Catalytic asymmetric synthesis of 2-alkyleneoxetanes through [2+2] annulation of allenoates with trifluoromethyl ketones

Article abstract of DOI:10.1002/adsc.201200237

The first example of a β-isocupreidine (β-ICD)-catalyzed highly enantioselective [2+2] annulation of allenoates with trifluoromethyl ketones has been disclosed, allowing the synthesis of optically active 2-alkyleneoxetanes in moderate to good yields along with good to high enantioselectivities and high diastereoselectivities. Further transformations of the cycloadducts have been also disclosed to afford biologically interesting 6-trifluoromethyl-5,6- dihydropyran-2-ones and trifluoromethyl β-keto acids in good yields. Copyright

Full text of DOI:10.1002/adsc.201200237

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DOI: 10.1002/adsc.201200237
Catalytic Asymmetric Synthesis of 2-Alkyleneoxetanes through
[2+2]Annulation of Allenoates with Trifluoromethyl Ketones
Qian-Yi Zhao,a Long Huang,a Yin Wei,b,* and Min Shia,b,*
a
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering,
East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, Peopleꢀs Republic of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, 354 Fenglin Lu, Shanghai 200032, Peopleꢀs Republic of China
E-mail: Mshi@mail.sioc.ac.cn
Received: March 7, 2012; Revised: March 20, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200237.
Abstract: The first example of a b-isocupreidine (b-
ICD)-catalyzed highly enantioselective [2+2]annu-
lation of allenoates with trifluoromethyl ketones
has been disclosed, allowing the synthesis of opti-
cally active 2-alkyleneoxetanes in moderate to good
yields along with good to high enantioselectivities
and high diastereoselectivities. Further transforma-
tions of the cycloadducts have been also disclosed
to afford biologically interesting 6-trifluoromethyl-
5,6-dihydropyran-2-ones and trifluoromethyl b-keto
acids in good yields.
amides,[7,8] we became interested in examining the re-
action of allenoates with trifluoromethyl ketones in
the presence of a chiral tertiary amine catalyst.
Herein, we report the first example of the catalytic
enantioselective [2+2]cycloaddition between allen-
AHCTUNGTREGoNNUN ates and trifluoromethyl ketones to give enantioen-
riched 2-alkyleneoxetanes in good yields and good to
high ee values.
We initiated our studies by examining the reaction
of allenoate 1a and trifluoromethylketone 2a in the
presence of various nitrogen-containing chiral organo-
catalysts (20 mol%) (Figure 1) in THF (Table 1).
First, quinidine, quinine and cinchonine were used as
the catalysts in this [2+2]cycloaddition reaction of 1a
with 2a in THF at 08C for 2 days, but unfortunately,
no product was observed and nearly all the starting
materials were recovered (Table 1, entries 1–3). Using
LB1 as the catalyst afforded E-oxetane 3aa[9a] in 25%
yield along with 21% ee in THF at 08C for 3 days
Keywords: allenoates; 5,6-dihydropyran-2-ones;
enantioselective [2+2]annulation; b-isocupreidine;
b-keto acids; oxetanes; trifluoromethyl ketones
Chiral oxetanes represent important motifs in (Table 1, entry 4). Gratifyingly, it was found that b-
a number of natural products and biologically active isocupreidine (b-ICD) was the more effective catalyst
compounds.[1] However, in contrast to their homolo- in this reaction, giving 3aa in 85% yield and 68% ee
gous heterocycles, such as oxiranes,[2] tetrahydrofur- within 2 days (Table 1, entry 5). Catalyst LB2 synthe-
ans[3] and tetrahydropyrans,[4] the synthetic ap- sized from b-ICD by protecting the OH group with
proaches to enantiomerically enriched oxetanes are tert-butylACTHUNRTGNE(GNU diphenyl)chlorosilane (TBDPSCl) could not
few in number and generally require multistep pro- catalyze this reaction under the standard conditions,
cesses.[1,5] Among the different synthetic routes, the suggesting that the C-6’-OH group of b-ICD is very
formal [2+2] cycloaddition[5c,d,6] is certainly one of the critical for the reaction (Table 1, entry 6). Another
most powerful methods for the construction of the Cinchona alkaloid-derived catalyst LB3 was also ex-
strained four-membered ring.
amined in this reaction, affording 3aa in 48% yield
Recently, an elegant synthesis of 2-alkyleneoxe- and 37% ee within 3 days (Table 1, entry 7). Next,
tanes involving a new DABCO-catalyzed regioselec- a solvent screening using b-ICD (20 mol%) as the cat-
tive [2+2]cycloaddition of trifluoromethyl ketones alyst disclosed that solvents such as toluene, CH2Cl2,
with allenoates was described by Ye[6a] and Miller.[6b] CH3CN and Et2O were not suitable media for this re-
While the synthetic potential of this transformation is action, affording merely traces of product (Table 1,
self-evident, its enantioselective version remains, to entries 8–11). Employing allenoates 1b and 1c with
the best of our knowledge, unknown to date. In con- more sterically bulky substituents, 3ba was obtained
nection with our ongoing project that deals with the in higher yield (90%) but with lower enantiomeric
catalytic potential of the Cinchona alkaloid-derived excess (31% ee) for allenoate 1b bearing a tert-butyl
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Figure 1. Screening of chiral nitrogen-containing catalysts for the asymmetric [2+2]cycloaddition.
Table 1. Optimization of the reaction conditions in the asymmetric [2+2]cycloaddition of 1 with 2a.[a]
[a]
The reaction was carried out on a 0.1-mmol scale, and the ratio of 1/2a was 1.0/2.0.
Isolated yield of E-3 with E:Z>20:1.
Determined by chiral HPLC.
The catalyst loading was 10 mol%.
The catalyst loading was 40 mol%.
NP=no product.
[b]
[c]
[d]
[e]
[f]
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Catalytic Asymmetric Synthesis of 2-Alkyleneoxetanes through [2+2]Annulation of Allenoates
Table 2. Additives screening for asymmetric [2+2]cycload-
dition of 1c with 2a.[a]
Table 3. Substrate scope of the asymmetric [2+2]cycloaddi-
tion of allenoates 1 with various trifluoromethyl ketones 2
catalyzed by b-ICD.[a]
[a]
The reaction was carried out on a 0.1-mmol scale, and
the ratio of 1c/2a was 1.0/2.0.
isolated yield of E-3ca with E:Z>20:1.
Determined by chiral HPLC.
[b]
[c]
ester group (Table 1, entry 12), while 3ca was ob-
tained with good yield (85% yield) and higher enan-
tiomeric excess (72% ee) for allenoate 1c bearing
a benzyl ester group (Table 1, entry 13), suggesting
that allenoate 1c is the optimal substrate for this reac-
tion. Further screening of temperatures and catalyst
loadings (Table 1, entries 14–19) revealed that carry-
ing out the reaction in the presence of 20 mol% b-
ICD in THF at À158C for 6 days represented the op-
[a]
The reaction was carried out on a 0.1-mmol scale, and
the ratio of 1/2 was 1.0/2.0.
Isolated yields E-3 with E:Z>20:1.
Determined by chiral HPLC.
The reactions were carried out at 08C for 7 days.
NP=no product.
[b]
[c]
[d]
[e]
timal reaction conditions, affording the desired prod- pleased to find that the ee value of 3ca was increased
uct E-oxetane 3ca[9b] in 80% yield with 80% ee value from 83% to 96% also along with good yields
(Table 1, entry 17).
(Table 2, entries 7 and 8). Moreover, other additives
The original optimal reaction conditions described such as phenol, benzoic acid and aniline were also
above are obviously not adequate for the asymmetric tested, giving the corresponding [2+2]annulation
version of this [2+2] annulation reaction, thus addi- product 3ca in 0–65% yields with 77–80% ee values
tive effects were further investigated in this reaction (Table 2, entries 9–11). Therefore, the best reaction
and the results are summarized in Table 2. Adding conditions have been identified as using 20 mol% of
0.2 equiv. methanol as the additive to the catalytic b-ICD as the catalyst, 10 equiv. H2O as the additive
system resulted in lower yield and ee value of 3ca and carrying out the reaction in THF at À158C for
(Table 2, entry 1). When employing other more steri- 6 days.
cally bulky alcohols such as diphenylmethanol, triphe-
nylmethanol, 2-naphthalenemethanol and 9-anthra- subsequently turned our attention to examine the sub-
ACHTUNGTRENNUNGcenemethanol as the additives, also no improvements strate scope of this interesting asymmetric [2+2]an-
With these optimal reaction conditions in hand, we
in the yield and ee value were observed (Table 2, en- nulation reaction with respect to a variety of trifluoro-
tries 2–5). However, when we turned to examine the methyl ketones and allenoates. The results of these
additive effect of 1 equiv. water in this reaction, a tiny experiments are summarized in Table 3. As can be
increase of the ee value (from 80% to 83%) with the seen from Table 3, 2,2,2-trifluoroacetophenone 2a and
same yield (80%) as that without the addition of H2O a variety of trifluoromethyl ketones 2b–2j having
was observed in this reaction (Table 2, entry 6 vs. electron-rich or electron-poor aromatic groups as R2
Table 1, entry 17). Upon increasing the employed or trifluoromethyl ketone 2k bearing a heteroaromatic
amount of water to 5 equiv. and 10 equiv., we were group such as 2-thienyl as R2 could react with elec-
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Scheme 1. Further transformations of the obtained [2+2]annulation products 3ch and 3ca.
tron-deficient allene 1c smoothly to give the corre- pounds which possess potent biological activities,[11,12]
sponding [2+2]cycloaddition products 3ca–3ck in and in view of the wide application of fluorinated
moderate to good yields along with 90–95% enantio- compounds in pharmaceuticals, agrochemistry and
meric excesses (Table 3, entries 1–11). When R2 is an materials,[13] the 6-trifluoromethyl-5,6-dihydropyran-2-
alkyl group, such as pentyl, the corresponding [2+ one 5 synthesized from 2-alkyleneoxetane 3ch should
2]cycloaddition product 3cl was also obtained in 66% be useful in organic synthesis. The absolute configura-
yield and 72% ee value (Table 3, entry 12). Since [2+ tion of products 3 was unambiguously assigned as the
2]cycloaddition products 3aa and 3ba from the reac- S-configuration on the basis of the X-ray crystallo-
tion of 2a with ethyl buta-2,3-dienoate 1a and tert- graphic analysis of the transformation product 5 (see
butyl buta-2,3-dienoate 1b were obtained in low Figure S1 in the Supporting Information for the de-
yields under the standard conditions in this reaction; tails).[14] A plausible mechanism for the formation of
increasing the temperature to 08C and prolonging the product 5 from compound 4 is also outlined in the
reaction time to 7 days are required for the formation Supporting Information (see Scheme S1 in the Sup-
of 3aa and 3ba in 68–73% yields and 78–85% ee porting Information for the details).[15,16] Treatment of
values (Table 3, entries 13 and 14). In the case of pen- 3ca with Pd/C under H2 in THF for 24 h gave the
tafluoroethyl ketone 2m, the desired product was ob- ring-opened b-keto acid 6 quantitatively, which could
tained in similar yield, affording 3cm in 75% yield be further transformed to the desired amide 7 in 75%
and 85% ee (Table 3, entry 15). However, in the cases yield and 92% ee from the reaction with meta-bro-
of difluoromethylated ketone 2n and monofluorome- moaniline (2.0 equiv.) in the presence of EDCI
thylated ketone 2o, no [2+2]cycloaddition product (3.0 equiv.) and HOBt (4.0 equiv.) in DMF, suggesting
was provided under the standard conditions (Table 3, the hydrogenolysis of a benzylic bond with retention
entries 16 and 17).
of optical activity in this novel case [Scheme 1, Eq.
To illustrate the synthetic utility of the thus ob- (2)].
tained, optically active [2+2]cycloaddition product 3,
Mechanistically, the reaction of trifluoromethyl ke-
further transformations of 3ch and 3ca were per- tones 2 with allenoates 1 in the presence of a chiral
formed. As shown in Scheme 1, upon hydrogenation tertiary amine catalyst (b-ICD) can take place
of 3ch with Pd/C in THF for 5 h, the corresponding through the processes shown in Scheme 2.[6,17] The nu-
product 4 was produced in 92% yield,[10] which could cleophilic addition of b-ICD to allenoate 1 produces
be further transformed to the 6-trifluoromethyl-5,6-di- the enolate intermediate A, which is in resonance
hydropyran-2-one 5 in 61% yield with the ee value with the allylic carbanion A’. The g-addition of A’ to
being retained during the reaction with N-ethyl-N’-(3- trifluoromethyl ketone gives the a,b-unsaturated ester
dimethylaminopropyl)carbodiimide
hydrochloride B, which undergoes an intramolecular Michael addi-
(EDCI) (3.0 equiv.) and 1-hydroxy N-hydroxybenzo- tion to give the ring-closed zwitterion C. The elimina-
triazole (HOBt) (4.0 equiv.) in N,N-dimethylform- tion of catalyst from C affords the product and regen-
ACHTUNGTRENNUNGamide (DMF) [Scheme 1, Eq. (1)]. Since 5,6-dihydro- erates b-ICD. A possible transition state model D
pyran-2-ones (a,b-unsaturated d-lactones) are widely using b-ICD as the catalyst is also shown in Scheme 2.
present in a number of natural and unnatural com- We hypothesized that the trifluoromethyl ketone
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Catalytic Asymmetric Synthesis of 2-Alkyleneoxetanes through [2+2]Annulation of Allenoates
Scheme 2. A plausible catalytic cycle for the asymmetric [2+2]annulation.
would be activated by both C-6’-OH of b-ICD and necessary. Optical rotations were determined at 589 nm
(sodium D line) by using a Perkin–Elmer-341 MC digital po-
larimeter; [a]d values are given in units of 10 degÀ1 cm2 gÀ1.
Chiral HPLC was performed on a Shimadzu SPD-10 A vp
series with chiral columns [Chiralpak AD-H, OD-H, OJ-H,
AS-H and Phenomenex Lux 5m Cellulose-2 columns 4.6ꢂ
250 mm (Daicel Chemical Ind., Ltd.)]. Commercially ob-
tained reagents were used without further purification. All
these reactions were monitored by TLC with silica gel-
coated plates. Flash column chromatography was carried out
by using silica gel at increased pressure.
H2O through three hydrogen bonds, which could be
stabilized as a six-membered ring. Then the zwitterion
homoenolate may preferentially add to the trifluoro-
methyl ketone from the Re face in a pseudo-intramo-
lecular manner, thus leading to intermediate E, which
after cyclization and elimination events would provide
the S-oxetane 3.
In summary, we have developed the first asymmet-
ric organocatalytic formal [2+2]cycloaddition of tri-
fluoromethyl ketones and allenoates using b-isocu-
preidine (b-ICD) as a catalyst to afford S-configured
2-alkyleneoxetanes in moderate to good yields along
with good to high diastereoselectivities and enantiose-
lectivities. Furthermore, useful transformations of the
corresponding 2-alkyleneoxetanes have been also
demonstrated, which provide a straightforward ap-
proach to the optically active and biologically inter-
esting trifluoromethyldihydropyranone and ring-
opened trifluoromethyl b-keto acid.
General Procedure for b-ICD-Catalyzed
[2+2]Annulation of Allenoates 1 with
Trifluoromethyl Ketones 2
Allenoate
1
(0.1 mmol), trifluoromethyl ketone
2
(0.2 mmol), b-ICD (0.02 mmol), and THF (0.5 mL) were
added into a Schlenk tube. The reaction mixture was stirred
at À158C for 6 days, the solvent was removed under reduced
pressure, and the residue was purified by flash column chro-
matography (PE/EA=20/1~10/1).
General Procedure for the Synthesis of 4 and 5
Experimental Section
Compound 3ch (43 mg, 0.10 mmol) was stirred in anhydrous
tetrahydrofuran (5.0 mL) in the presence of 10% palladium
on carbon (11.0 mg) under an atmosphere of hydrogen for
5 h. After removal of the catalyst through Celite, the filtrate
was concentrated under reduced pressure and the crude
product was chromatographed on silica gel (elution with pe-
troleum ether/EtOAc=1:4) to give compound 4.
General Methods
1H and 13C NMR spectra were recorded at 400 and 100 MHz
or 300 and 75 MHz, respectively. Low- and high-resolution
mass spectra were recorded by the EI or ESI method. The
used organic solvents were dried by standard methods when
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Compound 4 (26 mg, 0.10 mmol) was added to a solution
of N-ethyl-N’-(3-dimethylaminopropyl)carbodiimide hydro-
chloride (EDCI) (58 mg, 0.30 mmol) and 1-hydroxybenzo-
triazole (HOBt) (54 mg, 0.40 mmol) in N,N-dimethylform-
Wuitschik, M. Rogers-Evans, K. Mꢃller, E. M. Carreira,
Angew. Chem. 2010, 122, 9236–9251; Angew. Chem. Int.
Ed. 2010, 49, 9052–9067.
[2] a) Y. Shi, Acc. Chem. Res. 2004, 37, 488–496; b) O. A.
Wong, Y. Shi, Chem. Rev. 2008, 108, 3958–3987.
ACHTUNGTRENNUNGamide (DMF) (2.0 mL). The resulted mixture was stirred for
24 h at room temperature. Then, the solvent was removed
from the flask under reduced pressure. The resulting residue
was diluted with EtOAc, washed with saturated NaCl solu-
tion twice, and extracted by EtOAc. The organic layer was
dried over anhydrous Na2SO4 and concentrated under re-
duced pressure. The residue was chromatographed on silica
gel (elution with petroleum ether/EtOAc=2:1) to give com-
pound 5.
[3] K. A. Jørgensen, Eur. J. Org. Chem. 2004, 2093–2102.
[4] a) K. A. Jørgensen, Angew. Chem. 2000, 112, 3702–
3733; Angew. Chem. Int. Ed. 2000, 39, 3558–3588;
b) T. G. Kilroy, T. P. OꢀSullivan, P. J. Guiry, Eur. J. Org.
Chem. 2005, 4929–4949.
[5] a) K. Soai, S. Niwa, T. Yamanoi, H. Hikima, M. Ishiza-
ki, J. Chem. Soc. Chem. Commun. 1986, 1018–1019;
b) T. Sone, G. Lu, S. Matsunaga, M. Shibasaki, Angew.
Chem. 2009, 121, 1705–1708; Angew. Chem. Int. Ed.
2009, 48, 1677–1680; c) K. Mikami, K. Aikawa, J. Aida,
Synlett 2011, 2719–2724; d) K. Aikawa, Y. Hioki, N.
Shimizu, K. Mikami, J. Am. Chem. Soc. 2011, 133,
20092–20095.
[6] a) T. Wang, X.-Y. Chen, S. Ye, Tetrahedron Lett. 2011,
52, 5488–5490; b) L. B. Saunders, S. J. Miller, ACS
Catal. 2011, 1, 1347–1350. For an N-heterocyclic car-
bene-catalyzed [2+2+2]annulation of allenoates with
trifluoromethyl ketones, please see: c) L. Sun, T. Wang,
S. Ye, Chin. J. Chem. 2012, 30, 190–194.
Supporting Information
Experimental procedures, chiral HPLC traces, and spectro-
scopic data for all new compounds, X-ray crystal structures
and CIF data for 5 are available in the Supporting Informa-
tion.
Acknowledgements
[7] a) M. Shi, Y.-M. Xu, Angew. Chem. 2002, 114, 4689–
4692; Angew. Chem. Int. Ed. 2002, 41, 4507–4510;
b) M. Shi, Y.-M. Xu, Y.-L. Shi, Chem. Eur. J. 2005, 11,
1794–1802; c) M. Shi, Z.-Y. Lei, M.-X. Zhao, J.-W. Shi,
Tetrahedron Lett. 2007, 48, 5743–5746; d) M. Shi, X.-G.
Liu, Org. Lett. 2008, 10, 1043–1046; e) X.-Y. Guan, Y.
Wei, M. Shi, Chem. Eur. J. 2010, 16, 13617–13621; f) X.-
Y. Guan, Y. Wei, M. Shi, Eur. J. Org. Chem. 2010,
4098–4105; g) Q.-Y. Zhao, C.-K. Pei, X.-Y. Guan, M.
Shi, Adv. Synth. Catal. 2011, 353, 1973–1979; h) C.-K.
Pei, X.-C. Zhang, M. Shi, Eur. J. Org. Chem. 2011,
4479–4484; i) C.-K. Pei, M. Shi, Tetrahedron: Asymme-
try 2011, 22, 1239–1248; j) L. Huang, Y. Wei, M. Shi,
Org. Biomol. Chem. 2012, 10, 1396–1405.
[8] For reviews and other selected examples on Cinchona
alkaloids-derived organocatalysts in asymmetric cataly-
sis, see: a) A. Ting, J. M. Goss, N. T. McDougal, S. E.
Schaus, Top. Curr. Chem. 2010, 291, 145–200; b) S.-K.
Tian, Y. Chen, J. Hang, L. Tang, P. McDaid, L. Deng,
Acc. Chem. Res. 2004, 37, 621–631; c) H. C. Kolb, M. S.
VanNieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94,
2483–2547; d) S. France, D. J. Guerin, S. J. Miller, T.
Letcka, Chem. Rev. 2003, 103, 2985–3012; e) D. Basa-
vaiah, A. J. Rao, T. Satyanarayana, Chem. Rev. 2003,
103, 811–892; f) M. J. OꢀDonnell, Acc. Chem. Res. 2004,
37, 506–517; g) H. B. Jang, J. W. Lee, C. E. Song, Cin-
chona Alkaloids in Synthesis and Catalysis 2009, 197–
247; h) L.-W. Xu, J. Luo, Y. Lu, Chem. Commun. 2009,
1807–1821; i) G. Masson, C. Housseman, J. Zhu,
Angew. Chem. 2007, 119, 4698–4712; Angew. Chem.
Int. Ed. 2007, 46, 4614–4628; j) N. Abermil, G. Masson,
J. Zhu, Org. Lett. 2009, 11, 4648–4651; k) T. Marcelli,
J. H. V. Maarseveen, H. Hiemstra, Angew. Chem. 2006,
118, 7658–7666; Angew. Chem. Int. Ed. 2006, 45, 7496–
7504; l) R. P. Singh, B. M. Foxman, L. Deng, J. Am.
Chem. Soc. 2010, 132, 9558–9560; m) S. Saaby, M.
Bella, K. A. Jørgensen, J. Am. Chem. Soc. 2004, 126,
8120–8121; n) M. Bella, K. A. Jørgensen, J. Am. Chem.
We thank the Shanghai Municipal Committee of Science and
Technology (11JC1402600), National Basic Research Pro-
gram of China ACHTUNGTRENNUNG(973)-2010CB833302, the Fundamental Re-
search Funds for the Central Universities and the National
Natural Science Foundation of China for financial support
(21072206, 20872162, 20672127, 20732008, 21121062 and
20702013).
References
[1] a) S. J. Omura, Antibiotics 1984, 37, 1324–1332;
b) L. M. Dollinger, A. R. Howell, Bioorg. Med. Chem.
Lett. 1998, 8, 977–978; c) L. M. Dollinger, A. R.
Howell, J. Org. Chem. 1998, 63, 6782–6783; d) M. Ham-
berg, J. Svensson, B. Samuelsson, Proc. Natl. Acad. Sci.
USA 1975, 72, 2994–2998; e) M. C. Wani, H. L. Taylor,
M. E. Wall, P. Coggon, A. T. McPhail, J. Am. Chem.
Soc. 1971, 93, 2325–2327; f) J. R. Hanson, Nat. Prod.
Rep. 1999, 16, 209–219; g) G. Wuitschik, M. Rogers-
Evans, K. Mꢃller, H. Fischer, B. Wagner, F. Schuler, L.
Polonchuk, E. M. Carreira, Angew. Chem. 2006, 118,
7900–7903; Angew. Chem. Int. Ed. 2006, 45, 7736–7739;
h) G. Wuitschik, M. Rogers-Evans, A. Buckl, M. Ber-
nasconi, M. Mꢄrki, T. Godel, H. Fischer, B. Wagner, I.
Parrilla, F. Schuler, J. Schneider, A. Alker, W. B.
Schweizer, K. Mꢃller, E. M. Carreira, Angew. Chem.
2008, 120, 4588–4591; Angew. Chem. Int. Ed. 2008, 47,
4512–4515; i) G. Wuitschik, E. M. Carreira, M. Rogers-
Evans, K. Mꢃller, in: Process Chemistry in the Pharma-
ceutical Industry, (Eds.: K. Gadamasetti, T. Braish),
CRC, Boca Raton, 2008, pp 217–229; j) details can be
found in: G. Wuitschik, PhD Thesis, ETH Zurich (Swit-
zerland), 2008, DOI: 10.3929/ethz-a-005697432; k) G.
Wuischik, E. M. Carreira, B. Wagner, H. Fischer, I. Par-
rilla, F. Schuler, M. Rogers-Evans, K. Mꢃller, J. Med.
Chem. 2010, 53, 3227–3246; l) N. A. Meanwell, J. Med.
Chem. 2011, 54, 2529–2591; m) J. A. Burkhard, G.
6
asc.wiley-vch.de
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Catalytic Asymmetric Synthesis of 2-Alkyleneoxetanes through [2+2]Annulation of Allenoates
Soc. 2004, 126, 5672–5673; o) F. Zhong, G.-Y. Chen, Y.
Lu, Org. Lett. 2011, 13, 82–85; p) J.-B. Denis, G.
Masson, P. Retailleau, J. Zhu, Angew. Chem. 2011, 123,
5468–5472; Angew. Chem. Int. Ed. 2011, 50, 5356–5360;
q) Y. Liu, B. Sun, B. Wang, M. Wakem, L. Deng, J.
Am. Chem. Soc. 2009, 131, 418–419; r) P. I. Dalko, L.
Moisan, Angew. Chem. 2004, 116, 5248–5286; Angew.
Chem. Int. Ed. 2004, 43, 5138–5175; s) S.-S. Jew, H.-G.
Park, Chem. Commun. 2009, 7090–7103; t) S. Ogawa,
N. Shibata, J. Inagaki, S. Nakamura, T. Toru, M. Shiro,
Angew. Chem. 2007, 119, 8820–8823; Angew. Chem.
Int. Ed. 2007, 46, 8666–8669; u) F. Pesciaioli, P. Righi,
A. Mazzanti, G. Bartoli, G. Bencivenni, Chem. Eur. J.
2011, 17, 2842–2845; v) B. Tan, X. Zeng, W. W. Y.
Leong, Z. Shi, C. F. Barbas III, G. Zhong, Chem. Eur.
J. 2012, 18, 63–67; w) X. Dou, X. Han, Y. Lu, Chem.
Eur. J. 2012, 18, 85–89; x) J. Xu, Y. Hu, D. Huang, K.-
H. Wang, C. Xu, T. Niu, Adv. Synth. Catal. 2012, 354,
515–526; y) K. Asano, S. Matsubara, Org. Lett. 2012,
14, 1620–1623; z) W.-Q. Zhang, L.-F. Cheng, J. Yu, L.-
Z. Gong, Angew. Chem. 2012, 124, 4161–4164; Angew.
Chem. Int. Ed. 2012, 51, 4085–4088; aa) L. Liu, D. Wu,
S. Zheng, T. Li, X. Li, S. Wang, J. Li, H. Li, W. Wang,
Org. Lett. 2012, 14, 134–137; ab) H.-R. Tan, H. F. Ng, J.
Chang, J. Wang, Chem. Eur. J. 2012, 18, 3865–3870;
ac) X. Jiang, X. Shi, S. Wang, T. Sun, Y. Cao, R. Wang,
Angew. Chem. 2012, 124, 2126–2129; Angew. Chem.
Int. Ed. 2012, 51, 2084–2087; ad) B. Wu, J. Chen, M.-Q.
Li, J.-X. Zhang, X.-P. Xu, S.-J. Ji, X.-W. Wang, Eur. J.
Org. Chem. 2012, 1318–1327.
[12] For some other approaches to the construction of 5,6-
dihydropyran-2-ones, see: a) Q. Fan, L. Lin, J. Liu, Y.
Huang, X. Feng, G. Zhang, Org. Lett. 2004, 6, 2185–
2188; b) X. Moreau, B. Baz-Tejeda, J.-M. Campagne, J.
Am. Chem. Soc. 2005, 127, 7288–7289; c) J. Liu, X. Li,
J. Wang, X. Feng, Adv. Synth. Catal. 2006, 348, 939–
944; d) H. Du, D. Zhao, K. Ding, Chem. Eur. J. 2004,
10, 5964–5970; e) V. Boucard, G. Broustal, J. M. Cam-
pagne, Eur. J. Org. Chem. 2007, 225–236; f) L.-T. Shen,
P.-L. Shao, S. Ye, Adv. Synth. Catal. 2011, 353, 1943–
1948.
[13] a) P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-
VCH, Weinheim, 2004; b) R. Filler, Y. Kobayashi,
L. M. Yagupolskii, Organofluorine Compounds in Me-
dicinal Chemistry and Biomedical Applications, Elsevi-
er, Amsterdam, 1993; c) P. V. Ramachandran, Asym-
metric Fluoroorganic Chemistry, ACS Symposium
Series, ACS, Washington, DC, 2000; d) S. Rozen, Acc.
Chem. Res. 1988, 21, 307–312; e) J. A. Wilkinson,
Chem. Rev. 1992, 92, 505–519; f) S. Purser, P. R. Moore,
S. Swallow, V. Gouverneuer, Chem. Soc. Rev. 2008, 37,
320–330.
[14] CCDC 860697 (5) and CCDC 862129 (for absolute con-
figuration) contain the supplementary crystallographic
data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif. Crys-
tal data of 5: empirical formula: C18H12F3N3O3; formula
weight: 375.31; crystal color, habit: colorless, crystal di-
mensions: 0.20ꢂ0.12ꢂ0.08 mm; crystal system: mono-
clinic; lattice parameters: a=15.1675(4) ꢅ, b=
[9] a) The E configuration of oxetane 3aa was determined
by comparison of the spectroscopic data with those de-
scribed in ref.[6a] b) The E configuration of oxetane 3ca
was determined by comparison of the spectroscopic
data with those described in ref.[6b]
[10] a) D. J. Young, M. J. T. Robinson, J. Labelled Compd.
Radiopharm. 2000, 43, 121–126; b) Q.-Y. Zhao, Z.-L.
Yuan, M. Shi, Adv. Synth. Catal. 2011, 353, 637–643.
[11] a) K. Yasui, Y. Tamura, T. Nakatani, K. Kawada, M.
Ohtani, J. Org. Chem. 1995, 60, 7567–7574; b) A. Endo,
J. Med. Chem. 1985, 28, 401–410; c) E. S. Istvan, J. Dei-
senhofer, Science 2001, 292, 1160–1164; d) S. J. Shaw,
K. F. Sundermann, M. A. Burlingame, D. C. Myles,
B. S. Freeze, M. Xian, I. Brouard, A. B. Smith III, J.
Am. Chem. Soc. 2005, 127, 6532–6533.
7.5879(2) ꢅ,
c=14.8401(4) ꢅ,
a=908,
b=
101.8920(10)8, g=908, V=1671.28(8) ꢅ3; space group:
C2; Z=4; Dcalcd, =1.492 gcmÀ3; F000 =768; final R indi-
ces [I>2 sigma(I)] R1=0.0291, wR2=0.0839.
[15] a) S. Nagarajan, S. R. Wilson, K. L. Rinehart, J. Org.
Chem. 1985, 50, 2174–2178; b) M. Jiang, M. Shi, J. Org.
Chem. 2009, 74, 2516–2520.
[16] J. A. Morales-Serna, E. Garcꢆa-Rꢆos, J. Bernal, E.
Paleo, R. GaviÇo, J. Cꢇrdenas, Synthesis 2011, 1375–
1382.
[17] a) G.-L. Zhao, J.-W. Huang, M. Shi, Org. Lett. 2003, 5,
4737–4739; b) G.-L. Zhao, M. Shi, J. Org. Chem. 2005,
70, 9975–9984.
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COMMUNICATIONS
8 Catalytic Asymmetric Synthesis of 2-Alkyleneoxetanes
through [2+2]Annulation of Allenoates with
Trifluoromethyl Ketones
Adv. Synth. Catal. 2012, 354, 1 – 8
Qian-Yi Zhao, Long Huang, Yin Wei,* Min Shi*
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