The selective catalytic formation of β-boryl aldehydes through a base-free approach

Article abstract of DOI:10.1039/b901767d

(NHC)Cu(i) complexes are key in a new strategy to selectively add a boron unit at the β-position of α,β-unsaturated aldehydes in the absence of a base.

Full text of DOI:10.1039/b901767d

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www.rsc.org/obc | Organic & Biomolecular Chemistry
The selective catalytic formation of b-boryl aldehydes through
a base-free approach†
Amadeu Bonet,a Vanesa Lillo,a Jesu´s Ram´ırez,a M. Mar D´ıaz-Requejob and Elena Ferna´ndez*a
Received 27th January 2009, Accepted 26th February 2009
First published as an Advance Article on the web 11th March 2009
DOI: 10.1039/b901767d
Table 1 (NHC)CuCl- and [(NHC)Cu(NCCH3)]BF4-catalysed b-
(NHC)Cu(I) complexes are key in a new strategy to selec-
tively add a boron unit at the b-position of a,b-unsaturated
aldehydes in the absence of a base.
a
boration of crotonaldehyde with B2pin2
In the catalytic diboration of alkenes,1 the metal-mediated 1,4-
addition of diboron reagents to electron-deficient olefins is
the most convenient approach for preparing b-boryl carbonyl
compounds.2 Of particular interest is the recent work on the
asymmetric version of this reaction.3 Conceptually, only one
boryl unit from the diboron reagent is catalytically added to the
b-position of the substrate, affording the 1,4-hydroborated
Entry
Catalyst
Base
Conv. (%)b
(%)b,c
52
1
2
3
4
5
6
7
8
1
2
3
4
5
6
3
3
3
3
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOMe
NaOAc
—
99
99
99
99
99
99
99
99
99
80
43
60
39
48
39
59
41
33
75
product after
a hydrolytic workup. The range of a,b-
unsaturated carbonyl substrates that undergo 1,4-addition with
bis(pinacolato)diboron (B2pin2) is indeed broad.2,3 It includes
acetylenic esters,4 vinylic esters, vinylic ketones, vinylic nitriles and
vinylic phosphonates, and extends to allylic carbonates.5 However,
the metal-catalysed b-boration of the most challenging a,b-
unsaturated aldehydes has only previously been reported with Rh2d
and Pt2e catalysts because the reaction suffers from a competitive
1,2-diboron addition reaction.6 Taking advantage of the benefits
of copper-mediated B-addition reactions,2a we decided to establish
a general methodology for copper-catalysed b-boration of a,b-
unsaturated aldehydes (Scheme 1). To this end, and because of
their success in the selective diboration of alkenes and alkynes,7
and more recently in the carboxylation of organoboronic esters,8
we have investigated the potential of several complexes containing
the (NHC)Cu core as the catalyst for this reaction.
9
10d
NaOtBu
a Standard conditions: Substrate/Cu complex = 0.5/0.01, 3 mol% base,
1.1 eq. of bis(pinacolato)diborane (B2pin2), 2 eq. MeOH, THF, 25 ◦C, 6 h.
b Determined by 1H NMR. c The 1,2-diborated product was a byproduct.
d Temperature = 90 ◦C.
The catalytic effect of copper modified with NHC ligands on
the b-boration was first established when 2 mol% of complexes 1–6
were used as catalyst precursors to react crotonaldehyde (R = Me)
with B2pin2 in THF. A base and MeOH were added to enhance the
reactivity, in agreement with the optimised protocol suggested by
Yun et al.3 While the crotonaldehyde substrate was quantitatively
consumed in all cases (Table 1, entries 1–6), chemoselectivity on
the expected b-boryl carbonyl compound was only moderate. The
neutral IMesCuCl catalytic system was the most chemoselective
(Table 1, entry 3), within 6 h, at room temperature.
We next explored the role of the base, as it has been postulated
that it acts on the Cl- displacement from the precursor of catalyst
LCuCl and favours the transmetallation step between the Cu
catalytic species and the diboron, in the mechanism proposed
by Yun et al.3 The presence of a base might also stabilise the
fragments from the heterolytic cleavage of B2pin2, as we postulated
in a previous study.9 The nature of the base and even the need for it
were therefore taken into consideration. The b-boration of croton-
aldehyde in the presence of cationic catalyst precursor 3 provided
41%, 59% and 60% of the b-borated product when AcO-, MeO-
and tBuO- were used, respectively (Table 1, entries 3, 7–8). More
remarkably, the b-boration of crotonaldehyde proceeded in the
absence of a base, but the chemoselectivity was lower (Table 1, en-
try9). Onlyaslightincreaseinchemoselectivitywas observedwhen
the reaction temperature was higher (90 ◦C, Table 1, entry 10).
We envisaged the possibility of using (NHC)CuOR¢ as a catalyst
precursor to prevent the activation of the catalyst, and therefore
Scheme 1 Catalytic b-boration of a,b-unsaturated aldehydes.
aUniveridad 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
bUniveridad de Huleva Campus de El Carmen, 21007, Huelva, Spain
† Electronic supplementary information (ESI) available: Synthesis and
characterisation data for products and the general procedures employed
for the catalytic b-boration. See DOI: 10.1039/b901767d
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prevent the use of the base. To this end we prepared, for the first
time, the complex IPrCuOMe from the corresponding chloride, by
reacting with sodium methoxide (Scheme 2). The characterization
of the complex IPrCuOMe comes directly from spectroscopic data.
the reaction was completed within 20 min, and gave excellent yield
and chemoselectivity for the b-organoboronate derivative (Table 2,
entry 7).
Two significant advantages were observed when alkoxy cop-
per(I) complexes were used: higher catalytic activity and higher
chemoselectivity. Both trends can be seen in Fig. 1, which
compares activity and chemoselectivity within 80 minutes of
reaction. A similar acceleration of the hydroboration of viny-
larenes in the presence of AcO- as counterion in the catalyst
[Rh(OAc)(cod)]2/DPPB (1,4-bis(diphenylphosphino)butane) has
recently been reported, providing the most powerful and practical
approach to date.12
1
The H NMR spectrum shows a set of resonances that indicate
the existence of two equivalent aromatic substituents, as well
as two equivalent C–H groups in the imidazolydene ring, in a
similar manner to that previously observed for related complexes
of formulae (NHC)CuCl.10 This equivalence is also observed in
1
the corresponding resonances in the 13C{ H} NMR spectrum.
The most significant resonance is that of the OMe group, which
gives rise to a broad singlet centred at 3.78 ppm in the 1H
NMR spectrum. Heteronuclear experiments have shown that the
resonance of the carbon nucleus appears at 51.3 ppm as a very
broad hump.
Scheme 2 Synthesis of (NHC)CuOMe complex.
When catalyst precursor IPrCuOMe was involved in the b-
boration of crotonaldehyde in the absence of base, the substrate
was completely converted into the corresponding b-boryl aldehyde
(Table 2, entry 1). Significantly, the reaction time decreased from
6 h to 1 h. However, MeOH seems to be necessary under those new
reaction conditions, because the reaction is not completed in its
absence and the chemoselectivity decreases to 63% of the desired
product.
IPrCuOMe was also active in a series of related substrates
(Table 2, entries 2 and 3), although the conversion significantly
diminished in the b-boration of phenylcinnamate and required
longer reaction times for quantitative conversions (Table 2, entry
4). However, the 1,4 B-addition was also predominant in all these
cases. Because of the beneficial effect of the alkoxy moiety on the
copper complex we prepared the analogous IPrCuOtBu complex11
and used it for catalytic purposes. Improved catalytic activity
and chemoselectivity with IPrCuOtBu was observed in the b-
carbon of crotonaldehyde and phenylcinnamate (Table 2, entries
5 and 6). In the presence of a quarter of the catalyst loading,
Fig.
1 Catalytic profiles for b-boration of crotonaldehyde with
IPrCuOtBu (ꢀ), and [IPrCu(NCCH3)]BF4 (ꢀ). (a) % conversion and
(b) % chemoselectivity for 1,4 B-addition.
Our current understanding of this transformation suggests that
in the absence of base, the precursor of catalyst (NHC)CuOR
could react with the bis(pinacolato)diboron to promote a Cu-
boryl intermediate (Scheme 3). Hou et al.8 have recently reported
that IPrCuOtBu transmetallates arylboronic esters to afford the
corresponding arylcopper complex. However, no reaction was
observed between IPrCuCl and the borane unless the base KOtBu
was added to the media. In our study, the alkoxy group seems
to be crucial in favouring the heterolytic cleavage of the diboron,
transmetallating and stabilizing the second boryl unit as ROBpin.
Table 2 IPrCuOR¢-catalysed the base-free b-boration of crotonaldehyde
a
with B2pin2
Entry
R
IPrCuOR¢
Conv. (%)b
(%)b
1
2
3
4
5
6
7c
Me
Et
Pr
Ph
Me
Ph
Me
IPrCuOMe
IPrCuOMe
IPrCuOMe
IPrCuOMe
IPrCuOtBu
IPrCuOtBu
IPrCuOtBu
99
99
99
19
99
43
99
84
86
95
90
90
95
90
Scheme 3 Postulated transmetallation step.
Finally, and under the standard conditions of Table 2, we
studied the b-boration of more hindered a- and b-substituted
a,b-unsaturated aldehydes (Fig. 2). While 3-methylcrotonaldehyde
proceeded in a similar way to crotonaldehyde, the a-substituted
substrates (trans-2-methyl-2-butenal, trans-methyl-2-pentenal) did
not convert even after 16 h of reaction. Only 1-cyclohexene-1-
carboxaldehyde provided a slight conversion with quantitative
a Standard conditions: Substrate/Cu complex = 0.5/0.01, 1.1 eq. of
bis(pinacolato)diborane (B2pin2), 2 eq. MeOH, THF, 90 ◦C, 1 h.
b Determined by 1H NMR. c Catalyst loading 0.5 mol%, 20 minutes.
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Fig. 2 Catalytic b-boration of a- and b-substituted a,b-unsaturated
aldehydes.
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seem to have a considerable influence on the reaction outcome.
In conclusion, we have found a new strategy for the (NHC)Cu-
mediated chemoselective b-boration of a,b-unsaturated aldehy-
des with bis(pinacolato)diboron. In the absence of base, the
(NHC)CuOR catalyst precursors (where OR = OMe, OtBu)
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derivatives. These precursors are very stable synthons for use
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The Royal Society of Chemistry 2009
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