Efficient synthesis of 4-halo-2,5-dihydro-1,2-oxaphosphole 2-oxides from 1,2-allenylphosphonates and CuX2 and subsequent suzuki cross-coupling of the C-Cl bonds

Article abstract of DOI:10.1002/ejoc.201200228

A convenient and efficient synthesis of 4-halo-2,5-dihydro-1,2-oxaphosphole 2-oxides through CuX₂-mediated direct halocyclization of diethyl 1,2-allenylphosphonates was developed. The yields range from moderate to excellent. The efficiency of axial-to-central chirality transfer has also been studied. Further Suzuki cross-coupling of the resulting vinylic chlorides with dicyclohexyl(2,4,6-trimethoxyphenyl)phosphane (LB-Phos) as the ligand, was established. CuX₂-mediated direct halocyclization of diethyl 1,2-allenylphosphonates was developed to afford 4-halo-2,5-dihydro-1,2- oxaphosphole 2-oxides. The efficiency of axial-to-central chirality transfer and subsequent Suzuki cross-coupling of the resultingvinylic chlorides with dicyclohexyl(2,4,6-trimethoxyphenyl)phosphane (LB-Phos) as the ligand were also investigated. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Full text of DOI:10.1002/ejoc.201200228

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FULL PAPER
DOI: 10.1002/ejoc.201200228
Efficient Synthesis of 4-Halo-2,5-dihydro-1,2-oxaphosphole 2-Oxides from 1,2-
Allenylphosphonates and CuX2 and Subsequent Suzuki Cross-Coupling of the
C–Cl Bonds
Ning Xin[a] and Shengming Ma*[a,b]
Keywords: Synthetic methods / Cyclization / Cross-coupling / Chirality / Allenes / Phosphorous heterocycles
A convenient and efficient synthesis of 4-halo-2,5-dihydro-
1,2-oxaphosphole 2-oxides through CuX2-mediated direct
halocyclization of diethyl 1,2-allenylphosphonates was de-
veloped. The yields range from moderate to excellent. The
efficiency of axial-to-central chirality transfer has also been
studied. Further Suzuki cross-coupling of the resulting vin-
ylic chlorides with dicyclohexyl(2,4,6-trimethoxyphenyl)-
phosphane (LB-Phos) as the ligand, was established.
Herein, we present our recent results on direct chloro/
bromo-lactonization of 1,2-allenylphosphonates with CuX2
(Scheme 2) and Suzuki coupling of the corresponding cyclic
chlorides with dicyclohexyl(2,4,6-trimethoxyphenyl)phos-
phane (LB-Phos), which was developed in our group, as the
ligand.[12]
Introduction
Many phosphorus-containing compounds may be con-
sidered as potential insecticides, bactericides, fungicides,
and antibiotic reagents, because of their biological activi-
ties,[1] and such compounds exist widely in nature.[2] In re-
cent decades, a number of groups have studied the synthesis
and transformations of allenylphosphonates,[3–6] such as
palladium-catalyzed coupling reactions with 2-iodophenols,
2-iodobenzoic acids and 2-iodobenzyl alcohols,[3] cycload-
dition reactions,[4] selenochlorination with PhSeCl,[5] and
halocyclizations.[6] Several observations have already been
disclosed on the halocyclization of allenylphosphonates
with relatively active electrophiles such as bromine, sulfenyl-
and selenenylbromides, and mercuric acetate.[7] In the bro-
molactonization reactions, bromine was predominantly
used to produce bromine-containing oxaphospholene struc-
tures. Previously, we have observed that the nontoxic and
mild CuX2 could serve as an efficient halogenation reagent
with easier manipulation and better functional group toler-
ance in the cyclization of functionalized allenes, such as 2,3-
allenoic acids,[8] 2,3-allenamides,[9] and 2,3-allenoates[10]
(Scheme 1). Recently, we have developed the halocyclization
of monoesters of 1,2-allenylphosphonic acids giving 4-halo-
2,5-dihydro-1,2-oxaphosphole 2-oxides in good yields, in
which the monoesters were prepared in an extra step involv-
ing hydrolysis from diethers with excess NaOH in H2O.[11]
Scheme 1. Halocyclization of functionalized allenes with CuX2.
[a] Shanghai Key Laboratory of Green Chemistry and Chemical
Process, Department of Chemistry, East China Normal
University,
Scheme 2. Halolactonization of monoesters of 1,2-allenylphos-
phonic acids and 1,2-allenylphosphonates.
3663 North Zhongshan Road, Shanghai 200062, P. R. China
Fax: +86-21-6260-9305
E-mail: masm@sioc.ac.cn
[b] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200228.
Results and Discussion
1,2-Allenylphosphonates were prepared through inter-
molecular Claisen rearrangement of propargylic alcohols
Eur. J. Org. Chem. 0000, 0–0
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N. Xin, S. Ma
FULL PAPER
and P(OEt)2Cl.[13] We used diethyl (2-methylocta-2,3-dien- Table 2. CuBr2-mediated bromocyclization reaction of 1,2-allenyl-
phosphonates.[a]
4-yl)phosphonate (1a) as the substrate to screen a series of
different reaction conditions for the bromocyclization reac-
tion. The desired product was afforded in 82% yield when
1a was treated with 4.0 equiv. CuBr2 at 60 °C in N,N-di-
methylformamide (DMF), which was observed to be the
best conditions for the halocyclization of monoesters of 1,2-
allenylphosphonic acids[11] (Table 1, entry 1). A variety of
solvents such as toluene, acetonitrile, dichloromethane, eth-
anol, and tetrahydrofuran (THF) were tested: ethanol gave
the best result, whereas THF gave the product 2a with some
inseparable impurities (Table 1, entries 2–8). Increasing or
reducing the amount of CuBr2 only slightly changed the
yields (Table 1, entries 9–11). Finally, it was observed that
the best result was obtained when the reaction was con-
ducted with 2.2 equiv. CuBr2 in EtOH at 60 °C (Table 1,
entry 10).
Entry R1
R2
R3
Time
[h]
Yield of 2
[%][b]
1
2
nBu
Ph
Me
Me
Me
Me (1a)
Me (1b)
1
3
1
1
1
1
1
3
3
3
5
91 (2a)
69 (2b)
75 (2c)
77 (2d)
79 (2e)
88 (2f)
91 (2g)
85 (2h)
72 (2i)
81 (2j)
85 (2k)
3
4
allyl
Me (1c)
2-methylallyl Me
Me (1d)
5
6
7
8
2-chloroallyl Me
Me (1e)
nBu
nBu
Ph
–(CH2)5– (1f)
–(CH2)4– (1g)
–(CH2)5– (1h)
–(CH2)4– (1i)
Et (1j)
9
10
11
Ph
Ph
nBu
Et
nPr
Table 1. CuBr2-mediated bromocyclization reaction of 1a.[a]
nPr (1k)
[a] Reagents and conditions: 1 (0.3 mmol), CuBr2 (0.66 mmol),
EtOH (2 mL), 60 °C. [b] Isolated yield.
Table 3. CuCl2·2H2O-mediated chlorocyclization reaction of 1a.[a]
Entry CuBr2 [equiv.] Solvent
Time [h] Yield of 2a [%][b]
1
2
3
4
5
6
7
8
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
1.5
2.2
3.0
DMF
iPrOH
PrOH
EtOH
CH2Cl2
THF
MeCN
toluene
EtOH
EtOH
EtOH
1
2
2
2
1
1
2
1
13
1
82
76
60
86
76
94[c]
64
55
89
91
86
Entry CuCl2·2H2O Solvent
Time
[h]
T
[°C]
Yield of 3a
[equiv.]
[%][b]
1
2
3
4
5
6
7
8
9
4.0
4.0
4.0
4.0
4.0
3.0
2.2
3.0
3.0
CH2Cl2
EtOH
toluene
MeCN
THF
toluene
toluene
toluene
toluene
4
8
2
1
4
5
5
4
7
70
70
70
70
70
70
70
80
60
83
84
86
76
81
87
84
78
84
9
10
11
1
[a] The substrate 1a (0.3 mmol) and CuBr2 were dissolved in sol-
vent (2 mL) and the resulting mixture was heated at 60 °C. [b] Iso-
lated yield. [c] The product was contaminated with some insepa-
rable impurities with a purity of ca. 90%.
[a] Reagents and conditions: 1a (0.3 mmol), CuCl2·2H2O, solvent
With the optimized reaction conditions in hand, a range
of substituted substrates were examined and the reaction
was found to proceed smoothly to give 4-bromo-2,5-dihy-
dro-1,2-oxaphosphole 2-oxides 2 in moderate to good
(2 mL). [b] Isolated yield.
Moderate to excellent yields were observed in the
yields, indicating a broad substrate scope; R1 could be allyl, CuCl2·2H2O-mediated chlorocyclization reaction, although
alkyl, or phenyl groups whereas R2 and R3 could be alkyl longer reaction times were necessary (Table 4, entries 1–8).
groups (Table 2, entries 1–11).
When R2 and R3 were not the same, as expected, a mix-
Chlorides are a better potential halide source with re- ture of diastereoisomers were obtained in the presence of
spect to atom economy and safety. With the commercially 4.0 equiv. CuCl2·2H2O under otherwise identical conditions
available CuCl2·2H2O, the results of chlorocyclization un- (Scheme 3). The relative configuration of the two isomers
der different reaction conditions are summarized in Table 3. was unambiguously confirmed by an X-ray diffraction
In contrast to the results obtained in the former case, the study of cis-3k (Figure 1).[15]
reaction in toluene with 3.0 equiv. CuCl2·2H2O led to the
Furthermore, optically active substrate (Sa)-(–)-1n was
best result, considering the loading of each reagent (Table 3, synthesized from optically active (S)-1-phenylpenta-1-yn-3-
entry 6). The use of higher or lower temperatures gave in- ol according to a known procedure.[16] Under the standard
ferior results (Table 3, entries 8 and 9). It should be noted conditions, the reaction afforded a mixture of (S,S)-3k and
that electrophilic cyclization reactions with other typical cy- (S,R)-3k (Scheme 4) and the absolute configurations in
clization reagents (e.g., Cl2 or NCS), are not very conve- (S,S)-3k were unambiguously established by an X-ray dif-
nient.[14]
fraction analysis,[17] indicating the efficient transformation
2
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Direct Halocyclization of 1,2-Allenylphosphonates
Table 4. CuCl2·2H2O-mediated chlorocyclization reaction of 1,2-
allenylphosphonates.[a]
Entry R1
R2
R3
Time
[h]
Yield
[%][b]
1
2
3
nBu
Ph
Me
Me
Me
Me (1a)
Me (1b)
Me (1c)
5
24
22.5
85 (3a)
97 (3b)
68 (3c)
Figure 1. ORTEP representation of cis-3k.
allyl
2-methyl-
allyl
nBu
nBu
Ph
4
Me
Me (1d)
22.5
87 (3d)
5
6
7
8
–(CH2)5– (1f)
5
5
7
7
82 (3e)
72 (3f)
90 (3g)
83 (3h)
–(CH2)4– (1g)
–(CH2)5– (1h)
–(CH2)4– (1i)
Ph
[a] Reagents and conditions:
(0.9 mmol), toluene (2 mL), 70 °C. [b] Isolated yield.
1
(0.3 mmol), CuCl2·2H2O
Scheme 4. Synthesis and cyclization of optically active 1,2-allenyl-
phosphonate (Sa)-(–)-1n.
Figure 2. ORTEP representation of (S,S)-3k.
nation of the copper salt to the relatively electron-rich C=C
bond forms intermediate M1. Then, anti-oxy-metalation af-
fords the five-membered intermediate M2. Arbuzov type
Scheme 3. Chlorocyclization reaction of 1,2-allenylphosphonates.
of axial chirality from the easily available optically active dealkylation of the ethoxy groups mediated by a chloride
propargylic alcohol into the central chirality of the final anion leads to the formation of intermediates M4A and
products (Figure 2). Optically active diethyl 1,2-allenyl- M4B. Subsequently, C–X bond formation in the presence
phosphonate was also tested in the chlorocyclization; the of a second molecule of CuX2 generates the final product 3
results are summarized in Scheme 5.
together with two molecules of CuX.[8–10]
Based on these results and on previous reports,[10] we
We then studied the Suzuki cross-coupling reaction of
propose a possible mechanism (Scheme 6). Firstly, coordi- the C–Cl bonds in 3.[18] We have previously developed an
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N. Xin, S. Ma
FULL PAPER
Table 5. The Suzuki cross-coupling reaction of 4-chloro-2,5-dihy-
dro-1,2-oxaphosphole 2-oxides 3 with phenylboronic acid.[a]
Entry
R1
Time [h]
Yield of 4 [%][b]
1
2
3
nBu (3a)
Ph (3b)
allyl (3c)
5
17
10.5
75 (4a)
78 (4b)
55 (4c)
[a] Reagents and conditions: 3 (0.3 mmol), phenylboronic acid
(0.75 mmol), [PdCl2(LB-Phos)2] (0.015 mmol), K2CO3
(1.05 mmol), toluene (2 mL), reflux. [b] Isolated yield.
Scheme 5. Chorocyclization of optically active 1,2-allenylphos-
phonates.
Scheme 6. Proposed mechanism for the halocyclization.
Scheme 7. Suzuki coupling reaction of diastereoisomers of 3.
electron-rich, sterically bulky phosphane ligand, dicyclo-
hexyl(2,4,6-trimethoxyphenyl)phosphane
(LB-Phos),[12]
that can be used to selectively activate the relatively inert
C–Cl bond over the more reactive lactonic allylic C–O
bond.[12b] We used the prepared [PdCl2(LB-Phos)2] complex
as the catalyst and 3.5 equiv. K2CO3 as the base. The reac-
tion with phenylboronic acid in toluene at reflux proceeded
smoothly to afford the corresponding coupling products in
moderate to good yields (Table 5).
When R2 and R3 were not the same, Suzuki coupling of
both diastereoisomers could be conducted under standard
conditions to afford the corresponding products with sim-
ilar yields (Scheme 7).When optically active substrates were
used, coupling products were obtained in good yields with-
out apparent racemization (Scheme 8).
Scheme 8. Suzuki coupling reaction of optically active phosphona-
tes.
nient and efficient synthesis of 4-halo-2,5-dihydro-1,2-oxa-
phosphole 2-oxides in satisfactory yields and the subse-
quent Suzuki cross-coupling of the resulting vinylic chlor-
Conclusions
We have demonstrated a CuX2-mediated direct halocy- ides. Compared with the results described in the previous
clization of diethyl 1,2-allenylphosphonates for the conve- report,[11] this transformation shows better functional
4
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Direct Halocyclization of 1,2-Allenylphosphonates
1029 cm–1. MS (70 eV, EI): m/z (%) = 320 (84.04) [M]+, 182 (100).
group tolerance, requires fewer steps, and is simpler to per-
form. Furthermore, the axial chirality of substrate was
transferred efficiently to the central carbon atom in the fi-
nal, optically active 4-chloro-2,5-dihydro-1,2-oxaphosphole
2-oxides. Considering the high loading of functionalities,
ready availability of the optically active starting materials,
HRMS (EI): calcd. for C18H25O3P [M]+ 320.1541; found 320.1542.
Diethyl
(3,3-Tetramethylene-1-phenylpropa-1,2-dien-1-yl)phos-
phonate (1i): The reaction of 1,1-tetramethylene-3-phenylprop-2-
yn-1-ol (931.3 mg, 5 mmol), P(OEt)2Cl (1174.1 mg, 7.5 mmol), and
Et3N (708.3 mg, 7 mmol) afforded 1i (714.4 mg, 47%) as a liquid.
and potential application of phosphorus-containing com- 1H NMR (300 MHz, CDCl3): δ = 7.55 (d, J = 8.1 Hz, 2 H, 2 ϫ Ph-
H), 7.37–7.18 (m, 3 H, 3 ϫ Ph-H), 4.22–4.00 (m, 4 H, 2ϫ OCH2),
2.70–2.48 (m, 4 H), 1.86–1.70 (m, 4 H), 1.30 (t, J = 7.2 Hz, 6 H,
OCH2CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 204.9 (d, JP,C
= 4.5 Hz), 133.4 (d, JP,C = 10.6 Hz), 128.4, 127.6 (d, JP,C = 6.0 Hz),
127.1, 107.3 (d, JP,C = 15.8 Hz), 97.0 (d, JP,C = 191.5 Hz), 62.4 (d,
pounds, this reaction should be useful in organic synthesis.
Further studies in this area are in progress in our labora-
tory.
JP,C = 6.0 Hz), 31.1 (d, JP,C = 6.0 Hz), 27.3, 16.3 (d, JP,C
=
Experimental Section
6.0 Hz) ppm. 31P NMR (121.5 MHz, CDCl3): δ = 17.0 ppm. IR
General: Racemic starting materials 1a–n and optically active start-
ing materials (S)-(+)-1l, (S)-(+)-1m, and (S)-(–)-1n were prepared
according to known procedures.[11] The ee values were determined
by HPLC analysis using chiral columns under the conditions noted
in the procedures. For details of all analytical instruments used, see
ref.[12]
(neat): ν = 3537, 3479, 3058, 2959, 1943, 1598, 1491, 1442, 1388,
˜
1250, 1025 cm–1. MS (70 eV, EI): m/z (%) = 306 (33.02) [M]+, 168
(100). HRMS (EI): calcd. for C17H23O3P [M]+ 306.1385; found
306.1388.
Diethyl (3-Ethyl-1-phenylpenta-1,2-dien-1-yl)phosphonate (1j): The
reaction of 3-ethyl-1-phenylpenta-1-yn-3-ol (941.0 mg, 5 mmol),
P(OEt)2Cl (1174.1 mg, 7.5 mmol), and Et3N (708.3 mg, 7 mmol)
afforded 1j (854.1 mg, 55%) as a liquid. 1H NMR (300 MHz,
CDCl3): δ = 7.58 (d, J = 8.1 Hz, 2 H, 2 ϫ Ph-H), 7.37–7.18 (m, 3
H, 3 ϫ Ph-H), 4.22–4.00 (m, 4 H, 2ϫ OCH2), 2.28–2.10 (m, 4 H),
1.29 (t, J = 7.0 Hz, 6 H), 1.11 (t, J = 7.4 Hz, 6 H, 2ϫ
CH2CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 208.3 (d, JP,C
= 4.3 Hz), 133.4 (d, JP,C = 10.2 Hz), 128.4, 127.2 (d, JP,C = 5.9 Hz),
127.1, 112.3 (d, JP,C = 14.6 Hz), 98.9 (d, JP,C = 190.9 Hz), 62.2 (d,
JP,C = 6.2 Hz), 25.4 (d, JP,C = 6.0 Hz), 16.2 (d, JP,C = 6.7 Hz), 12.1
(d, JP,C = 2.0 Hz) ppm. 31P NMR (121.5 MHz, CDCl3): δ =
Synthesis of Starting Materials
Diethyl (6-Chloro-2-methylhepta-2,3,6-trien-4-yl)phosphonate (1e).
Typical Procedure: To a solution of 6-chloro-2-methylhepta-6-en-
3-yn-2-ol (1.2645 g, 8 mmol) and Et3N (1295.2 mg, 12.8 mmol) in
CH2Cl2 (15 mL), was added a solution of P(OEt)2Cl (2003.8 mg,
12.8 mmol) in CH2Cl2 (9 mL) dropwise at –78 °C. After the ad-
dition, the resulting mixture was warmed to room temp. and then
stirred at room temperature overnight. After complete conversion
of the corresponding propargylic alcohol (reaction monitored by
TLC; petroleum ether/ethyl acetate, 3:1) the solvent was evapo-
rated, then H2O (80 mL) and ethyl acetate (80 mL) were added.
The organic layer was separated and the organic layer was washed
with brine (80 mL) and dried with anhydrous Na2SO4. After fil-
tration and evaporation, the residue was purified by chromatog-
raphy on silica gel (petroleum ether/ethyl acetate, 5:1) to afford 1e
16.9 ppm. IR (neat): ν = 3059, 3026, 2959, 2904, 2869, 1943, 1598,
˜
1493, 1477, 1447, 1390, 1284, 1254, 1162, 1097, 1053, 1026 cm–1.
MS (70 eV, EI): m/z (%) = 308 (25.20) [M]+, 170 (100). HRMS
(EI): calcd. for C17H25O3P [M]+ 308.1541; found 308.1541.
Diethyl (7-Propyldeca-5,6-dien-5-yl)phosphonate (1k): The reaction
of 4-propyldeca-5-yn-4-ol (1980.0 mg, 10 mmol), P(OEt)2Cl
(2348.2 mg, 15 mmol), and Et3N (1416.8 mg, 14 mmol) afforded 1k
(1610.9 mg, 51%) as a liquid. 1H NMR (300 MHz, CDCl3): δ =
4.15–3.92 (m, 4 H, 2ϫ OCH2), 2.18–1.89 (m, 6 H), 1.50–1.20 (m,
14 H), 0.96–0.80 (m, 9 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ
= 205.6 (d, JP,C = 4.2 Hz), 106.0 (d, JP,C = 17.0 Hz), 93.6 (d, JP,C
= 189.2 Hz), 60.9 (d, JP,C = 2.9 Hz), 33.5 (d, JP,C = 5.4 Hz), 29.9
(d, JP,C = 6.6 Hz), 27.9 (d, JP,C = 8.3 Hz), 21.6, 20.0, 15.6 (d, JP,C
1
(1.1147 g, 50%) as a liquid. H NMR (300 MHz, CDCl3): δ = 5.24
(s, 1 H, =CHH), 5.21 (s, 1 H, =CHH), 4.14–3.94 (m, 4 H, 2ϫ
OCH2), 3.12 (d, J = 11.4 Hz, 2 H, CH2), 1.77 (s, 3 H), 1.75 (s, 3
H), 1.29 (t, J = 7.1 Hz, 6 H, OCH2CH3) ppm. 13C NMR
(75.4 MHz, CDCl3): δ = 208.7 (d, JP,C = 6.0 Hz), 139.3 (d, JP,C
7.5 Hz), 114.3, 98.9 (d, JP,C = 15.8 Hz), 87.8 (d, JP,C = 193.8 Hz),
62.1 (d, JP,C = 6.0 Hz), 39.2 (d, JP,C = 10.6 Hz), 19.2 (d, JP,C
6.8 Hz), 16.2 (d, JP,C = 6.8 Hz) ppm. 31P NMR (121.5 MHz,
=
=
CDCl ): δ = 17.6 ppm. IR (neat): ν = 2984, 2940, 2909, 1962, 1635,
˜
3
=
5.7 Hz), 13.1 ppm. 31P NMR (121.5 MHz, CDCl3):
δ =
1444, 1378, 1244, 1163, 1022 cm–1. MS (70 eV, EI): m/z (%) = 280
(7.25) [M(37Cl)]+, 278 (19.76) [M(35Cl)]+, 243 (100) (M – Cl)+.
HRMS (EI): calcd. for C12H20O3P35Cl [M]+ 278.0839; found
278.0831.
19.8 ppm. IR (neat): ν = 2959, 2932, 2872, 1951, 1725, 1462, 1392,
˜
1253, 1163, 1098, 1055, 1029 cm–1. MS (70 eV, EI): m/z (%) = 316
(30.17) [M]+, 245 (100). HRMS (EI): calcd. for C17H33O3P [M]+
316.2167; found 316.2169.
Diethyl
(3,3-Pentamethylene-1-phenylpropa-1,2-dien-1-yl)phos-
phonate (1h): The reaction of 1,1-pentamethylene-3-phenylprop-2-
Diethyl (Nona-3,4-dien-5-yl)phosphonate (1l): The reaction of non-
yn-1-ol (1001.5 mg, 5 mmol), P(OEt)2Cl (1174.2 mg, 7.5 mmol), 4-yn-3-ol (1822.9 mg,
13 mmol),
P(OEt)2Cl (3256.2 mg,
and Et3N (758.9 mg, 7.5 mmol) afforded 1h (1369.6 mg, 85%) as a
liquid. H NMR (300 MHz, CDCl3): δ = 7.57 (d, J = 8.1 Hz, 2 H,
20.8 mmol), and Et3N (2104.8 mg, 20.8 mmol) afforded 1l
1
(1176.6 mg, 55%) as a liquid. 1H NMR (300 MHz, CDCl3): δ =
2 ϫ Ph-H), 7.38–7.18 (m, 3 H, 3 ϫ Ph-H), 4.24–4.00 (m, 4 H, 2ϫ 5.50–5.35 (m, 1 H, CH=), 4.20–3.96 (m, 4 H, 2ϫ OCH2), 2.21–
OCH2), 2.40–2.20 (m, 4 H), 1.82–1.48 (m, 6 H), 1.30 (t, J = 6.9 Hz, 1.97 (m, 4 H), 1.54–1.19 (m, 10 H), 1.04 (t, J = 7.4 Hz, 3 H), 0.89
6 H, 2ϫ OCH2CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ =
205.8 (d, JP,C = 3.8 Hz), 133.3 (d, JP,C = 10.6 Hz), 128.4, 127.5 (d,
(t, J = 7.2 Hz, 3 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 208.0
(d, JP,C = 6.0 Hz), 95.0 (d, JP,C = 16.6 Hz), 94.7 (d, JP,C = 187.7 Hz),
JP,C = 5.3 Hz), 127.0, 105.9 (d, JP,C = 15.1 Hz), 94.6 (d, JP,C
190.8 Hz), 62.3 (d, JP,C = 6.0 Hz), 30.2 (d, JP,C = 6.0 Hz), 27.0 (d,
JP,C = 3.0 Hz), 25.7, 16.2 (d, JP,C = 6.0 Hz) ppm. 31P NMR 13.3 (d, JP,C = 3.8 Hz) ppm. 31P NMR (121.5 MHz, CDCl3): δ =
=
62.0 (d, JP,C = 6.0 Hz), 30.2 (d, JP,C = 6.8 Hz), 28.1 (d, JP,C
=
7.5 Hz), 22.1, 21.2 (d, JP,C = 6.8 Hz), 16.3 (d, JP,C = 6.8 Hz), 13.8,
(121.5 MHz, CDCl ): δ = 16.4 ppm. IR (neat): ν = 2982, 2932, 18.9 ppm. IR (neat): ν = 2964, 2933, 2873, 2734, 2232, 1952, 1636,
˜
˜
3
2855, 1945, 1597, 1493, 1445, 1391, 1340, 1316, 1256, 1163, 1053,
1460, 1392, 1301, 1244, 1164, 1098, 1052, 1023 cm–1. MS (70 eV,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O20228
/KAP1
Date: 25-05-12 10:23:31
Pages: 13
N. Xin, S. Ma
FULL PAPER
EI): m/z (%) = 260 (5.66) [M]+, 79 (100). HRMS (EI): calcd. for
3.8 Hz), 22.0, 16.3, 16.2, 13.7 (d, JP,C = 13.6 Hz) ppm. 31P NMR
C13H25O3P [M]+ 260.1541; found 260.1542.
(121.5 MHz, CDCl ): δ = 19.0 ppm. IR (neat): ν = 2959, 2932,
˜
3
2873, 1952, 1464, 1443, 1392, 1246, 1164, 1098, 1052, 1024 cm–1.
MS (70 eV, EI): m/z (%) = 274 (20.19) [M]+, 203 (100). HRMS
(EI): calcd. for C14H27O3P [M]+ 274.1698; found 274.1697.
Diethyl (Deca-5,6-dien-5-yl)phosphonate (1m): The reaction of dec-
5-yn-4-ol (2743.0 mg, 10 mmol), P(OEt)2Cl (2348.2 mg, 15 mmol),
and Et3N (1416.7 mg, 14 mmol) afforded 1m (1690.5 mg, 62%) as
a liquid. 1H NMR (300 MHz, CDCl3): δ = 5.45–5.28 (m, 1 H,
CH=), 4.18–3.95 (m, 4 H, 2ϫ OCH2), 2.20–1.95 (m, 4 H), 1.52–
1.26 (m, 12 H), 0.99–0.82 (m, 6 H) ppm. 13C NMR (75.4 MHz,
CDCl3): δ = 208.1 (d, JP,C = 6.0 Hz), 93.6 (d, JP,C = 188.2 Hz), 92.9
(d, JP,C = 15.8 Hz), 61.8 (d, JP,C = 5.9 Hz), 30.1, 30.0, 29.9 (d, JP,C
= 6.3 Hz), 28.0 (d, JP,C = 6.9 Hz), 22.2 (d, JP,C = 4.2 Hz), 21.9,
16.1 (d, JP,C = 6.4 Hz), 13.5 (d, JP,C = 13.3 Hz) ppm. 31P NMR
Diethyl (1-Phenylpenta-1,2-dien-1-yl)phosphonate [(Sa)-(–)-1n]: The
reaction of (S)-1-phenylpenta-1-yn-3-ol (801.1 mg, 5 mmol),
P(OEt)2Cl (1174.2 mg, 7.5 mmol), and Et3N (758.9 mg, 7.5 mmol)
afforded (Sa)-(–)-1n (580.6 mg, 41%) as a liquid; ee = 97% [HPLC
conditions: Chiralcel IC-H column; hexane/iPrOH = 95:5; 0.5 mL/
min; λ = 214 nm; tR = 53.9 (major), 57.8 (minor) min]; [α]2D0 = –52.5
1
(c = 1.06, CHCl3). H NMR (300 MHz, CDCl3): δ = 7.58 (d, J =
8.4 Hz, 2 H, 2 ϫ Ph-H), 7.40–7.19 (m, 3 H, 3 ϫ Ph-H), 5.86–5.73
(m, 1 H, CH=), 4.25–4.02 (m, 4 H, 2ϫ OCH2), 2.31–2.17 (m, 2 H,
CH2), 1.30 (t, J = 7.1 Hz, 6 H, 2ϫ OCH2CH3), 1.14 (t, J = 7.5 Hz,
3 H, CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 210.2 (d, JP,C
= 2.9 Hz), 132.2 (d, JP,C = 8.9 Hz), 128.2, 127.3, 127.2, 97.8 (d, JP,C
= 189.6 Hz), 96.1 (d, JP,C = 14.6 Hz), 62.3 (d, JP,C = 5.9 Hz), 21.0
(121.5 MHz, CDCl ): δ = 19.0 ppm. IR (neat): ν = 2959, 2932,
˜
3
2873, 1952, 1464, 1443, 1392, 1246, 1164, 1098, 1052, 1024 cm–1.
MS (70 eV, EI): m/z (%) = 274 (1.81) [M]+, 81 (100). HRMS (EI):
calcd. for C14H27O3P [M]+ 274.1698; found 274.1700.
Diethyl (1-Phenylpenta-1,2-dien-1-yl)phosphonate (1n): The reaction
of 1-phenylpenta-1-yn-3-ol (1602.3 mg, 10 mmol), P(OEt)2Cl
(2348.2 mg, 15 mmol), and Et3N (1416.7 mg, 14 mmol) afforded 1n
(1910.9 mg, 68%) as a liquid. 1H NMR (300 MHz, CDCl3): δ =
7.57 (d, J = 7.5 Hz, 2 H, 2 ϫ Ph-H), 7.40–7.19 (m, 3 H, 3 ϫ Ph-
H), 5.87–5.72 (m, 1 H, CH=), 4.26–4.01 (m, 4 H, 2ϫ OCH2), 2.32–
2.15 (m, 2 H, CH2), 1.30 (t, J = 7.2 Hz, 6 H, 2ϫ CH2CH3), 1.14
(t, J = 7.5 Hz, 3 H, CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ =
210.4 (d, JP,C = 4.5 Hz), 132.4 (d, JP,C = 8.3 Hz), 128.5, 127.5 (d,
(d, JP,C = 6.6 Hz), 16.0 (d, JP,C = 6.7 Hz), 13.0 (d, JP,C
=
2.3 Hz) ppm. 31P NMR (121.5 MHz, CDCl3): δ = 16.0 ppm. IR
(neat): ν = 3062, 2978, 2934, 2905, 1943, 1597, 1579, 1494, 1448,
˜
1391, 1369, 1245, 1163, 1097, 1051, 1021 cm–1. MS (70 eV, EI): m/z
(%) = 280 (11.07) [M]+, 128 (100). HRMS (EI): calcd. for
C15H21O3P [M]+ 280.1228; found 280.1226.
CuBr2-Mediated Bromocyclization Reaction of 1,2-Allenylphosphon-
ates Affording 4-Bromo-2,5-dihydro-1,2-oxaphosphole 2-Oxides 2
JP,C = 6.0 Hz), 127.4, 98.0 (d, JP,C = 189.2 Hz), 96.3 (d, JP,C
=
15.1 Hz), 62.5 (d, JP,C = 6.0 Hz), 21.2 (d, JP,C = 6.0 Hz), 16.2 (d,
4-Bromo-3-butyl-5,5-dimethyl-2-ethoxy-2,5-dihydro-1,2-oxaphos-
phole 2-Oxide (2a). Typical Procedure: A mixture of 1a (78.1 mg,
0.30 mmol) and CuBr2 (147.4 mg, 0.66 mmol) was stirred at 60 °C
in EtOH (2 mL). After 1 h, the reaction was complete (reaction
monitored by TLC; petroleum ether/ethyl acetate, 3:1). The solvent
was evaporated and the residue was subjected to column
chromatography on silica gel (petroleum ether/ethyl acetate, 5:1) to
afford 2a (84.9 mg, 91 %) as an oil.[11] 1H NMR (300 MHz,
CDCl3): δ = 4.22–3.90 (m, 2 H, OCH2), 2.42–2.00 (m, 2 H, CH2
from C4H9), 1.60–1.45 (m, 8 H, CH2 and 2 ϫ CH3), 1.45–1.15 (m,
5 H), 0.82 (t, J = 6.9 Hz, 3 H, OCH2CH3) ppm. 13C NMR
JP,C = 6.8 Hz), 13.2 (d, JP,C = 3.0 Hz) ppm. 31P NMR (121.5 MHz,
CDCl ): δ = 16.0 ppm. IR (neat): ν = 3062, 2978, 2934, 2905, 1943,
˜
3
1597, 1579, 1494, 1448, 1391, 1369, 1245, 1163, 1097, 1051,
1021 cm–1. MS (70 eV, EI): m/z (%) = 280 (11.07) [M]+, 128 (100).
HRMS (EI): calcd. for C15H21O3P [M]+ 280.1228; found 280.1226.
Diethyl (Nona-3,4-dien-5-yl)phosphonate [(Sa)-(+)-1l]: The reaction
of (S)-non-4-yn-3-ol (1402.5 mg, 10 mmol), P(OEt)2Cl (2348.2 mg,
15 mmol), and Et3N (1517.8 mg, 15 mmol) afforded (Sa)-(+)-1l
(1133.1 mg, 44%) as a liquid; ee Ͼ 99% [HPLC conditions: Chi-
ralcel IC-H column; hexane/iPrOH = 95:5; 0.5 mL/min; λ =
214 nm; tR = 33.4 (major), 35.1 (minor) min]; [α]2D0 = +35.2 (c =
1.04, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 5.48–5.31 (m, 1
H, CH=), 4.12–3.92 (m, 4 H, 2ϫ OCH2), 2.16–1.96 (m, 4 H), 1.50–
1.21 (m, 10 H), 1.00 (t, J = 7.4 Hz, 3 H), 0.85 (t, J = 7.2 Hz, 3
(75.4 MHz, CDCl3): δ = 143.2 (d, JP,C = 52.8 Hz), 128.3 (d, JP,C
=
150.8 Hz), 86.0 (d, JP,C = 4.0 Hz), 62.8 (d, JP,C = 6.8 Hz), 29.1 (d,
JP,C = 1.6 Hz), 27.3, 27.2 (d, JP,C = 3.2 Hz), 26.5, 22.2, 16.3 (d, JP,C
= 6.1 Hz), 13.5 ppm. MS (70 eV, EI): m/z (%) = 312 (1.16)
[M(81Br)]+, 310 (1.31) [M(79Br)]+, 41 (100).
H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 207.9 (d, JP,C
=
6.0 Hz), 94.9 (d, JP,C = 15.8 Hz), 94.5 (d, JP,C = 187.7 Hz), 61.9 (d,
JP,C = 6.0 Hz), 30.1 (d, JP,C = 6.8 Hz), 28.0 (d, JP,C = 6.8 Hz), 22.0,
4-Bromo-2-ethoxy-2,5-dihydro-5,5-dimethyl-3-phenyl-1,2-oxaphos-
phole 2-Oxide (2b): The reaction of 1b (84.1 mg, 0.30 mmol) and
CuBr2 (147.9 mg, 0.66 mmol) in EtOH (2 mL) afforded 2b
21.1 (d, JP,C = 6.8 Hz), 16.2 (d, JP,C = 6.8 Hz), 13.7, 13.2 (d, JP,C
=
3.0 Hz) ppm. 31P NMR (121.5 MHz, CDCl3): δ = 18.9 ppm. IR
1
(68.8 mg, 69%) as an oil. H NMR (300 MHz, CDCl3): δ = 7.67
(neat): ν = 2981, 2958, 2933, 2909, 2861, 2714, 1959, 1639, 1445,
˜
(d, J = 6.6 Hz, 2 H, 2 ϫ Ph-H), 7.48–7.32 (m, 3 H, 3 ϫ Ph-H),
4.18–3.96 (m, 2 H, OCH2), 1.65 (s, 3 H, CH3), 1.61 (s, 3 H, CH3),
1.17 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C NMR (75.4 MHz, CDCl3):
δ = 142.0 (d, JP,C = 45.5 Hz), 129.9 (d, JP,C = 10.0 Hz), 129.0 (d,
1379, 1294, 1243, 1164, 1097, 1052, 1023 cm–1. MS (70 eV, EI): m/z
(%) = 260 (16.04) [M]+, 79 (100). HRMS (EI): calcd. for
C13H25O3P [M]+ 260.1541; found 260.1542.
JP,C = 1.2 Hz), 128.5, 128.0 (d, JP,C = 6.2 Hz), 127.7 (d, JP,C
=
Diethyl (Deca-5,6-dien-5-yl)phosphonate [(Sa)-(+)-1m]: The reaction
of (S)-dec-5-yn-4-ol (925.5 mg, 6 mmol), P(OEt)2Cl (1408.9 mg,
9 mmol), and Et3N (911.0 mg, 9 mmol) afforded (Sa)-(+)-1m
(1028.3 mg, 62%) as a liquid; ee Ͼ 99% [HPLC conditions: Chi-
ralcel IC-H column; hexane/iPrOH = 95:5; 0.5 mL/min; λ =
214 nm; tR = 30.7 (major), 32.8 (minor) min]; [α]2D0 = +42.0 (c =
1.04, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 5.42–5.28 (m, 1
H, CH=), 4.18–3.90 (m, 4 H, 2ϫ OCH2), 2.20–1.92 (m, 4 H), 1.50–
1.20 (m, 12 H), 1.00–0.81 (m, 6 H) ppm. 13C NMR (75.4 MHz,
153.9 Hz), 86.4 (d, JP,C = 3.5 Hz), 63.6 (d, JP,C = 7.5 Hz), 27.2 (d,
JP,C = 3.8 Hz), 26.9 (d, JP,C = 1.4 Hz), 16.2 (d, JP,C = 5.6 Hz) ppm.
MS (70 eV, EI): m/z (%) = 333 (4.66) [M(81Br) + 1]+, 332 (32.15)
[M(81Br)]+, 331 (5.90) [M(79Br) + 1]+, 330 (32.72) [M(79Br)]+, 317
(40.53) [M(81Br) – CH3]+, 315 (41.20) [M(79Br) – CH3]+, 251
(50.35) [M – Br]+, 223 (100). HRMS (EI): calcd. for C13H16O3P79Br
[M]+ 330.0020; found 330.0023.
3-Allyl-4-bromo-2-ethoxy-2,5-dihydro-5,5-dimethyl-1,2-oxaphos-
CDCl3): δ = 208.2 (d, JP,C = 6.0 Hz), 93.8 (d, JP,C = 188.4 Hz), 93.1 phole 2-Oxide (2c): The reaction of 1c (73.3 mg, 0.30 mmol) and
(d, JP,C = 16.0 Hz), 62.0 (d, JP,C = 6.0 Hz), 30.10 (d, JP,C = 7.8 Hz),
30.06 (d, JP,C = 8.1 Hz), 28.1 (d, JP,C = 7.5 Hz), 22.3 (d, JP,C
CuBr2 (147.5 mg, 0.66 mmol) in EtOH (2 mL) afforded 2c
=
(66.5 mg, 75 %) as an oil.[11] 1H NMR (300 MHz, CDCl3): δ =
6
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Job/Unit: O20228
/KAP1
Date: 25-05-12 10:23:31
Pages: 13
Direct Halocyclization of 1,2-Allenylphosphonates
5.92–5.62 (m, 1 H, =CH), 5.24–4.92 (m, 2 H, =CH2), 4.17–3.88 (m,
3.6 Hz), 62.9 (d, JP,C = 6.9 Hz), 38.4 (d, JP,C = 3.2 Hz), 37.8 (d, JP,C
2 H, OCH2), 3.17–2.82 (m, 2 H, =CCH2), 1.49 (s, 3 H, CH3), 1.45 = 1.8 Hz), 29.3 (d, JP,C = 1.7 Hz), 27.6 (d, JP,C = 10.1 Hz), 24.4 (d,
(s, 3 H, CH3), 1.24 (t, J = 6.9 Hz, 3 H, CH3) ppm. 13C NMR JP,C = 3.8 Hz), 22.3, 16.4 (d, JP,C = 6.2 Hz), 13.6 ppm. MS (70 eV,
(75.4 MHz, CDCl3): δ = 144.2 (d, JP,C = 47.4 Hz), 131.6 (d, JP,C
2.5 Hz), 126.6 (d, JP,C = 154.1 Hz), 117.8, 86.3 (d, JP,C = 3.6 Hz),
63.4 (d, JP,C = 6.4 Hz), 31.8 (d, JP,C = 10.1 Hz), 27.3 (d, JP,C
=
EI): m/z (%) = 338 (10.74) [M(81Br)]+, 336 (10.82) [M(79Br)]+, 296
(98.70) [M(81Br) – C3H6]+, 294 (100) [M(79Br) – C3H6]+, 257 (93.32)
[M – Br]+.
=
2.6 Hz), 26.7 (d, JP,C = 1.6 Hz), 16.4 (d, JP,C = 6.3 Hz) ppm. MS
(70 eV, EI): m/z (%) = 297 (2.63) [M(81Br) + 1]+, 296 (22.97)
[M(81Br)]+, 295 (3.84) [M(79Br) +1]+, 294 (22.14) [M(79Br)]+, 268
(54.15) [M(81Br) – C2H4]+, 266 (53.45) [M(79Br) – C2H4]+, 215
(10.08) [M – Br]+, 105 (100).
4-Bromo-2-ethoxy-3-phenyl-1-oxa-2-phosphaspiro[4.5]dec-3-ene-
2-oxide (2h): The reaction of 1h (96.1 mg, 0.30 mmol) and CuBr2
(147.4 mg, 0.66 mmol) in EtOH (2 mL) afforded 2h (94.4 mg, 85%)
as a white solid; m.p. 126–127 °C (petroleum ether/ethyl acetate).
1H NMR (300 MHz, CDCl3): δ = 7.66 (d, J = 7.2 Hz, 2 H, 2 ϫ Ph-
H), 7.51–7.30 (m, 3 H, 3 ϫ Ph-H), 4.20–3.98 (m, 2 H, OCH2), 2.18–
1.90 (m, 2 H, cyclohexyl), 1.90–1.60 (m, 7 H, cyclohexyl), 1.32–1.12
(m, 4 H, OCH2CH3 and cyclohexyl) ppm. 13C NMR (75.4 MHz,
4-Bromo-2-ethoxy-2,5-dihydro-5,5-dimethyl-3-(2Ј-methylallyl)-1,2--
oxaphosphole 2-Oxide (2d): The reaction of 1d (77.5 mg,
0.30 mmol) and CuBr2 (147.4 mg, 0.66 mmol) in EtOH (2 mL) af-
forded 2d (70.9 mg, 77 %) as an oil.[11] 1H NMR (300 MHz, CDCl3): δ = 142.5 (d, JP,C = 45.8 Hz), 130.1 (d, JP,C = 10.0 Hz),
CDCl3): δ = 4.83 (s, 2 H, =CH2), 4.20–3.97 (m, 2 H, OCH2), 3.15– 129.0, 128.5, 128.2 (d, JP,C = 6.2 Hz), 127.7 (d, JP,C = 154.6 Hz),
2.90 (m, 2 H, =CCH2), 1.72 (s, 3 H, CH3), 1.54 (s, 3 H, CH3), 1.51
88.1 (d, JP,C = 3.4 Hz), 63.5 (d, JP,C = 6.2 Hz), 34.8 (d, JP, C
2.7 Hz), 34.6, 24.2, 21.3 (d, JP, C = 12.2 Hz), 16.3 (d, JP, C
=
=
(s, 3 H, CH3), 1.25 (td, J = 6.3, 1.1 Hz, 3 H, CH3) ppm. 13C NMR
(75.4 MHz, CDCl3): δ = 145.2 (d, JP,C = 47.6 Hz), 139.8 (d, JP,C
1.6 Hz), 126.9 (d, JP,C = 154.3 Hz), 113.4, 86.2 (d, JP,C = 3.9 Hz),
63.4 (d, JP,C = 6.6 Hz), 35.7 (d, JP,C = 9.4 Hz), 27.3 (d, JP, C
=
5.6 Hz) ppm. MS (70 eV, EI): m/z (%) = 373 (2.44) [M(81Br) + 1]+,
372 (12.05) [M(81Br)]+, 371 (3.40) [M(79Br) +1]+, 370 (13.23)
[M(79Br)]+, 291 (100) [M – Br]+. C16H20BrO3P (371.21): calcd. C
=
2.8 Hz), 26.9 (d, JP,C = 1.0 Hz), 22.1, 16.4 (d, JP,C = 5.9 Hz) ppm. 51.77, H 5.43; found C 51.79, H 5.49.
MS (70 eV, EI): m/z (%) = 311 (0.97) [M(81Br) +1]+, 310 (6.74)
4-Bromol-2-ethoxy-3-phenyl-1-oxa-2-phosphaspiro[4.4]non-3-ene 2-
oxide (2i): The reaction of 1i (91.5 mg, 0.30 mmol) and CuBr2
(147.6 mg, 0.66 mmol) in EtOH (2 mL) afforded 2i (76.9 mg, 72%)
[M(81Br)]+, 309 (1.08) [M(79Br) +1]+, 308 (6.87) [M(79Br)]+, 229
(6.48) [M – Br]+, 119 (100).
4-Bromo-3-(2Ј-chloroallyl)-2-ethoxy-2,5-dihydro-5,5-dimethyl-1,2-- as an oil. 1H NMR (300 MHz, CDCl3): δ = 7.76–7.64 (m, 2 H,
oxaphosphole 2-Oxide (2e): The reaction of 1e (83.4 mg,
2 ϫ Ph-H), 7.46–7.33 (m, 3 H, 3 ϫ Ph-H), 4.20–3.95 (m, 2 H,
0.30 mmol) and CuBr2 (147.3 mg, 0.66 mmol) in EtOH (2 mL) af-
OCH2), 2.36–2.14 (m, 2 H, cyclopentyl), 2.07–1.75 (m, 6 H, cy-
1
forded 2e (78.2 mg, 79%) as an oil. H NMR (300 MHz, CDCl3): clopentyl), 1.18 (t, J = 7.0 Hz, 3 H, OCH2CH3) ppm. 13C NMR
δ = 5.30 (s, 1 H, =CHH), 5.26 (s, 1 H, =CHH), 4.20–3.92 (m, 2 H,
OCH2), 3.42–3.21 (m, 2 H, =CCH2), 1.53 (s, 3 H, CH3), 1.50 (s, 3 9.7 Hz), 129.1, 128.9 (d, JP,C = 154.1 Hz), 128.6, 128.2 (d, JP,C
(75.4 MHz, CDCl3): δ = 140.1 (d, JP,C = 45.8 Hz), 130.2 (d, JP,C
=
=
H, CH3 ), 1.26 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13 C NMR
(75.4 MHz, CDCl3): δ = 147.3 (d, JP,C = 45.8 Hz), 136.2 (d, JP,C
2.6 Hz), 124.6 (d, JP,C = 157.2 Hz), 115.1, 86.6 (d, JP,C = 3.2 Hz),
63.7 (d, JP,C = 6.9 Hz), 37.1 (d, JP,C = 10.9 Hz), 27.3 (d, JP,C
3.2 Hz), 26.7 (d, JP,C = 1.9 Hz), 16.4 (d, JP, C = 6.4 Hz) ppm.
MS (70 eV, EI): m/z (%) = 330 (1.76) [M(81Br35Cl)]+, 328
(1.30) [M(7 9 Br3 5 Cl)]+ , 43 (100). HRMS (EI): calcd. for
C10H15O3P35Cl79Br [M]+ 327.9631; found 327.9630.
6.3 Hz), 96.3 (d, JP,C = 3.5 Hz), 63.7 (d, JP,C = 7.3 Hz), 38.6 (d, JP,C
= 2.9 Hz), 38.5 (d, JP,C = 2.0 Hz), 24.7 (d, JP,C = 1.4 Hz), 16.3 (d,
JP,C = 5.2 Hz) ppm. MS (70 eV, EI): m/z (%) = 358 (5.60) [M(81-
Br)]+, 356 (5.73) [M(79Br)]+, 277 (100) [M – Br]+. HRMS (EI):
calcd. for C15H18O3P 79Br [M]+ 356.0177; found 356.0177.
=
=
4-Bromo-2-ethoxy-5,5-diethyl-2,5-dihydro-3-phenyl-1,2-oxa-
phosphole 2-Oxide (2j): The reaction of 1j (92.8 mg, 0.30 mmol)
and CuBr2 (147.5 mg, 0.66 mmol) in EtOH (2 mL) afforded 2j
1
4-Bromo-3-butyl-2-ethoxy-1-oxa-2-phosphaspiro[4.5]dec-3-ene 2- (87.4 mg, 81%) as an oil. H NMR (300 MHz, CDCl3): δ = 7.72–
Oxide (2f): The reaction of 1f (90.2 mg, 0.30 mmol) and CuBr2
(147.2 mg, 0.66 mmol) in EtOH (2 mL) afforded 2f (93.0 mg, 88%)
7.60 (m, 2 H, 2 ϫ Ph-H), 7.48–7.32 (m, 3 H, 3 ϫ Ph-H), 4.30–4.01
(m, 2 H, OCH2), 2.00–1.82 (m, 4 H), 1.19 (t, J = 7.0 Hz, 3 H),
as an oil.[11] 1H NMR (300 MHz, CDCl3): δ = 4.16–3.96 (m, 2 H, 1.01–0.89 (m, 6 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 139.3
OCH2), 2.41–2.11 (m, 2 H, CH2 from C4H9), 1.92–1.75 (m, 2 H), (d, JP,C = 47.0 Hz), 131.0 (d, JP,C = 156.5 Hz), 130.4 (d, JP,C
1.75–1.40 (m, 9 H), 1.39–1.21 (m, 5 H), 1.16–1.00 (m, 1 H, cyclo- 9.9 Hz), 129.0 (d, JP,C = 1.6 Hz), 128.6, 128.2 (d, JP,C = 6.0 Hz),
hexyl), 0.85 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (75.4 MHz, 92.3 (d, JP,C = 1.9 Hz), 63.8 (d, JP,C = 6.5 Hz), 31.2 (d, JP, C
CDCl3): δ = 143.8 (d, JP,C = 48.6 Hz), 128.3 (d, JP,C = 153.0 Hz), 2.2 Hz), 30.8 (d, JP,C = 2.9 Hz), 16.5 (d, JP,C = 4.4 Hz), 7.2 (d, JP,C
87.8 (d, JP,C = 3.2 Hz), 62.9 (d, JP,C = 6.8 Hz), 35.0 (d, JP, C
=
=
=
= 2.9 Hz) ppm. MS (70 eV, EI): m/z (%) = 360 (15.82) [M+(81Br)],
356 (16.30) [M(79Br)]+, 331 (100) [M(81Br) – C2H5]+, 331 (100)
[M(79Br) – C2H5]+, 279 (46.07) [M – Br]+. HRMS (EI): calcd. for
C15H20O3P79Br [M]+ 358.0333; found 358.0336.
2.3 Hz), 34.3 (d, JP,C = 1.1 Hz), 29.3 (d, JP,C = 2.0 Hz), 27.4 (d, JP,C
= 10.3 Hz), 24.2, 22.3, 21.3, 21.2, 16.4 (d, JP,C = 5.4 Hz), 13.6 ppm.
MS (70 eV, EI): m/z (%) = 353 (2.54) [M(81Br) + 1]+, 352 (14.33)
[M(81Br)]+, 351 (3.82) [M(79Br) + 1]+, 350 (14.15) [M(79Br)]+, 310
(96.82) [M(81Br) – C3H6]+, 308 (100) [M(79Br) – C3H6]+, 271 (37.19)
[M – Br]+.
4-Bromo-3-butyl-2-ethoxy-2,5-dihydro-5,5-dipropyl-1,2-oxaphos-
phole 2-Oxide (2k): The reaction of 1k (95.0 mg, 0.30 mmol) and
CuBr2 (147.2 mg, 0.66 mmol) in EtOH (2 mL) afforded 2k
1
4-Bromo-3-butyl-2-ethoxy-1-oxa-2-phosphaspiro[4.4]non-3-ene 2- (94.2 mg, 85%) as an oil. H NMR (300 MHz, CDCl3): δ = 4.25–
Oxide (2g): The reaction of 1g (85.8 mg, 0.30 mmol) and CuBr2
(148.0 mg, 0.66 mmol) in EtOH (2 mL) afforded 2g (92.1 mg, 91%) 1.55 (m, 4 H), 1.55–1.20 (m, 9 H), 1.15–0.96 (m, 2 H), 0.96–0.70
as an oil.[11] 1H NMR (300 MHz, CDCl3): δ = 4.14–3.92 (m, 2 H, (m, 9 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 140.8 (d, JP,C
OCH2), 2.42–2.16 (m, 2 H, CH2 from C4H9), 2.18–1.96 (m, 2 H), 48.8 Hz), 130.6 (d, JP,C = 154.9 Hz), 91.2 (d, JP,C = 2.0 Hz), 62.9
4.00 (m, 2 H, OCH2), 2.41–2.10 (m, 2 H, CH2 from C4H9), 1.76–
=
1.96–1.62 (m, 6 H), 1.59–1.42 (m, 2 H), 1.38–1.20 (m, 5 H), 0.86
(d, JP,C = 6.8 Hz), 40.2 (d, JP,C = 1.3 Hz), 40.0 (d, JP,C = 2.3 Hz),
29.4 (d, JP,C = 2.3 Hz), 27.3 (d, JP,C = 10.0 Hz), 22.3, 16.5 (d, JP,C
(t, J = 7.2 Hz, 3 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 141.2
(d, JP,C = 47.6 Hz), 129.6 (d, JP,C = 151.9 Hz), 96.0 (d, JP, C
=
= 5.6 Hz), 15.8 (d, JP, C = 1.4 Hz), 13.8, 13.6 (d, JP, C
=
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20228
/KAP1
Date: 25-05-12 10:23:31
Pages: 13
N. Xin, S. Ma
10.4 Hz) ppm. MS (70 eV, EI): m/z (%) = 368 (2.54) [M(81Br)]+, 3.4 Hz), 26.3 (d, JP,C = 2.0 Hz), 22.0, 16.4 (d, JP,C = 6.6 Hz) ppm.
FULL PAPER
366 (2.58) [M(79Br)]+, 325 (100) [M(81Br) – C3H6]+, 323 (100)
MS (70 eV, EI): m/z (%) = 266 (8.17) [M(37Cl)]+, 264 (24.74)
[M(79Br) – C3H6]+, 287 (24.07) [M – Br]+. HRMS (EI): calcd. for [M(35Cl)]+, 119 (100).
C15H28O379BrP [M]+ 366.0959; found 366.0956.
3-Butyl-4-chloro-2-ethoxy-1-oxa-2-phosphaspiro[4.5]dec-3-ene 2-
CuCl2·2H2O-Mediated Chlorocyclization Reaction of 1,2-Allenyl-
phosphonates to Afford 4-Chloro-2,5-Dihydro-1,2-oxaphosphole 2-
Oxides 3
Oxide (3e): The reaction of 1f (90.0 mg, 0.30 mmol) and
CuCl2·2H2O (153.6 mg, 0.9 mmol) in toluene (2 mL) afforded 3e
(75.1 mg, 82%) as an oil. H NMR (300 MHz, CDCl3): δ = 4.18–
1
3.96 (m, 2 H, OCH2), 2.44–2.16 (m, 2 H), 1.90–1.41 (m, 11 H),
1.41–1.22 (m, 5 H), 1.20–1.05 (m, 1 H), 0.87 (t, J = 7.2 Hz, 3 H,
OCH2CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 150.8 (d, JP,C
= 50.5 Hz), 124.7 (d, JP,C = 157.9 Hz), 87.2 (d, JP,C = 3.0 Hz), 62.9
(d, JP,C = 7.0 Hz), 34.5 (d, JP,C = 2.4 Hz), 33.9 (d, JP,C = 1.5 Hz),
29.4 (d, JP,C = 1.6 Hz), 25.6 (d, JP,C = 9.3 Hz), 24.3, 22.4, 21.4,
21.2, 16.4 (d, JP,C = 5.4 Hz), 13.6 ppm. MS (70 eV, EI): m/z (%) =
308 (4.19) [M(37Cl)]+, 306 (12.54) [M(35Cl)]+, 271 (37.19)
[M – Cl]+, 266 (33.23) [M(37Cl) – C3H6]+, 264 (100) [M(35Cl) –
C3H6]+.
3-Butyl-4-chloro-2-ethoxy-2,5-dihydro-5,5-dimethyl-1,2-oxaphos-
phole 2-Oxide (3a). Typical Procedure I: A mixture of 1a (78.0 mg,
0.30 mmol) and CuCl2·2H2O (153.5 mg, 0.9 mmol) was stirred at
70 °C in toluene (2 mL) for 5 h. When the reaction was complete
(reaction monitored by TLC; petroleum ether/ethyl acetate, 3:1).
The solvent was evaporated, the residue was subjected to column
chromatography on silica gel (petroleum ether/ethyl acetate, 4:1) to
afford 3a (68.0 mg, 85 %) as an oil.[11] 1H NMR (300 MHz,
CDCl3): δ = 4.18–3.98 (m, 2 H, OCH2), 2.43–2.09 (m, 2 H, CH2
from C4H9), 1.57–1.42 (m, 8 H), 1.42–1.19 (m, 5 H), 0.84 (t, J =
7.2 Hz, 3 H, CH3 from C4H9) ppm. 13C NMR (75.4 MHz, CDCl3):
δ = 150.4 (d, JP,C = 50.0 Hz), 124.6 (d, JP,C = 157.7 Hz), 85.3 (d,
JP,C = 2.9 Hz), 62.9 (d, JP,C = 6.9 Hz), 29.3 (d, JP,C = 2.2 Hz), 26.7
(d, JP,C = 2.6 Hz), 26.0 (d, JP,C = 2.6 Hz), 25.3 (d, JP,C = 9.5 Hz),
22.3, 16.4 (d, JP,C = 6.2 Hz), 13.5 ppm. MS (70 eV, EI): m/z (%) =
268 (0.50) [M(37Cl)]+, 266 (1.67) [M(35Cl)]+, 240 (1.32) [M(37Cl) –
C2H4]+, 238 (1.94) [M(35Cl) – C2H4]+, 226 (5.49) [M(37Cl) –
C3H6]+, 224 (12.86) [M(35Cl) – C3H6]+, 43 (100).
3-Butyl-4-chloro-2-ethoxy-1-oxa-2-phosphaspiro[4.4]non-3-ene 2-
Oxide (3f): The reaction of 1g (85.9 mg, 0.30 mmol) and
CuCl2·2H2O (153.6 mg, 0.9 mmol) in toluene (2 mL) afforded 3f
(63.6 mg, 72 %) as an oil.[11] 1H NMR (300 MHz, CDCl3): δ =
4.16–3.92 (m, 2 H, OCH2), 2.48–2.17 (m, 2 H), 2.17–1.63 (m, 8 H),
1.63–1.43 (m, 2 H), 1.43–1.23 (m, 5 H), 0.90 (t, J = 7.4 Hz, 3 H,
OCH2CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 148.1 (d, JP,C
= 50.0 Hz), 126.0 (d, JP,C = 158.0 Hz), 95.3 (d, JP,C = 2.2 Hz), 63.0
(d, JP,C = 6.8 Hz), 37.9 (d, JP,C = 2.9 Hz), 37.3 (d, JP,C = 1.7 Hz),
4-Chloro-2-ethoxy-2,5-dihydro-5,5-dimethyl-3-phenyl-1,2-oxaphos-
phole 2-Oxide (3b): The reaction of 1b (84.2 mg, 0.30 mmol) and
CuCl2·2H2O (153.5 mg, 0.9 mmol) in toluene (2 mL) afforded 3b
29.4 (d, JP,C = 2.2 Hz), 25.6 (d, JP,C = 9.3 Hz), 24.5 (d, JP, C
=
2.9 Hz), 22.4, 16.5 (d, JP,C = 6.1 Hz), 13.6 ppm. MS (70 eV, EI):
m/z (%) = 294 (2.27) [M(37Cl)]+, 292 (6.79) [M(35Cl)]+, 257 (66.67)
[M – Cl]+, 252 (32.12) [M(37Cl) – C3H6]+, 250 (100) [M(35Cl) –
C3H6]+.
1
(83.8 mg, 97%) as an oil. H NMR (300 MHz, CDCl3): δ = 7.72
(d, JP,C = 6.9 Hz, 2 H, 2 ϫ Ph-H), 7.48–7.28 (m, 3 H, 3 ϫ Ph-H),
4.20–3.94 (m, 2 H, OCH2), 1.63 (s, 3 H, CH3), 1.60 (s, 3 H, CH3),
1.18 (t, J = 7.1 Hz, 3 H, OCH2CH3) ppm. 13C NMR (75.4 MHz,
4-Chloro-2-ethoxy-3-phenyl-1-oxa-2-phosphaspiro[4.5]dec-3-ene 2-
Oxide (3g): The reaction of 1h (96.1 mg, 0.30 mmol) and
CuCl2·2H2O (153.3 mg, 0.9 mmol) in toluene (2 mL) afforded 3g
(87.9 mg, 90%) as a white solid;[11] m.p. 121–122 °C (petroleum
ether/ethyl acetate). 1H NMR (300 MHz, CDCl3): δ = 7.86–7.60
(m, 2 H, Ph-H), 7.50–7.28 (m, 3 H, 3 ϫ Ph-H), 4.21–3.98 (m, 2 H,
OCH2), 2.07–1.90 (m, 2 H), 1.90–1.63 (m, 7 H), 1.40–1.10 (m, 4
CDCl3): δ = 148.9 (d, JP,C = 47.7 Hz), 129.0, 128.9 (d, JP, C
9.2 Hz), 128.4, 128.0 (d, JP,C = 6.8 Hz), 123.4 (d, JP,C = 159.3 Hz),
85.3 (d, JP,C = 3.1 Hz), 63.5 (d, JP,C = 6.5 Hz), 26.6 (d, JP, C
=
=
3.4 Hz), 26.2 (d, JP,C = 1.6 Hz), 16.2 (d, JP,C = 5.8 Hz) ppm. MS
(70 eV, EI): m/z (%) = 288 (1.56) [M(37Cl)]+, 286 (4.53) [M(35Cl)]+,
43 (100). HRMS (EI): calcd. for C13H16O3P35Cl [M]+ 286.0526;
found 286.0524.
H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 149.4 (d, JP, C
48.9 Hz), 129.2 (d, JP,C = 9.4 Hz), 129.0, 128.5, 128.2 (d, JP,C
=
=
3-Allyl-4-chloro-2-ethoxy-2,5-dihydro-5,5-dimethy-1,2-oxaphosphole
2-Oxide (3c): The reaction of 1c (73.3 mg, 0.30 mmol) and
CuCl2·2H2O (153.5 mg, 0.9 mmol) in toluene (2 mL) afforded 3c
(51.5 mg, 68 %) as an oil.[11] 1H NMR (300 MHz, CDCl3): δ =
5.88–5.69 (m, =CH), 5.22–5.00 (m, 2 H, =CH2), 4.16–3.98 (m, 2
H, OCH2), 3.13–2.98 (m, 2 H, =CCH2), 1.52 (s, 3 H), 1.48 (s, 3 H),
1.27 (t, J = 7.1 Hz, 3 H, OCH2CH3) ppm. 13C NMR (75.4 MHz,
CDCl3): δ = 151.2 (d, JP,C = 49.5 Hz), 131.7 (d, JP,C = 7.5 Hz),
122.8 (d, JP,C = 160.6 Hz), 117.7, 85.5 (d, JP,C = 2.9 Hz), 63.2 (d,
JP,C = 6.5 Hz), 29.8 (d, JP,C = 9.3 Hz), 26.7 (d, JP,C = 3.0 Hz), 26.1
(d, JP,C = 1.6 Hz), 16.4 (d, JP,C = 6.0 Hz) ppm. MS (70 eV, EI): m/z
(%) = 252 (3.31) [M(37Cl)]+, 250 (10.15) [M(35Cl)]+, 224 (11.76)
[M(37Cl) – C2H4]+, 222 (33.72) [M(35Cl) – C2H4]+, 43 (100).
6.6 Hz), 123.6 (d, JP,C = 159.8 Hz), 87.3 (d, JP,C = 2.5 Hz), 63.5 (d,
JP,C = 6.2 Hz), 34.3 (d, JP,C = 2.9 Hz), 34.1 (d, JP,C = 1.7 Hz), 24.3,
21.3 (d, JP,C = 12.2 Hz), 16.3 (d, JP,C = 6.0 Hz) ppm. MS (70 eV,
EI): m/z (%) = 328 (6.30) [M(37Cl)]+, 326 (16.78) [M(35Cl)]+, 291
(100) [M – Cl]+. C16H20ClO3P (326.76): calcd. C 58.81, H 6.17;
found C 58.70, H 6.12.
4-Chloro-2-ethoxy-3-phenyl-1-oxa-2-phosphaspiro[4.4]non-3-ene 2-
Oxide (3h)
4-Chloro-2-ethoxy-2,5-dihydro-5,5-dimethyl-3-(2Ј-methylallyl)-
-1,2-oxaphosphole 2-Oxide (3d): The reaction of 1d (77.9 mg,
0.30 mmol) and CuCl2·2H2O (154.0 mg, 0.9 mmol) in toluene
(2 mL) afforded 3d (69.4 mg, 87 %) as an oil.[11] 1H NMR
(300 MHz, CDCl3): δ = 4.86 (s, 2 H, =CH2), 4.23–4.01 (m, 2 H,
OCH2), 3.20–3.00 (m, 2 H, =CCH2), 1.76 (s, 3 H), 1.57 (s, 3 H),
1.54 (s, 3 H), 1.30 (t, J = 7.2 Hz, 3 H, OCH2CH3) ppm. 13C NMR
The reaction of 1i (91.8 mg, 0.30 mmol) and CuCl2·2H2O
(153.5 mg, 0.9 mmol) in toluene (2 mL) afforded 3h (77.8 mg, 83%)
as an oil. H NMR (300 MHz, CDCl3): δ = 7.74 (d, J = 7.5 Hz, 2
H, 2 ϫ Ph-H), 7.49–7.25 (m, 3 H, 3 ϫ Ph-H), 4.19–3.98 (m, 2 H,
OCH2), 2.38–2.12 (m, 2 H), 2.12–1.74 (m, 6 H), 1.20 (t, J = 6.6 Hz,
3 H, OCH2CH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 146.8
(d, JP,C = 47.6 Hz), 129.2 (d, JP,C = 10.0 Hz), 129.1, 128.6, 128.2
1
(75.4 MHz, CDCl3): δ = 152.2 (d, JP,C = 50.1 Hz), 140.0 (d, JP,C
1.9 Hz), 123.0 (d, JP,C = 160.4 Hz), 113.3, 85.4 (d, JP,C = 2.9 Hz),
63.4 (d, JP,C = 6.6 Hz), 33.7 (d, JP,C = 9.9 Hz), 26.7 (d, JP, C
=
=
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20228
/KAP1
Date: 25-05-12 10:23:31
Pages: 13
Direct Halocyclization of 1,2-Allenylphosphonates
(d, JP,C = 6.8 Hz), 124.8 (d, JP,C = 158.7 Hz), 95.4 (d, JP,C = 1.5 Hz),
δ = 145.0 (d, JP,C = 52.6 Hz), 126.6 (d, JP,C = 158.4 Hz), 82.3 (d,
JP,C = 2.9 Hz), 63.1 (d, JP,C = 6.9 Hz), 29.4 (d, JP,C = 2.5 Hz), 25.9
63.6 (d, JP,C = 6.9 Hz), 38.0 (d, JP,C = 3.2 Hz), 37.8 (d, JP, C
=
2.1 Hz), 24.7 (d, JP,C = 3.2 Hz), 16.3 (d, JP,C = 5.6 Hz) ppm. MS (d, JP,C = 2.4 Hz), 25.2 (d, JP,C = 9.5 Hz), 22.4, 16.4 (d, JP,C
=
(70 eV, EI): m/z (%) = 314 (1.46) [M(37Cl)]+, 312 (5.01) [M(35Cl)]+,
6.3 Hz), 13.6, 7.6 ppm. MS (70 eV, EI): m/z (%) = 268 (1.67)
277 (100) [M – Br]+. HRMS (EI): calcd. for C15H18O3P35Cl [M]+ [M(37Cl)]+, 266 (4.96) [M(35Cl)]+, 231 (23.13) [M – Cl]+, 226 (30.71)
312.0682; found 312.0682.
[M(37Cl) – C3H6]+, 224 (94.79) [M(35Cl) – C3H6]+, 43 (100). HRMS
(EI): calcd. for C11H20O3P35Cl [M]+ 266.0839; found 266.0838.
Syntheses of Optically Active 2,5-Dihydro-1,2-oxaphosphole 2-Ox-
ides
(S,R)-3i: oil; 98% ee [HPLC conditions: Chiralcel AS-H column;
hexane/iPrOH, 90:10; 0.5 mL/min; λ = 214 nm; tR = 13.0 (major),
15.6 (minor) min]; [α]2D0 = –23.9 (c = 1.60, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 4.78–4.62 (m, 1 H, CH), 4.30–4.04 (m, 2
H, OCH2), 2.49–2.21 (m, 2 H, CH2 from C4H9), 2.08–1.92 (m, 1
H, one proton from CH2), 1.74–1.45 (m, 3 H), 1.42–1.25 (m, 5 H),
0.99–0.85 (m, 6 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 145.2
3-Butyl-4-chloro-2-ethoxy-5-ethyl-2,5-dihydro-1,2-oxaphosphole 2-
Oxide (cis-3i, trans-3i). Typical Procedure II: A mixture of 1l
(78.2 mg, 0.30 mmol) and CuCl2·2H2O (204.9 mg, 1.2 mmol) were
stirred at 70 °C in toluene (2 mL). After 12 h, the reaction was com-
plete (reaction monitored by TLC; petroleum ether/ethyl acetate,
3:1). The reaction mixture was allowed to cool to room tempera-
ture, H2O (20 mL) and ether (20 mL) were then added and the
layers were separated. The organic layer was washed with brine
(20 mL) and dried with anhydrous Na2SO4. After filtration and
evaporation, the residue was purified by chromatography on silica
gel (petroleum ether/ethyl acetate/dichloromethane, 10:1:1; 40 cm
long column) to afford cis-3i (36.1 mg, 45%) and trans-3i (39.4 mg,
49%).
(d, JP,C = 53.3 Hz), 126.5 (d, JP,C = 160.1 Hz), 82.4 (d, JP, C
=
2.9 Hz), 63.3 (d, JP,C = 6.6 Hz), 29.5 (d, JP,C = 2.0 Hz), 25.8 (d, JP,C
= 2.1 Hz), 25.2 (d, JP,C = 9.1 Hz), 22.4, 16.6 (d, JP,C = 5.4 Hz),
13.6, 8.0 ppm. MS (70 eV, EI): m/z (%) = 268 (1.65) [M(37Cl)]+, 266
(4.72) [M(35Cl)]+, 231 (28.77) [M – Cl]+, 226 (33.28) [M(37Cl) –
C3H6]+, 224 (100) [M(35Cl) – C3H6]+. HRMS (EI): calcd. for
C11H20O3P35Cl [M]+ 266.0839; found 266.0839.
3-Butyl-4-chloro-2-ethoxy-2,5-dihydro-5-propyl-1,2-oxaphosphole 2-
Oxide (cis-3j, trans-3j): The reaction of 1m (82.2 mg, 0.3 mmol) and
CuCl2·2H2O (204.8 mg, 1.2 mmol) in toluene (2 mL) afforded cis-
3j (34.6 mg, 41%) and trans-3j (40.0 mg, 48%).
cis-3i: Oil. 1H NMR (300 MHz, CDCl3): δ = 4.72–4.61 (m, 1 H,
CH), 4.13–3.98 (m, 2 H, OCH2), 2.46–2.15 (m, 2 H, CH2 from
C4H9), 2.05–1.88 (m, 1 H, one proton from CH2), 1.77–1.59 (m, 1
H, one proton from CH2), 1.57–1.42 (m, 2 H, CH2 from C4H9),
1.38–1.22 (m, 5 H), 0.96–0.80 (m, 6 H) ppm. 13C NMR (75.4 MHz,
CDCl3): δ = 144.9 (d, JP,C = 52.0 Hz), 126.5 (d, JP,C = 158.5 Hz),
cis-3j: Oil. 1H NMR (300 MHz, CDCl3): δ = 4.75–4.63 (m, 1 H,
CH), 4.18–4.02 (m, 2 H, OCH2), 2.50–2.20 (m, 2 H, CH2 from
C4H9), 2.00–1.82 (m, 1 H, one proton from CH2), 1.74–1.26 (m, 10
H), 1.00–0.83 (m, 6 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ =
82.2 (d, JP,C = 2.9 Hz), 63.0 (d, JP,C = 6.9 Hz), 29.4 (d, JP, C
=
1.8 Hz), 25.8 (d, JP,C = 2.6 Hz), 25.1 (d, JP,C = 8.9 Hz), 22.3, 16.3
(d, JP,C = 6.5 Hz), 13.5, 7.5 ppm. 31P NMR (121.5 MHz, CDCl3): 145.5 (d, JP,C = 52.8 Hz), 126.2 (d, JP,C = 158.3 Hz), 81.5 (d, JP,C
δ = 34.0 ppm. IR (neat): ν = 2960, 2934, 2874, 1631, 1460, 1388, = 2.8 Hz), 63.2 (d, JP,C = 6.6 Hz), 35.1 (d, JP,C = 2.5 Hz), 29.5 (d,
1325, 1266, 1182, 1164, 1072, 1034 cm–1. MS(70 eV, EI): m/z (%) = JP,C = 2.5 Hz), 25.2 (d, JP,C = 9.8 Hz), 22.4, 17.1, 16.4 (d, JP,C
˜
=
268 (2.34) [M(37Cl)]+, 266 (5.53) [M(35Cl)]+, 231 (29.14) [M – Cl]+,
226 (34.98) [M(37Cl) – C3H6]+, 224 (100) [M(35Cl) – C3H6]+.
HRMS (EI): calcd. for C11H20O3P35Cl [M]+ 266.0839; found
266.0837.
6.7 Hz), 13.6 (d, JP,C = 6.6 Hz) ppm. MS (70 eV, EI): m/z (%) =
282 (2.79) [M(35Cl)]+, 280 (8.38) [M(35Cl)]+, 245 (25.70) [M – Cl]+,
240 (29.17) [M(37Cl) – C3H6]+, 238 (100) [M(35Cl) – C3H6]+.
HRMS (EI): calcd. for C12H22O3P35Cl [M]+ 280.0995; found
280.0992.
1
trans-3i: Oil. H NMR (300 MHz, CDCl3): δ = 4.75–4.61 (m, 1 H,
1
CH), 4.26–4.01 (m, 2 H, OCH2), 2.48–2.19 (m, 2 H, CH2 from
trans-3j: Oil. H NMR (300 MHz, CDCl3): δ = 4.76–4.66 (m, 1 H,
C4H9), 2.06–1.88 (m, 1 H, one proton from CH2), 1.72–1.42 (m, 3 CH), 4.24–4.09 (m, 2 H, OCH2), 2.50–2.20 (m, 2 H, CH2 from
H), 1.41–1.25 (m, 5 H), 0.96–0.81 (m, 6 H) ppm. 13C NMR
(75.4 MHz, CDCl3): δ = 145.1 (d, JP,C = 53.1 Hz), 126.4 (d, JP,C
C4H9), 2.00–1.85 (m, 1 H, one proton from CH2), 1.62–1.28 (m, 10
H), 1.00–0.85 (m, 6 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ =
145.7 (d, JP,C = 53.4 Hz), 126.0 (d, JP,C = 159.6 Hz), 81.4 (d, JP,C
= 3.5 Hz), 63.3 (d, JP,C = 6.9 Hz), 35.0 (d, JP,C = 2.0 Hz), 29.5 (d,
=
160.1 Hz), 82.3 (d, JP,C = 3.4 Hz), 63.2 (d, JP,C = 6.9 Hz), 29.4 (d,
JP,C = 2.2 Hz), 25.8 (d, JP,C = 1.1 Hz), 25.1 (d, JP,C = 9.6 Hz), 22.3,
16.5 (d, JP,C = 5.3 Hz), 13.6, 7.9 ppm. MS (70 eV, EI): m/z (%) =
268 (2.52) [M(37Cl)]+, 266 (6.01) [M(35Cl)]+, 231 (30.50) [M – Cl]+,
226 (34.63) [M(37Cl) – C3H6]+, 224 (100) [M(35Cl) – C3H6]+.
HRMS (EI): calcd. for C11H20O3P35Cl [M]+ 266.0839; found
266.0841.
JP,C = 1.7 Hz), 25.2 (d, JP,C = 9.8 Hz), 22.4, 17.5, 16.6 (d, JP,C
=
5.6 Hz), 13.6 (d, JP,C = 4.3 Hz) ppm. MS (70 eV, EI): m/z (%) =
282 (2.30) [M(35Cl)]+, 280 (6.02) [M(35Cl)]+, 245 (26.98) [M+ – Cl],
240 (32.48) [M(37Cl) – C3H6]+, 238 (100) [M(35Cl) – C3H6]+.
HRMS (EI): calcd. for C12H22O3P35Cl [M]+ 280.0995; found
280.0993.
3-Butyl-4-chloro-2-ethoxy-5-ethyl-2,5-dihydro-1,2-oxaphosphole 2-
Oxide [(S,S)-3i and (S,R)-3i]: The reaction of (Sa)-(+)-1l (78.0 mg, 3-Butyl-4-chloro-2-ethoxy-5-ethyl-2,5-dihydro-1,2-oxaphosphole 2-
0.3 mmol, ee Ͼ 99%) and CuCl2·2H2O (204.6 mg, 1.2 mmol) in tol- Oxide [(S,S)-3j, (S,R)-3j]: The reaction of (S)-1m (82.3 mg,
uene (2 mL) afforded (S,S)-3i (34.8 mg, 44 %) and (S,R)-3i 0.3 mmol, ee Ͼ 99%), and CuCl2·2H2O (204.9 mg, 1.2 mmol) in
(37.9 mg, 47%).
toluene (2 mL) afforded (S,S)-3j (36.2 mg, 43 %) and (S,R)-3j
(42.4 mg, 50%).
(S,S)-3i: 98% ee [HPLC conditions: Chiralcel AS-H column; hex-
ane/iPrOH, 90:10; 0.5 mL/min; λ = 214 nm; tR = 6.5 (minor),
6.9 (major) min]; [α]2D0 = +8.4 (c = 1.50, CHCl3); oil. 1H NMR
(S,S)-3j: Oil; 98% ee [HPLC conditions: Chiralcel AS-H column;
hexane/iPrOH, 90:10; 0.5 mL/min; λ = 214 nm; tR = 6.2 (minor),
(300 MHz, CDCl3): δ = 4.75–4.62 (m, 1 H, CH), 4.21–4.00 (m, 2 6.6 (major) min]; [α]2D0 = +12.6 (c = 0.20, CHCl3). 1H NMR
H, CH2 from C4H9), 2.50–2.20 (m, 2 H, one proton from CH2),
2.09–1.93 (m, 1 H, one proton from CH2), 1.80–1.64 (m, 1 H, one
proton from CH2), 1.64–1.46 (m, 2 H, CH2 from C4H9), 1.44–1.28
(m, 5 H), 1.02–0.84 (m, 6 H) ppm. 13C NMR (75.4 MHz, CDCl3):
(300 MHz, CDCl3): δ = 4.74–4.63 (m, 1 H, CH), 4.20–3.92 (m, 2
H, OCH2), 2.50–2.19 (m, 2 H, CH2 from C4H9), 2.00–1.80 (m, 1
H, one proton from CH2), 1.71–1.20 (m, 10 H), 1.00–0.80 (m, 6
H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 145.4 (d, JP, C
=
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O20228
/KAP1
Date: 25-05-12 10:23:31
Pages: 13
N. Xin, S. Ma
FULL PAPER
52.8 Hz), 126.0 (d, JP,C = 158.1 Hz), 81.4 (d, JP,C = 2.8 Hz), 63.0
(d, JP,C = 7.2 Hz), 35.0 (d, JP,C = 2.5 Hz), 29.4 (d, JP,C = 1.7 Hz),
25.1 (d, JP,C = 9.3 Hz), 22.3, 17.0, 16.3 (d, JP,C = 6.1 Hz), 13.5 (d,
JP,C = 6.2 Hz) ppm. MS (70 eV, EI): m/z (%) = 282 (1.49)
[M(37Cl)]+, 280 (3.96) [M(35Cl)]+, 245 (26.30) [M – Cl]+, 240 (34.35)
H, OCH2), 2.22–2.05 (m, 1 H, one proton from CH2), 1.95–1.78
(m, 1 H, one proton from CH2), 1.23 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.05 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR
(75.4 MHz, CDCl3): δ = 143.6 (d, JP,C = 50.3 Hz), 129.3 (d, JP,C
=
1.0 Hz), 128.8 (d, JP,C = 10.0 Hz), 128.7, 128.2 (d, JP,C = 6.8 Hz),
[M(37Cl) – C3H6]+, 238 (100) [M(35Cl) – C3H6]+. HRMS (EI): 125.2 (d, JP,C = 159.8 Hz), 82.5 (d, JP,C = 2.9 Hz), 63.7 (d, JP,C
=
calcd. for C12H22O3P35Cl [M]+ 280.0995; found 280.0999.
6.8 Hz), 26.0 (d, JP,C = 2.5 Hz), 16.3 (d, JP,C = 6.1 Hz), 7.8 ppm.
MS (70 eV, EI): m/z (%) = 288 (12.37) [M+(37Cl)], 286 (37.01)
[M+(35Cl)], 251 (84.15) [M+ – Cl], 223 (100). C13H16ClO3P (286.69):
calcd. C 54.46, H 5.63; found C 54.46, H 5.58.
(S,R)-3j: Oil; 98% ee [HPLC conditions: Chiralcel AS-H column;
hexane/iPrOH, 90:10; 0.5 mL/min; λ = 214 nm; tR = 10.8 (major),
13.7 (minor) min]; [α]2D0 = –36.8 (c = 0.22, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 4.78–4.64 (m, 1 H, CH), 4.28–4.04 (m, 2 (S,R)-4k: Oil; 94% ee [HPLC conditions: Chiralcel AS-H column;
H, OCH2), 2.48–2.21 (m, 2 H, CH2 from C4H9), 1.99–1.85 (m, 1
H, one proton from CH2), 1.63–1.27 (m, 10 H), 1.00–0.85 (m, 6
hexane/iPrOH, 90:10; 0.5 mL/min; λ = 214 nm; tR = 15.0 (major),
19.8 (minor) min]; [α]2D0 = –84.9 (c = 1.78, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 7.80–7.60 (m, 2 H, 2 ϫ Ph-H), 7.50–7.30
(m, 3 H, 3 ϫ Ph-H), 4.93–4.78 (m, 1 H, CH), 4.30–4.03 (m, 2 H,
OCH2), 2.22–2.05 (m, 1 H, one proton from CH2), 1.90–1.70 (m,
1 H, one proton from CH2), 1.22 (t, J = 7.2 Hz, 3 H, OCH2CH3),
1.04 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (75.4 MHz, CDCl3):
δ = 143.8 (d, JP,C = 50.7 Hz), 129.2 (d, JP,C = 1.1 Hz), 128.9 (d,
H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 145.6 (d, JP, C
=
53.3 Hz), 125.9 (d, JP,C = 160.4 Hz), 81.3 (d, JP,C = 3.6 Hz), 63.2
(d, JP,C = 6.7 Hz), 34.9 (d, JP,C = 0.8 Hz), 29.4 (d, JP,C = 2.6 Hz),
25.1 (d, JP,C = 9.8 Hz), 22.3, 17.4, 16.5 (d, JP,C = 5.4 Hz), 13.5 (d,
JP,C = 4.2 Hz) ppm. MS (70 eV, EI): m/z (%) = 282 (1.97) [M-
(37Cl)]+, 280 (5.36) [M(35Cl)]+, 245 (31.09) [M – Cl]+, 240 (34.41)
[M(37Cl) – C3H6]+, 238 (100) [M+(35Cl) – C3H6]. HRMS (EI): JP,C = 10.2 Hz), 128.6, 128.1 (d, JP,C = 6.5 Hz), 125.3 (d, JP,C
=
calcd. for C12H22O3P35Cl [M]+ 280.0995; found 280.1001.
161.6 Hz), 82.4 (d, JP,C = 2.7 Hz), 63.9 (d, JP,C = 6.4 Hz), 26.1 (d,
JP,C = 1.6 Hz), 16.4 (d, JP,C = 5.2 Hz), 8.1 ppm. MS (70 eV, EI):
m/z (%) = 288 (10.44) [M+(37Cl)], 286 (32.04) [M(35Cl)]+, 251
(72.15) [M – Cl]+, 223 (100). HRMS (EI): calcd. for C13H16O3P35Cl
[M]+ 286.0526; found 286.0534.
4-Chlorol-2-ethoxy-5-ethyl-2,5-dihydro-3-pheny-1,2-oxaphosphole 2-
Oxide (cis-3k, trans-3k): The reaction of 1n (84.1 mg, 0.3 mmol),
and CuCl2·2H2O (204.5 mg, 1.2 mmol) in toluene (2 mL) afforded
cis-3k (34.2 mg, 40%) and trans-3k (36.0 mg, 42%).
[PdCl2(LB-Phos)2]-Catalyzed Suzuki Cross-Coupling Reaction of 4-
Halo-2-ethoxy-2,5-dihydro-1,2-oxaphosphole 2-Oxides with Phen-
ylboronic Acids
cis-3k: White solid; m.p. 76–77 °C (petroleum ether/ethyl acetate).
1H NMR (300 MHz, CDCl3): δ = 7.82–7.68 (m, 2 H, 2 ϫ Ph-H),
7.50–7.32 (m, 3 H, 3 ϫ Ph-H), 4.92–4.78 (m, 1 H, CH), 4.20–3.98
(m, 2 H, OCH2), 2.21–2.04 (m, 1 H, one proton from CH2), 1.94–
1.76 (m, 1 H, one proton from CH2), 1.22 (t, J = 7.0 Hz, 3 H,
OCH2CH3), 1.04 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR
3-Butyl-2-ethoxy-2,5-dihydro-5,5-dimethyl-4-phenyl-1,2-oxaphos-
phole 2-Oxide (4a); Typical Procedure: To a Schlenk tube contain-
ing K2CO3 (145.1 mg, 1.05 mmol) dried with a heat gun, were
charged phenylboronic acid (91.5 mg, 0.75 mmol), [PdCl2(LB-
Phos)2] (13.5 mg, 0.015 mmol), 3a (80.0 mg, 0.3 mmol), and tolu-
ene (2 mL) sequentially under an Ar atmosphere. The mixture was
stirred under reflux until the reaction was complete (ca. 5 h) (reac-
tion monitored by TLC; petroleum ether/ethyl acetate, 3:1). The
reaction mixture was allowed to cool to room temperature, H2O
(10 mL) and diethyl ether (10 mL) were added and the layers were
separated. The organic layer was washed with brine (10 mL) and
dried with anhydrous Na2SO4. After filtration and evaporation, the
residue was purified by chromatography on silica gel (petroleum
ether/ethyl acetate/dichloromethane, 8:1:1; 40 cm long column) to
afford 4a (69.3 mg, 75 %) as an oil.[11] 1H NMR (300 MHz,
CDCl3): δ = 7.41–7.27 (m, 3 H, 3 ϫ Ph-H), 7.11–6.98 (m, 2 H,
2 ϫ Ph-H), 4.21–4.05 (m, 2 H, OCH2), 2.18–1.83 (m, 2 H, CH2
from C4H9), 1.50–1.25 (m, 11 H), 1.22–1.06 (m, 2 H, CH2 from
C4H9), 0.80–0.65 (m, 3 H, OCH2CH3) ppm. 13C NMR (75.4 MHz,
CDCl3): δ = 161.1 (d, JP,C = 24.3 Hz), 133.8 (d, JP,C = 22.1 Hz),
(75.4 MHz, CDCl3): δ = 143.6 (d, JP,C = 50.3 Hz), 129.3 (d, JP,C
10.6 Hz), 128.8 (d, JP,C = 10.2 Hz), 128.7, 128.2 (d, JP,C = 6.9 Hz),
125.2 (d, JP,C = 159.7 Hz), 82.5 (d, JP,C = 2.9 Hz), 63.7 (d, JP,C
=
=
6.9 Hz), 26.0 (d, JP,C = 3.2 Hz), 16.3 (d, JP,C = 6.2 Hz), 7.8 ppm.
MS (70 eV, EI): m/z (%) = 288 [M+(37Cl), 2.88], 286 [M+(35Cl),
8.65], 251 (22.52) [M+ – Cl], 102 (100). C13H16ClO3P (286.69):
calcd. C 54.46, H 5.63; found C 54.46, H 5.58.
trans-3k: Oil. 1H NMR (300 MHz, CDCl3): δ = 7.78–7.66 (m, 2 H,
2 ϫ Ph-H), 7.48–7.32 (m, 3 H, 3 ϫ Ph-H), 4.92–4.79 (m, 1 H, CH),
4.30–4.03 (m, 2 H, OCH2), 2.22–2.04 (m, 1 H, one proton from
CH2), 1.88–1.70 (m, 1 H, one proton from CH2), 1.22 (t, J =
7.2 Hz, 3 H, OCH2CH3), 1.04 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C
NMR (75.4 MHz, CDCl3): δ = 143.8 (d, JP,C = 51.3 Hz), 129.2,
129.0 (d, JP,C = 10.1 Hz), 128.6, 128.2 (d, JP,C = 6.5 Hz), 125.4 (d,
JP,C = 161.7 Hz), 82.4 (d, JP,C = 2.6 Hz), 63.9 (d, JP,C = 6.9 Hz),
26.2 (d, JP,C = 1.9 Hz), 16.4 (d, JP,C = 5.2 Hz), 8.2 ppm. MS (70 eV,
EI): m/z (%) = 288 (2.88) [M(37Cl)]+, 286 (10.13) [M(35Cl)]+, 251
(14.84) [M – Cl]+, 43 (100). HRMS (EI): calcd. for C13H16O3P35Cl
[M]+ 286.0526; found 286.0528.
128.4, 128.2, 127.8, 126.0 (d, JP,C = 155.7 Hz), 85.9 (d, JP, C
=
8.6 Hz), 62.4 (d, JP,C = 6.9 Hz), 30.4 (d, JP,C = 2.3 Hz), 27.3 (d, JP,C
= 2.3 Hz), 26.7 (d, JP,C = 1.5 Hz), 25.4 (d, JP,C = 12.4 Hz), 22.3,
16.5 (d, JP,C = 5.8 Hz), 13.5 ppm. MS (70 eV, EI): m/z (%) = 308
(2.45) [M]+, 266 (15.19) [M – C3H6]+, 43 (100).
4-Chloro-2-ethoxy-5-ethyl-2,5-dihydro-3-phenyl-1,2-oxaphosphole 2-
Oxide [(S,S)-3k, (S,R)-3k]: The reaction of (Sa)-(–)-1n (84.3 mg,
0.3 mmol, ee = 96%), and CuCl2·2H2O (204.5 mg, 1.2 mmol) in
toluene (2 mL) afforded (S,S)-3k (37.7 mg, 44%) and (S,R)-3k
(38.9 mg, 45%).
2-Ethoxy-2,5-dihydro-5,5-dimethyl-3,4-diphenyl-1,2-oxaphosphole 2-
Oxide (4b): The reaction of 3b (80.0 mg, 0.3 mmol), and K2CO3
(145.1 mg, 1.05 mmol), PhB(OH)2 (91.5 mg, 0.75 mmol),
[PdCl2(LB-Phos)2] (13.5 mg, 0.015 mmol) in toluene (2 mL), af-
(S,S)-3k: White solid; m.p. 85–86 °C (petroleum ether/ethyl acet-
ate); 95% ee [HPLC conditions: Chiralcel AS-H column; hexane/
iPrOH, 90:10; 0.5 mL/min; λ = 214 nm; tR = 9.0 (minor),
11.8 (major) min]; [α]2D0 = +12.2 (c = 1.70, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 7.76 (d, J = 8.1 Hz, 2 H, 2 ϫ Ph-H), 7.51–
1
forded 4a (76.8 mg, 78%) as an oil. H NMR (300 MHz, CDCl3):
δ = 7.44–7.24 (m, 5 H, 5 ϫ Ph-H), 7.22–7.08 (m, 5 H, 5 ϫ Ph-H),
4.28–4.05 (m, 2 H, OCH2), 1.64 (s, 3 H, CH3), 1.54 (s, 3 H, CH3),
1.27 (t, J = 7.0 Hz, 3 H, OCH2CH3) ppm. 13C NMR (75.4 MHz,
7.32 (m, 3 H, 3 ϫ Ph-H), 4.92–4.81 (m, 1 H, CH), 4.21–4.00 (m, 2 CDCl3): δ = 160.2 (d, JP,C = 23.0 Hz), 134.2 (d, JP,C = 20.9 Hz),
10
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20228
/KAP1
Date: 25-05-12 10:23:31
Pages: 13
Direct Halocyclization of 1,2-Allenylphosphonates
130.8 (d, JP,C = 13.1 Hz), 128.7, 128.6, 128.5 (d, JP,C = 2.0 Hz),
128.24, 128.21, 128.0 (d, JP,C = 1.0 Hz), 125.4 (d, JP,C = 158.6 Hz),
2.42–2.12 (m, 2 H, CH2 from C4H9), 1.65–1.13 (m, 11 H), 0.89–
0.69 (m, 6 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 155.1 (d,
JP,C = 26.8 Hz), 133.5 (d, JP,C = 21.6 Hz), 128.8, 127.5, 125.9 (d,
86.0 (d, JP,C = 7.8 Hz), 63.1 (d, JP,C = 6.4 Hz), 27.5 (d, JP, C
=
3.7 Hz), 26.8 (d, JP,C = 2.6 Hz), 16.4 (d, JP,C = 5.8 Hz) ppm. MS JP,C = 157.2 Hz), 82.1 (d, JP,C = 9.5 Hz), 62.6 (d, JP,C = 6.8 Hz),
(70 eV, EI): m/z (%) = 328 (8.92) [M]+, 313 (13.62) [M – CH3]+,
43 (100). HRMS (EI): calcd. for C19H21O3P [M]+ 328.1228; found
328.1230.
36.1 (d, JP,C = 2.6 Hz), 30.6 (d, JP,C = 2.0 Hz), 25.4 (d, JP, C
13.0 Hz), 22.6, 17.8, 16.5 (d, JP,C = 5.9 Hz), 13.6 (d, JP, C
=
=
6.0 Hz) ppm. MS (70 eV, EI): m/z (%) = 322 (13.84) [M]+, 280 (100)
[M – C3H6]+. HRMS (EI): calcd. for C18H27O3P [M]+ 322.1698;
found 322.1706.
3-Allyl-2-ethoxy-2,5-dihydro-5,5-dimethyl-4-phenyl-1,2-oxaphos-
phole 2-Oxide (4c): The reaction of 3c (75.2 mg, 0.3 mmol), and
K2CO3 (145.0 mg, 1.05 mmol), PhB(OH)2 (91.6 mg, 0.75 mmol),
[PdCl2(LB-Phos)2] (13.6 mg, 0.015 mmol) in toluene (2 mL), af-
forded 4c (48.1 mg, 55%) in oil.[11] 1H NMR (300 MHz, CDCl3):
δ = 7.46–7.31 (m, 3 H, 3 ϫ Ph-H), 7.16–7.02 (m, 2 H, 2 ϫ Ph-H),
5.86–5.63 (m, 1 H, CH), 5.10–4.90 (m, 2 H, =CH2), 4.25–4.02 (m,
2 H, OCH2), 2.99–2.62 (m, 2 H, CH2), 1.47 (s, 3 H, CH3), 1.45 (s,
3 H, CH3), 1.34 (t, J = 7.2 Hz, 3 H, OCH2CH3) ppm. 13C NMR
2-Ethoxy-2,5-dihydro-5,5-dimethyl-3,4-diphenyl-1,2-oxaphosphole 2-
Oxide (cis-4f): The reaction of cis-3k (86.0 mg, 0.3 mmol), and
K2CO3 (145.0 mg, 1.05 mmol), PhB(OH)2 (91.5 mg, 0.75 mmol),
[PdCl2(LB-Phos)2] (13.6 mg, 0.015 mmol) in toluene (2 mL), af-
forded cis-4f (89.6 mg, 91%) as a white solid; m.p. 93–94 °C (petro-
1
leum ether/ethyl acetate). H NMR (300 MHz, CDCl3): δ = 7.44–
7.19 (m, 8 H, 8 ϫ Ph-H), 7.19–7.08 (m, 2 H, 2 ϫ Ph-H), 5.40–5.25
(m, 1 H, CH), 4.20–3.94 (m, 2 H, OCH2), 1.90–1.69 (m, 1 H, one
proton from CH2), 1.65–1.45 (m, 1 H, one proton from CH2), 1.15
(t, J = 7.2 Hz, 3 H, CH3), 0.99 (t, J = 7.2 Hz, 3 H, OCH2CH3) ppm.
13C NMR (75.4 MHz, CDCl3): δ = 153.8 (d, JP,C = 25.6 Hz), 133.1
(d, JP,C = 21.1 Hz), 130.9 (d, JP,C = 12.7 Hz), 129.1, 128.9, 128.7
(d, JP,C = 6.4 Hz), 128.5, 128.2, 127.9, 125.7 (d, JP,C = 161.7 Hz),
(75.4 MHz, CDCl3): δ = 161.9 (d, JP,C = 24.8 Hz), 133.8 (d, JP,C
2.1 Hz), 133.5 (d, JP,C = 21.3 Hz), 128.49, 128.48, 127.8 (d, JP,C
=
=
1.7 Hz), 124.1 (d, JP,C = 158.0 Hz), 116.9, 86.1 (d, JP,C = 8.3 Hz),
62.8 (d, JP,C = 6.6 Hz), 30.1 (d, JP,C = 12.7 Hz), 27.3 (d, JP,C
=
2.7 Hz), 26.8 (d, JP,C = 2.0 Hz), 16.5 (d, JP,C = 6.1 Hz) ppm. MS
(70 eV, EI): m/z (%) = 292 (90.67) [M]+, 277 (11.01) [M – CH3]+,
141 (100).
83.0 (d, JP,C = 8.1 Hz), 63.3 (d, JP,C = 6.4 Hz), 26.8 (d, JP, C
=
3-Butyl-2-ethoxy-5-ethyl-2,5-dihydro-4-phenyl-1,2-oxaphosphole 2-
Oxide (cis-4d): The reaction of cis-3i (80.0 mg, 0.3 mmol), and
K2CO3 (145.0 mg, 1.05 mmol), PhB(OH)2 (91.5 mg, 0.75 mmol),
[PdCl2(LB-Phos)2] (13.6 mg, 0.015 mmol) in toluene (2 mL), af-
forded cis-4d (80.0 mg, 86 %) as an oil. 1H NMR (300 MHz,
CDCl3): δ = 7.49–7.30 (m, 3 H, 3 ϫ Ph-H), 7.14 (d, J = 7.2 Hz, 2
H, 2 ϫ Ph-H), 5.12–5.00 (m, 1 H, CH), 4.22–4.04 (m, 2 H, OCH2),
2.46–2.14 (m, 2 H, CH2 from C4H9), 1.78–1.61 (m, 1 H, one proton
from CH2), 1.61–1.48 (m, 2 H), 1.48–1.15 (m, 6 H), 0.93–0.75 (m,
2.3 Hz), 16.3 (d, JP,C = 5.1 Hz), 8.4 ppm. MS (70 eV, EI): m/z (%)
= 328 (12.29) [M]+, 299 (100) [M+ – C2H4]. C19H21O3P (328.35):
calcd. C 69.50, H 6.45; found C 69.33, H 6.43.
3-Butyl-2-ethoxy-5-ethyl-2,5-dihydro-4-phenyl-1,2-oxaphosphole 2-
Oxide [(S,S)-4d]: The reaction of (S,S)-3i (80.1 mg, 0.3 mmol, ee
= 98%), and K2CO3 (145.1 mg, 1.05 mmol), PhB(OH)2 (91.5 mg,
0.75 mmol), [PdCl2(LB-Phos)2] (13.5 mg, 0.015 mmol) in toluene
(2 mL), afforded (S,S)-4d (87.2 mg, 94%) as an oil. 98% ee [HPLC
conditions: Chiralcel AS-H column; hexane/iPrOH, 80:20; 0.5 mL/
min; λ = 230 nm; tR = 9.7 (minor), 12.9 (major) min]; [α]2D0 = +142.9
(c = 2.64, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.47–7.28 (m,
3 H, 3 ϫ Ph-H), 7.18–7.05 (m, 2 H, 2 ϫ Ph-H), 5.10–4.99 (m, 1 H,
CH), 4.20–4.00 (m, 2 H, OCH2), 2.42–2.14 (m, 2 H, CH2 from
C4H9), 1.74–1.61 (m, 1 H, one proton from CH2), 1.61–1.48 (m, 2
H, CH2 from C4H9), 1.48–1.15 (m, 6 H), 0.93–0.75 (m, 6 H) ppm.
13C NMR (75.4 MHz, CDCl3): δ = 154.6 (d, JP,C = 26.2 Hz), 133.4
6 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 154.5 (d, JP,C
=
26.5 Hz), 133.3 (d, JP,C = 22.2 Hz), 128.7, 128.6, 127.3, 126.2 (d,
JP,C = 157.1 Hz), 82.9 (d, JP,C = 9.0 Hz), 62.4 (d, JP,C = 6.7 Hz),
30.5 (d, JP,C = 1.7 Hz), 26.7 (d, JP,C = 1.4 Hz), 25.3 (d, JP, C
=
12.1 Hz), 22.5, 16.3 (d, JP,C = 6.2 Hz), 13.5, 8.2 ppm. MS (70 eV,
EI): m/z (%) = 308 (13.66) [M]+, 266 (100) [M+ – C3H6]. HRMS
(EI): calcd. for C17H25O3P [M]+ 308.1541; found 308.1540.
3-Butyl-2-ethoxy-5-ethyl-2,5-dihydro-4-phenyl-1,2-oxaphosphole 2-
Oxide (trans-4d): The reaction of trans-3i (80.0 mg, 0.3 mmol), and
K2CO3 (145.1 mg, 1.05 mmol), PhB(OH)2 (91.6 mg, 0.75 mmol),
[PdCl2(LB-Phos)2] (13.7 mg, 0.015 mmol) in toluene (2 mL), af-
forded trans-4d (77.8 mg, 84%) as an oil. 1H NMR (300 MHz,
CDCl3): δ = 7.46–7.29 (m, 3 H, 3 ϫ Ph-H), 7.12 (d, J = 7.5 Hz, 2
H, 2 ϫ Ph-H), 5.12–5.00 (m, 1 H, CH), 4.32–4.07 (m, 2 H, OCH2),
2.43–2.09 (m, 2 H, CH2 from C4H9), 1.75–1.43 (m, 3 H), 1.43–1.19
(m, 6 H), 0.92–0.75 (m, 6 H) ppm. 13C NMR (75.4 MHz, CDCl3):
δ = 154.9 (d, JP,C = 26.7 Hz), 133.5 (d, JP,C = 23.0 Hz), 128.7, 127.4
(d, JP,C = 1.2 Hz), 126.3 (d, JP,C = 159.0 Hz), 83.1 (d, JP,C = 9.1 Hz),
(d, JP,C = 21.6 Hz), 128.74, 128.70, 127.4, 126.3 (d, JP, C
=
157.3 Hz), 83.0 (d, JP,C = 8.7 Hz), 62.5 (d, JP,C = 6.4 Hz), 30.6 (d,
JP,C = 2.3 Hz), 26.8 (d, JP,C = 2.0 Hz), 25.4 (d, JP,C = 13.0 Hz),
22.6, 16.4 (d, JP,C = 5.7 Hz), 13.5, 8.3 ppm. MS (70 eV, EI): m/z
(%) = 308 (14.94) [M]+, 266 (100) [M – C3H6]+. HRMS (EI): calcd.
for C17H25O3P [M]+ 308.1541; found 308.1544.
3-Butyl-2-ethoxy-2,5-dihydro-4-phenyl-5-propyl-1,2-oxaphosphole 2-
Oxide [(S,S)-4e]: The reaction of (S,S)-3j (84.0 mg, 0.3 mmol, ee
= 98%), and K2CO3 (145.1 mg, 1.05 mmol), PhB(OH)2 (91.5 mg,
0.75 mmol), [PdCl2(LB-Phos)2] (13.7 mg, 0.015 mmol) in toluene
(2 mL), afforded (S,S)-4e (86.7 mg, 90%) as an oil. 98% ee [HPLC
conditions: Chiralcel AS-H column; hexane/iPrOH, 80:20; 0.5 mL/
62.6 (d, JP,C = 6.3 Hz), 30.7 (d, JP,C = 2.6 Hz), 26.6 (d, JP, C
=
1.1 Hz), 25.3 (d, JP,C = 12.7 Hz), 22.6, 16.6 (d, JP,C = 5.3 Hz), 13.6,
8.3 ppm. MS (70 eV, EI): m/z (%) = 308 (30.31) [M]+, 266 (100)
[M – C3H6]+. HRMS (EI): calcd. for C17H25O3P [M]+ 308.1541;
found 308.1539.
min; λ = 230 nm; tR = 12.8 (minor), 14.8 (major) min]; [α]2D0
=
+136.2 (c = 1.00, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.44–
7.29 (m, 3 H, 3 ϫ Ph-H), 7.11 (d, J = 6.9 Hz, 2 H, 2 ϫ Ph-H),
5.12–4.98 (m, 1 H, CH), 4.20–4.00 (m, 2 H, OCH2), 2.42–2.10 (m,
2 H, CH2 from C4H9), 1.61–1.12 (m, 11 H), 0.85–0.69 (m, 6
3-Butyl-2-ethoxy-2,5-dihydro-4-phenyl-5-propyl-1,2-oxaphosphole 2-
Oxide (cis-4e): The reaction of cis-3j (84.3 mg, 0.3 mmol), and
K2CO3 (145.0 mg, 1.05 mmol), PhB(OH)2 (91.5 mg, 0.75 mmol),
[PdCl2(LB-Phos)2] (13.6 mg, 0.015 mmol) in toluene (2 mL), af-
forded cis-4e (86.4 mg, 89 %) as an oil. 1H NMR (300 MHz,
CDCl3): δ = 7.48–7.30 (m, 3 H, 3 ϫ Ph-H), 7.20–7.03 (m, 2 H,
H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 155.1 (d, JP, C
26.6 Hz), 133.5 (d, JP,C = 23.0 Hz), 128.8, 127.5, 126.0 (d, JP,C
157.2 Hz), 82.1 (d, JP,C = 9.2 Hz), 62.6 (d, JP,C = 7.1 Hz), 36.1 (d,
JP,C = 2.2 Hz), 30.6 (d, JP,C = 2.3 Hz), 25.4 (d, JP,C = 12.4 Hz),
=
=
2 ϫ Ph-H), 5.13–4.99 (m, 1 H, CH), 4.21–4.01 (m, 2 H, OCH2), 22.6, 17.8, 16.5 (d, JP,C = 6.4 Hz), 13.6 (d, JP,C = 5.3 Hz) ppm. MS
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O20228
/KAP1
Date: 25-05-12 10:23:31
Pages: 13
N. Xin, S. Ma
FULL PAPER
(70 eV, EI): m/z (%) = 322 (12.77) [M]+, 280 (100) [M – C3H6]+.
[9]
a) S. Ma, H. Xie, Org. Lett. 2000, 2, 3801; b) S. Ma, H. Xie,
Tetrahedron 2005, 61, 251.
S. Ma, S. Wu, Tetrahedron Lett. 2001, 42, 4075.
S. Ma, F. Yu, X. Lian, J. Zhao, Y. Yu, J. Org. Chem. 2009, 74,
1130.
HRMS (EI): calcd. for C18H27O3P [M]+ 322.1698; found 322.1696.
[10]
[11]
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of all the products.
[12]
a) S. Ma, B. Lü, C. Fu, Tetrahedron Lett. 2010, 51, 1284; b) S.
Ma, B. Lü, C. Fu, Chem. Eur. J. 2010, 16, 6434; c) S. Ma, B.
Lü, P. Li, C. Fu, L. Xue, Z. Lin, Adv. Synth. Catal. 2011, 353,
100.
Acknowledgments
Financial support from the National Natural Science Foundation
of China (NSFC) (grant number 21172192) is appreciated. We
thank Mr. Bo Lü in this group for reproducing the results pre-
sented: 2e in Table 2, (S,S)-3i and (S,R)-3i in Scheme 5 and (S,S)-
4d in Scheme 8.
[13]
H. Altenbach, R. Korff, Tetrahedron Lett. 1981, 22, 5175.
[14] a) W. H. Carothers, G. J. Berchet, J. Am. Chem. Soc. 1933, 55,
1628; b) W. H. Mueller, P. E. Butler, K. Griesbaum, J. Org.
Chem. 1967, 32, 2651; c) M. L. Poutsma, J. Org. Chem. 1968,
33, 4080.
[15] Crystal data for compound cis-3k: C13H16ClO3P; MW =
286.68; orthorhombic; space group P2(1)2(1)2(1); final R in-
dices [IϾ2σ(I)], R1 = 0.0355, wR2 = 0.1015, R indices (all
data) R1 = 0.0368, wR2 = 0.1032; a = 6.0093(2) Å, b =
13.5764(5) Å, c = 17.8709(7) Å, α = 90°, β = 90°, γ = 90°; V =
1457.99(9) Å3; T = 296(2) K; Z = 4; reflections collected/
unique 16841/2567 (Rint = 0.0236), number of observations
[IϾ2σ(I)] 2178, parameters: 164. Supplementary crystallo-
graphic data have been deposited at the Cambridge Crystallo-
graphic Data Center. CCDC-862988 contains the supplemen-
tary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[16] K. Koosha, J. Berlan, M.-L. Capmau, W. Chodkiewicz, Bull.
Soc. Chim. Fr. 1975, 1291.
[17] Crystal data for compound (S,S)-3k: C13H16ClO3P; MW =
286.68; orthorhombic; space group P2(1)2(1)2(1); final R in-
dices [IϾ2σ(I)], R1 = 0.0359, wR2 = 0.1014, R indices (all
data) R1 = 0.0379, wR2 = 0.1036; a = 6.0101(4) Å, b =
13.5807(9) Å, c = 17.8837(12) Å, α = 90°, β = 90°, γ = 90°; V
= 1459.69(17) Å3; T = 296(2) K; Z = 4; reflections collected/
unique 16904/2569 (Rint = 0.0236), number of observations
[IϾ2σ(I)] 2431, parameters: 163, CCDC-862989.
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Received: February 27, 2012
Published Online: ᭿
12
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20228
/KAP1
Date: 25-05-12 10:23:31
Pages: 13
Direct Halocyclization of 1,2-Allenylphosphonates
Halocyclization
CuX2-mediated direct halocyclization of
diethyl 1,2-allenylphosphonates was devel-
oped to afford 4-halo-2,5-dihydro-1,2-oxa-
phosphole 2-oxides. The efficiency of axial-
to-central chirality transfer and subsequent
Suzuki cross-coupling of the resulting
vinylic chlorides with dicyclohexyl(2,4,6-
trimethoxyphenyl)phosphane (LB-Phos) as
the ligand were also investigated.
N. Xin, S. Ma* ............................... 1–13
Efficient Synthesis of 4-Halo-2,5-dihydro-
1,2-oxaphosphole 2-Oxides from 1,2-Allen-
ylphosphonates and CuX2 and Subsequent
Suzuki Cross-Coupling of the C–Cl Bonds
Keywords: Synthetic methods
/ Cycliz-
ation / Cross-coupling / Chirality / Allenes /
Phosphorous heterocycles
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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