Iron-catalyzed clean dehydrogenative coupling of alcohols with P(O)-H compounds: A new protocol for ROH phosphorylation

Article abstract of DOI:10.1039/c6dt02236g

An efficient oxygen-phosphoryl bond-forming reaction via iron-catalyzed cross dehydrogenative coupling has been developed. This transformation proceeds efficiently under oxidant- and halide-free reaction conditions with H₂ liberation, and represents a straightforward method to prepare valuable organophosphoryl compounds from the readily available alcohols and P(O)-H compounds.

Full text of DOI:10.1039/c6dt02236g

View Article Online
View Journal
Dalton
Transactions
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: C. Li, T. Chen and
L. Han, Dalton Trans., 2016, DOI: 10.1039/C6DT02236G.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/dalton

Please do not adjust margins
Dalton Transactions
Page 1 of 6
View Article Online
DOI: 10.1039/C6DT02236G
Journal Name
COMMUNICATION
Iron-Catalyzed Clean Dehydrogenative Coupling of Alcohols with
P(O)-H Compounds: a New Protocol for ROH Phosphorylation
Chunya Li,a Tieqiao Chen,*a and Li-Biao Han*b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
An efficient oxygen-phosphoryl bond-forming reaction via iron- produced a large amount of undesired byproducts. And what
catalyzed cross dehydrogenative coupling has been developed. was even worse, these oxidants could severely damage the
This transformation proceeds efficiently under the oxidant- and starting P(O)-H chemicals.7 A CDC reaction for the generation
halide-free reaction conditions with H2 liberation, and represents of a Z-P(O) bond, without the aid of an additive is ideal.10
a straightforward method to prepare valuable organophosphoryl
Herein, we disclose such an ideal clean CDC reaction that, to
compounds from the readily available alcohols and P(O)-H com- our surprise, the cheap and harmless iron can efficiently
pounds.
Phosphorus-oxygen bond-containing compounds have
extensive application in medicinal chemistry, agrochemistry
and material Synthetically, such
chemistry.1,2
catalyze the cross dehydrogenative coupling of alcohols with
hydrogen phosphoryl compounds under the oxidant-free and
halide-free conditions with liberation of H2 (Scheme 1). This
clean reaction has a good tolerance to functional groups and is
an efficient straightforward procedure for the preparation of
phosphoryl compounds. More importantly, due to the close
relevancy of phosphorus compounds to biological activity (vide
supra), this reaction could be a rarely readily applicable
process for their preparation because of the non-toxic feature
of iron.11,12
organophosphorus compounds are commonly prepared via
the substitution reaction of a halophosphoryl compound P(O)X,
directly3 or indirectly,4,5 with an alcohol ROH (Scheme 1).
However, P(O)X compounds are toxic and moisture-sensitive.
O
O
this new method
O
A mixture of diphenylphosphine oxide 1a and 2-
H
R`
R`
+
X
R2P
imtermediate
H
R2P
Fe
cat
phenylethanol 2a was stirred in toluene in the presence of 10
mol% Fe(AcAc)2 and 1,10-phenanthroline (1,10-phen) at 130 oC
for 24 h. The coupling product 3a was generated in 84% yield
(Table 1, entry 1).13 An almost quantitative yield of 3a was
obtained by adding 10 mol% K2CO3 to the mixture under
similar conditions (Table 1, entry 2). The iron catalyst and
ligand were essential for this transformation. In the absence of
the iron catalyst or ligand, only a trace amount of product was
detected (Table 1, entries 3-6). FeCl2 and Fe(AcAc)3 was also
effective (Table 1, entries 7 and 8), however when FeCl3, FeBr3
and metallic iron were used as the catalysts, the cross
dehydrogenative coupling was sluggish (Table 1, entries 9-11).
Other metal catalysts like CuCl2, CuO and PdCl2 were not
effective for this reaction (Table 1, entries 12-15). These
results also indicated that the active catalyst in this
transformation was iron, not the possible impurity copper in
the iron complex. As to the ligands, other nitrogen ligands such
O
O
+
H
R2P R`
-
2
O
halogen-free
oxidant-free
R = alkyl, aryl
O
H
+
X
R2P
strating material
HO
R`
Scheme 1. Biological and synthetic generation of an O-P(O) bond via phosphorylation
of an OH bond.
Cross dehydrogenative coupling reaction (CDC reaction) is
an efficient method for the construction of chemical bonds.6-9
The formation of a few Z-phosphoryl (Z = a carbon and/or
heteroatom) bonds by such a strategy via CDC reaction of a
P(O)-H bond and Z-H bond catalyzed by Cu, Pd etc were
reported.7,8 However, all these reactions require the co-use of
more than one equivalents of additives (oxidants or proton
acceptors as the sacrificial reagents) which, therefore,
as
1,2-bypyridyl,
TMEDA
(N,N,N',N'-
tetramethylethylenediamine) and Et3N also served well to
produce 3a in good yields (Table 1, entries 16-18). In addition,
Li2CO3 was as reactive as K2CO3 and 97% yield of 3a was
obtained under similar reaction conditions (Table 1, entries 19-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 2 of 6
View Article Online
DOI: 10.1039/C6DT02236G
COMMUNICATION
Journal Name
21). This reaction also took place readily in cyclohexane and and 1.2 mmol 2-phenylethanol in the presence of 1 mol%
dioxane (Table 1, entries 23 and 24). However, in DMF, the Fe(AcAc)2/1,10-phenanthroline and 10 mol% K2CO3 was heated
yield of the coupling product decreased (Table 1, entry 22). at 130 oC for 24 h.14 After removal of the volatiles under
o
The reaction also took place at 110 C, though the yield of 3a
Table 2. Iron-catalyzed cross dehydrogenative coupling of alcohols with
P(O)-H compounds.a
decreased (Table 1, entry 25).
Table 1. Fe-catalyzed cross dehydrogenative coupling of 2-phenylethanol
with diphenylphosphine oxide.a
aReaction conditions: 1a (0.24 mmol), 2a (0.2 mmol), 10 mol% M catalyst,
ligand (M/N = 1:2), 10 mol% base, toluene (1 mL), heated at 130 oC in a
c
sealed 25 mL glass tube, under nitrogen, 24 h. b Isolated yield. 10 equivs
alcohols were added. d 110 oC.
aReaction conditions: alcohol (0.24 mmol), P(O)-H compounds (0.2 mmol),
10 mol% Fe(AcAc)2, 10 mol% 1,10-phenanthroline, 10 mol% K2CO3,
toluene (1 mL), heated at 130 oC in a sealed 25 mL glass tube, under
nitrogen, 24 h. bIsolated yield. c10 equivs alcohols were added. d140 oC.
Scheme 2. Reaction of diphenyl phosphine oxide with 2-phenylethanol at 1 mmol scale
reduced pressure, the crude residues were passed through a
with 1 mol% iron catalyst.
SiO2 column by using ethyl acetate/ petroleum ether as the
eluent, the analytically pure product 3a was afforded in 92%
Interestingly, this reaction could proceed smoothly with a
lower loading of iron catalyst at 1 mmol scale. As shown in
Scheme 2, the mixture of 1 mmol diphenylphosphine oxide
isolated yield.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 3 of 6
View Article Online
DOI: 10.1039/C6DT02236G
Journal Name
COMMUNICATION
This CDC reaction is readily applicable to other substrates. As
To gain some information on the reaction, several control
shown in Table 2, a variety of alcohols efficiently coupled with experiments were performed. By addition of 2 equiv radical
P(O)-H compounds under similar reaction conditions to produce scavenger BHT (dibutylhydroxytoluene), the reaction of 1a
the corresponding phosphoryl compounds 3 in good to high and 2a proceeded smoothly under the standard reaction
yields. 2-Arylethanols with both electron-donating and electron- conditions to give the coupling product 3a in almost
withdrawing groups on the benzene rings were successfully quantitative yield. By using 10 mol% AIBN instead of iron
phosphorylated (Table 2, entries 1-8). Thus, substrates with catalyst, the reaction progressed sluggishly. These results
methyl, methoxyl and amino groups gave the corresponding indicated that this reaction would not be a radical process.
products in high yields (entries 2-4). Halogen atoms of F, Cl When Ph2P(O)D was allowed to react with 1a under the
and Br were tolerable under the present reaction standard reaction conditions,16 3a with no deuterium
1
conditions, producing the expected coupling products incorporation as indicated from H NMR spectroscopy was
which are further manipulable via transition metal- given in a quantitative yield, indicating that no protons in
catalyzed cross couplings (entries 5-7).15
A substrate products 3 were originated from P(O)-H compounds.
bearing an electron-withdrawing group CF3 was also Although the mechanism for this novel iron-catalyzed cross
phosphorylated and the coupling product 3h was generated dehydrogenative coupling was not clear,17 a reaction path
in 96% yield (entry 8). A heteroatom-containing alcohol, 2- involving P(O)-H bond activation by Fe complex to give Fe-H
(thiophen-2-yl)ethanol, also coupled readily with species,18,19 P(O)FeOR intermediate and dihydrogen
diphenylphosphine oxide 2a to produce the phosphoryl generation by ligand exchange of Fe-H species with alcohol
compound 3i in a high yield (entry 9). Simple primary ROH, and subsequent reductive elimination of the resulting
alcohols such as methanol, ethanol, butanol and ally alcohol P(O)FeOR intermediate perhaps applied to this reaction.
also worked well in the current iron-catalyzed system to
Conclusion
yield the corresponding coupling products in good yields
(entries 10-13). Secondary alcohols such as isopropyl
alcohol and cyclohexanol were also suitable substrates and
coupled smoothly with diphenylphosphine oxide 2a under
similar reaction conditions (entries 14 and 15). However,
tert-butyl alcohol did work under the reaction conditions,
which perhaps was due to the high steric hindrance of tert-
butyl alcohol.
In summary, we have disclosed the first iron-catalyzed
CDC reaction of alcohols with P(O)-H compounds which
produces high yields of phosphoryl compounds. This
transformation features simplicity and efficiency with a
cheap and non-toxic Fe catalyst for the construction of
oxygen-phosphoryl bonds since it is an oxidant- and
halogen-free process. This appears to be a rather general
phosphorylation method and a variety of alcohols and
hydrogen phosphoryl compounds can be employed as the
substrates in this coupling reaction.
As shown in Table 2, high yields of
3 could be obtained
from both electron-rich and electron-deficient benzylic
alcohols (entries 16-21). Thus, the derivatives of benzylic
alcohols with methyl group at 2-, 3- and 4-position on
benzene ring gave the corresponding products in good
yields (entries 17-19). (4-Chlorophenyl)methanol was
readily phosphorylated under the reaction conditions (entry
20). The substrate with an electron-withdrawing CN group
also gave the coupling product 3u in a good yield (entry 21).
As to the hydrogen phosphoryl compounds, both aromatic
and aliphatic secondary phosphine oxides served well as the
substrates and were converted to the corresponding
products in high yields (entries 22-24).
We gratefully acknowledge financial support from NSFC (No.s
21403062, 21573064, 21373080), HNNSF 2015JJ3039 and
Fundamental Research Funds for the Central Universities (Hunan
University).
Notes and references
1
(a) D. E. C. Corbridge, Phosphorus: Chemistry, Biochemistry
and Technology, Sixth Edition, CRC Press, New York, 2013; (b)
J. P. Majoral, New Aspects in Phosphorus Chemistry,
Springer, Berlin, Vol.s 1-5.
The synthetic value of this new reaction was further
demonstrated by the successful phosphorylation of (-
)menthol and borneol (Table 2, entries 25-27). Thus, under
similar iron-catalyzed CDC reaction conditions, both (-
)menthol and borneol were phosphorylated with
diphenylphosphine oxide to produce the corresponding
phosphoryl compounds 3y and 3z in 65% and 80% yields,
respectively (Table 2, entries 25 and 26). Under the reaction
conditions, the borneol also coupled with a five-membered
H-phosphonate 4,4,5,5-tetramethyl-1,3,2-dioxaphospholan-
e 2-oxide, giving the expected product 3aa in 37% yield
(Table 2, entry 27). These results clearly showed the
potential of this CDC reaction with the current non-toxic
iron catalyst.
2
(a) L. D. A. Quin, A Guide to Organophosphorus Chemistry,
Wiley Interscience, New York, 2000; (b) P. J. Murphy,
Organophosphorus Reagents, Oxford University Press:
Oxford, U.K., 2004; (c) F. E. Khasawneh, E. C. Sample and E. J.
Kamprath, The Role of Phosphorus in Agriculture, American
Society of Agronomy, Crop Science Society of America, Soil
Science Society of America, Madison, WI, 1980; (d) A. Paytan
and K. McLaughlin, Chem. Rev., 2007, 107, 563; (e) W. Tang
and X. Zhang, Chem. Rev., 2003, 103, 3029; (f) C. Queffélec,
M. Petit, P. Janvier, D. A. Knight and B. Bujoli, Chem. Rev.,
2012, 112, 3777; (g) T. Steinbach and F. R. Wurm, Angew.
Chem. Int. Ed., 2015, 54, 6098; (h) A. Bogomilova, M. Hohn,
M. Gunther, K. Troev, E. Wagner and L. Schreiner, Eur. J.
Pharm. Sci., 2013, 50, 410; (i) M. F. Rectenwald, J. R. Gaffen,
A. L. Rheingold, A. B. Morgan and J. D. Protasiewicz, Angew.
Chem. Int. Ed., 2014, 53, 4173.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 4 of 6
View Article Online
DOI: 10.1039/C6DT02236G
COMMUNICATION
Journal Name
3
(a) R. Engel, Handbook of Organophosphorus Chemistry, 10 CDC reactions with H2 evolution using three valent
Marcel Dekker, New York, 1998; (b) Y. Li, S. D. Aubert, E. G.
Maes and F. M. Raushel, J. Am. Chem. Soc., 2004, 126, 8888;
(c) W. P. Malachowski and J. K. Coward, J. Org. Chem., 1994,
59, 7625; (d) D. L. J. Clive and S. Kang, J. Org. Chem., 2001,
66, 6083; (e) M. Oliana, F. King, P. N. Horton, M. B.
Hursthouse and K. K. Hii, J. Org. Chem., 2006, 71, 2472.
Atherton-Todd-type reaction: (a) F. R. Atherton and A. R.
Todd, J. Chem. Soc., 1947, 674; (b) S. S. L. Corre, M. Berchel,
H. Couthon-Courvés, J.-P. Haelters and P.-A. Jaffrés, Bellstein
J. Org. Chem., 2014, 10, 1166; (c) Y. Zhou, G. Wang, Y. Saga,
R. Shen, M. Goto, Y. Zhao and L.-B. Han, J. Org. Chem., 2010,
75, 7924; (d) S. Cao, Y. Guo, J. Wang, L. Qi, P. Gao, H. Zhao
and Y. Zhao, Tetrahedron Lett., 2012, 53, 6302; (e) R. A.
Ashmus and T. L. Lowary, Org. Lett., 2014, 16, 2518; (f) E. M.
Georgiev, J. Kaneti, K. Troev and D. M. Roundhill, J. Am.
Chem. Soc., 1993, 115, 10964; (g) S. Li, T. Chen, Y. Saga and
phosphines RPH2 and R2PH were known: (a) M. C. Fermin
and D. W. Stephan, J. Am. Chem. Soc., 1995, 117, 12645; (b)
S. Xin, H.-G. Woo, J. F. Harrod, E. Samuel and A.-M. Lebuis, J.
Am. Chem. Soc., 1997, 119, 5307; (c) D. W. Stephan, Angew.
Chem. Int. Ed., 2000, 39, 314; (d) V. P. W. Bohm and M.
Brookhart, Angew. Chem. Int. Ed., 2001, 40, 4694; (e) R. Shu,
L. Hao, J. F. Harrod, H.-G. Woo and E. Samuel, J. Am. Chem.
Soc., 1998, 120, 12988; (f) A. R. McWilliams and H. Dorn, I.
Manners, Top. Curr. Chem., 2002, 120, 141; (g) H. Dorn, R. A.
Singh, J. A. Massey, J. M. Nelson, C. A. Jaska, A. J. Lough and
I. Manners, J. Am. Chem. Soc., 2000, 122, 6669; (h) A. J.
Roering, S. N. MacMillan, J. M. Tanski and R. Waterman,
Inorg. Chem., 2007, 46, 6855; (i) H. Dorn, R. A. Singh, J. A.
Massey, A. J. Lough and I. Manners, Angew. Chem. Int. Ed.,
1999, 38, 3321; (j) L.-B. Han and T. D. Tilley, J. Am. Chem.
Soc., 2006, 128, 13698.
4
L.-B. Han, RSC Adv., 2015,
Other methods via P(O)X intermediates, see (a) Y. Okamoto,
T. Kusano and S. Takamuku, Bull. Chem. Soc. Jpn., 1988, 61
3359; (b) M. Y. Berezkin, V. V. Turyginz, A. V. Khudenko, S. A.
Zhestkov, N. E. Kuz’mina, A. P. Tomilov and E. A. Fokin, Russ.
J. Electrochem., 2011, 47, 1272; (c) N. Liu, L.-L. Mao, B. Yang
and S.-D. Yang, Chem. Commun., 2014, 50, 10879.
5
, 71544.
11 For review and book on iron catalysis, see: (a) B. Plietker,
Iron Catalysis in Organic Chemistry, Wiley-VCH, Weinheim,
5
6
,
2008; (b) I. Bauer and H.-J. Knölker, Chem. Rev., 2015, 115
3170; (c) W. M. Czaolik, M. Mayer, J. Cvengroš and A. J. v.
Wangelin, ChemSusChem, 2009, , 396; (d) S. Enthaler, K.
,
2
Junge and M. Beller, Angew. Chem. Int. Ed., 2008, 47, 3317.
12 For book on iron-catalyzed cross dehydrogenative coupling
reaction, see: (a) M. Itazaki and H. Nakazawa, Top
Organomet. Chem., 2015, 50, 47; For selected examples on
iron-catalyzed CDC reactions forming a bond between main
group elements, see: (b) K. Fukumoto, M. Kasa, T. Oya, M.
Itazaki and H. Nakazawa, Organometallics, 2011, 30, 3461;
For review, see (a) C.-J. Li, Acc. Chem. Res., 2009, 42, 335; (b)
S. A. Girard, T. Knauber and C.-J. Li, Angew. Chem. Int. Ed.,
2014, 53, 74; (c) R. Waterman, Chem. Soc. Rev., 2013, 42
5629; (d) C. S. Yeung and V. M. Dong, Chem. Rev., 2011, 111
,
,
1215; (e) C.-J. Li, From C-H to C-C bonds: Cross-
Dehydrogenative-Coupling, Royal Society of Chemistry, 2014.
For review on CDC reaction involving P(O)-H compounds,
(c) A. K. L. Teo and W. Y. Fan, Chem. Commun., 2014, 50
,
7
8
7191; (d) S. Chang, E. Scharre and M. Brookhart, J. Mol.
Catal. A, 1998, 130, 107; (e) S. Rommel, L. Hettmanczyk, J. E.
M. N. Klein and B. Pleitker, Chem. Asian J., 2014, 9, 2140.
see: T. Chen, J.-S. Zhang, L.-B. Han, Dalton. Trans., 2016, 45
1843.
,
Selected examples on CDC reaction involving P(O)-H 13 The generation of dihydrogen was confirmed by GC, see SI.
compounds, see (a) C.-G. Feng, M. Ye, K.-J. Xiao, S. Li and J.- 14 This reaction was performed in a 25 mL glass tube. During
Q. Yu, J. Am. Chem. Soc., 2013, 135, 9322; (b) Y. Gao, G.
Wang, L. Chen, P. Xu, Y. Zhao, Y. Zhou and L.-B. Han, J. Am.
Chem. Soc., 2009, 131, 7956; (c) J. Yang, T. Chen, Y. Zhou, S.
Yin and L.-B. Han, Chem. Commun., 2015, 51, 3549; (d) T.
Wang, S. Chen, A. Shao, M. Gao, Y. Huang and A. Lei, Org.
Lett., 2015, 17, 118; (e) C. Li, T. Yano, N. Ishida and M.
the reaction, dihydrogen was removed twice at 6 h and 12 h
respectively. Otherwise, the yield was 64%. The results
indicated that the dihydrogen pressure would be a factor for
this reaction. When the reaction was conducted at 0.2 mmol
scale with 5 mol% iron catalyst, a quantitative yield was also
afforded.
Murakami, Angew. Chem. Int. Ed., 2013, 52, 9801; (f) J. 15 (a) C. C. C. J. Seechurn, M. O. Kitching, T. J. Colacot and V.
Fraser, L. J. Wilson, R. Blundell and C. J. Hayes, Chem.
Commun., 2013, 49 8919; (g) O. Berger and J.-L.
Montchamp, Chem. Eur. J., 2014, 20, 12385; (h) J. Yang, T.
Snieckus, Angew. Chem. Int. Ed., 2012, 51, 5062; (b) A. H.
Cherney, N. T. Kadunce and S. E. Reisman, Chem. Rev., 2015,
115, 9587.
,
Chen, Y. Zhou, S. Yin and L.-B. Han, Organometallics, 2015, 16 Ph2P(O)D (ca. 90% deuterium incorporation) was prepared
34 5095. All of these reactions are oxidative from the reaction of Ph2P(O)H with CD3OD, see W. Kong, E.
,
dehydrocouplings.
CDC reactions with H2 evolution for C-Z bonds formation. For
a highlight, see (a) K.-H. He and Y. Li, ChemSusChem, 2014,
2788; For examples, see (b) G. Zhang, C. Liu, H. Yi, Q. Meng,
C. Bian, H. Chen, J.-X. Jian, L.-Z. Wu and A. Lei, J. Am. Chem.
Soc., 2015, 137, 9273; (c) T. Mitkina, C. Stanglmair, W.
Setzer, M. Gruber, H. Kisch and B. König, Org. Biomol. Chem.,
2012, 10, 3556; (d) N. Zeug, J. Buecheler and H. Kisch, J. Am.
Chem. Soc., 1985, 107, 1459; (e) Q.-Y. Meng, J.-J. Zhong, Q.
Liu, X.-W. Gao, H.-H. Zhang, T. Lei, Z.-J. Li, K. Feng, B. Chen,
C.-H. Tung and L.-Z. Wu, J. Am. Chem. Soc., 2013, 135, 19052;
(f) J.-J. Zhong, Q.-Y. Meng, B. Liu, X.-B. Li, X.-W. Gao, T. Lei,
C.-J. Wu, Z.-J. Li, C.-H. Tung and L.-Z. Wu, Org. Lett., 2014, 16
1988; (g) X.-W. Gao, Q.-Y. Meng, J.-X. Li, J.-J. Zhong, T. Lei, X.-
B. Li, C.-H. Tung and L.-Z. Wu, ACS Catal., 2015, , 2391; (h)
A.-X. Zhou, L.-L. Mao, G.-W. Wang and S.-D. Yang, Chem.
Commun. 2014, 50, 8529; (i) R. He, Z.-T. Huang, Q.-Y. Zheng
and C. Wang, Angew. Chem. Int. Ed., 2014, 53, 4950; (j) X.-B.
Li, Z.-J. Li, Y.-J. Gao, Q.-Y. Meng, S. Yu, R. G. Weiss, C.-H. Tung
and L.-Z. Wu, Angew. Chem. Int. Ed., 2014, 53, 2085.
Merino and C. Nevado, Angew. Chem. Int. Ed., 2014, 53,
5078.
9
7
,
17 In the presence of 10 mol% K2CO3, benzaldehyde can couple
with diphenylphosphine oxide to produce 3p in 81% yield by
o
stirring the mixture at 130 C in toluene for 24 h. Under the
reaction conditions, the α-hydroxyl phosphoryl compound
(hydroxy(phenyl)methyl)diphenylphosphine oxide could
undergo isomerization to yield 3p in 63% yield. Considering
that iron complex could mediate dehydrogenation of
secondary alcohols under similar reaction conditions, a
reaction path via dehydrogenation of alcohol to aldehyde,
addition of P(O)-H compounds to aldehyde and subsequent
isomerization was initially considered. However, later it was
found that in the presence of even 1 mol% iron catalyst, the
reaction of benzaldehyde with diphenylphosphine oxide was
sluggish at 130 oC in toluene for 24 h and only a trace
amount of 3p was generated. Therefore, the above
mechanism perhaps did not apply to this reaction. The
deuteration experiment described in the text also did not
support the mechanism. For iron-catalyzed dehydrogenation
of secondary alcohols, see: (a) E. Alberico, P. Sponholz, C.
,
5
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 5 of 6
View Article Online
DOI: 10.1039/C6DT02236G
Journal Name
COMMUNICATION
Cordes, M. Nielsen, H.-J. Drexler, W. Baumann, H. Junge and
M. Beller, Angew. Chem. Int. Ed. 2013, 52, 14162; (b) H. Song,
B. Kang and S. H. Hong, ACS Catal. 2014, 4, 2889.
18 The activation of P(O)-H bond by other transition metal
complexes is well documented. For selected examples, see:
a) L.-B. Han, C. Zhang, H. Yazawa and S. Shimada, J. Am.
Chem. Soc., 2004, 126, 5080; b) L.-B. Han, C.-Q. Zhao, S.
Onozawa, M. Goto and M. Tanaka, J. Am. Chem. Soc., 2002,
124, 3842; c) L.-B. Han, N. Choi and M. Tanaka,
Organometallics, 1996, 15, 3259; d) L.-B. Han and M. Tanaka,
J. Am. Chem. Soc., 1996, 118, 1571; e) C.-Q. Zhao, L.-B. Han,
M. Goto and M. Tanaka, Angew. Chem. Int. Ed., 2001, 40
1929.
,
19 Fe-catalyzed reactions with hydrosilanes were proposed to
proceed via oxidative addition of a Si-H bond to Fe. See Ref.s
12b-12e.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Dalton Transactions
Page 6 of 6
View Article Online
DOI: 10.1039/C6DT02236G
Iron-Catalyzed Clean Dehydrogenative Coupling of Alcohols with P(O)-H
Compounds: a New Protocol for ROH Phosphorylation
Chunya Li, Tieqiao Chen and Li-Biao Han
An efficient oxygen-phosphoryl bond-forming reaction via iron-catalyzed cross
dehydrogenative coupling has been developed. This transformation proceeds efficiently under
the oxidant- and halide-free reaction conditions with H2 liberation, and represents a
straightforward method to prepare valuable organophosphoryl compounds from the readily
available alcohols and P(O)-H compounds.