Synthesis of 3-Arylbenzofuran-2-ylphosphines via Rhodium-Catalyzed Redox-Neutral C-H Activation and Their Applications in Palladium-Catalyzed Cross-Coupling of Aryl Chlorides

Article abstract of DOI:10.1021/acs.joc.7b01566

A new class of aryl-heteroarylphosphines, 3-arylbenzofuran-2-ylphosphines, was synthesized by [Cp?Rh(III)]-catalyzed redox-neutral cyclization of N-phenoxyacetamides with 1-alkynylphosphine sulfides and oxides followed by reduction. This step-economic reaction proceeds in excellent regioselectivity with a broad substrate scope. The application of the resulting air-stable trivalent-phosphine containing dicyclohexylphosphino moiety in palladium-catalyzed Suzuki-Miyaura coupling and Buchwald-Hartwig amination of aryl chlorides is also described.

Full text of DOI:10.1021/acs.joc.7b01566

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Article
Synthesis of 3-Arylbenzofuran-2-yl Phosphines via Rhodium-
Catalyzed Redox-Neutral C-H Activation and Their Applications
in Palladium-Catalyzed Cross-Coupling of Aryl Chlorides
Huanan Wang, Baiquan Wang, and Bin Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01566 • Publication Date (Web): 21 Aug 2017
Downloaded from http://pubs.acs.org on August 21, 2017
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Synthesis of 3ꢀArylbenzofuranꢀ2ꢀyl Phosphines via RhodiumꢀCatalyzed
RedoxꢀNeutral C−H Activation and Their Applications in PalladiumꢀCatalyzed
CrossꢀCoupling of Aryl Chlorides
†
†,‡,§
,†
Huanan Wang, Baiquan Wang,
and Bin Li,*
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†
‡
State Key Laboratory of ElementoꢀOrganic Chemistry, College of Chemistry, and Collaborative Innovation Center of
Chemical Science and Engineering, Nankai University, Tianjin 300071, People’s Republic of China
§
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, People’s Republic of China
ABSTRACT: A new class of arylꢀheteroarylphosphines, 3ꢀarylbenzofuranꢀ2ꢀyl phosphines, were
synthesized by [Cp*Rh(III)]ꢀcatalyzed redoxꢀneutral cyclization of Nꢀphenoxyacetamides with
1
ꢀalkynylphosphine sulfides and oxides followed by reduction. This stepꢀeconomic reaction
proceeds in excellent regioselectivity with a broad substrate scope. The application of the resulted
air stable trivalent phosphine containing dicyclohexylphosphino moiety in palladiumꢀcatalyzed
SuzukiꢀMiyaura coupling and BuchwaldꢀHartwig amination of aryl chlorides is also described.
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INTRODUCTION
Since recognition of the significant effects of supporting ligands on the improvement of reactivity
and stability of the catalyst, miscellaneous kinds of phosphines have been developed.
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Representatively, phosphine ligands based on the monophosphinobiaryl backbone [Figure 1(a)],
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which were first introduced by the group of Buchwald for Pdꢀcatalyzed crossꢀcoupling in 1998,
have been utilized in a wide variety of transitionꢀmetalꢀcatalyzed carbonꢀcarbon and
carbonꢀheteroatom bonds formation reactions. The novel structure permits the fineꢀtuning of steric
and electronic elements of the ligand. Density functional theory studies have also revealed that the
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interactions between palladium and the nonꢀphosphineꢀcontaining ring of the ligand [Figure 1(b)]
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can stabilize oxidative addition intermediates and facilitate the reduction elimination step.
Therefore, one class of heteroarylphosphine ligands with arylꢀheteroaryl monophosphine as the
main skeleton [Figure 1(c)] have been explored and identified as a unique type of supporting ligand
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for diverse transitionꢀmetalꢀcatalyzed transformations. In this context, a range of heteroaromatic
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compounds including imidazole, pyrrole, triazole, indole, and isoquinolinone based phosphines
Figure 1(d)] have been designed and synthesized by the groups of Beller, Zhang, Kwong,
Yorimitsu and Oshima, and others as well as ourselves. However, 3ꢀarylbenzofuranꢀ2ꢀyl
[
1
0
phosphines [Figure 1(e)], to the best of our knowledge, have remained elusive until now.
(
a)
(b)
(c)
R1
R
hetero
-
aryl
Y
P
R
PR2
X
PR2
Pd
R2
R1
(d)
R1
N
N
Ph
N
N
PR2
PR2
PR2
N
N
N
R1
PR2
R1
R2
R1
and regioisomers
R1
(e)
H
O
O
N
R1
PR2
R1
PR2
PPh2
N
R2
Me
and regioisomers
this work
Figure 1. (a) Structural backbone for biarylphosphines; (b) Palladiumꢀarene interaction; (c)
Structural backbone for arylꢀheteroarylphosphines; (d) Examples of previously developed
arylꢀheteroarylphosphines.
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On the other hand, the conventional synthetic methods for heteroarylphosphines are mostly
limited to the reactions of chlorophosphines with metalated heteroaromatic compounds.
Consequently, it is demanding to prepare the proper heteroaromatic compounds prior to
introduction of a phosphorus moiety, which commonly results in a multistep synthesis especially in
cases the heteroaryl compounds are not commercially available. In recent years, Rh(III)ꢀcatalyzed
oxidative coupling of C−H bonds with alkynes has been proven to be a straightforward and efficient
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approach to construct (hetero)cyclic compounds. In this regard, we previously disclosed the
oxidative coupling of Nꢀ(pivaloyloxy)benzamides with 1ꢀalkynylphosphine sulfides under rhodium
catalysis followed by desulfidation to afford phosphines containing an isoquinolinꢀ1(2H)ꢀone
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motif. But this catalytic system suffered from two main issues: low regioselectivity for
electronꢀrich
benzamide
substrates
and
poor
reactivity
for
sterically
bulky
(1ꢀalkynyl)dicyclohexylphosphine sulfide. In line with our interest in creation of new
organophosphine species and transitionꢀmetalꢀcatalyzed heterocycle synthesis through C−H
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coupling with alkynes,
described herein are our recent development of rhodiumꢀcatalyzed
1
3
redoxꢀneutral annulation of Nꢀphenoxyacetamides
with 1ꢀalkynylphosphine sulfides and
8c,14
oxides
(Scheme 1). The present catalytic process introduces a phosphorus moiety and a
substituent at the proper positions with concomitant formation of a benzofuranyl ring, which
provides a stepꢀeconomic and regioselective access to form 3ꢀarylbenzofuranꢀ2ꢀyl phosphine
derivatives. Note that, after reduction, the corresponding trivalent phosphine with
dicyclohexylphosphino moiety could serve as an efficient supporting ligand for palladiumꢀcatalyzed
SuzukiꢀMiyaura coupling and BuchwaldꢀHartwig amination of aryl chlorides.
Scheme 1. RhodiumꢀCatalyzed Oxidative Coupling of NꢀPhenoxyacetamides with
1ꢀAlkynylphosphine Derivatives Followed by Reduction to Form 3ꢀArylbenzofuran Based
2
ꢀPhosphines
√
Redoxꢀneutral CꢀH activation/annulation strategy
√Stepꢀeconomic and regioselective synthetic method
Broad substrate scope and good functional groups tolerance
√
√New ligands for Pdꢀcatalyzed crossꢀcoupling reactions of ArCl
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RESULTS AND DISCUSSION
We initiated our optimization experiments with the cyclization reaction of Nꢀphenoxyacetamide (1a)
with diphenyl(phenylethynyl)phosphine sulfide (2a) (Table 1). To our delight, treatment of 1a with
2
3 6 2
a (1.5 equiv) in the presence of [Cp*Rh(MeCN) ][SbF ] (10 mol %), CsOPiv (2 equiv), and
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o
HOAc (1 equiv) in DCM at 80 C for 20 hours led to the formation of annulated product
diphenyl(3ꢀphenylbenzofuranꢀ2ꢀyl)phosphine sulfide (3aa) in moderate NMR yield (43%, entry 1).
Importantly, the reaction occurred with virtually complete regioselectivity, as demonstrated by the
31
detection of one single regioisomer from the crude reaction mixture by P NMR. The structure of
3aa was confirmed by NMR analysis and HRMS spectrometry, as well as Xꢀray crystallography
15
(
see Table 1 and the Supporting Information). We then evaluated the effect of various reaction
parameters for the benchmark reaction. As to the solvent, CHCl , MeOH, CH CN, and PhCl were
less effective than DCM, while tAmOH, PhMe, DMSO, and DMF essential gave no products
entries 2ꢀ4 and Table S3 in the Supporting Information). Reserve the ratio of 1a/2a to 1.2/1 slightly
3
3
(
improved the efficieny (entry 6). Encouragingly, we found an enhanced chemical yield was
achieved by addition of AgOAc (entry 9), which significantly increased the reactivity than other
additive salts such as CsOPiv, CsOAc, and KOAc (entries 6ꢀ8). In addition, reducing the amount of
AgOAc (to 0.5 equiv) slightly affected the outcome of the transformation (entry 10). It was
observed that the ratio of 1.5/1 for 1a/2a was most optimal, affording product 3aa in 98% NMR
yield and 93% isolated yield (entry 11). A decrease in the amount of catalyst resulted in lower
conversion (entry 12). Furthermore, the reaction efficiency was not sensitive to the reaction
2 2
temperatures (entry 13). [Cp*RhCl ] is inferior to its cationic complex as catalyst (entry 14) and
[
(pꢀcymene)RuCl
]
2 2
was totally inactive under the present reaction conditions (entry 15).
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a
Table 1. Optimization of Reaction Conditions
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additives
(equiv)
yield
entry
1a/2a
solvent
b
(%)
1
2
3
4
5
6
7
8
9
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
1.2/1
1.2/1
1.2/1
1.2/1
1.2/1
1.5/1
1.5/1
1.5/1
1.5/1
1.5/1
CsOPiv (2.0)
CsOPiv (2.0)
CsOPiv (2.0)
CsOPiv (2.0)
CsOPiv (2.0)
CsOPiv (2.0)
CsOAc (2.0)
KOAc (2.0)
AgOAc (2.0)
AgOAc (0.5)
AgOAc (0.5)
AgOAc (0.5)
AgOAc (0.5)
AgOAc (0.5)
AgOAc (0.5)
DCM
43
MeOH
26
CHCl
3
29
DMF
0
CH
3
CN
13
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
b
53
46
40
96
1
1
1
1
1
1
0
1
2
3
4
5
89
c
c
98 (93)
88
d
e
f
98 (93)
90
g
0
a
Reactions in 0.2 mmol scale (0.1 M), [Rh] = [Cp*Rh(MeCN) ][SbF ] . Yield of crude reaction mixture determined by
3
6 2
31
c
d
P NMR (internal standard: trimethyl phosphate). Value in parentheses indicates isolated yield. [Rh] (5 mol %) was
e
o
f
g
used as catalyst. 60 C. [Cp*RhCl
2 2 2 2
] (5 mol %) was used as catalyst. [(pꢀcymene)RuCl ] (5 mol %) was used as
catalyst. DCM = dichloromethane, DMF = N,Nꢀdimethylformamide.
With the promising optimal conditions, the reaction scope of Nꢀphenoxyacetamides was first
investigated (Scheme 2). The annulation took place smoothly with Nꢀphenoxyacetamides bearing
diverse arene substituents to give the corresponding 2ꢀdiphenylthiophosphinylꢀ3ꢀphenylbenzofuran
derivatives in good to excellent yields. In this respect, both electronꢀrich and electronꢀpoor
Nꢀphenoxyacetamides were nearly equally effective in this reaction and many important functional
groups, including halides (3da−fa, 3ka, and 3la), ester (3ga), trifluoromethyl (3ha and 3ma), and
methoxy (3ja and 3oa), remained intact under the reaction conditions. For substrates bearing
metaꢀsubstituents, the catalytic process only occurred at the less steric hindered aromatic CꢀH bond
(
3ia−ma), as confirmed by Xꢀray crystallographic analysis of the structures of 3ja and 3ka (see the
1
5
Supporting Information). Additionally, orthoꢀsubstituted substrate 1n and disubstituted substrate
o were also reacted to provide the desired products 3na and 3oa, respectively. It is worthwhile
1
noting that all the generated products 3aaꢀoa were formed as a single regioisomer with
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diphenylthiophosphino moiety being installed at 2ꢀposition of benzofuran, thereby highlighting the
excellent regioselectivity of the present catalytic system.
a
Scheme 2. Scope of Nꢀphenoxyacetamides
ONHAc
R
[Cp*Rh(MeCN)3][SbF6]2
(10 mol %)
S
O
R
PPh2
1
(1.5 equiv)
AgOAc (0.5 equiv)
HOAc (1.0 equiv)
0
1
2
3
4
5
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9
0
1
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3
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1
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0
1
2
3
4
5
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7
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9
0
+
S
Ph
o
Ph
PPh2
DCM, 60 C, 20 h
3
2a
S
S
S
O
O
O
PPh2
PPh2
PPh2
Me
tBu
Ph
Ph
Ph
3
aa, 93% (X-ray)
3ba, 74%
3ca, 72%b
S
S
S
O
O
O
PPh2
PPh2
PPh2
F
Cl
Br
Ph
da, 73%b
Ph
Ph
3fa, 73%
3
3ea, 85%b
S
S
Me
S
O
O
O
PPh2
PPh2
PPh2
MeO2C
MeO
F3C
Ph
Ph
Ph
b
3
ga, 60%
3ha, 63%
3ia, 81%
3la, 73%
OMe
S
Cl
S
Br
S
O
O
O
PPh2
PPh2
PPh2
Ph
Ph
Ph
3
ja, 85% (X-ray)
3ka, 63% (X-ray)
Me
MeO
S
F3C
S
S
O
O
O
PPh2
PPh2
PPh2
Ph
Ph
ma, 61%
Ph
3oa, 75%b
3
3na, 78%
a
b
o
Reactions in 0.2 mmol scale (0.1 M), yields of isolated products. 80 C.
To further demonstrate the generality of this transformation, we next surveyed the scope with
respect to 1ꢀalkynylphosphine derivatives. The results are summarized in Scheme 3. Irrespective of
the electronic nature of arene substituents, 1ꢀalkynylphosphine sulfides 2b−f were readily converted
into products 3ab−af (69ꢀ93%) in reactions with 1a. While (oꢀtolylethynyl)diphenylphosphine
sulfide 2g is a suitable substrate to form 3ag in good yield, the cyclization did not occur when
((2,6ꢀdimethylphenyl)ethynyl)diphenylphosphine
sulfide
was
employed.
Gratifyingly,
(1ꢀnaphthalenylethynyl)diphenylphosphine sulfide 2h was also applicable for this reaction and the
corresponding product 3ah was isolated in reasonable yield. Notably, high conversion was achieved
with (1ꢀalkynyl)dicyclohexylphosphine sulfide 2i although an increase of the stoichiometry of 1a
was required. Thus, bulky phosphine products 3ai−3ci and 3oi were obtained in 66ꢀ90% isolated
yield. Furthermore, we prepared 3ai in large scale with comparable yield (2.0 mmol, 89% yield),
showing the preparative utility of this transformation. Alkyne 2j with diisopropylthiophosphino
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moiety was also a facile reactant for this catalytic process, whereas steric more bulky
ditertbutylthiophosphino analogue led to no reaction at all. Not only were phosphine sulfides
applicable to the reaction, but phosphine oxides worked as well. For example, 1ꢀalkynylphosphine
oxides PhCCP(O)R
present annulation protocol, giving rise to the desired products 3ak, 3bk, 3ek, and 3al in high yields
88ꢀ98%). Again, excellent regioselectivety was observed for all phosphinoacetylenes employed
2
(R = Ph, 1k; R = cyclohexyl, 1l) were verified to be active partners for the
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(
with the formation of one single regioisomer. Moreover, the structures of 3ai and 3ak were
15
unambiguously confirmed by Xꢀray crystallographic analysis (see the Supporting Information).
a
Scheme 3. Scope of (1ꢀAlkynyl)diphenylphosphine Derivatives
ONHAc
R
[Cp*Rh(MeCN)3][SbF6]2
(10 mol %)
O
E
PR2
1
(1.5 equiv)
R
2
+
AgOAc (0.5 equiv)
HOAc (1.0 equiv)
DCM, 60 C, 20-48 h
E
PR2
R1
R1
o
2
3
2
S
O
O
Ar = 4-MeC6H4, 3ab, 76%
Ar = 4-MeOC6H4, 3ac, 93%
Ar = 4-FC6H4, 3ad, 69%
Ar = 4-ClC6H4, 3ae, 85%
Ar = 4-BrC6H4, 3af, 74%
S
PPh2
Me
O
PPh2
b
3ag,
63%b,c
Ar
S
S
S
O
O
PPh2
PPh2
PCy2
Me
Ph
Me
3
ah,
ai, 83%b,c (X-ray)
3
N.R.b,c
64%b,c
9%b,c,d
8
S
S
MeO
S
O
O
O
PCy2
PCy2
PCy2
tBu
Me
Ph
Ph
3ci, 90%b,c
Ph
b,c
OMe
3oi, 75%
3
bi, 66%b,c
S
S
O
O
O
O
P(i-Pr)2
P(t-Bu)2
PPh2
Ph
Ph
Ph
3aj, 67%
N.R.b,c
3ak, 95% (X-ray)
O
O
O
O
O
O
PPh2
PPh2
PCy2
Me
bk, 98%
Cl
Ph
Ph
3ek, 88%
Ph
3al, 98%b
3
a
b
o
c
d
Reactions in 0.2 mmol scale (0.1 M), yields of isolated products. 80 C. 3.0 equiv of 1 was used. Reaction in 2.0
mmol scale (0.2 M). N.R. = No Reaction.
Subsequently, a series of experiments were carried out to gain insight into the mechanism of the
current reaction (see the Supporting Information for details). First, 1a was conducted with D O in
2
the absence of alkyne and 75% deuterium was incorporated at the two orthoꢀpositions of the
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directing group (eq 1). When the same reaction was performed in the presence of 2a, 38%
deuterium incorporation was detected in product 3aa (eq 2). These results suggested that, under the
reaction conditions, a reversible cyclometalation mode was involved. A kinetic isotope effect (KIE)
of k
reactions between 1a and [D
likely not involved in the rateꢀdetermining step.
H D
/k = 1.4 was observed in the intermolecular isotopic study of two parallel competition
]ꢀ1a (eq 3), thus demonstrating that the cleavage of the C−H bond is
5
0
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9
0
16,17
To our satisfaction, the annulated products, 2ꢀbenzofuranylphosphine sulfides and oxides, could
9
,13b,18
be reduced smoothly. Under the radical desulfidation reaction conditions,
the phosphine
sulfides 3aa, 3ca, 3ea, and 3ai were converted into the corresponding trivalent phosphines
quantitatively [Scheme 4(a)]. Meanwhile, treatment of the phosphine oxides 3ak and 3al with
trichlorosilane and triethylamine also afforded the trivalent phosphines 4aa and 4ai in quantitative
1
9
yield [Scheme 4(b)]. It is important to note that the phosphines 4 are stable under air, thus
allowing the purification by quick silica gel column chromatography without any special care.
Particularly, even the solution of 4ai are stable enough so that we could obtain the suitable single
1
5
crystals for Xꢀray crystal structure analysis by recrystallization of 4ai in EtOAc open to air.
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Scheme 4. Reduction of 2ꢀBenzofuranylphosphine Sulfides and Oxides
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60
a
Reactions in 0.1 mmol scale (0.05 M), yields of isolated products.
With the trivalent phosphines in hand, we next turned our attention to their applications as
supporting ligands in palladiumꢀcatalyzed aryl chloride transformations. As illustrated in Table 2,
2
the combination of Pd(OAc) and 4ai effectively catalyzed the SuzukiꢀMiyaura coupling of aryl
20
chlorides in the presence of a stoichiometric amount of CsF in dioxane. Under these conditions,
both electronꢀrich (entry 1) and electronꢀdeficient (entries 3ꢀ7) aryl chlorides are equally efficient,
and baseꢀsensitive functional groups are well tolerant. Not surprisingly, employment of
diphenylphosphino analogue, 4aa, as ligand resulted in poor reactivity (entry 6, 29% with 4aa vs
entry 5, 99% with 4ai). The chloride substrate 5b bearing orthoꢀsubstituent coupled with 6a
smoothly (entry 2). Apart from functionalized arylboronic acids, preliminary experiment showed
the reaction of nꢀbutylboronic acid 6d with chloride 5d proceeded to afford the coupling product 7g
without difficulty (entry 8). Interestingly, heteroaryl chloride, such as 2ꢀchloropyridine, was also
verified to be a reactive coupling partner (entry 9).
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a
Table 2. Palladium/4aiꢀCatalyzed SuzukiꢀMiyaura Coupling of Aryl Chlorides
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8
9
0
a
b
c
Reactions in 0.5 mmol scale (0.5 M). yields of isolated products. 4aa was used instead of 4ai as ligand.
2
In light of the good performance of Pd(OAc) /4ai in SuzukiꢀMiyaura couplings, this new
catalytic system was further examined in BuchwaldꢀHartwig amination reactions (Scheme 5). Brief
studies on the coupling of both electronꢀrich and orthoꢀsubstituted aryl chlorides were successful,
affording 9aꢀd in 83ꢀ90% yields. Meanwhile, not only secondary amines but also primary amines
were readily arylated with aryl chlorides under the reaction conditions.
a
Scheme 5. Palladium/4aiꢀCatalyzed BuckwaldꢀHartwig Amination of Aryl Chlorides
a
Reactions in 0.5 mmol scale (1.0 M), yields of isolated products.
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CONCLUSION
In summary, we have developed a stepꢀeconomic way to synthesize a new class of
arylꢀheteroarylphosphines, 3ꢀarylbenzofuranꢀ2ꢀyl phosphines, via Rh(III)ꢀcatalyzed C−H
activation/annulation of Nꢀphenoxyacetamides with 1ꢀalkynylphosphine sulfides and oxides
followed by reduction. This transformation proceeds in excellent regioselectivity with a broad
substrate scope for both Nꢀphenoxyacetamides and phosphinoacetylenes, thus allowing the
heteroaromatic phosphines to have different steric and electronic properties. A combination of the
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air stable trivalent phosphine, 3ꢀbenzylbenzofuranꢀ2ꢀyl dicyclohexylphosphine 4ai, with Pd(OAc)
2
provides active catalysts for both SuzukiꢀMiyaura coupling and BuchwaldꢀHartwig amination of
aryl chlorides. Efforts to expand the application of this new type of arylꢀheteroarylphosphine
ligands are currently underway.
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EXPERIMENTAL SECTION
General Procedures. All the reactions were carried out under argon atmosphere using standard
1
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19
13
Schlenk technique. H NMR (400 MHz), P NMR (162 MHz), F NMR (376 MHz) and C NMR
(
101 MHz) were recorded on Bruker AV400 NMR spectrometer with CDCl as solvent. Chemical
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shifts of H, C, P, and F NMR spectra are reported in parts per million (ppm). The residual
solvent signals were used as references and the chemical shifts converted to the TMS scale (CDCl3:
δ
H
= 7.26 ppm, δ
FTMS. [Cp*RhCl
procedures. 1ꢀAlkynylphosphine sulfides and oxides were prepared by treatment of the
C
= 77.00 ppm). HRMS were done on Agilent 6520 QꢀTOF LC/MS or Varian 7.0T
21
13a
2
]
2
and Nꢀphenoxyacetamides
were prepared according to the literature
2
2
corresponding 1ꢀalkynylphosphines with crystalline sulfur or H
2
O
2
.
1ꢀAlkynylphosphines were
2
2a
prepared by nucleophilic substitution reactions of chlorophosphines with 1ꢀlithioꢀ1ꢀalkynes or
22b
Sonogashira Coupling reactions of ethynyldiphenylphosphines with iodobenzenes according to
the literature procedures.
General Procedure 1: Rhodium(III)ꢀCatalyzed CꢀH Activation/Annulation of
Nꢀphenoxyacetamides (1) with 1ꢀalkynylphosphine derivatives (2) (Scheme 2 and 3). A mixture
of 1 (0.30 mmol, 1.5 equiv), 2 (0.2 mmol), [Cp*Rh(MeCN) ][SbF ] (16.7 mg, 0.02 mmol, 10
3
6 2
mol %), and AgOAc (16.7 mg, 0.1 mmol, 0.5 equiv) were weighted in a Schlenk tube equipped
with a stir bar. Dry DCM (2.0 mL) and HOAc (12 mg, 0.2 mmol, 1.0 equiv) was added and the
resulting mixture was then put in a preꢀheated oil bath at 60 °C for 20 h under vigorous stirring. The
reaction was cooled to room temperature and transferred to a 100 mL roundꢀbottomed flask using
2 2
CH Cl . Silica was added to the flask and volatiles were evaporated under reduced pressure. The
purification was performed by flash column chromatography on silica gel with petroleum
ether/EtOAc.
Diphenyl(3-phenylbenzofuran-2-yl)phosphine sulfide (3aa). The title compound was isolated by
silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white solid in 93%
1
yield (76.3 mg) following the general procedure 1; m.p.: 209ꢀ211 °C; H NMR (400 MHz, CDCl )
3
δ 7.89ꢀ7.84 (m, 4H), 7.57ꢀ7.51 (m, 2H), 7.44ꢀ7.39 (m, 3H), 7.38ꢀ7.29 (m, 7H), 7.18ꢀ7.15 (m, 3H);
1
3
1
C{ H} NMR (101 MHz, CDCl
3
) δ 156.2 (d, J = 8.7 Hz), 144.1 (d, J = 109.7 Hz), 132.0 (d, J =
1
1.2 Hz), 131.8 (d, J = 26.4 Hz), 131.6 (d, J = 2.8 Hz), 131.1 (d, J = 90.6 Hz), 130.3, 129.9, 128.4
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(
d, J = 8.5 Hz), 128.3, 128.0 (d, J = 27.9 Hz), 127.8, 126.9, 123.5, 121.4, 112.0; P NMR (162
+
MHz, CDCl
3
) δ 30.47; HRMS (ESI): Calcd for C26
H
20OPS [M+H] 411.0967, Found: 411.0965.
(5-Methyl-3-phenylbenzofuran-2-yl)diphenylphosph0ine sulfide (3ba). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 74% yield (62.8 mg) following the general procedure 1; m.p.: 218ꢀ220 °C; H NMR (400
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21
22
23
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27
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42
43
44
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47
48
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50
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58
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60
MHz, CDCl ) δ 7.86ꢀ7.81 (m, 4H), 7.43ꢀ7.39 (m, 3H), 7.34ꢀ7.30 (m, 7H), 7.23 (dd, J = 8.6, 1.2 Hz,
3
13
1
1
H), 7.16 (d, J = 2.1 Hz, 2H), 7.15 (d, J = 1.5 Hz, 1H), 2.42 (s, 3H); C{ H} NMR (101 MHz,
CDCl ) δ 154.8 (d, J = 8.6 Hz), 144.1 (d, J = 110.6 Hz), 133.2, 132.0 (d, J = 11.3 Hz), 131.8, 131.6,
31.2 (d, J = 90.1 Hz), 130.5, 129.9, 128.5 (d, J = 8.2 Hz), 128.3, 128.2 (d, J = 13.1 Hz), 127.8,
3
1
1
3
1
3
27.7, 120.9 (d, J = 5.3 Hz), 111.6, 21.3 (d, J = 6.5 Hz); P NMR (162 MHz, CDCl ) δ 30.41;
+
HRMS (ESI): Calcd for C27
H
22OPS [M+H] 425.1124, Found: 425.1124.
(5-(tert-Butyl)-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3ca). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 72% yield (67.1 mg) following the general procedure 1; m.p.: 221ꢀ223°C; H NMR (400
MHz, CDCl
3
) δ 7.86ꢀ7.81 (m, 4H), 7.52ꢀ7.49 (m, 2H), 7.45 (d, J = 8.6 Hz, 1H), 7.42ꢀ7.38 (m, 2H),
7
9
1
.36ꢀ7.33 (m, 3H), 7.31 (d, J = 3.2 Hz, 2H), 7.30 (d, J = 3.2 Hz, 1H), 7.18ꢀ7.16 (m, 3H), 1.33 (s,
13
1
H); C{ H} NMR (101 MHz, CDCl
3
) δ 154.6 (d, J = 8.3 Hz), 146.9, 144.2 (d, J = 110.7 Hz),
32.3 (d, J = 16.1 Hz), 132.0 (d, J = 11.1 Hz), 131.6 (d, J = 3.0 Hz), 131.3 (d, J = 89.9 Hz), 130.5,
129.9, 128.2 (d, J = 13.1 Hz), 128.0 (d, J = 8.3 Hz), 127.9, 127.7, 125.2, 117.0, 111.4, 34.8, 31.7;
3
1
+
P NMR (162 MHz, CDCl
Found: 467.1617.
5-Fluoro-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3da). The title compound was
3
) δ 30.37; HRMS (ESI): Calcd for C30H28OPS [M+H] 467.1593,
(
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 73% yield (62.5 mg) following the general procedure 1; m.p.: 164ꢀ166 °C; H NMR (400
MHz, CDCl
3
) δ 7.87ꢀ7.81(m, 4H), 7.48ꢀ7.40 (m, 3H), 7.35ꢀ7.31 (m, 6H), 7.19ꢀ7.12 (m, 5H);
13
1
C{ H} NMR (101 MHz, CDCl ) δ 159.6 (d, J = 241.1 Hz), 152.4 (d, J = 8.6 Hz), 146.2 (d, J =
3
1
08.4 Hz), 132.0 (d, J = 11.2 Hz), 131.9 (d, J = 5.2 Hz), 131.8 (d, J = 3.2 Hz), 130.8 (d, J = 90.2
Hz), 129.9, 129.7, 129.3 (dd, J = 10.2, 8.6 Hz), 128.3, 128.2, 128.0, 115.0 (d, J = 26.5 Hz), 112.9
31
19
3
(d, J = 9.5 Hz), 106.6 (d, J = 25.0 Hz); P NMR (162 MHz, CDCl ) δ 30.50; F NMR (376 MHz,
+
CDCl
3
) δ ꢀ119.16; HRMS (ESI): Calcd for C26
H
19FOPS [M+H] 429.0873, Found: 429.0874.
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(
5-Chloro-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3ea). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 85% yield (75.5 mg) following the general procedure 1; m.p.: 134ꢀ136 °C; H NMR (400
MHz, CDCl
.17ꢀ7.15 (m, 3H); C{ H} NMR (101 MHz, CDCl
Hz), 132.1, 132.0, 131.8 (d, J = 3.0 Hz), 131.3 (d, J = 15.9 Hz), 130.8 (d, J = 84.5 Hz), 129.9 (d, J
3
) δ 7.83 (m, 4H), 7.49 (d, J = 1.9 Hz, 1H), 7.44ꢀ7.70 (m, 3H), 7.37ꢀ7.29 (m, 7H),
13
1
7
3
) δ 154.6 (d, J = 8.4 Hz), 146.1 (d, J = 107.7
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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6
7
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0
=
8.3 Hz), 129.8, 129.6 (d, J = 33.8 Hz), 128.3 (d, J = 13.3 Hz), 128.1, 128.0, 127.2, 120.9, 113.1;
31
+
P NMR (162 MHz, CDCl
3
) δ 30.50; HRMS (ESI): Calcd for C26
H
19ClOPS [M+H] 445.0577,
Found: 445.0579.
5-Bromo-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3fa). The title compound was
(
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 73% yield (71.2 mg) following the general procedure 1; m.p.: 198ꢀ200 °C; H NMR (400
MHz, CDCl ) δ 7.86ꢀ7.80 (m, 4H), 7.65 (d, J = 1.5 Hz, 1H), 7.50 (dd, J = 8.8, 1.5 Hz, 1H),
3
13
1
7
.47ꢀ7.37 (m, 3H), 7.35ꢀ7.29 (m, 6H), 7.17ꢀ7.13 (m, 3H); C{ H} NMR (101 MHz, CDCl
3
) δ
1
54.9 (d, J = 8.3 Hz), 145.8 (d, J = 107.8 Hz), 132.0 (d, J = 11.4 Hz), 131.8 (d, J = 3.0 Hz), 131.1
(d, J = 15.6 Hz), 130.7 (d, J = 90.3 Hz), 130.4 (d, J = 8.3 Hz), 129.9, 129.7, 129.6, 128.3 (d, J =
31
1
3.2 Hz), 128.1, 128.0, 124.0, 116.7, 113.6; P NMR (162 MHz, CDCl
3
) δ 30.47; HRMS (ESI):
+
Calcd for C26
H
19BrOPS [M+H] 489.0072, Found: 489.0075.
Methyl 2-(diphenylphosphorothioyl)-3-phenylbenzofuran-5-carboxylate (3ga). The title
compound was isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1)
1
as a white solid in 60% yield (56.2 mg) following the general procedure 1; mp: 197ꢀ199 °C; H
NMR (400 MHz, CDCl
.7 Hz, 1H), 7.44ꢀ7.40 (m, 3H), 7.35ꢀ7.33 (m, 5H), 7.18ꢀ7.17 (m, 3H), 3.90 (s, 3H); C{ H} NMR
101 MHz, CDCl ) δ 166.7, 158.5 (d, J = 8.3 Hz), 145.9 (d, J = 107.6 Hz), 132.2, 132.1, 132.0,
3
) δ 8.26 (s, 1H), 8.13 (d, J = 8.8 Hz, 1H), 7.87ꢀ7.82 (m, 4H), 7.54 (d, J =
1
3
1
8
(
3
1
31.8 (d, J = 2.6 Hz), 130.6 (d, J = 90.4 Hz), 129.8, 129.6, 128.6 (d, J = 8.0 Hz), 128.3 (d, J = 13.2
31
Hz), 128.1, 128.0, 126.0, 124.0, 112.0, 52.2; P NMR (162 MHz, CDCl ) δ 30.50; HRMS (ESI):
3
+
Calcd for C28
H
22
O
3
PS [M+H] 469.1022, Found: 469.1018.
Diphenyl(3-phenyl-5-(trifluoromethyl)benzofuran-2-yl)phosphine sulfide (3ha). The title
compound was isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1)
1
as a white solid in 63% yield (60.2 mg) following the general procedure 1; mp: 134ꢀ136 °C; H
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NMR (400 MHz, CDCl
3
) δ 7.87ꢀ7.81 (m, 5H), 7.69ꢀ7.66 (m, 1H), 7.61 (d, J = 8.7 Hz, 1H),
13
1
7.45ꢀ7.41 (m, 2H), 7.36ꢀ7.31 (m, 6H), 7.21ꢀ7.16 (m, 3H); C{ H} NMR (101 MHz, CDCl
157.3 (d, J = 8.5 Hz), 146.6 (d, J = 107.0 Hz), 132.0 (d, J = 11.2 Hz), 131.9 (d, J = 3.2 Hz), 131.8
d, J = 15.6 Hz), 130.5 (d, J = 90.5 Hz), 129.7, 129.3, 128.6 (d, J = 8.5 Hz), 128.3 (d, J = 13.2 Hz),
3
) δ
(
1
28.2, 128.1, 126.4 (q, J = 32.2 Hz), 124.2 (d, J = 272.2 Hz), 123.9 (q, J = 3.4 Hz), 119.3 (q, J =
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
1
19
4
.2 Hz), 112.7; P NMR (162 MHz, CDCl ) δ 30.53; F NMR (376 MHz, CDCl ) δ ꢀ60.96; HRMS
3
3
+
(
ESI): Calcd for C27
19 3
H F OPS [M+H] 479.0841, Found: 479.0848.
(
6-Methyl-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3ia). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 81% yield (68.7 mg) following the general procedure 1; mp: 183ꢀ185 °C; H NMR (400
MHz, CDCl
3
) δ 7.87ꢀ7.81(m, 4H), 7.43ꢀ7.39 (m, 3H), 7.35ꢀ7.26 (m, 7H), 7.16ꢀ7.11 (m, 4H), 2.48 (s,
3H); C{ H} NMR (101 MHz, CDCl ) δ 156.7 (d, J = 8.1 Hz), 143.3 (d, J = 111.1 Hz), 137.6,
32.2, 132.1 (d, J = 11.2 Hz), 131.6, 131.3 (d, J = 90.0 Hz), 130.5, 129.9, 128.2 (d, J = 13.0 Hz),
27.8, 127.7, 126.1 (d, J = 8.4 Hz), 125.1 (d, J = 4.0 Hz), 120.9 (d, J = 3.2 Hz), 112.1 (d, J = 6.4
1
3
1
3
1
1
3
1
3
Hz), 21.8 (d, J = 7.2 Hz); P NMR (162 MHz, CDCl ) δ 30.35; HRMS (ESI): Calcd for
+
C H OPS [M+H] 425.1124, Found: 425.1125.
27
22
(
6-Methoxy-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3ja). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 85% yield (74.8 mg) following the general procedure 1; m.p.: 152ꢀ154 °C; H NMR (400
MHz, CDCl
3
) δ 7.87ꢀ7.81 (m, 4H), 7.42ꢀ7.38 (m, 3H), 7.34ꢀ7.29 (m, 6H), 7.14ꢀ7.13 (m, 3H), 7.00
13
1
(d, J = 2.1 Hz, 1H), 6.91 (dd, J = 8.7, 2.1 Hz, 1H), 3.84 (s, 3H); C{ H} NMR (101 MHz, CDCl
3
)
δ 160.0, 157.5 (d, J = 8.7 Hz), 142.6 (d, J = 112.4 Hz), 132.4 (d, J = 16.2 Hz), 132.0 (d, J = 11.3
Hz), 131.6 (d, J = 2.8 Hz), 131.3 (d, J = 90.2 Hz), 130.4, 129.8, 128.2 (d, J = 13.0 Hz), 127.8,
31
1
27.7, 121.7 (d, J = 8.5 Hz), 121.6, 113.6, 95.5, 55.7; P NMR (162 MHz, CDCl
3
) δ 30.16; HRMS
+
(
ESI): Calcd for C27
H
22
O
2
PS [M+H] 441.1073, Found: 441.1076.
(
6-Chloro-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3ka). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 63% yield (55.9 mg) following the general procedure 1; mp: 185ꢀ187 °C; H NMR (400
MHz, CDCl
3
) δ 7.86ꢀ7.80 (m, 4H), 7.53 (d, J = 1.6 Hz, 1H), 7.46ꢀ7.40 (m, 3H), 7.36ꢀ7.30 (m, 6H),
1
3
1
7
.28 (dd, J = 7.8, 1.7 Hz, 1H), 7.17ꢀ7.15 (m, 3H); C{ H} NMR (101 MHz, CDCl ) δ 156.1 (d, J =
3
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.5 Hz), 145.1 (d, J = 108.4 Hz), 132.9, 132.0 (d, J = 11.2 Hz), 131.8 (d, J = 3.0 Hz), 131.6, 130.7
(d, J = 90.3 Hz), 129.8, 129.7, 128.3 (d, J = 13.2 Hz), 128.02, 127.95, 127.1 (d, J = 8.3 Hz), 124.4,
31
+
122.0, 112.5; P NMR (162 MHz, CDCl ) δ 30.41; HRMS (ESI): Calcd for C H ClOPS [M+H]
3
26 19
4
45.0577, Found: 445.0577.
(6-Bromo-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3la). The title compound was
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 73% yield (71.2 mg) following the general procedure 1; mp: 193ꢀ195 °C; H NMR (400
MHz, CDCl
3
) δ 7.86ꢀ7.80 (m, 4H), 7.69 (s, 1H), 7.44ꢀ7.40 (m, 4H), 7.35ꢀ7.30 (m, 6H), 7.18ꢀ7.13
13
1
(m, 3H); C{ H} NMR (101 MHz, CDCl
3
) δ 156.3 (d, J = 8.2 Hz), 145.0 (d, J = 108.1 Hz), 132.0
(d, J = 11.3 Hz), 131.8 (d, J = 2.8 Hz), 131.6, 130.7 (d, J = 90.3 Hz), 129.8, 129.7, 128.3 (d, J =
3
1
13.2 Hz), 128.03, 127.96, 127.5 (d, J = 8.5 Hz), 127.1, 122.3, 120.5, 115.4; P NMR (162 MHz,
+
CDCl
3
) δ 30.42; HRMS (ESI): Calcd for C26
H
19BrOPS [M+H] 489.0072, Found: 489.0079.
Diphenyl(3-phenyl-6-(trifluoromethyl)benzofuran-2-yl)phosphine sulfide (3ma). The title
compound was isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1)
1
as a white solid in 61% yield (58.3 mg) following the general procedure 1; mp: 146ꢀ148 °C; H
NMR (400 MHz, CDCl ) δ 7.87ꢀ7.80 (m, 5H), 7.65 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.3 Hz, 1H),
3
13
1
7
1
.46ꢀ7.42 (m, 2H), 7.37ꢀ7.33 (m, 6H), 7.21ꢀ7.15 (m, 3H); C{ H} NMR (101 MHz, CDCl
3
) δ
55.2 (d, J = 8.3 Hz), 147.6 (d, J = 106.0 Hz), 132.1 (d, J = 11.2 Hz), 131.9 (d, J = 2.8 Hz), 131.5,
131.3 (d, J = 5.0 Hz), 130.7 (d, J = 90.4 Hz), 129.9, 129.6, 129.1 (d, J = 32.7 Hz), 128.4 (d, J =
13.3 Hz), 128.2, 128.1, 124.1 (d, J = 272.5 Hz), 122.1, 120.4 (d, J = 3.4 Hz), 109.8 (q, J = 4.1 Hz);
3
1
19
3 3
P NMR (162 MHz, CDCl ) δ 30.57; F NMR (376 MHz, CDCl ) δ ꢀ61.41; HRMS (ESI): Calcd
+
for C27
H
19
F
3
OPS [M+H] 479.0841, Found: 479.0849.
(7-Methyl-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3na). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 78% yield (66.1 mg) following the general procedure 1; m.p.: 209ꢀ211 °C; H NMR (400
MHz, CDCl ) δ 7.89ꢀ7.84 (m, 4H), 7.43ꢀ7.31 (m, 9H), 7.23ꢀ7.19 (m, 2H), 7.18ꢀ7.15 (m, 3H), 2.42
3
13
1
(s, 3H); C{ H} NMR (101 MHz, CDCl
3
) δ 155.3 (d, J = 8.0 Hz), 143.7 (d, J = 110.4 Hz), 132.2
(d, J = 16.2 Hz), 132.0 (d, J = 11.3 Hz), 131.6, 131.2 (d, J = 92.1 Hz), 130.6, 129.9, 128.2, 128.0,
31
3
127.81, 127.75, 127.6 (d, J = 19.8 Hz), 123.6, 122.2, 118.8, 14.8; P NMR (162 MHz, CDCl ) δ
+
3
0.46; HRMS (ESI): Calcd for C27
H
22OPS [M+H] 425.1124, Found: 425.1129.
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(
4,6-Dimethoxy-3-phenylbenzofuran-2-yl)diphenylphosphine sulfide (3oa). The title compound
was isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a
1
white solid in 75% yield (70.5 mg) following the general procedure 1; mp: 114ꢀ116 °C; H NMR
(
400 MHz, CDCl
.61 (d, J = 1.9 Hz, 1H), 6.28 (d, J = 1.7 Hz, 1H), 3.82 (s, 3H), 3.62 (s, 3H); C{ H} NMR (101
MHz, CDCl ) δ 161.0, 158.6 (d, J = 8.7 Hz), 155.5, 141.5 (d, J = 113.9 Hz), 132.4 (d, J = 16.6 Hz),
3
) δ 7.82ꢀ7.76 (m, 4H), 7.40ꢀ7.36 (m, 2H), 7.32ꢀ7.26 (m, 6H), 7.07ꢀ7.01 (m, 3H),
1
3
1
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
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26
27
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31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
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53
54
55
56
57
58
59
60
3
1
1
3
32.0 (d, J = 11.2 Hz), 131.5 (d, J = 90.4 Hz), 131.4 (d, J = 3.1 Hz), 131.0, 130.6, 128.1 (d, J =
31
3.1 Hz), 127.3, 126.8, 111.7 (d, J = 8.3 Hz), 95.2, 87.9, 55.7, 55.4; P NMR (162 MHz, CDCl
3
) δ
+
0.28; HRMS (ESI): Calcd for C28
H
24
O
3
PS [M+H] 471.1178, Found: 471.1177.
Diphenyl(3-(p-tolyl)benzofuran-2-yl)phosphine sulfide (3ab). The title compound was isolated by
silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white solid in 76%
1
yield (64.4 mg) following the general procedure 1; m.p.: 175ꢀ177 °C; H NMR (400 MHz, CDCl
3
)
δ 7.86ꢀ7.81 (m, 4H), 7.56ꢀ7.50 (m, 2H), 7.43ꢀ7.40 (m, 3H), 7.34ꢀ7.28 (m, 5H), 7.22 (d, J = 7.7 Hz,
13
1
2
3
H), 6.95 (d, J = 7.7 Hz, 2H), 2.28 (s, 3H); C{ H} NMR (101 MHz, CDCl ) δ 156.2 (d, J = 8.5
Hz), 143.8 (d, J = 110.2 Hz), 137.6, 132.3, 132.2 (d, J = 11.3 Hz), 131.5 (d, J = 2.6 Hz), 131.3 (d, J
31
=
90.1 Hz), 129.8, 128.6, 128.5, 128.2 (d, J = 13.2 Hz), 127.2, 126.8, 123.4, 121.5, 112.0, 21.2; P
+
NMR (162 MHz, CDCl
3
) δ 30.47; HRMS (ESI): Calcd for C27
H
22OPS [M+H] 425.1124, Found:
4
25.1123.
(3-(4-Methoxyphenyl)benzofuran-2-yl)diphenylphosphine sulfide (3ac). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 93% yield (81.8 mg) following the general procedure 1; m.p.: 213ꢀ215 °C; H NMR (400
3
MHz, CDCl ) δ 7.87ꢀ7.82 (m, 4H), 7.56 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 8.3 Hz, 1H), 7.43ꢀ7.39 (m,
13
1
3
1
1
1
H), 7.35ꢀ7.27 (m, 7H), 6.68 (d, J = 8.6 Hz, 2H), 3.76 (s, 3H); C{ H} NMR (101 MHz, CDCl ) δ
3
59.1, 156.2 (d, J = 8.5 Hz), 143.6 (d, J = 110.8 Hz), 132.1 (d, J = 11.2 Hz), 131.8 (d, J = 16.0 Hz),
31.6 (d, J = 3.0 Hz), 131.2 (d, J = 89.6 Hz), 131.1, 128.5 (d, J = 8.4 Hz), 128.2 (d, J = 13.2 Hz),
31
26.8, 123.4, 122.5, 121.4, 113.4, 112.1, 55.2; P NMR (162 MHz, CDCl ) δ 30.37; HRMS (ESI):
3
+
Calcd for C27
H
22
O
2
PS [M+H] 441.1073, Found: 441.1081.
(3-(4-Fluorophenyl)benzofuran-2-yl)diphenylphosphine sulfide (3ad). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 69% yield (59.2 mg) following the general procedure 1; m.p.: 180ꢀ182 °C; H NMR (400
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6
MHz, CDCl
3
) δ 7.79ꢀ7.74 (m, 4H), 7.42 (d, J = 7.9 Hz, 2H), 7.34 (d, J = 6.9 Hz, 3H), 7.26ꢀ7.17 (m,
1
3
1
3
6H), 6.78ꢀ6.74 (m, 3H); C{ H} NMR (101 MHz, CDCl ) δ 162.3 (d, J = 247.6 Hz), 156.2 (d, J =
7.8 Hz), 144.5 (d, J = 109.5 Hz), 132.0 (d, J = 11.2 Hz), 131.7 (d, J = 2.5 Hz), 131.6 (d, J = 8.2
Hz), 131.02, 130.95 (d, J = 90.0 Hz), 130.9, 128.3 (d, J = 12.7 Hz), 127.0, 126.3 (d, J = 3.4 Hz),
31
19
1
3
23.6, 121.1, 114.9 (d, J = 21.5 Hz), 112.1; P NMR (162 MHz, CDCl ) δ 30.24; F NMR (376
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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7
8
9
0
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2
3
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5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
MHz, CDCl ) δ ꢀ113.50; HRMS (ESI): Calcd for C H FOPS [M+H] 429.0873, Found: 429.0879.
3
26 19
(3-(4-Chlorophenyl)benzofuran-2-yl)diphenylphosphine sulfide (3ae). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 85% yield (75.5 mg) following the general procedure 1; m.p.: 194ꢀ196 °C; H NMR (400
MHz, CDCl
7.20ꢀ7.18 (m, 3H), 7.04 (d, J = 7.7 Hz, 2H); C{ H} NMR (101 MHz, CDCl
Hz), 144.8 (d, J = 108.8 Hz), 133.9, 132.1 (d, J = 11.4 Hz), 131.8 (d, J = 2.7 Hz), 131.22, 131.07 (d,
3
) δ 7.78ꢀ7.73 (m, 4H), 7.44ꢀ7.40 (m, 2H), 7.39ꢀ7.33 (m, 3H), 7.29ꢀ7.27 (m, 4H),
13
1
3
) δ 156.2 (d, J = 8.1
31
J = 90.2 Hz), 130.8 (d, J = 15.7 Hz), 128.9, 128.4, 128.3, 128.1, 127.1, 123.7, 121.1, 112.2; P
+
NMR (162 MHz, CDCl
45.0579.
3-(4-Bromophenyl)benzofuran-2-yl)diphenylphosphine sulfide (3af). The title compound was
3
) δ 30.27; HRMS (ESI): Calcd for C26
H
19ClOPS [M+H] 445.0577, Found:
4
(
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
1
solid in 74% yield (72.2 mg) following the general procedure 1; m.p.: 189ꢀ191 °C; H NMR (400
MHz, CDCl
3
) δ 7.85ꢀ7.80 (m, 4H), 7.52ꢀ7.43 (m, 5H), 7.36ꢀ7.33 (m, 4H), 7.28ꢀ7.26 (m, 3H), 7.20
13
1
(d, J = 7.4 Hz, 2H); C{ H} NMR (101 MHz, CDCl
3
) δ 156.2 (d, J = 8.1 Hz), 144.7 (d, J = 108.9
Hz), 132.1 (d, J = 11.4 Hz), 131.8 (d, J = 2.7 Hz), 131.5, 131.05, 130.99 (d, J = 90.5 Hz), 130.8 (d,
J = 15.7 Hz), 129.4, 128.4 (d, J = 13.2 Hz), 128.1 (d, J = 8.2 Hz), 127.1, 123.7, 122.2, 121.1, 112.2;
3
1
+
P NMR (162 MHz, CDCl ) δ 30.29; HRMS (ESI): Calcd for C H BrOPS [M+H] 489.0072,
3
26 19
Found: 489.0077.
Diphenyl(3-(o-tolyl)benzofuran-2-yl)phosphine sulfide (3ag). The title compound was isolated by
silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white solid in 63%
o
yield (53.3 mg) following the general procedure 1 but with 3.0 equiv of 1a at 80 C for 48 h; mp:
1
144ꢀ146 °C; H NMR (400 MHz, CDCl
3
) δ 7.83ꢀ7.75 (m, 4H), 7.56 (d, J = 8.3 Hz, 1H), 7.43ꢀ7.40
(m, 3H), 7.33 (br s, 4H), 7.24ꢀ7.20 (m, 2H), 7.13ꢀ7.10 (m, 1H), 7.05ꢀ7.00 (m, 3H), 2.03 (s, 3H);
1
3
1
3
C{ H} NMR (101 MHz, CDCl ) δ 156.1 (d, J = 8.2 Hz), 143.9 (d, J = 109.9 Hz), 136.8, 132.3 (d,
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J = 17.2 Hz), 132.1 (d, J = 4.3 Hz), 131.95 (d, J = 4.3 Hz), 131.69, 131.68 (d, J = 4.7 Hz), 131.2,
130.85, 130.83 (d, J = 16.5 Hz), 129.9, 129.6, 128.9 (d, J = 8.4 Hz), 128.28 (d, J = 3.0 Hz), 128.23,
31
128.1 (d, J = 3.0 Hz), 126.9, 125.3, 123.5, 121.5, 112.1, 20.3; P NMR (162 MHz, CDCl ) δ 29.99;
3
+
HRMS (ESI): Calcd for C27
H
22OPS [M+H] 425.1124, Found: 425.1125.
(3-(naphthalen-1-yl)benzofuran-2-yl)diphenylphosphine sulfide (3ah). The title compound was
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
o
solid in 64% yield (58.9 mg) following the general procedure 1 but with 3.0 equiv of 1a at 80 C for
1
4
7
0 h; mp: 207ꢀ209 °C; H NMR (400 MHz, CDCl
3
) δ 7.76ꢀ7.66 (m,7H), 7.59 (d, J = 8.3 Hz, 1H),
13
1
.48ꢀ7.45 (m, 2H), 7.38ꢀ7.37 (m, 2H), 7.34ꢀ7.28 (m, 2H), 7.26ꢀ7.16 (m, 5H), 7.06 (s, 2H); C{ H}
) δ 156.3 (d, J = 8.6 Hz), 145.4 (d, J = 110.5 Hz), 133.2, 131.9 (d, J = 3.6
NMR (101 MHz, CDCl
3
Hz), 131.8 (d, J = 3.5 Hz), 131.5 (d, J = 3.3 Hz), 131.40, 131.37, 131.34, 130.6, 130.5 (d, J = 1.7
Hz), 129.9 (d, J = 91.0 Hz), 129.5 (d, J = 36.1 Hz), 129.0, 128.6, 128.0 (d, J = 10.3 Hz), 127.8 (d, J
3
1
=
1.4 Hz), 127.7, 127.0, 126.0, 125.9, 125.8, 125.0, 123.5, 121.8, 112.2; P NMR (162 MHz,
+
CDCl
3
) δ 30.37; HRMS (ESI): Calcd for C30
H
22OPS [M+H] 461.1124, Found: 461.1125.
Dicyclohexyl(3-phenylbenzofuran-2-yl)phosphine sulfide (3ai). The title compound was isolated
by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white solid in 83%
o
yield (70.1 mg) following the general procedure 1 but with 3.0 equiv of 1a at 80 C; 89% yield (753
mg) of 3ai was isolated when the reaction was conducted in 2.0 mmol scale (0.2 M) with 3.0 equiv
o
1
3
of 1a at 80 C for 30 h. m.p.: 219ꢀ221 °C; H NMR (400 MHz, CDCl ) δ 7.59 (d, J = 8.2 Hz, 1H),
7.48ꢀ7.39 (m, 7H), 7.29ꢀ7.26 (m, 1H), 2.32ꢀ2.22 (m, 2H), 2.05ꢀ2.03 (m, 2H), 1.86ꢀ1.77 (m, 4H),
1.69 (br s, 4H), 1.60ꢀ1.58 (m, 2H), 1.47ꢀ1.43 (m, 2H), 1.31ꢀ1.28 (m, 2H), 1.23ꢀ1.16 (m, 4H);
1
3
1
C{ H} NMR (101 MHz, CDCl
2.3 Hz), 130.6, 129.4 (d, J = 7.6 Hz), 128.2, 127.7, 126.6, 123.3, 121.3, 111.6, 38.7 (d, J = 52.4
Hz), 26.49, 26.45, 26.4, 26.3 (d, J = 6.0 Hz), 25.5 (d, J = 35.6 Hz) (one signal missing due to
3
) δ 155.5 (d, J = 6.1 Hz), 142.4 (d, J = 84.6 Hz), 134.4 (d, J =
1
31
+
overlap); P NMR (162 MHz, CDCl
3
) δ 52.42; HRMS (ESI): Calcd for C26H32OPS [M+H]
4
23.1906, Found: 423.1905.
Dicyclohexyl(5-methyl-3-phenylbenzofuran-2-yl)phosphine sulfide (3bi). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white
o
solid in 66% yield (57.6 mg) following the general procedure 1 but with 3.0 equiv of 1a at 80 C;
1
m.p.: 113ꢀ115 °C; H NMR (400 MHz, CDCl
3
) δ 7.47ꢀ7.43 (m, 6H), 7.24 (d, J = 9.4 Hz, 1H), 7.15
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(
s, 1H), 2.40 (s, 3H), 2.29ꢀ2.21 (m, 2H), 2.04ꢀ2.01 (m, 2H), 1.85ꢀ1.76 (m, 4H), 1.68 (br s, 4H),
13
1
1.61ꢀ1.54 (s, 2H), 1.45ꢀ1.37 (m, 2H), 1.30ꢀ1.26 (m, 2H), 1.21ꢀ1.14 (m, 4H); C{ H} NMR (101
MHz, CDCl ) δ 154.0 (d, J = 6.3 Hz), 142.5 (d, J = 85.1 Hz), 134.2 (d, J = 12.6 Hz), 133.1, 130.8,
3
1
30.6, 129.5 (d, J = 7.7 Hz), 128.0 (d, J = 9.8 Hz), 127.7, 120.7, 111.1, 38.7 (d, J = 52.5 Hz), 26.51,
6.48, 26.4, 26.3 (d, J = 6.2 Hz), 25.6 (d, J = 36.3 Hz), 21.2. (one signal missing due to overlap);
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
1
+
P NMR (162 MHz, CDCl ) δ 52.32; HRMS (ESI): Calcd for C H OPS [M+H] 437.2063,
3
27 34
Found: 437.2072.
(5-(tert-Butyl)-3-phenylbenzofuran-2-yl)dicyclohexylphosphine sulfide (3ci). The title compound
was isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a
white solid in 90% yield (86.0 mg) following the general procedure 1 but with 3.0 equiv of 1a at 80
o
1
C; m.p.: 191ꢀ193 °C; H NMR (400 MHz, CDCl
3
) δ 7.52ꢀ7.49 (m, 7H), 7.37ꢀ7.34 (m, 1H),
2.39ꢀ2.19 (br s, 2H), 2.16ꢀ1.98 (br s, 2H), 1.86ꢀ1.61 (m, 10H), 1.47 (br s, 2H), 1.36ꢀ1.34 (m, 11H),
13
1
1
.23ꢀ1.20 (m, 4H); C{ H} NMR (101 MHz, CDCl ) δ 153.9, 146.7, 142.7 (d, J = 86.3 Hz), 134.8
3
(d, J = 13.4 Hz), 130.8, 129.1 (d, J = 4.9 Hz), 128.1, 127.8, 124.8, 117.0, 111.0, 38.8 (d, J = 52.7
31
Hz), 34.9, 31.8, 26.5, 26.44, 26.38, 25.6 (d, J = 36.1 Hz) (two signals missing due to overlap); P
+
NMR (162 MHz, CDCl ) δ 52.24; HRMS (ESI): Calcd for C H OPS [M+H] 479.2532, Found:
3
30 40
4
79.2537.
Dicyclohexyl(4,6-dimethoxy-3-phenylbenzofuran-2-yl)phosphine sulfide (3oi). The title
compound was isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 2/1)
as a white solid in 75% yield (72.5 mg) following the general procedure 1 but with 3.0 equiv of 1a
o
1
at 80 C; m.p.: 168ꢀ170 °C; H NMR (400 MHz, CDCl
3
) δ 7.41ꢀ7.35 (m, 5H), 6.71 (s, 1H), 6.25 (s,
1
4
H), 3.86 (s, 3H), 3.57 (s, 3H), 2.14ꢀ2.06 (m, 2H), 1.98ꢀ1.95 (m, 2H), 1.83ꢀ1.74 (m, 4H), 1.65 (br s,
13
1
H), 1.56ꢀ1.53 (m, 2H), 1.45ꢀ1.42 (m, 2H), 1.25ꢀ1.21 (m, 2H), 1.18ꢀ1.24 (m, 4H); C{ H} NMR
(101 MHz, CDCl
3
) δ 160.7, 157.8 (d, J = 6.8 Hz), 155.3, 139.8 (d, J = 88.1 Hz), 133.2 (d, J = 13.1
Hz), 131.8, 130.6, 127.6, 126.8, 112.2 (d, J = 7.7 Hz), 94.9, 87.8, 55.6 (d, J = 31.0 Hz), 38.7 (d, J =
31
5
2.9 Hz), 26.5 (d, J = 3.2 Hz), 26.4, 26.3, 25.6 (d, J = 28.9 Hz). P NMR (162 MHz, CDCl ) δ
3
+
5
2.37; HRMS (ESI): Calcd for C28
H
36
O
3
PS [M+H] 483.2117, Found: 483.2112.
Diisopropyl(3-phenylbenzofuran-2-yl)phosphine sulfide (3aj). The title compound was isolated by
silica gel column chromatography (eluent: Petroleum ether/EtOAc= 10/1) as a white solid in 67%
1
yield (45.8 mg) following the general procedure 1; m.p.: 144ꢀ146 °C; H NMR (400 MHz, CDCl
3
)
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δ 7.57ꢀ7.52 (m, 3H), 7.44ꢀ7.41 (m, 5H), 7.28 (d, J = 7.3 Hz, 1H), 2.63ꢀ2.55 (m, 2H), 1.28 (d, J =
13
1
6.5 Hz, 3H), 1.22 (br s, 6H), 1.17 (d, J = 6.5 Hz, 3H); C{ H} NMR (101 MHz, CDCl
3
) δ 155.5 (d,
J = 6.1 Hz), 142.7 (d, J = 84.5 Hz), 134.9 (d, J = 12.7 Hz), 130.7, 130.5, 129.4 (d, J = 7.8 Hz),
3
1
1
28.2, 127.8, 126.8, 123.4, 121.4, 111.5, 29.4 (d, J = 52.9 Hz), 17.1 (d, J = 1.9 Hz), 15.7; P NMR
+
(
162 MHz, CDCl
3
) δ 59.52; HRMS (ESI): Calcd for C20
H
24OPS [M+H] 343.1280, Found:
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
43.1285.
Diphenyl(3-phenylbenzofuran-2-yl)phosphine oxide (3ak). The title compound was isolated by
silica gel column chromatography (eluent: Petroleum ether/EtOAc= 2/1) as a white solid in 95%
1
yield (75.1 mg) following the general procedure 1; m.p.: 189ꢀ191 °C; H NMR (400 MHz, CDCl
3
)
δ 7.79ꢀ7.73 (m, 4H), 7.63 (d, J = 7.9 Hz, 1H), 7.52ꢀ7.43 (m, 6H), 7.40ꢀ7.36 (m, 4H), 7.31 (d, J =
1
3
1
7.1 Hz, 1H), 7.27 (d, J = 5.2 Hz, 1H), 7.26ꢀ7.24 (m, 2H); C{ H} NMR (101 MHz, CDCl
3
) δ 156.5
(d, J = 8.6 Hz), 144.8 (d, J = 128.1 Hz), 133.8 (d, J = 16.2 Hz), 132.0 (d, J = 2.6 Hz), 131.8, 131.7,
1
31.5 (d, J = 111.1 Hz), 130.1, 129.9, 128.3 (d, J = 12.6 Hz), 128.1, 128.0 (d, J = 8.7 Hz), 127.0,
31
1
3 20 2
23.5, 121.6, 112.1; P NMR (162 MHz, CDCl ) δ 17.49; HRMS (ESI): Calcd for C26H O P
+
[
M+H] 395.1195, Found: 395.1188.
(5-Methyl-3-phenylbenzofuran-2-yl)diphenylphosphine oxide (3bk). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 2/1) as a white solid
1
in 98% yield (80.0 mg) following the general procedure 1; m.p.: 133ꢀ135 °C; H NMR (400 MHz,
3
CDCl ) δ 7.76ꢀ7.71 (m, 4H), 7.47ꢀ7.45 (m, 4H), 7.40ꢀ7.35 (m, 7H), 7.25ꢀ7.23 (m, 3H), 2.43 (s, 3H);
1
3
1
C{ H} NMR (101 MHz, CDCl
3
) δ 155.0 (d, J = 8.7 Hz), 144.8 (d, J = 129.0 Hz), 133.6 (d, J =
16.3 Hz), 133.2, 132.0 (d, J = 2.7 Hz), 131.8, 131.7, 131.6 (d, J = 111.2 Hz), 130.2, 129.9, 128.4,
3
1
1
3
28.3 (d, J = 12.8 Hz), 128.03, 127.95, 121.0, 111.6, 21.2; P NMR (162 MHz, CDCl ) δ 17.55;
+
HRMS (ESI): Calcd for C H O P [M+H] 409.1352, Found: 409.1358.
27
22
2
(5-Chloro-3-phenylbenzofuran-2-yl)diphenylphosphine oxide (3ek). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether/EtOAc= 2/1) as a white solid
1
in 88% yield (75.3 mg) following the general procedure 1; m.p.: 132ꢀ134 °C; H NMR (400 MHz,
CDCl
7.40ꢀ7.36 (m, 5H), 7.28ꢀ7.25 (m, 3H); C{ H} NMR (101 MHz, CDCl
146.7 (d, J = 125.7 Hz), 133.2 (d, J = 16.0 Hz), 132.20, 132.17, 131.8, 131.7, 131.2 (d, J = 111.5
3
) δ 7.76ꢀ7.71 (m, 4H), 7.58 (d, J = 2.0 Hz, 1H), 7.50ꢀ7.46 (m, 2H), 7.44ꢀ7.42 (m, 3H),
13
1
3
) δ 154.8 (d, J = 8.5 Hz),
31
Hz), 129.8, 129.4 (d, J = 5.8 Hz), 128.5, 128.3, 128.2, 127.3, 121.1, 113.2; P NMR (162 MHz,
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2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
CDCl
3
) δ 17.30; HRMS (ESI): Calcd for C26
H
19ClO
2
P [M+H] 429.0806, Found: 429.0811.
Dicyclohexyl(3-phenylbenzofuran-2-yl)phosphine oxide (3al). The title compound was isolated by
silica gel column chromatography (eluent: Petroleum ether/EtOAc= 2/1) as a white solid in 98%
o
1
yield (79.8 mg) following the general procedure 1 at 80 C; m.p.: 139ꢀ141 °C; H NMR (400 MHz,
CDCl ) δ 7.65ꢀ7.56 (m, 4H), 7.47ꢀ7.37 (m, 4H), 7.31 (t, J = 7.5 Hz, 1H), 2.17ꢀ2.08 (m, 2H),
.02ꢀ1.99 (m, 2H), 1.82ꢀ1.66 (m, 8H), 1.54ꢀ1.36 (m, 4H), 1.31ꢀ1.14 (m,6H); C{ H} NMR (101
MHz, CDCl ) δ 156.0 (d, J = 6.9 Hz), 143.8 (d, J = 103.2 Hz), 134.7 (d, J = 11.4 Hz), 130.2, 130.1,
28.2 (d, J = 7.4 Hz), 128.1, 127.9, 126.4, 123.3, 121.4, 111.7, 36.2 (d, J = 69.9 Hz), 26.3 (d, J =
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
1
2
3
1
9
31
.0 Hz), 26.2 (d, J = 8.8 Hz), 25.7, 25.4 (d, J = 2.8 Hz), 24.5 (d, J = 3.0 Hz); P NMR (162 MHz,
+
CDCl
General Procedure 2: (Me
mixture of 3 (0.1 mmol, 1.0 equiv), AIBN (1.64 mg, 0.01 mmol, 10 mol %) were weighted in a
Schlenk tube equipped with a stir bar. Dry toluene (2.0 mL) and (Me Si) SiH (0.15 mmol, 1.5 equiv,
3
) δ 44.23; HRMS (ESI): Calcd for C26
H
32
O
2
P [M+H] 407.2134, Found: 407.2132.
3
3
Si) SiHꢀMediated Radical Desulfidation Reaction (Scheme 4a). A
3
3
3
7.3mg) were added and the resulting mixture was then put in a preꢀheated oil bath at 80 °C for 12
h under vigorous stirring. The reaction was cooled to room temperature and transferred to a 100 mL
roundꢀbottomed flask using CH Cl . Silica was added to the flask and volatiles were evaporated
2
2
under reduced pressure. The purification was performed by flash column chromatography on silica
gel with petroleum ether.
General Procedure 4: Deoxidation of Phosphine Oxides to Trivalent Phosphines (Scheme 4b).
A mixture of 3 (0.1 mmol, 1.0 equiv) were weighted in a Schlenk tube equipped with a stir bar. Dry
3 3
xylene (2.0 mL), HSiCl (0.83 mmol, 8.3 equiv, 112.4mg) and Et N (611.7 mg, 3.3 mmol, 33 equiv)
was added and the resulting mixture was then put in a preꢀheated oil bath at 150 °C for 48 h under
vigorous stirring. The reaction was cooled to room temperature and transferred to a 100 mL
2 2
roundꢀbottomed flask using CH Cl . Silica was added to the flask and volatiles were evaporated
under reduced pressure. The purification was performed by flash column chromatography on silica
gel with petroleum ether.
Diphenyl(3-phenylbenzofuran-2-yl)phosphine (4aa). The title compound was isolated by silica gel
column chromatography (eluent: Petroleum ether) as a white solid in 99% yield (37.4 mg)
following the general procedure 2 and 99% yield (37.4 mg) following the general procedure 3,
1
respectively; m.p.: 168ꢀ170 °C; H NMR (400 MHz, CDCl
3
) δ 7.53 (d, J = 7.6 Hz, 1H), 7.45 (d, J
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=
7.2 Hz, 2H), 7.43ꢀ7.41 (m, 7H), 7.36ꢀ7.32 (m, 1H), 7.26 (br s, 7H), 7.20ꢀ7.15 (m, 1H); C{ H}
NMR (101 MHz, CDCl ) δ 157.4, 150.4 (d, J = 36.3 Hz), 135.9 (d, J = 6.2 Hz), 133.9 (d, J = 28.2
Hz), 133.6 (d, J = 19.7 Hz), 131.9 (d, J = 1.4 Hz), 130.0 (d, J = 3.7 Hz), 128.8, 128.5, 128.4, 128.0
3
31
(
(
(
3
d, J = 6.4 Hz), 127.9, 125.7, 122.9, 120.7, 111.8; P NMR (162 MHz, CDCl ) δ ꢀ30.65; HRMS
+
ESI): Calcd for C26
H
20OP [M+H] 379.1246, Found: 379.1253.
10
11
12
13
14
15
16
17
18
19
20
21
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23
24
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26
27
28
29
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36
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38
39
40
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44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5-(tert-butyl)-3-phenylbenzofuran-2-yl)diphenylphosphine (4ca). The title compound was
isolated by silica gel column chromatography (eluent: Petroleum ether) as a white solid in 99%
1
yield (43.0 mg) following the general procedure 2; m.p.: 177ꢀ179 °C; H NMR (400 MHz, CDCl
3
)
δ 7.67 (s, 1H), 7.62 (d, J = 7.0 Hz, 2H), 7.54ꢀ7.51 (m, 6H), 7.47ꢀ7.42 (m, 3H), 7.35 (br s, 6H), 1.38
13
1
(s, 9H); C{ H} NMR (101 MHz, CDCl
3
) δ 155.7, 150.6 (d, J = 35.9 Hz), 146.1, 136.0 (d, J = 5.9
Hz), 134.2 (d, J = 27.8 Hz), 133.5 (d, J = 19.6 Hz), 132.1, 130.0 (d, J = 3.8 Hz), 128.7, 128.5 (d, J
31
= 7.4 Hz), 128.4, 127.8, 127.6 (d, J = 6.2 Hz), 123.8, 116.6, 111.2, 34.8, 31.8; P NMR (162 MHz,
+
CDCl ) δ ꢀ30.59; HRMS (ESI): Calcd for C H OP [M+H] 435.1872, Found: 435.1886.
3
30 28
(
5-chloro-3-phenylbenzofuran-2-yl)diphenylphosphine (4ea). The title compound was isolated by
silica gel column chromatography (eluent: Petroleum ether) as a white solid in 99% yield (40.8 mg)
1
following the general procedure 2; m.p.: 134ꢀ136 °C; H NMR (400 MHz, CDCl ) δ 7.53 (d, J =
3
1
.8 Hz, 1H), 7.46 (d, J = 7.5 Hz, 2H), 7.40ꢀ7.37 (m, 6H), 7.33 (d, J = 7.1 Hz, 1H), 7.29 (d, J = 6.5
1
3
1
3
Hz, 1H), 7.26ꢀ7.23 (m, 6H), 7.18 (dd, J = 8.8, 2.0 Hz, 1H); C{ H} NMR (101 MHz, CDCl ) δ
155.7, 152.3 (d, J = 38.9 Hz), 135.5 (d, J = 6.0 Hz), 133.7, 133.5, 133.3 (d, J = 27.8 Hz), 131.2 (d,
J = 1.9 Hz), 129.8 (d, J = 3.6 Hz), 129.4 (d, J = 6.0 Hz), 128.9, 128.6 (d, J = 7.8 Hz), 128.5, 128.2,
31
3
125.9, 120.3, 112.8; P NMR (162 MHz, CDCl ) δ ꢀ30.37; HRMS (ESI): Calcd for C26H19ClOP
+
[
M+H] 413.0857, Found: 413.0866.
Dicyclohexyl(3-phenylbenzofuran-2-yl)phosphine (4ai). The title compound was isolated by silica
gel column chromatography (eluent: Petroleum ether) as a white solid in 99% yield (38.6 mg)
following the general procedure 2 and 99% yield (38.6 mg) following the general procedure 3,
1
respectively; m.p.: 165ꢀ167 °C; H NMR (400 MHz, CDCl ) δ 7.61ꢀ7.56 (m, 4H), 7.49ꢀ7.45 (m,
3
2
H), 7.40ꢀ7.35 (m, 2H), 7.28ꢀ7.24 (m, 1H), 2.23ꢀ2.18 (m, 2H), 1.86ꢀ1.83 (m, 2H), 1.77ꢀ1.74 (m,
13
1
2H), 1.67ꢀ1.60 (m, 6H), 1.38ꢀ1.31 (m, 2H), 1.28ꢀ1.15 (m, 8H); C{ H} NMR (101 MHz, CDCl
156.9, 152.9 (d, J = 44.6 Hz), 134.2 (d, J = 23.0 Hz), 132.5, 130.1 (d, J = 3.1 Hz), 128.3, 127.4,
25.0, 122.5, 120.4, 111.4, 33.4 (d, J = 8.5 Hz), 30.6 (d, J = 17.2 Hz), 30.0 (d, J = 6.7 Hz), 27.2 (d,
3
) δ
1
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2
2
2
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5
5
5
5
5
5
5
5
5
6
3
1
3
J = 5.5 Hz), 27.1, 26.4 (one signal missing due to overlap); P NMR (162 MHz, CDCl ) δ ꢀ22.78;
+
HRMS (ESI): Calcd for C26
H
32OP [M+H] 391.2185, Found: 391.2195.
General Procedure 4: SuzukiꢀMiyaura CrossꢀCoupling Reactions using 4ai as Ligand (Table
). A mixture of boronoic acid 6 (0.75 mmol, 1.5 equiv), 4ai (14.6 mg, 0.0375 mmol, 7.5 mol %),
Pd(OAc) (2.81 mg, 0.0125 mmol, 2.5 mol %), CsF (227.9 mg, 1.5 mmol, 3.0 equiv) were weighted
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
in a Schlenk tube equipped with a stir bar. Dry dioxane (1.0 mL) and aryl chloride 5 (0.5 mmol, 1.0
equiv) was added and the resulting mixture was then put in a preꢀheated oil bath at 110 °C for 30 h
under vigorous stirring. The reaction was cooled to room temperature and transferred to a 100 mL
2 2
roundꢀbottomed flask using CH Cl . Silica was added to the flask and volatiles were evaporated
under reduced pressure. The purification was performed by flash column chromatography on silica
gel with petroleum ether/EtOAc.
1d
4-Methoxy-1,1'-biphenyl (7a). The title compound was isolated by silica gel column
chromatography (eluent: Petroleum ether) as a white solid in 98% yield (90.7 mg) following the
1
general procedure 4; H NMR (400 MHz, CDCl
3
) δ 7.55 (t, J = 8.3 Hz, 4H), 7.43 (t, J = 7.7 Hz,
1
3
1
2
H), 7.31 (t, J = 7.4 Hz, 1H), 6.99 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H); C{ H} NMR (101 MHz,
CDCl ) δ 159.1, 140.8, 133.7, 128.7, 128.1, 126.7, 126.6, 114.2, 55.3.
3
23
2
,5-Dimethyl-1,1'-biphenyl (7b). The title compound was isolated by silica gel column
chromatography (eluent: Petroleum ether) as a white solid in 93% yield (84.6 mg) following the
1
general procedure 4; H NMR (400 MHz, CDCl
3
) δ 7.53 (m, 2H), 7.44 (m, 3H), 7.28 (d, J = 8.3 Hz,
13
1
3
1H), 7.20 (d, J = 6.5 Hz, 2H), 2.47 (s, 3H), 2.36 (s, 3H); C{ H} NMR (101 MHz, CDCl ) δ 142.0,
141.7, 135.1, 132.1, 130.5, 130.2, 129.1, 128.0, 127.9, 126.6, 20.9, 19.9.
24
1
-([1,1'-Biphenyl]-4-yl)ethanone (7c). The title compound was isolated by silica gel column
chromatography (eluent: Petroleum ether) as a white solid in 96% yield (94.1 mg) following the
1
general procedure 4; H NMR (400 MHz, CDCl
3
) δ 8.04 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 8.5 Hz,
2
H), 7.63 (d, J = 7.1 Hz, 2H), 7.48 (t, J = 7.4 Hz, 2H), 7.41 (t, J = 7.3 Hz, 1H), 2.65 (s, 3H);
13
1
C{ H} NMR (101 MHz, CDCl ) δ 197.7, 145.7, 139.8, 135.8, 128.92, 128.88, 128.2, 127.23,
3
1
27.18, 26.6.
1
d
Methyl [1,1'-biphenyl]-4-carboxylate (7d). The title compound was isolated by silica gel column
chromatography (eluent: Petroleum ether) as a white solid in 99% yield (104.9 mg) following the
1
general procedure 4; H NMR (400 MHz, CDCl
3
) δ 8.11 (d, J = 8.5 Hz, 2H), 7.67 (d, J = 8.5 Hz,
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H), 7.65ꢀ7.61 (m, 2H), 7.47 (t, J = 7.4 Hz, 2H), 7.40 (t, J = 7.3 Hz, 1H), 3.95 (s, 3H); C{ H}
NMR (101 MHz, CDCl ) δ 166.9, 145.6, 139.9, 130.0, 128.9, 128.8, 128.1, 127.2, 127.0, 52.1.
3
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Methyl 3',5'-dimethyl-[1,1'-biphenyl]-4-carboxylate (7e). The title compound was isolated by
silica gel column chromatography (eluent: Petroleum ether) as a white solid in 99% yield (119.8 mg)
1
following the general procedure 4; H NMR (400 MHz, CDCl
3
) δ 8.09 (d, J = 8.6 Hz, 2H), 7.65 (d,
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3
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J = 8.6 Hz, 2H), 7.25 (s, 2H), 7.05 (s, 1H), 3.94 (s, 3H), 2.40 (s, 6H); C{ H} NMR (101 MHz,
CDCl
3
) δ 167.0, 145.8, 139.9, 138.4, 129.9, 129.7, 128.6, 127.0, 125.1, 52.0, 21.3.
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Methyl 4-(naphthalen-1-yl)benzoate (7f). The title compound was isolated by silica gel column
chromatography (eluent: Petroleum ether) as a white solid in 96% yield (126.3 mg) following the
1
general procedure 4; H NMR (400 MHz, CDCl
3
) δ 8.17 (d, J = 8.4 Hz, 2H), 7.94ꢀ7.89 (m, 2H),
7.85 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.56ꢀ7.54 (m, 1H), 7.53ꢀ7.50 (m, 1H), 7.47ꢀ7.42
13
1
(m, 2H), 3.98 (s,3H); C{ H} NMR (101 MHz, CDCl
3
) δ 167.0, 145.6, 139.1, 133.7, 131.2, 130.1,
1
29.6, 129.0, 128.4, 128.2, 126.9, 126.3, 126.0, 125.6, 125.3, 52.2.
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Methyl 4-butylbenzoate (7g). The title compound was isolated by silica gel column
chromatography (eluent: Petroleum ether) as a white solid in 65% yield (62.4 mg) following the
1
general procedure 4; H NMR (400 MHz, CDCl ) δ 7.94 (d, J = 8.3 Hz, 2H), 7.24 (d, J = 8.4 Hz,
3
2
H), 3.90 (s, 3H), 2.66 (t, J = 7.7 Hz, 2H), 1.65ꢀ1.57 (m, 2H), 1.40ꢀ1.30 (m, 2H), 0.92 (t, J = 7.3
13
1
Hz, 3H); C{ H} NMR (101 MHz, CDCl
3
) δ 167.2, 148.5, 130.9, 129.6, 128.7, 128.4, 127.6, 51.9,
35.7, 33.24, 22.3, 13.9.
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2-Phenylpyridine (7h). The title compound was isolated by silica gel column chromatography
1
(eluent: Petroleum ether) as an oil in 89% yield (69 mg) following the general procedure 4; H
3
NMR (400 MHz, CDCl ) δ 8.71ꢀ8.69 (m, 1H), 8.01ꢀ8.00 (m, 1H), 7.99ꢀ7.96 (m, 1H), 7.75ꢀ7.72 (m,
13
1
2
1
H), 7.50ꢀ7.47 (m, 2H), 7.44ꢀ7.40 (m, 1H), 7.25ꢀ7.21 (m, 1H); C{ H} NMR (101 MHz, CDCl ) δ
3
57.4, 149.6, 139.3, 136.8, 128.9, 128.7, 126.9, 122.1, 120.6.
General Procedure 5: Buchwald–Hartwig CrossꢀCoupling Reactions using 4ai as Ligand
Scheme 5). A mixture of 4ai (14.6 mg, 0.0375 mmol, 7.5 mol %), Pd(OAc) (2.81 mg, 0.0125
(
2
mmol, 2.5 mol %), NaOtBu (67.3 mg, 0.7 mmol, 1.4 equiv) were weighted in a Schlenk tube
equipped with a stir bar. Dry toluene (0.5 mL), aryl chloride 5 (0.5 mmol, 1.0 equiv) and amine 8
(0.6 mmol, 1.2 equiv) was added and the resulting mixture was then put in a preꢀheated oil bath at
1
20 °C for 30 h under vigorous stirring. The reaction was cooled to room temperature and
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2 2
transferred to a 100 mL roundꢀbottomed flask using CH Cl . Silica was added to the flask and
volatiles were evaporated under reduced pressure. The purification was performed by flash column
chromatography on silica gel with petroleum ether/EtOAc.
1d
4
-(4-methoxyphenyl)morpholine (9a). The title compound was isolated by silica gel column
chromatography (eluent: Petroleum ether/EtOAc= 100/1) as a white solid in 84% yield (80.6 mg)
0
1
2
3
4
5
6
7
8
9
0
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8
9
0
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following the general procedure 5; H NMR (400 MHz, CDCl ) δ 6.87 (t, J = 10.3 Hz, 4H), 3.87 (t,
3
13
1
3
J = 4.5 Hz, 4H), 3.77 (s, 3H), 3.07 (s, J = 4.5 Hz, 4H); C{ H} NMR (101 MHz, CDCl ) δ 154.0,
1
45.4, 117.8, 114.4, 66.9, 55.5, 50.8.
1e
4
-(p-tolyl)morpholine (9b). The title compound was isolated by silica gel column chromatography
(eluent: Petroleum ether/EtOAc= 100/1) as a white solid in 83% yield (73.2 mg) following the
1
general procedure 5; H NMR (400 MHz, CDCl
3
) δ 7.11 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 8.2 Hz,
13
1
3
2H), 3.99ꢀ3.75 (m, 4H), 3.27ꢀ2.91 (m, 4H), 2.29 (s,3H); C{ H} NMR (101 MHz, CDCl ) δ 149.1,
1
29.7, 129.6, 116.0, 66.9, 49.9, 20.4.
-methoxy-N-methyl-N-phenylaniline (9c). The title compound was isolated by silica gel column
1d
4
chromatography (eluent: Petroleum ether/EtOAc= 100/1) as a tan solid in 90% yield (95.9 mg)
1
following the general procedure 5; H NMR (400 MHz, CDCl ) δ 7.25 (dd, J = 9.0, 7.1 Hz, 2H),
3
13
1
7
.16ꢀ7.14 (m, 2H), 6.95ꢀ6.93 (m, 2H), 6.86ꢀ6.84 (m, 3H), 3.86 (s, 3H), 3.31 (s, 3H); C{ H} NMR
(
101 MHz, CDCl ) δ 156.3), 149.6, 142.1, 128.9, 126.2, 118.4, 115.7, 114.7, 55.5, 40.5.
3
1
e
N-benzyl-2,5-dimethylaniline (9d). The title compound was isolated by silica gel column
chromatography (eluent: Petroleum ether/EtOAc= 100/1) as a colorless oil in 83% yield (87.1 mg)
1
following the general procedure 5; H NMR (400 MHz, CDCl
3
) δ 7.42ꢀ7.36(m, 4H), 7.33ꢀ7.29 (m,
1
H), 6.98(d, J =2.0, 1H), 6.55ꢀ6.50 (m, 2H), 4.38 (s, 2H), 3.93 (br, 1H), 2.29 (s, 3H), 2.14 (s, 3H);
1
3
1
C{ H} NMR (101 MHz, CDCl ) δ 145.9, 139.5, 136.8, 129.9, 128.6), 127.7, 127.2, 119.0, 117.9,
3
110.9, 48.4, 21.5, 17.1.
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ASSOCIATED CONTENT
AUTHOR INFORMATION
Corresponding Author
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nklibin@nankai.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This research was supported by the grants of the National Natural Science Foundation of China
(21372121, 21672108, and 21421062) and Natural Science Foundation of Tianjin
(16JCZDJC31700).
Supporting information
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Additional experimental data, analytical data, and H, C, P, and F NMR spectra for all new
compounds (PDF); and crystallographic data for compounds 3aa, 3ja, 3ka, 3ai, 3ak, and 4ai (CIF).
This material is available free of charge e on the ACS Publications website.
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