Transition-metal-free diboration reaction by activation of diboron compounds with simple lewis bases

Article abstract of DOI:10.1002/anie.201101941

Changing behavior: A nucleophilic sp² carbene-type boryl moiety, formed upon interaction of tetraalkoxydiboranes and a Lewis base, can attack non-activated C=C bonds. Computational studies identify the interaction as the overlap between the strongly polarized B-B σ bond (HOMO) and the antibonding πorbital (LUMO) of the C=C bond. Conceptually, the normally electrophilic boron becomes nucleophilic and forces the olefin to act as an electrophile. Copyright

Full text of DOI:10.1002/anie.201101941

Communications
DOI: 10.1002/anie.201101941
Boron Chemistry
Transition-Metal-Free Diboration Reaction by Activation of Diboron
Compounds with Simple Lewis Bases**
Amadeu Bonet, Cristina Pubill-Ulldemolins, Carles Bo,* Henrik Gulyꢀs,* and Elena Fernꢀndez*
One of the most recent advances of organoboron chemistry is
the isolation and synthetic applications of anionic sp2 boron
nucleophiles with sensitive carbene-type structures[1] (I,
Scheme 1). Among other examples, I could be added to
benzaldehyde to afford the corresponding a-borylbenzyl
alcohol. This reactivity suggests a classic nucleophilic addition
mechanism.
Scheme 2. Nucleophilic conjugate addition of an sp2 boron unit to
Scheme 1. Anionic “carbene-type” boron nucleophile I and its addition
to benzaldehyde.
a,b-unsaturated carbonyl compounds.
More recently, Hoveydaꢀs and our research group inde-
pendently recognized that sp2 boron nucleophiles can also be
generated in situ from easily accessible, chemically resistant
diboron reagents and added to a,b-unsaturated carbonyl
compounds[2,3] (Scheme 2). Upon interaction with Lewis
bases, the diboron reagent becomes nucleophilic and is
capable of transferring the “intact” sp2 boryl group to
activated olefins in nucleophilic conjugate additions. Impor-
tantly, in boron conjugate additions the electrophilic counter-
part of the boron nucleophile is a proton, which usually
derives from alcohol additives or aqueous workup.
nucleophilic unsaturated substrates. Most importantly,
although the reaction conditions are very similar to those
we use for conjugate boron additions to activated olefins, the
chemoselectivity is different. Despite the presence of the
protic additive, usually MeOH, the electrophilic counterpart
of the nucleophilic boryl unit also derives from the activated
diboron reagent: the primary reaction is the Lewis base
catalyzed diboration of the substrate (Scheme 3).
Herein we demonstrate for the first time that the
reactivity of the Lewis acid–base adducts II far exceeds that
of common nucleophiles. By investigating the scope of
catalysts, substrates, and reactions for this novel catalytic
system, we discovered that, unlike ordinary nucleophilic
reagents, the in situ formed adducts II attack non-activated,
Scheme 3. Nucleophilic diboration of non-activated olefins with
diboron reagent, meditated by base/MeOH as catalyst.
[*] A. Bonet, C. Pubill-Ulldemolins, Dr. H. Gulyꢀs, Dr. E. Fernꢀndez
Dept. Quꢁmica Fꢁsica i Inorgꢂnica, Universitat Rovira I Virgili
43007 Tarragona (Spain)
The new reaction has several significant aspects. 1) The
product is formed by a reaction between a nucleophilic
substrate and a reagent that also has a pronounced nucleo-
philic character, representing an almost unknown reactivity.
2) Unlike in the case of conjugate additions, both boryl units
of the reagent are introduced to the substrate, resulting in an
atom-economic addition reaction of great practical impor-
tance. 3) Up to date, the only known method to add
tetralkoxydiboron compounds to non-activated alkenes was
the application of transition-metal complexes as catalysts.[4–8]
Since organoboranes are very important in organic synthesis
and biomedicine,[9–14] the transition-metal-free approach de-
scribed herein might be a very appealing alternative.
Fax: (+34)977-559-563
E-mail: henrik.gulyas@urv.cat
mariaelena.fernandez@urv.cat
Homepage: http://www.quimica.urv.net/tecat/catalytic_organo-
borane_chemistry.php
C. Pubill-Ulldemolins, Dr. C. Bo
Institute of Chemical Research of Catalonia, ICIQ (Spain)
E-mail: cbo@iciq.es
[**] We thank the Ministerio Ciencia e Innovaciꢃn for funding
(CTQ2010-16226, CTQ2008-06549-CO2-02/BQU and Consolider-
Ingenio 2010 CSD2006-0003).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201101941.
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Angew. Chem. Int. Ed. 2011, 50, 7158 –7161

The catalytic system for the nucleophilic diboration of
non-activated olefins is a combination of base and alcohol.
Both additives are crucial to achieve high activity. After the
screening of various bases and alcohols,[15] we have concluded
that, in THF solutions, a combination of Cs2CO3 and MeOH
provides synthetically useful conversions and chemoselectiv-
ities towards the diborated product. It is worth noting that
various other bases, such as methoxides (Li+, Na+, K+), or
NaOtBu give comparable results. Despite the fact that for
optimal activities MeOH is added in excess with respect to the
substrate, the formation of the “hydroborated” by-product
rarely exceeds 5 mol%. This simple catalytic system is
capable of mediating the addition of different diboron
reagents to various non-activated unsaturated substrates.
For example, in THF at 708C, bis(pinacolato)diboron (a)
could be added quantitatively to 1-octene (1) in the presence
of 15 mol% Cs2CO3 and 5 equivalents of MeOH, within 6 h
(Table 1, entry 1). Only traces of the “hydroborated” by-
product could be observed by GC analysis. Changing the n-
hexyl substituent to cyclohexyl (2) did not influence the
vinylcyclohexane was converted with close to complete
chemoselectivity into the desired diborated product
(Table 1, entry 2). Diboron reagents formed from 1,3-diols
and catechol (b, c, d) are less reactive than bis(pinacolato)-
diboron (a; Table 1, entries 2–5). The diboration of styrene
(3) required milder reaction conditions than that of the
aliphatic alkenes to obtain high selectivity (Table 1, entry 6).
The diboration of internal alkenes (4–6) provided crucial
information on the mechanism of the reaction. Unlike many
of the classic electrophilic additions such as halogenation of
alkenes, the nucleophilic diboration of non-activated olefins
always occurs in syn fashion. Thus, diboration of trans-hex-2-
ene (4) gives the diborated product in a 3:97 syn/anti ratio,
while cis-hex-2-ene (5) forms the corresponding diborated
product in 95:5 syn/anti ratio. Similarly, the diboration of
cyclohexene exclusively gives the cis diborated product
(Table 1, entries 7–9). Another interesting finding is that
nucleophilic diboration of allene 7 favors the formation of the
1,2-diborated product (Table 1, entry 10). This selectivity is in
contrast to most transition-metal-catalyzed diborations of
allenes, which usually provide the 2,3-diborated isomers as
primary products.[16–18]
=
reactivity of the C C double bond significantly; 92% of the
To understand the reactivity of
the Lewis acid–base adducts II, one
Table 1: Transition-metal-free diboration reaction of alkenes and allenes.[a]
has to take into account both 1) the
structure of the tetraalkoxydiboron
compounds and 2) the structural
changes they undergo upon the
interaction with appropriate Lewis
bases. Tetraalkoxydiboron com-
pounds do not have nucleophilic
character, and their electrophilicity,
which originates from the presence
of the virtually empty p orbitals of
Entry
Substrate
B2(OR)4
Base
Conv. [%]
Sel. [%][b]
Yield [%][c]
the boron atoms, is also consider-
ably suppressed as a result of elec-
tron donation from the nonbonding
pairs of the oxygen atoms
(Figure 1). Nevertheless, they can
establish Lewis acid–base interac-
tions with C,[2] N,[19–23] and O[24]
(isol. [%])[d]
1
2
a
a
Cs2CO3
Cs2CO3
98
92
99
97
97 (71)
89 (71)
3
4
5
2
2
2
b
c
d
Cs2CO3
Cs2CO3
Cs2CO3
73
99
99
99
72 (59)
60
59 (56)
85[e]
84[e] (82)[f]
nucleophiles.
The
structural
changes generated by such interac-
tions cannot be sufficiently repre-
sented with the classical Lewis for-
mulae.
6[g]
a
a
a
NaOtBu
Cs2CO3
Cs2CO3
82
74
92
99
81 (74)
69 (57)
83 (69)
96
7
[syn/anti 3:97]
95
Considering the Lewis structure
of adducts II, one would expect an
increased negative charge density
on the rehybridized, formally sp3
boron atom. According to our
DFT calculations carried out on
bis(pinacolato)diboron and on its
Lewis acid–base adduct with
CH3Oꢀ anion, the sp3 boron atom
loses negative charge density upon
the charge transfer from the Lewis
base, while the sp2, virtually intact
boron atom unambiguously gains
8
[syn/anti 95:5]
9[h]
a
a
NaOtBu
NaOtBu
84
95
99
83 (65)
76
92
10[i]
[1,2-diboron 87%]
[a] General conditions: substrate (0.5 mmol), diboron reagent (0.55 mmol), base (15 mol%), MeOH
(2.5 mmol), THF (2 mL), T=708C, t=6 h. [b] As well as the “hydroborated” by-product (<5%), in
certain cases traces of vinyl boronic esters (<1%) could be identified by GC-MS analysis. [c] Yield of the
diborated product determined by GC analysis. [d] Yield of isolated diborated product. [e] Based on an
internal standard. [f] Isolated as the corresponding diol. [g] T=458C, t=15 h. [h] T=708C, t=16 h.
[i] T=458C, t=20 h.
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7159

Communications
model substrate propylene and the MeOꢀ!bis(pinacolato)-
diboron adduct using various DFT methods.[26–28]
We identified two transitions states that can explain the
formation of the product and the “hydroborated” by-product.
In TS1 the sp2 boron atom of the activated diboron reagent
1
=
interacts with the unsubstituted carbon atom (C ) of the C C
ꢀ
ꢀ
double bond, while the B B bond weakens, and the negative
Figure 1. Polarization of the B B bond upon formation of the Lewis
acid–base adduct; Dq: difference between the Mulliken charges of the
boron atoms of the adduct (see DFT calculations in the Supporting
Information).[26–28]
charge density on the C2 carbon increases. Importantly, we
found that the interaction leading to TS1 is the overlap
ꢀ
between the strongly polarized B B s bond (HOMO) of the
activated diboron reagent and the antibonding p* orbital
(LUMO) of the olefin. Hence, the reactivity between the
reaction partners is clearly a nucleophilic attack of the
reagent towards the substrate. The increased negative charge
density on C2 in TS1 results in considerable kinetic lability
due to the positive inductive effect of the alkyl substituent.
The negatively charged C2 atom should be prone to attack any
electrophilic site, and the closest one in TS1 is the attacking
electron density with respect to its partial charge in the intact
bis(pinacolato)diboron. The loss of electron density on the sp3
boron atom, despite the direct charge transfer from the Lewis
base, can be rationalized by considering that upon rehybrid-
ization the boron atom loses the p-symmetric electron
donation from the oxygen atoms of the pinacolate moiety.
ꢀ
The net result of these structural changes is that in adducts II
boron atom, which is losing the B B bond as a result of
2
ꢀ
the B B bond becomes considerably polarized, and the sp
nucleophilic attack. The distribution of the negative charge
density among C1, C2, and the boron atom, might explain the
connection between TS1 and the intermediate I1, as well as
the formation of the second transition state structure TS2.
Protonation of the intermediate I1 gives the “hydroborated”
by-product.
boron atom gains a strong nucleophilic character.
We envisioned a mechanism for the organocatalytic
diboration of olefins in which methoxide anion, generated
in situ from MeOH with a catalytic amount of base, activates
the diboron reagent (Scheme 4). A similar adduct formed
from B2pin2 and KOtBu was reported by Marder and co-
workers.[25] To find evidence for the subsequent steps of the
catalytic cycle, we studied the possible interactions between a
Importantly, when electronic effects stabilize TS1
(increase its kinetic stability, and hence its lifetime) the
“hydroboration” side reaction becomes competitive with the
diboration reaction. This is the case when styrene (3) is the
substrate, whereby the phenyl ring can stabilize the increased
negative charge density on the C2 atom. The electronic
stabilizing effect is even more pronounced in the case of a,b-
unsaturated carbonyl compounds as substrates, for which the
“hydroborated” (b-borated) substrate is the only product of
the reaction.
Upon nucleophilic attack, there is overlap between the
ꢀ
ꢀ
strongly polarized B B s orbital and the C C p* orbital, and
ꢀ
the B(pin)(OMe) moiety becomes electrophilic and is
capable of interacting with the negatively charged olefin–
B(pin) fragment. This interaction can be described with the
second transition-state structure TS2, which directly leads to
the methoxide adduct of the diborated main product (I2),
rendering the overall process strongly exothermic (DG =
ꢀ27.2 kcalmolꢀ1). An interesting feature of the mechanism
is that although the nucleophilic boron atom attacks at the C1
atom, in the product it will be bonded to C2. Actually, this sort
of reaction sequence (R-TS1-TS2-I1,I2), which connects two
transition states and two products, resembles what Houk
called a bifurcation.[29]
In summary, we have reported a reaction that represents
very rare reactivity: a reaction between a nucleophilic reagent
and a nucleophilic substrate. The boron nucleophile is
generated from easily accessible, chemically resistant diboron
reagents, which also provide the electrophilic counterpart of
the nucleophilic boron moiety. Precisely this structural
feature, the possibility to subsequently create a nucleophilic
and an electrophilic site on the activated diboron reagent
along the reaction coordinate, makes this unusual reaction
pathway possible. The net result is a new, Lewis base
Scheme 4. Suggested catalytic cycle. Electronic energy (kcalmolꢀ1) and
Gibbs free energy (kcalmolꢀ1; in parentheses) computed at the M06
level relative to B2pin2·MeOꢀ adduct plus propylene. Methyl groups of
B2pin2 are omitted for clarity.
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towards a future industrial organoborane synthesis.
Received: March 18, 2011
Published online: June 17, 2011
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Keywords: boron · density functional calculations · Lewis bases ·
organocatalysis
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