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Table 1: Addition of ArZnX to 4-octyne (2a).[a]
Entry
Ar, reagent type (equiv)
Ligand
Yield [%][b]
1[c]
2
3
4-MeOC6H4, A (3)
Ph, B (1.1)
Ph, B (1.4)
Xantphos
Xantphos
DPEphos
dppe
70
90 (90)
3
0
4
Ph, B (1.4)
5
Ph, B (1.4)
Ph, B (1.4)
Ph, B (1.4)
dppp
PPh3
None
2
1
1
6[d]
7
8[e]
9[f]
10
11[c]
12
Ph, B (1.1)
Ph, B (1.1)
Ph, C (0.55)
4-MeOC6H4, D (1.5)
Ph, E (1.5)
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
69
7
74
99 (94)
77
[a] Reaction conditions: CoCl2 (5 mol%), ligand (5 mol%), 2a (0.3 or
0.6 mmol), ArZnX, THF, 608C, 4 h. See Scheme 2 for the type of the
arylzinc reagent. [b] Determined by GC using n-tridecane as an internal
standard. The E/Z ratio was >50:1 as determined by 1H NMR
spectroscopy and GC analysis. The yield of isolated product is shown in
parentheses. [c] CoCl2–Xantphos catalyst was used for both the zinc
insertion and addition reactions. [d] PPh3 (10 mol%) was used. [e] Per-
formed in THF/toluene (1:1). [f] Performed in THF/MeCN (1:1).
Scheme 3. Deuterium-labeling experiments.
H2O afforded the product [D5]-3bb, where one of the ortho-
deuterium atoms of the zinc reagent had almost completely
transferred to the vinylic position (Scheme 3b). These results
are reminiscent of Hayashiꢀs rhodium-catalyzed hydroaryla-
tion reaction (Scheme 1a),[5] and suggest a catalytic cycle
consisting of the following steps (Scheme 1b): 1) insertion of
the alkyne into an arylcobalt species generated from the
cobalt precatalyst and the arylzinc reagent,[8,10] 2) 1,4-cobalt
migration of the resulting alkenylcobalt species I to generate
an ortho-alkenylarylcobalt species II, and 3) transmetalation
between II and the arylzinc reagent to afford an ortho-
alkenylarylzinc species and regenerate the arylcobalt species.
The unique feature of this “migratory arylzincation”
reaction compared with the rhodium-catalyzed hydroaryla-
tion reaction is that the product bears a reactive aryl–zinc
bond, which can be intercepted by an external electrophile.
Thus, we explored the generality of the addition–migration
process using I2 as the electrophile (Scheme 4). A variety of
arylzinc reagents participated in the reaction with 5-decyne to
afford the corresponding 1-iodo-2-alkenylarenes in moderate
to good yields (4ab–4nb). Electron-donating, electron-with-
drawing, and potentially sensitive functional groups including
dimethylamino (4cb), carbonate (4eb), ester (4 fb), aldimine
(4gb), and tosyloxy (4lb) groups as well as heterocycles, such
as thienyl (4mb) and quinolinyl (4nb), groups were toler-
ated,[11] while the reaction of an ortho-substituted arylzinc
reagent was rather sluggish (3ob). Cobalt 1,4-migration was
also feasible for different alkynes including dialkyl-,
arylalkyl-, and silylalkylalkynes (see the corresponding prod-
ucts 4ac–4ah, 4ii, 3me). Note that the reaction of arylalkyl-
alkynes required the use of P(OPh)3 (10 mol%) as a coligand
to suppress E/Z isomerization. Without it, the reaction was
accompanied by a substantial degree of E/Z isomerization
(ca. 6:4–7:3). The reaction of diphenylacetylene afforded,
upon protonation, the adduct 3aj with a modest E/Z ratio,
which was not improved by the addition of P(OPh)3.[12]
Terminal alkynes such as phenylacetylene and 1-octyne and
sterically hindered alkynes such as bis(trimethylsilyl)acety-
lene did not participate in the reaction. While virtually no
regioselectivity was observed for 4-methylpent-2-yne (see the
corresponding product 4ad), arylalkyl- and silylalkylalkynes
underwent regioselective arylation on the acetylenic carbon
unexpectedly, the CoCl2–Xantphos catalyst promoted the
reaction of a phenylzinc reagent prepared from equimolar
amounts of ZnCl2·TMEDA and PhMgBr (type B reagent)
with 2a to afford the syn-adduct 3ba in 90% yield (Table 1,
entry 2). A preformed [CoCl2(Xantphos)] complex exhibited
an equally high catalytic activity as the catalyst generated
in situ. In contrast, no measurable catalytic activity was
obtained using other common phosphine ligands, such as
DPEphos, dppe, dppp, and PPh3,[6] or performing the reaction
under ligand-free conditions (Table 1, entries 3–7), while
a trace amount (1–3%) of the cyclotrimerization product of
2a was observed. The reaction was slightly slower in a THF/
toluene solvent mixture (Table 1, entry 8) and was signifi-
cantly retarded by the use of MeCN as a cosolvent (entry 9).
A diphenylzinc reagent (0.55 equiv) prepared from a 1:2
mixture of ZnCl2·TMEDA and PhMgBr (type C reagent)
afforded 3ba in 74% yield (Table 1, entry 10), thus indicating
transfer of both phenyl ligands on the zinc atom. Moreover,
the reactivity of the type A arylzinc reagent was enhanced
upon transmetalation with one equivalent of Me3SiCH2MgCl
(type D reagent),[9] thus resulting in the formation of 3aa in
a near quantitative yield (Table 1, entry 11). Naturally,
a mixed arylzinc reagent prepared from ZnCl2·TMEDA,
PhMgBr, and Me3SiCH2MgCl (type E reagent) was also
reactive (Table 1, entry 12). Note that the use of PhMgBr
instead of the phenylzinc reagents afforded only a trace
amount of the adduct 3ba, although alkyne 2a was consumed
by unidentified side reactions.
A critical difference between the present reaction and the
CoBr2-catalyzed arylzincation reported by Oshima and co-
workers[8] became clear from the results of deuterium-label-
ing experiments. When the reaction of 4-methoxyphenylzinc
reagent with 5-decyne was quenched with D2O, predominant
deuteration of the ortho position of the aryl group (93%)
rather than the vinylic position (7%) was observed
(Scheme 3a). Furthermore, the reaction of a pentadeuterio-
phenylzinc reagent with 5-decyne followed by quenching with
2
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
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