molecular orbital

HRMS High resolution mass spectrometry

K2CO3 Potassium carbonate

K3PO4 Tripotassium phosphate

KOAc Potassium acetate

LUMO Lowest unoccupied molecular orbital

MeCN Acetonitrile

MeLi Methyllithium

MeOH Methanol

N Nitrogen

NMR Nuclear magnetic resonance

N2 Dinitrogen

Na2SO4 Sodium sulfate

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OFET Organic field-effect transistor

OLED Organic light-emitting diode

OPV Organic photovoltaic

PAH Polycyclic aromatic hydrocarbon

PdCl2 Palladium (II) chloride

PCy3 Tricyclohexylphosphine

Pd(OAc)2 Palladium (II) acetate

Pd(PCy3)2Cl2 Dichlorobis(tricyclohexylphosphine)palladium (II) Pd(PPh3)2Cl2 Bis(triphenylphosphine)palladium (II) dichloride Pd(PPh3)4 Tetrakis(triphenylphosphine)palladium (0) Pd2(dba)3 Tris(dibenzylideneacetone)dipalladium (0)

PHA Polycyclic heteroaromatic

PhBF3K Potassium phenyltrifluoroborate

PivOH 2,2-Dimethylpropanoic acid

PPh3 Triphenylphosphine

Rh Rhodium

SCXRD Single-crystal X-ray diffraction

SiCl4 Silicon tetrachloride

1,2,4-TCB 1,2,4-Trichlorobenzene

THF Tetrahydrofuran

TLC Thin-layer chromatography

TOF Time-of-flight

UV/Vis spectroscopy Ultraviolet/visible spectroscopy

ZnCl2 Zinc chloride

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Introduction

Polycyclic aromatic hydrocarbons (PAHs) consist of two or more fused benzene rings. The simplest PAHs are naphthalene, anthracene, and phenanthrene (Figure 1). These π-electron conjugated systems have been extensively studied over the last few decades because of their intriguing optical and electronic properties^1-7and wide application in optoelectronics, fundamental science, and catalysis.^8-11 Currently, these compounds are further developed by incorporating heteroatoms into PAHs to obtain novel materials called polycyclic heteroaromatic (PHA) compounds.

Figure 1. Examples of PAH compounds with three, four, and five fused benzene rings.

The chemistry of heteroaromatic compounds is an interesting field that has been studied over nearly two centuries.¹² The heterocyclic science has been focused on developing a number of applications in organic/inorganic chemistry, biological chemistry, and material sciences.¹²

Currently, synthetic chemists are suggesting potential applications for graphene by studying large PAHs. However, the use of graphene as a semiconductor is restricted because the currently available technology does not provide access to this basic material. Furthermore, graphene does not have a bandgap that would enable its use in key applications.¹³ The bandgap of graphene can be controlled by cutting graphene into nanoribbons or by doping heteroatoms into graphene.

In molecular electronics, heteroatom doping of graphene is an innovative process for tuning the bandgap because it changes the frontier molecular orbital energy levels, thereby allowing the use of

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graphene in device applications. Thus, the incorporation of heteroatoms in graphene can help modulate its properties such as electrochemical action, charge polarization, bandgap opening, and n- or p-type semiconductor characteristics.^14-16 However, using the top-down doping techniques, which lead to the random incorporation of the dopants, it is impossible to control the position of the dopants. The use of high-temperature strategies has limitations in regard to controlling the doping positions.¹⁷ Therefore, a strategy is required for doping heteroatoms at the exact positions. Among the possible strategies, a bottom-up synthesis method can be used to place a desired dopant at a desired position.

Since the beginning of the PHA chemistry, nitrogen has been an essential "dopant" due to the accessibility of engineering techniques. Currently, considerable efforts are being undertaken toward the construction of large heteroaromatic skeletons containing boron¹⁸ or phosphorus.¹⁹ These various usable heteroatoms facilitate the design and synthesis of useful PHA molecules (Figure 2).

Figure 2. Examples of heteroatom-doped PAH compounds.

We focused on the doping of PAHs with boron and nitrogen for developing azaborine chemistry.

Boron-nitrogen heteroarenes are promising for practical applications in many areas of chemistry.^20-27 Studies into BN heteroarenes have shed light on many innovations in the synthesis of these compounds.

The substitution of a C-C bond with an isoelectronic and isosteric BN unit results in unique properties.

Isoelectronic species are atoms or molecules containing the same number of electrons but with different nuclear charges. In addition, isosteric molecules have the same number of atoms with a similar size, and the same valence electron numbers (Figure 3a).²¹

Despite the same total valence electron count, differences in molecular properties can be expected when replacing the C-C unit with the corresponding BN unit. The comparison between ethene and aminoborane is illustrated in Figure 3b. The dipole moment of ethene is zero due to the symmetry of

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the molecule,²⁸ and the bond-dissociation energy (BDE) is 174.1 kcal/mol, which includes the σ-bond contribution (109.1 kcal/mol) and the π-bond contribution (65 kcal/mol).^29,30 In contrast, aminoborane, which is the BN analog of ethene, has a dipole moment (1.84 D)³¹ and the BDE of aminoborane is 139.7 kcal/mol and is composed of the σ-bond contribution (109.8 kcal/mol) and the π-bond contribution (29.9 kcal/mol).³² Owing to these properties, CC/BN isosterism is the strategy to use for fine-tuning the frontier molecular orbitals of the target materials. Therefore, we chose BN-doped naphthalene, called 2,1-borazaronaphthalene, as our synthetic core system.

Figure 3. a.Isoelectronic relationship between CC and BN.b.Molecular consequences of BN/CC isosterism.

Although azaborine chemistry is an emerging field, studies on BN-containing molecules for further applications are still hampered by the limited number of available synthetic strategies. Thus, it is imperative to develop the azaborine chemistry and investigate new azaborine compounds. Furthermore, the functionalization of BN-containing molecules will enable us to synthesize various new azaborine derivatives.^33-36

We report a new functionalization of 2,1-borazaronaphthalene through the bottom-up synthetic approach, in which the hydrogens at the C1, C2, C3, and C4 positions were replaced by the desired aryl groups. Using this strategy, we expect to synthesize a considerable number of 2,1-borazaronaphthalene derivatives.

There have been similar studies about the functionalization of benzene and pyridine. First, Itami’s group reported the functionalization of benzene in 2015.³⁷ Benzene has six hydrogen atoms that can be replaced by other functional substituents. According to Burnside’s lemma,^38,39 the number of possible benzene derivatives with six different substituents is 4,291 (Figure 4a). Upon incorporating various substituents into benzene, its structural diversity becomes enormous. Second, Park’s group reported the functionalization of pyridine in 2013.⁴⁰ They provided a synthetic pathway for pyridine derivatives with five different substituents (Figure 4b). Inspired by these studies, we decided to incorporate various aryl groups into the BN-core of 2,1-borazaronaphthalene.

a b

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Figure 4. a. Structural diversity and synthesis of hexasubstituted benzenes. b. Functionalization of pyridine derivatives.

First, we searched for methods to synthesize 2,1-borazaronaphthlaenes. 2,1-Borazaronaphthalene is a BN-doped naphthalene molecule, which is a useful building block for larger functional BN-doped PAHs. However, there are only few reported synthetic methods for 2,1-borazaronaphthalenes:⁴¹ Dewar’s, Paetzold’s, and Pei’s synthesis (Scheme 1). In 1959, Dewar first reported the synthesis of 2,1- borazaronaphthalene using BCl3 (Scheme 1a).^42,43 He further functionalized 2,1-borazaronaphthalene boron with a phenyl group using an aryl Grignard reagent (Scheme 1a-1).⁴⁴ Paetzold synthesized the 2,1-borazaronaphthalene derivative using ZnCl2 and phenylacetylene to incorporate a phenyl group at the C4 position.^45,46 While Dewar utilized 2-ethenylaniline derivatives as starting molecules, Pei reported new a synthetic method using 2-ethynylaniline derivatives and dichlorophenylborane to replace hydrogens with other substituents at the C2 (B), C3, and C4 positions.⁴⁷

However, these methods for synthesizing 2,1-borazaronaphthalene derivatives have some limitations.⁴¹ All of these methods utilize BCl3 or PhBCl2, which limits the incorporation of various aryl groups into boron.

To overcome these problems, Molander and coworkers attempted to develop an adaptable, compact, and metal-free synthesis of 2,1-borazaronaphthalenes under mild reaction conditions.⁴¹ They generated R−BCl2 (R = aryl, alkynyl, alkenyl, and alkyl) reagents in situ using R−BF3K with SiCl4 and further incorporated the desired aryl groups on the boron atom. By modifying Molander’s and Pei’s

b a

16

methods, we developed our protocol for the synthesis of new 2,1-borazaronaphthalene derivatives with different aryl groups at the C1 (N), C2 (B), C3, and C4 positions.

Scheme 1. Synthetic methods for preparing 2,1-borazaronaphthalene.

To synthesize our target BN-doped PAHs, we carried out a retrosynthetic analysis (Figure 5). We envisioned that our target molecules can be prepared from 2,1-borazaronaphthalene compounds with four aryl groups via a cyclodehydrogenation reaction or an intramolecular Heck cross-coupling reaction.

Next, we drew inspiration from the synthesis of 2,1-borazaronaphthalene compounds by Molander’s and Pei’s approaches^41,47 and hypothesized the formation of the precursor for the target molecule from the N-aryl-(2-arylethynyl)aniline derivative and subsequent Suzuki-Miyaura cross-coupling reaction.

Then, we would prepare our key intermediates from 2-iodoaniline via the Buchwald-Hartwig cross- coupling reaction and the Sonogashira cross-coupling reaction. Based on this analysis, we selected 2- iodoaniline as our starting material. In this regard, we planned to synthesize the desired 2,1- borazaronaphthalene compounds with four aryl groups in four steps. Furthermore, we would carefully control the formation of new C-C bonds between aryl groups to extend the fused aromatic rings and systematically study the effects of the π-conjugation on BN-doped PAHs.

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Figure 5. Overall synthetic schemes designed through retrosynthetic analysis.

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Results and Discussion

We initially began our studies by synthesizing 2,1-borazaronaphthalene with four phenyl groups (4a) via sequential cross-coupling reactions and borylative cyclization (Scheme 2). First, we synthesized compound 1a in an isolated yield of 69% via the Chan-Lam cross-coupling reaction based on a known literature procedure.^48,49 Subsequently, we reacted 1a with phenylacetylene in the presence of Pd(PPh3)2Cl2 and CuI via the Sonogashira cross-coupling reaction, producing compound 2a in an isolated yield of 81%.

Scheme 2. Overall synthetic schemes for preparing compound 4a.

Next, to form the boron-nitrogen bond, we used Molander’s and Pei’s borylative cyclization reactions and obtained compound 3a in an isolated yield of 85%. According to Molander’s and Pei’s reports,^41,47 the proposed mechanism is shown in Scheme 3. First, dichlorophenylborane is generated in situ from potassium phenyltrifluoroborate and silicon tetrachloride. Then, dichlorophenylborane reacts with nitrogen with the removal of HCl to furnish the boron-nitrogen intermediate. Next, the alkynyl group reacts with the empty orbital of the boron atom. Subsequently, the halogen atom (X) attacks the electron-deficient alkyne to form 2,1-borazaronaphthalene. In addition, the halogen atom can be altered when a different halide source such as n-Bu4NBr or n-Bu4NI is added to the reaction mixture.

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Scheme 3. Proposed mechanism of the borylative cyclization reaction and synthesis of compounds 3a and 3b.

On the basis of this mechanism, we prepared compound 3b containing bromide at the C4 position.

Unfortunately, we could not completely separate 3b from the chloro-substituted compound. Thus, we obtained a mixture of bromo- and chloro-substituted compounds at a ratio of approximately 4:1, as shown in Figure 6, and used it in the next step without additional purification.

Figure 6. Superimposed ¹H NMR spectra of compound 3a, and 3b.

Finally, the halogen groups at the C4 position of 2,1-borazaronaphthalene allowed us to further introduce aryl groups. We synthesized compound 4a via the Suzuki-Miyaura cross-coupling reaction from compound 3b and phenylboronic acid in an isolated yield of 71% over two steps. Similarly, we

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obtained compound 4b from p-tolylboronic acid in an isolated yield of 72% over two steps (Scheme 4).

Scheme 4. Synthesis of compound 4b.

With compound 4a in hand, we performed the Scholl reaction using FeCl3 as an oxidant to synthesize the BN-doped PAHs. Unfortunately, we could not identify the product because of the unexpected formation of a mixture of compounds,^50-52 as revealed by TLC monitoring. Therefore, we planned to synthesize chloro-substituted 2,1-borazaronaphthalenes as alternatives to attempt the intramolecular Heck cross-coupling reaction and to control the formation of C-C bonds.

Using the appropriate reaction conditions associated with the reactions through the synthesis of compound 4a, we proceeded to synthesize 2,1-borazaronaphthalene derivatives with four different aryl groups using parallel approaches. First, we synthesized compound 4f, which has three chloro- substituents (Scheme 5). Most of the reactions involved in the synthesis of compound 4f were similar to those for compound 4a, as described previously. However, we found that compound 1b was not formed efficiently with 2-iodoaniline and 2-chlorophenylboronic acid by the Chan-Lam cross-coupling reaction that we previously adopted. To avoid this problem, we reacted 2-iodoaniline with 1-chloro-2- iodobenzene by the palladium-catalyzed Buchwald-Hartwig cross-coupling reaction. The reaction afforded the desired compound 1b in a reasonable yield (37%), which was used in the next step without additional optimization processes. Following the same reaction conditions as those for the synthesis of 4a, we synthesized 2d and 4f (via 3f) in isolated yields of 95% and 70% (over two steps), respectively.

In addition, compound 3f was obtained as a mixture of bromo- and chloro-substituted molecules at a ratio of approximately 6:1 (Figure S29).

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Scheme 5. Overall synthetic schemes for preparing the 2,1-borazaronaphthalene derivative, 4f with four different aryls.

With compound 4f in hand, we investigated the palladium-catalyzed intramolecular Heck cross- coupling reactions to form intramolecular C-C bonds. We could not identify our target product by TLC.

Thus, we anticipated the formation of numerous compounds during the reaction such as C-C single, double, and triple bonds, along with the formation of a five-membered ring (Scheme 6). We decided to design and prepare new compounds to ensure that the reaction proceeds with the six-membered ring compounds.

Scheme 6. Possible compounds from compound 4f.

Thus, we prepared compounds 4c, 4d, and 4e containing two chloro substituents in isolated yields of

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78%, 95%, and 76%, respectively (Scheme 7). Subsequently, we attempted to synthesize compounds 5c, 5d, and 5e via the intramolecular Heck cross-coupling reaction. However, we could not obtain the desired compounds. The detailed reaction conditions are summarized in Table 1. Under one set of reaction conditions, the starting material was recovered. Under another set of reaction conditions, the starting material decomposed to form two or more spots in the TLC analysis. When we used t-BuOK as a base, the starting materials rapidly decomposed in 5 min.

Scheme 7. Overall synthetic schemes for synthesis of compounds 4c, 4d, and 4e.

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Table 1. Failed intramolecular Heck cross-coupling reactions using compounds 4c, 4d, and 4e.

Entry Substrate Pd source Base Additive Solvent Yield (%)

1 4c Pd(OAc)2 K2CO3 PCy3 o-Xylene 0

2 4c Pd(OAc)2 DBU PCy3 DMF 0

3 4c Pd(OAc)2 KOAc PPh3 MeCN 0

4 4d Pd(OAc)2 Cs2CO3 PCy3 o-Xylene/H2O 0

5 4d Pd(OAc)2 Cs2CO3 PCy3 Pyridine 0

6 4d - t-BuOK - Pyridine 0

7 4e Pd(OAc)2 Cs2CO3 PCy3 o-Xylene/MeOH 0

8 4e Pd(OAc)2 Cs2CO3 PCy3 Pyridine/MeOH 0

9 4e Pd(OAc)2 KOAc PCy3 Pyridine 0

10 4e Pd(OAc)2 t-BuOK PCy3 Pyridine 0

11 4e Pd(dba)3 Cs2CO3 PPh3/PivOH o-Xylene 0

12 4e Pd(OAc)2 Cs2CO3 PCy3 o-Xylene 0

13 4e Pd(OAc)2 Cs2CO3 PCy3/PivOH DMA 0

14 4e Pd(PPh3)2Cl2 Cs2CO3 PCy3/PivOH DMA 0

15 4e Pd(PCy3)2Cl2 Cs2CO3 PivOH DMA 0

16^a 4e Pd(OAc)2 Cs2CO3 PCy3 o-Xylene/DMF 0

17^a 4e Pd(OAc)2 Cs2CO3 - DMA 0

This reaction was performed in a microwave at 190 °C.

Thus, we decided to synthesize the simple model compound 3c, which allows the formation of only one C-C bond. By introducing the biphenyl moiety, we could avoid the Suzuki-Miyaura cross- coupling step and quickly obtain 3c (Scheme 8). Then, we reacted 3c to test the palladium-catalyzed intramolecular Heck cross-coupling reaction. We observed that the BN bond dissociated under the reaction conditions that we tested, and re-cyclization occurred to form an indole ring (Table 2). We plan to apply other mild reaction conditions at room temperature using PdCl2 and carboxylic acid additives.⁵³

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Scheme 8. Overall synthetic schemes for synthesis of compound 3c.

Table 2. Reaction conditions for the synthesis of compound 6.

Entry Pd source Base Additive Solvent Time Yield (5c:6) (%)

1 Pd(OAc)2 Cs2CO3 PCy3 o-Xylene 3 d 0:55

2 Pd(PCy3)2Cl2 Cs2CO3 PivOH DMA 13 h 0:60

3^a Pd(PCy3)2Cl2 Cs2CO3 - DMA 10 min 0:88

a This reaction was performed in microwave at 190 °C.

All products were confirmed by ¹H and ¹³C NMR spectroscopy and HRMS. The molecular structure of compound 4a was confirmed using a single crystal structure, which was obtained by slow evaporation from a mixture of dichloromethane and hexane. The X-ray crystal data of compound 4a are summarized in the experimental section. The comparison between compound 4a and 1,2,3,4- tetraphenylnaphthalene⁵⁴ is illustrated in Figure 7. Unfortunately, the molecular structure of 4a was not fully solved. Because 4a is symmetric, we solved the structure using the pbcn space group, which is a way to get only one part of symmetry and print it like a décalcomanie. Thus, we obtained the molecular structure of 4a, in which B-N and C-C bonds co-exist in a 50:50 ratio. Compound 4a has a longer B-N bond (1.397 Å ) in comparison to that of 1,2,3,4-tetraphenylnaphthalene (1.381 Å ).

25

Figure 7. a. Molecular structure of compound 4a from single-crystal X-ray diffraction (SCXRD). b. Molecular structure of 1,2,3,4-tetraphenylnaphthalene from SCXRD.

Next, we characterized compound 4a and 1,2,3,4-tetraphenylnaphthalene by ultraviolet/visible (UV/Vis) spectroscopy. The absorption spectra of these compounds were recorded in CH2Cl2 solution (Figure 8). As in the case of benzene versus 1,2-dihydro-1,2-azaborine,⁵⁵ the BN-doped compound showed a redshifted absorption peak at λabs = 319 nm and a smaller HOMO-LUMO energy bandgap (3.89 eV) compared to that of 1,2,3,4-tetraphenylnaphthalene (λabs = 295 nm, 4.20 eV, respectively). In addition, compounds 4b, 4c, 4d, 4e, and 4f exhibited similar absorbance peaks (λabs = 326-328 nm) and HOMO-LUMO energy bandgaps in the range 3.78 to 3.80 eV (Figure 9).

a b

1.397 Å 1.381 Å

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Figure 9. UV/Vis absorption spectroscopy of 4b, 4c, 4d, 4e, and 4f in DCM.

Figure 8. UV/Vis absorption spectroscopy of compounds 4a and 1,2,3,4-tetraphenylnaphthalene in DCM.

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Summary and Future Work

We have described the design and synthetic strategies of 2,1-borazaronaphthalene derivatives and BN-doped PAHs with extended π-conjugation. The synthesis of 2,1-borazaronaphthalene derivatives with four different aryl groups is advantageous because each aryl group can be introduced at the desired position via a bottom-up approach. In addition, this convenient, efficient, and modular protocol involves simple synthetic steps.

Currently, we are in the process of screening intramolecular Heck cross-coupling reactions to prepare the desired number of C-C bonds at the desired positions.

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References

1. Y. Geng, A. Tang, K. Tajima, Q. Zeng, E. Zhou, J. Mater. Chem. A 2019, 7, 64–96.

2.Z. Cai, M. A. Awais, N. Zhang, L. Yu, Chem 2018, 4, 2538–2570.

3. W. Jiang, Y. Li, Z. Wang, Chem. Soc. Rev. 2013, 42, 6113–6127.

4. F. Jäkle, Chem. Rev. 2010, 110, 3985–4022.

5. T. Baumgartner, R. Réau, Chem. Rev. 2006, 106, 4681–4727.

6. U. H. F. Bunz, J. U. Engelhart, B. D. Lindner, M. Schaffroth, Angew. Chem. Int. Ed. 2013, 52, 3810–

3821.

7. M. Brasholz, Angew. Chem. Int. Ed. 2017, 56, 10280–10281.

8. Q. Ye, C. Chi, Chem. Mater. 2014, 26, 4046–4056.

9. L. A. Ponomarenko, F. Schedin, M. I. Katsnelson, R. Yang, E. W. Hill, K. S. Novoselov A. K. Geim, Science 2008, 320, 356–358.

10. J. Wu, W. Pisula, K. Müllen, Chem. Rev. 2007, 107, 718–747.

11. J. E. Anthony, Chem. Rev. 2006, 106, 5028–5048.

12. M. Stępien, E. Gońka, M. Żyła, N. Sprutta, Chem. Rev. 2017, 117, 3479–3716.

13. F. Schwierz, Nat. Nanotechnol. 2010, 5, 487−496.

14. X. Wang, G. Sun, P. Routh, D.-H. Kim, W. Huang, P. Chen, Chem. Soc. Rev. 2014, 43, 7067−7098.

15.U. N. Maiti, W. J. Lee, J. M. Lee, Y. Oh, J. Y. Kim, J. E. Kim, J. Shim, T. H. Han, S. O. Kim, Adv.

Mater. 2014, 26, 40−67.

16. J. Duan, S. Chen, M. Jaroniec, S. Z. Qiao, ACS Catal. 2015, 5, 5207−5234.

17. S. Zhang, S. Tsuzuki, K. Ueno, K. Dokko, M. Watanabe, Angew. Chem. Int. Ed. 2015, 54, 1302−1306.

18. A. Escande, M. J. Ingleson, Chem. Commun. 2015, 51, 6257−6274.

19. T. Baumgartner, Acc. Chem. Res. 2014, 47, 1613−1622.

20. M. J. D. Bosdet, W. E. Piers, Can. J. Chem. 2009, 87, 8−29.

21. A. J. Ashe, Organometallics 2009, 28, 4236−4248.

29

22. P. G. Campbell, A. J. V. Marwitz, S.-Y. Liu, Angew. Chem. Int. Ed. 2012, 51, 6074−6092.

23. X.-Y. Wang, J.-Y. Wang, J. Pei, Chem. Eur. J. 2015, 21, 3528−3539.

24. A. Hübner, M. Bolte, H.-W. Lerner, M. Wagner, Angew. Chem. Int. Ed. 2014, 53, 10408−10411.

25. A. Hübner, T. Kaese, M. Diefenbach, B. Endeward, M. Bolte, H.-W. Lerner, M. C. Holthausen, M.

Wagner, J. Am. Chem. Soc. 2015, 137, 3705−3714.

26. D.-T. Yang, S. K. Mellerup, X. Wang, J.-S. Lu, S. Wang, Angew. Chem. Int. Ed. 2015, 54, 5498−5501.

27. Y.-G. Shi, D.-T. Yang, S. K. Mellerup, N. Wang, T. Peng, S. Wang, Org. Lett. 2016, 18, 1626−1629.

28. R. H. Pritchard, C. W. Kern, J. Am. Chem. Soc. 1969, 91, 1631–1635.

29. S. J. Blanksby, G. B. Ellison, Acc. Chem. Res. 2003, 36, 255–263.

30. I. Alkorta, J. Elguero, Struct. Chem. 1998, 9, 59–63.

31. M. Sugie, H. Takeo, C. Matsumura, Chem. Phys. Lett. 1979, 64, 573–575.

32. D. J. Grant, D. A. Dixon, J. Phys. Chem. A 2006, 110, 12955–12962.

33. J. Pan, J. W. Kampf, A. J. Ashe, Org. Lett. 2007, 9, 679−681.

34. A. N. Brown, B. Li, S.-Y. Liu, J. Am. Chem. Soc. 2015, 137, 8932−8935.

35. A. N. Brown, B. Li, S.-Y. Liu, Tetrahedron 2019, 75, 580−583.

36.A. W. Baggett, M. Vasiliu, B. Li, D. A. Dixon, S.-Y. Liu, J. Am. Chem. Soc. 2015, 137, 5536−5541.

37. S. Suzuki, Y. Segawa, K. Itami, J. Yamaguchi, Nat. Chem. 2015, 7, 227–233.

38. W. Burnside, Theory of Groups of Finite Order, Cambridge Univ. Press 1897.

39. G. Pólya, R.C. Reade, Combinatorial Enumerations of Groups, Graphs, and Chemical Compounds, Springer 1987.

40. N. S. Y. Loy, A. Singh, X. Xu, C.-M. Park, Angew. Chem. Int. Ed. 2013, 52, 2212–2216.

41. S. R. Wisniewski, C. L. Guenther, O. A. Argintaru, G. A. Molander, J. Org. Chem. 2014, 79, 365–

378.

42. M. J. S. Dewar, R. Dietz, J. Chem. Soc. 1959, 2728–2730.

43. M. J. S. Dewar, J. Hashmall, V. P. Kubba, J. Org. Chem. 1964, 29, 1755–1757.

44. M. J. S. Dewar, R. Dietz, V. P. Kubba, A. R. Lepley, J. Am. Chem. Soc. 1961, 83, 1754–1756.

30

45. P. I. Paetzold, G. Stohr, H. Maisch, H. Lenz, Chem. Ber. 1968, 101, 2881–2888.

46. P. Paetzold, C. Stanescu, J. R. Stubenrauch, M. Bienmüller, U. Englert, Z. Anorg. Allg. Chem. 2004, 630, 2632–2640.

47. F.-D. Zhuang, J.-M. Han, S. Tang, J.-H. Yang, Q.-R. Chen, J.-Y. Wang, J. Pei, Organometallics 2017, 36, 2479–2482.

48. I. Melnika, K. Bringis, M. Katkevics, Chem. Heterocycl. Compd. 2013, 49, 529–539.

49. J. H. Park, E. Kim, Y. K. Chung, Org. Lett. 2008, 10, 4719–4721.

50. J. L. Ormsby, T. D. Black, C. L. Hilton, Bharat, B. T. King, Tetrahedron 2008, 64, 11370–11378.

51. X. Dou, X. Yang, G. J. Bodwell, M. Wagner, V. Enkelmann, K. Müllen, Org. Lett. 2007, 9, 2485–

2488.

52. C. Tönshoff, M. Müller, T. Kar, F. Latteyer, T. Chassé, K. Eichele, H. F. Bettinger, ChemPhysChem 2012, 13, 1173–1181.

53. Y. Tanji, N. Mitsutake, T. Fujihara, Y. Tsuji, Angew. Chem. Int. Ed. 2018, 57, 10314–10317.

54. W. H. Ojara, H. L. Gustafson, C. R. Ojala, Acta Cryst. 1994, 50, 1602–1604.

55. A. J. V. Marwitz, M. H. Matus, L. N. Zakharov, D. A. Dixon, S.-Y. Liu, Angew. Chem. Int. Ed. 2009, 48, 973–977.

31

Experimental Data

General information and procedures

All chemicals were purchased from TCI, Combi-Blocks, Daejung Chemicals, or Samchun Chemical. All chemicals and solvents were used without further purification, unless otherwise noted.

Solvents such as 1,2,4-trichlorobenzene (TCB) and o-xylene were dried with 3 Å molecular sieves. The glassware was oven dried at 110°C overnight. All reactions were performed under dry argon, unless otherwise noted. Analytical thin-layer chromatography (TLC) was performed on silica gel coated glass sheets with F254 indicator. Flash chromatography was performed using Isolera Spektra System (Biotage) according to the manufacturer’s recommended protocols. All yields given refer to isolated yields.

All intermediates and the product were characterized with a combination of ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, UV-vis spectroscopy, and single crystal X-ray diffraction (SCXRD). The ¹H and ¹³C spectra were recorded on a Bruker AVANCE III HD (400.2 MHz), an Agilent 400M NMR. Data were reported as follows: chemical shifts in ppm (δ), multiplicity (s = singlet, d = doublet, br = broad singlet, m = multiplet), coupling constants J (Hz), and integration.

The chemical shifts for the NMR data were referenced as follows: for samples in CDCl3, the ¹H NMR was referenced to tetramethylsilane at 0.00 ppm, and the ¹³C NMR was referenced to the solvent peak at 77.16 ppm. Accurate mass measurements via electrospray ionization (ESI) high resolution mass spectrometry (HRMS) were obtained on a JEOL AccuTOF4G+DART time-of-flight (TOF) instrument.

UV-vis spectra were recorded on a Jasco V-760 spectrophotometer with a quartz cuvette (path length, 1 cm). Spectroscopic grade dichloromethane was used to measure the absorption spectroscopy.

32

Detailed experimental protocols

The experimental procedure and spectroscopic data for all compounds are reported in here.

However, several spectroscopic data (typically ¹H, ¹³C NMR) are not fully characterized; 1) the aromatic carbon ipso to the boron atom was not observed on ¹³C NMR due to quadrupolar relaxation; 2) compounds 3b, 3d, 3e, and 3f were reported as a mixture of products since they could not be isolated from chloro-substituted compounds.

Scheme S1. Synthesis of compounds 4a and 4b.

The compounds 1a¹ and 2a² were prepared efficiently via Chan-Lam cross-coupling reaction and Sonogashira cross-coupling reaction by following previously reported methods.

A. 2-([1,1'-Biphenyl]-2-ylethynyl)-N-phenylaniline (2b).

To a mixture of 1a (2.4 g, 8.0 mmol), Pd(PPh3)2Cl2 (0.11 g, 0.16 mmol), CuI (0.06 g, 0.32 mmol) in Et3N (50 mL) was added 4-ethynylbiphenyl (1.7 mL, 9.6 mmol) under argon atmosphere. Then, the reaction mixture was stirred at room temperature for 6 h. After finishing the reaction, the solvent was removed in vacuo. The resulting mixture was dissolved in EtOAc. The organic layer was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (100/0 to 86/14 hexanes/CH2Cl2)over silica gel to give 2b as a yellow solid (2.7 g, 97% yield). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.66–7.61 (m, 3H), 7.38–7.37 (m, 2H), 7.36–7.31 (m, 4H), 7.29–7.25 (m, 2H), 7.23–7.19 (m, 1H), 7.14–7.08 (m, 2H), 7.04–6.99 (m, 1H), 6.96 (dd, J = 8.8, 2 Hz, 2H), 6.76–6.72 (m, 1H), 6.01 (s, 1H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 145.1, 143.5, 141.4, 140.8, 132.8, 132.6, 129.6, 129.4, 129.17, 129.15, 128.5, 128.2, 127.8, 127.2, 122.7, 121.7, 121.1, 118.9, 113.1, 110.0, 95.4, 88.8; HRMS m/z calcd for C26H20N [M + H]⁺ 346.1590, found 346.1595 (Δ = 1.4 ppm).

B. 4-Chloro-1,2,3-triphenyl-1,2-dihydrobenzo[e][1,2]azaborinine (3a).

To a 100 mL Schlenk flack under argon atmosphere were added 2a (0.21 g, 0.78 mmol) and

33

PhBF3K (0.29 g, 1.6 mmol) in 1,2,4-trichlorobenzene (3.0 mL), and the reaction mixture was subjected to degas and backfill with argon for three times. Then, SiCl4 (0.20 mL, 1.2 mmol) and Et3N (0.10 mL, 0.78 mmol) were added to the flask sequentially. The reaction mixture was stirred at 220 °C for 48 h.

After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (eluent: 100/0 to 67/33 hexanes/CH2Cl2)over silica gel to give 3a as a white solid (0.26 g, 85% yield). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 8.46 (dd, J = 8.0, 2 Hz, 1H), 7.41–7.28 (m, 4H), 7.25–7.17 (m, 3H), 7.14–7.06 (m, 5H), 6.96 (dd, J = 8.4, 1 Hz, 1H), 6.92–6.81 (m, 5H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 143.7, 143.4, 143.2, 142.0, 132.8, 129.6, 129.3, 129.14, 129.10, 127.6, 127.4, 127.2, 126.4, 126.3, 125.9, 123.6, 122.2, 118.2 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation. One aromatic carbon was not observed due to the accidental overlap.); HRMS m/z calcd for C26H20BClN [M + H]⁺ 392.1372, found 392.1378 (Δ = 1.5 ppm).

C. 4-Bromo-1,2,3-triphenyl-1,2-dihydrobenzo[e][1,2]azaborinine (3b).

To a 100 mL Schlenk flack under argon atmosphere were added 2a (0.25 g, 0.93 mmol) and PhBF3K (0.35 g, 1.9 mmol) in 1,2,4-trichlorobenzene (3.5 mL), and the reaction mixture was subjected to degas and backfill with argon for three times. Then, SiCl4 (0.16 mL, 1.4 mmol) and Et3N (0.10 mL, 0.70 mmol) were added to the flask sequentially. The reaction mixture was stirred at 220 °C for 48 h.

After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (eluent: 100/0 to 67/33 hexanes/CH2Cl2)over silica gel to give 3b as a white solid (0.36 g, Br : Cl = 4 : 1

).

¹H NMR (400.2 MHz, CDCl3) ppm, δ; 8.51–

8.44 (m, 1H), 7.39–7.28 (m, 4H), 7.24–7.16 (m, 3H), 7.13–7.08 (m, 3H), 7.06–7.04 (m, 2H), 6.93 (d, J

= 8.4 Hz, 1H), 6.89–6.81 (m, 5H)

;

¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 144.7, 143.5, 143.1, 139.0, 132.9, 132.8, 130.9, 129.7, 129.4, 129.3, 127.5, 127.3, 126.5, 126.4, 126.0, 124.7, 122.6, 118.3 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation. One aromatic carbon was not observed due to the accidental overlap.); HRMS m/z calcd for C26H20BBrN [M + H]⁺ 436.0867, found 436.0874 (Δ = 1.6 ppm).

D. 3-([1,1'-Biphenyl]-2-yl)-4-chloro-1,2-diphenyl-1,2-dihydrobenzo[e][1,2]azaborinine (3c).

To a 100 mL Schlenk flack under argon atmosphere were added 2b (0.13 g, 0.56 mmol) and PhBF3K (0.21 g, 1.1 mmol) in 1,2,4-trichlorobenzene (2.0 mL), and the reaction mixture was subjected to degas and backfill with argon for three times. Then, SiCl4 (0.10 mL, 0.84 mmol) and Et3N (0.10 mL, 0.56 mmol) were added to the flask sequentially. The reaction mixture was stirred at 220 °C for 48 h.

After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (100/0 to 75/25 hexanes/CH2Cl2) over silica gel to

34

give 3c as a white solid (0.16 mg, 59% yield). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 8.47–8.44 (m, 1H), 7.43–7.24 (m, 6H), 7.19–7.02 (m, 7H), 6.87–6.83 (m, 2H), 6.78–6.75 (m, 2H), 6.72–6.67 (m, 3H), 6.29 (dd, J = 7.6, 1 Hz, 2H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 144.6, 143.30, 143.27, 141.4, 140.6, 140.5, 133.2, 131.1, 129.8, 129.7, 129.6, 129.1, 129.0, 128.6, 127.5, 127.4, 127.1, 127.0, 126.6, 126.41, 126.37, 125.9, 123.7, 122.1, 118.2 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation); HRMS m/z calcd for C32H23BClNNa [M + Na]⁺ 490.1510, found 490.1515 (Δ = 1.0 ppm).

E. 1,2,3,4-Tetraphenyl-1,2-dihydrobenzo[e][1,2]azaborinine (4a).

To a mixture of 3b (2.0 g, 4.6 mmol), phenylboronic acid (1.1 g, 9.2 mmol), and Pd(PPh3)4 (0.27 g, 0.23 mmol) in toluene (60 mL) was added K3PO4 (0.97 g, 4.6 mmol) in H2O (6.0 mL) under argon atmosphere. The reaction mixture was refluxed for 36 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (100/0 to 80/20 hexane/CH2Cl2) over silica gel to give compound 4a as a white solid (1.9 g, 71% yield starting from compound 2a). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.49 (dd, J = 8.4, 2 Hz, 1H), 7.33–7.17 (m, 11H), 7.11–7.07 (m, 1H), 7.00 (d, J = 8.4 Hz, 1H), 6.90–6.75 (m, 10H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 152.4, 144.2, 143.5, 142.3, 140.1, 133.0, 130.6, 130.4, 129.6, 129.3, 129.2, 128.0, 127.7, 127.0, 126.74, 126.68, 126.3, 126.1, 126.0, 124.5, 121.3, 118.0 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation, One aromatic carbon was not observed due to the accidental overlap.); HRMS m/z calcd for C32H25BN [M + H]⁺ 434.2064, found 434.2069 (Δ = 1.2 ppm).

F. 1,2,3-Triphenyl-4-(p-tolyl)-1,2-dihydrobenzo[e][1,2]azaborinine (4b).

To a mixture of 3b (2.0 g, 3.9 mmol), p-tolylboronic acid (1.1 g, 7.8 mmol), and Pd(PPh3)4 (0.23 g, 0.20 mmol) in toluene (50 mL) were added K3PO4 (1.67 g, 7.8 mmol) in H2O (5.0 mL) under argon atmosphere. The reaction mixture was refluxed for 13 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (eluent: 100/0 to 80/20 hexanes/CH2Cl2) over silica gel to give compound 4b as a white solid (1.3 g, 72% yield starting from compound 2a). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.46 (dd, J

= 8.4, 2 Hz, 1H), 7.35–7.27 (m, 5H), 7.23–7.19 (m, 4H), 7.12–7.01 (m, 7H), 6.94 (d, J = 8.0 Hz, 2H), 6.88–6.85 (m, 3H), 6.73 (t, J = 8.0 Hz, 1H), 2.30 (s, 3H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 153.1, 143.9, 143.0, 141.9, 136.8, 136.4, 134.3, 131.9, 129.5, 129.4, 129.1, 128.5, 128.4, 128.3, 127.3, 127.1, 127.0, 126.4, 126.2, 121.3, 118.1, 21.4 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation. Two aromatic carbons were not observed due to the accidental overlap.);

HRMS m/z calcd for C33H27BN [M + H]⁺ 448.2232, found 448.2215 (Δ = 3.8 ppm).

35 Scheme S2. Synthesis of compounds 4c, 4d and 4e.

G. 2-((2,6-Dichlorophenyl)ethynyl)-N-phenylaniline (2c).

To a mixture of 1,3-dichloro-2-ethynylbenzene (0.70 g, 4.1 mmol), Pd(PPh3)2Cl2 (0.05 g, 0.07 mmol), CuI (0.03 mg, 0.14 mmol) in Et3N (20 mL) was added 1a (0.6 mL, 3.4 mmol) under argon atmosphere. The reaction mixture was stirred at 70 °C for 1 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The resulting mixture was dissolved in EtOAc.

The organic layer was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (eluent: 100/0 to 86/14 hexanes/CH2Cl2) over silica gel to give 2c as a green solid (1.2 g, 89% yield). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.54 (dd, J = 8.0, 2 Hz, 1H), 7.36–7.31 (m, 5H), 7.26–7.21 (m, 3H), 7.15 (t, J = 8.0 Hz, 1H), 7.05–7.01 (m, 1H), 6.97 (s, 1H), 6.84–

6.80 (m, 1H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 145.5, 141.5, 136.5, 132.7, 130.6, 129.6, 129.0, 127.7, 123.5, 122.7, 120.2, 119.0, 113.1, 109.2, 97.0, 90.1; HRMS m/z calcd for C20H14Cl2N [M + H]⁺ 338.0498, found 338.0510 (Δ = 3.6 ppm).

H. 4-Bromo-3-(2,6-dichlorophenyl)-1,2-diphenyl-1,2-dihydrobenzo[e][1,2]azaborinine (3d).

To a 100 mL Schlenk flack under argon atmosphere were added 2c (0.05 g, 1.3 mmol), PhBF3K (0.47 g, 2.7 mmol), and n-Bu4NBr (1.2 g, 3.9 mmol) in 1,2,4-trichlorobenzene (5.0 mL), and the reaction mixture was subjected to degas and backfill with argon for three times. Then, SiCl4 (0.22 mL, 1.9 mmol) and Et3N (0.18 mL, 1.3 mmol) were added to the flask sequentially. The reaction mixture was stirred at 220 °C for 20 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (eluent: 100/0 to 75/25 hexanes/CH2Cl2)over silica gel to give 3d as a white solid (0.67 g, Br : Cl = 4 : 1). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 8.48–8.42 (m, 1H), 7.44–7.40 (m, 1H), 7.37–7.28 (m, 3H), 7.25–7.19 (m, 3H), 7.15–7.12 (m, 2H), 7.04–6.56 (m, 4H), 6.93–6.85 (m, 3H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ;

143.5, 143.2, 142.3, 140.2, 134.0, 132.0, 131.8, 130.7, 129.8, 129.33, 129.27, 128.3, 127.6, 127.4, 126.8, 126.4, 124.5, 122.5, 118.4 (The aromatic carbon ipso to the boron atom was not observed due to

36

quadrupolar relaxation.); HRMS m/z calcd for C26H18BBrCl2N [M + H]⁺ 506.0070, found 506.0071 (Δ

= 0.2 ppm).

I. 4-Bromo-3-(2,6-dichlorophenyl)-1-phenyl-2-(p-tolyl)-1,2-dihydrobenzo[e][1,2]azaborinine (3e).

To a 100 mL Schlenk flack under argon atmosphere were added 2c (2.1 g, 5.5 mmol), potassium p-tolyltrifluoroborate (2.2 g, 11 mmol), and n-Bu4NBr (5.3 g, 16 mmol) in 1,2,4-trichlorobenzene (20 mL), and the reaction mixture was subjected to degas and backfill with argon for three times. Then, SiCl4 (0.95 mL, 8.2 mmol) and Et3N (0.76 mL, 5.5 mmol) were added to the flask sequentially. The reaction mixture was stirred at 220 °C for 20 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (eluent:

100/0 to 80/20 hexanes/CH2Cl2)over silica gel to give 3e as a white solid (2.5 g, Br : Cl = 3 : 1). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 8.46–8.40 (m, 1H), 7.40–7.36 (m, 1H), 7.33–7.28 (m, 3H), 7.25–

7.18 (m, 3H), 7.14–7.11 (m, 2H), 7.02–6.97 (m, 1H), 6.95–6.93 (m, 1H), 6.89–6.86 (m, 2H), 6.68–6.66 (m, 2H), 2.06 (s, 3H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 143.5, 143.2, 142.4, 140.0, 136.2, 134.0, 132.1, 131.9, 130.5, 129.6, 129.3, 129.2, 128.2, 127.5, 127.20, 127.16, 124.3, 122.3, 118.3, 21.4 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation.); HRMS m/z calcd for C27H20BBrCl2N [M + H]⁺ 520.0227, found 520.0228 (Δ = 0.2 ppm).

J. 3-(2,6-Dichlorophenyl)-1,2,4-triphenyl-1,2-dihydrobenzo[e][1,2]azaborinine (4c).

To a mixture of 3d (0.67 g, 1.22 mmol), phenylboronic acid (0.30 g, 2.44 mmol), and Pd(PPh3)4

(0.07 g, 0.06 mmol) in toluene (60 mL) was added K3PO4 (0.52 g, 2.44 mmol) in H2O (1.5 mL) under argon atmosphere. The reaction mixture was refluxed for 48 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (100/0 to 80/20 hexanes/CH2Cl2) over silica gel to give compound 4c as a white solid (0.39 g, 60% yield starting from compound 2c). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.44 (dd, J = 8.0, 2 Hz, 1H), 7.42–7.39 (m, 2H), 7.35–7.20 (m, 10H), 7.12–7.06 (m, 3H), 7.03 (dd, J = 8.8, 1 Hz, 1H), 6.93 (d, J = 8.0 Hz, 2H), 6.88–6.85 (m, 2H), 6.73–6.69 (m, 1H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 153.0, 143.9, 143.0, 141.8, 139.4, 134.3, 131.9, 129.5, 129.3, 129.2, 128.6, 128.5, 127.6, 127.4, 127.3, 127.1, 126.4, 126.2, 126.0, 121.4, 118.2 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation. Two aromatic carbons were not observed due to the accidental overlap.);

HRMS m/z calcd for C32H23BCl2N [M + H]⁺ 502.1301, found 502.1302 (Δ = 0.2 ppm).

K. 3-(2,6-Dichlorophenyl)-1,2-diphenyl-4-(p-tolyl)-1,2-dihydrobenzo[e][1,2]azaborinine (4d).

To a mixture of 3e (1.2 g, 2.3 mmol), p-tolylboronic acid (0.63 g, 4.7 mmol), and Pd(PPh3)4 (0.14 g, 0.12 mmol) in toluene (70 mL) was added K3PO4 (0.99 g, 4.7 mmol) in H2O (3.0 mL) under argon atmosphere. The reaction mixture was refluxed for 48 h. After cooling the reaction mixture to room

37

temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (100/0 to 80/20 hexane/CH2Cl2) over silica gel to give compound 4d as a white solid (1.2 g, 96% yield starting from compound 2c). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.46 (dd, J = 8.0, 2 Hz, 1H), 7.35–7.27 (m, 5H), 7.23–7.19 (m, 3H), 7.12–7.05 (m, 6H), 7.02 (d, J = 8.4 Hz, 1H), 6.93 (d, J = 8.0 Hz, 2H), 6.88–6.83 (m, 3H), 6.72 (t, J = 8.0 Hz, 1H), 2.29 (s, 3H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 153.1, 143.9, 143.0, 141.9, 136.8, 136.4, 134.3, 131.9, 129.5, 129.4, 129.1, 128.5, 128.4, 128.3, 127.3, 127.1, 127.0, 126.4, 126.2, 121.3, 118.1, 21.4 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation. Two aromatic carbons were not observed due to the accidental overlap.); HRMS m/z calcd for C33H25BCl2N [M + H]⁺ 516.1457, found 516. 1457 (Δ = 0 ppm).

L. 3-(2,6-Dichlorophenyl)-1-phenyl-2,4-di-p-tolyl-1,2-dihydrobenzo[e][1,2]azaborinine (4e).

To a mixture of 3e (2.0 g, 3.85 mmol), p-tolylboronic acid (1.05 g, 7.70 mmol), and Pd(PPh3)4

(0.22 g, 0.19 mmol) in toluene (60 mL) was added K3PO4 (1.63 g, 7.70 mmol) in H2O (5 mL) under argon atmosphere. The reaction mixture was refluxed for 24 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (100/0 to 75/25 hexanes/CH2Cl2) over silica gel to give compound 4e as a white solid (1.60 g, 76% yield starting from compound 2c). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.45 (dd, J = 8.0, 2 Hz, 1H), 7.34–7.19 (m, 8H), 7.11–7.08 (m, 1H), 7.06 (d, J = 8.0 Hz, 2H), 7.00 (dd, J = 8.40, 1 Hz, 1H), 6.95–6.92 (m, 4H), 6.74 (t, J = 8.0 Hz, 1H), 6.66 (d, J = 7.6 Hz, 2H), 2.29 (s, 3H), 2.06 (s, 3H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 153.0, 144.1, 143.1, 142.1, 136.7, 136.5, 135.7, 134.3, 132.1, 129.6, 129.3, 129.1, 128.5, 128.3, 128.2, 127.3, 127.1, 127.0, 126.2, 121.2, 118.1, 21.5, 21.4 (The aromatic carbon ipso to the boron atom was not observed due to quadrupolar relaxation. Two aromatic carbons were not observed due to the accidental overlap.); HRMS m/z calcd for C34H27BCl2N [M + H]⁺ 530.1614, found 530.1617 (Δ = 0.6 ppm).

Scheme S3. Synthesis of compounds 4f.

38 M. 2-Chloro-N-(2-iodophenyl)aniline (1b).

To a mixture of 2-iodoaniline (0.10 g, 0.46 mmol), Pd2(dba)3 (0.02 g, 0.02 mmol), dppf(0.03 g, 0.05 mmol) and NaO^tBu (0.06 g, 0.64 mmol) in toluene (5.0 mL) was added 2-chloro-2-iodobenzene (0.07 ml, 0.55 mmol) under argon atmosphere. The reaction mixture was refluxed for 18 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The resulting mixture was dissolved in EtOAc. The organic layer was washed with brine, dried over Na2SO4, and concentrated.

The crude product was purified by column chromatography (100/0 to 95/5 hexanes/CH2Cl2) over silica gel to give compound 1b as a yellow solid (0.06 g, 37% yield). ¹H NMR (400.2 MHz, CDCl3) ppm, δ;

7.82 (dd, J = 8.0, 1 Hz, 1H), 7.39 (dd, J = 8.0, 2 Hz, 1H), 7.26–7.23 (m, 2H), 7.21 (dd, J = 8.4, 2 Hz, 1H), 7.16–7.12 (m, 1H), 6.90–6.85 (m, 1H), 6.73–6.69 (m, 1H), 6.29 (s, 1H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 142.6, 139.9, 139.4, 130.1, 129.2, 127.5, 123.7, 123.3, 121.9, 118.4, 117.4, 91.4; HRMS m/z calcd for C12H10ClIN [M + H]⁺ 329.9541, found 329.9549 (Δ = 2.4 ppm).

N. 2-Chloro-N-(2-((2,6-dichlorophenyl)ethynyl)phenyl)aniline (2d).

To a mixture of 1,3-dichloro-2-ethynylbenzene (0.05 g, 0.29 mmol), Pd(PPh3)2Cl2 (4.0 mg, 0.01 mmol), CuI (2.0 mg, 0.01 mmol) in Et3N (2.0 mL) was added 1b (0.12 mL, 0.35 mmol) under argon atmosphere. The reaction mixture was stirred at 70 °C for 3 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The resulting mixture was dissolved in EtOAc.

The organic layer was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (eluent: 100/0 to 95/5 hexanes/CH2Cl2) over silica gel to give 2d as a yellow solid (0.10 g, 95% yield). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.59 (d, J = 7.6 Hz, 1H), 7.45 (dd, J = 8.0, 2 Hz, 1H), 7.41 (dd, J = 8.0, 2 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.28–7.23 (m, 2H), 7.21–7.14 (m, 2H), 6.96–6.89 (m, 3H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 144.1, 138.6, 136.8, 133.2, 130.21, 130.19, 129.0, 127.5, 127.3, 124.7, 123.2, 122.7, 120.4, 119.6, 114.8, 110.9, 96.3, 89.9;

HRMS m/z calcd for C20H13Cl3N [M + H]⁺ 372.0108, found 372.0112 (Δ = 1.1 ppm).

O. 4-Bromo-1-(2-chlorophenyl)-3-(2,6-dichlorophenyl)-2-phenyl-1,2-

dihydrobenzo[e][1,2]azaborinine (3f).

To a 100 mL Schlenk flack filled argon gas were added 2d (0.83 g, 2.2 mmol), PhBF3K (0.82 mg, 2.6 mmol) and n-Bu4NBr (2.2 g, 6.6 mmol) in 1,2,4-trichlorobenzene (10 mL), and the reaction mixture was subjected to degas and backfill with argon for three times. Then, SiCl4 (0.40 mL, 2.2 mmol) and Et3N (0.30 mL, 1.7 mmol) were added to the flask sequentially. The reaction mixture was stirred at 220 °C for 20 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (eluent: 100/0 to 80/20 hexanes/CH2Cl2)over silica gel to give 3f as a white solid (1.0 g, Br : Cl = 6 : 1). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 8.50–8.44 (m, 1H), 7.46–7.35 (m, 3H), 7.24–7.19 (m, 5H), 7.12–7.08 (m, 2H), 7.05–

39

7.01 (m, 1H), 6.96–6.87 (m, 3H), 6.81–6.79 (m, 1H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 142.1, 142.0, 140.8, 140.6, 134.1, 134.0, 133.1, 131.2, 131.1, 130.9, 130.3, 130.2, 129.0, 128.4, 127.8, 127.6, 127.5, 127.2, 126.5, 124.6, 122.8, 117.4; HRMS m/z calcd for C26H17BBrCl3N [M + H]⁺ 539.9679, found 539.9690 (Δ = 2.0 ppm).

P. 1-(2-Chlorophenyl)-3-(2,6-dichlorophenyl)-2-phenyl-4-(p-tolyl)-1,2-

dihydrobenzo[e][1,2]azaborinine (4f).

To a mixture of 3f (88 mg, 0.16 mmol), p-tolylboronic acid (44 mg, 0.32 mmol), and Pd(PPh3)4

(9.0 mg, 0.01 mmol) in toluene (8.0 mL) were added K3PO4 (69 mg, 0.33 mmol) in H2O (0.2 mL) under argon atmosphere. The reaction mixture was refluxed for 17 h. After cooling the reaction mixture to room temperature, the solvent was removed in vacuo. The crude product was purified by column chromatography (100/0 to 80/20 hexanes/CH2Cl2) over silica gel to give compound 4f as a white solid (72 mg, 70% yield starting from compound 2d, 0.10 g). ¹H NMR (400.2 MHz, CDCl3) ppm, δ; 7.48 (dd, J = 8.0, 2 Hz, 1H), 7.41–7.39 (m, 1H), 7.36–7.26 (m, 4H), 7.23–7.10 (m, 5H), 7.07 (t, J = 8.4 Hz, 2H), 6.96–6.92 (m, 2H), 6.90–6.84 (m, 4H), 6.73 (t, J = 8.4 Hz, 1H), 2.30 (s, 3H); ¹³C NMR (100.6 MHz, CDCl3) ppm, δ; 153.5, 141.8, 141.6, 141.5, 136.8, 136.3, 134.5, 134.1, 133.2, 131.3, 130.2, 129.6, 128.8, 128.7, 128.57, 128.55, 128.3, 128.2, 127.6, 127.4, 127.1, 127.0, 126.7, 126.3, 121.6, 117.1, 21.4;

HRMS m/z calcd for C33H24BCl3N [M + H]⁺ 550.1068, found 550.1071 (Δ = 0.6 ppm).

40

Compiled NMR characterization data

Figure S1. The ¹H NMR spectrum obtained for compound 2b.

41 Figure S2. The ¹³C NMR spectrum obtained for compound 2b.

42 Figure S3. The ¹H NMR spectrum obtained for compound 3a.

43 Figure S4. The ¹³C NMR spectrum obtained for compound 3a.

44 Figure S5. The ¹H NMR spectrum obtained for compound 3b.

45 Figure S6. The ¹³C NMR spectrum obtained for compound 3b.

.

46 Figure S7. The ¹H NMR spectrum obtained for compound 3c.

47 Figure S8. The ¹³C NMR spectrum obtained for compound 3c.

48 Figure S9. The ¹H NMR spectrum obtained for compound 4a.

49 Figure S10. The ¹³C NMR spectrum obtained for compound 4a.

50 Figure S11. The ¹H NMR spectrum obtained for compound 4b.