Control of remote stereochemistry using phosphine oxides: Formal synthesis of any stereoisomer diol (RR, RS, SR or SS) bearing 1,5-reIated stereogenic centres across an E double bond

Article abstract of DOI:10.1039/a903371h

γ-Alkenyl β-hydroxy phosphine oxides have been epoxidised stereoselectively to give γ,5-epoxy β-hydroxy phosphine oxides with high anti stereoselectivity. The y-anisyl or γ-furyl ring of γ-aryl β-hydroxy phosphine oxides have been cleaved oxidatively to reveal a carboxylic acid and a ketone respectively. In the latter case, the ketone was reduced highly stereoselectively to give (4R*,5S*,6R*)-8-benzyloxy-6-diphenylphosphinoyloctane-l,4,5- triol as a single diastereoisomer with three controlled stereogenic centres. This method was then applied to the synthesis of three of the diastereoisomers of 8-benzyloxy-6-diphenylphosphinoyldodecane-l,4,5-triol with four controlled stereogenic centres; the middle two stereogenic centres were removed using an -selective Horner-Wittig elimination to give either diastereoisomer of 8-benzyloxydodec-5-ene-l,4-diol with 1,5-related stereogenic centres across an ￡alkene.

Full text of DOI:10.1039/a903371h

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Control of remote stereochemistry using phosphine oxides:
formal synthesis of any stereoisomer diol (RR, RS, SR or SS)
bearing 1,5-related stereogenic centres across an E double bond
Adam Nelson*† and Stuart Warren
University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 1EW
Received (in Cambridge) 27th April 1999, Accepted 3rd June 1999
γ-Alkenyl β-hydroxy phosphine oxides have been epoxidised stereoselectively to give γ,δ-epoxy β-hydroxy phosphine
oxides with high anti stereoselectivity. The γ-anisyl or γ-furyl ring of γ-aryl β-hydroxy phosphine oxides have been
cleaved oxidatively to reveal a carboxylic acid and a ketone respectively. In the latter case, the ketone was reduced
highly stereoselectively to give (4R*,5S*,6R*)-8-benzyloxy-6-diphenylphosphinoyloctane-1,4,5-triol as a single
diastereoisomer with three controlled stereogenic centres. This method was then applied to the synthesis of three of
the diastereoisomers of 8-benzyloxy-6-diphenylphosphinoyldodecane-1,4,5-triol with four controlled stereogenic
centres; the middle two stereogenic centres were removed using an E-selective Horner–Wittig elimination to give
either diastereoisomer of 8-benzyloxydodec-5-ene-1,4-diol with 1,5-related stereogenic centres across an E alkene.
directed
epxodation
Introduction
In the preceding paper,1 we outlined a general strategy for the
HO
synthesis of allylically functionalised compounds2,3 with 1,4-
R
Me
related stereogenic centres across double bonds of fixed con-
figuration.4 In this paper, we take this strategy one stage further
H
H
H
Ph2P
in the synthesis of alkenyl diols with 1,5-related stereogenic
centres across an E double bond. We have shown that the
diphenylphosphinoyl group5 can be used to control the 1,3,4-
related stereogenic centres in β-hydroxy phosphine oxides 1.1
We now describe methods which allow the R2 group of
phosphine oxides 1 to be transformed into a prochiral unit (as
in 2) which can be functionalised stereoselectivity (for example
by alkene epoxidation, ketone reduction) to give phosphine
oxides 3 with four stereogenic centres (Scheme 1). Horner–
O
12 → 6 or 9
Fig. 1
Results and discussion
Stereoselective epoxidation of ã,ä-unsaturated â-hydroxy
phosphine oxides
Initially, we looked at epoxidation as a means of introducing
a γ stereogenic centre into molecules of general structure 2
(X = CH2). We chose to use racemic β-hydroxy phosphine
HO
HO
R3
R1
OBn
Reveal prochiral
unit
R1
OBn
R2
oxides 5 and 8 as models of 2 (X = CH2). Epoxidation of
Ph2PO
5 and 8 with MCPBA gave the epoxides 6 and 9 with high
diastereoselectivity and in excellent yield; in both cases, the
epoxide oxygen of the products was on the opposite face to the
hydroxy group as shown in Scheme 2. Earlier work suggested
that the epoxides were formed by directed epoxidation of
the conformation 12 in which 1,2-allylic strain is minimised
(Fig. 1).3 Epoxides similar to 6 and 9 are extremely sensitive to
Payne rearrangement,3,6 so the crude reaction mixtures were
treated directly with lithium benzenethiolate,7 in the presence
of a PhSH buffer, to give the diols 7 and 10. We also tried
unsuccessfully to open the epoxide 6 with the anions of 5-
bromouracil and 6-chloropurine.8,9 Horner–Wittig elimination
of the β-hydroxy phosphine oxide 10 gave the Z-allylic alcohol
11 in poor yield.‡
Ph2PO
X
1
2
Stereoselective
functionalisation
HO
R3
R1
OBn
Horner−Wittig
R3
γ′ R1
γ
α
β
elimination
Ph2PO
Y
Y
OBn
4
3
Scheme 1
Many features of this epoxidation route were unsatisfactory.
To start with, the syntheses of optically active allylic alcohols 1
(R2 = alkenyl) were neither flexible nor stereoselective.1 In any
case, precedent suggested that epoxidation of the syn isomers
of 6 and 9 would have been low yielding and unselective.3
Furthermore, we had been unable to find conditions which
Wittig elimination will then be used to “harvest” the middle
two stereogenic centres to give alkenes 4 with a controlled 1,5
chiral relationship. The aim of the work was to develop
methods which allow the general synthesis of any stereo-
isomer of the β-hydroxy phosphine oxides 3 and hence the
alkenes 4.
† Present address: School of Chemistry, University of Leeds, Leeds, UK
LS2 9JT.
‡ In the light of previous work, these low-yielding eliminations were,
perhaps, to be expected (ref. 8).
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998
1983

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Table 1 Acylation and oxidative cleavage of the β-hydroxy phosphine oxides 16, 20 and 24
Acylation
Oxidative cleavage
Transformation
Conditionsa Product
Starting
material
β-acyloxy phos- Yield
Yield
(%)
Yield
(%)
Entry
Conditionsa
(a)
phine oxide
(%)
Conditionsa
(b)
Product
1a
1b
2
3
4
5
6
16
17
95
81
18
91
(c)
(d)
(e)
—
19
19
23
—
29
32
38
55
44
18
—
59
55
61
b
20
25
16
20
—
(a)
(a)
(f)
(f)
—
21
25
27
30
36
(b)
(b)
(b)
(b)
(b)
22
26
28
31
37
>98
>98
b
b
b
72
75
—
(c)
(c)
(c)
a Reagents and conditions: (a) PhCOCl, cat. DMAP, Et3N; (b) cat. RuCl3, NaIO4, CH2Cl2–MeCN–H2O; (c) SOCl2, MeOH; (d) CH2N2; (e) CDI,
MeNHOMeؒHCl, CH2Cl2; (f) Ac2O, pyridine. b Crude product was the acid by 400 MHz 1H NMR spectroscopy.
OBn
OH
OH
OH
NaH, nBu4NI
OBn
OBn
(a)
An
quant.
O
BnBr, THF
>98%
Ph2PO
14
Ph2PO
Ph2PO
Ph2PO
MeO
6
5
13
95:5 mixture
cat. RuCl3, NaIO4
MeCN–CCl4–H2O
14%
(b) 37%
OH
O
O
Ph
PhS
HO
O
Ph
Ph2PO
7
Ph2PO
15
O
MeO
OH
OH
Scheme 3
(a)
94%
OBn
OBn
O
vein, the β-hydroxy phosphine oxide 13 was converted into the
phthalimide 36 using the chemistry described in Scheme 5;
the benzyl ether of 34 was easily removed by hydrogenolysis
and the alcohol of 35 was substituted by phthalimide, using a
Mitsunobu reaction.11
The benzoates 17, 21 and 25 and the acetates 27, 30 and
36 were oxidised to the corresponding acids using sodium
periodate and catalytic ruthenium trichloride in a 1:1:1
mixture of acetonitrile, water and carbon tetrachloride
(Schemes 4 and 5; Table 1). Practically, we found that about 15
equivalents of sodium periodate were necessary for the reaction
to reach completion; it was also necessary to use considerably
more solvent12 than that recommended by Sharpless10 to
allow efficient stirring of the reaction mixture. The crude
Ph2PO
Ph2PO
9
8
89:11 mixture
(b)
77%
OH
PhS
OBn
(c)
14%
OBn
PhS
HO
HO
Ph2PO
11
10
Scheme 2 Reagents and conditions: (a) M-CPBA, Na2HPO4, CH2Cl2,
0 ЊC; (b) PhSLi, PhSH, THF; (c) NaH, DMF.
1
reaction mixtures were analysed by H NMR and were almost
exclusively the required carboxylic acids. The efficiency and
chemoselectivity of these oxidation reactions is remarkable;
in each case, the anisyl ring is selectively oxidised in the
presence of three phenyl rings, each of which is protected by a
neighbouring carbonyl or phosphinoyl group.
promoted clean Horner–Wittig elimination of diols like 10.
These problems led us to abandon this strategy.
Oxidative cleavage of the anisyl ring of â-anisyl â-acyloxy
phosphine oxides
Ideally, we wanted to develop simple and efficient ways to
convert the crude acids into useful prochiral units. For example,
the acid 18 was converted into the methyl ester 19 by treatment
with acidic methanol solution (entry 1) or diazomethane (entry
2, Table 1); the methyl ester 19 was, however, resistant to attack
by a variety of organometallic reagents and could be converted
in only 52% yield into the diol 33 using lithium aluminium
hydride. We have previously synthesised similar diphenylphos-
phinoyl diols using the Sharpless asymmetric dihydroxylation
reaction.13 The acid 22 was converted in low yield into the
Weinreb amide 23 using carbonyl diimidazole and N,O-
dimethylhydroxylamine hydrochloride.14
An alternative strategy for the synthesis of molecules similar to
2 (X = O; R3 = OH) involved the oxidative cleavage of the aro-
matic ring of phosphine oxides similar to 1 (R2 = p-MeOC6H4).
To start with, we chose to work with models of the phosphine
oxides 1 (R2 = p-MeOC6H4) such as 13. The β-hydroxy phos-
phine oxide 13 was protected as the dibenzyl ether 14; oxidation
of the dibenzyl ether 14 under Sharpless’s conditions10 gave
only diester 15 in low yield (Scheme 3). Evidently, the benzyl
ethers of 14 are more susceptible to oxidation under these
conditions than the anisyl ring.
We protected the β-hydroxy phosphine oxides 16, 20 and 24
as benzoates 17, 21 and 25 and acetates (e.g. 27 or 30) because
these functional groups were known to be stable to oxidation
under Sharpless’s conditions (Scheme 4; Table 1).10 In a similar
Most of the problems associated with protecting β-hydroxy
phosphine oxides as benzoates were easily solved by using an
acetate protecting group instead (entries 4–6, Table 1). The
1984
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998

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HO
BzO
BzO
BzO
HO2C
(b)
(c) or (d)
(a)
MeO2C
Ph2PO
Ph2PO
Ph2PO
Ph2PO
MeO
MeO
19
16
17
18
HO
BzO
Me
N
OBz
OBz
HO
(a)
(b)
(e)
MeO
Ph2PO
Ph2PO
Ph2PO
Ph2PO
O
O
MeO
MeO
23
20
21
22
HO
BzO
BzO
Me
Me
(a)
Me
Ph2PO
(b)
(b)
(b)
HO2C
Ph2PO
Ph2PO
MeO
MeO
24
25
26
HO
AcO
HO
AcO
HO2C
(f)
(g)
MeO2C
Ph2PO
Ph2PO
Ph2PO
Ph2PO
MeO
MeO
29
16
27
28
HO
AcO
HO
AcO
HO2C
(f)
(g)
MeO2C
Ph2PO
Ph2PO
Ph2PO
Ph2PO
MeO
MeO
32
20
30
31
HO
HO
Ph2PO
33
Scheme 4 Reagents and conditions: (a) PhCOCl, cat. DMAP, Et3N; (b) cat. RuCl3, NaIO4, CH2Cl2–MeCN–H2O; (c) SOCl2, MeOH; (d) CH2N2; (e)
CDI, MeNHOMeؒHCl, CH2Cl2; (f) Ac2O, pyridine; (g) conc. HCl, MeOH.
acetate group in phosphine oxides 27, 30 and 36 was unaffected
by the strongly oxidising reaction conditions, and was easy to
remove by acid-catalysed methanolysis,§ giving the required
methyl esters 29, 32 and 38 in good isolated yields over the
two steps. We were particularly pleased that the phthalimide
ring of 38 remained intact. Remarkably, we observed no epim-
erisation (by enolisation) of any of the products, despite the
acidic conditions of the methanolysis step. The protection of
the β-hydroxy phosphine oxides 32 and 38 as MOM acetals
was very slow (though high yielding), reflecting the particu-
larly hindered nature of the secondary alcohols (Scheme 6).¶
Unfortunately, the esters 39 and 40 did not react cleanly with a
variety of organometallic and reducing reagents.
rather surprising in view of the many Mitsunobu reactions
in which phthalimide replaces a secondary hydroxy group.11
Perhaps the nearby electron-withdrawing diphenylphosphinoyl
group promotes the elimination of intermediate 45.
At this stage, this strategy was abandoned since no efficient
way to functionalise the methyl ester groups stereoselectively
(revealed by oxidative cleavage of the anisyl rings) had been
found. Furthermore, most of the reaction sequences developed
had been rather long because we could not find a protecting
group which was stable to both ruthenium-catalysed oxidations
and the nucleophilic reactions required by the second half of
the route.
The final door to the strategy was closed with the discovery
that phthalimide did not displace the secondary alcohol of 43
cleanly (Scheme 7). Instead, we isolated a single product which
we believe to be allylic phosphine oxide 44. This result was
â-(2-Furyl) â-hydroxy phosphine oxides as masked â-hydroxy
ã-keto phosphine oxides
Oxidation of the unprotected β-hydroxy phosphine oxide 46
with MCPBA gave the enone 47 as an 83:17 mixture of ano-
mers (Scheme 8).|| This oxidation had achieved exactly what
§ These conditions have been found to be the best conditions for the
deprotection of β-acetoxy phosphine oxides (ref. 15).
¶ For examples of other β-hydroxy phosphine oxides which must be
more hindered than most secondary alcohols, see ref. 15.
|| For a review of furans in synthesis, see ref. 16. For examples of
synthetic applications of furans, see ref. 17.
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998
1985

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OH
OAc
OBn
OBn
Ac2O, pyridine
89%
Ph2PO
Ph2PO
MeO
MeO
34
13
H2 / Pd / C
MeOH, 78%
O
OAc
OAc
phthalimide
OH
N
Ph2PO
DEAD, Ph3P, THF
73%
Ph2PO
O
MeO
MeO
36
35
cat. RuCl3, NaIO4
CH2Cl2−MeCN−H2O
O
O
HO
AcO
HO2C
conc. HCl, MeOH
61% over 2 steps
N
N
MeO2C
Ph2PO
O
Ph2PO
O
37
38
H
Scheme 5
OH
MeOCH2Cl
Et3N, CH2Cl2
O
OMe
R1
MeO
MeO
86%
O
HO
Ph2PO
32
Ph2PO
39
R2
O
O
51 → 49
O
Fig. 2
OH
MeO
N
reactions are syn selective, and proceed under Felkin control
(Fig. 2).21
Ph2PO
38
O
O
An obvious development of this work was to study the effect
of cerium trichloride on the outcome of the reduction of 47.
Luche’s reduction conditions22 are well known to promote
1,2 reduction of α,β-unsaturated ketones, but the addition of
the Lewis-acidic cerium trichloride can also dramatically alter
the stereochemical course of reactions.23 Reduction of enone 47
using Luche’s conditions did indeed leave the double bond
intact, and once more a single diastereomer (48) was obtained
(Scheme 8). The stereochemistry of 48 was proved by catalytic
hydrogenation to an 85:15 mixture of triol 49 and starting
material. Evidently, the reduction of 47 with sodium boro-
hydride in the presence of cerium() chloride proceeded
with the same stereochemical sense as reduction with sodium
borohydride alone.
MeOCH2Cl
Et3N, CH2Cl2
86%
O
O
OMe
MeO
N
Ph2PO
40
O
O
Scheme 6
Horner–Wittig elimination of 49 using potassium hydroxide
in DMSO gave the alkene 50, albeit in poor yield. Remarkably,
alkene 50 was obtained as the (E) geometric isomer, indicating
that the Horner–Wittig elimination had not been stereospecific.
There are many examples of Horner–Wittig eliminations in
which the usual syn stereospecificity has been lost,24 and these
examples are usually explained by a particularly easy retro-
Horner–Wittig addition which can compete with the olefination
process. In this case, however, we propose an alternative
explanation which builds on other Horner–Wittig eliminations
of β,γ-dihydroxy phosphine oxides.13 Base-catalysed elimin-
ation of 49, to give the vinyl phosphine oxide 52, followed by
readdition of hydroxide to give 53 would provide a means by
we wanted; the furan ring of 46 had been transformed into a
prochiral unit (a ketone) suitable for further functionalisation.
Stereoselective functionalisation of the enone 47 was also sur-
prisingly easy; the open-chain triol 49, with its three controlled
stereogenic centres, was obtained as a single diastereomer simply
by reducing18 47 with sodium borohydride. Presumably, open-
ing of the hemiacetal of 47 and reduction of the resulting
aldehyde is followed by 1,4-addition and stereoselective 1,2-
reduction of the enone.** Available evidence20 suggests that such
** The reduction of similar methyl acetals was completely 1,2-regio-
selective (ref. 19).
1986
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998

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OAc
OH
OAc
H2 / Pd / C
MeOH
Ac2O, pyridine
87%
Bu
Bu
OBn
Bu
Ph2PO
52%
(72% based on recovered starting
material)
OH
Ph2PO
Ph2PO
OBn
MeO
MeO
MeO
43
42
41
PPh3, DEAD
THF, 63%
phthalimide
OAc
H
OAc
Bu
Bu
Ph2PO
Ph2PO
O
MeO
MeO
PPh3
44
45
Scheme 7
OH
OH
OBn
HO
OBn
HO
Ph2PO
Ph2PO
O
HO
48
single isomer
51
NaBH4, CeCl3
EtOH
OH
OH
36%
OBn
MCPBA
65%
O
H2 / Pd / C
OBn
Ph2PO
46
O
Ph2PO
O
NaBH4
EtOH
66%
47
83:17 mixture
OH
KOH, DMSO
35%
OBn
OBn
HO
HO
HO
(E)-50
single isomer
Ph2PO
HO
49
single isomer
Scheme 8
−
HO
R1
OH
OH
O
OBn
OBn
PPh2
HO
HO
Ph2PO
Ph2PO
slow
HO
HO
49
HO
R
53
52
fast
OBn
HO
HO
HO
(Z)-50
OBn
HO
(E)-50
Scheme 9
which 49 could be converted into 53 under the reaction con-
ditions (Scheme 9). Horner–Wittig elimination of 53 would
then give the observed (E)-alkene 50.
55 and 58 with high stereoselectivity (Scheme 10). Previously,
this sequence of reactions had been studied using the anti β-
hydroxy phosphine oxide 46 (Scheme 8); we were pleased to find
that reduction was equally stereoselective with syn phosphine
oxides 54 and 57.†† Removal of the middle two stereogenic
centres of triols 55 and 58 by Horner–Wittig elimination was
Synthesis of unsaturated diols with 1,5-related stereogenic
centres across an E alkene
The stage was now set for the synthesis of some molecules with
remote stereogenic centres across a double bond. Oxidation of
the furan rings of 54 and 57, followed by reduction with sodium
borohydride introduced the fourth stereogenic centre of triols
†† A similarly remote stereogenic centre has been observed to have a
remarkable effect on the rate and stereoselectivity of some diphenyl-
phosphinoyl alkenes [ref. 3(a)].
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998
1987

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OH
OH
4
8
(c)
HO
(a),(b)
36%
HO
HO
OBn
41%
Ph2PO
55
HO
OBn
Ph2PO
54
O
OBn
56; ca. 80:20
[α]D = +10.1
(c 0.91 in CDCl3)
OH
OH
4
8
(c)
(a),(b)
57%
HO
HO
27%
HO
OBn
Ph2PO
HO
OBn
Ph2PO
57
O
OBn
59; >95:5
58
[α]D = +4.7
(c 0.91 in CDCl3)
OH
OH
(c)
(a),(b)
44%
HO
HO
34%
Ph2PO
HO
OBn
HO
OBn
Ph2PO
O
OBn
61
62
60
74:26 61:64
74:26 60:63
OH
OH
(c)
(a),(b)
47%
HO
HO
25%
Ph2PO
HO
OBn
HO
OBn
Ph2PO
O
OBn
64
69:31 64:61
65
63
70:30 63:60
Scheme 10 Reagents and conditions: (a) MCPBA, CH2Cl2; (b) NaBH4, EtOH; (c) KOH, DMSO, 55 ЊC.
Table 2 Chemical shift differences in Mosher’s diesters 70–73
δ(HX–HY)
completely E-selective, giving unsaturated diols 56 and 59 in
rather low yield.25
This approach was easily extended to cyclohexyl-substituted
diols 62 and 65.25 Unfortunately, it was not possible to separate
the 1,3syn and 1,3anti isomers 60 and 63, so diols 62 and 65 were
isolated as mixtures. Nevertheless, the 1,5-relationship between
the stereogenic centres of diols 62 and 65 was partly (between
2:1 and 3:1) controlled which is a remarkable feat considering
the remoteness (in space) of the stereogenic centres.
Mosher’s
diester X
Mosher’s
diester Y
Entry
HM
HN
HO,OЈ
1
2
70
72
71
70
Ϫ0.08
ϩ0.08
Ϫ0.09
ϩ0.08
Ϫ0.03
ϩ0.04
The conversion of 66 into the diol 56 was also studied and,
once again, the Horner–Wittig elimination of an anti β-hydroxy
phosphine oxide (68) gave an E alkene (Scheme 11). Never-
theless, the fact that our Horner–Wittig eliminations ignored
the relative stereochemistry of the α and β stereogenic centres
of 55, 58 and 68 meant that both 1,5syn and 1,5anti diols 56 and
59 could be made from the same starting material 66. This had
been possible because 57 was synthesised from 66 using an
oxidation–reduction sequence.1
was the same (within experimental error) as that of the pre-
cursor1 74 (84% ee). The absolute stereochemistry of the stereo-
genic centre at C-4 (and hence the relative stereochemistry) of
59 was determined using Mosher’s method27 (Table 2).‡‡
The diastereomeric purity of 56 was measured by conversion
into the corresponding Mosher’s diesters; the ratio of peaks in
1
the 500 MHz H NMR spectrum of these Mosher’s esters was
74:26 which reflects the ratio of (4R):(4S) diols in the starting
material (Table 2).27 The diol was known to have 84% ee. The
74:26 ratio of peaks observed does not correspond to the
known enantiomeric excess (which would require a ratio of
92:8) so 56 must be contaminated with its diastereoisomer
59 (i.e. 72 ϩ 71:70 ϩ 73 was 74:26). We estimate that the
diastereomeric purity of 56 was 80:20.
Despite the inevitably E-selective Horner–Wittig elimination
of the triols 55, 58 and 68, the use of single diastereomers
throughout the reaction sequences described in Schemes 10
and 11 is still of fundamental importance. The stereochemistry
of the β-hydroxy phosphine oxide unit of triols 55, 58 and 68
still controlled the gradual transmission of stereochemical
information from the stereogenic centre γЈ to phosphorus. The
relative configuration of the β-hydroxy phosphine oxide unit
may not determine the geometry of the alkene products, but
these stereogenic centres still act as temporary “relay” centres.
Determining the diastereomeric purity of compounds
with remote stereogenic centres is a very difficult task indeed.26
Summary
We have developed stereoselective methods which allow com-
plete control over the stereochemistry of the products. In the
preceding paper,1 we described asymmetric syntheses of all
four diastereomeric phosphine oxides 1 (R2 = aryl). The work
described in this paper allowed us to transform some aromatic
R2 groups in phosphine oxides 1 into prochiral units, by oxid-
ative cleavage of either an anisyl ring or a furan ring, which were
1
Careful comparison of the 500 MHz H NMR spectra of 56
and 59 allowed us to measure the diastereomeric purity of
59 confidently as >95:5. We derivatised the diols 56 and 59 as
(R)-MTPA (“Mosher’s”) diesters. The diol 59 was essentially
diastereomerically pure (>95:5), so the ratio of diastereomeric
esters obtained (70:71 89:11) reflected the enantiomeric purity
of 59. The measured enantiomeric excess of 59 was 78%, which
‡‡ Mosher’s correlation has been applied to similar secondary allylic
alcohols (ref. 28).
1988
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998

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O
HM
HO HO'
O
HM
HO HO'
Ph OMe
4S
F3C
MeO Ph
4R
F3C
MeO Ph
8R
8S
Cl
O
O
Ph OMe
F3C
Ph OMe
HN
OBn
HN
OBn
O
O
O
F3C
F3C
O
O
69
70
71
HM
HO HO'
O
HM
HO HO'
O
4S
4R
F3C
F3C
8S
8R
O
O
Ph OMe
Ph OMe
HN
OBn
HN
OBn
MeO Ph
MeO Ph
O
O
F3C
F3C
O
O
72
73
O
HO
Me
Bu3Sn
Me
OBn
Ph2P
R
OBn
OBn
74
75
76
phosphine oxide chemistry. Our work is neatly complemented
by some methodology which has been reported by Thomas;
transmetallation of chiral allylic stannanes such as 75, and
reaction with aldehydes, gives homoallylic alcohols (e.g. 76)
with 1,5-related stereogenic centres across a (Z)-double bond.29
OH
Ph2PO
66
O
OBn
95%
Experimental
MCPBA
CH2Cl2
General methods have been described previously.1 Carbon
NMR spectra were recorded with broad band proton
decoupling and Attached Proton Test. Plus (ϩ) and minus (Ϫ)
symbols after the carbon NMR chemical shift indicate odd and
even numbers of attached protons respectively.
OH
O
(2R*,3S*,4S*)-4-Diphenylphosphinoyl-1,2-epoxy-2-methyl-
octan-3-ol 6
Ph2PO
O
OBn
67
77:23 mixture
m-Chloroperbenzoic acid (57–85% by weight, 1.94 g, ca. 7.9
mmol) was added over 20 min to a stirred solution of (3R*,
4S*)-4-diphenylphosphinoyl-2-methyloct-1-en-3-ol1 5 (1.00 g,
2.8 mmol) and disodium hydrogen phosphate (2.16 g, 15.2
mmol) in dry dichloromethane (40 cm3) at 0 ЊC. The reaction
mixture was stirred for 16 h at 0 ЊC, quenched with sodium
iodide (1.2 g, 7.9 mmol) and sodium thiosulfate (1.1 g, 7.9
mmol) and extracted with dichloromethane (3 × 30 cm3).
The combined organic extracts were washed with saturated
sodium bicarbonate solution (30 cm3) and brine (30 cm3) and
evaporated under reduced pressure to give the epoxide 6 (1.06 g,
>98%, 95:5 ratio of diastereomers) as an oil, Rf 0.28 (EtOAc)
(Found: MHϩ, 359.1799. C21H27O3P requires MH, 359.1776);
νmax/cmϪ1 (CHCl3) 3383 (br s, OH), 1438 (P–Ph) and 1161
68%
NaBH4, EtOH
OH
HO
Ph2PO
HO
OBn
68
KOH,
DMSO
23%
(P᎐O); δH (400 MHz; CDCl3) 7.9–7.75 (4 H, m), 7.6–7.25 (6 H,
᎐
m, Ph2PO), 4.07 (1 H, d, 11.4, CHOH), 3.70 (1 H, br s, OH),
2.99 (1 H, d, J 5.1, CHAHBO), 2.61 (1 H, d, J 5.1, CHAHBO),
2.44 (1 H, m, PCH), 1.89 (1 H, m), 1.62 (1 H, m), 1.31 (3 H, s,
Me), 1.3–0.9 (4 H, m) and 0.66 (3 H, t, J 7.2, Me); δC (100 MHz;
HO
HO
OBn
3
CDCl3) 132–128 (m, Ph2PO), 69.8ϩ (CHOH), 57.9Ϫ (d, JPC
17.3, MeC), 51.3Ϫ (CH2O), 40.2ϩ (d, 1JPC 68.8, PCH), 32.1Ϫ (d,
2JPC 6.6), 22.8Ϫ, 21.6Ϫ, 18.7ϩ (Me) and 13.6ϩ (Me); m/z (FAB)
359.2 (60%, MHϩ), 229.1 (80), 202.1 (100, Ph2POH) and 201.1
(85, Ph2POH).
56
Scheme 11
suitable for further functionalisation. Stereoselective reduction
of the intermediate ketones gave the triols 55, 58 and 68 with
four controlled stereogenic centres. Horner–Wittig elimination
of these triols was E-selective, yielding the diols 56 and 59 with
1,5-related stereogenic centres across an E alkene. This is the
most remote chiral relationship which has been controlled using
(2R*,3S*,4R*)-6-Benzyloxy-4-diphenylphosphinoyl-1,2-epoxy-
2-methylhexan-3-ol 9
By the same general method, the allylic alcohol1 8 (547 mg,
1.36 mmol) gave the epoxide 9 (534 mg, 94%, 89:11 ratio of
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998
1989

View Article Online
diastereomers) as an oil, Rf 0.28 (EtOAc) (Found: Mϩ Ϫ C3H5O,
in dry DMF (2 cm3) at 20 ЊC. The reaction was stirred at
60 ЊC for 1 h, cooled to 20 ЊC, diluted with saturated brine
(10 cm3) and extracted into Et2O (3 × 10 cm3). The combined
organic extracts were washed with water (10 cm3) and saturated
brine (10 cm3), dried (MgSO4) and evaporated under reduced
pressure to give a crude product which was purified by
flash chromatography eluting with 4:1 hexane–EtOAc to give
the alkene 11 (4.1 mg, 14%) as an oil, Rf 0.50 (3:1 hexane–
EtOAc); νmax/cmϪ1 (CHCl ) 3500 (br s, OH), 1630 (C᎐C), 1437
379.1464. C22H29O3P requires M Ϫ C3H5O, 379.1463); νmax
/
cmϪ1 (CHCl ) 3389 (br s, OH), 1438 (P–Ph) and 1160 (P᎐O);
᎐
3
δH (400 MHz; CDCl3) 8.0–7.75 (4 H, m), 7.5–7.22 (6 H, m,
Ph2PO), 4.34 (1 H, d, J 11.9, PhCHAHB), 4.26 (1 H, d, J 11.9,
PhCHAHB), 4.12 (1 H, d, J 11.2, CHOH), 3.81 (1 H, br s, OH),
3.35 (1 H, m, CHAHBOBn), 3.13 (1 H, m, CHAHBOBn), 3.05
(1 H, d, J 5.1, CHAHBO), 2.88 (1 H, dt, 5.5 and 3JPH 9.4, PCH),
2.54 (1 H, d, J 5.1, CHAHBO), 2.3–2.0 (2 H, m) and 1.27 (3 H,
s, Me); δC (63 MHz; CDCl3) 138.2Ϫ (ipso-Ph), 132–127 (m,
᎐
3
(P–Ph) and 1160 (P᎐O); δ (400 MHz; CDCl3) 7.4–7.1 (10 H,
᎐
H
3
Ph2PO), 72.8Ϫ (OCH2Ph), 69.3ϩ (CHOH), 67.8Ϫ (d, JPC 6.8,
m, Ph and PhS), 5.59 (1 H, br d, J 12.1, CH᎐CHCH ), 5.46
᎐
2
PhCH2O), 57.9Ϫ (d, 3JPC 17.6, MeCO), 50.8Ϫ (CH2O), 35.7ϩ (d,
1JPC 69.9, PCH), 22.8Ϫ and 18.5ϩ (Me); m/z 379.1463 (20%,
Mϩ Ϫ C3H5O), 271.1 (80) and 201.0 (100, Ph2PO).
(1 H, td, J 8.2 and 11.8, CH᎐CHCH ), 4.53 (2 H, AB q, J 12.1,
᎐
2
PhCH2), 3.81 (1 H, br s, OH), 3.50 (2 H, m, CH2OBn), 3.17
(1 H, d, J 12.7, PhSCHAHB), 3.09 (1 H, d, J 12.7, PhSCHAHB),
2.74 (1 H, m), 2.59 (1 H, m) and 1.38 (3 H, s, Me); δC (100 MHz;
CDCl3) 136.9ϩ (CH᎐CH), 129–127 (m, Ph and PhS), 125.9ϩ
᎐
(2R*,3R*,4S*)-4-Diphenylphosphinoyl-2-methyl-1-phenyl-
sulfanyloctan-2,3-diol 7
(CH᎐CH), 73.7ϩ (MeCOH), 73.2Ϫ, 68.9Ϫ, 48.3Ϫ (PhSCH2),
᎐
28.9Ϫ and 28.4ϩ (Me).
n-Butyllithium (0.26 cm3 of a 1.3 mol dmϪ3 solution in hexanes,
0.33 mmol) was added dropwise to a stirred solution of
benzenethiol (37 µl, 0.36 mmol) in dry THF (10 cm3). A solu-
tion of the phosphine oxide 6 (109 mg, 0.30 mmol) in dry
THF (5 cm3) was added dropwise by cannula to the reaction
mixture which was stirred for 30 min, quenched with saturated
ammonium chloride solution (15 cm3) and extracted with
dichloromethane (3 × 10 cm3). The combined organic extracts
were washed with saturated sodium bicarbonate solution
(30 cm3), dried (MgSO4) and evaporated under reduced pres-
sure to give a crude product which was purified by flash
chromatography eluting with 2:1 EtOAc–hexane to give the
diol 7 (52 mg, 37%) as minute needles, mp 146–147 ЊC (from
EtOAc–hexane); Rf 0.32 (3:2 EtOAc–hexane) (Found: C, 68.7;
H, 7.05; P, 6.8%; MHϩ, 469.1978. C27H33O3PS requires C, 69.2;
H, 7.10; P, 6.6%; MH, 469.1966); νmax/cmϪ1 (CHCl3) 3346 (br
(1R*,2S*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)hexyl
acetate 27
(1R*,2S*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)-
hexan-1-ol1 16 (1.245 g, 3.05 mmol) was dissolved in pyridine
(10 cm3) and acetic anhydride (10 cm3), and the reaction
mixture was stirred for 3 days. The reaction was diluted with
ethyl acetate (30 cm3), washed with hydrochloric acid (2 × 30
cm3), saturated aqueous sodium bicarbonate solution (30 cm3),
saturated brine (30 cm3) and saturated aqueous copper()
nitrate solution (30 cm3), dried (MgSO4) and evaporated under
reduced pressure to give a crude product. Purification by flash
chromatography eluting with EtOAc gave the ester 27 (992 mg,
72%) as needles, mp 185–186 ЊC (from EtOAc–hexane); Rf 0.38
(EtOAc) (Found: C, 72.3; H, 7.00; P, 6.9%; Mϩ, 450.1952.
C27H31PO4 requires C, 72.0; H, 6.95; P, 6.9%; M, 450.1960);
νmax/cmϪ1 (CHCl3) 1741 (C=O) and 1438 (P–Ph); δH (200 MHz;
CDCl3) 7.95–7.25 (10 H, m, Ph2PO), 7.13 (2 H, d, J 8.7, Ar),
6.70 (2 H, d, J 8.7, Ar), 6.20 (1 H, dd, J 4.7 and 8.7, CHOAc),
s, OH), 1438 (P–Ph) and 1159 (P᎐O); δ (200 MHz; CDCl3)
᎐
H
3
8.0–7.1 (15 H, m, Ph2PO and PhS), 4.02 (1 H, br d, JPH 14.5,
CHOH), 3.89 (1 H, br s, OH), 3.37 (1 H, d, J 13.4, CHAHBSPh),
3.05 (1 H, d, J 13.4, CHAHBSPh), 2.89 (1 H, s, OH), 2.69 (1 H,
m, PCH), 2.5–0.9 (6 H, m), 1.27 (3 H, s, Me) and 0.58 (3 H, t,
J 7.2, Me); δC (50 MHz; CDCl3) 155.9ϩ (ipso-Ph), 137–126
3
3.68 (3 H, s, OMe), 2.73 (1 H, qd, J 5.0 and JPH 9.9, PCH),
2.0–0.85 (9 H, m) and 0.56 (3 H, t, J 6.7, Me); δC (50 MHz;
CDCl3) 169.2Ϫ (C=O), 158.9Ϫ (ipso-Ar), 133–127 (m, Ph2PO
and remaining Ph), 113.5ϩ (Ar), 72.4ϩ (CHOAc), 55.0ϩ (OMe),
3
(m, Ph2PO), 74.8Ϫ (d, JPC 13.3, CMeOH), 72.9ϩ (CHOH),
1
44.6Ϫ (PhSCH2), 37.4ϩ (d, JPC 68.8, PCH), 32.4Ϫ and 22.8ϩ
(Me); m/z (FAB) 469.2 (80%, MHϩ).
44.9ϩ (d, JPC 67.8, PCH), 31.0Ϫ (d, JPC 6.8), 23.7Ϫ, 22.3Ϫ,
20.7ϩ (OAc) and 13.2ϩ (Me); m/z 450.1 (5%, Mϩ) and 202.1
(100, Ph2POH).
1
2
(2R*,3R*,4S*)-6-Benzyloxy-4-diphenylphosphinoyl-2-methyl-1-
phenylsulfanylhexane-2,3-diol 10
(1R*,2R*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)hexyl
acetate 30
By the same general method, the epoxide 9 (480 mg, 1.15 mmol)
gave a crude product which was purified by flash chromato-
graphy eluting with EtOAc, to give the diol 10 (465 mg, 77%,
72% from 8) as plates, mp 141–142 ЊC (from EtOAc–hexane);
Rf 0.32 (3:2 EtOAc–hexane) (Found: C, 69.9; H, 6.40; P, 5.8%;
MHϩ, 547.2076. C32H35O4PS requires C, 70.3; H, 6.45; P, 5.7%;
MH, 547.2072); νmax/cmϪ1 (CHCl3) 3383 (br s, OH), 1438
By the same general method, (1R*,2R*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)hexan-1-ol1 20 (2.20 g, 5.39
mmol), pyridine (17.5 cm3) and acetic anhydride (17.5 cm3)
gave a crude product after 2 days. Purification by flash chrom-
atography eluting with EtOAc gave the ester 30 (1.81 g, 75%) as
an oil, Rf 0.47 (EtOAc) (Found: Mϩ, 450.1954. C27H31PO4
requires M, 450.1960); νmax/cmϪ1 (CHCl ) 1738 (C᎐O), 1438
(P–Ph) and 1160 (P᎐O); δH (400 MHz; CDCl3) 7.85–7.1 (20 H,
᎐
m, Ph2PO and PhS), 4.40 (1 H, d, J 12.0, PhCHAHB), 4.21 (1 H,
d, J 12.1, PhCHAHB), 4.08 (1 H, br s, OH), 4.06 (1 H, br d, 3JPH
14.0, CHOH), 3.34 (1 H, br s, OH), 3.30 (1 H, m, CHAHBOBn),
3.27 (1 H, d, J 13.0, CHAHBSPh), 3.17 (1 H, d, J 12.9,
CHAHBSPh), 2.98 (1 H, m, CHAHBOBn), 2.87 (1 H, dt, J 4.4
and 9.5, PCH), 2.49 (1 H, m) and 1.89 (1 H, m); δC (50 MHz;
CDCl3) 137.8Ϫ (ipso-Ph), 136.9Ϫ (ipso-Ph), 132–125 (m, Ph2PO),
᎐
3
(P–Ph) and 1178 (P᎐O); δ (200 MHz; CDCl3) 8.0–7.4 (10 H,
᎐
H
m, Ph2PO), 7.29 (2 H, d, J 8.6, Ar), 6.83 (2 H, d, J 8.6, Ar), 6.03
(1 H, dd, J 8.3 and 9.9, CHOAc), 3.74 (3 H, s, OMe), 2.96 (1 H,
qd, J 4.8 and 3JPH 9.6, PCH), 1.6–0.8 (6 H, m), 1.3 (3 H, s, OAc)
and 0.47 (3 H, t, J 6.7, Me); δ (50 MHz; CDCl ) 168.2Ϫ (C᎐O),
᎐
C
3
159.3Ϫ (ipso-Ar), 135–128 (m, Ph2PO and remaining Ph),
113.6ϩ (Ar), 74.3ϩ (CHOAc), 55.1ϩ (OMe), 42.6ϩ (d, 1JPC 68.5,
3
75.0Ϫ (d, JPC 12.1, CH2OBn), 72.6Ϫ (PhCH2), 72.9ϩ (CHOH),
72.3ϩ (CHOH), 68.3Ϫ (CMeOH), 43.7Ϫ (PhSCH2), 34.1ϩ
PCH), 29.5Ϫ (d, JPC 6.0), 25.2Ϫ, 22.3Ϫ, 20.0ϩ (OAc) and 13.1ϩ
2
1
(d, JPC 69.0, PCH), 23.1ϩ (Me) and 22.3Ϫ; m/z (FAB) 547.2
(Me); m/z 450.1 (5%, Mϩ) and 202.1 (100, Ph2POH).
(70%, MHϩ), 201.0 (80, Ph2PO) and 91.1 (100, Bn).
(1R*,2S*)-4-Benzyloxy-2-diphenylphosphinoyl-1-(4-methoxy-
phenyl)butyl acetate 34
(Z)-6-Benzyloxy-2-methyl-1-phenylsulfanylhex-3-en-2-ol 11
Sodium hydride (16 mg of a 60% dispersion in oil, 0.40 mmol)
was added to a stirred solution of the diol 10 (51 mg, 96 µmol)
By the same general method, (1R*,2S*)-4-benxyloxy-2-di-
phenylphosphinoyl-1-(4-methoxyphenyl)butan-1-ol1 13 (3.48
1990
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998

View Article Online
g, 7.16 mmol), pyridine (25 cm3) and acetic anhydride (25 cm3)
gave a crude product after 1 day. Purification by flash chrom-
atography eluting with EtOAc gave the ester 34 (3.37 g, 89%) as
an oil, Rf 0.33 (EtOAc) (Found: Mϩ Ϫ Ac, 485.1882. C32H33PO5
requires M Ϫ Ac, 485.1882); νmax/cmϪ1 (CHCl ) 1741 (C᎐O);
mmol) gave a crude product after 2 days. Purification by flash
chromatography eluting with 2:1 EtOAc–hexane gave the
ester 21 (2.97 g, 81%) as needles, mp 181–183 ЊC (from EtOAc–
hexane); Rf 0.53 (EtOAc) (Found: C, 74.4; H, 6.45; P, 6.1%; Mϩ,
512.2116. C32H33PO4 requires C, 74.4; H, 6.65; P, 6.2%; M,
512.2109); νmax/cmϪ1 (CHCl ) 1719 (C᎐O) and 1438 (P–Ph);
᎐
3
1438 (P–Ph) and 1193 (P᎐O); δ (200 MHz; CDCl3) 8.0–7.25
᎐
᎐
H
3
(17 H, m, Ph2PO, Ph and remaining Ar), 6.77 (2 H, d, J 8.7, Ar),
6.23 (1 H, dd, J 3.3 and 9.1, CHOAc), 4.01 (2 H, AB q, J 12.9,
CH2Ph), 3.73 (3 H, s, OMe), 3.2–2.9 (3 H, m, PCH and
CH2OBn) and 2.25 (2 H, m); δC (50 MHz; CDCl3) 169.2Ϫ
δH (400 MHz; CDCl3) 8.12 (2 H, dd, J 1.3 and 8.5, ortho-Bz),
8.0–7.3 (13 H, m, Ph2PO and remaining Bz), 7.18 (2 H, d, J 8.7,
Ar), 6.82 (2 H, d, J 8.7, Ar), 6.38 (1 H, t, J 9.0, CHOBz), 3.86
(3 H, s, OMe), 3.13 (1 H, m, PCH), 1.7–0.8 (6 H, m) and 0.54
(C᎐O), 158.9Ϫ, 155.7Ϫ (ipso-Ar and Ph), 133–126 (m, Ph2PO
(3 H, t, J 7.4, Me); δC (63 MHz; CDCl3) 164.9Ϫ (C᎐O), 159.4Ϫ
᎐
᎐
and remaining Ph), 113.6ϩ (Ar), 72.2Ϫ (OCH2Ph), 71.7ϩ
(ipso-Ar), 135–126 (m, Ph2PO and remaining Ar and Bz),
1
(CHOAc), 67.9Ϫ (CH2OBn), 55.1ϩ (OMe), 40.5ϩ (d, JPC 68.1,
113.8ϩ (Ar), 75.2ϩ (CHOBz), 55.2ϩ (OMe), 43.3ϩ (d, 1JPC 68.1,
PCH), 34.0Ϫ and 20.7ϩ (OAc); m/z 485.2 (5%, Mϩ Ϫ Ac), 202.1
PCH), 29.9Ϫ (d, JPC 5.9), 25.6Ϫ, 24.6Ϫ and 13.4ϩ (Me); m/z
2
(100, Ph2POH), 201.0 (75, Ph2POH) and 91.1 (90, Bn).
512.2 (75%, Mϩ), 202.1 (85, Ph2POH) and 105 (100, PhCO).
(1S,2R,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-(4-methoxy-
phenyl)octyl acetate 42
(1R*,2S*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)propyl
benzoate 25
By the same general method, the phosphine oxide 41 (251 mg,
0.46 mmol), pyridine (2.5 cm3) and acetic anhydride (2.5 cm3)
gave a crude product after 2 days. Purification by flash chrom-
atography eluting with EtOAc gave the ester 42 (234 mg, 87%)
as an oil, Rf 0.51 (EtOAc); [α]D20 ϩ2.8 (c 0.91 in CHCl3) (Found:
Mϩ, 584.2691. C36H41PO5 requires M, 584.2693); νmax/cmϪ1
By the same general method, (1R*,2S*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)propan-1-ol1 24 (451 mg, 31.23
mmol) gave a crude product after 2 days. Purification by flash
chromatography eluting with 2:1 EtOAc–hexane gave the ester
25 (1.51 g, >98%) as needles, mp 165–166 ЊC (from EtOAc–
hexane); Rf 0.51 (EtOAc) (Found: C, 73.5; H, 5.60; P, 6.6%; Mϩ,
470.1635. C29H27PO4 requires C, 74.0; H, 5.80; P, 6.6%; M,
470.1647); νmax/cmϪ1 (CHCl ) 1723 (C᎐O) and 1438 (P–Ph);
(CHCl ) 1740 (C᎐O), 1438 (P–Ph) and 1192 (P᎐O); δ (200
᎐
᎐
3
H
MHz; CDCl3) 7.9–7.2 (15 H, m, Ph2PO and Ph), 7.13 (2 H, d,
J 8.7, Ar), 6.76 (2 H, d, J 8.8, Ar), 6.15 (1 H, dd, J 2.9 and 10.5,
CHOAc), 4.22 (1 H, d, J 12.0, PhCHAHB), 3.91 (1 H, d, J 12.0,
PhCHAHB), 3.75 (3 H, s, OMe), 2.94 (1 H, m, CHOBn), 2.73
(1 H, quin, J 5.9, PCH), 2.1 (2 H, m), 1.98 (3 H, s, OAc), 1.3–0.9
(6 H, m) and 0.78 (3 H, t, J 7.3, Me); δC (50 MHz; CDCl3)
᎐
3
δH (200 MHz; CDCl3) 7.95 (2 H, dd, J 1.3 and 7.2, ortho-Bz),
7.9–7.3 (13 H, m, Ph2PO and remaining Bz), 7.15 (2 H, d, J 8.7,
Ar), 6.72 (2 H, d, J 8.7, Ar), 6.39 (1 H, dd, J 4.8 and 8.5,
CHOBz), 3.65 (3 H, s, OMe), 2.93 (1 H, qd, J 5.0 and 2JPH 10.1,
PCH) and 1.30 (3 H, dd, J 7.3 and 3JPH 16.0, Me); δC (50 MHz;
169.4Ϫ (C᎐O), 159.0Ϫ (ipso-Ar), 139.1Ϫ (ipso-Ar), 134–127 (m,
CDCl3) 164.6Ϫ (C᎐O), 158.9Ϫ (ipso-Ar), 133–127 (m, Ph2PO
᎐
᎐
Ph2PO, Ph and remaining Ar), 113.6ϩ (Ar), 76.7ϩ (d, J 4.0,
and remaining Ar and Bz), 113.6ϩ (Ar), 73.1ϩ (CHOBz), 54.9ϩ
1
1
CHOBn), 72.7ϩ (CHOAc), 55.2ϩ (OMe), 41.0ϩ (d, JPC 67.8,
(OMe), 39.7ϩ (d, JPC 68.5, PCH) and 8.3ϩ (Me); m/z 470.2
PCH), 32.9Ϫ, 28.2Ϫ, 26.6Ϫ, 22.6Ϫ, 20.9ϩ (OAc) and 13.9ϩ (Me);
(80%, Mϩ), 365.1 (100, M Ϫ PhCO) and 202.1 (95, Ph2POH).
m/z 587.1 (45%, Mϩ), 541.3 (80, M Ϫ Ac) and 232.1 (100).
(1R*,2S*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)butane-
1,4-diyl bis(benzyl ether) 14
(1R*,2S*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)hexyl
benzoate 17
Benzyl bromide (0.75 mmol) was added dropwise to a stirred
solution of (1R*,2S*)-4-benzyloxy-2-diphenylphosphinoyl-1-
(4-methoxyphenyl)butan-1-ol1 (262 mg, 0.54 mmol), sodium
hydride (28 mg, 60% dispersion in oil, 0.7 mmol) and tetra-n-
butylammonium iodide (5 mg, 13 µmol) in dry THF (10 cm3)
at room temperature. The reaction was stirred for 3 days,
quenched with water (10 cm3), extracted with dichloromethane
(3 × 10 cm3), dried (MgSO4) and evaporated under reduced
pressure to give a crude product. Purification by flash chrom-
atography eluting with 1:1 EtOAc–hexane, to give the dibenzyl
ether 14 (322 mg, >98%) as an oil, Rf 0.49 (EtOAc) (Found:
Mϩ Ϫ Bn, 485.1878. C37H37O4P requires M Ϫ Bn, 485.1882);
νmax/cmϪ1 (CHCl ) 1437 (P–Ph) and 1201 (P᎐O); δH (200 MHz;
Triethylamine (1.78 g, 17.4 mmol) and benzoyl chloride (2.17 g,
15.3 mmol) were added dropwise to a solution of (1R*,2S*)-2-
diphenylphosphinoyl-1-(4-methoxyphenyl)hexan-1-ol 16 (1.245
g, 3.05 mmol) and N,N-dimethylaminopyridine (99 mg, 0.81
mmol) in dry dichloromethane (20 cm3) at room temperature.
The reaction was stirred for 3 days, quenched with water
(20 cm3), extracted with dichloromethane (3 × 20 cm3), dried
(MgSO4) and evaporated under reduced pressure to give a
crude product. Purification by flash chromatography eluting
with 2:1 EtOAc–hexane gave the ester 17 (1.51 g, 95%) as
needles, mp 144–145 ЊC (from EtOAc–hexane); Rf 0.51 (EtOAc)
(Found: C, 74.4; H, 6.70; P, 6.0%; Mϩ, 512.2114. C32H33PO4
requires C, 74.4; H, 6.65; P, 6.2%; M, 512.2109); νmax/cmϪ1
᎐
3
CDCl3) 8.0–7.1 (22 H, m, Ph2PO, 2 × Ph and remaining Ar),
3
(CHCl ) 1721 (C᎐O), 1438 (P–Ph) and 1212 (P᎐O); δ (200
6.76 (2 H, br d, J 8.7, Ar), 5.01 (1 H, dd, J 4.3 and JPH 7.9,
᎐
᎐
3
H
MHz; CDCl3) 8.01 (2 H, dd, J 1.3 and 7.2, ortho-Bz), 7.9–7.3
(13 H, m, Ph2PO and remaining Bz), 7.13 (2 H, d, J 8.7, Ar),
6.71 (2 H, d, J 8.7, Ar), 6.32 (1 H, dd, J 4.8 and 8.5, CHOBz),
CHOBn), 4.37 (1 H, d, J 11.3, PhCHAHB), 4.18 (1 H, d, J 11.3,
PhCHAHB), 4.10 (2 H, AB q, J 11.8, PhCH2), 3.75 (3 H,
s, OMe), 3.3–2.9 (2 H, m, CH2OBn) and 2.3–2.1 (2 H, m);
δC (50 MHz; CDCl3) 158.9Ϫ, 155.9Ϫ, 138.4Ϫ (ipso-Ph), 138.0Ϫ
(ipso-Ph), 134–127 (m, Ph2PO and remaining Ar and 2 × Ph),
2
3.71 (3 H, s, OMe), 2.88 (1 H, qd, J 5.0 and JPH 10.1, PCH),
2.1–1.8 (2 H, m), 1.05 (4 H, m) and 0.62 (3 H, t, J 7.0, Me);
δC (50 MHz; CDCl3) 169.2Ϫ (C᎐O), 159.1Ϫ (ipso-Ar), 134–127
113.6ϩ (Ar), 77.9ϩ (CHOBn), 72.3Ϫ, 70.7Ϫ, 68.6Ϫ (d, JPC 17.0,
3
᎐
(m, Ph2PO and remaining Ar and Bz), 113.7ϩ (Ar), 73.8ϩ
CH2OBn), 55.1ϩ (OMe), 43.2ϩ (d, JPC 68.4, PCH) and 24.5Ϫ;
1
1
(CHOBz), 55.2ϩ (OMe), 45.2ϩ (d, JPC 67.3, PCH), 31.0Ϫ
m/z 485.2 (45%, Mϩ Ϫ Bn) and 91.1 (100, Bn).
(d, 2JPC 6.2), 24.1Ϫ, 22.6Ϫ and 13.5ϩ (Me); m/z 512.2 (10%, Mϩ)
and 105 (100, PhCO).
(1R*,2S*)-2-Diphenylphosphinoyl-4-hydroxy-1-(4-methoxy-
phenyl)butyl acetate 35
(1R*,2R*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)hexyl
A solution of (1R*,2S*)-4-benzyloxy-2-diphenylphosphinoyl-
1-(4-methoxyphenyl)butyl acetate 34 (510 mg, 0.97 mmol) and
palladium on carbon (5% by weight, 48 mg) in methanol
(20 cm3) was degassed and flushed with argon, degassed and
benzoate 21
By the same general method, (1R*,2R*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)hexan-1-ol1 20 (2.93 g, 7.18
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998
1991

View Article Online
flushed with hydrogen (×2), and stirred for 3 days under a
hydrogen atmosphere. The reaction mixture was filtered
through Celite with dichloromethane (50 cm3) and evaporated
under reduced pressure to give a crude product which was
purified by flash chromatography eluting with 5% methanol
in EtOAc, to give the alcohol 35 (330 mg, 78%) as minute
needles, mp 164–165 ЊC (from EtOAc–hexane); Rf 0.43 (EtOAc)
(Found: C, 68.4; H, 7.25; P, 8.0%; Mϩ, 438.1601. C25H27O5P
requires C, 68.4; H, 7.20; P, 8.0%; M, 438.1596); νmax/cmϪ1
134–128 (m, Ph2PO and remaining Ar), 126.8ϩ (Ar), 122.9ϩ
(Ar), 113.6ϩ (Ar), 71.7ϩ (CHOAc), 54.8ϩ (OMe), 42.4ϩ (d,
3
1JPC 67.0, PCH), 37.7Ϫ (d, JPC 5.2, CHN), 22.6Ϫ and 21.0ϩ
(OAc); m/z 524.2 (10%, Mϩ Ϫ Ac), 202.1 (90, Ph2POH) and
77.0 (100, Ph).
(1S,2R,3E)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)oct-3-
enyl acetate 44
Diethyl azodicarboxylate (0.29 cm3, 1.82 mmol) was added
dropwise to a solution of (1S,2R,4R)-2-diphenylphosphinoyl-
4-hydroxy-1-(4-methoxyphenyl)octyl acetate 43 (610 mg, 1.24
mmol), triphenylphosphine (493 mg, 1.88 mmol) and phthal-
imide (220 mg, 1.50 mmol) in dry THF (30 cm3) at 20 ЊC. The
reaction was stirred for 16 h and evaporated under reduced
pressure to give a crude product which was purified by flash
chromatography eluting with 1:1 EtOAc–hexane and then
EtOAc to give the allylic phosphine oxide 44 (373 mg, 63%) as
an oil, Rf 0.29 (EtOAc); [α]D20 Ϫ1.7 (c 0.91 in CHCl3) (Found:
Mϩ, 476.2112. C29H33O4P requires M, 476.2116); νmax/cmϪ1
(CHCl ) 3379 (OH), 1743 (C᎐O) and 1438 (P–Ph); δ (400
᎐
3
H
MHz; CDCl3) 7.9–7.4 (10 H, m, Ph2PO), 7.07 (2 H, d, J 8.7,
3
Ar), 6.74 (2 H, d, J 8.7, Ar), 6.13 (1 H, dd, J 3.9 and JPH 8.5,
CHOAc), 3.72 (3 H, s, OMe), 3.63 (1 H, m), 3.48 (1 H, m), 3.00
(1 H, m), 2.08 (1 H, m), 2.04 (1 H, m) and 1.94 (3 H, s, OAc);
δ (100 MHz; CDCl ) 169.2Ϫ (C᎐O), 159.2Ϫ (ipso-Ar), 132–127
᎐
C
3
(m, Ph2PO and remaining Ar), 114.0ϩ (Ar), 72.3ϩ (CHOAc),
60.4Ϫ (d, JPC 5.0, CH2OH), 55.2ϩ (OMe), 42.7ϩ (d, JPC 66.8,
PCH), 27.4Ϫ and 20.9ϩ (OAc); m/z 438.2 (10%, Mϩ) and 202.1
(100, Ph2POH).
3
1
(CHCl ) 1740 (C᎐O), 1612 (C᎐C), 1437 (P–Ph) and 1176 (P᎐O);
᎐
᎐
᎐
3
(1S,2R,4R)-2-Diphenylphosphinoyl-4-hydroxy-1-(4-methoxy-
phenyl)octyl acetate 43
δH (200 MHz; CDCl3) 7.9–7.1 (10 H, m, Ph2PO), 7.08 (2 H, d,
J 8.7, Ar), 6.68 (2 H, d, J 8.7, Ar), 6.20 (1 H, dd, J 4.5 and 3JPH
8.5, CHOAc), 5.05 (2 H, m, CH᎐CH), 3.71 (3 H, s, OMe), 2.86
(1 H, m), 2.52 (2 H, m), 1.98 (3 H, s, Ac), 1.9–1.75 (2 H, m), 1.15
᎐
A solution of (1S,2R,4R)-4-benzyloxy-2-diphenylphosphinoyl-
1-(4-methoxyphenyl)octyl acetate 42 (191 mg, 0.32 mmol) and
palladium on carbon (5% by weight, 16 mg) in methanol
(10 cm3) was agitated under an atmosphere of hydrogen (4 atm)
for 2 days, filtered through Celite with dichloromethane
(50 cm3) and evaporated under reduced pressure to give a crude
product which was purified by flash chromatography eluting
with EtOAc to give the alcohol 43 (84 mg, 52%, 72% based on
recovered starting material) as minute needles, mp 170–171 ЊC
(from EtOAc–hexane); Rf 0.22 (EtOAc) (Found: C, 70.3; H,
7.25; P, 6.2%; Mϩ Ϫ H, 495.2295. C29H35O5P requires C, 70.4;
H, 7.15; P, 6.2%; M Ϫ H, 495.2300); νmax/cmϪ1 (CHCl3) 3359
(OH), 1743 (C᎐O), 1438 (P–Ph) and 1176 (P᎐O); δ (400 MHz;
(2 H, m) and 0.82 (3 H, t, J 7.3, Me); δC (50 MHz; CDCl3)
169.2Ϫ (C᎐O), 159.0Ϫ (ipso-Ar), 132–127 (m, Ph2PO and
᎐
remaining Ar), 113.4ϩ (Ar), 72.7ϩ (CHOAc), 55.1ϩ (OMe),
45.1ϩ (d, 1JPC 68.1, PCH), 34.2Ϫ, 28.6Ϫ, 27.7Ϫ, 22.2Ϫ, 20.8ϩ (Ac)
and 13.6ϩ (Me); m/z 476.2 (15%, Mϩ), 433 (40, M Ϫ Ac), 277
(100) and 201.1 (35, Ph2PO).
(2R*,3S*)-2-Benzoyloxy-3-diphenylphosphinoylbutanoic acid 26
Sodium periodate (1.15 g, 5.4 mmol) was added to a stirred
solution of the benzoate 25 (181 mg, 0.39 mmol) in 3:2:2
water–acetonitrile–carbon tetrachloride (3.5 cm3). The reaction
mixture was stirred until the phases were clear, ruthenium
chloride (2 mg, 1 µmol) added, the reaction mixture stirred for
16 h, quenched with water (10 cm3) extracted with dichloro-
methane (3 × 10 cm3), dried (MgSO4) and evaporated under
reduced pressure to give a crude product which was the acid 26,
Rf 0.0 (EtOAc) (Found: MHϩ, 409.1210. C23H21O5P requires
MH, 409.1205); νmax/cmϪ1 (CHCl3) 3600–2300 (OH), 1724
(C᎐O), 1438 (P–Ph) and 1199 (P᎐O); δ (400 MHz; CDCl3)
᎐
᎐
H
CDCl3) 7.9–7.4 (10 H, m, Ph2PO), 7.07 (2 H, d, J 8.6, Ar), 6.73
(2 H, d, J 8.6, Ar), 6.12 (1 H, dd, J 4.3 and 3JPH 7.9, CHOAc),
3.75 (3 H, s, OMe), 3.70 (1 H, m), 3.56 (1 H, m), 3.06 (1 H,
m, PCH), 2.2–0.95 (10 H, m) and 0.78 (3 H, t, J 7.3, Me);
δ (100 MHz; CDCl ) 169.2Ϫ (C᎐O), 159.1Ϫ (ipso-Ar), 132–126
᎐
C
3
(m, Ph2PO and remaining Ar), 113.9ϩ (Ar), 72.8ϩ (CHOAc),
68.2ϩ (CHOH), 55.2ϩ (OMe), 42.3ϩ (d, 1JPC 66.4, PCH), 37.3Ϫ,
31.9Ϫ, 27.8Ϫ, 22.5Ϫ, 21.0ϩ (OAc) and 13.9ϩ (Me); m/z 495.2
(10%, Mϩ Ϫ H), 435.2 (100) and 201.1 (60, Ph2PO). Recovered
starting material was also obtained (51 mg, 27%).
᎐
᎐
H
10.25 (1 H, br s, CO2H), 7.95–7.25 (15 H, m, Ph2PO and Ph),
5.59 (1 H, dd, J 1.9 and 3JPH 9.8, CHOBz), 3.39 (1 H, dqd, J 1.9,
7.2 and 2JPH 10.5, PCH) and 1.38 (3 H, dd, J 7.2 and 3JPH 15.8,
Me); δC (50 MHz; CDCl3) 170.2Ϫ, 169.9Ϫ, 165.1Ϫ, 133–128 (m,
Ph2PO and remaining Ar), 70.6ϩ (CHOBz), 35.0ϩ (d, 1JPC 69.9,
PCH) and 7.4ϩ (Me); m/z (FAB) 409.1 (100%, MHϩ).
(1R*,2S*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)-4-
phthalimidobutyl acetate 36
Diethyl azodicarboxylate (0.71 cm3, 4.52 mmol) was added
dropwise to a solution of (1R*,2S*)-2-diphenylphosphinoyl-4-
hydroxy-1-(4-methoxyphenyl)butyl acetate 35 (1.34 g, 3.06
mmol), triphenylphosphine (1.20 g, 4.58 mmol) and phthal-
imide (532 mg, 3.64 mmol) in dry THF (60 cm3) at 20 ЊC. The
reaction was stirred for 16 h and evaporated under reduced
pressure to give a crude product which was purified by flash
chromatography eluting with 78:17:5 EtOAc–hexane–
methanol and HPLC eluting with 0.8% methanol in chloro-
form, to give the phthalimide 36 (1.26 g, 73%) as an oil, HPLC
retention time 19 min; Rf 0.34 (EtOAc) (Found: Mϩ Ϫ Ac,
524.1617. C33H30NO6P requires M Ϫ Ac, 524.1627); νmax/cmϪ1
(1R*,2S*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)butane-
1,4-diyl dibenzoate 15
By the same general method, the diether 14 (55 mg, 95 µmol),
sodium periodate (280 mg, 1.31 mmol) and ruthenium tri-
chloride (3 mg, 1.5 µmol) gave a crude product which was
purified by flash chromatography eluting with 3:1 EtOAc–
hexane to give the diester 15 (8 mg, 14%) as an oil, Rf 0.52
(EtOAc); δH (200 MHz; CDCl3) 8.1–7.1 (22 H, m, Ph2PO and
2
2 × Bz), 6.73 (2 H, d, J 6.7, Ar), 6.35 (1 H, dd, J 3.5 and JPH
9.0, ArCH), 4.02 (2 H, t, J 5.1, CH2OBz), 3.68 (3 H, s, OMe),
3.19 (1 H, m, PCH) and 2.50 (2 H, m).
(CHCl ) 1770 (imide C᎐O), 1741 (C᎐O), 1708 (imide C᎐O) and
᎐
᎐
᎐
3
1438 (P–Ph); δH (400 MHz; CDCl3) 8.0–7.4 (14 H, m, Ph2PO
and Ar), 6.98 (2 H, d, J 8.7, Ar), 6.43 (2 H, d, J 8.7, Ar), 6.11
(1 H, dd, J 3.3 and 3JPH 8.7, CHOAc), 3.48 (3 H, s, OMe), 3.28
(1 H, td, J 5.0 and 13.9, NCHAHB), 3.12 (1 H, ddd, J 5.0, 8.9
(2R*,3S*)-2-Benzoyloxy-3-diphenylphosphinoylheptanoic acid
18
By the same general method, (1R*,2S*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)hexyl benzoate 17 (401 mg, 0.78
mmol), sodium periodate (2.54 g, 11.8 mmol) and ruthenium
trichloride (3 mg, 1.5 µmol) gave a crude product which was
2
and 13.9, NCHAHB), 2.90 (1 H, qd, J 4.0 and JPH 9.2, PCH),
2.23 (2 H, m) and 1.99 (3 H, Ac); δC (50 MHz; CDCl3) 169.3Ϫ,
168.4Ϫ (C᎐O × 3), 158.7Ϫ (ipso-Ar), 155.8ϩ (Ar), 133.5ϩ (Ar),
᎐
1992
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998

View Article Online
dissolved in ethyl acetate (10 cm3) and extracted with saturated
sodium bicarbonate solution (3 × 5 cm3). The combined
aqueous fractions were acidifed to pH 1, extracted with dichloro-
methane (3 × 5 cm3) and the organic fractions were washed
with brine (10 cm3) to give the acid 18 (320 mg, 91%) as an oil,
Rf 0.0 (EtOAc) (Found: Mϩ, 450.1624. C26H27O5P requires M,
450.1599); νmax/cmϪ1 (CHCl ) 3600–2800 (OH), 1721 (C᎐O) and
Methyl (2R*,3S*)-3-diphenylphosphinoyl-2-hydroxyheptanoate
29
By the same general method, (1R*,2S*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)hexyl acetate 27 (505 mg, 1.12
mmol), sodium periodate (4.0 g, 18.7 mmol) and ruthenium
trichloride (40 mg, 0.2 mmol) gave a crude product (550 mg)
which was the acid 28, Rf 0.0 (EtOAc) (Found: Mϩ, 390.1626.
C26H29O4P requires M, 390.1596); νmax/cmϪ1 (CHCl3) 3700–
᎐
3
1438 (P–Ph); δH (400 MHz; CDCl3) 10.25 (1 H, br s, CO2H),
3
8.0–7.21 (15 H, m, Ph2PO and Ph), 5.52 (1 H, br d, JPH 9.8,
2700 (OH), 1744 (C᎐O), 1438 (P–Ph) and 1205 (P᎐O); δ (400
᎐
᎐
H
CHOBz), 3.32 (1 H, m, PCH), 2.1–0.8 (6 H, m) and 0.66 (3 H,
MHz; CDCl3) 7.9–7.3 (10 H, m, Ph2PO), 6.4 (1 H, br s, CO2H),
3
t, J 6.7, Me); δC (50 MHz; CDCl3) 170.6Ϫ (d, JPC 5.6, CO2H),
3
5.52 (1 H, dd, J 2.5 and JPH 14.9, CHOAc), 3.19 (1 H, m,
164.9Ϫ (PhCO), 133–128 (m, Ph2PO and Ar), 69.4ϩ (CHOBz),
PCH), 2.0–1.1 (6 H, m), 1.79 (3 H, s, OAc) and 0.75 (3 H, t,
1
2
39.7ϩ (d, JPC 69.0, PCH), 30.1Ϫ (d, JPC 8.1), 23.4Ϫ, 22.3Ϫ and
13.4ϩ (Me); m/z 450.2 (1%, Mϩ), 202.1 (100, Ph2POH) and
105.0 (95, PhCO).
3
J 7.2, Me); δC (100 MHz; CDCl3) 170.4Ϫ (d, JPC 13.4, C᎐O),
᎐
169.6Ϫ (MeCO), 132–128 (m, Ph2PO), 69.5ϩ (CHOAc), 39.8ϩ
1
2
(d, JPC 69.0, PCH), 30.3Ϫ (d, JPC 10.0), 23.9Ϫ, 22.4Ϫ, 20.2Ϫ
(OAc) and 13.6ϩ (Me); m/z 390.2 (10%, Mϩ), 294 (100) and 69.3
(100). A portion of the crude product (148 mg) was dissolved in
methanol (10 cm3), concentrated hydrochloric acid was added
(4 cm3) and the reaction stirred at 50 ЊC for 1 day. The reaction
was quenched with water (10 cm3), extracted with dichloro-
methane (3 × 10 cm3), dried (MgSO4) and evaporated to give a
crude product, which was purified by flash chromatography
eluting with 5% methanol in EtOAc to give the ester 29 (68 mg,
59%) as an oil, Rf 0.40 (EtOAc) (Found: Mϩ, 360.1490.
C20H25O4P requires M, 360.1490); νmax/cmϪ1 (CHCl3) 3387
(OH), 1732 (C᎐O), 1438 (P–Ph) and 1221 (P᎐O); δ (400 MHz;
Methyl (2R*,3S*)-2-benzoyloxy-3-diphenylphosphinoyl-
heptanoate 19
By the same general method, (1R*,2S*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)hexyl benzoate 17 (1.00 g, 1.96
mmol), sodium periodate (6.34 g, 29.6 mmol) and ruthenium
trichloride (10 mg, 5 µmol) gave a crude product (950 mg).
A portion of this product (143 mg) was dissolved in methanol
(5 cm3) and thionyl chloride (10 µl, 0.14 mmol) was added. The
reaction mixture was stirred for 36 h, quenched with saturated
sodium bicarbonate (5 cm3), extracted with dichloromethane
(3 × 5 cm3), dried (MgSO4) and evaporated to give a crude
product which was purified by flash chromatography eluting
with 1:1 EtOAc–hexane, to give the ester 19 (75 mg, 55%) as an
oil, Rf 0.59 (EtOAc) (Found: Mϩ, 464.1722. C27H29O5P requires
M, 464.1725); νmax/cmϪ1 (CHCl ) 1720 (C᎐O) and 1437 (P–Ph);
᎐
᎐
H
3
CDCl3) 7.95–7.4 (10 H, m, Ph2PO), 4.63 (1 H, d, JPH 12.1,
CHOH), 4.31 (1 H, br s, OH), 3.73 (3 H, s, OMe), 2.88 (1 H, m,
PCH), 1.92 (1 H, m), 1.55 (1 H, m), 1.3–0.9 (4 H, m) and 0.71
(3 H, t, J 7.3, Me); δC (100 MHz; CDCl3) 173.1Ϫ (d, JPC 17.4,
3
C᎐O), 132–128 (m, Ph PO), 68.8ϩ, 52.3ϩ (OMe), 41.0ϩ (d,
᎐
᎐
3
2
2
δH (400 MHz; CDCl3) 8.0–7.2 (15 H, m, Ph2PO and Ph), 5.51
1JPC 68.9, PCH), 30.4Ϫ (d, JPC 9.5), 22.5Ϫ, 22.4Ϫ and 13.6ϩ
(1 H, dd, J 1.8 and 3JPH 11.3, CHOBz), 3.74 (3 H, s, OMe), 3.16
(Me); m/z 360.1 (10%, Mϩ), 245.1 (60) and 202.1 (100,
2
(1 H, dtd, J 1.8, 6.6 and JPH 11.2, PCH), 1.96 (2 H, m), 1.25
Ph2POH).
(4 H, m) and 0.79 (3 H, t, J 7.0, Me); δC (100 MHz; CDCl3)
3
169.9Ϫ (d, JPC 15.9, CO2Me), 165.3Ϫ (PhCO), 133–126 (m,
Methyl (2R*,3S*)-3-diphenylphosphinoyl-2-hydroxyheptanoate
32
Ph2PO and Ar), 69.8ϩ (CHOBz), 52.7ϩ (OMe), 40.5ϩ (d,
1JPC 68.5, PCH), 30.5Ϫ (d, JPC 8.6), 23.7Ϫ, 22.5Ϫ and 13.7ϩ
2
By the same general method, (1R*,2R*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)hexyl acetate 30 (1.02 g, 2.26
mmol), sodium periodate (8.0 g, 37.0 mmol) and ruthenium
trichloride (100 mg, 0.5 mmol) gave a crude product (0.91 g)
which was the acid 31, Rf 0.0 (EtOAc) (Found: Mϩ Ϫ H,
389.1511. C26H29O4P requires M Ϫ H, 389.1514); νmax/cmϪ1
(Me); m/z 464.2 (10%, Mϩ), 202.1 (70, Ph2POH), 105.0 (100,
PhCO) and 77 (65, Ph).
(2R*,3R*)-2-Benzoyloxy-3-diphenylphosphinoyl-N-methoxy-N-
methylheptanamide 23
By the same general method, (1R*,2R*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)hexyl benzoate 21 (380 mg, 0.74
mmol), sodium periodate (2.31 g, 10.8 mmol) and ruthenium
trichloride (4 mg, 2 µmol) gave a crude product (400 mg). A
portion of this product (180 mg) was dissolved in dry dichloro-
methane (5 cm3), carbonyldiimidazole (71 mg, 0.44 mmol) was
added, the mixture was stirred for 10 min and N-methoxy-N-
methylammonium chloride (46 mg, 0.46 mmol) was added. The
reaction mixture was stirred for 16 h, diluted with dichloro-
methane (10 cm3), washed with dilute hydrochloric acid (0.3
mol dmϪ3, 2 × 10 cm3), saturated sodium bicarbonate solution
(10 cm3) and brine (10 cm3), dried (MgSO4) and evaporated
to give a crude product which was purified by flash chrom-
atography eluting with 3:1 EtOAc–hexane to give the amide
23 (33 mg, 18%) as an oil, Rf 0.32 (EtOAc) (Found: Mϩ Ϫ
MeONMe, 433.1574. C28H32NO5P requires M Ϫ MeONMe,
433.1568); νmax/cmϪ1 (CHCl ) 1718 (C᎐O), 1664 (amide C᎐O),
(CHCl ) 3500–2500 (OH), 1742 (C᎐O), 1438 (P–Ph) and 1195
᎐
3
(P᎐O); δ (400 MHz; CDCl3) 10.5–10.0 (1 H, br s, CO2H),
᎐
H
3
7.9–7.4 (10 H, m, Ph2PO), 5.53 (1 H, dd, J 2.3 and JPH 17.3,
CHOAc), 3.14 (1 H, m, PCH), 1.81 (3 H, s, OAc), 1.65–1.1
(6 H, m) and 0.73 (3 H, t, J 7.1, Me); δC (100 MHz; CDCl3)
169.5Ϫ, 168.9Ϫ, 133–128 (m, Ph2PO), 70.1ϩ (CHOAc), 40.5ϩ
1
2
(d, JPC 67.1, PCH), 30.0Ϫ (d, JPC 10.9), 25.1Ϫ, 21.9Ϫ, 20.1ϩ
(OAc) and 13.4ϩ (Me); m/z 389.2 (10%, Mϩ Ϫ H) and 201.0
(Ph2PO). The crude product was dissolved in methanol
(60 cm3), concentrated hydrochloric acid was added (20 cm3)
and the reaction was stirred at 50 ЊC for 1 day. The reaction was
quenched with water (60 cm3), extracted with dichloromethane
(3 × 50 cm3), dried (MgSO4) and evaporated to give a crude
product, which was purified by flash chromatography eluting
with EtOAc to give the ester 32 (432 mg, 55%) as an oil, Rf
0.38 (EtOAc) (Found: Mϩ, 360.1490. C20H25O4P requires M,
360.1490); νmax/cmϪ1 (CHCl ) 3370 (OH), 1733 (C᎐O) and
᎐
᎐
᎐
3
3
1422 (P–Ph) and 1213 (P᎐O); δ (400 MHz; CDCl3) 8.03–7.79
1438 (P–Ph); δH (400 MHz; CDCl3) 7.9–7.3 (10 H, m,
Ph2PO), 5.05 (1 H, d, J 8.8, OH), 4.50 (1 H, ddd, J 2.8, 8.7
and JPH 26.8, CHOH), 3.15 (3 H, s, OMe), 2.84 (1 H, tdd,
᎐
H
(4 H, m), 7.48–7.1 (11 H, m, Ph2PO and remaining Ph), 6.02
(1 H, dd, J 8.4 and 12.8, CHOBz), 3.86 (3 H, s, OMe), 3.21
(1 H, m, PCH), 3.13 (3 H, s, NMe), 1.69 (2 H, m), 1.4–1.0 (4 H,
m) and 0.71 (3 H, t, J 7.3, Me); δC (100 MHz; CDCl3) 168.7Ϫ,
165.8Ϫ, 134–127 (m, Ph2PO and Ar), 69.4ϩ (CHOBz), 61.1ϩ
3
J 2.7, 8.0 and 1.08, PCH), 2.0–1.1 (6 H, m) and 0.75 (3 H,
t, J 6.9, Me); δC (100 MHz; CDCl3) 173.2Ϫ, 132–128 (m,
2
Ph2PO), 70.5ϩ (d, JPC 4.5, CHOH), 51.6ϩ (OMe), 40.0ϩ (d,
1
2
2
(OMe), 39.8ϩ (d, JPC 69.4, PCH), 30.2ϩ (NMe), 30.4Ϫ (d, JPC
7.5), 24.4Ϫ, 22.5Ϫ and 13.5ϩ (Me); m/z 433.2 (20%, Mϩ Ϫ
MeONMe) and 105.0 (100, PhCO).
1JPC 66.8, PCH), 29.5Ϫ (d, JPC 11.1), 25.5Ϫ, 22.0Ϫ and 13.0ϩ
(Me); m/z 360.1 (50%, Mϩ), 301.1 (65, Mϩ Ϫ MeCO) and 201.1
(100, Ph2PO).
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998
1993

View Article Online
Methyl (2R*,3S*)-3-diphenylphosphinoyl-2-hydroxy-5-
phthalimidopentanoate 38
Methyl (2R*,3R*)-3-diphenylphosphinoyl-2-methoxymethoxy-
heptanoate 39
By the same general method, (1R*,2S*)-2-diphenylphos-
phinoyl-1-(4-methoxyphenyl)-4-phthalimidobutyl acetate 36
(978 mg, 1.72 mmol), sodium periodate (7.62 g, 35.6 mmol) and
ruthenium trichloride (10 mg, 5 µmol) gave a crude product
which was the acid 37, Rf 0.0 (EtOAc) (Found: MHϩ, 506.1369.
C27H24NO7P requires MH, 506.1398); νmax/cmϪ1 (CHCl3) 3800–
Methoxymethyl chloride (0.22 cm3, 0.29 mmol) and diisoprop-
ylethylamine (0.42 cm3, 2.4 mmol) were added dropwise to a
stirred solution of methyl (2R*,3S*)-3-diphenylphosphinoyl-2-
hydroxyheptanoate 32 (218 mg, 0.61 mmol) in dry dichloro-
methane (5 cm3) at 0 ЊC. The solution was stirred for 1 h,
allowed to warm to room temperature, stirred for a further
7 days, quenched with aqueous saturated sodium carbonate
(10 cm3), extracted with dichloromethane (3 × 5 cm3), dried
(MgSO4) and evaporated under reduced pressure to give a
crude which was purified by flash chromatography eluting with
EtOAc to give the methoxymethyl ether 39 (210 mg, 86%) as an
oil, Rf 0.38 (EtOAc) (Found: Mϩ, 404.1742. C22H29O5P requires
M, 404.1752); νmax/cmϪ1 (CHCl ) 1743 (C᎐O), 1437 (P–Ph),
2500 (OH), 1740–1650 (C᎐O) and 1206 (P᎐O); δ (400 MHz;
᎐
᎐
H
CDCl3) 8.70 (1 H, br s, CO2H), 7.9–7.4 (14 H, m, Ph2PO and
Ar), 5.45 (1 H, dd, J 1.4 and 3JPH 13.2, CHOAc), 3.58 (1 H, m),
3.35 (1 H, m), 2.5–2.0 (3 H, m) and 1.98 (3 H, s, OAc); δC (100
MHz; CDCl3) 170.4Ϫ (d, 3JPC 13.2, C᎐O), 169.0Ϫ, 168.0Ϫ, 133.8ϩ
᎐
(Ar), 133–128 (m, Ph2PO and remaining Ar), 128.2ϩ (Ar),
1
116.4Ϫ (Ar), 68.7ϩ (CHOAc), 37.9ϩ (d, JPC 70.8, PCH), 36.8Ϫ
᎐
3
2
(d, JPC 9.7), 23.4Ϫ and 20.3ϩ (OAc); m/z (FAB) 506.1 (80%,
1182 (P᎐O); δ (400 MHz; CDCl3) 7.8–7.2 (10 H, m, Ph2PO),
᎐
H
MHϩ) and 307.1 (100). The crude product was dissolved in
methanol (60 cm3), concentrated hydrochloric acid was added
(20 cm3) and the reaction was stirred at 50 ЊC for 5 h. The
reaction was quenched with water (60 cm3), extracted with
dichloromethane (3 × 50 cm3), dried (MgSO4) and evaporated
to give a crude product, which was purified by flash chrom-
atography eluting with EtOAc to give the ester 38 (412 mg,
61%) as an oil, Rf 0.38 (EtOAc) (Found: MHϩ, 478.1538.
C26H24NO6P requires MH, 478.1419); νmax/cmϪ1 (CHCl3) 3449
4.46 (1 H, d, J 7.0, MeOCHAHB), 4.42 (1 H, dd, J 6.6 and 3JPH
13.2, CHOMOM), 4.34 (1 H, d, J 7.0, MeOCHAHB), 3.59 (3 H,
s, OMe), 2.99 (1 H, m, PCH), 1.7–1.0 (6 H, m) and 0.70 (3 H, t,
J 7.2, Me); δC (50 MHz; CDCl3) 133–128 (m, Ph2PO), 96.7Ϫ
(OCH2O), 75.3ϩ (CHOMOM), 56.2ϩ, 52.0ϩ (OMe × 2), 41.5ϩ
1
2
(d, JPC 69.8, PCH), 29.8Ϫ (d, JPC 8.2), 25.3Ϫ, 22.4Ϫ and 13.6ϩ
(Me); m/z 404.2 (20%, Mϩ), 202.1 (100, Ph2POH) and 201.1
(100, Ph2PO).
(OH), 1710 (C᎐O), 1438 (P–Ph) and 1219 (P᎐O); δ (400 MHz;
᎐
᎐
H
Methyl (2R*,3S*)-3-diphenylphosphinoyl-2-methoxymethoxy-5-
phthalimidopentanoate 40
CDCl3) 8.0–7.3 (14 H, m, Ph2PO and Ar), 4.66 (1 H, br s, OH),
4.62 (1 H, d, 3JPH 10.5, CHOH), 3.60 (3 H, s, OMe), 3.41 (1 H,
td, J 5.5 and 14.0, NCHAHB), 3.22 (1 H, ddd, J 5.7, 8.9 and
14.0, NCHAHB), 3.01 (1 H, m, PCH) and 2.2 (2 H, m); δC (100
MHz; CDCl3) 168.5Ϫ (C᎐O × 3), 134–128 (m, Ph PO and
By the same general method, methyl (2R*,3S*)-3-diphenyl-
phosphinoyl-2-hydroxy-5-phthalimidopentanoate 38 (375 mg,
0.89 mmol), diisopropylethylamine (1.26 cm3, 7.2 mmol) and
methoxymethyl chloride (0.66 cm3, 0.89 mmol) gave a crude
product after 10 days which was purified by flash chrom-
atography eluting with 2% methanol in EtOAc to give the
methoxymethyl ether 40 (362 mg, 87%) as an oil, Rf 0.29
(EtOAc) (Found: MHϩ, 522.1661. C28H28NO7P requires MH,
522.1682); νmax/cmϪ1 (CHCl ) 1772 (imide C᎐O), 1747 (C᎐O),
᎐
2
remaining Ar), 123.1ϩ (Ar), 113.6ϩ (Ar), 70.2ϩ, 52.6ϩ (OMe),
38.2ϩ (d, JPC 68.7, PCH), 36.9Ϫ (d, JPC 5.3) and 22.5Ϫ;
m/z 478.1 (FAB, MHϩ), 279 (100, EI) and 201.1 (90, EI,
Ph2PO).
1
2
Methyl (2R*,3S*)-2-benzoyloxy-3-diphenylphosphinoyl-
᎐
᎐
3
heptanoate 19
1712 (imide C᎐O), 1438 (P–Ph) and 1173 (P᎐O); δH (400 MHz;
᎐ ᎐
CDCl3) 7.85–7.2 (14 H, m, Ph2PO and Ar), 4.62 (3 H, m,
CHOCH2OMe), 3.63 (3 H, s, OMe), 3.45 (2 H, m), 3.26 (3
H, m, OMe), 2.94 (1 H, m) and 2.45–2.1 (2 H, m); δC (50
Diazomethane30 (ca. 0.3 mol dmϪ3 in Et2O) was added drop-
wise to a solution of acid 18 in ethyl acetate (6 cm3) until
a yellow colour persisted. The reaction was quenched by
dropwise addition of acetic acid until the reaction mixture
was colourless, and evaporated under reduced pressure to
give a crude product which was purified by flash chrom-
atography eluting with EtOAc, to give the methyl ester 19
(150 mg, 44%), identical spectroscopically with that obtained
previously.
3
MHz; CDCl3) 171.9Ϫ (d, JPC 14.4, C᎐O), 167.9Ϫ (C᎐O),
᎐
᎐
134–128 (m, Ph2PO and remaining Ar), 122.9ϩ (Ar), 96.4Ϫ
(OCH2O), 72.1ϩ (CHOMOM), 56.3ϩ, 52.1ϩ (OMe × 2), 39.5ϩ
(d, JPC 69.2, PCH), 37.0Ϫ (d, JPC 9.3) and 22.3Ϫ; m/z
(FAB) 522.1 (100%, MHϩ), 279 (80), 201.1 (75, Ph2PO) and
154.1 (100).
1
3
(2R*,3S*)-3-Diphenylphosphinoylheptane-1,2-diol 33
(2R*,6R*,1ЈS*)- and (2S*,6R*,1ЈR*)-2-(3Ј-Benzyloxy-1Ј-di-
phenylphosphinoylpropyl)-6-hydroxy-3,6-dihydro-2H-pyran-3-
one 47
Methyl ester 19 (260 mg, 056 mmol) in dry THF (5 cm3) was
added by cannula dropwise to a stirred suspension of lithium
aluminium hydride (127 mg, 3.36 mmol) in dry THF (5 cm3) at
20 ЊC. The reaction was stirred for 2 h, quenched with water
(10 cm3), extracted with dichloromethane (3 × 10 cm3), dried
(MgSO4) and evaporated under reduced pressure to give a
crude product which was purified by flash chromatography
eluting with 5% methanol in EtOAc to give the diol 33 (96 mg,
52%) as an oil, Rf 0.23 (5% methanol in EtOAc) (Found:
Mϩ Ϫ CH2OH, 301.1354. C19H25O3P requires M Ϫ CH2OH,
301.1357); νmax/cmϪ1 (CHCl3) 3387 (OH), 1438 (P–Ph) and 1223
m-Chloroperbenzoic acid (328 mg, 57–85% by weight, ca. 1.34
mmol) was added to a stirred solution of (1R*,2S*)-4-benzyl-
oxy-2-diphenylphosphinoyl-1-(2-furyl)butan-1-ol1 46 (596 mg,
1.34 mmol) in dry dichloromethane (12 cm3) at 0 ЊC. The
reaction mixture was stirred for 2 days, diluted with dichloro-
methane (10 cm3) washed with saturated sodium carbonate
solution (20 cm3), saturated sodium thiosulfate solution
(20 cm3) and saturated sodium carbonate solution (20 cm3),
dried (MgSO4) and evaporated under reduced pressure to give
a crude product which was purified by flash chromatography
eluting with 5% methanol in EtOAc to give the enone 47 (401
mg, 65%, 83:17 mixture of hemiacetal epimers) as a foam, Rf
0.25 (EtOAc) (Found: MHϩ, 463.1644. C27H27O5P requires
MH, 463.1674); νmax/cmϪ1 (CHCl ) 3268 (br, OH), 1696 (C᎐O),
(P᎐O); δ (400 MHz; CDCl3) 7.9–7.7 (4 H, m), 7.55–7.4 (6 H,
᎐
H
m), 5.17 (1 H, m, CHOH), 3.79 (1 H, dd, J 5.6 and 11.3,
CHAHBOH), 3.48 (1 H, dd, J 5.2 and 11.3, CHAHBOH), 3.38
(1 H, br s, OH), 2.47 (1 H, m, PCH), 1.84 (1 H, br s, OH),
1.8–1.0 (6 H, m) and 0.72 (3 H, t, J 7.3, Me); δC (100 MHz;
᎐
3
CDCl3) 133–128 (m, Ph2PO), 70.8ϩ (CHOH), 63.5Ϫ (d, JPC
1628 (C᎐C), 1438 (P–Ph) and 1166 (P᎐O); δ (400 MHz;
3
᎐
᎐
H
1
12.1, CH2OH), 40.2ϩ (d, JPC 68.9, PCH), 32.1Ϫ, 32.9Ϫ, 22.5Ϫ
CDCl3) 8.0–7.8 (4 H, m), 7.6–7.2 (11 H, m, Ph2PO and Ph),
and 13.5ϩ (Me); m/z 301.1 (20%, Mϩ Ϫ CH2OH), 201.1 (100,
6.96 (1 H, br d, J 10.2, CH ᎐CH min), 6.85 (1 H, dd, J 3.6 and
᎐
A
B
Ph2PO) and 77.0 (60, Ph).
10.2, CH ᎐CH maj), 6.09 (1 H, br d, J 10.2, CH ᎐CH min),
᎐
A
᎐
B
A
B
1994
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998

View Article Online
5.99 (1 H, dd, J 1.0 and 10.3, CH ᎐CH maj), 5.62 (1 H, br s,
(4S,5S,6R,8R)-8-Benzyloxy-6-diphenylphosphinoyldodecane-
1,4,5-triol 68
᎐
A
B
OCHOHmaj ϩ min), 4.91 (1 H, d, J 13.4, PCHCHOmaj ϩ min),
4.28 (1 H, d, J 11.9, PhCHAHBmaj), 4.22 (1 H, d, J 11.9,
PhCHAHBmaj), 3.75 (1 H, m, CHAHBOBnmin), 3.63 (1 H, br q,
J 8.1, CHAHBOBnmaj), 3.4–3.2 (1 H, m, PCH and CHAHB-
OBnmaj ϩ min) and 2.3–2.0 (2 H, m); δC (100 MHz; CDCl3)
195.7Ϫ (C᎐O), 151.0ϩ (CH᎐CHmin), 146.6ϩ (CH᎐CHmaj), 138.4Ϫ
By the same general method, enone 67 (1.35 g, 2.60 mmol) and
sodium borohydride (691 mg, 18.2 mmol) gave a crude product
which was purified by flash chromatography eluting with 10%
methanol in EtOAc, to give the triol 68 (927 mg, 68%) as an oil,
[α]D20 ϩ17.3 (c 0.21 in CHCl3) (Found: Mϩ Ϫ C4H9O2, 435.2102.
C31H41O5P requires M Ϫ C4H9O2, 435.2089); Rf 0.21 (7%
methanol–EtOAc); νmax/cmϪ1 (CHCl3) 3441 (OH), 1438 (P–Ph)
᎐
᎐
᎐
(ipso-Phmaj ϩ min), 132–126 (m, Ph2PO and Ph), 91.3ϩ (OCHO-
Hmin), 87.3ϩ (OCHOHmaj), 76.3ϩ (PCHCHOmin), 72.5Ϫ
(CH2Phmaj ϩ min), 68.1Ϫ (d, 3JPC 11.3, CH2OBnmaj ϩ min), 34.3ϩ (d,
1JPC 72.8, PCHmaj), 24.1Ϫ (min) and 23.8Ϫ (maj); m/z (FAB)
463.3 (60%, MHϩ) and 307.1 (100).
and 1160 (P᎐O); δH (400 MHz; CDCl3) 7.7–7.1 (15 H, m, Ph2PO
᎐
and Ph), 4.68 (1 H, d, J 12.6, PhCHAHB), 4.25 (1 H, d, J 12.6,
PhCHAHB), 3.73 (1 H, t, J 9.2, OCHAHB), 3.7–3.5 (3 H, m),
2.98 (1 H, t, J 5.8, CHOH), 2.6–2.5 (3 H, m), 2.1–1.85 (8 H, m),
0.80 (3 H, t, J 7.0, Me) and 0.50 (2 H, m); δC (100 MHz; CDCl3)
137.3Ϫ (ipso-Ph), 132–126 (m, Ph2PO and Ph), 76.1ϩ, 74.0ϩ,
(2S,6R,1ЈR,3ЈR)- and (2S,6S,1ЈR,3ЈR)-2-(3Ј-Benzyloxy-1Ј-di-
phenylphosphinoylheptyl)-6-hydroxy-3,6-dihydro-2H-pyran-3-
one 67
3
1
71.1ϩ (d, JPC 11.5, CHOH), 69.3Ϫ, 63.0Ϫ, 33.4ϩ (d, JPC 70.8,
PCH), 31.7Ϫ, 30.3Ϫ, 29.7Ϫ, 26.5Ϫ, 25.3Ϫ, 22.5Ϫ and 14.0ϩ (Me);
m/z (FAB) 435.2 (65%, Mϩ Ϫ C4H9O2), 202.1 (80, Ph2POH)
and 91.0 (100, Bn).
By the same general method, (1S,2R,4R)-4-benzyloxy-2-
diphenylphosphinoyl-1-(2-furyl)octan-1-ol1 66 (1.52 g, 3.02
mmol) and m-chloroperbenzoic acid (840 mg, 57–85% by
weight, ca. 3.41 mmol) gave a crude product after 16 h which
was purified by flash chromatography eluting with 5% methanol
in EtOAc) to give the enone 67 (1.49 g, 95%, 77:23 mixture of
hemiacetal epimers) as a foam, Rf 0.53 (10% methanol in
EtOAc); [α]D20 ϩ47.5 (c 0.20 in CHCl3) (Found: MHϩ, 519.2337.
C31H35O5P requires MH, 519.2300); νmax/cmϪ1 (CHCl3) 3459
(2Z,4R*,5S*,6R*)-8-Benzyloxy-6-diphenylphosphinoyloct-2-
ene-1,4,5-triol 48
Cerium trichloride heptahydrate (527 mg, 1.41 mmol) and
enone 47 (590 mg, 1.28 mmol) were stirred in ethanol (25 cm3)
for 10 min and sodium borohydride (336 mg, 8.84 mmol) was
added. The reaction mixture was stirred for 1 h, quenched with
water (25 cm3), extracted with dichloromethane (3 × 20 cm3),
dried (MgSO4) and evaporated under reduced pressure to give
a crude product which was purified by flash chromatography
eluting with 10% methanol in EtOAc to give the triol 48
(213 mg, 36%) as an oil, Rf 0.21 (7% methanol–EtOAc) (Found:
Mϩ Ϫ C4H7O2, 379.1474. C27H31O5P requires M Ϫ C4H7O2,
379.1463); νmax/cmϪ1 (CHCl ) 3421 (OH), 1654 (C᎐C) and 1438
(OH), 1695 (C᎐O), 1601 (C᎐C), 1423 (P–Ph) and 1202 (P᎐O);
᎐
᎐
᎐
δH (400 MHz; CDCl3) 8.1–7.2 (4 H, m, Ph2PO and Ph), 6.95
(1 H, br d, J 10.3, CH ᎐CH min), 6.80 (1 H, dd, J 3.3 and 10.2,
᎐
A
B
CH ᎐CH maj), 6.03 (1 H, br d, J 10.3, CH ᎐CH min), 5.98 (1 H,
᎐
᎐
A
B
A
B
d, J 10.2, CH ᎐CH maj), 5.80 (1 H, br s, OCHOHmaj), 5.20
᎐
A
B
(1 H, br s, OCHOHmin), 4.98 (1 H, d, J 14.4, PCHCHOmaj ϩ min),
4.5–4.0 (2 H, m), 3.60 (1 H, m, CHOBnmaj ϩ min), 3.00 (1 H, m,
PCHmaj ϩ min), 2.3 (2 H, m), 1.9 (2 H, m), 1.5–1.1 (4 H, m) and
0.90 (3 H, t, J 7.0, Memaj ϩ min); δC (100 MHz; CDCl3) 195.4Ϫ
(C᎐Omaj), 150.9ϩ (CH᎐CHmin), 146.4ϩ (CH᎐CHmaj), 139.2Ϫ
᎐
3
(P–Ph); δH (400 MHz; CDCl3) 7.80 (2 H, ddd, J 1.1, 7.7 and
8.8), 7.6–7.3 (13 H, m, Ph2PO and Ph), 5.88 (1 H, td, J 7.0 and
11.0, CH ᎐CH ), 5.48 (1 H, dd, J 8.3 and 11.0, CH ᎐CH ),
᎐
᎐
᎐
(ipso-Phmaj), 133–126 (m, Ph PO, CH᎐CH and Ph), 91.7ϩ
᎐
᎐
᎐
A
2
A
B
B
(OCHOHmin), 87.5ϩ (OCHOHmaj), 76.6ϩ (d, JPC 10.3,
4.92 (1 H, br s, OH), 4.53 (1 H, d, J 11.8, PhCHAHB), 4.52 (1 H,
br s, OH), 4.32 (1 H, br s, OH), 4.30 (1 H, d, J 11.8, PhCHAHB),
4.13 (1 H, m), 3.97 (1 H, m), 3.82 (1 H, t, J 8.8), 3.55 (1 H, m),
3.40 (1 H, quin, J 4.0), 2.92 (2 H, m), 2.35 (1 H, m) and 1.85
(1 H, m); δC (100 MHz; CDCl3) 137.3Ϫ (ipso-Ph), 133–127 (m,
3
CHOBn), 71.8ϩ, 69.5Ϫ (CH2Phmaj), 60.4Ϫ (CH2Phmin), 36.5ϩ
(d, JPC 72.4, PCHmaj ϩ min), 32.5Ϫ, 27.9Ϫ, 26.9Ϫ (maj), 22.6Ϫ (d,
1
JPC 4.3) and 14.2ϩ (Me); m/z (FAB) 519.2 (65%, MHϩ) and
201.0 (100, Ph2PO).
2
Ph2PO and Ph), 73.1Ϫ (CH2Ph), 72.5ϩ (d, JPC 2.7, CHOH),
3
3
68.6Ϫ (d, JPC 5.0, CHOBn), 67.0ϩ (d, JPC 11.6, CHOH),
58.3Ϫ (CH2OH), 33.8ϩ (d, 1JPC 70.0, PCH) and 21.0Ϫ; m/z (FAB)
379.1 (55%, Mϩ Ϫ C4H7O2), 201.0 (100, Ph2PO) and 91.1 (95,
Bn).
(4R*,5S*,6R*)-8-Benzyloxy-6-diphenylphosphinoyloctane-
1,4,5-triol 49
Sodium borohydride (563 mg, 14.8 mmol) was added to a
solution of 47 (943 mg, 2.11 mmol) in absolute ethanol (5 cm3)
and stirred for 16 h at room temperature. Hydrochloric acid
(3.0 mol dmϪ3, five drops) and water (10 cm3) were added to
the reaction mixture, the majority of the ethanol removed
under reduced pressure, the aqueous suspension extracted
with dichloromethane (3 × 10 cm3), and the combined organic
fractions dried (MgSO4) and evaporated under reduced
pressure to give a crude product which was purified by flash
chromatography eluting with 10% methanol in EtOAc to give
the triol 49 (620 mg, 66%) as an oil, Rf 0.21 (7% methanol–
EtOAc) (Found: Mϩ Ϫ C4H9O2, 379.1463. C27H33O5P requires
M Ϫ C4H9O2, 379.1463); νmax/cmϪ1 (CHCl3) 3425 (OH), 1438
Catalytic hydrogenation of 48
(2Z,4R*,5R*,6S*)-8-Benzyloxy-6-diphenylphosphinoyloct-2-
ene-1,4,5-triol 48 (76 mg, 0.16 mmol) and palladium on carbon
(5% w/w, 8 mg) in ethyl acetate (5 cm3) were stirred under an
atmosphere of hydrogen (1 atm) for 4 h. The reaction mixture
was filtered through Celite and evaporated under reduced
pressure to give a crude product. Analysis of the crude product
by 1H NMR revealed an 85:15 mixture of 49 and starting
material.
(4S,5R,6R,8R)-8-Benzyloxy-6-diphenylphosphinoyldodecane-
1,4,5-triol 58
(P–Ph) and 1199 (P᎐O); δ (400 MHz; CDCl3) 8.0–7.2 (15 H,
᎐
H
m, Ph2PO and Ph), 4.57 (1 H, d, J 12.1, PhCHAHB), 4.28 (1 H,
d, J 12.1, PhCHAHB), 3.79 (1 H, t, J 9.2, OCHAHB), 3.62 (1 H,
quin, J 5.8), 3.57 (2 H, m), 3.37 (1 H, qd, J 1.4 and 7.0, CHOH),
2.84 (2 H, m, OCH and PCH), 2.30 (1 H, m), 1.97 (1 H, m), 1.83
(1 H, m), 1.77 (2 H, quin, J 6.5) and 1.33 (1 H, quin, J 8.6);
δC (100 MHz; CDCl3) 137.3Ϫ (ipso-Ph), 132–127.5 (m, Ph2PO
m-Chloroperbenzoic acid (202 mg, 57–85% by weight, ca. 0.82
mmol) was added to a stirred solution of the phosphine oxide
57 (365 mg, 0.73 mmol) in dry dichloromethane (8 cm3) at 0 ЊC.
The reaction mixture was stirred for 16 h, diluted with dichloro-
methane (10 cm3), washed with saturated sodium carbonate
solution (20 cm3), saturated sodium thiosulfate solution (20
cm3) and saturated sodium carbonate solution (20 cm3), dried
(MgSO4) and evaporated under reduced pressure to give a
residue, which was dissolved in ethanol (10 cm3). Sodium
3
and Ph), 73.4ϩ (CHOH), 72.8Ϫ, 70.8ϩ (d, JPC 11.5, CHOH),
3
1
69.6Ϫ (d, JPC 4.8, CHOBn), 62.4Ϫ, 33.7ϩ (d, JPC 70.3, PCH),
30.2Ϫ, 29.1Ϫ and 21.0Ϫ; m/z (FAB) 379.2 (65%, Mϩ Ϫ C4H9O2),
201.0 (100, Ph2PO) and 91.0 (90, Bn).
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998
1995

View Article Online
borohydride (173 mg, 4.6 mmol) was added to the the reaction
mixture which was stirred for 1 h, quenched with water (10 cm3)
and the solvent removed under reduced pressure to give a
residue which was diluted with water (20 cm3), extracted with
dichloromethane (3 × 20 cm3), dried (MgSO4) and evaporated
under reduced pressure to give a crude product which was
purified by flash chromatography eluting with 10% methanol–
EtOAc to give the triol 58 (180 mg, 57%) as an oil, Rf 0.21 (7%
methanol–EtOAc); [α]D20 Ϫ7.3 (c 0.20 in CHCl3) (Found:
Mϩ Ϫ C4H9O2, 435.2135. C31H41O5P requires M Ϫ C4H9O2,
435.2089); νmax/cmϪ1 (CHCl3) 3389 (OH) and 1423 (P–Ph);
δH (400 MHz; CDCl3) 7.7–7.3 (15 H, m, Ph2PO and Ph), 5.8*
(1 H, br s, OH), 4.68 (1 H, d, J 12.1, PhCHAHB), 4.25 (1 H, d,
J 12.1, PhCHAHB), 4.10* (1 H, br s, OH), 3.6 (5 H, m), 2.67
(1 H, m), 2.56 (1 H, m), 2.0–0.9 (11 H, m) and 0.76 (3 H, t, J 6.8,
Me); δC (50 MHz; CDCl3) 137.4Ϫ (ipso-Ph), 132–128 (m, Ph2PO
(4S,5R,6R,8S)-8-Benzyloxy-8-cyclohexyl-6-diphenylphos-
phinoyloctane-1,4,5-triol 64
By the same general method, the furan1 63 (382 mg, 0.73 mmol,
70:30 mixture of isomers), m-chloroperbenzoic acid (346 mg,
57–85% by weight, ca. 1.4 mmol) and sodium borohydride
(194 mg, 5.1 mmol) gave a crude product which was purified by
flash chromatography eluting with 10% methanol in EtOAc to
give the triol 64 (186 mg, 47%, 69:31 mixture of diastereomers)
as an oil, spectroscopically identical to that obtained previously,
[α]D20 Ϫ3.6 (c 1.01 in CHCl3).
(E)-8-Benzyloxyoct-5-ene-1,4-diol 50
Potassium hydroxide (79 mg, 2.1 mmol) and (4R*,5S*,6R*)-
8-benzyloxy-6-diphenylphosphinoyloctane-1,4,5-triol 49 (201
mg, 0.43 mmol) were stirred in DMSO (10 cm3) at 55 ЊC for
2 h. The reaction mixture was quenched with water (10 cm3),
extracted with Et2O (3 × 10 cm3), dried (MgSO4) and evapor-
ated under reduced pressure to give a crude product which
was purified by flash chromatography eluting with EtOAc to
give the alkene 50 (37 mg, 35%) as an oil, Rf 0.77 (10%
methanol–EtOAc) (Found: MHϩ, 251.1626. C15H22O3 requires
MH, 251.1647); νmax/cmϪ1 (CHCl ) 3450 (OH) and 1654 (C᎐C);
1
and Ph), 76.3ϩ, 73.5ϩ, 71.2ϩ, 69.8Ϫ, 62.7Ϫ, 40.2ϩ (d, JPC 65.8,
PCH), 31.9Ϫ, 30.1Ϫ, 29.0Ϫ, 27.6Ϫ, 26.6Ϫ, 22.4Ϫ and 14.0ϩ (Me);
m/z (FAB) 435.2 (35%, Mϩ Ϫ C4H9O2), 216.1 (90) and 91.0
(100, Bn).
(4R,5S,6S,8R)-8-Benzyloxy-6-diphenylphosphinoyldodecane-
1,4,5-triol 55
᎐
3
δH (400 MHz; CDCl3) 7.4–7.25 (5 H, m, Ph), 5.66 (1 H, td,
J 6.4 and 15.8, CH᎐CHCH ), 5.55 (1 H, dd, J 6.6 and 15.5,
By the same general method, furan1 54 (1.24 g, 2.47 mmol),
m-chloroperbenzoic acid (780 mg, 57–85% by weight, ca. 3.2
mmol) and sodium borohydride (253 mg, 6.7 mmol) gave
a crude product which was purified by flash chromatography
eluting with 10% methanol–EtOAc, to give the triol 55 (467 mg,
36%, 40% based on recovered starting material) as an oil,
Rf 0.21 (7% methanol–EtOAc); [α]D20 ϩ7.1 (c 0.80 in CHCl3)
(Found: Mϩ Ϫ C3H7O, 465.2195. C31H41O5P requires M Ϫ
C3H7O, 465.2194); νmax/cmϪ1 (CHCl3) 3398 (OH), 1423 (P–Ph)
᎐
2
CH᎐CHCH ), 4.51 (2 H, s, PhCH ), 4.09 (1 H, m, CHOH), 3.62
᎐
2
2
(2 H, m, CH2O), 3.49 (2 H, t, J 6.2, CH2O), 2.61 (2 H, br s,
2 × OH), 2.38 (2 H, q, J 6.6, CH᎐CHCH ) and 1.62 (4 H, m);
᎐
2
δC (100 MHz; CDCl3) 138.4ϩ (ipso-Ph), 134.9ϩ (CH᎐CH),
᎐
128.8ϩ, 127.9ϩ, 72.9Ϫ, 72.6ϩ (CHOH), 69.7Ϫ, 62.8Ϫ, 34.2Ϫ, 32.6Ϫ
and 28.4Ϫ; m/z (FAB) 251.2 (20%, MHϩ) and 91.1 (100, Bn).
(4S,5E,8R)-8-Benzyloxydodec-5-ene-1,4-diol 59
and 1222 (P᎐O); δ (400 MHz; CDCl ) 7.9–7.2 (15 H, m, Ph PO
᎐
H
3
2
By the same general method, (4S,5R,6R,8R)-8-benzyloxy-6-
diphenylphosphinoyldodecane-1,4,5-triol 58 (129 mg, 0.25
mmol) and potassium hydroxide (45 mg, 1.18 mmol) gave
a crude product which was purified by flash chromatography
eluting with EtOAc to give the alkene 59 (20.6 mg, 27%) as
an oil, Rf 0.38 (EtOAc); [α]D20 ϩ4.7 (c 0.91 in CDCl3) (Found:
Mϩ Ϫ OH, 289.2173. C19H28O3 requires M Ϫ OH, 289.2167);
and Ph), 5.30 (1 H, br s, OH), 4.59 (1 H, d, J 11.1, PhCHAHB),
4.42 (1 H, d, J 11.1, PhCHAHB), 4.10 (1 H, OH), 3.7–3.45 (5 H,
m), 3.21 (1 H, t, J 11.9), 2.10 (1 H, m), 2.0–1.0 (11 H, m) and
0.85 (3 H, t, J 7.3, Me); δC (100 MHz; CDCl3) 138.0Ϫ (ipso-Ph),
132.5–128 (m, Ph2PO and Ph), 74.5ϩ, 72.0ϩ, 71.4Ϫ, 62.9Ϫ (one
peak next to O missing), 37.2ϩ (d, 1JPC 66.2, PCH), 32.6Ϫ, 31.2Ϫ,
29.9Ϫ, 29.4Ϫ, 27.2Ϫ, 22.8Ϫ and 13.9ϩ (Me); m/z (FAB) 465.2
(45%, Mϩ Ϫ C3H7O), 202.1 (75, Ph2POH), 201.1 (70, Ph2PO)
and 91.1 (100, Bn). Also obtained was starting material
(110 mg, 11%), spectroscopically identical to that obtained
previously.
νmax/cmϪ1 (CHCl3) 3411 (br s, OH), 1642, 1602 and 1560 (C᎐C
᎐
and Ph); δH (400 MHz; CDCl3) 7.38–7.23 (5 H, m, Ph), 5.68
(1 H, td, J 7.0 and 15.5, CH᎐CHCH ), 5.55 (1 H, dd, J 6.8 and
᎐
2
15.5, CH᎐CHCH ), 4.52 (1 H, d, J 11.6, PhCH H ), 4.48 (1 H,
᎐
2
A
B
d, J 11.6, PhCHAHB), 4.10 (1 H, q, J 6.4, CHOH), 3.63 (2 H, m,
CH2OH), 3.42 (1 H, quin, J 7.1, CHOBn), 2.30 (2 H, t, J 6.2,
(4R,5S,6S,8S)-8-Benzyloxy-8-cyclohexyl-6-diphenylphos-
phinoyloctane-1,4,5-triol 61
CH᎐CHCH ), 1.73 (1 H, br s, OH), 1.7–1.2 (10 H, m) and 0.90
᎐
2
(3 H, t, J 6.7, Me); δC (100 MHz; CDCl3) 138.9Ϫ (ipso-Ph),
135.3ϩ (CH᎐CH), 128.3ϩ, 127.9ϩ, 127.7ϩ, 127.5ϩ, 78.6ϩ, 72.7ϩ,
᎐
By the same general method, furan1 60 (270 mg, 0.51 mmol,
74:26 mixture of diastereomers), m-chloroperbenzoic acid (246
mg, 57–85% by weight, ca. 1.0 mmol) and sodium borohydride
(135 mg, 3.6 mmol) gave a crude product which was purified by
flash chromatography eluting with 10% methanol in EtOAc to
give the triol 61 (121 mg, 44%, 74:26 mixture of diastereomers)
as an oil, Rf 0.30 (10% methanol–EtOAc); [α]D20 ϩ19.0 (c 0.05 in
CHCl3) (Found: Mϩ Ϫ C4H9O2, 461.2242. C33H43O5P requires
M Ϫ C4H9O2, 461.2246); νmax/cmϪ1 (CHCl3) 3386 (OH) and
1438 (P–Ph); δH (400 MHz; CDCl3) 7.9–7.2 (15 H, m, Ph2PO
and Ph), 5.78 (1 H, br s, OHmin), 5.69 (1 H, d, J 3.1, OHmaj), 5.08
(1 H, br s, OHmaj), 4.68 (1 H, d, J 11.1, PhCHAHBmin), 4.63 (1 H,
d, J 12.1, PhCHAHBmaj), 4.28 (1 H, d, J 12.1, PhCHAHBmaj), 4.24
(1 H, d, J 11.1, PhCHAHBmin), 3.79 (1 H, m), 3.28 (3 H, m)
and 2.1–0.4 (14 H, m); δC (100 MHz; CDCl3) 137.5Ϫ (ipso-
Phmaj ϩ min), 132–127.5 (m, Ph2PO and Ph), 81.7ϩ (maj), 81.0ϩ
(min), 74.9ϩ (maj), 73.5ϩ (min), 72.4Ϫ (maj), 72.1ϩ (maj),
70.9Ϫ, 62.9Ϫ, 36.5Ϫ, 34.2Ϫ, 33.5Ϫ, 28.9Ϫ, 27.6Ϫ, 22.7Ϫ and 14.1ϩ
(Me); m/z (FAB) 289.2 (20%, Mϩ Ϫ OH) and 91.1 (100, Bn).
Integration of the 500 MHz NMR spectrum of the Mosher’s
diester31 of this material indicated a ratio of (4S):(4R) stereo-
isomers of 89:11.
(4R,5E,8R)-8-Benzyloxydodec-5-ene-1,4-diol 56
By the same general method, (4R,5S,6S,8R)-8-benzyloxy-6-
diphenylphosphinoyldodecane-1,4,5-triol 55 (174 mg, 0.34
mmol) and potassium hydroxide (61 mg, 1.61 mmol) gave
a crude product which was purified by flash chromatography
eluting with EtOAc to give the alkene 56 (41.2 mg, 41%) as an
oil, Rf 0.38 (EtOAc); [α]D20 ϩ10.1 (c 0.91 in CDCl3) (Found:
Mϩ Ϫ C4H10O2, 216.1515. C19H28O3 requires M Ϫ C4H10O2,
216.1514); νmax/cmϪ1 (CHCl3) 3422 (br s, OH), 1642, 1602 and
1560 (C᎐C and Ph); δ (400 MHz; CDCl3) 7.36–7.23 (5 H, m,
᎐
H
1
71.3ϩ (min), 62.9Ϫ (min ϩ min), 40.5ϩ (d, JPC 66.2, PCHmaj),
Ph), 5.66 (1 H, td, J 7.0 and 15.4, CH᎐CHCH ), 5.53 (1 H, dd,
᎐
2
1
40.1ϩ (d, JPC 65.9, PCHmin) and 31–26 (several peaks); m/z
J 6.7 and 15.4, CH᎐CHCH ), 4.52 (1 H, d, J 11.7, PhCH H ),
᎐
2
A
B
(FAB) 461.2 (40%, Mϩ Ϫ C4H9O2), 201.0 (45, Ph2PO) and 91.1
4.46 (1 H, d, J 11.7, PhCHAHB), 4.08 (1 H, m, CHOH), 3.62
(2 H, m, CH2OH), 3.44 (1 H, m, CHOBn), 2.55 (1 H, br s, OH),
(100, Bn).
1996
J. Chem. Soc., Perkin Trans. 1, 1999, 1983–1998

View Article Online
as implied here); (b) J. P. Clayden, PhD Thesis, University of
Cambridge, 1992; (c) H. J. Mitchell, PhD Thesis, University of
Cambridge, 1995.
4 H. Mitchell, A. Nelson and S. Warren, J. Chem. Soc., Perkin Trans.
1, 1999, 1899.
5 J. Clayden and S. Warren, Angew. Chem., Int. Ed. Engl., 1996, 35,
241.
6 A.-F. Sévin, thèse, Docteur en Sciences, Université de Paris Sud
(Orsay), 1991.
7 R. S. Torr and S. Warren, J. Chem Soc., Perkin Trans. 1, 1983, 1169.
8 J. Clayden, A. B. McElroy and S. Warren, J. Chem. Soc., Perkin
Trans. 1, 1995, 1913.
2.29 (2 H, m, CH᎐CHCH ), 1.65–1.2 (10 H, m) and 0.88 (3 H,
᎐
2
t, J 6.7, Me); δC (100 MHz; CDCl3) 138.8Ϫ (ipso-Ph), 135.3ϩ
(CH᎐CH), 128.3ϩ, 127.8ϩ, 127.7ϩ, 127.5ϩ, 78.6ϩ, 72.7ϩ, 70.9Ϫ,
᎐
62.8Ϫ, 36.5Ϫ, 34.3Ϫ, 33.5Ϫ, 28.9Ϫ, 27.6Ϫ, 22.8Ϫ and 14.1ϩ (Me);
m/z 216.2 (45%, Mϩ Ϫ C4H10O2), 105.0 (80) and 91.1 (100, Bn).
Integration of the 500 MHz NMR spectrum of the Mosher’s
diester31 of this material indicated a ratio of (4R):(4S) stereo-
isomers of 74:26.
(4R,5E,8S)-8-Benzyloxy-8-cyclohexyloct-5-ene-1,4-diol 62
9 (a) G. V. Bindu Madhaven, D. P. C. McGee, R. M. Rydzewski,
R. Boehme, J. C. Martin and E. J. Prisbe, J. Med. Chem., 1998, 31,
1798; (b) K. Biggadike, A. D. Borthwick, A. M. Exall, B. E. Kirk,
S. M. Roberts and P. Youds, J. Chem. Soc., Chem. Commun., 1987,
1083; (c) T. Seita, M. Kinoshita and M. Imoto, Bull. Chem. Soc.
Jpn., 1973, 46, 1572; (d) H. Baumgartner, C. Marschner, P. Pucher
and H. Griengl, Tetrahedron Lett., 1991, 32, 611.
By the same general method, (4R,5S,6S,8S)-8-benzyloxy-
8-cyclohexyl-6-diphenylphosphinoyloctane-1,4,5-triol 61 (105
mg, 0.19 mmol) and potassium hydroxide (34 mg, 0.89 mmol)
gave a crude product which was purified by flash chroma-
tography eluting with EtOAc, to give the alkene 62 (21.2 mg,
34%) as an oil, Rf 0.36 (EtOAc); [α]D20 ϩ6.4 (c 0.89 in CHCl3)
(Found: MNaϩ, 355.2261. C21H32O3 requires MNa, 355.2249);
10 P. H. J. Carlsen, T. Katsuki, V. S. Martin and K. B. Sharpless,
J. Org. Chem., 1981, 46, 3936.
νmax/cmϪ1 (CHCl ) 3407 (OH) and 1662 (C᎐C); δ (400 MHz;
᎐
3
H
11 (a) D. L. Hughes, Org. React., 1992, 42, 335; (b) J. Mulzer and
C. Brand, Tetrahedron, 1986, 42, 5961; (c) A. V. Rama Rao,
D. Subhas Bose, M. K. Gurjar and T. Ravindranathan, Tetrahedron,
1989, 45, 7031; (d) G. L. Grunewald, V. M. Paradkar, D.
Pazhenchevsky, M. A. Pleiss, D. L. Sall, W. L. Seibel and M. J. Reitz,
J. Org. Chem., 1983, 48, 2321; (e) H. Ida, N. Yamazaki and
C. Kibayashi, J. Chem. Soc., Chem. Commun., 1987, 746.
12 P. F. Schuda, M. B. Cichowicz and M. R. Heimann, Tetrahedron
Lett., 1983, 24, 3829.
13 (a) A. Nelson, P. O’Brien and S. Warren, Tetrahedron Lett., 1995, 36,
2685; (b) A. Nelson and S. Warren, J. Chem. Soc., Perkin Trans. 1,
1997, 2645.
14 (a) P. Theisen and C. H. Heathcock, J. Org. Chem., 1988, 53,
2374; (b) I. Paterson, R. D. Norcross, R. A. Ward, P. Romea and
M. A. Lister, J. Am. Chem. Soc., 1994, 116, 11287.
CDCl3) 7.4–7.25 (5 H, m, Ph), 5.76 (1 H, td, J 7.1 and 15.4,
CH᎐CHCH ), 5.51 (1 H, dd, J 6.7 and 15.4, CH᎐CHCH ), 4.52
᎐
᎐
2
2
(1 H, d, J 11.5, PhCHAHB), 4.40 (1 H, d, J 11.5, PhCHAHB),
4.11 (1 H, m, CHOH), 3.62 (2 H, m, CH2OH), 3.19 (1 H, q, J
5.3, CHOBn), 2.35 (2 H, m, CH᎐CHCH ), 1.9–0.9 (15 H, m); δ
᎐
2
C
(100 MHz; CDCl ) 138.9Ϫ (ipso-Ph), 134.9ϩ (CH᎐CH), 128.2ϩ,
᎐
3
127.9ϩ, 127.7ϩ, 127.5ϩ, 83.3ϩ, 72.7ϩ, 71.8Ϫ, 62.9Ϫ, 41.0ϩ
(CHCHOBn), 34.2Ϫ, 33.5Ϫ, 33.4Ϫ, 29.0Ϫ, 28.9Ϫ, 28.7Ϫ, 26.6Ϫ
and 26.3Ϫ; m/z 203.1 (100%, CHOBncHex), 111.1 (90) and 91.1
(100, Bn).
(4S,5E,8S)-8-Benzyloxy-8-cyclohexyloct-5-ene-1,4-diol 65
By the same general method, (4S,5R,6R,8S)-8-benzyloxy-
8-cyclohexyl-6-diphenylphosphinoyloctane-1,4,5-triol 64 (140
mg, 0.25 mmol) and potassium hydroxide (44 mg, 1.16 mmol)
gave a crude product which was purified by flash chromatog-
raphy eluting with EtOAc to give the alkene 65 (20.6 mg,
25%) as an oil, Rf 0.36 (EtOAc); [α]D20 ϩ8.6 (c 0.45 in CHCl3)
(Found: MNaϩ, 355.2261. C21H32O3 requires MNa, 355.2249);
15 J. Clayden and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1993,
2913.
16 B. H. Lipshutz, Chem. Rev., 1986, 86, 795.
17 (a) C. Poirel, P.-Y. Renard and J.-Y. Lallemand, Tetrahedron Lett.,
1994, 35, 6485; (b) S. F. Martin and P. W. Zinke, J. Org. Chem., 1991,
56, 6600; (c) F. E. Ziegler and R. T. Wester, Tetrahedron Lett., 1984,
25, 617; (d) P. DeShong, D. M. Simpson and M.-T. Lin, Tetrahedron
Lett., 1989, 30, 2885; (e) J. Raczko, A. Golebiowski, J. W. Krajewski,
P. Gluzinski and J. Jurczak, Tetrahedron Lett., 1990, 31, 3797;
( f ) P. M. Carbateas and G. L. Williams, J. Heterocycl. Chem., 1974,
11, 819; (g) R. Antonioletti, L. Arista, F. Bonadies, L. Locati and
A. Scettri, Tetrahedron Lett., 1993, 34, 7089; (h) J. M. J. Williams,
Synlett, 1996, 705; (i) S. F. Martin and P. W. Zinke, J. Am. Chem.
Soc., 1989, 111, 2311; (j) P. DeShong, R. E. Waltermire and
H. L. Ammon, J. Am. Chem. Soc., 1988, 110, 1901; (k) R. C. D.
Brown and P. J. Kocienski, Synlett, 1994, 417; (l) S. F. Martin,
W.-C. Lee, G. J. Pacofsky, R. P. Gist and R. A. Mulhern, J. Am.
Chem. Soc., 1994, 116, 4674.
18 T. Kametani, M. Tsubuki and T. Honda, Chem. Pharm. Bull., 1988,
36, 3706.
19 (a) T. Honda, the late T. Kametani, K. Kanai, Y. Tatsuzaki and
M. Tsubuki, J. Chem. Soc., Perkin Trans. 1, 1990, 1733; (b) P. G.
Sammes and D. Thetford, J. Chem. Soc., Perkin Trans. 1, 1988, 111;
(c) M. Kasakabe, T. Kitano, Y. Kobayashi and F. Sato, J. Org.
Chem., 1989, 54, 2085.
νmax/cmϪ1 (CHCl ) 3413 (OH) and 1669 (C᎐C); δ (400 MHz;
᎐
3
H
CDCl3) 7.4–7.25 (5 H, m, Ph), 5.76 (1 H, td, J 7.1 and 15.4,
CH᎐CHCH ), 5.51 (1 H, dd, J 6.7 and 15.4, CH᎐CHCH ), 4.52
᎐
᎐
2
2
(1 H, d, J 11.5, PhCHAHB), 4.49 (1 H, d, J 11.5, PhCHAHB),
4.11 (1 H, m, CHOH), 3.62 (2 H, m, CH2OH), 3.19 (1 H, q,
J 5.3, CHOBn), 2.35 (2 H, m, CH᎐CHCH ) and 1.9–0.9 (15 H,
᎐
2
m); δC (100 MHz; CDCl3) 138.9Ϫ (ipso-Ph), 135.0ϩ (CH᎐CH),
᎐
128.2ϩ, 127.9ϩ, 127.8ϩ, 127.5ϩ, 83.4ϩ, 72.7ϩ, 71.8Ϫ, 62.9Ϫ, 41.0ϩ
(CHCHOBn), 34.2Ϫ, 33.5Ϫ, 33.4Ϫ, 29.0Ϫ, 28.9Ϫ, 28.7Ϫ, 26.6Ϫ,
26.4Ϫ and 26.3Ϫ; m/z 203.1 (100%, CHOBncHex), 111.1 (90)
and 91.1 (100, Bn).
(4R,5E,8R)-8-Benzyloxydodec-5-ene-1,4-diol 56
By the same general method, (4R,5S,6R,8R)-8-benzyloxy-
6-diphenylphosphinoyldodecane-1,4,5-triol 68 (306 mg, 0.58
mmol) and potassium hydroxide (107 mg, 2.81 mmol) gave
a crude product which was purified by flash chromatography
eluting with EtOAc to give the alkene 56 (41.3 mg, 23%) as an
oil, spectroscopically identical to that obtained previously.
20 T. Nakata, T. Tanaka and T. Oishi, Tetrahedron Lett., 1983, 24,
2653.
21 (a) M. Chérest, H. Felkin and N. Prudent, Tetrahedron Lett., 1968,
2199; (b) N. T. Anh and O. Eisenstein, Nouv. J. Chem., 1977, 1,
61; (c) N. T. Anh, Top. Curr. Chem., 1980, 88, 145; (d) M. N.
Paddon-Row, N. G. Rondan and K. N. Houk, J. Am. Chem. Soc.,
1983, 104, 7162.
22 (a) J.-L. Luche, J. Am. Chem. Soc., 1978, 100, 2226; (b) A. L. Gemal
and J.-L. Luche, J. Am. Chem. Soc., 1981, 103, 5454.
References
1 A. Nelson and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1999,
preceding paper.
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Paper 9/03371H
1998
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