Construction of Bulky Ligand Libraries by Ru(II)-Catalyzed P(III)-Assisted ortho-C-H Secondary Alkylation

Assisted ortho-C −H Secondary Alkylation

Article

(II)

(III)

Construction of Bulky Ligand Libraries by Ru -Catalyzed P -

Ming Li, Jun-Yang Tao, Liang-Neng Wang, Jia-Wei Li, Yue-Jin Liu,* and Ming-Hua Zeng*

Cite This: https://doi.org/10.1021/acs.joc.1c01329

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sı Supporting Information

ABSTRACT: Modiﬁcation of commercially available biaryl mono-

(

II)

(III)

phosphine ligands via ruthenium -catalyzed P -directed-cata-

lyzed ortho C−H secondary alkylation is described. The use of

highly ring-strained norbornene as a secondary alkylating reagent is

the key to this transformation. A series of highly bulky ligands with

a norbornyl group were obtained in excellent yields. The modiﬁed

ligands with secondary alkyl group outperformed common

substituted phosphines in the Suzuki−Miyaura cross-coupling

reaction at a ppm mole level of Pd catalyst.

phosphine ligands via P-directed Ru⁽^I^I⁾-catalyzed ortho C−H

alkylation reaction (Scheme 1).

Norbornene is an eﬀective alkylating reagent widely used in

INTRODUCTION

■

Due to the important role of phosphine ligands in the ﬁeld of

metal catalysis, the design and synthesis of tertiary phosphine

ligands have always been the focus and frontier of organic

the ﬁeld of C−H activation owing to its unique electronic and

synthesis. The introduction of bulky substituents in the ortho

steric properties. Inspired by these elegant work and our

position of tertiary phosphine is a common and eﬀective

strategy for designing phosphine ligands, as the existence of

highly sterically hindered substituents cannot only inhibit the

ligand conversion but also improve the metal catalytic activity.

With this strategy, a series of general and eﬃcient phosphine

recent studies on C−H functionalization, especially tertiary

Scheme 1. Direct Synthesis of ortho Secondary Alkyl-

Substituted Phosphines via Strategy of P-Directed C−H

Activation

ligands, such as XPhos, BrettPhos, and RockPhos have been

alkyl substituted phosphines mainly relies on the traditional

multistep synthetic route, which survived under harsh

conditions, poor tolerance of functional groups, and low

eﬃciency, thus limiting the eﬃcient synthesis and development

of new phosphines.

Late-stage diversiﬁcation through regioselective C−H bond

functionalization of phosphorus compounds has recently

emerged as a suitable alternative to prepare new phosphines.

To avoid catalyst poisoning, the phosphorus atom has to be

(

oxidized to act as a P directing group. In 2014, Clark et al.

(

III)

demonstrated that P

could act as a directing group in Ir-

catalyzed C−H bond borylation of JohnPhos derivatives.₈

Since then, a series of novel ligands via ortho C−H borylation,

10a,11

arylation, alkylation, alkenylation,

and silylation of

phosphines have been successfully developed. However, direct

installation of bulky secondary alkyl groups into phosphine

ligands via P-directed ortho C−H activation remains a

challenge because of the sterically hindered eﬀect. As far as

we know, there are only two examples reported about ortho

secondary alkylated phosphine products, and the yields are not

Received: June 7, 2021

very high (44% and 60%). Herein, we report a general and

eﬃcient synthesis of ortho secondary alkyl-substituted

XXXX American Chemical Society

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

phosphines meta secondary alkylation, we envision that by

selecting norbornene as the alkylating reagent, the selectivity of

secondary alkylation reaction of phosphines may change from

the meta to ortho position via ortho-metalation and

subsequent insertion reaction. If this transformation can be

achieved, a series of bulky ortho-secondary alkyl-substituted

ligands would be eﬃciently prepared from commercially

available phosphines. These highly sterically hindered

phosphines will improve the eﬃciency of palladium catalyzed

Suzuki coupling reaction by accelerating oxidative addition and

reductive elimination steps.

norbornene 2a was conﬁrmed by X-ray analysis of

disubstituted product 3aa. Notably, this ruthenium-catalyzed

alkylation of phosphines had excellent stereoselectivity giving

two of the four possible isomers, which was conﬁrmed by

NMR characterization of 3a. Unfortunately, the isomers could

not be separated by column chromatography. When increasing

the amount of norbornene, the ratio of mono- and

disubstituted products reduced to 11:1, indicating the

equivalent of NBE is signiﬁcant to achieve high mono-

selectivity (entry 2). Other ligands were investigated in this

system (entries 3−6). Highly sterically hindered alkyl acid

ligand (1-AdCO H) was also eﬀective for this transformation,

RESULTS AND DISCUSSION

although with medium yield (60%) and high selectivity

(mono/di = 15:1) (entry 3). Amino acid ligands, such as H-

L-Phe-OH, H-L-Leu-OH and H-L-lle-OH were also tested,

slightly lower yields (70−86%) of product were observed,

perhaps due to their highly steric eﬀects (entries 4−6). A low

yield (52%) and selectivity (mono/di = 10:1) was observed in

the absence of ligand, which showed that L-alanine played an

important role in this reaction (entry 7). No product is

generated without addition of NaOAc and ruthenium complex,

highlighting both the base and ruthenium catalyst were

essential in this transformation (entries 8 and 9). Finally, to

demonstrate the irreplaceable norbornene, a series of other

alkenes (2b−2h) were tested. Linear and cyclic alkenes such as

■

To test our ideas, we initiated our study by choosing

commercially available [1,1′-biphenyl]-2-yldiphenylphosphane

(

1a) and norbornene (2a) as model substrates. To our delight,

the desired ortho secondary alkylated product 3a was obtained

in 98% yield with excellent monoselectivity (mono/di > 20:1)

and high stereoselectivity (exo/endo > 20:1) by using 2.5 mol

[RuCl (p-cymene)] , 30 mol % H-L-Ala-OH, and 2.0 equiv

of NaOAc in 2-Me-THF at 160 °C for 12 h (Table 1, entry 1).

The ortho-selectivity and exoaddition of the hydroarylation of

2 2

Table 1. Optimization of the Reaction Conditions

-hexene (2b) and cyclohexene (2c) were ineﬀective for this

reaction. Activated alkenes such as cyclohexanone (2e and 2f),

H-pyrrole-2,5-dione (2g), and cyclopropane (2h) had little

activities for this transformation. These results highlighted the

unique activity of norbornene and proved the key role of ring

strain in achieving the ortho secondary alkylation.

Having the optimized reaction conditions, the generality of

this ortho secondary alkylation of tertiary phosphine was

examined (Scheme 2). To our delight, the reaction had high

stereoselectivity and provided exoalkylation products. For

example, phosphines with diverse common groups such as

MeO (1b, 1h), Me (1c, 1j, 1l), F (1d, 1f, 1i, 1n), Cl (1e, 1g,

k, 1o), Ph (1m), COMe (1p), and CO Me (1q) could react

with norbornene 2a, aﬀording the corresponding exoalkylated

products in moderate to high yields (3b−3q, 41−86%) and

high selectivity (mono/di = 10:1−20:1). Substituted phos-

phines at the ortho, meta, or para positions could react

smoothly, generating the desired products. Notably, biar-

ylphosphines with an ortho-MeO (1h) group was also eﬀective

for this reaction, giving the desired monosecondary alkylated

product in medium yield (3h, 44%). However, the binaphthyl-

and dicyclohexyl-based phosphines had low activities for this

reaction, probably due to the steric hindrance eﬀect. Notably,

the substituted norbornenes with Ac and CN groups could

undergo this ortho-alkylation reaction smoothly, aﬀording the

corresponding products in moderate yields (3r, 58%; 3s, 52%).

The alkylated phosphine 3a with Ad group at the ortho

position could further react with norbornene 2a but give a low

yield of dialkylated product 3aa due largely to steric hindrance.

Thus, a series of new largely steric phosphines with diﬀerent

electronic properties were prepared for the ﬁrst time.

Unfortunately, substrates such as JohnPhos, CyJohnPhos,

and CataCXium as well as norbornadiene had little activity

in this transformation, giving a trace amount of products (3t−

3w), probably due to unsuitable steric and electronic

properties.

Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), [RuCl (p-

cymene)] (2.5 mol %), H-L-Ala-OH (30 mol %), and NaOAc (2.0

equiv) in 1 mL of 2-Me-THF at 160 °C under argon, 12 h. Ratio of

a/3aa was determined by P NMR using PPh₃as an internal

standard. Yield of product was determined by H NMR using

CH Br as an internal standard. Diastereoselectivity (dr = 1:1) was

To prove the practicality of this protocol, a gram-scale

reaction of 2-diphenylphosphinobiphenyl (1a) and norbornene

determined by P NMR.

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

Scheme 2. Scope of ortho-Alkylation Reaction

Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), [RuCl (p-cymene)] (2.5 mol %), H-L-Ala-OH (30 mol %), and NaOAc (2.0 equiv) in 1 mL

of 2-Me-THF at 160 °C under argon, 12 h. Isolated yield. P NMR yield.

(

2a) was carried out under standard conditions. To our

mol ppm level (Scheme 3a). 4-Bromoanisole (4a) and

phenylboronic acid (5a) were selected as substrates in the

presence of 0.001 mol % PdCl (PPh ) (10 mol ppm). To our

delight, 1.2 g of alkylated products was obtained in 88% yield

(

for details see the Supporting Information).

3 2

Palladium catalyzed Suzuki−Miyaura reaction is one of the

delight, our secondary alkyl-substituted phosphine (3a)

showed excellent catalytic activity and provided the desired

biaryl product (6a) in almost perfect yield (95%). In

comparison, the unsubstituted biarylphosphine (1a) gave a

low yield of product, indicating the importance of the alkyl

most eﬀective cross-coupling reactions for the construction of

C−C bond. However, the high cost and toxicity of the Pd-

system limit its wide application in chemical and pharmaceut-

ical. Using low catalyst loadings will decrease the cost of the

catalyst and the toxicity of the reaction system, making the

reaction more attractive to industry. When the palladium-

loading at a level of 10 mol ppm, the price and toxicity of

group. Linear alkylated phosphine (L1)

and arylated

15a

phosphine (L4) previously reported by our group as well

as the common used XPhos (L5) were also tested in low

catalyst loading, but they gave lower yields (81%, 75%, and

83%). This result showed that the large secondary alkyl group

played a key role in promoting the activity of palladium

catalyst would remove the concern. We expected with our

highly sterically hindered Buchwald-phosphines, the palladium-

catalyzed Suzuki−Miyaura reaction could be conducted at the

J. Org. Chem. XXXX, XXX, XXX−XXX

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Article

Scheme 3. Synthetic Application

substituted substrates for both aryl bromides and arylboronic

acids could react in the presence of 3a, aﬀording largely steric

di- or tri-substituted biaryls. To further prove the generality of

our largely steric ligands, the phosphine of 3a was further

extended to Sonogashira and Heck reactions (Scheme 3c). To

our delight, medium to high yields of alkenylated product 8a

and alkynylation product 8b could be obtained under common

conditions in the presence of 3a ligand. These results proved

that installation of a bulky secondary alkyl group into ligand

could obviously improve the catalytic activity of phosphine and

these ligands may have potential in the ﬁeld of metal catalysis.

To gain insights into the mechanism of ruthenium catalyzed

ortho secondary alkylation reaction of tertiary phosphines, the

six-membered cycloruthenium complex (Int A) was prepared

from 1a and ruthenium catalyst ﬁrst (for details see the

15b

Supporting Information).

As we expected, Int A could

replace the [RuCl (p-cymene)] as a catalyst for alkylation and

deliver the product 3a in 53% yield (Scheme 4a). When using

Scheme 4. Mechanistic Studies

Reaction conditions: 4 (0.5 mmol), 5 (0.65 mmol), PdCl (PPh )

3 2

(

0.001 mol %), ligand (0.01 mol %), and K PO (2.0 equiv) in 0.6 mL

of THF and 0.4 mL of H O at 100 °C under argon, 10 h. ArOTf as

coupling reagent. ArCl as coupling reagent, PdCl (PPh ) (0.01 mol

3 2

), 3a (0.1 mol %). PdCl (PPh ) (0.01 mol %), 3a (0.1 mol %).

2 3 2

PdCl (PPh ) (1 mol %), 3a (10 mol %).

3 2

a stoichiometric amount of Int A as the substrate, 49% yield of

alkylated products (3a and 3aa) were observed (Scheme 4b).

These experimental results implicated the Int A may be an

intermediate relating to the catalytic cycle. Next, a deuterium

exchange experiment was conducted under standard con-

catalyst. Other common ortho-substituted biarlyphosphines

with Me N (PhDavePhos, L2) and OMe (L3) were also

studied, but low activities were observed (37% and 42%) in 10

mol ppm of Pd-catalyst. These results demonstrated the high

catalytic activity of our secondary alkylated phosphines. Using

the phosphine product (3a) and 0.001 mol % of palladium

catalyst, a series of biaryl compounds (6a−6l) with electron-

withdrawing and electron-donating substituent groups were

prepared in moderate to excellent yields (Scheme 3b).

Notably, less active ArOTf and ArCl could be active using

our phosphine ligand. Morever, the substrates containing

heterocycle such as furan and quinoline were also tolerant with

a higher load of Pd catalyst (6m and 6n). Furthermore, ortho-

ditions with addition of methanol-d , and 40% of deuterium

substitution at the ortho position of isolated product was

observed (Scheme 4c), indicating that the C−H bond cleavage

is reversible. At last, parallel experiments of 1a or 1a-d with 2a

revealed a kinetic isotope eﬀect (KIE) of 2.3, suggesting that

C−H bond cleavage might be the rate-determining step

(Scheme 4d).

Based on these experimental results, we proposed a plausible

mechanistic process for this C−H secondary alkylation

(Scheme 5). First, the active Ru(II) species I is generated in

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

structures were solved by direct methods and reﬁned by full-matrix

least-squares method on F using SHELXTL-2014. All non-hydrogen

Scheme 5. Proposed Catalytic Cycle

atoms were reﬁned with anisotropic displacement parameters. The

hydrogen atoms of the ligand were generated geometrically. High-

resolution mass spectra (HRMS) were recorded on the Thermo

Scientiﬁc Exactive Plus (orbitrap) equipped with an electrospray

ionization (ESI) ionization source.

Preparation of Starting Materials. Materials were purchased

from Alfa-Aesar, Laajoo, Macklin, Adamas, Bidepharm, and Aladdin

and used as received. All the solvents were purchased from

commercial suppliers and puriﬁed by standard procedures as speciﬁed

in Purification of Laboratory Chemicals.

General Procedure for Ru(II)-Catalyzed Direct ortho-

Selective Secondary Alkylation. To a 25 mL Schlenk tube was

added 1 (0.2 mmol, 1.0 equiv), 2 (0.4 mmol, 2.0 equiv), [RuCl (p-

cymene)] (3.1 mg, 2.5 mol %), H-L-Ala-OH (5.3 mg, 30 mol %),

and NaOAc (32.8 mg, 2.0 equiv). The tube was purged with Ar three

times, followed by the addition of 2-Me-THF (1 mL). The mixture

was stirred at 160 °C in the heating module for 12 h. The solution

was then cooled to room temperature, and the solvent was removed

under vacuum directly. The crude product was puriﬁed by column

chromatography on silica gel aﬀording the alkylated products 3.

Evaluation of the Developed Ligands in Suzuki−Miyaura

Couplings. A stock solution of PdCl (PPh ) (1.4 mg) with 3a (8.6

3 2

mg) in THF (10 mL) was initially prepared with continuous stirring

at room temperature under a nitrogen atmosphere for 5 min. To a 25

mL Schlenk tube was added the stock solution (25 μL), and the

solvent was removed under vacuum directly. Then, 4-bromoanisole 4a

the presence of H-L-Ala-OH and KOAc. Then, the phosphine

a coordinates with the Ru(II) species I to form the Ru

complex II, which undergoes C−H activation generating the

six-membered cycloruthenated complex III. Next, coordination

of the NBE with complex III followed by exoinsertion into the

Ru−C bond delivers the intermediate IV. Finally, the

alkylation product 3a generates after protonation of IV and

regenerates the active complex I.

(0.5 mmol, 93.0 mg, 1.0 equiv), phenylboronic acid 5a (0.65 mmol,

9.3 mg, 1.3 equiv), and K PO (212 mg, 2.0 equiv) was added to the

Schlenk tube. The tube was purged with Ar three times, followed by

the addition of H O (0.4 mL) and THF (0.6 mL). The mixture was

stirred at 100 °C in the heating module for 10 h. The solution was

then cooled to room temperature, and the solvent was removed under

vacuum directly. The crude product was puriﬁed by column

CONCLUSION

chromatography on silica gel (R = 0.4, hexane) aﬀording the pure

product 6a (white solid, 87.4 mg, 95% yield).

■

In summary, we have developed the ﬁrst ruthenium-catalyzed

Evaluation of the Developed Ligands in Heck Reaction. To

a 25 mL Schlenk tube was added 1-bromo-2-methylbenzene 4g (0.5

mmol, 85.0 mg, 1.0 equiv), ethyl acrylate 7a (1.5 mmol, 150.1 mg, 3.0

equiv), PdCl (PPh ) (0.1 mol %), 3a (1 mol %), and K CO (2.0

(

III)

-directed ortho-selective C−H secondary alkylation, which

provides straight and eﬃcient access to highly sterically

hindered tertiary phosphines. By selection of highly ring-

tensioned norbornene as the alkylating reagent, we change the

regioselectivity from the meta to the ortho position. A series of

new highly steric biarylphosphines with norbornyl group were

obtained with high yields and monoselectivity from commer-

cially available starting materials. The excellent catalytic

activities of these phosphine ligands were demonstrated in

the palladium-catalyzed Suzuki−Miyaura cross-coupling reac-

tion. This work will have signiﬁcant potentials in the ﬁeld of

metal catalysis and ligand development. Other applications and

more detailed mechanistic investigations are underway in our

lab.

equiv). The tube was purged with Ar three times, followed by the

addition of toluene (0.5 mL). The mixture was stirred at 100 °C in

the heating module for 10 h. The solution was then cooled to room

temperature, and the solvent was removed under vacuum directly.

The crude product was puriﬁed by column chromatography on silica

gel (R = 0.3, EA/hexane = 1/50) aﬀording the pure product 8a

(

colorless oil, 70.3 mg, 74% yield).

Evaluation of the Developed Ligands in Sonogashira

Reaction. To a 25 mL Schlenk tube was added 1-methoxy-4-

methylbenzene 4a′ (0.5 mmol, 61.0 mg, 1.0 equiv), ethynylbenzene

b (0.55 mmol, 56.1 mg, 1.1 equiv), PdCl (PPh ) (0.1 mol %), 3a (1

2 3 2

mol %), CuI (5 mol %), and Et N (1.5 equiv). The tube was purged

with Ar three times, followed by the addition of toluene (0.5 mL).

The mixture was stirred at 100 °C in the heating module for 10 h.

The solution was then cooled to room temperature, and the solvent

was removed under vacuum directly. The crude product was puriﬁed

EXPERIMENTAL SECTION

■

General Information. All reactions were carried out in a ﬂame-

dried, sealed Schlenk reaction tube under an atmosphere of argon.

Analytical thin layer chromatography (TLC) was performed on silica

gel plates with F-254 indicator, and compounds were visualized by

irradiation with UV light. Flash column chromatography was carried

by column chromatography on silica gel (R = 0.7, hexane) aﬀording

the pure product 8b (colorless oil, 58.3 mg, 56% yield).

Crystallography. Single crystals of 3aa and 3k suitable for X-ray

diﬀraction were grown by layering methanol on the dichloromethane

solutions. The diﬀraction data of crystals were collected on a Rigaku

XtaLAB Synergy CCD diﬀractometer with graphite monochromated

Cu-Kα radiation (λ = 1.54056 Å) at 293 or 100 K. Absorption

corrections were applied by SADABS. The non-hydrogen atoms were

reﬁned anisotropically, and the hydrogen atoms were generated

geometrically with isotropic thermal parameters. All the structures

were solved by direct methods and reﬁned by full-matrix least-squares

out using silica gel (200−300 mesh) at increased pressure. The H,

C, P, and F NMR spectroscopic data were recorded on Bruker

Mercury Plus 400 MHz NMR spectrometers. Chemical shifts (δ) for

H and C are referenced to internal solvent resonances and reported

relative to SiMe . Chemical shifts for P are reported relative to an

external 85% H PO standard. The diﬀraction data of crystals were

collected on a Rigaku XtaLAB Synergy CCDC diﬀractometer with

graphite monochromated Cu-Kα radiation (λ = 1.54056 Å) at 293 or

00 K. Absorption corrections were applied by SADABS. All the

method on F using Olex2. The CCDC reference number is 2059805

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

for 3aa and 2070266 for 3k. The ellipsoid contour is 50% probability

in the caption for the image of the 3aa and 3k.

133.7, 133.6, 133.5, 132.6, 132.5, 132.5, 132.4, 130.5 (d, J = 3.0 Hz),

130.4 (d, J = 3.0 Hz), 128.6, 128.5, 128.4, 128.2, 128.1, 125.6, 125.2,

124.7, 124.5, 117.9, 117.8, 117.7, 117.6, 117.5, 117.4, 117.3, 114.7 (d,

J = 20.2 Hz), 114.6 (d, J = 20.2 Hz), 44.3, 43.6, 41.8, 41.6, 38.4, 37.4,

Analytical Characterization Data of Products. (2′-(Bicyclo-

[

2.2.1]heptan-2-yl)-[1,1′-biphenyl]-2-yl)diphenylphosphane (3a).

Puriﬁcation by column chromatography on silica gel (EA/hexane =

37.0, 36.8, 36.1, 31.1, 30.6, 28.6, 28.5; P NMR (162 MHz, CDCl ) δ

/100) yielded 3a (84.7 mg, 98%) as a colorless oil. m/d > 20:1, dr =

−16.0, −17.0; F NMR (377 MHz, CDCl ) δ −112.9, −113.0.

HRMS (ESI) m/z: [M + H] calcd for C H FP 451.1985; found

.2:1. H NMR (400 MHz, CDCl ) δ 7.44−7.38 (m, 1.5H), 7.36−

31 29

.32 (m, 9H), 7.25−7.17 (m, 5.5H), 7.05−6.97 (m, 1H), 6.85 (d, J =

.6 Hz, 0.5H), 6.78 (d, J = 6.8 Hz, 0.5H), 2.56 (t, J = 6.8 Hz, 1H),

.46 (s, 0.5H), 2.27 (s, 1H), 2.20 (s, 0.5H), 1.75−1.66 (m, 1.5H),

.50−1.38 (m, 3H), 1.27 (d, J = 9.6 Hz, 0.5H), 1.15−0.88 (m, 3H);

451.1979.

(2′-(Bicyclo[2.2.1]heptan-2-yl)-5-chloro-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3e). Puriﬁcation by column chromatography on

silica gel (EA/hexane = 1/100) yielded 3e (61.5 mg, 66%) as a

C{1H} NMR (101 MHz, CDCl ) δ 148.3 (d, J = 32.3 Hz), 148.2

colorless oil. m/d > 20:1, dr = 1.2:1. H NMR (400 MHz, CDCl ) δ

(

d, J = 32.3 Hz), 145.7, 145.0, 141.2 (d, J = 7.1 Hz), 140.9 (d, J = 7.1

7.37 (d, J = 7.6 Hz, 0.5H), 7.31−7.29 (m, 7.5H), 7.20−7.12 (m, 5H),

7.08−7.05 (m, 1H), 7.01−6.93 (m, 1H), 6.76 (d, J = 7.2 Hz, 0.5H),

6.70 (dd, J = 7.6, 1.2 Hz, 0.5H), 2.52−2.44 (m, 1.5H), 2.27 (s, 1H),

2.17 (s, 0.5H), 1.72−1.63 (m, 1.5H), 1.47−1.42 (m, 3H), 1.27 (s,

Hz), 138.0, 137.8 (d, J = 12.1 Hz), 137.5 (d, J = 12.1 Hz), 136.8 (d, J

11.1 Hz), 136.6 (d, J = 11.1 Hz), 134.2, 134.1, 134.0, 133.9, 133.8,

33.7, 133.6, 130.8, 130.7, 130.6, 130.5, 130.4, 128.6, 128.5, 128.4,

28.3, 127.7 (d, J = 9.1 Hz), 127.4 (d, J = 8.1 Hz), 125.5, 125.1,

24.5, 124.4, 44.3, 43.6, 41.8, 41.7, 41.5, 38.4, 38.3, 37.4, 36.9, 36.8,

0.5H), 1.15−0.88 (m, 3H); C{1H} NMR (101 MHz, CDCl ) δ

149.9 (d, J = 33.3 Hz), 149.8 (d, J = 32.3 Hz), 145.6, 144.9, 139.9 (d,

J = 7.1 Hz), 139.6 (d, J = 7.1 Hz), 137.5, 137.4, 137.3, 137.2, 137.0,

136.9, 135.9, 135.7, 135.6, 135.2, 134.7, 134.6, 134.0, 133.8, 133.6,

130.7, 130.6 (d, J = 3.0 Hz), 130.5 (d, J = 3.0 Hz), 130.4, 128.7,

128.6, 128.5, 128.4, 128.2, 128.1, 127.7, 127.5, 125.6, 125.2, 124.6,

124.5, 44.4, 44.3, 43.7, 41.8, 41.6, 38.5, 38.4, 37.5, 37.0, 36.8, 36.1,

6.1, 31.1, 30.6, 28.6, 28.5; P NMR (162 MHz, CDCl ) δ −14.4,

−

15.5. HRMS (ESI) m/z: [M + H] calcd for C H P 433.2080;

31 30

found 433.2076.

(

2′-(Bicyclo[2.2.1]heptan-2-yl)-5-methoxy-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3b). Puriﬁcation by column chromatography

on silica gel (EA/hexane = 1/100) yielded 3b (75.8 mg, 82%) as a

colorless oil. m/d = 15:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

31.2, 30.6, 28.6, 28.5; P NMR (162 MHz, CDCl ) δ −15.5, −16.5.

HRMS (ESI) m/z: [M + H] calcd for C H ClP 467.1690; found

31 29

.40 (d, J = 8.0 Hz, 0.5H), 7.34−7.30 (m, 7.5H), 7.24−7.19 (m, 4H),

.12−6.99 (m, 2H), 6.90−6.87 (m, 2H), 6.83−6.77 (m, 1H), 3.83 (s,

H), 2.59 (s, 1H), 2.45 (s, 0.5H), 2.28 (s, 1H), 2.45 (s, 0.5H), 1.75−

.67 (m, 1.5H), 1.49−1.42 (m, 3H), 1.28 (d, J = 7.6 Hz, 0.5H), 1.16−

467.1682.

(2′-(Bicyclo[2.2.1]heptan-2-yl)-4-ﬂuoro-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3f). Puriﬁcation by column chromatography on

silica gel (EA/hexane = 1/100) yielded 3f (66.6 mg, 74%) as a

colorless oil. m/d > 20:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

.86 (m, 3H); ¹³C{1H} NMR (101 MHz, CDCl ) δ 159.8, 159.7,

50.1 (d, J = 34.3 Hz), 145.6, 145.0, 141.3 (d, J = 7.1 Hz), 141.1 (d, J

7.37−7.28 (m, 8H), 7.20−7.06 (m, 6H), 7.00−6.92 (m, 1H), 6.84−

6.80 (m, 1H), 6.75 (d, J = 7.2 Hz, 0.5H), 6.70 (dd, J = 7.6, 0.8 Hz,

0.5H), 2.48 (t, J = 8.0 Hz, 1H), 2.43 (s, 0.5H), 2.28−2.25 (m, 1H),

2.15 (s, 0.5H), 1.72−1.63 (m, 1.5H), 1.47−1.38 (m, 3H), 1.27 (s,

6.1 Hz), 138.7, 138.6, 138.5, 138.4, 138.3, 136.0, 135.6, 133.8,

33.7, 133.6, 133.5, 133.4, 130.5 (d, J = 3.0 Hz), 130.4 (d, J = 4.0

Hz), 128.4, 128.3, 128.2, 127.8 (d, J = 9.1 Hz), 127.6 (d, J = 9.1 Hz),

27.5, 125.6, 125.2, 124.6, 124.4, 116.0 (d, J = 6.1 Hz), 115.6 (d, J =

.1 Hz), 113.8, 113.7, 55.4, 44.2, 43.8, 41.9, 41.7, 38.5, 37.4, 36.9,

6.8, 36.1, 31.1, 30.7, 28.6, 28.5; P NMR (162 MHz, CDCl ) δ

0.5H), 1.13−0.89 (m, 3H); C{1H} NMR (101 MHz, CDCl ) δ

162.0 (d, J = 248.5 Hz), 146.0, 145.3, 144.0 (d, J = 31.3 Hz), 143.8

(d, J = 30.3 Hz), 140.1, 140.0, 139.9, 139.8, 139.7, 137.1, 137.0, 136.7,

136.6, 134.1 (d, J = 6.1 Hz), 133.9, 133.7 (d, J = 6.1 Hz), 132.3 (d, J =

12.1 Hz), 132.0 (d, J = 13.1 Hz), 131.0 (d, J = 3.0 Hz), 130.9 (d, J =

3.0 Hz), 128.8, 128.7, 128.6, 128.5, 128.4, 128.0, 127.9, 125.6, 125.1,

124.5, 124.4, 120.3 (d, J = 20.2 Hz), 119.9 (d, J = 21.2 Hz), 115.7 (d,

−

16.4, −17.4, −18.9, −19.8. HRMS (ESI) m/z: [M + H] calcd for

C H OP 463.2185; found 463.2179.

(

2′-(Bicyclo[2.2.1]heptan-2-yl)-5-methyl-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3c). Puriﬁcation by column chromatography on

silica gel (EA/hexane = 1/100) yielded 3c (41.9 mg, 47%) as a

colorless oil. m/d > 20:1, dr = 1.2:1. H NMR (400 MHz, CDCl ) δ

J = 15.2 Hz), 115.5 (d, J = 15.2 Hz), 44.4, 44.3, 43.6, 41.7, 38.4, 37.5,

37.0, 36.8, 36.1, 31.2, 30.6, 28.6, 28.5; P NMR (162 MHz, CDCl ) δ

−13.7, −14.8; F NMR (377 MHz, CDCl ) δ −114.9. HRMS (ESI)

m/z: [M + H] calcd for C H FP 451.1985; found 451.1982.

.35 (d, J = 7.6 Hz, 0.5H), 7.30−7.26 (m, 7.5H), 7.20−7.13 (m, 4H),

.11−7.09 (m, 1.5H), 7.01−6.93 (m, 2.5H), 6.83 (d, J = 7.2 Hz,

.5H), 6.75 (d, J = 7.6 Hz, 0.5H), 2.51 (t, J = 8.0 Hz, 1H), 2.41 (s,

.5H), 2.36 (d, J = 3.6 Hz, 3H), 2.23 (s, 1H), 2.16 (s, 0.5H), 1.71−

.62 (m, 1.5H), 1.47−1.35 (m, 3H), 1.22 (d, J = 9.6 Hz, 0.5H), 1.11−

(2′-(Bicyclo[2.2.1]heptan-2-yl)-4-chloro-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3g). Puriﬁcation by column chromatography

on silica gel (EA/hexane = 1/100) yielded 3g (80.2 mg, 86%) as a

colorless oil. m/d > 20:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

.83 (m, 3H); ¹³C{1H} NMR (101 MHz, CDCl ) δ 148.4 (d, J =

2.3 Hz), 148.3 (d, J = 33.3 Hz), 145.7, 145.1, 141.4 (d, J = 7.1 Hz),

41.2 (d, J = 6.1 Hz), 138.5, 138.4, 138.3, 138.2, 138.1, 137.9, 134.4,

34.0, 133.9, 133.8, 133.7, 133.6, 133.5, 133.2, 133.1, 133.0, 131.5 (d,

7.39−7.30 (m, 8.5H), 7.23−7.08 (m, 6.5H), 7.00−6.93 (m, 1H), 6.74

(d, J = 7.6 Hz, 0.5H), 6.68 (d, J = 7.6 Hz, 0.5H), 2.51−2.43 (m,

1.5H), 2.28−2.25 (m, 1H), 2.16 (s, 0.5H), 1.72−1.64 (m, 1.5H),

J = 6.1 Hz), 131.3 (d, J = 6.1 Hz), 130.7, 130.6, 128.4, 128.3, 128.2,

1.47−1.39 (m, 3H), 1.28 (s, 0.5H), 1.15−0.89 (m, 3H); C{1H}

27.7, 127.6, 125.5, 125.1, 124.5, 124.4, 44.3, 44.2, 43.8, 41.8, 41.6,

8.5, 37.5, 36.9, 36.8, 36.1, 31.1, 30.5, 28.6, 28.5, 21.4; P NMR (162

NMR (101 MHz, CDCl ) δ 146.5 (d, J = 31.3 Hz), 146.4 (d, J = 31.3

Hz), 145.8, 145.1, 139.9, 139.8, 139.7, 139.6, 139.5, 136.9, 136.9 (d, J

= 12.1 Hz), 136.6 (d, J = 12.1 Hz), 134.1, 133.9, 133.7, 133.5, 133.4,

133.0, 132.1 (d, J = 6.1 Hz), 131.8 (d, J = 5.1 Hz), 130.8 (d, J = 3.0

Hz), 130.7 (d, J = 4.0 Hz), 128.8, 128.7, 128.6, 128.5, 128.4, 128.1,

MHz, CDCl ) δ −15.4, −16.4. HRMS (ESI) m/z: [M + H] calcd for

C H P 447.2236; found 447.2227.

(

2′-(Bicyclo[2.2.1]heptan-2-yl)-5-ﬂuoro-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3d). Puriﬁcation by column chromatography

on silica gel (EA/hexane = 1/100) yielded 3d (56.7 mg, 63%) as a

colorless oil. m/d > 20:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

28.0, 125.6, 125.2, 124.6, 124.5, 44.4, 44.3, 43.6, 41.7, 38.5, 38.4,

7.5, 37.0, 36.8, 36.1, 31.2, 30.6, 28.6, 28.5; P NMR (162 MHz,

CDCl ) δ −13.6, −14.8. HRMS (ESI) m/z: [M + H] calcd for

C H ClP 467.1690; found 467.1683.

.38 (d, J = 7.6 Hz, 0.5H), 7.33−7.29 (m, 7H), 7.20−7.10 (m, 5.5H),

.04−6.99 (m, 2H), 6.97−6.91 (m, 1H), 6.79 (d, J = 7.6 Hz, 0.5H),

.73 (dd, J = 7.6, 1.2 Hz, 0.5H), 2.55−2.50 (m, 1H), 2.44 (s, 0.5H),

.27 (s, 1H), 2.18 (s, 0.5H), 1.73−1.63 (m, 1.5H), 1.46−1.44 (m,

.5H), 1.27 (s, 0.5H), 1.14 (d, J = 9.6 Hz, 0.5H), 1.10−0.86 (m, 3H);

(

2′-(Bicyclo[2.2.1]heptan-2-yl)-6′-methoxy-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3h). Puriﬁcation by column chromatography

on silica gel (EA/hexane = 1/100) yielded 3h (40.7 mg, 44%) as a

colorless oil. m/d > 20:1, dr = 1:1. H NMR (400 MHz, CDCl ) δ

7.46−7.40 (m, 1H), 7.34−7.27 (m, 7.5H), 7.25−7.14 (m, 6.5H), 7.03

(d, J = 8.0 Hz, 0.5H), 6.95 (d, J = 8.0 Hz, 0.5H), 6.68 (d, J = 8.4 Hz,

0.5H), 6.63 (d, J = 8.0 Hz, 0.5H), 3.24 (d, J = 23.6 Hz, 3H), 2.33−

2.30 (m, 1.5H), 2.22 (s, 1H), 2.14 (d, J = 3.2 Hz, 0.5H), 1.73 (d, J =

C{1H} NMR (101 MHz, CDCl ) δ 162.9 (d, J = 251.5 Hz), 162.8

(

d, J = 250.5 Hz), 150.8 (d, J = 19.2 Hz), 150.5 (d, J = 19.2 Hz),

45.5, 144.9, 140.2, 140.1, 139.9, 139.8, 137.9, 137.8, 137.7, 137.6,

37.5, 137.4, 136.3 (d, J = 8.1 Hz), 135.9 (d, J = 8.1 Hz), 133.9,

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

.6 Hz, 0.5H), 1.65−1.58 (m, 1H), 1.47−1.32 (m, 3H), 1.22 (d, J =

.6 Hz, 0.5H), 1.09 (d, J = 10.0 Hz, 0.5H), 0.96−0.76 (m, 2.5H);

(2′-(Bicyclo[2.2.1]heptan-2-yl)-4′-methyl-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3l). Puriﬁcation by column chromatography on

C{1H} NMR (101 MHz, CDCl ) δ 157.0 (d, J = 14.1 Hz), 157.0

silica gel (EA/hexane = 1/100) yielded 3l (36.6 mg, 41%) as a

colorless oil. m/d > 20:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

(

d, J = 15.2 Hz), 147.6, 147.0, 144.8 (d, J = 35.4 Hz), 144.6 (d, J =

.38−7.34 (m, 1H), 7.30−7.28 (m, 7H), 7.21−7.09 (m, 7H), 6.84−

.78 (m, 1H), 6.71 (d, J = 7.6 Hz, 0.5H), 6.65 (d, J = 7.6 Hz, 0.5H),

.50 (t, J = 7.6 Hz, 1H), 2.41 (s, 0.5H), 2.37 (s, 3H), 2.24 (s, 1H),

.17 (s, 0.5H), 1.72−1.63 (m, 1.5H), 1.48−1.36 (m, 3H), 1.22 (d, J =

4.3 Hz), 138.5 (d, J = 13.1 Hz), 138.2 (d, J = 13.1 Hz), 137.9, 137.8,

37.5 (d, J = 9.1 Hz), 137.3 (d, J = 10.1 Hz), 134.7, 134.4, 133.9,

33.8, 133.7, 133.6, 133.5, 131.3 (d, J = 6.1 Hz), 130.9 (d, J = 6.1

Hz), 130.0 (d, J = 7.1 Hz), 129.7 (d, J = 7.1 Hz), 129.1, 128.9, 128.7,

.2 Hz, 0.5H), 1.12−0.85 (m, 3H); C{1H} NMR (101 MHz,

28.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.3, 127.2, 118.1, 117.6,

07.4, 107.2, 54.9, 54.8, 44.3, 44.1, 42.0, 41.9, 41.8, 38.4, 37.6, 36.8,

6.7, 36.1, 31.2, 30.7, 28.6, 28.5; P NMR (162 MHz, CDCl ) δ

CDCl ) δ 148.5 (d, J = 33.3 Hz), 148.4 (d, J = 32.3 Hz), 145.3, 144.8,

38.5 (d, J = 7.1 Hz), 138.2 (d, J = 7.1 Hz), 138.1, 138.0, 137.8,

37.7, 137.2, 137.1, 136.8 (d, J = 11.1 Hz), 136.6 (d, J = 10.1 Hz),

34.4, 134.0, 133.9, 133.8, 133.7, 133.6, 131.0 (d, J = 5.1 Hz), 130.7

−

14.6, −15.5. HRMS (ESI) m/z: [M + H] calcd for C H OP

63.2185; found 463.2176.

(d, J = 5.1 Hz), 130.6, 130.5, 128.6, 128.5, 128.4, 128.3, 127.3 (d, J =

(

2′-(Bicyclo[2.2.1]heptan-2-yl)-6′-ﬂuoro-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3i). Puriﬁcation by column chromatography on

silica gel (EA/hexane = 1/100) yielded 3i (46.8 mg, 52%) as a

colorless oil. m/d > 20:1, dr = 1:1. H NMR (400 MHz, CDCl ) δ

9.1 Hz), 126.4, 126.0, 125.2 (d, J = 12.1 Hz), 44.2, 44.2, 43.5, 41.8,

41.4, 38.4, 37.4, 36.9, 36.8, 36.1, 31.1, 30.6, 28.6, 21.9, 21.8; P NMR

(162 MHz, CDCl

calcd for C32 32P 447.2236; found 447.2234.

) δ −14.9, −15.9. HRMS (ESI) m/z: [M + H]

.44−7.37 (m, 1H), 7.35−7.23 (m, 10.5H), 7.20−7.11 (m, 4H), 7.03

(

d, J = 7.6 Hz, 0.5H), 6.87 (t, J = 8.4 Hz, 0.5H), 6.80 (t, J = 8.4 Hz,

(2′-(Bicyclo[2.2.1]heptan-2-yl)-[1,1′:4′,1″-terphenyl]-2-yl)-

.5H), 2.30−2.16 (m, 2.5H), 2.01 (d, J = 3.2 Hz, 0.5H), 1.64 (d, J =

diphenylphosphane (3m). Puriﬁcation by column chromatography

on silica gel (EA/hexane = 1/100) yielded 3m (77.2 mg, 76%) as a

colorless oil. m/d = 12:1, dr = 1.1:1. H NMR (400 MHz, CDCl

7.65 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 1.6 Hz, 0.5H), 7.54 (d, J = 1.2

Hz, 0.5H), 7.48−7.31 (m, 11H), 7.25−7.17 (m, 7H), 6.90 (d, J = 7.6

Hz, 0.5H), 6.83 (d, J = 7.6 Hz, 0.5H), 2.61 (t, J = 8.4 Hz, 1H), 2.52

(s, 0.5H), 2.31−2.26 (m, 1.5H), 1.80−1.72 (m, 1.5H), 1.55−1.42 (m,

3H), 1.31 (s, 0.5H), 1.15−0.91 (m, 3H); C{1H} NMR (101 MHz,

CDCl ) δ 148.0 (d, J = 32.3 Hz), 147.9 (d, J = 31.3 Hz), 146.1, 145.5,

.6 Hz, 0.5H), 1.52−1.27 (m, 4H), 1.20 (d, J = 9.6 Hz, 0.5H), 1.03−

.70 (m, 3H); ¹³C{1H} NMR (101 MHz, CDCl ) δ 160.0 (d, J =

) δ

43.4 Hz), 159.8 (d, J = 244.4 Hz), 149.1, 148.3, 141.8 (d, J = 28.3

Hz), 141.4 (d, J = 27.3 Hz), 137.9 (d, J = 11.1 Hz), 137.8 (d, J = 12.1

Hz), 137.7, 137.5, 137.4, 137.1 (d, J = 13.1 Hz), 136.8 (d, J = 13.1

Hz), 134.6, 134.2, 134.1 (d, J = 10.1 Hz), 133.9 (d, J = 10.1 Hz),

33.6 (d, J = 11.1 Hz), 133.4 (d, J = 11.1 Hz), 131.3 (d, J = 5.1 Hz),

30.9 (d, J = 6.1 Hz), 129.2 (d, J = 8.1 Hz), 129.0, 128.9 (d, J = 9.1

Hz), 128.8, 128.7, 128.6, 128.5, 128.3 (d, J = 7.1 Hz), 128.2 (d, J =

141.8, 141.7, 140.4, 140.3, 140.1, 137.8 (d, J = 9.1 Hz), 137.7 (d, J =

9.1 Hz), 137.7, 137.5, 137.4, 136.9 (d, J = 11.1 Hz), 136.7 (d, J = 11.1

Hz), 134.2, 134.1, 134.0, 133.9, 133.8, 133.7, 131.2 (d, J = 13.1 Hz),

131.1 (d, J = 14.1 Hz), 130.9 (d, J = 6.1 Hz), 130.6 (d, J = 5.1 Hz),

128.8, 128.5, 128.4, 128.3, 127.5, 127.4, 127.3, 127.2, 124.4, 124.0,

123.3, 123.2, 44.4, 43.7, 41.8, 41.6, 38.5, 37.6, 37.0, 36.8, 36.2, 31.1,

.1 Hz), 128.1, 128.0, 121.3, 121.2, 120.7, 120.6, 112.4, 112.2, 112.0,

4.5, 44.3, 44.2, 42.1, 41.6, 37.8, 37.6, 36.9, 36.5, 35.7, 30.9, 30.5,

8.5, 28.4; P NMR (162 MHz, CDCl ) δ −13.7, −13.8, −14.7,

−

14.8; ¹⁹F NMR (377 MHz, CDCl ) δ −110.9, −111.0. HRMS

(

ESI) m/z: [M + H] calcd for C H FP 451.1985; found 451.1982.

(

2′-(Bicyclo[2.2.1]heptan-2-yl)-5′-methyl-[1,1′-biphenyl]-2-yl)-

30.6, 28.7, 28.5; P NMR (162 MHz, CDCl

−17.9. HRMS (ESI) m/z: [M + H] calcd for C H P 509.2393;

found 509.2395.

) δ −14.1, −15.2, −16.9,

diphenylphosphane (3j). Puriﬁcation by column chromatography on

silica gel (EA/hexane = 1/100) yielded 3j (41.9 mg, 47%) as a

colorless oil. m/d > 20:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

(2′-(Bicyclo[2.2.1]heptan-2-yl)-4′-ﬂuoro-[1,1′-biphenyl]-2-yl)-

.41−7.35 (m, 1H), 7.32−7.28 (m, 7.5H), 7.25−7.08 (m, 7.5H), 6.49

diphenylphosphane (3n). Puriﬁcation by column chromatography

on silica gel (EA/hexane = 1/100) yielded 3n (72.1 mg, 80%) as a

.5H), 2.26−2.19 (m, 1.5H), 2.06 (d, J = 6.4 Hz, 3H), 1.72−1.65 (m,

colorless oil. m/d > 20:1, dr = 1:1. H NMR (400 MHz, CDCl

) δ

.5H), 1.47−1.39 (m, 3H), 1.23 (d, J = 9.6 Hz, 0.5H), 1.14−0.90 (m,

7.41−7.35 (m, 1H), 7.30−7.28 (m, 7H), 7.24−7.10 (m, 6H), 7.06−

6.98 (m, 1H), 6.75−6.60 (m, 2H), 2.48 (t, J = 8.0 Hz, 1H), 2.38 (s,

0.5H), 2.26−2.24 (m, 1H), 2.14 (s, 0.5H), 1.67−1.58 (m, 1.5H),

H); ¹³C{1H} NMR (101 MHz, CDCl ) δ 148.3 (d, J = 32.3 Hz),

48.2 (d, J = 31.3 Hz), 142.5, 142.0, 141.0 (d, J = 7.1 Hz), 140.8 (d, J

7.1 Hz), 138.1 (d, J = 7.1 Hz), 138.0 (d, J = 7.1 Hz), 137.8, 137.6,

37.5, 137.1 (d, J = 11.1 Hz), 136.9 (d, J = 11.1 Hz), 134.3 (d, J = 9.1

Hz), 134.1 (d, J = 9.1 Hz), 134.0, 133.8, 133.7, 133.6, 131.9, 131.8,

1.45−1.39 (m, 3H), 1.24 (s, 0.5H), 1.13−0.82 (m, 3H); C{1H}

NMR (101 MHz, CDCl ) δ 162.6 (d, J = 245.4 Hz), 162.5 (d, J =

245.4 Hz), 148.5 (d, J = 7.1 Hz), 147.8 (d, J = 7.1 Hz), 147.3 (d, J =

15.2 Hz), 147.0 (d, J = 15.2 Hz), 137.6 (d, J = 4.0 Hz), 137.5 (d, J =

4.0 Hz), 137.4, 137.3, 137.2, 137.1, 137.0, 136.9, 136.8, 136.6, 136.5,

134.2, 134.1, 133.9, 133.7, 132.2 (d, J = 3.0 Hz), 132.1 (d, J = 3.0

Hz), 132.0 (d, J = 3.0 Hz), 131.9 (d, J = 3.0 Hz), 131.0 (d, J = 6.1

Hz), 130.7 (d, J = 5.1 Hz), 128.6, 128.5, 128.4, 127.6, 127.5, 112.7 (d,

J = 22.2 Hz), 112.2 (d, J = 22.2 Hz), 111.3 (d, J = 12.1 Hz), 111.0 (d,

J = 12.1 Hz), 44.4, 43.6, 41.7, 41.6, 38.4, 37.4, 36.9, 36.7, 36.0, 31.0,

30.6 (d, J = 5.1 Hz), 130.4 (d, J = 6.1 Hz), 128.6, 128.5, 128.4,

28.3, 128.2, 127.3, 127.2, 125.3, 125.0, 44.0, 43.9, 43.5, 42.0, 41.9,

1.4, 38.6, 37.3, 36.9, 36.8, 36.2, 31.1, 30.6, 28.7, 28.6, 20.8; P NMR

(

2′-(Bicyclo[2.2.1]heptan-2-yl)-5′-chloro-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3k). Puriﬁcation by column chromatography on

silica gel (EA/hexane = 1/100) yielded 3k (39.1 mg, 42%) as a

30.5, 28.5, 28.4; P NMR (162 MHz, CDCl ) δ −14.2, −15.3; F

colorless oil. m/d > 20:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

NMR (377 MHz, CDCl ) δ −114.4, −114.5. HRMS (ESI) m/z: [M

+ H] calcd for C H FP 451.1985; found 451.1982.

.40−7.28 (m, 8H), 7.25 (s, 0.5H), 7.22−7.10 (m, 7.5H), 6.66 (d, J =

.6 Hz, 0.5H), 6.59 (d, J = 2.4 Hz, 0.5H), 2.51−2.47 (m, 1H), 2.41 (s,

.5H), 2.25−2.23 (m, 1H), 2.11 (d, J = 2.8 Hz, 0.5H), 1.65−1.56 (m,

.5H), 1.44−1.35 (m, 3H), 1.24 (d, J = 9.6 Hz, 0.5H), 1.12−0.84 (m,

(2′-(Bicyclo[2.2.1]heptan-2-yl)-4′-chloro-[1,1′-biphenyl]-2-yl)-

diphenylphosphane (3o). Puriﬁcation by column chromatography

on silica gel (EA/hexane = 1/100) yielded 3o (50.3 mg, 54%) as a

H); ¹³C{1H} NMR (101 MHz, CDCl ) δ 146.7 (d, J = 31.3 Hz),

colorless oil. m/d > 20:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

46.5 (d, J = 32.3 Hz), 144.4, 143.7, 142.7 (d, J = 7.1 Hz), 142.4 (d, J

7.1 Hz), 137.4 (d, J = 13.1 Hz), 137.3 (d, J = 12.1 Hz), 137.2,

7.41−7.35 (m, 1H), 7.32−7.28 (m, 7.5H), 7.23−7.10 (m, 6.5H),

6.97−6.90 (m, 1H), 6.70 (d, J = 8.0 Hz, 0.5H), 6.64 (d, J = 8.0 Hz,

0.5H), 2.48 (t, J = 8.0 Hz, 1H), 2.40 (s, 0.5H), 2.26−2.24 (m, 1H),

2.14 (s, 0.5H), 1.68−1.61 (m, 1.5H), 1.48−1.36 (m, 3H), 1.27 (s,

37.1, 136.9, 136.7, 134.3 (d, J = 7.1 Hz), 134.1 (d, J = 6.1 Hz),

34.0, 133.9, 133.8, 133.7, 133.6, 133.5, 130.8 (d, J = 3.0 Hz), 130.6

(

d, J = 3.0 Hz), 130.5, 130.3, 130.2, 130.0, 128.9, 128.8, 128.7, 128.6,

0.5H), 1.14−0.84 (m, 3H); C{1H} NMR (101 MHz, CDCl ) δ

28.5, 128.4, 127.8, 127.7, 127.6, 126.8, 126.5, 43.9, 43.6, 41.7, 41.6,

147.9, 147.1 (d, J = 33.3 Hz), 146.9 (d, J = 31.3 Hz), 139.6 (d, J = 7.1

Hz), 139.3 (d, J = 6.1 Hz), 137.6, 137.5, 137.4, 137.1 (d, J = 12.1 Hz),

136.9 (d, J = 12.1 Hz), 136.8, 136.7, 134.2, 134.1, 133.9, 133.8, 133.7,

133.5, 132.0 (d, J = 3.0 Hz), 131.8 (d, J = 3.0 Hz), 130.8 (d, J = 6.1

8.4, 38.4, 37.4, 37.0, 36.8, 36.0, 31.1, 30.5, 28.6, 28.4; P NMR (162

MHz, CDCl ) δ −13.6, −14.8. HRMS (ESI) m/z: [M + H] calcd for

C H ClP 467.1690; found 467.1687.

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

Hz), 130.5 (d, J = 5.1 Hz), 128.7, 128.6, 128.5, 128.4, 127.7, 127.6,

NMR (101 MHz, CDCl ) δ 147.8 (d, J = 31.3 Hz), 147.7 (d, J = 32.3

−

25.9, 125.5, 124.6, 124.5, 44.4, 43.6, 41.6, 41.5, 38.3, 37.4, 36.9, 36.7,

Hz), 143.8, 143.1, 141.3 (d, J = 8.1 Hz), 141.0 (d, J = 6.1 Hz), 137.7,

137.5, 137.4, 137.3, 136.9 (d, J = 12.1 Hz), 136.7 (d, J = 12.1 Hz),

134.3, 134.1, 134.0, 133.9, 133.8, 133.7, 131.1 (d, J = 3.0 Hz), 130.9

(d, J = 3.0 Hz), 130.6 (d, J = 5.1 Hz), 130.3 (d, J = 6.1 Hz), 128.8,

128.7, 128.6, 128.5, 128.4, 128.3, 128.0, 127.9, 127.7, 127.6, 125.3,

125.1, 125.0, 124.6, 123.7, 123.6, 43.2, 43.1, 42.4, 42.3, 41.2, 40.0,

6.1, 31.1, 30.6, 28.5, 28.4; P NMR (162 MHz, CDCl ) δ −14.2,

15.3. HRMS (ESI) m/z: [M + H] calcd for C H ClP 467.1690;

31 29

found 467.1688.

-(2-(Bicyclo[2.2.1]heptan-2-yl)-2′-(diphenylphosphanyl)-[1,1′-

biphenyl]-4-yl)ethan-1-one (3p). Puriﬁcation by column chromatog-

raphy on silica gel (EA/hexane = 1/100) yielded 3p (78.7 mg, 83%)

37.4, 37.0, 36.7, 36.3, 34.9, 30.3, 30.1; P NMR (162 MHz, CDCl ) δ

as a colorless oil. m/d > 20:1, dr = 1.2:1. H NMR (400 MHz,

−14.5, −15.7. HRMS (ESI) m/z: [M + H] calcd for C H NP

CDCl ) δ 7.97 (dd, J = 21.2, 1.6 Hz, 1H), 7.60−7.54 (m, 1H), 7.44−

458.2028; found 458.2032.

.27 (m, 8H), 7.25−7.13 (m, 6H), 6.93 (d, J = 8.0 Hz, 0.5H), 6.86 (d,

4-Methoxy-1,1′-biphenyl (6a). Puriﬁcation by column chroma-

J = 8.0 Hz, 0.5H), 2.61 (d, J = 1.2 Hz, 3H), 2.57−2.54 (m, 1H), 2.48

tography on silica gel (EA/hexane = 1/50) yielded 6a (87.4 mg, 95%)

(

s, 0.5H), 2.30−2.27 (m, 1H), 2.17 (d, J = 2.8 Hz, 0.5H), 1.76−1.65

as a white solid. H NMR (400 MHz, CDCl ) δ 7.60−7.55 (m, 4H),

7.45 (t, J = 7.2 Hz, 2H), 7.34 (tt, J = 7.2, 1.2 Hz, 1H), 7.03−6.99 (m,

m, 2H), 1.50−1.31 (m, 3H), 1.16−0.85 (m, 3H); C{1H} NMR

101 MHz, CDCl ) δ 198.4, 198.3, 147.3 (d, J = 32.3 Hz), 147.2 (d, J

2H), 3.87 (s, 3H).

4-Methyl-1,1′-biphenyl (6b).

32.3 Hz), 146.5 (d, J = 7.1 Hz), 146.4, 146.3 (d, J = 6.1 Hz), 145.8,

37.4, 137.3, 137.2, 137.0, 136.4 (d, J = 13.1 Hz), 136.4 (d, J = 12.1

Hz), 136.3, 136.2, 134.4, 134.3, 134.0, 133.9 (d, J = 3.0 Hz), 133.8,

33.7 (d, J = 3.0 Hz), 133.6, 131.0, 130.9, 130.2 (d, J = 6.1 Hz), 130.0

d, J = 6.1 Hz), 128.8, 128.7, 128.6, 128.5, 128.4, 127.9, 127.8, 125.4,

Puriﬁcation by column chroma-

tography on silica gel (hexane) yielded 6b (75.6 mg, 90%) as a white

solid. H NMR (400 MHz, CDCl ) δ 7.70−7.67 (m, 2H), 7.60 (d, J =

8.0 Hz, 2H), 7.54−7.50 (m, 2H), 7.42 (tt, J = 7.2, 1.2 Hz, 1H), 7.35

(

−

(d, J = 8.0 Hz, 2H), 2.49 (s, 3H).

25.1, 124.9, 124.8, 44.3, 43.7, 41.7, 41.5, 38.3, 38.2, 37.5, 37.0, 36.8,

Methyl [1,1′-Biphenyl]-4-carboxylate (6c).

Puriﬁcation by

6.0, 31.1, 30.6, 28.6, 28.5, 26.8; P NMR (162 MHz, CDCl ) δ

column chromatography on silica gel (EA/hexane = 1/20) yielded

14.4, −15.4. HRMS (ESI) m/z: [M + H] calcd for C H OP

6c (54.1 mg, 51%) as a white solid. H NMR (400 MHz, CDCl ) δ

75.2185; found 475.2184.

8.11 (dt, J = 8.4, 1.6 Hz, 2H), 7.68−7.61 (m, 4H), 7.49−7.45 (m,

2H), 7.42−7.38 (m, 1H), 3.95 (s, 3H).

Methyl 2″-(dicyclohexylphosphanyl)-[1,1′:2′,1″-terphenyl]-3-

carboxylate (3q). Puriﬁcation by column chromatography on silica

3-Methyl-1,1′-biphenyl (6d).

Puriﬁcation by column chroma-

gel (EA/hexane = 1/100) yielded 3q (72.5 mg, 74%) as a colorless

tography on silica gel (hexane) yielded 6d (68.9 mg, 82%) as a

colorless oil. H NMR (400 MHz, CDCl ) δ 7.70−7.68 (m, 2H),

7.55−7.49 (m, 4H), 7.43 (t, J = 7.6 Hz, 2H), 7.27 (d, J = 7.6 Hz, 1H),

oil. m/d = 10:1, dr = 1:1. H NMR (400 MHz, CDCl ) δ 8.02 (dd, J

21.2, 1.2 Hz, 1H), 7.69−7.62 (m, 1H), 7.43−7.28 (m, 8H), 7.24−

.14 (m, 6H), 6.88 (d, J = 7.6 Hz, 0.5H), 6.81 (d, J = 8.0 Hz, 0.5H),

.92 (s, 3H), 2.58−2.53 (m, 1H), 2.48 (s, 0.5H), 2.29−2.26 (m, 1H),

.16 (d, J = 2.8 Hz, 0.5H), 1.77−1.66 (m, 1.5H), 1.46−1.36 (m, 3H),

2.52 (s, 3H).

3-Chloro-1,1′-biphenyl (6e).

Puriﬁcation by column chroma-

tography on silica gel (hexane) yielded 6e (83.7 mg, 89%) as a light

.30 (s, 0.5H), 1.15−0.88 (m, 3H); C{1H} NMR (101 MHz,

yellow oil. H NMR (400 MHz, CDCl ) δ 7.63−7.58 (m, 3H), 7.52−

CDCl ) δ 167.5, 147.3 (d, J = 32.3 Hz), 147.2 (d, J = 32.3 Hz), 146.2,

7.47 (m, 3H), 7.44−7.35 (m, 3H).

46.1, 145.9, 145.5, 137.5, 137.3, 137.2, 137.0, 136.4 (d, J = 12.1 Hz),

36.3 (d, J = 12.1 Hz), 134.2, 134.0, 133.9, 133.8, 133.7, 133.6, 130.9

1-([1,1′-Biphenyl]-3-yl)ethan-1-one (6f).

Puriﬁcation by col-

umn chromatography on silica gel (EA/hexane = 1/20) yielded 6f

(

d, J = 3.0 Hz), 130.7 (d, J = 3.0 Hz), 130.2 (d, J = 6.1 Hz), 130.0 (d,

(78.4 mg, 80%) as a colorless oil. H NMR (400 MHz, CDCl ) δ

8.05−8.02 (m, 2H), 7.69−7.62 (m, 4H), 7.49−7.46 (m, 2H), 7.43−

7.39 (m, 1H), 2.64 (s, 3H).

18a

4,4′-Dimethoxy-1,1′-biphenyl (6g).

Puriﬁcation by column

chromatography on silica gel (EA/hexane = 1/20) yielded 6g (91.0

mg, 85%) as a light yellow solid. H NMR (400 MHz, CDCl

) δ 7.50

-(5-(2′-(Diphenylphosphanyl)-[1,1′-biphenyl]-2-yl)bicyclo-

(dt, J = 8.8, 2 Hz, 4H), 6.98 (dt, J = 8.8, 2 Hz, 4H), 3.86 (s, 6H).

[

2.2.1]heptan-2-yl)ethan-1-one (3r). Puriﬁcation by column chro-

4-Methoxy-4′-methyl-1,1′-biphenyl (6h).

Puriﬁcation by col-

umn chromatography on silica gel (EA/hexane = 1/50) yielded 6h

matography on silica gel (EA/hexane = 1/20) yielded 3r (54.8 mg,

8%) as a colorless oil. m:d > 20:1, dr = 1.1:1. H NMR (400 MHz,

(95.0 mg, 96%) as a colorless oil. H NMR (400 MHz, CDCl ) δ

CDCl ) δ 7.42−7.36 (m, 1H), 7.33−7.28 (m, 9H), 7.22−7.11 (m,

7.63−7.54 (m, 4H), 7.32 (d, J = 7.6 Hz, 2H), 7.07−7.05 (m, 2H),

H), 7.02−6.95 (m, 1H), 6.80 (d, J = 7.2 Hz, 0.5H), 6.76 (dd, J = 7.6,

.2 Hz, 0.5H), 2.57−2.47 (m, 2.5H), 2.32−2.21 (m, 1.5H), 2.11 (d, J

3.91 (s, 3H), 2.49 (s, 3H).

4-Methoxy-1,1′:4′,1″-terphenyl (6i).

Puriﬁcation by column

2.0 Hz, 3H), 1.78−1.61 (m, 2H), 1.56−1.42 (m, 1.5H), 1.32 (d, J =

chromatography on silica gel (EA/hexane = 1/50) yielded 6i (123.5

mg, 95%) as a white solid. H NMR (400 MHz, CDCl ) δ 7.68−7.58

0.0 Hz, 0.5H), 1.21−0.96 (m, 2H); C{1H} NMR (101 MHz,

CDCl ) δ 210.2, 148.1 (d, J = 32.3 Hz), 148.0 (d, J = 32.3 Hz), 144.9,

(m, 8H), 7.46 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.6 Hz, 1H), 7.00 (d, J

44.1, 141.2 (d, J = 7.1 Hz), 140.9 (d, J = 7.1 Hz), 137.8 (d, J = 6.1

= 8.4 Hz, 2H), 3.87 (s, 3H).

Hz), 137.7 (d, J = 5.1 Hz), 137.7, 137.5, 137.4, 137.0 (d, J = 11.1 Hz),

4-Fluoro-4′-methoxy-1,1′-biphenyl (6j). Puriﬁcation by column

36.7 (d, J = 12.1 Hz), 134.2, 134.0, 133.8, 130.9 (d, J = 3.0 Hz),

30.8 (d, J = 3.0 Hz), 130.7 (d, J = 6.1 Hz), 130.5 (d, J = 5.1 Hz),

28.7, 128.6, 128.5, 128.4, 128.3, 127.9, 127.8, 127.5, 127.4, 125.3,

24.8, 124.7, 54.1, 54.0, 43.9, 43.8, 43.4, 41.5, 41.3, 40.4, 40.2, 38.0,

chromatography on silica gel (EA/hexane = 1/50) yielded 6j (87.9

mg, 87%) as a white solid. H NMR (400 MHz, CDCl ) δ 7.53−7.46

(m, 4H), 7.11 (tt, J = 8.8, 2 Hz, 2H), 6.98 (dt, J = 8.8, 2 Hz, 2H), 3.86

(s, 3H).

18e

5.4, 34.0, 33.8, 33.5, 29.1; P NMR (162 MHz, CDCl ) δ −14.4,

4-Chloro-4′-methoxy-1,1′-biphenyl (6k).

Puriﬁcation by col-

−

15.5. HRMS (ESI) m/z: [M + H] calcd for C H OP 475.2180;

umn chromatography on silica gel (EA/hexane = 1/50) yielded 6k

found 475.2185.

(100.3 mg, 92%) as a white solid. H NMR (400 MHz, CDCl ) δ

-(2′-(Diphenylphosphanyl)-[1,1′-biphenyl]-2-yl)bicyclo[2.2.1]-

7.52−7.47 (m, 4H), 7.40−7.38 (m, 2H), 7.01−6.97 (m, 2H), 3.86 (s,

heptane-2-carbonitrile (3s). Puriﬁcation by column chromatography

on silica gel (EA/hexane = 1/30) yielded 3s (47.5 mg, 52%) as a

colorless oil. m/d > 20:1, dr = 1.1:1. H NMR (400 MHz, CDCl ) δ

3H).

1-(4-Methoxyphenyl)naphthalene (6l). Puriﬁcation by column

chromatography on silica gel (EA/hexane = 1/50) yielded 6l (110.0

7.42−7.35 (m, 1H), 7.33−7.28 (m, 8H), 7.24−7.09 (m, 7H), 7.06−

6.98 (m, 1H), 6.84 (d, J = 6.4 Hz, 0.5H), 6.77 (dd, J = 7.2 Hz, 0.5H),

2.61 (s, 1H), 2.54 (d, J = 3.6 Hz, 0.5H), 2.46 (t, J = 7.2 Hz, 1H), 2.29

mg, 94%) as a white solid. H NMR (400 MHz, CDCl ) δ 8.06−7.91

(m, 3H), 7.61−7.49 (m, 6H), 7.12 (d, J = 8.8 Hz, 2H), 3.95 (s, 3H).

3-(4-Methoxyphenyl)furan (6m).

Puriﬁcation by column

(

d, J = 3.6 Hz, 0.5H), 2.22−2.10 (m, 1H), 1.88−1.63 (m, 3H), 1.54−

chromatography on silica gel (EA/hexane = 1/25) yielded 6m

.49 (m, 1H), 1.36−1.26 (m, 1.5H), 0.97−0.91 (m, 0.5H); C{1H}

(69.6 mg, 80%) as a white solid. H NMR (400 MHz, CDCl ) δ 7.67

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Complete contact information is available at:

Article

(

s, 1H), 7.47 (s, 1H), 7.44−7.42 (m, 2H), 6.95−6.91 (m, 2H), 6.67

Ministry of Education Key Laboratory for the Synthesis and

Application of Organic Functional Molecules, and College of

Chemistry and Chemical Engineering, Hubei University,

Wuhan 430062, China; Department of Key Laboratory for

the Chemistry and Molecular Engineering of Medicinal

Resources, School of Chemistry and Pharmaceutical Sciences,

Guangxi Normal University, Guilin 541004, China;

orcid.org/0000-0002-7227-7688; Email: zmh@

mailbox.gxnu.edu.cn

s, 1H), 3.83 (s, 3H).

3-(4-Methoxyphenyl)quinoline (6n).

Puriﬁcation by column

chromatography on silica gel (EA/hexane = 1/25) yielded 6n (56.4

mg, 48%) as a white solid. H NMR (400 MHz, CDCl ) δ 9.16 (d, J =

.4 Hz, 1H), 8.25 (d, J = 2.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.86

d, J = 8.0 Hz, 1H), 7.72−7.65 (m, 3H), 7.59−7.55 (m, 1H), 7.08−

.04 (m, 2H), 3.88 (s, 3H).

-Methoxy-2′-methyl-1,1′-biphenyl (6o).

umn chromatography on silica gel (EA/hexane = 1/50) yielded 6o

(

Puriﬁcation by col-

(

26.7 mg, 27%) as a colorless oil. H NMR (400 MHz, CDCl ) δ

.36−7.32 (m, 1H), 7.27−7.13 (m, 5H), 7.03−6.45 (m, 2H), 3.76 (s,

Authors

H), 2.14 (s, 3H).

Ming Li − Department of Hubei Collaborative Innovation

Center for Advanced Chemical Materials, Ministry of

Education Key Laboratory for the Synthesis and Application

of Organic Functional Molecules, and College of Chemistry

and Chemical Engineering, Hubei University, Wuhan

2,2′,6-Trimethyl-1,1′-biphenyl (6p).

Puriﬁcation by column

chromatography on silica gel (hexane) yielded 6p (17.6 mg, 18%) as a

colorless oil. H NMR (400 MHz, CDCl ) δ 7.30−7.25 (m, 2H),

.24−6.99 (m, 5H), 1.97 (s, 3H), 1.95 (s, 6H).

19a

Ethyl (E)-3-(o-Tolyl)acrylate (8a).

Puriﬁcation by column

430062, China

chromatography on silica gel (EA/hexane = 1/50) yielded 8a (70.3

mg, 74%) as a colorless oil. H NMR (400 MHz, CDCl ) δ 7.98 (d, J

Jun-Yang Tao − Department of Hubei Collaborative

Innovation Center for Advanced Chemical Materials,

Ministry of Education Key Laboratory for the Synthesis and

Application of Organic Functional Molecules, and College of

Chemistry and Chemical Engineering, Hubei University,

Wuhan 430062, China

Liang-Neng Wang − Department of Hubei Collaborative

Innovation Center for Advanced Chemical Materials,

Ministry of Education Key Laboratory for the Synthesis and

Application of Organic Functional Molecules, and College of

Chemistry and Chemical Engineering, Hubei University,

Wuhan 430062, China

Jia-Wei Li − Department of Hubei Collaborative Innovation

Center for Advanced Chemical Materials, Ministry of

Education Key Laboratory for the Synthesis and Application

of Organic Functional Molecules, and College of Chemistry

and Chemical Engineering, Hubei University, Wuhan

430062, China

16.0 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.28−7.25 (m, 1H), 7.23−

.19 (m, 2H), 6.36 (d, J = 16.0 Hz, 1H), 4.27 (q, J = 7.2 Hz, 2H),

.44 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H).

-Methoxy-4-(phenylethynyl)benzene (8b).

Puriﬁcation by

column chromatography on silica gel (hexane) yielded 8b (58.3

mg, 56%) as a colorless oil. H NMR (400 MHz, CDCl ) δ 7.53−7.46

(

m, 4H), 7.37−7.31 (m, 3H), 6.89 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H).

Scale Up Synthesis. To a 50 mL Schlenk tube was added 2-

diphenylphosphinobiphenyl 1a (3 mmol, 1.02 g, 1.0 equiv),

norbornene 2a (9 mmol, 0.85 g, 3.0 equiv), [RuCl (p-cymene)]

(

45.8 mg, 0.025 equiv), H-L-Ala-OH (80.1 mg, 0.3 equiv), and

NaOAc (492 mg, 2.0 equiv). The tube was purged with Ar three

times, followed by the addition of 2-Me-THF (9 mL). The mixture

was stirred at 160 °C in an oil bath for 24 h. The solution was then

cooled to room temperature and the solvent was removed under

vacuum directly. The crude product was puriﬁed by column

chromatography on silica gel (R = 0.8, EA/hexane = 1/50) aﬀording

the alkylated products 3a and 3aa (white solid, 1.2 g, 83% yield, m/d

1:1). The ratio of 3a and 3aa was about 1:1 by ³¹P NMR yield

analyzed with PPh as an internal standard.

https://pubs.acs.org/10.1021/acs.joc.1c01329

ASSOCIATED CONTENT

sı Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.1c01329.

■

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

Copies of H, C{1H}, P NMR, F NMR, and single-

■

(

crystal X-ray analysis of 3aa and 3k (PDF )

This work was supported by the NSF of Guangxi Province

Grant No. 2017GXNSFDA198040) and the BAGUI talent

Accession Codes

program (Grant No. 2019AC26001).

CCDC 2059805 and 2070266 contain the supplementary

crystallographic data for this paper. These data can be obtained

free of charge via www.ccdc.cam.ac.uk/data_request/cif , or by

emailing data_request@ccdc.cam.ac.uk , or by contacting The

Cambridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.

REFERENCES

■

(

1) (a) Gru

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Chem. Rev. 2011 , 111 , 2119. (e) Ni, H.; Chan, W.-L.; Lu, Y.

Phosphine-Catalyzed Asymmetric Organic Reactions. Chem. Rev.

AUTHOR INFORMATION

Corresponding Authors

■

Yue-Jin Liu − Department of Hubei Collaborative Innovation

Center for Advanced Chemical Materials, Ministry of

Education Key Laboratory for the Synthesis and Application

of Organic Functional Molecules, and College of Chemistry

and Chemical Engineering, Hubei University, Wuhan

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Aryl Amination Catalyst with Broad Scope Guided by Consideration

of Catalyst Stability. J. Am. Chem. Soc. 2020, 142, 15027.

30062, China; orcid.org/0000-0003-4226-0890;

Email: liuyuejin@hubu.edu.cn

Ming-Hua Zeng − Department of Hubei Collaborative

Innovation Center for Advanced Chemical Materials,

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

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