Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

Article abstract of DOI:10.3762/bjoc.14.118

The cobalt/chromium-catalyzed three-component coupling of aryl iodides, allenes, and aldehydes has been developed to afford multi-substituted homoallylic alcohols in a diastereoselective manner. Control experiments for understanding the reaction mechanism reveal that the cobalt catalyst is involved in the oxidative addition and carbometalation steps in the reaction, whereas the chromium salt generates highly nucleophilic allylchromium intermediates from allylcobalt species, without the loss of stereochemical information, to allow the addition to aldehydes.

Full text of DOI:10.3762/bjoc.14.118

Three-component coupling of aryl iodides, allenes, and
aldehydes catalyzed by a Co/Cr-hybrid catalyst
Kimihiro Komeyama*, Shunsuke Sakiyama, Kento Iwashita, Itaru Osaka and Ken Takaki
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2018, 14, 1413–1420.
Department of Applied Chemistry, Graduate School of Engineering,
Hiroshima University, 1-4-1 Higashi-Hiroshima City 739-8527, Japan
doi:10.3762/bjoc.14.118
Received: 15 March 2018
Accepted: 22 May 2018
Published: 11 June 2018
Email:
Kimihiro Komeyama* - kkome@hiroshima-u.ac.jp
*
Corresponding author
This article is part of the thematic issue "Cobalt catalysis".
Guest Editor: S. Matsunaga
Keywords:
chromium; cobalt; diastereoselective; homoallyl alcohols; hybrid
catalyst; three-component coupling
© 2018 Komeyama et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
The cobalt/chromium-catalyzed three-component coupling of aryl iodides, allenes, and aldehydes has been developed to afford
multi-substituted homoallylic alcohols in a diastereoselective manner. Control experiments for understanding the reaction mecha-
nism reveal that the cobalt catalyst is involved in the oxidative addition and carbometalation steps in the reaction, whereas the
chromium salt generates highly nucleophilic allylchromium intermediates from allylcobalt species, without the loss of stereochemi-
cal information, to allow the addition to aldehydes.
Introduction
Carbon–carbon bond formation is the fundamental and central such as aldehydes (Scheme 1, top) [1]. In contrast, π-electro-
transformation of synthetic organic chemistry. The elaboration philic carbon-connected late transition metals B facilitate the
and extension of a carbon framework via a series of carbon–car- carbometalation of carbon–carbon multiple bonds, leading to
bon bond-forming reactions are extremely important for medici- multi-substituted carbon frameworks (Scheme 1, bottom) [2,3].
nal chemistry and agrochemical and natural product synthesis. The nucleophilic and π-electrophilic organometallic intermedi-
In these bond formations, organometallics play an essential role ates are used properly in their favorable circumstances.
because they possess various reactivities depending on the
central metal ions that they own. For example, carbon has Transmetalation is one of the most vital elemental processes
strong nucleophilicity when bonded to metals with low electro- used to drastically change the reactivity of organometallics, in-
negativity, as demonstrated in the reaction of organolithium, volving a wide range of transition metal-catalyzed reactions.
organomagnesium, organozinc, and organochromium A, to For example, transmetalation between an organonickel (or
facilitate addition reactions of appropriate carbon electrophiles organocobalt) complex and chromium salt results in the forma-
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Beilstein J. Org. Chem. 2018, 14, 1413–1420.
Scheme 1: Nucleophilic and π-electrophilic characters of organometallics depending on the central metals.
tion of a highly nucleophilic organochromium species, which diastereoselective multi-substituted homoallyl alcohols employ-
enables efficient addition to aldehydes to give substituted sec- ing a cobalt/chromium hybrid catalyst (Scheme 5).
ondary alcohols, as demonstrated in the Nozaki–Hiyama–Kishi
(
NHK) reaction (Scheme 2) [4-9]. Although the catalyst combi- Results and Discussion
nation allows the use of organic halides as carbon nucleophiles, Initially, suitable reaction conditions were investigated for the
a multicomponent coupling reaction using a similar catalyst three-component coupling reaction between iodobenzene (1a),
combination has had limited success [10-12].
5-phenylpenta-1,2-diene (2a), and 4-methylbenzaldehyde (3a)
in the presence of CoBr2 (10 mol %), CrCl3 (20 mol %), and
We have recently demonstrated the high π-electron affinity of manganese powder (2.0 equiv), using trimethylsilyl chloride
an organocobalt species that enabled a variety of alkyne func- (TMSCl, 1.2 equiv) as a trapping reagent [7]. These results are
tionalization reactions to proceed via carbocobaltation summarized in Table 1. The absence of a ligand afforded the
(
Scheme 3) [13-15]. Furthermore, a combination of the cobalt homoallyl alcohol 4a in 25% yield as a syn/anti (80:20) mix-
and chromium catalyst could be applied to alkynyl iodoarene ture of diastereomers, the ratio of which was determined by the
cyclization/borylation to form cyclized vinylboronic esters, in coupling constant between the two protons at the C1- and
which transmetalation between the generated vinylcobalt and C2-positions of 4a; a coupling value of 3J = ca. 5.0 Hz indicat-
chromium salt was a critical step (Scheme 4) [16]. As part of ed the syn-form, and a coupling value of 3J = ca. 8.0 Hz indicat-
our continuing work on the cobalt-catalyzed functionalization ed the anti-form (Table 1, entry 1) [17]. The addition of PPh3
of carbon–carbon unsaturated bonds, a three-component cou- (20 mol %) resulted in an increase in the product yield to 45%
pling method is herein reported for the direct synthesis of highly with a similarly diastereomer ratio (Table 1, entry 2). The use of
Scheme 2: Ni/Cr or Co/Cr-catalyzed NHK reaction.
Scheme 3: Functionalization of alkynes via carbocobaltation.
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Beilstein J. Org. Chem. 2018, 14, 1413–1420.
Scheme 4: Cyclization/borylation of alkynyl iodoarenes using the Co/Cr catalyst.
Scheme 5: Three-component coupling of aryl iodides, arenes, and aldehydes using Co/Cr catalyst (this work).
the chromium catalyst, Mn reductant, and TMSCl was crucial tested (Table 1, entries 5–12), and after the screening of several
for the coupling (Table 1, entries 3–5). Thus, the removal of phosphines and pyridine-type ligands, the latter ligands were
CrCl3 resulted in the formation of a trace amount of 4a with the found to be the most effective for use in the coupling reaction.
complete consumption of allene 2a, whereas most of iodoarene Consequently, we found that iminopyridine L3 was the best
1
a and aldehyde 3a remained unreacted after the reaction was choice of ligand, and when used, it resulted in the three-compo-
completed (Table 1, entry 3). Using a Zn reductant instead of nent product 4a being obtained in 69% yield with a diastereose-
Mn resulted in a negligible amount of coupling product lectivity ratio of 92:8 (Table 1, entry 13). Additionally,
(
Table 1, entry 4), wherein 1a was completely consumed [18]. preformed CoBr2(L3) gave a similar result (Table 1, entry 14).
Reaction conditions without the use of TMSCl produced 4a in a During the transformation, the chromium catalyst ligands inhib-
catalytic amount (Table 1, entry 5). Other ligands were also ited the reaction (Table 1, entries 15–17). Also, the reaction was
Table 1: Screening of the reaction conditions.a
entry
ligand (x mol %)
Cr catalyst
NMR yield (%)
isomer ratiob
1
2
3
none
CrCl3
CrCl3
none
CrCl3
CrCl3
CrCl3
CrCl3
CrCl3
CrCl3
25
80:20
85:15
82:18
–
PPh3 (20)
PPh3 (20)
PPh3 (20)
PPh3 (20)
dppe (10)
dppb (10)
dppf (10)
xantphos (10)
45
5
4
5
6
7
8
9
c
trace
18
d
86:14
91:9
–
8
trace
trace
trace
–
–
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Beilstein J. Org. Chem. 2018, 14, 1413–1420.
Table 1: Screening of the reaction conditions.a (continued)
10
11
12
13
14e
15
16
17
2,2′-bpy (10)
L1 (10)
L2 (10)
L3 (10)
–
CrCl3
45
52
64
69
65
48
24
21
92:8
93:7
91:9
92:8
91:9
94:6
92:8
91:9
CrCl3
CrCl3
CrCl3
CrCl3
L3 (10)
L3 (10)
L3 (10)
CrCl3(bpy)
CrCl3(L3)
Cr(salen)Cl
aReaction conditions: 1a (0.25 mmol), 2a (0.38 mmol), and 3a (0.25 mmol). bThe ratio (syn:anti) was determined from the 1H NMR of the crude prod-
uct. cZn was used instead of Mn. dWithout the presence of TMSCl. eCoBr2(L3) was used instead of CoBr2.
highly dependent on the solvent used; for example, dimethyl- sponding homoallylic alcohols with similar diastereomer ratios
formamide (DMF), tetrahydrofuran (THF), 1,4-dioxane, and (4a–f). Additionally, alkyl aldehydes were also successfully
toluene did not result in any formation of 4a.
used in the coupling reaction, albeit resulting in slightly lower
yields (4g, 4g’, 4g” and 4h). Next, the generality of the reac-
With the optimized conditions in hand, the use of aldehydes in tion was investigated using aryl iodides (Scheme 7) and allenes
the Co/Cr-catalyzed three-component coupling reaction was (Scheme 8). Although aryl bromides and chlorides did not
explored, as shown in Scheme 6. Electron-rich and electron- participate in the coupling, a diverse set of functional groups
deficient aryl aldehydes, as well as 2-furylaldehyde, were well such as methoxy (4j), halogens (4k and 4l), trifluoromethyl
tolerated in the reaction, leading to the formation of the corre- (4m), cyano (4n), and ester (4o) substituents at the para-posi-
Scheme 6: Screening of aldehydes in the Co/Cr-catalyzed three-component coupling reaction. All yields are determined after isolation. The values in
brackets indicate the diastereomer ratio of the syn and anti products, determined from 1H NMR spectra.
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Beilstein J. Org. Chem. 2018, 14, 1413–1420.
Scheme 7: Screening of aryl iodides in the Co/Cr-catalyzed three-component coupling reaction. All yields are determined after isolation. The values in
brackets indicate the diastereomer ratio of the syn and anti products, determined from 1H NMR spectra.
Scheme 8: Screening of allenes in the Co/Cr-catalyzed three-component coupling reaction. All yields are determined after isolation. The values in
brackets indicate the diastereomer ratio of the syn and anti products, determined from 1H NMR.
tion of the phenyl ring were successfully used in the reaction, allenes; it was also used with heteroatom-containing functional-
giving rise to the desired coupling products in good yields ized allenes to afford the syn-homoallylic alcohols 4u, 4u’ and
(
47–79%). The homoallylic alcohols 4p–t were formed with a 4w in reasonably good yields (Scheme 8).
high degree of syn-selectivity because of meta- and ortho-
substituted aryl iodides also being well tolerated in the reaction. During the investigation of allenes, it was observed that, when
The protocol was not only limited to the coupling of simple oxygen substituents were present at the allenyl position, cou-
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Beilstein J. Org. Chem. 2018, 14, 1413–1420.
pling products with reversed diastereoselectivity were obtained tion, but is a highly nucleophilic species. According to these
(
Scheme 9). Thus, treatment of 4-benzyloxybuta-1,2-diene (5) findings, the reversed diastereoselectivity in Scheme 9 might be
with 1 and 3a under identical reaction conditions mainly due to stereoelectronic effects [21,22]. Thus, the σ*(C–O) bond
afforded the anti-configured homoallylic alcohols 7–10 in stabilizes the forming σ(Co–C) bond in the transition state C of
4
6–65% yield. A similar reversed diastereoselectivity was ob- the carbocobaltation step (Scheme 11), facilitating the further
served in the coupling reaction of silyloxy allene 6, leading to selective formation of the branched allylcobalt species D which
1
1 in 46% yield (anti/syn = 73:27).
could be converted into the thermodynamically more stable (E)-
allylcobalt species E because of the flexible C(vinyl)–C(allyl)
A stoichiometric reaction using phenylchromium(II or III) single bond. The generated compound E then undergoes trans-
reagents, generated from the reaction of CrCl2 or CrCl3(thf)2 metalation with the chromium salt to give the (E)-allyl-
with phenyllithium [19,20], in the presence of allene 2a and chromium species F. In contrast, the carbometalation of a
aldehyde 3c provided diarylmethanes in 78–85% yields without simple allene produces (Z)-allylcobalt species E′ and the corre-
the visible consumption of allene 2a (Scheme 10, reaction 1). sponding (Z)-allylchromium product F′ would be provided
Furthermore, in the absence of the CrCl3 catalyst, allene 2a was through a transition state such as C′, in which the cobalt center
utterly consumed, whereas most of iodide 1a and aldehyde 3d is connected to a less sterically hindered terminal allene carbon
were recovered unreacted (Scheme 10, reaction 2). These [23].
results indicate that the arylcobalt, rather than the arylchromium
intermediate, promoted the allene carbometalation. Additional- On the basis of these results, a plausible catalytic cycle for the
ly, it is thought that the vinylcobalt generated was converted to cobalt/chromium-catalyzed three-component coupling reaction
vinylchromium, which would be inactive in the oligomeriza- is shown in Scheme 12. The three-component coupling starts
Scheme 9: Reversed diastereoselectivity using allenyl ethers 5 and 6. a4-chlorobenzaldehyde was used instead of 3a.
Scheme 10: Stoichiometric reaction of phenylchromium(II or III) reagents (reaction 1) and the three-component coupling without CrCl3 catalyst (reac-
tion 2).
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Beilstein J. Org. Chem. 2018, 14, 1413–1420.
Scheme 11: The origin of the diastereoselectivity in the present three-component coupling.
Scheme 12: Plausible reaction mechanism of the three-component coupling.
with the oxidative addition of an aryl iodide 1 to a low-valent Conclusion
cobalt species to form an arylcobalt species G that reacts with The cobalt/chromium-catalyzed three-component coupling reac-
an allene 2 to stereoselectively generate an allylcobalt H via tion of aryl iodides, allenes, and aldehydes to produce highly
carbocobaltation. Rapid transmetalation between H and the substituted homoallylic alcohols in a diastereoselective manner
chromium salt [8,9] triggers the transfer of the cobalt allyl has been demonstrated. In the coupling reaction, two catalysts
group to the chromium to afford I and the highly nucleophilic played individual roles; the cobalt catalyst activated aryl iodides
allylchromium species J, which retains the same stereochemi- to form arylcobalt species, which then performed allene carbo-
cal information on the olefinic moiety as that of H. The cobaltation to form stereo-defined substituted (Z)-allylcobalt
allylchromium species J reacts with the aldehyde 3 at the γ-po- intermediates. The chromium catalyst transformed the gener-
sition of the allyl metal unit via a cyclic six-membered transi- ated allylcobalt intermediates into highly nucleophilic
tion state K to give the chromium alkoxide L [24]. Finally, the allylchromium species, without the isomerization of the olefinic
Cr–O bond is cleaved by TMSCl, generating the active moiety, via transmetalation between the generated allylcobalt
chromium salt for the transmetalation and the silyl ether M, the intermediate and the chromium salt. Moreover, it was found
desilylation of which with a fluoride anion results in the forma- that an oxygen atom present at the allenyl position resulted in a
tion of a homoallylic alcohol 4.
reversed diastereoselectivity of the homoallylic alcohol prod-
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Supporting Information
Supporting Information File 1
Experimental part.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-118-S1.pdf]
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Itaru Osaka - https://orcid.org/0000-0002-9879-2098
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