Synthesis of 3-hydroxy-1-alkenylboronates via phosphine stabilized borylzirconacyclopropenes

Article abstract of DOI:10.1039/b811287h

Zirconacyclopropenylboronates can be stabilized to dimerization by complexation with tributylphosphine; the phosphine stabilized zirconacycle boronates react with aliphatic and aromatic ketones and aldehydes at C2 of the triple bond to give the previously

Full text of DOI:10.1039/b811287h

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Synthesis of 3-hydroxy-1-alkenylboronates via phosphine stabilized
borylzirconacyclopropeneswz
Abed Al Aziz Al Quntar,ac Alina Botvinik,a Abraham Rubinsteinb and
Morris Srebnik*a
Received (in Cambridge, UK) 3rd July 2008, Accepted 7th August 2008
First published as an Advance Article on the web 29th September 2008
DOI: 10.1039/b811287h
Zirconacyclopropenylboronates can be stabilized to dimeriza-
tion by complexation with tributylphosphine; the phosphine
stabilized zirconacycle boronates react with aliphatic and
aromatic ketones and aldehydes at C2 of the triple bond to give
the previously unknown 3-hydroxyvinylboronates in 61–80%
isolated yields.
Scheme 1 Formation and reaction of 1,1-gem-borazirconocenes.
zirconacycles.25 With this in mind we tried to zirconate
1-2-(hex-1-ynyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with
the Negishi reagent (Cp2ZrCl2/2BuLi)26 in the presence of
various stabilizing ligands. The results are the subject of this
communication.
Vinylboronates are valuable but relatively inert compounds1
and can be synthesized by various methods.2,3 Their utility lies
in the ability to transfer the vinyl group from boron to other
elements1 and metals.4–9 For instance, facile carbon–carbon
bond forming reactions between vinylboronates and vinyl/aryl
halides occur by palladium catalysis in the presence of base
(Suzuki–Miyaura coupling),10,11 or by transfer to zinc and
subsequent reaction with aldehydes.4 Other methods include
intramolecular transfer mediated by halides (Zweifel diene
synthesis)12 or cycloaddition reactions13 to list but a few
reactions. Using highly functionalized vinylboronates enables
the synthesis of more complex structures.14 We have
previously prepared vinylboronates by hydrozirconation of
1-alkynylboronates to give 1,1-borazirconocenes and demons-
trated that it was possible to selectively react the CSp2–Zr
bond to give highly substituted vinylboronates, which could
then be reacted with a different electrophile to provide tri-
substituted alkenes in a highly stereo- and regioselective
manner (Scheme 1).15–23
The best results were obtained with tributylphosphine.
Other ligands suh as tri-n-octylphosphine and triphenyl-
phosphine gave inferiors results (entries a, b, Table 1). Phos-
phites (entries d–f), and triethylamine (entry g) were ineffective
in stabilizing the borylzirconacylopropenes. Only diborylated
1,3-butadienes were obtained with the latter.
When 1-heptynylboronate was zirconated with the Negishi
reagent in the presence of tributylphosphine and worked up
with HCl/ether only one product was obtained, 5. No trace of
the homo-coupling product was observed whereas workup
with D2O gave the dideuterio product 6, indicating that the
intermediate zirconacyclopropene was indeed stabilized by the
phosphine ligand (Scheme 2).
This is the first time we were able to successfully prepare
stable borylzirconacyclopropenes. Phosphine stabilized 2 was
then reacted with a series of aldehydes and ketones. Workup
of 3 with HCl/ether provided 3-hydroxy-1-alkenylboronates 4
(Scheme 2, Table 2).
The use of the Negishi reagent (Cp2ZrCl2/2n-BuLi) with
1-alkynylboronates, on the other hand, leads to mixtures of
1,3-butadienes, the result of homocoupling.24 It is known
that blocking the empty zirconium d orbital can stabilize
a Department of Medicinal Chemistry and Natural Products, School of
Pharmacy, Hebrew University, Jerusalem, 91120, Israel.
E-mail: morris.srebnik@ekmd.huji.ac.il; Fax: 972-2-675-8201;
Tel: 972-2-675-7301
Table 1 Ligand effect on the synthesis of 4
b Department of Pharmaceutics, School of Pharmacy, Hebrew
University, Jerusalem, 91120, Israel
c Department of Material Engineering, Faculty of Engineering,
Al Quds University, Abu Dies, Palestinian Authority
w Electronic supplementary information (ESI) available: Full analy-
tical and experimental data for 4. 1H and 13C NMR spectra for 4.
See DOI: 10.1039/b811287h
Entry
Ligand
% Yield 4b
z The results reported here are included in the dissertation project of
Alina Botvinik in partial fulfilment of her PhD degree requirements at
The Hebrew University of Jerusalem. A.B. is also the recipient of a
student fellowship from the Hebrew University and expresses her
gratitude. The study was supported by a research grant no. 1358/05
from the Israeli Science Foundation. Morris Srebnik and Abraham
Rubinstein are affiliated with the David R. Bloom Center of
Pharmacy.
a
b
c
d
e
f
(n-Oct)3P
Ph3P
(Bu)3P
(MeO)3P
(EtO)3P
(EtO)2POH
Et3N
15
17
81
—
—
—
—
g
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 5589–5591 | 5589

View Article Online
hindered ketones like benzophenone gave little product
(GC/MS) and this was also not isolated.
1
The regioselectivity of 4 was determined by H NMR data.
The presence of a singlet in the double bond region is
indicative of the coupling of the aldehydes and ketones having
3
occurred on C2. On the other hand, the JHH coupling
constant (13.5 Hz) of the hydrogens on C1 and C2 to boron
in compound
5 demonstrates cis stereochemistry. This
coupling constant is consistent with the one we obtained by
hydrozirconation. Regarding the mechanism (Scheme 1), the
tributylphosphine group must first depart. The uncomplexed
zirconacyclopropene then reacts faster with the aldehyde or
ketone than it dimerizes.
Scheme 2 Mechanism of formation of 4.
Borylzirconacyclopentenes, however, are stable and react
with aldehydes and ketones to form 5-hydroxy-1-alkenyl-
boronates.27 Phosphine stabilized 2 was then reacted with a
series of aldehydes and ketones. Workup of 3 with HCl/ether
provided 3-hydroxy-1-alkenylboronates 4 (Scheme 2, Table 2).
That insertion of an aldehyde or ketone does indeed go
through 3 which was demonstrated by working up the reaction
of cyclopropylphenyl ketone with D2O (eqn (1)). The mono
deuterated product 7 was obtained, as expected, if 3 was an
intermediate.
Both aliphatic (Table 2, 4a–h) and aromatic alkynyl-
boronates (Table 2, 4i) may be used. Insertion proceeds well
with various ketones and aldehydes as indicated in Table 2.
Both aliphatic and aromatic ketones and aldehydes are
successfully inserted in satisfactory isolated yields. However,
difficulty was encountered with relatively hindered aldehydes
or ketones.
In conclusion, whereas hydrozirconation places zirconium on the
same atom at boron, insertion of aldehydes or ketones into the
borylzirconacyclopropenes occurs at the carbon distal to boron,
apparently for steric reasons. The two reactions, thus, comple-
ment one another and provide access to various substituted
vinylboronates useful for subsequent transformations.28
For instance, 2-methoxybenzaldehyde and 2,4-dichloro-
benzaldehyde gave little product (GC/MS) and these were
not isolated) whereas anisaldehyde reacted satisfactorily. Also
Table 2 Formation and isolated yields of 4
Aldehyde/ketone
4
R
R1
R2
Yield (%)e
Acetone
Cyclopropylphenyl ketone
a
b
n-Bu
n-Bu
CH3
CH3
C6H5
75
73
a-Tetralone
c
n-Bu
61
Acetone
Cyclopropylphenyl ketone
d
e
n-Pent
n-Pent
CH3
CH3
C6H5
76
81
Cyclohexanone
f
n-Pent
68
Benzaldehyde
Anisaldehyde
Acetone
g
h
i
n-Pent
n-Pent
C6H5
e
C6H5
4-MeOC6H4
CH3
H
H
CH3
73
77
80
2 n-BuLi, THF, ꢁ78 1C. b(n-Bu)3P. cR1R2C(O). dHCl/ether. Conversion was 498% as determined by GC/MS and 11B NMR for all reactions.
a
ꢀc
This journal is The Royal Society of Chemistry 2008
5590 | Chem. Commun., 2008, 5589–5591

View Article Online
12 G. Zweifel, N. L. Polston and C. C. Whitney, J. Am. Chem. Soc.,
1968, 90, 6243–6245.
Notes and references
1 A. Pelter, K. Smith and H. C. Brown, Borane Reagents, Academic
Press, New York, 1988.
2 K. Smith and A. Pelter, in Comprehensive Organic Synthesis, ed. B.
M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, p. 703.
3 B. Marciniec, M. Jankowska and C. Pietraszuk, Chem. Commun.,
2005, 663–665.
4 M. Srebnik, Tetrahedron Lett., 1991, 32, 2449–2452.
5 E. Hupe, M. I. Calaza and P. Knochel, J. Organomet. Chem., 2003,
680, 136–142.
6 N. Miyaura, M. Itoh and A. Suzuki, Tetrahedron Lett., 1976,
255–258.
13 G. Hilt and P. Bolze, Synthesis, 2005, 2091–2115.
14 J.-P. Corbet and G. Mignani, Chem. Rev., 2006, 106, 2651–2710.
15 B. Zheng and M. Srebnik, J. Organomet. Chem., 1994, 474, 49–53.
16 L. Deloux, E. Skrzypczak-Jankun, B. V. Cheesman, M. Sabat and
M. Srebnik, J. Am. Chem. Soc., 1994, 116, 10302–103023.
17 B. Zheng and M. Srebnik, J. Org. Chem., 1995, 60, 3278–3279.
18 L. Deloux and M. Srebnik, J. Org. Chem., 1995, 60, 3276–3277.
19 S. Pereira and M. Srebnik, Organometallics, 1995, 14, 3127–3128.
20 S. Pereira and M. Srebnik, J. Org. Chem., 1995, 60, 4316–4217.
21 B. Zheng and M. Srebnik, Synth. Commun., 1996, 26, 393–396.
22 L. Deloux and M. Srebnik, Tetrahedron Lett., 1996, 37, 2735–2738.
23 L. Deloux and M. Srebnik, J. Org. Chem., 1994, 59, 6871–6873.
24 G. Desurmont, R. Klein, S. Uhlenbrock, E. Laloe, L. Deloux, C.
M. Giolando, Y. W. Kim, S. Pereira and M. Srebnik, Organome-
tallics, 1996, 15, 3323–3328.
7 R. Quintanilla and T. E. Cole, Tetrahedron, 1995, 51,
4297–4308.
8 D. A. Singleton and S. W. Leung, J. Organomet. Chem., 1997, 544,
157–161.
9 H. Noth and H. Vahrenka, J. Organomet. Chem., 1968, 11,
399–405.
25 L. Stahl and R. D. Ernst, Adv. Organomet. Chem., 2008, 55,
137–199.
10 N. T. S. Phan, M. V. D. Sluys and C. W. Jones, Adv. Synth. Catal.,
2006, 348, 609–679.
11 S. Kotha, K. Lahiri and D. Kashinath, Tetrahedron, 2002, 58,
9633–9695.
26 E. Negishi and T. Takahashi, Acc. Chem. Res., 1994, 27, 124–130.
27 A. A. Quntar and M. Srebnik, Org. Lett., 2004, 6, 4243–4244.
28 H. Li, P. J. Carroll and P. J. Walsh, J. Am. Chem. Soc., 2008, 130,
3521–3531.
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 5589–5591 | 5591