Synthesis of allyl phosphine oxides/boranes via Horner reaction of bis(diphenylphosphine)ethane monoxide reagent with an aldehyde

Article abstract of DOI:10.1016/S0040-4020(03)01057-3

The Horner-Wittig addition-elimination reaction using bis(diphenylphosphine)ethane monoxide [DIPHOS(O)] with an aldehyde affords Z-allyl phosphine oxides/boranes. Alternatively, the stereoselective Lewis acid mediated intermolecular reduction of its γ-ketobisphosphoranes and stereoselective intramolecular reduction of γ-ketophosphine·borane derivatives followed by elimination of diphenylphosphinate affords E-allyl phosphine oxides/boranes with good to high selectivity. Allyl phosphine oxides are common intermediates in the synthesis of polyenes.

Full text of DOI:10.1016/S0040-4020(03)01057-3

Tetrahedron 59 (2003) 7177–7187
Synthesis of allyl phosphine oxides/boranes via Horner reaction of
bis(diphenylphosphine)ethane monoxide reagent with an aldehyde
*
Salvacion T. Cacatian and Philip L. Fuchs
Department of Chemistry, Purdue University, 560 Oval Dr., W. Lafayette, IN 47907, USA
Received 27 May 2003; revised 3 July 2003; accepted 3 July 2003
Abstract—The Horner–Wittig addition–elimination reaction using bis(diphenylphosphine)ethane monoxide [DIPHOS(O)] with an
aldehyde affords Z-allyl phosphine oxides/boranes. Alternatively, the stereoselective Lewis acid mediated intermolecular reduction of its
g-ketobisphosphoranes and stereoselective intramolecular reduction of g-ketophosphine·borane derivatives followed by elimination of
diphenylphosphinate affords E-allyl phosphine oxides/boranes with good to high selectivity. Allyl phosphine oxides are common
intermediates in the synthesis of polyenes.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
Allyl phosphine oxides 2, are common precursors for the
synthesis of conjugated polyenes 1 (Scheme 1), upon
reaction with aldehydes. Bisphosphorus reagents initially
appear to be interesting candidates. Previously, bis-Wittig,
bis-Horner–Wittig, and bis-HWE have been employed to
prepare olefin and aryl polymers. More specifically,
bisphosphorus reagents bis(diphenylphosphine oxide)
Numerous natural products containing conjugated polyenes
have been synthesized using the current state-of-the-art Pd-
mediated coupling1 of a vinyl halide and vinyl metal that
have, in turn, been prepared from aldehydes/enones.
Traditional methods using stabilized Wittig or Horner–
Wadsworth–Emmons also necessitate functional group
transformations to install a phosphorous moiety or to
unmask a latent aldehyde.
ethane4 and an in situ generated Ph3P¼CHCH2PO(OR)2
5
have been reported. These reagents have not been
extensively developed and/or have shown limitations such
as restricted aldehyde types, lack of regio- and stereocon-
trol, and low yields. The attraction of 4 was the possibility of
a one pot bis-olefination reaction. Other encouraging
attributes included its availability,6 the potential for a
stereocontrolled Horner-addition, regiocontrol due to oxi-
datively-differentiated bis-phosphines, and the well-known
ease of work-up (the phosphinic acid anion is washed away
with water). Additionally, the Horner reaction of simple
alkyl7 and allyl8 phosphine oxides 2 have been extensively
studied, providing a solid base of experimental and spectral
data.
In conjunction with our program to synthesize a collection
of polypropionate segments with carbonyl differentiated
termini,2 we have also been investigating new methods for
the formation of polyenes, specifically the ubiquitous 1,3-
diene moiety3 and methyl substituted versions thereof. We
specifically sought development of a method that joined two
aldehydes, with concomitant addition of the two central
carbons.
2. Results and discussion
2.1. Horner–Wittig addition–elimination using
DIPHOS(O) 4
Scheme 1. Synthesis of polyenes via allyl phosphine oxides.
We wish to report our study on the use of 4 as a Horner
reagent for the synthesis of 2, a key diene precursor
(Scheme 1).8 Initial investigation of a one pot method, via
addition of dimethylformamide as a cosolvent and Kþ/Naþ
cation exchange prior to warming to room temperature,
afforded unacceptably low yields of 2 due to incomplete
Keywords: polyenes; Horner–Wittig reaction; addition–elimination
reaction.
*
Corresponding author. Tel.: þ1-765-494-5242; fax: þ1-765-494-7679;
e-mail: pfuchs@purdue.edu
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01057-3

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S. T. Cacatian, P. L. Fuchs / Tetrahedron 59 (2003) 7177–7187
Table 1. Horner–Wittig addition using DIPHOS(O) 4
Scheme 2. Synthesis of g-ketobisphosphorane derivatives 7–9.
THF with 1.2 equiv. of nBuLi to afford a deep orange–red
solution.12 After 20–25 min, 1 equiv. of aldehyde is added
as a THF solution. This was followed by functionalization
of the remaining phosphine via addition of 30% hydrogen
peroxide or BH3·DMS to afford alcohols 5 and 6,
respectively. The primary Horner olefination reaction of
alcohols 5b–c and 6a–c was generally initiated by
treatment with NaH in DMF at 25–308C. This served to
eliminate diphenylphosphinate anion providing allylic
phosphorus species 2b–c and 3a–c in 51–96% yield.13
Although small amounts of vinyl phosphine oxides and
vinyl phosphine·boranes stemming from isomerization of
2/3 were observed, the elimination reaction was uniformly
stereospecific.
R
X
Additivea
Alcohol
Anti/synb (yield)
1
2
3
4
5
6
7
8
Me
Me
Me
Me
nPr
nPr
nPr
O
–
5a
6a
6a
6a
5b
5b
6b
5c
5c
6c
5d
75:25 (55%)
75:25 (57%)
83:17 (74%)
75:25 (64%)
75:25 (85%)
86:14 (46%)
75:25 (85%)
89:11 (91%)c
87:13 (50%)
89:11 (73%)
50:50 (79%)
BH3
BH3
BH3
O
O
BH3
O
O
BH3
O
–
HMPA
TMEDA
–
HMPA
–
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
iPr
–
HMPA
–
–
9
10
11
a
1 equiv. additive, added 15 min before addition of aldehyde.
Anti/syn ratios determined by 31P NMR.
2 equiv. hydrocinnamaldehyde.
b
c
2.2. Stereoselective reduction of g-ketobisphosphine
oxide and g-ketophosphine·borane derivatives
elimination, retro-aldol, and b-elimination side reactions. A
standard Warren protocol was adopted where the alcohol
intermediates were isolated as the bisphosphine oxide 5 or
the phosphine·borane9 6 respectively, in 50–91% yield
(Table 1). The Horner addition reactions of 4 only gave
moderate diastereoselectivity, favoring the anti alcohol
adducts.7a,10 The aldehyde with the larger alkyl group,
hydrocinnamaldehyde gave the highest anti alcohol ratio
$87:13. Aldehydes with smaller or branched substituents
provided alcohols with lower selectivity. Additives such as
HMPA11 were only beneficial when the aldehyde was small,
R¼Me, nPr. TMEDA11 did not provide any improvement.
Typical conditions involved deprotonation of 4 at 2788C in
Stereoselective reduction of the g-ketobisphosphine oxides
and g-ketophosphine·boranes was also investigated.
Ketones 7/8 were primarily obtained by Swern14 oxidation
of alcohols 5 and 6. g-Ketobisphosphine oxide 7b was also
acquired in 45% yields, using Warren’s modified conditions
of lithiated 4 with ethyl buytrate at 2908C, followed by
oxidation.7a Deprotection of phosphine·borane 8c with
DABCO9b in toluene afforded ketone 9c with no evidence
of borane-mediated ketone reduction.14 (Scheme 2)
2.2.1. Intermolecular reduction. Preliminary studies using
Table 2. Lewis acid assisted reduction of ketones 7–9
Entry
Ketone
R
X
Solvent
Lewis acid
H2
Alcohol
X
Anti/syn (yield%)a
1
2
3
4
5
6
7
8
7b
8c
7c
7c
7c
7a
7d
8b
9c
8a
8b
8c
7c
9c
nPr
O
BH3
O
O
O
O
O
BH3
CH2Cl2
CH2Cl2
EtOH
–
–
LiBH4
LiBH4
NaBH4
LiBH4
LiBH4
LiBH4
LiBH4
LiBH4
LiBH4
LiBH4
LiBH4
LiBH4
LiBH4
LiBH4
5b
6c
5c
5c
5c
5a
5d
6b
6c
6a
6b
6c
5c
6c
O
BH3
O
O
O
33:67 (97%)
13:87 (98%)
17:83 (93%)
2:98 ($98%)
1:99 ($98%)
2:98 ($99%)
1:99 (98%)
33:67 ($98%)
30:70 (91%)
17:83 (69%)
6:94 (79%)
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
Me
iPr
nPr
(CH2)2Ph
Me
nPr
CeCl3
CeCl3
CeCl3
CeCl3
CeCl3
CeCl3
CeCl3
Ti(OiPr)4
Ti(OiPr)4
Ti(OiPr)4
TiCl4
TiCl4
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
O
O
BH3
BH3
BH3
BH3
BH3
O
9
10
11
12
13
14
BH3
BH3
BH3
O
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
6:94 ($98%)
20:80 (98%)
63:37 (93%)
BH3
1.3 equiv. Lewis acid. 5 equiv. reducing agent was added at 2788C.
Anti/syn ratio determined by 31P NMR.
a

S. T. Cacatian, P. L. Fuchs / Tetrahedron 59 (2003) 7177–7187
7179
completely dissolve in either tetrahydrofuran or methylene
chloride solvent, thus likely changing Lewis acid–substrate
ratios. This is further supported by the high coordination
ability of cerium. The syn favored reduction of 8 with
Ti(OiPr)4/LiBH4/CH2Cl2 is attributed to formation of a
reduction intermediate according to Felkin Anh guidelines.
Ti(OiPr)4 apparently is bulky enough to favor complexation
with one lewis base. The largest substituent, the 2-diphenyl-
phosphine oxide, is expected to be perpendicular to the
carbonyl whereupon hydride delivery occurs opposite the
phosphine oxide (transition state A, Scheme 3).
Scheme 3. Proposed Felkin–Anh transition state model of Ti(OiPr)4/LiBH4
reduction of g-ketophosphine·borane.
Warren’s7a modified reduction procedures (NaBH4/EtOH,
CeCl3/NaBH4/EtOH) afforded good selectivity but were
quite substrate related. Other protocols such as CeCl3/
LiBH4/CH2Cl2 and TiCl4/LiBH4/CH2Cl2 appeared less
substrate dependent15,16 and were, therefore, further investi-
gated. The use of cerium trichloride provided excellent
yields of alcohols 5 with high syn specificity. The selectivity
was found to be most dependent on the functionalization of
the distal phosphine. In the case of g-ketobisphosphine
oxides 7, high diastereoselectivity was obtained (#2:98
ratio) and was independent of the size of R. In contrast,
g-ketophosphine·borane 8b and ketophosphine 9c (X¼lone
pair) afforded lower ratios. Additionally, high syn
selectivity is achieved when using Ti(OiPr)4 with phos-
phine·borane 8a–c. (Table 2)
The TiCl4/LiBH4/CH2Cl2 method15 was anticipated to favor
formation of the anti alcohol due to chelation transition state
C where the phosphinomethyl substituent is pseudoaxial,
avoiding steric interaction with the R substituent
(Scheme 4). As in the case of 5-alkyl-1,3-dioxanes,17 the
presence of only lone pairs in the two 1,3-diaxial positions
nicely accommodates the axial phosphinomethyl group with
minimal steric destabilization. Axial attack with a hydride is
favored since a lower energy chair intermediate E will form
as opposed to a twist boat conformation D via equatorial
hydride attack. The unexpected syn isomer is obtained in a
20:80 ratio with 7b (Entry 13, Table 2). Compound 9c
(X¼lone pair) is the only substrate that favors the formation
of an anti alcohol which is isolated as the borane-protected
alcohol 6c, albeit only a 63:37 anti/syn ratio is achieved.
Ketone 9c (X¼lone pair), is protected in situ with borane
that is generated during the reduction.18 g-Ketobisphos-
phine oxide 7c and ketophosphine 9c both bear an additional
Lewis base which competes for chelation. The competitive
chelation (B/C vs. F) is likely the cause for the lowered
selectivity. Using the DIPHOS(O) methodology, anti
alcohols are obtained with higher diastereoselectivity during
initial Horner addition.
The intermolecular reduction selectivity, when using CeCl3,
does not follow previously reported trends leading us to
believe the reduction of substrates 7–9 may be governed by
different Lewis acid–substrate complexes. Upon prolonged
mixing of CeCl3 and the ketone substrate, the CeCl3 did not
2.2.2. Intramolecular reduction. Addition of TiCl4 to
g-ketophosphine·borane 8c served to initiate intramolecular
reduction (Table 3).19 Similar to the intermolecular
reductions, TiCl4 was expected to form a six membered
ring with the b-ketophosphine oxide favoring conformation
C and C0 [rotational isomer] (Scheme 5). In conformation
C0, a hydride would add syn to the phosphinomethyl.
Additionally, TiCl4 was necessary to activate the carbonyl
for reduction.19 Heating g-ketophosphine·borane 8c in
toluene at reflux afforded no reduction product. Confor-
mation C0, as opposed to B0, is the expected transition state
Table 3. TiCl4 mediated intramolecular reduction of ketones 8c
Entry
[CH2Cl2]
Lewis acid
T (8C)
Anti/syn (yield%)a
1
2
3
4
0.1
TiCl4
TiCl4
TiCl4
BF3·OEt2
25
25
278
25
20:80 (98%)
5:95 (93%)b
13:87 (78%)
20:80 (90%)c
0.003
0.003
0.003
a
Anti/syn ratio determined by 31P NMR.
30 min, 20 equiv. K2CO3 or polyvinylpyridine.
12 h.
b
c
Scheme 4. Proposed closed chain transition states for the reduction of
ketones 7,9 with TiCl4/LiBH4.

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S. T. Cacatian, P. L. Fuchs / Tetrahedron 59 (2003) 7177–7187
Scheme 7. Synthesis of trisubstituted allyl phosphine oxides/boranes 12/13.
pounds BD3-8c (R¼(CH2)2Ph) with 8a (R¼Me) followed
by standard Horner reaction resulted in ,5^5% deuterium
incorporation in the elimination products 2a hence demon-
strating intramolecular reduction. The rate of reduction was
not a factor as the cross reduction of BD3-8a (R¼Me) with
8c (R¼(CH2)2Ph) provided similar deuterium incorporation
in 2c (Schemes 6 and 7).
Scheme 5. Closed chain transition states for intramolecular reduction.
that leads to reduction where the phosphinomethyl takes a
pseudoaxial position instead of a pseudoequatorial position.
Reduction via C0 leads to an unfavored twist boat reduction
transition state D0, instead of the lower energy chair
transition state E0, but is favored since it avoids the 1,3-
diaxial type interactions encountered in conformation B0.
Preliminary experiments showed TiCl4 in methylene
chloride to be the best reaction system. Reduction occurred
faster and afforded higher selectivity when compared to
BF3·Et2O. The addition of highly Lewis acidic TiCl4
catalyzed intramolecular reduction in less than one minute
at room temperature. When followed by peroxide oxidation
this reaction afforded syn-5c with good selectivity 20:80
anti/syn in .90% yields. The selectivity was further
improved to 5:95 anti/syn by diluting the solution and
adding crushed potassium carbonate or polyvinyl pyridine.
Lowering the reaction temperature still afforded good
selectivity, justifying C0 leading to reduction, since the
lower energy conformer increases at lower temperatures.
The lowered activation energy of the intramolecular
reaction overcomes the formation of a higher energy
disfavored twist boat conformation D0 upon “pseudoaxial”
attack. Cross reactions using deuterated borane20 com-
2.3. Trisubstituted allyl phosphoranes
Trisubstituted alkenes, such as 1-methyl-1,3-dienes, are
very desirable targets which can be obtained from
trisubstituted allyl phosphine oxides. Reactions with methyl
ketones and 4 gave poor selectivity. Therefore methylations
of the g-ketobisphosphine oxides 7 and g-ketobisphos-
phine·boranes 8 were attempted. Ketones 7c and 8c were
employed as initial substrates in nucleophilic methylation
reactions to provide alcohols 10 and 11. Horner–Wittig
elimination of these alcohols gave the trisubstituted allyl
phosphines 12 and 13 in 50–79% yield (over two steps).
Study of these reactions revealed that the methylation of 7c
and 8c worked best with trimethylaluminum in methylene
chloride and methyl organocerium in tetrahydrofuran,21
respectively. Grignard reagent MeMgBr was too basic and
other non-basic reagents such as methyltitaniumtrichlor-
ide22 or methylmanganesechloride23 afforded no product
when applied to ketone 7b or catalyzed unwanted
intramolecular reduction with ketone 8b. Trimethyl-
aluminum was used on substrate 7c which delivered the
syn-10 alcohol with 14:86 ratio in 61% conversion.
Elimination of 10 then provided the E-12 alkene in 50%
yield. The syn alcohol is again attributed to Felkin–Anh
transition state A, followed by intermolecular methyl
addition. Comparisons with 8c using Me3Al could not be
achieved because of competing intramolecular reduction.
The use of MeCeCl2 on ketone 8c afforded the expected
anti-11 alcohol whereupon elimination afforded the alkene
Z-12 in 92:8 Z/E ratio in 50% yield over two steps. The Z
assignment was further confirmed by deprotection of anti-
11 with DABCO9b and elimination to afford Z-12 in 68%
yield. The selectivity’s attributed to intramolecular transfer
from a MeCeCl2 ketone complex similar to that of transition
state A (Scheme 3).15
Scheme 6. Determination of intramolecular reduction via deuterated cross
reactions.

S. T. Cacatian, P. L. Fuchs / Tetrahedron 59 (2003) 7177–7187
7181
2.4. 31-Phosphorus NMR
4. Experimental
The 31P NMR of alcohols syn-5/6 and anti-5/6 revealed
coupling constants and chemical shifts that were useful in
assigning stereochemistry. The syn-5/6 alcohols evidenced
larger coupling constants (JP–P¼43–52 Hz) compared to
the anti-5/6 alcohols which displayed smaller coupling
constants (JP–P¼24–36 Hz).24 The difference in coupling
constants between the syn- and anti-5/6 alcohols is
attributed to a change in dihedral angle F between the
two phosphorus nuclei (P1 and P2), similar to a Karplus type
correlation.25 In turn, the P1–P2 F is affected by the
conformation of the hydroxyl bearing carbon C3. The
expected C3 conformation, has the larger R group anti to
the large P2 substituent. The hydrogen bonding does not
have an affect on this conformation.26 The syn-5/6 alcohols
JP–P correlates to a theoretical maximum value (50 Hz)
associated with bisphosphines.27 The anti-5/6 alcohols have
a decreased coupling constant due to interactions between
the distal phosphine P1 and the substituents on C3. The
additional gauche interaction between the methylene
phosphine P1 with the hydroxyl and alkyl substituent of
the anti alcohol (H) compared to a single gauche interaction
with the alkyl substituent in the syn alcohol (G) instigates
rotation of the C1–C2 bond and a decrease in the dihedral
angle between P1 and P2 (H0). With respect to methyl
carbinols 10 and 11, JP–P for both isomers are also closer in
size (JP–P¼32–38 Hz) indicating the P1–P2 F in syn-10/11
alcohols has shifted. The reason is easily seen in projection
H/H0, where Y¼Me for alcohols syn-10/11 instead of Y¼H
for alcohols syn-5/6, introducing an additional 1,3-diaxial
type interaction causing P1 to rotate away from the C3
substituents. (Scheme 8)
4.1. Synthesis of anti-5/6 alcohols
General procedure for the reaction of 4. To a solution of 4
(4.82 mmol) in 161 mL THF at 2788C nBuLi (2.8 mL,
2.1 M hexanes) was added dropwise to afford an orange
solution. After stirring for 25 min at 2788C the solution
color darkened to a deep orange–red color. A tetrahydro-
furan solution (1.2 M) of freshly distilled butanal
(4.82 mmol) was transferred dropwise to lithiated 4. The
reaction color slowly changed to a light yellow color. The
reaction continued to stir for 30 min. A saturated
ammonium chloride solution was then added at 2788C, to
minimize formation of elimination products, and the
reaction was allowed to warm to room temperature. A
slight excess of 30% H2O2 was added. The mixture was
washed with water then saturated sodium bisulfite. The
organic layer was then washed with brine, dried (MgSO4),
and filtered. The solvent was evaporated to afford a white
solid and purified using column chromatography (EtOAc/
hex).
General procedure for the synthesis of 6. To a solution of 4
(7.25 mmol) in 242 mL THF at 2788C nBuLi (4.1 mL,
2.1 M hexanes) was added dropwise. After stirring for
25 min at 2788C, a THF solution (1.2 M) of freshly distilled
acetaldehyde (7.25 mmol) was transferred dropwise. The
reaction continued to stir for 30 min. BH3·DMS (22 mmol,
2 M DMS) was then added and the reaction was allowed to
warm to 2108C over 4 h. The excess borane was then
quenched with excess water until hydrogen evolution
ceased. The organic layer was separated from the aqueous
layer. The aqueous layer was extracted with EtOAc. The
organic layers were combined and washed with brine
solution dried (MgSO4), and filtered.
4.1.1. anti-3,4-Bis-(diphenylphosphinoyl)-butan-2-ol
1
(anti-5a). White solid: Rf¼0.48 (90% EtOAc/MeOH). H
NMR (300 MHz, CDCl3) d 0.90 (3H, d, J¼6 Hz),
2.48–2.65 (1H, m), 2.81–3.11 (2H, m), 4.24 (1H, m), 4.5
(1H, br s), 7.28–7.96 (20H, m). 13C NMR (75 MHz, CDCl3)
d 22.85 (d, J¼11 Hz), 22.88 (d, J¼68 Hz), 37.9, 64.3,
127.9–133.1. 31P NMR (121 MHz, CDCl3) d 31.9, 40.0
(JP–P¼35 Hz). HRMS (CI) mixed sample calculated for
C28H28O3P2 475.1592, observed 475.1598.
4.1.2. anti-1,2-Bis-(diphenylphosphinoyl)-hexan-3-ol
(anti-5b). A white solid was isolated with .95% purity.
1
Mp 125–1278C; Rf¼0.20 (EtOAc). H NMR (300 MHz,
CDCl3) d 0.52 (3H, t, J¼7 Hz), 0.88 (1H, m), 1.01–1.28
(3H, m), 2.49–2.65 (1H, m), 2.93–3.20 (2H, m), 3.98–4.04
(1H, m), 4.50 (1H, br s), 7.30–7.93 (20H). 13C NMR
(75 MHz, CDCl3) d 13.4, 18.7 (d, J¼68 Hz), 36.7 (d,
J¼71 Hz), 38.8 (d, J¼11 Hz), 68.1, 128.5–133.6. 31P NMR
(121 MHz, CDCl3) d 31.6, 41.0 (JP–P¼34 Hz). HRMS (CI)
mixed sample calculated for C30H32O3P2 503.1905,
observed 503.1905.
Scheme 8. Newman projections of alcohols 5, 6 and 10, 11.
3. Conclusion
DIPHOS(O) 4 is a valuable reagent for the formation of
polyene systems with carbonyl starting materials via allyl
phosphorane intermediates. Initial stereoselective olefin
synthesis is supplied via Horner–Wittig addition, stereo-
selective ketone reduction, intramolecular phosphine·
borane ketone reduction, or stereoselective nucleophilic
methylation.
4.1.3. anti-1,2-Bis-(diphenylphosphinoyl)-5-phenyl-pen-
tan-3-ol (anti-5c). White solid (.95% purity): mp 98–
1
998C, Rf¼0.40 (EtOAc). H NMR (300 MHz, CDCl3) d
1.18–1.29 (1H, m), 1.50–1.62 (1H, m), 2.32–2.40 (1H, m),

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S. T. Cacatian, P. L. Fuchs / Tetrahedron 59 (2003) 7177–7187
2.42–2.67 (2H, m), 2.95–3.12 (2H, m), 4.00–4.07 (1H, m),
4.39 (1H, br s), 6.82–7.85 (25H, m). 13C NMR (75 MHz,
CDCl3) d 23.1 (d, J¼69 Hz), 31.8, 37.2 (dd, J¼67, 4 Hz),
38.9 (d, J¼10 Hz), 67.5, 125.3–141.3. 31P NMR (121 MHz,
CDCl3) d 32.5, 40.4 (JP–P¼36 Hz).
(0.45 mmol) was added. After stirring for 1 h LiBH4
(0.88 mL, 2 M THF) was added. The reaction was kept at
2788C for 2 h before slowly warming up to room
temperature over 12 h. The reaction was slowly quenched
with water. The aqueous layer was extracted with CH2Cl2.
The combined organic layers were then washed with brine,
dried (Na2SO4), and filtered.
4.1.4. anti-2-Diphenylphosphinoyl (diphenylphosphine·
borane-butan-3-ol) (anti-6a). White solid. Mp 142–1508C
(slight dec.), Rf¼0.54 (EtOAc). 1H NMR (300 MHz,
CDCl3) d 0.4–1.7 (3H, br m), 0.78 (3H, d, J¼6 Hz),
2.23–2.40 (1H, m), 3.01–3.15 (1H, m), 3.22–3.30 (1H, dt,
J¼20, 6 Hz), 3.98 (1H, br s), 4.19–4.27 (1H, m, J¼11,
6 Hz), 6.96–7.93 (20H, m). 13C NMR (75 MHz, CDCl3) d
18.1 (d, J¼34 Hz), 21.4 (d, J¼14 Hz), 39.1 (dd, J¼64,
3 Hz), 64.9, 128.4–132.8. 31P NMR (121 MHz, CDCl3) d
21.0 (br m), 42.2 (JP–P¼33 Hz). 11B NMR (96 MHz,
CDCl3) d 40 (br s). HRMS (ESI) mixed sample calculated
for C28H32O2P2B 473.3927, observed 473.3926. Anal.
Calcd C, 71.20; H, 6.62; P, 13.12; B, 2.29. Found: C,
70.82; H, 6.65; P, 12.76; B, 2.46
General procedure for the intramolecular reduction of
ketone 8c to affordsyn-5c alcohol. To a solution of ketone 8c
(0.070 mmol) in 23 mL of CH2Cl2 at 258C polyvinyl
pyridine (60 mg) was added. After stirring for 5 min, neat
TiCl4 (0.091 mmol) was quickly added and the reaction was
allowed to stir for another 30 min. The solvent was
evaporated and the crude solid was redissolved in THF.
The reaction solution was treated with 2 mL 30% H2O2.
This solution was allowed to stir for 24 h before washing
with water followed by sodium bisulfite wash. The organic
layer was washed with brine, dried over Na2SO4, and
filtered.
4.1.5. anti-2-Diphenylphosphinoyl(diphenylphosphine·
borane-hexan-3-ol) (anti-6b). The 75:25 anti/syn mixture
afforded a white solid: mp 38–458C (slight dec.); Rf¼0.57
(EtOAc). 1H NMR (300 MHz, CDCl3) d 0.47 (3H, t,
J¼7 Hz), 0.6–1.8 (3H, br m), 0.77–1.20 (4H, m), 2.22–
2.39 (1H, m), 3.09–3.36 (2H, m), 3.98 (1H, m), 4.18 (1H, s),
6.96–7.97 (20H, m). 13C NMR (75 MHz, CDCl3) d 13.4,
18.5 (d, J¼35 Hz), 18.9, 37.5, 38.0 (d, J¼53 Hz), 68.9,
128.2–133.2. 31P NMR (121 MHz, CDCl3) d 21.4 (br m),
42.5 (d, JP–P ¼33 Hz). Anal. Calcd for C30H35BO2P2
(500.36): C, 72.01; H, 7.05. Found: C, 71.88; H, 7.25.
4.2.1. syn-3,4-Bis-(diphenylphosphinoyl)-butan-2-ol
(syn-5a). White solid: Rf¼0.64 (9:1 EtOAc/MeOH). 1H
NMR (300 MHz, CDCl3) d 1.43 (3H, d, J¼7 Hz),
2.25–2.40 (1H, m), 2.80–3.00 (2H, m), 4.03–4.10 (1H,
m), 6.05 (1H, br s), 7.34–7.87 (20H, m). 13C NMR
(75 MHz, CDCl3) d 20.7, 23.5 (d, J¼66 Hz), 40.8 (d,
J¼64 Hz), 65.4, 129.1–132.6. 31P NMR (121 MHz, CDCl3)
d 34.2, 35.8 (JP–P¼51 Hz).
4.2.2. syn-1,2-Bis-(diphenylphosphinoyl)-hexan-3-ol
(syn-5b). White solid (.95% purity): mp 140–1428C;
Rf¼0.30 (EtOAc). 1H NMR (300 MHz, CDCl3) d 0.78 (3H,
t, J¼8 Hz), 1.16–1.32 (1H, m), 1.50–1.80 (3H, m), 2.29–
2.44 (1H, m), 2.81–3.01 (2H, m), 3.79 (1H, app t, J¼9 Hz),
4.40 (1H, br s), 7.36–7.76 (20H, m). 13C NMR (75 MHz,
CDCl3) d 13.6, 19.5, 23.8 (d, J¼66 Hz), 36.5, 40.3, (d,
J¼63 Hz), 69.0 (d, J¼4 Hz), 128.7–132.3. 31P NMR
(121 MHz, CDCl3) d 34.5, 36.0 (JP–P¼51 Hz).
4.1.6. anti-2-Diphenylphosphinoyl-5-phenyl(diphenyl-
phosphine·borane-pentan-3-ol) (anti-6c). White foam:
1
mp 128–1328C; Rf¼0.45 (EtOAc). H NMR (300 MHz,
CDCl3) d 0.4–1.7 (3H, m), 1.05–1.30 (2H, m), 2.23–2.54
(3H, m), 3.12–3.39 (2H, m), 3.82 (1H, br s), 4.04 (1H, m),
6.75–7.93 (25H, m). 13C NMR (75 MHz, CDCl3) d 18.6 (d,
J¼34 Hz), 31.9, 37.1 (d, J¼13 Hz), 38.3 (dd, J¼68, 3 Hz),
68.4, 125.4–141.2. 31P NMR (121 MHz, CDCl3) d 21.0 (br
s), 42.3 (JP–P¼34 Hz). Anal. Calcd for C35H37BO2P2
(562.43): C, 74.74; H, 6.63. Found: C, 74.86; H, 6.63.
4.2.3. syn-1,2-Bis-(diphenylphosphinoyl)-5-phenyl-pen-
tan-3-ol (syn-5c). White solid (.95% purity). Mp 128–
1
1328C; Rf¼0.45 (EtOAc). H NMR (300 MHz, CDCl3) d
2.01–2.13 (1H, m), 2.18–2.31 (1H, m), 2.34–2.46 (1H, m),
2.58–2.68 (1H, m), 2.81–3.20 (3H, m), 3.82 (1H, t,
J¼10 Hz), 4.47 (1H, br s), 7.10–7.68 (25H, m). 13C NMR
(75 MHz, CDCl3) d 23.9 (d, J¼66 Hz), 32.2, 35.9, 40.4 (d,
J¼61 Hz), 67.9 (d, J¼4 Hz), 125–142. 31P NMR
(121 MHz, CDCl3) d 34.4, 36.2 (JP–P¼52 Hz). HRMS
(CI) mixed sample calculated for C35H34O3P2 564.1878,
observed 564.1878.
4.2. Synthesis of syn-5/6 alcohols
General procedure for the intermolecular reduction of
ketones 7 using CeCl3/LiBH4. A flask containing CeCl3
(0.081 mmol) was placed in a 08C ice bath whereupon
freshly distilled CH2Cl2 (1 mL) was added dropwise to form
a suspension. The CeCl3 was removed from the ice bath and
allowed to stir at room temperature for 2 h. Ketone 7c
(0.063 mmol) was dissolved in CH2Cl2 (5 mL), cannulated
into the CeCl3 solution and stirred for 1 h. The mixture was
cooled to 2788C and LiBH4 (0.10 mL, 2 M THF) was
added. The reaction was kept at 2788C for 2 h before slowly
warming to room temperature over 12 h. The reaction was
slowly quenched with 5% HCl solution followed by
aqueous workup.
4.2.4. syn-2-Diphenylphosphinoyl (diphenylphosphine·
borane-butan-3-ol) (syn-6a). Using the Ti(OiPr)4/LiBH4
reduction method the alcohol (115 mg, 69%) was obtained
with a 20:80 anti/syn ratio. A white solid was obtained with
mp 142–1508C (slight dec.) and Rf¼0.52 (EtOAc). 1H
NMR (300 MHz, CDCl3) d 0.4–1.7 (3H, br m), 0.92 (3H, d,
J¼7 Hz), 2.03 (1H, ap q, J¼14 Hz), 2.72 (1H, br s), 3.10–
3.26 (2H, m), 3.61 (1H, ap q, J¼25, 6 Hz), 6.71–7.88 (20H,
m). 13C NMR (75 MHz, CDCl3) d 22.3 (d, J¼34 Hz), 23.5,
38.5 (d, J¼66 Hz), 69.0 (d, J¼5 Hz), 114–134.5. 31P NMR
(121 MHz, CDCl3) d 19.4 (br m), 39.8 (JP–P¼43 Hz).
General procedure for the intermolecular reduction of
ketones 8 using Ti(OiPr)4/LiBH4. To a solution of ketone 8a
(0.35 mmol) in CH2Cl2 (12 mL) at 2788C Ti(OiPr)4

S. T. Cacatian, P. L. Fuchs / Tetrahedron 59 (2003) 7177–7187
7183
4.2.5. syn-2-Diphenylphosphinoyl(diphenylphosphine·
borane-hexan-3-ol) (syn-6b). Using the Ti(OiPr)4/LiBH4
reduction method, ketone 8b (0.067 mmol) was reduced to
afford alcohol syn-6b (26.0 mg, 79%) with 6:94 anti/syn
ratio. White solid: mp 135–1378C (slight dec.); Rf¼0.57
(EtOAc). 1H NMR (300 MHz, CDCl3) d 0.40 (3H, t,
J¼7 Hz), 0.5–1.8 (3H, br m), 0.85–0.95 (2H, m),
0.98–1.13 (2H, m), 1.23–1.42 (2H, m), 2.11 (1H, m),
3.29 (1H, m), 4.06 (1H, br s), 7.30–7.94 (20H, m). 13C
NMR (75 MHz, CDCl3) d 13.1, 19.3, 22.5 (d, J¼34 Hz),
37.1 (d, J¼65 Hz), 39.2 (d, J¼2 Hz), 73.0 (d, J¼5 Hz),
127.8–133.6. 31P NMR (121 MHz, CDCl3) d 19.1, 40.4
(JP–P¼44 Hz).
NMR (300 MHz, CDCl3) d 1.77 (3H, s), 2.48 (1H,
dq), 3.19–3.30 (1H, m), 4.19 (1H, ap q), 7.36–7.76
(20H, m). 13C NMR (75 MHz, CDCl3) d 27.3 (ABX),
31.9, 48.7 (ABX), 128.5–132.7, 202.3 (d, J¼3 Hz). 31P
NMR (121 MHz, CDCl3) d 30.9 (ap s). HRMS (CI) calc
for C28H26O3P2 473.1435, observed 473.1432.
4.3.2. 1,2-Bis-(diphenylphosphinoyl)-hexan-3-one (7b).
Using Warren’s modification after purification (100%
EtOAc to 10% EtOAc/MeOH) the ketone (22.9 mg, 45%
isolated) was obtained as a white solid: mp¼212–2158C,
Rf¼0.23 (EtOAc). 1H NMR (300 MHz, CDCl3) d 0.53 (3H,
t, J¼7 Hz), 1.05–1.18 (2H, m), 1.81–2.11 (2H, m), 2.47–
2.53 (1H, m), 3.23–3.34 (1H, m), 4.21 (1H, ap d, J¼11 Hz),
7.33–7.79 (20H, m). 13C NMR (75 MHz, CDCl3) d 13.1,
16.1, 27.0 (ABX), 47.7 (ABX), 128.4–132.8, 204.2. 31P
NMR (121 MHz, CDCl3) d 31.1 (ap s). HRMS (CI) calcd.
for C30H30O3P2 501.1748, found 501.1733.
4.2.6. syn-2-Diphenylphosphinoyl-5-phenyl(diphenyl-
phosphine·borane-pentan-3-ol) (syn-6c). Using the
Ti(OiPr)4/LiBH4
reduction
method,
ketone
8c
(0.029 mmol) was reduced to afford the alcohol (16.2 mg,
.98%), as an oil with 6:94 anti/syn ratio. Rf¼0.67 (EtOAc).
1H NMR (300 MHz, CDCl3) d 0.40–1.60 (3H, m),
1.43–1.55 (1H, m), 1.62–1.75 (1H, m), 2.07–2.23 (2H,
m), 2.41–2.50 (1H, m), 3.19–3.48 (3H, m), 4.45 (1H, br s),
6.68–7.94 (25H, m). 13C NMR (125 MHz, CDCl3) d 22.6
(d, J¼33 Hz), 32.3, 37.5 (d, J¼65 Hz), 38.4, 73.0 (d,
J¼4 Hz), 125.1–1419. 31P NMR (121 MHz, CDCl3) d 18.1
(br m), 40.4 (JP–P¼43 Hz). 11B NMR (96 MHz, CDCl3) d
240 (br s).
4.3.3. 1,2-Bis-(diphenylphosphinoyl)-5-phenyl-pentan-3-
one (7c). White solid: mp 218–2218C, Rf¼0.21 (EtOAc).
1H NMR (300 MHz, CDCl3) d 2.21–2.50 (4H, m), 2.50–
2.64 (1H, m), 3.31–3.35 (1H, m), 4.18–4.29 (1H, ap q,
J¼11 Hz), 6.88 (2H, m), 7.15–7.25 (3H, m), 7.4–7.9 (20H,
m). 13C NMR (75 MHz, CDCl3) d 27.2, (d, J¼66 Hz),
29.0, 47.1, 47.8 (d, J¼33 Hz), 123.5–132.5, 140.6, 203.5
(d, J¼8 Hz). 31P NMR (121 MHz, CDCl3) d 30.7, 31.2
(JP–P¼43 Hz). HRMS (EI) calcd for C35H32O3P2 562.1827,
found 562.1813.
4.3. General procedure for the synthesis of g-keto-
phosphines 7–9
4.3.4. 2-Diphenylphosphinoyl(diphenylphosphine·
borane butan-3-one) (8a). Using the general Swern
procedure, the oxidation of alcohol 6a (1.33 mmol) afforded
the ketone (270 mg, 43%) as a fluffy white solid: mp 136–
1408C (slight dec.), Rf¼0.47 (EtOAc). 1H NMR (300 MHz,
CDCl3) d 0.4–1.9 (3H, br s), 1.67 (3H, s), 2.4 (1H, dt, J¼15,
10 Hz), 3.3 (1H, ap q, J¼14, 11, 2 Hz), 4.2 (1H, dt, J¼14,
11 Hz), 7.34–7.81 (20H, m). 13C NMR (75 MHz, CDCl3) d
23.0 (dd, J¼36, 2 Hz), 32.1, 50.4 (dd, J¼51, 2 Hz), 127.2–
133.1, 201.8 (d, J¼4 Hz). 31P NMR (121 MHz, CDCl3) d
18.5 (br s), 31.2 (JP–P¼40 Hz). 11B NMR (96 MHz, CDCl3)
d 240 (br s). LRMS (EI) 469 (M2H). LRMS (CI) 469
(M2H). HRMS (CI) calculated for C30H30O3P2 (M2H)
469.1658, observed 469.1666. Anal. Calcd (470.29): C,
71.51; H, 6.22; P, 13.17. Found: C, 71.39; H, 6.13; P, 13.03.
General procedure for the Swern oxidation of alcohols.14
To a solution of dimethyl sulfoxide (9.30 mmol) in CH2Cl2
(60 mL) at 2788C oxalyl chloride (9.30 mmol) was added
dropwise. After letting stir for 10 min, alcohol 6a
(1.80 mmol) in CH2Cl2 (4 mL) was cannulated over. The
reaction warmed to 2508C bath and allowed to stir for 2 h.
The temperature was then lowered to 2788C prior to
addition of triethylamine (18.6 mmol). The reaction was
then allowed to warm to room temperature over 4 h. The
reaction was washed with brine, dried (Na2SO4), and
filtered. The solvent was removed via roto-evaporator to
afford a white solid.
General procedure for the synthesis of ketones 7 using
Warren’s modifications. To a solution of 1.25 (0.118 mmol)
in THF (4 mL) at 2958C nBuLi (0.056 mL, 2.1 M hexanes)
was added and allowed to stir for 20 min. Ethyl butyrate
(0.236 mmol) was added dropwise. The orange-colored
solution changed to a yellow solution after warming to
2788C over 30 min. The reaction was quenched at 2788C
with ammonium chloride and allowed to warm to room
temperature. The mixture was extracted with EtOAc,
washed with brine, dried (MgSO4), and filtered. The
solvent was removed via roto-evaporator to afford a white
solid. General procedures for the synthesis of 10, 11
alcohols.
4.3.5. 2-Diphenylphosphinoyl(diphenylphosphine·
deuteroborane butan-3-one) (BD3-8a). Using the general
Horner–Wittig procedure followed by Swern oxidation, the
product was isolated as a white solid with mp 129–1328C
(slight dec.); Rf¼0.53 (EtOAc). 1H NMR (300 MHz,
CDCl3) d 1.68 (3H, s), 2.41 (1H, dt, J¼15, 10 Hz), 3.30
(1H, q, J¼13 Hz), 4.21 (1H, q, J¼13 Hz), 7.39–7.80 (20H,
m). 13C NMR (75 MHz, CDCl3) d 22.9 (d, J¼33 Hz), 32.1,
50.3 (d, J¼53 Hz), 127.1–133.0, 201.8 (d, J¼4 Hz). 31P
NMR (121 MHz, CDCl3) d 18.4 (br s), 31.1 (JP–P¼40 Hz).
11B NMR (MHz, CDCl3) d 241 (br s). HRMS (CI, M2D)
calculated for C28H26D3BO2P2 471.1781, found 471.1792.
Anal. Calcd for (473.31): C, 71.05; H, 6.81. Found: C,
70.07; H, 6.95.
4.3.1. 3,4-Bis-(diphenylphosphinoyl)-butan-2-one (7a).
Using the Swern oxidation, after purification by
chromatography (100% EtOAc to 10% EtOAc/MeOH)
the ketone (603 mg, 71%) was obtained as a white
4.3.6. 2-Diphenylphosphinoyl(diphenylphosphine·
borane hexan-3-one) (8b). Swern oxidation of alcohol 6b
1
solid: mp 185–1878C, Rf¼0.45 (1:9 EtOAc/MeOH). H

7184
S. T. Cacatian, P. L. Fuchs / Tetrahedron 59 (2003) 7177–7187
(4.12 mmol) afforded ketone 8b (1.16 g, 57%) as a white solid
1
1,2-methylation with Me3Al. To a solution of ketone 7c
(0.20 mmol) in 5 mL CH2Cl2 at 08C was added Me3Al
(0.90 mL, 2 M toluene). The mixture was allowed to reach
258C and stirred at this temperature for 48 h. The reaction
was cooled to 08C and quenched with 5% HCl. After
aqueous work up removal of solvent, the crude product (ca.
61% conversion) was chromatographed (100% EtOAc) to
afford the mixture of alcohols (42 mg, 36%). A purified
fraction (5:95 anti/syn) afforded a white solid with
with mp¼141–1428C (slight dec.); Rf¼0.58 (EtOAc). H
NMR (300 MHz, CDCl3) d 0.4–1.6 (3H, br m), 0.48 (3H, t,
J¼8 Hz), 0.99 (2H, m, J¼7 Hz), 1.91 (2H, t, J¼7 Hz), 2.37
(1H, dt, J¼16, 10 Hz), 3.35 (1H, ap q, J¼16 Hz), 4.20 (1H, ap
q, J¼14 Hz), 7.33–7.80 (20H, m). 13C NMR (75 MHz,
CDCl3) d 12.9, 15.9, 22.7 (d, J¼35 Hz), 47.3, 49.2 (d,
J¼52 Hz), 126.7–133.0, 203.5 (d, J¼4 Hz). 31P NMR
(121 MHz, CDCl3) d 18.2 (br m), 31.6 (JP–P¼41 Hz). 11B
NMR(96 MHz,CDCl3)d241(brs). LRMS(EI)497(M2H).
HRMS (EI) Calculated for C30H33BO2P2 (M2H) 497.1971,
observed 497.1986. Anal. Calcd (498.34): C, 72.30; H, 6.67.
Found: C, 71.94; H, 6.46.
1
mp¼185–1898C, Rf¼0.40. H NMR (300 MHz, CDCl3) d
0.98 (3H, s), 2.02 (2H, m), 2.42–2.80 (3H, m), 2.88–3.01
(1H, m), 3.39–3.46 (1H), 5.28 (1H, br s), 6.89–7.98 (25H,
m). 13C NMR (75 MHz, CDCl3) d 25.8 (d, J¼68 Hz), 27.6
(d, J¼6 Hz), 29.9, 42.1 (dd, J¼64, 4 Hz), 42.4 (d, J¼3 Hz),
74.5, 125.4–142.3. 31P NMR (121 MHz, CDCl3) d 32.1,
37.9 (JP–P¼31 Hz). HRMS (CI) calculated for the mixed
sample for C36H36O3P2 579.2218, found 579.2213.
4.3.7. 2-Diphenylphosphinoyl-5-phenyl(diphenyl-
phosphine·borane pentan-3-one) (8c). After Swern
oxidation purification (70% EtOAc/hexanes) afforded the
ketone (639 mg, 82%) as a white foam: mp¼164–1668C
(slightdec.);Rf¼0.67(EtOAc). 1HNMR(300 MHz,CDCl3)d
0.40–1.60(3H, d), 2.09–2.23(4H,m), 2.36(1H,dt), 3.32(1H,
ap q), 4.14 (1H, ap q, J¼13 Hz), 6.83–7.21 (5H, m), 7.23–
7.84 (20H, m) 13C NMR (75 MHz, CDCl3) d 22.9 (d,
J¼35 Hz), 28.9, 47.4, 49.3 (d, J¼52 Hz), 125.8, 126.9–133.3,
140.4, 202.9 (d, J¼4 Hz). 31P NMR (121 MHz, CDCl3) d 18.6
(br m), 31.3 (JP–P¼41 Hz). 11B NMR (96 MHz, CDCl3) d
240 (br s). Anal. Calcd for C35H35BO2P2 (560.41): C, 75.01;
H, 6.30. Found: C, 74.72; H, 6.26.
4.4.2. anti-2-Diphenylphosphinoyl-3-methyl-5-phenyl
(diphenylphosphine·borane pentan-3-ol) (anti-11). To a
freshly made solution of MeCeCl2 (1.40 mmol) in 9 mL of
THF at 2788C was cannulated a solution of ketone 8c
(0.182 mmol) in 1 mL of THF. The mixture was stirred at
this temperature for 2 h. Afterward, the solution was
allowed to reach room temperature over 12 h, quenched
with ammonium chloride, extracted with EtOAc, and dried
over MgSO4. After removal of solvent, the crude reaction
was chromatographed (70% EtOAc/hexanes) to afford the
alcohol anti-11 (65.9 mg, 63%), with a 92:8 anti/syn ratio,
as a white foam: mp 75–808C (slight dec.), Rf¼0.63
4.3.8. 2-Diphenylphosphinoyl-5-phenyl(diphenyl-
phosphine·deuteroborane pentan-3-one) (BD3-8c).20
Following the procedure for Horner–Wittig addition
alcohol BD3-6c (440 mg, 85%) was oxidized using Swern
conditions to the ketone (370 g, 78%) as a white solid with
mp 156–1608C (slight dec.). 1H NMR (300 MHz, CDCl3) d
2.18–2.28 (4H, m), 2.42 (1H, dt, J¼15, 10 Hz), 3.37 (1H, ap
q, J¼13 Hz), 4.19 (1H, ap q, J¼13 Hz), 6.80–7.26 (5H, m),
7.39–7.99 (20H, m). 13C NMR (75 MHz, CDCl3) d 22.8 (d,
J¼34 Hz), 28.9, 47.3, 49.2 (d, J¼53 Hz), 125.8–140.4,
202.9 (d, J¼4 Hz). 31P NMR (121 MHz, CDCl3) d 18.1 (br
m), 31.1 (JP–P¼40 Hz). Anal. Calcd for C35H32D3BO2P2
(563.43): C, 74.61; H, 6.80. Found: C, 74.10; H, 6.73.
1
(EtOAc) mp H NMR (300 MHz, CDCl3) d 0.6–1.7 (3H,
m), 1.04–1.47 (2H, m), 1.31 (3H, s), 2.50 (2H, t, J¼9 Hz),
2.50–2.64 (1H, m), 3.08–3.22 (1H, m), 3.61 (1H, m,
J¼22 Hz), 4.29 (1H, br s), 6.70–8.06 (25H, m). 13C NMR
(75 MHz, CDCl3) d 21.7 (d, J¼35 Hz), 26.8 (d, J¼4 Hz),
29.1, 43.1 (d, J¼9 Hz), 43.1 (d, J¼65 Hz), 74.9, 125.2–
141.6. 31P NMR (121 MHz, CDCl3) d 20.8 (br s), 41.1
(JP–P¼28 Hz). Minor isomer 31P NMR (121 MHz, CDCl3)
d 21 (br s), 42.6 (JP–P¼30 Hz). HRMS (CI) calculated.
for C36H39BO2P2 577.2596, found 577.2597. Anal. Calcd:
C, 75.01; H, 6.82; P, 10.75. Found: C, 74.63; H, 6.72; P,
10.51.
4.3.9. 2-(Diphenylphosphinoyl)-5-phenyl(diphenyl-
phosphinoyl pentan-3-one) (9c). A solution of ketone 8c
(0.68 mmol) and DABCO9a,14 (1.19 mmol) in toluene was
heated at 408C for 12 h. The reaction was allowed to cool for
24 h upon which time the ketone crystallized out of solution.
The toluene was carefully pipetted out and after further
removal of solvent, 368 mg (.99%) was isolated; mp 175–
1858C. Plug silica gel filtration of an aliquot afforded a white
solid:mp190–1938C;Rf¼0.78(EtOAc).1HNMR(300 MHz,
CDCl3) d 2.31(1H, t, J¼13 Hz), 2.58–2.89(5H, m), 3.54(1H,
q, J¼12 Hz), 7.01–7.61 (25H, m). 13C NMR (75 MHz,
CDCl3) d 25.2 (d, J¼20 Hz), 29.2, 46.6 (d, J¼12 Hz), 52.5
(dd, J¼53, 17 Hz), 125.9–140.7, 204.6. 31P NMR (121 MHz,
CDCl3) d 215.5, 30.4 (JP–P¼37 Hz). HRMS (CI) calculated
for C35H32O2P2 547.1956, observed 547.1958.
4.4.3. anti-1,2-Bis-(diphenylphosphinoyl)-3-methyl-5-
phenyl-pentan-3-ol (anti-10). A solution of alcohol anti-
11 (0.081 mmol) and DABCO9b (0.162 mmol) in toluene,
open to atmosphere, was heated at 408C for 12 h to afford
(29.8 mg, 64%). Additionally, the alcohol is a minor
component from the alkylation of ketone 7c with Me3Al
and was isolated via column chromatography (SiO2, 70%
EtOAc/hexanes to 100%) to afford a sample of .90:10 anti/
syn ratio. White solid: mp 185–1888C; Rf¼0.30 (EtOAc).
1H NMR (300 MHz, CDCl3) d 1.32 (3H, s), 1.39 (2H, m),
2.40–2.68 (3H, m), 2.89–3.05 (1H, m), 3.23–3.41 (1H, m),
5.13 (1H, s), 6.71–7.84 (25H, m). 13C NMR (75 MHz,
CDCl3) d 25.2, 25.4 (d, J¼68 Hz), 29.4, 41.5 (d, J¼63 Hz),
44.7, 73.6, 125.3–142.1. 31P NMR (121 MHz, CDCl3) d
32.9, 35.7 (JP–P¼32 Hz).
4.4. General procedures for the synthesis of 10, 11
alcohols
4.5. General procedure for the synthesis of allyl
phosphine oxides/boranes
4.4.1. syn-1,2-Bis-(diphenylphosphinoyl)-3-methyl-5-
phenyl-pentan-3-ol (syn-10). General procedure for the
To a solution of alcohol syn-5b (0.167 mmol, 5:95 anti/syn)

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7185
in DMF (2 mL) at 08C NaH (60% oil dispersion, 0.20 mmol)
was added. The reaction was then removed from the ice bath
and allowed to stir for 1 h. The reaction was quenched with
ammonium chloride. The aqueous solution was extracted
with ethyl acetate. The combined ethyl acetate fractions
were washed with 50% lithium chloride solution. The ethyl
acetate was dried (MgSO4), then filtered. After evaporation,
(47 mg, .99%) the product contained 1% vinyl phosphine
oxide analog and 5% Z-2b.
4.5.6. E-diphenylphosphine·borane-2-butene (E-3a).
Clear oil with 6:94 Z/E ratio (1H NMR). 1H NMR
(300 MHz, CDCl3) d 0.51–1.42 (3H, q, J¼96 Hz), 1.59
(3H, t, J¼5 Hz), 2.98 (2H, dd, J¼12, 7 Hz), 5.32–5.50 (2H,
m), 7.41–7.71 (10H, m). 13C NMR (75 MHz, CDCl3) d 18.0
(d, J¼2 Hz), 30.6 (d, J¼36 Hz), 120.3 (d, J¼6 Hz), 131.4
(d, J¼12 Hz), 128.6–132.5. 31P NMR (121 MHz, CDCl3) d
17.0 (br m).
4.5.7. Z-diphenylphosphine·borane-2-hexene (Z-3b).
Elimination of alcohol anti-6b (0.56 mmol, 86:14 anti/
syn) afforded Z-3b (130 mg, 82%) as an oil. 1H NMR
(300 MHz, CDCl3) d 0.54–1.40 (3H, m), 0.81 (3H, t,
J¼7 Hz), 1.21 (2H, m, J¼7 Hz), 1.83 (2H, m), 3.05 (2H, dd,
J¼13, 8 Hz), 5.34–5.50 (1H, m), 5.51–5.57 (1H, m), 7.41–
7.78 (10H, m). 13C NMR (75 MHz, CDCl3) d 13.7, 22.3 (d,
J¼2 Hz), 26.6 (d, J¼36 Hz), 29.4 (d, J¼2 Hz), 118.6 (d,
J¼5 Hz), 135.0 (d, J¼11 Hz), 128.6–132.5. 31P NMR
(121 MHz, CDCl3) d 16.6 (br m). LRMS (EI) 281 (M2H),
268 (M2BH3). LRMS (CI) 281 (M2H). HRMS (EI) calcd
for C18H24BP (M2H) 281.1630, found 281.1600.
4.5.1. E-Diphenylphosphinoyl-2-hexene (E-2b). White
solid: mp 34–368C, Rf¼0.40 (EtOAc). 1H NMR (300 MHz,
CDCl3) d 0.75 (3H, t, J¼7 Hz), 1.24 (2H, m, J¼7 Hz), 1.91
(2H, m), 3.08 (2H, dd, J¼14, 7 Hz), 5.45 (2H, m), 7.46–7.76
(10H, m). 13C NMR (75 MHz, CDCl3) d 13.4, 22.2
(d, J¼3 Hz), 34.7 (d, J¼2 Hz), 34.9 (d, J¼70 Hz), 118.1
(d, J¼9 Hz), 137.2 (d, J¼12 Hz), 128.4–133.3.
4.5.2. Z-Diphenylphosphinoyl-2-hexene (Z-2b). Elimin-
ation of alcohol anti-5b (0.086 mmol) afforded 21 mg
(88%) of Z-2b. Isolated as a white solid: mp 81–838C;
Rf¼0.40 (EtOAc). 1H NMR (300 MHz, CDCl3) d 0.81 (3H,
t, J¼7 Hz), 1.22 (2H, m, J¼7 Hz), 1.87 (2H, m), 3.14 (2H,
dd, J¼15, 7 Hz), 5.42–5.59 (2H, m), 7.44–7.78 (10H, m).
13C NMR (75 MHz, CDCl3) d 13.7, 22.3 (d, J¼2 Hz), 29.5
(d, J¼2 Hz), 30.2 (d, J¼70 Hz), 117.4 (d, J¼8 Hz), 128.4–
133.5, 135.2 (d, J¼59, 11 Hz). HRMS (EI) sample calcd for
C18H21OP 284.1330, observed 284.1335.
4.5.8. Z-5-phenyl-diphenylphosphine·borane-2-pentene
1
(Z-3c). Clear oil. H NMR (300 MHz, CDCl3) d 0.3–1.7
(3H, m), 2.12 (2H, m), 2.41 (2H, m), 2.88, (2H, dd, J¼13,
7 Hz), 5.27–5.37 (1H, m), 5.42–5.54 (1H, m), 6.97–7.58
(15H, m). 13C NMR (75 MHz, CDCl3) d 25.5 (d, J¼36 Hz),
29.3 (d, J¼2 Hz), 35.2 (d, J¼2 Hz), 119.3 (d, J¼5 Hz),
133.9 (d, J¼11 Hz), 125.9–141.5. 31P NMR (121 MHz,
CDCl3) d 15.9 (br m, J¼71 Hz). HRMS (EI) calcd for
C23H26BP (M2H) 343.1787, found 343.1798.
4.5.3. E-5-phenyl-diphenylphosphinoyl-2-pentene
(E-2c). Elimination of alcohol syn-5c (0.173 mmol)
afforded 30.5 mg (51%) of E-2c. Isolated as a white solid:
1
mp 120–1258C. H NMR (300 MHz, CDCl3) d 2.20 (2H,
4.5.9. E-5-phenyl-diphenylphosphine·borane-2-pentene
1
(E-3c). Clear oil. H NMR (300 MHz, CDCl3) d 0.2–1.8
m), 2.45 (2H, t, J¼7 Hz), 2.99 (2H, dd, J¼15, 6 Hz), 5.42
(2H, m), 6.96–7.17 (5H, m), 7.35–7.66 (10H, m). 13C NMR
(75 MHz, CDCl3) d 34.3 (d, J¼2 Hz), 34.8 (d, J¼68 Hz),
35.5 (d, J¼3 Hz), 118.7 (d, J¼10 Hz), 136.2 (d, J¼12 Hz),
128.2–141.5. HRMS (CI) sample calculated for C23H23OP
347.1565, observed 347.1561.
(3H, m), 2.11–2.18 (2H, m), 2.44 (2H, q, J¼8 Hz), 2.86–
2.94 (2H, m), 5.34–5.38 (2H, m), 6.98–7.61 (15H, m). 13C
NMR (75 MHz, CDCl3) d 30.6 (d, J¼36 Hz), 34.2 (d,
J¼2 Hz), 35.5 (d, J¼4 Hz), 120.0 (d, J¼6 Hz), 135.6 (d,
J¼11 Hz), 125.8–141.5.
4.5.4. Z-5-phenyl-diphenylphosphinoyl-2-pentene (Z-2c).
Elimination of alcohol anti-5c (1.10 mmol) afforded
242 mg (63%) of Z-2c. White solid: mp 90–958C. 1H
NMR (300 MHz, CDCl3) d 2.14 (2H, m), 2.42 (2H, t,
J¼8 Hz), 2.98 (2H, dd, J¼13, 8 Hz), 5.44–5.54 (1H, m),
5.58 –5.66 (1H, m), 7.00–7.18 (5H, m, Ph), 7.37–7.68
(10H, m). 13C NMR (75 MHz, CDCl3) d 28.9, 29.9 (d,
J¼70 Hz), 34.9, 117.9 (d, J¼9 Hz), 133.8 (d, J¼12 Hz),
128.0 – 141.2. HRMS (EI) sample calcd for C23H23OP
346.1486, observed 346.1486.
4.5.10. E-3-methyl-5-phenyl-(diphenylphosphinoyl pent-
2-ene) (E-12). White solid: mp 172–1758C dec. Rf¼0.38.
1H NMR (300 MHz, CDCl3) d 1.49 (3H, s), 2.26 (2H, t,
J¼8 Hz), 2.59 (2H, t, J¼8 Hz), 3.08 (2H, dd, J¼15, 8 Hz),
5.27 (1H, q, J¼8 Hz), 7.09–7.74 (15H, m). 13C NMR
(75 MHz, CDCl3) d 16.5, 30.9 (d, J¼70 Hz), 34.3, 41.5,
112.9 (d, J¼8 Hz), 140.7, 125.7–141.9.
4.5.11. Z-3-methyl-5-phenyl-(diphenylphosphinoyl pent-
2-ene) (Z-12). After standard borane deprotection of anti-11
and standard elimination a white solid was isolated in
(25 mg) 68% yield with a mp 79–818C. 1H NMR
(300 MHz, CDCl3) d 1.71 (3H, s), 2.19 (2H, t, J¼8 Hz),
2.53 (2H, t, J¼8 Hz), 2.90 (dd, 2H, J¼15, 8 Hz), 5.25 (1H,
q, J¼8 Hz), 7.00–7.72 (15H, m). 13C NMR (75 MHz,
CDCl3) d 24.6, 30.2 (d, J¼74 Hz), 33.7, 33.9, 113.4 (d,
J¼8 Hz), 140.4, 125.9–141.9. HRMS (EI) calcd on a mixed
sample for C24H25OP 360.1643, found 360.1643.
4.5.5. Z-diphenylphosphine·borane-2-butene (Z-3a).
Elimination of alcohol anti-6a (2.67 mmol) afforded
1
503 mg (75%) of Z-3a. Isolated as a clear oil. H NMR
(300 MHz, CDCl3) d 0.40–1.70 (3H, br m), 1.43 (3H, m),
3.03 (2H, dd, J¼13 Hz), 5.35–5.46 (1H, m), 5.56–5.68
(1H, m), 7.40–7.71 (10H, m). 13C NMR (75 MHz, CDCl3) d
12.9 (d, J¼2 Hz), 25.2 (d, J¼37 Hz), 119.6 (d, J¼6 Hz),
129.1 (d, J¼11 Hz), 128.6–132.4. 31P NMR (121 MHz,
CDCl3) d 17.3 (ap d, JP–P¼71 Hz) 11B NMR (96 MHz,
CDCl3) d 239 (d, J¼54 Hz). LRMS (EI): 253 (M2H), 240
(M2BH3). LRMS (CI) 253 (M2H). HRMS (CI) calcd for
C16H20BP (M2H) 253.1317, found 253.1308.
4.5.12. Z-3-methyl-5-phenyl-(diphenylphosphine·borane
pent-2-ene) (Z-13). Elimination of alcohol anti-11
(.092 mmol) using standard NaH/DMF conditions afforded
the alkene (26 mg, 79%), with 92:8 anti/syn ratio, as an oil.

7186
S. T. Cacatian, P. L. Fuchs / Tetrahedron 59 (2003) 7177–7187
1H NMR (300 MHz, CDCl3) d 0.35–0.62 (3H, br, m), 1.70
(3H, d, J¼3 Hz), 2.16 (2H, t, J¼8 Hz), 2.52 (2H, t, J¼8 Hz),
2.80 (2H, dd, J¼12, 8 Hz), 5.16 (1H, q, J¼7 Hz), 7.10–7.64
(15H, m). 13C NMR (75 MHz, CDCl3) d 23.4 (d, J¼2 Hz),
25.7 (d, J¼37 Hz), 33.6 (d, J¼2 Hz), 33.9 (d, J¼2 Hz),
114.6 (d, J¼5 Hz), 139.9 (d, J¼11 Hz), 125.9–141.9.
HRMS (CI, M2H) calculated on a mixed sample for
C24H28BP 357.1943.1643, found 360.1943.
R.-q.; Schlosser, M. Synlett 1996, 1195–1196, see also 1197–
1198.
9. (a) Imamoto, Y.; Kusumoto, Y.; Suzuki, N.; Sato, K. J. Am.
Chem. Soc. 1985, 107, 5301–5303. (b) Brisset, H.; Gourdel,
Y.; Pellon, P.; Le Corre, M. Tetrahedron Lett. 1993, 34,
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Corre, M. Tetrahedron Lett. 1993, 34, 1011–1012. (d) Pellon,
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Acknowledgements
11. Buss, A.; Warren, S. Tetrahedron Lett. 1983, 24, 3931–3934.
12. Beta elimination of the distal phosphine occurs only when
lithiated/metalated 4 is warmed to room temperature
(a) Spangler, C. W.; McCoy, R. K.; Dembek, A. A.; Sapochak,
L. S.; Gates, B. D. J. Chem. Soc., Perkin Trans. 1 1989,
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The authors would like to thank Dr Douglas Lantrip for
assistance with manuscript preparation, Professor
Alexander Wei for helpful discussions of 31P NMR, the
Boron Research Center for access to 11B NMR, and Arlene
Rothwell and Dr Karl Wood for mass spectrometry services.
13. Gourdel, Y.; Ghanimi, K. A.; Pellon, P.; Le Corre, M.
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