Angewandte
Communications
Chemie
leads to a decrease of enantioselectivities (entries 3 and 14).
were carried out based on the proposed mechanism.[8e] In
Interestingly, both alkyl (entry 4) and aryl substitution
(entries 5–12) on the alkyne afford good yields and excellent
enantioselectivities. Moreover, the stereoelectronics of the
aryl substitution pattern has an interesting impact on the yield
and enantioselectivity. For example, the electron-donating
groups at the para position of aryl group were favorable for
both reactivity and enantioselectivity (entries 6 and 7),
whereas electron-withdrawing groups (such as COOMe) are
completely unreactive even at high temperature and with
prolonged reaction time (entry 8). Nevertheless, electron-
withdrawing groups at the meta position of aryl group provide
high yields and maintain the excellent enantioselectivities
(entries 9–11), whereas ortho substitution and disubstitution
was not tolerated and led to unexpected olefin isomerization
product (not shown) and lower enantioselectivity (entry 12),
respectively. Interestingly, RhI-DuanPhos performs better
than RhI-TangPhos for 2d, 2l, 2m and 2o (entries 3, 11, 12,
14), which suggest that the latter system was sensitive to the
stereoelectronic nature of the substrates. In addition, all the
carbon, oxygen and nitrogen-tethered functionalized alkyne
substrates provided excellent enantiocontrol (entries 13, 16
and 17), which might partially attribute to chelation control
through the coordination of rhodium to the carbonyl group.[15]
Whereas, the use of oxygen-bridged 1,6-enyne that has
a phenyl group in alkyne position leads to significantly
lower enantioselectivity (entry 15). Overall, substituted
alkynes significantly decrease the reactivity but improve
enantioselectivity, which contrasts the impact of substituents
on the alkene moiety that exert favorable effect on reactivity
but decrease enantioselectivity.
these theoretical results, the reaction pathway starts with
tetra-coordinated square planar RhI-diphosphine enyne com-
plexes 1B1 and 1T1 (S-BINAP in 1B1, S,S,R,R-TangPhos in
1T1, Scheme 1). From these square planar RhI complexes, the
Scheme 1. Reaction pathways for RhI-catalyzed cycloisomerization.
oxidative cyclization of 1,6-enynes occurs through transition
states, TS1-2B1 and TS1-2T1 to give the key intermediates, RhIII-
metallacyclopentene 2B1 and 2T1. During this process, the
methyl group on the terminal carbon of olefin gets closer to
metal center and the steric effect between this methyl group
and the substitutes on phosphine ligand increases accordingly,
thus the transition states are distorted to be semi-tetrahedron
coordinated. From 2B1 and 2T1, a b-H elimination and
reductive elimination occur fast with small reaction barriers.
At last, the ligand transfer happens to yield the product and
regenerate 1B1 and 1T1. It is obvious that the oxidative
cyclization process in the reaction pathways in Scheme 1 is the
rate determining step because this step has higher barrier than
the other steps from the energy analysis. However TS1-2T1 is
more relatively stable than TS1-2B1, showing that the cyclo-
isomerization of (E)-1,6-enyne can be catalyzed by RhI-
Tangphos rather than RhI-BINAP. At the same time, this
reaction step defines the enantioselectivity of the product
because other oxidative cyclization modes which give R-
isomer have higher barriers than the oxidative cyclization
steps in Scheme 1 (Figures S30 and S33 in SI). It is aso
revealed that TS1-2B1 is relatively more unstable than TS1-2B3
where (Z)-1,6-enyne is involved (Figure S31 in SI), while TS1-
Encouraged by these interesting results among (E)-1,6-
enyne, we then tried to testify whether (Z)-1,6-enynes are also
applicable under the optimized reaction condition. Interest-
ingly, both RhI-TangPhos and RhI-DuanPhos exhibited com-
parable reactivity and enantioselectivity to that of RhI-
BINAP[8] for the (Z)-1,6-enyne 3 (Table 3, entries A and B).
Additionally, RhI-TangPhos was also proved effective for the
mixture of (E)-1,6-enyne 1a and (Z)-1,6-enyne 3, albeit with
a slight decreace of enantioselectivity (entry C).
To gain more insights into the essence that why RhI-
TangPhos performs better than RhI-BINAP for the cyclo-
isomerization reaction of (E)-1,6-enynes, DFT calculations
Table 3: RhI-catalyzed cycloisomerization of (Z)-1,6-enynes.[a]
Entry
Ratio
Yield [%][b]
ee [%][c]
has comparable relative energy to TS1-2T3 where cis-1,6-
1a:3
2T1
enyne is involved (Figure S34 in SI). These results are
consistent with the experimental observation that RhI-
BINAP can catalyze the cycloisomerization reaction of (Z)-
1,6-enynes, but not (E)-1,6-enynes. However, RhI-TangPhos
works both for (E)- and (Z)-1,6-enynes.
A
0:1
0:1
1:1
61
65
81
99
À98
86
B[d]
C
[a] Reactions were run with substrates (0.1 mmol) in the presence of
5 mol% [{Rh(L5)(COD)}BF4] in degassed 1,2-dicholoroethane at 258C
for 0.25–1 h. [b] Isolated yields. [c] Determined by HPLC using a chiral
stationary phase. [d] [{Rh(L4)(NBD)}BF4] was used as the catalyst.
In order to gain insight into the catalytic ability of these
two catalysts towards (E)-1,6-enynes, we analyze the struc-
Angew. Chem. Int. Ed. 2016, 55, 6295 –6299
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Deng, Xu
