Organic Letters
Letter
a
Table 3. Scope of Substrates Containing Acyclic Alkenes
Scheme 2. Synthetic Transformations of Cyclopentadienyl
Benzoate 6a
conditions, affording cyclopentenone 6h′ in a much improved
61% yield and with a slightly lower ee (87%). For cycloheptene
substrate 4i, cyclopentadienyl ester 6i was unstable. As such,
the hydrolytic conditions in entry 5 of Table 1 were employed
to afford 5,7-fused enone 6i′ in 84% yield (entry 8). However,
the ee value is moderate, which may be due to a relatively slow
cyclization of the bent allene intermediate of type C and hence
its increased level of racemization8a or conversion to achiral
pentadienyl cations of type A.
To further explore the reaction scope, we turned our
attention to substrates featuring acyclic CC bonds for the
synthesis of chiral cyclopentadienyl esters without ring fusion.
As shown in Table 3, under the optimized conditions, these
reactions proceeded smoothly, affording the tetrasubstituted
cyclopentadienes in good to excellent yields and with excellent
enantiomeric excesses (entries 1−7). Electron-withdrawing
groups on the substrate phenyl ring (entries 6 and 7) are
tolerated, albeit in lower yet serviceable yields. Under the
standard conditions, the reaction of 4q resulted in a
complicated mixture, which is attributed to 1,5-hydride shifts
of the cyclopentadiene moiety. When 4q was subjected to the
hydrolytic conditions, to our surprise, the cyclopentenone
product 6q′ barely exhibits any ee. This result indicates the
steric hindrance offered by the R1 group is essential for
hindering the formation of the corresponding achiral
pentadienyl cation and/or the allene racemization.
To demonstrate the synthetic utilities of this chemistry, we
carried out a scale-up synthesis of 6a (Scheme 2). Hence, with
only 1 mol % catalyst loading, 0.51 g of the product of high
enantiomeric purity (94% ee) was isolated, although the
reaction required overnight and the yield was slightly
decreased due to the much lower catalyst loading. The
reactions of 6a were then pursued first with the isolated
material. For example, it underwent the Lewis acid-promoted
Diels−Alder reaction with methyl acrylate at −40 °C to deliver
bridged tricycle 7 in 84% yield while maintaining the ee value,
and its epoxidation by DMDO smoothly afforded the cis-fused
α′-hydroxycyclopentenone 8 upon hydrolytic workup. The
endo nature of the major isomer of 7 is confirmed by two-
dimensional NMR studies. One-pot processes without the
isolation of 6a were also demonstrated. For example, the
Diels−Alder reaction with N-phenylmaleimide smoothly
a
Reaction conditions: 5 mol % tBuBrettPhosAuCl, 5 mol % NaBARF,
b
0.2 mmol 4 (0.05 M in toluene), rt, 3 h. With 5% tBuBrettPhosAuCl,
10% AgSbF6, and wet DCM applied.
chloride abstractor, the undesired hydrolysis was completely
shut down, and 6a was formed in 91% yield while maintaining
the excellent ee value (entry 13). Similar phenomena were
detected with PhCF3 or DCM as the solvent, albeit the yields
were slightly lower (entry 14 or 15, respectively).
With the optimized reaction conditions in hand, we first
probed the reaction scope by varying the n-pentyl group of 4a.
As shown in Table 2, the sterically more demanding cyclohexyl
(entry 1), a methyl (entry 2), a benzyl (entry 3), and an
oxygenated alkyl group (entry 4) are all readily accommodated,
and the cyclopentadienyl esters were isolated in good to
excellent yields and with ≥92% ee. Incorporation of a
heteroatom such as O (entry 5) and N (entry 6) in the
cyclohexene ring led to lower yields, but the chirality transfer
remained efficient. When 4h contained a dihydronaphthalene
ring as the substrate, the reaction was quite slow under
standard conditions (entry 7). It was accelerated at 60 °C. Due
to the contamination of side products, the cyclopentadienyl
ester product was subsequently hydrolyzed under acidic
C
Org. Lett. XXXX, XXX, XXX−XXX
Zhao, Ke
