attack of oxodiene 2 from bottom face. To avoid the steric
hindrance between the R2 group of oxodiene and (Z)-B (not
shown), oxodiene would approach the re face. As a result,
product 3m is forced to adopt the S configuration. According
to this plausible reaction model, the same sense of asymmetric
induction is believed to be in operation for 3a–3l. Although
the mechanistic hypothesis of the interaction between the
oxygen atom of the ester group and ammonium in inter-
mediate B is not solid evidence, it does account for the
observed stereochemical outcome, including E/Z selectivity
and enantioselectivity. The exact catalytic mechanism still
needs more investigations.
In summary, we have reported the asymmetric
[4+2] annulations of allenoate with oxodienes using commer-
cially available cinchona catalysts. This reaction protocol
provides a facile entry to substituted 2H-pyrans 3 with good to
excellent enantiomeric excess. Notably, both enantiomeric
products can be readily obtained simply through switching the
catalyst and reaction solvent. One limitation of the method,
however, is the prerequisite cyano substituent in oxodiene 2.
This substituent acts as a strong electron-withdrawing group
to match the reactivity of zwitterionic intermediate B.
Presumably, the interaction of the ester group and the
aminium in zwitterions B is essential for the desired
stereochemical outcome. Further investigations of the reac-
tion mechanism and synthetic transformation are currently
underway.
Scheme 3. Elucidation of E/Z selectivity in 3a. Py=pyridine.
conformation might be further consolidated with the forma-
tion of enolate D1 (short distance between the a hydrogen
and the b oxygen) (Scheme 3), whose stereochemical
arrangement enables 3a to be produced with E selectivity
via elimination of amine catalyst. In the cases of pyridine and
quinoline, however, the positive charge of ammonium in B
might be weakened by the delocalization effects of its
attached aromatic ring, so is the oxygen–ammonium electro-
static interaction mentioned above. Thus, the steric hindrance Experimental Section
General procedure: A mixture of oxodiene 2a (0.3 mmol) and QN-
between the pyridyl ring and the ester group in B might
become the dominating factor, which mainly leads to the (E)-
B form (long distance between the a hydrogen and the
b oxygen; Scheme 3). Consequently, enolate D2 would be
formed, which is responsible for the formation of (Z)-3a.[17]
After establishing the mechanism for the observed
E/Z selectivity in 3a, we then focused on the enantioselec-
tivity. The absolute configuration of 3m was determined to be
S by X-ray crystal structure analysis (see the Supporting
Information).[18] The observed enantioselectivity can be
explained by the proposed reaction model shown in
Scheme 4.[19] In the process of CA catalysis, we believe that
the quinoline moiety in the catalyst might play a dual steric
role in the asymmetric induction. One is to push the ester
group of (Z)-B to its opposite side, thus rendering intermedi-
ate (Z)-B to adopt the arrangement as depicted in Scheme 4.
The other is to shield the upper face of (Z)-B, thus guiding the
OMe (20.2 mg, 20 mol%) was introduced into a Schlenk tube
(25 mL) containing toluene (4 mL) and stirred at ꢀ308C. To this
reaction mixture, a solution of allenoate 1 (0.6 mmol, 2.0 equiv) in
toluene (4 mL) was slowly added over 20 min. After 36 h, the mixture
was warmed to RT and then directly subjected to column chromatog-
raphy on silica gel (petroleum ether/EtOAc 10:1!5:1 gradient) to
give the product 3a as slight yellow solid (86.4 mg, 70% yield,
m.p 105–1088C). 1H NMR (400 MHz, CDCl3): d = 7.88 (d, J = 6.8 Hz,
2H), 7.55–7.47 (m, 3H),7.39–7.26 (m, 10H), 5.89 (s, 1H), 5.14 (d, J =
12.8 Hz, 1H), 5.09 (d, J = 12.8 Hz, 1H), 3.96 (t, J = 6.0 Hz, 1H), 3.86
(dd, J = 15.6 Hz, J = 6.0 Hz, 1H), 3.31 ppm (dd, J = 15.6 Hz, J =
6.0 Hz, 1H). 13C NMR (100 MHz, CDCl3): d = 165.9, 163.2, 161.3,
139.4, 135.8, 131.4, 131.1, 129.0, 128.6, 128.5, 128.2, 128.0, 127.9, 127.2,
118.2, 102.7, 89.9, 66.0, 38.5, 29.5 ppm. HRMS (EI) calcd for
26
C27H21NO3 407.1521, found 407.1525. ½aꢁD ¼ + 103.3 degcm3 gꢀ1 dmA1
(c = 2.21 gcmꢀ3 in CHCl3); 90% ee (HPLC on a chiral stationary
phase using a Chiralcel AD-H column, n-hexane/isopropanol = 90:10,
0.9 mLminꢀ1, lmax 254 nm, tR = 15.8 min and 26.7 min).
Received: February 7, 2011
Published online: April 26, 2011
Keywords: [4+2] annulations · allenoates· asymmetric catalysis·
.
cinchona catalysts · organocatalysis
Scheme 4. Plausible reaction model.
Angew. Chem. Int. Ed. 2011, 50, 5361 –5364
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5363