Efficient synthesis of (P-chirogenic) o -boronated phosphines from sec -phosphine boranes

Article abstract of DOI:10.1021/acs.orglett.5b00167

An efficient synthesis of boronated phosphines with an o-phenylene-bridge prepared from sec-phosphine boranes and using benzyne chemistry is reported. Successive reactions of sec-phosphine boranes with n-BuLi and 1,2-dibromobenzene, and then with boron re

Full text of DOI:10.1021/acs.orglett.5b00167

Letter
pubs.acs.org/OrgLett
Efficient Synthesis of (P-Chirogenic) o‑Boronated Phosphines from
sec-Phosphine Boranes
Jerome Bayardon,* Julie Bernard, Emmanuelle Remond,† Yoann Rousselin, Raluca Malacea-Kabbara,
́
̂
́
and Sylvain Juge*
́
́ ́ ́ ́
Institut de Chimie Moleculaire de l’Universite de Bourgogne (ICMUB-StereochIM) UMR CNRS 6302, 9 Avenue Alain Savary, BP
47870, 21078 Dijon cedex, France
S
* Supporting Information
ABSTRACT: An efficient synthesis of boronated phosphines
with an o-phenylene-bridge prepared from sec-phosphine boranes
and using benzyne chemistry is reported. Successive reactions of
sec-phosphine boranes with n-BuLi and 1,2-dibromobenzene, and
then with boron reagents, afford the o-boronatophenylphosphine
derivatives in 71% yields. The use of P-chirogenic sec-phosphine
boranes leads to the free boronated phosphines with retention of
configuration at the P-center after decomplexation. The reaction
of P-chirogenic o-boronatophenylphosphine with KHF2 affords the corresponding trifluoroborated phosphine with ee >98%.
Scheme 1. Synthesis of o-Boron-arylphosphine Derivatives
ecently, boronated phosphines R′2P(Y)BR2 have received
Rparticular attention due to their unusual reactivity arising
from the presence of a Lewis acid and base pair without a donor−
acceptor bond.1 These compounds are also called “Frustrated
Lewis Pairs” (FLPs) and have demonstrated their utility for the
activation of dihydrogen and binding of small molecules such as
CO2, alkene, alkynes, enals, NO, SO2, etc.1,2
Interestingly, boronated phosphines have shown promising
properties in coordination chemistry,3 transition-metal catalysis,4
organocatalysis,5 and also for anion binding.6 To date, few chiral
boronated phosphines such as 1−3 were described and used in
asymmetric reactions (Figure 1).7
our knowledge, only the ferrocenyl derivatives 2 and 9 were
reported as chiral o-boronated organophosphorus derivatives.7c,8
As an example, compound 9 was prepared via a diastereoselective
o-lithiation of the chiral ferrocenyl precursor 8 (Scheme 1b).8
Our group recently described a powerful method for the
stereoselective synthesis of P-chirogenic o-bromo- or o-iodo-
phenylphosphines from secondary phosphine boranes, using
aryne chemistry.9,10 We then extended this method to the
synthesis of P-chirogenic o-boronatophenylphosphine borane
complexes and their corresponding free phosphines.10
Figure 1. Examples of chiral boronated phosphines.
Chiral and achiral o-boronatophenylphosphine boranes 12
were synthesized in two steps from the sec-phosphine boranes 10
by successive reaction with 1,2-dibromobenzene 4 and
borylation (Table 1). Thus, the o-bromophenylphosphine
boranes 11a, 11b and 11c were first prepared in 75%, 63%,
and 55% yields, respectively, from the reaction of the
corresponding sec-phosphine boranes 10a−c with n-butyllithium
(1.2 equiv) and 1,2-dibromobenzene 4, following a procedure
reported in the literature (entries 1,3,9).9 Under similar
conditions, when P-chirogenic (S)-ferrocenylphenylphosphine
Despite the abundant organophosphorus chemistry, relatively
few versatile methods exist allowing the borylation of
arylphosphines at the ortho position. Usually, the preparation
of o-phenylene-bridged boron-phosphines such as 7 is achieved
by borylation of the o-bromophenyl phosphine 5, previously
prepared from 1,2-dibromobenzene 4 (Scheme 1a). However,
this method is highly dependent on the unstable o-lithiated
bromobenzene and its reactivity at very low temperature with
chlorophosphine R″2PCl (Scheme 1a).2b,3a,4e,5b,c
So far, the nature of the substituents at the P-center in
boronated phosphines such as 7 remained limited, and no
example of chiral derivatives has been described. To the best of
Received: January 18, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b00167
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(99% ee, entry 10).9 After metal−halide exchange with n-
butyllithium, o-bromophenylphosphine borane 11a led to the
corresponding o-lithiated derivative. It was then trapped by
isopropyl pinacolatoborate 6a to afford the o-boronatophenyl
diphenylphosphine borane 12a in 51% isolated yield (entry 1). In
the case of dicyclohexyl(o-bromophenyl)phosphine borane 11b,
the reaction with the boron reagent 6a led to the o-
boronatophenylphosphine borane 12b in 66% yield (entry 3).
Crystals of 12b were obtained from methylene chloride/
methanol and analyzed by X-ray diffraction (Figure 2). This
Table 1. Synthesis of the o-Boronated Phosphine Boranes 12
Figure 2. View of o-boronatophenylphosphine borane 12b. The thermal
ellipsoids are drawn at the 50% probability level. H atoms are omitted for
clarity. Selected bond lengths [Å], angles [deg], and dihedral angles
[deg]: P1−C19 1.846(1), P1−B1 1.893(2), C1−P1−C19 104.80(6),
C1−P1−C7 111.05(6), C19−P1−B1 114.57(8), B1−P1−C1−C6
34.24(14), B1−P1−C19−C24 −66.78(12).
structure consists of a distorted tetrahedral geometry at the P
atom (typical for phosphine borane adducts). The boronato
substituents are in staggered conformation with respect to both
cyclohexyl substituents, and the B atoms are in a trigonal planar
environment (Figure 2).
In addition, when the borylation reaction is performed with
the chloro(dicyclohexyl)boron reagent 6b, the o-bromophenyl-
phosphine boranes 11a−c provide the corresponding dicyclo-
hexylboronatophenylphosphine boranes 12c−e in yields ranging
from 53% to 71% (entries 5, 7, 9). Finally, the reaction of (S)-
ferrocenylphosphine borane 11d with butyllithium and then with
reagents 6a−c affords the corresponding (S)-o-boronatophenyl-
phosphine boranes 12f−h without racemization in 43% to 60%
yields (entries 10, 12, 13).
The recrystallization of 12f and 12h in hexane and a
dichloromethane/hexane mixture, respectively, provided crystals
suitable for X-ray diffraction analyses. The ORTEP views of their
structures are shown in the Supporting Information and Figure 3,
respectively.
The B atom is in a trigonal planar environnement in the
pinacolatoboronatophosphine borane 12f and in a fac-trivacant
octahedron for the P-chirogenic bis(mesityl)boronatophosphine
borane 12h (Figure 3). The ferrocenyl Cp rings are parallel
within 3.34(17)° or 1.61(19)° for 12f and 12h, respectively, and
the (S)-configuration of the P atom in both cases is deduced from
the refinement of the Flack parameter. Bond lengths and angles
are availaible in the Supporting Information.
a
b
Prepared according to a procedure outlined in ref 10. Prepared
c
d
according to a procedure outlined in ref 9. Isolated yields. Yield
using a one-pot procedure starting from 10. 99% ee; determined by
HPLC on chiral column.
e
It should be noted that both boron atoms B1 and B2 are very
closed in the compound 12h (B1−B2 = 2.865(4) Å) (Figure 3).
The quality of the data obtained by X-ray diffraction analysis
made it possible to locate the protons in the Fourier difference
map and to show that proton H1B is taken in an agostic
interaction (B1−H1B = 1.21(3) Å, B2···H1B = 1.80(3) Å, B1−
borane 10d,10 previously prepared from (R)-chloroferrocenyl-
phenylphosphine borane, was used, (S)-o-bromophenylphos-
phine borane 11d was stereoselectively obtained in 47% yield
with complete retention of the configuration at the P-center
B
DOI: 10.1021/acs.orglett.5b00167
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Scheme 3. Preparation of Free o-Boronatophenylphosphines
16
Figure 3. View of o-boronated phosphine borane 12h. The thermal
ellipsoids are drawn at the 50% probability level. H atoms are omitted for
clarity. Selected bond lengths [Å], angles [deg], and dihedral angles
[deg]: B1−P1 1.918(1), C3−P1 1.790(2), C17−P1 1.816(2), C3−P1−
B1 114.51(11), C3−P1−C17 105.51(10), C17−P1−B1 106.76(11),
C17−P1−C12 108.75(10), C4−C3−P1−B1 −141.8(2), C13−C12−
P1−B1 24.0(2).
Table 2. Preparation of Free o-Boronatophenylphosphines 16
H1B···B2 = 143(2)°) (see Supporting Information). Moreover
B2 is almost in a tetrahedral environment with angles of C32−
B2−C23 = 121.7(2)°, C23−B2−C22 = 112.6(2)°, and C22−
B2−C32 = 120.4(2)° (Figure 3).
Interestingly, when the synthesis is performed according to a
one-pot procedure by successive reactions of 10a−d with 1,2-
dibromobenzene 4 and 2 equiv of n-BuLi, then, with the boron
reagents 6, the o-boronated phosphine boranes 12 are obtained
in similar yields to those obtained via the o-bromo intermediate
11, ranging from 39% to 71% (entries 2, 4, 6, 8, 11, 14). The
synthesis of o-boronated phosphine borane 12 by this one-pot
procedure is likely to occur via a mechanism involving the
benzyne intermediate 13 (Scheme 2). Thus, the reaction begins
a
Method A: decomplexation using DABCO; Method B: reaction with
b
c
n-BuLi and then the boron reagent 6a. Isolated yields. 99% ee by
HPLC on chiral column.
Scheme 2. Proposed Mechanism for the Formation of o-
Boronatophenylphosphine Boranes 12
In the second case, o-bromophenylphosphine 15 was previously
prepared by decomplexation of its borane complex 11 with
DABCO according to a described procedure9 (Scheme 3). Thus,
the reaction of the enantiomerically pure P-chirogenic o-
bromophenyl phosphine 15a9 with n-butyllithium at −78 °C
led to the o-lithiated anion by metal−halide exchange, which
subsequently was trapped with the boron reagent 6a, to afford
the corresponding o-boronatophenyl phosphine 16c in 58% yield
and 99% ee (Scheme 3, method B; Table 2, entry 3).
with the deprotonation of the secondary phosphine borane 10,
giving the corresponding phosphide, while the excess of n-BuLi
promotes the formation of benzyne 13 by LiBr elimination.
Reaction of phosphide borane with benzyne 13 leads to the o-
lithiated phosphine borane 14, which is trapped by the boron
reagent 6 to afford the corresponding o-boronated phosphine
borane 12 (Scheme 2).
On the other hand, the free chiral or achiral o-boronato-
phenylphosphines 16 can be obtained by either decomplexation
of their borane complexes 12 using DABCO (Scheme 3, method
A) or direct borylation of o-bromophenylphosphines 15
(Scheme 3, method B). The results are summarized in Table 2.
According to the former case, the o-boronatophenyl
phosphine boranes 12a and 12f were deprotected with
DABCO at rt to afford the corresponding free phosphines 16a,
16b in 88% and 80% yields, respectively (Table 2, entries 1, 2). It
should be noted that the borane decomplexation of 12f was
achieved stereospecifically, because the HPLC analysis on the
chiral column did not show any racemization for 16b (entry 2).
As the boronate compounds could be easily converted into
their trifluoroborate derivatives, also useful in transition metal
catalyzed cross-coupling reactions,11 the preparation of P-
chirogenic o-trifluoroboratophenyl phosphines was made.
Thus, treatment of 16c with KHF2 leads to the P-chirogenic
phosphine 17 in 43% yield (ee >98%) (Scheme 4).
In conclusion, the synthesis of chiral and achiral o-boronated
phosphine borane complexes was achieved in good to high
isolated yields, starting from sec-phosphine boranes and using
aryne chemistry. This methodology is based on two key steps by
Scheme 4. Preparation of the P-Chirogenic o-
Trifluoroboratophenylphosphine 17
C
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Stephan, D. W.; Kehr, G.; Erker, G. Chem. Sci. 2013, 4, 213. (k) Stute, A.;
successive reactions of the sec-phosphine boranes, first with 1,2-
dibromobenzene and then with a boron reagent. When the
synthesis is performed using P-chirogenic sec-phosphine boranes,
the o-boronatophenyl derivatives are obtained without race-
mization and with complete retention of the configuration at the
P-center, as established by X-ray analysis. The decomplexation of
the borane adducts under basic conditions provides the
corresponding free o-boronatophenylphosphine in yields up to
88%. The use of this new and efficient method for the
preparation of achiral or P-chirogenic o-boronated phosphines
appears to be promising for the development and the
applications of this interesting class of ambiphilic compounds.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Chem., Int. Ed. 2007, 46, 8050. (b) Basle,
Bouhadir, G.; Bourissou, D. Chem. Commun. 2012, 48, 4495.
(c) Courtemanche, M.-A.; Legare, M.-A.; Maron, L.; Fontaine, F.-G. J.
Am. Chem. Soc. 2013, 135, 9326.
́
O.; Porcel, S.; Ladeira, S.;
Experimental data, selected spectral data for all new compounds,
and X-ray data for compounds 12b, 12f, and 12h. This material is
available free of charge via the Internet at http://pubs.acs.org.
́
́
(6) (a) Kim, Y.; Hudnall, T. W.; Bouhadir, G.; Bourissou, D.; Gabbaï,
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AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: jerome.bayardon@u-bourgogne.fr.
*E-mail: sylvain.juge@u-bourgogne.fr.
Present Address
†Universite
́
de Montpellier, IBMM UMR 5247, case 1703, place
E. Bataillon, 34095 Montpellier, France.
Notes
(7) (a) Borner, A.; Ward, J.; Kortus, K.; Kagan, H. B. Tetrahedron:
̈
Asymmetry 1993, 4, 2218. (b) Fields, L. B.; Jacobsen, E. N. Tetrahedron:
Asymmetry 1993, 4, 2229. (c) Siwert, I.; Vidovic, D.; Aldridge, S. J.
Organomet. Chem. 2011, 696, 2528. (d) Ghattas, G.; Chen, D.; Pan, F.;
Klankermayer, J. Dalton Trans. 2012, 42, 9026. (e) Chen, D.;
Klankermayer, J. Top. Curr. Chem. 2013, 334, 1.
(8) Vinci, D.; Mateus, N.; Wu, X.; Hancock, F.; Steiner, A.; Xiao, J. Org.
Lett. 2006, 8, 215.
The authors declare no competing financial interest.
(9) Bayardon, J.; Laureano, H.; Diemer, V.; Dutartre, M.; Das, U.;
ACKNOWLEDGMENTS
The authors are grateful for the financial support provided by the
CNRS (Centre National de la Recherche Scientifique), the
Rousselin, Y.; Henry, J.-C.; Colobert, F.; Leroux, F. R.; Juge,
Chem. 2012, 77, 5759.
(10) Juge, S.; Bayardon, J.; Laurea
Leroux, F.; Rem
007724 A1.
(11) (a) Darses, S.; Genet
(b) Molander, G. A.; Jean-Gerard, L. Org. React. 2013, 79, 1.
́
S. J. Org.
■
́
́
no, H.; Henry, J.-C; Colobert, F.;
ond, E. US 20140142325; EP 2731956; WO 2013
́
̀
Ministere de l’Education Nationale et de la Recherche, the
Conseil Regional de Bourgogne (Grants 3MIM, Pari II-smt8),
and the Agence Nationale pour la Recherche (Grant
07BLAN292-01 MetChirPhos). It is also a pleasure to thank M.
J. Eymin, M. J. Penouilh, Dr. F. and Dr. M. Picquet at the Institut
̂
, J. P. Chem. Rev. 2008, 108, 288.
́
́ ́
de Chimie Moleculaire de l’Universite de Bourgogne, for their
technical assistance.
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