Iminopyridine oxazoline iron catalyst for asymmetric hydroboration of 1,1-disubtituted aryl alkenes

Article abstract of DOI:10.1021/ol503282r

The highly regio- and enantioselective iron-catalyzed anti-Markovnikov hydroboration of 1,1-disubstituted aryl alkenes is reported by using a novel chiral iminopyridine oxazoline (IPO) ligand, in which the iminopyridine group is proposed to stabilize the iron and chiral oxazoline group to control enantioselectivity. This distinct class of reactive IPO ligands will likely be of high value for a large variety of asymmetric transformations using first-row transition metals.

Full text of DOI:10.1021/ol503282r

Letter
pubs.acs.org/OrgLett
Iminopyridine Oxazoline Iron Catalyst for Asymmetric
Hydroboration of 1,1-Disubtituted Aryl Alkenes
Jianhui Chen, Tuo Xi, and Zhan Lu*
Department of Chemistry, Zhejiang University, Hangzhou 310027, China
*
S Supporting Information
ABSTRACT: The highly regio- and enantioselective iron-catalyzed anti-
Markovnikov hydroboration of 1,1-disubstituted aryl alkenes is reported by
using a novel chiral iminopyridine oxazoline (IPO) ligand, in which the
iminopyridine group is proposed to stabilize the iron and chiral oxazoline
group to control enantioselectivity. This distinct class of reactive IPO
ligands will likely be of high value for a large variety of asymmetric
transformations using first-row transition metals.
7
ydroboration of alkenes is one of the most useful methods
minimally toxic, cheap, and commercially available base metal.
Although chiral iron catalysts have been used in several types of
reactions thus far, asymmetric reductive reactions catalyzed using
low valent iron catalysts were limited to the reduction of ketones
H
to access alkylboronic acid derivatives, which are widely
1
used in modern organic synthesis. Chiral boronic acid
derivatives could be synthesized by hydroboration of alkenes
with stoichiometric amounts of chiral hydroborating com-
8
,9
and imines. To our best knowledge, there has been no report
on asymmetric hydroboration of carbon−carbon double bonds
by chiral iron catalysts. Herein, we report a highly regio- and
enantioselective iron-catalyzed anti-Markovnikov hydroboration
reaction of 1,1-disubstituted aryl alkenes with HBPin using the
newly designed chiral iminopyridine oxazoline (IPO) iron
catalyst (eq 3).
To begin this study, we elected to study the hydroboration of
α-methylstyrene with HBPin as the model reaction to test our
hypothesis, based on the iron-catalyzed racemic hydroboration.
Using biiminopyridine ligands, which can stabilize center
2
pounds. A more efficient strategy is the transition-metal-
catalyzed asymmetric hydroboration of alkenes with the boronic
compounds using catalytic amounts of chiral ligands. Asymmetric
hydroboration of terminal alkenes catalyzed by chiral transition
metal complexes is primarily selective for Markovinov
3
regioselectivity. However, the enantioselective hydroboration
4
−6
of 1,1-disubstituted alkenes is still a challenge.
Low
enantioselectivity and in some cases poor regioselectivity were
obtained through rhodium- and iridium-catalyzed reactions of
4
1
,1-disubstituted alkenes with catecholborane (eq 1). Recently,
an iridium-catalyzed asymmetric hydroboration of 1,1-disub-
stituted alkenes with HBPin was reported using a chiral Phox-
5
ligand to achieve high regioselectivity (eq 1). However, only
Scheme 1. Design, Synthesis, and X-ray Structure of Iron
Compound 2
moderate enantioselectivity was observed in most cases. Another
work involves the chiral NHC-copper-catalyzed enantioselective
6
hydroboration of 1,1-disubstituted alkenes with (BPin) (eq 2).
2
A long reaction time of 2 days at low temperature (−50 °C) is
required to afford high regioselectivity and >90% ee, in the case of
two acyclic α-substituted styrenes. Iron is a naturally abundant,
Received: November 12, 2014
©
XXXX American Chemical Society
A
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Letter
Table 1. Optimization Studies for Asymmetric Hydroboration of Alkenes
a
b
entry
cat.
solvent (M)
reductant
Mg
temp
yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
2
2
2
2
2
2
2
2
2
2
2
THF (0.25)
THF (0.25)
THF (0.25)
THF (0.25)
THF (0.25)
toluene (0.25)
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
nr
−
−
−
83
Et Zn
2
nr
EtMgBr
nr
PhMgBr
NaBHEt3
NaBHEt3
NaBHEt3
NaBHEt3
NaBHEt3
NaBHEt3
NaBHEt3
NaBHEt3
NaBHEt3
NaBHEt3
NaBHEt3
<20
26
92.9
92.1
95
93 (85)
88(81)
98 (93)
96 (83)
100(98)
97(88)
<5
Et O (0.25)
2
Et O (0.5)
2
95
Et O (1)
2
93.7
96.0
95.7
−
10
11
12
13
14
15
Et O (0.5)
2
Et O (0.5)
2
−10
0
3+FeCI2
Et O (0.5)
2
4+FeCI
Et O (0.5)
2
0
6
−
−
−
2
c
1+[Ru]
Et O (0.5)
2
0
nr
d
1+[lr]
Et O (0.5)
2
0
nr
b
a
1
Yields determined by H NMR analysis using TMSbenzene as an internal standard. Isolated yield in parentheses. ee values determined by chiral
c
d
HPLC analysis. [Ru]: Ru(PPh ) Cl . [Ir]: [Ir(COD)Cl] .
3
3
2
2
a
Scheme 2. Asymmetric anti-Markovnikov Hydroboration of Alkenes
a
Standard conditions: Unless otherwise noted, 6 (1 mmol), HBPin (0.5 mmol), 2 (0.025 mmol), NaBHEt (0.075 mmol) in 1 mL of Et O at 0 °C
3
2
under nitrogen for 1 h. b 2 (0.05 mmol), NaBHEt (0.15 mmol). Toluene instead of Et O at −10 °C. Toluene instead of Et O. 2 (0.05 mmol),
NaBHEt (0.15 mmol), toluene instead of Et O.
c
d
e
3
2
2
3
2
1
0
metals, we used well-defined pyridylbisoxazoline (4) as the
ligand. Unfortunately, the catalytic reactions did not work well.
Subsequently, we attempted to combine the chiral oxazoline and
imino group on the same molecule and designed a new type of
chiral iminopyridine oxazoline ligand, in which the iminopyridine
group is postulated to stabilize the iron and the chiral oxazoline
group to control the enantioselectivity. The newly designed chiral
complex 2 could be easily synthesized by combining iron
dichloride with the corresponding ligand, identified by elemental
analysis and X-ray, and is stable under anitrogen atomsphere up
to a year.
12
We also studied the hydroboration of styrene 6a with HBpin
(5)to test the reactivity of our chiral iron complex 2 (IPO·FeCl2).
First, several reductants (entries 1−5, Table 1) were screened;
11
iminopyridine oxazoline ligand 1 can be easily synthesized from
commercially available starting materials (Scheme 1). The iron
Mg, Et Zn, and EtMgBr displayed poor reactivities (entries 1−3).
2
The reaction using PhMgBr and NaBHEt3 as reductants
B
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Organic Letters
Letter
exhibited similar reactivities, but the latter displayed better
enantioselectivity. To our delight, despite the modest reactivity,
the regio- and enantioselectivity were excellent. Solvents play an
important role in affecting reactivity (entries 5−7); good yields
were obtained using both toluene and ether, and a slightly better
enantioselectivity is observed in ether. The reaction concen-
tration also had an effect on the reactivity with 0.5 M being the
most optimal. The reaction at 0 °C increased the enantiose-
lectivity; further decreasing the temperature did not lead to an
improvement in the ee. The standard reaction conditions involve
in a Schlenk line, not necessarily in a glovebox. A series of useful
chiral borate compounds were easily synthesized and isolated
with 100% atom efficiency under mild conditions. It is also an
efficient way to construct a chiral carbon center at the benzyl
position. Current efforts in our laboratory are underway to
understand the mechanistic intricacies of this process and
develop new base-metal-catalyzed asymmetric reactions based
on the IPO ligand.
ASSOCIATED CONTENT
Supporting Information
■
6
a (1 mmol, 2 equiv), HBpin (0.5 mmol), 2 (5 mol %), and
*
S
NaBHEt (15 mol %) in Et O (1 mL) at 0 °C as the standard
conditions. In addition, 7a was observed in <5% or 6% yield when
3
2
Experimental procedures and characterization data for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
the catalyst was FeCl with the Pyox ligand (entry 12) or Pybox
2
ligand (entry 13); 7a was not observed when the reaction was
performed with ruthenium or iridium with the IPO ligand
AUTHOR INFORMATION
Corresponding Author
(
entries 14and 15), whichshows ironwith the novelIPO ligand is
more efficient than noble transition metals.
■
With the optimal set of conditions, the scope of this reaction is
shown in Scheme 2. We observed that the reaction can be
successfully initiated with a variety of substituted styrenes,
including electron-rich and -deficient styrenes. The reaction can
tolerate protected phenol, aniline, thiophenol, and benzyl
alcohol. Para-, meta-, or ortho-fluorinated α-methylstyrene can
react in good yields and enantioselectivity. The reaction of
chloro-styrene with HBpin gave exclusively hydroboration
products without any dehalogenated sideproducts. Strongly
electron-deficient substituents, such as the trifluoromethyl group,
also led to high enantioselectivity (92% ee) and regioselectivity.
Hydroboration of 2-(prop-1-en-2-yl)naphthalene gave 7o in 93%
yield with 95% ee. The reaction of α-alkyl-substituted styrenes
proceeded smoothly to yield the corresponding products in good
enantioselectivities (87−91% ee). Interestingly, ferrocenyl olefin
*
E-mail: luzhan@zju.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was conducted using funds from the “Thousand
Youth Talents Plan”, the Fundamental Research Funds for the
Central Universities (2013QNA3022), and the Starting Funds
from Zhejiang University.
REFERENCES
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,1-disubstituted aryl alkenes with pinacolborane. This newly
designed chiral iminopyridine oxazoline ligand, together with the
environmentally benign iron catalyst, provides a highly efficient
system compared to other noble transition metal catalytic
systems in similar reactions. The reaction can be readily operated
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(
12) CCDC number is 1029987.
D
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