Platinum-catalyzed diboration using a commercially available catalyst: Diboration of aldimines to α-aminoboronate esters

Article abstract of DOI:10.1021/ol006008v

equation presented Commercially available Pt(cod)Cl₂ catalyzes the diboration of alkenes, alkynes, and aldimines using bis(catecholato)diboron (cod = 1,5-cyclooctadiene). Catalyzed aldimine diboration provides the first direct route to α-aminoboronate esters. The diboration product from N-benzylidene-2,6-dimethylaniline is structurally characterized.

Full text of DOI:10.1021/ol006008v

ORGANIC
LETTERS
2000
Vol. 2, No. 14
2105-2108
Platinum-Catalyzed Diboration Using a
Commercially Available Catalyst:
Diboration of Aldimines to
r-Aminoboronate Esters
Grace Mann, Kevin D. John, and R. Tom Baker*
Los Alamos Catalysis InitiatiVe, Chemistry DiVision, Los Alamos National Laboratory,
MS J514, Los Alamos, New Mexico 87545
weg@lanl.goV
Received May 2, 2000
ABSTRACT
Commercially available Pt(cod)Cl2 catalyzes the diboration of alkenes, alkynes, and aldimines using bis(catecholato)diboron (cod ) 1,5-
cyclooctadiene). Catalyzed aldimine diboration provides the first direct route to r-aminoboronate esters. The diboration product from
N-benzylidene-2,6-dimethylaniline is structurally characterized.
Boronic acids and boronate esters are useful molecules in
organic chemistry and biochemistry. These molecules are
important intermediates in organic synthesis.1 Boronic acids
and boronate esters are used in palladium2- and nickel3-
catalyzed cross-coupling reactions and, more recently, cop-
per-catalyzed reactions to form new carbon-carbon bonds.4
Ongoing research has led to their recent use as linkers for
solid-phase synthesis,5 in macrocyclic chemistry,6 in organo-
metallic synthesis,7 and for new organic transformations.8
Furthermore, boronic acids have been studied as fructose
sensors,9 and R-aminoboronic acids, [RR′NCHR′′B(OH)2],
are known to bind strongly to serine proteases and related
enzymes.10
The preparation of a wide variety of boronic acids and
boronate esters with excellent control of regio-, diastereo-,
and enantioselectivity has become possible with the advent
of metal-catalyzed hydroboration and diboration of unsatur-
ated organic substrates.11 While diboration of alkynes can
be catalyzed by Pt(PPh3)412 or Pt(PPh3)2(C2H4),13 the dibor-
14
(1) Matteson, D. S. Tetrahedron 1989, 45, 1859-1885.
(2) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483.
(3) Trost, B. M.; Spagnol, M. D. J. Chem. Soc., Perkin Trans. 1 1995,
2083-2096.
(4) Chan, D. M. T.; Monaco, K. L.; Wang, R. P.; Winters, M. P.
Tetrahedron Lett. 1998, 39, 2933-2936.
(5) Carboni, B.; Pourbaix, C.; Carreaux, F.; Deleuze, H.; Maillard, B.
Tetrahedron Lett. 1999, 40, 7979-7983.
(6) Farfan, N.; Hopfl, H.; Barba, V.; Ochoa, M. E.; Santillan, R.; Gomez,
E.; Gutierrez, A. J. Organomet. Chem. 1999, 581, 70-81.
(7) Minutolo, F.; Katzenellenbogen, J. A. Organometallics 1999, 18,
2519-2530.
(8) (a) Batey, R. A.; MacKay, D. B.; Santhakumar, V. J. Am. Chem.
Soc. 1999, 121, 5075-5076. (b) Petasis, N. A.; Zavialov, I. A. J. Am. Chem.
Soc. 1998, 120, 11798-11799.
ation of terminal alkenes using B2cat2 or B2pin2 employs
(9) Norrild, J. C.; Eggert, H. J. Chem. Soc., Perkin Trans. 2 1996, 2583-
2588.
(10) (a) Tsilikounas, E.; Kettner, C. A.; Bachovchin, W. W. Biochemistry
1992, 31, 12839-12846. (b) Skordalakes, E.; Tyrell, R.; Elgendy, S.;
Goodwin, C. A.; Green, D.; Dodson, G.; Scully, M. F.; Freyssinet, J. M.
H.; Kakkar, V. V.; Deadman, J. J. J. Am. Chem. Soc. 1997, 119, 9935-
9936. (c) Coutts, S. J.; Kelly, T. A.; Snow, R. J.; Kennedy, C. A.; Barton,
R. W.; Adams, J.; Krolikowski, D. A.; Freeman, D. M.; Campbell, S. J.;
Ksiazek, J. F.; Bachovchin, W. W. J. Med. Chem. 1996, 39, 2087-2094.
(11) Marder, T. B.; Norman, N. C. Top. Catal. 1998, 5, 63-73.
(12) Ishiyama, T.; Yamamoto, M.; Miyaura, N. Chem. Commun. 1996,
2073-2074.
10.1021/ol006008v CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/17/2000

gold,15 platinum,16 and rhodium17 catalysts, none of which
are commercially available. The diboration of carbon-
heteroatom double bonds18 is a potentially direct route to a
variety of biologically active R-functionalized boronate
esters.19 We report herein that commercially available
Pt(cod)Cl2, 1, catalyzes the diboration of terminal alkenes,
vinylarenes, and alkynes using B2cat2, as well as the first
metal-catalyzed diboration of aldimines to form R-amino-
boronate esters.
ylene (entry 5), is accomplished in 3 h at 55 °C with use of
5 mol % of 1.
Reaction of aldimines and B2cat2 in the presence of 3-5
mol % of 1 affords rac-R-aminoboronate esters in good
yields (Table 2).22 This catalyst precursor effects the dibo-
Table 2. Pt(cod)Cl2-Catalyzed Diboration of Aldiminesa
Excellent yields are obtained when 1 is used as a
precatalyst for the diboration of terminal alkenes, vinylarenes,
and alkynes (Table 1).20 Reaction of benzene solutions of
Table 1. Pt(cod)Cl2-Catalyzed Diborationa
a Reaction conditions: 0.25 mM substrate, 1.1 equiv of B2cat2, 3-5 mol
% of 1, 3 h at 25 °C in benzene. b Yields determined by 1H NMR
spectroscopy with respect to an internal standard from an average of at
least two runs. Yield in parentheses refers to an isolated yield. c Reaction
was stirred at 55 °C for 3 h.
ration of sterically hindered aldimines, such as N-benzyl-
idene-2,6-dimethylaniline (entry 1) and N-benzylidene-2,6-
diisopropylaniline (entry 2), in 87% and 95% yield,
respectively. A comparatively lower yield (66%) of R-amino-
boronate ester is obtained when N-benzylidene-4-anisidine
is used as a substrate (entry 3). The rac-R-aminoboronate
a Reaction conditions: 0.25 mM substrate, 1.1 equiv of B2cat2, 3-5 mol
% of 1, 3 h at 25 °C in benzene. b Yields determined by 1H NMR
spectroscopy with respect to an internal standard from an average of at
least two runs. Yields in parentheses refer to isolated yields. c Yields of
isolated product are lower due to the similarities in solubilities of the product
and the degradation product of the catalyst. d Reaction was stirred at 55 °C
for 3 h.
(17) Dai, C. Y.; Robins, E. G.; Scott, A. J.; Clegg, W.; Yufit, D. S.;
Howard, J. A. K.; Marder, T. B. Chem. Comm. 1998, 1983-1984.
(18) Cameron, T. M.; Baker, R. T.; Westcott, S. A. Chem. Commun.
1998, 2395-2396.
4-vinylanisole, 4-chlorostyrene, or 1-octene with 3-5 mol
% of 1 and 1.1 equiv of B2cat2 at room temperature forms
diboration products in greater than 90% yield (Table 1,
entries 1-3).21 Diboration of terminal alkynes, such as
1-octyne (entry 4), and internal alkynes, such as ditolylacet-
(19) Jadhav, P. K.; Man, H. J. Org. Chem. 1996, 61, 7951-7954.
(20) Typical procedure, 1H NMR yield (Table 1, entry 1): a 2 mL
screw-capped vial equipped with a mini-stir bar was charged with 1 (1.7
mg, 0.005 mmol, 3 mol % of Pt), B2cat2 (38.0 mg, 0.16 mmol),
4-vinylanisole (18.0 mg, 0.13 mmol), and trimethoxybenzene as standard
(17.6 m g, 0.10 mmol) under N2. Benzene-d6 (0.5 mL) was added to the
vial, and the solution was stirred for 3 h, after which time the solution was
transferred to a NMR tube. The yield of the diboration product was obtained
(13) (a) Lesley, G.; Nguyen, P.; Taylor, N. J.; Marder, T. B.; Scott, A.
J.; Clegg, W.; Norman, N. C. Organometallics 1996, 15, 5137-5154. (b)
Anderson, K. M.; Lesley, M. J. G.; Norman, N. C.; Orpen, A. G.; Starbuck,
J. New J. Chem. 1999, 23, 1053-1055.
(14) (a) B2cat2 and B2pin2 are commercially available, and a variety of
diboron reagents may be easily prepared from diols or amino alcohols and
commercially available B2(NMe2)4. (b) Ishiyama, T.; Matsuda, N.; Murata,
M.; Ozawa, F.; Suzuki, A.; Miyaura, N. Organometallics 1996, 15, 713-
720.
(15) Baker, R. T.; Nguyen, P.; Marder, T. B.; Westcott, S. A. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1336.
(16) (a) Ishiyama, T.; Yamamoto, M.; Miyaura, N. Chem. Comm. 1997,
689-690. (b) Iverson, C. N.; Smith, M. R., III. Organometallics 1997, 16,
2757.
1
with respect to trimethoxybenzene by H NMR spectroscopy.
(21) Like other reported Pt catalysts, complex 1 does not mediate the
diboration of acyclic internal alkenes. The only reported diboration of
internal alkenes uses a Rh catalyst. See: ref 17.
(22) Typical procedure, isolated yield (Table 2, entry 1): a 20 mL
screw-capped vial equipped with a stir bar was charged with 1 (14.4 mg,
0.038 mmol, 3 mol %), B2cat2 (125.3 mg, 0.53 mmol), N-benzylidene-2,6-
dimethylaniline (101.5 mg, 0.49 mmol), and 2.0 mL of benzene under N2.
The reaction was stirred for 3 h, after which time the vial was placed in a
-5 °C freezer. The benzene solvent was removed by sublimation under
vacuum to yield a dark brown powder. The solid was then dissolved in 2.0
mL of ether, and the solution was placed in a -35 °C freezer overnight,
after which time the product precipitated as a white solid.
2106
Org. Lett., Vol. 2, No. 14, 2000

ester, 2, derived from the diboration of N-benzylidene-2,6-
dimethylaniline was isolated by removal of benzene solvent
followed by precipitation from an ether/hexanes solution.
X-ray quality crystals of 2 obtained from toluene/hexanes
solution contained both R- and S-isomers; the molecular
structure of the R-isomer is shown in Figure 1,23 confirming
nitrogen at room temperature for 5 h, a dark brown
homogeneous solution is formed. This solution catalyzes the
diboration of aldimines. A mixture of Pt(cod)Br2 and B2cat2
requires stirring for over 24 h before the solution becomes
homogeneous. This solution also catalyzes the diboration of
aldimines, albeit in a slightly lower yield than 1. Reaction
of Pt(cod)I2 with B2cat2 does not become homogeneous even
upon stirring for over 1 week. Reaction of Pt(dicyclopenta-
diene)Cl2 with B2cat2 immediately forms a brown homoge-
neous solution, but use of this catalyst solution results in
significantly lower yields of diboration product. The effective
alkene diboration catalyst, Pt(dba)2 (dba ) dibenzylidene-
acetone), also mediates the diboration of aldimines, but over
20 mol % is required for complete conversion of the starting
aldimine. No reaction is observed between 1 and B2pin2 by
11B NMR spectroscopy, and their mixtures did not catalyze
diboration reactions.
Donor ligands inhibit the aldimine diboration reaction.
Addition of phosphines such as triphenylphosphine or 1,1′-
bis(diphenylphosphino)ferrocene deactivates the catalyst
toward diboration. These results are similar to the diboration
of alkynes catalyzed by Pt complexes in which the presence
of added phosphines severely decreased catalyst activity.13a
Even coordinating solvents such as THF reduce the catalyst
activity; less than 5% diboration product is observed when
THF is used as a solvent. This is in contrast to the excellent
yields obtained using benzene or methylene chloride. Fur-
thermore, rhodium phosphine complexes are ineffective
catalysts for aldimine diboration. Wilkinson’s catalyst, RhCl-
(PPh3)3, gives significantly more hydroboration25 than dibo-
ration, and cationic rhodium complexes with chelating
bis(phosphine) ligands are inactive.
The first step in the mechanism of platinum-catalyzed
diboration is proposed to be oxidative addition of the boron-
boron bond to a Pt(0) complex.11 The reduction of air- and
water-stable 1 by B2cat2 takes place in situ to form a
catalytically active Pt(0) complex. This is evidenced by a
sharp peak observed at 28 ppm in the 11B NMR spectrum
of the dark brown solution formed by mixing 1 and B2cat2,
indicative of ClBcat formation. Diboration product is ob-
served immediately by 1H NMR spectroscopy when a
catalytic amount of this solution is added to N-benzylidene-
2,6-dimethylaniline and B2cat2. In contrast, an induction
period of ca. 1 h is required before any diboration product
is observed when 1 is used directly.
Figure 1. Molecular structure of (2,6-Me2-Ph)N(Bcat)CHPh(Bcat),
2. Thermal ellipsoids are drawn at 50% probability. Only the
R-isomer is shown, and hydrogen atoms are omitted for clarity.
1
our H, 13C, and 11B NMR spectral assignments. The only
other reported crystal structures of R-aminoboronate esters
are those in which the nitrogen is contained in a pyrrolidine
ring.24
Metal-catalyzed diboration of aldimines to form R-ami-
noboronate esters is selective for diaryl aldimines. Mild
reaction conditions are sufficient for substrates containing
bulky or electron-donating substituents on the aryl group
bound to the nitrogen. Thus far, significant yields of
diboration products have not been observed for simple
aliphatic aldimines. Initial attempts to selectively deborate
the N-B bond of the product (H2O and anhydrous HCl in
ether) resulted in predominant formation of starting material.
The chemical origin of this reactivity is currently being
investigated, and new protocols for deboration are being
explored.
In conclusion, we have developed a general method for
the diboration of terminal alkenes, vinylarenes, alkynes, and
aldimines using a commercially available catalyst precursor.
Furthermore, we have developed a direct route to R-ami-
noboronate esters via Pt-catalyzed diboration of aldimines.
Investigations into the scope and mechanism of metal-
catalyzed diboration of aldimines are currently in progress.
Catalyst effectiveness depends on the Pt-bound halide,
diene, and diboron reagent employed. Upon stirring a
heterogeneous mixture of 1 and B2cat2 in benzene under
(23) Crystal data for 2: M ) 894.17, monoclinic, a ) 8.4702(5) Å, b )
16.3243(11) Å, c ) 32.945(2) Å, â ) 90.4990(10)°, V ) 4555.1(5) Å3, T
) 203(2) K, space group ) P2(1)/c, Z ) 4, Mo KR, λ ) 0.71073 Å, Dc )
1.304 g/cm3, 14042 reflections collected, 6317 unique (R(int) ) 0.0493),
residuals of R1 ) 0.0663 and wR2 ) 0.1241 with I > 2σ(I), 613 variable
parameters used in the refinement, goodness-to-fit on F2 ) 1.038. CCDC
deposition number 144949.
(24) (a) Snow, R. J.; Bachovchin, W. W.; Barton, R. W.; Campbell, S.
J.; Coutts, S. J.; Freeman, D. M.; Gutheil, W. G.; Kelly, T. A.; Kennedy,
C. A.; Krolikowski, D. A.; Leonard, S. F.; Pargellis, C. A.; Tong, L.; Adams,
J. J. Am. Chem. Soc. 1994, 116, 10860-10869. (b) Kelly, T. A.; Fuchs, V.
U.; Perry, C. W.; Snow, R. J. Tetrahedron 1993, 49, 1009-1016.
Acknowledgment. We thank Tom M. Cameron for
preliminary aldimine diboration experiments, Professors
Stephen A. Westcott and Richard D. Broene for useful
(25) Hydroboration products are proposed to arise from “backwards”
insertion of the aldimine into the M-B bond, followed by â-H elimination
of the aldimine C-H. Details will follow in the full paper.
Org. Lett., Vol. 2, No. 14, 2000
2107

discussions, and the Department of Energy’s Laboratory
Directed Research and Development (LDRD) program for
financial support of this work.
data. This material is available free of charge via the Internet
at http://pubs.acs.org.
Supporting Information Available: Detailed experi-
mental procedures and characterization and crystallographic
OL006008V
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Org. Lett., Vol. 2, No. 14, 2000