Iron-catalyzed chemo- and stereoselective hydromagnesiation of diarylalkynes and diynes

Article abstract of DOI:10.1021/ja307631v

Diarylalkynes are chemo- and stereoselectively hydromagnesiated in high yields at room temperature with an iron species generated in situ from FeCl ₂and EtMgBr. Functional groups such as bromide, iodide, amine, phenoxide, and alkene are well tolerated. Under similar conditions, diynes are chemo-, regio-, and stereoselectively hydromagnesiated. The resulting alkenylmagnesium compounds are a platform for further functionalization as a one-pot reaction.

Full text of DOI:10.1021/ja307631v

Communication
pubs.acs.org/JACS
Iron-Catalyzed Chemo- and Stereoselective Hydromagnesiation of
Diarylalkynes and Diynes
Laurean Ilies, Takumi Yoshida, and Eiichi Nakamura*
Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
S
* Supporting Information
ABSTRACT: Diarylalkynes are chemo- and stereoselec-
tively hydromagnesiated in high yields at room temper-
ature with an iron species generated in situ from FeCl2
and EtMgBr. Functional groups such as bromide, iodide,
amine, phenoxide, and alkene are well tolerated. Under
similar conditions, diynes are chemo-, regio-, and stereo-
selectively hydromagnesiated. The resulting alkenylmagnesi-
um compounds are a platform for further functionalization as
a one-pot reaction.
The reaction did not proceed at all in the absence of the iron
catalyst (see the Supporting Information for details). Iron salts
other than FeCl2, such as Fe(acac)2, Fe(acac)3, or FeCl3,
afforded 2 with slightly lower yields (76−79%). Other primary
alkyl (e.g., hexyl) magnesium reagents performed equally well,
but bulky (isobutyl) or secondary alkyl (cyclohexyl, cyclo-
pentyl) reagents were greatly inferior. Because the reaction
does need a ligand, we could consider that the olefin generated
atalytic hydrometalation, such as hydromagnesiation, of
Can alkyne via a transient metal hydride species was
established in the 1980s for titanium1 and nickel2 but has been
hardly developed since then. We3 and others4−6 have noticed
that the iron species generated from the reaction of an iron salt
with an alkylmagnesium halide7 may be a viable catalytic species
for hydromagnesiation of C−C double bonds. There have also
been recent reports on iron-catalyzed hydrosilylation8 and
hydroboration9 of C−C multiple bonds. We report here the
chemo- and stereoselective preparation of alkenylmagnesium
compounds via cis-selective hydromagnesiation of diarylalkynes
and diynes with EtMgBr as a hydride source and FeCl2 as a
catalyst. The reaction typically completes within 15 min at room
temperature in the presence of 5 mol % of FeCl2 in diethyl ether
without the need for any added ligand. Notably, the conditions
tolerate the presence of functional groups such as bromide, iodide,
amine, phenoxide, and alkene, which are known to be sensitive to
reductive conditions. The reaction regioselectively reduces only
one of the two acetylenic bonds in a diyne with good cis-
selectivity. Hydromagnesiation of a conjugated diyne has seldom
been recorded in the literature, and hydrometalation of an internal
diyne, only rarely.10
by β-elimination and the acetylenic substrate may act as ligands
on the iron intermediate.6 The presence of added 1-hexene did
not affect the yield. Addition of bi- or terpyridine-type ligands
did not affect the yield either, whereas mono- or diphosphine
ligands shut off the reaction. The use of a smaller amount of
EtMgBr resulted in lower conversion of the starting material,
but the necessity for 2 equiv of this reagent is unclear. 1 equiv is
used as a hydrogen source and can be traced at the end of the
reaction as the alkene product, and the excess EtMgBr is not
consumed during the reaction (Supporting Information). The
hydrogen on the product originates from EtMgBr, as
unequivocally demonstrated by the deuterium-labeling experi-
ment shown in eq 2.
The hydromagnesiation of diphenylacetylene (1.03 g, 5.6
mmol) with EtMgBr (9.66 mL, 1.16 M in diethyl ether, 11.2
mmol) and FeCl2 (36 mg, 0.28 mmol) in diethyl ether (20 mL)
at room temperature for 15 min, followed by trapping with 1 M
hydrochloric acid (30 mL) or allyl bromide (1.2 mL, 14 mmol),
gave (Z)-stilbene (2, 0.97 g, 94% yield) and 1,2-diphenyl-1,
4-pentadiene (3, 0.88 g, 72%), respectively, with high (Z)-
stereoselectivity (eq 1, E = H or allyl). The allylation reaction
may have taken place under the influence of an iron catalyst
that was still present after the hydromagnesiation reaction.11
We did not observe the formation of overreduction products
such as 1,2-diphenylethane. Alkenes were largely unreactive
under these conditions.
A variety of diarylalkynes undergo the hydromagnesiation
reaction, as shown in Table 1. Electron-rich (entries 4 and 9)
and electron-deficient (entries 5 and 6) alkynes reacted equally
well. Steric hindrance did not affect the yield, and the
stereoselectivity was excellent (entry 4). An important feature
of this reaction is the tolerance of halides, including bromide
Received: August 2, 2012
Published: October 3, 2012
© 2012 American Chemical Society
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Journal of the American Chemical Society
Communication
deprotonated hydroxyl group (entry 11) were also tolerated. We
note that when substrates containing O or N atoms were used, the
stereoselectivity slightly decreased, perhaps because coordination
of these atoms to the iron species accelerates the isomerization
process.12 An enyne (entry 12) was selectively hydromagnesiated
at the alkyne site to chemoselectively produce a 1,3-diene in
moderate yield. The lower stereoselectivity may suggest
coordination of the alkene site to the iron species. We note that
the reaction of these asymmetrical alkynes proceeded without
regioselectivity (Supporting Information).
Table 1. Iron-Catalyzed Hydromagnesiation of Various
Diarylalkynes and Subsequent Functionalization
a
The alkenylmagnesium intermediate can be further reacted
with electrophiles in a one-pot reaction (entries 13−17). The
reaction with allyl bromide (entry 13 and eq 1) stereoselectively
gave a 1,4-diene. The reaction with N,N-dimethylformamide
(DMF, entry 14) produced an (E)-β-unsaturated aldehyde, and
the reaction with benzaldehyde (entry 15) gave an allylic alcohol,
both with high stereoselectivity. Notably, a dithienylacetylene
(entry 16) also participated in the hydrometalation reaction
stereoselectively to give an (E)-alkenylsilane after trapping with
the corresponding chlorosilane. Iron-catalyzed hydromagnesiation
of diphenylacetylene, following a one-pot nickel-catalyzed cross-
coupling with aryl iodides, gave triarylalkenes (entry 17).
Alkylalkynes reacted poorly under these reaction conditions
(data not shown). This allowed site-selective hydrometalation of
diyne compound 4 at the diarylalkyne site to produce enyne 5
with high stereoselectivity (eq 3), together with a small amount
of diene (7%).
The alkenylmagnesium intermediate can be functionalized in
a one-pot sequence involving iron catalysis. This was illustrated
by a signature reaction of iron catalysis that we reported some
time ago.13 The vinyl Grignard reagent generated in situ reacts
with an o-iodobenzylamine to produce first the corresponding
aryl radical and then afford an α-alkenylation of the amine via
1,5-hydrogen transfer (eq 4).
a
Reaction conditions: diarylalkyne (0.30 mmol), FeCl2 (5 mol %),
EtMgBr (0.60 mmol) in Et2O stirred at rt (25 °C) for 15 min. See the
b
c
Supporting Information for details. Isolated yield. Determined by
d
e
Under similar reaction conditions, 1,3-diynes (7) can be
chemo-, regio-, and stereoselectively hydromagnesiated at one
of the triple bonds, leaving another intact (eq 5 and Table 2).
GC. Reaction with 1 g of substrate. Fe(acac)3 (2.5 mol %) was used
f
g
as a catalyst. (Z)-Stilbene was obtained in 3% yield. (Z)-Stilbene was
obtained in 4% yield. FeCl2 (10 mol %) and EtMgBr (1.2 mmol)
were used. NiCl2(PPh3)2 (5 mol %) was used as a catalyst.
h
i
(entry 7) and iodide (entry 8), where only a trace amount of
dehalogenated material was observed. This is surprising in light
of the previous reports on the iron-mediated reduction of aryl
halides5 and suggests an extremely high affinity of the iron
species for the alkyne. A dimethylamino group (entry 10) and a
Both electron-deficient (entry 2) and electron-rich substrates
(entries 3 and 4) reacted with high chemo- and regioselectivity,
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Communication
a
Table 2. Iron-Catalyzed Hydromagnesiation of 1,3-Diynes
AUTHOR INFORMATION
Corresponding Author
nakamura@chem.s.u-tokyo.ac.jp
■
yield
b
c
d
entry
R1
R2
electrophile
E
(%) E/Z
8:9
1
2
3
4
5
6
Ph
4-FC6H4
Ph
4-FC6H4
D+
D
D
D
D
D
63 14:86 >99:1
Notes
D+
63 11:89
55 25:75
65 22:78
55 17:83
97:3
97:3
The authors declare no competing financial interest.
4-MeC6H4 4-MeC6H4
4-MeOC6H4 4-MeOC6H4
D+
D+
97:3
ACKNOWLEDGMENTS
■
Ph
Ph
Me3Si
Ph
D+
98:2
We thank MEXT for financial support (KAKENHI Specially
Promoted Research No. 22000008 to E.N., and Grant-in-Aid
for Young Scientists (B) No. 23750100 to L.I.).
DMF
CHO 50 97:3
>99:1
a
Reaction conditions: 1,3-diyne (0.30 mmol), FeCl2 (5 mol %),
EtMgBr (0.60 mmol), in Et2O stirred at rt (25 °C) for 15 min. See the
Supporting Information for details. Isolated yield. Determined by
b
c
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d
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■
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ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and physical properties of the
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
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