Table 2: (Continued)
Experimental Section
General procedure for the iridium-cata-
lyzed enantioselective allylic alkylation:
Entry
Substr.
X
Conds.
Prod.
Yield
[%][a]
ee
[mol%]
[%][b]
A flame-dried Schlenk tube was cooled
to RT and filled with argon. {[Ir-
(cod)Cl}2], phosphoramidite ligand L2,
THF, and propylamine were then added
11
1k
4
B
95
93[d]
to this flask. The reaction mixture was
heated at 508C for 30 min and then the
volatile solvents were removed in vacuo
to give a pale yellow solid. After that,
allylic carbonate 1 (0.20 mmol, dissolved
in THF or 1,4-dioxane) and lithium
[a] Yield of isolated product. [b] Determined by HPLC on a chiral stationary phase. [c] The results in the
parentheses were obtained for a 1 mmol reaction scale. [d] d.r. 11:1, for the minor diastereoisomer,
80% ee. Ts=4-toluenesulfonyl.
carbonate (29.6 mg, 0.40 mmol) were
added. The reaction mixture was stirred
cyclohexadienone products, thus forming the six-member
spiro ring in good yields with excellent ee (60–68% yields, 91–
96% ee; Table 2, entries 1 and 2). Formation of the six-
membered ring also proceeded smoothly starting from the
2,6-diisopropylphenol-derived substrate 1c (65% yield,
89% ee; Table 2, entry 3). The NTs linked five-member-ring
formation was also achieved in good to excellent yields and
ee values for substrates 1d–e (65–92% yields, 88–95% ee;
Table 2, entries 4 and 5). The reaction proceeded smoothly for
the carbocyclic ring formation. Good to excellent yields and
excellent ee values were obtained for the allylic dearomatiza-
tion reaction of 1 f–j, varying substituents on 2,6-positions of
the phenol and ester groups in the substrates (75–95% yields,
85–97% ee; Table 2, entries 6–10). Notably, when substrate
1k was used, two stereogenic centers were generated.
Fortunately, the asymmetric allylic dearomatization of 1k
led to the product in 95% yield and 11:1 d.r. (93% ee and
80% ee, respectively; Table 2, entry 11,).
for 24 h at 508C. Then, the crude reaction mixture was filtrated
through celite and washed with EtOAc. The solvent was then
removed under reduced pressure, and the resulting residue was
purified by column chromatography on silica gel (eluents: petroleum
ether/ethyl acetate 6:1 to 2:1) to afford the desired product 2.
Received: January 11, 2011
Revised: February 23, 2011
Published online: April 7, 2011
Keywords: allylic dearomatization · hexadienones · iridium ·
phenols · spiro compounds
.
C. A. Sꢁnchez, G. R. Gꢀmez, Chem. Rev. 2007, 107, 1580; e) S.
[2] Selected examples for diastereoselective dearomatization: a) J.
The absolute configuration of the dearomatization prod-
ucts was assigned by comparison with literature report.[11,12]
The stereocontrol of the allylic dearomatization reaction is
also in accord with the general rule for the iridium-catalytic
system (Scheme 2).[5b–d]
[3] Selected examples: a) R. Imbos, A. J. Minnaard, B. L. Feringa, J.
128, 2552; d) N. T. Vo, R. D. M. Pace, F. OꢃHar, M. J. Gaunt, J.
[4] Selected examples: a) M. Takamura, K. Funabashi, M. Kanai, M.
10784; c) E. Ichikawa, M. Suzuki, K. Yabu, M. Albert, M. Kanai,
S.-G. Kim, C. J. Sinz, W.-J. Xiao, D. W. C. MacMillan, Proc. Natl.
Marguerit, K. Bathany, A. Ozanne-Beaudenon, T. Buffeteau, D.
S. L. Buchwald, J. Am. Chem. Soc. 2009, 131, 6676; i) S. Jones, B.
5841; k) J. Qi, A. B. Beeler, Q. Zhang, J. A. Porco, Jr., J. Am.
Scheme 2. Plausible working model.
In summary, we have developed the first iridium-cata-
lyzed intramolecular asymmetric allylic dearomatization
reaction of phenols. The reaction provides facile access to
enantioenriched, substituted spirocyclohexadienone deriva-
tives with up to 97% ee. Further extension of the reaction
scope and investigation of applications for the spiro-
cyclohexadienone products are currently underway.
Angew. Chem. Int. Ed. 2011, 50, 4455 –4458
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4457