Table 1: Effect of ligands or additives on the product selectivity and
participate in the carbometalation reaction. Notably, highly
reactive functional groups, such as methoxycarbonyl (Table 2,
entry 9) and cyano groups (Table 2, entry 10),[22] were com-
patible under the present reaction conditions. When less
reactive oxabicyclic alkenes such as 1l (Table 2, entry 12) and
1m (Table 2, entry 13) were employed, a higher catalyst
loading and longer reaction time were required to achieve
smooth conversion. Azabicyclic alkenes 1n and 1o also take
part in the reaction, thereby affording the arylated products
3n and 3o in 94% and 96% yield, respectively (Table 2,
entries 14 and 15). The reaction of nonsymmetrical substrate
1p took place such that the aryl group is introduced to the
olefinic terminus distal from the methyl group to give a
mixture of regioisomers 3p and 3p’. The regioselectivity of
carbometalation is estimated at approximately 4:1 (3p/3p’),
thus suggesting that the steric interaction between the methyl
group and the introduced phenyl group is dominant (Table 2,
entry 16).[23]
reactivity.[a]
Entry
Ligand
t [h]
Yield [%][b]
3a
4a
1a
1
2
3
4
5
6
7
8
none
tmeda (1.5 equiv)
nmp (1.5 equiv)
dppe
dppp
dppb
L1 (dppbz)
L2
L3
L4
L5
(R)-binap
15
2
15
5
5
5
5
4
2
5
0
0
6
87
99
90
8
22
95
12
17
5
12
0
1
3
6
0
0
0
0
87
70
3
88
83
95
89
<1
2
9
10
11[c]
12
11
27
59[d]
0
71
33
6
5
The carbometalation intermediate 2a was sufficiently
stable at 08C and it could be trapped with various electro-
philes. The treatment of 2a with CD3COOD gave the
corresponding deuterated product 5a in 92% yield with
greater than 96% deuterium incorporation and more than
99% cis selectivity (Scheme 3). The cis configuration was
[a] The reactions of 1a with diphenylzinc (1.5 equiv) were carried out in
THF/toluene (1:1) at 08C for 2–15 h in the presence of FeCl3 (1 mol%)
1
and ligand (2 mol%). [b] Yield based on H NMR spectroscopy. [c] The
reaction was performed at 258C. [d] No chiral induction was observed.
significantly affect the product distributions: in the presence
of 1,2-bis(diphenyphosphino)ethane (dppe; Table 1, entry 4),
l,3-bis(diphenylphosphino)propane (dppp; Table 1, entry 5),
dppbz (L1; Table 1, entry 7), and related diphosphine ligands
(L2–L4; Table 1, entries 8–10), the exo-arylated compound
1,2,3,4-tetrahydro-2-phenyl-1,4-epoxynaphthalene (3a) was
isolated as the main product. Given that dppb exhibited no
positive effect on the yield of 3a (Table 1, entry 6), the bite
angle of diphosphine ligands is essential to attenuate the
reactivity of the iron catalyst. Regarding the dppbz congeners,
electron-donating ligand L2 decreased the yield of 3a
(Table 1, entry 8), whereas electron-deficient phosphine L3
significantly improved the yield. Thus, the reaction of 1a with
diphenylzinc proceeded at 08C in the presence of FeCl3 and
L3 and afforded 3a in 95% yield (Table 1, entry 9). The
ligand with difluorophenyl groups L4 was slightly less
effective and the one with trifluorophenyl groups L5 slowed
down the reaction and inversed the carbometalation/ring-
opening selectivity (Table 1, entries 10 and 11). Furthermore,
(R)-2,2’-bis(diphenylphosphino)-1,1’-binaphthyl [(R)-binap],
which was effective in the enantioselective carbozincation of
cyclopropenone acetals,[4a] promoted the ring-opening reac-
tion to obtain 4a, but unfortunately, in a racemic form
(Table 1, entry 12).
The scope of the present iron-catalyzed carbometalation
is summarized in Table 2. Treatment of 1 with 1.5 equivalents
of diarylzinc reagents were typically performed at 08C in the
presence of FeCl3 (1 mol%) and L3 (2 mol%). A range of
oxabicyclic alkenes bearing fluoro groups (1b; Table 2,
entry 2) and methoxy groups (1c and 1d; Table 2, entries 3
and 4) reacted smoothly and gave the arylated products 3b–
3d in excellent yield. Electron-rich (Table 2, entries 5–7) and
electron-deficient (Table 2, entries 8–10) arylzinc reagents as
well as a heteroarylzinc reagents (Table 2, entry 11), can
Scheme 3. Electrophilic trapping of carbozincation product 2a.[18] Reac-
tion conditions: a) the same procedure as described in Table 1
(Y=Ph); b) the same procedure as (a) but using PhZnCH2SiMe3
instead of PhZn (Y=CH2SiMe3); c) CD3COOD; d) I2; e) allyl bromide,
cat. CuBr·SMe2; f) MeCOCl, CuBr, CuBr·SMe2.
confirmed by the fact that both bridgehead protons of 5a
were observed as a pair of singlets in the 1H NMR spectrum.
1
This observation is consistent with the fact that no H–1H
coupling was generally observed between bridgehead protons
and vicinal endo protons in similar heterobicyclic com-
pounds.[10b,d,e] Other electrophiles such as iodine, allyl bro-
mide, and acetyl chloride worked well and gave the corre-
sponding products 5b–5d in 91%, 93%, and 77% yield,
respectively, with good cis selectivity. Notably, the use of
ArZnCH2SiMe3 for the generation of 2a (Y= CH2SiMe3) was
essential to trap 2a with acetyl chloride to obtain 5d in high
yield.
In summary, we have developed an iron-catalyzed, highly
diastereoselective carbometalation of various oxa- and aza-
Angew. Chem. Int. Ed. 2011, 50, 454 –457
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
455