Ni and Pd mediate asymmetric organoboron synthesis with ester functionality at the β-position

Article abstract of DOI:10.1039/b909341a

Catalytic systems based on Ni and Pd complexes modified with chiral P-P ligands can be used in a convenient strategy for enantioselectively adding a boron unit to the β-position of α,β-unsaturated esters.

Full text of DOI:10.1039/b909341a

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Ni and Pd mediate asymmetric organoboron synthesis with ester functionality
at the b-position†
Vanesa Lillo,a Michael J. Geier,b Stephen A. Westcottb and Elena Ferna´ndez*a
Received 11th May 2009, Accepted 27th July 2009
First published as an Advance Article on the web 3rd September 2009
DOI: 10.1039/b909341a
Catalytic systems based on Ni and Pd complexes modified with chiral P-P ligands can be used in a
convenient strategy for enantioselectively adding a boron unit to the b-position of a,b-unsaturated
esters.
Introduction
Results and discussion
The metal-mediated 1,4-addition reaction of diboron reagents
to a,b-unsaturated olefins is a new methodology for preparing
b-boryl carbonyl compounds.1 One boryl unit from the diboron
reagent can be catalytically added by Cu,2 Pt,3 Rh4 and Ni5
catalytic systems to the b-position of the substrate, affording the
1,4-hydroborated product after a hydrolytic workup (Scheme 1a).
Interestingly, the hydroboration of these substrates does not afford
the same product, but the boron enolate instead3a (Scheme 1b).
Advantageously, the b-boration originates a stereogenic center at
the b-carbon, so induction of enantioselectivity can be achieved
with the appropriate chiral catalyst. However, to the best of our
knowledge, the successful enantioselective b-boration/oxidation
of a,b-unsaturated esters and nitriles has been described in the
literature only by Yun and co-workers2d,6a using CuCl and the
phosphines (R)-(S)-Josiphos or (R)-(S)-NMe2-PPh2-Mandyphos
to afford e.e. values up 91%. The same authors have extended this
study to a,b-unsaturated ketones and amides.6b,c
Taking advantage of the benefits that nickel and palladium com-
plexes provide for the cross-coupling reaction with organoboron
compounds,8 we decided to establish a general methodology for
using these metals to catalyse the b-boration of a,b-unsaturated
esters in an attempt to induce asymmetry on the organoboron
product. To this end, we first investigated the potential of Ni(cod)2
modified with chiral bidentate ligands (Fig. 1), in the b-boration
of the model substrate ethyl-trans-crotonate (R1 = Me, R2
=
OEt) with bis(pinacolato)diboron (B2pin2) as the boron source.9
Table 1 shows that when ligand (R)-(S)-Mandyphos, (R)-Ph-
MeOBiphep and (R)-(S)-Josiphos modified the Ni(0) complex, the
enantioselectivity was only moderate in the quantitative formation
of the b-borylated ester (entries 1–3), while in the presence of
the chiral ligand (R)-(R)-Walphos it was low (Table 1, entry 4).
Enantioselectivity was also low with the P,N-ligand (R)-Quinap
despite the successful asymmetric induction in the Rh-catalysed
diboration of alkenes10 (Table 1, entry 5). However, the use of
ligand (R)-(S)-Taniaphos provided very high enantioselection on
the b-borylated ester with values up to 95% e.e., which was an
improvement on those values observed by Yun et al. for the same
substrate with the catalytic system CuCl/(R)-(S)-Josiphos (e.e.
90%).2d,6
Scheme 1
We have also found that complexes containing the (NHC)Cu
core, (NHC = N-heterocyclic carbene ligand), catalysed the
selective b-boration of a,b-unsaturated a-methyl substituted esters
and aldehydes under mild conditions, and the use of chiral NHC
ligands induced a certain degree of enantioselection in the final
products, (i.e. up to 73% for isobutyl angelate).7
aUniversidad Rovira i Virgili, C/Marcel.l´ı Domingo s/n. 43005 Tarragona,
Spain. E-mail: mariaelena.fernandez@urv.cat; Fax: +34 977 559563; Tel:
+34 977 558046.
Fig. 1 P,P-ligands and P,N-ligands used in this work.
bMount Allison University, 63C York Street, Sackville, New Brunswick, E4L
1G8, Canada
The presence of the base seemed to have a crucial influence
on the catalytic activity of the catalyst, because when a lower
amount of Cs2CO3 was used, the activity and enantioselectivity
observed for the Ni(0)/Taniaphos catalytic system diminished
† Electronic supplementary information (ESI) available: Experimen-
tal procedure for the metal-catalyzed asymmetric b-boration of a,b-
unsaturated esters with bis(pinacolato)diboron; characterization data for
compounds. See DOI: 10.1039/b909341a
4674 | Org. Biomol. Chem., 2009, 7, 4674–4676
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Table 1 Ni-catalyzed asymmetric 1,4-addition reaction of (B2pin2)a
Table 2 Pd-catalyzed asymmetric 1,4-addition reaction of (B2pin2)a
Entry
Substrate R2
L
Conversion (%)b
e.e. (%)c
Entry
Substrate R2
L
Conversion (%)b
e.e. (%)c
1
2
3
4
5
6
7
8
9
10
11
12h
13h
14h
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OMe
OiBu
OiBu
OiBu
OEt
OMe
1
2
3
4
5
6
6e
6f
6
6
3
3
3
3
<50
51
63
65
10
12
95
90
85
92g
98
90
96
81
79
1
2
3
4
5
6
7
8
OiBu
OiBu
OiBu
OiBu
OiBu
OiBu
OEt
OMe
OiBu
OEt
1
5
2
4
6
3
3
3
3
3
3
29
41
24
8
98 (83)d
83
93 (86)d
82
56
75
90
86
91
87
13
3
95
99 (79)d
99 (78)d
91
31
60
99 (81)d
99 (79)d
77
87
99 (85)d
99 (81)d
97
9e
10e
11e
99
90
OMe
5
91
a Standard conditions: Substrate/Pd2(dba)3 = 0.5/0.0125, diphosphine
(0.025 mmol), 1.5 eq. Cs2CO3, 1.5 eq. of bis(pinacolato)diborane (B2pin2),
solvent: toluene (5 mL)/MeOH (0.25 mL), T:25 ◦C, 4 h. Conversions
and selectivity values are an average of two reactions. b Determined by
1H NMR. c Determined by G. C. d Isolated yield. e Substrate/Pd(OAc)2 =
0.5/0.025.
99 (80)d
91
a Standard conditions: Substrate/Ni(cod)2 = 0.5/0.025, diphosphine
(0.025 mmol), 1.5 eq. Cs2CO3, 1.5 eq. of bis(pinacolato)diborane (B2pin2),
solvent: toluene (5 mL)/MeOH (0.25 mL), T:25 ◦C, 4 h. Conversions
and selectivity values are an average of two reactions. b Determined by 1H
NMR. c Determined by G. C. on the acylated product. d Isolated yields.
e 1 eq. Cs2CO3. f 0.5 eq. Cs2CO3. g Determined by HPLC on the alcohol
derivative. h NiCl2.
enantioselection was provided by Pd2(dba)3/(R)-(S)-Taniaphos
(entry 5) and Pd2(dba)3/(R)-(S)-Josiphos (entry 6), which afforded
enantioselectivity with values of up to 91% e.e., depending on the
ester moiety of the substrate (Table 2, entries 6–8). Surprisingly,
when Pd(II) was tested as the catalyst precursor in Pd(OAc)2/
(R)-(S)-Josiphos, the conversion was only comparable to that
obtained with Pd(0), while the enanatioselectivity diminished
significantly (Table 2, entries 9–11). This fact could be related
to the plausible partial oxidation of the ligands by Pd(OAc)2.13
From a mechanistic point of view, we can assume that the
catalytic cycle for Pd(0) is similar to that proposed by Oshima
et al.,5 where Ni(0) species react with substrate a,b-unsaturated
esters and amides to generate the h -coordinated complex, fol-
lowed by further reactivity with bis(pinacolato)diboron to favour
the formation of h -coordinated boryl-nickel(II) complexes. An
eventual reductive elimination provides the boryl enolate product,
which is susceptible to protonolysis and affords the b-boryl ester
product.
(Table 1 entries 7–8). The nature of the base is also influential
because when NaOH, NaOAc or NaOtBu was used instead of
Cs2CO3, only a small conversion into the corresponding product
was observed. The effect of the base as an activator of diboron has
also been observed by Oshima et al.11 and our group in the Pd-
and Au-catalysed diboration reaction.12
With the aim of exploring the scope of the Ni(0)/Taniaphos
catalytic system, we carried out a series of experiments with
a range of a,b-unsaturated esters under the optimized reaction
conditions. Changing the ester moiety from OMe to OiBu, we
found that the bulkiest iso-butyl-trans-crotonate ester was the
most effective substrate, as far as the enantioselection induced
by the metal center was concerned, with values up to 98%
e.e. (Table 1, entries 9–10). These results contrast with the
tendency observed by Yun et al.,2d,6 for enantioselectivity to be
independent of the nature of the ester moiety when CuCl/(R)-(S)-
Josiphos was used as the catalytic system. The b-boration of iso-
butyl-trans-crotonate with Ni(0)/(R)-(S)-Josiphos also provides
a significant increase in enantioselectivity with e.e values up to
90% (Table 1, entry 11). Interestingly, when the nickel source of
the catalyst precursor was Ni(II) in NiCl2/(R)-(S)-Josiphos, the
activity and enantioselectivity were slightly better than obtained
using Ni(cod)2/(R)-(S)-Josiphos (Table 1, compare entries 3 and
11 with entries 12–13).
2
3
One of the key steps in this proposal is the transformation of the
2
3
h -coordinated metal complex to the corresponding h -complex
on reaction with B2pin2, (Scheme 2). However, as Kurosawa et al.14
and Morken et al.15 have previously observed, the Lewis acidity
of boron could promote this pathway in palladium and nickel-
mediated reactions, respectively. We are still considering the role
of Ni(II) and Pd(II) complexes as precursors of catalysts in the
We then checked whether Pd(0) modified with the phosphine
ligands could perform the b-boration reaction under identical re-
action conditions to those used for Ni(0). We were very pleased to
observe that catalyst precursor Pd2(dba)3 performed this reaction
and became the first example of palladium-mediated b-boration of
a,b-unsaturated carbonyl compounds. Table 2 shows how the b-
boration of iso-butyl-trans-crotonate with Pd2(dba)3 modified with
(R)-(S)-Mandyphos and (R)-Quinap remained unfinished after
4 h of reaction. Enantioselection was low (Table 2, entries 1–2).
However, when the chiral ligands involved in the modification
of Pd2(dba)3 were (R)-Ph-MeOBiphep and (R)-(R)-Walphos, the
conversion of the reaction was higher and e.e. values rose to 56%
and 75%, respectively (Table 2, entries 3–4). More satisfactory
Scheme 2
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catalytic cycle, as they have proved to be as active and selective as
Ni(0) and Pd(0).
6 (a) J.-E. Lee and J. Yun, Angew. Chem., Int. Ed., 2008, 47, 145; (b) H.-S.
Sim, X. Feng and J. Yun, Chem.–Eur. J., 2009, 15, 1939; (c) H. Chea,
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7 V. Lillo, A. Prieto, A. Bonet, M. M. D´ıaz Requejo, J. Ram´ırez, P. J.
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9 Typical b-boration procedure: The precursor of the catalyst complex
(0.025 mmol of metal) and diphosphine (0.025 mmol) were placed
in a schlenck and dissolved with toluene (3 mL) under nitrogen. The
suspension was stirred for 10 minutes and Cs2CO3 (244 mg, 0.75 mmol)
was added. Afterwards, a solution of alkyl (E)-crotonate, (0.5 mmol of
methyl (E)-crotonate, or ethyl (E) crotonate or i-butyl (E)-crotonate)
and bis(pinacolato)diboron (191 mg, 0.75 mmol) in toluene (2 mL) was
then added. Finally MeOH (0.25 mL) and water (14 mL, 0.75 mmol)
were added, and the mixture was allowed to stir at room temperature
for 4 h. The resulting mixture was poured into water (10 mL) and the
product was extracted with hexane/ethyl acetate (20:1). The combined
organic layer was dried over sodium sulfate, and concentrated in vacuo.
Silica gel column purification (hexane: ethyl acetate = 40:1) gave the
alkyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butanoate in 80%
for methyl derivative, 75% for ethyl derivative and 77% for i-butyl
derivative.
Conclusions
Although nickel-catalysed reactions with diboron reagents are
quite rare,16 we are pleased to have promoted not only the first
Ni-mediated asymmetric boron addition reaction, but also the
first described palladium b-boration of a,b-unsaturated esters,
inducing asymmetry in the presence of chiral ligands. Further
work on the tandem b-boration/cross-coupling reaction with Ni
and Pd complexes is currently underway.
Acknowledgements
We thank MEC for funding (CTQ2007-60442BQU and
Consolider-Ingenio 2010 CSD-0003). V. L. thanks MEC for the
FPI-Grant.
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4676 | Org. Biomol. Chem., 2009, 7, 4674–4676
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