Enantioselective synthesis of functionalized 3,4-dihydropyran derivatives organocatalyzed by a novel fluorinated-diphenylprolinolether

Article abstract of DOI:10.1016/j.tet.2009.09.103

A novel fluorinated diarylprolinol silyl ether catalyst have been designed and it successfully applicated in?the first asymmetric Michael addition-cyclization reaction between 1,3-dicarbonyl compounds with α,β-unsaturated aldehydes at room temperature. The products were isolated in good yields with high diastereoselectivities and enantioselectivities.

Full text of DOI:10.1016/j.tet.2009.09.103

Tetrahedron 65 (2009) 10016–10021
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Enantioselective synthesis of functionalized 3,4-dihydropyran derivatives
organocatalyzed by a novel fluorinated-diphenylprolinolether
*
Chuanming Yu , Fei Zheng, Haiwei Ye, Weihui Zhong
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel fluorinated diarylprolinol silyl ether catalyst have been designed and it successfully applicated
in the first asymmetric Michael addition–cyclization reaction between 1,3-dicarbonyl compounds with
Received 7 August 2009
Received in revised form
21 September 2009
Accepted 25 September 2009
Available online 30 September 2009
a,
b-unsaturated aldehydes at room temperature. The products were isolated in good yields with high
diastereoselectivities and enantioselectivities.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Pyrans
Fluorinated diphenylprolinolether
Organocatalyst
Domino reactions
1. Introduction
apply them in the first asymmetric Michael addition–cyclization
reaction between 1,3-dicarbonyl compounds and -unsaturated
a,b
In recent years, the development of asymmetric reactions using
small organic molecules as catalysts has grown rapidly and it has
become the eminent strategy in contemporary organic synthesis.1
Particularly, among the various organocatalysts reported recently,
the incredibly high efficient diarylprolinols derivatives serve as
a reliable and powerful synthetic tool for organocatalytic asym-
metric reactions.2 Moreover, Moorthy et al. successfully applied
perfluorophenylamide catalyst to enantioselective Aldol reaction
with a broad substrate scope compared to other aryl catalysts.3 The
perfluorophenylamide catalyst can indeed work efficiently with
only a marginal sacrifice of the enantioselectivity and diaster-
eoselectivity in various nonpolar and polar solvents. These general
and readily available catalysts represent an important starting point
for the investigation of new asymmetric processes, due to they often
avoid the need for multiple screening processes of catalysts to de-
termine the asymmetric reaction conditions. In recent years, more
attention has been paid to optimization of the structure of the chiral
catalyst so as to achieve good to excellent selectivity and catalytic
activity.4 Hydrogen bonding plays a vital role in organocatalytic
asymmetric reactions. It was found that fluorine engaged in C–H/F
hydrogen bonding easily. It prompted us to envision that it might be
possible to develop a novel fluorinated diarylprolinol ether and
aldehydes giving the corresponding 3,4-dihydropyran derivatives.
Pyranderivativesarepolyfunctionalizedstructuresthatcommonly
appear in numerous natural products and biologically active com-
pounds.5 Based on their biological and structural properties, synthetic
CHO
HO
O
O
O
Michael
R
cyclization
R
O
Scheme 1. Organocatalytic synthesis of 3,4-dihydropyrans.
methods that yield 3,4-dihydropyrans derivatives have thus received
muchresearchinterest. Thecommonwaytoaccess3,4-dihydropyrans
is, by inverseelectron-demand HDA reactions of unsaturated carbonyl
compounds with electron- rich alkenes6 and others methods.7 How-
ever, to the best of our knowledge, few studies have been reported
about enantioselective synthesis of 3,4-dihydropyran. Recently,
Ar
Ar
OTMS
a)
b)
c)
COOH
COOCH3
N
H
N
Boc
d), e)
N
H
3a, Ar = 3,4,5-F3C6H2
, Ar = 3-FC6H4
1
2
3c
Scheme 2. The synthesis of the novel fluorinated diarylprolinol ethers. Condition: a)
SOCl2, CH3OH; b) Boc2O, Et3N; c) ArMgBr, 2-MeTHF, 5 h, rt, yield: 70.2%; d) HCl/AcOEt,
2 h, rt; e) TMSCl, Et3N, CH2Cl2, 2 h, rt.
* Corresponding author. Tel./fax: þ86 571 88320752.
E-mail address: pharmlab@zjut.edu.cn (C. Yu).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.103

C. Yu et al. / Tetrahedron 65 (2009) 10016–10021
10017
Jøgensen8 and Gong9 revealed that the silyl-protected diarylprolinol
ethers catalyzed chemoselective and enantioselective synthesis of
pyran derivatives (Scheme 1). We herein reported facile synthesis of
novel fluorinated diarylprolinol ether and its application in the initial
Table 2
Solvent and additive screening for the reaction of 4a and 5aa
1. 3a (10 mol%)
solvent,additive
AcO
O
R
O
O
CHO
R
2.Ac2O, CH2Cl2
Et3N, DMAP
Michael addition of 1,3-dicarbonyl compounds to
a,b-unsaturated
aldehydes followed by a subsequent cyclization reaction.
O
4a
5a
6a
, R=4-MeOC6H4
2. Results and discussion
Entry Solvent
Additive
T
ꢀ C Yieldb (%) drc
eed (%)
2.1. Preparation of fluorinated diarylprolinol ethers
1
H2O
PhCO2H
PhCO2H
PhCO2H
PhCO2H
RT
RT
RT
RT
RT
RT
RT
RT
RT
50
40
62
65
52
89
75
63
80
74
71
40
>25:1 65
2
3
DMF
Et2O
>25:1 73
10:1 76
15:1 75
17:1 77
>25:1 84
20:1 60
>25:1 59
12:1 67
>25:1 80
>25:1 81
>25:1 83
As our primary goal, we designed a broad set of novel fluori-
4
CH3OH
nated diarylprolinol ether from
2.2. Enantioselective Michael addition–cyclization reaction
As a model reaction, the reaction of -unsaturated aldehyde 4a
L-proline (Scheme 2).
5
Toluene PhCO2H
6
7
8
9
10
11e
12f
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
PhCO2H
NH4Cl
CF3COOH
4-MeOC6H4CO2H
2,3,4,5-F4 C6H4CO2H RT
a,b
with 1,3-dicarbonyl compound 5a was investigated in the presence
of various chiral secondary amines catalysts, using PhCO2H as
additive in solvent CH2Cl2, followed by acetylation to give the 3,4-
dihydropyran derivative 6a as shown in Table 1. To our delight, the
results showed that altering the number of fluorine atoms of cat-
alysts plays a critical role in achieving good yields and high level of
stereoselectivities. The novel fluorinated diarylprolinol silyl ether
catalyst 3a afforded the 3,4-dihydropyran 6a in high yield with
good enantioselectivity and diastereoselectivity (Table 1, entry 2).
The Michael addition–cyclization reaction can be carried out in
various nonpolar and polar solvents (Table 2, entries 1–6), such as
CH2Cl2, Et2O, H2O, DMF, CH3OH and toluene. Among them, CH2Cl2
was the best one. In addition, the primary investigation showed that
benzoic acid as additive could give good yield and enantioselectivity
up to 84% (Table 2, entry 6). More experiments showed that suitable
acid additives were necessary to obtain excellent yield and enan-
tioselectivity.10 For example, low enantioselectivity was observed
when using strongly acid TFA, while slightly weak acid NH4Cl also
induced low yield and enantioselectivity (Table 2, entries 7, 8).
Moreover, the influence of some substituted benzoic acids produced
on the reaction was also investigated (Table 2, entries 9, 10).
PhCO2H
PhCO2H
0
-50
a
Reactions conditions: The mixture of 4a (1.1 mmol), 5a (1 mmol), 10 mol % 3a
catalyst, 10 mol % additive, 1 mL of solvent was stirred for 12 h, then the acetylation
was performed.
b
Isolated yield based on 5a.
c
Diastereomeric ratio was determined by 1H NMR spectroscopy or HPLC.
d
Determined by chiralstationary phase HPLC.
Reaction time prolonged to 18 h.
Reaction time prolonged to 36 h.
e
f
Table 3
Reaction of
a
,
b-unsaturated aldehydes 4 with 1,3-dicarbonyl compounds 5 catalyzed
by 3aa
R2
O
O
AcO
O
R2
R2 R2
R1
O
O
2
5a
, R =CH3
3a
1,
(10 mol%),
5b, R2=H
AcO
AcO
CH2Cl2, PhCO2H
O
O
CHO
2, Ac2O,CH2Cl2,
Et3N,DMAP
R1
R1
O
O
5c
O
O
Table 1
R3
R3
Catalyst screening for the reaction of 4a and 5aa
4
R1
6a-6p
O
3
5d
, R =CH3
5e, R3=OCH2CH3
1. cat (10%)
CH2Cl2, PhCO2H
AcO
O
O
O
CHO
R
2.Ac2O,CH2Cl2,
Et3N,DMAP
Entry R1
1,3-Dicarbonyl Product Yieldb (%) drc
compounds
eed (%)
R
O
4a
5a
6a
, R=4-MeOC6H4
1
2
3
4
5
6
7
4-CH3OC6H4 5a
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
89
74
83
76
83
73
84
40
45
92
94
80
82
72
50
70
>25:1 84
F
F
4-CH3C6H4
4-FC6H4
4-ClC6H4
C6H5
3-CH3C6H4
3-ClC6H4
2-CF3C6H4
5a
5a
5a
5a
5a
5a
5a
>25:1 90
>25:1 84
>25:1 86
11:1 83
15:1 90
>25:1 86
>25:1 83
>25:1 90
8:1 91
>25:1 87
>25:1 81
>25:1 84
5:1 88
F
F
F
F
CO2H
N
N
N
F
H
H
N
H
OTMS
OTMS
H
F
OR
, R=TMS
8e
9e
10
11
12
13
14
15
16
3a
3c
3d
1
2-CH3OC6H4 5a
3b, R=H
CH3
CH2CH2CH3
2-furyl
5a
5a
5a
Entry
Cat
Yieldb (%)
drc
ee d (%)
1
2
3
4
5
1
<5
89
52
75
85
nd
>25:1
nd
15:1
10:1
nd
84
15
67
35
4-CH3OC6H4 5b
4-CH3OC6H4 5c
4-CH3OC6H4 5d
4-CH3OC6H4 5e
3a
3b
3c
3d
8:1 20
6:1 87
a
Reactions conditions: The mixture of 4 (1.1 mmol), 5 (1 mmol), 10 mol % 3a
catalyst, 10 mol % benzoic acid, 1 mL of CH2Cl2, was stirred at room temperature for
12 h, then the acetylation was performed.
a
Reactions conditions: The mixture of 4a (1.1 mmol), 5a (1 mmol), 10 mol %
catalyst, 10 mol % benzoic acid, 1 mL of CH2Cl2 was stirred for 12 h then the acety-
lation was performed.
b
Isolated yield based on 5.
b
c
Isolated yield based on 5a.
Diastereomeric ratio determined by 1H NMR spectroscopy.
c
d
Diastereomeric ratio was determined by 1H NMR spectroscopy or HPLC.
Determined by chiralstationary phase HPLC.
3 equiv a,b-unsaturated aldehydes were used.
d
e
Determined by chiralstationary phase HPLC.

10018
C. Yu et al. / Tetrahedron 65 (2009) 10016–10021
However, the reaction was performed at lower temperature (0
derivatives in good yields with high enantioselectivities and
diastereoselectivities.
or ꢁ50 ꢀC) led to some loss of catalytic efficiency, but without any
increase in the ee value (Table 2, entries 11, 12). The fluorinated
diarylprolinol derivatives could indeed work efficiently at room
temperature.
4. Experimental
With the optimized reaction conditions, we embarked on a
systematic evaluation of the catalytic system in variety of sub-
4.1. General details
stituted
(Table 3). In most cases, aromatic
afforded good yields and enantioselectivities (Table 3, entries 1–7,
83–90% ee). In the case of ortho-substituted aromatic -un-
saturated aldehydes lower yields were observed due to 1,2-addition
side reaction (Table 3, entries 8, 9). This process was then extended
a
,
b
-unsaturated aldehydes and 1,3-dicarbonyl compounds
Analytical grade solvents and commercially available reagents
were used without further purification. The flash column chro-
matography was carried out over silica gel (200–400mesh), pur-
chased from Qingdao Haiyang Chemical Co., Ltd. Optical rotations
were measured on a Perkin Elmer Model 341 digital polarimeter,
Melting points were determined on a Bu¨chi B-540 capillary melting
point apparatus. IR spectra was recorded on an AVATAR-370,
samples were prepared as KBr plates. Mass spectra were measured
with Thermo Finnigan LCQ-Advantage. 1H NMR and 13C NMR
spectra were recorded at VARAIN–400 or BRUKER AVANCE III–500
using CDCl3 as the solvent with tetramethylsilane (TMS) as an in-
ternal standard at room temperature. Chemical shifts are given in
a,b-unsaturated aldehydes
a,b
to alkyl and heterocyclic -unsaturated aldehydes. Performing
a
,b
the reaction with alkyl a,b-unsaturated aldehydes increased to
94% yield with good diastereoselectivities and enantioselectivities
(Table 3, entries 10, 11). Heteroaromatic substituent also gave sat-
isfactory result (Table 3, entry 12). To explore further the potential
of this Michael addition–cyclization reaction other 1,3-dicarbonyl
compounds were tested. The acyclic ethyl 3-oxobutanoate 5e could
give good enantioselectivity up to 87% ee (Table 3, entry 16). But
entane-2,4-dione 5d gave enantioselectivity only 20% ee (entry 15),
the reversibility of the Michael addition reaction performed with
entane-2,4-dione might explain the low enantioselectivity.11
Encouraged by the good results of fluorinated substituted di-
arylprolinol silyl ether catalyst 3a, we attempted to design per-
fluoro-diarylprolinol catalyst, but we just obtained the unexpected
product 3e without catalytic activity (Fig. 1).
d
relative to TMS, the coupling constants J are given in Hertz. The
low-resolution mass spectra were obtained with the Thermo Trace
GC Ultra-DSQ II and Agilent 6120 (Quadrapole LC–MS) mass spec-
trometer. High resolution mass spectral (HRMS) analyze were
measured on an Agilent 6210 TOF LC/MS using ESI or EI (electro-
spray ionization) techniques. Enantiomeric excesses of products
were determined by HPLC using a Daicel Chiralcel AS-H or OD-H
column and eluting with n-hexane/i-PrOH.
4.2. Typical procedure for the catalyzed synthesis of 3,4-
dihydropyran derivatives
F
N
F
F
F
F
A
mixture of catalyst 3a (0.1 mmol, 10 mol %), PhCO2H
F
F
(0.1 mmol, 10 mol %) and -unsaturated aldehyde 4 (1.1 mmol) in
a,b
OH
F
F
2 mL CH2Cl2 was stirred for 5 min at room temperature. Then the
1,3-dicarbonyl compounds 5 (1 mmol) were added. The reaction
mixture was stirred at room temperature for the given time
(monitored by TLC). To the reaction mixture was added CH2Cl2
(2 mL), Ac2O (3 mmol), Et3N (0.2 mL) and DMAP (0.1 mmol,
10 mol %) and stirred at ambient temperature for about 2 h. The
reaction mixture was quenched with H2O (20 mL), extracted with
CH2Cl2 (3ꢂ10 mL), dried over Na2SO4, the solvent was evaporated
under vacuum, and the residue was purified by flash column
chromatography over silica gel (AcOEt/petroleum ether 2:1–8:1) to
provide products 6a–k.
Figure 1. Compound 3e.
The proposed mechanism for the silyl-protected diarylprolinols
catalyzed the reaction course was summarized by Jøgensen et al.8
The fluorinated catalyst 3a possibly is attributed to the enhanced
catalytic activity and stronger binding of the substrate via hydrogen
bonding in the transition state (Scheme 3).
F
F
F
4.3. Experimental data of compound
OTMS
F
N
4.3.1. (S)-2-[Bis-(3,4,5-trifluoro-phenyl)-trimethylsilanyloxymethyl]-
pyrrolidine (3a). Viscous oil; IR (KBr): 2959, 1525, 1339 cmꢁ1 1H
;
H
O
F
F
NMR (400 MHz, CDCl3):
3.93 (t, J¼6.8 Hz, 1H), 2.97–2.91 (m, 1H), 2.83–2.77 (m, 1H), 1.67 (s,
d
¼7.21–7.14 (m, 2H), 7.00–6.94 (m, 2H),
R
1H), 1.63–1.55 (m, 2H), 1.53–1.39 (m, 2H), 0.01(s, 9H); 13C NMR
O
(100 MHz, CDCl3):
d
¼151.9 (dd, J1¼6.8 Hz, J2¼22.7 Hz, 2C), 149.4
Scheme 3. Possible catalytic transition state for the present catalytic system.
(dd, J1¼6.1 Hz, J2¼19.0 Hz, 2C), 142.6 (d, J¼4.6 Hz), 141.1 (d,
J¼4.6 Hz), 140.1 (d, J¼14.4 Hz), 137.5 (d, J¼14.4 Hz), 112.6–111.5 (m,
4C), 81.5, 64.8, 47.2, 27.4, 24.9, 2.2 (d, J¼29.6, 3C); MS (ESI): m/z
(%)¼434 (100) [Mþþ1]; HRMS (ESI) Calculated for C20H21F6NOSi
20
3. Conclusion
(Mþ), 433.1297; found: 433.1298; [
a
]
¼ꢁ28.2 (c 0.75, CHCl3).
D
In summary, we have developed a novel fluorinated diaryl-
prolinol silyl ether catalyst and applied it to promote the enantio-
selective synthesis of 3,4-dihydropyran derivatives via Michael
addition–cyclization reaction of 1,3-dicarbonyl compounds with
4.3.2. (S)-2-[Bis-(3-fluoro-phenyl)-trimethylsilanyloxymethyl]-pyr-
rolidine (3c). Viscous oil; 1H NMR (400 MHz, CDCl3):
d
¼7.31–
7.23(m, 4H), 7.18–7.11 (m, 2H), 6.98–6.95 (m, 2H), 4.04 (t, J¼7.6 Hz,
1H), 2.95–2.84 (m, 2H), 1.68 (br s, 1H); 1.65–1.43 (m, 4H), 0.00 (s,
a
,b
-unsaturated aldehydes at mild reaction conditions. The attrac-
9H); 13C NMR (100 MHz, CDCl3):
J¼7.6 Hz), 149.2 (d, J¼6.1 Hz), 148.1 (d, J¼6.0 Hz), 129.8–128.9 (m,
2C), 123.3 (d, J¼84.2 Hz, 1C), 121.0 (t, J¼4.4 Hz, 1C), 115.5–112.4 (m,
d
¼163.7 (d, J¼8.3 Hz), 161.2 (d,
tive features of this process were the practicability and the mild
reaction conditions, which provide a series of 3,4-dihydropyran

C. Yu et al. / Tetrahedron 65 (2009) 10016–10021
10019
4C), 82.4, 65.1, 46.9 (d, J¼27.3 Hz), 27.5, 25.4; 2.22 (dd, J1¼29.6 Hz,
J2¼19.0 Hz, 3C); MS (ESI): m/z (%)¼362 (100) [Mþþ1], HRMS (ESI)
2965, 1769, 1628, 838 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d¼7.25 (d,
J¼8.4 Hz, 2H), 7.08 (d, J¼8.4 Hz, 2H), 6.11 (dd, J1¼2.4 Hz, J2¼8.4 Hz,
1H), 4.02 (br s, 1H), 2.47 (d, J¼16.4 Hz, 1H), 2.33 (d, J¼17.6 Hz, 1H),
2.28 (d, J¼16.4 Hz, 1H), 2.22 (d, J¼16.0 Hz, 1H), 2.15 (dd, J1¼6.0 Hz,
J2¼8.4 Hz,1H), 2.11(s, 3H), 2.07–2.02 (m,1H),1.15 (s, 3H),1.09 (s, 3H);
Calculated for C20H25F2NOSi (Mþ): 361.1673, found: 361.61673;
20
[
a]
¼ꢁ66.1 (c 0.11, CHCl3).
D
4.3.3. (9S,9aS)-5,6,7,8-Tetrafluoro-9-(perfluorophenyl)-2,3,9,9a-
tetrahydro-1H-pyrrolo[1,2-a]indol-9-ol (3e). Yellow solid; mp 98.9–
100.2 ꢀC; IR (KBr): 3416, 3161, 1492, 1304 cmꢁ1; 1H NMR (400 MHz,
13C NMR (100 MHz, CDCl3):
d
¼196.3, 169.0, 168.1, 142.1, 132.3, 128.8,
128.6, 111.9, 89.7, 50.7, 42.0, 34.3, 32.6, 32.1, 28.7, 28.2, 20.9; MS (EI):
m/z (%)¼348 (10) [Mþ], 306 (25), 288 (60), 277(100), 253 (20); HRMS
(EI) Calculated for C19H21ClO4 (Mþ): 348.1128, found: 348.1120; The
ee was determined by HPLC analysis using a Chiralpak OD-H column
CDCl3):
2.08–1.93 (m, 2H), 1.63–1.58 (m, 1H), 1.04–0.95 (m, 1H); 13C NMR
(100 MHz, CDCl3):
¼146.4–133.2 (m, CHꢂ10), 115.2 (d, J¼17.8 Hz),
114.7, 80.0, 77.3–76.7 (m, 1C), 51.8, 28.5, 26.7; 19F NMR (372 MHz,
CDCl3):
d¼4.31–4.26 (m, 1H), 3.70–3.65(m, 1H), 3.30–3.22 (m, 1H),
d
[hexane/iPrOH (82:18)]; flow rate 1.0 mL/min; smajor¼11.0 min,
25
sminor¼10.1 min, 84% ee; [
a
]
¼þ95.1, (c 0.7, CH2Cl2).
D
d
¼ꢁ138.6 (d, J¼13.8 Hz, 2F), ꢁ143.6 (dd, J1¼21.2 Hz,
J2¼13.8 Hz, 1F), ꢁ154.7 to ꢁ155.0 (m, 1F), ꢁ154.7 to ꢁ154.8 (m, 1F),
4.3.8. (2R,4S)-7,7-Dimethyl-5-oxo-4-phenyl-3,4,5,6,7,8-hexahydro-
2H-chromen-2-yl acetate (6e). Yellow solid; mp 100.2–102.0 ꢀC; IR
(KBr): 2961, 1745, 1360, 700 cmꢁ1; major diastereoisomer: 1H NMR
ꢁ155.0, ꢁ160.1 to ꢁ160.2(m, 2F), ꢁ168.8 to ꢁ169.0 (m, 1F); MS (EI):
m/z (%)¼413 (100) [Mþ], MS (EI) Calculated for C17H8F9NO (Mþ):
20
413.0462, found: 413.0466; [
a
]
¼ꢁ152.6 (c 0.30, CHCl3).
(400 MHz, CDCl3):
d
¼7.30–7.26 (m, 2H), 7.20–7.13 (m, 3H), 6.12 (dd,
D
J1¼3.2 Hz, J2¼9.2 Hz, 1H), 4.07 (s, 1H), 2.49 (d, J¼17.6 Hz, 1H), 2.38
(d, J¼17.2 Hz, 1H), 2.30 (d, J¼16.0 Hz, 1H), 2.23 (d, J¼16.4 Hz, 1H),
2.19–2.13 (m, 1H), 2.10 (s, 3H), 2.10–2.04 (m, 1H), 1.16 (s, 3H), 1.10 (s,
4.3.4. (2R,4S)-4-(4-Methoxyphenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-
hexahydro-2H-chromen-2-yl acetate (6a). Yellow solid; mp 131.1–
133.5 ꢀC; IR (KBr): 2957, 1759, 11 632, 870 cmꢁ1; 1H NMR (400 MHz,
3H); 13C NMR (100 MHz, CDCl3):
d¼196.4, 169.1, 167.9, 143.4, 128.6,
CDCl3):
d
¼7.06 (d, J¼8.4 Hz, 2H), 6.82 (d, J¼8.4 Hz, 2H), 6.11 (dd,
127.2, 126.5, 112.0, 89.9, 50.7, 42.0, 34.3, 33.1, 32.1, 28.2, 28.1, 20.9;
MS (ESI): m/z (%)¼315 (100) [Mþþ1]; HRMS (ESI) Calculated for
C19H22O4 (Mþ): 314.1518, found: 314.1530; The ee was determined
by HPLC analysis using a Chiralpak OD-H column [hexane/iPrOH
J1¼3.2 Hz, J2¼8.8 Hz,1H), 4.02 (s,1H), 3.76 (s, 3H), 2.47 (d, J¼17.2 Hz,
1H), 2.37 (d, J¼17.2 Hz, 1H), 2.29 (d, J¼16.0 Hz, 1H), 2.22 (d,
J¼16.0 Hz,1H), 2.13–2.11 (m, 1H), 2.11 (s, 3H), 2.10–2.04 (m, 1H),1.15
(s, 3H),1.09 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
¼196.7,169.0,167.7,
(82:18)]; flow rate 1.0 mL/min; smajor¼11.9 min, sminor¼8.0 min,
25
158.1, 135.4, 128.2, 114.0, 112.2, 89.9, 55.1, 50.7, 42.0, 34.4, 32.3, 32.0,
28.7, 28.1, 20.8; MS (ESI): m/z (%)¼367 (100) [MþNa]þ, HRMS (ESI)
Calculated for C20H24O5(MþNa)þ: 367.1624, found: 367.1615; The ee
was determined by HPLC analysis using a Chiralpak OD-H column
89% ee; [
a
]
¼ꢁ3.1, (c 0.85, CH2Cl2).
D
4.3.9. (2R,4S)-7,7-Dimethyl-5-oxo-4-m-tolyl-3,4,5,6,7,8-hexahydro-
2H-chromen-2-yl acetate (6f). Yellow solid; mp 77.6–80.3 ꢀC; IR
(KBr): 2958, 1762, 1618, 765 cmꢁ1; major diastereoisomer: 1H NMR
[hexane/iPrOH (82:18)]; flow rate 1.0 mL/min; Tmajor¼15.3 min,
25
sminor¼10.5 min, 84% ee; [
a
]
¼þ56.1, (c 2.4, CH2Cl2).
(400 MHz, CDCl3):
d
¼7.16 (t, J¼7.6, 1H), 7.00–6.91 (m, 3H), 6.11 (dd,
D
J1¼2.8 Hz, J2¼8.8 Hz, 1H), 4.03 (s, 1H), 2.43 (d, J¼17.6 Hz, 1H), 2.37
(d, J¼17.6 Hz, 1H), 2.30 (d, J¼7.6 Hz, 1H), 2.31 (s, 3H), 2.29–2.25 (m,
1H), 2.21–2.14 (m, 1H), 2.13 (s, 3H), 2.12–2.05 (m, 1H), 1.16 (s, 3H),
4.3.5. (2R,4S)-7,7-Dimethyl-5-oxo-4-p-tolyl-3,4,5,6,7,8-hexahydro-
2H-chromen-2-yl acetate (6b). Yellow solid; mp 129.4–129.9 ꢀC; IR
(KBr): 3128, 2958, 1748, 1628 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
1.10 (s, 3H); 13C NMR (100 MHz, CDCl3):
d¼196.5, 169.1, 168.0, 143.4,
d
¼7.09 (d, J¼8.0 Hz, 2H), 7.03 (d, J¼8.0 Hz, 2H), 6.12 (dd, J1¼2.8 Hz,
138.2, 128.5, 128.1,127.9, 124.2, 112.1, 89.9, 50.7, 42.0, 34.3, 33.1, 32.1,
28.7, 28.2, 21.5, 20.9; MS (ESI): m/z (%)¼351 (100) [MþNa]þ; HRMS
(ESI) Calculated for C20H24O4 (MþNa)þ: 351.1675, found: 351.1670;
The ee was determined by HPLC analysis using a Chiralpak OD-H
J2¼8.8 Hz, 1H), 4.03 (s, 1H), 2.48 (d, J¼17.6 Hz, 1H), 2.37 (d,
J¼17.6 Hz, 1H), 2.31–2.20 (m, 5H), 2.18–2.12 (m, 1H), 2.10 (s, 3H),
2.08–2.03 (m, 1H), 1.15 (s, 3H), 1.09 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
¼196.4, 169.1, 167.8, 140.5, 136.0, 129.3, 127.1, 112.3, 90.0,
column [hexane/iPrOH (82:18)]; flow rate 1.0 mL/min; smajor
¼
25
50.8, 42.1, 34.4, 32.8, 32.1, 28.7, 28.2, 22.7, 20.9; MS (ESI): m/z
(%)¼329 (100) [Mþþ1], HRMS (ESI) Calculated for C20H24O4 (Mþ):
328.1675, found: 328.1670; The ee was determined by HPLC
analysis using a Chiralpak OD-H column [hexane/iPrOH (82:18)];
8.0 min, sminor¼15.8 min, 82% ee; [
a]
¼102.5, (c 0.48, CH2Cl2).
D
4.3.10. (2R,4S)-4-(3-Chlorophenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-
hexahydro-2H-chromen-2-yl acetate (6g). Yellow viscous oil; IR
flow rate 1.0 mL/min; smajor¼10.6 min, sminor¼7.6 min, 90% ee;
(KBr): 2960, 1748, 1624, 872 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
25
[
a]
¼þ122.3, (c 0.52, CH2Cl2).
d
¼7.24–7.16 (m, 2H), 7.12 (s, 1H), 7.02 (d, J¼7.2 Hz, 1H), 6.10 (dd,
D
J1¼2.8 Hz, J2¼8.4 Hz, 1H), 4.02 (t, J¼5.2 Hz, 1H), 2.50 (d, J¼17.2 Hz,
1H), 2.37 (d, J¼18.0 Hz, 1H), 2.31 (d, J¼10.4 Hz, 1H), 2.27 (d,
J¼13.6 Hz, 1H), 2.21–2.16 (m, 1H), 2.14 (s, 3H), 2.12–2.05 (m, 1H),
4.3.6. (2R,4S)-4-(4-Fluorophenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-
hexahydro-2H-chromen-2-yl acetate (6c). Yellow solid; mp 98.7–
100.2 ꢀC; IR (KBr): 2964, 1759, 1626, 844 cmꢁ1; 1H NMR (400 MHz,
1.16 (s, 3H), 1.10 (s, 3H); 13C NMR (100 MHz, CDCl3):
d¼196.3, 169.0,
CDCl3):
d
¼7.11 (dd, J1¼5.2 Hz, J2¼8.4 Hz, 2H), 6.97 (t, J¼8.4 Hz, 2H),
168.3, 145.7, 134.5, 129.9, 127.5, 126.8, 125.4, 111.6, 89.7, 50.7, 42.1,
34.3, 33.0, 32.1, 28.7, 28.2, 20.9; MS (EI): m/z (%)¼348 (10) [Mþ], 306
(25), 288 (70), 277 (100), 253 (30); HRMS (EI) Calculated
for C19H21ClO4 (Mþ): 348.1128, found: 348.1120; The ee was de-
termined by HPLC analysis using a Chiralpak OD-H column [hex-
6.11(dd, J1¼2.8 Hz, J2¼8.8 Hz,1H), 4.04 (s,1H), 2.48 (d J¼17.6 Hz,1H),
2.37 (d, J¼18.4 Hz, 1H), 2.38 (d, J¼17.2 Hz, 1H), 2.29 (d, J¼16.4 Hz,
1H), 2.23 (d, J¼16.4 Hz,1H), 2.20–2.12 (m,1H), 2.12 (s, 3H), 2.07–2.02
(m,1H),1.15 (s, 3H),1.10 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
¼196.4,
169.1,168.04,161.6 (d, J¼243.4 Hz,1C),139.2, 128.7 (d, J¼8.3 Hz, 2C),
115.5 (d, J¼21.2 Hz, 2C), 112.1, 89.8, 50.8, 42.01, 34.4, 32.5, 32.1, 28.7,
28.2, 20.9; MS (ESI): m/z (%)¼333 (100) [Mþþ1], HRMS (ESI) Calcu-
lated for C19H21FO4 (Mþ): 332.1424, found: 332.1440; The ee was
determined by HPLC analysis using a Chiralpak OD-H column
ane/iPrOH (82:18)]; flow rate 1.0 mL/min; smajor¼12.9 min, sminor¼
25
9.0 min, 86% ee; [
a
]
¼þ83.4, (c 1.36, CH2Cl2).
D
4.3.11. (2R,4S)-7,7-Dimethyl-5-oxo-4-(2-(trifluoromethyl)phenyl)-
3,4,5,6,7,8-hexahydro-2H-chromen-2-yl acetate (6h). Yellow viscous
oil; IR (KBr): 2958, 1758, 1632, 1397, 733 cmꢁ1; 1H NMR (400 MHz,
[hexane/iPrOH (82:18)]; flow rate 1.0 mL/min; smajor¼10.1 min,
25
sminor¼8.4 min, 84% ee; [
a
]
¼þ101.2, (c 0.51, CH2Cl2).
CDCl3):
d
¼7.67 (d, J¼7.6 Hz, 1H), 7.42 (t, J¼7.6 Hz, 1H), 7.29 (t,
D
J¼7.6 Hz, 1H), 7.17 (d, J¼7.6 Hz, 1H), 6.27 (dd, J1¼2.8 Hz, J2¼7.2 Hz,
1H), 4.38 (t, J¼6.0,1H), 2.49 (d, J¼17.6 Hz,1H), 2.39 (d, J¼17.6 Hz,1H),
2.36–2.22 (m, 3H), 2.12 (s, 3H), 2.03–1.97 (m,1H),1.15 (s, 3H),1.09 (s,
4.3.7. (2R,4S)-4-(4-Chlorophenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-
hexahydro-2H-chromen-2-yl acetate (6d). Viscous oil; IR (KBr):

10020
C. Yu et al. / Tetrahedron 65 (2009) 10016–10021
3H); 13C NMR (100 MHz, CDCl3):
d
¼195.9, 169.2, 168.1, 143.0, 131.9,
1754, 1633, 833 cmꢁ1
J¼8.8 Hz, 2H), 6.82 (d, J¼8.0 Hz, 2H), 6.09 (dd, J1¼2.8 Hz, J2¼8.8 Hz,
1H), 4.03 (s, 1H), 3.76 (s, 3H), 2.62–2.48 (m, 2H), 2.41–2.33 (m, 2H),
2.17–2.11 (m, 1H), 2.16 (s, 3H), 2.08–2.01 (m, 3H); 13C NMR
;
1H NMR (400 MHz, CDCl3):
d¼7.06 (d,
127.8, 126.5, 112.6, 89.4, 50.7, 42.1, 34.0, 32.0, 29.3, 28.4, 20.9; MS
(ESI): m/z (%)¼383 (100) [Mþþ1]; HRMS (ESI) Calculated for
C20H21F3O4 (Mþ): 382.1392, found:382.1399, The eewas determined
by HPLC analysis using a Chiralpak AS-H column [hexane/iPrOH
(100 MHz, CDCl3):
d
¼196.6, 169.6, 169.1, 158.3, 135.4, 128.2, 114.1,
(79:21)]; flow rate 1.0 mL/min; smajor¼6.3 min, sminor¼7.4 min, 83%
113.6, 89.9, 55.2, 36.6, 34.4, 32.4, 28.4, 20.9, 20.8; MS (EI): m/z
(%)¼316 (40) [Mþ], 274 (35), 256 (95), 245 (100), 231 (45), HRMS
(EI) Calculated for C18H20O5 (Mþ): 316.1311, found: 316.1312; The ee
was determined by HPLC analysis using a Chiralpak OD-H column
25
ee; [a
]
¼115.0 (c 0.16, CH2Cl2).
D
4.3.12. (2R,4S)-4-(2-Methoxyphenyl)-7,7-dimethyl-5-oxo-
3,4,5,6,7,8-hexahydro-2H-chromen-2-yl acetate (6i). Yꢁel1low solid;
[hexane/iPrOH (82:18)]; flow rate 1.0 mL/min; smajor¼22.5 min,
25
mp 89.7–92.0 ꢀC; IR (KBr): 2958, 1762, 1618, 765 cm
;
1H NMR
sminor¼15.5 min, 84% ee; [
a]
¼70.8, (c 0.5, CH2Cl2).
D
(400 MHz, CDCl3):
d
¼7.19–7.15 (m, 1H), 6.89–6.82 (m, 3H), 6.03 (dd,
J1¼3.2 Hz, J2¼9.6 Hz, 1H), 4.40 (s, 1H), 3.86 (s, 3H), 2.50 (d,
J¼17.6 Hz, 1H), 2.37 (d, J¼17.6 Hz, 1H), 2.31 (d, J¼16.0 Hz, 1H), 2.23
(d, J¼16.0 Hz, 1H), 2.19–2.14 (m, 1H), 2.10 (s, 3H), 2.08–2.02 (m, 1H),
4.3.17. (2R,4S)-4-(4-Methoxyphenyl)-5-oxo-2,3,4,5,6,7-hexahy-
drocyclopenta[b]pyran-2-yl acetate (6n). Yellow viscous oil; IR
(KBr): 2925, 1754, 1637, 869 cmꢁ1; major diastereoisomer: 1H NMR
1.17 (s, 3H), 1.09 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
¼196.4, 169.2,
(400 MHz, CDCl3):
d
¼7.07 (d, J¼8.8 Hz, 2H), 6.84 (d, J¼8.8 Hz, 2H),
168.4, 156.0, 130.94, 127.8, 120.3, 111.7, 110.5, 90.6, 55.2, 50.8, 42.1,
32.1, 31.8, 29.0, 28.0, 27.5, 21.0; MS (ESI): m/z (%)¼345 (100)
[Mþþ1], HRMS (ESI) Calculated for C20H24O5 (Mþ): 344.1624,
found: 344.1618; The ee was determined by HPLC analysis using
6.37 (dd, J1¼2.4 Hz, J2¼6.4 Hz,1H), 3.81 (br s,1H), 3.78 (s, 3H), 2.70–
2.65 (m, 2H), 2.51–2.47 (m, 2H), 2.22–2.17 (m, 1H), 2.15 (s, 3H),
2.05–1.97 (m,1H); 13C NMR (100 MHz, CDCl3):
d¼202.1,181.8,168.9,
158.3, 132.8, 128.2, 116.9, 114.0, 91.3, 55.1, 34.5, 33.3, 31.1, 25.8, 20.8;
MS (EI): m/z (%)¼302 (20) [Mþ], 242 (100), 231 (40), 216 (65);
HRMS (EI) Calculated for C17H18O5 (Mþ): 302.1154, found: 302.1158;
The ee was determined by HPLC analysis using a Chiralpak OD-H
a Chiralpak OD-H column [hexane/iPrOH (82:18)]; flow rate 1.0 mL/
25
min; smajor¼15.8 min, sminor¼32.3 min, 83% ee; [
a
]
¼58.2, (c 0.44,
D
CH2Cl2).
column [hexane/iPrOH (82:18)]; flow rate 1.0 mL/min; smajor
¼
25
4.3.13. (2R,4R)-4,7,7-Trimethyl-5-oxo-3,4,5,6,7,8-hexahydro-2H-
chromen-2-yl acetate (6j). Yellow solid; mp 55.9–57.9 ꢀC; IR (KBr):
3133, 2959, 1759, 1629 cmꢁ1; major diastereoisomer: 1H NMR
32.7 min, sminor¼30.1 min, 88% ee; [
a]
¼þ40.4 (c 0.53, CH2Cl2).
D
4.3.18. (2R,4S)-5-Acetyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihy-
dro-2H-pyran-2-yl acetate (6o). Yellow viscous oil; IR (KBr): 2932,
1758, 1677, 836 cmꢁ1; major diastereoisomer: 1H NMR (400 MHz,
(400 MHz, CDCl3):
d¼6.27 (dd, J1¼2.8 Hz, J2¼9.2 Hz, 1H), 2.90 (br s,
1H); 2.34–2.27 (m, 2H), 2.60–2.19 (m, 2H), 2.15 (s, 3H),1.95–1.87 (m,
1H), 1.81 (dt, J1¼3.2, J2¼6.8, 1H), 1.16 (d, J¼6.8 Hz, 3H), 1.07 (s, 3H),
CDCl3):
d
¼7.14–7.09 (m, 2H), 6.86–6.81 (m, 2H), 6.04 (dd, J1¼2.8 Hz,
1.04 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
¼197.4, 169.4, 166.3, 115.2,
J2¼7.6 Hz, 1H), 3.98 (t, J¼5.2 Hz, 1H), 3.78 (s, 3H), 2.27 (s, 3H), 2.23–
90.0, 51.0, 41.9, 32.9, 32.0, 28.6, 27.8, 22.2, 21.0, 20.5; MS (ESI): m/z
(%)¼253 (100) [Mþþ1], HRMS (ESI) Calculated for C14H20O4 (Mþ):
252.1362, found: 252.1355; The ee was determined by HPLC analysis
2.21 (m, 1H), 2.12 (s, 3H), 2.05–1.96 (m, 1H), 1.71 (s, 3H); 13C NMR
(100 MHz, CDCl3):
d¼199.6, 169.3, 160.8, 158.5, 135.5, 128.5, 114.4,
90.3, 89.0, 55.3, 36.3, 34.8, 29.7, 21.1, 20.1; MS (ESI): m/z (%)¼305
(100) [Mþþ1], HRMS (ESI) Calculated for C17H20O5 (Mþ): 304.1311,
found: 304.1315; The ee was determined by HPLC analysis using a
using a Chiralpak OD-H column [hexane/iPrOH (82:18)]; flow rate
25
1.0 mL/min; smajor¼6.2 min, sminor¼5.7 min, 92% ee; [
a
]
¼63.5, (c
D
0.52, CH2Cl2).
Chiralpak OD-H column [hexane/iPrOH (98:2)]; flow rate 1.0 mL/
25
min; smajor¼18.7 min, sminor¼19.9 min, 20% ee; [
a
]
¼ꢁ36.2, (c 0.26,
D
4.3.14. (2R,4R)-7,7-Dimethyl-5-oxo-4-propyl-3,4,5,6,7,8-hexahydro-
CH2Cl2).
2H-chromen-2-yl acetate (6k). Yellow viscous oil; IR (KBr): 3133,
2959, 1759, 1629 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d¼6.25 (dd,
4.3.19. (2R,4S)-Ethyl 2-acetoxy-4-(4-methoxyphenyl)-6-methyl-3,4-
dihydro-2H-pyran-5-carboxylate (6p). Yellow viscous oil, IR (KBr):
2932, 1758, 1708, 1249 cmꢁ1, major diastereoisomer: 1H NMR
J1¼2.8 Hz, J2¼9.6 Hz, 1H), 2.77 (br s, 1H), 2.29–2.17 (m, 3H), 2.15 (s,
3H), 2.02–1.97 (m,1H),1.82–1.74 (m,1H),1.68–1.62 (m,1H),1.42–1.19
(m, 4H), 1.06 (s, 3H), 1.04 (s, 3H), 0.91 (t, J¼7.2 Hz, 3H); 13C NMR
(400 MHz, CDCl3):
d
¼7.12–7.08 (m, 2H), 6.83 (m, 2H), 6.09 (dd,
(100 MHz, CDCl3):
d
¼197.2, 169.4, 166.4, 114.6, 90.2, 51.0, 41.9, 32.0,
J1¼2.8 Hz, J2¼7.6 Hz, 1H), 4.00–3.92 (m, 3H), 3.78 (s, 3H), 2.31 (s,
29.3, 28.5, 28.0, 27.0, 21.0, 20.0, 14.0; MS (ESI): m/z (%)¼281 (100)
[Mþþ1], HRMS (ESI) Calculated for C16H24O4 (Mþ): 280.1675, found:
280.1678; The ee was determined by HPLC analysis using a Chiralpak
3H), 2.27–2.13 (m, 1H), 2.11 (s, 3H), 2.01–1.99 (m, 1H), 0.97 (t,
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
¼169.3, 167.5, 161.2,
d
158.2, 136.5, 128.3,113.9,105.4, 89.3, 59.8, 55.2, 35.4, 34.5, 21.0,19.5,
13.9; MS (EI): m/z (%)¼334 (5) [Mþ], 289 (10), 274 (100), 245(60),
HRMS (EI) Calculated for C18H22O6 (Mþ): 334.1416, found: 334.
1418; The ee was determined by HPLC analysis using a Chiralpak
OD-H column [hexane/iPrOH (82:18)]; flow rate 1.0 mL/min;
smajor¼5.8 min, sminor¼6.7 min, 87% ee; [
25
a
]
¼74.6, (c 0.59, CH2Cl2).
D
4.3.15. (2R,4R)-4-(Furan-2-yl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hex-
OD-H column [hexane/iPrOH (98:2)]; flow rate 1.0 mL/min; smajor
¼
25
ahydro-2H-chromen-2-yl acetate (6l). Yellow viscous oil; IR (KBr):
11.6 min, sminor¼10.8 min, 88% ee; [
a
]
D
¼119.0, (c 0.42, CH2Cl2).
2958, 1758, 1632, 1397, 733 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
¼7.28 (d, J¼6.0 Hz, 1H), 6.25–6.22 (m, 2H), 5.97 (d, J¼3.2 Hz, 1H),
4.16 (s, 1H), 2.43–2.29 (m, 4H), 2.14 (s, 3H), 2.04–1.97 (m, 2H), 1.11
(s, 3H), 1.08 (s, 3H); 13C NMR (100 MHz, CDCl3):
Acknowledgements
d¼196.3, 169.1,
We thank the National Natural Science Foundation of China
[20676123 and 20876147] for financial support.
168.0, 155.3, 141.4, 110.3, 106.3, 90.6, 50.7, 42.0, 32.2, 30.7, 28.6, 28.1,
27.3, 20.9; MS (EI): m/z (%)¼304 (20) [Mþ], 262 (35), 244 (100),
215(30), HRMS (EI) Calculated for C17H20O5 (Mþ): 304.1311, found:
304.1309; The ee was determined by HPLC analysis using a Chir-
alpak OD-H column [hexane/iPrOH (82:18)]; flow rate 1.0 mL/min;
smajor¼8.6 min, sminor¼7.7 min,81% ee; [
References and notes
25
1. (a) Enders, D.; Wang, C.; Bats, J. W. Angew. Chem., Int. Ed. 2008, 47, 7539–7542;
(b) Hong, B. C.; Nimje, R. Y.; Sadani, A. A.; Liao, J. H. Org. Lett. 2008, 12, 2345–
2348; (c) Ibrahem, I.; Zhao, G. L.; Rios, R.; Vesely, J.; Sunde´n, H.; Dziedzic, P.;
a
]
¼81.9, (c 0.52, CH2Cl2).
D
4.3.16. (2R,4S)-4-(4-Methoxyphenyl)-5-oxo-3,4,5,6,7,8-hexahydro-
´
Cordova, A. Chem.dEur. J. 2008, 14, 7867–7879; (d) Melchiorre, P. Angew. Chem.,
2H-chromen-2-yl acetate(6m). Yellow viscous oil; IR (KBr): 2944,
Int. Ed. 2009, 48, 2–7; (e) Galzerano, P., Bencivenni, G.; Pesciaioli, F.; Mazzanti,

C. Yu et al. / Tetrahedron 65 (2009) 10016–10021
10021
A.; Giannichi, B.; Sambri, L.; Bartoli, G.; Melchiorre, P. Chem.dEur. J. 2009, 15,
7846–7849.
H.; Jang, D. S.; Yoo, J. L.; Lee, Y. M.; Kim, Y. S.; Cho, J. H.; Kim, J. S. J. Nat. Prod.
2008, 71, 713–715.
2. (a) Alema´n, J.; Cabrera, S.; Maerten, E.; Overgaard, J.; Jøgensen, K. A. Angew.
Chem., Int. Ed. 2007, 46, 5520–5523; (b) Rueping, M.; Sugiono, E.; Merino, E.
Angew. Chem., Int. Ed. 2008, 47, 3046–3049; (c) Rueping, M.; Merino, E.; Su-
giono, E. Adv. Synth. Catal. 2008, 350, 2127–2131; (d) Hayashi, Y.; Obi, K.; Ohta,
Y.; Okamura, D.; Ishikawa, H. Chem. Asian. J. 2009, 4, 246–249; (e) Hayashi, Y.;
Gotoh, H.; Masui, R.; Ishikawa, H. Angew. Chem., Int. Ed. 2008, 47, 4012–4015; (f)
Wang, Y. C.; Li, P. F.; Liang, X. M.; Ye, J. X. Adv. Synth. Catal. 2008, 350, 1383–1389.
3. Moorthy, J. N.; Saha, S. Eur. J. Org. Chem. 2009, 739–748.
4. (a) Tan, B.; Zeng, X.; Lu, Y.; Chua, P. J.; Zhong, G. Org. Lett. 2009, 9, 1927–1930;
(b) Zu, L.; Wang, J.; Li, H.; Wang, W. Org. Lett. 2006, 14, 3077–3079; (c) Yu, Z. P.;
Liu, X. H.; Zhou, L.; Lin, L. L.; Feng, X. M. Angew. Chem., Int. Ed. 2009, 48, 1–5; (d)
Chu, Q.; Yu, M. S.; Curran, D. P. Org. Lett. 2008, 5, 749–752; (e) Wu, J.B.; Ni, B.;
Headley, A.D. Org. Lett. 2009, 15, 3354–3356.
6. (a) Palasz1, A.; Jelska1, K.; Ozo´g, M.; Serda, P. Monatshefte. Fu¨r. Chemie. 2007, 38,
˙
481–488; (b) Emerson, W. S.; Birum, G. H.; Longley, R. I. J. Am. Chem. Soc. 1953,
75, 1312–1313; (c) Zhao, Y.; Wang, X. J.; Liu, J. T. Synlett 2008, 1017–1020; (d)
Bunnelle, W. H.; Meyer, L. A. J. Org. Chem. 1988, 53, 4038–4042; (e) Al-Badri, H.;
Collignon, N.; Maddaluno, J.; Masson, S. Chem. Commun. 2000, 1191–1192.
7. (a) Itoh, K.; Kanemasa, S. Tetrahedron Lett. 2003, 44, 1799–1802; (b) Itoh, K.;
Hasegawa, M.; Tanaka, J.; Kanemasa, S. Org. Lett. 2005, 6, 979–981; (c) Katritzky,
A. R.; Denisko, O. V. J. Org. Chem. 2002, 67, 3104–3108; (d) Schmidt, B.; Wild-
emann, H. Eur. J. Org. Chem. 2000, 3145–3163; (e) Li, G. Q.; Dai, L. X.; You, S. L.
Org. Lett. 2009, 7, 1623–1625; (f) Yamamoto, Y.; Kirai, N. Org. Lett. 2008, 24,
5513–5516.
8. Franke, P. T.; Richter, B.; Jøgensen, K. A. Chem.dEur. J. 2008, 14, 6317–6321.
9. Zhu, M. K.; Wei, Q.; Gong, L. Z. Adv. Synth. Catal. 2008, 350, 1281–1285.
10. (a) Xin, J. G.; Chang, L.; Hou, Z. R.; Shang, D. J.; Liu, X. H.; Feng, X. M. Chem.dEur.
J. 2008, 14, 3177–3181; (b) Bonini, B. F.; Capito`, E.; Comes-Franchini, M.; Fochi,
M.; Ricci, A.; Zwanenburg, B. Tetrahedron: Asymmetry 2006, 17, 3135–3143.
11. Franke, P. T.; Johansen, R. L.; Bertelsen, S.; Jøgensen, K. A. Chem. Asian. J. 2008, 3,
216–224.
5. (a) Kumar, S.; Malachowski, W. P.; DuHadaway, J. B.; LaLonde, J. M.; Carroll, P. J.;
Jaller, D.; Metz, R.; Prendergast, G. C.; Muller, A. J. J. Med. Chem. 2008, 51, 1706–
1718; (b) Goddard-Borger, E. D.; Ghisalberti, E. L.; Stick, R. V. Eur. J. Org. Chem.
2007, 3925–3934; (c) Rahman, A.; Nasreen, A.; Akhtar, F.; Shekhani, M. S.;
Clardy, J.; Parvez, M.; Choudhary, M. I. J. Nat. Prod. 1997, 60, 472–474; (d) Yoo, N.