Catalytic β-boration/oxidation of 1-azadienes

Article abstract of DOI:10.1002/asia.200900311

A highly efficient Cu-catalyzed C-B bond formation has been developed to transform 1-azadienes into β-imino boronate esters when reacted with bis(pinacolato)diboron and a base. A series of functionalized imines and oximes were found to react under very mi

Full text of DOI:10.1002/asia.200900311

COMMUNICATION
DOI: 10.1002/asia.200900311
Catalytic b-Boration/Oxidation of 1-Azadienes
Cristina Sole and Elena Fernꢀndez*[a]
Dedicated to Dr. J. M. Brown on his 35 years at Oxford University
Metal-mediated B addition to the Cb atom of a,b-unsatu-
rated carbonyl compounds, which is traditionally called the
b-boration reaction, has been developed as an attractive
route for the synthesis of valuable functionalized products,[1]
and it is even available in a convenient asymmetric ver-
sion.[2] The great stability of the anionic carbonyl moiety
guarantees the success of the catalytic Michael addition re-
action with MeOH as the electrophilic reagent (Scheme 1).
We anticipated that the analogous b-boration/oxidation of
a,b-unsaturated imines would provide an alternative synthe-
sis of b-boryl imino derivatives as interesting intermediates
toward b-aminoalcohols.
Scheme 2. Catalytic diboration of imines.
and it was particularly interesting that catecholborane
(HBcat) reacted initially at the more reactive imine func-
tionality to give unsaturated borylamines[4] (Scheme 3).
However, to the best of our knowledge, no previous studies
have been made about the catalytic B addition on electron-
deficient olefins with a conjugated imine functional group.
Scheme 1. Catalytic b-boration of a,b-unsaturated carbonyl compounds.
Scheme 3. Catalytic hydroboration of allylimine.
The catalytic B addition to imines and allylimines has
been successfully carried out through metal-catalyzed dibo-
ration and hydroboration, respectively. Therefore bis(cathe-
colato)diboron (B2cat2) was efficiently added to aldimines in
We were interested in determining how the electronic
nature of the imino group could stabilize the anionic inter-
mediates in the ionic borylation process. We therefore fo-
cused on preparing a series of a,b-unsaturated imines and
oximes with different electronic and steric properties. To
this end, the related ketones reacted with substituted amines
and hydroxylamine in the presence of montmorillonite K-10
(MK10)[5] (Scheme 4). The condensation of these reactants
with MK10 is comparable to the use of molecular sieves in
terms of catalytic and dehydrating properties.[6] Yields of
pure isolated a,b-unsaturated imines were high and compa-
rable to other synthetic methods described in the litera-
ture.[7,8]
the presence of [PtACHTUNGTRENNUNG(cod)Cl2], providing the first direct route
to a-aminoboronate esters[3] (Scheme 2). Alternatively, rho-
dium complexes mediated the hydroboration of allylimines
[a] C. Sole, Dr. E. Fernꢀndez
Dept. Quꢁmica Fꢁsica i Inorgꢂnica
C/Marcel.lꢁ Domingo s/n, 43005 Tarragona (Spain)
Fax : (+34)977559563
E-mail: mariaelena.fernandez@urv.cat
The uncatalyzed addition of one equivalent of bis(pinaco-
lato)diboron (B2pin2) or bis(cetecholato)diboron (B2cat2) to
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.200900311.
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the quantitative transformation into the desired product
(Table 1, entry 3). Alternative bases such as NaOAc,
NaOMe, and NaOH were also highly efficient at promoting
total conversion (Table 1, entries 4–6).
The base has a perceptible beneficial influence on the re-
action outcome. It probably acts on the ClÀ displacement
from the catalyst precursor and favors the transmetalation
step between the Cu-OR catalytic species and the diboron
reagent.[10] Recently we have demonstrated that
(NHC)CuOMe (NHC=N-heterocyclic carbene ligands) can
promote the b-boration of crotonaldehyde even in the ab-
sence of the base.[11] Shibasaki et al.[7a] also attributed
LiOiPr the role of an effective generator of active nucleo-
phile allylcopper from CuF/phosphine and allylboronate. In
this context, we have postulated a reaction mechanism
based on a catalytic cycle in which the base favors the cleav-
age of the diboron reagent to promote the formation of the
boryl copper intermediate. The formation of the metallo-en-
amine intermediate might be slower than the related anionic
carbonyl moiety from the ketone. However, the fact that
MeOH does not seem to be necessary to accelerate the re-
action might indicate that the reactivity of the metallo-en-
amine towards the electrophile is quicker, as was expected
(Scheme 5).
Scheme 4. Synthesis of a,b-unsaturated imines and oximes (% yields of
isolated product and syn/anti ratio).
the imine (E)-1-phenyl-N-(4-phenylbutan-2-ylidene)methan-
amine (1) did not lead to any borylated product at room
temperature. Therefore, the catalytic version was suggested
instead. Since the use of inexpensive metals for the catalytic
b-boration of a,b-unsaturated carbonyl compounds is con-
sidered to be the main goal of this reaction,[1g] we selected
catalytic systems based on CuI salts modified with phosphine
ligands. In early reports by Miyaura et al.,[1a,b] copper effi-
ciently promoted the selective b-boron addition from dibor-
on to a,b-unsaturated ketones, esters, and nitriles, and trans-
metalation from diboron to CuI salts was the key step in the
À
mechanistic cycle, favoring the formation of B Cu species.
When imine 1 and B2pin2 reacted in the presence of 3 mol%
of CuCl, no b-borated product was observed. B2cat2 was not
so reactive in this reaction, despite previous related studies
on Cu-catalyzed alkene diboration reaction.[9] However,
when PCy3 was added as the modifying ligand, conversions
into the b-boryl imino derivative of about 32% were ob-
served (Table 1, entry 1). Results were similar when MeOH
was added as an additive, despite the enhanced reaction out-
come observed by Yun et al.[2a] (Table 1, entry 2). However,
the addition of one equivalent of NaOtBu as base favored
Table 1. Cu-mediated catalytic b-boration of a,b-unsaturated imines with
B2pin2.[a]
Scheme 5. Plausible mechanism for b-boration of a,b-unsaturated imines
with B2pin2.
Entry Imine Catalytic system Additive Base
Conv. [%][b]
1
2
3
4
5
6
7
8
1
1
1
1
1
1
2
3
4
1
1
CuCl/PCy3
CuCl/PCy3
CuCl/PCy3
CuCl/PCy3
CuCl/PCy3
CuCl/PCy3
CuCl/PCy3
CuCl/PCy3
CuCl/PCy3
CuCl/PPh3
CuCl/josiphos
–
–
–
32
29
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
NaOtBu 99
In order to gain further insight into the accelerated metal-
lo-enamine pathway with the electrophile, a competitive re-
action experiment was carried out in which a,b-unsaturated
imine and ketone reacted with B2pin2 under the same reac-
tion conditions but in the absence of MeOH. As Figure 1
shows, while imine 1 is consistently transformed into the b-
borated product, the related ketone stays almost unreacted.
Under optimized reaction conditions, imines 2 and 3 were
also conveniently b-borated (Table 1, entries 7 and 8). The
electronic and steric nature of R in the imino group does
NaOAc
NaOMe
NaOH
NaOtBu 99
NaOtBu 99
NaOtBu 34
NaOtBu 99
NaOtBu 99
99
99
99
9
10
11
[a]Standard
conditions:
substrate/Cu=1:0.03.
B2pin2 =1.1 equiv,
NaOtBu=9 mol%, MeOH=20 mL Solvent: THF (2.5 mL). T=258C, t=
6 h. [b] Determined by H NMR spectroscopy.
1
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C. Sole and E. Fernꢀndez
COMMUNICATION
work will be devoted to the “in situ” reduction of the C=N
bond but also to the asymmetric version of the reaction.
Experimental Section
General methodology for the synthesis of the imines and oxime: To a so-
lution of the corresponding amine or hydroxylamine (5 mmol) in CHCl2
(25 mL) was added the ketone (5 mmol) and montmorillonite K10 (1 g).
The resulting solution was stirred for 16 h at room temperature, and then
filtered through celite. Neat a,b-unsaturated imine or oxime was ob-
tained after distillation.
Typical catalytic b-boration of a,b-unsaturated imines and oxime: Bis(ca-
techolato)diboron (1.1 equiv) was added to a solution of the catalyst
(2 mol%) and base (3 mol%) in tetrahydrofuran (2 mL) under nitrogen.
The solution was stirred for 5 min and the substrate (0.05 mmol) was
then added with 2 mL of MeOH. The mixture was stirred for 6 h at room
Figure 1. Competitive b-boration of imine (E)-1-phenyl-N-(4-phenylbu-
tan-2-ylidene)methanamine (~) and trans-4-phenyl-3-buten-2-one (&)
with B2pin2.
1
temperature. The products obtained were analyzed by H NMR spectros-
copy to determine the degree of conversion and the nature of the reac-
tion products. Products were purified by flash column. (E)-N-(4-phenyl-
4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-ylidene)butan-1-
amine: 1H NMR (400 MHz, CDCl3): d=7.71–7.19 (m, 5H), 3.54 (t, J=
8 Hz, 2H), 3.03 (dd, J=20, 8 Hz, 1H), 2.81 (dd, J=20, 8 Hz, 1H), 2.65
(m, 1H), 2.18 (s, 3H), 1.43 (m, 2H), 1.24 (m, 14H), 0.88 ppm (t, J=8 Hz,
3H); 13C NMR (CDCl3, 100.6 MHz): d=160.99, 134.62, 129.00, 128.35,
127.07, 87.76, 61.72, 52.15, 32.70, 29.73, 27.79, 21.21, 13.98 ppm; 11B NMR
(CDCl3, 128.3 MHz): d=21.72 ppm. (E)-N-(4-phenyl-4-(4,4,5,5-tetra-
not seem to influence the B addition reaction. However,
when the oxime 4 was b-borated, only 34% of the substrate
was transformed under mild reaction conditions (Table 1,
entry 9). Higher reaction temperatures did not allow the re-
action to go to completion. Alternative ligands were used
with identical success, in the presence of NaOtBu as base,
À
but no asymmetry was induced in the new C B bond even
methyl-1,3,2-dioxaborolan-2-yl)butan-2-ylidene)aniline:
1H NMR
though chiral ligands were used (Table 1, entries 10 and 11).
To the best of our knowledge, b-imino boronate esters
have only been previously prepared by Whiting et al.,[12]
through an elegant condensation of b-keto boronate esters
and primary amines, in the presence of molecular sieves.
The corresponding b-keto boronate compound was prepared
by alkylation of an enolate with an a-haloboronate ester[13]
and alternatively via the hydrogenolysis of the oxime ether
derivative.[11] Our methodology allows the synthesis of b-
imino boronate esters even with substituents at the b-posi-
tion of the C=N bond.
(400 MHz, CDCl3): d=7.46–7.19 (m, 10H), 3.09 (m, 1H), 2.91 (m, 1H),
2.64 (m, 1H), 2.19 (s, 3H), 1.32 ppm (m, 12H); 13C NMR (CDCl3,
100.6 MHz): d=169.99, 148.93, 145.35, 132.77, 132.42, 131.39, 131.08,
130.11, 129.46, 87.27, 52.63, 29.53, 25.62, 19.67 ppm; 11B NMR (CDCl3,
128.3 MHz): d=21.38 ppm. (E)-1-phenyl-N-(4-phenyl-4-(4,4,5,5-tetra-
methyl-1,3,2-dioxaborolan-2-yl)butan-2-ylidene)methanamine: 1H NMR
(400 MHz, CDCl3): d=7.35–7.07 (m, 10H), 4.80 (dd, J=12 Hz, 1H), 4.65
(dd, J=12 Hz, 1H), 3.03 (dt, J=20, 8 Hz, 1H), 2.77 (dd, J=20, 8 Hz,
1H), 2.25 (m, 1H), 2.10 (s, 3H), 1.19 ppm (m, 12H); 13C NMR (CDCl3,
100.6 MHz): d=167.90, 139.54, 136.63, 136.24, 132.94, 128.37, 126.65,
126.34, 125.7, 88.16, 51.19, 36.72, 29.40, 22.17, 13.25 ppm; 11B NMR
(CDCl3, 128.3 MHz): d=21.18 ppm.
The oxidation protocol: A solution of sodium perborate (2.5 mmol) in
THF/water (1:1, 4 mL) was added to the reaction mixture of the b-bora-
tion before product purification. The mixture was stirred vigorously for
4 h. After this time, it was quenched with a saturated solution of NaCl
and then extracted into AcOEt (3ꢄ20 mL). The organic phase was dried
over MgSO4, followed by evaporation under reduced pressure to remove
the solvent. The b-iminoalcohols were purified by flash chromatography
with hexane/ethyl acetate (5:1) as an eluent. (E)-3-(benzylimino)-1-phe-
nylbutan-1-ol: 1H NMR (CDCl3, 300 MHz): d=7.80–7.20 (m, 10H), 5.11
(dd, J=20, 12, MHz, 1H), 4.77 (s, 2H), 2.87–2.79 (m, 2H), 2.13 ppm (s,
3H); 13C NMR (CDCl3, 67.5 MHz): d=162.97, 136.14, 132.76, 128.20,
127.05, 69.74, 55.13, 51.27, 18.9 ppm. (E)-3-(butylimino)-1-phenylbutan-1-
ol: 1H NMR (300 MHz, CDCl3): d=7.74–7.25 (m, 5H), 5.03 (dd, J=20,
12.3 Hz, 1H), 3.56 (t, J=20, 6.8 Hz, 2H), 2.88–2.72 (m, 2H), 2.13 (s 3H),
1.65–1.59 (m, 2H), 1.38–1.31 (m, 2H), 1.07 ppm (t, J=7.6 Hz, 3H);
13C NMR (CDCl3, 67.5 MHz): d=162.69, 128.72, 128.59, 128.32, 127.68,
69.82, 51.98, 34.66, 30.79, 24,84, 18.94, 13.82 ppm. (E)-1-phenyl-3-(phenyl-
imino)butan-1-ol: 1H NMR (CDCl3, 300 MHz): d=7.80–7.20 (m, 10H),
5.11 (dd, J=17.6, 11 Hz 1H), 2.87–2.79 (m, 2H), 2.13 ppm (s, 3H);
13C NMR (CDCl3, 67.5 MHz): d=169.71, 129.12, 128.54, 127.32, 127.68,
126.239, 125.614, 69.82, 51.98, 19.54 ppm.
Eventually, the b-imino boronate intermediates were effi-
ciently oxidized into their b-iminoalcohols in the presence
of NaBO3 as oxidizing reagent (Scheme 6). Remarkably, this
Scheme 6. Oxidation of b-imino boronate esters.
was the first time that these products had been prepared, al-
though the b-oxime boronate ester failed to be oxidized
under these reaction conditions.
We can conclude at this point that b-iminoalcohols can be
easily prepared in high yields through a copper-mediated b-
boration/oxidation reaction in the presence of a diboron re-
Acknowledgements
À
agent. A base seems to be beneficial for quantitative C B
bond formation in the intermediate compounds. Further
This work was supported by CTQ2007-60442/BQU and Consolider In-
genio2010 CSD-0003.
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Chem. Asian J. 2009, 4, 1790 – 1793

Catalytic b-Boration/Oxidation of 1-Azadienes
nez-Alcaraz, R. Perez-Ossorio, J. Chem. Soc. Perkin Trans. 1 1989,
751; d) K. Abdur-Rashid, A. J. Lough, R. H. Morris, Organometal-
lics 2001, 20, 1047; e) M. J. Ackland, T. N. Danks, M. E. Howells, J.
Chem. Soc. Perkin Trans. 1 1998, 813; f) Ch.-H. Cheng, J. Chin.
Chem. Soc. 1988, 35, 261; g) W. T. Brady, C. H. Shieh, J. Org. Chem.
1983, 48, 2499; h) K. Parthasarathy, M. Jeganmohan, Ch.-H. Cheng,
Org. Lett. 2008, 10, 325; i) A. M. Chibiryaev, N. D. Kimpre, A. V.
Tkachev, Tetrahedron Lett. 2000, 41, 8011.
Keywords: boration
b-iminoalcohols
·
copper
·
imines
·
oximes
·
[1] a) K. Takahashi, T. Isiyama, N. Miyaura, Chem. Lett. 2000, 982;
b) K. Takahashi, T. Isiyama, N. Miyaura, J. Organomet. Chem. 2001,
625, 47; c) H. Ito, H. Yamanaka, J. Tateiwa, A. Hosomi, Tetrahedron
Lett. 2000, 41, 682; d) Y. G. Lawson, M. J. G. Lesley, T. B. Marder,
N. C. Norman, C. R. Rice, Chem. Commun. 1997, 2051; e) T. B.
Marder, Organomet. Chem. 2008, 34, 46; f) L. Dang, Z. Lin, T. B.
Marder, Organometallics 2008, 27, 4443; g) V. Lillo, A. Bonet, E.
Fernandez, Dalton Trans. 2009, 2889.
[2] a) S. Mun, J.-E. Lee, J. Yun, Org. Lett. 2006, 8, 4887; b) J.-E. Lee, J.
Yun, Angew. Chem. 2008, 120, 151; Angew. Chem. Int. Ed. 2008, 47,
145; c) H.-S. Sim, X. Feng, J. Yun, Chem. Eur. J. 2009, 15, 1939;
d) V. Lillo, A. Prieto, A. Bonet, M. M. Dꢁaz Requejo, J. Ramꢁrez,
P. J. Pꢅrez, E. Fernꢀndez, Organometallics 2009, 28, 659; e) W. J.
Fleming, H. Mꢆller-Bunz, V. Lillo, E. Fernꢀndez, P. J. Guiry, Org.
Biomol. Chem. 2009, 7, 2520; f) H. Chea, H.-S. Sim, J. Yun, Adv.
Synth. Catal. 2009, 351, 855.
[3] G. Mann, K. D. John, R. T. Baker, Org. Lett. 2000, 2, 2105.
[4] C. M. Vogels, P. E. OꢇConnor, T. E. Phillips, K. J. Watson, M. P.
Shaver, P. G. Hayes, S. A. Westcott, Can. J. Chem. 2001, 79, 1898.
[5] a) R. Margalef-Catalꢂ, C. Claver, P. Salagre, E. Fernandez, Tetrahe-
dron Lett. 2000, 41, 6583; b) J. Ramꢁrez, E. Fernꢀndez, Tetrahedron
Lett. 2007, 48, 3841.
[6] a) Y. L. Janin, E. Bisagni, Synthesis 1993, 57; b) J. L. Garcꢁa Ruano,
A. Lorente, J. H. Rodriguez, Tetrahedron Lett. 1992, 33, 5637; c) D.
Armesto, A. Ramos, R. Perez-Ossorio, W. M. Horspool, J. Chem.
Soc. Perkin Trans. 1 1986, 91; d) K. Taguchi, F. H. Westheimer, J.
Org. Chem. 1971, 36, 1570.
[8] For related 1-azadienes, see: a) D. A. Colby, R. G. Bergman, J. A.
Ellman, J. Am. Chem. Soc. 2008, 130, 3645; b) F. Basuli, H. Anee-
tha, J. C. Huffman, D. J. Mindiola, J. Am. Chem. Soc. 2005, 127,
17992; c) F. Palacios, J. Vicario, D. Aparicio, J. Org. Chem. 2006, 71,
7690; d) X. Xu, X. Xu, Y. Chen, J. Sun, Organometallics 2008, 27,
758; e) P. Singh, G. Bhargava, M. P. Mahajan, Tetrahedron 2006, 62,
11267.
[9] L. Dang, H. Zhao, Z. Lin, T. B. Marder, Organometallics 2008, 27,
1178.
[10] a) V. V. Grushin, H. Alper, Organometallics 1993, 12, 1890; b) T.
Moriya, N. Miyaura A. Suzuki, Synlett 1994, 149; c) T. Ishiyama, M.
Murata, N. Miyaura, J. Org. Chem. 1995, 60, 7508; d) V. Lillo, E.
Mas-Marzꢀ, A. M. Segarra, J. J. Carbꢈ, C. Bo, E. Peris, E. Fernan-
dez, Chem. Commun. 2007, 380; e) N. Miyaura, T. Ishiyama, H.
Sasaki, M. Ishikawa, M. Satoh, A. Suzuki, J. Am. Chem. Soc. 1989,
111, 314; f) N. Miyaura, K. Yamada, H. Suginome, A. Suzuki, J. Am.
Chem. Soc. 1985, 107, 972; g) C. Kleeberg, L. Dang, Z. Lin, T. B.
Marder, Angew. Chem. 2009, 121, 5454; Angew. Chem. Int. Ed.
2009, 48, 5350; h) N. P. Mankad, D. S. Laitar, J. P. Sadighi, Organo-
metallics 2004, 23, 3369.
[11] A. Bonet, V. Lillo, J. Ramꢁrez, M. M. Dꢁaz-Requejo, E. Fernandez,
Org. Biomol. Chem. 2009, 7, 1533.
[12] R. J. Mears, H. E. Sailes, J. P. Watts, A. Whiting, J. Chem. Soc.
Perkin Trans. 1 2000, 3250.
[7] a) R. Wada, T. Shibuguchi, S. Makino, K. Oisaki, M. Kanai, M. Shi-
basaki, J. Am. Chem. Soc. 2006, 128, 7687; b) C. Palomo, J. M. Aiz-
purua, J. M. Garcia, R. Galarza, M. Legido, R. Urchegui, P. Roman,
A. Luque, J. Server-Carrio, A. Linden, J. Org. Chem. 1997, 62, 2070;
c) D. Armesto, S. Esteban, W. M. Horspool, J. A. F. Martin, P. Marti-
[13] a) A. Whiting, Tetrahedron Lett. 1991, 32, 1503; b) R. J. Mears, A.
Whiting, Tetrahedron 1993, 49, 177.
Received: July 24, 2009
Published online: October 15, 2009
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