1,3-Stereocontrol with phosphine oxides: Asymmetric synthesis of all four diastereoisomers of a γ′-benzyloxy β-hydroxy phosphine oxide

Article abstract of DOI:10.1039/a903370j

This paper describes how optically active phosphine oxides with a γ′ stereogenic centre [for example, (R)-1-diphenylphosphinoylheptan-3-yl benzyl ether] can be lithiated and reacted with aldehydes and esters. The reactions exhibit moderate levels of 1,3 asymmetric induction and models are proposed to explain the stereoselectivity observed in terms of the configurational instability and the known structure of lithiated phosphine oxides. We have developed complementary methods for the asymmetric synthesis of all four diastereomeric β-hydroxy phosphine oxides 4-benzyloxy-2-diphenylphosphinoyl-l-(2-furyl)octan-l-ol and our approach constitutes a formal synthesis of all eight possible stereoisomers. A series of similar β-hydroxy phosphine oxides were eliminated to give optically active homoallylic alcohol derivatives.

Full text of DOI:10.1039/a903370j

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1,3-Stereocontrol with phosphine oxides: asymmetric synthesis of
all four diastereoisomers of a ãЈ-benzyloxy â-hydroxy phosphine
oxide
Adam Nelson*† and Stuart Warren
University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 1EW
Received (in Cambridge) 21st April 1999, Accepted 3rd June 1999
This paper describes how optically active phosphine oxides with a γЈ stereogenic centre [for example, (R)-1-
diphenylphosphinoylheptan-3-yl benzyl ether] can be lithiated and reacted with aldehydes and esters. The reactions
exhibit moderate levels of 1,3 asymmetric induction and models are proposed to explain the stereoselectivity
observed in terms of the configurational instability and the known structure of lithiated phosphine oxides. We have
developed complementary methods for the asymmetric synthesis of all four diastereomeric β-hydroxy phosphine
oxides 4-benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)octan-1-ol and our approach constitutes a formal synthesis
of all eight possible stereoisomers. A series of similar β-hydroxy phosphine oxides were eliminated to give optically
active homoallylic alcohol derivatives.
5 and alkenyl oxazolidinones6 such as 6 with 1,4-related stereo-
genic centres across an alkene.
Introduction
We have established the diphenylphosphinoyl (Ph2PO) group as
a remarkably powerful stereodirecting group in organic syn-
thesis and we have developed many methods for controlling
relative stereochemistry using phosphine oxides.1 In particular,
we have used a contiguous chiral centres approach, which is
outlined in Scheme 1, in syntheses of racemic and optically
This strategy for remote stereocontrol requires methods
which control stereogenic centres on both sides of the diphenyl-
phosphinoyl substituent (see Scheme 1). We have developed
many ways to control stereogenic centres α, β and γ to phos-
phorus7 but rather fewer methods allow us to control stereo-
genic centres βЈ and γЈ to phosphorus. Recently, we have
described how the lithium derivatives of phosphine oxides with
a βЈ stereogenic centre (e.g. 7) can be reacted with a range of
electrophiles; in these reactions, stereogenic centres α, and often
also β, to phosphorus can be introduced with high stereo-
selectivity (→8; Scheme 2).5b We have rationalised this
Y
HO
Y
Horner−Wittig
R1
R1
γ
α
R2
β
R2
β'
elimination
X
Ph2PO
X
1
2
Me
Me
Ph OH
Scheme 1 The contiguous chiral centres strategy.
1. BuLi, THF, −78 ºC
β' Ph
Ph
active compounds with 1,4-related stereogenic centres across a
double bond of controlled configuration.2 In each of these
syntheses, the diphenylphosphinoyl group was first used to
control the relative configuration of four or five contiguous
stereogenic centres (as in 1), two of which (α and β to phos-
phorus) were subsequently removed in a stereospecific Horner–
Wittig elimination (1→2; Scheme 1).‡ This strategy has been
applied to the synthesis of a variety of functionalised com-
pounds, such as the allylic alcohols3,4 3 and 4, the allylic sulfide5
2. Ph(CO)Bu, −78 ºC
3. NH4Cl
Ph2PO
Ph2PO
7
8
Scheme 2
behaviour in terms of the structure8 and configurational
instability9 of lithiated phosphine oxides. In this paper, we
report how the influence of the diphenylphosphinoyl group can
be pushed one stage further. Homochiral and racemic phos-
phine oxides with a stereogenic centre γЈ to phosphorus (of
general structure 9) are used to control the formation of new
PhS
Me
PhS
OH
OH
OH
R
Me OH
HO
3
4
Ph2PO
OH
OBn
OR'
9
10
O
O
Me
Me
NBn
stereogenic centres α and β to phosphorus, and in certain cases,
it is possible to synthesise any of the diastereomeric products at
will. The products can be exploited in the synthesis of allylic
alcohols (e.g. 10) with 1,5-related stereogenic centres across an
E-alkene.10,11
Ph
PhS
5
6
† Present address: School of Chemistry, University of Leeds, Leeds, UK
LS2 9JT.
‡ In this paper, all elaborated phosphine oxides are drawn with the
hydroxy group which ultimately takes part in the Horner–Wittig elimin-
ation to the left of the diphenylphosphine group. The double bond
formed by the final Horner–Wittig elimination always joins the α and
β carbon atoms; carbon atoms on the other side of the diphenylphos-
phinoyl group are labelled βЈ, γЈ, etc.
Results and discussion
Horner–Wittig additions of some prochiral phosphine oxides
As a starting point for our synthetic studies, we compared the
reactions of the prochiral phosphine oxides 12, 14 and 16 to
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1963

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Table 1 Horner–Wittig additions of prochiral phosphine oxides to aldehydes (Scheme 4)
Entry
Starting
material
R1
R2
Major
product
Crude ratioa,b
17:18 anti:syn
Yieldc
17 ϩ 18 (%)
1
2
3
4
5
6
16
16
16
12
12
12
Et
Et
Et
OBn
OBn
OBn
p-MeOC6H4
17a
17b
17c
17d
17e
17f
72:28
51:49
59:41
80:20
82:18
82:19
71 ϩ 26
47 ϩ 45
56 ϩ 34
73d
(E)-MeCH᎐CMe
᎐
CH2᎐᎐CMe
p-MeOC6H4
2-furyl
63d
CH2᎐᎐CMe
82d
1
a By 400 MHz H NMR. b Stereochemistry assigned using an established coupling constant correlation (ref. 13). c Yield of purified diastereomers.
d Yield of anti diastereomer.
O
O
NaH, Bu4NI
Ph2P
OBn
Ph2P
OH
OH
endo
BnBr, THF, 86%
H
Li
O
12
14
11
13
O
P
NO2
O
O
H
NaH, Bu4NI, THF
THF
R2
Ph2P
O
Ph2P
R1
15, 26%
exo
→ 17
Scheme 3
Fig. 1
a similar transition state in which R1 has flipped into an endo
position, since the 1,3 diaxial interaction between an endo R2
and one of the phenyl rings on phosphorus would be severe.
The reaction of the phosphine oxide 16 with unsaturated alde-
hydes was, however, virtually stereorandom, giving an almost
1:1 mixture of 17b–c and 18b–c (entries 2–3, Table 1). This
observation14 can be explained by suggesting that slim,
unsaturated R2 groups can compete effectively with hydrogen
for the rather hindered axial endo position (Fig. 1).
NO2
Br
15
investigate the effect of potentially coordinating substitiuents
on the yield and stereoselectivity of Horner–Wittig additions.
The syntheses of phosphine oxides 12 and 14 are outlined in
Scheme 3.
Phosphine oxides 12 and 16 were treated with a slight excess
of butyllithium at Ϫ78 ЊC, and after ten minutes, 1.1 equiv-
alents of freshly distilled aldehyde were added (Scheme 4, Table
The reactions of 12 (with its potentially coordinating benzyl
OH
OH
OH
Ph2PO
Ph2PO
17a (anti)
OH
O
R1
1. BuLi, THF
MeO
MeO
R2
−78 ºC
Ph2P
R1
18a (syn)
2. R2CHO
Ph2PO
12 R1 = OBn
16 R1 = Et
OH
17
+
OH
Ph2PO
Ph2PO
R1
R2
17b (anti)
18b (syn)
17c (anti)
18c (syn)
Ph2PO
18
OH
OH
Scheme 4
OBn
OBn
1). The reactions of alkyl phosphine oxide 16 were very similar
(both in terms of selectivity and yield) to those previously
studied.12 For example, reaction of lithiated 16 with p-
anisaldehyde gave an excellent (97%) yield of the anti β-hydroxy
phosphine oxide 17a and the syn β-hydroxy phosphine oxide
18a in a 3:1 ratio (entry 1, Table 1).§ The stereoselectivity of
Horner–Wittig additions has been rationalised in terms of the
structure of lithiated phosphine oxides;8 the aldehyde is
thought to displace one of the solvent molecules from the
lithium atom of 19, and rotate into a position in which carbon–
carbon bond formation is possible. The transition state leading
to the major (anti) product, 17, may resemble a “book” in
which both substituents, R1 and R2, are on the less hindered exo
face (Fig. 1). The minor (syn) isomer, 18, presumably forms via
Ph2PO
Ph2PO
O
MeO
17d (anti)
18d (syn)
17e (anti)
18e (syn)
OH
O
Li
OBn
O
Ph2P
O
Ph2PO
R1
19
17f (anti)
18f (syn)
N
Ph2PO
§ The relative stereochemistry of the products was determined using an
established 3JPH coupling constant correlation (ref. 13).
20
1964
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

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preference for the “inside” or the “outside” face of the
chelate.
endo
Horner–Wittig additions of chiral phosphine oxides with a ãЈ
stereogenic centre
H
Li
O
O
P
H
Recently, Okuma described the addition of dilithiated γЈ-
hydroxy phosphine oxides 21 with aldehydes (Scheme 5).17 In
this study, optically active phosphine oxides 21, which had been
classically resolved, were dilithiated and were found to react
diastereoselectively with aldehydes, giving diols 22 and 23 in
good yield and with good 1,3-stereoselectivity.
R2
OBn
inside
exo /
outside
→ 17
Fig. 2
We synthesised the optically active diols (R)-25 and (R)-28 by
asymmetric dihydroxylation of the alkenes 24 and 27 using the
conditions and ligand recommended by Sharpless (Scheme 6).18
The enantiomeric excesses of the diols 25 and 28 were deter-
mined by derivatisition with Mosher’s acid chloride (R)-30.19
The optically active epoxides (R)-26 and (R)-29 were syn-
thesised from the diols 25 and 28 using the stereospecific
sequence of reactions introduced by Sharpless.20 The epoxides
26, 29, 33 and 34 were opened with the lithium derivative of
ether) are remarkable because the stereoselectivities observed
are at least as good as those observed with 16 (compare entries
4–6 with entries 1–3, Table 1).¶ In contrast, the nitrogen of
amine 20, with its ability to coordinate lithium, disrupted the
usual stereochemical course of the Horner–Wittig reaction.16
The attempted Horner–Wittig addition of 14 to p-anisaldehyde
gave, however, only a complex mixture of products.
Our results strongly suggest the formation of a chelate in
which the benzyl ether has displaced the second solvent
molecule from lithium (Fig. 2). In this structure, the chelating
R1 group is held on the exo face of the transition state so the
stereoselectivity is eroded only when R2 flips into an endo
position. These observations bode well for the reactions of
chiral versions of 12 (of general structure 9) since a substitu-
ent next to the chelating benzyl ether may have a profound
O
O
Ph
33
34
methyldiphenylphosphine oxide and the alcohols 21 obtained
were protected using standard conditions (Scheme 7). We have
previously synthesised optically active alcohols 21 by reduction
of γ-hydroxy vinyl phosphine oxides.21
O
Ph2P
R1
We studied the Horner–Wittig reactions of protected versions
of the γЈ-hydroxy phosphine oxides 21. Our aim was simple: to
find out which pairs of phosphine oxides and aldehydes reacted
stereoselectively, giving β-hydroxy phosphine oxides 35–38 in
reasonable yield; the crude ratio of products was determined in
each case by 400 MHz 1H NMR spectroscopy, and the mixtures
of anti β-hydroxy phosphine oxides 35 and 36 were separated
from the syn isomers 37 and 38 by flash chromatography. The
results of this study are presented in Scheme 8 and Table 2.
We found that the yield and stereoselectivity of our reactions
were best with aromatic aldehydes (compare entries 1–4 with
entries 5–7, Table 2). In these cases, we were able to isolate good
yields (60–82%) of mixtures of anti β-hydroxy phosphine
oxides 35 and 36. Furthermore, there was some control
(between 2:1 to 3:1) over the 1,3 relationship between the
chiral centres α and γЈ to phosphorus. In each case, the relative
stereochemistry across the new carbon–carbon bond was
OH
21
1. BuLi
2. THF, 0 ºC
3. R2CHO, –78 ºC
OH
OH
R1
R1
R2
R2
+
Ph2PO
22
Ph2PO
OH
OH
23
22 : 23 3:2 to 9:1
yields up to 78%
3
assigned using an established JPH coupling constant corre-
lation.13 The geminal coupling constants between the benzylic
protons of benzyl ethers 35–38 (of general structure 39) were
found to depend remarkably on the relative stereochemistry of
the 1,3-related stereogenic centres (Table 3); the major products
Scheme 5
¶ For the effect of a β-oxido substituent on the stereoselectivity of the
Horner–Wittig addition, see ref. 15.
(DHQD)2PYR (1 mol%)
OsCl3 (0.75 mol%)
K3Fe(CN)6, K2CO3
HO
(a), 49%
1:1 H2O–ButOH
20 ºC
98% yield
or (b), 35%
O
OH
O
24
(R)-25, 84% ee
(R)-26
Ph
Cl
F3C OMe
(R)-30
(DHQD)2PYR (1 mol%)
OsCl3 (5 mol%)
K3Fe(CN)6, K2CO3
(a), 38%
HO
1:1 H2O–ButOH
20 ºC
O
OH
(R)-28, 89% ee
27
(R)-29
72% yield
Scheme 6 Reagents and conditions: (a) (i) (MeO)3CMe, PPTS, CH2Cl2; (ii) AcBr, CH2Cl2; (iii) K2CO3, MeOH; (b) (1) (MeO)3CMe, PPTS, CH2Cl2;
(ii) AcBr, CH2Cl2; (iii) KOH, MeOH, ether; (iv) distill.
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1965

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Table 2 Horner–Wittig additions of chiral phosphine oxides to aldehydes in THF (Scheme 8)
Starting
material
Major
product
Crude ratioa,b
35:36:37:38
Yieldc
35 ϩ 36 (%)
Ratioa
35:36
Yieldd
35 (%)
Yieldd
36 (%)
Entry
R1
R2
R3
1
2
3
4
5
6
7
31a
31b
31c
31b
31a
31a
32
Et
2-furyl
2-furyl
2-furyl
p-MeOC6H4
p-MeCH᎐CMe
CH2᎐᎐CMe
CH2᎐᎐CMe
Bn
Bn
Bn
Bn
Bn
Bn
CH2OMe
35a
35b
35c
35d
35e
35f
35g
73:18:5:5
75:25:0:0
70:21:9:0
64
61
82
60
35
19
38
78:22
82:18
78:22
61:39
60:40
62:38
55:45
36
23
—
33
—
—
—
9e
18
—
5
—
—
—
Bu
C6H11
Bu
Et
Et
Et
f
62:38:0:0
g
᎐
g
42:32:16:0
1
3
a By 400 MHz H NMR. b Anti:syn stereochemistry (35 ϩ 36:37 ϩ 38) across the new carbon–carbon bond assigned using an established JPH
coupling constant correlation (ref. 13). c Yield of mixture after flash chromatography. d Yield of purified isomer after preparative HPLC. e 85:15
mixture of 36a:35a. f Cyclohexyl. g Not measured; all four diastereoisomers present.
O
NaH, Bu4NI
BnBr, THF
Ph2P
O
O
1. BuLi, THF, −78 ºC
88%
Ph2P
OBn
31a
32
Ph2P
2. 33
95%
Me
OH
O
MeOCH2Cl, Et3N
CH2Cl2
21a
Ph2P
>98%
O
OMe
O
NaH, Bu4NI
O
O
BnBr, THF
1. BuLi, THF, −78 ºC
Ph2P
Ph2P
Ph2P
93%
2. (R)-26
Me
Me
Me
OH
(R)-21b
68%
OBn
(R)-31b
O
NaH, Bu4NI
BnBr, THF
O
O
1. BuLi, THF, −78 ºC
2. (R)-29
Ph2P
Ph2P
Ph2P
56% over 2 steps
OH
(R)-21c
OBn
(R)-31c
O
NaH, Bu4NI
BnBr, THF
O
O
1. BuLi, THF, −78 ºC
Ph2P
Ph
Ph2P
Ph
OBn
Ph2P
88%
2. 34
91%
OH
31d
21d
Scheme 7
OH
OH
by significant quantities of syn products 37e–f and 38e–f. On
moving from aromatic to unsaturated aldehydes, the control
over the relative stereochemistry across the new carbon–carbon
bond was eroded from at least 90:10 to about 70:30. The
control over the more remote (1,3) chiral relationship was worse
as well. We tried to improve the situation by studying the
addition of the MOM acetal 32 to methacrolein, but the yield
and stereoselectivity were broadly the same (compare entry 7
with entries 5–6, Table 2).
Our analysis of the stereoselectivity of these Horner–Wittig
additions is broadly similar to that of the reactions of
phosphine oxide 12 (see Fig. 2), but with the added complic-
ation of the chiral centre already present in phosphine oxides
31. We explain the high anti selectivity of these reactions in the
same way as before: the chelating benzyl ether is held on the exo
face of the “book-like” transition states 41 and 42, so provided
that R2 is reasonably large (and forced to be on the exo face),
high anti stereoselectivity is assured (Scheme 9). When the size
of R2 is decreased, it can compete with hydrogen for one of the
more hindered endo positions, lowering the anti selectivity of
the reaction.
R1
R1
OR3
R2
R2
OR3
Ph2PO
Ph2PO
O
R1
1. BuLi, –78 ºC
35
Ph2P
36
2. R2CHO, –78 ºC
OH
OR3
31 R3 = Bn
32 R3 = CH2OMe
OH
R1
R1
OR3
R2
R2
OR3
Ph2PO
37
Ph2PO
38
Scheme 8
of each of the addition reactions in THF (Table 2) had
2JHH ≈ 12.0 Hz, suggesting that the sense of the 1,3-induction
was the same in each case. The relative stereochemistry of the
products was determined by conversion of the alcohol 35b into
a product (10) of known stereochemistry.11 We were able to
separate the 1,3anti alcohols 35a–b and 35d from the 1,3syn
alcohols 36a–b and 36d by preparative HPLC.
The reactions of benzyl ether 31a with unsaturated aldehydes
were much less encouraging (entries 5–6, Table 2). The isolated
yields of the products were poor, and were accompanied
The high anti selectivity of the additions to aromatic alde-
hydes (entries 1–4, Table 2) has allowed us to analyse some of
1966
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

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Table 3 Geminal coupling constant between benzylic protons in benzyl ethers 35–38
Compound
R1
R2
35 2JAB/Hz
36 2JAB/Hz
37 2JAB/Hz
38 2JAB/Hz
35–38a
35–38b
35–38c
35–38d
35–38h
35–38i
35–38j
Et
2-furanyl
2-furanyl
2-furanyl
p-MeOC6H4
Ph
Ph
Ph
12.1
12.1
12.2
12.1
12.1
—
11.0
10.9
10.9
11.1
11.1
—
—
—
Bu
C6H11
Bu
Et
Bu
Ph
11.0
11.0
11.1
—
11.1
11.0
12.0
12.1
11.8
—
11.9
11.6
a
11.9
11.0
maximum value
minimum value
12.2
11.9
11.1
10.9
11.1
11.0
12.1
11.6
a Cyclohexyl.
the factors which underlie the 1,3 stereocontrol observed. To a
first approximation, the only populated transition states are 41
and 42. Lithiated phosphine oxides are configurationally
unstable,9 even on the timescale of their reaction with alde-
hydes, so all of the material can choose which pathway is
followed. The R1 side chain of phosphine oxides 31 has an
approximately 3:1 preference for the “outside” position of 41
over the “inside” position of chelated structure 42, which trans-
lates into an approximately 3:1 ratio of products 35 and 36.
We also investigated the effect of solvent on the stereo-
selectivity of our Horner–Wittig additions and the results of
this study are presented in Scheme 8 and Table 4. The effect of
DME on the reaction of the phosphine oxide 31a with furfural
was broadly the same as that of THF, though the reaction was
marginally less anti selective (compare entry 1, Table 4 with
entry 1, Table 2).||
The effect of toluene, a less coordinating solvent, was studied
in the hope that this would promote chelation control and
increase the diastereoselectivity of the reactions.23 The crude
1
reaction mixtures were analysed by H NMR and the two anti
diastereomers (35 and 36) were isolated by flash chrom-
atography. On moving from THF to toluene, we found that the
anti selectivity of the Horner–Wittig additions was lowered
considerably (entries 2–5, Table 4 and Scheme 8).** For example,
the reactions of 31a–b with aromatic aldehydes (entries 3–5,
Table 4) produced significant quantities (up to 25% of the crude
reaction mixture) of the two syn diastereomers 37 and 38, but
these isomers were not observed when the reaction was
performed in THF. As before, an addition to an unsaturated
aldehydes was even less selective (entry 2, Table 4).
There was, however, one very positive side to these results;
the control over the 1,3-related chiral centres had been reversed.
The ratio of the two anti diastereomers had been changed from
a good selectivity (between 3:1 and 4:1) in favour of the 1,3syn
alcohol 35 to a modest preference (up to 2:1) for the 1,3anti
diastereomer 36.†† The yields for the isolated anti isomers were
rather low, partly because the addition was less anti selective
than in THF, but we were pleased to have developed a com-
plementary route to the 1,3anti isomer 36.
OH
OH
Ph2PO
35a
Ph2PO
36a
O
O
OBn
OBn
O
OBn
OH
OH
Ph2PO
Ph2PO
O
OBn
38a
37a
OH
OH
Ph2PO
O
OBn
Ph2PO
O
OBn
35−38b
35−38c
The reversal in stereoselectivity is difficult to explain, but one
possibility is that the aggregation state of our lithiated phos-
phine oxide reagents has changed on moving from THF to
toluene. Coordination of lithium by THF tends to break-up
organolithiums aggregates, so perhaps the reactive species in
toluene is a dimer like 43.24 The change in solvent lowers the
magnitude of, and reverses the sense of the 1,3-stereocontrol.
OH
OH
Ph2PO
OH
Ph2PO
OBn
MeO
35−38d
35−38e
OH
OH
Stereoselective acylation and reduction of chiral phosphine oxides
with a ãЈ stereogenic centre
The diastereoselective acylation of chiral phosphine oxides 31
was much easier to study than the corresponding Horner–
Wittig additions because the reaction leads to the formation of
only one new stereogenic centre.25 The acylation of phosphine
oxides 31 gave good yields of β-keto phosphine oxides 44 and
45 with moderate levels of 1,3-stereocontrol (Scheme 10 and
Table 5). The ketones 44 and 45 were rather susceptible to
Ph2PO
Ph2PO
35−38f
O
O
OBn
35−38g
OH
OH
Ph
Ph
Ph2PO
35−38i
Ph2PO
35−38h
OBn
OBn
|| DME can have a remarkable effect on the yield of some organolithium
reactions (ref. 22).
HO
** We have previously noted that Horner–Wittig additions are less anti
selective in toluene than in THF (ref. 12).
R2
OH
R1
Ph
OBn
†† We use the stereochemical designator 1,3syn to indicate that functional
groups attached to two carbons with a 1,3-relationship are both above
or both below the plane of the illustration. Similarly, the designator
1,3anti indicates that the 1,3-related functional groups are on opposite
sides of the illustration.
Ph
Ph2PO
O
Ph
Ph2PO
HA HB
35−38j
39
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1967

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Table 4 Effect of solvent on the stereoselectivity of Horner–Wittig additions of chiral phosphine oxides (Scheme 8)
Starting
material
Major
product
Crude ratioa,b
35:36:37:38
Yieldc
35 ϩ 36 (%)
Ratioa
35:36
Entry
R1
R2
Solvent
1
2
3
4
5
31a
31a
31a
31b
31b
Et
Et
Et
Bu
Bu
2-furyl
CH2᎐᎐CMe
Ph
2-furyl
p-MeOC6H4
DME
35a
36f
36h
36d
36b
57:19:11:13
17:39:20:25
25:51:19:6
46
33
38
56
33
77:23
29:71
34:66
43:57
44:56
toluene
toluene
toluene
toluene
34:43:25:0
d
a 400 MHz 1H NMR. b Anti:syn stereochemistry (35 ϩ 36:37 ϩ 38) across the new carbon–carbon bond assigned using an established 3JPH coupling
constant correlation (ref. 13). c Yield of mixture after flash chromatography. d Not measured.
Table 5 Stereoselective acylation and reduction of chiral phosphine oxides (Scheme 10)
Acylation
Reduction
Starting
material
Crude ratioa
44:45
Yieldb
44 ϩ 45 (%)
Ratioa
44:45
Major
product
Yieldb
37 ϩ 38 (%)
Ratio
37:38
Yieldc Yieldc
37 (%) 38 (%)
Entry
R1
R2
1
2
3
4
31b
31b
31c
31d
Bu
Bu
C6H11
Ph
2-furyl
Ph
2-furyl
Ph
72:28
60
74
60
82
63:37
65:35
69:31
80:20
37b
37i
37c
37j
97
46
71
93
63:37
70:30
71:29
72:28
76
—
—
—
21
—
—
—
d
e
67:33
79:31
1
a By 400 MHz H NMR. b Yield of mixture after flash chromatography. c Yield of purified isomer after preparative HPLC. d Not measured; all
diastereoisomers present. e Cyclohexyl.
OH
inside
R1
R2
H
Li
R1
Bn
O
O
Ph2PO
OBn
R1
BnO
Ph
Li
O
P
Ph2PO
1, 3syn-40
OBn
R1
35
H
P
Ph
Li
O
O
outside /
exo
H
R2
endo
41
Li
fast
Ph
OBn
P
R1
endo
Ph
OH
Li
R1
R1
OBn
H
Li
O
R2
O
43
Ph2PO
1, 3anti-40
OBn
P
Ph2PO
36
H
OBn
R2
outside /
R1
H
exo
inside
42
Scheme 9
The most likely explanation for the reversed 1,3 stereocontrol
(on moving from the reactions of aldehydes to those of
ketones) is quite simply that the diastereomeric lithium deriv-
ative 1,3anti-40 is the more reactive diastereomer in acylation
reactions (Scheme 11).‡‡ Once again, the configurational instab-
ility of lithiated phosphine oxides is central to the outcome of
the reaction; both transition states 46 and 47 are accessible to
the rapidly interconverting mixture of organolithiums 1,3syn-
and 1,3anti-40.
O
OH
R1
R1
R2
R2
Ph2PO
Ph2PO
O
OBn
OBn
1. BuLi, THF
R1
–78 ºC
NaBH4, EtOH
44
37
Ph2P
2. R2CO2Et
O
OH
OBn
R1
OBn
R1
R2
R2
31
Ph2PO
Ph2PO
OBn
45
38
Our results are rather similar to, though less impressive
than, some allylation reactions reported by Beak.26 In these
experiments, a pair of rapidly interconverting organolithium
reagents, which were diastereomeric by virtue of coordination
Scheme 10
epimerisation and therefore we chose to convert the mixtures of
products directly into the syn β-hydroxy phosphine oxides 37
and 38.12 Remarkably, and in contrast to the corresponding
additions to aldehydes in THF (Table 2), the acylation of phos-
phine oxides 31 was found to be 1,3anti selective. Once again, the
1,3-stereochemistry of the alcohols 37 and 37 could be deter-
mined using the coupling constant correlation described in
Table 3.
‡‡ We have assumed that the SE2 reactions of the lithiated phosphine
oxides with carbonyl electrophiles proceed with retention of con-
figuration. This is reasonable in the light of recent evidence (ref. 8) that
aldehydes precoordinate to the lithium atom, ensuring a 90Њ angle
between the old (C–Li) and new (C–C) bonds.
1968
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

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R1
that mixtures of anti isomers 35 and 36 were readily isolated by
Li
Ph2PO
R1
Li
Ph2PO
fast
flash chromatography. Mixtures of anti β-hydroxy phosphine
oxides 35 and 36 were added to a suspension of sodium hydride
in DMF, and after work-up, alkenes (Z)-49 were isolated
in reasonable yield (Scheme 13). Attempted Horner–Wittig
elimination of a mixture of 35b and 36b using generally more
reliable conditions (KOH in DMSO) was not successful; none
OBn
1,3anti-40
OBn
1,3syn-40
1
of the required alkene (Z)-49a was observed in the H NMR
spectrum of the crude reaction mixture.
endo
inside
Bn
We were pleased to find that these Horner–Wittig elimin-
ations were completely stereospecific: none of the thermo-
dynamically favoured (E) isomers were observed. This result
was perhaps surprising, since elimination of a mixture of 36d
and 35b gave a poor 30% yield of alkene (Z)-49b accompanied
by a 23% yield of p-anisaldehyde, indicating that the reverse
H
EtO
Li
O
O
O
O
Li
O
P
P
R1
H
H
OBn
R2
outside /
exo
R1
46 → 37
EtO
endo
R2
outside /
exo
H
inside
Horner–Wittig addition was
a competing side-reaction.
47 → 38
This process has been proposed to explain the stereochemical
“leakage” of many Horner–Wittig eliminations.31
Scheme 11
Similarly, mixtures of the syn β-hydroxy phosphine oxides 37
and 38 were eliminated under the same reaction conditions to
yield the corresponding E-alkenes (E)-49 (Scheme 14). In fact,
the synthetic route described in Schemes 13 and 14 outlines the
formal synthesis of all four stereoisomers of these homoallylic
alcohol derivatives since the enantiomeric benzyl ethers could
have been synthesised simply by using a different ligand in the
AD reaction used to introduce the asymmetry. Previously,
racemic homoallylic alcohol derivatives (similar to 49) have
been made (as E and Z mixtures) using the Wittig32 and
Julia33 olefination reactions and (as single compounds) using a
palladium-catalysed coupling reaction.34 Okuma has prepared
optically active homoallylic alcohols using phosphine oxide
chemistry.17
We briefly looked at the possibility of developing a stereo-
selective route to trisubstituted alkenes. To this end, we added
the lithiated secondary phosphine oxide 51 to benzaldehyde
(Scheme 15) but we isolated a mixture of all four diastereomers
of β-hydroxy phosphine oxide 52. Nevertheless, elimination of
this mixture gave a 64:36 mixture of trisubstituted alkenes 53,
indicating that there had been some asymmetric induction
across the new carbon–carbon bond in the addition step.
by (Ϫ)-sparteine reacted with allyl chloride and allyl tosylate to
give enantiomeric products; the configurational instability of
the intermediate organolithiums was necessary for these
dynamic kinetic resolutions.27
Preparation of â-hydroxy phosphine oxides by oxidation–
stereoselective reduction
We have described stereoselective routes to three (35, 36 and 37)
of the four diastereomers of a β-hydroxy phosphine oxide and
we needed to develop a complementary route to the remaining
isomers 38. An approach which involves the oxidation of the
anti alcohols (35 or 36) with Dess–Martin’s periodinane§§ 48
to the corresponding ketones (45 or 44), and syn-selective
reduction12 with sodium borohydride (→38 or 37) is presented
in Scheme 12 and Table 6. The remote stereogenic centre in
these molecules acts as handle for determining whether the
intermediate ketones epimerised under the reaction conditions;
in two cases (entries 1 and 2, Table 6), we analysed the crude
reaction mixture after oxidation with Dess–Martin’s reagent
and were pleased to find that no enolisation had occurred.¶¶
This approach also allowed us to correlate the stereo-
chemistry of anti β-hydroxy phosphine oxides 35 and 36 with
syn β-hydroxy phosphine oxides 37 and 38.
The intermediate crude β-keto phosphine oxides (44 or 45)
were treated with a large excess of sodium borohydride;
unfortunately, epimerisation of the intermediate β-keto phos-
phine oxides occurred when the reaction was performed on a
large scale (compare entry 1 with entry 2, Table 6). Epimerisa-
tion of β-keto phosphine oxide has previously been observed
under Luche’s reduction conditions (sodium borohydride with
added cerium trichloride).25 We were able to solve this problem
by cooling the reaction mixture to 0 ЊC and adding the sodium
borohydride in small portions over 30 minutes. In this way,
epimerisation was often avoided altogether (entries 2 and 4,
Table 6). Even when the reaction was performed on a larger
scale (entry 3b, Table 6), the relative stereochemistry of the 1,3-
related stereogenic centres remained largely intact, and in this
case, we were able to separate the syn isomers of 37b and 38b by
preparative HPLC.
Summary
In this paper, we have described complementary routes to all
four diastereomeric alcohols 35b, 36b, 37b and 38b from the
same phosphine oxide 31b. These reaction sequences are sum-
marised in Scheme 16. Anti β-hydroxy phosphine oxides (35
and 36) were synthesised by adding the lithium derivative of a
phosphine oxide (e.g. 31b) to an aldehyde; it was possible to
control the 1,3 chiral relationship in these molecules by careful
choice of solvent. The stereoselectivities of these addition
reactions in THF and toluene are at their best (and oppose one
another) when aromatic aldehydes (like furfural) are used.
Alternatively, reduction of β-keto phosphine oxides 44 and
45 with sodium borohydride was highly syn selective, and
allowed the synthesis of syn β-hydroxy phosphine oxides 37 and
38. In this way, ketones 44 (synthesised by oxidation of alcohols
35) and 45 (obtained by acylation of phosphine oxides 31) were
reduced to give the syn diastereomers of 38 and 37. The success
of our complementary routes hinges on the configurational
instability of lithiated phosphine oxides; access to 1,3syn and
1,3anti diastereomeric series was possible because aldehydes and
esters reacted preferentially with different isomers of a rapidly
equilibrating mixture of lithiated phosphine oxides 40 (Schemes
9 and 11).
Synthesis of optically active E and Z protected homoallylic
alcohols
We have already explained that the Horner–Wittig additions of
phosphine oxides 31 to aromatic aldehydes were almost com-
pletely anti selective across the new carbon–carbon bond, and
In fact, our synthesis of the four diasteromers 35b, 36b, 37b
and 38b constitutes a formal synthesis of all eight stereo-
isomers; the other enantiomeric series could have been accessed
simply by choosing a different alkaloid ligand in the asym-
metric dihydroxylation reaction used to synthesise benzyl ether
§§ Dess–Martin’s periodinane (ref. 28) is the best (ref. 29) reagent for the
preparation of base-sensitive ketones.
¶¶ Previous workers have not been faced by the problem of epimeris-
ation of β-keto phosphine oxides and have simply used chromium
reagents in the oxidation step (ref. 30).
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1969

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Table 6 Oxidation and stereoselective reduction of β-hydroxy phosphine oxides (Scheme 12)
Reduction
Major
Starting
mixture
35:36
Oxidation
product
Starting
material
Yield over 2 stepsb
38 ϩ 37 (%)
Ratio
38:37
Yieldc
38 (%)
Entry
R1
R2
ratioa 45:44
T/ЊC
product
e
e
e
1d
2
35d
31b
31c
35b
31d
Bu
Bu
Bu
Bu
p-MeOC6H4
p-MeOC6H4
2-furyl
2-furyl
2-furyl
>95:5
15:85
>95:5
>95:5
78:22
>95:5
20
0
20
0
38d
37b
38b
38b
38c
69
83
83
80
90
51:49
13:87
>95:5
81:19
75:25
15:85
g
3af
3bh
4
g
g
53
i
e
C6H11
0
a By 400 MHz 1H NMR. b Yield of mixture after flash chromatography. c Yield of purified isomer after preparative HPLC. d Reaction on a 1.1 g scale.
e Not purified by preparative HPLC. f Reaction on a 80 mg scale. g Not measured. h Reaction on a 600 mg scale. i Cyclohexyl.
OH
O
OH
NaBH4
EtOH
R1
OBn
R1
OBn
Dess−Martin
R1
OBn
R2
R2
R2
Ph2PO
38
Ph2PO
45
Ph2PO
35
AcO
OAc
OAc
I
O
OH
O
O
OH
NaBH4
EtOH
R1
OBn
R1
OBn
Dess−Martin
R1
OBn
48
R2
R2
R2
Ph2PO
Ph2PO
Ph2PO
36
44
37
Scheme 12
O
OH
Bu
Ph2P
Bu
OBn
NaH, DMF
49%
O
Ph2PO
OBn
(Z)-49a, 84% ee
O
1. BuLi, THF, –78 ºC
Ph
35b:36b 82:18
, –78 → 20 ºC
2.
O
OH
MeO
Bu
NaH, DMF
30%
Bu
3. NaH, Bu4NI
BnBr, THF
Ph2PO
Ph
Ph
OBn
OBn
MeO
OBn
Ph2PO
Ph2PO
51
OH
(Z)-49b, 84% ee
80%
36b:35b 72:28
OH
50
86:14 mixture
Ph
Ph
Ph
NaH, DMF
60%
Ph
1. BuLi
2. PhCHO
OBn
Ph2PO
OBn
36j:35j 65:35
(Z)-49c, 100 % ee
Scheme 13
OH
Ph
OBn
Ph
3. NaH, DMF
Ph
OBn
Ph
OH
35% over 2 steps
Ph2PO
52
NaH, DMF
62%
Bu
Bu
OBn
Ph
Ph
53
E:Z 64:36
Ph2PO
OBn
(E)-49d, 84% ee
37i:38i 72:28
Scheme 15
OH
31b. The β-hydroxy phosphine oxides were valuable inter-
mediates in the synthesis of optically active homoallylic alcohol
derivatives 49.
Bu
OBn
(E)-49b, 84% ee
Bu
NaH, DMF
Ph2PO
37d:38d 72:28
OBn
MeO
19%
MeO
Experimental
All solvents were distilled before use. THF and Et2O were
freshly distilled from lithium aluminium hydride whilst CH2Cl2
and toluene were freshly distilled from calcium hydride. Tri-
phenylmethane was used as indicator for THF. n-Butyllithium
was titrated against diphenylacetic acid before use. All
non-aqueous reactions were carried out under argon using
oven-dried glassware.
OH
NaH, DMF
60%
Ph
OBn
Ph
Ph
Ph
Ph2PO
37j:38j 72:28
OBn
(E)-49c, 100 % ee
Scheme 14
1970
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

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OH
OH
O
(a)
Bu
OBn
(a)
Bu
OBn
Ph2P
Ph2PO
35b
Ph2PO
36b
O
THF
O
OBn
31b
toluene
(b)
(c), (d)
O
OH
OH
Bu
OBn
Bu
OBn
Bu
OBn
(d)
Ph2PO
Ph2PO
Ph2PO
O
O
O
37b
38b
Scheme 16 Reagents and conditions: (a) (i) BuLi; (ii) furfural; (b) (i) BuLi, THF; (ii) ethyl 2-furoate; (c) Dess–Martin periodinane; (d) NaBH4, EtOH.
Flash column chromatography was carried out using Merck
Kieselgel 60 (230–400 mesh) according to the method of Still,
Kahn and Mitra.35 Thin layer chromatography was carried out
on commercially available pre-coated plates (Merck silica
Kieselgel 60F254). Proton and carbon NMR spectra were
recorded on Bruker WM 200, WM 250, WM 400 or AMX 500
Fourier transform spectrometers using an internal deuterium
lock. Chemical shifts are quoted in parts per million downfield
of tetramethylsilane and values of coupling constants (J) are
given in Hz. The presence of an asterisk (*) after the proton
NMR chemical shift indicates that the signal disappears after a
D2O “shake”. 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.
Melting points were measured on a Reichart hot stage
microscope or a Buchi 510 melting point apparatus and are
uncorrected. Infra red spectra were recorded on a Perkin-Elmer
1600 (FT-IR) spectrophotometer. Mass spectra were recorded
on a Kratos double-beam mass spectrometer using a DS503
data system for high resolution analysis. Electron Impact was
used unless Fast Atom Bombardment (ϩFAB) is indicated.
Microanalyses were carried out by the staff of the University
Chemical Laboratory using Carlo Erba 1106 or Perkin-Elmer
240 automatic analysers. Optical rotations were recorded on a
Perkin-Elmer 241 polarimeter (using the sodium D line; 589
nm) and [α]D20 are given in units of 10Ϫ1 deg cm2 gϪ1. (R)-Pirkle’s
reagent is (R)-(Ϫ)-2,2,2-trifluoro-1-(9-anthryl)ethanol.
m) and 0.88 (3 H, t, J 7.1, Me); δC (50 MHz; CDCl3) 72.3ϩ
(CHOH), 66.7Ϫ (CH2OH), 32.8Ϫ, 27.7Ϫ, 22.6Ϫ and 14.0ϩ (Me).
1
Integration of the 500 MHz H NMR spectrum of the Mosh-
er’s diesters of this material showed it to have 84% ee.
(R)-1-Cyclohexylethane-1,2-diol 28
By the same general method, vinylcyclohexane (6.2 cm3, 45.5
mmol), (DHQD)2PYR (465 mg, 0.53 mmol), potassium carb-
onate (21.7 g, 157 mmol), potassium ferricyanide (50.0 g, 152
mmol) and osmium trichloride (300 mg, 2.22 mmol) gave a
crude product after stirring for 3 days with a mechanical stirrer.
Flash chromatography, eluting with Et2O, gave the diol36 28
(4.73 g, 72%) as a liquid, [α]D20 Ϫ2.0 (c 0.64 in CHCl3) (lit.36
Ϫ4.17, c 1.73 in CHCl3) (Found: Mϩ Ϫ OH, 127.1125. C8H16O2
requires M Ϫ OH, 127.1122); νmax/cmϪ1 (CHCl3) 3413 (OH); δH
(400 MHz; CDCl3) 3.65 (1 H, m, CHOH), 3.62 (1 H, dd, J 2.9
and 2JHH 11.1, CHAHBOH), 3.41 (1 H, dd, J 6.6 and 2JHH 11.1,
CHAHBOH), 2.20–1.10 (11 H, m) and 0.88 (3 H, t, J 7.1, Me);
m/z 127.1 (18%, M Ϫ OH) and 95.1 (100). Integration of the
1
500 MHz H NMR spectrum of the Mosher’s diesters of this
material showed it to have 89% ee.
(R)-Butyloxirane 26
By the method of Sharpless,20 trimethyl orthoacetate (864 mg,
6.5 mmol) was added dropwise to a solution of the diol 25 (780
mg, 6.0 mmol) and pyridinium toluene-p-sulfonate (16 mg, 65
µmol) in dry dichloromethane (10 cm3). After stirring for 15
min, the reaction mixture was evaporated to dryness and the
vessel evacuated on a trolley pump for 2 min. The reaction
mixture was dissolved in dry dichloromethane (10 cm3) and
acetyl bromide (885 mg, 7.2 mmol) was added dropwise at 0 ЊC.
The reaction mixture was warmed to 20 ЊC, stirred for 30 min
and evaporated under reduced pressure. Potassium carbonate
(1.43 g, 10.4 mmol) and methanol (20 cm3) were added, and the
reaction was stirred for 75 min. The reaction was quenched
with water (10 cm3), extracted with Et2O (3 × 10 cm3) and evap-
orated under reduced pressure (with no heat) to give a crude
product. Distillation from MgSO4 (bp 117–119 ЊC, lit.38 118–
129 ЊC) gave the epoxide38 26 (330 mg, 49%) as a liquid, [α]D20
ϩ13.7 (c 1.34 in Et2O; 84% ee); νmax/cmϪ1 (CHCl3) no character-
istic peaks; δH (400 MHz; CDCl3) 2.81 (1 H, m, CHO), 2.65 (1
H, app. t, J 4.5, CHAHBO), 2.36 (1 H, dd, J 2.7 and 5.1, CHA-
HBO), 1.5–1.25 (6 H, m) and 0.82 (3 H, t, J 7.1, Me); δC (50
MHz; CDCl3) 52.4ϩ (CHO), 47.1Ϫ (CH2O), 32.2Ϫ, 28.1Ϫ, 22.5Ϫ
and 14.0ϩ (Me).
(R)-Hexane-1,2-diol 25
By the method of Sharpless,36 hydroquinidine 2,5-diphenyl-
pyrimidine-4,6-diyl diether [(DHQD)2PYR] (1.63 g, 1.83
mmol),potassiumcarbonate(83.5g,605mmol),potassiumferri-
cyanide (192 g, 605 mmol) and osmium trichloride (500 mg,
1.59 mmol) were stirred in 1:1 tBuOH–water (20 cm3) at 25 ЊC.
The solution was cooled to 0 ЊC whereupon some of the
dissolved salts precipitated. Hex-1-ene (17.0 g, 202 mmol) was
immediately added. The slurry was stirred vigorously for 3 days.
Sodium sulfite (291 g, 3.1 mol) was added, the temperature
allowed to warm to 20 ЊC and the slurry stirred for a further 30
min. EtOAc (1000 cm3) was added to the reaction mixture, and
the aqueous fraction extracted with EtOAc (3 × 1000 cm3),
washed with water (1000 cm3) and brine (1000 cm3), dried
(MgSO4) and evaporation gave a crude product. Flash chroma-
tography, and eluting with Et2O, gave the diol37 25 (22.55 g,
98%) as a liquid, [α]D20 ϩ7.51 (c 2.5 in Et2O) (lit.37 ϩ15.2, neat);
νmax/cmϪ1 (CHCl3) 3475 (OH); δH (400 MHz; CDCl3) 3.67 (1 H,
(R)-Cyclohexyloxirane 29
By the same general method, trimethyl orthoacetate (4.78 cm3,
2
m, CHOH), 3.62 (1 H, dd, J 2.9 and JHH 11.1, CHAHBOH),
3.41 (1 H, dd, J 6.6 and 2JHH 11.0, CHAHBOH), 1.45–1.25 (6H,
37.4 mmol), (R)-cyclohexylethane-1,2-diol (4.62 g, 32.1 mmol),
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1971

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pyridinium toluene-p-sulfonate, acetyl bromide (2.8 cm3, 37.5
mmol) and potassium carbonate (7.6 g, 55.1 mmol) gave a
crude product which was stored over freshly activated molec-
ular sieves to give the epoxide39 29 (1.52 g, 38%) as a liquid, [α]D20
Ϫ2.0 (neat; 89% ee) (lit.39 ϩ2.1 for S isomer, neat); νmax/cmϪ1
(CHCl3) no characteristic peaks; δH (400 MHz; CDCl3) 2.71
(2 H, m), 2.51 (1 H, t, J 4.2, CHAHBO), 1.85 (1H, m), 1.8–1.6 (4
H, m) and 1.3–1.0 (6 H, m); δC (50 MHz; CDCl3) 56.7ϩ (CHO),
46.0Ϫ (CH2O), 29.7Ϫ, 28.8Ϫ, 26.3Ϫ, 25.7Ϫ and 25.5Ϫ.
the alcohol21 21b (7.91 g, 68% based on epoxide) as an oil, [α]D20
Ϫ8.4 (c 1.26 in CHCl3; 84% ee), spectroscopically identical to
that obtained previously.
(S)-1-Cyclohexyl-3-diphenylphosphinoylpropyl benzyl ether 31c
n-Butyllithium (7.4 cm3 of a 1.3 mol dmϪ3 solution in hexanes,
9.6 mmol) was added dropwise to the phosphine oxide (1.87 g,
8.7 mmol) in dry THF (30 cm3) at 0 ЊC. After 15 min, the
epoxide (R)-29 (993 mg, 7.9 mmol) was added dropwise, and
the reaction was stirred for a further 4 h at 20 ЊC, quenched with
saturated ammonium chloride solution (30 cm3), extracted with
dichloromethane (3 × 20 cm3), dried (MgSO4) and evaporated
under reduced pressure to give a crude product which was dried
on a vacuum pump for 2 h. The residue was dissolved in dry
THF (40 cm3), tetra-n-butylammonium iodide (144 mg, 0.39
mmol) added in one portion, sodium hydride (504 mg, 60%
dispersion in oil, 12.6 mmol) added in several portions and the
reaction mixture was stirred until no further gas was evolved.
Benzyl bromide (1.5 cm3, 12.7 mmol) was added dropwise to
the reaction mixture, which was stirred for 16 h, quenched with
water (30 cm3), extracted with dichloromethane (3 × 25 cm3),
dried (MgSO4) and evaporated under reduced pressure to give a
crude product which was purified by flash chromatography,
eluting with EtOAc, to give the benzyl ether 31c (1.90 g, 56%
based on epoxide 29) as plates, mp 135–137 ЊC (from EtOAc–
hexane); Rf 0.51 (EtOAc); [α]D20 ϩ3.1 (c 1.30 in CHCl3; 89% ee)
(Found: Mϩ Ϫ Bn, 341.1670. C28H33O2P requires M Ϫ Bn,
(R)-Butyloxirane 26
By the method of Sharpless,20 trimethyl orthoacetate (2.56 cm3,
20.1 mmol) was added dropwise to a solution of (R)-hexane-
1,2-diol (1.99 g, 16.9 mmol) and pyridinium toluene-p-sulfonate
(45 mg, 0.19 mmol) in dry dichloromethane (15 cm3).18 After
stirring for 15 min, the reaction mixture was evaporated to dry-
ness and the vessel evacuated on a trolley pump for 2 min. The
reaction mixture was dissolved in dry dichloromethane (15 cm3)
and acetyl bromide (1.45 cm3, 19.6 mmol) was added dropwise
at 0 ЊC. The reaction mixture was warmed to 20 ЊC, stirred for
30 min, poured into dilute hydrochloric acid (1.0 mol dmϪ3, 25
cm3), extracted with dichloromethane (3 × 15 cm3), dried
(MgSO4) and evaporated under reduced pressure. The residue
was dissolved in dry Et2O (30 cm3), powdered potassium
hydroxide (1.48 g, 26.4 mmol) and dry methanol (0.81 cm3)
were added, and the reaction was stirred for 2.5 h. The reaction
mixture was filtered through a pad of potassium carbonate,
which was washed thoroughly with Et2O. The solvent was
then removed by careful distillation using a Vigreux column.
Distillation from MgSO4 (bp 117–119 ЊC, lit.38 118–129 ЊC)
gave the epoxide 26 (587 mg, 35%) as a liquid, spectroscopically
identical to that obtained previously.
341.1670); νmax/cmϪ1 (CHCl ) 1437 (P–Ph) and 1232 (P᎐O); δ
᎐
3
H
(400 MHz; CDCl3) 7.8–7.2 (15 H, m, Ph2PO and Ph), 4.42 (1 H,
d, J 11.5, PhCHAHB), 4.38 (1 H, d, J 11.5, PhCHAHB), 3.19
(1 H, m, CHOBn) and 2.4–0.8 (15 H, m); δC (100 MHz; CDCl3)
3
138.8Ϫ (ipso-Ph), 134–127.5 (m, Ph2PO and Ph), 83.3ϩ (d, JPC
13.4, CHOBn), 71.7Ϫ (PhCH2), 40.5ϩ, 29.3Ϫ, 28.5Ϫ, 26.5Ϫ,
1
26.2Ϫ, 24.8Ϫ (d, JPC 72.0, PCH2), 21.9Ϫ and 21.8Ϫ; m/z 341.2
1-Diphenylphosphinoylpentan-3-ol 21a
(20%, Mϩ Ϫ Bn), 201.0 (50, Ph2PO) and 91.1 (100, Bn).
n-Butyllithium (15 cm3 of a 1.6 mol dmϪ3 solution in hexanes,
24.0 mmol) was added dropwise to methyldiphenylphosphine
oxide (20.9 mmol) in dry THF (100 cm3) at 0 ЊC. After 15 min,
the epoxide (22.0 mmol) was added dropwise, and the reaction
was stirred for a further 4 h at 20 ЊC, quenched with saturated
ammonium chloride solution (100 cm3), extracted with di-
chloromethane (3 × 100 cm3), dried (MgSO4) and evaporated
under reduced pressure to give a crude product, which was
purified by flash chromatography, eluting with 7% methanol in
EtOAc, to give the alcohol 21a (5.71 g, 95%) as an oil, Rf 0.20
(EtOAc) (Found: Mϩ Ϫ H, 287.1190. C17H21O2P requires
M Ϫ H, 287.1201); νmax/cmϪ1 (CHCl3) 3344 (br, OH), 1437
(1S,3R)- and (1S,3S)-3-Diphenylphosphinoyl-1-phenylbutyl
benzyl ether 51
By the same general method, ethyldiphenylphosphine oxide
(4.23 g, 18.3 mmol), (R)-styrene oxide (1.91 cm3, 16.7 mmol),
tetra-n-butylammonium iodide (305 mg, 0.82 mmol), sodium
hydride (1.07 g, 60% dispersion in oil, 26.5 mmol) and benzyl
bromide (3.18 cm3, 27.9 mmol) gave a crude product which was
purified by flash chromatography, eluting with EtOAc, to give
the benzyl ether 51 (5.66 g, 80% based on the epoxide over 2
steps, 86:14 mixture of diastereomers) as an oil, Rf 0.51
(EtOAc); [α]D20 Ϫ26.3 (c 2.85 in CHCl3; 100% ee) (Found: MHϩ,
441.1987. C29H29O2P requires MH, 441.1983); νmax/cmϪ1
(P–Ph) and 1173 (P᎐O); δ (400 MHz; CDCl3) 7.8–7.2 (10 H,
᎐
H
m, Ph2PO), 3.56 (2 H, m, CHOH and OH), 2.28 (2 H, m,
PCH2), 1.86 (1 H, m, PCH2HAHB), 1.65 (1 H, m, PCH2HAHB),
1.45 (2 H, m, CH2Me) and 0.88 (3 H, t, J 7.4, Me); δC (100
MHz; CDCl3) 133–128 (m, Ph2PO), 72.8ϩ (d, 3JPC 9.7, CHOH),
(CHCl ) 1438 (P–Ph) and 1176 (P᎐O); δ (400 MHz; CDCl3)
᎐
3
H
7.8–7.1 (20 H, m, Ph2PO and Ph × 2), 4.33 (1 H, d, J 11.8,
PhCHAHB), 4.22 (1 H, t, J 6.5, CHOBn), 4.09 (d, J 11.8,
PhCHAHB), 2.25 (1 H, m), 2.1–1.9 (2 H, m) and 1.16 (3 H, dd,
2
1
30.1Ϫ, 29.0Ϫ (d, JPC 9.7), 26.3Ϫ (d, JPC 71.0, PCH2) and 10.1ϩ
(Me); m/z 287.1 (20%, Mϩ Ϫ H), 259.1 (80, M Ϫ Et), 215.1 (80,
Ph2POCH2) and 202.1 (100, Ph2POH).
3
J 7.1 and JPH 14.6, Me); δC (100 MHz; CDCl3) 141.8Ϫ (ipso-
Phmin), 141.0Ϫ (ipso-Phmaj), 138.5Ϫ (ipso-Phmin), 138.4Ϫ (ipso-
3
Phmaj), 132–126 (m, Ph2PO and Ph × 2), 79.9ϩ (d, JPC 12.3,
CHOBnmaj), 77.9ϩ (d, 3JPC 12.7, CHOBnmin), 70.4Ϫ (PhCH2min),
70.3Ϫ (PhCH2maj), 38.1Ϫ (min), 37.6Ϫ (maj), 28.5ϩ (d, 1JPC 72.0,
PCH2maj), 28.2ϩ (d, 1JPC 72.3, PCH2min), 13.6ϩ (Memaj) and 11.7ϩ
(Memin); m/z (FAB) 441 (75%, MHϩ), 333.3 (100, M Ϫ BnO).
3-Diphenylphosphinoyl-1-phenylpropan-1-ol 21d
By the same general method, methyldiphenylphosphine oxide
(4.00 g, 18.5 mmol) and styrene oxide (2.29 cm3, 20.0 mmol)
gave a crude product which was purified by flash chrom-
atography, eluting with 7% methanol in EtOAc, to give the
alcohol21 21d (5.67 g, 91%) as needles, mp 139–141 ЊC, spectro-
scopically identical to that obtained previously.
3-Diphenylphosphinoylpropyl benzyl ether 12
3-Diphenylphosphinoylpropan-1-ol 11 (3.50 g, 13.5 mmol) was
dissolved in dry THF (80 cm3), tetra-n-butylammonium iodide
(246 mg, 0.67 mmol) added in one portion, sodium hydride (868
mg, 60% dispersion in oil, 21.7 mmol) added in several portions
and the reaction mixture was stirred until no further gas was
evolved. Benzyl bromide (2.56 cm3, 21.7 mmol) was added
dropwise to the reaction mixture, which was stirred for 16 h,
(R)-1-Diphenylphosphinoylheptan-3-ol 21b
By the same general method, methyldiphenylphosphine oxide
(8.86 g, 41.0 mmol) and the epoxide (R)-26 (4.40 cm3, 36.5
mmol) gave a crude product which was purified by flash
chromatography, eluting with 5% methanol in EtOAc, to give
1972
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

View Article Online
quenched with water (50 cm3), extracted with dichloromethane
(3 × 50 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 benzyl ether 12 (4.05 g, 86%) as needles, mp 64–66 ЊC (from
EtOAc–hexane); Rf 0.20 (EtOAc) (Found: C, 75.3; H, 6.55; P,
8.8%; Mϩ Ϫ Bn, 259.0880. C22H21O2P requires C, 75.4; H, 6.60;
P, 8.8%; M Ϫ Bn, 259.0889); νmax/cmϪ1 (CHCl3) 1437 (P–Ph)
and 2 × Ph), 4.46 (1 H, d, J 11.8, PhCHAHB), 4.42 (1 H, t, J 6.3,
CHOBn), 4.24 (1 H, d, J 11.8, PhCHAHB), 2.45 (1 H, m), 2.25
(1 H, m) and 2.08 (2 H, m); δC (50 MHz; CDCl3) 141.1Ϫ (ipso-
Ph), 138.4Ϫ (ipso-Ph), 132–126ϩ (m, Ph2PO and remaining Ph),
3
80.9Ϫ (d, JPC 14.0, CHOBn), 70.4Ϫ (PhCH2), 29.9Ϫ and 25.7Ϫ
1
(d, JPC 72.4, PCH2); m/z 335.1 (100%, Mϩ Ϫ Bn), 201.0 (50,
Ph2PO) and 91.1 (60, Bn).
and 1171 (P᎐O); δ (400 MHz; CDCl3) 7.74–7.2 (15 H, m,
᎐
H
3-Diphenylphosphinoylpropyl 4-nitrobenzyl ether 14
Ph2PO and Ph), 4.38 (2 H, s, PhCH2), 3.49 (2 H, t, J 6.0,
CH2OBn), 2.36 (2 H, m) and 1.91 (2 H, m); δC (63 MHz;
CDCl3) 138.3Ϫ (ipso-Ph), 133–127 (m, Ph2PO and remaining
By the same general method, 3-diphenylphosphinoylpropan-1-
ol 13 (1.55 g, 5.98 mmol), tetra-n-butylammonium iodide (176
mg, 0.49 mmol), sodium hydride (386 mg, 60% dispersion in oil,
9.7 mmol) and 4-nitrobenzyl bromide (2.06 g, 9.6 mmol) gave a
crude product which was purified by flash chromatography,
eluting with 5% methanol in EtOAc, to give the 4-nitrobenzyl
ether 14 (0.60 g, 26%) as an oil; Rf 0.20 (EtOAc) (Found:
Mϩ Ϫ ArCH2, 259.0890. C22H22NO4P requires M Ϫ ArCH2,
3
Ph), 72.8Ϫ (PhCH2), 70.0Ϫ (d, JPC 14.4, CH2OBn), 26.5Ϫ (d,
1JPC 72.5, PCH2) and 22.0Ϫ; m/z 259.1 (100%, Mϩ Ϫ Bn), 201.0
(70, Ph2PO) and 91.1 (85, Bn).
1-Diphenylphosphinoylpentan-3-yl benzyl ether 31a
By the same general method, 1-diphenylphosphinoylpentan-3-
ol 21a (1.02 g, 3.54 mmol), tetra-n-butylammonium iodide 65
mg, 0.18 mmol), sodium hydride (228 mg, 60% dispersion in oil,
5.7 mmol) and benzyl bromide (0.67 cm3, 5.7 mmol) gave a
crude product which was purified by flash chromatography,
eluting with EtOAc, to give the benzyl ether 31a (1.17 g, 90%) as
an oil, Rf 0.30 (EtOAc) (Found: Mϩ Ϫ Bn, 287.1196. C24H25O2P
requires M Ϫ Bn, 287.1223); νmax/cmϪ1 (CHCl3) 1437 (P–Ph)
259.0889); νmax/cmϪ1 (CHCl ) 1683 (C᎐O), 1521 (NO ), 1423
᎐
3
2
(P–Ph), 1344 (NO ) and 1161 (P᎐O); δ (400 MHz; CDCl ) 8.20
᎐
2
H
3
(2 H, d, J 8.6, Ar), 7.8–7.4 (12 H, m, Ph2PO and remaining Ar),
4.52 (2 H, s, ArCH2), 3.56 (2 H, t, J 6.5, CH2OCH2Ar), 2.5–2.3
(2 H, m, PCH2) and 2.05–1.9 (2 H, m); δC (50 MHz; CDCl3)
155.9ϩ (Ar), 145.9Ϫ (Ar), 133–127ϩ (m, Ph2PO and remaining
Ar), 123.5ϩ, 71.4Ϫ (ArCH2), 70.6Ϫ (d, 3JPC 14.3, CH2OCH2Ar),
1
2
26.3Ϫ (d, JPC 72.3, PCH2) and 21.9Ϫ (d, JPC 3.5, PCH2CH2);
m/z 259.1 (100%, Mϩ Ϫ ArCH2), 215.1 (50, Ph2POCH2) and
201.1 (55, Ph2PO).
and 1171 (P᎐O); δ (400 MHz; CDCl ) 7.8–7.1 (15 H, m, Ph PO
᎐
H
3
2
and Ph), 4.42 (2 H, AB q, J 11.7, PhCH2), 3.39 (1 H, dq, J 4.3
and 6.1, CHOBn), 2.38 (1 H, dddd, J 4.8, 10.5, 11.9 and 15.4,
PCHAHB), 2.24 (1 H, dddd, J 4.3, 11.9, 12.8 and 14.0,
PCHAHB), 2.0–1.4 (4 H, m) and 0.87 (3 H, t, J 7.5, Me); δC (63
MHz; CDCl3) 144.7Ϫ (ipso-Ph), 135–128 (m, Ph2PO and
1-Diphenylphosphinoylpentan-3-yl methoxymethyl ether 32
Methoxymethyl chloride (1.3 cm3, 17.2 mmol) and diisopropyl-
ethylamine (2.45 cm3, 14.0 mmol) were added dropwise to a
solution of 1-diphenylphosphinoylpentan-3-ol 21a (1.04 g, 3.6
mmol) in dry dichloromethane (40 cm3) at 0 ЊC. The solution
was stirred for 1 h, allowed to warm to room temperature,
stirred for a further 15 h, quenched with saturated sodium
carbonate (50 cm3), extracted with dichloromethane (3 × 50
cm3), dried (MgSO4) and evaporated under reduced pressure to
give a crude product which was purified by flash chrom-
atography, eluting with 5% methanol in EtOAc, to give the
methoxymethyl ether 32 (1.20 g, 100%) as an oil; Rf 0.22
(EtOAc) (Found: Mϩ Ϫ Bn, 333.1622. C19H25O3P requires
M Ϫ Bn, 333.1622); νmax/cmϪ1 (CHCl3) 1437 (P–Ph) and 1200
3
remaining Ph), 80.7ϩ (d, JPC 13.6, CHOBn), 71.7Ϫ (CH2Ph),
27.0Ϫ, 25.8Ϫ (d, 1JPC 72.5, PCH2), 25.6Ϫ (d, 2JPC 3.0, PCH2CH2)
and 10.6ϩ (Me); m/z 287.1 (100%, Mϩ Ϫ Bn), 201.0 (70,
Ph2PO), 105 (90) and 91.1 (90, Bn).
(R)-1-Diphenylphosphinoylheptan-3-yl benzyl ether 31b
By the same general method, (R)-1-diphenylphosphinoyl-
heptan-3-ol 21b (7.73 g, 24.5 mmol), tetra-n-butylammonium
iodide (200 mg, 0.54 mmol), sodium hydride (1.58 mg, 60% dis-
persion in oil, 39.5 mmol) and benzyl bromide (4.65 cm3, 39.3
mmol) gave a crude product which was purified by flash
chromatography, eluting with 4:1 EtOAc–hexane, to give the
benzyl ether 31b (9.23 g, 93%) as an oil, Rf 0.41 (EtOAc); [α]D20
ϩ4.3 (c 1.93 in CHCl3; 84% ee) (Found: Mϩ Ϫ Bn, 349.1355.
C26H29O2P requires M Ϫ Bn, 349.1355); νmax/cmϪ1 (CHCl3)
1438 (P–Ph) and 1200 (P᎐O); δ (400 MHz; CDCl3) 7.8–7.25
(P᎐O); δ (400 MHz; CDCl3) 7.8–7.25 (10 H, m, Ph2PO), 4.57
᎐
H
(2 H, AB q, J 6.7, OCH2OMe), 3.51 (1 H, m, CHOMOM), 3.31
(3 H, OMe), 2.49 (1 H, m, PCHAHB), 2.27 (1 H, m, PCHAHB),
1.89 (1 H, m), 1.73 (1 H, m), 1.52 (2 H, m) and 0.84 (3 H, t,
J 7.4, Me); δC (50 MHz; CDCl3) 134–128ϩ (m, Ph2PO), 95.3Ϫ
(OCH2O), 78.3ϩ (d, 3JPC 14.7, CHOMOM), 55.4ϩ (OMe), 25.8Ϫ
᎐
H
(15 H, m, Ph2PO and Ph), 4.44 (1 H, d, J 11.7, PhCHAHB), 4.37
(1 H, d, J 11.7, PhCHAHB), 3.44 (1 H, quin, J 5.8, CHOBn),
2.5–1.1 (10 H, m) and 0.85 (3 H, t, J 6.7, Me); δC (63 MHz;
CDCl3) 138.6Ϫ (ipso-Ph), 134–127 (m, Ph2PO and remaining
Ph), 78.3ϩ (d, 3JPC 13.8, CHOBn), 70.6Ϫ (CH2Ph), 32.9Ϫ, 27.4Ϫ,
1
(d, JPC 68.4, PCH2), 25.6Ϫ, 24.2Ϫ and 9.4ϩ; m/z 333.2 (40%,
Mϩ), 287.1 (100, M Ϫ MeOCH2) and 201.0 (80, Ph2PO).
(1R*,2S*)-2-Diphenylphosphinoyl-1-(4-methoxyphenyl)hexan-1-
ol 17a
1
24.9Ϫ, 24.7Ϫ (d, JPC 73.0, PCH2) and 13.9ϩ (Me); m/z 287.1
(100%, Mϩ Ϫ Bn), 201.0 (70, Ph2PO), 105 (90) and 91.1 (90,
n-Butyllithium (9.1 cm3 of a 1.3 mol dmϪ3 solution in hexanes,
11.8 mmol) was added dropwise to pentyldiphenylphosphine
oxide (7.27 g, 11.0 mmol) in dry THF (30 cm3) at Ϫ78 ЊC. After
15 min, freshly distilled p-anisaldehyde (3.7 cm3, 30.5 mmol)
was added dropwise, the reaction was stirred for 30 min at
Ϫ78 ЊC, warmed gradually to room temperature over 1 h,
quenched with water (30 cm3), extracted with dichloromethane
(3 × 30 cm3), dried (MgSO4) and evaporated under reduced
pressure to give a crude product. Analysis of the crude product
by 400 MHz 1H NMR showed it to consist of a 72:28 ratio of
17a:18a. Purification by flash chromatography, eluting with
1:1 EtOAc–hexane to give the alcohol 17a (7.70 g, 71%) as
needles, mp 141–142 ЊC (from EtOAc–hexane); Rf 0.48 (EtOAc)
(Found: C, 73.5; H, 7.25; P, 7.7%; Mϩ, 408.1845. C25H29O3P
requires C, 73.5; H, 7.60; P, 7.2%; M, 408.1854); νmax/cmϪ1
Bn).
3-Diphenylphosphinoyl-1-phenylpropyl benzyl ether 31d
By the same general method, 3-diphenylphosphinoyl-1-
phenylpropan-1-ol 21d (1.29 g, 3.85 mmol), tetra-n-
butylammonium iodide (60 mg, 0.19 mmol), sodium hydride
(247 mg, 60% dispersion in oil, 6.2 mmol) and benzyl bromide
(0.73 cm3, 6.2 mmol) gave a crude product which was purified
by flash chromatography, eluting with EtOAc, to give the benzyl
ether 31d (1.44 g, 88%) as needles, mp 139–141 ЊC (from
EtOAc–hexane); Rf 0.46 (EtOAc) (Found: C, 78.9; H, 6.35; P,
7.4%; Mϩ Ϫ Bn, 335.1200. C28H27O2P requires C, 78.9; H, 6.40;
P, 7.3%; M Ϫ Bn, 335.1201); νmax/cmϪ1 (CHCl3) 1437 (P–Ph)
and 1173 (P᎐O); δ (400 MHz; CDCl ) 7.7–7.2 (20 H, m, Ph PO
᎐
H
3
2
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1973

View Article Online
(CHCl ) 3382 (OH), 1439 (P–Ph) and 1163 (P᎐O); δ (200
C᎐CH H ), 5.93 (1 H, br s, C᎐CH H ), 4.63 (s, OH), 4.38 (1 H,
᎐ ᎐
A B A B
᎐
3
H
MHz; CDCl3) 8.0–7.3 (10 H, m, Ph2PO), 7.23 (2 H, br d, J 8.6,
br d, 3JPH 10.4, CHOH), 2.29 (1 H, q, J 6.9, PCH), 1.9–0.7 (6 H,
3
Ar), 6.81 (2 H, br d, J 8.7, Ar), 5.22 (1 H, br d, JPH 9.1,
m), 1.61 (3 H, s, Me) and 0.62 (3 H, t, J 6.7, Me); δC (63 MHz;
3
CHOH), 4.83 (1 H, br s, OH), 3.74 (3 H, s, OMe), 2.36 (1 H, br
q, J 5.1, PCH), 2.0–0.6 (6 H, m) and 0.45 (3 H, t, J 7.4, Me); δC
(50 MHz; CDCl3) 158.4Ϫ (ipso-Ar), 134.5–126 (m, Ph2PO and
remaining Ar), 113.6ϩ (Ar), 70.4ϩ (CHOH), 55.1ϩ (OMe), 44.6ϩ
CDCl3) 143.0Ϫ (d, JPC 13.8, C᎐CH ), 133–128 (m, Ph PO),
᎐
2
2
111.8Ϫ (C᎐CH ), 71.9ϩ (d, 2JPC 2.3, CHOH), 39.5ϩ (d, 1JPC 68.6,
᎐
2
PCH), 32.4Ϫ (d, JPC 5.1), 22.6Ϫ, 20.7Ϫ, 19.8ϩ (Me) and 13.5ϩ
2
(Me); m/z (FAB) 343.2 (20%, MHϩ), 229.1 (100) and 202.1 (60,
Ph2POH).
1
2
(d, JPC 66, PCH), 31.8Ϫ (d, JPC 5.6), 22.2Ϫ, 20.5Ϫ and 13.2ϩ
(Me); m/z 408.2 (20%, Mϩ), 229.1 (95) and 135 (100, ArCHO).
Also obtained was the alcohol 18a (2.86 g, 26%) as needles,
mp 174–176 ЊC (from EtOAc–hexane); Rf 0.23 (EtOAc)
Also obtained was the alcohol 18c (0.93 g, 34%) as an oil, Rf
0.38 (EtOAc) (Found: Mϩ, 342.1740. C27H27O2P requires M,
342.1749); νmax/cmϪ1 (CHCl ) 3357 (br s, OH), 1653 (C᎐C),
᎐
3
(Found: Mϩ, 408.1853. C25H29O3P requires M, 408.1854); νmax
/
1438 (P–Ph) and 1149 (P᎐O); δ (400 MHz; CDCl3) 7.9–7.35
᎐
H
cmϪ1 (CHCl ) 3363 (OH), 1438 (P–Ph) and 1173 (P᎐O); δ (200
(10 H, m, Ph PO), 5.05 (d, J 4.8, OH), 4.96 (1 H, br s, C᎐CH -
᎐
᎐
3
H
2
A
MHz; CDCl3) 7.8–7.2 (10 H, m, Ph2PO), 7.17 (2 H, br d, J 8.6,
Ar), 6.66 (2 H, br d, J 8.6, Ar), 5.54 (1 H, d, J 5.1, OH), 4.98 (1
H, td, J 5.5 and 3JPH 16.7, OH), 3.68 (3 H, s, OMe), 2.66 (1 H,
dq, J 4.0 and 7.1, PCH), 1.6–0.8 (6 H, m) and 0.58 (3 H, t, J 6.7,
Me); δC (50 MHz; CDCl3) 158.7Ϫ (ipso-Ar), 135–127 (m, Ph2PO
H ), 4.74 (1 H, br s, C᎐CH H ), 4.37 (1 H, ddd, J 5.1, 7.0 and
᎐
B A B
3JPH 15.5, CHOH), 2.57 (1 H, m, PCH), 2.2–0.8 (6 H, m), 1.66
(3 H, s, Me) and 0.77 (3 H, t, J 7.3, Me); δC (63 MHz; CDCl3)
3
144.4Ϫ (d, JPC 8.7, C᎐CH ), 134–128 (m, Ph PO), 113.9Ϫ
᎐
2
2
(C᎐CH ), 76.5ϩ (d, 2JPC 4.0, CHOH), 39.1ϩ (d, 1JPC 67.6, PCH),
᎐
2
and remaining Ar), 113.2ϩ (Ar), 70.4ϩ (d, JPC 3.1, CHOH),
30.5Ϫ (d, 2JPC 8.3), 26.5Ϫ, 22.6Ϫ, 17.6ϩ (Me) and 13.6ϩ (Me); m/z
2
1
2
55.0ϩ (OMe), 44.6ϩ (d, JPC 66.5, PCH), 31.8Ϫ (d, JPC 9.1),
26.2Ϫ, 22.2Ϫ and 13.4ϩ (Me); m/z 408.2 (40%, Mϩ), 229.1 (100)
and 202.1 (60, Ph2POH).
342.2 (10%, Mϩ), 229.1 (100) and 202.1 (60, Ph2POH).
(1R*,2S*)-4-Benzyloxy-2-diphenylphosphinoyl-1-(4-methoxy-
phenyl)butan-1-ol 17d
(2E,4R*,5S*)-5-Diphenylphosphinoyl-3-methylnon-2-en-4-ol 17b
By the same general method, 3-diphenylphosphinoylpropyl
benzyl ether 12 (3.61 g, 10.3 mmol) and p-anisaldehyde (1.43
cm3, 11.4 mmol) in THF gave a crude product. Analysis of the
crude product by 400 MHz 1H NMR showed it to consist of a
80:20 ratio of 17d:18d. Purification by flash chromatography
eluting with 1:1 EtOAc–hexane gave the alcohol 17d (3.68 g,
73%) as an oil, Rf 0.53 (EtOAc) (Found: Mϩ, 468.1972.
C30H31O4P requires M, 486.1959); νmax/cmϪ1 (CHCl3) 3440
(OH) and 1438 (P–Ph); δH (400 MHz; CDCl3) 8.0–7.05 (17 H,
m, Ph2PO, Ph and remaining Ar), 6.85 (2 H, br d, J 8.7, Ar),
5.24 (1 H, d, J 9.0, CHOH), 4.88 (1 H, s, OH), 4.00 (2 H, AB q,
J 13.0, PhCH2), 3.77 (3 H, OMe), 2.86 (2 H, m, CH2OBn), 2.63
(1 H, dt, J 5.5 and 9.2, PCH) and 2.4–1.8 (2 H, m); δC (100
MHz; CDCl3) 158.6Ϫ (ipso-Ar), 138.4Ϫ (ipso-Ph), 135–126 (m,
Ph2PO and remaining Ar and Ph), 113.5ϩ (Ar), 72.1Ϫ (PhCH2),
By the same general method, pentyldiphenylphosphine oxide
(1.97 g, 7.3 mmol) and trans-2-methylbut-2-enal (0.77 cm3, 8.0
mmol) in THF gave a crude product. Analysis of the crude
product by 400 MHz 1H NMR showed it to consist of a 51:49
ratio of 17b:18b. Purification by flash chromatography eluting
with 3:2 EtOAc–hexane gave the alcohol 17b (1.22 g, 47%) as
needles, mp 131–132 ЊC (from EtOAc–hexane); Rf 0.51 (EtOAc)
(Found: C, 74.4; H, 8.35; P, 8.8%; Mϩ, 356.1889. C28H29O2P
requires C, 74.1; H, 8.35; P, 8.7%; M, 356.1905); νmax/cmϪ1
(CHCl ) 3367 (br s, OH), 1673 (C᎐C), 1437 (P–Ph) and 1164
᎐
3
(P᎐O); δ (400 MHz; CDCl3) 8.0–7.35 (10 H, m, Ph2PO), 5.73
᎐
H
(1 H, q, J 6.9, C᎐CH), 4.54 (s, OH), 4.36 (1 H, br d, 3JPH 10.0,
᎐
CHOH), 2.28 (1 H, q, J 5.2, PCH), 1.78 (2 H, m), 1.58 (3 H, d,
J 7.0, Me), 1.56–0.8 (4 H, m), 1.48 (3 H, s, Me) and 0.62 (3 H, t,
J 7.0, Me); δC (63 MHz; CDCl3) 133–128 (m, Ph2PO and
3
69.9ϩ (CHOH), 68.3Ϫ (d, JPC 7.4, CH2OBn), 55.1ϩ (OMe),
2
C᎐CH), 119.9ϩ (C᎐CH), 72.4ϩ (d, JPC 2.4, CHOH), 39.7ϩ (d,
40.2ϩ (d, 1JPC 67.5, PCH) and 21.2Ϫ; m/z 486.2 (30%, Mϩ), 377.1
(90), 135.0 (95, CH2CH2OBn) and 77.0 (100, Ph).
᎐
᎐
1JPC 67.9, PCH), 32.5Ϫ (d, JPC 5.7, PCHCH2), 22.6Ϫ, 21.1Ϫ,
2
14.1ϩ (d, JPC 2.4, CH᎐CMe), 13.5ϩ (Me) and 13.1ϩ (Me); m/z
4
᎐
356.2 (20%, Mϩ), 229.1 (100) and 202.1 (50, Ph2POH).
(1R*,2S*)-4-Benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)butan-
1-ol 17e
Also obtained was the alcohol 18b (1.15 g, 45%) as an oil, Rf
0.37 (EtOAc) (Found: Mϩ, 356.1910. C28H29O2P requires M,
356.1905); νmax/cmϪ1 (CHCl ) 3430 (br s, OH), 1670 (C᎐C),
By the same general method, 3-diphenylphosphinoylpropyl
benzyl ether 12 (1.08 g, 3.09 mmol) and furfural (0.28 cm3, 3.40
mmol) in THF gave a crude product. Analysis of the crude
product by 400 MHz 1H NMR showed it to consist of a 82:18
ratio of 17e:18e. Purification by flash chromatography eluting
with 4:1 EtOAc–hexane gave the alcohol 17e (1.13 g, 82%) as an
oil, Rf 0.44 (EtOAc) (Found: Mϩ, 446.1651. C27H27O4P requires
M, 446.1647); νmax/cmϪ1 (CHCl3) 3376 (OH) and 1148 (P–Ph);
δH (400 MHz; CDCl3) 7.93–7.21 (16 H, m, Ph2PO, Ph and
remaining Ar), 6.34 (1 H, d, J 3.2, Ar), 6.29 (1 H, dd, J 1.8 and
3.1, Ar), 5.26 (1 H, d, J 9.4, CHOH), 4.83 (1 H, br s, OH), 4.17
(2 H, AB q, J 11.9, PhCH2), 3.15–2.95 (2 H, m), 2.73 (1 H, dt,
J 5.0 and 8.8, PCH), 2.22 (1H, m) and 1.93 (1 H, m); δC (100
᎐
3
1437 (P–Ph) and 1148 (P᎐O); δ (400 MHz; CDCl ) 7.9–7.3 (10
᎐
H
3
H, m, Ph PO), 5.48 (1 H, q, J 6.7, C᎐CH), 5.09 (d, J 5.0, OH),
᎐
2
4.28 (1 H, td, J 5.6 and 3JPH 15.6, CHOH), 2.54 (1 H, m, PCH),
1.7–0.8 (6 H, m), 1.42 (3 H, s, Me), 1.36 (3 H, d, J 7.3) and 0.73
3
(3 H, t, J 7.3, Me); δC (63 MHz; CDCl3) 135.0 (d, JPC 8.4,
CH᎐C), 134–128 (m, Ph PO), 122.7ϩ (C᎐CH), 77.7ϩ (d, JPC
2
᎐
᎐
2
1
3.9, CHOH), 39.8ϩ (d, JPC 67.7, PCH), 30.5Ϫ (d, JPC 9.1,
PCHCH2), 26.5Ϫ, 22.6Ϫ, 13.7ϩ (Me), 12.9ϩ (Me) and 12.2ϩ
(Me); m/z 356.2 (25%, Mϩ), 229.1 (100) and 202.1 (55,
Ph2POH).
2
(3R*,4S*)-4-Diphenylphosphinoyl-2-methyloct-1-en-3-ol 17c
3
MHz; CDCl3) 154.2Ϫ (d, JPC 14.2, ipso-Ar), 141.0Ϫ (ipso-Ph),
133–127 (m, Ph2PO and remaining Ar and Ph), 110.7ϩ, 106.6ϩ
By the same general method, pentyldiphenylphosphine oxide
(2.13 g, 7.9 mmol) and methacrolein (0.71 cm3, 8.6 mmol) in
THF gave a crude product. Analysis of the crude product by
3
(Ar × 2), 72.5Ϫ (PhCH2), 68.0ϩ (d, JPC 8.1, CHOBn), 66.8ϩ
(CHOH), 37.8ϩ (d, 1JPC 69.4, PCH) and 22.2Ϫ; m/z 446.2 (90%,
1
Mϩ), 202.1 (100, Ph2POH) and 91.1 (95, Bn).
400 MHz H NMR showed it to consist of a 59:41 ratio of
17c:18c. Purification by flash chromatography eluting with 3:2
EtOAc–hexane gave the alcohol 17c (1.52 g, 56%) as needles, mp
129–130 ЊC (from EtOAc–hexane); Rf 0.50 (EtOAc) (Found: C,
73.5; H, 8.00; P, 9.2%; MHϩ, 343.1827. C27H27O2P requires C,
73.7; H,7.95; P, 9.1%; MH, 343.1824); νmax/cmϪ1 (CHCl3) 3382
(3R*,4S*)-6-Benzyloxy-4-diphenylphosphinoyl-2-methylhex-1-
en-3-ol 17f
By the same general method, 3-diphenylphosphinoylpropyl
benzyl ether 12 (989 mg, 2.83 mmol) and methacrolein (0.25
cm3, 3.1 mmol) in THF gave a crude product. Analysis of the
(br s, OH), 1653 (C᎐C), 1438 (P–Ph) and 1164 (P᎐O); δ (400
᎐
᎐
H
MHz; CDCl3) 8.0–7.4 (10 H, m, Ph2PO), 5.21 (1 H, br s,
1974 J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

View Article Online
crude product by 400 MHz 1H NMR showed it to consist of a
80:20 ratio of 17f:18f. Purification by flash chromatography
eluting with 1:1 EtOAc–hexane gave the alcohol 17f (722 mg,
63%) as an oil, Rf 0.46 (EtOAc) (Found: MHϩ, 421.1933.
C26H29O3P requires MH, 421.1932); νmax/cmϪ1 (CHCl3) 3387 (br
474.1959); νmax/cmϪ1 (CHCl3) 3359 (OH), 1438 (P–Ph) and 1188
(P᎐O); δ (400 MHz; CDCl ) 7.8–7.7 (2 H, m), 7.55–7.25 (14 H,
᎐
H
3
m, Ph2PO, Ph and remaining Ar), 6.38 (1 H, dd, J 0.9 and 3.1,
Ar), 6.27 (1 H, dd, J 1.8 and 3.2, Ar), 5.22 (1 H, br d, J 9.9,
CHOH), 4.76 (1 H, br s, OH), 4.31 (1 H, d, J 12.1, PhCHAHB),
4.05 (1 H, d, J 12.1, PhCHAHB), 2.86 (1 H, m), 2.32 (1 H, m),
2.05 (1 H, m), 1.80 (1 H, m), 1.5–1.3 (2 H, m) and 0.49 (3 H, t,
J 7.5, Me); δC (100 MHz; CDCl3) 153.9Ϫ (d, 3JPC 13.9, ipso-Ar),
141.1ϩ (Ar), 138.9Ϫ (ipso-Ph), 132–127 (m, Ph2PO and Ph),
110.4ϩ (Ar), 106.9ϩ (Ar), 77.5ϩ, 69.7Ϫ (PhCH2), 67.5ϩ, 38.0ϩ (d,
1JPC 68.6, PCH), 26.2Ϫ, 25.6Ϫ and 9.0ϩ (Me); m/z 474.2 (10%,
Mϩ), 229.1 (90), 201.1 (100, Ph2PO) and 91.1 (90, Bn).
s, OH), 1654 (C᎐C), 1438 (P–Ph) and 1164 (P᎐O); δ (400 MHz;
᎐
᎐
H
CDCl ) 7.9–7.2 (15 H, m, Ph PO and Ph), 5.24 (br s, C᎐CH -
᎐
3
2
A
H ), 4.94 (br s, C᎐CH H ), 4.65 (1 H, s, OH), 4.40 (1 H, d,
᎐
B
A
B
J 10.3, CHOH), 4.35 (1 H, d, J 12.0, PhCHAHB), 4.23 (1 H, d,
J 12.0, PhCHAHB), 3.31 (1 H, m), 3.05 (1 H, m), 2.78 (1 H, br q,
J 5.7, PCH), 2.3–1.9 (2 H, m) and 1.63 (3 H, s, Me); δC (50
3
MHz; CDCl3) 143.2Ϫ (d, JPC 13.6, CH ᎐C Me), 138.5Ϫ (ipso-
᎐
2
Ph), 131–126 (m, Ph2PO and remaining Ph), 111.7Ϫ (CH ᎐C
Also obtained was the alcohol 36a (23 mg, 9%, 85:15 ratio of
diastereomers) as an oil, retention time 16.5 min; Rf 0.51
(EtOAc) (Found: Mϩ, 528.2423. C29H31O4P requires M,
528.2429); νmax/cmϪ1 (CHCl3) 3354 (OH) and 1439 (P–Ph); δH
(400 MHz; CDCl3) 7.8–7.7 (4 H, m), 7.55–7.3 (12 H, m, Ph2PO,
Ph and remaining Ar), 6.35 (2 H, m, Ar), 5.24 (1 H, br d, J 8.7,
CHOH), 5.01 (1 H, br s, OH), 4.44 (1 H, d, J 11.0, PhCHAHB),
4.02 (d, J 11.0, PhCHAHB), 3.13 (1 H, t, J 8.5, PCH), 2.9–2.75
(2 H, m), 1.7–1.2 (3 H, m) and 0.63 (3 H, t, J 7.5, Me); δC (100
MHz; CDCl3) 154.4Ϫ (d, 3JPC 14.6, ipso-Ar), 140.7ϩ (Ar), 139.2Ϫ
(ipso-Ph), 133–127 (m, Ph2PO and remaining Ph), 110.9ϩ (Ar),
᎐
2
Me), 72.4Ϫ (PhCH2), 71.6ϩ (CHOH), 68.4Ϫ (d, JPC 6.2,
2
CHOBn), 35.0ϩ (d, 1JPC 69.8, PCH), 21.4Ϫ and 19.5ϩ (Me); m/z
(FAB) 421.2 (25%, MHϩ), 244.1 (90) and 229.1 (100).
(1S,2R,4R)- and (1R,2S,4R)-4-Benzyloxy-2-diphenylphosphin-
oyl-1-(4-methoxyphenyl)octan-1-ol 35d and 36d
By the same general method, (R)-1-diphenylphosphinoyl-
heptan-3-yl benzyl ether 31b (7.58 g, 18.8 mmol) and p-
anisaldehyde (2.52 cm3, 20.7 mmol) in THF gave a crude
1
product. Analysis of the crude product by 400 MHz H NMR
3
106.6ϩ (Ar), 79.4ϩ (d, JPC 68.6, CHOBn), 71.6Ϫ (PhCH2),
showed it to be an 62:38 ratio of 35d:36d. Purification by flash
chromatography eluting with 3:2 EtOAc–hexane gave the
alcohols 35d and 36d (6.16 g, 60%, 61:39 ratio of diastereo-
mers) as an oil. Further purification by HPLC eluting
with chloroform gave the alcohol 35d (2.34 g, 23%) as an oil,
retention time 19.5 min; Rf 0.62 (EtOAc); [α]D20 ϩ22.8 (c 0.2 in
CHCl3; 84% ee) (Found: Mϩ, 542.2581. C34H39O4P requires M,
542.2586); νmax/cmϪ1 (CHCl3) 3431 (OH) and 1438 (P–Ph); δH
(400 MHz; CDCl3) 7.9–7.1 (17 H, m, Ph2PO, Ph and remaining
Ar), 6.83 (2 H, d, J 8.8, Ar), 5.19 (1 H, br d, J 9.9, CHOH), 4.80
(1 H, s, OH), 4.10 (1 H, d, J 12.1, PhCHAHB), 3.93 (1 H, d,
J 12.1, PhCHAHB), 3.77 (3 H, OMe), 2.64 (1 H, m), 2.33 (1 H,
m), 2.1–0.9 (8 H, m) and 0.75 (3 H, t, J 6.6, Me); δC (100 MHz;
CDCl3) 158.8Ϫ (ipso-Ar), 139.2Ϫ (ipso-Ph), 134–126 (m, Ph2PO
66.5ϩ (CHOH), 38.0ϩ (d, 1JPC 68.5, PCH), 26.2Ϫ, 26.1Ϫ and 8.8ϩ
(Me); m/z 428.2 (55%, Mϩ), 201.1 (95, Ph2PO) and 91.1 (100,
Bn).
(1S,2R,4R)- and (1R,2S,4R)-4-Benzyloxy-2-diphenyl-
phosphinoyl-1-(2-furyl)octan-1-ol 35b and 36b
By the same general method, (R)-1-diphenylphosphinoyl-
heptan-3-yl benzyl ether 31b (6.34 g, 15.6 mmol) and furfural
(1.42 cm3, 17.2 mmol) in THF gave a crude product. Analysis
1
of the crude product by 400 MHz H NMR showed it to be a
75:25 ratio of 35b:36b. Purification by flash chromatography
eluting with 2:1 EtOAc–hexane gave the alcohols 35b and 36b
(4.72 g, 61%, 82:18 ratio of diastereomers) as an oil. Further
purification by HPLC eluting with chloroform gave the alcohol
35b (2.54 mg, 33%) as an oil, retention time 15 min; Rf 0.56
(EtOAc); [α]D20 ϩ23.0 (c 0.80 in CHCl3; 84% ee) (Found: MHϩ,
503.2394. C31H35O4P requires MH, 503.2351); νmax/cmϪ1
(CHCl3) 3358 (OH) and 1438 (P–Ph); δH (400 MHz; CDCl3)
7.77 (2 H, ddd, J 1.4, 7.7 and 9.5), 7.6–7.25 (14 H, m, Ph2PO, Ph
and remaining Ar), 6.38 (1 H, br d, J 3.3, Ar), 6.28 (1 H, dd,
J 1.8 and 3.2, Ar), 5.24 (1 H, br d, J 10.2, CHOH), 4.82 (1 H, d,
J 1.8, OH), 4.30 (1 H, d, J 12.1, PhCHAHB), 4.09 (1 H, d, J 12.1,
PhCHAHB), 2.88 (1 H, m, PCH), 2.43 (1 H, m, CHOBn), 2.12
3
and remaining Ph and Ar), 113.5ϩ (Ar), 76.6ϩ (d, JPC 3.6,
PhCHOBn), 71.0ϩ (CHOH), 69.2Ϫ (PhCH2), 55.2ϩ (OMe),
1
40.7ϩ (d, JPC 67.5, PCH), 33.1Ϫ, 27.1Ϫ, 25.9Ϫ, 22.7Ϫ and 14.0ϩ
(Me); m/z 542.3 (45%, Mϩ), 135.0 (90) and 91.1 (100, Bn).
Also obtained was the alcohol 36d (1.71 g, 18%) as an oil,
retention time 17 min; Rf 0.62 (EtOAc); [α]D20 Ϫ14.6 (c 0.56 in
CHCl3; 84% ee) (Found: Mϩ, 542.2581. C34H39O4P requires M,
542.2586); νmax/cmϪ1 (CHCl3) 3398 (OH) and 1438 (P–Ph); δH
(400 MHz; CDCl3) 7.9–7.2 (15 H, m, Ph2PO and Ph), 7.14 (2 H,
d, J 8.7, Ar), 6.82 (2 H, d, J 8.7, Ar), 5.17 (1 H, br d, J 8.8,
CHOH), 4.94 (1 H, s, OH), 4.24 (1 H, d, J 11.1, PhCHAHB),
3.81 (3 H, OMe), 3.69 (1 H, d, J 11.1, PhCHAHB), 2.84 (1 H, t,
J 7.6, PCH), 2.3–2.15 (2 H, m), 1.55 (1 H, m), 1.3–0.83 (6 H, m)
and 0.77 (3 H, t, J 7.2, Me); δC (100 MHz; CDCl3) 158.7Ϫ (ipso-
Ar), 139.3Ϫ (ipso-Ph), 135–126 (m, Ph2PO and remaining Ph
3
(1 H, dddd, J 3.9, 5.3, 13.2 and JPH 22.0, PCHCHAHB), 1.95
(1 H, dddd, J 4.3, 6.5, 15.3 and 3JPH 17.7, PCHCHAHB), 1.8–0.8
(6 H, m) and 0.76 (3 H, t, J 7.3, Me); δC (100 MHz; CDCl3)
3
153.9Ϫ (d, JPC 13.8, ipso-Ar), 141.0ϩ (Ar), 138.9Ϫ (ipso-Ph),
132–127 (m, Ph2PO and Ph), 110.3ϩ (Ar), 106.8ϩ (Ar), 77.3ϩ (d,
3JPC 4.1, CHOBn), 69.6Ϫ (PhCH2), 67.4ϩ (CHOH), 38.0ϩ (d,
1JPC 68.6, PCH), 32.8Ϫ, 26.9Ϫ, 26.7Ϫ, 22.5Ϫ and 13.9ϩ (Me); m/z
(FAB) 503.2 (10%, MHϩ), 229.1 (80), 202.1 (75, Ph2POH) and
91.1 (100, Bn).
3
and Ar), 113.6ϩ (Ar), 78.6ϩ (d, JPC 9.1, PhCHOBn), 71.2Ϫ
1
(PhCH2), 69.5ϩ (CHOH), 55.3ϩ (OMe), 40.6ϩ (d, JPC 67.4,
PCH), 33.4Ϫ, 26.8Ϫ, 26.0Ϫ, 22.8Ϫ and 13.9ϩ (Me); m/z 542.3
(55%, Mϩ), 201.0 (95, Ph2PO) and 91.0 (100, Bn).
Also obtained was alcohol 36b (0.40 g, 5%) as an oil,
retention time 13 min; Rf 0.56 (EtOAc); [α]D20 0.0 (c 1.81 in
CHCl3; 84% ee) (Found: MHϩ, 503.2392. C31H35O4P requires
M, 503.2351); νmax/cmϪ1 (CHCl ) 3354 (C᎐O) and 1439 (P–Ph);
(1R*,2S*,4S*)- and (1R*,2S*,4R*)-4-Benzyloxy-2-diphenyl-
phosphinoyl-1-(2-furyl)hexan-1-ol 35a and 36a
By the same general method, 1-diphenylphosphinoylpentan-3-
yl benzyl ether 31a (216 mg, 0.57 mmol) and furfural (55 µl,
0.66 mmol) in THF gave a crude product. Analysis of the crude
᎐
3
δH (400 MHz; CDCl3) 7.85–7.2 (16 H, m, Ph2PO, Ph and
remaining Ar), 6.34 (2 H, m, Ar), 5.21 (1 H, d, J 9.5, OH), 5.00
(1 H, m, CHOH), 4.44 (1 H, d, J 10.9, PhCHAHB), 4.04 (1 H, d,
J 10.9, PhCHAHB), 3.12 (1 H, t, J 8.5, PCH), 2.30 (1 H, m,
CHOBn), 2.21 (1 H, m), 1.7–0.8 (7 H, m) and 0.82 (3 H, t, J 7.3,
1
product by 400 MHz H NMR showed it to be a 73:18:5:5
ratio of diastereomers. Purification by flash chromatography
eluting with 2:1 EtOAc–hexane gave the alcohols 35a and 36a
(171 mg, 64%, 78:22 ratio of diastereomers) as an oil. Further
purification by HPLC eluting with chloroform gave the alcohol
35a (95 mg, 36%) as an oil, retention time 18.5 min; Rf 0.51
(EtOAc) (Found: Mϩ, 474.1945. C29H31O4P requires M,
3
Me); δC (100 MHz; CDCl3) 154.5Ϫ (d, JPC 14.4, ipso-Ar),
140.6Ϫ (ipso-Ph), 133–127 (m, Ph2PO and remaining Ph and
Ar), 110.9ϩ (Ar), 106.6ϩ (Ar), 78.4ϩ (d, 3JPC 9.4, CHOBn), 71.6Ϫ
1
(PhCH2), 66.5ϩ (CHOH), 38.0ϩ (d, JPC 68.7, PCH), 33.5Ϫ,
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1975

View Article Online
27.0Ϫ, 26.8Ϫ, 22.7Ϫ and 14.0ϩ (Me); m/z 503.2 (50%, MHϩ) and
202.1 (100, Ph2POH).
Also obtained was a mixture of 35b and 36b (1.30 g, 17%,
2-enal (15 µl, 0.14 mmol) in THF gave a crude product which
was purified by flash chromatography eluting with 3:2 EtOAc–
hexane to give the alcohols 35e and 36e (10 mg, 19%, 62:38
mixture of diastereomers) as an oil, Rf 0.53 (EtOAc) (Found:
Mϩ, 462.2328. C29H37O3P requires M, 462.2324); νmax/cmϪ1
73:27 mixture of diastereomers).
(CHCl ) 3362 (br OH), 1438 (P–Ph) and 1161 (P᎐O); δ (400
᎐
(1S,2R,4S)- and (1R,2S,4S)-4-Benzyloxy-4-cyclohexyl-2-
diphenylphosphinoyl-1-(2-furyl)butan-1-ol 35c and 36c
3
H
MHz; CDCl3) 7.8–7.1 (15 H, m, Ph2PO and Ph), 5.73 (1 H, q,
J 6.9, MeCH᎐Cmaj), 5.67 (1 H, q, J 6.9, MeCH᎐Cmin), 4.51 (1 H,
᎐
᎐
d, J 11.1 PhCHAHBmaj), 4.45 (1 H, d, J 12.0, PhCHAHBmin), 4.35
(1 H, br d, J 10.9, CHOHmin), 4.31 (1 H, br d, J 10.5, CHO-
Hmaj), 4.19 (1 H, d, J 11.1, PhCHAHBmaj), 4.05 (1 H, d, J 12.0,
PhCHAHBmin), 3.16 (1 H, m, CHOBnmaj), 2.77 (1 H, t, J 7.7,
PCHmaj), 2.57 (1 H, m, min), 2.40 (1 H, m, min), 2.2–1.1 (4 H,
m), 1.59 (3 H, d, J 6.8, Memaj ϩ min), 1.45 (3 H, s, Memin), 1.38
(3 H, s, Memaj), 0.77 (3 H, t, J 7.5, Memaj) and 0.53 (3 H, t, J 7.5,
Memin); m/z 462.2 (20%, Mϩ) and 229 (100).
By the same general method, (S)-3-diphenylphosphinoyl-
1-cyclohexylpropyl benzyl ether 31c (790 mg, 1.83 mmol) and
furfural (181 µl, 2.21 mmol) in THF gave a crude product.
Analysis of the crude product by 400 MHz 1H NMR showed it
to be a 70:21:9 ratio of diastereomers. Purification by flash
chromatography eluting with 2:1 EtOAc–hexane gave the
alcohols 35c and 36c (786 mg, 82%, 78:22 mixture of diastere-
omers) as an oil, Rf 0.56 (EtOAc); [α]D20 ϩ10.8 (c 0.21 in CHCl3;
89% ee) (Found: Mϩ, 528.2429. C33H37O4P requires M,
528.2430); νmax/cmϪ1 (CHCl3) 3445 (OH), 1423 (P–Ph) and 1210
Also obtained was the alcohol 38e (8 mg, 15%, >95:5 ratio of
diastereomers) as an oil, Rf 0.40 (EtOAc) (Found: Mϩ,
462.2327. C29H37O3P requires M, 462.2324); νmax/cmϪ1 (CHCl3)
(P᎐O); δ (400 MHz; CDCl3) 7.75–7.2 (16 H, Ph2PO, Ph and
᎐
H
remaining Ar), 6.36 (1 H, m, Armaj ϩ min), 6.24 (1 H, dd, J 1.8
and 3.2, Armaj), 6.08 (1 H, dd, J 1.9 and 3.2, Armin), 5.20 (1 H, br
d, J 9.5, CHOHmaj ϩ min), 5.04 (1 H, br s, OHmin), 4.80 (1 H, br s,
OHmaj), 4.49 (1 H, d, J 11.9, PhCHAHBmin), 4.34 (1 H, d, J 12.2,
PhCHAHBmaj), 4.11 (1 H, d, J 12.2, PhCHAHBmaj), 4.05 (1 H, d,
J 11.8, PhCHAHBmin), 3.08 (1 H, t, J 8.2, PCHmin), 2.82 (1 H, m,
PCHmaj) and 2.3–0.5 (13 H, m); δC (100 MHz; CDCl3) 153.9Ϫ (d,
3JPC 13.4, ipso-Armaj), 139.2Ϫ (ipso-Phmin), 139.1Ϫ(ipso-Phmaj),
133–127 (m, Ph2PO and remaining Ar and Ph), 110.9ϩ (Armin),
3362 (br OH), 1438 (P–Ph) and 1175 (P᎐O); δ (400 MHz;
᎐
H
CDCl3) 7.8–7.1 (15 H, m, Ph2PO and Ph), 5.62 (1 H, q, J 5.3,
CHOH), 5.47 (1 H, q, J 6.6, MeCH᎐C), 4.63 (1 H, d, J 11.0
᎐
PhCHAHB), 4.19 (1 H, d, J 11.0, PhCHAHB), 4.23 (1 H, m,
CHOH), 3.41 (1 H, m, CHOBn), 3.05 (1 H, m, PCH), 1.7–1.4 (4
H, m), 1.38 (3 H, s, Me), 1.32 (1 H, d, J 6.6, Me) and 0.74 (3 H,
t, J 7.5, Me); m/z 462.2 (25%, Mϩ) and 229 (100).
(3R*,4S*,6S*)- and (3R*,4S*,6R*)-4-Diphenylphosphinoyl-6-
methoxymethoxy-2-methyloct-1-en-3-ol 35g and 36g
3
110.3ϩ (Armaj), 106.9ϩ (Armaj), 106.6ϩ (Armin), 82.6ϩ (d, JPC
10.3, PhCHOBnmin), 80.4ϩ (PhCHOBnmaj), 72.6Ϫ (PhCH2min),
70.3Ϫ (PhCH2maj), 67.5ϩ (CHOHmaj), 66.3ϩ (CHOHmin), 40.7ϩ
By the same general method, 1-diphenylphosphinoylpentan-3-
yl methoxymethyl ether 32 (596 mg, 1.79 mmol) and meth-
acrolein (0.58 cm3, 1.98 mmol) in THF gave a crude product.
1
1
(d, JPC 71.5, PCHmin), 38.2ϩ (d, JPC 68.4, PCHmaj) and 30–22
(m); m/z 528.2 (80%, Mϩ), 201.0 (95, Ph2PO) and 91.1 (100, Bn).
1
Analysis of the crude product by 400 MHz H NMR showed
it to be a 41:32:16:10 ratio of diastereomers. Purification by
flash chromatography eluting with 1:1 EtOAc–hexane gave
the alcohols 35g and 36g (275 mg, 38%, 55:45 mixture of
diastereomers) as an oil, Rf 0.58 (EtOAc) (Found: MHϩ,
403.2039. C23H31O5P requires MH, 403.2038); νmax/cmϪ1
(3R*,4S*,6S*)- and (3R*,4S*,6R*)-6-Benzyloxy-4-diphenyl-
phosphinoyl-2-methyloct-1-en-3-ol 35f and 36f
By the same general method, 1-diphenylphosphinoylpentan-3-
yl benzyl ether 31a (319 mg, 0.81 mmol) and methacrolein (74
µl, 0.91 mmol) in THF gave a crude product. Analysis of the
(CHCl ) 3405 (br OH), 1654 (C᎐C), 1438 (P–Ph) and 1200
᎐
3
1
crude product by 400 MHz H NMR showed it to be a 60:40
(P᎐O); δ (400 MHz; CDCl3) 8.0–7.25 (10 H, m, Ph2PO), 5.24
᎐
H
(1 H, br s, OHmin), 5.18 (1 H, br s, OHmaj), 4.96 (1 H, br s,
ratio of 35f and 36f. Purification by flash chromatography elut-
ing with 1:1 EtOAc–hexane gave the alcohols 35f and 36f (129
mg, 35%, 60:40 mixture of diastereomers) as an oil, Rf 0.53
(EtOAc) (Found: Mϩ Ϫ BnOCHEt, 299.1187. C28H33O3P
requires M Ϫ BnOCHEt, 299.1201); νmax/cmϪ1 (CHCl3) 3358
C᎐CH H min), 4.92 (1 H, br s, C᎐CH H min), 4.86 (1 H, br s,
᎐
᎐
᎐
᎐
A
B
A
B
C᎐CH H maj), 4.75 (1 H, br s, C᎐CH H maj), 4.52 (2 H, AB q,
A
B
A
B
J 6.4, OCHAHBOmin), 4.48 (1 H, d, J 6.1, OCHAHBOmaj), 4.41
(1 H, d, J 10.6, CHOHmaj), 4.35 (1 H, d, J 10.6, CHOHmin), 4.32
(1 H, d, J 6.2, OCHAHBOmaj), 3.34 (3 H, s, OMemaj), 3.32 (3 H, s,
OMemin), 3.30 (1 H m, CHOMOMmaj), 2.70 (1 H, m, 2.62
CHOMOMmin), 2.42 (1 H, m, PCHmaj), 2.20 (1 H, m, PCHmin),
2.0–1.0 (4 H, m), 1.64 (3 H, s, Memaj), 1.60 (3 H, s, Memin),
0.72 (3 H, t, J 7.6, Memin) and 0.51 (3 H, t, J 7.5, Memaj);
(br OH), 1438 (P–Ph) and 1163 (P᎐O); δ (400 MHz; CDCl3)
᎐
H
8.0–7.2 (15 H, m, Ph PO and Ph), 5.26 (1 H, br s, C᎐CH H min),
᎐
᎐
2
A
B
5.23 (1 H, br s, C᎐CH H maj), 4.99 (1 H, br s, C᎐CH H maj),
᎐
A
B
A
B
4.91 (1 H, br s, C᎐CH H min), 4.82 (1 H, br s, OHmaj), 4.77 (1 H,
᎐
A
B
br s, OHmin), 4.55 (1 H, d, J 11.1, PhCHAHBmin), 4.50 (1 H, d,
J 12.1, PhCHAHBmaj), 4.39 (1 H, d, J 11.6, CHOHmaj), 4.35 (1 H,
d, J 11.4, CHOHmin), 4.24 (1 H, d, J 11.1, PhCHAHBmin), 4.05
(1 H, d, J 12.1, PhCHAHBmaj), 3.36 (1 H, m, min), 2.82 (1 H, t,
J 8.1, PCHmin), 2.62 (1 H, q, J 8.0, PCHmaj), 2.4–1.2 (8 H, m),
0.77 (3 H, t, J 7.4, Memaj) and 0.51 (3 H, t, J 7.1, Memin); δC (100
3
δC (100 MHz; CDCl3) 143.4Ϫ (d, JPC 13.9, CH ᎐Cmin),
᎐
2
142.7Ϫ (d, JPC 13.4, CH ᎐Cmaj), 133–128 (m, Ph2PO), 112.1Ϫ
3
᎐
2
(CH ᎐Cmaj), 111.8Ϫ (CH ᎐Cmin), 96.2Ϫ (OCH2Omaj), 96.1Ϫ
᎐
᎐
2
2
(OCH2Omin), 79.6ϩ (d, JPC 8.8, CH2OMOMmaj/min), 79.6ϩ
3
(CH2OMOMmin/maj), 72.6ϩ (CHOHmaj), 71.1ϩ (d, JPC 2.2, CH-
2
MHz; CDCl3) 143.5Ϫ (d, JPC 14.0, CH ᎐Cmin), 142.2Ϫ (d, JPC
3
3
1
᎐
2
OHmin), 55.5ϩ (OMemin), 55.5ϩ (OMemaj), 35.3ϩ (d, JPC 69.3,
13.2, CH ᎐Cmaj), 139.1Ϫ (ipso-Phmaj ϩ min), 133–127 (m, Ph2PO
᎐
2
PCHmaj ϩ min), 27.7Ϫ (maj), 27.4Ϫ (min), 25.7Ϫ (maj), 25.5Ϫ (min),
19.5ϩ (Memin), 19.5ϩ (Memaj), 9.4ϩ (Memaj) and 9.0ϩ (Memin);
m/z (FAB) 403.2 (10%, MHϩ), 229 (100) and 201.1 (60, Ph2PO).
and remaining Ph), 112.1Ϫ (CH ᎐Cmaj), 111.8Ϫ (CH ᎐Cmin),
᎐
᎐
2
2
79.5ϩ (d, JPC 9.0, PhCHOBnmin), 77.2ϩ (CHOHmaj), 72.6ϩ (d,
3
3JPC 2.2, PhCHOBnmaj), 70.9ϩ (CHOHmin), 70.7Ϫ (PhCH2min),
69.7Ϫ (PhCH2maj), 35.3ϩ (d, JPC 69.6, PCHmaj), 35.2ϩ (d, JPC
69.2, PCHmin), 25.0Ϫ, 19.6Ϫ (min), 19.5Ϫ (maj), 8.9ϩ (Memaj) and
8.6ϩ (Memin); m/z 299.1 (4%, Mϩ Ϫ BnOCHEt) and 201.1 (35,
Ph2PO).
1
1
(1R*,2S*,4R*)- and (1R*,2S*,4S*)-4-Benzyloxy-2-diphenyl-
phosphinoyl-1-phenylhexan-1-ol 36h and 35h
By the same general method, 1-diphenylphosphinoylpentan-3-
yl benzyl ether 31a (279 mg, 0.70 mmol) and benzaldehyde (83
µl, 0.81 mmol) in toluene with lithiation at Ϫ78 ЊC for 1 h gave a
(2E,4R*,5S*,7S*)- and (2E,4R*,5S*,7R*)-7-Benzyloxy-5-
diphenylphosphinoyl-3-methylnon-2-en-4-ol 35e and 36e
1
crude product. Analysis of the crude product by 400 MHz H
NMR showed it to be a 25:51:19:6 ratio of 35h:36h:37h:38h.
Purification by flash chromatography, eluting with 1:1 EtOAc–
hexane gave the alcohols 36h and 35h (164 mg, 65%, 74:26
By the same general method, 1-diphenylphosphinoylpentan-3-
yl benzyl ether 31a (43 mg, 0.11 mmol) and trans-2-methylbut-
1976
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

View Article Online
mixture of diastereomers) as an oil, Rf 0.51 (EtOAc) (Found:
Mϩ Ϫ BnH, 392.1545. C31H33O3P requires M Ϫ BnH,
392.1541); νmax/cmϪ1 (CHCl3) 3364 (br OH), 1591 (Ph), 1438
Purification by flash chromatography eluting with 2:1 EtOAc–
hexane gave the alcohols 35a and 36a (121 mg, 46%, 77:23 ratio
of diastereomers) as an oil, spectroscopically identical to that
obtained previously.
(P–Ph) and 1160 (P᎐O); δ (400 MHz; CDCl3) 7.9–6.9 (20 H,
᎐
H
m, Ph2PO and Ph × 2), 5.23 (1 H, d, J 10.1, CHOHmaj ϩ min),
5.10 (1 H, br s, OHmaj), 4.86 (1 H, br s, OHmin), 4.23 (1 H, d,
J 11.1, PhCHAHBmaj), 4.09 (1 H, d, J 12.1, PhCHAHBmin), 3.88
(1 H, d, J 12.1, PhCHAHBmin), 3.62 (1 H, d, J 11.1, PhCHA-
HBmaj), 2.92 (1 H, t, J 8.1, PCHmaj), 2.67 (1 H, m, PCHmin), 2.4–
0.9 (4 H, m), 0.57 (3 H, t, J 7.4, Memaj), 0.41 (3 H, t, J 7.4,
(2S,4R)- and (2R,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-
phenyloctan-1-one 44i and 45i
By the same general method, (R)-1-diphenylphosphinoyl-
heptan-3-yl benzyl ether 31b (1.03 g, 2.53 mmol) and ethyl
benzoate (0.40 cm3, 2.78 mmol) gave a crude product which
was purified by flash chromatography eluting with 2:1 EtOAc–
hexane, to give the ketones 44i and 45i (959 mg, 74%, 65:35
ratio of diastereomers) as an oil, Rf 0.48 (EtOAc); [α]D20 ϩ12.6
(c 0.70 in CHCl3; 84% ee) (Found: Mϩ Ϫ Bu, 453.1616.
C33H35O3P requires Mϩ Ϫ Bu, 453.1619); νmax/cmϪ1 (CHCl3)
3
Memin); δC (100 MHz; CDCl3) 142.5Ϫ (d, JPC 14.7, ipso-Phmaj),
141.8Ϫ (d, 3JPC 13.8, ipso-Phmin), 139.3Ϫ, 139.2Ϫ(ipso-Phmaj ϩ min),
3
133–125 (m, Ph2PO and remaining 2 × Ph), 79.6ϩ (d, JPC 9.1,
3
PhCHOBnmaj), 78.7ϩ (d, JPC 3.5, PhCHOBnmin), 71.3ϩ (CHO-
Hmin), 71.2Ϫ (PhCH2maj), 69.8ϩ (CHOHmaj), 69.3Ϫ (PhCH2min),
40.5ϩ (d, 1JPC 67.6, PCHminϩmaj), 26.1Ϫ (maj), 25.8Ϫ (min), 25.4Ϫ
(maj), 25.2Ϫ (min), 9.2ϩ (Memin) and 8.9ϩ (Memaj); m/z 392.1541
(80%, Mϩ Ϫ BnH) and 229.1 (100).
1678 (C᎐O), 1434 (P–Ph) and 1220 (P᎐O); δ (400 MHz;
᎐
᎐
H
CDCl3) 7.9–7.1 (20 H, m, Ph2PO and Ph × 2), 4.99 (1 H, ddd,
J 1.9, 11.5 and 2JPC 13.9, PCHmin), 4.74 (1 H, ddd, J 3.0, 9.3 and
2JPC 16.2, PCHmaj), 4.46 (1 H, d, J 11.5, PhCHAHBmaj), 4.31
(1 H, d, J 11.7, PhCHAHBmin), 4.22 (1 H, d, J 11.7, PhCHA-
HBmin), 4.11 (1 H, d, J 11.5, PhCHAHBmaj), 3.41 (quin, J 6.1,
CHOBnmin), 3.28 (1 H, m, CHOBnmaj), 2.65 (1 H, m, maj), 2.58
(1 H, m, min), 2.30 (1 H, m, min), 2.00 (1 H, m, maj), 1.7–1.1
(7 H, m), 0.82 (3 H, t, J 7.3, Memaj) and 0.79 (3 H, t, J 7.2,
(3R*,4S*,6R*)- and (3R*,4S*,6S*)-6-Benzyloxy-4-diphenyl-
phosphinoyl-2-methyloct-1-en-3-ol 36f and 35f
By the same general method, 1-diphenylphosphinoylpentan-3-
yl benzyl ether 31a (312 mg, 0.79 mmol) and methacrolein (75
µl, 0.92 mmol) in toluene with lithiation at Ϫ78 ЊC for 1 h gave a
1
Memin); δC (63 MHz; CDCl3) 197.6Ϫ (C᎐Omaj/min), 197.5Ϫ
crude product. Analysis of the crude product by 400 MHz H
᎐
(C᎐Omin/maj), 138.6Ϫ (ipso-Phmin), 138.4Ϫ (ipso-Phmaj), 132–127
NMR showed it to be a 17:39:20:25 ratio of 35f:36f:37f:38f.
Purification by flash chromatography eluting with 1:1 EtOAc–
hexane gave the alcohols 36f and 35f (118 mg, 33%, 71:29
mixture of diastereomers) as an oil, spectroscopically identical
to that obtained previously.
Also obtained were the alcohols 37f and 38f (71 mg, 20%,
>95:5 mixture of diastereomers) as an oil, Rf 0.24 (1:1 hexane–
EtOAc); δH (400 MHz; CDCl3) 8.8–7.2 (15 H, m, Ph2PO and
᎐
(m, Ph2PO and remaining Ph), 78.1ϩ (d, 3JPC 10.4, CHOBnmin),
77.2ϩ (d, JPC 12.6, CHOBnmaj), 70.5Ϫ (PhCH2maj), 70.4Ϫ
3
1
1
(PhCH2min), 48.3ϩ (d, JPC 56.7, PCHmin), 46.9ϩ (d, JPC 57.3,
PCHmaj), 33.2Ϫ, 33.1Ϫ, 32.7Ϫ, 32.3Ϫ, 27.2Ϫ (min), 26.9Ϫ (maj),
22.7Ϫ (maj), 22.6Ϫ (min), 14.2ϩ (Memaj) and 14.0ϩ (Memin); m/z
453.2 (10%, Mϩ), 320.1 (80, Ph2POCHC(O)Ph), 201.0 (100,
Ph2PO) and 105.0 (80, PhCO).
Ph), 5.64 (1 H, d, J 4.2, OH), 4.90 (1 H, br s, C᎐CH H ), 4.63 (1
᎐
A
B
H, d, J 11.0, PhCH H ), 4.30 (2 H, m, C᎐CH H and
PhCHAHB), 3.47 (1 H, m, CHOBn), 3.05 (1 H, m, PCH), 1.8–
1.2 (7 H, m) and 1.05 (3 H, d, J 7.5, Me).
᎐
A
B
A
B
(2S,4S)- and (2R,4S)-4-Benzyloxy-1,4-diphenyl-2-diphenyl-
phosphinoylbutan-1-one 44j and 45j
By the same general method, (S)-3-diphenylphosphinoyl-
1-phenylpropyl benzyl ether 31d (1.05 g, 2.45 mmol) and ethyl
benzoate (0.42 cm3, 2.6 mmol) in THF gave a crude product.
Analysis of the crude product by 400 MHz 1H NMR showed it
to be a 79:21 ratio of 44j and 45j. Purification by flash chrom-
atography eluting with 3:2 EtOAc–hexane gave the ketones 44j
and 45j (1.08 g, 82%, 80:20 mixture of diastereomers) as an oil,
Rf 0.54 (EtOAc); [α]D20 Ϫ3.9 (c 1.29 in CHCl3; 100% ee) (Found:
Mϩ Ϫ BnH, 443.1407. C35H31O3P requires M Ϫ BnH,
443.1407); νmax/cmϪ1 (CHCl ) 1674 (C᎐O), 1438 (P–Ph) and
(1R,2S,4R)- and (1S,2R,4R)-4-Benzyloxy-2-diphenylphosphin-
oyl-1-(4-methoxyphenyl)octan-1-ol 36d and 35d
By the same general method, (R)-1-diphenylphosphinoyl-
heptan-3-yl benzyl ether 31b (243 mg, 0.59 mmol) and p-
anisaldehyde (90 µl, 0.72 mmol) in toluene with lithiation at
Ϫ78 ЊC for 45 min gave a crude product. Purification by flash
chromatography eluting with 3:2 EtOAc–hexane gave the
alcohols 36b and 35b (120 mg, 38%, 56:44 ratio of diastereo-
mers) as an oil, spectroscopically identical to that obtained
previously.
᎐
3
1182 (P᎐O); δ (400 MHz; CDCl ) 7.8–7.1 (25 H, m, Ph PO and
᎐
H
3
2
Ph × 3), 5.21 (1 H, ddd, J 2.1, 11.1 and 13.9, PCHmaj), 4.59
(1 H, ddd, J 2.7, 9.7 and 17.1, PCHmin), 4.34 (1 H, d, J 11.4
PhCHAHBmaj), 4.30 (1 H, m, CHOBnmaj ϩ min), 4.24 (1 H, d,
J 11.5, PhCHAHBmin), 4.04 (1 H, d, J 11.5, PhCHAHBmin), 4.02
(1 H, d, J 11.5, PhCHAHBmaj), 2.85 (1 H, m, min), 2.77 (1 H, m,
maj), 2.4–2.2 (1 H, m, majϩmin); δC (100 MHz; CDCl3) 197.4Ϫ
(C᎐Omaj), 197.0Ϫ (C᎐Omin), 141.2Ϫ (ipso-Phmaj), 140.5Ϫ (ipso-
(1R,2S,4R)- and (1S,2R,4R)-4-Benzyloxy-2-diphenylphosphin-
oyl-1-(2-furyl)octan-1-ol 36b and 35b
By the same general method, (R)-1-diphenylphosphinoyl-
heptan-3-yl benzyl ether 31b (320 mg, 0.79 mmol) and furfural
(72 µl, 0.87 mmol) in toluene with lithiation at Ϫ78 ЊC for 30
min gave a crude product. Analysis of the crude product by 400
᎐
᎐
Phmin), 138.4Ϫ, 138.0Ϫ (ipso-Phmaj), 137.8Ϫ, 137.7Ϫ (ipso-Phmin),
132–126 (m, Ph2PO and remaining 3 × Ph), 80.7ϩ (d, 3JPC 10.6,
1
MHz H NMR showed it to be a 34:43:25 mixture of dia-
3
PhCHOBnmin), 79.0ϩ (d, JPC 12.2, PhCHOBnmaj), 70.6Ϫ
stereomers. Purification by flash chromatography eluting with
2:1 EtOAc–hexane gave the alcohols 36b and 35b (224 mg,
57:43 ratio of diastereomers) as an oil, spectroscopically iden-
tical to that obtained previously.
1
(PhCH2maj), 70.4Ϫ (PhCH2min), 48.9ϩ (d, JPC 56.2, PCHmin),
1
47.8ϩ (d, JPC 57.0, PCHmaj) and 30.2Ϫ (maj ϩ min); m/z 443.1
(10%, Mϩ Ϫ Bu), 409.2 (55, Mϩ Ϫ Bn), 201.0 (100, Ph2PO) and
91.1 (75, Bn).
(1R*,2S*,4S*)- and (1R*,2S*,4R*)-4-Benzyloxy-2-diphenyl-
phosphinoyl-1-(2-furyl)hexan-1-ol 35a and 36a
(2S,4R)- and (2R,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-(2-
furyl)octan-1-one 44b and 45b
By the same general method, 1-diphenylphosphinoylpentan-3-
yl benzyl ether 31a (211 mg, 0.56 mmol) and furfural (55 µl,
0.66 mmol) in DME, with lithiation at Ϫ78 ЊC for 30 min, gave
a crude product. Analysis of the crude product by H NMR
showed it to be a 57:19:11:13 ratio of 35a:36a:37a:38a.
By the same general method, (R)-1-diphenylphosphinoyl-
heptan-3-yl benzyl ether 31b (781 mg, 1.92 mmol) and ethyl 2-
furoate (0.29 cm3, 2.11 mmol) gave a crude product. Analysis of
the crude product by 400 MHz 1H NMR showed that it was a
1
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1977

View Article Online
72:28 mixture of 44b and 45b. Purification by flash chrom-
atography eluting with 3:1 EtOAc–hexane gave the ketones 44b
and 45b (575 mg, 60%, 63:37 ratio of diastereomers) as an oil,
Rf 0.42 (EtOAc); [α]D20 ϩ13.3 (c 0.61 in CHCl3; 84% ee) (Found:
Mϩ Ϫ Bu, 443.1407. C31H33O4P requires M Ϫ Bu, 443.1407);
νmax/cmϪ1 (CHCl ) 1711 (C᎐O) and 1438 (P–Ph); δH (400 MHz;
and evaporated under reduced pressure to give a crude product
which was mainly the ketone 44b (85:15 mixture of diastereo-
mers), Rf 0.59 (EtOAc); [α]D20 ϩ17.3 (c 0.30 in CHCl3; 84% ee)
(Found: MHϩ, 541.2486. C34H37O4P requires MH, 541.2508);
νmax/cmϪ1 (CHCl ) 1718 (C᎐O), 1422 (P–Ph) and 1201 (P᎐O); δ
᎐
᎐
3
H
(400 MHz; CDCl3) 8.0–7.1 (17 H, m, Ph2PO, Ph and remaining
᎐
3
CDCl3) 7.95–7.2 (15 H, m, Ph2PO and Ph), 7.12 (1 H, m, Armaj),
7.10 (1 H, m, Armin), 6.93 (1 H, d, J 3.6, Armaj), 6.91 (1 H, d,
J 3.6, Armin), 6.27 (1 H, dd, J 1.7 and 3.7, Armaj), 6.25 (1 H, dd,
J 1.7 and 3.5, Armin), 4.80 (1 H, ddd, J 1.8, 11.6 and 2JPH 14.3,
PCHmaj), 4.54 (1 H, ddd, J 1.4, 9.9 and 2JPH 14.3, PCHmin), 4.41
(1 H, d, J 11.4, PhCHAHBmaj), 4.34 (1 H, d, J 11.5, PhCHA-
HBmin), 4.21 (1 H, d, J 11.5, PhCHAHBmin), 4.18 (1 H, d, J 11.4,
PhCHAHBmaj), 3.5–3.3 (2 H, m, PCH and CHOBn), 2.7–2.5 (1
H, m, maj ϩ min), 2.22 (1 H, m, min), 1.95 (1 H, m, maj), 1.7–1.1
(7 H, m), 0.83 (3 H, t, J 7.3, Memaj) and 0.79 (3 H, t, J 7.3,
Ar), 6.66 (2 H, br d, J 8.8, Ar), 4.97 (1 H, ddd, J 2.0, 11.4 and
2
2JPH 14.9, PCHmaj), 4.73 (1 H, ddd, J 2.9, 9.2 and JPH 17.1,
PCHmin), 4.44 (1 H, d, J 11.4, PhCHAHBmaj), 4.31 (1 H, d,
J 11.4, PhCHAHBmin), 4.23 (1 H, d, J 11.5, PhCHAHBmin), 4.09
(1 H, d, J 11.4, PhCHAHBmaj), 3.77 (3 H, s, OMe), 3.41 (1 H,
quin, J 6.1, CHOBnmin), 3.28 (1 H, m, CHOBnmaj), 2.65–2.45
(1 H, m), 1.95 (1 H, m), 1.6–1.1 (6 H, m) and 0.83 (3 H, t, J 6.8,
Me); m/z (FAB) 541.3 (70%, MHϩ), 433.3 (50, M Ϫ OBn) and
307.1 (100). The crude product was dissolved in ethanol (3 cm3),
sodium borohydride (22 mg, 0.61 mmol) was added, the solu-
tion was stirred for 3 h, quenched with water (5 cm3) and dilute
hydrochloric acid until effervescence had finished and the
solvent removed under reduced pressure. The residue was
diluted with water (10 cm3), extracted with dichloromethane
(3 × 10 cm3), dried (MgSO4) and evaporated to give a crude
product which was purified by flash chromatography eluting
with 2:1 EtOAc–hexane to give the alcohol 37d (38 mg, 73%,
87:13 mixture of diastereomers) as an oil, Rf 0.54 (EtOAc); [α]D20
ϩ4.4 (c 0.09 in CHCl3; 84% ee) (Found: MHϩ, 543.2694.
C34H39O4P requires M, 543.2664); νmax/cmϪ1 (CHCl3) 3456
Memin); δC (100 MHz; CDCl3) 185.3Ϫ (C᎐Omin), 185.1Ϫ
᎐
(C᎐Omaj), 153.2Ϫ (Armaj), 152.9Ϫ (Armin), 146.3Ϫ (Armaj), 146.1Ϫ
᎐
(Armin), 138.6Ϫ (ipso-Phmaj), 138.4Ϫ (ipso-Phmin), 132–128 (m,
Ph2PO and remaining Ph), 117.8ϩ (Armaj), 117.7ϩ (Armin),
3
112.5ϩ (Armaj ϩ min), 78.4ϩ (d, JPC 11.2, CHOBnmaj), 77.2ϩ
(CHOBnmin), 70.7Ϫ (PhCH2maj), 70.4Ϫ (PhCH2min), 49.0ϩ (d, 1JPC
1
56.1, PCHmin), 47.1ϩ (d, JPC 57.3, PCHmaj), 33.3Ϫ (maj), 33.1Ϫ
(min), 31.6Ϫ (maj ϩ min), 27.1Ϫ (maj ϩ min), 22.7Ϫ (maj),
22.6Ϫ (min), 14.2ϩ (Memaj/min) and 14.0ϩ (Memin/maj); m/z 443.1
(25%, Mϩ Ϫ Bu), 409.2 (55, Mϩ Ϫ Bn), 201.0 (100, Ph2PO) and
91.1 (75, Bn).
(OH), 1423 (P–Ph) and 1206 (P᎐O); δ (200 MHz; CDCl3)
᎐
H
7.75–7.13 (15 H, m, Ph2PO, Ph), 7.10 (2 H, d, J 8.7, Armaj ϩ min),
6.66 (2 H, br d, J 8.7, Armaj), 6.59 (2 H, br d, J 8.7, Armin), 5.94
(1 H, d, J 4.4, OHmaj), 5.55 (1 H, d, J 7.1, OHmin), 5.01 (1 H,
ddd, J 5.4, 6.5 and 2JPH 19.6, CHOHmin), 4.93 (1 H, ddd, J 4.5,
7.0 and 2JPH 16.3, CHOHmaj), 4.46 (1 H, d, J 11.1, PhCHAHBmaj),
4.36 (1 H, d, J 11.8, PhCHAHBmin), 4.14 (1 H, d, J 11.1,
PhCHAHBmaj), 4.12 (1 H, d, J 11.8, PhCHAHBmin), 3.73 (3 H, s,
OMemaj), 3.68 (3 H, s, OMemin), 3.15 (1 H, m CHOBn), 2.68
(1 H, m, PCHmin), 2.60 (1 H, m, PCHmaj), 1.6–0.8 (8 H, m), 0.79
(3 H, t, J 7.2, Memaj) and 0.78 (3 H, t, J 7.2, Memin); δC (50 MHz;
CDCl3) 158.9Ϫ (ipso-Armaj), 158.8Ϫ (ipso-Armin), 138.8Ϫ (ipso-
Phmaj), 138.7Ϫ (ipso-Phmin), 134–127.5 (m, Ph2PO and remaining
Ar and Ph), 113.5ϩ (Armaj), 113.3ϩ (Armin), 77.3ϩ (min), 76.6ϩ
(2S,4S)- and (2R,4S)-4-Benzyloxy-4-cyclohexyl-2-diphenyl-
phosphinoyl-1-(2-furyl)butan-1-one 44c and 45c
By the same general method, (S)-1-diphenylphosphinoyl-3-
cyclohexylpropan-3-yl benzyl ether 31c (812 mg, 1.88 mmol)
and ethyl 2-furoate (0.31 cm3, 2.31 mmol) gave a crude product.
1
Analysis of the crude product by 400 MHz H NMR showed
that it was a 67:33 mixture of 44c and 45c. Purification by flash
chromatography eluting with 2:1 EtOAc–hexane gave the
ketones 44c and 45c (700 mg, 78%, 69:31 ratio of diastereo-
mers) as an oil, Rf 0.44 (EtOAc); [α]D20 ϩ3.7 (c 1.47 in CHCl3;
89% ee) (Found: Mϩ Ϫ C6H11, 443.1405. C33H35O4P requires
M Ϫ C6H11, 443.1412); νmax/cmϪ1 (CHCl ) 1715 (C᎐O), 1438
3
(maj), 75.9ϩ (min), 74.2ϩ (d, JPC 3.3, CHOBn), 71.1Ϫ (PhC-
᎐
3
(P–Ph) and 1174 (P᎐O); δH (400 MHz; CDCl3) 8.0–7.05 (16 H,
H2maj), 70.2Ϫ (PhCH2min), 55.2ϩ, 55.2ϩ (OMemaj ϩ min), 41.6ϩ (d,
᎐
1
m, Ph2PO, Ph and remaining Ar), 6.92 (d, J 3.5, Armaj), 6.88 (1
H, dd, J 0.4 and 4.3, Armin), 6.29 (1 H, dd, J 1.6 and 3.6, Armaj),
6.21 (1 H, dd, J 1.9 and 3.6, Armin), 4.75 (1 H, ddd, J 1.6, 11.8
and 2JPH 19.7, PCHmaj), 4.46 (1 H, ddd, J 3.1, 9.4 and 2JPH 17.0,
PCHmin), 4.42 (1 H, d, J 11.9, PhCHAHBmaj), 4.31 (1 H, d,
J 11.2, PhCHAHBmin), 4.22 (1 H, d, J 12.4, PhCHAHBmin), 4.18
(1 H, d, J 11.6, PhCHAHBmaj), 3.24 (1 H, m, CHOBnmin), 3.11
1JPC 67.4, PCHmin), 40.3ϩ (d, JPC 66.9, PCHmaj), 33.4Ϫ (maj),
32.7Ϫ (min), 31.9Ϫ (maj), 31.6Ϫ (min), 26.9Ϫ (min), 26.8Ϫ (maj),
22.8Ϫ (maj), 22.7Ϫ (min) and 13.6ϩ (Memaj ϩ min); m/z 542.3 (5%,
Mϩ), 201.0 (70, Ph2PO) and 91 (100, Bn).
(1R,2R,4R)- and (1S,2S,4R)-4-Benzyloxy-2-diphenylphosphin-
oyl-1-(4-methoxyphenyl)octan-1-ol 38d
(1 H, m, CHOBnmaj), 2.49 (1 H, m, PCHmin) and 2.3–0.8 (14 H,
3
m); δC (50 MHz; CDCl3) 185.3Ϫ (C᎐O), 152.8Ϫ (d, JPC 15.6,
By the same general method, (1S,2R,4R)-4-benzyloxy-2-
diphenylphosphinoyl-1-(4-methoxyphenyl)octan-1-ol 35d (1.10
g, 2.03 mmol) and Dess–Martin periodinane (1.17 g, 3.05
mmol) gave a crude product which was the ketone 45d , spectro-
scopically identical to the minor isomer obtained earlier, δC (50
MHz; CDCl ) 195.5Ϫ (C᎐O), 163.2Ϫ (ipso-Ar), 138.4Ϫ (ipso-Ph),
᎐
ipso-Ar), 138.8Ϫ (ipso-Ph), 132.5–127 (m, Ph2PO and remaining
Ph), 117.9ϩ (Armaj), 117.8ϩ (Armin), 112.5ϩ (Armaj ϩ min), 81.8ϩ
(d, JPC 12.0, CHOBn), 71.6Ϫ (PhCH2maj), 71.1Ϫ (PhCH2min),
3
47.2ϩ (d, JPC 57.6, PCHmin) and 29–25 (m); m/z 443.2 (65%,
1
M Ϫ C6H11), 310.1 (85), 201.1 (65, Ph2PO) and 91.1 (100, Bn).
᎐
3
133–127 (m, Ph2PO and remaining Ar), 113.3ϩ (Ar), 78.1ϩ (d,
3JPC 24.4, CHOBn), 70.3Ϫ (PhCH2), 55.3ϩ (OMe), 47.5ϩ (d, 1JPC
57.5, PCH), 33.0Ϫ, 32.4Ϫ, 27.1Ϫ, 22.5Ϫ and 13.6ϩ (Me). The
crude product was dissolved in ethanol (40 cm3), sodium boro-
hydride (354 mg, 9.31 mmol) added, stirred for 3 h, quenched
with water (50 cm3) and dilute hydrochloric acid until effer-
vescence had finished and the solvent removed under reduced
pressure. The residue was diluted with water (100 cm3),
extracted with dichloromethane (3 × 60 cm3), dried (MgSO4)
and evaporated to give a crude product which was purified by
flash chromatography eluting with 2:1 EtOAc–hexane to give
the alcohols 38d and 37d (803 mg, 69%, 51:49 mixture of
diastereomers) as an oil, spectroscopically identical to that
obtained previously.
(1S,2S,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)-
octan-1-ol 37b
A solution of (1R,2S,4R)-4-benzyloxy-2-diphenylphosphinoyl-
1-(2-furyl)octan-1-ol 36b (52 mg, 96 µmol, 86:14 mix-
ture 36b:35b) in dry dichloromethane (2 cm3) was added to a
stirred solution of Dess–Martin periodinane (55 mg, 0.15
mmol) in dry dichloromethane (2 cm3) by cannula at 0 ЊC. The
reaction was stirred for 30 min, warmed to room temperature,
stirred for 1 h, diluted with dichloromethane (5 cm3), quenched
with saturated aqueous sodium thiosulfate solution (5 cm3) and
saturated aqueous sodium bicarbonate solution (5 cm3),
extracted with dichloromethane (3 × 5 cm3), dried (MgSO4)
1978
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

View Article Online
(1R,2R,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)-
octan-1-ol 38b
to give a crude product which was purified by flash chrom-
atography eluting with 2:1 EtOAc–hexane to give the alcohols
37b and 38b (1.87 g, 97%, 63:37 mixture) as an oil. Purification
by HPLC, eluting with chloroform, gave the alcohol 37b (1.46 g,
76%, 90:10 ratio of 37b:38b) as an oil, retention time 12.5 min;
Rf 0.52 (EtOAc); [α]D20 ϩ4.8 (c 0.46 in CHCl3; 84% ee) (Found:
Mϩ, 502.2268. C29H31O4P requires M, 502.2273); νmax/cmϪ1
By the same general method, (1S,2R,4R)-4-benzyloxy-2-
diphenylphosphinoyl-1-(2-furyl)octan-1-ol 35b (80 mg, 0.16
mmol) and Dess–Martin periodinane (203 mg, 0.48 mmol) gave
a crude product which was dissolved in ethanol (5 cm3) and
cooled to 0 ЊC. Sodium borohydride (24 mg, 0.64 mmol) added
in one portion, the reaction mixture was stirred for 2 h,
quenched with water (10 cm3) and dilute hydrochloric acid
added until effervescence had finished. The solvent was
removed under reduced pressure the residue diluted with water
(10 cm3), extracted with dichloromethane (3 × 10 cm3), dried
(MgSO4) and evaporated to give a crude product which was
purified by flash chromatography eluting with 2:1 EtOAc–
hexane to give the alcohol 38b (66 mg, 83%) as an oil, Rf 0.59
(EtOAc); [α]D20 ϩ10.3 (c 0.21 in CHCl3; 84% ee) (Found: MHϩ,
503.2391. C29H31O4P requires MH, 503.2351); νmax/cmϪ1
(CHCl ) 3324 (OH), 1438 (P–Ph) and 1192 (P᎐O); δ (200
᎐
3
H
MHz; CDCl3) 7.8–7.1 (16 H, m, Ph2PO, Ph and remaining Ar),
6.18 (1 H, d, J 3.3, Ar), 6.06 (1 H, dd, J 1.8 and 3.2, Ar), 6.02
(1 H, d, J 6.2, OH), 5.03 (1 H, td, J 6.1 and 3JPH 18.7, CHOH),
4.55 (1 H, d, J 11.0, PhCHAHB), 4.36 (1 H, d, J 11.0,
PhCHAHB), 3.42 (1 H, m, CHOBn), 2.95 (1 H, m, PCH), 1.8–
1.05 (8 H, m) and 0.83 (3 H, t, J 6.8, Me); δC (100 MHz; CDCl3)
3
154.3Ϫ (d, JPC 8.4, Ar), 138.7Ϫ (ipso-Ph), 132.5–127.5 (m,
Ph2PO and remaining Ar and Ph), 110.4ϩ (Ar), 107.8ϩ (Ar),
3
76.6ϩ (d, JPC 11.0, CHOBn), 71.5Ϫ (PhCH2), 68.9ϩ (CHOH),
1
37.8ϩ (d, JPC 67.9, PCH), 33.6Ϫ, 31.5Ϫ, 26.9Ϫ, 22.8Ϫ and 14.0ϩ
(CHCl ) 3385 (OH), 1438 (P–Ph) and 1206 (P᎐O); δ (200
᎐
(Me); m/z 502.2 (10, Mϩ), 202.1 (60, Ph2POH) and 91.1 (100,
Bn).
3
H
MHz; CDCl3) 7.6–7.3 (15 H, m, Ph2PO and Ph), 7.08 (1 H, d,
J 1.1, Ar), 6.16 (1 H, d, J 3.2, Ar), 6.01 (1 H, dd, J 1.8 and 3.2,
Also obtained was the alcohol 38b (404 mg, 21%, >97:3 ratio
of diastereomers), retention time 14 min, spectroscopically
identical to that obtained previously.
3
Ar), 5.42 (1 H, br s, OH), 5.08 (1 H, dd, J 5.1 and JPH 18.7,
CHOH), 4.49 (1 H, d, J 12.0, PhCHAHB), 4.25 (1 H, d, J 12.0,
PhCHAHB), 3.00 (1 H, quin, J 5.1, CHOBn), 2.71 (1 H, qd,
J 5.5 and 2JPH 8.0, PCH), 2.1–1.8 (2 H, m), 1.5–0.9 (6 H, m) and
(1S,2S,4S)-4-Benzyloxy-4-cyclohexyl-2-diphenylphosphinoyl-1-
(2-furyl)butan-1-ol 37c
0.79 (3 H, t, J 7.3, Me); δC (100 MHz; CDCl3) 154.3Ϫ (d, JPC
3
5.6, Ar), 138.7Ϫ (ipso-Ph), 133–127 (m, Ph2PO and remaining
Ar and Ph), 110.2ϩ (Ar), 107.7ϩ (Ar), 77.0ϩ (CHOH), 70.2ϩ (d,
By the same general method, (2S,4S)-4-benzyloxy-4-
cyclohexyl-2-diphenylphosphinoyl-1-(2-furyl)butan-1-one 44c
(640 mg, 1.21 mmol, 69:31 mixture of 44c:45c) and sodium
borohydride (92 mg, 2.42 mmol), with addition of the sodium
borohydride over 10 min at 0 ЊC, gave a crude product which
was purified by flash chromatography eluting with 2:1 EtOAc–
hexane to give the alcohols 37c and 38c (454 g, 71%, 71:29
mixture of diastereomers) as an oil, Rf 0.50 (EtOAc); [α]D20 ϩ5.0
(c 0.38 in CHCl3; 89% ee) (Found: Mϩ, 528.2430. C33H37O4P
requires M, 528.2429); νmax/cmϪ1 (CHCl3) 3368 (OH), 1438 (P–
1
3JPC 9.2, CHOBn), 70.2Ϫ (PhCH2), 39.2ϩ (d, JPC 68.7, PCH),
32.8Ϫ, 30.9Ϫ, 26.9Ϫ, 22.7Ϫ and 13.9ϩ (Me); m/z (FAB) 503.2
(80%, MHϩ) and 201.0 (100, Ph2PO).
In
a
separate experiment, (1S,2R,4R)-4-benzyloxy-2-
diphenylphosphinoyl-1-(2-furyl)octan-1-ol 35b (620 mg, 1.23
mmol) gave, with addition of sodium borohydride over 30 min,
the alcohols 38b and 37b (490 mg, 80% over 2 steps) as a 81:19
mixture of diastereomers. Purification by HPLC, eluting with
chloroform, gave the alcohol 38b (325 mg, 53% over 2 steps) as
an oil, retention time 13.5 min, spectroscopically identical to
that obtained previously.
Ph) and 1204 (P᎐O); δ (400 MHz; CDCl ) 7.75–7.15 (15 H, m,
᎐
H
3
Ph2PO and Ph), 7.12 (1 H, dd, J 0.9 and 1.7, Armaj), 7.00 (1 H, d,
J 0.9, Armin), 6.16 (1 H, d, J 3.2, Armaj), 6.08 (1 H, d, J 3.2, Armin),
6.06 (1 H, dd, J 1.8 and 3.2, Armaj), 6.01 (1 H, d, J 5.7, OHmaj),
5.89 (1 H, dd, J 1.8 and 3.2, Armin), 5.62 (1 H, d, J 8.5, OHmin),
5.0 (1 H, m, CHOH), 4.59 (1 H, d, J 11.0, PhCHAHBmaj), 4.52
(1 H, d, J 12.1, PhCHAHBmin), 4.39 (1 H, d, J 11.0, PhCHA-
HBmaj), 4.29 (1 H, d, J 12.1, PhCHAHBmin), 3.38 (1 H, m,
CHOBnmaj), 2.82 (1 H, m, CHOBnmin), 2.68 (1 H, m, PCHmaj),
2.60 (1 H, m, PCHmin) and 2.2–0.5 (13 H, m); δC (50 MHz;
CDCl3) 154.5Ϫ (d, 3JPC 4.1, ipso-Armin), 154.2Ϫ (d, 3JPC 8.6, ipso-
Armaj), 138.9Ϫ (ipso-Phmin), 138.8Ϫ (ipso-Phmaj), 133–126 (m,
Ph2PO, Ph and remaining Ar), 110.3ϩ (Armaj), 109.9ϩ (Armin),
(1R,2R,4S)-4-Benzyloxy-4-cyclohexyl-2-diphenylphosphinoyl-1-
(2-furyl)butan-1-ol 38c
By the same general method, (1S,2R,4S)-4-benzyloxy-4-cyclo-
hexyl-2-diphenylphosphinoyl-1-(2-furyl)octan-1-ol 35c (600
mg, 1.15 mmol, 78:22 mixture of 35c and 36c) and Dess–
Martin periodinane (1.46 mg, 3.45 mmol) gave a crude product
which was dissolved in ethanol (30 cm3) and cooled to 0 ЊC.
Sodium borohydride (350 mg, 9.2 mmol) was added over 30
min, the reaction mixture was stirred for 2 h, quenched with
water (30 cm3) and dilute hydrochloric acid added until effer-
vescence had finished. The solvent was removed under reduced
pressure, the residue diluted with water (30 cm3), extracted with
dichloromethane (3 × 30 cm3), dried (MgSO4) and evaporated
to give a crude product which was purified by flash chrom-
atography eluting with 2:1 EtOAc–hexane to give the alcohol
38c (537 mg, 90%, 75:25 mixture of diastereomers) as an oil,
spectroscopically identical to that obtained previously, [α]D20 ϩ5.9
(c 0.29 in CHCl3; 84% ee).
3
107.6ϩ (Armaj), 107.3ϩ (Armin), 81.4ϩ (d, JPC 9.6, CHOBnmin),
80.8ϩ (d, 3JPC 9.6, CHOBnmaj), 72.5Ϫ (PhCH2maj), 71.1ϩ (CHO-
Hmin), 70.6Ϫ (PhCH2min), 68.9ϩ (CHOHmaj), 38.2ϩ (d, 1JPC 67.5,
PCHmin), 37.7ϩ (d, 1JPC 67.6, PCHmaj) and 30–25 (m); m/z 528.2
(90%, Mϩ), 201.0 (95, Ph2PO) and 91.1 (100, Bn).
(1S,2S,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-phenyloctan-
1-ol 37i
By the same general method, (2S,4R)-4-benzyloxy-2-
diphenylphosphinoyl-1-phenyloctan-1-one 44i (476 mg, 0.93
mmol, 65:35 mixture of 44i and 45i) and sodium borohydride
(283 mg, 7.4 mmol), with addition of the sodium borohydride
over 20 min at 0 ЊC, gave a crude product which was purified by
flash chromatography eluting with 2:1 EtOAc–hexane to give
the alcohols 37i and 38i (216 g, 46%, 70:30 mixture of diaster-
eomers) as an oil, Rf 0.45 (EtOAc); [α]D20 ϩ10.4 (c 0.38 in CHCl3;
84% ee) (Found: MHϩ, 513.2543. C33H37O3P requires MH,
513.2558); νmax/cmϪ1 (CHCl3) 3347 (OH), 1438 (P–Ph) and 1211
(P᎐O); δ (200 MHz; CDCl3) 7.8–7.0 (20 H, m, Ph2PO and
(1S,2S,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)-
octan-1-ol 37b
(2S,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)octan-
1-one 44b (1.93 g, 0.16 mmol, 72:28 mixture of diastereomers)
was dissolved in ethanol (200 cm3), sodium borohydride (1.05 g,
30.7 mmol) added, stirred for 3 h, quenched with water (100
cm3) and dilute hydrochloric acid added until effervescence had
finished and the solvent removed under reduced pressure. The
residue was diluted with water (200 cm3), extracted with
dichloromethane (3 × 200 cm3), dried (MgSO4) and evaporated
᎐
H
2 × Ph), 6.07 (1 H, d, J 4.5, OHmaj), 5.70 (1 H, d, J 6.3, OHmin),
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982
1979

View Article Online
5.06 (1 H, ddd, J 5.5, 6.9 and 3JPH 16.3, CHOHmin), 4.92 (1 H,
diphenylphosphinoyl-1-(4-methoxyphenyl)octan-1-ol 36d (320
3
ddd, J 4.5, 7.1 and JPH 16.3, CHOHmaj), 4.44 (1 H, d, J 11.1,
mg, 0.59 mmol, 72:28 mixture of 36d and 36d) and sodium
hydride (35 mg of a 60% dispersion in oil, 0.89 mmol) gave a
crude product which was purified by flash chromatography elut-
ing with 4:1 hexane–EtOAc to give the alkene (Z)-49b (57 mg,
30%) as a liquid, Rf 0.79 (1:1 EtOAc–hexane); [α]D20 ϩ25.1 (c
1.00 in CHCl3; 84% ee) (Found: Mϩ, 324.2090. C22H28O2
PhCHAHBmaj), 4.32 (1 H, d, J 11.9, PhCHAHBmin), 4.11 (1 H, m,
PhCHAHBmaj ϩ min), 3.21 (1 H, m, CHOBnmaj ϩ min), 2.78 (1 H,
m, PCHmin), 2.51 (1 H, m, PCHmaj) and 2.3–0.9 (8 H, m) and
0.79 (3 H, t, J 7.0, Memaj ϩ min); δC (50 MHz; CDCl3) 142.4Ϫ
(ipso-Phmin), 142.3Ϫ (ipso-Phmaj), 139.8Ϫ (ipso-Phmaj), 138.7Ϫ
(ipso-Phmin), 132–126.5 (m, Ph2PO and remaining 2 × Ph),
requires M, 324.2089); νmax/cmϪ1 (CHCl ) 1607 (C᎐C); δ (400
᎐
3
H
3
77.4ϩ (m, min), 76.7–76.6ϩ (m, majϩmin), 74.8ϩ (d, JPC 3.3,
MHz; CDCl3) 7.35 (4 H, m, Ph), 7.28 (1 H, m, Ph), 7.24 (2 H, d,
J 11.7, Ar), 6.89 (2 H, d, J 11.7, Ar), 6.45 (1 H, br d, J 11.7,
CH᎐CHCH ), 5.69 (1 H, td, J 7.2 and 11.7, CH᎐CHCH ), 4.56
CHOBnmaj), 71.2Ϫ (PhCH2maj), 70.4Ϫ (PhCH2min), 41.3ϩ (d, 1JPC
1
66.9, PCHmin), 40.0ϩ (d, JPC 66.9, PCHmaj), 33.4Ϫ (maj), 32.6Ϫ
᎐
᎐
2
2
(min), 32.0Ϫ (maj), 31.8Ϫ (min), 26.9Ϫ, 26.8Ϫ, 22.8Ϫ, 22.7Ϫ, 14.3ϩ
and 14.0ϩ (Me); m/z (FAB) 513.3 (60, MHϩ), 229.1 (75), 201.0
(Ph2PO) and 91.1 (100, Bn).
(1 H, d, J 11.6, PhCHAHB), 4.49 (1 H, d, J 11.6, PhCHAHB),
3.81 (3 H, s, OMe), 3.51 (1 H, quin, J 6.0, CHOBn), 2.60 (2 H,
m, CH᎐CHCH ), 1.55 (2 H, m), 1.45–1.2 (4 H, m) and 0.89
᎐
2
(3 H, t, J 7.2, Me); δC (100 MHz; CDCl3) 158.2Ϫ (ipso-Ar),
138.9Ϫ (ipso-Ph), 130.3Ϫ, 129.9ϩ, 129.8ϩ, 128.3ϩ, 127.7ϩ, 127.1ϩ,
113.6ϩ (Ar), 78.9ϩ (CHOBn), 70.9Ϫ (PhCH2), 55.2ϩ (OMe),
33.7Ϫ, 32.9Ϫ, 29.5Ϫ, 22.8Ϫ and 14.0ϩ (Me); m/z 324.2 (30%, Mϩ)
and 91.1 (100, Bn). Also obtained was p-anisaldehyde (18 mg,
23%).
(1S,2S,4S)- and (1R,2R,4S)-4-Benzyloxy-1,4-diphenyl-2-
diphenylphosphinoylbutan-1-ol 37j
By the same general method, ketones 44j and 45j (338 mg, 0.66
mmol, 80:20 mixture) and sodium borohydride (50 mg, 1.32
mmol) with slow addition of the sodium borohydride over 20
min at 0 ЊC gave the alcohols 37j and 38j (315 mg, 93%, 72:28
mixture of diastereomers) as an oil, Rf 0.46 (EtOAc); [α]D20 ϩ264
(c 2.14 in CHCl3; 100% ee) (Found: Mϩ, 532.2156. C35H33O3P
requires M, 532.2167); νmax/cmϪ1 (CHCl3) 3344 (br, OH), 1438
(1R,3Z)-1,4-Diphenylbut-3-en-1-yl benzyl ether 49c
By the same general method, (1S,3R,4S)-1,4-diphenyl-3-
diphenylphosphinoylbutyl benzyl ether 36j (252 mg, 0.49 mmol,
65:35 mixture of 36j and 35j) and sodium hydride (29 mg of a
60% dipersion in oil, 0.74 mmol) gave a crude product, which
was purifed by flash chromatography eluting with 30:1 hexane–
Et2O to give the alkene (Z)-49c (91 mg, 60%, Z:E >95:5 mix-
ture) as a liquid, Rf 0.85 (1:1 EtOAc–hexane); [α]D20 Ϫ12.7 (c 0.75
in CHCl3; 100% ee) (Found: MNaϩ, 337.1566. C22H28O2
requires MNa, 337.1568); νmax/cmϪ1 (CHCl ) 1630 (C᎐C) and
(P–Ph) and 1195 (P᎐O); δ (400 MHz; CDCl3) 7.9–7.1 (25 H,
᎐
H
m, Ph2PO and Ph × 3), 6.26 (1 H, d, J 2.6, OHmaj), 5.86 (1 H, d,
J 5.7, OHmin), 5.08 (1 H, td, J 5.8 and 17.7, CHOHmin), 4.99
(1 H, ddd, J 2.6, 8.4 and 12.9, CHOHmaj), 4.21 (1 H, d, J 11.0
PhCHAHBmaj), 3.81 (d, J 11.6, PhCHAHBmin), 3.92 (1 H, d,
J 11.0, PhCHAHBmaj), 3.81 (d, J 11.6, PhCHAHBmin), 3.55 (1 H,
td, J 8.7 and 13.2, PCHmaj), 3.05 (1 H, m, CHOBnmaj) and 2.0–
1.8 (2 H, m); δC (100 MHz; CDCl3) 142.6Ϫ (ipso-Phmaj), 142.4Ϫ
(ipso-Phmin), 142.3Ϫ (ipso-Phmin), 141.7Ϫ (ipso-Phmaj), 140.7Ϫ
(ipso-Phmin), 138.7Ϫ (ipso-Phmaj), 133–126 (m, Ph2PO and
remaining 3 × Ph), 80.4ϩ (d, 3JPC 9.0, CHOBnmin), 79.3ϩ (d, 3JPC
᎐
3
1596 (Ph); δH (400 MHz; CDCl3) 7.5–7.2 (15 H, Ph × 3), 6.45
(1 H, d, J 11.7, PCH), 5.81 (1 H, td, J 7.1 and 11.7, CH᎐CHPh),
᎐
4.55 (1 H, d, J 11.8, PhCHAHB), 4.47 (1 H, dd, J 5.7 and 7.7,
PhCHOBn), 4.33 (1 H, d, J 11.9, PhCHAHB), 2.99 (1 H, m) and
2.81 (1 H, m); δC (100 MHz; CDCl3) 141.9Ϫ, 138.9Ϫ, 137.4Ϫ
(ipso-Ph × 3), 132.9ϩ, 132–126 (m, remaining Ph × 3), 81.2ϩ
(CHOBn), 70.5Ϫ (PhCH2) and 37.4Ϫ; m/z (FAB) 337.2 (100,
MNaϩ).
2
3
9.1, CHOBnmaj), 76.2ϩ (d, JPC 2.0, CHOBnmin), 75.1ϩ (d, JPC
2.2, CHOBnmaj), 70.7Ϫ (CH2Phmaj), 70.3ϩ (CH2OBnmin), 41.0ϩ
(d, 1JPC 67.2, PCHmin), 40.8ϩ (d, 1JPC 66.7, PCHmaj), 35.8Ϫ (maj)
and 35.5Ϫ (maj); m/z 532.2 (30%, Mϩ) and 229.1 (100).
(1Z,4R)-1-(2-Furyl)oct-1-en-4-yl benzyl ether 49a
(1E,4R)-1-(4-Methoxyphenyl)oct-1-en-4-yl benzyl ether 49b
(1R,2S,4R)-4-Benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)-
octan-1-ol 35b (463 mg, 0.92 mmol, 82:18 mixture
35b:36b) in DMF (6 cm3) was added dropwise by cannula to a
stirred suspension of sodium hydride (55 mg of a 60% disper-
sion in oil, 1.38 mmol) in DMF (12 cm3) at 20 ЊC. The reaction
mixture was heated at 60 ЊC for 45 min, poured into saturated
ammonium chloride solution (15 cm3), extracted with dichloro-
methane (3 × 10 cm3), and the combined organic fractions
washed with water (3 × 25 cm3), dried (MgSO4) and evaporated
to give a crude product which was purified by flash chrom-
atography eluting with 30:1 hexane–EtOAc to give the alkene
(Z)-49a (140 mg, 49%) as a liquid, Rf 0.30 (30:1 hexane–
EtOAc); [α]D20 Ϫ2.5 (c 0.9 in CHCl3; 84% ee) (Found: BnO-
CHBuϩ, 177.1274. C19H24O2 requires BnOCHBu, 177.1279);
By the same general method, (1S,2S,4R)-4-benzyloxy-2-
diphenylphosphinoyl-1-(4-methoxyphenyl)octan-1-ol 37d (268
mg, 0.49 mmol, 72:18 mixture of 37d and 38b) and sodium
hydride (29 mg of a 60% dispersion in oil, 0.74 mmol) gave a
crude product which was purified by flash chromatography elut-
ing with 30:1 hexane–EtOAc to give the alkene (E)-49b (99 mg,
62%) as a liquid, Rf 0.27 (20:1 hexane–EtOAc); [α]D20 Ϫ1.7 (c
1.13 in CHCl3) (Found: Mϩ, 324.2089. C22H28O2 requires M,
324.2089); νmax/cmϪ1 (CHCl ) 1609 (C᎐C); δ (400 MHz;
᎐
3
H
CDCl3) 7.4–7.25 (7 H, m, Ph and remaining Ar), 6.87 (2 H, d,
J 8.7, Ar), 6.43 (1 H, br d, J 15.8, CH᎐CHCH ), 6.13 (1 H, td,
᎐
2
J 7.2 and 15.8, CH᎐CHCH ), 4.62 (1 H, d, J 11.7, PhCH H ),
᎐
2
A
B
4.56 (1 H, d, J 11.7, PhCHAHB), 3.83 (3 H, s, OMe), 3.52 (1 H,
quin, J 5.8, CHOBn), 2.48 (2 H, br t, J 5.9, CH᎐CHCH ), 1.7–
᎐
2
νmax/cmϪ1 (CHCl ) 1603 (C᎐C); δ (400 MHz; CDCl ) 7.45–7.25
1.3 (6 H, m) and 0.93 (3 H, t, J 7.3, Me); δC (100 MHz; CDCl3)
158.8Ϫ (ipso-Ar), 139.0Ϫ (ipso-Ph), 131.3ϩ, 130.6Ϫ, 128.3ϩ,
127.8ϩ, 127.4ϩ, 127.3ϩ, 124.8ϩ, 113.9ϩ (Ar), 79.1ϩ (CHOBn),
74.5Ϫ (PhCH2), 55.3ϩ (OMe), 37.7Ϫ, 33.8Ϫ, 27.7Ϫ, 22.9Ϫ and
14.1ϩ (Me); m/z 324.2 (40%, Mϩ), 147.1 (85, ArCH᎐CHCH )
᎐
3
H
3
(6 H, m, Ph and remaining Ar), 6.42 (1 H, dd, J 1.9 and 3.3,
Ar), 6.30 (2 H, m, Ar and CH᎐CHCH ), 5.70 (1 H, td, J 7.3 and
᎐
2
11.9, CH᎐CHCH ), 4.63 (1 H, d, J 11.6, PhCH H ), 4.55 (1 H,
᎐
2
A
B
d, J 11.6, PhCHAHB), 3.60 (1 H, quin, J 5.8, CHOBn), 2.80
᎐
2
(2 H, m, CH᎐CHCH ), 1.8–1.3 (6 H, m) and 0.93 (3 H, t, J 7.3,
and 91.1 (100, Bn).
᎐
2
Me); δC (100 MHz; CDCl3) 153.4Ϫ (ipso-Ar), 141.4Ϫ (ipso-Ph),
128.3ϩ, 127.8ϩ, 127.4ϩ, 120.6ϩ, 118.6ϩ, 111.1ϩ (Ar), 109.2ϩ (Ar),
78.8ϩ (CHOBn), 70.9Ϫ (PhCH2), 33.9Ϫ, 33.6Ϫ, 27.7Ϫ, 22.9Ϫ and
14.2ϩ (Me); m/z 177.1 (60, BnOCHBu) and 91.1 (100, Bn).
(1E,4R)-1-Phenyloct-1-en-4-yl benzyl ether 49d
By the same general method, (1S,2S,4R)-4-benzyloxy-2-
diphenylphosphinoyl-1-phenyloctan-1-ol 37i (200 mg, 0.39
mmol, 70:30 mixture of 37i and 38i) and sodium hydride (23
mg of a 60% dispersion in oil, 0.58 mmol) gave a crude product
which was purified by flash chromatography eluting with 30:1
(1Z,4R)-1-(4-Methoxyphenyl)oct-1-en-4-yl benzyl ether 49b
By the same general method, (1S,2R,4R)-4-benzyloxy-2-
1980
J. Chem. Soc., Perkin Trans. 1, 1999, 1963–1982

View Article Online
3 D. Hall, A.-F. Sévin and S. Warren, Tetrahedron Lett., 1991, 32,
hexane–EtOAc to give the alkene (E)-49d (22 mg, 19%) as a
liquid, Rf 0.81 (1:1 EtOAc–hexane); [α]D20 Ϫ9.8 (c 0.04 in CHCl3)
7123.
4 H. J. Mitchell and S. Warren, Tetrahedron Lett., 1996, 37, 2105.
5 (a) C. Guéguen, P. O’Brien, S. Warren and P. Wyatt, J. Organomet.
Chem., 1997, 529, 279; (b) C. Guéguen, P. O’Brien, H. R. Powell,
P. R. Raithby and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1998,
3405.
(Found: Mϩ, 294.1998. C21H26O requires M, 294.1984); νmax
/
cmϪ1 (CHCl ) 1601 (C᎐C); δ (400 MHz; CDCl ) 7.4–7.15 (5 H,
᎐
3
H
3
m, Ph), 6.46 (1 H, br d, J 15.8, CH᎐CHCH ), 6.26 (1 H, td, J 7.2
᎐
2
and 15.6, CH᎐CHCH ), 4.61 (1 H, d, J 11.7, PhCH H ), 4.54
᎐
2
A
B
6 (a) J. Clayden, E. W. Collington, R. B. Lamont and S. Warren,
Tetrahedron Lett., 1993, 34, 2203; (b) J. Clayden and S. Warren,
J. Chem. Soc., Perkin Trans. 1, 1998, 2923.
(1 H, d, J 11.7, PhCHAHB), 3.51 (1 H, quin, J 5.8, CHOBn),
2.49 (2 H, br t, J 6.0, CH᎐CHCH ), 1.7–1.2 (6 H, m) and 0.91
᎐
2
(3 H, t, J 7.3, Me); δC (100 MHz; CDCl3) 138.9Ϫ, 137.7Ϫ (ipso-
Ph × 2), 131.9ϩ, 128.4ϩ, 128.3ϩ, 127.8ϩ, 127.4ϩ, 127.0ϩ, 126.9ϩ,
126.0ϩ, 78.9ϩ (CHOBn), 71.1Ϫ (PhCH2), 37.6Ϫ, 33.7Ϫ, 27.6Ϫ,
22.8Ϫ and 14.1ϩ (Me); m/z 324.2 (30%, Mϩ) and 91.1 (100, Bn).
7 For some examples, see: (a) J. Clayden and S. Warren, J. Chem. Soc.,
Perkin Trans. 1, 1994, 2811; (b) J. Eames, H. J. Mitchell, A. Nelson,
P. O’Brien, S. Warren and P. Wyatt, Tetrahedron Lett., 1995, 36, 1719;
(c) J. Eames, H. J. Mitchell, A. Nelson, P. O’Brien, S. Warren and
P. Wyatt, J. Chem. Soc., Perkin Trans. 1, 1999, 1095; (d) P. O’Brien
and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1996, 2117; (e)
P. O’Brien and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1996, 2129;
( f ) A. Nelson and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1997,
2145.
8 (a) D. R. Armstrong, D. Barr, M. G. Davidson, G. Hutton,
P. O’Brien, R. Snaith and S. Warren, J. Organomet. Chem., 1997,
529, 29; (b) J. E. Davies, R. P. Davies, L. Dunbar, P. R. Raithby,
M. G. Russell, R. Snaith, S. Warren and A. E. H. Wheatley, Angew.
Chem., Int. Ed. Engl., 1997, 36, 2334.
9 (a) P. O’Brien and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1996,
2567; (b) P. O’Brien, H. R. Powell, P. R. Raithby and S. Warren,
J. Chem. Soc., Perkin Trans. 1, 1997, 1031.
10 Preliminary communication: A. Nelson and S. Warren, Tetrahedron
Lett., 1998, 39, 1633.
11 A. Nelson and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1999,
following paper.
12 A. D. Buss and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1985,
2307.
(1S,3E)-1,4-Diphenylbut-3-en-1-yl benzyl ether 49c
By the same general method, (1S,3S,4S)-1,4-diphenyl-3-
diphenylphosphinoylbutyl benzyl ether 37j (207 mg, 0.40 mmol,
72:28 mixture of 37j and 38j) and sodium hydride (24 mg of a
60% dipersion in oil, 0.60 mmol) gave a crude product, which
was purifed by flash chromatography eluting with 30:1 hexane–
Et2O to give the alkene (E)-49c (91 mg, 60%, E:Z >95:5 mix-
ture) as a liquid, Rf 0.33 (30:1 hexane–EtOAc); [α]D20 Ϫ23.2 (c
2.40 in CHCl3; 100% ee) (Found: MNaϩ, 337.1566. C22H28O2
requires MNa, 337.1566); νmax/cmϪ1 (CHCl ) 1630 (C᎐C) and
᎐
3
1596 (Ph); δH (400 MHz; CDCl3) 7.45–7.2 (15 H, Ph × 3), 6.44
(1 H, d, J 15.8, PCH), 6.24 (1 H, td, J 7.2 and 15.8, CH᎐CHPh),
᎐
4.53 (1 H, d, J 11.9, PhCHAHB), 4.44 (1 H, dd, J 5.6 and 7.8,
PhCHOBn), 4.30 (1 H, d, J 11.9, PhCHAHB), 2.78 (1 H, m) and
2.62 (1 H, m); δC (100 MHz; CDCl3) 141.9Ϫ, 138.5Ϫ, 137.7Ϫ
(ipso-Ph × 3), 132.1ϩ, 128–126 (m, remaining Ph × 3), 81.4ϩ
(CHOBn), 70.5Ϫ (PhCH2) and 41.9Ϫ; m/z (FAB) 337.2 (100,
MNaϩ).
13 A. D. Buss, W. B. Cruse, O. Kennard and S. Warren, J. Chem. Soc.,
Perkin Trans. 1, 1984, 243 (There is a mistake in this paper; HA and
HB have been transposed in structures 10 and 11).
14 J. Clayden, E. W. Collington, J. Elliott, S. J. Martin, A. B. McElroy,
S. Warren and D. Waterson, J. Chem. Soc., Perkin Trans. 1, 1993,
1849.
(1S,3E)- and (1S,3Z)-1,4-Diphenyl-3-methylbut-3-en-1-yl benzyl
ether 53
15 J. Clayden and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1994,
1529.
n-Butyllithium (2.3 cm3 of a 1.3 mol dmϪ3 solution in hexanes,
3.0 mmol) was added dropwise to the phosphine oxide 51
(1.16g, 2.72 mmol) in dry THF (10 cm3) at Ϫ78 ЊC. After 15
min, freshly distilled furfural (0.25 cm3, 3.0 mmol) was added
dropwise, the reaction was stirred for 30 min at Ϫ78 ЊC,
warmed gradually to room temperature over 1 h, quenched
with water (10 cm3), extracted with dichloromethane (3 × 10
cm3), dried (MgSO4) and evaporated under reduced pressure to
give a crude product. By the general method described above, a
portion of this crude product (239 mg, ca. 0.46 mmol) and
sodium hydride (28 mg, 0.70 mmol) gave the alkenes 53 (58 mg,
35% over 2 steps, E:Z 64:36 mixture) as a liquid, Rf 0.38 (30:1
hexane–EtOAc); [α]D20 Ϫ19.2 (c 2.20 in CHCl3; 100% ee) (Found:
PhCHOBn, 197.0975. C23H24O requires PhCHOBn, 197.0966);
16 D. Cavalla, W. B. Cruse and S. Warren, J. Chem. Soc., Perkin Trans.
1, 1987, 1883.
17 K. Okuma, Y. Tanaka, H. Ohta and H. Matsuyama, Bull. Chem.
Soc. Jpn., 1993, 66, 1623.
18 H. C. Kolb, M. S. VanNieuwenhze and K. B. Sharpless, Chem.
Rev., 1994, 94, 2483.
19 J. A. Dale, D. L. Dull and H. S. Mosher, J. Org. Chem., 1969, 34,
2543.
20 H. C. Kolb and K. B. Sharpless, Tetrahedron, 1992, 48, 10515.
21 (a) J. Clayden, A. Nelson and S. Warren, Tetrahedron Lett., 1997, 38,
3471; (b) B. Bartels, J. Clayden, C. Gonzalez Martín, A. Nelson,
M. G. Russell and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1999,
1807.
22 D. J. Hart and W.-L. Wu, Tetrahedron Lett., 1996, 37, 5283 and
references therein.
23 For example, see: (a) M. L. F. Cadman, L. Crombie, S. Freeman and
J. Mistry, J. Chem. Soc., Perkin Trans. 1, 1995, 1397; (b) A. Alexakis,
N. Lensen, J.-P. Tranchier, P. Mangeney, J. Feneau-Dupont and J. P.
Declercq, Synthesis, 1995, 1038.
νmax/cmϪ1 (CHCl ) 1630 (C᎐C) and 1596 (Ph); δ (400 MHz;
᎐
3
H
CDCl3) 7.45–7.25 (15 H, Ph × 3), 6.40 (1 H, dd, J 1.9 and 3.3,
PCHmaj), 6.35 (1 H, dd, J 1.8 and 3.3, PCHmin), 4.61 (1 H, dd,
J 5.9 and 8.0, CHOBnmin), 4.50 (1 H, m, CHOBnmaj and
PhCHAHBmaj ϩ min), 4.29 (1 H, d, J 12.0, PhCHAHBmin), 4.28
(1 H, d, J 12.0, PhCHAHBmaj), 3.02 (1 H, dd, J 8.0 and 13.2,
CHAHBmin), 2.72 (1 H, mmaj ϩ min), 2.46 (1 H, dd, J 5.0 and 13.8,
CHAHBmaj), 1.93 (3 H, d, J 0.9, Memaj) and 1.76 (3 H, d, J 1.0,
24 T. L. Brown, Pure Appl. Chem., 1970, 23, 447.
25 Preliminary communication: D. Cavalla, C. Guéguen, A. Nelson,
M. G. Russell and S. Warren, Tetrahedron Lett., 1996, 38, 7465.
26 S. Thayumanavan, S. Lee, C. Liu and P. Beak, J. Am. Chem. Soc.,
1994, 116, 9755.
27 (a) R. Noyori, M. Tokunaga and M. Kitamura, Bull. Chem. Soc.
Jpn., 1995, 68, 36; (b) R. S. Ward, Tetrahedron: Asymmetry, 1995, 6,
1475.
28 (a) D. B. Dess and J. C. Martin, J. Org. Chem., 1983, 48, 4155; (b)
D. B. Dess and J. C. Martin, J. Am. Chem. Soc., 1991, 113, 7277; (c)
R. E. Ireland and L. Liu, J. Org. Chem., 1993, 58, 2899.
29 R. J. Boeckmann Jr., in Encyclopaedia for Organic Synthesis, ed.
L. A. Paquette, Wiley, New York, 1995, vol. 7, p. 4982.
30 G. Hutton, T. Jolliff, H. Mitchell and S. Warren, Tetrahedron Lett.,
1995, 36, 7905.
Memin); δC (100 MHz; CDCl3) 153.6Ϫ (CMe᎐CHmaj), 153.2Ϫ
᎐
(CMe᎐CHmin), 142.5Ϫ (min), 142.2Ϫ (maj), 138.4Ϫ (maj), 135.9Ϫ
᎐
(min), 134.7Ϫ (maj, ipso-Ph), 128.5–126.5 (m, remaining
Ph × 3), 116.6ϩ (maj), 116.1ϩ (min), 81.8ϩ (CHOBnmin), 80.3ϩ
(CHOBnmaj), 70.4Ϫ (PhCH2maj ϩ min), 31.9Ϫ (CH2maj ϩ min), 26.1ϩ
(Memin) and 19.2ϩ (Memaj); m/z 197.1 (85%, PhCHOBn) and
91.1 (100, Bn).
31 (a) E. W. Collington, J. G. Knight, C. J. Wallis and S. Warren,
Tetrahedron Lett., 1989, 30, 877; (b) K. M. Brown, N. J. Lawrence,
J. Liddle, F. Muhammad and D. A. Jackson, Tetrahedron Lett.,
1994, 35, 6733; (c) B. Lythgoe, T. A. Moran, M. E. N. Nambudiry
and S. Ruston, J. Chem. Soc., Perkin. Trans. 1, 1976, 2386; (d)
E. Vedejs, J. B. Campbell, R. C. Gadwood, J. D. Rodgers, K. L.
Spear and Y. Watanabe, J. Org. Chem., 1982, 47, 1534; (e) J. M.
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