Improved dimethylzinc-promoted vinylation of nitrones with vinylboronic esters

Article abstract of DOI:10.1016/j.jorganchem.2010.07.009

Vinylboronic esters derived from 4,4,6-trimethyl-[1,3,2]dioxaborinane react with nitrones in the presence of dimethylzinc; nucleophilic addition of the vinyl group onto nitrones produces N-allylic hydroxylamines in fair yields. The sequence is compatible with various functional groups on the vinylic moiety. The mechanism and kinetic aspects are discussed on the basis of DFT calculations.

Full text of DOI:10.1016/j.jorganchem.2010.07.009

Journal of Organometallic Chemistry 695 (2010) 2447e2454
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Improved dimethylzinc-promoted vinylation of nitrones with vinylboronic esters
Nageswaran PraveenGanesh a, Cristina de Candia a, Antony Memboeuf b, György Lendvay b,
,
Yves Gimbert a, Pierre Y. Chavant a
*
a Département de Chimie Moléculaire, UMR 5250-ICMG FR2607, CNRS-Université Joseph Fourier BP 53, 38041 Grenoble cedex 9, France
b Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, P.O. Box 17, H-1525, Budapest, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Vinylboronic esters derived from 4,4,6-trimethyl-[1,3,2]dioxaborinane react with nitrones in the pres-
ence of dimethylzinc; nucleophilic addition of the vinyl group onto nitrones produces N-allylic
hydroxylamines in fair yields. The sequence is compatible with various functional groups on the vinylic
moiety. The mechanism and kinetic aspects are discussed on the basis of DFT calculations.
Ó 2010 Elsevier B.V. All rights reserved.
Received 4 June 2010
Received in revised form
8 July 2010
Accepted 8 July 2010
Available online 16 July 2010
Keywords:
Vinylboronates
Allyl-hydroxylamines
Transmetallation
Boron
Zinc
1. Introduction
of boronic acids with 2,2-dimethylpropane-1,3-diol is awell-known,
convenient procedure [5]. The corresponding esters can be easily
In the course of our study on the reactivity of nitrones with
functionalized organometallics, we have shown [1] that vinyl-
boronic esters of pinacol (4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxa-
borolane) 1 could, in the presence of dimethylzinc, transfer their
vinyl substituent to nitrones 2 to yield N-hydroxy-allylamines 3 in
fair yields. The starting pinacol esters were conveniently prepared
in pure trans form by hydroboration of alkynes with pinacolborane
[2] (4,4,5,5-tetramethyl-1,3,2-dioxaborolane). The hydroboration
step was compatible with functional groups in propargylic position
[3], thus highly functional vinylboronic esters like 1b (Scheme 1)
were readily accessible. However, in the addition step the pina-
colboronate esters 1 reacted sluggishly and our process required
rather harsh conditions. When a-substituted boronic esters were
used in these conditions, they decomposed and very poor yields
were attained [1] (Scheme 1).
We assumed that the poor reactivity of the pinacolborane
derivatives was due to steric hindrance around the boron. Thus, we
considered using unhindered vinylboronic esters. Our first choice
was 5,5-dimethyl-2-vinyl-1,3,2-dioxaborinanes 4[4]. Theprotection
handled and stored. In order to prepare samples of these vinyl-
boronic esters, we used the one-pot sequence proposed by Hoff-
mann et al. [6] starting from dicyclohexylborane (Scheme 2). The
4,4-dimethyl-2-vinyl-1,3,2-dioxaborinanes 4a,b were purified by
flash chromatography. They can be stored in neat form at room
temperature.
2. Reaction of 4,4-dimethyl-2-vinyl-1,3,2-dioxaborinanes 4a,b
with dimethylzinc and nitrone 2a
Very interestingly, the esters 4a,b reacted with nitrones and
dimethylzinc (3 M equiv.) to yield N-allyl-hydroxylamines 3 in 3 h
at 20 ꢀC (Scheme 3). The best solvents were toluene and
dichloromethane; the reactions were slower in THF.
Chai et al. [7] described the transmetallation of unhindered 2-
vinyl-1,3-dioxaborinanes with diethylzinc at 20 ꢀC. A related
preparation of vinylzinc species from vinylboronic acids and
diethylzinc should also be noted [8].
The enhanced reactivity of the unhindered boronic esters 4
compared to pinacol esters 1 allowed much milder conditions,
which were compatible with more functionalized molecules.
Reaction of the ether-substituted pinacol vinylboronate 1b
required 60 ꢀC in DMF and led mainly to degradation products
* Corresponding author. Tel.: þ33 476635796.
E-mail address: Pierre-Yves.Chavant@ujf-grenoble.fr (P.Y. Chavant).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.07.009

2448
N. PraveenGanesh et al. / Journal of Organometallic Chemistry 695 (2010) 2447e2454
1) DMF
Ph
O
N
O
B
60°C, 3.5h
HO
R1
Me2Zn
R1
Ph
Ph
N
O
2) H2O
Ph
3
1
2a
3a: R1 = n- Bu: 90 %
3b: R1 = t-BuO-CH2: 14 %
Scheme 1. Reaction of pinacol esters 1 with nitrones.
Bu
O
B
1) Cy2BH
2) 2 NMO
OH
OH
H
O
Bu
O
Cy
O
B
84 %
resp.
4a
resp.
Cy
O
R1
THF
O
B
O-tert-Bu
H
O
tert-Bu
70%
4b
Cy : Cyclohexyl
NMO : N-methyl-morpholine oxide
Scheme 2. Preparation of 4a,b.
(14% yield of 3b, Scheme 1). The corresponding unhindered
boronic ester 4b reacted at 20 ꢀC with the same nitrone 2a in 82%
yield (Scheme 3). Thus, unhindered boronic esters 4 would clearly
enlarge the scope of the method, without losing the practical
advantages of using air- and chromatography-stable reagents, if
they could be readily accessible by hydroboration [9]. But unlike
hydroboration with pinacolborane, reaction of alkynes with 5,5-
dimethyl-1,3,2-dioxaborinane leads to mixtures. We [10] and
others [11] observed that 5,5-dimethyl-1,3,2-dioxaborinane is
prone to a fast disproportionation, releasing in situ BH3 which
reacts with more than one alkyne.
The initial experiments clearly showed that the reactions with 6
could be run at lower temperatures and with less dimethylzinc
than with pinacol boronic esters 1. The reaction proceeded to
completion in 36 h at room temperature. Nevertheless, we found
that slightly higher temperatures (40 ꢀC) led to faster reaction and
cleaner products. The reaction was best performed in toluene. For
better yields, a rather large excess (3 M equiv.) of dimethylzinc is
necessary.
Thus, we submitted a variety of vinylboronic esters to reaction
with selected nitrones, in the presence of 3 M equiv. of dime-
thylzinc in toluene at 40 ꢀC. We were particularly interested in
Thus the readily prepared, hindered pinacol esters 1 are not
reactive enough and the unhindered, reactive esters 4 are not easily
prepared. We looked for a compromise.
testing the
able by our former work [10]. The results are illustrated in Table 1.
The reaction proceeds generally in good isolated yields.
a-functionalized vinylboronic esters made easily avail-
a
-
oxygenated vinylboronic esters can be used successfully, giving
access to highly functional derivatives.
3. 4,4,6-Trimethyl-2-vinyl-1,3,2-dioxaborinanes 6
The use of MPB-derived boronic esters 6 is a clear improvement
over our precedent use of pinacol-protected boronic esters, both in
terms of accessibility [10] of the reagents 6 and their reactivity.
To compare more accurately the reactivity of 1a, 4a and 6a, we
submitted them to competition experiments. Equal amounts of two
different 2-hex-1-enyl-boronic esters were put in the same reac-
tion mixture in the presence of excess dimethylzinc and excess
nitrone. The conversion of the boronic esters was monitored by gas
chromatography and the ratio of initial rates was estimated. At
40 ꢀC pinacol ester 1a reacted 5 times slower than the MPB ester 6a.
We demonstrated earlier [10] that the use of 4,4,6-trimethyl-
1,3,2-dioxaborinane 5 (Methyl Pentanediol Borane, MPBH) [12] for
the hydroboration of 1-alkynes [13] provided a convenient and
efficient method to 4,4,6-trimethyl-2-vinyl-1,3,2-dioxaborinanes 6
(Scheme 4). This hydroboration is easy, robust, and gives access to
a large array of highly functionalized vinylboronic esters. Moreover,
the hydroborating agent MPBH is inexpensive, very stable, easily
prepared and stored [14].
In the expectation that compounds 6 could be a compromise
between unreactive 1 and poorly accessible 4, we submitted the
boronic esters 6 to the same conditions as 4.
O
B
R1
O
B
R1
O
H
cat Cp2ZrHCl
Tol or DCM, rt
O
OH
O
Me2Zn 3 equiv.
H2O
Ph
N
O
B
Ph
N
Ph
R1
MPBH 5
6a-i
O
R1
toluene, 20°C, 10h
Ph
4a,b
3a,b
1
1
1
2a
a: R = Ph b: R = H c: R = 1-cyclohexenyl
1
1
1
3a: R1 = n-Bu 75 %
3b: R1 = CH2-O-tert-Bu 82 %
d: R = n-Bu e: R = CH O-tert-Bu f: R = CH OMe
2 2
1
1
1
g: R = CH OAc h: R = Si(Me) i: R = CH -Cl
2
3
2
Scheme 3. Reaction of 4a,b, dimethylzinc and 2a.
Scheme 4. Hydroboration of alkynes with MPBH 5 [14].

N. PraveenGanesh et al. / Journal of Organometallic Chemistry 695 (2010) 2447e2454
2449
Table 1
Reaction of MPB esters 6aeI with nitrones 2aec.
1)Me Zn 3 equiv.
2
toluene, 40°C, 10h
2) H O
2
R2
R3
OH
R2
O
N
O
B
N
R1
O
R1
R3
2a-c
3a-i
6a-i
O
N
O
N
Ph
Ph
Ph
N
O
2a
2b
2c
.
Entry
1
Vinylboronate 6
Nitrone 2
Product 3
%Yield
OH
N
Ph
MPB
n-Bu
2a
76
84
77
Ph
n -Bu
3a
OH
Ph
N
MPB
Ph
2
3
2a
2a
Ph
Ph
3c
OH
Ph
N
MPB
Ph
3d
OH
N
Ph
4
2a
60
MPB
Ph
3e
OH
Ph
N
MPB
O-tert-Bu
O-tert-Bu
5
6
2a
2a
80
75
Ph
3b
OH
OH
Ph
N
N
MPB
MPB
OMe
OMe
Ph
Ph
3f
Ph
OAc
OAc
7
2a
63
60
3g
OH
OH
Ph
N
MPB
MPB
Si(Me)3
8
9
2a
2a
Ph
SiMe3
Cl
3h
3i
Ph
N
Cl
31
Ph
(continued on next page)

2450
Table 1 (continued)
N. PraveenGanesh et al. / Journal of Organometallic Chemistry 695 (2010) 2447e2454
Entry
Vinylboronate 6
Nitrone 2
Product 3
%Yield
64
MPB
Ph
10
2b
MPB
MPB
Ph
11
12
2c
2c
61
66
n-Bu
In turn, 6a reacted 4 times slower than the unhindered 4a at 40 ꢀC,
and more than 9 times at 60 ꢀC. So, a strong influence of steric
factors appeared clearly.
This vinylmethylzinc would react in a separate step with the
nitrone to produce the allylic hydroxylamine (Scheme 5, pathway
1). Such an organozinc species can transfer selectively the vinyl
group to various electrophiles [9]. With vinylboronic esters of the 1,
4, and 6 families, we attempted to obtain boron-to-zinc trans-
metallation in the absence of electrophile. It turned out that the
reaction products were never stable in the reaction conditions, and
degradation always occurred.
According to the second mechanistic hypothesis, the reactive
species is a tetracoordinate boronate complex formed from the
boronic ester and dimethylzinc. This anionic boronate complex
would coordinate with the nitrone and transfer the vinyl group
(Scheme 5, pathway 2) directly from the boron atom. Such an
“ate” complex has been postulated [4,20] in other analogous
reactions.
4. Mechanism
Two mechanisms can be considered for this reaction (Scheme 5).
According to the first hypothesis, the reacting species is vinyl-
methylzinc issued from a boron-to-zinc exchange. Analogous
transmetallations are largely documented: Srebnik [15,16] and
Oppolzer [9b,c] found than vinylboranes can be transmetallated to
vinylzinc species by the action of diethylzinc. Then, addition onto
aldehydes can be achieved in the presence of various amino-
alcohol catalysts [8]. Also related is the aryl transfer from
a “Ph3BEt2Zn” entity proposed by Tamaru [17], and the formation of
arylzinc [18] and vinylzinc [8] reagents from boronic acids
described by Bolm et al. The studies on the transmetallation of
alkylboranes by Knochel’s group [19] should also be mentioned.
As we are interested in designing a strategy towards an enan-
tioselective version of the reaction, it is very important to identify
which is the actual mechanism of the reaction. If it goes through
path 1: transmetallation followed by addition of methyl-vinyl-zinc
‡
O
B
Me2Zn
Me
Zn Me
O
B
Zn
Me
R1
O
O
R1
R1
R2
O
N
R3
path 2: direct transfer from boronate complex
Me2Zn
R2
Zn Me
Me
O
O
B
N
O
B
O
B
R3
O
N
O
R1
O
R1
R2
Me
O
Zn
R1
R3
Scheme 5. Possible mechanisms for the reaction sequence.

N. PraveenGanesh et al. / Journal of Organometallic Chemistry 695 (2010) 2447e2454
2451
pathway 1, transmetallation and the CeC bond formation are two
separate bimolecular steps. In this case, we are dealing with the
question of making the addition of a nitrone and an alkylvinylzinc
enantioselective. Such a question has been extensively studied and
solved with aldehydes as the ultimate electrophiles and amino-
alcohols as catalysts [21]. Alternatively, if the reaction takes place
according to pathway 2 through an “ate” complex, chirality on the
starting vinylboronate would still be present in the reactive inter-
mediate, and therefore influence the stereochemistry of the final
adduct. In this case, the application of chiral enantiopure vinyl-
boronates from chiral diols could ensure the enantioselectivity of
the reaction.
Both pathways were investigated computationally at DFT level
for the model system where R1 ¼ H, and the methyl substituents
in the pinacoleester part of vinylboronate are also replaced by H
atoms. The Gibbs free energies for both reaction pathways are
presented in Fig. 1. Using Gibbs energies in lieu of conventional
electronic energies is useful mainly because entropic contribu-
tions are accounted for and are naturally included in the
discussion.
although not surprisingly, the zinc atom is always anchored to an
O atom of the boronate ester.
According to the mechanism of pathway 2, dimethylzinc A and
nitrone B form, without any barrier, the adduct G. Reaction of
G with the vinylboronate ester C leads through transition state K to
intermediate L, where a methyl group has moved from zinc to
boron. This methyl transfer requires here only 24.5 kcal/mol
(against 28.7 kcal/mol in the absence of nitrone) and is endo-
thermic by 13.8 kcal/mol referring to energies of separated starting
reagents G and C. We can conclude that the methyl transfer from
zinc to boron is facilitated when dimethylzinc is initially coordi-
nated by nitrone: the Gibbs free energy is lower and the trans-
formation is not endothermic.
The next step corresponds to the formation of the CeC bond to
yield adduct N exothermically (16.5 kcal/mol). The free energy of
the transition state
M is 18.5 kcal/mol above intermediate
L (31.9 kcal/mol above the reactants). We can conclude that the
formation of the CeC bond is more difficult in pathway 2: the
reaction has to go through a free energy barrier of 18.5 kcal/mol
instead of 7.3 kcal/mol in the absence of the boronate as in the
(E þ B)2W step of pathway 1. Overall, in pathway 2 nitrone
catalyses the Zn-to-B methyl transfer but direct transfer of the vinyl
group from the boronate to the nitrone is not favored.
In summary, the expected rate-determining steps, according to
the energetics presented in Fig. 1, are for pathway 1 the transfer of
vinyl from B to Zn (to I through H) and for pathway 2 the
formation of the CeC bond (to N through M; N is a van der Waals
complex of F and W).
The two reaction pathways, however, do not take place sepa-
rately. Because the initial barriers in both channels are high, the
reaction proceeds slowly and does not disturb the thermodynam-
ical equilibrium significantly. Barrier K is lower than barrier H, but
much lower than barrier M. This means that the initial reactants,
complexes AC, G, GC and complex L are in equilibrium. The relative
concentration of these intermediate species is determined by their
relative free energy according to the van’t Hoff equation:
The mechanism corresponding to pathway 1 consists in two
major steps. The first is the transmetallation reaction between bor-
onate ester C and dimethylzinc A. When A, Zn(CH3)2 and C (vinyl-
boronate ester) interact, they initially form a compound AC. From
that, intermediate I is formed, featuring a tetracoordinated boron
atom carrying both a vinyl and a methyl group. Formation of I from
A and C occurs via the transition state H, requiring an activation free
energy of 28.7 kcal/mol with respect to the reactants. This step is
endothermic by 17.7 kcal/mol. The BeC (eCH]CH2) bond in I
ꢀ
(1.660 A) is much longer than the same bond in boronate ester
ꢀ
C (1.550 A). Transformation of I to form vinylmethylzinc E requires
a low activation energy (3.9 kcal/mol). This step is exothermic by
17.7 kcal/mol with respect to I, and as awhole the transmetallation is
essentially thermoneutral referring to starting reagents A, B and C
(0.9 kcal/mol is necessary to form separated E and F).
The second step of pathway 1 is a bimolecular reaction of the
vinylmethylzinc E produced in the first step, and nitrone B. E and B
give a complex (EB) via a barrierless process, exothermic by
4.1 kcal/mol with respect to reactants.
½productꢂ
½reactantꢂ
D
G0ðTÞ=RT
KeqðTÞ ¼
¼ eꢁ
The formation of the CeC bond, yielding W, requires 7.3 kcal/
mol (through transition state X) and is strongly exothermic
The key is the balance between the relative concentration of the
reactant of the rate-determining step of each pathway (AC and L,
respectively) and the rate coefficient of their removal by the same
process (via H and M, resp.). Complex L has 6.6 kcal/mol higher free
(
D
Gr ¼ ꢁ24.8 kcal/mol). In conclusion, the rate-determining step of
pathway 1 would be the formation of I, corresponding to the
methyl transfer from zinc to the boron atom. It is worth noting that,
Fig. 1. Gibbs free energies for both reaction pathways. The reference energy is the sum of energies of the separated reactants. TS are shown in italics, spectators are in parenthesis
and bimolecular steps indicated using dotted lines.

2452
N. PraveenGanesh et al. / Journal of Organometallic Chemistry 695 (2010) 2447e2454
energy than AC, thus the concentration of AC will be higher. On the
other hand, the activation free energy for reaction AC / I is
21.9 kcal/mol and that for reaction L / M is 18.5 kcal/mol, i.e. the
latter reaction is faster. Both the relative concentrations and the
rate coefficients depend on the temperature (T). At a given
6.3. General procedure for the reaction of 3,3,5-trimethyl-2-vinyl-
1,3,2-dioxaborinanes 6, nitrone 2 and dimethylzinc
In a 10 mL Schlenk vessel under nitrogen, dimethylzinc (2 M
solution in toluene, 0.5 ml, 1.0 mmol, 2.0 equiv.) was added to
a mixture of nitrone 2 (0.5 mmol) and vinylborane 6 [1] (0.6 mmol) in
anhydrous toluene (0.5 mL). The mixture was stirred at 40 ꢀC for 16 h.
Hydrolysis was performed at 20 ꢀC by addition of a saturated ammo-
nium chloride solution (2 ml) and the mixture was extracted with
DCM (3 ꢃ 5 ml). The collected organic phases were dried over sodium
sulphate and concentrated under reduced pressure. The crude mate-
rial was purified by column chromatography (cyclohexane/EtOAc).
T, numerical values of the relative rate of the two processes, r1=r2
¼
kH½ACꢂ=kM½Lꢂ can be used to decide which channel dominates. At
40 ꢀC, the optimal experimental temperature for the reaction, the
relative concentration [AC]/[L] ¼ 42200, i.e. the key intermediate of
pathway 1 is much more abundant than that of pathway 2. On the
other hand, the ratio of the respective rate coefficients, calculated
according to the thermodynamic formulation of the transition-
D
G
s=RT
state-theory: k ¼ kBT=heꢁ
is kH/kM ¼ 0.00414, which is
clearly too small to counterbalance the concentration ratio. Really,
the ratio of the rates of the rate-determining steps is r1/r2 ¼ 174,
which means that pathway 1 dominates. Increasing the tempera-
ture would change this ratio, but even at 100 ꢀC it is 70, so the
dominant channel remains pathway 1.
6.3.1. N-Benzyl-N-(1-phenyl-hept-2-enyl)-hydroxylamine 3a [1]
Prepared according to the General Procedure from N-benzyli-
dene-benzylamine N-oxide 2a (0.5 mmol, 105 mg) and dioxabor-
olane 6d (0.6 mmol,126 mg) in 76% yield (112 mg). Colorless oil. TLC:
Rf ¼ 0.52 (cyclohexane/ethyl acetate, 50:50); 1H NMR (200 MHz,
CDCl3/TMS):
d
¼ 0.87 (t, J ¼ 6.8 Hz, 3H), 1.20e1.45 (m, 4H), 2.05 (q,
J ¼ 6.4 Hz, 2H), 3.68 (d, J ¼ 13.5 Hz, 1H), 3.83 (d, J ¼ 13.5 Hz, 1H), 4.17
(d, J ¼ 7.6 Hz, 1H), 5.19 (s, 1H), 5.64 (dt, J ¼ 6.4, 15.6 Hz, 1H), 5.80 (dd,
J ¼ 7.6, 15.6 Hz, 1H), 7.15e7.40 (m, 10H) ppm; 13C NMR (75 MHz,
5. Conclusion
We have shown here that vinylboronic esters issued from the
easy hydroboration of 1-alkynes with 4,4,6-trimethyl-[1,3,2]dioxa-
borinane, can be readily activated by the reaction of dimethylzinc in
the presence of nitrones as electrophiles. An important advantage of
the method is that the vinylboronate can carry functional groups in
allylic position. This chemoselective addition provides highly func-
tionalized N-hydroxy-allylamines in good yields. The DFT study
coupled with a kinetic analysis indicates that the mechanism of this
reaction is an in situ Boron-to-Zinc transmetallation, possibly
favored by the nitrone itself acting as a ligand. It is followed by
a separate step, addition of the vinylzinc species to the nitrone.
CDCl3/TMS):
d
¼ 14.4, 22.7, 29.3, 31.8, 61.5, 75.1, 127.5, 127.6, 128.4,
128.6, 128.9, 129.5(br.), 129.8, 135.2, 138.7, 142.4 ppm; LRMS (EI,
70 eV): m/z (%) ¼ 295 (2) [Mþ], 213 (7), 212 (9), 173 (30), 91 (100);
HRMS calcd. for C20H26NO 296.2014, found 296.2001.
6.3.2. N-Benzyl-N-(4-tert-butoxy-1-phenyl-but-2-enyl)-
hydroxylamine 3b
Prepared according to the General Procedure from N-benzyli-
dene-benzylamine N-oxide 2a (0.5 mmol, 105 mg) and dioxa-
borolane 6e (0.6 mmol, 144 mg) in 80% yield (130 mg). Colorless
oil. Rf
(400 MHz, CDCl3/TMS):
¼
0.3 (Cyclohexane/ethyl acetate 70:30); 1H NMR
d
¼ 1.18 (s, 9H), 3.70e3.90 (m, 2H), 3.91
(dd, J ¼ 5.5 Hz, 4J ¼ 1.3 Hz, 2H), 4.28 (d, J ¼ 8.4 Hz, 1H), 5.78 (dt,
J ¼ 15.5 Hz, J ¼ 5.5 Hz, 1H), 5.52 (s, 1H), 6.00 (ddt, J ¼ 15.5 Hz,
J ¼ 8.4 Hz, 4J ¼ 1.3 Hz, 1H), 7.21e7.42 (m, 10H) ppm; 13C NMR
6. Experimental
6.1. Computational methods
(75 MHz, CDCl3/TMS):
d
¼ 27.0, 61.3, 62.3, 73.2, 74.7, 127.0, 127.3,
DFT calculations were carried out with the G98 system of
programs [22]. Stationary points (reactants, transition structures,
pre-reaction complexes and products) were located at the B3LYP/6-
31G(d) level [23] and identified as minima or first-order saddle
points by diagonalizing the Hessian matrices. Transition structures
were found to have only one negative eigenvalue with the corre-
sponding eigenvector involving the formation of the newly created
bonds and elongation of the breaking ones. The minimum energy
reaction path was also calculated starting from each transition
structure (IRC analysis [24]) to make sure that they correspond to
the elementary step. Gibbs free energies were derived using the
conventional rigid rotor e harmonic oscillator approximation
based on the calculated vibrational frequencies.
128.1, 128.2, 128.5, 129.2., 130.8, 131.8, 138.4, 141.3 ppm; MS (DCI,
NH3/isobutane): m/z 326 (M
C21H27O2N1Na 348.1934, found 348.1933.
þ
H)þ; HRMS: calcd. for
6.3.3. N-Benzyl-N-(1,3-diphenyl-allyl)-hydroxylamine 3c [1]
Prepared according to the General Procedure from N-benzyli-
dene-benzylamine N-oxide 2a (0.5 mmol, 105 mg) and dioxabor-
olane 6a (0.6 mmol, 139 mg) in 84% yield (133 mg). Pale yellow
solid. Rf
(300 MHz, CDCl3/TMS)
¼
0.5 (Cyclohexane/ethylacetate, 60:40); 1H NMR
d
ppm 1.50 (1H), 3.84 (d, J ¼ 13.1 Hz, 1H),
3.99 (d, J ¼ 13.1 Hz, 1H), 4.47 (d, J ¼ 7.9 Hz, 1H), 6.53 (dd, J ¼ 15.9,
7.9 Hz, 1H), 6.63 (d, J ¼ 15.9 Hz, 1H), 7.5e7.0 (m, 15H); 13C NMR
(75 MHz, CDCl3/TMS)
d ppm: 62.1, 75.7, 126.5, 127.2, 127.5, 127.7,
128.06, 128.3, 128.5, 128.7, 128.7, 129.3; HRMS calcd. for C22H22NO:
6.2. Reaction of 4,4-dimethyl-2-vinyl-1,3,2-dioxaborinanes 4a,b,
nitrone 2a and dimethylzinc
315.1623, found 316.1695.
6.3.4. N-Benzyl-N-(1-phenyl-allyl)-hydroxylamine 3d
In a 10 mL Schlenk vessel under nitrogen, vinylboronate 4 [6]
(1.5 mmol) and nitrone 2 (1 mmol, 210 mg) were dissolved in
4 mL toluene. At room temperature, a solution of dimethylzinc was
added (2 M in toluene, 1.5 mL, 3 mmol) and the mixture was stirred
for at 20 ꢀC for 10 h. Hydrolysis was performed at 20 ꢀC by addition
of a saturated NaHCO solution (2 ml) and the mixture was extracted
with DCM (3 ꢃ 5 ml). The gathered organic phases dried over
sodium sulphate and concentrated under reduced pressure, the
hydroxylamines 3a,b were purified by chromatography on silica gel
(cyclohexane 80/ethyl acetate 20).
Prepared according to the General Procedure from N-benzyli-
dene-benzylamine N-oxide 2a (0.5 mmol, 105 mg) and dioxabor-
olane 6c (0.6 mmol, 92 mg) in 77% yield (92 mg). Oil. 1H NMR
(300 MHz, CDCl3/TMS)
d
ppm: 3.70 (d, J ¼ 13.4 Hz, 1H), 3.74 (d,
J ¼ 13.4 Hz, 1H), 4.21 (d, J ¼ 8.4 Hz, 1H), 5.17e5.25 (m, 2H), 5.75 (s,
1H), 6.12 (ddd, J ¼ 8.4 Hz, J ¼ 17.2 Hz, J ¼ 10.2 Hz, 1H), 7.19e7.39 (m,
10 H); 13C NMR (75 MHz, CDCl3/TMS)
d ppm: 61.0, 75.3, 117.7, 172.2,
127.4, 128.1, 128.2, 128.6, 129.4, 137.7, 138.0, 141.0; MS (DCI, NH3/
isobutane) m/z ¼ 240 (M þ H)þ; HRMS calcd. for C16H18NO
240.1382, found 240.1381.

N. PraveenGanesh et al. / Journal of Organometallic Chemistry 695 (2010) 2447e2454
2453
6.3.5. N-Benzyl-N-(3-cyclohex-1-enyl-1-phenyl-allyl)-
hydroxylamine 3e [1]
Prepared according to the General Procedure from N-benzyli-
dene-benzylamine N-oxide 2a (0.5 mmol, 105 mg) and dioxabor-
olane 6c (0.6 mmol, 141 mg) in 60% yield (96 mg). Colorless oil.
Rf ¼ 0.60 (cyclohexane/ethyl acetate, 50:50). 1H NMR: (300 MHz,
134.1, 137.9, 140.4 ppm; IR (film) ύ ¼ 3530, 3060, 3027, 2920, 2847,
1495, 1454, 1028, 969, 745, 697 cm1; MS (DCI, NH3/isobutane)
m/z ¼ 288 (M þ H)þ; HRMS calcd. for C17H19ClNO 288.1155; found
288.1137.
6.3.10. N-Benzyl-N-(1-cyclohexyl-3-phenyl-allyl)-hydroxylamine 3j
Prepared according to the General Procedure from N-cyclo-
hexylidene-benzylamine N-oxide (0.5 mmol, 109 mg) and dioxa-
borolane 6a (0.6 mmol, 139 mg) in 64% yield (103 mg); colorless
oil.1.25e1.35 (m, 1H), 1.45e1.68 (m, 7H), 1.77e2.0 (m, 3H), 3.68 (d,
J ¼ 13.0 Hz, 1H), 3.71 (d, J ¼ 13.0 Hz,1H), 4.27 (d, 1H, J ¼ 6.8 Hz), 3.14
(dd,1H, J ¼ 6.4, 8.3 Hz), 4.27 (d,1H, J ¼ 6.8 Hz), 5.94 (dd,1H, J ¼ 15.2,
8.3 Hz), 6.63 (d, 1H, 15.2 Hz), 7.20e7.36 (m, 10H); 13C NMR (75 MHz,
CDCl3/TMS):
d
ppm ¼ 1.45e1.55 (m, 4H), 1.95e2.15 (m, 4H), 3.60 (d,
J ¼ 13.8 Hz,1H), 3.86 (d, J ¼ 13. 8 Hz,1H), 4.22 (d, J ¼ 8.7 Hz,1H), 4.49
(s, 1H), 5.65e5.80 (m, 2 H), 6.17 (d, J ¼ 15.8 Hz, 1 H), 7.10e7.44 (m,
10 H); 13C NMR: (75 MHz, CDCl3/TMS):
d
ppm ¼ 22.5, 22.6, 24.7, 26.0,
61.5, 75.6, 125.2, 127.2, 127.4, 128.0, 128.4, 129.3, 130.2, 135.4, 136.7,
138.7,142.2 ppm; MS (CI): m/z (%) ¼ 320 (M þ Hþ, 3), 302 (7), 214 (8),
197 (100). HRMS calcd. for C22H26NO 320.2014, found 320.2070.
CDCl3/TMS):
d
¼ 136.7, 135.9, 135.2, 132.1, 129.2, 129.1, 128.8, 128.5,
6.3.6. N-Benzyl-N-(4-methoxy-1-phenyl-but-2-enyl)-
hydroxylamine 3f
127.6, 69.8, 64.3, 40.57, 29.7, 25.9, 25.6, 2.5 ppm; HRMS calcd. for
C22H28NO: 322.2171, found 322.2166.
Prepared according to the General Procedure from N-benzy-
lidene-benzylamine N-oxide (0.5 mmol, 105 mg) and dioxabor-
olane 6f (0.6 mmol, 119 mg) in 75% yield (106 mg). Colorless oil.
6.3.11. 1-Styryl-3,4-dihydro-1H-isoquinolin-2-ol 3k
Prepared according to the General Procedure from 1,2,3,4-Tet-
rahydroisoquinoline-N-oxide (0.5 mmol, 66 mg) and dioxaborinane
6a (0.6 mmol, 139 mg) in 61% yield (77 mg). Colorless oil. 1H NMR
TLC: Rf
(400 MHz, CDCl3)
¼
0.4 (cyclohexane/ethyl acetate, 60:40); 1H NMR
d
ppm 3.24 (s, 3H), 3.58 (s, 1H), 3.70 (d,
J ¼ 13.2 Hz, 1H), 3.79 (d, J ¼ 13.2 Hz, 1H), 3.86 (d, J ¼ 5.6 Hz, 2H),
4.24 (d, J ¼ 8.4 Hz, 1H), 5.71 (dt, J ¼ 15.4, 5.6 Hz, 1H), 6.03 (dd,
J ¼ 15.4, 8.4 Hz, 1H), 7.40e7.16 (m, 10H); 13C NMR (75 MHz,
(400 MHz, CDCl3)
d
¼ 2.87e2.92 (m, 1H), 3.08e3.17 (m, 2H),
3.51e3.54 (m, 1H), 4.49 (d, 1H, J ¼ 8.0 Hz), 6.30 (dd, 1H, J ¼ 15.6,
8.0 Hz), 6.72 (d, 1H, J ¼ 15.6 Hz), 7.1e7.2 (m, 4H), 7.3e7.4 (m, 3H),
CDCl3)
d
¼ 27.6, 58.5, 61.9, 73.2, 74.7, 127.8, 128, 128.9, 129.2,
7.4e7.45 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 28.6, 53.9, 71.9,126.2,
130.1, 130.4, 130.5, 133.3, 138.8, 141.8 ppm; HRMS: calcd. for
126.7, 127.0, 127.9, 128.1, 128.4, 128.7, 133.4, 135.3, 135.5, 136.7,
C18H22NO2 284.1651, found 284.1659.
129.5 ppm; HRMS calcd. for C17H17NONa: 274.1208; found 274.1223.
6.3.7. Acetic acid 4-(benzyl-hydroxy-amino)-4-phenyl-but-2-enyl
ester 3g
6.3.12. 1-Hex-1-enyl-3,4-dihydro-1H-isoquinolin-2-ol 3l [1]
Prepared according to the General Procedure from 1,2,3,4-Tet-
rahydroisoquinoline-N-oxide (0.5 mmol, 66 mg) and dioxaborinane
6d (0.6 mmol, 126 mg) in 66% yield (77 mg). Colorless oil. Rf ¼ 0.4
Prepared according to the General Procedure from N-benzyli-
dene-benzylamine N-oxide (0.5 mmol, 105 mg) and dioxaborolane
6g (0.6 mmol, 136 mg) in 63% yield (98 mg). Colorless oil. Rf ¼ 0.6
(CHCl3/MeOH, 80:20); 1H NMR (300 MHz, CDCl3)
d ppm: 0.94 (t,
(Cyclohexane/EtOAc 60:40); 1H NMR (300 MHz, CDCl3)
d
ppm: 2.06
3H, J ¼ 7.1 Hz), 1.3e1.5 (m, 4H), 2.15e2.21 (m, 2H), 2.90e2.96 (m,
1H), 3.03e3.18 (m, 2H), 3.49e3.53 (m, 1H), 4.27 (d, 1H, J ¼ 6.8 Hz),
5.52 (dd, 1H, J ¼ 15.2, 8.3 Hz), 5.87e5.78 (m, 1H), 7.19e7.10 (m, 4H);
(s, 3H), 3.82 (d, J ¼ 13.5 Hz, 1H), 3.96 (d, J ¼ 13.5 Hz, 1H), 4.51 (d,
J ¼ 8.0 Hz, 1H), 4.55 (dt, J ¼ 16.0 Hz, J ¼ 8.0 Hz, 2H), 4.65 (br s, 1H),
5.85 (d, J ¼ 16.0 Hz, 1H), 5.88 (m, 1H), 7.0e7.3 (m, 10H); 13C NMR
13C NMR (75 MHz, CDCl3)
d ppm: 13.9, 22.3, 28.3, 31.4, 32.1, 53.5,
(75 MHz, CDCl3)
d
ppm 21.0, 61.3, 65.2, 71.8, 124.9, 128.4, 128.5,
71.4, 125.9, 126.6, 127.9, 128.1, 129.7, 133.3, 135.9, 137.0 ppm; LRMS
(CI): m/z (%) ¼ 232 (6), 231 (19), 214 (12), 172 (25), 148(80), 129
(100).
128.8, 128.9, 135.64, 138.2, 141.2, 170.6; HRMS: calcd. for
C19H21NO3Na 334.1419; found 334.1405.
6.3.8. N-Benzyl-N-(1-phenyl-3-trimethylsilanyl-allyl)-
hydroxylamine 3h
Acknowledgements
Prepared according to the General Procedure from N-benzyli-
dene-benzylamine N-oxide (0.5 mmol, 105 mg) and dioxaborolane
6h (0.6 mmol, 138 mg) in 60% yield (94 mg). Colorless oil. 1H NMR
We thank CECIC for providing computer facilities, the CNRS and
the J. Fourier University (Grenoble) for financial support.
(400 MHz, CDCl3/TMS):
d
¼ 0.05 (s, 9H), 3.72 (d, J ¼ 13.5 Hz, 1H),
3.85 (d, J ¼ 13.5 Hz, 1H), 4.26 (d, J ¼ 7.7 Hz, 1H), 5.3 (Br s, 1H), 5.92
(d, J ¼ 18.6 Hz, 1H), 6.30 (dd, J ¼ 18.6 Hz, J ¼ 7.7 Hz, 1H), 7.23e7.42
References
(m, 11H) ppm; 13C NMR (75 MHz, CDCl3/TMS):
d
¼ ꢁ1.1, 61.4, 77.4,
[1] S.U. Pandya, S. Pinet, P.Y. Chavant, Y. Vallée, Eur. J. Org. Chem. (2003) 3621.
[2] (a) C.E. Tucker, J. Davidson, P. Knochel, J. Org. Chem. 57 (1992) 3482;
(b) T. Ohmura, Y. Yamamoto, N. Miyaura, J. Am. Chem. Soc. 122 (2000) 4990;
(c) S. Pereira, M. Srebnik, Tetrahedron Lett. 37 (1996) 3283;
(d) S. Pereira, M. Srebnik, Organometallics 14 (1995) 3127.
[3] (a) C.M. Vogels, S.A. Westcott, Curr. Org. Chem. 9 (2005) 687;
(b) K. Shirakawa, A. Arase, M. Hoshi, Synthesis (2004) 1814.
127.3, 127.5, 128.3, 128.4, 128.7, 129.5, 134.1, 138.3, 141.2, 145.0 ppm;
MS (ESI): 312 (100) (M þ H)þ, 310 (29), 350 (16), (M þ K)þ, 334 (14)
(M þ Na)þ; HRMS calcd. for C19H26O1N1Si1 312.1778, found
312.1775.
[4] Y. Kobayashi, Y. Nakayama, R. Mizojiri, Tetrahedron 54 (1998) 1053.
[5] D.G. Hall, Boronic Acids. Wiley-VCH, Weinheim, 2005.
[6] R.W. Hoffmann, S. Dresely, Synthesis (1988) 103.
[7] Z. Chai, X.-Y. Liu, J.-K. Zhang, G. Zhao, Tetrahedron: Asymmetry 18 (2007) 724.
[8] F. Schmidt, J. Rudolph, C. Bolm, Synthesis (2006) 3625.
[9] The preparation of 4 for this study used dicyclohexylborane in the first step, to
yield vinyl-dicyclohexylboranes. These can be readily transmetallated with
diethylzinc, thus if dicyclohexylborane is involved, it is practically useless to
proceed to the esters 4: (a) W. Oppolzer, R.N. Radinov, E. El-Sayed, J. Org.
Chem. 66 (2001) 4766;
6.3.9. N-Benzyl-N-(4-chloro-1-phenyl-but-2-enyl)-hydroxylamine
3i
Prepared according to the General Procedure from N-benzyli-
dene-benzylamine N-oxide (0.5 mmol, 105 mg) and dioxaborolane
6i (0.6 mmol, 122 mg) in 31% yield (44 mg). Colorless oil. 1H NMR
(300 MHz, CDCl3/TMS):
d
¼ 3.71 (d, J ¼ 13.4 Hz, 1H), 3.75 (d,
J ¼ 13.4 Hz, 1H), 4.00 (d, J ¼ 6.9 Hz, 2H), 4.25 (d, J ¼ 8.4 Hz, 1H),
5.79 (dt, J ¼ 15.2 Hz, J ¼ 6.9, 1H), 6.09 (dd, J ¼ 15.2 Hz, J ¼ 8.4 Hz,
1H), 7.20e7.36 (m, 10H) ppm; 13C NMR (75 MHz, CDCl3/TMS):
(b) W. Oppolzer, R.N. Radinov, J. De Brabander, Tetrahedron Lett. 36 (1995) 2607;
(c) W. Oppolzer, R.N. Radinov, J. Am. Chem. Soc. 115 (1993) 1593;
(d) W. Oppolzer, R.N. Radinov, Helv. Chim. Acta 75 (1992) 170;
(e) W. Oppolzer, R.N. Radinov, Tetrahedron Lett. 29 (1988) 5645.
d
¼ 44.4, 61.3, 73.6, 127.3, 127.7, 128.1, 128.3, 128.7, 129.1, 129.3,

2454
N. PraveenGanesh et al. / Journal of Organometallic Chemistry 695 (2010) 2447e2454
[10] (a) D.S. Matteson, Product subclass 1: hydroboranes, in: , Science of Synthesis,
vol. 6, 2004, pp. 5e79;
(b) D.J. Pasto, V. Balasubramaniyan, P.W. Wojtkowski, Inorg. Chem. 8 (1969) 594.
[11] N. PraveenGanesh, S. d’Hondt, P.Y. Chavant, J. Org. Chem. 72 (2007) 4510.
[12] W.G. Woods, P.L. Strong, J. Am. Chem. Soc. 88 (1966) 4667.
[13] R.H. Fish, J. Org. Chem. 88 (1973) 158.
[14] N. PraveenGanesh, P.Y. Chavant, Eur. J. Org. Chem. (2008) 4690.
[15] K.A. Agrios, M. Srebnik, J. Organomet. Chem. 444 (1993) 15.
[16] M. Srebnik, Tetrahedron Lett. 32 (1991) 2449.
[17] K. Shibata, M. Kimura, K. Kojima, S. Tanaka, Y. Tamaru, J. Organomet. Chem.
624 (2001) 348.
[20] Y. Kobayashi, Y. Tokoro, K. Watatani, Eur. J. Org. Chem. (2000) 3825.
[21] Recent reviews: (a) V. Dimitrov, K. Kostova, Lett. Org. Chem. 3 (2006)
176;
(b) M. Yus, D.J. Ramon, Pure Appl. Chem. 77 (2005) 2111.
[22] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
V.G. Zakrzewski, J.A. Montgomery Jr., R.E. Stratmann, J.C. Burant, S. Dapprich,
J.M. Millam, A.D. Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone,
M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski,
G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma, D.K. Malick, A.D. Rabuck,
K. Raghavachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz, B.B. Stefanov,
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R.L. Martin,
D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez,
M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, J.L. Andres,
C. Gonzalez, M. Head-Gordon, E.S. Replogle, J.A. Pople, Gaussian 98, Revision A.6.
Gaussian, Inc., Pittsburgh, PA, 1998.
[18] (a) F. Schmidt, J. Rudolph, C. Bolm, Adv. Synth. Catal. 349 (2007) 703;
(b) F. Schmidt, R.T. Stemmler, J. Rudolph, C. Bolm, Chem. Soc. Rev. 35 (2006) 454;
(c) J. Rolland, X.C. Cambeiro, C. Rodríguez-Escrich, M.A. Pericas, Beilstein J. Org.
Chem. 5 (2009) 56.
[19] (a) E. Hupe, P. Knochel, K.J. Szabo, Organometallics 21 (2002) 2203;
(b) E. Hupe, P. Knochel, Org. Lett. 3 (2001) 127;
[23] (a) A.D. Becke, J. Chem. Phys. 98 (1993) 5648;
(b) C. Lee, W. Yang, R.G. Parr, Phys. Rev. B. 37 (1988) 785.
(c) F. Langer, L. Schwink, A. Devasagayaraj, P.-Y. Chavant, P. Knochel, J. Org.
Chem. 61 (1996) 8229.
[24] (a) K. Fukui, Acc. Chem. Res. 14 (1981) 363;
(b) M. HeadeGordon, J.A. Pople, J. Chem. Phys. 89 (1988) 5777.