.
Angewandte
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similar regio- and diastereoselectivity (entry 4). Other allylic
bromide substrates bearing tosylamides were also suitable for
this process and gave the products 2e–g in good yields
(
entries 5–7). Replacement of the terminal methyl group with
a pentyl group produced 1h in a moderate yield (entry 8). In
addition, the substrates 1i–k, containing a phthalimide group,
exhibited high reactivity and regioselectivity in this trans-
formation (entries 9–11). The substrate 1l with a benzyl group
at the terminal carbon atom afforded the fluorination product
2
l in 45% yield, combined with a dehydrofluorination side
product (entry 12). Further studies indicated that other
functional groups, such as a ketone (1m), oxime ether (1n),
and ester (1o), were also compatible under the reaction
conditions to give fluorination products in high regioselectiv-
ity (entries 13–15). However, the substrate 1p having an
allylic ester was not compatible with the reaction conditions
because of its instability. The yield was slightly increased to
3
3% when 1 equivalent of CuBr was used (entry 16). Finally,
the allylbromide substrate 1q, which lacks a heteroatom-
containing functional group, did not show any reactivity
under the standard reaction conditions, even at higher
temperature (entry 17).
Fluorination of allylic chlorides was also conducted, and
we found that this type of substrate presented similar regio-
and diastereoselectivity, but slightly lower reactivity (Table 2,
entries 18–20). For instance, the substrates 1r–t could be
smoothly transformed into the desired products in moderate
yields under modified reaction conditions (elevated reaction
temperature of 508C and a catalyst loading of 30 mol%).
Compared to the allylbromide substrate 1o, the reaction of 1t
gave a small amount of regioisomer, which possibly resulted
from the slightly higher reaction temperature (entry 20). It is
worth noting that most of substrates having functional groups
exhibited excellent reactivities and regioselectivities, but
III
These observations indicate that either a p-allyl/Cu com-
[17]
plex or an allylic carbon cationic intermediate might be
involved in the CÀF bond formation. However, addition of
carbon cationic scavengers did not influence the reaction
[
18]
yields. Furthermore, compared to the 1:1 d.r. value in direct
substitution fluorination of 1a by AgF (Table 1, entry 5), an
improved diastereoselectivity (4–5:1) was observed in the
copper-catalyzed fluorination. The above data suggests that
an allylic fluorination process involving a carbon cationic
species is unlikely.
Additionally, the necessity of a functional group in the
substrate for the success of the allylic fluorination indicates
that precoordination of the functional group and the cop-
per(I) catalyst plays an important role. Notably, instead of
a simple CuBr catalyst, the ligated copper catalyst (Phen)-
CuBr exhibited low reactivity (for 1i), and the four-coordi-
[16]
there is a limitation when it comes to internal allylic halides.
Interestingly, treatment of the mixture of regioisomers 1u
and 1u’ under the standard reaction conditions afforded the
single isomer 2i in 65% yield [Eq. (1)]. For the mixture of
isomers 1v and 1v’, having one more carbon atom on the
carbon chain, the reaction also proceeded smoothly to give
the fluorinated product 2v in moderate yield, but with a small
amount of the regioisomer 2v’ [Eq. (2)]. For the homoallylic
ester substrate, the mixture of 1w and 1w’ also exhibited
similar reactivity to afford the two isomers 2w and 2w’,
respectively, but with a slightly diminished regioselectivity
nated copper catalyst (Phen)CuBr·PPh gave an inferior yield
3
[
Eq. (3)]. The decreased regioselectivity might be attributed
[Eq. (4)]. These results verified that the introduction of
to longer carbon chain separating the coordination site and
the reactive center, thus weakening the coordination between
the heteroatom and copper. Furthermore, the low regiose-
lectivity of the substrate 1w under standard reaction con-
ditions might also result from weaker coordination of the
ester and the copper(I) compared to the imide coordination
for substrate 1v.
Although the mechanistic details of this transformation
are not clear at the moment, preliminary observations provide
some insight to this transformation. First, the reactions of the
isomers 1a and 1d afforded the same product 2a with similar
reactivity and selectivity (Table 2, entries 1 versus 4). The
mixture of 1u and 1u’ gave the single isomer 2i [Eq (1)].
a ligand possibly reduces the precoordination of the substrate
with the copper catalyst, and results in lower reactivity.
Finally, the mixture of Et N·3HF and CuBr did not
3
19]
[
provide a new fluorine signal, thus suggesting that a CuF
4
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!
Zhang, Zuxiao
