Accessing molecularly complex azaborines: Palladium-catalyzed Suzuki-Miyaura cross-couplings of brominated 2,1-borazaronaphthalenes and potassium organotrifluoroborates

Article

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Open Access on 07/01/2015

Accessing Molecularly Complex Azaborines: Palladium-Catalyzed

Suzuki−Miyaura Cross-Couplings of Brominated

2,1-Borazaronaphthalenes and Potassium Organotriﬂuoroborates

Gary A. Molander* and Steven R. Wisniewski

Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia,

Pennsylvania 19104-6323, United States

S

* Supporting Information

ABSTRACT: Despite their potential applications in both

medicinal chemistry and materials science, there have been

limited reports on the functionalization of 2,1-borazaronaph-

thalenes since their discovery in 1959. To access new chemical

space and build molecular complexity, the Suzuki−Miyaura

cross-coupling of brominated 2,1-borazaronaphthalenes has

been investigated. The palladium-catalyzed cross-coupling proceeds with an array of potassium (hetero)aryltriﬂuoroborates

in high yield with low catalyst loadings under mild reaction conditions. By the use of a high-yielding bromination of various

2,1-borazaronaphthalenes to generate electrophilic azaborine species, a library of 3-(hetero)aryl and 3,6-diaryl-2,1-

borazaronaphthalenes has been synthesized.

The promise of azaborines in these ﬁelds led us to develop a

method to synthesize the core of 2,1-borazaronaphthalene, the

B−N analogue of naphthalene (eq 1).⁵2,1-Borazaronaphthalenes

INTRODUCTION

■

The replacement of a CC bond with a B−N bond in an

aromatic system results in azaborines, heterocycles that retain

most of the aromatic character and thermal stability associated

with their CC analogues.¹Installation of the B−N bond

desymmetrizes the heterocycle, allowing functionalization at

various positions around the ring with complete regiochemical

control. This permits access to elaborate azaborines, the

corresponding carbon analogues of which cannot easily be

prepared. Because B−N bonds are isoelectronic with CC

double bonds, azaborines have been examined as isosteres

for all-carbon aromatics in medicinal chemistry.²Azaborines

have demonstrated antifungal activity against several diﬀerent

fungi^2gin addition to exhibiting antibacterial activity against

Gram-negative bacteria.^2c,dFurthermore, the azaborine deriv-

atives of ethylbenzene can bind the hydrophobic pocket of

the L99A mutant of the T4 lysozyme as well as inhibit the

ethylbenzene dehydrogenase (EbDH) enzyme.^2a,bThere-

fore, the synthesis of complex azaborines can provide access

to novel drug candidates, thereby aiding the exploration of

novel chemical space.³

Additionally, the replacement of a CC bond with a B−N

bond in a polycyclic aromatic hydrocarbon (PAH) decreases

the HOMO−LUMO gap of the material, which often results

in chemiluminescent materials.⁴Thus, in addition to their

applications in medicinal chemistry, the isosteric replacement of

CC with B−N has led to the synthesis of classes of com-

pounds that serve as organic light-emitting diodes (OLEDs)^4d

and organic ﬁeld-eﬀect transistors (OFETs).^4cConsequently,

functionalization of azaborine cores is anticipated to provide

access to new classes of compounds with potentially diﬀerent

and impactful photophysical properties.

synthesized through this route are stable toward both strong

acid (pH 2 at 37 °C) and base (Cs₂CO₃/H₂O at 60 °C), thus

demonstrating their aromatic nature. However, the synthesis

of an azaborine core is only the starting point because further

functionalization of these molecules allows facile access to

novel, increasingly complex molecules.

The method developed for accessing the core of 2,1-

borazaronaphthalenes permitted the synthesis of a library

of over 50 compounds with various substitutions.⁵This con-

vergent, modular route utilized simple starting materials

under mild reaction conditions to aﬀord a highly functionalized

azaborine core, allowing selective substitution around the 2,1-

borazaronaphthalene system by starting from an N- or aryl-

substituted 2-aminostyrene to synthesize 1-, 2-, 5-, 6-, 7-, or

8-substituted 2,1-borazaronaphthalenes. However, it was

not possible to access 3-substituted-2,1-borazaronaphthalenes

through this method, as the reaction between potassium

phenyltriﬂuoroborate and (E)-2-styrylaniline did not provide

any of the desired product (eq 2).

An alternative method was therefore required for substitution

at the 3-position of these azaborines, and thus, a diﬀerent

Received: May 28, 2014

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The bromination and chlorination of 2-methyl-2,1-borazaro-

naphthalene (1) were ﬁrst reported by Dewar in 1961 (eq 3).¹⁰

retrosynthetic disconnection was envisioned (Scheme 1). A

Suzuki−Miyaura cross-coupling⁶between brominated 2,1-

borazaronaphthalenes and potassium (hetero)aryltriﬂuoroborates⁷

was proposed to elaborate the 2,1-borazaronaphthalenes.

Through such a protocol, a library of (hetero)arylated azaborines

could be synthesized easily from a brominated starting

material, thereby building substantial molecular complexity

over two short steps. Only two isolated examples of the cross-

coupling of halogenated azaborines and aryl nucleophiles have

been previously reported.⁸

To this day, these two halogenated 2,1-borazaronaphthalenes

remain the only 3-substituted-2,1-borazaronaphthalenes re-

ported in the literature. The addition of bromine to a solution

of 1 in acetic acid resulted in a 60% isolated yield of the desired

product. A major halogenated, deboronated side product was

generated in 29% yield as a result of the harsh reaction con-

ditions. More recently, the bromination of 1,2-dihydro-1,2-

azaborine, the B−N isostere of benzene, was reported to

provide the desired product in 91% yield under milder reac-

tion conditions.¹¹Utilizing these modiﬁed conditions for the

bromination of 2,1-borazaronaphthalene by changing the

solvent from acetic acid to dichloromethane and cooling the

reaction to 0 °C enabled the desired 3-bromo-2,1-borazaro-

naphthalenes to be easily synthesized. The rate of addition of

bromine was vital to the success of the reaction: a rate of ∼1

mmol/h resulted in a high yield for many 2,1-borazaronaph-

thalenes, while more rapid addition of bromine caused the

reaction to exotherm, resulting in decomposition of the 2,1-

borazaronaphthalene. Brominations could also be carried out in

a shorter period of time by conducting the reaction at −78 °C.

The bromination conditions were applied to an array of 2,1-

borazaronaphthalenes to access 3-bromo-2,1-borazaronaphtha-

lenes in high yield (Table 1). Free N-H 2,1-borazaronaph-

thalenes with alkyl substituents on boron were brominated in

yields of up to 99% (entries 1−5). Bromination of 2-aryl-2,1-

borazaronaphthalenes with either electron-withdrawing or

electron-donating groups on the arene aﬀorded the desired

products in yields of 81−99% (entries 8−10, 13−17, and 19).

Brominated heteroaryl-containing 2,1-borazaronaphthalenes

were obtained in variable yields (entries 11, 12, and 18).

Substitution on nitrogen did not interfere with the bromina-

tion, and the desired products were obtained in modest to

excellent yields (entries 6, 7, and 13−19). The brominated

products 2r and 2t were synthesized in lower yield as a result of

the formation of side products resulting from multiple additions

of bromine. Interestingly, good to excellent yields of the

brominated borazines were achieved even in the presence of

what might be considered to be activated arenes (entries 9, 12,

14, and 19). The extraordinary reactivity of the 2,1-borazaronaph-

thalene toward electrophilic aromatic substitution was further

demonstrated in the cases of substrates 2g, 2m, 2n, and 2t,

where the azaborine core was brominated in preference to

either an allyl group¹²on nitrogen or an alkyne¹³on boron

(entries 7, 13, 14, 20).

Scheme 1. Retrosynthetic Disconnection To Access 3-Aryl-

2,1-borazaronaphthalenes

Boronic acids and many boronic acid surrogates are capable

of undergoing transmetalation in cross-coupling reactions

because an activated palladium complex interacts with a vacant

orbital on the boron.⁹Because of the B−N bond, the empty p

orbital on boron within the azaborine is occupied by electron

donation from the nitrogen. This feature contributes to the

azaborine’s aromatic stability but was anticipated to reduce its

ability to participate in transmetalation. Therefore, we expected

selectivity in transmetalation such that the cross-coupling

would proceed with the external organoboron nucleophile,

leaving the B−C bond of the azaborine intact.

Reported herein is the cross-coupling of 3-bromo-2,1-

borazaronaphthalenes with an array of potassium (hetero)-

aryltriﬂuoroborates, providing access to 3-(hetero)aryl-2,1-

borazaronaphthalenes. This cross-coupling represents the ﬁrst

reported cross-coupling between an electrophilic brominated

azaborine and a nucleophilic organometallic reagent. In this

work, 26 2,1-borazaronaphthalenes with various substitutions

on boron and nitrogen were brominated, and 43 diﬀerent cross-

coupled 2,1-borazaronaphthalenes were obtained utilizing a

palladium-catalyzed Suzuki−Miyaura cross-coupling reaction.

The method was then extended to show a second site-selective

bromination and subsequent cross-coupling to access diarylated

products. The methods developed herein demonstrate that

the unique site-selective emplacement of groups about the

azaborine core allows more diverse and precise elaboration of

these systems with far greater ease and higher selectivities than

with naphthalene itself.

RESULTS AND DISCUSSION

Attempts to synthesize 2,1-borazaronaphthalenes from

electron-poor 2-aminostyrenes (i.e., 2-amino-5-triﬂuoromethyl-

styrene) were unsuccessful under our developed conditions.

However, N-substituted 2-aminostyrenes are suitable substrates

for the synthesis of azaborines. Substitution of the all-carbon

ring of the 2,1-borazaronaphthalene does not aﬀect the

bromination because the corresponding products were isolated

in good yields (entries 21 and 22).

The desired 3-bromo-2,1-borazaronaphthalenes were synthe-

sized with aryl, heteroaryl, alkynyl, and alkyl substituents on

boron. However, the presence of an alkene on boron resulted

in dibromination of the alkene as the major product (eq 4).

■

2,1-Borazaronaphthalenes exhibit reactivity toward electrophilic

aromatic substitution that is complementary to that of their

CC counterparts because the B−N bond desymmetrizes the

molecule, with diﬀerent positions being activated relative to

those in naphthalene. Because azaborines are generally less aromatic

than their CC analogues,¹2,1-borazaronaphthalenes are also

activated toward electrophilic aromatic substitution, and in

general such reactions take place under milder reaction condi-

tions. Therefore, initial eﬀorts were focused on the bromination

of 2,1-borazaronaphthalenes through an electrophilic aromatic

substitution to generate the required electrophilic partner.

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Table 1. Scope of the Bromination of 2,1-Borazaronaphthalenes

a

Reaction conditions (unless otherwise noted): 1.0 equiv of 2,1-borazaronaphthalene, 1.1 equiv of Br₂, CH₂Cl₂, 0 °C to rt. The reaction was

performed at −40 °C to rt.

such an extent that both the mono- and dibromination reac-

tions proceed with complete regiochemical control. Resonance

structures can be used to rationalize activation of C3 and C6,

but such an analysis indicates that C8 should also be activated

(Scheme 2).

The same result was evident in the bromination of an alkenyl-

substituted arene, where addition of bromine resulted in

Scheme 2. Resonance Forms of 2,1-Borazaronaphthalenes

dibromination of the alkene followed by bromination of the

arene.¹⁴

The addition of a second equivalent of bromine to the 2,1-

borazaronaphthalene resulted in site-selective dibromination at

the 3- and 6-positions of the 2,1-borazaronaphthalene (eq 5),

This observed selectivity of electrophilic aromatic substitu-

tion at C3 and C6 was reinforced and reﬁned by a rudimentary

DFT calculation¹⁵analyzing the HOMO of the 2,1-borazaronaph-

thalene. This calculation, completed at the B3LYP/6-31G(d)

level of theory, detailed the electron density of the HOMO of

2,1-borazaronaphthalene (Figure 1). The increased electron

density at the fused carbons (C4a and C8a) suggests that C4a

should be nucleophilic. However, addition of an electrophile

at C4a would break the aromaticity in both rings of the

azaborine, resulting in a higher energy barrier for reaction,

providing the desired product in excellent yield and again

demonstrating extraordinary complementarity to naphthalene

systems in terms of both selectivity and structural diversity.

As noted previously, the isosteric replacement of CC with

B−N eﬀectively desymmetrizes the molecule and selectively

activates the system for electrophilic aromatic substitution to

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one-step process resulting in the addition of bromine to a highly

functionalized molecule.

Upon the synthesis of the brominated 2,1-borazaronaph-

thalenes, investigations of the Suzuki−Miyaura cross-coupling

reaction were conducted. 3-Bromo-2-methyl-2,1-borazaronaph-

thalene 2a and potassium phenyltriﬂuoroborate were chosen

as model substrates in the reaction to synthesize 2-methyl-3-

phenyl-2,1-borazaronaphthalene (3a) (eq 6).

Figure 1. DFT-calculated HOMO of 2,1-borazaronaphthalene

[calculated at the B3LYP/6-31G(d) level of theory].

thereby disfavoring addition at this carbon. The carbon with the

highest electron density in the HOMO is C3, with an electron

density of 0.342, whereas C6 is a close second with an electron

density of 0.325. The electron density of C8 is only 0.024,

showing the lack of nucleophilicity of this carbon relative to C3

and C6. Similar calculations for substrates with substitution

around the azaborine (i.e., 2u and 2v) show a similar trend,

conﬁrming the high reactivity at the 3-position.

Computational studies of brominated intermediates are

equally informative in rationalizing the site selectivity ob-

served.¹⁵A series of calculations at the B3LYP/6-31G(d) level

of theory evaluated the relative energies of the intermediates

formed after addition of bromine to 2-methyl-2,1-borazaro-

naphthalene 1 (Figure 2). The relative energy of the intermediate

Initially, stability tests were performed to ensure that 2,1-

borazaronaphthalenes would be stable in basic media at the

elevated temperatures required for the cross-coupling. Heating

of the 2,1-borazaronaphthalenes at 60 °C in a 1:1 THF/H₂O

solvent system with 3 equiv of Cs₂CO₃resulted in complete

recovery of the 2,1-borazaronaphthalenes. Initial reaction

conditions for the cross-coupling of phenyltriﬂuoroborate

with the brominated azaborine 2a were determined through a

limited screening process. Of the palladium sources and ligands

tested in this initial screen, the (t-Bu₃P)(aminobiphenyl)

palladium chloride precatalyst (commercially available t-Bu₃P-

Pd-G2; Figure 3) was chosen for future study as it contained a

Figure 3. Structure of t-Bu₃P-Pd-G2.

Figure 2. Relative energies for the addition of bromine to 2-methyl-

2,1-borazaronaphthalene intermediates [calculated at the B3LYP/

6-31G(d) level of theory].

relatively inexpensive phosphine ligand and demonstrated high

conversion of the starting material.

Optimization continued by variation of the temperature, sol-

vent, and catalyst loading with Cs₂CO₃as the base (Table 2).

With a solvent system of 1:1 dioxane/H₂O, a reaction tem-

perature of 40 °C resulted in incomplete conversion after 18 h

for the bromination at C3 is much lower than those at C6 and

C8, explaining the ﬁrst bromination at the 3-position. This

calculation conﬁrms that addition occurs ﬁrst on the B−N

ring because it is both less aromatic and less thermally stable

than a CC ring, which in turn increases its reactivity.¹⁶

Addition of a second equivalent of bromine results in addition

to the CC ring of the 2,1-borazaronaphthalene, speciﬁcally

at the 6-position, because the intermediate derived from

addition at that site is ∼2 kcal/mol lower in energy than that

of the C8-brominated intermediate.

Table 2. Optimization of the Cross-Coupling of 3-Bromo-2-

methyl-2,1-borazaronaphthalene with Potassium

Phenyltriﬂuoroborate

The impact of the site-selective bromination can be demon-

strated by comparison with the bromination of naphthalene.

Unlike 2,1-borazaronaphthalenes, which undergo electrophilic

aromatic substitution selectively at the 3-position, the natural

site for electrophilic aromatic substitution of naphthalene is the

1-position.¹⁷In fact, the bromination of 2-methylnaphthalene

to form 1-bromo-2-methylnaphthalene proceeds in 87% yield¹⁸

whereas the bromination of the corresponding azaborine 1

yields 3-bromo-2-methyl-2,1-borazaronaphthalene (2a) in 99%

yield, demonstrating complementary electrophilic aromatic

substitutions of the CC and B−N analogues to access

molecules with diﬀerent substitution patterns.

product-to-internal standard

a

entry

variation from above conditions

ratio

1

2

3

4

5

6

7

8

9

40 °C reaction temperature

60 °C reaction temperature

1.11

2.04

2.08

1.36

1.73

1.99

1.67

2.00

2.02

1:1 CPME/H₂O as solvent, 60 °C

1:1 toluene/H₂O as solvent, 60 °C

1:1 THF/H₂O as solvent, 60 °C

b

1 mol % [Pd]

b

0.5 mol % [Pd]

b

0.25 M concentration

b

0.5 M concentration

a

Furthermore, to install a halogen at the 3-position of naph-

thalene requires either a directing group under harsh reaction con-

ditions¹⁹or a gold-catalyzed cyclization in the presence of NIS.²⁰

The corresponding bromination of 2,1-borazaronaphthalene is a

Determined by HPLC with the addition of 10 mol % 4,4′-di-tert-

butylbiphenyl as an internal standard. Entries 2, 3, 6, 8, and 9 resulted

b

in complete conversion of the starting material. Reaction completed

at 60 °C with 1:1 CPME/H₂O as the solvent.

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(entry 1); however, increasing the temperature to 60 °C

provided complete conversion to the desired product in 18 h

(entry 2). Various solvents were then screened in this reaction.

No side products were observed with any solvent, meaning the

solvent aﬀected only the rate of the reaction. Both cyclopentyl

methyl ether (CPME) and dioxane aﬀorded complete conver-

sion to the desired product, whereas toluene and THF did not

(entries 3−5). CPME was chosen as the cosolvent in the reaction

because of its more favorable properties relative to dioxane.

Optimization then continued with a solvent system of 1:1

CPME/H₂O. Because of the increased temperature, decreasing

the palladium loading to 1 mol % resulted in complete conversion

(entry 6), but when the catalyst loading was further decreased to

0.5 mol %, starting material remained after 18 h (entry 7). The

concentration of the reaction was also screened, and complete

conversion was achieved with a concentration of 0.5 M (entries 8

and 9). Therefore, 1 mol % t-Bu₃P-Pd-G2, 3 equiv of Cs₂CO₃,

and 1:1 CPME/H₂O at 60 °C for 18 h were used as the standard

cross-coupling conditions.

electron-poor (entries 10−13) aryltriﬂuoroborates were exam-

ined. All of the aryltriﬂuoroborates utilized were successfully

cross-coupled without employing an excess of the organo-

triﬂuoroborate, providing the desired 3-aryl-2,1-borazaronaph-

thalenes in yields of 53−98%. Aryltriﬂuoroborates with ortho

(entry 3), meta (entries 2, 8−12, 14), and para (entries 4, 5,

and 13) substitution aﬀorded the desired products in high

yield. Both 1- and 2-naphthyltriﬂuoroborate were successful

nucleophiles in this reaction, and the products were obtained in

yields of 93% and 95%, respectively (entries 6 and 7). When a

disubstituted aryltriﬂuoroborate was subjected to the reac-

tion, the product was synthesized in 73% yield (entry 9). The

scalable nature of the cross-coupling was demonstrated by

performing the reaction on a 4.5 mmol scale with 0.5 mol %

t-Bu₃P-Pd-G2, which provided the desired products in high

yield (entries 1 and 2).

To expand the range of nucleophiles, 3-bromo-2-methyl-2,1-

borazaronaphthalene was coupled with a variety of potassium

heteroaryltriﬂuoroborates (Table 4). The thienyltriﬂuorobo-

rates were successfully cross-coupled, aﬀording the desired

products in yields of 84% and 86% (entries 2 and 3). Other

heteroaryltriﬂuoroborates, including furyl and isoxazolyl, were

successfully coupled, and the corresponding 3-heteroaryl-2,1-

borazaronaphthalenes were synthesized in yields up to 72%

The general reaction conditions were applied to a

representative set of potassium aryltriﬂuoroborates with

3-bromo-2-methyl-2,1-borazaronaphthalene as the electrophilic

partner in the cross-coupling reaction (Table 3). To investigate

the method fully, both electron-rich (entries 1−8) and

Table 3. Scope of the Cross-Coupling with Potassium Aryltriﬂuoroborates

Reaction conditions (unless otherwise noted): 1.0 equiv of 3-bromo-2-methyl-2,1-borazaronaphthalene, 1.0 equiv of potassium aryltriﬂuoroborate,

a

b

1 mol % t-Bu₃P-Pd-G2, 3.0 equiv of base, 1:1 CPME/H₂O, 60 °C, 18 h. Reaction concentration of 0.1 M. Reaction completed on a 4.5 mmol scale

with 0.5 mol % t-Bu₃P-Pd-G2.

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Table 4. Scope of the Cross-Coupling with Potassium

Heteroaryltriﬂuoroborates

Table 5. Scope of Cross-Coupling of 3-Bromo-2-alkyl-2,1-

borazaronaphthalenes

Reaction conditions: 1.0 equiv of 3-bromo-2-alkyl-2,1-borazaronaph-

thalene, 1.0 equiv of potassium 3-methoxyphenyltriﬂuoroborate, 1 mol %

t-Bu₃P-Pd-G2, 3.0 equiv of base, 1:1 CPME/H₂O, 60 °C, 18 h.

cross-coupling of 3-bromo-2-(β,β,β-triﬂuoroethyl)-2,1-borazaro-

naphthalene was obtained in 67% yield, providing access to

ﬂuorinated 2,1-borazaronaphthalenes (entry 3). Secondary cyclic

(cyclobutyl and cyclopropyl) and noncyclic (isopropyl) substituents

on boron aﬀorded the corresponding cross-coupled product in

yields of 70%, 84%, and 77%, respectively (entries 4−6).

Reaction conditions (unless otherwise noted): 1.0 equiv of 3-bromo-2-

methyl-2,1-borazaronaphthalene, 1.0 equiv of potassium heteroaryltri-

ﬂuoroborate, 1 mol % t-Bu₃P-Pd-G2, 3.0 equiv of base, 1:1 CPME/

a

H₂O, 60 °C, 18 h. Reaction concentration of 0.1 M.

(entries 4 and 5). Larger heteroaryltriﬂuoroborates, such as

4-dibenzofuranyl- and 4-dibenzothienyltriﬂuoroborate, were

eﬃcient as nucleophiles in the coupling, furnishing the products

in yields of 54% and 52%, respectively, after the concentration

of the reaction was lowered to 0.1 M (entries 6 and 7).

To demonstrate the versatility of this method, other

3-bromo-2-alkyl-2,1-borazaronaphthalenes were synthesized

and subjected to the standard cross-coupling conditions with

potassium 3-methoxyphenyltriﬂuoroborate as the nucleophilic

partner (Table 5). All six brominated 2,1-borazaronaphthalenes

provided the desired products in good to excellent yields.

Brominated N-substituted B-alkyl 2,1-borazaronaphthalenes

were successful electrophiles in this cross-coupling reaction.

Benzyl and allyl substituents on nitrogen did not aﬀect the

cross-coupling, providing the desired products in yields of 93%,

and 83%, respectively (entries 1 and 2). The product from the

After viable reaction conditions for the coupling of 3-bromo-

2-alkyl-2,1-borazaronaphthalenes were determined, the cou-

pling of the corresponding 3-bromo-2-aryl-2,1-borazaronaph-

thalenes was investigated. Although transmetalation of the

B-alkyl systems would likely never compete with those of the

arylboron nucleophiles, aryl groups are much more easily

transferred. Therefore, there was concern that 3-bromo-2-aryl-

2,1-borazaronaphthalenes would not be stable in the cross-coupling

reaction, with the potential that the B-aryl group of the

azaborine could compete with the nucleophilic aryltriﬂuoro-

borate in the reaction, resulting in a mixture of products.

Fortunately, subjecting 3-bromo-2-phenyl-2,1-borazaronaph-

thalene (2h) to the reaction conditions with 1 equiv of either

potassium phenyltriﬂuoroborate or phenylboronic acid resulted

in the desired cross-coupled product 11a in a yield of 77% or

54%, respectively (Table 6, entry 1). On the basis of these

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an N-Boc-indolyltriﬂuoroborate was employed as the nucleo-

phile in the reaction (entry 8).

Table 6. Scope of the Cross-Coupling with Various

Potassium (Hetero)aryltriﬂuoroborates

To demonstrate the versatility of this method, other

3-bromo-2-(hetero)aryl-2,1-borazaronaphthalenes were synthe-

sized and subjected to the standard cross-coupling conditions

with potassium 3-methoxyphenyltriﬂuoroborate as the nucleo-

philic partner (Table 7). Two additional 3-bromo-2-aryl-2,1-

Table 7. Scope of Cross-Coupling of 3-Bromo-2-

(hetero)aryl-2,1-borazaronaphthalenes

Reaction conditions: 1.0 equiv of 3-bromo-2-(hetero)aryl-2,1-borazaro-

naphthalene, 1.0 equiv of potassium 3-methoxyphenyltriﬂuoroborate,

1 mol % t-Bu₃P-Pd-G2, 3.0 equiv of base, 1:1 CPME/H₂O, 60 °C, 18 h.

borazaronaphthalenes were subjected to the cross-coupling

reaction, and the corresponding products were isolated in yields

of 62% and 50% (entries 1 and 2). Heteroaryl-containing 2,1-

borazaronaphthalenes were also successful electrophiles for the

coupling. When the electrophile was 3-bromo-2-(3-thienyl)-

2,1-borazaronaphthalene, the desired product was obtained

in 24% yield (entry 3). Steric hindrance of the 2,1-

borazaronaphthalene can aﬀect the success of the coupling

reaction. For example, 3-bromo-2-(4-dibenzofuranyl)-2,1-

borazaronaphthalene could serve as the electrophilic partner

in this reaction but aﬀorded the desired product in only 32%

yield (entry 4).

After the analysis of the scope of the cross-coupling to

include both B-alkyl- and B-aryl-2,1-borazaronaphthalenes,

studies were directed toward accessing doubly cross-coupled

products. Addition of 2 equiv of 3-methoxyphenyltriﬂuorobo-

rate to 3,6-dibromo-2-methyl-2,1-borazaronaphthalene (2v)

provided the desired product in 97% isolated yield (eq 7).

Reaction conditions (unless otherwise noted): 1.0 equiv of 3-bromo-2-

phenyl-2,1-borazaronaphthalene, 1.0 equiv of potassium (hetero)-

aryltriﬂuoroborate, 1 mol % t-Bu₃P-Pd-G2, 3.0 equiv of base, 1:1

CPME/H₂O, 60 °C, 18 h. Phenylboronic acid was utilized as the

nucleophile.

a

results, the scope of the cross-coupling was analyzed with an

array of potassium (hetero)aryltriﬂuoroborates (Table 6).

Aryltriﬂuoroborates with either para or meta substitution

provided the desired product in yields of 71% and 32%,

respectively (entries 2 and 3). Several heteroaryltriﬂuoroborates

were successful nucleophiles in this coupling, such as thienyl,

furyl, and isoxazolyl, aﬀording the cross-coupled products in

yields of 70%, 80%, and 88%, respectively (entries 5−7). The

desired cross-coupled product was obtained in 75% yield when

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The overall impact of the approaches to borazine synthesis

described herein can be appreciated by comparing these tactics

to those utilized for the construction of various substituted

naphthalenes. For example, the most convenient synthesis

of 2,3-disubstituted naphthalenes provides the symmetrical

products in good to excellent yields,²¹but unsymmetrical

naphthalenes would result in a mixture of products. The

cross-coupling route described herein allows direct and site-

speciﬁc installation of a (hetero)aryl unit at the C3 position,

thus alleviating the limitation of obtaining regioisomeric

products.

In a similar scenario, the products of the cross-coupling of

brominated N-substituted 2,1-borazaronaphthalenes are isos-

teric to 1,2,3-trisubstituted naphthalenes, whose synthesis often

results in mixtures of regioisomers.^22,23In the case of the 2,1-

borazaronaphthalenes, bromination and subsequent cross-

coupling allow a library of (hetero)arylated azaborines to be

synthesized with complete regiocontrol.

Unfortunately, the cross-coupling was not selective upon

addition of 1 equiv of potassium aryltriﬂuoroborate. There-

fore, to access doubly cross-coupled products utilizing diﬀerent

potassium (hetero)aryltriﬂuoroborates, the product of one

cross-coupling had to be subjected to a second site-selective

bromination. In the case of cross-coupling products 3a and 3b,

the second bromination proceeded at the 6-position to yield

6-bromo-3-(3-methoxyphenyl)-2-methyl-2,1-borazaronaphthalene

(9a) and 6-bromo-3-phenyl-2-methyl-2,1-borazaronaphtha-

lene (9b), respectively, in moderate to good yields (eq 8).

Lastly, the products obtained using the 3,6-diaryl-2,1-

borazaronaphthalenes are isosteres of 2,3,6-trisubstituted

naphthalenes. There are currently no examples of naphthalenes

with this substitution pattern,²⁴whereas the corresponding

cross-couplings described herein allow the ready synthesis of

such site-speciﬁc polysubstituted 2,1-borazaronaphthalenes in

high yield.

Rather remarkably, the borazine was brominated eﬀectively at

its second most reactive site in the presence of the electron-

rich methoxy-substituted arene.

These brominated 2,1-borazaronaphthalenes reacted with

an array of potassium (hetero)aryltriﬂuoroborates to provide

access to highly substituted 2,1-borazaronaphthalenes (Table 8).

CONCLUSIONS

■

The ﬁrst general method for the Suzuki−Miyaura cross-

coupling of a halogenated azaborine has been reported. 2,1-

Borazaronaphthalenes undergo site-selective bromination at

the 3-position, whereupon addition of a second equivalent of

bromine allows access to 3,6-dibromo-2,1-borazaronaphthalenes.

In this work, 26 diﬀerent brominated 2,1-borazaronaphthalenes

were synthesized in high yield. These brominated 2,1-

borazaronaphthalenes are suitable electrophiles in the Suzuki−

Miyaura cross-coupling reaction with an array of potassium

(hetero)aryltriﬂuoroborates.

Table 8. Scope of the Cross-Coupling with Various

Potassium Organotriﬂuoroborates

Furthermore, this cross-coupling easily builds molecular

complexity within this family of azaborines. Most of the

research conducted on azaborines has primarily focused on

their synthesis, with limited studies of their reactivity as

isosteres of the all-carbon analogues. Before this study, bromine

and chlorine were the only two substituents reported at the

3-position of 2,1-borazaronaphthalene, and they were synthe-

sized in low to moderate yields in the early 1960s. The methods

described herein expand the substitution at the C3 position to

include aryl and heteroaryl substituents. Most importantly,

however, the protocols developed demonstrate that 2,1-

borazaronaphthalenes are stable toward palladium catalysis,

thereby allowing access to highly functionalized molecules and

opening the door to the exploration of azaborines in other

transition-metal-catalyzed reactions.

Reaction conditions: 1.0 equiv of 6-bromo-3-aryl-2-methyl-2,1-

borazaronaphthalene, 1.0 equiv of potassium (hetero)aryltriﬂuoroborate,

1 mol % t-Bu₃P-Pd-G2, 3.0 equiv of base, 1:1 CPME/H₂O, 60 °C, 18 h.

EXPERIMENTAL SECTION

■

General Considerations. t-Bu₃P-Pd-G2 was synthesized accord-

ing to the literature.²⁵CPME was dried using a J. C. Meyer solvent

system. Standard benchtop techniques for handling air-sensitive

reagents were employed. Melting points (°C) are uncorrected. NMR

spectra were recorded on a 400 or 500 MHz spectrometer. ¹⁹F NMR

chemical shifts were referenced to external CFCl₃(0.0 ppm). ¹¹B

NMR spectra were obtained on a spectrometer equipped with the

appropriate decoupling accessories. All of the ¹¹B NMR chemical shifts

were referenced to external BF₃·OEt₂(0.0 ppm), with a negative sign

A 3,5-disubstituted aryltriﬂuoroborate reacted with 9a to provide

the cross-coupled product 10a in 86% isolated yield (entry 1).

Heteroaryltriﬂuoroborates were also eﬃcient nucleophiles for

this reaction, as 3-thienyltriﬂuoroborate and 3-furyltriﬂuoro-

borate reacted with 9b to aﬀord the desired products in 84%

and 69% yield, respectively (entries 2 and 3).

H

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The Journal of Organic Chemistry

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indicating an upﬁeld shift. Data are presented as follows: chemical shift

(multiplicity, coupling constant, integration). Chemical shifts (δ) are

reported in parts per million and coupling constants (J) in hertz.

Multiplicities are abbreviated as follows: s = singlet, d = doublet,

t = triplet, m = multiplet, br = broad. Analytical thin-layer chromatography

(TLC) was performed on TLC silica gel plates (0.25 mm) precoated with

a ﬂuorescent indicator. Standard ﬂash chromatography procedures were

followed using 32−63 μm silica gel. Visualization was eﬀected with

ultraviolet light. HRMS data were obtained by either ESI or CI using a

TOF mass spectrometer

Synthesis of Potassium Organotriﬂuoroborates. 3-Vinyl-

phenylboronic acid, 4-naphthalene-1-ylphenylboronic acid, and

3-methoxy-5-methylphenylboronic are commercially available. They

were converted to the corresponding potassium triﬂuoroborates upon

treatment with sat. aq. KHF₂.²⁶

1438, 760 cm⁻¹. HRMS (CI) m/z calcd for C₁₂H₁₄BN [M]⁺183.1219,

found 183.1212.

2-(3-Methoxyphenyl)-2,1-borazaronaphthalene. Obtained as an

oﬀ-white solid (834 mg, 71%, 5 mmol scale). Mp 80−82 °C. ¹H NMR

(500 MHz, acetone-d₆) δ 9.77 (br s, 1H), 8.18 (d, J = 11.5 Hz, 1H),

7.70−7.66 (m, 2H), 7.63−7.60 (m, 2H), 7.46−7.42 (m, 1H), 7.39−

7.35 (m, 1H), 7.31−7.27 (m, 1H), 7.21−7.17 (m, 1H), 7.00−6.97 (m,

1H), 3.85 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.6, 145.4,

141.0, 129.0, 129.0, 128.2, 125.6, 125.4, 120.7, 118.5, 118.1, 114.9,

54.4. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 34.0. IR (neat) 3368,

3051, 2406, 1566, 1250, 1039, 763 cm⁻¹. HRMS (CI) m/z calcd for

C₁₅H₁₄BNO [M]⁺235.1168, found 235.1177.

2-(3-Methoxyphenyl)-1-(4-methylbenzyl)-2,1-borazaronaphtha-

lene. Obtained as an oﬀ-white solid (569 mg, 56%, 3 mmol scale). Mp

1

113−115 °C. H NMR (500 MHz, CDCl₃) δ 8.15 (d, J = 11.2 Hz,

1H), 7.73 (d, J = 7.6 Hz, 1H), 7.40−7.36 (m, 2H), 7.31−7.28 (m,

1H), 7.23−7.20 (m, 1H), 7.17−7.11 (m, 3H), 7.09−7.01 (m, 4H),

6.92−6.88 (m, 1H), 5.43 (br s, 2H), 3.66 (s, 3H), 2.34 (s, 3H). ¹³C

NMR (125.8 MHz, CDCl₃) δ 162.2, 158.8, 145.3, 141.2, 136.6, 130.2,

129.3, 128.8, 128.5, 127.2, 125.6, 124.8, 120.9, 117.2, 117.0, 113.9,

54.8, 52.3, 21.0. ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.3. IR (neat)

2995, 1548, 1415, 1255, 1225, 1028, 766 cm⁻¹. HRMS (CI) m/z calcd

for C₂₃H₂₂BNO [M]⁺339.1794, found 339.1781.

Potassium 3-Vinylphenyltriﬂuoroborate. White solid. Mp

1

>250 °C. H NMR (500 MHz, DMSO-d₆) δ 7.46 (br s, 1H), 7.3

(d, J = 6.8 Hz, 1H), 7.18 (d, J = 7.1 Hz, 1H), 7.13−7.10 (m, 1H),

6.72−6.67 (m, 1H), 5.70 (d, J = 17.9 Hz, 1H), 5.14 (d, J = 10.8 Hz,

1H). ¹³C NMR (125.8 MHz, DMSO-d₆) δ 138.7, 135.2, 131.8, 129.9,

126.9, 123.5, 112.2. ¹¹B NMR (128.38 MHz, DMSO-d₆) δ 3.4. ¹⁹F

NMR (338.8 MHz, DMSO-d₆) δ −139.6. IR (neat) 1322, 1260, 1056,

957, 794, 662 cm⁻¹. HRMS (ESI) m/z calcd for C₈H₇BF₃[M − K]⁻

171.0593, found 171.0586.

1-Allyl-2-methyl-2,1-borazaronaphthalene. Obtained as a yellow

1

Potassium 4-Naphthalen-1-ylphenyltriﬂuoroborate. White solid.

Mp >250 °C. ¹H NMR (500 MHz, DMSO-d₆) δ 7.96−7.94 (m, 2H),

7.89−7.86 (m, 1H), 7.63−7.60 (m, 2H), 7.55−7.40 (m, 4H), 7.30−

7.27 (m, 2H). ¹³C NMR (125.8 MHz, DMSO-d₆) δ 141.3, 137.2,

133.9, 131.9, 131.5, 128.6, 128.3, 127.3, 127.0, 126.3, 126.1, 126.0,

125.9. ¹¹B NMR (128.38 MHz, DMSO-d₆) δ 3.7. ¹⁹F NMR (338.8

MHz, DMSO-d₆) δ −139.0. IR (neat) 3058, 2920, 1647, 1394, 1217,

773 cm⁻¹. HRMS (ESI) m/z calcd for C₁₆H₁₁BF₃[M − K]⁻271.0906,

found 271.0906.

oil (285 mg, 52%, 3 mmol scale). H NMR (500 MHz, acetone-d₆) δ

7.91 (d, J = 11.2 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.52−7.59 (m,

1H), 7.46−7.42 (m, 1H), 7.17−7.14 (m, 1H), 6.81−6.78 (m, 1H),

6.08−6.02 (m, 1H), 5.09 (d, J = 10.5 Hz, 1H), 4.91 (d, J = 17.4 Hz,

1H), 4.70−4.68 (m, 2H), 0.81 (s, 3H). ¹³C NMR (125.8 MHz,

acetone-d₆) δ 144.0, 141.5, 134.7, 130.0, 128.1, 126.6, 120.2, 115.5,

114.6, 48.9. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 39.2. IR (neat)

3008, 1609, 1551, 1412, 1353, 1219, 757 cm⁻¹. HRMS (ESI) m/z

calcd for C₁₂H₁₄BN [M]⁺183.1219, found 183.1215.

Potassium 3-Methoxy-5-methylphenyltriﬂuoroborate. White

solid. Mp >250 °C. ¹H NMR (500 MHz, acetone-d₆) δ 6.94 (s,

1H), 6.89 (s, 1H), 6.48 (s, 1H), 3.69 (s, 3H), 2.22 (s, 3H). ¹³C NMR

(125.8 MHz, acetone-d₆) δ 158.8, 136.3, 124.8, 113.5, 112.1, 54.0,

20.7. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 4.3. ¹⁹F NMR (338.8

MHz, acetone-d₆) δ −142.1. IR (neat) 2918, 1588, 1321, 1287, 1021,

956, 850, 803 cm⁻¹. HRMS (ESI) m/z calcd for C₈H₉BOF₃[M − K]⁻

189.0694, found 189.0693.

Synthesis of 2,1-Borazaronaphthalanes. 2,1-Borazaronaphtha-

lenes were synthesized according to the literature procedure.⁵

2-(β,β,β-Triﬂuoroethyl)-2,1-borazaronaphthalene. Obtained as an

oﬀ-white solid (130 mg, 21%, 3 mmol scale). Mp 59−61 °C. ¹H NMR

(500 MHz, acetone-d₆) δ 9.74 (br s, 1H), 8.13 (d, J = 11.2 Hz, 1H),

7.70 (d, J = 7.7 Hz, 1H), 7.56−7.52 (m, 1H), 7.47−7.43 (m, 1H),

7.23−7.18 (m, 1H), 6.94−6.90 (m, 1H), 2.42−2.30 (m, 2H). ¹³C

NMR (125.8 MHz, acetone-d₆) δ 145.3, 140.3, 129.2, 128.4, 127.3 (q,

J = 278 Hz), 125.3, 121.1, 118.3. ¹¹B NMR (128.38 MHz, acetone-d₆)

δ 33.8. IR (neat) 3361, 2970, 1563, 1278, 1236, 1102, 1032, 768 cm⁻¹.

HRMS (CI) m/z calcd for C₁₀H₉BNF₃[M]⁺211.0780, found

211.0778.

1-Allyl-2-(3-methoxyphenyl)-2,1-borazaronaphthalene. Obtained

as a yellow oil (486 mg, 59%, 3 mmol scale). H NMR (500 MHz,

1

acetone-d₆) δ 8.13 (d, J = 11.2 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H),

7.64−7.61 (m, 1H), 7.56−7.51 (m, 1H), 7.35−7.31 (m, 1H), 7.28−

7.23 (m, 1H), 7.18−7.14 (m, 2H), 6.95−6.89 (m, 2H), 6.18−6.11 (m,

1H), 5.22−5.17 (m, 1H), 4.99−4.93 (m, 1H), 4.85−4.82 (m, 2H),

3.81 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.1, 145.2,

141.0, 136.1, 130.1, 128.7, 128.5, 127.0, 124.3, 121.0, 117.3, 116.7,

114.9, 113.3, 54.3, 50.3. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.2.

IR (neat) 3009, 2939, 2830, 1549, 1413, 1281, 1049, 764 cm⁻¹. HRMS

(ESI) m/z calcd for C₁₈H₁₉BNO [M + H]⁺276.1560, found 276.1564.

1-Benzyl-2-(4-triﬂuoromethylphenyl)-2,1-borazaronaphthalene.

Obtained as a white solid (585 mg, 54%, 3 mmol scale). Mp

84−86 °C. ¹H NMR (500 MHz, CDCl₃) δ 8.33−8.30 (m, 1H), 7.89−

7.72 (m, 5H), 7.55−7.35 (m, 6H), 7.28−7.19 (m, 3H), 5.53 (s, 2H).

¹³C NMR (125.8 MHz, CDCl₃) δ 146.3, 141.3, 139.2, 132.9, 132.5 (q,

J = 226 Hz), 130.8, 130.2 (d, J = 32 Hz), 129.2, 127.8, 127.4, 125.9,

124.6 (d, J = 3 Hz), 123.8, 121.8, 117.4, 52.8. ¹¹B NMR (128.38 MHz,

CDCl₃) δ 37.1. IR (neat) 2923, 1551, 1233, 859, 762, 682, 632 cm⁻¹.

HRMS (CI) m/z calcd for C₂₂H₁₇BNF₃[M]⁺363.1406, found

363.1403.

2-(4-Fluorophenyl)-1-(4-methoxybenzyl)-2,1-borazaronaphtha-

lene. Obtained as a white solid (700 mg, 68%, 3 mmol scale). Mp 95−

97 °C. ¹H NMR (500 MHz, CDCl₃) δ 8.19 (d, J = 11.5 Hz, 1H), 7.77

(d, J = 7.3 Hz, 1H), 7.60−7.57 (m, 2H), 7.46−7.41 (m, 2H), 7.28−

7.25 (m, 1H), 7.11−7.09 (m, 5H), 6.92−6.90 (m, 2H), 5.43 (s, 2H),

3.83 (s, 3H). ¹³C NMR (125.8 MHz, CDCl₃) δ 163.1 (d, J = 245 Hz),

158.5, 145.5, 141.2, 134.5 (d, J = 7 Hz), 131.02, 130.3, 128.6, 127.3,

126.7, 121.1, 117.1, 114.7 (d, J = 20 Hz), 114.3, 55.2, 51.8. ¹¹B NMR

(128.38 MHz, CDCl₃) δ 37.2. IR (neat) 3027, 1550, 1414, 1234, 787,

761, 731 cm⁻¹. HRMS (CI) m/z calcd for C₂₂H₁₉BNOF [M]⁺

343.1544, found 343.1540.

2-Isopropyl-2,1-borazaronaphthalene. Obtained as an oﬀ-white

1

solid (650 mg, 76%, 5 mmol scale). Mp 59−61 °C. H NMR (500

MHz, acetone-d₆) δ 9.06 (br s, 1H), 8.01 (d, J = 11.5 Hz, 1H), 7.6 (d,

J = 7.6 Hz, 1H), 7.53−7.49 (m, 1H), 7.40−7.35 (m, 1H), 7.13−7.09

(m, 1H), 6.87−6.82 (m, 1H), 1.56−1.48 (m, 1H), 1.18−1.11 (m, 6H).

¹³C NMR (125.8 MHz, acetone-d₆) δ 144.5, 140.7, 128.9, 127.8, 125.2,

120.2, 118.2, 19.6. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.9. IR

(neat) 3361, 2940, 1560, 1438, 1056, 1035, 761 cm⁻¹. HRMS (CI)

m/z calcd for C₁₁H₁₄BN [M]⁺171.1219, found 171.1223.

2-Cyclobutyl-2,1-borazaronaphthalene. Obtained as an oﬀ-white

1

solid (379 mg, 69%, 3 mmol scale). Mp 63−64 °C. H NMR (500

MHz, acetone-d₆) δ 9.09 (br s, 1H), 8.02 (d, J = 11.5 Hz, 1H), 7.61 (d,

J = 7.8 Hz, 1H), 7.51−7.48 (m, 1H), 7.39−7.35 (m, 1H), 7.14−7.09

(m, 1H), 6.90−6.85 (m, 1H), 2.47−2.40 (m, 1H), 2.27−2.11 (m, 5H),

2.07−2.00 (m, 1H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 144.5,

140.7, 128.9, 127.8, 125.2, 120.2, 118.0, 25.5, 22.1. ¹¹B NMR (128.38

General Procedure for the Bromination of 2,1-Borazaro-

naphthalenes. To a ﬂame-dried 100 mL round-bottom ﬂask with

a stir bar was added the corresponding 2,1-borazaronaphthalene

(2.0 mmol). The ﬂask was sealed with a rubber septum, evacuated

under vacuum, and purged with Ar three times. Anhydrous CH₂Cl₂

MHz, acetone-d ) δ 37.7. IR (neat) 3363, 2960, 2934, 2858, 1560,

6

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(10 mL) was added, and the ﬂask was cooled to 0 °C. Bromine

(352 mg, 2.2 mmol, 1.1 equiv) in CH₂Cl₂(10 mL) was added under

Ar at a rate of 1.1 mmol/h. After the addition, the reaction mixture was

slowly warmed to rt. The reaction was monitored by TLC, and when

it was complete (usually after warming to rt), the reaction mixture was

concentrated in vacuo. The crude 2,1-borazaronaphthalene was

puriﬁed by ﬂash column chromatography with 0−30% CH₂Cl₂/

hexane as the eluent to provide the desired 3-bromo-2,1-borazaro-

naphthalene.

3-Bromo-2-methyl-2,1-borazaronaphthalene (2a). Obtained as

an oﬀ-white solid (1969 mg, 99%, 9 mmol scale). Mp 115−117 °C. ¹H

NMR (500 MHz, acetone-d₆) δ 9.63 (br s, 1H), 8.29 (s, 1H), 7.62 (d,

J = 7.8 Hz, 1H), 7.47−7.42 (m, 2H), 7.17−7.14 (m, 1H), 0.79 (s, 3H).

¹³C NMR (125.8 MHz, acetone-d₆) δ 144.3, 140.2, 128.6, 128.55,

124.9, 121.2, 118.2. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 39.2. IR

(neat) 3361, 2940, 1560, 1438, 1056, 1035, 761 cm⁻¹. HRMS (CI)

m/z calcd for C₉H₉BrBN [M]⁺221.0011, found 221.0019.

3-Bromo-2-(β,β,β-triﬂuoroethyl)-2,1-borazaronaphthalene (2b).

Obtained as an oﬀ-white solid (138 mg, 96%, 0.5 mmol scale). Mp

61−63 °C. ¹H NMR (500 MHz, acetone-d₆) δ 9.87 (br s, 1H), 8.44 (s,

1H), 7.71−7.64 (m, 2H), 7.53−7.49 (m, 1H), 7.26−7.23 (m, 1H),

2.55−5.49 (m, 2H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 146.2,

139.5, 129.3, 128.8, 128.7 (q, J = 274 Hz), 125.2, 122.3, 118.8. ¹¹B

NMR (128.38 MHz, acetone-d₆) δ 33.4. IR (neat) 3361, 2970, 1563,

1278, 1236, 1102, 1032, 768 cm⁻¹. HRMS (CI) m/z calcd for

C₁₀H₈BrBNF₃[M]⁺288.9885, found 288.9884.

38.9. IR (neat) 3031, 1607, 1362, 1216, 913, 760, 741 cm⁻¹. HRMS

(CI) m/z calcd for C₁₂H₁₃BBrN [M]⁺261.0324, found 261.0330.

3-Bromo-2-phenyl-2,1-borazaronaphthalene (2h). Obtained as

1

an oﬀ-white solid (840 mg, 99%, 3 mmol scale). Mp 84−86 °C. H

NMR (500 MHz, acetone-d₆) δ 9.90 (br s, 1H), 8.54 (s, 1H), 7.95−

7.92 (m, 2H), 7.75−7.71 (m, 2H), 7.54−7.51 (m, 1H), 7.45−7.40 (m,

3H), 7.27−7.23 (m, 1H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 146.7,

140.1, 133.5, 128.9, 128.8, 128.5, 127.4, 124.9, 121.6, 118.6. ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 34.0. IR (neat) 3371, 3052, 1552, 1420,

1009, 761, 748, 702 cm⁻¹. HRMS (CI) m/z calcd for C₁₄H₁₁BrBN

[M]⁺283.0168, found 283.0174.

3-Bromo-2-(3-methoxyphenyl)-2,1-borazaronaphthalene (2i).

Obtained as an oﬀ-white solid (325 mg, 52%, 2 mmol scale). Mp

107−109 °C. ¹H NMR (500 MHz, acetone-d₆) δ 9.87 (br s, 1H), 8.54

(s, 1H), 7.72−7.69 (m, 2H), 7.53−7.48 (m, 3H), 7.37−7.34 (m, 1H),

7.26−7.23 (m, 1H), 7.01−6.97 (m, 1H), 3.84 (s, 3H). ¹³C NMR

(125.8 MHz, acetone-d₆) δ 159.0, 146.8, 140.1, 128.9, 128.6, 128.5,

125.8, 124.9, 121.7, 119.0, 118.6, 114.4, 54.5. ¹¹B NMR (128.38 MHz,

acetone-d₆) δ 37.8. IR (neat) 3323, 2970, 2933, 1557, 1427, 1252,

1047, 791 cm⁻¹. HRMS (CI) m/z calcd for C₁₅H₁₄BBrNO [M + H]⁺

314.0352, found 314.0341.

3-Bromo-2-(4-ﬂuorophenyl)-2,1-borazaronaphthalene (2j). Ob-

tained as an oﬀ-white solid (274 mg, 91%, 2 mmol scale). Mp 114−

1

116 °C. H NMR (500 MHz, acetone-d₆) δ 9.89 (br s, 1H), 8.50 (s,

1H), 7.99−7.96 (m, 2H), 7.69−7.66 (m, 2H), 7.52−7.49 (m, 1H),

7.24−7.18 (m, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 163.6 (d,

J = 246 Hz), 146.8, 140.1, 135.9 (d, J = 7.5 Hz), 128.9, 128.5, 124.9,

121.7, 118.6, 114.3 (d, J = 20.2 Hz). ¹¹B NMR (128.38 MHz, acetone-d₆)

δ 33.1. IR (neat) 3376, 3055, 1615, 1593, 1425, 1214, 800, 757 cm⁻¹.

HRMS (CI) m/z calcd for C₁₄H₁₀BBrFN [M]⁺301.0074, found

301.0080.

3-Bromo-2-(3-thienyl)-2,1-borazaronaphthalene (2k). Obtained

as a light-brown solid (305 mg, 53%, 2 mmol scale). Mp 66−68 °C. ¹H

NMR (500 MHz, acetone-d₆) δ 9.91 (br s, 1H), 8.52 (s, 1H), 8.35−

8.32 (m, 1H), 7.83 (d, J = 4.9 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.66

(d, J = 8.1 Hz, 1H), 7.57−7.54 (m, 1H), 7.53−7.48 (m, 1H), 7.25−

7.20 (m, 1H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 146.8, 140.0,

133.7, 132.0, 128.9, 128.5, 124.8, 124.7, 121.5, 118.4. ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 30.9. IR (neat) 3749, 2977, 2349, 1557,

758 cm⁻¹. HRMS (CI) m/z calcd for C₁₂H₁₀BBrNS [M + H]⁺

289.9810, found 289.9810.

3-Bromo-2-isopropyl-2,1-borazaronaphthalene (2c). Obtained as

1

an oﬀ-white solid (488 mg, 98%, 2 mmol scale). Mp 57−69 °C. H

NMR (500 MHz, acetone-d₆) δ 9.26 (br s, 1H), 8.33 (s, 1H), 7.65−

7.57 (m, 2H), 7.45−7.41 (m, 1H), 7.20−7.15 (m, 1H), 1.85−1.80 (m,

1H), 1.19−1.15 (m, 6H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 145.5,

140.1, 128.6, 128.5, 125.0, 121.4, 118.5, 18.6. ¹¹B NMR (128.38 MHz,

acetone-d₆) δ 38.0. IR (neat) 3373, 2956, 2852, 1610, 1558, 1424,

1137, 849, 757 cm⁻¹. HRMS (CI) m/z calcd for C₁₁H₁₃BrBN [M]⁺

249.0324, found 249.0330.

3-Bromo-2-cyclopropyl-2,1-borazaronaphthalene (2d). Obtained

as an oﬀ-white solid (689 mg, 93%, 3 mmol scale). Mp 83−85 °C. ¹H

NMR (500 MHz, acetone-d₆) δ 8.87 (br s, 1H), 8.28 (s, 1H), 7.61−

7.58 (m, 1H), 7.46−7.42 (m, 1H), 7.41−7.38 (m, 1H), 7.14−7.10 (m,

1H), 0.88−0.86 (m, 2H), 0.85−0.82 (m, 2H), 0.77−0.73 (m, 1H). ¹³C

NMR (125.8 MHz, acetone-d₆) δ 144.6, 140.3, 128.6, 128.5, 124.7,

121.0, 118.1, 6.1. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.2. IR

(neat) 3374, 2954, 1557, 1428, 1105, 925, 848, 748 cm⁻¹. HRMS (CI)

m/z calcd for C₁₁H₁₁BrBN [M]⁺247.0168, found 247.0159.

3-Bromo-2-cyclobutyl-2,1-borazaronaphthalene (2e). Obtained

as an oﬀ-white solid (506 mg, 97%, 2 mmol scale). Mp 84−86 °C. ¹H

NMR (500 MHz, acetone-d₆) δ 9.33 (br s, 1H), 8.28 (s, 1H), 7.64−

7.60 (m, 2H), 7.46−7.42 (m, 1H), 7.19−7.15 (m, 1H), 2.65−2.61 (m,

1H), 2.26−2.15 (m, 5H), 1.97−1.93 (m, 1H). ¹³C NMR (125.8 MHz,

acetone-d₆) δ 145.0, 140.0, 128.6, 128.5, 125.0, 121.4, 118.5, 25.0, 21.8.

¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.1. IR (neat) 3353, 2979,

1612, 1557, 1428, 1205, 927, 757 cm⁻¹. HRMS (CI) m/z calcd for

C₁₂H₁₃BrBN [M]⁺261.0324, found 261.0330.

3-Bromo-2-benzyl-2-methyl-2,1-borazaronaphthalene (2f). Ob-

tained as an oﬀ-white solid (886 mg, 95%, 3 mmol scale). Mp 75−77 °C.

¹H NMR (500 MHz, acetone-d₆) δ 8.34 (s, 1H), 7.65−7.63 (m, 1H),

7.40−7.33 (m, 2H), 7.23−7.12 (m, 6H), 5.38 (s, 2H), 0.97 (s, 3H). ¹³C

NMR (125.8 MHz, acetone-d₆) δ 144.8, 140.6, 138.0, 129.5, 128.8,

128.6, 127.0, 126.0, 125.7, 121.3, 116.3, 51.6. ¹¹B NMR (128.38 MHz,

acetone-d₆) δ 37.3. IR (neat) 2917, 1608, 1359, 1028, 753, 735, 722,

697 cm⁻¹. HRMS (CI) m/z calcd for C₁₆H₁₅BrBN [M]⁺311.0481,

found 311.0490.

3-Bromo-2-(4-dibenzofuranyl)-2,1-borazaronaphthalene (2l).

Obtained as an oﬀ-white solid (663 mg, 89%, 2 mmol scale). Mp

1

132−134 °C. H NMR (500 MHz, acetone-d₆) δ 10.33 (br s, 1H),

8.66 (s, 1H), 8.18−8.13 (m, 2H), 7.96 (d, J = 7.3 Hz, 1H), 7.82 (d,

J = 7.9 Hz, 1H), 7.78−7.76 (m, 1H), 7.63−7.57 (m, 2H), 7.53−7.47

(m, 2H), 7.41−7.38 (m, 1H), 7.34−7.31 (m, 1H). ¹³C NMR (125.8

MHz, acetone-d₆) δ 159.0, 156.0, 147.0, 140.0, 133.2, 129.3, 128.9,

127.3, 125.3, 124.3, 123.2, 123.0, 122.6, 122.2, 121.8, 120.9, 119.0,

111.8. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 33.5. IR (neat) 3382,

3036, 1567, 1185, 748, 726 cm⁻¹. HRMS (CI) m/z calcd for

C₂₀H₁₃BBrNO [M]⁺373.0274, found 373.0276.

1-Allyl-3-bromo-2-phenyl-2,1-borazaronaphthalene (2m). Ob-

tained as a white solid (513 mg, 53%, 3 mmol scale). Mp 109−

1

111 °C. H NMR (500 MHz, acetone-d₆) δ 8.51 (s, 1H), 7.78−7.74

(m, 1H), 7.63−7.56 (m, 2H), 7.50−7.47 (m, 2H), 7.43−7.37 (m, 3H),

7.33−7.28 (m, 1H), 6.03−5.96 (m, 1H), 5.13 (d, J = 10.5 Hz, 1H),

4.94−4.90 (m, 1H), 4.73−4.71 (m, 2H). ¹³C NMR (125.8 MHz,

acetone-d₆) δ 146.1, 140.0, 135.0, 131.4, 129.6, 129.0, 127.8, 127.4,

126.4, 121.9, 117.1, 115.3, 51.4. ¹¹B NMR (128.38 MHz, acetone-d₆) δ

39.3. IR (neat) 2979, 1607, 1586, 1544, 1368, 1245, 965, 701 cm⁻¹.

HRMS (ESI) m/z calcd for C₁₇H₁₅BrBN [M]⁺323.0481, found

323.0494.

1-Allyl-3-bromo-2-methyl-2,1-borazaronaphthalene (2g). Ob-

1-Allyl-3-bromo-2-(3-methoxyphenyl)-2,1-borazaronaphthalene

(2n). Obtained as a yellow oil (324 mg, 46%, 2 mmol scale). ¹H NMR

(500 MHz, acetone-d₆) δ 8.52 (s, 1H), 7.80−7.78 (m, 1H), 7.64−7.55

(m, 2H), 7.34−7.30 (m, 2H), 7.06−6.94 (m, 2H), 6.96−6.93 (m, 1H),

6.05−6.00 (m, 1H), 5.17−5.13 (m, 1H), 4.95−4.92 (m, 1H), 4.76−

4.73 (m, 2H), 3.80 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ

158.9, 146.1, 140.0, 135.2, 129.6, 129.0, 128.7, 126.4, 123.5, 121.9,

1

tained as a yellow oil (781 mg, 98%, 3 mmol scale). H NMR (500

MHz, acetone-d₆) δ 8.25 (s, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.48 (d,

J = 3.4 Hz, 2H), 7.20−7.16 (m, 1H), 6.08−6.00 (m, 1H), 5.13−5.08

(m, 1H), 4.94−4.90 (m, 1H), 4.74−4.72 (m, 2H), 0.92 (s, 3H). ¹³C

NMR (125.8 MHz, acetone-d₆) δ 144.5, 140.5, 134.1, 129.5, 128.7,

125.8, 121.1, 115.9, 115.0, 50.0. ¹¹B NMR (128.38 MHz, acetone-d₆) δ

J

dx.doi.org/10.1021/jo5011894 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

117.0, 116.8, 115.2, 113.2, 54.3, 51.4. ¹¹B NMR (128.38 MHz,

acetone-d₆) δ 36.5. IR (neat) 2953, 1644, 1545, 1366, 1282, 1048, 763

cm⁻¹. HRMS (ESI) m/z calcd for C₁₈H₁₈BrBNO [M + H]⁺354.0665,

found 354.0657.

1H), 7.34−7.31 (m, 2H), 7.28−7.25 (m, 1H), 7.14−7.10 (m, 3H),

7.00−6.97 (m, 1H), 5.35 (s, 2H), 2.34 (s, 3H), 1.00 (s, 3H). ¹³C NMR

(500 MHz, CDCl₃) δ 144.5, 140.8, 138.9, 137.8, 129.2, 128.7, 127.0,

125.7, 123.9, 122.6, 116.2, 51.9, 22.1. ¹¹B NMR (500 MHz, CDCl₃) δ

38.1. IR (neat) 2926, 1590, 1452, 1364, 809, 685 cm⁻¹. HRMS (CI)

m/z calcd for C₁₇H₁₇BNBr [M]⁺325.0637, found 325.0647.

1-Benzyl-3-bromo-2-phenyl-2,1-borazaronaphthalene (2o). Ob-

tained as an oﬀ-white solid (710 mg, 95%, 2 mmol scale). Mp 121−

1

124 °C. H NMR (500 MHz, acetone-d₆) δ 8.58 (br s, 1H), 7.79 (d,

1-Benzyl-3-bromo-6,7-dimethoxy-2-methyl-2,1-borazaronaph-

thalene (2v). Obtained as a white solid (24 mg, 64%, 0.1 mmol scale).

J = 7.6 Hz, 1H), 7.49−7.41 (m, 4H), 7.36−7.30 (m, 3H), 7.28−7.23

(m, 3H), 7.20−7.17 (m, 1H), 7.14−7.09 (m, 2H), 5.39 (s, 2H). ¹³C

NMR (125.8 MHz, acetone-d₆) δ 146.4, 140.0, 138.4, 131.5, 129.7,

129.0, 128.6, 127.9, 127.5, 126.8, 126.7, 125.5, 122.0, 117.5, 53.0. ¹¹B

NMR (128.38 MHz, acetone-d₆) δ 37.3. IR (neat) 3025, 1606, 1545,

1367, 1355, 1243, 971, 763, 723, 703 cm⁻¹. HRMS (CI) m/z calcd for

C₂₁H₁₇BrBN [M]⁺373.0637, found 373.0638.

1

Mp 96−98 °C. H NMR (500 MHz, CDCl₃) δ 8.17 (s, 1H), 7.31−

7.22 (m, 3H), 7.15−7.11 (m, 2H), 6.93 (s, 1H), 6.73 (s, 1H), 5.31 (s,

2H), 3.89 (s, 3H), 3.67 (s, 3H), 1.01 (s, 3H). ¹³C NMR (500 MHz,

CDCl₃) 150.3, 144.4, 140.1, 138.1, 136.2, 129.1, 127.5, 126.0, 119.7,

110.0, 55.2, 55.9, 52.9. ¹¹B NMR (500 MHz, CDCl₃) δ 37.9. IR (neat)

2924, 1258, 1029, 823, 810, 751, 687, 609 cm⁻¹. HRMS (CI) m/z

calcd for C₁₈H₁₉BNO₂Br [M]⁺371.0692, found 371.0683.

1-Benzyl-3-bromo-2-(4-triﬂuoromethylphenyl)-2,1-borazaro-

naphthalene (2p). Obtained as an oﬀ-white solid (211 mg, 48%,

1 mmol scale). Mp 55−57 °C. ¹H NMR (500 MHz, acetone-d₆) δ 8.61

(s, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.71−7.67 (m, 4H), 7.46−7.42 (m,

2H), 7.29−7.25 (m, 3H), 7.21−7.18 (m, 1H), 7.13−7.11 (m, 2H),

5.36 (s, 2H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 147.0, 140.1,

138.3, 132.3, 130.1, 129.8, 129.5 (q, J = 4 Hz), 128.9, 128.0, 127.3,

127.1, 127.0 (q, J = 272 Hz), 125.8, 122.5, 117.7, 53.4. ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 36.5. IR (neat) 3029, 1546, 1323, 1122,

834, 725 cm⁻¹. HRMS (CI) m/z calcd for C₂₂H₁₆BrBF₃N [M]⁺

441.0511, found 441.0511.

2-(1,2-Dibromopropyl)-2,1-borazaronaphthalene (2w). Obtained

as an oﬀ-white solid (221 mg, 34%, 2 mmol scale). Mp 91−93 °C. ¹H

NMR (500 MHz, acetone-d₆) δ 9.60 (br s, 1H), 8.13 (d, J = 11.6 Hz,

1H), 7.69−7.67 (m, 1H), 7.51−7.43 (m, 2H), 7.21−7.17 (m, 1H),

6.93−6.91 (m, 1H), 4.91−4.85 (m, 1H), 4.23 (d, J = 10.7 Hz, 1H),

1.98 (d, J = 6.4 Hz, 3H). ¹³C NMR (500 MHz, acetone-d₆) δ 145.9,

139.7, 129.2, 128.4, 125.5, 121.2, 118.4, 50.5, 25.4. ¹¹B NMR (500

MHz, acetone-d₆) δ 34.0. IR (neat) 3360, 2978, 1614, 1562, 1441, 760

cm⁻¹. HRMS (CI) m/z calcd for C₁₁H₁₃BBr₂N [M + H]⁺327.9508,

found 327.9509.

3-Bromo-2-(4-ﬂuorophenyl)-1-(4-methoxybenzyl)-2,1-borazaro-

naphthalene (2q). Obtained as an oﬀ-white solid (207 mg, 49%,

1 mmol scale). Mp 68−70 °C. ¹H NMR (500 MHz, acetone-d₆) δ 8.56

(s, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.53−7.41 (m, 4H), 7.27−7.24 (m,

1H), 7.13−7.10 (m, 2H), 7.04−7.00 (m, 2H), 6.87−6.85 (m, 2H),

5.31 (s, 2H), 3.71 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 162.8

(d, J = 245 Hz), 158.8, 146.4, 140.0, 133.7 (d, J = 8 Hz), 130.0, 129.7,

129.0, 126.7, 126.6, 122.0, 117.5, 114.3 (d, J = 20 Hz), 114.0, 54.5,

52.4. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.5. IR (neat)

2971, 1550, 1414, 1234, 762, 625 cm⁻¹. HRMS (CI) m/z calcd for

C₂₂H₁₈BrBNOF [M]⁺421.0649, found 421.0654.

1-Benzyl-3-bromo-2-(3-thienyl)-2,1-borazaronaphthalene (2r).

Obtained as an oﬀ-white solid (237 mg, 25%, 2.5 mmol scale). Mp

66−68 °C. ¹H NMR (500 MHz, acetone-d₆) δ 8.56 (s, 1H), 7.81−7.80

(m, 1H), 7.56−7.54 (m, 1H), 7.50−7.48 (m, 1H), 7.46−7.41 (m, 2H),

7.32−7.29 (m, 2H), 7.27−7.21 (m, 3H), 7.16−7.14 (m, 2H), 5.44 (s,

2H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 146.3, 138.6, 131.7, 131.0,

129.7, 129.6, 129.0, 128.7, 126.9, 126.6, 125.5, 124.8, 122.0, 117.4,

53.2. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 36.3. IR (neat) 2958,

1733, 1540, 758, 719 cm⁻¹. HRMS (CI) m/z calcd for C₁₉H₁₅BrBNS

[M]⁺379.0202, found 379.0208.

6-Bromo-3-(3-methoxyphenyl)-2-methyl-2,1-borazaronaphtha-

lene (9a). Obtained as an oﬀ-white solid (167 mg, 51%, 1 mmol scale).

Mp 100−102 °C. ¹H NMR (500 MHz, acetone-d₆) δ 9.47 (br s, 1H),

7.72 (s, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.55−7.51 (m, 2H), 7.44−7.41

(m, 1H), 7.17−7.14 (m, 1H), 6.90−6.87 (m, 1H), 6.82−6.80 (m, 1H),

3.80 (s, 3H), 0.65 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ

159.3, 147.1, 141.6, 140.8, 133.0, 129.5, 128.5, 124.6, 120.8, 117.9,

115.7, 113.7, 113.4, 55.1. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.4.

IR (neat) 3382, 2987, 1616, 1457, 1345, 122, 1014, 759 cm⁻¹. HRMS

(CI) m/z calcd for C₁₆H₁₆BBrNO [M + H]⁺328.0508, found 328.0518.

6-Bromo-3-phenyl-2-methyl-2,1-borazaronaphthalene (9b). Ob-

tained as an oﬀ-white solid (240 mg, 81%, 1 mmol scale). Mp

1

96−98 °C. H NMR (500 MHz, acetone-d₆) 9.58 (br s, 1H), 7.86−

7.83 (m, 2H), 7.51−7.48 (m, 1H), 7.44−7.38 (m, 5H), 7.30−7.28 (m,

1H), 0.88 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 144.6, 140.1,

139.4, 131.3, 130.6, 128.3, 128.2, 126.8, 126.3, 119.7, 112.6. ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 37.6. IR (neat) 3350, 2961, 1606, 1439,

1313, 821, 702 cm⁻¹. HRMS (CI) m/z calcd for C₁₅H₁₃BBrN [M]⁺

297.0324, found 297.0330.

General Procedure for the Dibromination of 2,1-Borazaro-

naphthalenes. To a ﬂame-dried 100 mL round-bottom ﬂask with

a stir bar was added the corresponding 2,1-borazaronaphthalene (2.0

mmol). The ﬂask was sealed with a rubber septum, evacuated under

vacuum, and purged with Ar three times. Anhydrous CH₂Cl₂was

added (10 mL), and the ﬂask was cooled to 0 °C. Bromine (703 mg,

4.4 mmol, 2.2 equiv) in CH₂Cl₂(10 mL) was added under Ar at a rate

of 1.1 mmol/h. After the addition, the reaction mixture was slowly

warmed to rt. The reaction was monitored by TLC, and when it was

complete (usually after warming to rt), the reaction mixture was con-

centrated in vacuo. The crude 2,1-borazaronaphthalene was puriﬁed by

ﬂash column chromatography with 0−30% CH₂Cl₂/hexane as the

eluent to provide the desired 3,6-dibromo-2,1-borazaronaphthalene.

3,6-Dibromo-2-methyl-2,1-borazaronaphthalene (2x). Obtained

as an oﬀ-white solid (822 mg, 92%, 3 mmol scale). Mp 80−82 °C. ¹H

NMR (500 MHz, acetone-d₆) δ 9.70 (br s, 1H), 8.26−8.22 (m, 1H),

7.77 (s, 1H), 7.52−7.50 (m, 1H), 7.40−7.38 (m, 1H), 0.78 (s, 3H).

¹³C NMR (125.8 MHz, acetone-d₆) δ 143.2, 139.1, 131.2, 130.5, 126.4,

3-Bromo-2-(3-methoxyphenyl)-1-(4-methylbenzyl)-2,1-borazaro-

naphthalene (2s). Obtained as an oﬀ-white solid (337 mg, 81%,

1

1 mmol scale). Mp 116−118 °C. H NMR (500 MHz, acetone-d₆) δ

8.57 (s, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.47−7.42 (m, 2H), 7.29−7.26

(m, 2H), 7.10−7.05 (m, 2H), 7.03−7.00 (m, 4H), 6.90−6.87 (m, 1H),

5.35 (s, 2H), 3.66 (s, 3H), 2.24 (s, 3H). ¹³C NMR (125.8 MHz,

acetone-d₆) δ 158.9, 146.4, 140.0, 136.3, 135.5, 129.6, 129.2, 129.0,

128.7, 126.7, 125.5, 123.5, 121.9, 117.5, 116.7, 113.4, 54.2, 52.8, 20.0.

¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.0. IR (neat) 3048, 1406,

1336, 1313, 1094, 875, 792, 704 cm⁻¹. HRMS (CI) m/z calcd for

C₂₃H₂₁BrBNO [M]⁺417.0900, found 417.0913.

3-Bromo-2-(hex-1-yn-1-yl)-2,1-borazaronaphthalene (2t). Ob-

1

tained as a yellow oil (83 mg, 29%, 1 mmol scale). H NMR (500

MHz, acetone-d₆) δ 9.96 (br s, 1H), 8.40 (s, 1H), 7.66 (d, J = 8.1 Hz,

1H), 7.59−7.57 (m, 1H), 7.50−7.47 (m, 1H), 7.22−7.19 (m, 1H),

2.40 (t, J = 6.8 Hz, 2H), 1.59−1.49 (m, 4H), 0.95−0.90 (m, 3H). ¹³C

NMR (500 MHz, acetone-d₆) δ 145.1, 139.6, 128.8, 128.5, 124.7,

121.6, 118.1, 109.5, 30.5, 21.5, 19.1, 12.9. ¹¹B NMR (500 MHz,

acetone-d₆) δ 26.4. IR (neat) 3649, 2956, 2931, 1613, 1556, 997, 799,

759 cm⁻¹. HRMS (CI) m/z calcd for C₁₄H₁₅BNBr [M]⁺287.0481,

found 287.0481.

120.2, 113.1. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.5. IR (neat)

3350, 2961, 1554, 1423, 1195, 911, 861, 811 cm⁻¹. HRMS (CI) m/z

calcd for C₉H₈Br₂BN [M]⁺298.9117, found 298.9125.

General Procedure for the Cross-Coupling of 3-Bromo-2,1-

Borazaronaphthalenes. In a Biotage microwave vial equipped with

a stir bar were successively introduced t-Bu₃P-Pd-G2 (3.8 mg,

7.5 μmol, 1 mol %), potassium (hetero)aryltriﬂuoroborate (0.75

mmol, 1 equiv), 3-bromo-2-methyl-2,1-borazaronaphthalene (167 mg,

1-Benzyl-3-bromo-2,7-dimethyl-2,1-borazaronaphthalene (2u).

Obtained as a white solid (50 mg, 77%, 0.2 mmol scale). Mp 85−

1

87 °C. H NMR (500 MHz, CDCl₃) δ 8.25 (s, 1H), 7.47−7.44 (m,

K

dx.doi.org/10.1021/jo5011894 | J. Org. Chem. XXXX, XXX, XXX−XXX

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0.75 mmol, 1 equiv), and Cs₂CO₃(731 mg, 2.25 mmol, 3 equiv). The

vial was sealed with a cap lined with a disposable Teﬂon septum,

evacuated under vacuum, and purged with Ar three times. Degassed

CPME (0.75 mL) and degassed H₂O (0.75 mL) were added under Ar.

The resulting mixture was heated at 60 °C and stirred for 18 h. After

cooling to rt, the vial was uncapped, and the reaction mixture was

diluted with EtOAc (3 mL) and H₂O (3 mL). The reaction mixture

was extracted with EtOAc (3 × 3 mL) and dried (MgSO₄). The

solvent was removed in vacuo, and the product was puriﬁed by rapid

ﬂash column chromatography on silica gel or neutral alumina using

0 to 20% CH₂Cl₂/hexane as the eluent for most 2,1-borazaronaph-

thalenes. Several heteroaryl 2,1-borazaronaphthalenes required

20−80% CH₂Cl₂/hexane as the eluent. The cross-couplings for Tables

5−8 were completed on a 0.5 mmol scale.

3-Phenyl-2-methyl-2,1-borazaronaphthalene (3a). Obtained as a

yellow oil (161 mg, 98%). ¹H NMR (500 MHz, acetone-d₆) δ 9.41 (br

s, 1H), 7.91 (s, 1H), 7.69 (d, J = 7.69 Hz, 1H), 7.51−7.45 (m, 3H),

7.43−7.40 (m, 3H), 7.30−7.27 (m, 1H), 7.17−7.14 (m, 1H), 0.84 (s,

3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 145.0, 141.2, 140.3, 129.3,

128.1, 128.0, 127.9, 125.8, 125.0, 120.5, 117.5. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 37.3. IR (neat) 3373, 3054, 1613, 1563, 1454,

1421, 756, 700 cm⁻¹. HRMS (CI) m/z calcd for C₁₅H₁₄BN [M]⁺

219.1219, found 219.1223.

3-(3-Methoxyphenyl)-2-methyl-2,1-borazaronaphthalene (3b).

Obtained as a yellow oil (177 mg, 95%). ¹H NMR (500 MHz,

acetone-d₆) 9.43 (br s, 1H), 7.93 (s, 1H), 7.69 (d, J = 7.6 Hz, 1H),

7.49 (d, J = 8.3 Hz, 1H), 7.42−7.38 (m, 1H), 7.34−7.30 (m, 1H),

7.17−7.13 (m, 1H), 7.04−7.00 (m, 2H), 6.88−6.85 (m, 1H), 3.83 (s,

3H), 0.81 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.7, 146.5,

141.1, 140.3, 129.3, 129.0, 127.9, 124.9, 120.5, 120.5, 117.5, 113.7,

111.3, 54.5. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.4. IR (neat)

3346, 3001, 1573, 1461, 1225, 1019, 753 cm⁻¹. HRMS (CI) m/z calcd

for C₁₆H₁₆BNO [M]⁺249.1325, found 249.1325.

3-(2-Methoxyphenyl)-2-methyl-2,1-borazaronaphthalene (3c).

Obtained as a yellow oil (176 mg, 94%). ¹H NMR (500 MHz,

acetone-d₆) δ 9.28 (br s, 1H), 7.76 (s, 1H), 7.64 (d, J = 7.6 Hz, 1H),

7.48 (d, J = 8.3 Hz, 1H), 7.40−7.37 (m, 1H), 7.29−7.26 (m, 1H),

7.21−7.19 (m, 1H), 7.14−7.11 (m, 1H), 7.01−6.98 (m, 2H), 3.74 (s,

3H), 0.62 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 156.5, 141.0,

140.3, 134.4, 129.5, 129.0, 127.6, 127.5, 125.0, 120.4, 120.3, 117.5,

110.4, 54.5. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.6. IR (neat)

3372, 2997, 2939, 2832, 1596, 1458, 1417, 1220, 759, 750, 702 cm⁻¹.

HRMS (CI) m/z calcd for C₁₆H₁₆BNO [M]⁺249.1325, found

249.1317.

(m, 1H), 7.59−7.55 (m, 1H), 7.54−7.51 (m, 1H), 7.49−7.44 (m, 2H),

7.41−7.37 (m, 1H), 7.34−7.31 (m, 1H), 7.20−7.16 (m, 1H), 0.49 (s,

3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 143.4, 142.3, 140.6, 133.8,

131.8, 129.2, 128.1, 128.0, 127.7, 136.4, 126.3, 125.7, 125.5, 125.4,

125.3, 124.8, 120.6, 117.7. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.6.

IR (neat) 3369, 3053, 2980, 1613, 1566, 1421, 777, 759 cm⁻¹. HRMS

(CI) m/z calcd for C₁₉H₁₆BN [M]⁺269.1376, found 269.1368.

3-(2-Naphthyl)-2-methyl-2,1-borazaronaphthalene (3g). Ob-

1

tained as a colorless solid (192 mg, 95%). Mp 87−89 °C. H NMR

(500 MHz, acetone-d₆) δ 9.50 (br s, 1H), 8.04 (s, 1H), 7.95−7.85 (m,

4H), 7.74−7.71 (m, 1H), 7.67−7.64 (m, 1H), 7.54−7.51 (m, 1H),

7.50−7.41 (m, 3H), 7.19−7.16 (m, 1H), 0.81 (s, 3H). ¹³C NMR

(125.8 MHz, acetone-d₆) δ 142.7, 141.6, 140.4, 133.8, 132.1, 129.3,

128.0, 127.8, 127.7, 127.5, 127.3, 126.1, 125.9, 125.7, 125.2, 125.0,

120.1, 117.6. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.3. IR (neat)

3366, 3053, 2979, 1561, 1308, 758, 744 cm⁻¹. HRMS (CI) m/z calcd

for C₁₉H₁₆BN [M]⁺269.1376, found 269.1372.

3-(3-Vinylphenyl)-2-methyl-2,1-borazaronaphthalene (3h). Ob-

tained as a yellow oil (128 mg, 71%). ¹H NMR (500 MHz, acetone-d₆)

δ 9.45 (br s, 1H), 7.93 (s, 1H), 7.73−7.69 (m, 1H), 7.56−7.47 (m,

2H), 7.44−7.34 (m, 4H), 7.17−7.13 (m, 1H), 6.86−6.80 (m, 1H),

5.86 (d, J = 17.4 Hz, 1H), 5.25 (d, J = 10.8 Hz, 1H), 0.81 (s, 3H). ¹³C

NMR (125.8 MHz, acetone-d₆) δ 145.3, 141.2, 140.3, 137.4, 137.2,

129.2, 128.2, 127.9, 127.7, 125.9, 124.9, 123.6, 120.5, 117.5, 113.0. ¹¹B

NMR (128.38 MHz, acetone-d₆) δ 37.4. IR (neat) 2917, 2848, 1596,

1422, 1161, 1036, 761 cm⁻¹. HRMS (CI) m/z calcd for C₁₆H₁₆BNO

[M]⁺249.1325, found 249.1325.

3-(3-Methoxy-5-triﬂuoromethylphenyl)-2-methyl-2,1-borazaro-

1

naphthalene (3i). Obtained as a yellow oil (174 mg, 73%). H NMR

(500 MHz, acetone-d₆) δ 9.53 (br s, 1H), 8.00 (s, 1H), 7.72 (d, J = 7.6

Hz, 1H), 7.51−7.48 (m, 1H), 7.46−7.42 (m, 1H), 7.34 (s, 1H), 7.26

(s, 1H), 7.19−7.15 (m, 2H), 3.93 (s, 3H), 0.81 (s, 3H). ¹³C NMR

(125.8 MHz, acetone-d₆) δ 160.0, 147.7, 142.0, 140.1, 130.9 (q, J = 32

Hz), 129.5, 128.4, 126.6 (q, J = 260 Hz), 124.6, 120.6, 117.6, 117.4,

116.8 (q, J = 3.7 Hz), 107.9 (q, J = 3.7 Hz), 55.0. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 37.4. IR (neat) 3378, 2940, 2842, 1598, 1354,

1121, 1057, 759, 692 cm⁻¹. HRMS (CI) m/z calcd for C₁₇H₁₅BNOF₃

[M]⁺317.1199, found 317.1207.

3-(3-Nitrophenyl)-2-methyl-2,1-borazaronaphthalene (3j). Ob-

1

tained as an oﬀ-white solid (105 mg, 53%). Mp 135−137 °C. H

NMR (500 MHz, acetone-d₆) δ 9.56 (br s, 1H), 8.26 (s, 1H), 8.13 (d,

J = 7.8 Hz, 1H), 8.00 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.72 (d, J = 7.8

Hz, 1H), 7.67−7.64 (m, 1H), 7.51−7.48 (m, 1H), 7.47−7.42 (m, 1H),

7.18−7.15 (m, 1H), 0.80 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆)

δ 148.4, 146.7, 142.5, 140.6, 134.4, 129.6, 129.3, 128.6, 124.5, 122.3,

120.7, 120.5, 117.6. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.5. IR

(neat) 3376, 3054, 2967, 1609, 1579, 1417, 1253, 879, 759, 749, 698

cm⁻¹. HRMS (CI) m/z calcd for C₁₅H₁₃BN₂O₂[M]⁺264.1070, found

264.1080.

3-(4-Naphthalen-1-ylphenyl)-2-methyl-2,1-borazaronaphthalene

(3d). Reaction performed with a concentration of 0.1 M. Obtained as

an oﬀ-white solid (173 mg, 67%). Mp 73−75 °C. ¹H NMR (500 MHz,

acetone-d₆) δ 9.49 (br s, 1H), 8.03−8.01 (m, 2H), 8.00−7.98 (m, 1H),

7.97−7.95 (m, 1H), 7.73−7.71 (m, 1H), 7.60−7.57 (m, 2H), 7.53−

7.45 (m, 8H), 7.17−7.15 (m, 1H), 0.91 (s, 3H). ¹³C NMR (125.8

MHz, acetone-d₆) δ 144.1, 141.4, 140.4, 140.1, 138.2, 134.0, 131.6,

129.8, 129.7, 129.3, 128.3, 128.1, 128.0, 127.5, 126.8, 126.0, 125.7,

125.6, 125.4, 125.0, 120.6, 117.5. ¹¹B NMR (128.38 MHz, acetone-d₆)

δ 37.4. IR (neat) 3375, 3051, 1614, 1565, 1425, 1220, 844, 800, 777,

759 cm⁻¹. HRMS (CI) m/z calcd for C₂₅H₂₀BN [M]⁺345.1689, found

345.1690.

3-(3-Methoxycarbonylphenyl)-2-methyl-2,1-borazaronaphthalene

1

(3k). Obtained as a yellow oil (182 mg, 88%). H NMR (500 MHz,

acetone-d₆) δ 9.45 (br s, 1H), 8.18 (s, 1H), 7.93 (s, 2H), 7.73−7.69

(m, 2H), 7.52−7.47 (m, 2H), 7.44−7.42 (m, 1H), 7.17−7.13 (m, 1H),

3.90 (s, 3H), 0.80 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ

166.6, 145.3, 141.7, 140.5, 132.6, 130.2, 129.4, 128.9, 128.3, 128.2,

126.7, 124.8, 120.6, 117.6, 51.4. ¹¹B NMR (128.38 MHz, acetone-d₆) δ

37.4. IR (neat) 3354, 3051, 2949, 1711, 1567, 1436, 1306, 756 cm⁻¹.

HRMS (ESI) m/z calcd for C₁₇H₁₇BNO₂[M + H]⁺278.1352, found

278.1342.

3-(3-Fluorophenyl)-2-methyl-2,1-borazaronaphthalene (3l). Ob-

tained as a yellow oil (160 mg, 90%). ¹H NMR (500 MHz, acetone-d₆)

δ 9.48 (br s, 1H), 7.93 (s, 1H), 7.69 (d, J = 7.6 Hz, 1H), 7.49 (d, J =

8.1 Hz, 1H), 7.43−7.40 (m, 2H), 7.27−7.24 (m, 1H), 7.20−7.13 (m,

2H), 7.05−7.02 (m, 1H), 0.81 (s, 3H). ¹³C NMR (125.8 MHz,

acetone-d₆) δ 163.8 (d, J = 248 Hz), 147.6 (d, J = 7.6 Hz), 141.7,

140.5, 129.70 (d, J = 8.8 Hz), 129.3, 128.2, 124.7, 120.1 (d, J = 2.5

Hz), 120.6, 117.6, 116.5 (d, J = 20.1 Hz), 112.3 (d, J = 11.2 Hz). ¹¹B

NMR (128.38 MHz, acetone-d₆) δ 37.0. IR (neat) 3376, 3054, 2967,

1609, 1579, 1417, 1253, 879, 759, 749, 698 cm⁻¹. HRMS (CI) m/z

calcd for C₁₅H₁₃BNF [M]⁺237.1125, found 237.1120.

3-(4-Methylphenyl)-2-methyl-2,1-borazaronaphthalene (3e). Ob-

1

tained as an oﬀ-white solid (156 mg, 89%). Mp 53−55 °C. H NMR

(500 MHz, acetone-d₆) δ 9.41 (br s, 1H), 7.88 (s, 1H), 7.67 (d, J = 7.8

Hz, 1H), 7.48 (d, J = 7.48 Hz, 1H), 7.40−7.37 (m, 1H), 7.35−7.33

(m, 2H), 7.21−7.19 (m, 2H), 7.15−7.12 (m, 1H), 2.35 (s, 3H), 0.81

(s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 142.0, 140.7, 140.2,

135.1, 129.2, 128.7, 127.9, 127.7, 125.0, 120.5, 117.5, 20.2. ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 37.5. IR (neat) 3383, 3022, 2938, 1613,

1566, 1454, 1425, 879, 822, 759, 749 cm⁻¹. HRMS (CI) m/z calcd for

C₁₆H₁₆BN [M]⁺233.1376, found 233.1374.

3-(1-Naphthyl)-2-methyl-2,1-borazaronaphthalene (3f). Ob-

tained as a yellow oil (187 mg, 93%). Mp 58−60 °C. ¹H NMR

(500 MHz, acetone-d₆) δ 9.55 (br s, 1H), 7.93 (d, J = 8.1 Hz, 1H),

7.87 (s, 1H), 7.84−7.82 (m, 1H), 7.78 (d, J = 8.6 Hz, 1H), 7.70−7.76

L

dx.doi.org/10.1021/jo5011894 | J. Org. Chem. XXXX, XXX, XXX−XXX

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1

3-(4-Triﬂuoromethylphenyl)-2-methyl-2,1-borazaronaphthalene

(3m). Obtained as an oﬀ-white solid (156 mg, 88%). Mp 116−118 °C.

¹H NMR (500 MHz, acetone-d₆) 9.54 (br s, 1H), 7.95 (s, 1H), 7.73−

7.69 (m, 3H), 7.63−7.61 (m, 2H), 7.52−7.49 (m, 1H), 7.45−7.42 (m,

1H), 7.17−7.14 (m, 1H), 0.80 (s, 3H). ¹³C NMR (125.8 MHz,

acetone-d₆) δ 149.2, 142.2, 140.6, 129.5, 128.6, 128.5, 127.3 (q, J = 32

Hz), 124.8 (q, J = 276 Hz), 124.9 (q, J = 3.8 Hz), 123.7, 120.7, 117.6.

¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.1. IR (neat) 3346, 3030,

1614, 1334, 1325, 110, 1071, 762, 755 cm⁻¹. HRMS (CI) m/z calcd

for C₁₆H₁₃BNF₃[M]⁺287.1093, found 287.1093.

oﬀ-white solid (125 mg, 54%). Mp 63−65 °C. H NMR (500 MHz,

acetone-d₆) δ 9.56 (br s, 1H), 8.13 (s, 1H), 8.09 (d, J = 7.6 Hz, 1H),

8.00 (dd, J = 7.1 Hz, 1.5 Hz, 1H), 7.74−7.71 (m, 1H), 7.59−7.54 (m,

2H), 7.49−7.41 (m, 4H), 7.38−7.34 (m, 1H), 7.19−7.17 (m, 1H),

0.73 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 155.9, 153.5,

142.8, 140.6, 129.8, 129.4, 128.3, 127.6, 127.0, 124.7, 124.4, 123.9,

123.0, 122.7, 120.7, 120.6, 118.6, 117.7, 111.4. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 37.6. IR (neat) 3374, 3052, 2968, 1614, 1566,

1425, 1187, 777, 749 cm⁻¹. HRMS (CI) m/z calcd for C₂₁H₁₆BNO

[M]⁺309.1325, found 309.1313.

3-(4-Dibenzothienyl)-2-methyl-2,1-borazaronaphthalene (4g).

3-(3-Cyanophenyl)-2-methyl-2,1-borazaronaphthalene (3n). Ob-

tained as an oﬀ-white solid (145 mg, 79%). Mp 61−63 °C. H NMR

1

Reaction performed with a concentration of 0.1 M. Obtained as an

1

(500 MHz, acetone-d₆) δ 9.59 (br s, 1H), 8.00 (s, 1H), 7.81 (s, 1H),

7.78−7.73 (m, 2H), 7.70−7.67 (m, 1H), 7.65−7.60 (m, 1H), 7.52−

7.49 (m, 1H), 7.46−7.43 (m, 1H), 7.17−7.14 (m, 1H), 0.79 (s, 3H).

¹³C NMR (125.8 MHz, acetone-d₆) δ 146.3, 142.3, 140.6, 132.7, 131.3,

129.5, 129.3, 129.2, 128.5, 124.6, 120.7, 118.7, 117.6, 112.1. ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 37.5. IR (neat) 3338, 2980, 1558, 1260,

1088, 945, 793 cm⁻¹. HRMS (CI) m/z calcd for C₁₆H₁₃BN₂[M]⁺

244.1172, found 244.1174.

oﬀ-white solid (127 mg, 52%). Mp 62−64 °C. H NMR (500 MHz,

acetone-d₆) δ 9.63 (br s, 1H), 8.31 (d, J = 7.8 Hz, 1H), 8.22 (d, J = 7.8

Hz, 1H), 8.10 (s, 1H), 7.90−7.88 (m, 1H), 7.72−7.70 (m, 1H), 7.59−

7.54 (m, 2H), 7.50−7.45 (m, 3H), 7.38−7.35 (m, 1H), 7.21−7.18 (m,

1H), 0.66 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 142.1, 140.8,

140.2, 139.5, 138.6, 136.1, 135.5, 129.4, 128.5, 126.6, 126.4, 124.8,

124.4, 124.3, 122.5, 121.8, 120.7, 119.3, 117.7. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 38.2. IR (neat) 3366, 3056, 2980, 1707, 1567,

1440, 1021, 749 cm⁻¹. HRMS (CI) m/z calcd for C₂₁H₁₆BNS [M]⁺

325.1097, found 325.1086.

3-(N-Boc-indol-5-yl)-2-methyl-2,1-borazaronaphthalene (4a).

1

Obtained as an oﬀ-white solid (150 mg, 56%). Mp 80−82 °C. H

3-(3-Methoxyphenyl)-2-methyl-1-benzyl-2,1-borazaronaphthalene

NMR (500 MHz, acetone-d₆) δ 9.42 (br s, 1H), 8.20 (d, J = 8.3 Hz,

1H), 7.94 (s, 1H), 7.70−7.67 (m, 1H), 7.66−7.64 (m, 2H), 7.50−7.48

(m, 1H), 7.44−7.38 (m, 2H), 7.16−7.13 (m, 1H), 6.69−6.67 (m, 1H),

1.69 (s, 9H), 0.83 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ

149.4, 141.0, 140.2, 139.7, 133.8, 130.8, 129.1, 127.7, 126.0, 125.0,

124.8, 120.5, 120.0, 117.5, 114.5, 107.4, 83.3, 27.3. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 37.5. IR (neat) 3375, 2976, 1730, 1370, 1160,

1134, 759, 749, 727 cm⁻¹. HRMS (CI) m/z calcd for C₂₂H₂₃BN₂O₂

[M]⁺358.1853, found 358.1856.

1

(5a). Obtained as a yellow oil (157 mg, 93%). H NMR (500 MHz,

acetone-d₆) 7.92 (s, 1H), 7.74 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.3 Hz,

1H), 7.35−7.27 (m, 4H), 7.23−7.21 (m, 1H), 7.20−7.16 (m, 3H),

7.01−6.98 (m, 2H), 6.90−6.87 (m, 1H), 5.44 (s, 2H), 3.83 (s, 3H),

0.86 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.6, 146.8,

141.8, 141.0, 138.5, 130.3, 128.9, 128.6, 128.3, 126.7, 126.1, 125.7,

120.9, 120.8, 115.8, 114.1, 111.3, 54.5, 50.9. ¹¹B NMR (128.38 MHz,

acetone-d₆) δ 39.5. IR (neat) 3027, 1734, 1604, 1368, 1046, 727 cm⁻¹.

HRMS (CI) m/z calcd for C₂₃H₂₂BNO [M]⁺339.1794, found

339.1786.

3-(3-Thienyl)-2-methyl-2,1-borazaronaphthalene (4b). Obtained

1

as an oﬀ-white solid (145 mg, 86%). Mp 62−64 °C. H NMR (500

3-(3-Methoxyphenyl)-2-methyl-1-allyl-2,1-borazaronaphthalene

MHz, acetone-d₆) δ 9.41 (br s, 1H), 8.10 (s, 1H), 7.67−7.64 (m, 1H),

7.47−7.44 (m, 2H), 7.40−7.37 (m, 3H), 7.16−7.13 (m, 1H), 0.90 (s,

3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 145.8, 140.41, 140.4, 129.4,

128.1, 128.0, 128.0, 125.2, 120.8, 120.8, 117.9. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 37.2. IR (neat) 3372, 3052, 2938, 1612, 1563,

1426, 878, 777, 758, 748 cm⁻¹. HRMS (CI) m/z calcd for C₁₃H₁₂BNS

[M]⁺225.0784, found 225.0789.

1

(5b). Obtained as a yellow oil (120 mg, 83%). H NMR (500 MHz,

acetone-d₆) 7.85 (s, 1H), 7.72 (d, J = 7.3 Hz, 1H), 7.56−7.53 (m, 1H),

7.49−7.45 (m, 1H), 7.33−7.28 (m, 1H), 7.21−7.17 (m, 1H), 6.95−

6.93 (m, 2H), 6.88−6.84 (m, 1H), 6.14−6.07 (m, 1H), 5.13 (d,

J = 10.5 Hz, 1H), 4.97 (d, J = 17.4 Hz, 1H), 4.81−4.79 (m, 2H), 3.83

(s, 3H), 0.84 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.6,

146.8, 141.5, 140.8, 134.7, 130.3, 128.9, 128.2, 125.9, 120.8, 120.6,

115.4, 114.7, 114.0, 111.2, 54.5, 49.3. ¹¹B NMR (128.38 MHz,

acetone-d₆) δ 39.3. IR (neat) 3648, 2979, 1734, 1367, 1047, 761 cm⁻¹.

HRMS (CI) m/z calcd for C₁₉H₂₀BNO [M]⁺289.1638, found

289.1649.

3-(2-Thienyl)-2-methyl-2,1-borazaronaphthalene (4c). Obtained

as a yellow oil (142 mg, 84%). ¹H NMR (500 MHz, acetone-d₆) δ 9.50

(br s, 1H), 8.13 (s, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.47−7.44 (m, 1H),

7.42−7.39 (m, 1H), 7.36−7.34 (m, 1H), 7.28−7.25 (m, 1H), 7.16−

7.13 (m, 1H), 7.11−7.08 (m, 1H), 0.95 (s, 3H). ¹³C NMR (125.8

MHz, acetone-d₆) δ 147.7, 140.1, 139.8, 129.1, 128.0, 127.6, 124.6,

124.5, 123.9, 120.8, 117.5. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.0.

IR (neat) 3371, 3056, 2945, 1612, 1560, 1426, 1336, 877, 757, 693

cm⁻¹. HRMS (CI) m/z calcd for C₁₃H₁₂BNS [M]⁺225.0784, found

225.0784.

3-(3,5-Dimethylisoxazol-4-yl)-2-methyl-2,1-borazaronaphthalene

(4d). Obtained as an oﬀ-white solid (91 mg, 51%). Mp 69−71 °C. ¹H

NMR (500 MHz, acetone-d₆) δ 9.58 (br s, 1H), 8.27 (s, 1H), 7.6 (d,

J = 7.3 Hz, 1H), 7.47−7.41 (m, 2H), 7.16−7.13 (m, 1H), 1.58 (s, 3H),

1.39 (s, 3H), 0.81 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ

163.1, 158.3, 144.1, 140.6, 129.1, 128.3, 124.5, 120.5, 118.3, 117.7,

10.5, 9.7. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 38.1. IR (neat) 3372,

3052, 2967, 1613, 1566, 1449, 1187, 777, 749 cm⁻¹. HRMS (CI) m/z

calcd for C₁₄H₁₅BN₂O [M]⁺238.1277, found 238.1283.

3-(3-Furanyl)-2-methyl-2,1-borazaronaphthalene (4e). Obtained

as a yellow oil (113 mg, 72%). ¹H NMR (500 MHz, acetone-d₆) δ 9.41

(br s, 1H), 8.09 (s, 1H), 7.79 (s, 1H), 7.67−7.65 (m, 1H), 7.61−7.58

(m, 1H), 7.47−7.43 (m, 1H), 7.38−7.35 (m, 1H), 7.14−7.11 (m, 1H),

6.87−6.89 (m, 1H), 0.89 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆)

δ 142.9, 139.9, 139.7, 138.8, 128.9, 128.6, 127.5, 124.9, 120.5, 117.4,

109.4. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.5. IR (neat) 3362,

2932, 1614, 1426, 1031, 872, 760 cm⁻¹. HRMS (CI) m/z calcd for

C₁₃H₁₂BNO [M]⁺209.1012, found 209.1006.

3-(3-Methoxyphenyl)-2-(β,β,β-triﬂuoroethyl)-2,1-borazaronaph-

1

thalene (5c). Obtained as a yellow oil (71 mg, 67%). H NMR (500

MHz, acetone-d₆) δ 9.66 (br s, 1H), 8.03 (s, 1H), 7.77 (d, J = 7.8 Hz,

1H), 7.70 (d, J = 8.1 Hz, 1H), 7.51−7.48 (m, 1H), 7.37−7.33 (m,

1H), 7.28−7.24 (m, 1H), 6.98−6.96 (m, 2H), 6.91−6.88 (m, 1H),

3.84 (s, 3H), 2.48 (q, J = 14.2 Hz, 2H). ¹³C NMR (125.8 MHz,

acetone-d₆) δ 159.9, 145.6, 143.0, 139.7, 129.4, 129.2, 128.9 (q, J = 272

Hz), 128.5, 125.0, 121.6, 120.5, 118.2, 113.7, 111.6, 54.5. ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 33.6. IR (neat) 3408, 2961, 1699, 1596,

1240, 1038, 760 cm⁻¹. HRMS (ESI) m/z calcd for C₁₇H₁₄BNOF₃

[M − H]⁻316.1121, found 316.1120.

3-(3-Methoxyphenyl)-2-isopropyl-2,1-borazaronaphthalene (5d).

Obtained as a yellow oil (107 mg, 77%). ¹H NMR (500 MHz,

acetone-d₆) δ 9.12 (br s, 1H), 7.87 (s, 1H), 7.67 (d, J = 7.6 Hz, 1H),

7.61 (d, J = 8.1 Hz, 1H), 7.42−7.39 (m, 1H), 7.33−7.30 (m, 1H),

7.17−7.14 (m, 1H), 6.98−6.96 (m, 2H), 6.88−6.86 (m, 1H), 3.83 (s,

3H), 1.93−1.90 (m, 1H), 1.10−1.07 (m, 6H). ¹³C NMR (125.8 MHz,

acetone-d₆) δ 159.6, 146.9, 142.1, 140.3, 129.1, 128.9, 127.9, 124.7,

120.7, 120.4, 117.9, 113.7, 111.1, 54.5, 19.3. ¹¹B NMR (128.38 MHz,

acetone-d₆) δ 38.5. IR (neat) 3380, 2938, 1732, 1574, 1461, 1280,

760 cm⁻¹. HRMS (CI) m/z calcd for C₁₈H₂₀BNO [M]⁺277.1638,

found 277.1637.

3-(3-Methoxyphenyl)-2-cyclopropyl-2,1-borazaronaphthalene

1

3-(4-Dibenzofuranyl)-2-methyl-2,1-borazaronaphthalene (4f).

(5e). Obtained as yellow oil (115 mg, 84%). H NMR (500 MHz,

Reaction performed with a concentration of 0.1 M. Obtained as an

acetone-d₆) δ 8.64 (br s, 1H), 7.88 (s, 1H), 7.66 (d, J = 7.8 Hz, 1H),

M

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7.48 (d, J = 8.3 Hz, 1H), 7.37−7.31 (m, 2H), 7.15−7.10 (m, 3H),

6.68−6.65 (m, 1H), 3.83 (s, 3H), 0.83−0.80 (m, 2H), 0.75−0.72 (m,

2H), 0.54−0.50 (m, 1H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.6,

146.3, 141.0, 140.4, 129.2, 128.9, 127.9, 124.7, 120.7, 120.4, 117.6,

113.9, 111.3, 54.5, 6.4. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.6. IR

(neat) 3382, 2993, 1597, 1464, 1258, 1046, 760 cm⁻¹. HRMS (CI)

m/z calcd for C₁₈H₁₈BNO [M]⁺275.1481, found 275.1476.

3-(3-Furanyl)-2-phenyl-2,1-borazaronaphthalene (6f). Obtained

as a dark-yellow oil (104 mg, 80%). H NMR (500 MHz, acetone-d₆)

1

δ 9.61 (br s, 1H), 8.24 (s, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.66−7.64

(m, 1H), 7.60−7.57 (m, 2H), 7.49−7.43 (m, 2H), 7.39−7.37 (m, 3H),

7.23−7.21 (m, 2H), 6.85 (s, 1H). ¹³C NMR (125.8 MHz, acetone-d₆)

δ 142.6, 140.8, 140.0, 139.8, 132.6, 129.0, 128.2, 128.0, 127.9, 127.5,

125.2, 121.2, 118.1, 109.9. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 35.3.

IR (neat) 3353, 2979, 1706, 1506, 1318, 951, 815, 703 cm⁻¹. HRMS

(CI) m/z calcd for C₁₈H₁₄BNO [M]⁺271.1168 found 271.1156.

3-(3,5-Dimethylisoxazol-4-yl)-2-phenyl-2,1-borazaronaphthalene

3-(3-Methoxyphenyl)-2-cyclobutyl-2,1-borazaronaphthalene

1

(5f). Obtained as yellow oil (101 mg, 70%). H NMR (500 MHz,

acetone-d₆) δ 9.18 (br s, 1H), 7.88 (s, 1H), 7.68 (d, J = 7.6 Hz, 1H),

7.63 (d, J = 7.8 Hz, 1H), 7.43−7.40 (m, 1H), 7.30−7.27 (m, 1H),

7.17−7.14 (m, 1H), 6.96−6.92 (m, 2H), 6.86−6.83 (m, 1H), 3.82 (s,

3H), 2.75−2.70 (m, 1H), 2.12−2.04 (m, 5H), 1.93−1.85 (m, 1H). ¹³C

NMR (125.8 MHz, acetone-d₆) δ 159.6, 146.5, 141.6, 140.2, 129.2,

128.8, 127.9, 124.9, 120.7, 120.3, 117.8, 113.4, 111.2, 54.5, 25.6, 21.5.

¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.4. IR (neat) 3381,

2962, 1596, 1461, 1046, 758, 703 cm⁻¹. HRMS (CI) m/z calcd for

C₁₉H₂₀BNO [M]⁺289.1638, found 289.1635.

2,3-Diphenyl-2,1-borazaronaphthalene (6a). Obtained as a white

solid (108 mg, 77%). Mp 106−108 °C. ¹H NMR (500 MHz, acetone-d₆)

δ 9.70 (br s, 1H), 8.07 (s, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.73−7.70

(m, 1H), 7.50−7.45 (m, 3H), 7.31−7.22 (m, 9H). ¹³C NMR (125.8

MHz, acetone-d₆) δ 144.6, 143.3, 140.4, 133.5, 129.3, 128.6, 128.3,

128.1, 127.8, 127.3, 125.8, 125.2, 121.1, 118.2. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 35.3. IR (neat) 3371, 3051, 2923, 1560, 1420,

1307, 756 cm⁻¹. HRMS (CI) m/z calcd for C₂₀H₁₆BN [M]⁺281.1376,

found 281.1371.

3-(4-Fluorophenyl)-2-phenyl-2,1-borazaronaphthalene (6b). Ob-

tained as a yellow oil (106 mg, 71%). ¹H NMR (500 MHz, acetone-d₆)

δ 9.70 (br s, 1H), 8.06 (s, 1H), 7.77−7.75 (m, 1H), 7.71 (d, J = 8.1

Hz, 1H), 7.48−7.45 (m, 3H), 7.31−7.24 (m, 6H), 7.06−7.01 (m, 2H).

¹³C NMR (125.8 MHz, acetone-d₆) δ 161.6 (d, J = 243 Hz), 143.4,

140.8 (d, J = 2.5 Hz), 140.4, 133.4, 130.3 (d, J = 7.5 Hz), 129.4, 128.4,

128.2, 127.4, 125.1, 121.1, 118.2, 114.5 (d, J = 21 Hz). ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 34.8. IR (neat) 3381, 3050, 2979, 2348,

1698, 1218, 834, 753 cm⁻¹. HRMS (CI) m/z calcd for C₂₀H₁₅BFN

[M]⁺299.1282, found 299.1280.

1

(6g). Obtained as a white solid (132 mg, 88%). Mp 80−82 °C. H

NMR (500 MHz, acetone-d₆) δ 9.84 (br s, 1H), 8.04 (s, 1H), 7.78−

7.74 (m, 2H), 7.54−7.50 (m, 3H), 7.34−7.29 (m, 3H), 7.26−7.23 (m,

1H), 2.11 (s, 3H), 1.86 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ

163.4, 158.5, 146.0, 140.7, 132.8, 129.2, 128.7, 128.5, 127.6, 124.8,

121.2, 118.4, 118.3, 10.5, 9.8. ¹¹B NMR (128.38 MHz, acetone-d₆) δ

34.5. IR (neat) 3378, 1615, 1423, 1156, 756, 709 cm⁻¹. HRMS (ESI)

m/z calcd for C₁₉H₁₈BN₂O [M + H]⁺301.1512, found 301.1521.

3-(N-Boc-indol-5-yl)-2-phenyl-2,1-borazaronaphthalene (6h).

1

Obtained as an oﬀ-white solid (168 mg, 75%). Mp 96−98 °C. H

NMR (500 MHz, acetone-d₆) δ 9.65 (br s, 1H), 8.11 (s, 1H), 8.07−

8.04 (m, 1H), 7.79−7.77 (m, 1H), 7.73−7.71 (m, 1H), 7.63−7.62 (m,

1H), 7.53−7.47 (m, 4H), 7.29−7.21 (m, 5H), 6.57−6.56 (m, 1H),

1.67 (s, 9H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 149.4, 143.4,

140.3, 139.4, 133.5, 130.7, 129.2, 128.1, 128.0, 127.3, 125.9, 125.5,

125.3, 121.1, 120.5, 118.2, 114.2, 107.3, 83.3, 59.6, 27.4. ¹¹B NMR

(128.38 MHz, acetone-d₆) δ 35.1. IR (neat) 3371, 2975, 1731, 1370,

1162, 1135, 764, 752 cm⁻¹. HRMS (ESI) m/z calcd for

C₂₇H₂₅BN₂O₂Na [M + Na]⁺443.1907, found 443.1902.

2-(4-Fluorophenyl)-3-(3-methoxyphenyl)-2,1-borazaronaphthalene

(7a). Obtained as an oﬀ-white solid (102 mg, 62%). Mp 74−76 °C. ¹H

NMR (500 MHz, acetone-d₆) δ 9.73 (br s, 1H), 8.08 (s, 1H), 7.77 (d,

J = 7.8 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.53−7.44 (m, 3H), 7.25−

7.18 (m, 2H), 7.05−7.00 (m, 2H), 6.87−6.80 (m, 3H), 3.67 (s, 3H).

¹³C NMR (125.8 MHz, acetone-d₆) δ 163.2 (d, J = 250 Hz), 159.5,

145.9, 143.3, 140.4, 135.7, 135.6, 129.4, 128.9, 128.4, 125.1, 121.2,

120.9, 118.2, 114.1 (d, J = 20.5 Hz), 111.6, 54.3. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 34.6. IR (neat) 3371, 2928, 1595, 1570, 1417,

1277, 1161, 760 cm⁻¹. HRMS (CI) m/z calcd for C₂₁H₁₈BNOF

[M + H]⁺330.1465, found 330.1466.

3-(3-Nitrophenyl)-2-phenyl-2,1-borazaronaphthalene (6c). Ob-

tained as an oﬀ-white solid (52 mg, 32%). Mp 140−142 °C. ¹H NMR

(500 MHz, acetone-d₆) δ 9.83 (br s, 1H), 8.25 (s, 1H), 8.22 (s, 1H),

8.13−8.08 (m, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.75−7.72 (m, 1H),

7.68−7.65 (m, 1H), 7.54−7.50 (m, 2H), 7.46−7.43 (m, 2H), 7.33−

7.24 (m, 4H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 148.2, 146.4,

144.5, 140.7, 135.1, 133.3, 129.7, 129.0, 128.9, 128.3, 127.5, 124.9,

122.9, 121.4, 120.5, 118.3. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 35.4.

IR (neat) 3371, 3051, 2780, 1560, 1286, 1264, 756, 699 cm⁻¹. HRMS

(ESI) m/z calcd for C₂₀H₁₅BN₂O₂Na [M + Na]⁺349.1124, found

349.1125.

2,3-Bis(3-Methoxyphenyl)-2,1-borazaronaphthalene (7b). Ob-

1

tained as an oﬀ-white solid (185 mg, 50%). Mp 85−87 °C. H NMR

(500 MHz, acetone-d₆) δ 9.68 (br s, 1H), 8.10 (s, 1H), 7.79−7.77 (m,

1H), 7.72−7.70 (m, 1H), 7.49−7.46 (m, 1H), 7.24−7.18 (m, 3H),

7.09−7.05 (m, 2H), 6.90−6.86 (m, 3H), 6.81−6.79 (m, 1H), 3.67 (s,

3H), 3.65 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.4, 158.9,

146.0, 143.1, 140.4, 129.3, 128.7, 128.4, 128.3, 125.6, 125.1, 121.2,

120.9, 118.6, 118.2, 114.2, 113.9, 115.6, 54.3, 54.1. ¹¹B NMR (128.38

MHz, acetone-d₆) δ 34.8. IR (neat) 3344, 3006, 2938, 1597, 1223,

1037, 786, 703 cm⁻¹. HRMS (ESI) m/z calcd for C₂₂H₂₁BNO₂[M + H]⁺

342.1665, found 342.1650.

3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-2-phenyl-2,1-borazaro-

naphthalene (6d). Obtained as an oﬀ-white solid (88 mg, 52%). Mp

55−57 °C. ¹H NMR (500 MHz, acetone-d₆) δ 9.61 (br s, 1H), 8.04 (s,

1H), 7.76 (d, J = 7.8 Hz, 1H), 7.70−7.68 (m, 1H), 7.53−7.51 (m,

2H), 7.47−7.43 (m, 1H), 7.33−7.27 (m, 3H), 7.23−7.20 (m, 1H),

6.82 (s, 1H), 6.74−6.72 (m, 2H), 4.25−4.20 (m, 4H). ¹³C NMR

(125.8 MHz, acetone-d₆) δ 143.3, 142.7, 142.3, 140.2, 137.8, 133.3,

129.2, 128.1, 128.0, 127.3, 125.2, 121.7, 121.1, 118.1, 117.0, 116.4,

65.2, 64.1. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 37.8. IR (neat)

3355, 2980, 1560, 1506, 1412, 1307, 1281, 1244, 754 cm⁻¹. HRMS

(CI) m/z calcd for C₂₂H₁₉BNO₂[M + H]⁺340.1509, found 340.1516.

2-Phenyl-3-(3-thienyl)-2,1-borazaronaphthalene (6e). Obtained

3-(3-Methoxyphenyl)-2-(3-thienyl)-2,1-borazaronaphthalene

1

(7c). Obtained as a yellow oil (39 mg, 24%). H NMR (500 MHz,

acetone-d₆) δ 9.74 (br s, 1H), 8.01 (s, 1H), 7.75 (d, J = 8.1 Hz, 1H),

7.66 (d, J = 8.1 Hz, 1H), 7.57−7.55 (m, 1H), 7.48−7.45 (m, 1H),

7.39−7.36 (m, 1H), 7.27−7.18 (m, 3H), 6.93−6.84 (m, 3H), 3.73 (s,

3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.4, 146.5, 143.1, 140.3,

132.0, 131.9, 129.3, 128.8, 128.3, 124.9, 124.3, 121.0, 120.8, 118.0,

114.0, 111.7, 54.3. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 32.2. IR

(neat) 3374, 2924, 1562, 1261, 852, 761, 685 cm⁻¹. HRMS (CI) m/z

calcd for C₁₉H₁₇BNOS [M + H]⁺318.1124, found 318.1109.

2-(4-Dibenzofuranyl)-3-(3-methoxyphenyl)-2,1-borazaronaph-

thalene (7d). Obtained as a white solid (64 mg, 32%). Mp 71−73 °C.

¹H NMR (500 MHz, acetone-d₆) δ 10.11 (br s, 1H), 8.24 (s, 1H),

8.08−8.04 (m, 2H), 7.87 (d, J = 7.8 Hz, 1H), 7.78−7.76 (m, 1H),

7.55−7.41 (m, 4H), 7.37−7.34 (m, 1H), 7.31−7.25 (m, 2H), 7.13−

7.10 (m, 1H), 6.94−6.92 (m, 1H), 6.91−6.90 (m, 1H), 6.71−6.68 (m,

1H), 3.53 (s, 3H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 159.4, 158.9,

155.8, 145.9, 143.1, 140.0, 132.8, 129.5, 128.7, 128.4, 126.9, 125.3,

124.1, 122.8, 122.5, 122.3, 121.4, 120.7, 120.6, 120.5, 118.3, 113.6,

1

as an oﬀ-white solid (100 mg, 70%). Mp 72−74 °C. H NMR (500

MHz, acetone-d₆) δ 9.63 (br s, 1H), 8.22 (s, 1H), 7.75 (d, J = 7.8 Hz,

1H), 7.70−7.67 (m, 1H), 7.56−7.52 (m, 2H), 7.47−7.43 (m, 1H),

7.36−7.29 (m, 4H), 7.23−7.20 (m, 1H), 7.16−7.14 (m, 1H),

7.08−7.06 (m, 1H). ¹³C NMR (125.8 MHz, acetone-d₆) δ 145.1,

142.3, 140.2, 133.1, 129.2, 128.4, 128.2, 128.1, 127.4, 125.2, 124.6,

121.2, 120.8, 118.2. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 35.0. IR

(neat) 3372, 2979, 2919, 1613, 1559, 1423, 754 cm⁻¹. HRMS (CI)

m/z calcd for C₁₈H₁₄BNS [M]⁺287.0940, found 287.0939.

N

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111.7, 111.4, 54.2. ¹¹B NMR (128.38 MHz, acetone-d₆) δ 33.9. IR

(neat) 3390, 3051, 2929, 1564, 1450, 1165, 756 cm⁻¹. HRMS (ESI)

m/z calcd for C₂₇H₂₁BNO₂[M + H]⁺402.1665, found 402.1673.

3,6-Bis(3-Methoxyphenyl)-2-methyl-2,1-borazaronaphthalene

tiﬁc and Johnson Matthey are acknowledged for their donation

of palladium salts. Professors William P. Dailey and Marisa C.

Kozlowski (University of Pennsylvania) are acknowledged for

helpful insight in performing the computational study. Dr.

Rakesh Kohli (University of Pennsylvania) is acknowledged for

obtaining HRMS data.

1

(8). Obtained as a yellow oil (172 mg, 97%). H NMR (500 MHz,

acetone-d₆) δ 9.50 (br s, 1H), 8.04−8.01 (m, 2H), 7.75−7.71 (m, 1H),

7.57−7.55 (m, 1H), 7.39−7.27 (m, 4H), 7.03−7.01 (m, 2H), 6.90−

6.86 (m, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 0.85 (s, 3H). ¹³C NMR

(125.8 MHz, acetone-d₆) δ 160.3, 159.7, 146.4, 142.2, 141.3, 139.9,

133.3, 129.7, 129.0, 127.4, 126.9, 125.1, 120.5, 118.9, 118.0, 113.7,

112.2, 112.1, 111.4, 54.6, 54.5. ¹¹B NMR (128.38 MHz, acetone-d₆) δ

38.6. IR (neat) 3366, 2954, 1733, 1576, 1038, 933, 776, 699 cm⁻¹.

HRMS (CI) m/z calcd for C₂₃H₂₃BNO₂[M + H]⁺356.1822, found

356.1829.

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2,1-borazaronaphthalene (10a). Obtained as an oﬀ-white solid

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1

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ASSOCIATED CONTENT

■

S

* Supporting Information

1

Copies of H, ¹³C, and ¹¹B NMR spectra for all compounds as

well as atom coordinates and total energies for the DFT calcula-

tions. This material is available free of charge via the Internet at

http://pubs.acs.org.

AUTHOR INFORMATION

Corresponding Author

*E-mail: gmolandr@sas.upenn.edu.

■

Notes

The authors declare no competing ﬁnancial interest.

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ACKNOWLEDGMENTS

■

This research was supported by the NIGMS (R01 GM-081376)

and Eli Lilly. Frontier Scientiﬁc is acknowledged for their generous

donation of potassium organotriﬂuoroborates. Frontier Scien-

O

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dx.doi.org/10.1021/jo5011894 | J. Org. Chem. XXXX, XXX, XXX−XXX

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Accessing molecularly complex azaborines: Palladium-catalyzed Suzuki-Miyaura cross-couplings of brominated 2,1-borazaronaphthalenes and potassium organotrifluoroborates

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