Neighboring group participation of phosphine oxide functionality in the highly regio- and stereoselective iodohydroxylation of 1,2-allenylic diphenyl phosphine oxides

Article abstract of DOI:10.1021/jo8013462

(Chemical Equation Presented) Two sets of reaction conditions were established to enable the highly regio- and stereoselective iodohydroxylation of 1,2-allenylic diphenyl phosphine oxides, yielding (E)-2-iodo-3-hydroxy-1- alkenyl diphenyl phosphine oxides

Full text of DOI:10.1021/jo8013462

Neighboring Group Participation of Phosphine Oxide Functionality
in the Highly Regio- and Stereoselective Iodohydroxylation of
1,2-Allenylic Diphenyl Phosphine Oxides
Hao Guo,† Rong Qian,‡ Yinlong Guo,‡ and Shengming Ma*,†
State Key Laboratory of Organometallic Chemistry and Shanghai Mass Spectrometry Center,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, People’s Republic of China
masm@mail.sioc.ac.cn
ReceiVed June 21, 2008
Two sets of reaction conditions were established to enable the highly regio- and stereoselective
iodohydroxylation of 1,2-allenylic diphenyl phosphine oxides, yielding (E)-2-iodo-3-hydroxy-1-alkenyl
diphenyl phosphine oxides with very high stereoselectivity. The scope of this reaction was examined
extensively. Notably, studies on the reactivity of optically active substrates indicated that the axial chirality
in the starting allenes may be efficiently transferred to the center chirality of the products with no discernible
loss of enantiopurity. Due to the importance of phosphine-containing compounds, both as reagents and
ligands, this reaction shows potentials in organic synthesis. Investigations using ESI-MS technology on
the 18O-labeled product, which was prepared using 18O-water as the solvent, indicated that the 18O atom
was bound to phosphorus in the final product and the oxygen atom of the hydroxyl comes from the
phosphinyl functionality of the allene reactant. These results provided solid evidence for the formation
of a five-membered cyclic intermediate from the neighboring group participation of the diphenylphosphinyl
group. To the best of our knowledge, this is the first time that the neighboring group participation of this
type of group was observed.
Introduction
sulfides5 or selenides5b led to a stereoselective route to (Z)-2-halo-
3-hydroxy-1-alkenyl sulfides or selenides, in which the opposite
stereoselectivity was observed. Recently, we also reported the
iodohydroxylation of non-heteroatom-substituted allenes affording
4-(3′-hydroxy-2′-iodoalk-1′(Z)-enyl)-2(5H)-furanone derivatives.6
Allenylic phosphonates, phosphine oxides, or phosphonic acids are
a class of important allene chemicals.7 Recently, we have reported
the hydroarylation of allenylic phosphonates,8 the semihydroge-
nation of allenylic phosphonates and phosphine oxides,9 and the
2-Iodo-substituted alkenols are a class of important chemicals
and applied in many transformations since they have iodide,
carbon-carbon double bond, and hydroxyl functionalities.1 Thus,
highly selective methods to prepare this type of compounds are
highly desirable. During the continuous research work of the
hydrohalogenation reaction of electron-deficient allenes in our
group,2 we observed the halohydroxylation of allenylic sulfoxides3
and sulfones,4 which provided an approach for the highly stereo-
selective synthesis of (E)-2-halo-3-hydroxy-1-alkenyl sulfoxides
and sulfones. Further research in the halohydroxylation of allenylic
(2) (a) Ma, S.; Shi, Z.; Li, L. J. Org. Chem. 1998, 63, 4522. (b) Ma, S.;
Wei, Q. J. Org. Chem. 1999, 64, 1026. (c) Ma, S.; Li, L.; Xie, H. J. Org. Chem.
1999, 64, 5325. (d) Ma, S.; Li, L.; Wei, Q.; Xie, H.; Wang, G.; Shi, Z.; Zhang,
J. Pure Appl. Chem. 2000, 72, 1739. (e) Ma, S.; Wei, Q. Eur. J. Org. Chem.
2000, 1939. (f) Ma, S.; Li, L. Synlett 2001, 1206. (g) Ma, S.; Xie, H.; Wang,
G.; Zhang, J.; Shi, Z. Synthesis 2001, 713.
(3) (a) Ma, S.; Wei, Q.; Wang, H. Org. Lett. 2000, 2, 3893. (b) Ma, S.; Ren,
H.; Wei, Q. J. Am. Chem. Soc. 2003, 125, 4817.
(4) Zhou, C.; Fu, C.; Ma, S. Tetrahedron 2007, 63, 7612.
* To whom correspondence should be addressed. Fax: (+86)21-64167510.
† State Key Laboratory of Organometallic Chemistry.
‡ Shanghai Mass Spectrometry Center.
(1) (a) Negishi, E.; Ay, M.; Gulevich, Y. V.; Noda, Y. Tetrahedron Lett.
1993, 34, 1437. (b) Cope´ret, C.; Ma, S.; Sugihara, T.; Negishi, E. Tetrahedron
1996, 52, 11529. (c) Takasu, K.; Ohsato, H.; Kuroyanagi, J.; Ihara, M. J. Org.
Chem. 2002, 67, 6001. (d) Li, H.; Morin, C. Tetrahedron Lett. 2004, 45, 5673.
(e) Ramana, G. V.; Rao, B. V. Tetrahedron Lett. 2005, 46, 3049.
(5) (a) Ma, S.; Hao, X.; Huang, X. Org. Lett. 2003, 5, 1217. (b) Ma, S.;
Hao, X.; Meng, X.; Huang, X. J. Org. Chem. 2004, 69, 5720.
(6) Gu, Z.; Deng, Y.; Shu, W.; Ma, S. AdV. Synth. Catal. 2007, 349, 1653.
7934 J. Org. Chem. 2008, 73, 7934–7938
10.1021/jo8013462 CCC: $40.75 2008 American Chemical Society
Published on Web 09/12/2008

Neighboring Group Participation of Phosphine Oxide
SCHEME 1. Preparation of 1,2-Allenylic Diphenyl Phosphine Oxides 1a-r
TABLE 1. Iodohydroxylation of 1a under Different Conditionsa
(E)-3a was also formed with a ratio of (E)-2a/(E)-3a being
24:76, which was different from the results of the halohydroxy-
lation of allenylic sulfoxides3 or sulfones.4 The configurations
of the CdC bonds in (E)-2 and (E)-3 were determined by the
X-ray diffraction study of (E)-2a12 (see Figure S1 in the
Supporting Information) and (E)-3p13 (vide infra) (see Figure
S2 in the Supporting Information).
NMR yield (%)b
(E)-2a (E)-3a
18
23
47
entry
CH3CN:H2O
(E)-2a:(E)-3ab
1
2
3
4
5:1
3:1
1:1
1:3
1:5
0:100
1:5
1:5
56
55
33
4
24:76
29:71
59:41
96:4
>99:1
92.8
On the basis of this result, we set to study the solvent effect
(entries 1-6, Table 1). The results indicated that the ratio of
CH3CN and H2O has a profound effect on this reaction: as
expected, with the increased amount of H2O, both the selectivity
of the iodohydroxylation product (E)-2a versus diiodination
product (E)-3a and the yield of (E)-2a went up, but when we
used pure H2O as the solvent, the ratio of (E)-2a/(E)-3a went
down to 92:8 (entry 6, Table 1). The best result was given when
CH3CN:H2O ) 1:5 was used as the solvent, affording (E)-2a
as the only product in 78% isolated yield (entry 5, Table 1).
When the reaction was carried out at 60 °C, the yield was lower
(entry 7, Table 1). Finally, we also checked the influence of
the amount of I2 (entry 8, Table 1). Surprisingly, with 3 equiv
of I2, the selectivity of (E)-2a/(E)-3a dropped (entry 6, Table
1). Thus, we applied Conditions A (4 equiv of I2, CH3CN:H2O
) 1:5, and rt) for the reaction of 1,2-allenylic diphenyl
phosphine oxides.
87
5
90 (78)c
86
0
7
6
7d
8e
60
0
>99:1
95:5
95
5
a The reaction was carried out at rt for 24 h using 1a (0.1 mmol) and
b
1
I2 (4.0 equiv). Determined by 300 MHz H NMR analysis of the crude
reaction mixture using CH2Br2 as the internal standard. c Isolated yield.
d The reaction was carried out at 60 °C for 20 h. e The reaction was
carried out for 37 h using I2 (3.0 equiv).
cyclization-Heck reaction of allenylic phosphonic acids with
alkenes or allyl bromide.10 Subsequently, we wish to see the effect
of phosphine oxide on determining the regio- and stereose-
lectivity in the iodohydroxylation of 1,2-allenylic diphenyl
phosphine oxides.
Then we investigated this reaction of different 1,2-allenylic
diphenyl phosphine oxides 1a-l under Conditions A. It was
observed that alkyl groups may be introduced into the different
position of allene moiety, affording (E)-2-iodo-3-hydroxy-1-
alkenyl diphenyl phosphine oxides (E)-2 as the only product in
the isolated yields of 56-93% (entries 1-10, Table 2). In
addition, 1-phenyl-3-alkyl-1,2-allenylic diphenyl phosphine
oxides 1k and 1l could also be applied under Conditions A,
affording (E)-2k and (E)-2l in 79 and 85% isolated yield (entries
11 and 12, Table 2). However, when we tried this reaction of
propa-1,2-dienyl diphenyl phosphine oxide 1m under Conditions
A, a complicated reaction mixture was generated. We also tried
1,3,3-trisubstituted 1,2-allenylic diphenyl phosphine oxides 1n
and 1o under Conditions A, and no expected product was
formed, and 66 and 76% of the starting materials were
recovered, respectively. Their low reactivities may be explained
by the steric effect of the fully substituted nature of these 1,2-
allenylic diphenyl phosphine oxides.
Results and Discussion
It is known that 1,2-allenylic diphenyl phosphine oxides 1
can be easily prepared from the reaction of corresponding
propargylic alcohols with Ph2PCl.11 Eighteen such compounds
were synthesized accordingly (Scheme 1).
We first tried the iodohydroxylation of hexa-1,2-dien-3-yl
diphenyl phosphine oxide 1a with 4 equiv of I2 at rt in CH3CN:
H2O ) 5:1 (entry 1, Table 1); the iodohydroxylation product
1
(E)-2a was generated in a yield of 18% by H NMR analysis
as the only stereoisomer. In addition, the corresponding diiodide
(7) For some typical works reported in this field, see: (a) Palacios, F.;
Aparicio, D.; Garc´ıa, J. Synlett 1994, 260. (b) Palacios, F.; Aparicio, D.; Garc´ıa,
J. Tetrahedron 1996, 52, 9609. (c) Palacios, F.; Aparicio, D.; de los Santos,
J. M.; Rodr´ıguez, E. Tetrahedron 1998, 54, 599. (d) Rubin, M.; Markov, J.;
Chuprakov, S.; Wink, D. J.; Gevorgyan, V. J. Org. Chem. 2003, 68, 6251. (e)
Palacios, F.; Aparicio, D.; Lo´pez, Y.; de los Santos, J. M. Tetrahedron Lett.
2004, 45, 4345. (f) Palacios, F.; Aparicio, D.; Lo´pez, Y.; de los Santos, J. M.
Tetrahedron 2005, 61, 2815. (g) Wu, Z.; Huang, X. Synlett 2005, 526. (h) Mei,
Y.; Liu, J.; Liu, Z. Synthesis 2007, 739.
(8) Ma, S.; Guo, H.; Yu, F. J. Org. Chem. 2006, 71, 6634.
(9) Guo, H.; Zheng, Z.; Yu, F.; Ma, S.; Holuigue, A.; Tromp, D. S.; Elsevier,
C. J.; Yu, Y. Angew. Chem., Int. Ed. 2006, 45, 4997.
(10) (a) Ma, S.; Yu, F.; Zhao, J. Synlett 2007, 583. (b) Yu, F.; Lian, X.; Ma,
S. Org. Lett. 2007, 9, 1703.
In order to study the possibility of chirality transfer and the
steric chemical outcome of this reaction, we also studied the
reaction of optically active 1,2-allenylic diphenyl phosphine
oxides (R)-1c, (S)-1c, (R)-1e, and (S)-1e, which were easily
prepared from the corresponding optically active propargylic
(11) (a) Schmittel, M.; Kiau, S.; Siebert, T.; Strittmatter, M. Tetrahedron
Lett. 1996, 37, 7691. For an early report using a different solvent and base, see:
(b) Boisselle, A. P.; Meinhardt, N. A. J. Org. Chem. 1962, 27, 1828.
(12) For crystal data of (E)-2a, see Supporting Information.
(13) For crystal data of (E)-3p, see Supporting Information.
J. Org. Chem. Vol. 73, No. 20, 2008 7935

Guo et al.
TABLE 2. Iodohydroxylation of 1a-l under Conditions Aa,b
TABLE 3. Iodohydroxylation of 1p Using Different Amount of
a
AgNO3
NMR yield (%)b
entry
1 (R1, R2, R3)
time (h)
isolated yield of (E)-2 (%)
entry
AgNO3 (equiv)
(E)-2p
(64)c
71
(E)-3p
(E)-2p:(E)-3pb
1
2
3
4
5
6
7
8
1a (n-Pr, H, H)
1b (Me, H, H)
1c (H, Me, H)
1d (H, n-Pr, H)
1e (H, n-C5H11, H)
1f (H, Me, Me)
1g (H, Et, Et)
1h (H, -(CH2)4-)
1i (Et, Me, H)
1j (n-Bu, n-Pr, H)
1k (Ph, Me, H)
1l (Ph, n-Pr, H)
24
21
8
9
9
5
8
9
21
8
(E)-2a (76)
(E)-2b (70)
(E)-2c (67)
(E)-2d (82)
(E)-2e (80)
(E)-2f (93)
(E)-2g (84)
(E)-2h (56)
(E)-2i (80)
(E)-2j (77)
(E)-2k (79)
(E)-2l (85)
1
2
3
4
(16)c
11
3
2
0
72:28
87:13
96:4
98:2
>99:1
3
4
5
6
3
82
97
5
>99 (87)c
6d
complicated
a The reaction was carried out at rt using 1p (0.1 mmol) and I2 (4.0
equiv) in 6 mL of solvent (CH3CN:H2O ) 1:5) for 24 h. b Determined
by 300 MHz 1H NMR analysis of the crude reaction mixture using
CH2Br2 as the internal standard. c Isolated yield. d I2 (2.0 equiv) was
applied.
9
10
11
12
24
23
a The reaction was carried out at rt using 1 (0.2 mmol) and I2 (4.0
equiv) in 6 mL of solvent (CH3CN:H2O ) 1:5). b The regio- and
stereoselectivities were determined by 300 MHz 1H NMR analysis of
the crude reaction mixture.
TABLE 4. Iodohydroxylation of 1-Aryl-Substituted 1,2-Allenylic
Diphenyl Phosphine Oxides under Conditions Ba,b
SCHEME 2. Preparation of Optically Active 1,2-Allenylic
Diphenyl Phosphine Oxides (R)-1c, (S)-1c, (R)-1e, and (S)-1e
entry
1 (Ar, R)
1p (Ph, H)
1q (p-CHOC6H4, H)
1r (p-MeC6H4, H)
1k (Ph, Me)
time (h)
isolated yield of (E)-2 (%)
1
2
3
4
5
24
48
61
24
22
(E)-2p (84)
(E)-2q (57)
(E)-2r (77)
complicated
complicated
1l (Ph, n-Pr)
a The reaction was carried out at rt using 1 (0.2 mmol), I2 (4.0 equiv),
and AgNO3 (6.0 equiv) in 6 mL of solvent (CH3CN:H2O ) 1:5). b The
regio- and stereoselectivities were determined by 300 MHz 1H NMR
analysis of the crude reaction mixture.
SCHEME 3. Iodohydroxylation of (R)-1c, (S)-1c, (R)-1e, and
(S)-1e under Conditions A
the reaction conditions for this substrate, AgNO3 was applied
to remove the I– in the reaction mixture. The results indicated
that the ratio of (E)-2p/(E)-3p increased when more AgNO3
was used (entries 2-5, Table 3). The best result was observed
when 6 equiv of AgNO3 were applied, affording (E)-2p in 87%
isolated yield as the only product. With fewer amounts of I2
and AgNO3, the reaction was complicated (entry 6, Table 3).
Thus, we applied Conditions B (4.0 equiv of I2, 6.0 equiv of
AgNO3, CH3CN:H2O ) 1:5, and rt) for the iodohydroxylation
of 3-unsubstituted 1-aryl-substituted 1,2-allenylic diphenyl phos-
phine oxides.
Some typical results under Conditions B are listed in Table
4. For the 1-aryl-substituted propa-1,2-dienyl phosphine oxides
1p-r, the 1-aryl group may be either electron-withdrawing or
-donating group substituted, affording only the E-products (E)-
2p-r (entries 1-3, Table 4). The reaction of 1-phenyl-3-alkyl-
1,2-allenylic diphenyl phosphine oxides 1k and 1l under
Conditions B turned out to be complicated (compare entries 11
and 12, Table 2 with entries 4 and 5, Table 4).
We also tried the iodohydroxylation of 1,3,3-trisubstituted
1,2-allenylic diphenyl phosphine oxides 1n and 1o under
Conditions B. Disappointingly, the resulting reaction mixtures
were both complicated. To study whether AgNO3 was needed
to avoid the formation of the diiodide product when an
electron-donating group was introduced to the 1-phenyl
group, the iodohydroxylation of 1r under Conditions A was
tried, which yielded a 66:34 mixture of iodohydroxylation
alcohols with Ph2PCl according to the literature procedure
(Scheme 2).11,14 When these optically active 1,2-allenylic
diphenyl phosphine oxides (R)-1c, (S)-1c, (R)-1e, and (S)-1e
were treated with I2 and H2O, the axial chirality of the allene
moiety was smoothly transferred into the center chirality of the
allylic alcohols (R)-(E)-2c, (S)-(E)-2c, (R)-(E)-2e, and (S)-(E)-
2e efficiently (Scheme 3). The absolute configurations of the
chiral center connecting the hydroxy group were determined
by the X-ray diffraction study of (R)-(E)-2c15 (see Figure S3 in
the Supporting Information).
When we tried to extend this chemistry to 1-phenyl(propa-
1,2-dienyl) diphenyl phosphine oxide 1p (Conditions A), a
mixture of iodohydroxylation product (E)-2p and diiodide (E)-
3p (72:28) was formed (entry 1, Table 3). In order to optimize
(14) Boisselle, A. P.; Meinhardt, N. A. J. Org. Chem. 1962, 27, 1828.
(15) The absolute configuration of (R)-(E)-2c was determined by the Flack
parameter. For crystal data of (R)-(E)-2c, see Supporting Information.
7936 J. Org. Chem. Vol. 73, No. 20, 2008

Neighboring Group Participation of Phosphine Oxide
SCHEME 4. ESI-MS/MS Study for the [M + H]+ Ions of
(E)-2a at m/z ) 427 and (E)-2a* at m/z ) 429
neighboring group participation effect of the diphenylphosphinyl
group was observed for the first time. Due to the importance of
phosphine-containing 2-iodo-substituted 2-alkenols1 for further
coupling reaction, reduction of the phosphine oxide functional-
ity, and transformation of the hydroxyl group, this reaction may
show a broad range of utility in organic synthesis. Further studies
on the scope and the synthetic applications of this reaction are
being carried out in our laboratory.
Experimental Section
Typical Procedure I for the Synthesis of the Starting Materi-
als. Synthesis of Hexa-1,2-dien-3-yl diphenyl phosphine oxide
(1a):11 To a solution of hex-2-yn-1-ol (979 mg, 10.0 mmol) and
Et3N (2.1 mL, d ) 0.726 g/mL, 1.5 g, 15.1 mmol) in THF (30
mL) was added Ph2PCl (2.7 mL, d ) 1.229 g/mL, 3.3 g, 15.0 mmol)
dropwise at -78 °C. After the addition, the cooling bath was
removed, and the reaction mixture was allowed to warm up to room
temperature naturally. After complete conversion of the corre-
sponding propargylic alcohol as monitored by TLC (ether), the
mixture was filtered off. Evaporation of the solvent and flash
chromatography on silica gel (eluent: petroleum ether/ether ) 1:1)
afforded 1.826 g (65%) of 1a: solid, mp 70-72 °C (ethyl acetate/
petroleum ether); 1H NMR (300 MHz, CDCl3) δ 7.78-7.67 (m, 4
H), 7.58-7.40 (m, 6 H), 4.70 (dt, J ) 17.4, 3.6 Hz, 2 H), 2.25-2.12
(m, 2 H), 1.61-1.46 (m, 2 H), 0.90 (t, J ) 7.5 Hz, 3 H); 13C NMR
SCHEME 5. Proposed Mechanism
product (E)-2r and diiodide (E)-3r together with an unidenti-
fied byproduct, indicating that AgNO3 is still required (eq
1).
(CDCl3, 75.4 MHz) δ 210.8 (d, JPC ) 6.9 Hz), 131.61 (d, JPC
2.7 Hz), 131.58 (d, JPC ) 104.7 Hz), 131.49 (d, JPC ) 10.5 Hz),
)
128.1 (d, JPC ) 11.7 Hz), 97.3 (d, JPC ) 100.8 Hz), 77.2 (d, JPC
)
13.3 Hz), 29.0 (d, JPC ) 5.7 Hz), 21.3 (d, JPC ) 6.0 Hz), 13.5 (d,
In terms of reaction mechanism, we carried out this iodohy-
droxylation of 1a using water and 18O-labeled water. The normal
product (E)-2a and the 18O-labeled product (E)-2a* were isolated
and studied by ESI-MS technique (see Figures S4 and S5 in
the Supporting Information). The ESI-MS/MS spectra showed
that the [M + H]+ ion of (E)-2a at m/z ) 427 fragmented to
yield the daughter ion at m/z ) 409 while that of (E)-2a* at
m/z ) 429 displayed the same type of fragmentation to yield
the corresponding daughter ion at m/z ) 411 (Scheme 4). It
should be noted that the treatment of (E)-2a at rt in the mixed
solvent of CH3CN:H218O ) 1:5 for 24 h yielded (E)-2a* in
only e1.5%. These results led to the conclusion that the 18O
atom was bound to phosphorus in the final products, indicating
that the oxygen atom of the hydroxyl comes from the phosphinyl
of the allene reactant and water attacks the phosphorus atom.
On the basis of these results, a possible mechanism was
proposed (Scheme 5). In the first step, the iodonium intermediate
4a is produced by the reaction of the relatively electron-rich
carbon-carbon double bond with I+. Subsequently, a five-
membered intermediate 5a is formed via neighboring group
participation of the oxygen atom of the diphenylphosphinyl
group, which is similar to what was observed in the iodohy-
droxylation of allenylic sulfoxides3b or the bromohydroxylation
of allenylic sulfones.4 Finally, the water molecule attacks at the
positively charged phosphorus atom to cleave the P-O bond,
which results in the formation of final product (E)-2a*.
JPC ) 2.3 Hz); 31P NMR (121.5 MHz, CDCl3) δ 30.6; MS (m/z)
282 (M+, 20.18), 201 (100); IR (neat) 1936, 1438, 1190, 1118 cm-1
.
Anal. Calcd for C18H19OP: C, 76.58; H, 6.78. Found: C, 76.40; H,
6.91.
Typical Procedure II (Conditions A). Synthesis of 1-Hydroxy-
2-iodohex-2(E)-en-3-yl diphenyl phosphine oxide ((E)-2a): A solu-
tion of I2 (203 mg, 0.80 mmol) and 1a (56 mg, 0.20 mmol) in
CH3CN (1 mL) and H2O (5 mL) was stirred at rt, and the reaction
was monitored by TLC (eluent: ether). When the reaction was
complete, saturated sodium thiosulfate was added to remove the
excess I2. Then the mixture was extracted with ethyl acetate (10
mL × 3), and the organic layer was dried over MgSO4. Filtration
and evaporation afforded the crude reaction mixture, which was
1
analyzed with 300 MHz H NMR spectra. Flash chromatography
on silica gel (eluent: ether) afforded 65 mg (76%) of (E)-2a: solid,
mp 130-132 °C (ether); 1H NMR (300 MHz, CDCl3) δ 7.71-7.55
(m, 6 H), 7.53-7.43 (m, 4 H), 5.24 (t, J ) 7.2 Hz, 1 H), 4.76 (d,
J ) 7.2 Hz, 2 H), 2.19-2.04 (m, 2 H), 1.05-0.91 (m, 2 H), 0.55
(t, J ) 7.2 Hz, 3 H); 13C NMR (CDCl3, 75.4 MHz) δ 139.9 (d, JPC
) 77.1 Hz), 132.2 (d, JPC ) 2.9 Hz), 131.4 (d, JPC ) 10.3 Hz),
131.2 (d, JPC ) 103.6 Hz), 128.4 (d, JPC ) 12.1 Hz), 128.3 (d, JPC
) 10.9 Hz), 72.0 (d, JPC ) 7.5 Hz), 44.2 (d, JPC ) 12.1 Hz), 20.1,
13.6; 31P NMR (121.5 MHz, CDCl3) δ 31.0; MS (ESI) (m/z) 427
(M+ + 1); IR (neat) 3313, 1574, 1462, 1437, 1171, 1116, 1097,
1045 cm-1. Anal. Calcd for C18H20O2PI: C, 50.72; H, 4.73. Found:
C, 50.59; H, 4.70.
Typical Procedure III (Conditions B). Synthesis of 3-Hydroxy-
2-iodo-1-phenylprop-1(E)-enyl diphenyl phosphine oxide ((E)-
2p): A solution of AgNO3 (206 mg, 1.22 mmol), 1p (64 mg, 0.20
mmol), and I2 (204 mg, 0.80 mmol) in CH3CN (1 mL) and H2O (5
mL) was stirred at rt, and the reaction was monitored by TLC
(eluent: ether). When the reaction was complete, saturated sodium
thiosulfate was added to remove the excess I2. Then the mixture
was extracted with ethyl acetate (10 mL × 3), and the organic layer
was dried over MgSO4. Filtration and evaporation afforded the crude
Conclusions
In conclusion, we have developed a highly regio- and
stereoselective iodohydroxylation reaction of 1,2-allenylic di-
phenyl phosphine oxides, which yields (E)-2-iodo-3-hydroxy-
1-alkenyl diphenyl phosphine oxides. The mechanism as well
as the stereochemistry is the same as we observed in the
halohydroxylation of 1,2-allenylic sulfoxides3 and sulfones.4 The
1
reaction mixture, which was analyzed with 300 MHz H NMR
spectra. Flash chromatography on silica gel (eluent: petroleum ether/
ethyl acetate ) 1:1) afforded 77 mg (84%) of (E)-2p: solid, mp
J. Org. Chem. Vol. 73, No. 20, 2008 7937

Guo et al.
149-151 °C (ethyl acetate/petroleum ether); 1H NMR (300 MHz,
CDCl3) δ 7.59-7.42 (m, 6 H), 7.41-7.28 (m, 4 H), 7.16-7.01
(m, 3 H), 6.64 (d, J ) 7.8 Hz, 2 H), 5.81 (t, J ) 7.8 Hz, 1 H), 5.00
(dd, J ) 1.8, 7.8 Hz, 2 H); 13C NMR (CDCl3, 75.4 MHz) δ 143.5
(d, JPC ) 9.8 Hz), 143.1 (d, JPC ) 78.3 Hz), 132.2 (d, JPC ) 2.9
Hz), 132.1 (d, JPC ) 10.3 Hz), 130.7 (d, JPC ) 106.5 Hz), 130.5
(d, JPC ) 10.9 Hz), 128.9 (d, JPC ) 3.5 Hz), 128.3 (d, JPC ) 12.4
Hz), 128.2 (d, JPC ) 1.7 Hz), 127.6 (d, JPC ) 2.3 Hz), 72.7 (d, JPC
) 6.3 Hz); 31P NMR (121.5 MHz, CDCl3) δ 30.1; MS (ESI) (m/z)
499 (M + K+), 483 (M + Na+), 461 (M+ + 1); IR (neat) 3301,
1578, 1486, 1437, 1168, 1116, 1098, 1071 cm-1. Anal. Calcd for
C21H18O2PI: C, 54.80; H, 3.94. Found: C, 54.61; H, 4.05.
purified with flash chromatography on silica gel (eluent: petroleum
ether/ethyl acetate ) 1:1) to afford 60 mg (69%) of (E)-2a* (86%
of 18O incorporation): solid, mp 130-131 °C (ethyl acetate/
petroleum ether); 1H NMR (300 MHz, CDCl3) δ 7.71-7.54 (m, 6
H), 7.53-7.42 (m, 4 H), 5.26 (t, J ) 6.9 Hz, 1 H), 4.77 (d, J ) 6.9
Hz, 2 H), 2.19-2.04 (m, 2 H), 1.07-0.90 (m, 2 H), 0.55 (t, J )
7.2 Hz, 3 H); 13C NMR (CDCl3, 75.4 MHz) δ 140.5 (d, JPC ) 77.2
Hz), 132.5 (d, JPC ) 2.1 Hz), 131.7 (d, JPC ) 10.6 Hz), 131.4 (d,
JPC ) 103.9 Hz), 128.6 (d, JPC ) 11.7 Hz), 127.8 (d, JPC ) 10.3
Hz), 73.0 (d, JPC ) 7.3 Hz), 44.6 (d, JPC ) 12.3 Hz), 20.3, 13.8;
31P NMR (121.5 MHz, CDCl3) δ 30.9; MS (ESI) (m/z) 451 (M +
Na+), 429 (M+ + 1); IR (neat) 3319, 1581, 1461, 1438 cm-1
;
Synthesis of 1,2-Diiodohex-2(E)-en-3-yl diphenyl phosphine
oxide ((E)-3a): A solution of I2 (205 mg, 0.81 mmol) and 1a (55
mg, 0.20 mmol) in CH3CN (5 mL) and H2O (1 mL) was stirred at
rt, and the reaction was monitored by TLC (eluent: ether). When
the reaction was complete, saturated sodium thiosulfate was added
to remove the excess I2. Then the mixture was extracted with ethyl
acetate (10 mL × 3), and the organic layer was dried over MgSO4.
Filtration and evaporation afforded the crude reaction mixture,
which was analyzed with 300 MHz 1H NMR spectra. Flash
chromatography on silica gel (eluent: petroleum ether/ether ) 2:1)
afforded 36 mg (42%) of (E)-2a and 40 mg (37%) of (E)-3a. (E)-
HRMS (ESI) (m/z) calcd for C18H21IO18OP+ [M+ + 1] 429.0366,
found 429.0351. The incorporation of 18O was obtained by
calculating the ratio of the intensities of the [M + H]+ ion peak of
C18H21IO2P+ and C18H21IO18OP+ in the same ESI-MS spectra of
the (E)-2a* sample prepared in this reaction:16
I′
I + I′
10635477.4
× 100% )
× 100% ) 86%
1752612 . 2 + 10635477 . 4
I ) the intensity of the [M + H]+ ion peak of 426.96
(referred to C18H21IO2P+)
1
3a: solid, mp 89-90 °C (ethyl acetate/petroleum ether); H NMR
I ′ )the intensity of the [M + H]+ ion peak of 428.94
(300 MHz, CDCl3) δ 7.72-7.43 (m, 10 H), 5.40 (s, 2 H), 2.14-1.98
(referred to C18H21IO18OP+)
(m, 2 H), 1.01-0.86 (m, 2 H), 0.53 (t, J ) 7.2 Hz, 3 H); 13C NMR
(CDCl3, 75.4 MHz) δ 139.4 (d, JPC ) 86.0 Hz), 132.3 (d, JPC
)
Treatment of (E)-2a at Room Temperature in the Mixed
Solvent of CH3CN:H218O ) 1:5. A solution of (E)-2a (86 mg, 0.20
mmol) in CH3CN (0.2 mL) and H218O (1.0 mL) was stirred at rt
for 24 h in a glovebox under a nitrogen atmosphere. Then the
mixture was extracted with ethyl acetate (5 mL × 3), and the
organic layer was dried over MgSO4. Filtration and evaporation
afforded 80 mg (93%) of (E)-2a. The incorporation of 18O should
be e1.5% as analyzed by ESI-MS study.
3.0 Hz), 131.7 (d, JPC ) 10.2 Hz), 131.3 (d, JPC ) 104.0 Hz), 128.6
(d, JPC ) 12.3 Hz), 125.2 (d, JPC ) 9.3 Hz), 44.8 (d, JPC ) 12.6
Hz), 20.4 (d, JPC ) 1.1 Hz), 17.6 (d, JPC ) 7.2 Hz), 13.7; 31P NMR
(121.5 MHz, CDCl3) δ 28.9; MS (ESI) (m/z) 559 (M + Na+), 537
(M+ + 1); IR (neat) 1567, 1461, 1436, 1193, 1156, 1116 cm-1
.
Anal. Calcd for C18H19OPI2: C, 40.32; H, 3.57. Found: C, 40.63;
H, 3.75.
Synthesis of 18O-Labeled 1-Hydroxy-2-iodohex-2(E)-en-3-yl di-
phenyl phosphine oxide ((E)-2a*): The starting material 1a was
dried in vacuo over P2O5 at rt for 3 days. MeCN was first treated
with CaH2 under reflux in an argon atmosphere for 24 h. Then the
distilled MeCN was treated with P2O5 under reflux in an argon
atmosphere for another 24 h. After distillation, the generated
anhydrous MeCN was kept with molecular sieve in the glovebox
under nitrogen atmosphere. H218O (92%) was bought from J&K
Chemical Ltd. All the operation was carried out in the glovebox
under nitrogen atmosphere.
Acknowledgment. We are grateful to the National Natural
Science Foundation of China (Grant Nos. 20732005 and
20423001). We thank Jinbo Zhao in this group for reproducing
the results presented in entries 2 and 5 in Table 2 and the first
reaction in Scheme 3.
Supporting Information Available: Detailed experimental
procedure, the spectroscopic data not listed in the main text,
1H/13C/31P NMR spectra for all compounds, and the.CIF files
of (E)-2a, (E)-3p, and (R)-(E)-2c. This material is available free
of charge via the Internet at http://pubs.acs.org.
A solution of I2 (207 mg, 0.81 mmol) in CH3CN (0.2 mL) and
H218O (0.4 mL) was stirred at rt for 6 h. Then it was added into a
solution of 1a (57 mg, 0.20 mmol) in H218O (1 mL), which had
also been stirred at rt for 6 h. CH3CN (0.2 mL × 3) and H218O
(2.6 mL) were sequentially used to wash the container for 1a, with
the resulting solution being transferred into the reaction mixture.
After being stirred at rt for 24 h, the reaction mixture was directly
JO8013462
(16) Meng, Z.; Limbach, P. A. Anal. Chem. 2005, 77, 1891.
7938 J. Org. Chem. Vol. 73, No. 20, 2008