Direct Michael addition of alkenes via a cobalt-dinitrosyl mediated vinylic C-H functionalization reaction

Article abstract of DOI:10.1021/ja204564z

We report a one-pot, direct C-H functionalization reaction of alkenes mediated by [CpCo(NO)₂]. All intermediates in the proposed reaction sequence have been characterized. A variety of Michael acceptors can be utilized with the one-pot procedure to give the desired cyclic tetra-alkyl-substituted, γ,δ-unsaturated compounds in good yields. We also provide a preliminary result for catalytic turnover in both base and [CpCo(NO) ₂].

Full text of DOI:10.1021/ja204564z

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Direct Michael Addition of Alkenes via a Cobalt-Dinitrosyl Mediated
Vinylic CÀH Functionalization Reaction
Chen Zhao, F. Dean Toste,* and Robert G. Bergman*
Department of Chemistry, University of California, Berkeley, California 94720, United States
S Supporting Information
b
Scheme 1. Vinylic CÀH Functionalization Reaction of
ABSTRACT: We report a one-pot, direct CÀH functiona-
Alkenes Mediated by [CpCo(NO)2]
lization reaction of alkenes mediated by [CpCo(NO)2]. All
intermediates in the proposed reaction sequence have been
characterized. A variety of Michael acceptors can be utilized
with the one-pot procedure to give the desired cyclic tetra-
alkyl-substituted, γ,δ-unsaturated compounds in good yields.
We also provide a preliminary result for catalytic turnover in
both base and [CpCo(NO)2].
Scheme 2. Cycloaddition of 2a to [CpCo(NO)2]
he Michael addition of vinyl anion synthons to enones is a
T
powerful synthetic transformation that forms new carbonÀ
carbon (CÀC) bonds and produces γ,δ-unsaturated ketones.
While these compounds have traditionally been accessed by the
stoichiometric addition of vinyl organometallic reagents, such as
organocuprates, to Michael acceptors,1 the need for improved
substrate scope and functional group tolerance has provided
impetus for the development of other methods. Over the past
two decades, 1,4-addition of alkenes,2 alkynes,3 and allenes4 to
enones have been reported; however, intramolecular addition of
alkenyl nucleophiles to enones remains challenging, as the organo-
metallic moiety has to be generated in the presence of the
reactive Michael acceptor.5 This problem could be circumvented
by the chemoselective generation of a nucleophile directly from a
vinylic CÀH bond,6 followed by its conjugate addition to the
enone. We now report the application of our recently developed
CÀH functionalization reaction of the sp2-carbons of simple
olefins mediated by [CpCo(NO)2] (Scheme 1)7,8 to a one-pot,
direct vinylic CÀH funtionalization reaction of alkenes.
Table 1. Reaction Conditions for the Cyclization of Cobalt
Complex 3 to Give Complex 4 and/or 5a
We envisioned the cyclization reaction summarized in Scheme 1
and began by studying the individual steps of this overall trans-
formation. It has previously been reported that upon heating,
cobalt complex 19 is in equilibrium with the free olefin and the
reactive intermediate [CpCo(NO)2] at 75 °C. This latter species
can be trapped by a different alkene to give the corresponding
cobalt dinitrosoalkane complex.10,11 Thus, when complex 1 and
10 equiv of 2a were heated in toluene, complex 3 was obtained in
65% yield (Scheme 2).
was also obtained in 83% yield. The lability of the [CpCo(NO)2]
fragment in 4 has precedent in our previous studies and, due
to their thermal instability, cobalt dinitrosoalkane complexes of
cyclohexene have previously only been generated and studied
in situ.10 Further support was provided by a control experiment,
in which heating complex 4 in THF for 30 min at 75 °C gave 5a in
93% yield.
Treatment of3with 10 mol % of Verkade’s base at room tempera-
ture not only led to the corresponding cyclized cobalt complex 4
but also gave the desired organic product 5a (Table 1, entry 2).
While repeating the cyclization at À78 °C had no effect on this
product distribution, when complex 3 was heated in the presence
of 10 mol % of either Verkade’s base or t-BuOK, 5a was obtained
exclusively in much improved yields (entries 3 and 4). Furthermore,
when complex 4 was heated with 10 mol % of Verkade’s base, 5a
Received: May 18, 2011
Published: June 23, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/ja204564z J. Am. Chem. Soc. 2011, 133, 10787–10789
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Table 2. Reaction Optimization of 2a to 5a Mediated by 1
Table 3. Substrate Scope of the One-Pot CÀH Functionali-
zation Reaction Mediated by Complex 1a
entry conc. of 2a (M)
base
mol % time (h) yield of 5aa
1
2
3
4
5
6
7
0.1
Verkade’s
Verkade’s
Verkade’s
LiCp
10
10
10
15
15
20
25
53
72
53
48
24
24
24
55%
70%
78%
46%
75%
85%
72%
0.2
0.33
0.33
0.33
0.33
0.33
P1-tBu
P1-tBu
P1-tBu
a Yields are determined by 1H NMR spectroscopy with trimethoxyben-
zene as internal standard.
Having verified each step in the proposed reaction sequence
outlined in Scheme 1, we envisioned effecting the overall
transformation in one step. An initial reaction between stoichio-
metric amounts of 1 and 2a in the presence of 10 mol % of
Verkade’s base at 75 °C led to a 55% yield of 5a over 53 h
(Table 2, entry 1). By increasing the concentration of 2a and
employing 20 mol % of P1-tBu phosphazene base, 5a was
obtained in 85% yield in 24 h (entry 6). Control experiments
between 2a and 20 mol % of either Verkade’s or P1-tBu
phosphazene base at 75 °C for 3 days led to no desired product
and only recovered starting material.
We next surveyed the scope of the one-pot CÀH functiona-
lization reaction. As shown by Table 3, a variety of Michael accep-
tors can be utilized to give the corresponding tetra-alkyl-substituted
alkene products in moderate to good yields (entries 1À6). In our
initial reports,7 R,β-unsaturated esters were ineffective as electro-
philes for functionalization of cobalt dinitrosoalkane complexes;
however, substrate 2b (entry 2) cyclized to give the desired
product in good yield. It is noteworthy that although substrate
2f was synthesized as a mixture of cis and trans isomers (see
Supporting Information), this mixture reacted readily to give 5f.
Substrates containing cyclic alkenyl groups can also give the desired
tricyclic products (entries 7À8). We believe that the cyclopentyl
group of 2g is advantageous since strained alkenes bind
[CpCo(NO)2] much more effectively than simple, unstrained
olefins.11 This argument is exemplified by the low yield obtained
with substrate 2h. Furthermore, intermolecular coupling between
norbornene and simple cyclic enones was achieved in one step
to give the corresponding products in good yields and excellent
dr (entries 10À11).12
a General condition: 1.2 equiv of 1, P1-tBu (20 mol %), 75 °C, 24 h,
1
benzene (0.33 M). b Yields are determined by H NMR spectroscopy
with trimethoxybenzene as an internal standard. c P1-tBu (100 mol %),
second equiv of 1 added after 12 h of heating, followed by additional
e
heating for 24 h. d 1.2 equiv of 1, P1-tBu (10 mol %), 24 h. 2 equiv
f
of enone, 1.2 equiv of 1, P1-tBu (10 mol %), 95 °C, 24 h. Isolated
yields.
Scheme 3. Catalytic Vinyl CÀH Functionalization
While cobalt is an affordable and readily available transition
metal, rendering the reaction outlined in Scheme 1 catalytic in
[CpCo(NO)2] would further improve upon the chemistry of this
class of ligand-based CÀH functionalization reaction. Although
base-mediated decomposition of [CpCo(NO)2] and the forma-
tion of a cobalt dimer 6,11 a stable and inactive species, have thus
far limited catalytic turnover, substrate 2g cyclized to give 60%
yield of 5g with 20 mol % of complex 1 (Scheme 3).
nuleophiles directly from vinyl CÀH bonds, which can add to a
variety of internal, and some external Michael acceptors in a 1,4-
fashion. This strategy also gives rise to tri- and tetra-alkyl-
substituted alkene products, where the olefin is γ,δ-unsaturated
with respect to the electron-withdrawing functional groups. Efforts
toward improving the catalytic reaction and extension to other
transition metals are underway.
In conclusion, we have developed a simple one-pot, CÀH
functionalization reaction of alkenes mediated by complex 1.
This methodology allows for the chemoselective generation of
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’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures and
b
full characterization for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
fdtoste@berkeley.edu; rbergman@berkeley.edu
’ ACKNOWLEDGMENT
We acknowledge NSF for financial support in the form of a
research grant to RGB (CHE-0841786). We would also like to
acknowledge Mark Crimmin, Jerome Volkman, Miles Johnson,
and W. Christopher Boyd for helpful discussions.
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