Angewandte
Chemie
Herein, we describe a method for the synthesis of b-
borated carbonyl compounds by reacting B2pin2 with either
a,b-unsaturated esters or ketones in the presence of chiral
phosphine catalyts. The reaction is metal free, and only
requires tertiary phosphorus compounds, MeOH, and a base
as additives.
deficient olefins with copper (NaOtBu preferred), nickel,
palladium, and iron (Cs2CO3 preferred), although its role is
still a matter of discussion.[5e,9,10] It has been postulated that a
base preactivates the transition-metal precursor to facilitate
the transmetalation between the complex and the diboron
reagent,[11] but the direct interaction of the base with the
We first optimized the reaction conditions using ethyl-
crotonate as a model substrate, B2pin2 as the boron source,
and PPh3 (the most common achiral phosphine) as the
catalyst. The reactions were carried out in tetrahydrofuran at
708C. Moderate conversions values were observed in the
presence of either 4 or 10 mol% phosphine, Cs2CO3, and
using either MeOH or iPrOH as an additive (Table 1,
diboron reagents could facilitate the heterolytic cleavage, and
[12]
À
thus the metal boryl bond formation.
The substrate scope was then investigated under opti-
mized reaction conditions using PPh3 and DPPF as catalysts
(Scheme 3). Structure—activity relationships in the b-bora-
Table 1: Phosphine-mediated catalytic b-boration of ethylcrotonate with
B2pin2.[a]
Entry Phosphine (mol%) Base
Additive Conversion [%][b]
1
2
3
4
5
6
7
8
PPh3 (4)
PPh3 (4)
PPh3 (4)
PPh3 (10)
PPh3 (20)
PPh3 (4)
–
MeOH
–
0
12
54
63
99
49
21
32
39
42
27
37
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
NaOtBu
K2CO3
CsF
MeOH
MeOH
MeOH
iPrOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
=
O PPh3 (4)
DTBPMB (4)
DPPF (4)
DPPF (4)
DPPF (4)
DPPF (4)
Scheme 3. Substrate scope for the phosphine-mediated b-boration
reaction. Conditions: phosphine (4 mol%), Cs2CO3 (15 mol%), MeOH
(2.5 mmol), THF, 708C, 6 h. Yield in parentheses is the yield of
isolated product. DPPF=bis(diphenylphosphino)ferrocene.
9
10
11
12
[a] Standard conditions: substrate (0.5 mmol), phosphine (4–20 mol%),
base (15 mol%), MeOH (2.5 mmol), THF (2 mL), 708C, 6 h. [b] Con-
version calculated using G.C. analysis and confirmed by 1H NMR
spectroscopy.
tion of a,b-unsaturated esters showed a certain trend. Higher
conversions were observed when the ester moieties were less
sterically hindered. The a,b-unsaturated ketones were less
sensitive to structural changes, and they were all readily
converted into their corresponding organoboranes with PPh3.
Having identified the appropriate conditions, we focused
our efforts on obtaining asymmetric induction in the model
reaction. Chiral monophosphorus compounds, as well as
diphosphines, were explored as catalysts at a 4 mol% loading
in the b-boration of ethylcrotonate (Scheme 4, Table 2). The
fairly basic (+)-neomenthyldiphenylphosphine (3) provided
good conversion, but no asymmetric induction (Table 2,
entry 1). However, to our delight, chiral monodentate phos-
phoramidite ligands 4, 5, and 6 induced a certain degree of
enantioselectivity (35% ee with 5, Table 2 entry 3; 31% ee
with 6, entry 7), which was considerably higher than the
enantioselectivities achieved with the copper(I)–phosphora-
midite complexes reported by Yun and co-workers (< 7%
ee).[5b]
entries 1—4 and 6). Complete conversion was achieved by
using 20% PPh3 (Table 1, entry 5). The first two experiments
also demonstrate that both the base and the alcohol are
essential additives for this reaction.
=
Hoveyda and co-workers found that O PPh3 could also
promote moderate b-boration of 2-cyclohexen-1-one, even in
the absence of a base.[7] Under our reaction conditions, O
=
PPh3 was much less active than PPh3 (Table 1, entry 7 versus
entry 3). Diphosphines 1 and 2 also catalyzed the b-boration
of ethylcrotonate, but less efficiently than PPh3. Whilst 1,2-
bis(di-tert-butylphosphinomethyl)benzene (DTBPMB) only
afforded 32% conversion (Table 1, entry 8), 1,1’-bis(diphe-
nylphosphino)ferrocene (DPPF), a diphosphine containing a
ferrocene backbone, resulted in a 39% conversion of the
substrate (Table 1, entry 9). The nature of the base was also
studied: NaOtBu and CsF were found to be as effective as
Cs2CO3 (Table 1, entries 10–12). The need for a base has also
been observed in the metal-mediated b-boration of electron-
When the reaction was carried out at room temperature,
the enantioselectivity increased slightly, whilst the activity
decreased (Table 2, entry 4). The influence of the base on the
asymmetric induction was also studied. We observed that the
Angew. Chem. Int. Ed. 2010, 49, 5130 –5134
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5131