Tandem eneyne-phosphaallene/Myers type cyclization via base-induced isomerisation of enediynephosphine

Article abstract of DOI:10.1016/S0022-328X(01)01392-4

A reaction cascade involving room temperature base-induced ynephosphine-phosphaallene rearrangement and Myers-Saito type cycloaromatization of the ene-yne-allenephosphine intermediate is described.

Full text of DOI:10.1016/S0022-328X(01)01392-4

Journal of Organometallic Chemistry 643–644 (2002) 342–349
www.elsevier.com/locate/jorganchem
Tandem eneyne-phosphaallene/Myers type cyclization via
base-induced isomerisation of enediynephosphine
b
G. Baba a, C.G. Tea b, S.A. Toure´ , M. Lesvier c, J.-M. Denis c,*
a De´partement de Chimie, Uni6ersite´ de Lome´, B.P. 4574 Lome´, Togo
b Chimie Organique Structurale, Uni6ersite´ de Cocody, B.P. 22 Abidjan, Coˆte d’I6oire
c Synthe`se et e´lectrosynthe`se organiques, e´quipe associe´e au CNRS, Uni6ersite´ de Rennes 1, Campus de Beaulieu, F35042 Rennes, France
Received 16 July 2001; accepted 9 October 2001
Dedicated to Professor Franc¸ois Mathey on the occasion of his 60th birthday
Abstract
A reaction cascade involving room temperature base-induced ynephosphine-phosphaallene rearrangement and Myers–Saito
type cycloaromatization of the ene-yne-allenephosphine intermediate is described. © 2002 Elsevier Science B.V. All rights
reserved.
Keywords: Ene-diyne; Ene-yne-allenephosphine; Phosphaallene; Ynephosphine; Rearrangement; Cycloaromatization
Myers–Saito cyclization occurs usually at lower tem-
perature (80 °C) [3] or at the physiological temperature
1. Introduction
for some simple acyclic mimic structures of natural
products such as 1–3 [4–7]. A cyclization at a subambi-
ent temperature (10 °C) has even been observed with a
Thermal cycloaromatization of ene-diyne (Bergman
type cyclization A) and enyne-allene (Myers–Saito type
cyclization B) play a fundamental role in the mode of
compound bearing a substituted allenic sulfide [8]. The
action of natural enediyne antitumor antibiotics [1].
ease of the Myers–Saito cycloaromatization is related
The DNA cleaving ability of these structures is related
to the formation of a diradical intermediate.
to the short distance between yne and allene functions.
Efforts have been also oriented towards cycloaroma-
tization of conjugated structures containing hetero-sub-
stituted chromophores such as 4 [9] and 5 [10] (Scheme
1).
All the eneyne-allene mimic chromophores 1–5 are
highly reactive species. Most of them have however,
been isolated and characterized. Due to their high
reactivity, they are commonly formed by a reaction
cascade starting from stable precursors and in situ
thermally transformed into the corresponding aromatic
derivatives via a biradical intermediate in the presence
of [1–4]-dimethylbutadiene as hydrogen donor atom.
Bergman reactions usually proceed at high tempera-
ture (150 °C). The ease of cyclization of these conju-
Compounds such as 1–5 are of interest both for mech-
anistic studies and for their potential DNA cleaving
gated enediynes strongly depends on the distance
abilities. More generally, chromophores, which are able
between carbons C1 and C6 [2]. By contrast, the
to induce cycloaromatization at the physiological tem-
perature via a biradical intermediate, are potentially
useful for the design of new antibiotic agents. Herein,
we report that the ene-ynephosphaallene 6 formed by
* Corresponding author. Tel./fax: +33-299-286279.
E-mail address: jmdenis@univ-rennes1.fr (J.-M. Denis).
0022-328X/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)01392-4

G. Baba et al. / Journal of Organometallic Chemistry 643–644 (2002) 342–349
343
[13]. Only the VGSR technique allowed the complete
characterization of the structure (1H-, 31P- and 13C-
NMR).
The phenyl P-phosphaallene 10 bearing an isopropyl
group on the phosphorus atom was expected to be
more stable than the corresponding P-methylphos-
phaallene. However, access by the VGSR technique
should be not possible since volatility of the product
was expected to be too weak to allow vaporization on
a solid base (K2CO3). We choose consequently another
way involving the base-induced rearrangement in solu-
tion of the enediyne P-ipropylphosphine precursor 7b.
The synthesis was first developed on a simple structure
7a (RꢀPh) to precise the experimental conditions and
was then extended to 7b in which the ene-yne chro-
mophore takes the place of the phenyl group. The
retrosynthetic route was presented on Scheme 3.
Ynephosphines 7a,b were prepared by reduction of the
phosphine oxides 8a,b with silane as a reducing agent
[14], the later compounds being themselves obtained by
condensation of the corresponding alkynyl lithium on
P-chlorodiethylaminophosphine 11 followed by acidic
hydrolysis of the resulting ynephosphine 9a,b.
Scheme 1.
Scheme 2.
base-induced rearrangement of the ene-diyne 7b phos-
phine precursor led at room temperature to the corre-
sponding phenylphosphine structure 16 via a Myers–
Saito type cyclization.
2.1. Ynephosphine 7a and phosphaallene 10
The P-chlorodiethylaminophosphine starting material
11 was obtained on molar scale by monoamination of
PCl3 at −40 °C with diethylamine followed by con-
2. Results and discussion
i
densation of the Grignard reagent derived from PrCl
1-Phosphaallenes ꢁPꢀCꢀCꢂ are isoelectronic to kete-
nes. Their syntheses and chemical properties are well
documented [11]. The bulky substituted derivatives are
stable at room temperature. They are obtained by
various synthetic routes, such as phospha-Wittig and
Peterson-type reactions. The simple derivatives substi-
tuted by primary alkyl groups are not stable at room
temperature and consequently need special approaches.
As an example, H2CꢀCꢀPꢁMe was prepared in solution
or under vacuum gas–solid reaction (VGSR) [12], ei-
ther by dehydrohalogenation of chlorovinylphosphine
or by base-induced rearrangement of the ethynyl-
methylphosphine (Scheme 2). Oligomerization was ob-
served in solution around −20 °C (detection by 31P)
(overall yield 64% in distilled compound) [15]. Reaction
of lithium phenylacetylide at −78 °C on ClPN(Et2)iPr
11 led to the phenylaminophosphine 9a (79% yield after
distillation). The product was fully charaterized by
NMR spectroscopy (1H, 13C, 31P) and HRMS. The
crude phosphine oxide 8a (purity \95%, yield 78%)
was then obtained in good yield by acidic hydrolysis of
9a on solid acid (Amberlyst 15) in THF in the presence
of one equivalent of water [16]. Like other secondary
ethynylphosphine oxides, 8a is not thermally stable.
Polymerization and CꢁP bond cleavage were observed
during the distillation. The crude product can however,
be kept in the fridge for months without decomposi-
tion. NMR and HRMS data are in good agreement
Scheme 3.

344
G. Baba et al. / Journal of Organometallic Chemistry 643–644 (2002) 342–349
(0 °C). Consequently, the decomposition of the phos-
phaallene at this temperature is probably too fast to
allow observation by NMR spectroscopy. Evidence for
the formation of 10 was however, given by performing
the reaction from −20 to 20 °C in the presence of an
i
excess of propanethiol. The two expected vinylphos-
phine diastereomeric adducts 12%, 12¦ (l 31P 16.3 and
32.6 ppm) were isolated as an oil and characterized by
1H- and 31P-NMR and by HRMS (Scheme 4).
Scheme 4.
with the structure. The product was used in the subse-
quent reaction as such.
2.2. Ynephosphine 7b
An important CꢁP cleavage was observed by reduc-
tion of 8a with AlHCl2 [17]. Reduction with PhSiH3 in
pentane for 2 h at 30 °C gave the expected free phos-
phine 7a in 70% yield [13]. The stability of this com-
pound is too weak to allow distillation. The residual
impurities which were present after evacuation of
volatile compounds under vacuum are mainly
polysiloxanes (around 5%). The NMR and HRMS data
confirmed the structure. The crude product can be kept
for weeks in solution under neutral gas in the fridge.
Attempts to detect the phosphaallene 10 by low
temperature base-induced rearrangement of the free
ynephosphine 7a with DBU were unsuccessful. By
monitoring the 31P-NMR experiments, the signal of 7a
The methodology developed above was then ex-
tended to the synthesis of the ene-diynephosphine 7b
(Schemes 5 and 6). (Z)-methoxy-ene-diyne 13 was ob-
tained
by
coupling
silylacetylene
on
(Z)-
dichloroethylene in the presence of Pd(PPh3)4, copper
n
iodide and butylamine [18] followed by coupling the
resulting (Z)-chloroene-yne silane on propargylic ether
under similar catalytic conditions (Scheme 5) [19]. Desi-
lylation of 13 with lithium hydroxide in a THF–H2O
mixture [20] led to the terminal acetylene 14 which was
fully characterized after purification by flash chro-
matography. The overall yield from dichloroethene was
35%. Compound 14 was not very stable and should be
kept in the fridge.
1
(lP= −73 ppm, JPH 217 Hz, d) was continuously
observed from −78 to −10 °C, but intensity de-
creased slowly above this temperature to completely
disappear around 0 °C. This transformation was ac-
companied by the formation of a complex mixture
(signals 17 and 33 ppm) attributed to the products
resulting from the oligomerization of phosphaallene 10.
We have previously observed that the rearrangement of
secondary phosphines substituted by a primary alkyl
group on phosphorus occurred around −20 °C, allow-
ing thus the characterization of the phosphaallene be-
fore oligomerization [13]. Due to the presence of the
isopropyl group the temperature required for the rear-
rangement of the P-isopropylphosphine 7a is higher
Ene-diyne P-phosphineamine 9b was obtained by P-
alkylation of the lithium ene-yne acetylide with
ClPN(Et2)iPr 11 in THF at −78 °C (Scheme 6). The
crude oil was purified by distillation to afford 9b in 76%
yield (b.p. 87 °C, 1 mmHg). The product was fully
characterized by NMR (31P, 13C, 1H) and HRMS.
Acidic hydrolysis of 9b on Amberlyst 15 in the presence
of one equivalent of water led to the ene-diynephosphi-
neoxide 8b [15]. The compound is not stable at room
temperature and should be kept in solution in the fridge
(yield estimated for the crude product 85%, determina-
tion by 31P, purity \95%). However, it can be purified
by flash chromatography on silica gel (yield of the
Scheme 5.
Scheme 6.

G. Baba et al. / Journal of Organometallic Chemistry 643–644 (2002) 342–349
345
chromophore. Signals observed from 17 to 33 ppm are
resulting from the oligomerization of the phosphaallene
intermediate 6.
As expected, the thiophosphine isomeric adducts 15%
and 15¦ were obtained by a sequence involving low
temperature rearrangement of 7b (−80]20 °C) in-
duced by a strong Lewis (DBU or DABCO) and trap-
ping in situ the reactive phosphaallene intermediate 6
Scheme 7.
i
by propanethiol (Scheme 7). Adducts were also ob-
served with triethylamine and pyridine, but with the
purified compound 52%) and was fully characterized by
NMR spectroscopy and HRMS.
later base at a higher temperature (20 °C). Adducts 15
Reduction of the ene-diyne phosphine oxide 8b was
critical. With Cl2AlH in THF the desired free phos-
phine 7b was formed in a poor yield, the main products
resulting from a CꢁP cleavage. Reduction with HSiCl3
in pentane gave the expected product 7b in a poor yield,
accompanied by undetermined by-products. Reduction
by phenylsilane in pentane gave the best results (yield
60%). The free phosphine 7b was too unstable to be
purified by distillation or by flash chromatography. The
crude mixture obtained after elimination under vacuum
of excess of reagent and volatile siloxanes was analyzed
by NMR spectroscopy. The 31P-NMR presented a sig-
nal at 31l −73 ppm, (1JPH 217.5 Hz), in good agree-
ment with the structure. The presence of polysiloxanes
(15%) and ene-diyne 14 (20%) resulting from a partial
CꢁP cleavage did not allow to fully attribute all the
carbons of the chromophore. Finally, the structure was
completely assigned by NMR and HRMS analysis of
the recovered phosphine oxide 8b resulting from a
spontaneous oxidation of 7b in the presence of air
(Scheme 6). Compound 7b presented a lower stability
than 7a. It was thermally unstable above 40 °C and
should be used as prepared or kept in a freezer at
−16 °C.
1
were fully characterized by H-, 13C- and 31P-NMR (lP
16.6 and 32.3 ppm) and HRMS spectrometry.
As shown in Section 1, electrocyclization of the
mimic structures of natural products such as 1–5 oc-
curred at the physiological temperature. Since the ene-
ynephosphine phosphaallene intermediate 6b was
formed at room temperature in the presence of a weak
base (pyridine) under high dilution conditions, the cy-
cloaromatization of this chromophore was expected.
The rearrangement of 7b was consequently performed
at room temperature with pyridine as a Lewis base in a
benzene solution containing [1–4]cyclohexadiene as a
hydrogen donor atom. The resulting solution analyzed
by 31P after 2 days showed that 7b nearly disappeared.
The signals from 17 to 33 ppm corresponding to the
oligomerization of phosphaallene 6 were observed.
However, a new signal at l −33 ppm (1JPH 213 Hz)
corresponding to a secondary free phosphine (Pl) ap-
peared. A similar reaction was then performed in a
flask in a 10 mmol scale. After evacuation of the
solvent and oxidation in air, a secondary phosphine
oxide (PO) was observed by 31P-NMR analysis (lP 42
1
ppm, JPH 467 Hz) of the crude mixture and then
isolated by flash chromatography on silica gel. This
product can result from electrocyclization of 6 (com-
pound 16) followed by oxidation of the resulting free
phosphine Pl. The 31P-NMR data and HRMS (molecu-
lar ion 228.091, calculated 228.091) for PO are in favor
of the expected phenylphosphine oxide 17. However,
the amount of product was too small (yield B5%) to
get a complete characterization. The synthesis of the
authentic samples 16 and 17 was carried out to confirm
the structures of Pl and PO (Scheme 8). Synthesis of
phosphine oxide 17 involved the condensation of the
lithium derivative of 2-bromo benzylmethylether on the
chloroaminophosphine 11 followed by acidic hydrolysis
with Amberlyst 15 of the resulting 2-aminoisopropyl-
2.3. Phosphaallene 6 and cycloaromatization
Attempts to detect the transient phosphaallene 6 by
low temperature rearrangement of 7b with a Lewis base
and monitoring the low temperature 31P-NMR experi-
ments were unsuccessful. The temperature of the rear-
rangement with DBU was observed at
a lower
temperature for 7b (−40 °C) than that observed for 7a
(−20 °C). With pyridine, the rearrangement of 7b was
also observed (20 °C, 4 days), but not that of 7a. These
properties probably result from a stronger PꢁH acidity
of 7b with regard of 7a, induced by the ene-diyne
Scheme 8.

346
G. Baba et al. / Journal of Organometallic Chemistry 643–644 (2002) 342–349
Scheme 9.
phosphine benzylmethylether 18. The product 17 was
fully characterized by NMR (1H, 13C, 31P) and by
HRMS. The free phosphine 16 was finally obtained by
4.2. Preparation of 9a
A solution of butyllithium (62.6 ml, 110 mmol, 1.6 M
in C6H14) was added at −78 °C to a solution of
phenyl acetylene (100 mmol, 10.2 g) in THF (250 ml).
The reaction was stirred at this temperature for 30 min
and a solution of P-chlorodiethylaminoisopropylphos-
phine 11 [14] (98 mmol) in THF (20 ml) was slowly
added. The reaction was slowly warmed to room tem-
perature (r.t.). The solvent was then removed under
vacuum and the residue washed with C5H12 (30 ml).
The C5H12 solution was then filtered on celite under a
nitrogen pressure. The resulting oil obtained after evap-
oration of the solvent was distilled. B.p. 60 °C (1
mmHg), yield 68%.
1
reduction of 17 with phenylsilane (lP −33 ppm, JPH
213 Hz) and was fully characterized.
These results confirmed the former analysis: 31P and
HRMS data of 17 correspond to those of PO, the free
phosphine 16 (Pl) resulted from the electrocyclization of
the transient intermediate 6 (Scheme 9).
3. Conclusion
A secondary ene-diynephosphine was converted at
room temperature in the presence of a weak base
(pyridine) into a phenylphosphine derivative in a reac-
tion cascade involving base-induced ynephosphine-
phosphaallene rearrangement and Myers–Saito
electrocyclization of the ene-yneallenephosphine inter-
mediate. Efforts have to be carried out to do this
sequence potentially useful for the design of bioactive
molecules. This work shows the interest of low-coordi-
nate species such phosphaallenes for extension of fun-
damental reactions and for the design of new
intermediates.
31P-NMR (CDCl3): l 42.0 (m). H-NMR (300 MHz,
1
CDCl3): l 0.89 (dd, 3H, 3JPHa=8.1 Hz, 3JHaH=7.0 Hz,
3
CHa3CH); 0.93 (t, 6 H, JHH=7.0 Hz, CH2CH3); 0.95
3
(dd, 3H, JPHa%=9.3 Hz, 3JHa%H=6.7 Hz, CHCHa%3);
2
3
1.95 (dh, H, JPH=8.4 Hz, JHH=7.0 Hz, CH3CH);
3
3
2.88 (qd, 4H, JPH=9.8 Hz, JHH=7.1 Hz, CH2CH3);
7.09 and 7.23 (m, 5 Harom). 13C-NMR (75 MHz,
1
3
CDCl3) l: 14.74 (qdm JCH=125.5 Hz, JCP=4.0 Hz,
1
2
CH3CH2); 17.56 (qddq, JCHa=126.7 Hz, JCP=23.2
Hz, 2JCH=5.0 Hz, 3JCH=4.7 Hz, CHa3CH); 18.68
1
(qddq, JCHa%=127.5 Hz, 2JCP=22.0 Hz, 2JCH=4.6
3
1
Hz, JCH=4.0 Hz, CHCHa%3); 28.26 (dh, JCH=131.3
1
Hz, 2JCH=4.0 Hz, CHCH3); 44.86 (tdm, JCH=134.5
2
1
Hz, JCP=13.6 Hz, CH2CH3); 90.73 (dd, JCP=35.6
3
2
4. Experimental
Hz, JCH=3.1 Hz, CꢃCꢁP); 104.17 (dm, JCP=3.6 Hz,
CꢃCꢁP); 123.5; 128.25 and 131.47, Carom). HRMS Calc.
for C15H22NP: 247.1499. Found: 247.146.
4.1. General
Caution: Free phosphines are highly oxidizable and
potentially toxic molecules. All reactions should be car-
ried out under an inert atmosphere in a well-6entilated
hood.1H (300 MHz)-, 13C (75 MHz)- and 31P (121
MHz)-NMR spectra were recorded on a Bruker AC-
300P spectrometer and HRMS (high resolution mass
spectrometry) experiments were performed on a Varian
MAT 311 instrument. THF was freshly distilled
under Ar from LiAlH4. All the reactions involving
water- and air-sensitive chemicals were carried out un-
der nitrogen.
4.3. Preparation of 8a
Amberlyst® 15 (4.7 meq g−1, 6.4 g, 30 mmol) were
added to a solution of THF (30 ml) containing 0.2 ml
of water. The mixture was stirred under nitrogen and
then cooled at −40 °C. A solution of phenyl-
aminophosphine 9a (2.47 g, 10 mmol) in THF (10 ml)
was then slowly added and the stirring was maintained
for 30 min. The reaction mixture was then warmed to
r.t. After filtration, the residue was washed with C5H12
(2×10 ml) and the combined organic layer was con-

G. Baba et al. / Journal of Organometallic Chemistry 643–644 (2002) 342–349
347
centrated under reduced pressure. The yield in the
crude product 8a was 78%, (purity \95%). For ana-
lytic purpose, the resulting oil was purified by flash
chromatography (eluent: EtOAc) to afford a colourless
oil (yield of purified product 32%). The oil can be kept
on the fridge under a nitrogen mantle.
(1 N) in excess (15 mmol). After elimination of the
ammonium salts by filtration under a nitrogen pressure,
volatile products were eliminated under reduced pres-
1
sure. The crude oil was analyzed (31P and H).
As a mixture of the two isomers 12%, 12¦. 31P-NMR
1
(121 MHz, CDCl3): l 16.30 and 32.6 ppm. H-NMR
1
2
31P-NMR: l 12.00 (ddh, JPHc=507.5 Hz, JPHb
=
(300 MHz, CDCl3): l 1.1 (m, 3H, (CH3)2CHS); 1.2 (dd,
20.8 Hz, 3JPHa=13.6 Hz). 1H-NMR (300 MHz, CDCl3)
3
3
6H, JHH=6.8 Hz, JPH=2.2 Hz, (CHa3)2CHP); 1.28
l:126 (dd, 6H, 3JPHa=13.6 Hz, 3JHaHb=7.1 Hz,
3
3
(dd, 3H, JHH=6.8 Hz, JPH=3.8 Hz, (CHa%3)2CHP);
1.85 (m, H, (CH3)2CHS); 2.95 (m, H, (CH3)2CHP); 6.2;
6.65–6.7 and 7–7.1 (vinylic protons); 7.15–7.60
(Harom). HRMS for C14H21PS, Calc.: 252.1102. Found:
252.107. HRMS for C11H14PS [M−iPr]: Calc.
209.0554. Found: 209.056; m/z (%): 252 (22); 210 (17);
209 (53); 135 (12); 134 (21); 133 (100).
2
3
CHa3CHc); 2.08 (dhd, H, JPHb=20.8 Hz, JHbHa=7.1
1
Hz, 3JHbHc=2.4 Hz, CHbCHa3); 7.21 (dd, H, JPHc
=
3
507.5 Hz, JHcHb=2.4 Hz, PꢁHc); 7.32 and 7.51 (m, 5
H
arom). 13C-NMR (75 MHz, CDCl3)ꢀ: l 14.28 (qdm,
1JCHa=128.7 Hz, 2JCP=14.0 Hz, CHbCHa3); 28.96
(ddm, 1JCHb=129.4 Hz, 1JCP=80.5 Hz, CHbCHa3);
1
2
3
79.58 (ddd, JCP=148.5 Hz, JCHc=16.2 Hz, JCHb
=
2
2.6 Hz, CꢃCꢁP); 104.54 (dm, JCP=26.2 Hz, CꢃCꢁP);
119.28; 128.53; 130.79 and 132.36, Carom). HRMS, Calc.
for C11H13OP: 192.0704. Found: 192.069; m/z (%): 192
(45.14); 150 (100); 149 (89.98); 102 (70.77); 43 (35.60);
41 (35.62); 28 (54.59).
4.6. Preparation of 9b
Ene-diyne P-phosphineamine 9b was prepared by
following the protocol already described for 9a. At the
end of the reaction, the solvent was removed under
vacuum and the residue washed with C5H12 (30 ml).
The C5H12 solution was then filtered on celite under a
nitrogen pressure. The organic phase was concentrated
under vacuum and the resulting crude oil (yield 87%,
purity \95%) was used in the state in the following.
31P-NMR (121 MHz, CDCl3)ꢀ: l 42.25 (m). 1H-
4.4. Preparation of 7a
Phenylsilane (2.7 mmol) in C5H12 (3 ml) was slowly
added to a solution of phosphine oxide 8a (2.6 mmol)
in C5H12 (4 ml). After heating for 4 h at 30 °C, the
mixture was allowed to r.t. Solvent, excess of reagent
and siloxane were then removed under vacuum. The
crude phosphine (yield 70%) was used in this state in
3
NMR (300 Hz, CDCl3): l 0.96 (dd, 3H, JHaHc=7.0
3
3
Hz, JPHa=5.2 Hz, CHa3CHc); 1.01 (t, 6H, JHH=7.2
Hz, 2 CH3CH2); 1.03 (dd, 3H, 3JHa%Hc=7.0 Hz,
3JPHa%=6.0 Hz, CHa%3CHc); 2.02 (dh, H, 2JPHc=8.5 Hz,
3JHcHa=3JHcHa%=7.0 Hz, CHcCH3); 2.96 (dq, 4H,
the following (main impurities polysiloxanes 5%).
1
31P-NMR (121 MHz, CDCl3): l −73 (dhd, JPH
=
3
2
1
217.5 Hz, JPH=16.0 Hz, JPH=12.4 Hz). H-NMR
3
3JPH=9.9 Hz, JHH=7.1 Hz, 2 CH2CH3); 3.32 (s, 3H,
3
(300 MHz, CDCl3): l 1.33 (ddd, 6H, JPH=16.0 Hz,
5
OCH3); 4.18 (d, 2H, JHH=2.0 Hz, CH2O); 5.74 (ddm,
3JHH=6.9 Hz, JHH=1.1 Hz, (CH3)2CH); 2.20 (dhd,
4
5
H, 3JHb%Hb=10.9 Hz, JPHb%=1.0 Hz, CHb=CHb%);
H, 2JPH=12.4 Hz, 3JHH=6.9 Hz, 3JHH=5.4 Hz,
3
4
5.87 (dd, H, JHbHb%=10.9 Hz, JPHb=1.4 Hz, CHb=
CHb%). 13C-NMR (75 MHz, CDCl3): l 14.63 (qdm,
1JCH=126.0 Hz, 3JCP=4.4 Hz, CH2CH3); 17.32 (qddq,
1JCHa=126.7 Hz, 2JCP=23.3 Hz, 2JCHc=5.2 Hz,
1
CHCH3); 4.12 (dd, H, JPH=217.5 Hz, PꢁH); 7.32 and
7.51 (m, 5 Harom). 13C-NMR (75 MHz, CDCl3): l 21.97
1
2
(qdm, JCH=127.1 Hz, JCP=13.3 Hz, CH3CHCH3);
22.12 (qdm, 1JCH=126.8 Hz, 2JCP=14.7 Hz,
CH3CHCH3); 23.03 (dh, 1JCH=132.1 Hz, 1JCP=3.4
1
3JCHa%=4.4 Hz, CHCHa3); 18.53 (qddq, JCHa%=127.2
Hz, 2JCP=22.7 Hz, 2JCHc=5.1 Hz, 3JCHa=4.3 Hz,
2
1
Hz, JCH=4.1 Hz, CHCH3); 83.00 (m, JCP=19.5 Hz,
CꢃCꢁP); 105.30 (m, 2JCP=1.5 Hz, CꢃCꢁP); 123.2;
128.6; 131.74 and 133.4; Carom). HRMS for C11H13P:
Calc. 176.0755. Found: 176.075; m/z (%): 177 (7); 176
(37); 135 (5); 134 (25); 133 (100); 77 (2); 44 (42); 43 (19);
41 (13). HRMS for C8H6P [M−iPr] Calc. 133.0207.
Found: 133.019.
2
CHCHa%3); 28.00 (dh, 1JCHc=131.6 Hz, JCHa
=
2JCHa%=3.9 Hz, CHcCH3); 44.89 (tdm, 1JCH=134.7
Hz, JCP=13.4 Hz, CH2CH3); 57.57 (qt, JCH=141.7
2
1
3
1
Hz, JCH=5.3 Hz, OCH3); 60.34 (tq, JCH=147.7 Hz,
3JCH=5.5 Hz, CH2O); 83.92 (dt, 2JCH=14.2 Hz,
3JCH=5.0 Hz, CꢃCꢁCH2O); 92.71 (td, JCH=7.2 Hz,
2
3JCH=5.0 Hz, CꢃCꢁCH2O); 99.58 (dm, 1JCP=38.1 Hz,
CꢃCꢁP); 101.47 (dd, 2JCHb=12.2 Hz, 2JCP=3.5 Hz,
4.5. Preparation of 12%, 12¦
1
3
CꢃCꢁP); 118.06 (dd, JCH=143.8 Hz, JCP=3.2 Hz,
CHbꢀCHb%); 119.96 (dd, 1JCH=142.4 Hz, 4JCP=2.5
Hz, CHbꢀCHb%). HRMS for C15H24NOP: Calc.
265.1595. Found: 265.159; m/z (%): 265 (26); 223 (14);
222 (100); 193 (14); 151 (5); 119 (4); 107 (6); 95 (5); 69
(5); 43 (5); 42 (12); 41 (11).
A solution of DBU (1.52 g, 10 mmol) in C6H5CH3 (5
ml) was slowly added to a cooled (−40 °C) C6H5CH3
solution (10 ml) containing of 2-propanethiol (1.52 g,
20 mmol) and 7a (0.88 g, 5 mmol). The mixture was
then quenched at 0 °C with a solution of HCl in ether

348
G. Baba et al. / Journal of Organometallic Chemistry 643–644 (2002) 342–349
4.7. Preparation of 8b
sure. The crude oil was analyzed (31P and 1H) as a
mixture of the two isomers 15%, 15¦.
31P-NMR (121 MHz, CDCl3): l 32.3 and 16.6 ppm.
1H-NMR (300 MHz, CDCl3) l: 1.06 (m, 6H,
Compound 8b is prepared according to the protocol
already used for the preparation of 8a (yield 85% in
crude product, purity \95%). For analytic purpose,
the product was purified by flash chromatography (elu-
3
2
(CH3)2CHS); 1.29 (dd, 6 H, JHH=6.6 Hz, JPH=0.7
Hz, (CH3)2CHP); 1.85 (m, H, (CH3)2CHP); 2.95 (m, 6
H, (CH3)2CHS); 3.36 (s, 3H, OCH3); 4.25 (s, 2H,
ent, EtOAc) in a 50% yield.
1
31P-NMR (121 MHz, CDCl3): l 11.69 (ddh, JPHd
=
3
CH2O); 5.45 (d, JHH=12.7 Hz, PꢁH); 6.20–6.45; 7–
506.6 Hz, 2JPHc=20.8 Hz, JPHa:3JPHa%:15.7 Hz).
3
7.20. HRMS, Calc. for C14H23OPS: 270.12072. Found:
270.120; m/z (%): 43 (100); 42 (12); 41 (43); 39 (14); 28
(12).
1H-NMR (300 MHz, CDCl3): l 1.16, 3H, JPHa=14.7
3
3
3
Hz, JHaHc=7.1 Hz, CHcCHa3); 1.24 (dd, 3H, JPHa%
=
13.6 Hz, 3JHa%Hc=7.1 Hz, CHcCHa%3); 2.11 (dhd, H,
3
2
2JPHc=20.8 Hz, JHcHa=3JHcHa%=7.3 Hz, JHcHd=2.0
Hz, CHcCH3); 3.33 (s, 3H, OCH3); 4.21 (d, 2H,
4.10. Preparation of 2-aminoisopropylphosphine
benzylmethylether (18)
3
5JHHb%=1.8 Hz, CH2O); 5.88 (dd, H, JHbHb%=11.0 Hz,
3
4JPHb=2.7 Hz, CHbꢀCHb%); 6.09 (dd, H, JHb%Hb=11.0
5
1
Hz, JPHb%=0.5 Hz, CHbꢀCHb%); 7.04 (dd, H, JPHd
=
18s obtained by oxiethoxyphenylpA solution of
butyllithium (10.4 ml, 16.6 mmol in 1.6 M in hexane)
was added at −78 °C to a solution of bromo-2 benzyl-
methylether (14.9 mmol, 3 g) in THF (30 ml). The
solution was stirred at this temperature for 30 min, then
slowly allowed to warm to −60 °C and finally cooled
at −78 °C. Diethylaminophosphine 11 (2.17 g, 14.87
mmol) in THF (5 ml) was then adduct and the reaction
mixture was allowed to warm at r.t. The solvent was
removed under vacuum and the residue washed with
C5H12 (2× 30 ml). The C5H12 solution was then
filtered on celite under a nitrogen pressure. The result-
ing oil obtained after evaporation of the combined
organic layer was distilled. B.p. 85 °C (1 mmHg), yield
80%.
506.6 Hz, JHdHc=2.0 Hz, PꢁHd). 31C-NMR (75 MHz,
3
CDCl3): l 14.4 (qdm, 1JCHa=1JCHa%=128.9 Hz, 2JCP
=
17.6 Hz, CHa3CHc); 29.07 (ddm, 1JCHc=130.2 Hz,
1JCP=80.4 Hz, CHcCH3); 57.82 (qt, JCH=141.8 Hz,
1
3JCH=5.4 Hz, OCH3); 60.24 (tq, 1JCH=147.7 Hz,
3JCH=5.7 Hz, CH2O); 82.86 (dt, JCHb%=13.9 Hz,
2
3JCH=5.0 Hz, CꢃCꢁCH2O); 86.60 (ddm, JCP=145.1
1
2
2
Hz, JCHd=15.0 Hz, CꢃCꢁP); 96.21 (td, JCH=7.4 Hz,
3JCHb%=4.9 Hz, CꢃCꢁCH2O); 100.64 (ddd, JCP=25.5
2
3
2
Hz, JCHd=15.4 Hz, JCHb=5.5 Hz, CꢃCꢁP); 116.62
(dd, 1JCH=171.8 Hz, 3JCP=4.5 Hz, CHbꢀCHb%);
125.30 (dd, 1JCH=168.9 Hz, 4JCP=3.1 Hz,
CHbꢀCHb%). HRMS, Calc. for C11H15O2P: 210.0810.
Found: 210.080, m/z (%): 210 (11); 195 (44); 179 (11);
168 (3.46); 95 (14); 70 (11); 69 (27).
1
31P-NMR (121 MHz, CDCl3): l 53 ppm. H-NMR
(300 MHz, CDCl3): l 0.30 (t, 6H, 3JHH=7.1 Hz,
CH2CH3); 0.70 (dd, 3 H, 3JPH=18.5 Hz, 3JHH=6.8
Hz, CH3CHCH3); 0.98 (dd, 3H, 3JPH=15.2 Hz,
3JHH=6.9 Hz, CH3CHCH3); 2.26 (h, H, 3JHH=7.0 Hz,
CH3CH); 2.71 (m, 4H, CH2CH3); 3.23 (s, 3H, CH3O);
4.8. Preparation of 7b
Free ene-diyne phosphine 7b was formed according
to the protocol used for 7a. Yield in crude product
60%. 31P-NMR (121 MHz, CDCl3): l −73 pp (dm);
1JPH=217.5 Hz. Presence of impurities prevents obten-
tion of all the NMR data. The product was indirectly
characterized by spontaneous oxidation in air and com-
parison of the corresponding oxide with the authentic
sample 8b.
2
4.52 (d, H, JHa%Hb%=12.7 Hz, CHa%Hb%O); 4.75 (dd, H,
2JHb%Ha%=12.7 Hz, 4JPH=3.3 Hz, CHa%Hb%O); Harom
7.03 (td, H, JHH=7.4 Hz, JPH=1.4 Hzc); 7.12 (td, H,
:
3
5
4
3
3JHH=7.4 Hz, JHH=1.5 Hz); 7.26 (dt, H, JHH=7.4
Hz, 4JHH=1.9 Hz); 7.33 (ddd, H, 3JHH=7.5 Hz,
3JPH=3.7 Hz, 4JHH=0.6 Hz). 13C-NMR, (75 MHz,
1
3
CDCl3): l 14.60 (qdm, JCH=125.4 Hz, JCP=3.1 Hz,
CH2CH3); 18.0 (m, 2JCP=27.6 Hz, CH3CHCH3); 19.22
2
1
(m, JCP=18.9 Hz, CH3CHCH3); 22.67 (ddm, JCH
=
=
4.9. Preparation of 15%, 15¦
1
1
128 Hz, JCP=9.2 Hz, CH3CH); 44.22 (tdq, JCH
133.6 Hz, 2JCP=14.3 Hz, 2JCH=4.3 Hz, CH2CH3);
A solution of DBU (0.152 g, 1 mmol) in C6H5CH3 (1
ml) was slowly added to a cooled (−20 °C) C6H5CH3
solution (1 ml) containing of i-propanethiol (0.152 g, 2
mmol) and 7b (0.21 g, 1 mmol). The mixture was then
quenched at 0 °C with a solution of HCl in ether (1 N)
in excess (15 mmol). After elimination of the ammo-
nium salts by filtration under a nitrogen pressure,
volatile products were eliminated under reduced pres-
58.29 (qt, 1JCH=140.8 Hz, 3JCH=3.9 Hz, CH3O);
1
3
3
72.31 (tdq, JCH=141.7 Hz, JCP=26.8 Hz, JCH=5.0
Hz, CH2O); Carom: 126.62 (dd, 1JCH=160.4 Hz, 2JCH
=
1
7.7 Hz); 127.46 (ddm, JCH=160.0 Hz, JCP 4.7 Hz);
1
2
128.65 (dt, JCH=160.5 Hz, JCH=7.6 Hz); 128.77 (dt,
1JCH=159.4 Hz, JCH=8.3 Hz); 136.36 (dm, JCP
=
2
3
1
21.9 Hz); 143.15 (dm, JCP=22.6 Hz).

G. Baba et al. / Journal of Organometallic Chemistry 643–644 (2002) 342–349
349
2
1
7.7 Hz, JCP=2.7 Hz); 128.70 (ddm, JCH=160.6 Hz,
4.11. Preparation of 2-isopropylphosphineoxide
benzylmethylether 17
3JCH=7.6 Hz, JCP=3.5 Hz); 134.59 (dm, JCP=16.5
Hz); 136.24 (dm, JCH=165.8 Hz); 141.72 (dm, JCP
3
1
1
3
=
5.7 Hz). HRMS, Calc. for C11H17OP: 196.1017. Found:
196.102.
Prepared by following the protocol used for 8a. Yield
85% after purification by flash chromatography on
silica gel (eluent EtOAc).
1
31P-NMR (121 MHz, CDCl3): l 42.0 (d, JPH=465
1
Hz), 31P-NMR (121 MHz, C6D6): l 39 (d, JPH=466.4
References
Hz). 1H-NMR (200 MHz, CDCl3) l: 1.15 (dd, 3H,
3JPH=20 Hz, 3JHH=7.2 Hz CH3CHCH3); 1.20 (dd,
[1] For a review, see J.W. Grissom, G.U. Gunawardena, D. Kling-
berg, D. Huang, Tetrahedron 52 (1996) 6453.
[2] K.C. Nicolaou, G. Zuccarello, Y. Ogawa, E.J. Schweiger, T.
Kumazawa, J. Am. Chem. Soc. 110 (1988) 4866.
[3] K.C. Nicolaou, P. Maligres, J. Shin, E. de Leon, D. Rideout, J.
Am. Chem. Soc. 112 (1990) 7825.
[4] R. Nagata, H. Yamanaka, E. Okazaki, I. Saito, Tetrahedron
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[5] J.W. Grissom, D. Klingberg, Tetrahedron Lett. 36 (1995) 6607.
[6] J.W. Grissom, B.J. Slattery, Tetrahedron Lett. 35 (1994) 5137.
[7] S. Braverman, Y. Zafrani, S. Rahimipour, Tetrahedron Lett. 42
(2001) 2911.
[8] A.G. Meyers, P.S. Dragovich, J. Am. Chem. Soc. 111 (1989)
9130.
[9] (a) L.S. Liebeskind, S. Riesinger, J. Org. Chem. 58 (1993) 408;
(b) R.W. Sullivan, V.M. Coghlan, S.A. Munk, M.W. Reed,
H.W. Moore, J. Org. Chem. 59 (1994) 2276.
3
3
3H, JPH=17.5 Hz, JHH=7.1 Hz, CH3CHCH3); 2.30
2
3
(dh, H, JPH=10.8 Hz, JHH=7.2 Hz, CH3CH); 3.40
2
(s, 3H, OCH3); 4.6 and 4.7 (2×2H, JHH=11.7 Hz,
CH2O); 7.16 (dd, H, 1JPH=465 Hz, 3JHH=3.4 Hz,
PꢁH); 7.4–7.8 (m, 4 Harom). 13C-NMR (50 MHz,
1
CDCl3): l 15.0 (qm, JCH=128.3 Hz, CH3CH); 27.78
1
1
(ddm, JCH=128.0 Hz, JCP=59.2 Hz, CH3CH); 57.10
1
3
(qt, JCH=142.6 Hz, JCH=3.5 Hz, OCH3); 71.64 (tq,
1JCH=143 Hz, JCH=5.0 Hz, JCP=4.6 Hz, CH2O);
124.22–139.14 (Carom). HRMS, Calc. for C10H14O2P
[M−CH3]+: 197.0731. Found: 177.0725.
3
3
4.12. Preparation of the free 2-i-propylphosphine
benzylmethylether 16
[10] M.-J. Wu, C.-F. Lin, S.-H. Chen, F.-C. Lee, J. Chem. Soc.
Perkin Trans. 1 (1999) 2875.
[11] For review see J. Escudie´, H. Ranaivonjatovo, L. Rigon, Chem.
Rev. 100 (2000) 3639.
Prepared by following the protocol used for 7a.
1
31P-NMR (121 MHz, CDCl3): l −33.5 (d, JPH
=
[12] For a review on the VGSR technique, see J.-M. Denis, A.-C.
Gaumont, Gas-Phase Reactions in Organic Synthesis, Gordon
and Breach Science Publishers, New York, 1997, pp. 195–235.
[13] (a) J.-C. Guillemin, T. Janati, J.-M. Denis, P. Guenot, P. Savig-
nac, Tetrahedron Lett. 35 (1994) 245;
(b) J.-C. Guillemin, T. Janati, J.-M. Denis, J. Chem. Soc. Chem.
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[14] J.-F. Pilard, G. Baba, A.-C. Gaumont, J.-M. Denis, Synlett
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(b) R.H. Neilson, Inorg. Chem. 20 (1981) 1679.
[16] G. Baba, J.-F. Pilard, K. Tantaoui, A.-C. Gaumont, J.-M.
Denis, Tetrahedron Lett. 36 (1995) 4421.
[17] A.-C. Gaumont, X. Morise, J.-M. Denis, J. Org. Chem. 57
(1992) 4292.
[18] D. Guillerm, G. Linstrumelle, Tetrahedron Lett. 26 (1985) 3811.
[19] (a) P. Magnus, P. Carter, J. Elliot, R. Lewis, J. Harling, T.
Pitterna, W.E. Bauta, S. Fortt, J. Am. Chem. Soc. 114 (1992)
2544;
(b) A.S. Kende, C.A. Smith, J. Org. Chem. 53 (1988) 2655.
[20] J.F. Kadow, M.G. Saulnier, M.M. Tun, D.R. Langley, D.M.
Vyas, Tetrahedron Lett. 30 (1989) 3499.
1
213 Hz). H-NMR (300 MHz, CDCl3) l: 1;10 (dd, 3H,
3
3JPH=10.4 Hz, JHH=6.9 Hz, CH3CHCH3); 1.12 (dd,
3
3
3H, JPH=17.4 Hz, JHH=7.0 Hz, CH3CHCH3); 2.10
3
2
(hd, H, JHH=7.0 Hz, JPH=1.5 Hz, CH3CH); 3.3 (s,
3H, OCH3); 3.8 (dd, H, JPH=2.3 Hz, JHH=7.4 Hz,
PꢁH); 4.4 and 4.5 (d, 2×2H, JHH=5.3 Hz, CH2O); 4
Harom: 7.03 (td, H, JPH=7.3 Hz, JHH=1.3 Hz); 7.21
1
3
2
3
4
3
4
(td, H, JHH=7.4 Hz, JHH=1.5 Hz); 7.31 (ddd, H,
3JHH=7.4 Hz, JPH=2.7 Hz, JHH=1.2 Hz); 7.40 (ddd,
H, JPH=12.7 Hz, JPH=7.0 Hz, JHH=1.2 Hz. 13C-
3
3
4
1
NMR (75 MHz, CDCl3): l 21.42 (m, JCH=126.3 Hz,
2JCP=19.0 Hz, CH3CHCH3); 22.94 (qm, JCH=126.4
1
2
1
Hz, JCP=3.7 Hz, CH3CHCH3); 24.28 (ddm, JCH
=
=
1
1
131.8 Hz, JCP=8.1 Hz, CH3CH); 58.07 (qt, JCH
141.0 Hz, 3JCH=3.6 Hz, CH3O); 73.84 (tdq,
1JCH=141.6 Hz, 3JCP=14.7 Hz, 3JCH=4.9 Hz,
1
3
CH2O); Carom: 127.60 (dddm, JCH=161.4 Hz, JCH
=