Identification of a four-center intermediate in a Grignard addition reaction to a P-S bond

Article abstract of DOI:10.1016/j.tet.2007.10.015

The reaction between tert-butylmagnesium chloride (or tert-pentylmagnesium chloride) and the particular phosphorus-sulfur bond of a benzothiadiphospholic system showed, for the first time, evidence of formation of intermediates with a four-center structure. The possibility, for the phosphorus atom, to have very stable hypervalent coordinations makes it possible to observe its hypervalent states during the course of a reaction. The benzothiadiphosphole, with its bicyclic folded structure, further stabilizes the hypervalent coordinations thus making the intermediates sufficiently stable to be detected during the course of the reaction by ³¹P NMR spectroscopy, which revealed the nature and the stability of the species involved in this reaction, carried out also using other Grignard reagents.

Full text of DOI:10.1016/j.tet.2007.10.015

Tetrahedron 63 (2007) 12595–12600
Identification of a four-center intermediate in a Grignard
addition reaction to a P–S bond
*
Graziano Baccolini, Carla Boga and Marzia Mazzacurati
Department of Organic Chemistry, ‘A. Mangini’, Alma Mater Studiorum—Universita’ di Bologna,
Viale Risorgimento 4, 40136 Bologna—Italy
Received 18 July 2007; revised 14 September 2007; accepted 4 October 2007
Available online 6 October 2007
Abstract—The reaction between tert-butylmagnesium chloride (or tert-pentylmagnesium chloride) and the particular phosphorus–sulfur
bond of a benzothiadiphospholic system showed, for the first time, evidence of formation of intermediates with a four-center structure.
The possibility, for the phosphorus atom, to have very stable hypervalent coordinations makes it possible to observe its hypervalent states
during the course of a reaction. The benzothiadiphosphole, with its bicyclic folded structure, further stabilizes the hypervalent coordinations
thus making the intermediates sufficiently stable to be detected during the course of the reaction by 31P NMR spectroscopy, which revealed the
nature and the stability of the species involved in this reaction, carried out also using other Grignard reagents.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
The nature of the mechanism by which a Grignard reagent re-
acts with electrophiles is still an open question. This probably
means that different intermediates can be accounted for this
process depending on the reaction conditions and the electro-
philic system used. There are two possible reaction routes: the
polar concerted mechanism, which is hypothesized to proceed
via a four-center transition state, and the stepwise electron-
transfer mechanism.1 The above two mechanisms may com-
pete and the products from the two processes will often be
the same. However, the problem with this reaction is that it
is not known precisely what happens during the initial step
ofthisadditionreaction. Itshouldbenotedthatthe phosphorus
atom can have very stable hypervalent coordinations2 making
it possible to observe hypervalent states during the course of
areaction. Inthecaseofthe carbonatom, bycontrast, thesehy-
pervalent states are possible but very difficult to be identified.3
Recently, we reported4 a simple, efficient, and atom-eco-
nomic new method for the preparation of symmetric and
asymmetric secondary phosphines. The sequential addition,
at room temperature, of equivalent amounts of the Grignard
reagents R1MgX and R2MgX to a solution of benzothia-
diphosphole (1) gave phosphines 2 and compound 3, the res-
idue of starting reagent 1, which can be regenerated simply
by reacting 3 with PCl3 (Scheme 1). The intermediate of this
PCl3
1) R1MgX
2) R2MgX
P2
P
P
S
S
P1 R2
R1
S
Herein we report for the first time the firm evidence for
possible intermediates formed during the initial stage of a
Grignard addition reaction between t-BuMgCl or t-PentMgCl
and a P–S bond. These intermediates have been identified by
31P NMR spectroscopy and have a four-center structure, in
agreement with that of the classic four-center transition state
that has been hypothesized for this type of reaction, and they
are assumed to present a carbon atom in a hypervalent state.
The reaction course was monitored by 31P NMR spectros-
copy for other Grignard reagents.
S
1
MgX
MgX
A
R1, R2 = alkyl, aryl
H3O+
H
P
R1R2PH
+
SH SH
2(30-85%)
Keywords: Hypervalent phosphorus intermediates; Phosphines; Grignard
addition reactions.
3 (90%)
* Corresponding author. Tel.: +39 051 2093616; fax: +39 051 2093654;
e-mail: baccolin@ms.fci.unibo.it
Scheme 1. Synthesis of secondary phosphines with recycle of starting
reagent 1.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.015

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G. Baccolini et al. / Tetrahedron 63 (2007) 12595–12600
reaction was hypothesized to be a pentacoordinate phospho-
rus species such as A.
mixture. As expected, no signals characteristic of reagent
1 were observed in the spectrum, but two new sets of dou-
1
1
blets [d¼38.1 (d, JP–P¼275 Hz), 9.6 (d, JP–P¼275 Hz)]
To evaluate whether secondary phosphines are also formed
using Grignard reagents bearing bulky groups, we attempted
to react 1 with tert-butylmagnesium chloride (Scheme 2).
strongly upfield with respect to those of 1 [d¼86.8 (d, 1JP–P
¼
208 Hz), 66.7 (d, 1JP–P¼208 Hz)] were observed, suggesting
the presence of a new species containing a P–P bond. In ad-
dition, these latter signals remained for several hours indi-
cating the good stability of this intermediate. The 1H NMR
spectrum of the crude reaction mixture in THF-d8 contains
signals characteristic of the presence of two non-equivalent
aromatic rings as well as a doublet with a coupling constant
of 14 Hz in the region of tert-butylic protons, which is
ascribed to a3JP–H coupling. This was confirmed by exami-
nation of the 13C NMR spectrum, which contained two dou-
blets of doublets, centered at 37.2 and 29.9 ppm, which can
be assigned, respectively, to the tertiary and methylic carbon
atoms of the tert-butyl group each coupled with two
phosphorus atoms linked in a P–P bond. Furthermore, to de-
termine which phosphorus is adjacent to the tert-butyl moi-
Δ
T: 90-100 °C
4-5 min
1
R1MgX
P2
R1MgX
1
S
P1
R1
1) 2 R2MgX
2) H2O
S
(R2)2PH
+ 3
XMg
2
4*a,b,c
1
ety, we carried out a H, 31P heteronuclear multiple bond
P2
P2
correlation experiments (HMBC, Fig. 1) optimized for cou-
pling constant of 12.5 Hz (close to the observed three bond
3JP–H coupling constant of the methyl signal of the tert-butyl
moiety). The HMBC spectrum showed a cross peak indicat-
ing a correlation between the proton resonance of the methyl
doublet at 1.14 ppm and that of the 31P doublet at 38.1 ppm.
R1MgX
S
S
S
R1
P1
R1
P1
R1
S
MgX
XMg
MgX
5c,e,f
4c,e,f
Δ
H3O+
T: 90-100 °C
The spectrum additionally showed cross couplings in the
aromatic region indicating connections with the phosphorus
atom signal at 9.6 ppm (Fig. 1). The NMR spectroscopic
data are consistent with a structure such as 4*a, which
contains a P–P–C(CH)3 structure and is characterized by
non-symmetric aromatic rings. Such a configuration could
form if one of the sulfur atoms in 1 coordinates with the mag-
nesium atom of tert-butylmagnesium chloride. To verify the
thermal instability of this intermediate, as indicated by the
GC–MS data, after removal of the solvent, the crude reaction
mixture containing only 4*a was heated to 90–100 ꢀC, then
re-dissolved in THF and analyzed by 31P NMR spectros-
copy. After about 4–5 min at this temperature, we observed
the disappearance of the signals corresponding to 4*a and
the concomitant appearance of signals related to starting
compound 1 (see Fig. 2).
5-10 min
(R1)2PH
+ 3
1
2c,e,f
a : R1 = t-Bu; b : R1 = t-Pent
c : R1 = i-Pr ; d : R1 = Ph3C
e : R1 = n-Bu; f : R1 = Ph
R2: n-Bu, Ph; X = Br, Cl
Scheme 2.
GC–MS analysis of the reaction mixture showed only start-
ing reagent 1, indicating that the reaction between 1 and
tert-butylmagnesium chloride does not proceed even in the
presence of an excess of Grignard reagent. Surprisingly,
however, when we subsequently added a less hindered
Grignard reagent, R2MgX (Scheme 2) to the reaction mixture
containing 1 and tert-butylmagnesium chloride, GC–MS
analysis of the reaction mixture again showed only com-
pound 1, indicating that 1 also does not react with this new
Grignard reagent. Given that, in the absence of tert-butyl-
magnesium chloride, R2MgX easily reacts4 with 1 to afford
the corresponding secondary symmetrical phosphine R22PH,
our finding of no apparent reaction between 1 and R2MgX
was unexpected. A plausible explanation would be that in
the reaction mixture, 1 reacts with the tert-butyl Grignard
to form an unstable intermediate, and that this intermediate
decomposes in the GC injector such that the GC–MS analy-
sis indicates that only compound 1 is present. Thus, we
conjectured that the tert-butylmagnesium chloride may
have complexed with the S–P bond of 1, thus hindering
the subsequent attack of the less hindered Grignard reagent.
To gain more information about the hypothesized interaction
between reagent 1 and tert-butylmagnesium chloride, we
recorded a 31P NMR spectrum of the final crude reaction
Figure 1. 1H and 31P HMBC spectrum of intermediate 4*a in THF-d8.

G. Baccolini et al. / Tetrahedron 63 (2007) 12595–12600
12597
86.8 66.7
31P NMR spectrum in THF
a
b
c
of starting reagent 1
38.1
9.6
Intermediate 4*a, formed after
addition of t-butylmagnesuim
chloride to compound 1
31P NMR spectrum of the reaction
mixture containing intermediate 4*a
after heating at 90-100 °C for 4-5 min.
that shows reformation of starting
reagent 1.
150
100
50
0
-50
-100
-150
ppm
Figure 2. 31P NMR spectra in THF of the reaction between benzothiadiphosphole 1 and tert-butylmagnesium chloride.
The fact that simple heating at 90–100 ꢀC is sufficient to
break the phosphorus–carbon bond, which is typically a
very strong bond, with reformation of starting reagent 1, sup-
ports the hypothesis that the intermediate has a structure like
that of 4*a (Scheme 2), in which the magnesium atom is
coordinated both with the sulfur atom and, with a labile
interaction, with the carbon atom of the tert-butyl group.
In addition, this behavior, together with spectroscopic infor-
mation, supports the proposed structure bearing two phos-
phorus–sulfur bonds. In fact, if 4*a contains only one P–S
bond, the reformation of 1 by simple heating seems to be
very improbable.
under a positive flow of argon, was heated at 90–100 ꢀC for
4–5 min and, after dissolution in THF, showed, at 31P NMR
analysis, complete disappearance of signals related to 4*c
and concomitant appearance of those of starting reagent 1.
Addition of a further amount of iso-propylmagnesium chlo-
ride to this reaction mixture produced disappearance of sig-
nals of starting reagent 1 and appearance of signals of 4*c.
Furthermore, after about 24 h from the addition of a large ex-
cess (>5 equiv) of iso-propylmagnesium chloride to 1, the
31P NMR spectrum of the reaction mixture showed disap-
pearance of signals related to intermediates 4*c and 4c and
appearance of a new couple of doublet [(d¼14.3 (d, 1JP–P
¼
1
177 Hz), ꢁ53.9 (d, JP–P¼177 Hz)] ascribed to the penta-
coordinate intermediate 5c. After addition of acidic water,
signals of 5c disappeared and concomitantly signals of diiso-
propylphosphine 2c and compound 3 appeared. The reaction
does not occur with tritylmagnesium chloride (case d), prob-
ably too hindered and consequently not able to form coordi-
nation intermediates with reagent 1.
In order to check whether the behavior showed by the reac-
tion between compound 1 and tert-butylmagnesium chloride
could be observed in other cases, we carried out the reaction
with Grignard reagents characterized by different steric
hindrance (Scheme 2). We found that the reaction between
compound 1 and tert-pentylmagnesium chloride produces
intermediate 4*b, which, when heated, went back to starting
reagents, as previously observed for 4*a. It is interesting to
note that, in the case b (see related spectra in Supplementary
data), after partial reformation of starting reagent 1 by heat-
ing 4*b for 1–2 min at 90–100 ꢀC, we added a further
amount of tert-pentylmagnesium chloride obtaining again
disappearance of signals of 1 and enhancement of those of
4*b. This latter reaction mixture, after further heating, again
reverted to 1, clearly indicating the reversibility of the
process.
In contrast, when we carried out the reaction between 1 and
1 equiv of n-butylmagnesium bromide (case e, Fig. 3) or
phenylmagnesium bromide (case f), we observed in the
31P NMR spectrum the presence of starting material 1 to-
gether with two couples of doublets ascribed to intermediate
4e [d¼15.8 and 12.2 (1JP–P¼258 Hz)] or 4f [d¼27.6 and
14.0 (1JP–P¼265 Hz)] and to pentacoordinate intermediate
5e (or 5f).
When a further equivalent of Grignard reagent was added to
the above solution the 31P NMR spectrum showed complete
conversion of starting reagent 1 and only presence of one
couple of doublets, which is in accord with stable pentacoor-
dinate phosphorus species such as 5e [d¼ꢁ31.6 and ꢁ43.3
A different behavior was observed with iso-propylmagne-
sium chloride, less sterically hindered than the cases a and
b. In the case c, immediately after the addition of 1 equiv
of iso-propylmagnesium chloride to reagent 1 we observed,
at 31P NMR, two couples of doublets, ascribed to intermedi-
(1JP–P¼169 Hz)] or 5f [d¼ꢁ8.3 and ꢁ45.3 (1JP–P
¼
1
1
ates 4*c [d¼30.1 (d, JP–P¼262 Hz), 10.4 (d, JP–P
¼
179 Hz)], respectively. In fact, after addition of water to
these reaction mixtures we observed the immediate disap-
pearance of signals of 5e (or 5f) and the concomitant
262 Hz)] and 4c [d¼28.5 (d, 1JP–P¼266 Hz), 15.1 (d, 1JP–P
¼
266 Hz)]. The reaction mixture, after removal of the solvent

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G. Baccolini et al. / Tetrahedron 63 (2007) 12595–12600
Table 1. 31P NMR signals, in THF, of intermediates 4*a,b,d, 4d–f, and 5d–f
86.8 66.7
Starting reagent 1
Intermediate
d1P (ppm)
d2P (ppm)
4*a
4*b
4*c
4c
4e
4f
5c
38.1 (JP–P¼275 Hz)
40.4 (JP–P¼281 Hz)
30.1 (JP–P¼262 Hz)
28.5 (JP–P¼266 Hz)
15.8 (JP–P¼258 Hz)
27.6 (JP–P¼265 Hz)
14.3 (JP–P¼177 Hz)
ꢁ31.6 (JP–P¼169 Hz)
ꢁ8.3 (JP–P¼179 Hz)
9.6 (JP–P¼275 Hz)
a
12.1 (JP–P¼281 Hz)
10.4 (JP–P¼262 Hz)
15.1 (JP–P¼266 Hz)
12.2 (JP–P¼258 Hz)
14.0 (JP–P¼265 Hz)
ꢁ53.9 (JP–P¼177 Hz)
ꢁ43.3 (JP–P¼169 Hz)
ꢁ45.3 (JP–P¼179 Hz)
86.8 66.7 15.8 12.2 -31.6 -43.3
4e 5e
5e
5f
b
c
1
corresponding 4* precursors; and the fact that we did not ob-
serve signals related to intermediates 4*,e,f might be due to
the limited steric hindrance of the Grignard reagents used
that makes these intermediates not detectable, which being
transformed, immediately after their formation, into 4e,f.
In line with this is the fact that when iso-propylmagnesium
chloride with a steric hindrance between that of cases a,b
and that of n-butylmagnesium bromide, both intermediates,
4*c and 4c were observed. These findings confirm that the
behavior of iso-propyl Grignard reagent falls in a ‘border
line’situation between that of cases a,b and e,f. The contem-
poraneous presence of the two intermediates 4*c and 4c
suggest the presence of an equilibrium between the two in-
termediates, which in cases a,b is completely shifted toward
4*a,b whereas in cases e,f is shifted in opposite sense.
5e
3, δ = - 53.4
2e, δ = - 68.3
d
150
100
50
0
-50
-100
-150 ppm
Figure 3. 31P NMR spectra of the reaction between benzothiadiphosphole 1
and n-butylmagnesium bromide carried out in the NMR tube in THF. (a)
Spectrum of the starting reagent 1. (b) After addition of 1 equiv of the
Grignard reagent with respect to 1 (presence of intermediate 4e and traces
of 5e and starting material 1). (c) After addition of a further equivalent of
Grignard reagent (only presence of 5e). (d) Spectrum obtained after addition
of acidic water of the previous reaction mixture c, showing formation of
dibutylphosphine (2e) and compound 3.
In order to make an easy comparison, 31P NMR chemical
shifts of intermediates 4*a,b,c, 4c,e,f, and 5c,e,f are
collected in Table 1.
As it can be seen, the chemical shift of the signal related to
the P1 phosphorus atom linked to the carbon atom of the tert-
butyl and the tert-pentyl moieties, at 38.1 and 40.4 ppm for
intermediates 4*a and 4*b, respectively, is significantly
different from that of intermediates 4c,e,f, whereas, as ex-
pected, chemical shifts related to the P2 phosphorus atom
fall in the same region of the spectrum for both intermediates
4* and 4. In addition, on going from intermediates 4c,e,f
toward pentacoordinated 5c,e,f, both signals related to the
P1 and P2 phosphorus atoms are strongly upfield, as expected
as a consequence of a coordination change from a tetra to
a pentacoordinated phosphorus intermediate.5
appearance of signals of the corresponding secondary phos-
phine 2e (or 2f) and of the compound 3, residue of reagent 1
(Fig. 3).
It has to be noted that a simple heating at 90–100 ꢀC of a mix-
ture of intermediates 4e,f and 5e,f was not able to give 1 in
appreciable amounts. This might indicate a different strength
of the phosphorus–carbon bond both for 4e,f and 5e,f with
respect to 4*a,b, in agreement with the observed trend, to-
ward upfields, of the corresponding 31P NMR chemical
shifts. Then, in 4e,f (Scheme 2) the C–Mg bond is completely
broken and, consequently, a total coordination (onlypartial in
the case of 4*a,b) between sulfur and MgX group occurs.
In other words, we observed a different behavior depending
on the steric hindrance of the Grignard reagent. Actually,
with bulky reagents, such as tert-butyl- and tert-pentylmag-
nesium chloride, the reaction only gave formation of the
four-center intermediates 4*a,b, which can be reverted
to starting reagent 1 by simple heating, whereas with iso-
propylmagnesium chloride both intermediates 4*c and 4c
were observed and, in the other cases (e,f), only 4e and 4f
were detected. Finally, once formed intermediate 4, the reac-
tion can proceed also toward intermediates 5.
In agreement with this proposed mechanism and with the
two different structures 4* and 4, it is observed that the at-
tack of the second equivalent of RMgX (R¼n-butyl, phenyl)
to 4 is favored with respect to that of the first equivalent of
the same Grignard to 1. In fact, as reported above, the addi-
tion of only 1 equiv (or less) of n-butylmagnesium bromide
(or phenylmagnesium bromide) to compound 1 produces al-
ways 31P NMR signals of both 4e and 5e (or 4f and 5f) to-
gether, obviously, with those of unreacted 1 (see Fig. 3 and
Fig. 3, Supplementary data for case f). This behavior can
be due to the complete coordination between sulfur and
magnesium atoms in intermediates 4e,f that makes the adja-
cent phosphorus atom more active to undergo the second
attack of the Grignard reagent with respect to the first one.
3. Conclusion
In conclusion, here we have reported the first experimental
evidence of an intermediate formed during the initial stage
of a Grignard addition reaction. This intermediate has
a four-center structure and derives from the reaction between
sterically hindered Grignard reagents (tert-butylmagnesium
The observation of intermediates such as 4e,f clearly implies
that the reaction proceeds through the formation of the

G. Baccolini et al. / Tetrahedron 63 (2007) 12595–12600
12599
chloride, tert-pentylmagnesium chloride, or iso-propylmag-
nesium chloride) and a particular phosphorus–sulfur bond of
compound 1, which, with its bicyclic folded structure, stabi-
lizes the hypervalent intermediates involved in this Grignard
addition. This feature made the intermediates sufficiently
stable to monitor the reaction course by 31P NMR spectros-
copy, thereby revealing the nature and stability of all the
species involved in this reaction, carried out also using other
Grignard reagents.
31P NMR (242.77 MHz, THF-d8, 25 ꢀC, H3PO4 ext. std):
d (ppm)¼38.1 (d, 1JP–P¼275 Hz), 9.6 (d, 1JP–P¼275 Hz).
4.2.2. Intermediate 4*b. 1H NMR (400 MHz, THF-d8,
25 ꢀC): d (ppm)¼7.54 (d, J¼8.5 Hz, 1H), 7.46 (d, J¼
8.0 Hz, 2H), 7.12 (d, J¼8.0 Hz, 1H), 6.74 (d, J¼7.8 Hz,
1H), 6.07 (br d, J¼2 Hz, 1H), 2.38 (s, 3H), 2.02 (s, 3H),
1.60–1.45 (m, 2H), 1.10 (d, JP–H¼11 Hz, 6H), 1.06–0.97
(m, 3H); 13C NMR (100.56 MHz, THF-d8, 25 ꢀC): d (ppm)¼
151.3 (d, J¼4 Hz), 148.2 (d, J¼26 Hz), 142.4 (d, J¼27 Hz),
136.5, 135.0, 134.5 (d, J¼10 Hz), 133.8 (d, J¼33 Hz),
132.1, 130.9, 130.2, 128.9, 125.2 (d, J¼6 Hz), 39.0 (dd,
4. Experimental
2
1JP–C¼37 Hz, JP–C¼11 Hz, C(CH3)2), 32.9 (d, J¼6 Hz),
2
3
4.1. General procedures
23.6 (dd, JP–C¼12 Hz, JP–C¼6 Hz, C(CH3)2), 23.0 (dd,
3
2JP–C¼12 Hz, JP–C¼7 Hz, C(CH3)2), 20.3 (s, CH3), 20.1
1H, 13C, and 31P NMR spectra were recorded at 600 (or 400),
150.82, and 242.77 (or 161.89) MHz, respectively. Chemical
shifts are referenced to solvent (THF-d8, 1.8 and 26.7 ppm
for 1H and 13C NMR, respectively) and to H3PO4 (ext. std)
for 31P NMR spectra. J values are given in hertz. THF was
distilled from sodium benzophenone ketyl. All Grignard re-
agents used, except tritylmagnesium chloride (Ph3CMgCl),
which was prepared according to Gilman,6 are commercially
available. Air and moisture sensitive solutions and reagents
were handled in a dried apparatus under an atmosphere of
argon.
(s, CH3), 8.3 (d, J¼12 Hz, CH3); 31P NMR (242.77 MHz,
1
THF-d8, 25 ꢀC, H3PO4 ext. std): d (ppm)¼40.4 (d, JP–P
¼
281 Hz), 12.1 (d, 1JP–P¼281 Hz).
4.3. Formation of the intermediates 4*c, 4c, and 5c
To a solution of compound 1 (0.306 g, 1.0 mmol), dissolved
in 10 mL of THF, 1.0 equiv of iso-propylmagnesium chlo-
ride (2.0 M in THF) was added. After 1 min the 31P NMR
spectrum of the crude reaction mixture showed the presence
of compounds 4*c and 4c. This reaction mixture treated
with a further amount of iso-propylmagnesium chloride
(2.0 equiv) showed again the presence of signals related to
4*c and 4c, but with time signals corresponding to com-
pound 5c appeared. After 24 h, the conversion from 4c to
5c was almost complete. Addition of acidic water to this re-
action mixture produced disappearance of signals of 5c, and
appearance of those of diisopropylphosphine (2c) [31P NMR
4.2. Formation of intermediates 4*a and 4*b: general
procedure
To a solution of compound 1 (0.030 g, 0.098 mmol), dis-
solved in 3 mL of THF-d8, a solution of Grignard reagent
(tert-butyl- or tert-pentylmagnesium chloride, 1.5 equiv)
was added. After about 5–10 min the reaction mixture, ana-
lyzed by GC–MS analysis, showed only the presence of the
starting reagent 1. A sample of the same crude reaction mix-
ture, analyzed by 31P NMR spectroscopy, showed the pres-
1
(THF): d¼ꢁ15.2 ppm (br d, JP–H¼199 Hz)] and of com-
1
pound 3 [31P NMR (THF): d¼ꢁ53.4 ppm (br d, JP–H
¼
228 Hz)]. In another experiment, 31P NMR spectrum of a
solution containing intermediate 4*c, after removal of the
solvent under a positive flow of argon was heated at 90–
100 ꢀC for 4–5 min and after dissolution in THF, showed,
at 31P NMR analysis, complete disappearance of signals re-
lated to 4*c and concomitant appearance of those of starting
reagent 1. Addition of a further amount of iso-propylmagne-
sium chloride to this reaction mixture produced again dis-
appearance of signals of starting reagent 1 and appearance
of signals of 4*c.
1
ence of signals of 4*, which was characterized also by H
1
NMR, 13C NMR, and, in the case of 4*a, also by H–31P
HMBC NMR. The remaining reaction mixture, after removal
of the solvent under a positive flow of argon, was heated at
90–100 ꢀC for 4–5 min and, after dissolution in THF-d8,
showed, at 31P NMR analysis, complete disappearance of sig-
nals related to 4* and concomitant appearance of those of
starting reagent 1 (Fig. 1). If the reaction is carried out with
equimolar amount of reagents, a longer reaction time is re-
quired to have complete conversion of the starting reagent 1
into intermediate 4*. Addition of other Grignard reagents to
this intermediate did not give changes in the spectrum. All
attempts of crystallization of 4* did not lead to the formation
of crystals suitable for X-ray diffraction analysis.
4.3.1. Intermediate 4*c. 31P NMR (161.89 MHz, THF,
1
25 ꢀC, H3PO4 ext. std): d (ppm)¼30.1 (d, JP–P¼262 Hz),
10.4 (d, 1JP–P¼262 Hz).
4.3.2. Intermediate 4c. 31P NMR (161.89 MHz, THF, 25 ꢀC,
1
H3PO4 ext. std): d (ppm)¼28.5 (d, JP–P¼266 Hz), 15.1 (d,
4.2.1. Intermediate 4*a. 1H NMR (600 MHz, THF-d8,
25 ꢀC): d (ppm)¼7.58 (d, J¼10.7 Hz, 1H), 7.53 (d, J¼
7.9 Hz, 1H), 7.29 (d, J¼6.5 Hz, 1H), 7.20 (d, J¼8.4 Hz,
1H), 6.94 (d, J¼8.3 Hz, 1H), 6.21 (br d, J¼3 Hz, 1H), 2.34
1JP–P¼266 Hz).
4.3.3. Intermediate 5c. 31P NMR (161.89 MHz, THF,
1
25 ꢀC, H3PO4 ext. std): d (ppm)¼14.3 (d, JP–P¼177 Hz),
3
(s, 3H), 2.04 (s, 3H), 1.14 (d, JP–H¼14 Hz, 9H); 13C NMR
ꢁ53.9 (d, 1JP–P¼177 Hz).
(150.82 MHz, THF-d8, 25 ꢀC): d (ppm)¼152.5 (dd, J¼4,
1 Hz), 149.7 (d, J¼25 Hz), 143.6 (dd, J¼26, 2 Hz), 137.8,
136.4, 136.0 (d, J¼9 Hz), 135.3 (d, J¼33 Hz), 133.4 (d, J¼
4 Hz), 132.4, 131.7, 130.3, 126.7 (d, J¼6 Hz), 37.2 (dd,
4.4. Formation of intermediates 4e,f and 5e,f: general
procedure
2
2
1JP–C¼31 Hz, JP–C¼18 Hz, C(CH3)3), 29.3 (dd, JP–C
¼
To a solution of compound 1 (0.306 g, 1.0 mmol), dissolved
in 10 mL of THF, 1.0 equiv of n-butylmagnesium bromide
3
14 Hz, JP–C¼6 Hz, C(CH3)3), 22.5 (s, CH3), 22.3 (s, CH3);

12600
G. Baccolini et al. / Tetrahedron 63 (2007) 12595–12600
(or phenylmagnesium bromide) was added. After 1 min the
31P NMR spectrum of the crude reaction mixture showed
presence of starting material 1 together with compounds
4e (or 4f) and 5e (or 5f). When a further equivalent of
Grignard reagent was added to the above solution containing
intermediate 4e (or 4f), the corresponding 31P NMR spec-
trum showed complete conversion of starting reagent 1
and presence of intermediate 5e (or 5f). Addition of acidic
water to this solutions gave compound 3 together with
di(n-butyl)phosphine (2e) (or diphenylphosphine (2f)). 31P
NMR spectra of solutions containing intermediates 4 and/
or 5, after heating at 90–100 ꢀC for 5–10 min, resulted
unchanged.
Supplementary data
Experimental procedures, characterization data, behavior,
and spectra of intermediates 4*b, 4*c, 4c, 4f, 5c, and 5f
are provided. Supplementary data associated with this article
can be found in the online version, at doi:10.1016/
j.tet.2007.10.015.
References and notes
1. (a) Holm, T.; Crossland, I. Mechanistic Features of the
Reactions of Organomagnesium Compounds in Grignard
Reagents New Developments; Richey, H. G., Jr., Ed.; Wiley:
Chichester, UK, 2000, Chapter 1; (b) Garst, J. F.; Soriaga, M. P.
Coord. Chem. Rev. 2004, 248, 623–652; (c) Hoffmann, R. W.;
Holzer, B. Chem. Commun. 2001, 491–492.
2. (a) Holmes, R. R. Pentacoordinated Phosphorus Structure and
Spectroscopy; ACS Monograph 175; American Chemical
Society: Washington, DC, 1980; Vols. I and II; (b) Holmes,
R. R. Acc. Chem. Res. 1998, 31, 535–542; (c) Arduengo, J. A.,
III; Stewart, C. A. Chem. Rev. 1994, 94, 1215–1237; (d)
Wong, C. Y.; Kennepohl, D. K.; Cavell, R. G. Chem. Rev.
1996, 96, 1917–1951.
3. For a recent work about hypervalent pentacoordinate carbon
compounds, see: Yamashita, M.; Yamamoto, Y.; Akiba, K.;
Hashizume, D.; Iwasaki, F.; Takagi, N.; Nagase, S. J. Am.
Chem. Soc. 2005, 127, 4354–4371 and references cited
therein.
4. (a) Baccolini, G.; Boga, C.; Galeotti, M. Angew. Chem. 2004,
116, 3120–3122; (b) Baccolini, G.; Boga, C.; Mazzacurati,
M.; Sangirardi, F. Org. Lett. 2006, 8, 1677–1680.
4.4.1. Intermediate 4e. 31P NMR (161.89 MHz, THF, 25 ꢀC,
1
H3PO4 ext. std): d (ppm)¼15.8 (d, JP–P¼258 Hz), 12.2 (d,
1JP–P¼258 Hz).
4.4.2. Intermediate 4f. 31P NMR (161.89 MHz, THF, 25 ꢀC,
1
H3PO4 ext. std): d (ppm)¼27.6 (d, JP–P¼265 Hz), 14.0 (d,
1JP–P¼265 Hz).
4.4.3. Intermediate 5e. 31P NMR (161.89 MHz, THF, 25 ꢀC,
1
H3PO4 ext. std): d (ppm)¼ꢁ31.6 (d, JP–P¼169 Hz), ꢁ43.3
(d, 1JP–P¼169 Hz).
4.4.4. Intermediate 5f. 31P NMR (161.89 MHz, THF, 25 ꢀC,
H3PO4 ext. std): d (ppm)¼ꢁ8.3 (d, 1JP–P¼179 Hz), ꢁ45.3 (d,
1JP–P¼179 Hz).
Acknowledgements
5. Phosphorus-31 NMR Spectroscopy in Stereochemical Analysis;
Verkade, J. G., Quin, L., Eds.; Methods in Stereochemical
Analysis; VCH: Deerfield Beach, FL, 1987; Vol. 8.
6. Gilman, H.; Zoellner, E. A. J. Am. Chem. Soc. 1929, 51, 3493–
3496.
ꢀ
Work supported by Alma Mater Studiorum–Universita di
Bologna (ex 60%) and MIUR (PRIN 2004). We thank
Dr. Paolo Frizzera and Dr. Andrea Mazzanti for technical
support in HMBC experiment.