Generation and reactions of an unsubstituted n-heterocyclic carbene boryl anion

Article abstract of DOI:10.1002/anie.201004215

Lying low: A lithiated unsubstituted N-heterocyclic carbene (NHC) boryl anion can be generated by reduction, and trapped by electrophiles (see scheme; dipp=2,6-diisopropylphenyl) to provide new substituted NHC boranes. It is yet another example of a low-v

Full text of DOI:10.1002/anie.201004215

Communications
DOI: 10.1002/anie.201004215
N-Heterocyclic Carbenes
Generation and Reactions of an Unsubstituted N-Heterocyclic
Carbene Boryl Anion**
Julien Monot, Andrey Solovyev, Hꢀlꢁne Bonin-Dubarle, ꢂtienne Derat, Dennis P. Curran,*
Marc Robert, Louis Fensterbank,* Max Malacria,* and Emmanuel Lacꢃte*
In memory of Marc Julia
Complexation of a boron atom by an N-heterocyclic carbene
has been enlisted to make an assortment of unusual low-
valent boron compounds[1] and rare boron-containing reactive
intermediates including boryl radicals[2,3a] and borenium
ions.[3] Such species have interesting fundamental properties
and are potentially useful reagents in organic synthesis,
among other applications.
ization of the unusual N-heterocyclic carbene (NHC) borole
anion B.[7] Theoretical studies suggested that this anion was
stabilized by aromaticity; in other words, it is a boron
analogue of the tetraphenylcyclopentadienyl anion. Both A
and B were generated by reductive metalation.
We became interested in the generation and reactions of
unsubstituted NHC boryl anions in the context of a program
of studying applications of new NHC boranes (NHC–BH2R)
in both small-molecule and polymer synthesis.[8] The usual
synthesis of such complexes by complexation of substituted
boranes with free NHCs[9] is limited because boranes are
reactive towards nucleophiles (whereas NHC boranes are
usually stable) and because certain classes of boranes are not
easily available by hydroboration or other means. Herein we
report that the lithium derivative of the prototypical NHC
boryl anion C can be generated by reductive lithiation, and
trapped by assorted electrophiles to provide new substituted
NHC boranes.
Nucleophilic boron reagents are extremely rare.[4] Recent
reviews list only two characterized boryl anions.[5] The
tricyclohexylphosphine boryl anion A reported by Imamoto
and Hikasaka[6] can be considered an analogue of the
unknown parent dianion (:BH32À). Very recently, Braunsch-
weig and co-workers described the generation and character-
Several attempts to deprotonate 1,3-bis-(2,6-diisopropyl-
phenyl)imidazol-2-ylidene borane (1; see Scheme 1) with
various strong bases did not lead to the desired boryl anion, so
we moved quickly to reductive approaches to anion forma-
tion. However, precedent from Robinson and co-workers was
not necessarily encouraging. They reduced an NHC–BBr3
complex with potassium graphite to produce novel dimers
with boron–boron bonds.[1a] If boryl anions are involved in
this process, then they must have reacted rapidly with the
starting material or other reaction intermediates.
[*] Dr. J. Monot, A. Solovyev, Prof. D. P. Curran
Department of Chemistry, University of Pittsburgh
Pittsburgh, PA 15260 (USA)
Fax: (+1)412-624-9861
E-mail: curran@pitt.edu
Boryl iodide 2 can be made rapidly in essentially
quantitative yield in situ by reaction of 1 (2 equiv) with
iodine (1 equiv) in benzene (Scheme 1). As a prelude to
reductive metalations, we studied electrochemical reduction
Dr. H. Bonin-Dubarle, Dr. ꢀ. Derat, Prof. L. Fensterbank,
Prof. M. Malacria, Dr. E. Lacꢁte
Institut Parisien de Chimie Molꢂculaire (UMR CNRS 7201)
UPMC Univ Paris 06
4 place Jussieu, C. 229, 75005 Paris (France)
Fax: (+33)1-4427-7360
E-mail: louis.fensterbank@upmc.fr
max.malacria@upmc.fr
emmanuel.lacote@upmc.fr
Prof. M. Robert
Laboratoire d’Electrochimie Molꢂculaire (UMR CNRS 7591),
Universitꢂ Paris Diderot, 75013 Paris (France)
[**] We thank UPMC, UP7, CNRS, IUF (M.M., L.F., M.R.), the French
ANR (grant 08-CEXC-011-01), and the US NSF (CHE-0645998) for
financial support. Technical assistance was generously offered by FR
2769 (UPMC). A.S. thanks the University of Pittsburgh for a
Graduate Excellence Fellowship. Dr. Damodaran Krishnan (Pitt.),
Dr. Steven J. Geib (Pitt.) and Ms. Sage Bowser (Pitt.) are gratefully
acknowledged for NMR and X-ray diffraction assistance.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201004215.
Scheme 1. Reductive metalation and quenching with diethyl carbonate.
TMEDA=N,N,N’,N’-tetramethylethylenediamine.
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Chemie
of 2. Initial voltammetric measurements were obtained at a
millimetric glassy carbon electrode. A single reduction wave
was observed at À2.51 V versus a saturated calomel electrode
(SCE). The wave current of 2 was comparable to that of
oxidation of ferrocene (see the Supporting Information). This
suggests that, like ferrocene, complex 2 accepts only one
electron to give the corresponding boryl radical NHC–BH2C
(D, see Figure 1), which is not reduced under the electro-
chemical conditions. Again, this precedent is not especially
encouraging.
successful electrophilic trapping experiments are collected in
Table 1. Ethyl acetate provided the acetyl borane complex 3b
resulting from an addition/elimination reaction of the anion 4
(entry 2), whereas 1,2-adducts were isolated from either
aromatic (entry 3) or aliphatic aldehydes (entry 4). Crystals
were grown from the acyl borane complex 3b and X-ray
analysis confirmed the proposed structure for 3b (see the
Supporting Information). Quenching with an oxirane pro-
Table 1: Formation of functional NHC boranes by reaction of an NHC
boryl anion with electrophiles.[a]
Entry Electrophile
Product
3
Yield [%][b]
68[c]
=
1
2
(EtO)2C O
3a
EtOAc
3b
3c
3d
39
44
45
3
4
Figure 1. Structures calculated at the B3LYP/SVP level for the species
given in the reaction equation. a) HOMO of iodide 2, b) radical D
(spin density), c) HOMO of anion C, d) the electrostatic potential
mapped onto electronic density for anion C.
5
6
3e
3 f
34[d]
The large negative electrochemical potential of iodide 2
(and presumably the resulting radical) suggested that a very
powerful chemical reductant would be needed. Electrochem-
ical measurements with di-tert-butylbiphenyl (DBB) indi-
cated that lithium di-tert-butylbiphenylide (LDBB) might be
suitable since the wave for DBB reduction was less than
À2.9 V (see the Supporting Information).[10] Indeed, of the
several reductants screened LDBB was the only one to
produce significant concentrations of anion as measured by
the yields of products isolated by trapping with diethyl
carbonate.
PhCN
51
7
CH2CHCH2Br
3g
3h
3i
36[e]
22
8
9
nBuI
35
10
nBuCl
3i
46
11
12
3j
54[e]
3k
57
In
a typical small scale experiment (Scheme 1), 2
(0.075 mmol) was added to excess LDBB (0.17m THF
solution, 4 equiv) in the presence of TMEDA. After
5 minutes at À788C, excess diethyl carbonate (12 equiv) was
added. Direct flash chromatography on silica gel of the crude
reaction mixture provided the stable NHC ethoxycarbonyl-
borane complex 3a in 61% yield. In a larger scale experiment,
0.6 mmol of 2 was reacted with a smaller excess of the LDBB
(2.5 equiv) and diethyl carbonate (1.5 equiv). This provided
3a in comparable yield (67%) after purification. These results
suggest the intermediacy of the lithiated boryl anion 4.[11]
This reductive metalation procedure proved to be surpris-
ingly versatile and the putative boryl anion C reacted with a
range of electrophiles to provide new diversely substituted
borane complexes (NHC–BH2E). The results of the most
13
14
3l
50
CH2Cl2
C6F6
3m 38[f]
15
3n
27
[a] Reaction conditions: 2 (0.075 mmol) was added to excess LDBB
(0.17m THF solution, 4 equiv) in the presence of TMEDA. After
5 minutes at À788C, excess electrophile (12 equiv) was added. Where
needed, protic quenching by methanol was carried out before workup.
The main by-product of most experiments was NHC borane 1. [b] Yield of
isolated product. [c] Used 4 equiv of electrophile. [d] 5 was also isolated
(30%). [e] The reaction was conducted on 0.6 mmol of 2. [f] Used
2 equiv of electrophile.
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Communications
vided the expected ring-opened product 3e (entry 5) along
The HOMO of free anion C shows high electron density
on the boron atom delocalized into the NHC ring
(Figure 1c,d). Just as the radical D is loosely analogous to a
benzyl radical, the anion C is loosely analogous to a benzyl
anion. As such, the anion C is structurally different from both
the phosphine boryl anion A[16] and NHC boryl anion B.
In summary, we have generated an unsubstituted NHC
boryl anion in situ by reduction of a readily available boryl
iodide with LDBB. The anion can be trapped with a diverse
range of electrophiles to give an assortment of new types of
NHC boranes that would be difficult or impossible to access
with existing methods. These compounds form a very small
family of tricoordinate boryl anions. Its unusual features in
reactions with electrophiles (for example, para addition to
benzonitrile and substitution of adamantyl iodide) warrant
additional mechanistic study, as radical mechanisms might be
possible. The availability of the new classes of NHC borane
products (acyl boranes, a-boryl alcohols, etc.) opens the door
to the study of their properties and chemistry.
with the double adduct 5 (30%). Compound 5 presumably
arises from deprotonation of 3e on the imidazolyl ring.[12]
Accordingly, the imidazolylidene protons on NHC borane
complexes must be weakly acidic; a property that merits
additional study.
Interestingly, benzonitrile did not give the standard
1,2-addition product expected from highly reactive anions.
The para-substituted product 3 f (entry 6) was isolated
instead. This product resembles those observed by Imamoto
in reactions of anion A.[6]
Alkyl halides delivered the corresponding B-alkyl deriv-
atives 3g–l (entries 7–13) in useful yields whereas hexafluoro-
benzene provided the addition/elimination product 3n
(entry 15). Again, the observations were unusual, with less
reactive halides like butyl chloride, isopropyl iodide, and
adamantyl iodide (entries 10, 12–13) generally providing
better yields than more reactive ones like butyl iodide and
crotyl chloride (entries 8–9). Interestingly, the reaction with
dichloromethane produced the methylated product 3m, not
the chloromethylated product (entry 14).
Received: July 9, 2010
Published online: September 17, 2010
Most of the products in Table 1 are members of new
classes of substituted NHC boranes that would be difficult to
make by the current method of hydroboration and subse-
quent complexation. The free acyl boranes needed to make
3a and 3b, for example, are rare and reactive types of
molecules.[13] The unsaturated boranes needed to make 3g,
3h, and 3j would doubtless hydroborate themselves. The a-
boryl alcohols 3c and 3d and the isopropyl borane 3k are all
formally products of hydroboration with regioselectivity
opposite to a classical hydroboration reaction. And products
3e and 3 f are formally analogous to hydroboration products
of an enol and a benzyne, respectively.
To complement the experiments, we conducted DFT
calculations on the starting iodide 2 and the intermediate
radical D and free anion C.[14] Figure 1 shows diagrams of the
lowest unoccupied molecular orbital (LUMO) of iodide 2
(Figure 1a), the spin density radical on D (Figure 1b), the
highest occupied molecular orbital (HOMO) of anion C
(Figure 1c), and the electrostatic potential mapped onto the
electronic density on C (Figure 1d).
Keywords: anions · boron · carbenes · nucleophilic addition ·
nucleophilic substitution
.
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À
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À
stable radical anion. Instead, B I bond cleavage occurs
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of D is similar to that of other NHC boryl radicals
(Figure 1b),[2,8d] with a spin density partially on the boron
atom and partially delocalized throughout the NHC ring. The
radical D resists electrochemical reduction but is chemically
reduced by LDBB to C. The calculated electron affinity for
this reduction to the boryl anion is + 42.1 kcalmolÀ1. This may
explain why one needs a powerful reducing agent to generate
4.
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[11] 11B NMR studies showed the formation of a triplet at d =
À18.1 ppm (at À708C) at the expense of the starting material
under the reaction conditions. The triplet disappeared upon
warming to RT (see the Supporting Information). We attribute
these signals to the intermediate lithiated boryl anion 4 (C is the
cation-free anion).
[16] Imamoto also suggested delocalization of boryl anion to d-
orbitals of phosphorus and some double bond character in [(c-
=
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