Manganese-Mediated Intermolecular Arylation of H-Phosphinates and Related Compounds

Article abstract of DOI:10.1002/chem.201404507

The intermolecular radical functionalization of arenes with aryl and alkyl H-phosphinate esters, as well as diphenylphosphine oxide and H-phosphonate diesters, is described. The novel catalytic Mn^II/excess Mn^IVsystem is a convenient

Full text of DOI:10.1002/chem.201404507

DOI: 10.1002/chem.201404507
Communication
&
Radical Arylation
Manganese-Mediated Intermolecular Arylation of H-Phosphinates
and Related Compounds
Olivier Berger and Jean-Luc Montchamp*[a]
89%). The novel catalytic Mn(OAc)2/excess MnO2 system was
Abstract: The intermolecular radical functionalization of
also proposed as an alternative to the traditional excess
arenes with aryl and alkyl H-phosphinate esters, as well as
Mn(OAc)3 reagent.[13]
diphenylphosphine oxide and H-phosphonate diesters, is
Herein, we are reporting a process for the intermolecular ar-
described. The novel catalytic MnII/excess MnIV system is
ylation of various P(O)H-containing compounds using our
a convenient and inexpensive solution to directly convert
Mn(OAc)2/MnO2 system. We started by studying the arylation
Csp2ÀH into CÀP bonds. The reaction can be employed to
of PhP(O)(OBu)H with benzene (5 equiv) under various condi-
functionalize P-stereogenic H-phosphinates since it is ste-
tions. While aryl-H-phosphinate esters are generally more reac-
reospecific. With monosubstituted aromatics, the selectivi-
tive than alkyl-H-phosphinates, the compounds are also more
ty for para-substitution increases in the order
prone to oxidation.[14] With 3 equivalents of Mn(OAc)3, the iso-
(RO)2P(O)H<R1P(O)(OR)H<Ph2P(O)H, a trend that may be
lated yield of Ph2P(O)(OBu) was 40%. Table 1 summarizes the
explained by steric effects.
results of the optimization using Mn(OAc)2/MnO2.
Acetic acid was used throughout since other solvents such
as DMSO, DMF, tert-amyl alcohol (tAmOH), and CH3CN were
Functionalizing aromatic CÀH bonds directly into CÀP bonds
completely unsatisfactory (no product). Also, higher tempera-
has become the focus of much research in recent years. Two
major strategies exist: 1) metal-catalyzed CÀH activation, and
2) radical arylation. Both methods have been used with H-
ture and/or conducting the reaction in air gave significantly
poorer results even in acetic acid.
Using 2 equivalents of MnO2 as the oxidant (Table 1, entry 1)
gave a modest yield of product. Increasing the amount further
gave a significant improvement (entry 2). The role of added
base was then investigated (entries 3–6) showing that AcONa
gave the best result, even though the improvement is small
(entry 6 versus entry 2). Because the H-phosphinate can be oxi-
phosphonate
diesters
to
prepare
arylphosphonates
(Scheme 1). Yu[1] and Murakami[2] recently reported a similar re-
action using palladium and silver acetate (Eq. (1) in Scheme 1).
Diarylphosphine oxides also reacted successfully.[1] Using the
Pd/K2S2O8 system, Li reported the Pd-catalyzed phosphoryla-
tion of thiazoles and oxazoles,[3] and Huang that of coumar-
ins.[4] On the other hand, Effenberger pioneered the radical
arene phosphorylation catalyzed or mediated by silver (Eq. (2)
in Scheme 1).[5] Related reactions were then reported by
others.[6–8] Finally, Mn(OAc)3 has been used successfully (Eq. (3)
in Scheme 1).[9–11] It should be noted that Ishii reported a cata-
lytic version ((EtO)2P(O)H (3 equiv), Mn(OAc)2 (5 mol%),
Co(OAc)2 (5 mol%), O2 (0.5 atm)) although the usefulness of
this reaction has not been demonstrated.[12]
Recently, we reported a study of the manganese-catalyzed
and mediated radical reactions of H-phosphinates.[13] Whereas
the intermolecular arylation reaction was poor (OctP(O)-
(OCy)H+benzene (10 equiv)+Mn(OAc)3·2H2O (2 equiv), AcONa
(2 equiv), AcOH reflux, 37% yield), excellent results were ob-
tained for intramolecular cyclizations with H-phosphinate, H-
phosphonate, and secondary phosphine oxide precursors (49–
[a] Dr. O. Berger, Prof. J.-L. Montchamp
Department of Chemistry, Box 298860
Texas Christian University
Fort Worth, Texas 76133 (USA)
Fax: (+1)817-257-5851
E-mail: j.montchamp@tcu.edu
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201404507.
Scheme 1. Literature methods for arene phosphorylation.
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Table 1. Optimization of the reaction conditions.[a]
Entry
R
MnO2 [equiv]
Base (3 equiv)
Time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Et
iBu
Cy
Bu
Bu
Bu
2
3
3
3
3
3
3
3
3
3
3
3
3
-
-
16
16
16
16
16
16
2+2[c]
2+2[c]
2+2[c]
2+2[c]
2+2[c]
2+2[c]
2+2[c]
2+2[c]
2+2[c]
2+2[c]
34
47
5
41
44
52
64
53[d]
40[e]
52[f]
43
56
60
29-32
36
22
K3PO4
Al2O3
K2CO3
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
9
10
11
12
13
14
15
16
[g]
–
–
[h]
[i]
–
[a] PhP(O)(OR)H (1 mmol), benzene (5 mmol), AcOH (5 mL). Commercial
activated MnO2 was used. For additional details, see the Supporting Infor-
mation [b] All yields are isolated. [c] PhP(O)(OBu)H was added slowly over
2 h, and the reaction continued for another 2 h. [d] Mn(OAc)2·4H2O was
used instead of anhydrous Mn(OAc)2. [e] Mn(OAc)2 was omitted.
[f] 5 mol% MnCO3 was used instead of Mn(OAc)2. [g] KMnO4 (0.5–
1.5 equiv) was used instead of MnO2. [h] Mn(OAc)2 (3 equiv) was used in-
stead of MnO2. [i] BaMnO4 (1.5 equiv) was used instead of MnO2.
dized directly to the phosphonic acid monoester, a slow-addi-
tion protocol was then implemented (entry 7), which resulted
in a significant improvement in yield (64%). Using Mn(OAc)2
tetrahydrate as catalyst decreased the yield by 10% (entry 8),
while omitting MnII altogether gave a significant drop (entry 9
versus entry 7). Replacing Mn(OAc)2 with MnCO3 was less satis-
factory (entry 10). Then the role of the ester group was investi-
gated (entries 11–13). The more hydrolytically resistant esters
gave better results, although nBu was still best. This is perhaps
due to a trade-off between steric hindrance and electronic ef-
fects. Finally, replacing excess MnO2 with other oxidants
(KMnO4, BaMnO4, and Mn(OAc)2) was investigated but unsatis-
factory (entries 14–16).
Scheme 2. Scope of the arene phosphorylation. [a] 2 equiv MesH was used.
[b] 1 equiv MesH was used.
Once the optimal conditions were identified (Table 1,
entry 7), the scope of the reaction could be investigated.
Scheme 2 shows the results for a combination of H-phosphi-
nates and arenes. Phenyl-H-phosphinate esters were successful
with isolated yields ranging from moderate to excellent. Inter-
estingly, the arylation of mesitylene gave 3k in excellent yield
(81%). Furthermore, although reducing the amount of mesity-
lene reduced the yield slightly, the same product could be ob-
tained in 72 or 70% yield using only 2 or 1 equiv of MesH, re-
spectively. We previously synthesized a related compound
through Pd-catalyzed cross-coupling of MesI in 61% yield.[15]
Unlike in the phosphorylation of arenes under various condi-
tions, H-phosphinates appear to be more selective for para-
substitution.[5–11]
Uracil, flavone, and coumarin were successfully functional-
ized (3p–r) but a thiazole gave a mixture of regioisomers 3o.
P-Stereogenic PhP(O)(OMen)H reacted with MesH with excel-
lent stereoselectivity but moderate yield of 3t probably due to
steric hindrance. The crude mixture already contains 3t in the
same diastereoisomeric ratio and most of the mass balance
must be oxidized starting material since arylation is slow.[13] Im-
portantly, other H-phosphinates including unactivated alkyl de-
rivatives reacted successfully (3v–z). In the case of 3z the reac-
tion was again stereospecific and the yield higher than with
PhP(O)(OMen)H, again pointing to steric effects. The fact that
the reaction was developed to use only 1 equivalent of P(O)H
reagent is important, especially when considering the asym-
metric synthesis of P-stereogenic compounds. Unlike literature
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Scheme 3. Scope of the arylation with Ph2P(O)H and (RO)2P(O)H. [a] 1 equiv
ArH was used.
Scheme 4. Arylation to exploit a mixture of HOCH2P(O)(OMen)H 6, or en-
riched diastereoisomer 10.
reactions with H-phosphonate diesters, the reaction appears
more selective for substitution at the para-position with mono-
substituted aromatics (3e, 3 f, 3h, 3j, 3x). Regardless, our MnII/
MnIV system appears to be a convenient method to phosphor-
ylate arenes. However, electron-poor nitrobenzene was com-
pletely unreactive. It should be noted that, in our hands, other
reagent systems reported in the literature for the arylation of
H-phosphonate diesters (and some of their variations) were un-
satisfactory when applied to PhP(O)(OBu)H: for example, with
MesH AgNO3/K2S2O8 gave only a trace amount of product.
However, AgNO3/MnO2 gave a 78% yield of PhP(O)(OBu)Mes
instead of 81% with our cheaper method.
mother liquor was achieved through our Pd-catalyzed cross-
coupling.[15] Based on the present methodology, the direct ary-
lation with benzene was investigated (Scheme 4).
The arylation of HOCH2P(O)(OMen)H 6 failed, perhaps be-
cause of deformylation (oxidative cleavage of the CH2OH
moiety by MnO2). Acetylation gave intermediate 7 in quantita-
tive yield. The arylation of acetate 7 was conducted on a multi-
gram scale using a simple addition funnel to add the H-phos-
phinate to the benzene/Mn(OAc)2/MnO2 mixture (Scheme 4).
Arylation took place without kinetic resolution to produce
phosphinate 8 in 78% yield. Deprotection and crystallization at
room temperature then gave the highly enriched diastereoiso-
mer 9.[18] Diasteroisomer 10[18] was similarly arylated stereospe-
cifically to afford known 11,[18] thereby establishing the abso-
lute configuration of the phosphorus atom and overall reten-
tion for the reaction. The higher yield (78%) observed for 8 in-
stead of 48% for 11 is attributed to the larger scale in the
preparation of 8. As with cross-coupling, the method is stereo-
complementary since 9 and 11 only differ in their absolute
configuration at phosphorus. However, the entire process
using the present methodology is ten times cheaper than the
one using Pd-catalyzed cross-coupling.[16,18]
Next, we examined other P(O)-compounds since diarylphos-
phine oxides have seldom been employed,[1] and the literature
with H-phosphonate diesters involves significantly more ex-
pensive conditions.[16] Our results are shown on Scheme 3.
With Ar2P(O)H, Yu’s yields ranged from 39 to 48% (46% with
Ph2P(O)H).[1] Our method gave yields that are comparable or
much higher but with regular arenes (5a–e). Selectivity for the
para position is higher with Ph2P(O)H (compare 5a to 3 f and
5g). This is likely a steric effect, as Ph2P(O)H did not react with
mesitylene. In Yu’s work, both (PhO)2P(O)H and (BnO)2P(O)H
were unsatisfactory (trace amount),[1] whereas our method is
successful with both substrates, even though our reaction with
(PhO)2P(O)H only gives moderate yields (5 f, 5g). Presumably
this is due to the much faster oxidation of (PhO)2P(O)H.[17] Ex-
cellent results are seen for compounds 5h and 5i. Compound
5h was made by Effenberger in 64% yield.[5] Again, reducing
the amount of ArH to just one equivalent resulted in a 10–
15% lower yield, but this result is still very satisfactory consid-
ering the equimolar stoichiometry (5b, 5i).
In conclusion, we have developed a general intermolecular
CÀH to CÀP transformation based on the novel catalytic MnII/
excess MnIV system. Not only is the reaction simpler and
cheaper than any of the related literature methods, but the ar-
ylation of H-phosphinates is disclosed for the first time. Fur-
thermore, the reactions of Ph2P(O)H and (RO)2P(O)H are also
described. We surmise that the use of MnO2 in organic synthe-
sis might see a revival based on the reaction system described
Finally, we recently disclosed a general solution to the prep-
aration of P-stereogenic compounds based on RPO2H2 (R=H,
C).[18] Improving the recovery of HOCH2P(O)(OMen)H in the
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Communication
[1] C.-G. Feng, M. Ye, K.-J. Xiao, S. Li, J.-Q. Yu, J. Am. Chem. Soc. 2013, 135,
9322–9325.
[2] C. Li, T. Yano, N. Ishida, M. Murakami, Angew. Chem. 2013, 125, 9983–
9986; Angew. Chem. Int. Ed. 2013, 52, 9801–9804.
herein. Our laboratory will investigate further developments of
this reaction, including extending its scope and improving its
para-regioselectivity.
[3] C. Hou, Y. Ren, R. Lang, X. Hu, C. Xia, F. Li, Chem. Commun. 2012, 48,
5181–5183.
Experimental Section
[4] X. Mi, M. Huang, J. Zhang, C. Wang, Y. Wu, Org. Lett. 2013, 15, 6266–
6269.
Butyl mesityl phenylphosphinate 3k
[5] F. Effenberger, H. Kottmann, Tetrahedron 1985, 41, 4171–4182.
[6] H. Wang, X. Li, F. Wu, B. Wan, Synthesis 2012, 44, 941–945.
[7] C.-B. Xiang, Y.-J. Bian, X.-R. Mao, Z.-Z. Huang, J. Org. Chem. 2012, 77,
7706–7710.
[8] X. Mao, X. Ma, S. Zhang, H. Hu, C. Zhu, Y. Cheng, Eur. J. Org. Chem.
2013, 4245–4248.
[9] a) X.-J. Mu, J.-P. Zou, Q.-F. Qian, W. Zhang, Org. Lett. 2006, 8, 5291–
5293; b) W. Xu, J.-P. Zou, W. Zhang, Tetrahedron Lett. 2010, 51, 2639–
2643; c) X.-Q. Pan, J.-P. Zou, G.-L. Zhang, W. Zhang, Chem. Commun.
2010, 46, 1721–1723; d) P. Zou, Y.-J. Jiang, J.-P. Zou, W. Zhang, Synthesis
2012, 44, 1043–1050; e) W.-B. Sun, Y.-F. Ji, X.-Q. Pan, S.-F. Zhou, J.-P.
Zou, W. Zhang, Synthesis 2013, 45, 1529–1533.
[10] S. E. Kim, S. H. Kim, C. H. Lim, J. N. Kim, Tetrahedron Lett. 2013, 54,
1697–1699.
[11] G.-W. Wang, C.-Z. Wang, J.-P. Zou, J. Org. Chem. 2011, 76, 6088–6094.
[12] T. Kagayama, A. Nakano, S. Sakaguchi, Y. Ishii, Org. Lett. 2006, 8, 407–
409.
[13] H. C. Fisher, O. Berger, F. Gelat, J.-L. Montchamp, Adv. Synth. Catal. 2014,
356, 1199–1204.
[14] a) J.-L. Montchamp, Acc. Chem. Res. 2014, 47, 77–87; b) C. Petit, F. Fꢁ-
court, J.-L. Montchamp, Adv. Synth. Catal. 2011, 353, 1883–1888.
[15] O. Berger, C. Petit, E. L. Deal, J.-L. Montchamp, Adv. Synth. Catal. 2013,
355, 1361–1373.
To a suspension of Mn(OAc)2 (8.7 mg, 0.05 mmol, 5 mol%), MnO2
(261 mg, 3 mmol, 3 equiv), sodium acetate (246 mg, 3 mmol,
3 equiv) and mesitylene (0.70 mL, 5 mmol, 5 equiv) in acetic acid
(2.5 mL) at 708C under N2 was added a solution of butyl phenyl-H-
phosphinate (198 mg, 1 mmol, 1 equiv) in acetic acid (2.5 mL) over
2 h via a syringe pump. The reaction mixture was then stirred for
an additional 2 h at 708C under N2. Ethyl acetate (30 mL) and
a 0.2m aqueous solution of Na2S2O4 saturated with NaHCO3
(40 mL) were added. The suspension was stirred vigorously for
5 min, filtered through celite and the two layers were separated.
The organic layer was washed with a 0.2m aqueous solution of
Na2S2O4 saturated with NaHCO3 (40 mL), a saturated aqueous solu-
tion of NaHCO3 (40 mL) and brine (40 mL), dried over MgSO4, fil-
tered and concentrated under vacuum to afford 3k as a colorless
oil (257 mg, 81%). 31P NMR (162 MHz, CDCl3): d=35.0 ppm (s);
1H NMR (400 MHz, CDCl3): d=7.55–7.66 (m, 2H), 7.24–7.40 (m, 3H),
6.81 (s, 2H), 3.95 (dm, J=48.0 Hz, 2H), 2.44 (s, 6H), 2.18 (s, 3H),
1.63 (quint., J=6.9 Hz, 2H), 1.35 (sextuplet, J=7.2 Hz, 2H),
0.83 ppm (t, J=7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): d=143.6 (d,
J
PCC =11.3 Hz, 2C), 141.8 (d, JPCCCC =2.3 Hz), 134.5 (d, JPC =134 Hz),
[16] The approximate commercial costs (per mol of limiting reagent) for var-
ious systems are as follows: 5 mol% Mn(OAc)2 +3 equiv MnO2: $48;
10 mol% AgNO3 +2 equiv K2S2O8: $106; 20 mol% AgOAc+4 equiv
K2S2O8: $232; 10 mol% Pd(OAc)2 +2 equiv AgOAc: $1484; 3 equiv Mn-
(OAc)3·2H2O: $3195. For cross-coupling 2 mol% Pd(OAc)2 +2.2 mol%
Xantphos: $516; 2 mol% Pd(OAc)2 +2.2 mol% dppf: $187. Admittedly,
the costs of waste disposal would also need to be considered.
[17] L. Gavara, C. Petit, J.-L. Montchamp, Tetrahedron Lett. 2012, 53, 5000–
5003.
131.4 (d, JPCCCC =2.3 Hz), 130.7 (d, JPCC =13.1 Hz, 2C), 130.3 (d,
J
PCCC =10.9 Hz, 2C), 128.3 (d, JPCCC =13.2 Hz, 2C), 124.0 (d, JPC
=
=
131 Hz), 63.8 (d, JPOC =5.9 Hz), 32.6 (d, JPOCC =6.6 Hz), 23.4 (d, JPCCC
3.0 Hz, 2C), 21.0, 18.9, 13.6 ppm; HRMS (EI+) m/z calcd for
C19H25O2P ([M]+): 316.1592; found: 316.1586.
Acknowledgements
[18] O. Berger, J.-L. Montchamp, Angew. Chem. 2013, 125, 11587–11590;
Angew. Chem. Int. Ed. 2013, 52, 11377–11380.
We gratefully acknowledge the National Science Foundation
(CHE-1262254) for financial support.
Keywords: manganese
·
P-chiral
·
phosphinate
·
P-
Received: July 22, 2014
stereogenic · radical arylation
Published online on August 14, 2014
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