Facile synthesis of bisphosphine monoxides from Morita–Baylis–Hillman carbonates

Article abstract of DOI:10.1080/10426507.2015.1100192

A facile two-step synthesis of bisphosphine monoxides (BPMOs, with both the phosphine and phosphine oxide moieties within one molecule) from readily available Morita–Baylis–Hillman (MBH) carbonates was realized. Under the catalysis of DABCO, the MBH carbo

Full text of DOI:10.1080/10426507.2015.1100192

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Facile Synthesis of Bisphosphine Monoxides from
Morita-Baylis-Hillman Carbonates
Rong Zhou, Kai Zhang & Rongfang Liu
To cite this article: Rong Zhou, Kai Zhang & Rongfang Liu (2016): Facile Synthesis of
Bisphosphine Monoxides from Morita-Baylis-Hillman Carbonates, Phosphorus, Sulfur, and
Silicon and the Related Elements, DOI: 10.1080/10426507.2015.1100192
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1100192
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Date: 15 April 2016, At: 00:04

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Facile Synthesis of Bisphosphine Monoxides from Morita-Baylis-Hillman Carbonates
Rong Zhou,*a Kai Zhang,a and Rongfang Liua
a
College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan,
030024, P. R. China
Email: zhourong@tyut.edu.cn
Running title:
Synthesis of Bisphosphine Monoxides
Abstract A facile two-step synthesis of bisphosphine monoxides (with both the phosphine and
phosphine oxide moieties within one molecule) from readily available Morita-Baylis-Hillman
(MBH) carbonates was realized. Under the catalysis of DABCO, the MBH carbonates undergo
allylic phosphorylation reaction with diphenylphosphine oxide or diethyl phosphonate to give
monophosphine oxides bearing an activated alkene moiety; subsequent base-catalyzed
hydrophosphination of the prepared monophosphine oxide with HPPh2 readily affords the
bisphosphine monoxides.
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Key words Morita-Baylis-Hillman carbonates; bisphosphine monoxides; hydrophosphination;
allylic alkylation; monophosphine oxides
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INTRODUCTION
Bisphosphine monoxides (BPMOs) are an important class of compounds widely used in
medicinal research[1] as well as metal catalysis[2]. Due to the presence of both the soft (phosphorus)
and hard (oxygen) Lewis base centers on one molecule, BPMOs frequently function as important
hemilabile ligands[2,3] enabling the coordination to various transition metals to form labile metal
chelates which can easily generate reactive, coordinatively unsaturated species.[2, 4] As a result,
transition metal-BPMO complexes are often capable of catalyzing various reactions under mild
conditions with high selectivities, as witnessed by the valuable processes such as
hydroformylation[2,5], olefin hydrocarboxylation[2], methanol carbonylation[2] and other important
transformations[6]. The development of efficient synthetic methods for BPMOs has therefore
attracted great efforts from chemists and a series of approaches have been accordingly established.
Generally, the existing synthetic approaches for BPMOs mainly focus on the following two
strategies: one involves characteristic coupling of two monophosphines with different oxidation
states; the other is based on the selective mono oxidation of bidentate tertiary phosphines.[2]
Although these strategies have been proved effective in preparing BPMOs with specific structures,
they still suffer from limitations such as tedious manipulation, harsh conditions, low yields, and
poor selectivities. Thus, the development of new facile approaches for efficient assembly of
BPMOs remains highly desirable.
Recently, a class of so-called modified MBH derivatives such as halides, acetates, and tert-butyl
carbonates, which could be easily prepared from Morita-Baylis-Hillman adducts, have emerged as
versatile substrates in a number of valuable transformations.[7] For example, the MBH derivatives
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were proved to be versatile C3 and C1 synthons in a series of phosphine-catalyzed [3 + n] (n = 2, 3,
4, 6) and [1 + 4] annulations with electrophiles, affording synthetically useful multifunctional
cyclic and heterocyclic compounds.[8] In addition, the MBH derivatives were also reported to
undertake allylic alkylation reactions with nucleophiles under the catalysis of phosphine or tertiary
amine Lewis bases, producing functionalized products bearing an electrophilic terminal alkene
subunit.[9] With these diverse reactivity patterns of MBH derivatives, recently, we demonstrated a
phosphine-trigged tandem [3 + 4] annulation of MBH carbonates with 1,4-diheteroatom
dinucleophiles, providing an efficient access to seven-membered 1,4-heterocycles.[10] Detailed
mechanistic studies unveiled that the reaction proceeded through a phosphine-catalyzed allylic
alkylation followed by a general base-promoted intramolecular Michael cyclization (Scheme 1, eq
a). Inspired by this strategy, we envisioned that, the allylic carbonate could undertake an allylic
alkylation with phosphine oxide nucleophile (e.g. diphenylphosphine oxide, diethyl phosphonate)
under the catalysis of a Lewis base,[9e] forming monophosphine oxide bearing an activated alkene
moiety. Subsequent hydrophosphination of the prepared monophosphine oxide with phosphine
such as HPPh2 would afford the bisphosphine monoxides (Scheme 1, eq b). Thus, a new facile
entry for bisphosphine monoxides would be developed, which involves two C-P bond forming
reactions under metal-free conditions. Recently, the metal-free or metal-catalyzed C-P bond
formations have attracted extensive interest from chemists.[11] Herein, we reported the results
from such an investigation in detail.
RESULTS AND DISCUSSION
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Our initial efforts focused on the preparation of monophosphine oxides via allylic alkylation of
MBH carbonates with phosphine oxide nucleophiles. As can be seen in Table 1, under the
catalysis of DABCO (20 mol %), the allylic alkylation reaction of heteroaryl-substituted MBH
carbonate 1a and diphenylphosphine oxide 2a uneventfully occurred in common solvents such as
toluene, CH2Cl2 and THF (entries 1-3), with THF affording the best yield of product 3a (entry 3).
Using THF as the medium, the reactions of diphenylphosphine oxide 2a with aryl-substituted
allylic carbonate 1b, alkyl-substituted allylic carbonate 1c, as well as non-substituted allylic
carbonate 1d proceeded smoothly to deliver their corresponding allylic alkylation products in
moderate to excellent yields (entries 4-6). Apart from diphenylphosphine oxide 2a, diethyl
phosphonate 2b was also a viable substrate in the reaction with allylic carbonate 1a, affording
product 3e in good yield (entry 7). So, a series of monophosphine oxides with variable
substituents were conveniently prepared under very mild conditions in good yields.
Subsequently, we investigated the hydrophosphination of monophosphine oxide with HPPh2 to
deliver the bisphosphine monoxide. With the reaction of 3d and HPPh2 as a model, a brief survey
on the reaction conditions was carried out. In view of the hydrophosphination reaction was best
run in basic conditions, different bases were examined.[2,12] As depicted in Table 2, with t-BuOK
or EtONa employed as the base in different equivalents, the hydrophosphination reaction
smoothly occurred in THF, toluene, as well as ethanol, but afforded the bisphosphine monoxide
4a in inferior yields (entries 1-6). When the reaction was conducted using 20 mol % Et4NOH (25
wt.% in aqueous solution) as the base catalyst in CH3CN, the yield of 4a was improved
significantly in shorter time (entry 7). Increasing the loading of Et4NOH to 1.0 equiv led to a
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disorder reaction outcome (entry 8). Thus, the optimal conditions for the hydrophosphination
reaction were established.
Under the optimal conditions, all the monophosphine oxides prepared above smoothly
underwent the hydrophosphination reaction with HPPh2, affording their corresponding
bisphosphine monoxides in moderate to good yields (Table 3, entries 1-5). The structures of
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monophosphine oxides 3 and bisphosphine monoxides 4 were identified by 1H, C, P NMR, as
well as HRMS-ESI measurements. Thus, an efficient synthesis of functionalized bisphosphine
monoxides with a C3 spacer was realized through a simple two-step reaction. Due to the easy
variation of substituents on the starting MBH carbonates, this strategy is convenient to assemble
bisphosphine monoxides with good functional diversity.
CONCLUSIONS
In summary, we have developed a facile two-step synthesis of functionalized bisphosphine
monoxides from MBH carbonates. The approach involves a DABCO-catalyzed allylic
phosphorylation, followed by a base-promoted intermolecular hydrophosphination. Compared
with the existed entries for bisphosphine monoxides, the newly established method features such
merits as readily available of the materials, mild conditions, good yields and selectivities, which
make this method potentially useful for preparing bisphosphine monoxides for metal catalysis and
medicinal research. Future efforts in our laboratory will be directed toward further expanding the
scope and developing asymmetric versions of these transformations.
EXPERIMENTAL
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Reactions involving air-sensitive compounds were performed under a N2 atmosphere. Solvents
were purified prior to use according to conventional procedures. Nuclear magnetic resonances
(1H, 13C, and 31P) were recorded on Bruker 400 MHz NMR spectrometer in CDCl3 with
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tetramethylsilane (TMS) as the internal reference (for H and C NMR) or with 85% H3PO4 as
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the external standard (for P NMR). Column chromatography was performed on silica gel (200-
300 mesh) using a mixture of petroleum ether/ethyl acetate as eluant. MBH carbonates were
prepared according to our previously reported procedures.[13]
Typical procedure for the synthesis of monophosphine oxides
To a solution of MBH carbonate 1 (0.5 mmol), nucleophile 2 (0.6 mmol) in solvent (5.0 mL)
was added DABCO (12 mg, 0.1 mmol). The resulting mixture was stirred at room temperature
until MBH carbonate 1 was completely consumed, as monitored by TLC. Then the solvent was
removed on a rotary evaporator under reduced pressure and the residue was subjected to column
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chromatographic isolation on silica gel (gradient elution, petroleum ether (bp 60–90 C) / ethyl
acetate) to give monophosphine oxide 3.
Ethyl 2-((diphenylphosphoryl)(furan-2-yl)methyl)acrylate (3a), table 1 entry 3. Prepared
according to the typical procedure in 97% yield as an oil; 1H NMR (400 MHz, CDCl3): δ 1.14 (t,
J = 7.1 Hz, 3H), 4.00 (q, J = 7.1 Hz, 2H), 5.38 (d, J = 10.7 Hz, 1H), 6.22 (dd, J = 3.1, 1.9 Hz,
1H), 6.39 (t, J = 2.5 Hz, 1H), 6.51 - 6.53 (m, 2H), 7.23 (t, J = 0.84 Hz, 1H), 7.38 - 7.48 (m, 6H),
7.69 - 7.71 (m, 2H), 7.75 - 7.80 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 14.0, 39.9 (d, J = 67.0
Hz), 61.3, 109.7 (d, J = 4.4 Hz), 110.7, 128.3 (d, J = 11.9 Hz), 130.9, 131.1, 131.2, 131.3,
131.5, 131.6, 131.8, 132.3 (d, J = 20,0 Hz), 133.7 (d, J = 3.8 Hz), 142.1, 148.7 (d, J = 4.2 Hz),
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165.9 (d, J = 5.8 Hz); P NMR (160 MHz): δ 30.4; HRMS-ESI calcd for C22H22O4P (M + H)+
381.1250, found 381.1255.
Ethyl 2-((diphenylphosphoryl)(4-nitrophenyl)methyl)acrylate (3b), table 1 entry 4. Prepared
according to the typical procedure in 91% yield as an oil; 1H NMR (400 MHz, CDCl3): δ 1.19 (t,
J = 7.1 Hz, 3H), 4.05 - 4.14 (m, 2H), 5.15 (d, J = 8.4 Hz, 1H), 6.50 (d, J = 1.5 Hz, 1H), 6.84 (d,
J = 1.9 Hz, 1H), 7.29 - 7.32 (m, 2H), 7.38 - 7.42 (m, 1H), 7.47 - 7.55 (m, 7H), 7.88 (dd, J =
13
11.0, 7.0 Hz, 2H), 8.02 (d, J = 8.7 Hz, 2H); C NMR (100 MHz, CDCl3): δ 13.9, 45.7 (d, J =
65.8 Hz), 61.6, 123.3, 128.4 (d, J = 11.8 Hz), 128.8 (d, J = 11.7 Hz), 130.7, 130.8, 130.9, 131.0,
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131.1, 131.9, 132.0, 135.8, 142.7 (d, J = 4.7 Hz), 147.0, 165.9 (d, J = 9.4 Hz); P NMR (160
MHz): δ 32.2; HRMS-ESI calcd for C24H22NO5PNa (M + Na)+ 458.1128, found, 458.1122
Ethyl 3-(diphenylphosphoryl)-2-methylenehexanoate (3c), table 1 entry 5. Prepared according
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to the typical procedure in 66% yield as a white solid; m.p. 83~84 C; H NMR (400 MHz,
CDCl3): δ 0.74 (t, J = 7.3 Hz, 3H), 1.04 (t, J = 7.1 Hz, 3H), 1.12 - 1.19 (m, 1H), 1.25 - 1.33 (m,
1H), 1.64 (br s, 1H), 1.79 (br s, 1H), 3.84 - 3.92 (m, 3H), 6.13 (d, J = 4.4 Hz, 1H), 6.36 (d, J =
4.8 Hz, 1H), 7.26 - 7.32 (m, 3H), 7.40 - 7.43 (m, 3H), 7.62 (dd, J = 7.0, 4.0 Hz, 2H), 7.81 - 7.86
(m, 2H);13C NMR (100 MHz, CDCl3): δ 13.5, 13.9, 20.4 (d, J = 12.7 Hz), 31.6, 37.6, 38.0 (d, J
= 68.6 Hz), 60.9, 128.0 (d, J = 11.2 Hz), 128.6 (d, J = 11.0 Hz), 130.6 (d, J = 10.8 Hz), 130.9,
131.0, 131.1, 131.2, 131.5, 132.9 (d, J = 15.0 Hz), 135.8 (d, J = 5.2 Hz), 166.7 (d, J = 5.3 Hz);
31P NMR (160 MHz): δ 32.4; HRMS-ESI calcd for C21H26O3P (M + H)+ 357.1614, found
357.1620
Ethyl 2-((diphenylphosphoryl)methyl)acrylate (3d), table 1 entry 6. A known compound, and
the characterization data are in accordance with the literature.[14] Prepared according to the typical
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procedure in 98% yield as a white solid; m.p. 82~83 oC; 1H NMR (400 MHz, CDCl3): δ 1.14 (t, J
= 7.1 Hz, 3H), 3.47 (d, J = 14.7 Hz, 2H), 4.00 (q, J = 7.1 Hz, 2H), 6.00 (d, J = 4.3 Hz, 1H), 6.36
13
(d, J = 4.6 Hz, 1H), 7.45 - 7.51 (m, 6H), 7.74 - 7.79 (m, 4H); C NMR (100 MHz, CDCl3): δ
13.9, 32.0 (d, J = 67.8 Hz), 61.1, 128.4 (d, J = 11.8 Hz), 129.7 (d, J = 7.7 Hz), 130.6 (d, J = 8.4
Hz), 131.1 (d, J = 9.4 Hz), 131.9, 132.9, 166.1 (d, J = 4.4 Hz); 31P NMR (160 MHz): δ 30.35.
Ethyl 2-((diethoxyphosphoryl)(furan-2-yl)methyl)acrylate (3e), table 1 entry 7. Prepared
according to the typical procedure in 80% yield as an oil; 1H NMR (400MHz, CDCl3): δ 1.21 (t, J
= 7.1 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H), 3.93 - 4.02 (m, 1H), 4.04 - 4.13
(m, 3H), 4.24 (q, J = 7.1 Hz, 2H), 4.87 (d, J = 26.1 Hz, 1H), 6.25 (d, J = 4.4 Hz, 1H), 6.33 (br s,
1H), 6.41 (t, J = 2.9 Hz, 1H), 6.54 (d, J = 4.8 Hz, 1H), 7.29 (s, 1H); 13C NMR (100 M, CDCl3):
δ 13.9, 16.0, 16.1, 38.1 (d, J = 142.6 Hz), 61.1, 62.5 (d, J = 7.2 Hz), 62.9 (d, J = 6.9 Hz), 108.8
(d, J = 5.6 Hz), 110.5, 129.2 (d, J = 7.3 Hz), 134.1 (d, J = 5.2 Hz), 142.0, 148.4 (d, J = 4.8 Hz),
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165.7 (d, J = 7.8 Hz); P NMR (160 MHz): δ 21.4; HRMS-ESI calcd for C14H21O6PNa (M +
Na)+ 339.0968, found 339.0960.
Typical procedure for the hydrophosphination reaction
Under a N2 atmosphere, to a solution of monophosphine oxide 3 (0.5 mmol), HPPh2 2 (130 μL,
0.75 mmol) in CH3CN (6.0 mL) was added 25 wt.% aqueous solution of Et4NOH (58.8~73.5 mg,
0.1~0.125 mmol). The resulting mixture was stirred at room temperature until the monophosphine
oxide 3 was completely consumed, as monitored by TLC. Degassed H2O (5.0 mL) was then
added and the mixture was extracted with degassed CH2Cl2 (3 × 10 mL). The organic layers were
combined and dried over anhydrous MgSO4. After filtration, the solvent was removed on a rotary
evaporator under reduced pressure and the residue was subjected to flash column
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chromatographic isolation on silica gel (gradient elution, petroleum ether (bp 60–90 C) / ethyl
acetate) to give bisphosphine monoxide 4.
Ethyl 3-(diphenylphosphino)-2-((diphenylphosphoryl)methyl)propanoate (4a), table 3 entry 1.
Prepared according to the typical procedure in 76% yield as an oil; 1H NMR (400 MHz, CDCl3):
δ 0.98 (t, J = 7.1 Hz, 3H), 2.39 (ddd, J = 20.1, 13.7, 6.3 Hz, 2H), 2.61 - 2.69 (m, 1H), 2.72 -
2.86 (m, 2H), 3.68 (q, J = 7.1 Hz, 2H), 7.15 - 7.21 (m, 7H), 7.27 - 7.37 (m, 9H), 7.58 - 7.62 (m,
4H); 13C NMR (100 MHz, CDCl3): δ 13.5, 31.9 (d, J = 10.9 Hz), 32.6 (ddd, J = 32.5, 15.1, 8.4
Hz), 36.7 (d, J = 18.2 Hz) , 60.5, [128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 130.3, 130.4, 130.5,
130.6, 131.4, 132.2, 132.4, 132.5, 132.6, 133.4] (the 13C NMR signals of the benzene rings
31
overlapped and could not be identified), 137.2 (d, J = 11.5 Hz), 173.6 (dd, J = 7.4, 2.9 Hz); P
NMR(160 MHz): δ 31.3, -20.4; HRMS-ESI calcd for C30H31O3P2 (M + H)+ 501.1734, found
501.1739.
Ethyl 2-((diphenylphosphino)methyl)-3-(diphenylphosphoryl)-3-(furan-2-yl)propanoate (4b),
table 3 entry 2. Prepared according to the typical procedure in 83% yield as a oil; 1H NMR (400
MHz, CDCl3): δ 1.00 (t, J = 7.1 Hz, 3H), 2.16 - 2.24 (m, 1H), 2.71 (ddd, J = 7.3, 4.6, 2.7 Hz,
1H), 3.30 (br s, 1H), 3.80 (q, J = 7.1 Hz, 2H), 4.29 - 4.37 (m, 1H), 6.10 (d, J = 1.4 Hz, 2H), 7.11
(s, 1H), 7.17 - 7.24 (m, 5H), 7.28 - 7.33 (m, 6H), 7.37 - 7.46 (m, 5H), 7.56 - 7.63 (m, 2H), 7.77 -
7.83 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 13.8, 30.3 (d, J = 14.3 Hz), 43.8 (d, J = 19.5 Hz),
44.9 (dd, J = 69.1, 10.8 Hz), 60.6, 110.5 (d, J = 5.4 Hz), 110.6, 128.1, 128.2, 128.3, 128.4,
128.5, 128.6, 130.6, 131.0, 131.1, 131.2, 131.6 (d, J = 14.3 Hz), 132.5 (d, J = 18.8 Hz), 132.9
(d, J = 19.3 Hz), 133.5, 137.4 (d, J = 13.2 Hz), 138.0 (d, J = 12.0 Hz), 141.7 (d, J = 2.3 Hz),
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147.9 (d, J = 4.8 Hz), 172.4 (d, J = 13.3 Hz); P NMR (160 MHz): δ 30.9, -19.7; HRMS-ESI
calcd for C34H32O4P2Na (M + Na)+ 589.1668, found 589.1664.
Ethyl 2-((diphenylphosphino)methyl)-3-(diphenylphosphoryl)-3-(4-nitrophenyl)propanoate (4c),
table 3 entry 3. Prepared according to the typical procedure in 76% yield as a white solid; m.p. >
173 oC; 1H NMR (400 MHz, CDCl3): δ 0.88 (t, J = 7.1 Hz, 3H), 1.97 (t, J = 11.7 Hz, 1H), 2.41 -
2.45 (m, 1H), 3.46 (br s, 1H), 3.68 (q, J = 7.1 Hz, 2H), 4.18 (t, J = 7.7 Hz, 1H), 7.03 (t, J = 7.5
Hz, 2H), 7.16 - 7.24 (m, 5H), 7.27 - 7.32 (m, 5H), 7.42 - 7.54 (m, 8H), 7.91 (d, J = 8.6 Hz, 2H),
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8.00 - 8.04 (m, 2H); C NMR (100 MHz, CDCl3): δ 13.7, 30.0 (d, J = 14.8 Hz), 45.2 (d, J =
19.0 Hz), 50.2 (dd, J = 65.9, 9.7 Hz), 60.7, 122.9, [128.2, 128.3, 128.4, 128.5, 128.6, 128.7,
128.9, 129.0, 129.1, 130.5, 130.6, 130.8, 130.9, 131.1, 131.2, 131.5, 131.9, 132.3, 132.5, 132.6,
132.8, 133.9] (the 13C NMR signals of the benzene rings overlapped and could not be identified),
137.2 (d, J = 13.2 Hz), 137.7 (d, J = 11.6 Hz), 143.0 (d, J = 4.4 Hz), 146.9, 172.4 (d, J = 12.3
Hz); 31P NMR (160 MHz): δ 29.5, -21.0; HRMS-ESI calcd for C36H34NO5P2 (M + H)+ 622.1907,
found 622.1908.
Ethyl 2-((diphenylphosphino)methyl)-3-(diphenylphosphoryl)hexanoate (4d), table 3 entry 4.
Two separable diastereomers were afforded in 52% overall yield according to the typical
1
procedure. The major isomer: 46% yield; an oil; H NMR (400 MHz, CDCl3): δ 0.61 (t, J = 7.2
Hz, 3H), 0.83 - 0.87 (m, 1H), 1.06 - 1.10 (m, 1H), 1.16 (t, J = 7.1 Hz, 3H), 1.51 - 1.63 (m, 2H),
2.38 - 2.45 (m, 1H), 2.49 - 2.54 (m, 1H), 2.74 - 2.83 (m, 1H), 2.94 - 2.97 (m, 1H), 3.79 - 3.87
(m, 1H), 3.90 - 3.98 (m, 1H), 7.27 - 7.29 (m, 7H), 7.35 - 7.39 (m, 5H), 7.40 - 7.46 (m, 4H), 7.76
13
- 7.85 (m, 4H); C NMR (100 MHz, CDCl3): δ 13.8, 21.4 (d, J = 7.6 Hz), 28.3, 28.9 (dd, J =
13.1, 6.6 Hz), 40.2 (d, J = 9.7 Hz), 41.1 (d, J = 9.7 Hz), 41.7 (d, J = 18.8 Hz), 60.7, [128.2,
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128.3, 128.4, 128.5, 128.6, 128.8, 130.6, 130.7, 130.9, 131.0, 131.2, 131.4, 132.1, 132.3, 132.4,
133.0, 133.3, 133.7] (the 13C NMR signals of the benzene rings overlapped and could not be
31
identified), 137.9 (d, J = 11.5 Hz), 173.0 (d, J = 10.4 Hz); P NMR (160 MHz): δ 33.3, -18.5;
HRMS-ESI calcd for C33H36O3P2Na (M + Na)+ 565.2032, found 565.2037. The minor isomer:
31
6% yield; an oil; P NMR (160 MHz): δ 35.3, -14.7; HRMS-ESI calcd for C33H36O3P2Na (M +
Na)+ 565.2032, found 565.2021.
Ethyl 3-(diethoxyphosphoryl)-2-((diphenylphosphino)methyl)-3-(furan-2-yl)propanoate (4e),
table 3 entry 5. Two separable diastereomers were afforded in 66% combined yield according to
the typical procedure. The major isomer: 63% yield; an oil;1H NMR (400 MHz, CDCl3): δ 1.13
(t, J = 7.0 Hz, 3H), 1.19 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H), 2.17 (td, J = 11.6, 2.8 Hz,
1H), 2.34 - 2.39 (m, 1H), 3.04 - 3.09 (m, 1H), 3.76 (d, J = 8.4 Hz, 1H), 3.80 - 3.87 (m, 1H), 3.92
- 4.06 (m, 5H), 6.29 - 6.31 (m, 1H), 6.35 (s, 1H), 7.25 - 7.27 (m, 4H), 7.32 - 7.33 (m, 3H), 7.37
13
(s, 1H), 7.39 - 7.44 (m, 2H), 7.47 - 7.51 (m, 1H); C NMR (100 MHz, CDCl3): δ 13.9, 16.0,
16.1, 28.9 (dd, J = 14.6, 8.8 Hz), 41.4 (dd, J = 142.7, 10.1 Hz), 42.8 (d, J = 21.0 Hz), 60.8, 62.1
(d, J = 7.1 Hz), 62.8 (d, J = 6.7 Hz), 110.2 (d, J = 6.4 Hz), 110.7, 128.2 (d, J = 5.7 Hz), 128.3
(d, J = 7.2 Hz), 128.9, 130.6 (d, J = 11.4 Hz), 132.1 (d, J = 18.4 Hz), 133.3 (d, J = 20.0 Hz),
137.1 (d, J = 13.7 Hz), 138.5 (d, J = 12.3 Hz), 142.3 (d, J = 2.5 Hz), 147.3 (d, J = 6.2 Hz),
31
172.8 (d, J = 8.2 Hz); P NMR(160 MHz): δ 22.5, -19.4; HRMS-ESI calcd for C26H32O6P2Na
(M + Na)+ 525.1566, found 525.1563. The minor isomer: 3% yield; an oil; 1H NMR (400MHz,
CDCl3): δ 1.04 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H), 2.40 (td, J
= 13.6, 2.4 Hz, 1H), 2.94 - 2.99 (m, 1H), 3.12 - 3.18 (m, 1H), 3.72 - 3.76 (m, 1H), 3.78 - 3.86
(m, 3H), 3.96 - 3.98 (m, 1H), 4.02 - 4.08 (m, 2H), 6.23 - 6.24 (m, 1H), 6.27 - 6.29 (m, 1H), 7.28
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- 7.34 (m, 6H), 7.38 - 7.42 (m, 2H), 7.46 - 7.49 (m, 3H); C NMR (100 MHz, CDCl3): δ 13.9,
16.1, 16.2, 29.6 (d, J = 13.9 Hz), 41.9 (d, J = 143.4, 10.8 Hz), 44.1 (d, J = 19.8 Hz) , 60.5, 62.2
(d, J = 6.9 Hz), 62.7 (d, J = 6.9 Hz), 109.0 (d, J = 6.6 Hz), 110.5, 128.3 (d, J = 6.6 Hz), 128.4
(d, J = 6.4 Hz), 128.8, 130.9 (d, J = 9.4 Hz), 132.5 (d, J = 18.7 Hz), 133.1 (d, J = 19.6 Hz),
137.4 (d, J = 13.4 Hz), 138.3 (d, J = 11.9 Hz), 141.9 (d, J = 2.6 Hz), 148.4 (d, J = 7.7 Hz),
172.4 (d, J = 16.6 Hz); 31P NMR (160 MHz): δ 23.1, -19.9; HRMS-ESI calcd for C26H33O6P2 (M
+ H)+ 503.1747, found 503.1740.
ACKNOWLEDGMENTS
Financial support from the National Natural Science Foundation of China (Grant No.
21502135), the Natural Science Foundation of Shanxi (Grant No. 2014021015-3), and the
Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi
(Grant No. 2014114) is gratefully acknowledged. The authors also gratefully appreciate Professor
Zhengjie He of Nankai University for his long-term support.
SUPPORTING INFORMATION
Copies of 1H, 13C, and 31P NMR spectra of compounds 3 and 4. This material can be found via
the ‘‘Supplementary Content’’ section of this article’s webpage.
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Table 1. Preparation of monophosphine oxides via allylic alkylation of MBH carbonatesa
entry
R1
R
solvent
toluene
CH2Cl2
THF
yield (%)b
3a, 51
1
2
3
4
5
6
7
2-furyl, 1a
2-furyl, 1a
2-furyl, 1a
4-NO2C6H5, 1b
n-Pr, 1c
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
OEt, 2b
3a, 70
3a, 97
THF
3b, 91
3c, 66
THF
THF
H, 1d
3d, 98
3e, 80%
CH2Cl2
2-furyl, 1a
a General conditions: A mixture of MBH carbonate 1 (0.5 mmol), nucleophile 2 (0.6 mmol),
and DABCO (12 mg, 0.1 mmol) in solvent (5.0 mL) was stirred at room temperature for 24 h.
b Isolated yield.
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Table 2. Survey on the model hydrophosphination reaction conditionsa
entry
1
base ([equiv.])b
t-BuOK (0.2)
t-BuOK (0.2)
t-BuOK (0.3)
EtONa (0.2)
EtONa (1.0)
EtONa (1.0)
Et4NOH (0.2)
Et4NOH (1.0)
solvent
THF
time (h)
yield of 4a (%)c
24
23
23
24
24
17
6
39
2
toluene
THF
37
3
34
4
THF
28
5
THF
27
6
EtOH
CH3CN
CH3CN
44
7d
8d
76
1
disorder
a General conditions: under a N2 atmosphere, to a solution of 3d (157 mg, 0.5 mmol) and
HPPh2 (130 μL, 0.75 mmol) in solvent (6.0 mL) was added the base in a specified equivalent, and
the resulting mixture was stirred at room temperature for a indicated time.
b The equivalents were relative to 3d.
c Isolated yield.
d Et4NOH was used as 25 wt.% aqueous solution.
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Table 3. Hydrophosphination of the monophosphine oxidesa
entry
1
R
R1
time (h)
yield (%)b
4a, 76
4b, 83
4c, 76
Ph
Ph
Ph
Ph
OEt
6
H, 3d
2
2
2-furyl, 3a
4-NO2C6H5, 3b
n-Pr, 3c
2-furyl, 3e
3
7
4c
2
4d, 52
4e, 66
5d
19
a General conditions: under a N2 atmosphere, to a solution of momophosphine oxide 3 (0.5 mol)
and HPPh2 (130 μL, 0.75 mmol) in CH3CN (6.0 mL) was added 25 wt.% aqueous Et4NOH
(0.1~0.125 mmol), and the resulting mixture was stirred at rt for a specified time.
b Isolated yield.
c Two separable diastereomers were isolated in 46% and 6% yields, respectively.
d Two separable diastereomers were isolated in 63% and 3% yields, respectively.
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Scheme 1. Synthesis of functionalized molecules from MBH carbonates
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