Iron-catalyzed cross coupling of P-H/C-O bonds: Efficient synthesis of α-alkoxyphosphorus compounds

Article abstract of DOI:10.1039/c5dt02454d

An efficient P-C bond-formation through iron-catalyzed cross coupling of P-H/C-O bonds is developed for the first time. This reaction proceeds efficiently to produce the corresponding valuable α-alkoxyphosphorus compounds under mild conditions with a wide generality.

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DOI: 10.1039/C5DT02454D
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ARTICLE TYPE
Iron-Catalyzed Cross Coupling of P-H/C-O Bonds: Efficient Synthesis
of α-Alkoxyphosphorus Compounds
Xue Li,a Tieqiao Chen,*a Yuta Sagab and Li-Biao Han*c
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
(Table 1, entry 2). The iron catalyst is important. In the absence
of iron catalyst, only a trace amount of product was detected
(entry 5). The reaction efficiency could be further improved.
An efficient P-C bonding-formation through iron-catalyzed
cross coupling of P-H/C-O bonds is developed for the first
time. This reaction proceeds efficiently to produce the
corresponding valuable α-alkoxyphosphorus compounds
o
45 When the reaction was performed at 65 C, the coupling product
3a was given in 90% yield (entry 6). Further elevating the
reaction temperature to 80 oC, 94% yield of 3a was afforded
under similar reaction conditions (entry 7). This transformation
also took place readily in dioxane (entry 8). Other selected
50 solvent such as DMF, DMSO, ethyl acetate and toluene also
served well (entries 9-12). When acetal 1a was allowed to react
10 under mildconditions with a wide generality.
α-Alkoxyphosphorus compounds are important intermediates
in organic synthesis.1 Some of these compounds are also
bioactive.2 Conventional procedures for their synthesis either use
the Arbuzov reactions of α-chloroethers with phosphites or via a
15 two-step reaction: addition of a P(O)H compound to an aldehyde
generating the corresponding α-hydroxy phosphoryl compound
first which then reacts with an alkyl iodide to give the
product.1a,3,4,5 The reaction of acetals with trialkylphosphite
(RO)3P can also produce such compounds; however an equivalent
20 amount of a strong Lewis acid such as BF3.Et2O was used.3,5
Herein, we report an iron-catalysed efficient coupling of
P(O)H compounds with acetals (Scheme 1).6 Thus, in the
presence of a catalytic amount of a simple FeCl3, P-H/C-O cross
couplings of P-H compounds with acetals proceed efficiently to
25 produce the corresponding α-alkoxyphosphoryl compounds in
high yields. This reaction formally belongs to the transition
metal-catalyzed cross coupling which is a powerful method for
the synthesis of organophosphorus compounds.7-9 These reactions
are usually mediated by palladium and nickel complexes;7 little is
30 known about iron catalysed C-P bond forming reactions.8
o
with equivalent diphenylphosphine oxide in dioxane at 80 C, 89%
yield of 3a was also provided (entry 13).
Table
1 Iron-catalyzed cross coupling of diethylphosphite with
55 (dimethoxymethyl)benzene.a
Scheme 1 Synthesis of α-alkoxyphosphorus compounds via iron-
a
catalyzed cross coupling of P-H/C-O bonds.
Reaction conditions: 0.24 mmol (dimethoxymethyl)benzene 1a, 0.2
mmol diphenylphosphine oxide 2a, 10 mol% catalyst and 0.2 mL solvent
b
We commenced our work with the investigation on the
were heated at the temperature indicated for 10 hours. GC yield using
tridecane as an internal standard. c 0.2 mmol 1a was used.
35 reactivity
of
(dimethoxymethyl)benzene
1a
and
diphenylphosphine oxide 2a, and the obtained results are
compiled in Table 1. After a screening on the metal catalysts such
as FeCl2, FeCl3, ZnCl2 and AlCl3, we found that FeCl3 could
serve as an efficient catalyst for this transformation (entries 1-4).
40 Thus, catalyzed by 10 mol% FeCl3, the reaction of 1a and 2a took
place smoothly in THF at 50 oC to produce 3a in 51% yield
60
This method is applicable to other substrates. As shown in
Table 2, a variety of acetals can react with P-H compounds under
similar reaction conditions to produce the corresponding α-
alkoxyphosphorus compounds efficiently. Thus, aromatic acetals
with electron-rich groups on benzene ring such as methyl,
65 methoxy and ester group readily coupled with diphenylphosphine
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DOI: 10.1039/C5DT02P45a4gDe 2 of 4
oxide to generate the expected products in high yields. This
the corresponding α-methoxyphosphorus compounds via
transformation showed high tolerance to the valuable halogen
transition metal catalyzed cross coupling. Substrate bearing nitro
group was also phosphorylated successfully to give 3h in 35%
15 yield under similar reaction conditions. Worth noting is that (E)-
(3,3-dimethoxyprop-1-en-1-yl)benzene served as the efficient
substrate to produce 3i in 82% yield. High yield of the
phosphorylated isochromane 3j was obtained from the cross
coupling reaction of 1-methoxyisochromane with 2a. Under
20 similar reaction conditions, heteroaromatic acetals like 3-
(dimethoxymethyl)furan underwent phosphorylation reaction
with diphenylphosphine oxide readily, generating the expected
product 3k in 78% yield. The aliphatic acetals 1,1-
Table 2 Synthesis of α-alkoxyphosphorus compounds via iron-catalyzed
P-H/C-O cross coupling.a
dimethoxyoctane
also coupled with 2a to furnish the
25 corresponding product in 51% yield. Other secondary phosphine
oxide like phenylbutylphosphine oxide and dibutylphosphine
oxide could also be converted to the expected products in the
current catalytic system, albeit therelatively low yields.
In addition to secondary phosphine oxide, H-phosphinate and
30 H-phosphonate also could be applied to this iron-catalyzed
transformation. Thus, by heating the reaction temperature to 120
oC, the cross coupling of H-phosphinate Ph(EtO)P(O)H with 1a
took place to produce the corresponding product 3o in 52% yield.
Both dibutylphosphite and diethylphosphite served as the
35 efficient substrates, reacting with 1a smoothly to afford 3p and
3q in 91% and 80% yields, respectively. Other selected acetals
bearing functional groups also readily coupled with
diethylphosphite
to
produce
the
corresponding
α-
alkoxyphosphorus compounds in moderate to high yields.
40
Interestingly, the highly coordinative secondary phosphine
could also be employed as the substrate in the present iron-
catalyzed P-H/C-O cross coupling. Thus, mediated by 10 mol%
FeCl3, the reaction of (dimethoxymethyl)benzene with
o
diphenylphosphine in dioxane at 80 C proceeded smoothly to
45 produce the corresponding α-methoxyphosphorus compounds 3y
in 91% yield.
A plausible reaction mechanism for this iron-catalyzed P-H/C-
O cross coupling was proposed as shown in Scheme 2.10 FeCl3 is
firstly coordinated to P-H compounds to give an iron complex
50 4,11 which undergoes deprotonation and leads to species 5. The
species 5 reacts with acetals via a plausible oxonium cation and
iron complex12 to produce the corresponding α-alkoxyphosphorus
compounds and regenerate thecatalyst FeCl3.
a
5
Reaction conditions for secondary phosphine oxide: 0.24 mmol acetals,
0.2 mmol P-H compounds, 10 mol% FeCl3 and 0.2 mL dioxane were
o
heated at 80 C for 10 hours; For other hydrogen phosphoryl compounds:
0.60 mmol acetals, 0.4 mmol P-H compounds, 10 mol% FeCl3 and 0.2
mL dioxane were heated at 120 oC for 10 hours. Isolated yield. b THF was
10 used as the solvent. c Isolatedas 3a.
55 Scheme 2 A plausible reaction mechanism for the iron-catalyzed P-H/C-
O cross coupling.
groups such as Cl, Br, I, facilitating further functionalization of
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Page 3 of 4
Dalton Transactions
Chem. Res., 2015, 48, 886; (e) R. Jana, T. P. Pathak and M. S.
Sigman, Chem. Rev., 2011,111, 1417.
In summary, we disclosed an efficient iron-catalyzed P-H/C-O
cross coupling for the construction of P-C bonds. This
transformation could proceed efficiently with a ligand-free and
environmentally benign iron catalytic system to produce the
corresponding α-alkoxyphosphorus compounds in high yields
from the easily available P-H compounds and acetals with a wide
generality.
70 9 There are few examples on iron catalyzed synthesis of or-
ganophosphorus compounds, see: (a) M. Kamitani, M. Itazaki, C.
Tamiya and H. Nakazawa, J. Am. Chem. Soc., 2012, 134, 11932; (b)
W. Han and A. R. Ofial, Chem. Commun., 2009, 6023; (c) W. Han,
P. Mayer andA. R. Ofial, Adv. Synth. Catal., 2010,352, 1667.
75 10 When 1 mol% CuCl2 was loaded instead as the catalyst for the cross
coupling of 1a and 2a, 15% yield of 3a was generated under similar
reaction conditions; however only a trace amount of 3a was
detectable when 1 mol% CuCl, 0.5 mol% Cu2O or 0.5 mol% CuCl2
was employed. These results clearly indicatethat it was iron, not the
5
Notes and references
a State Key Laboratory of Chemo/Biosensing andChemometrics, College
80
85
90
possible impuritycopper, catalyzedthereaction.
10 of Chemistry and Chemical Engineering,HunanUniversity, Changsha
410082, China. E-mail:chentieqiao@hnu.edu.cn;
11 P(O)H compounds exhibite good coordinating capbility toward
transition metals: (a) T. M. Shaikh, C.-M. Weng and F.-E Hong,
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b KatayamaChemical Industries Co.,Ltd.,26-22, 3-Chome,
Higasinaniwa-cho, Amagasaki,Hyogo660-0892, Japan;
c National Institute of AdvancedIndustrial ScienceandTechnology
15 (AIST), Tsukuba, Ibaraki 305-8565, Japan.E-mail: libiao-han@aist.go.jp
† Electronic Supplementary Information (ESI) available: [General
information, experimental procedures, characterized data and copies of 1H,
13C and31P NMR spectra forproducts]. See DOI: 10.1039/b000000x/
‡ Partial financial supports from NFSC (21403062, 21373080), HNNSF
20 2015JJ3039,the Fundamental Research Funds forthe Central Universities
(Hunan University)are gratefullyacknowledged.
12 I. Suzuki, M. Yasuda and A. Baba, Chem. Commun., 2013, 49,
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DOI: 10.1039/C5DT02454D
IronꢀCatalyzed Cross Coupling of PꢀH/CꢀO Bonds: Efficient
Synthesis of αꢀAlkoxyphosphorus Compounds
Xue Li, Tieqiao Chen, Yuta Saga, and Li-Biao Han
An efficient PꢀC bondingꢀformation through ironꢀcatalyzed cross coupling of PꢀH/CꢀO bonds is developed
for the first time. This reaction proceeds efficiently to produce the corresponding valuable αꢀ
alkoxyphosphorus compounds under mild conditions with a wide generality.