The synthesis and characterisation of novel o-substituted benzyldi-t-butylphosphine-boranes

Article abstract of DOI:10.1016/j.tetlet.2008.12.006

The novel compounds o-(chloromethyl)benzyldi-t-butylphosphine-borane and o-(methoxymethyl)benzyldi-t-butylphosphine-borane have been synthesised in 54% and 51% yields, respectively, and have been fully characterised. An improved method for the synthesis o

Full text of DOI:10.1016/j.tetlet.2008.12.006

Tetrahedron Letters 50 (2009) 834–835
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
The synthesis and characterisation of novel o-substituted
benzyldi-t-butylphosphine–boranes
*
Kathryn M. Allan, John L. Spencer
School of Chemical and Physical Sciences, Victoria University of Wellington, Kelburn, Wellington 6012, New Zealand
a r t i c l e i n f o
a b s t r a c t
Article history:
The novel compounds o-(chloromethyl)benzyldi-t-butylphosphine–borane and o-(methoxymethyl)ben-
zyldi-t-butylphosphine–borane have been synthesised in 54% and 51% yields, respectively, and have been
Received 24 October 2008
Revised 25 November 2008
Accepted 3 December 2008
Available online 7 December 2008
fully characterised. An improved method for the synthesis of
reported.
a
-chloro-a0-methoxy-o-xylene is also
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Phosphine–boranes
Ligand synthesis
Substituted o-xylenes
Cs-Symmetric ligands
Following the commercial success of 1,2-bis[(di-t-butylphosph-
The synthesis of 1 was achieved via the reaction of a,
a0-di-
ino)methyl]benzene as an ancillary chelating ligand for the palla-
chloro-o-xylene with lithium di-t-butylphosphide–borane in
diethyl ether at room temperature (Scheme 1).6 The reaction of
stoichiometric quantities of the reactants results in a statistical dis-
tribution of products, and therefore a theoretical maximum 50%
yield of the desired product. However, using an excess of the xy-
lene reagent increases the proportion of the desired product, and
unreacted starting material can be removed from the crude prod-
uct by sublimation (and recycled for use in subsequent reactions).
The borane protecting group is key to this synthetic strategy for
three reasons: most importantly it prevents cyclisation to the cor-
responding cyclic phosphonium ion, it also renders the product an
easily handled air-stable crystalline solid and it protects the phos-
phorus atom from oxidation and other side reactions in any subse-
dium-catalysed methoxycarbonylation of ethene,1
a lot of
interest has been generated in phosphine ligands containing an
o-xylene-based backbone. A number of subsequent patents have
been granted for catalytic processes that utilise 1,2-bis[(di-t-buty-
lphosphino)methyl]benzene,2 and the use of phosphine substitu-
ents other than t-butyl groups has also been investigated.3 There
are also recent examples wherein the two donor groups of the li-
gand are not identical in that the substituents on each phosphorus
atom differ.4,5
The synthesis of these Cs-symmetric diphosphine ligands is not
straightforward, as it is usually necessary to differentially substi-
tute the two donor atom positions of a starting material with
higher symmetry such as
lo-o-xylene. At present, the synthesis of these ligands is achieved
through conversion of
a0-dihydroxy-o-xylene to a cyclic sulfite,
a, a,
a0-dihydroxy-o-xylene or an a0-diha-
a,
BH3
followed by Ru-catalysed oxidation to the corresponding cyclic sul-
fate and then by two sequential nucleophilic substitution steps
with different lithium phosphides4 or lithium phosphide–boranes.5
This synthetic methodology is limited, however, by the availability
of the two nucleophilic reagents for the final synthetic steps. Here-
in, we report the synthesis and characterisation of the novel com-
pounds o-(chloromethyl)benzyldi-t-butylphosphine–borane 1 and
o-(methoxymethyl)benzyldi-t-butylphosphine–borane 2 (Fig. 1),
as potentially versatile reagents for the synthesis of Cs-symmetric
diphosphine ligands of this type.
PBut2
R
1
2
R = Cl
R = OMe
Figure 1. o-Substituted benzyldi-t-butylphosphine–boranes.
Cl
Cl
(2 equiv)
BH3
PBut2
Cl
BH3
But2PLi
Et2O, -60 °C to rt
1 54%
Scheme 1. Synthesis of o-(chloromethyl)benzyldi-t-butylphosphine-borane 1.
* Corresponding author. Tel.: +64 4 463 5119; fax: +64 4 463 5241.
E-mail address: john.spencer@vuw.ac.nz (J.L. Spencer).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.12.006

K. M. Allan, J. L. Spencer / Tetrahedron Letters 50 (2009) 834–835
835
2. For examples, see: (a) Bunel, E. E.; Clark, D. A. W.O. Patent 2002048094, 2002;
Chem. Abstr. 2002, 137, 47592.; (b) Itsuno, S.; Ooka, K.; Sagae, T.; Inoue, T. J.P.
Patent 2005247703, 2005; Chem. Abstr. 2005, 143, 307307.; (c) Keep, A. K.;
Collard, S.; Hooper, M. W.; Colacot, T. J. W.O. Patent 2007029031, 2007; Chem.
Abstr. 2007, 146, 329185.; (d) Eastham, G. R.; Waugh, M.; Richards, P. I. W.O.
Patent 2008075108, 2008; Chem. Abstr. 2008, 149, 106861.
3. For examples, see: (a) Sesto, B.; Consiglio, G. Chem. Commun. 2000, 1011–1012;
(b) Gridnev, I. D.; Higashi, N.; Imamoto, T. Organometallics 2001, 20, 4542–
4553; (c) Li, R.-X.; Li, X.-J.; Wong, N.-B.; Tin, K.-C.; Zhou, Z.-Y.; Mak, T. C. W. J.
Mol. Catal. A: Chem. 2002, 178, 181–190; (d) Raebiger, J. W.; Miedaner, A.;
Curtis, C. J.; Miller, S. M.; Anderson, O. P.; DuBois, D. L. J. Am. Chem. Soc. 2004,
126, 5502–5514.
NaOMe (0.5 equiv)
MeOH, reflux
Cl
Cl
Cl
OMe
3 62%
a
-chloro-a0-methoxy-o-xylene 3.
Scheme 2. Synthesis of
Cl
OMe
4. Leone, A.; Consiglio, G. Helv. Chim. Acta 2005, 88, 210–215.
5. Rucklidge, A. J.; Morris, G. E.; Slawin, A. M. Z.; Cole-Hamilton, D. J. Helv. Chim.
Acta 2006, 89, 1783–1800.
BH3
PBut2
OMe
BH3
3
But2PLi
6. Preparation of o-(chloromethyl)benzyldi-t-butylphosphine-borane 1: A mixture of
di-t-butylphosphine (24 mmol) and borane-dimethylsulfide complex
(28 mmol) was stirred in THF (15 mL) under a nitrogen atmosphere for 2 h,
and the solvent was evaporated under reduced pressure. The resulting white
solid was dissolved in ether (50 mL) and cooled to 0 °C, and a solution of n-BuLi
in hexanes (24 mmol) was added dropwise with stirring. The mixture was
stirred at room temperature for 15 min, then cooled to ꢀ60 °C and a solution of
Et2O, 0 °C to rt
2 51%
Scheme 3. Synthesis of o-(methoxymethyl)benzyldi-t-butylphosphine-borane 2.
a,
a0-dichloro-o-xylene (70 mmol) in ether (50 mL) was added. After warming
quent reaction steps. The borane protecting group is easily re-
moved at any stage with an amine base.7
Attempts have been made to convert 1 into 2 using various
sources of methoxide, however in all cases, abstraction of the bor-
ane protecting group occurred followed by cyclisation of the start-
ing material to the corresponding cyclic phosphonium chloride. For
to room temperature, the mixture was stirred for 2 h. The resulting solution
was filtered and the solvent evaporated under reduced pressure, leaving a pale
yellow solid. Unreacted
a,
a0-dichloro-o-xylene was sublimed from the crude
material at 50 °C and ꢁ0.1 mmHg overnight, and the desired product 1 was
recrystallised from n-hexane. White crystals, mp 110 °C, yield 54%. 1H NMR d
(500 MHz, C6D6): 0.8–1.5 (br q, J = 95.0 Hz, 3H, BH3), 1.05 (d, J = 12.3 Hz, 18H,
But), 3.11 (d, J = 12.0 Hz, 2H, CH2P), 4.72 (s, 2H, CH2Cl), 6.89 (m, 1H, ArH), 6.98
(m, 2H, ArH), 7.57 (d, J = 7.5 Hz, 1H, ArH); 13C NMR d (125 MHz, C6D6): 21.91 (d,
J = 22.9 Hz, CH2P), 28.27 (d, J = 1.4 Hz, But), 32.98 (d, J = 24.3 Hz, But), 46.21 (s,
CH2Cl), 127.54 (d, J = 2.3 Hz, ArC), 128.70 (d, J = 1.4 Hz, ArC), 131.39 (d,
J = 1.4 Hz, ArC), 132.29 (d, J = 3.3 Hz, ArC), 135.01 (d, J = 3.2 Hz, ArC), 137.24
(d, J = 4.1 Hz, ArC); 31P NMR d (121 MHz, C6D6): 47.90 (m); IR (film from
CH2Cl2): 2377 (BH), 2969-2870 cmꢀ1 (CH); HRMS calcd for C16H29BClP
[M+Na]+: m/z = 321.1686; found: 321.1685; Anal. Calcd for C16H29BClP: C,
64.4; H, 9.8. Found: C, 64.1; H, 9.9.
this reason, the synthesis of 2 requires the use of
a -
-chloro-a0
methoxy-o-xylene 3. This compound was first synthesised by
Murahashi in crude form8 and subsequently synthesised and iso-
lated successfully by Mann and Stewart in 1954, requiring at least
three reaction steps from a commercially available material.9 To
the best of our knowledge, there have been no other published syn-
theses of this material. We have developed an improved method for
the synthesis of 3, requiring only one reaction step and producing
yields similar to those of Mann and Stewart.
7. Brunel, J. M.; Faure, B.; Maffei, M. Coord. Chem. Rev. 1998, 178-180, 665–698.
8. Murahashi, S. Sci. Papers Inst. Phys. Chem. (Jpn.) 1936, 30, 180–194.
9. Mann, F. G.; Stewart, F. H. C. J. Chem. Soc. 1954, 2819–2822.
10. Preparation of
in methanol (30 mL) was added dropwise to a refluxing solution of
a
-chloro-a0-methoxy-o-xylene 3: A solution of NaOMe (11 mmol)
As shown in Scheme 2, a,
a0-dichloro-o-xylene was treated with
a, -
a0
sodium methoxide in methanol at reflux.10 Again, the reaction of
stoichiometric quantities of the reactants resulted in a statistical
distribution of products, and therefore a theoretical maximum
50% yield of the desired product. However, when a solution of so-
dium methoxide in methanol was added dropwise to a refluxing
dichloro-o-xylene (22 mmol) in methanol (30 mL) over 30 min. Reflux was
continued for 1 h, after which the cooled mixture was concentrated to half
volume under reduced pressure. H2O (40 mL) was added and the mixture was
extracted with ether (2 ꢂ 40 mL). The combined organic layer was washed
with brine (25 mL) and dried (MgSO4), and the solvent evaporated under
reduced pressure to give a yellow liquid containing compound 3,
o-xylene and
a0-dimethoxy-o-xylene. The a0-dimethoxy-o-xylene
byproduct was removed by elution through silica gel column with 5%
EtOAc in n-hexane (Rf = 0.31). Elution through a silica gel column with 10%
toluene in n-hexane was then used to separate the unreacted
a,
a0-dichloro-
a
,
a,
solution of excess
a,
a0-dichloro-o-xylene, the resulting yield of
a
compound 3 increased considerably. The desired product can be
isolated via two flash column chromatography steps to give an
overall yield of 62%. This method is significantly more atom eco-
nomic and time efficient than previously reported methods.
Compound 3 can be combined with lithium di-t-butylphos-
phide–borane in diethyl ether at 0 °C to generate the o-substituted
benzyldi-t-butylphosphine–borane 2 as an air-stable white crystal-
line solid in a 51% yield (Scheme 3).11
a,
a0-dichloro-o-
xylene (Rf = 0.54) and pure compound 3 (Rf = 0.17). Clear liquid, yield 62%. 1H
NMR d (500 MHz, CDCl3): 3.42 (s, 3H, OCH3), 4.60 (s, 2H, CH2O), 4.71 (s, 2H,
CH2Cl), 7.32 (m, 2H, ArH), 7.38 (m, 2H, ArH); 13C NMR d (125 MHz, CDCl3):
43.80 (s, CH2Cl), 58.54 (s, OCH3), 72.39 (s, CH2O), 128.57 (s, ArC), 128.94 (s,
ArC), 129.65 (s, ArC), 130.43 (s, ArC), 136.09 (s, ArC), 136.72 (s, ArC); IR (liquid
film): 1088 (CO), 3068–2823 cmꢀ1 (CH); Anal. Calcd for C9H11ClO: C, 63.4; H,
6.5. Found: C, 63.8; H, 6.6.
11. Preparation of o-(methoxymethyl)benzyldi-t-butylphosphine-borane 2: A mixture
of di-t-butylphosphine (3 mmol) and borane-dimethylsulfide complex
(3 mmol) was stirred in THF (4 mL) under a nitrogen atmosphere for 2 h, and
the solvent was evaporated under reduced pressure. The resulting white solid
was dissolved in ether (30 mL) and cooled to 0 °C, and a solution of n-BuLi in
hexanes (3 mmol) was added dropwise with stirring. The mixture was stirred
In conclusion, we have synthesised novel o-substituted benzyldi-
t-butylphosphine–boranes, whichare potentially useful reagentsfor
the synthesis of new phosphine ligands containing an o-xylene-
based backbone. We have also developed a new method for the syn-
at room temperature for 30 min, then cooled to 0 °C and a solution of a-chloro-
thesis of a
-chloro-a0-methoxy-o-xylene, which is more atom eco-
a0-methoxy-o-xylene 3 (3 mmol) in ether (20 mL) was added. After warming to
room temperature, the mixture was stirred overnight. The resulting solution
was filtered and the solvent evaporated under reduced pressure, leaving a clear
liquid. The desired product 2 was recrystallised from n-hexane. White crystals,
mp 77 °C, yield 51%. 1H NMR d (500 MHz, C6D6): 1.0–1.8 (br q, J = 95.0 Hz, 3H,
BH3), 1.08 (d, J = 12.5 Hz, 18H, But), 3.09 (s, 3H, OCH3), 3.16 (d, J = 12.5 Hz, 2H,
CH2P), 4.44 (s, 2H, CH2O), 6.99 (t, J = 8.0 Hz, 1H, ArH), 7.11 (d, J = 7.5 Hz, 2H,
ArH), 8.10 (d, J = 8.0 Hz, 1H, ArH); 13C NMR d (125 MHz, C6D6): 21.16 (d,
J = 24.4 Hz, CH2P), 28.18 (d, J = 1.0 Hz, But), 33.06 (d, J = 24.8 Hz, But), 57.54 (s,
OCH3), 74.36 (s, CH2O), 126.75 (d, J = 1.9 Hz, ArC), 130.66 (d, J = 1.0 Hz, ArC),
131.92 (d, J = 2.9 Hz, ArC), 135.50 (d, J = 2.9 Hz, ArC), 136.55 (d, J = 5.3 Hz, ArC),
(other ArC obscured by solvent peak); 31P NMR d (121 MHz, C6D6): 47.30 (m);
IR (film from CH2Cl2): 1070 (CO), 2380 (BH), 2967–2871 cmꢀ1 (CH); HRMS
calcd for C17H32BOP [M+Na]+: m/z = 317.2182; found: 317.2180; Anal. Calcd for
C17H32BOP: C, 69.4; H, 11.0. Found: C, 69.2; H, 11.1.
nomic and time efficient than previously reported methods.
Acknowledgement
We gratefully acknowledge Dr. Joanne E. Harvey for her invalu-
able advice.
References and notes
1. Tooze, R. P.; Eastham, G. R.; Whiston, K.; Wang, X. L. W. O. Patent 9619434,
1996; Chem. Abstr. 1996, 125, 145592.
CAUTION This compound has been reported to be strongly lachrymatory, and to
cause headaches, and visual and gastric disturbance.9