Mixed diboration of alkenes in a metal-free context

Article abstract of DOI:10.1039/c4cc08743g

Experimental and theoretical rationalization on regioselective mixed diboration of alkenes, with the unsymmetrical diboron reagent Bpin-Bdan, providing the protecting Bdan moiety in the internal position.

Full text of DOI:10.1039/c4cc08743g

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Mixed diboration of alkenes in a metal-free
context†
Cite this: Chem. Commun., 2015,
51, 1693
Nuria Miralles, Jessica Cid, Ana B. Cuenca, Jorge J. Carbo* and Elena Fernandez*
´
´
Received 3rd November 2014,
Accepted 8th December 2014
DOI: 10.1039/c4cc08743g
www.rsc.org/chemcomm
Experimental and theoretical rationalization on regioselective mixed despite the fact that several efforts have been devoted to per-
diboration of alkenes, with the unsymmetrical diboron reagent Bpin– form mixed diboration reactions, only Bpin–Bdan (dan = 1,8-
Bdan, providing the protecting Bdan moiety in the internal position.
diaminonaphthalene) has been successfully activated by Ir and
Pt complexes and applied to the diboration of alkynes, giving
Catalytic diboration reactions have been deeply studied from two the 1-alkene 1,2-diboronate derivative as the major regioisomer
standard perspectives: (1) the use of symmetrical diborons such with the protecting Bdan unit at the terminal position.10
as B2pin2 and B2cat2 (pin = pinacolate and cat = catecholate) and Interestingly, organoboranes with C-Bdan moieties are particularly
(2) the need of transition metal complexes to activate the diborons easy to handle since the dan moiety acts as a masking group on B.11
and transfer the two boryl units to unsaturated substrates pro- Alternative unsymmetrical diboron compounds of the type pinB–
moting the 1,2-addition.1–3 Even nanoporous materials have been B[(NR)2C6H4] (R = Me, Bn, SiMe3) have been recently isolated, but
used to strategically activate the symmetrical diboron reagents to their application in catalysis has not yet been developed.12
enhance the chemoselectivity of the reaction, avoiding secondary
reactions involved in boryl addition.4 But two recent stalwart unsymmetrical diborons, such as Bpin–Bdan, with an alkoxide to
linchpins have changed the concept of diboration reactions. generate the corresponding Lewis acid–base adduct and conduct
Combining both challenges, we became interested in activating
First, the diboron reagent can be activated by simple alkoxides,5 an easy mixed diboration reaction, in the absence of metals or
to enhance the nucleophilic character of the trivalent boryl moiety additives. Our goal was challenging, as the control of the diborated
and force the olefin to act as an electrophile (Scheme 1).6 This regioisomer in the organocatalytic approach could be a matter
pull–push effect of diborons7 has gained potential application not of concern. Nevertheless previous studies have shown that the
only in enantioselective and diastereoselective diborations,8 but MeOÀ - Bpin–Bdan adduct is formed preferentially because
also in generating unusual stereoselectivity in the elegant trans the p-donation from the lone pair of nitrogen to the empty
1,2-diboration assisted by a propargylic alcohol unit.9
orbital of boron protects the Bdan moiety from alkoxide
The second interesting input is the use of unsymmetrical attack.13 These conditions allowed the selective delivery of Bdan
diborons to difunctionalise targeted compounds. However, as a nucleophile. In this scenario, our objective in the present
work is to activate the Bpin–Bdan reagent with methoxide and
control the regioselective addition of Bdan and Bpin moieties to
alkenes (Scheme 1).
We first attempted to find the optimal conditions for the
diboration of allylbenzene (1) with Bpin–Bdan. When the reac-
tion was carried out in THF as a solvent, at 70 1C, and 2 eq. of
MeOH/30 mol% of Cs2CO3, (in order to mimic the reaction
conditions used with B2pin2),5 we found that no diborated
product was formed. Introducing MeOH as the solvent seemed
Scheme 1 Mixed organocatalytic diboration of alkenes with the MeOÀ
Bpin–Bdan adduct.
-
to favour the reaction outcome, and moderate conversion from
substrate 1 was achieved (Table 1, entry 1). The 1H NMR spectra
of the crude reaction show two different groups of signals for the
diborated product in a ratio of 4/1. The 1H, NOESY 1D experiment
demonstrated that the major diborated regioisomer contained the
´
´
`
Department Quımica Fısica i Inorganica, University Rovira i Virgili,
´
C/MarcelÁlı Domingo s/n, Tarragona, Spain. E-mail: mariaelena.fernandez@urv.cat,
j.carbo@urv.cat
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4cc08743g Bdan moiety in the internal position. We next performed the
This journal is ©The Royal Society of Chemistry 2015
Chem. Commun., 2015, 51, 1693--1696 | 1693

View Article Online
Communication
ChemComm
Table
1
MeOÀ assisted mixed diboration of terminal alkenes with
Bpin–Bdana
Scheme 2 Reactivity of vinylarenes with the MeOÀ - Bpin–Bdan adduct,
(X = Me, Cl, H).
Cs2CO3 Conv.b
(mol%) (%)
[IY (%)]c a
In the second set of experiments, internal olefins were sub-
jected to the organocatalytic mixed diboration reaction and cis-3-
hexene (7) was moderately converted into the desired product 8,
despite the amount of base used (Table 2, entry 1). The 1,2-addition
of Bpin and Bdan moieties to cyclic olefins took place in a syn
fashion, (Table 1, entries 2–4), and despite the moderate conversion
of the internal olefins to the diborated product, compound 10
could be isolated in up to 42% IY (Table 2, entry 2).
Entry Substrate
1
a/b
30
56
80/20 30
30
50
81
88
97/3 38
94/6 40
2
In order to have more insight into the mechanism of the metal-
free mixed diboration reaction, we conducted DFT calculations14
with the aim to understand the intrinsic control of the regio-
selectivity. Bo and co-workers have computationally characterised
the mechanism of the organocatalytic diboration reaction of non-
activated olefins with the B2pin2 reagent.5 They proposed the
nucleophilic attack of the boron reagent towards the substrate
through an interaction between the strongly polarised B–B s-bond
of the activated diboron reagent and the antibonding p* orbital of
the olefin.5 We used this proposal as a starting point to analyse the
origin of the regioselectivity in diboration. Fig. 1 depicts the energy
profile yielding the pathways of the two possible regioisomers.
Initially, the methoxide ions generated from MeOH in the
presence of the base can form two different Lewis acid–base
3
4
30
30
48
42
92/8 20
88/12 17
5
30
65
92/18 25
30
75
85
11
91/9 70
80/20 62
90/10 —
50
6
30d
a
Reaction conditions: substrate (0.5 mmol), Bpin–Bdan (1.1 eq.),
b
MeOH (2 mL), 70 1C, 12 h. Conversion and regioselectivity calculated
by GC/MS from an average of two essays. Isolated yield of regioisomer
c
a after purification by flash chromatography (see the ESI for details).
d
30 mol% NaOMe.
Table
2
MeOÀ assisted mixed diboration of internal alkenes with
Bpin–Bdana
mixed diboration reaction with vinylcyclohexane and in the
presence of 30 mol% of Cs2CO3; conversion was high (81%) but
even more interestingly, the regioselectivity was almost quantitative
for the diborated product with Bdan in the internal position
(Table 1, entry 2). A similar trend was observed with 50 mol% of
Cs2CO3, with a slight increase in the global conversion (88%).
Subsequently, terminal olefins of variable alkyl chain lengths were
subjected to the same organocatalytic diboration reaction with
Bpin–Bdan, and despite the amount of base used, conversions were
very high and regioselectivity was favoured towards the regioisomer
with the Bdan moiety in the internal position, by an average ratio of
9/1 (Table 1, entries 3–6). Isolated yields of the major regioisomer
were in general low since the mixed diborated product partially
decomposed along the purification procedure (flash chromato-
graphy). However, product 6a could be successfully isolated in up
to 70% IY, (Table 1, entry 6), as we noted that the longer the aliphatic
chain, the higher is the stability of the diborated product. For com-
parison, when NaOMe was used as base (30 mol%), the diboration
of 6 was significantly diminished (Table 1, entry 6).
Cs2CO3 Conv.b
(mol%) (%)
Entry Substrate
Product
[IY (%)]c
30
50
55
62
17
24
1
2
3
50
50
49
67
42
32
4
50
59
21
This new methodology to obtain mixed diborated products
in the absence of transition metal complexes has a substrate
scope limitation, because when vinylarenes were exposed to the
diboration reaction with Bpin–Bdan under the same conditions,
only the hydroborated product with Bdan in the terminal position
was observed at the end of the reaction (Scheme 2).
a
Reaction conditions: substrate (0.5 mmol), Bpin–Bdan (1.1 eq.),
b
MeOH (2 mL), 70 1C, 12 h. Conversion and calculated by GC/MS from
an average of two essays. Isolated yield of regioisomer a after purifica-
tion by flash chromatography (see the ESI for details).
c
1694 | Chem. Commun., 2015, 51, 1693--1696
This journal is ©The Royal Society of Chemistry 2015

View Article Online
ChemComm
Communication
Fig. 1 Calculated energy profile for the organocatalytic diboration of propene with the Bpin–Bdan diboron reagent in the presence of MeOÀ. Solid lines
correspond to the attack of the Bdan moiety and dashed lines correspond to the attack of the Bpin moiety. Electronic energies and Gibbs free energies in
MeOH (in parentheses) in kcal molÀ1
.
adducts with the unsymmetrical Bpin–Bdan: MeOÀ - Bpin– and a methoxide molecule (see Fig. 1). These results are in good
Bdan (Ra) and MeOÀ - Bdan–Bpin (Rb). Recently, we have agreement with experimentally observed quantitative selectivity for
shown that the Bpin moiety is a stronger Lewis acid than Bdan, Bdan addition in the internal position, albeit with non-negligible
and consequently, the former adduct Ra is 7.4 kcal molÀ1 lower formation of the opposite regioisomer. Moreover, they explain
in energy than Rb.13 Here, Gibbs free energies including solvent the observed regioselectivity that is opposite to that found for
effects via a continuum model show the same trends (Fig. 1).14 diboration of alkynes by Ir and Pt complexes.10 In our case, the
The energy barrier for the interconversion between the two adducts alkoxide Lewis base does not only activate the boron–boron
is modest (17.0 and 9.6 kcal molÀ1 for Ra - Rb and Rb - Ra, bond, but also inverts its polarity driving diboron addition to a
respectively), and more importantly, lower than the energy required specific regioisomer.
to transfer the boron moieties to alkenes (see below).
Finally, we performed additional calculations to gain some
Diboration occurs sequentially through two connected tran- insight into the substrate dependence of the reaction outcome:
sition states (TS1 and TS2).5 In TS1, the nucleophilic sp2 boryl diboration vs. hydroboration. The mechanistic proposal by Bo
unit interacts with the terminal carbon of the alkene.15 Then, and co-workers can also explain the hydroboration side reac-
the quaternised boron atom becomes electrophilic and capable tion.5 According to this mechanism, when the system reaches
of interacting with the negatively charged olefin-boryl fragment, transition state TS1, the reaction path bifurcates connecting
as described in TS2. Nucleophilic boryl attack on the terminal with transition state TS2 or with intermediate I1 that yields
carbon to reach TS1 is the most energy demanding step and the hydroboration product via protonation and releases Bpin–OMe
one that determines the regioselectivity. As expected,13 the (see Scheme 3). For styrene, the computed energy of TS1a and
computed energy barrier for the attack of the Bdan group in I1a is lowered substantially compared to propene (Scheme 3).
Ra (+31.9 kcal molÀ1) is higher than that for the Bpin group The phenyl substituent of the alkene stabilizes the negative
in Rb, (+26.5 kcal molÀ1). However, owing to the relatively low charge generated at the internal alkene carbon, as well as the
energy barrier for interconversion of Ra and Rb (see Fig. 1), the negative charge of intermediate I1a. Thus, the formation of
product distribution should be determined by the relative hydroborated products is favoured for vinylarenes, which is in
energy between the transition states of both paths, TS1a and full agreement with the experimental findings.
TS1b. Thus overall, the attack on the alkene through the Bdan
In summary, we have found that mixed diboration reactions
moiety (TS1a) is lower in energy than through Bpin (TS1b) by with the Bpin–Bdan reagent, can be carried out in a metal-free
2 kcal molÀ1. The transition state TS1a is connected with another context, with high control of regioselectivity, locating the Bdan
lower energy-lying transition state, TS2a, in which the Bdan moiety unit in the internal position. Ten new diborated products have
shifts to the internal olefinic carbon and the Bpin(OMe) moiety been isolated, most of them in a pure form but some as a
binds to the terminal carbon leading to the diborated product, Pa, mixture of the two regioisomers. The B nucleophile in the Bdan
This journal is ©The Royal Society of Chemistry 2015
Chem. Commun., 2015, 51, 1693--1696 | 1695

View Article Online
Communication
ChemComm
J. Org. Chem., 2005, 70, 9538; (m) L. T. Kliman, S. N. Mlynarski and
J. P. Morken, J. Am. Chem. Soc., 2009, 131, 13210; (n) J. R. Coombs,
F. Haeffner, L. T. Kliman and J. P. Morken, J. Am. Chem. Soc., 2013,
135, 11222; (o) N. Iwadate and M. Suginome, J. Am. Chem. Soc., 2010,
´
132, 2548; (p) V. Lillo, M. R. Fructos, J. Ramırez, A. A. C. Braga,
´
´
´
F. Maseras, M. M. Dıaz-Requejo, P. J. Perez and E. Fernandez,
Chem. – Eur. J., 2007, 13, 2614–2621; (q) H. Yoshida, S. Kawashima,
Y. Takemoto, K. Okada, J. Ohshita and K. Takaki, Angew. Chem.,
Int. Ed., 2012, 51, 235; (r) C. J. Adams, R. A. Baber, A. S. Batsanov,
G. Bramham, J. P. H. Charmant, M. F. Haddow, J. A. K. Howard,
W. H. Lam, Z. Lin, T. B. Marder, N. C. Norman and A. G. Orpen, Dalton
Trans., 2006, 1370.
Scheme 3 Proposed mechanism for hydroboration of propene and styrene
leading to Bdan transfer. Calculated electronic energies for styrene (and in
´
´
4 (a) J. Ramırez, M. Sanau´ and E. Fernandez, Angew. Chem.,
Int. Ed., 2008, 47, 5194; (b) Q. Chen, J. Zhao, Y. Ishikawa, N. Asao,
Y. Yamamoto and T. Jin, Org. Lett., 2013, 15, 5766.
brackets for propene) in kcal molÀ1
.
´
´
5 A. Bonet, C. Pubill-Ulldemolins, C. Bo, H. Gulyas and E. Fernandez,
Angew. Chem., Int. Ed., 2011, 50, 7158.
moiety is generated from the easily accessible, chemically resistant
diboron reagent Bpin–Bdan and methoxide. The possibility to
subsequently create an electrophilic Bpin unit on the activated
diboron reagent makes the mixed diboration possible. Calcula-
tions on the energy profile for the organocatalytic diboration of
propene with the Bpin–Bdan diboron reagent in the presence of
alkoxide, support the experimental observation and rationalise
the reaction outcome.
´
´
´
6 (a) J. Cid, H. Gulyas, J. J. Carbo and E. Fernandez, Chem. Soc. Rev.,
´
´
2012, 41, 3558; (b) J. Cid, J. J. Carbo and E. Fernandez, Chem. – Eur. J.,
2012, 18, 12794.
7 (a) K. Lee, A. R. Zhugralin and A. H. Hoveyda, J. Am. Chem. Soc.,
2009, 131, 7253; (b) A. Bonet, H. Gulyas and E. Fernandez, Angew.
Chem., Int. Ed., 2010, 49, 5130; (c) C. Pubill-Ulldemolins, A. Bonet,
´
´
´
´
C. Bo, H. Gulyas and E. Fernandez, Chem. – Eur. J., 2012, 18, 1121;
´
´
(d) C. Sole and E. Fernandez, Angew. Chem., Int. Ed., 2013, 52, 11351;
(e) H. Ito, Y. Horita and E. Yamamoto, Chem. Commun., 2012, 48, 8006;
´
( f ) I. Ibrahem, P. Breistein and A. Cordova, Chem. – Eur. J., 2012,
18, 5175; (g) H. Wu, S. Radomkit, J. M. O’Brien and A. H. Hoveyda,
J. Am. Chem. Soc., 2012, 134, 8277; (h) C. Kleeberg, A. G. Crawford,
A. S. Batsanov, P. Hodgkinson, D. C. Apperley, M. S. Cheung, Z. Y. Lin
Notes and references
´
and T. B. Marder, J. Org. Chem., 2012, 77, 785; (i) C. Sole, H. Gulyas and
1 The original Pt mediated diboration of alkynes: T. Ishiyama, N. Matsuda,
N. Miyaura and A. Suzuki, J. Am. Chem. Soc., 1993, 115, 11018; the
original Rh mediated diboration of alkenes: T. R. Baker, P. Nguyen,
T. B. Marder and S. A. Westcott, Angew. Chem., Int. Ed. Engl., 1995,
34, 1336; the original Pt mediated diboration of alkenes: T. Ishiyama,
M. Yamamoto and N. Miyaura, Chem. Commun., 1997, 689.
´
E. Fernandez, Chem. Commun., 2012, 48, 3769.
´
´
8 (a) A. Bonet, C. Sole, H. Gulyas and E. Fernandez, Org. Biomol.
Chem., 2012, 10, 9677; (b) Th. P. Blaisdell, Th. C. Caya, L. Zhang,
A. Sanz-Marco and J. P. Morken, J. Am. Chem. Soc., 2014, 136, 9256.
9 Y. Nagashima, K. Hirano, R. Takita and M. Uchiyama, J. Am. Chem.
Soc., 2014, 136, 8532.
2 Reviews: (a) J. Takaya and N. Iwasawa, ACS Catal., 2012, 2, 1993;
(b) M. Suginome and T. Ohmura, In Boronic Acids, Wiley-VCH, 10 N. Iwadate and M. Suginome, J. Am. Chem. Soc., 2010, 132, 2548.
New York, 2nd edn, 2011, vol. 1, 171; (c) H. E. Burks and J. P. 11 (a) H. Noguchi, K. Hojo and M. Suginome, J. Am. Chem. Soc., 2007,
´
Morken, Chem. Commun., 2007, 4717; (d) J. Ramırez, V. Lillo, A. M.
129, 758; (b) N. Iwadate and M. Suginome, J. Organomet. Chem., 2009,
694, 1713; (c) H. Noguchi, T. Shioda, Ch.-M. Chou and M. Suginome,
Org. Lett., 2008, 10, 377; (d) L. Iannazzo, K. P. C. Vollhardt, M. Malacria,
C. Aubert and V. Gandon, Eur. J. Org. Chem., 2011, 3283; (e) X. Feng,
H. Jeon and J. Yun, Angew. Chem., Int. Ed., 2013, 52, 3989;
( f ) H. Yoshida, Y. Takemoto and K. Takaki, Chem. Commun.,
2014, 50, 8299.
Segarra and E. Fernandez, C. R. Chim., 2007, 10, 138; (e) T. Ishiyama
and N. Miyaura, Chem. Rec., 2004, 3, 271; ( f ) T. B. Marder and
N. C. Norman, Top. Catal., 1998, 63.
3 (a) T. Ishiyama, N. Matsuda, M. Murata, F. Ozawa, A. Suzuki and
N. Miyaura, Organometallics, 1996, 15, 713; (b) T. Ishiyama, T. Kitano
and N. Miyaura, Tetrahedron Lett., 1998, 39, 2357; (c) T. Ishiyama,
S. Momota and N. Miyaura, Synlett, 1999, 1790; (d) F. Y. Yang and 12 C. Borner and Ch. Kleeberg, Eur. J. Inorg. Chem., 2014, 2486.
´
´
C.-H. Cheng, J. Am. Chem. Soc., 2001, 123, 761; (e) J. B. Morgan, 13 J. Cid, J. J. Carbo and E. Fernandez, Chem. – Eur. J., 2014, 20, 3616.
S. P. Miller and J. P. Morken, J. Am. Chem. Soc., 2003, 125, 8702; 14 Calculations were performed using Gaussian09 (B3LYP functional)
( f ) N. F. Pelz, A. R. Woodward, H. E. Burks, H. E. Sieber and
J. D. Morken, J. Am. Chem. Soc., 2004, 126, 16328; (g) J. D. Sieber and
J. P. Morken, J. Am. Chem. Soc., 2006, 128, 74; (h) H. Y. Cho and J. P.
Morken, J. Am. Chem. Soc., 2008, 130, 16140; (i) T. Ishiyama and
N. Miyaura, J. Organomet. Chem., 2000, 611, 392; ( j) G. Lesley,
P. Nguyen, N. J. Taylor, T. B. Marder, A. J. Scott, W. Clegg and
and the 6-31g(d,p) basis set. In parenthesis we also provide the free
energy corrections including the solvent effect of methanol (e = 32.613)
that introduced into the optimised vacuum geometries by using the
IEFPCM continuum model. Main discussion used electronic energies
because DG values overestimate the entropic cost for bimolecular
processes. See the ESI† for details.
N. C. Norman, Organometallics, 1996, 15, 5137; (k) R. L. Thomas, 15 We have also considered the attack to the internal carbon of the
F. E. S. Souza and T. B. Marder, J. Chem. Soc., Dalton Trans., 2001,
1650; (l) S. Trudeau, J. B. Morgan, M. Shrestha and J. P. Morken,
alkene but the corresponding TSs are 2 and 5 kcal molÀ1 higher
than TS1a and TS1b. See the ESI† for details.
1696 | Chem. Commun., 2015, 51, 1693--1696
This journal is ©The Royal Society of Chemistry 2015