New boranophosphorylation reagents, dimethyl boranophosphate monopotassium salt and tetramethyl boranopyrophosphate

Full text of DOI:10.1021/ja972276l

J. Am. Chem. Soc. 1997, 119, 9925-9926
New Boranophosphorylation Reagents, Dimethyl
9925
Boranophosphate Monopotassium Salt and
Tetramethyl Boranopyrophosphate
Tsuneo Imamoto,*,1a Eiji Nagato,1a Yoshiyuki Wada,1b
Hideki Masuda,1b Kentaro Yamaguchi,1c and
Tadafumi Uchimaru1d
Department of Chemistry, Faculty of Science and
Chemical Analysis Center, Chiba UniVersity
Yayoi-cho, Inage-ku, Chiba 263, Japan
Ogawa and Company Ltd., Okayama Laboratory
Shoocho, Katsuta, Okayama 709-43, Japan
National Institute of Materials and Chemical Research
Science City 305, Japan
Figure 1. ORTEP drawing for compound 1. Selected bond distances
(Å) and angles (deg): P(1)-B(1), 1.895(6), P(1)-O(1), 1.490(3); P(1)-
O(2), 1.597(4); P(1)-O(3), 1.612(3); O(1)-K(1), 2.656(3); B(1)-
P(1)-O(1), 116.4(2); O(1)-P(1)-O(2), 110.2(2); O(2)-P(1)-O(3),
96.8(2); O(3)-P(1)-B(1), 113.4(2); B(1)-P(1)-O(2), 114.1(2); O(1)-
P(1)-O(3), 103.6(2); P(1)-O(1)-K(1), 132.3(2).
ReceiVed July 9, 1997
Boranophosphates, which have an isoelectronic relationship
with phosphates, are useful compounds, like thiophosphates, in
biochemical and molecular biological investigations.2 They
have also anticipated utility as carriers of 10B in boron neutron
capture therapy (BNCT) for the treatment of cancer.3 This class
of compounds, including borano derivatives of oligonucleotides,
was previously synthesized by the reactions of phosphites and
related substrates with borane.4 Although the method affords
the products in good yields, it essentially requires tricoordinate
phosphorus compounds as the precursors.
Scheme 1
We envisioned that various boranophosphates might be
synthesized by a simpler procedure via an electrophilic or a
nucleophilic substitution, as shown in Scheme 1. The methods
would employ nucleophilic or electrophilic reagents containing
a boranophosphate building block. To realize this idea, we
prepared new reagents, dimethyl boranophosphate monopotas-
sium salt (1) and tetramethyl boranopyrophosphate (2), and
examined their reactivities toward various electrophiles or
nucleophiles.
boranophosphate anion interacts with the potassium ion as a
monodentate ligand; no apparent coordinative interaction be-
tween the boranato group and the potassium ion is observed.8
The reactivities of compound 1 toward alkyl halides, chlo-
rosilanes, and acid chlorides were examined, and the results
are summarized in Table 1. It is noted that compound 1
underwent facile SN2 reactions with alkyl halides possessing
an oxygen functional group at the R-position. Another notable
fact is that carboxylic and boranophosphoric mixed anhydrides
were readily obtained by the reactions with acid chlorides.
Compound 1 (2 mol) reacted with 1 mol of methanesulfonyl
chloride in acetonitrile to give tetramethyl boranopyrophosphate
2 as an oil in excellent yield (eq 1).9 The pyrophosphate 2
reacted with lithium alkoxides of simple alcohols to give the
corresponding boranophosphates in good yields.10 The utility
of this method is substantiated by the synthesis of a borano
functionalized nucleotide (eq 2).
Potassium salt 1 was obtained as good crystalline solids by
the hydrolysis of trimethyl boranophosphate with KOH in
methanol, followed by recrystallization from acetonitrile.5,6 This
salt was stable under neutral or basic conditions, while it
gradually decomposed on contact with hydrochloric acid with
evolution of hydrogen. X-ray crystallographic analysis of 1 was
undertaken, and its crystal structure is shown in Figure 1.7 The
(5) Preparation of compound 1: To an ice-cold solution of 13.8 g (0.1
mol) of trimethyl boranophosphate in methanol (50 mL) was added 8.5 g
of powdered potassium hydroxide. The mixture was stirred at 0 °C for 30
min, and it was gradually warmed to 60 °C. After the mixture was stirred
at the same temperature for 5 h, the solvent was removed under reduced
pressure and the residual solid was recrystallized from acetonitrile to give
14.2 g (87%) of compound 1 as colorless needles: mp 169.5-170.5 °C;
(1) (a) Department of Chemistry, Faculty of Science, Chiba University.
(b) Ogawa and Co., Ltd. (c) Chemical Analysis Center, Chiba University.
(d) National Institute of Materials and Chemical Research.
3
1H NMR (D2O, TSP) δ -0.2∼0.8 (br q, 3H), 3.54 (d, JPH ) 10.2 Hz);
2
13C NMR (D2O, TSP) δ 53.2 (d, JCP ) 4.9 Hz); 31P NMR (D2O, H3PO4)
(2) For representative reviews on chemically modified phosphates, see:
(a) Eckstein, F. Acc. Chem. Res. 1979, 12, 204-210. (b) Frey, P. A.
Tetrahedron 1982, 38, 1541-1567. (c) Eckstein, F. Angew. Chem., Int.
Ed. Engl. 1983, 22, 423-439. (d) Uhlmann, E.; Peyman, A. Chem. ReV.
1990, 90, 543-584. (e) Stein, C. A.; Cheng, Y.-C. Science 1993, 261,
1004-1012. (f) Baraniak, J.; Stec, W. J. ReV. Heteroatom Chem. 1993, 8,
143-164.
(3) For representative reviews on BNCT, see: (a) Hawthorne, M. F.
Angew. Chem., Int. Ed. Engl. 1993, 32, 950-984. (b) Nemoto, H. Synth.
Org. Chem. Jpn. 1994, 52, 1044-1052.
(4) (a) Reetz, T. J. Am. Chem. Soc. 1960, 82, 5039-5042. (b) Sood,
A.; Shaw, B. R.; Spielvogel, B. F. J. Am. Chem. Soc. 1990, 112, 9000-
9001. (c) Spielvogel, B. F.; Sood, A.; Shaw, B. R.; Hall, I. H. Pure Appl.
Chem. 1991, 63, 415-418. (d) Tomasz, J.; Shaw, B. R.; Porter, K.;
Spielvogel, B. F.; Sood, A. Angew. Chem., Int. Ed. Engl. 1992, 31, 1373-
1375. (e) Chen, Y.-Q.; Qu, F.-C.; Zhang, Y.-B. Tetrahedron Lett. 1995,
36, 745-748. (f) Zhang, J.; Terhorst, T.; Matteucci, M. D. Tetrahedron
Lett. 1997, 38, 4957-4960.
δ 94.5 (q, JPB ) 144 Hz); 11B NMR (128 MHz, D2O, B(OMe)3) δ -60.7
(d, JBP ) 144 Hz); IR (KBr) 2920, 2380, 1080, 1015, 785 cm-1
. Anal.
Calcd for C2H9BKO3P: C, 14.83; H, 5.60. Found: C, 14.92; H, 5.55.
(6) Other potassium salts ((RO)2P(BH3)OK: R ) Et, PhCH2) were also
obtained in high yields. On the other hand, the corresponding lithium or
sodium salts were not obtained as good crystalline solids, although the
trialkyl boranophosphates were subjected to hydrolysis on treatment with
LiOH or NaOH.
(7) Crystal data of 1: orthorhombic, Pccn; a ) 11.4209(8) Å, b )
19.957(3) Å, c ) 6.681(2) Å; V ) 1522.8(5) Å3; Dcalc ) 1.413 g cm-3
;
F(000) ) 672; µ(Cu KR) ) 75.86 cm-1; λ(Cu KR) ) 1.54178 Å; 1357 re-
flections measured, 924 observed (I > 1.5σ(I)); 73 variables; R ) 0.049,
Rw ) 0.064, GOF ) 1.55.
(8) X-ray crystallographic analysis of (MeO)2P(O)OK was also carried
out in order to compare its structure with compound 1. Both compounds
exhibit an analogous crystal structure except that two anionic oxygen atoms
of (MeO)2P(O)OK interact with the potassium atom.
S0002-7863(97)02276-2 CCC: $14.00 © 1997 American Chemical Society

9926 J. Am. Chem. Soc., Vol. 119, No. 41, 1997
Communications to the Editor
Table 1. Reactions of Compound 1 with Electrophiles
In summary, we have prepared new reagents, dimethyl
boranophosphate monopotassium salt and tetramethyl bor-
anopyrophosphate, and have demonstrated that these reagents
react with reactive organic halides or lithium alkoxides in a
nucleophilic or electrophilic manner. These facts open new and
simple synthetic routes to various boranophosphates derivatives
including borano analogues of naturally occurring phosphates.
(9) Preparation of compound 2: Methanesulfonyl chloride (0.93 mL, 12
mmol) was added to a solution of 1 (3.24 g, 20 mmol) in acetonitrile (30
mL) at 0 °C, and the mixture was stirred at room temperature for 4 h. The
precipitated solid was removed by filtration, and the filtrate was concentrated
under reduced pressure. The residual oil was passed through a short column
of silica gel with ethyl acetate to give compound 2 (2.26 g, 98%) as a
colorless oil: Rf ) 0.23 (silica gel, ethyl acetate-hexane 1:5); 1H NMR
a All reactions were carried out in acetonitrile at room temperature.
b Isolated yield. c The structure of this compound was unequivocally
determined by single crystal X-ray analysis.
Acknowledgment. The authors thank Professor Hiroshi Takaku,
Chiba Institute of Technology, for valuable discussions.
3
(CDCl3) δ -0.1 to -1.2 (br q, 6H), 3.85 (d, JHP ) 11.5 Hz); 31P NMR
(CDCl3) δ 110.6-111.8 (m); 11B NMR (CDCl3) δ -62.4 (d, JBP ) 87.3
Hz); IR (neat) 2960, 2440, 1040, 860 cm-1; HRMS (FAB) calcd for
C4H17B2O5P2 (M - H) 229.074, found 229.074. This compound violently
decomposed at about 130 °C.
(10) A mixed anhydride, 2,4,6-Me3C6H2COOP(BH3)(MeO)2, also reacted
with lithium alkoxides to give the corresponding boranophosphates.
Supporting Information Available: Spectral data of new bor-
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JA972276L