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enantioselectivity of 98% ee with 96% yield was attainable in
the current model, despite a prolonged reaction time.
cation, Krapcho dealkoxycarbonylation, and AlCl3-mediated
trans-tert-butylation has been illustrated for de-tert-butyla-
tion[18] of the addition product 3aa (Scheme 2), thus affording
the de-tert-butylated phenol 5 in 58% yield over three steps
To evaluate the scope and limitations of this asymmetric
methodology, various chemically stable p-QMs (1a–p) in the
presence of the matching donor 2a were subsequently
subjected to the above optimized reaction conditions
(Table 3). In most cases, this reaction proceeded smoothly
with excellent enantioselectivity and in high yield. For
Table 3: Generality of asymmetric 1,6-conjugate addition/aromatization
of p-QMs.[a,b]
Scheme 2. De-tert-butylation and desilylation of diarylalkanes. a) KOH/
MeOH (0.1m), THF, RT, 99% yield; b) NaI, H2O, DMSO, 1608C, 70%
yield; c) AlCl3, benzene, 608C, 85% yield, 98% ee; d) CF3CO2H, CCl4,
RT, 86% yield, 98% ee; e) ICl, CH2Cl2, RT, 80% yield, 97% ee.
DMSO=dimethylsulfoxide, THF=tetrahydrofuran.
without erosion of optical purity. To expand the generality of
this method, the C7-alkyl-substituted p-QMs 1j (R1 = R2 =
tBu, R1’’ = H, R3 = Me) and 1k (R1 = R2 = R3 = tBu, R1’’ = H)
were also examined (Table 3). Compared with the result for
the product 3ja (2 h, 95% yield and 89% ee), the steric bulk
of the tert-butyl group on C7 of 1k obviously slowed this 1,6-
conjugate addition (72 h, 33% yield) despite the excellent
stereocontrol for 3ka (98% ee).
In addition to the above investigation on the influence of
the substituents at C7, the p-QMs 1l–p (R3 = Ph; R1,R2 =
alkyl, aryl, silyl; Table 3) bearing non-tert-butyl substituents
at C2 and C6 were also probed for this asymmetric catalytic
1,6-conjugate addition. In comparison with the aforemen-
tioned ee value and yield of 3aa obtained from 1a, the less
bulky substituents at C2 and C6 of 1l (R1 = R2 = Me, R1’’ = H,
R3 = Ph) and 1m (R1 = R2 = iPr, R1’’ = H, R3 = Ph) may
account for an increased reaction rate, thus giving the
analogous enantioselectivities and yields for 3la and 3ma.
When using the p-QM 1n (R1 = R2 = R3 = Ph, R1’’ = H) with
the sp2-hybridized phenyl substituent located at C2 and C6,
the reactivity was maintained, but a decrease in enantiose-
lectivity was observed for the formation of 3na at À608C.
[a] Performed with 1a–p (0.05 mmol) and 2a (0.055 mmol) in the
presence of K2CO3 (0.15 mmol) and the catalyst 4d (0.0005 mmol) in
toluene (0.5 mL) at À408C. The yields refer to the isolated products, and
the ee values were determined by HPLC analysis using a chiral stationary
phase. [b] The absolute configuration of 3da was established by X-ray
crystallographic analysis, and accordingly the reaction enantioselectivity
in other cases was assigned by analogy. [c] Performed at À608C.
Importantly, because of the potential application in function-
2
À
alization and transformation reactions of the C(sp ) Si bond
example, while using the p-QMs 1a–i (R1 = R2 = tBu, R1’’ =
H, R3 = aryl) with a series of electron-neutral, electron-
deficient, or electron-rich aryls at C7, the diarylalkanes 3aa–
ia could be obtained in 97–99% ee and 80–96% yield, and the
absolute configuration of 3da was determined unambiguously
by X-ray crystallographic analysis.[17] Notably, as exemplified
for the formation of 3aa, the present asymmetric 1,6-
conjugate addition/aromatization of p-QMs can be carried
out on gram scale (90% yield, 98% ee). In such examples, the
bulky tert-butyl group, which is often used as a positional
protective group for access to many aromatic compounds in
organic synthesis,[18] was preinstalled in the starting p-QMs
because of the requirement of their chemical stabilization.
Notably, a three-step protocol consisting of the transesterifi-
in organic synthesis,[19] the bis(silyl)-substituted p-QM 1o
(R1 = R2 = Me3Si, R1’’ = H, R3 = Ph) was designed and exam-
ined in this reaction. Interestingly this addition proceeded
quickly, and the desired product 3oa was afforded with 98%
ee in 94% yield. Further treatment of 3oa with CF3CO2H and
ICl gave the ipso-protodesilylated phenol 6 and ipso-iodode-
silylated phenol 7, respectively, in good yields without
noticeable loss of the ee value (Scheme 2). Moreover, 1p
(R1 + R1’’ = 1,3-butadiene-1,4-diyl, R2 = H, R3 = Ph) with sub-
stituents at C2 and C3 was also considered in this case, but
disappointingly a modest enantioselectivity of 40% ee for 3pa
was achieved (Table 3).
To further understand the influence of the stereochemis-
try of exocyclic methylene substituents of p-QMs on the
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ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
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