on Water C(sp3)-H Functionalization/C-O/C-N Bonds Formations: Synthesis of Functionalized Oxazolidines and Imidazolidines

Article abstract of DOI:10.1021/acs.joc.6b01850

On water oxidative C(sp³)-H functionalization/C-O/C-N bonds formations using tetrabutylammonium iodide as the catalyst and tert-butyl hydroperoxide in water (T-Hydro) as the oxidant affords a potential route for the construction of functionalized oxazolidines and imidazolidines. The reaction is simple, regioselective, and effective at moderate temperature with broad substrate scope. In the case of optically active substrates, the oxidative cyclization can be accomplished with high optical purities.

Full text of DOI:10.1021/acs.joc.6b01850

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Article
“On Water” C(sp3)-H Functionalization/C-O/C-N Bonds Formations:
Synthesis of Functionalized Oxazolidines and Imidazolidines
Vanaparthi Satheesh, Mani Sengoden, and Tharmalingam Punniyamurthy
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01850 • Publication Date (Web): 06 Oct 2016
Downloaded from http://pubs.acs.org on October 7, 2016
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“On Water” C(sp3)-H Functionalization/C-O/C-N Bonds Formations:
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Synthesis of Functionalized Oxazolidines and Imidazolidines
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Vanaparthi Satheesh, Mani Sengoden and Tharmalingam Punniyamurthy*
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Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India.
On water oxidative C(sp3)ꢀH functionalization/CꢀO/CꢀN bonds formations using tetrabutylammonium
iodide (TBAI) as the catalyst and tertꢀbutyl hydroperoxide in water (TꢀHydro) as the oxidant affords a
potential route for the construction of functionalized oxazolidines and imidazolidines. The reaction is
simple, regioselective and effective at moderate temperature with broad substrate scope. In case of
optically active substrates, the oxidative cyclization can be accomplished with high optical purities.
INTRODUCTION
Water is highly abundant, inexpensive, nontoxic and nonflammable. Thus, its use as a solvent for
organic synthesis is attractive.1,2 Oxazolidines3,4 and imidazolidines5,6 are privileged structural scaffolds
that exist in many bioactive compounds (Figure 1). They are also widely employed as auxiliaries,
catalysts and ligands for transitionꢀmetalꢀcatalysts.7,8 Generally, they are prepared by the condensation
of aldehydes with the 1,2ꢀamino alcohols7c and 1,2ꢀdiamines,5a respectively. The alternative methods for
the synthesis of oxazolidines and imidazolidines include the cycloaddition3a,5b,9 conjugate addition3b and
azaꢀWacker reaction.3d,10 The selective functionalization of CꢀH bonds is an efficient strategy for the
conversion of prefunctionalized simple substrates into complex molecules with structural diversity.11
Among them, the direct oxidative functionalization of CꢀH bond next to nitrogen is attractive from both
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the synthetic and enzymatic aspects.12,13 More recently, Rhꢀcomplex has been shown to catalyze the
oxidative coupling of N,Nꢀdimethylaniline with MeOH,14 while Ruꢀcomplex is employed for the
amination of benzylic CꢀH bond adjacent to nitrogen in the presence of visible light.5d Herein, we
present a simple and efficient on water metalꢀfree regioselective oxidative crossꢀcoupling of C(sp3)ꢀH
bonds adjacent to nitrogen with alkyl OꢀH and NꢀH bonds to furnish oxazolidines and imidazolidines
from 1,2ꢀamino alcohols and 1,2ꢀdiamines bearing N,Nꢀarylalkyl and N,Nꢀalkylsulfonyl substituents
using TBAI in the presence of TꢀHydro14 at moderate temperature under air. This reaction also allows
the transformation of optically active substrates into the corresponding oxazolidines and imidazolidines
without the loss of the optical purity that are broadly useful as chiral auxiliaries and chiral ligands for
asymmetric synthesis.7,8 The broad substrate scope, free from the contamination of metalꢀsalts,
simplified product isolation and use of water as the solvent are the significant practical features.
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Figure 1. Examples of bioactive oxazolidine and imidazolidine containing natural products.
RESULTS AND DISCUSSION
First, the optimization of the reaction conditions was performed using amino alcohol 1a as a model
substrate in the presence of iodides and oxidants on water (Table 1). Gratifyingly, the reaction occurred
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to produce oxazolidine 2a in 55% when 1a was stirred with 15 mol % of TBAI and 2 equiv of TꢀHydro
at room temperature under air (entry 1). The use of 30% H2O2 and diꢀtertꢀbutyl peroxide (DTBP) in
place of Tꢀhydro led to inferior results (entries 2ꢀ3). However, increasing the reaction temperature (60
°C) furnished the target product in 100% conversion and selectivity (entries 4ꢀ5). Similar results were
observed using N2 atmosphere (entry 5). In a set of iodides screened, TBAI, NaI, KI and I2, the former
furnished the best results (entries 6ꢀ8). Decreasing the amount of TBAI (10 mol %) or TꢀHydro (1.5
equiv) led to the formation of 2a in < 65% yield (entry 9). A control experiment confirmed that the
target heterocycle was not observed in the absence of TBAI (entry 10).
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Table 1. Optimization of the Reaction Conditions
yield (%)a,b
entry
catalyst (15 mol %)
oxidant (2 equiv)
temp (°C)
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8
TBAI
TBAI
TBAI
TBAI
TBAI
NaI
TꢀHydro
30% H2O2
DTBP
rt
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rt
5
rt
0
TꢀHydro
TꢀHydro
TꢀHydro
TꢀHydro
TꢀHydro
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80
95(100)c,d
0
KI
0
I2
30
9
TBAI
ꢀ
TꢀHydro
TꢀHydro
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60
61e,65f
0
10
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aAmino alcohol 1a (0.5 mmol), catalyst (15 mol %), oxidant (1 mmol), H2O (1 mL), 24 h. Isolated
b
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3
c
1
d
e
f
yield. Determined by 400 MHz H NMR. Under N2 atmosphere. TBAI (10 mol %) used. TꢀHydro
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(0.75 mmol) used.
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Having the optimal conditions, the reaction of amino alcohols 1b-m having substitution in Nꢀaryl
ring was investigated (Scheme 1). The substrate 1b bearing substitution at 2ꢀposition with methyl group
showed no product 2b formation, which may be due to the steric hindrance of the methyl functionality.
However, the reaction of 1c-e containing substitution at 3ꢀposition with ethyl, methyl and
trifluoromethyl groups gave 2c-e in 55ꢀ86% yields. Similarly, the substrates 1f-i having substitution at
4ꢀposition with bromo, chloro, isopropyl and methyl groups produced the corresponding oxazolidines
2f-i in 77ꢀ88% yields. In contrast, 1j with strong electron withdrawing nitro group failed to produce 2j,
which may be due to the delocalization of nitrogen lone pair in Nꢀaryl ring towards the nitro group and
not available for the single electron transfer (SET) reduction of iodine to Iꢀ (Scheme 10, step ii).
However, the reaction of 1k and 1l bearing 3,4ꢀdimethyl and 3,5ꢀdichloro functionalities furnished 2k
and 2l in 85 and 70% yields, respectively, whereas 1m containing 4ꢀazobenzene substituent afforded 2m
in good yield.
Next, the reaction of the substrates bearing substitution at 2ꢀaryl ring was explored (Scheme 2). The
substrate 1n bearing 2ꢀchloro substituent underwent reaction to provide 2n in 75% yield. The reaction
of 1o-q having substitution at 3ꢀposition with methoxy, methyl and nitro functionalities furnished the
target oxazolidines 2o-q in 65ꢀ87% yields, whereas 1r-u containing substitution at 4ꢀposition with
acetoxy, bromo, chloro and fluoro groups afforded the corresponding substituted oxazolidines 2r-u in
78ꢀ85% yields.
The reaction of the substrates bearing substitution in both aryl rings was further examined (Scheme
3). Substrate 1v having substitution at 3ꢀposition with methyl and ethyl groups underwent reaction to
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give 2v in 86% yield. The reaction of 1w-x having substitution at 4ꢀposition with chloro, fluoro, methyl
and acetoxy functionalities afforded 2w and 2x in 82% and 84% yields, respectively. The reaction
condition is also compatible for the cyclization of tetrahydroisoquinoline derivative 1y, affording the
tricyclic oxazolidine 2y in good yield (Scheme 4). Under these conditions, Nꢀethyl substrate 1z showed
no cyclization and the formation of 2z was not observed.
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Scheme 1. Reaction of N-Aryl Substituted Substrates
O
Me
N
N
TBAI (15 mol%)
OH
R
R
Ph
Ph
T-Hydro (2 equiv)
1b-m
R = EWG, EDG
2b-m
H2O, 60 °C, 17-30 h
O
O
O
Me
N
Ph
Me
N
N
Ph
2d, 24 h, 84%
Ph
2c, 20 h, 86%
2b, 30 h, 0 %
O
O
O
F3C
N
N
N
Ph
Ph
Ph
Cl
Br
2e, 30 h, 55%
2g, 24 h, 81%
2f, 24 h, 77%
O
N
O
N
O
N
Ph
Ph
2h, 17 h, 88%
O2N
Ph
Me
2j, 30 h, 0%
2i, 24 h, 84%
O
N
O
O
Cl
Me
Me
N
N
Ph
Ph
Ph
N
Ph
N
Cl
2k, 20 h, 85%
2l, 26 h, 70%
2m, 30 h, 47%
aSubstrate 1b-m (0.5 mmol), TBAI (15 mol %), TꢀHydro (1 mmol),
H2O (1 mL), 60 °C. bIsolated yield.
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Scheme 2. Reaction of 2-Aryl Substituted Substrates
5
6
Me
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8
9
N
O
N
Ph
OH
TBAI (15 mol%)
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R
R
Ph
T-Hydro (2 equiv)
H2O, 60 oC
2n-u
1n-u
R = EWG, EDG
O
N
O
O
Cl
OMe
Me
N
N
Ph
Ph
Ph
2p, 24 h, 81%
2n, 28 h, 75%
2o, 18 h, 87%
O
N
O
O
NO2
N
N
Ph
Ph
Ph
Br
OAc
2r, 18 h, 85%
2q, 30 h, 65%
2s, 24 h, 79%
O
O
N
N
Ph
Ph
Cl
F
2t, 24 h, 78%
2u, 24 h, 84%
aSubstrate 1n-u (0.5 mmol), TBAI (15 mol %), TꢀHydro (1
mmol), H2O (1 mL), 60 °C. bIsolated yield.
Having these results, we further studied the reaction of analogue diamines to produce imidazolidines
(Scheme 5). The best results observed in the presence of a few drops (200 ꢀl) of 1,2ꢀdichloroethane
(DCE), which assists the solid substrate to be gummy and float on the surface of water. The substrate 3a
underwent reaction to give imidazolidine 4a in 81% yield. Next, the reaction of the substrates bearing
substitution in Nꢀaryl ring was performed. As above, the reaction of 3b containing 2ꢀmethyl group
showed no cyclization to furnish 4b. However, the substrates 3c-d having substitution at 3ꢀposition with
methyl and ethyl functionalities afforded imidazolidines 4c-d in 82% yield. Similarly, the substrates 3e-
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g bearing substitution at 4ꢀposition with chloro, isopropyl and methyl groups underwent cyclization to
afford the corresponding imidazolidines 4e-g in 75ꢀ84% yields, whereas 3h with Nꢀfluorene furnished
4h in 61% yield. In addition, the substrate 3i having Nꢀphenylsulfonyl substituent underwent reaction to
furnish imidazoline 4i in 75% yield.
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Scheme 3. Reaction of N- and 2-Aryl Substituted Substrates
aSubstrate 1v-x (0.5 mmol), TBAI (15 mol %), TꢀHydro (1
mmol), H2O (1 mL), 60 °C. bIsolated yield.
Scheme 4. Reaction of Tetrahydroisoquinoline and N-Ethyl Substrates
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Next, the reaction of tetrahydroisoquinoline derivatives was investigated (Scheme 6). The substrate
3j underwent reaction to provide imidazolidine 4j in 63% yield. Similarly, the reaction of 3k and 3l
bearing 2ꢀchloro and 3ꢀmethyl groups in 2ꢀaryl ring afforded imidazolidines 4k and 4l in 56 and 67%
yields, respectively, whereas 3m-n bearing at 4ꢀposition with bromo and fluoro groups produced
imidazolidines 4m-n in 57ꢀ59% yields. In addition, the substrate 3o with 2,4ꢀdimethyl groups
underwent reaction to furnish 4o in 62% yield, while 3p with Nꢀphenylsulfonyl instead of Nꢀtosyl
functionality cyclized to afford 4p in 60% yield.
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Scheme 5. Reaction of N-Aryl Substituted Substrates
O
O
S Ar
N
Me
N
O
TBAI (15 mol%)
T-Hydro (2 equiv)
O
N
S
N
Ar
R
R
H
Ph
Few drops DCE, H2O, 60 oC
R = Cl, alkyl
Ph
3a-i
4a-i
Ts
N
Ts
N
Ts
N
Me
N
Me
N
N
Ph
Ph
Ph
Ph
4a, 4 h, 81%
4c, 4 h, 82%
4b, 4 h, 0%
Ts
N
Ts
N
Ts
N
N
N
N
Ph
Ph
iPr
Ph
Cl
4d, 4 h, 82%
4e, 4h,75%
4f, 4 h, 84%
Ts
N
Ts
N
O
S
O
Ph
N
N
N
N
Ph
4g, 4 h, 82%
Ph
Ph
Me
Ph
4h, 5 h, 61%
4i, 4 h, 75%
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aSubstrate 3a-i (0.5 mmol), TBAI (15 mol %), TꢀHydro (1
1
2
3
b
mmol), DCE (few drops), H2O (1 mL), 60 °C. Isolated
4
5
6
yield.
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Scheme 6. Reaction of Tetrahydroisoquinoline Derivatives
TBAI (15 mol%)
T-Hydro (2 equiv)
N
R
N
Few drops DCE, H2O, 60 C
R = EDG, EWG
N
R
Ar
S
O
NHSO2Ar
3j-p
4j-p
O
Cl
N
N
N
Ph
N
N
N
Me
Ts
Ts
Ts
4j, 5 h, 63%
4l 5 h, 67%
4k, 6 h, 56%
Me
X
N
N
Me
Ph
N
N
N
N
PhO2S
Ts
Ts
4m, X = F, 6 h, 59%
4n, X = Br, 5 h, 57%
4o, 5 h, 62%
4p, 5 h, 60%
aSubstrate 3j-p (0.5 mmol), TBAI (15 mol %), TꢀHydro (1 mmol), DCE
(few drops), water (1 mL), 60 °C. bIsolated yield.
Finally, the reaction of the substrates with substitution in 2ꢀaryl ring was pursued (Scheme 7). The
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substrates 3q-r bearing substitution at 2ꢀposition with chloro and methyl groups produced
imidazolidines 4q and 4r in 76 and 73% yields, respectively. The reaction of 3s-t having substitution at
3ꢀposition with bromo and chloro functionalities furnished imidazolidines 4s-t in 78ꢀ80% yields.
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Similarly, the substrates 3u-z containing substitution at 4ꢀposition with acetoxy, chloro, bromo, fluoro,
methyl and chlormethyl groups underwent reaction to afford the corresponding imidazolidines 4u-z in
73ꢀ81% yields. In addition, 3aa with 2,4ꢀdimethyl groups crossꢀcoupled to give 4aa in 72% yield,
whereas 3ab having naphthyl functionality furnished imidazolidine 4ab in 71% yield.
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Scheme 7. Reaction of 2-Aryl Substituted Substrates
Me
Ts
N
Ts
Ph
N
TBAI (15 mol%)
T-Hydro (2 equiv)
N
H
N
R
Few drops DCE, H2O, 60 oC
R = EWG, EDG
R
Ph
4q-ab
3q-ab
Ts
Ts
Ts
N
N
N
Cl
Me
Br
N
N
N
Ph
Ph
4r, 4 h, 73%
Ts
Ph
4q, 4 h, 76%
4s, 4 h, 78%
Ts
N
Ts
N
N
N
Cl
N
N
Ph
Ph
Ph
Cl
OAc
4t, 4 h, 80%
4u, 3 h, 77%
4v, 4 h, 80%
Ts
N
Ts
Ts
N
N
N
N
N
Ph
Ph
Ph
Cl
Br
F
4x, 4 h, 79%
4y 4 h, 79%
4w, 5 h, 73%
Ts
Ts
N
Ts
N
N
Me
N
N
N
Ph
Ph
Ph
Me
Me
4z, 4 h, 81%
4ab, 3 h, 71%
4aa, 4 h, 72%
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aSubstrate 3q-ab (0.5 mmol), TBAI (15 mol %), TꢀHydro
(1 mmol), DCE (few drops), water (1 mL), 60 °C. bIsolated
yield.
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In case of optically active substrates, the reaction proceeded with high optical purities (Scheme 8).
The reaction of 1a’, 1c’ 3a’ and 3g’ was performed as the representative examples. The substrates 1a’
and 1c’ underwent reaction to produce 2a’ and 2c’ in 99% and 98% ee, respectively, while the reaction
of 3a’ and 3g’ produced the target heterocycles 4a’ and 4g’ in 97% ee. These results suggest that the
reaction provides potential route to construct oxazolidines and imidazolidines with high optical purities.
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Scheme 8. Reaction of Optically Active Substrates
Scheme 9. Radical Scavenger Experiments
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Scheme 10. Proposed Reaction Pathway
.
tBuOOH
1/2 I2
+
tBuO
XH
(i)
I
+
+ OH
R'
R'
1/2 I2
(ii)
N
N
*
*
.
XH
XH
XH
R
R +
I
+
Ar
Ar
a
R'
R'
.
tBuO
N
+ tBuOH
N
(iii)
(iv)
*
*
XH
.
R
R +
Ar
b
Ar
a
R'
R'
OH
N
+
N
*
*
H2O
+
X
R
R
+
Ar
c
Ar
b
R'
R'
R
X
N
*
N
X
(v)
R
*
Ar
Ar
2 or 4
c
R = aryl; R ' = H, benzyl; X = O, N-SO2Ar
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The Journal of Organic Chemistry
To get insight into the catalytic pathway, the reaction of 1a and 3a was performed with BHT
1
2
(Scheme 9).15 HRMS analysis of the reaction mixtures revealed the formation of BHT adducts 5a and
5b as the sole products, which suggests that the reaction involves a radical intermediate (see the
supporting information). Thus, the oxidation of TBAI by TꢀHydro may give iodine, tertꢀbutoxyl radical
and hydroxyl ion (Scheme 10, step i). Single electron transfer (SET) reduction of iodine may regenerate
the catalyst with the formation of the radical cation a (Scheme 10, step ii).16 Homolysis of methyl CꢀH
bond is induced by tertꢀbutoxyl radical may give the iminium b, which may convert into the target
heterocycles 2 and 4 via the intermediate c (Scheme 10, steps iv and v). The tertiary benzylic CꢀH bond
is intact, which may be due to its steric hindrance towards the tertꢀbutoxyl radical compared to that of
the methyl CꢀH bond. In these reactions, TBAI and TBHP are dissolved in water, while the substrates 1
and 3 are floated on the surface of the water, and the mixture is stirred. After completion, the products 2
and 4 are separated out as colorless solid or liquid on the surface of water, which can be easily isolated.
The reaction may take place in the interface of oilꢀwater droplets.1,2
3
4
5
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CONCLUSION
We described the oxidative crossꢀcoupling of Nꢀalkyl CꢀH bond with alkyl OꢀH and NꢀH bonds for the
construction of the functionalized oxazolidines and imidazolidines using TBAI in the presence of Tꢀ
Hydro at moderate temperature. The use of water as the solvent, metalꢀfree condition, regioselectivity,
simplified product isolation and broad substrate scope are the salient features. Optically active
substrates can be converted enantiospecifically to the corresponding oxoazolidines and imidazolidines.
EXPERIMENTAL SECTION
General Information. TꢀHydro, DTBP (98%), I2, 30% aq. H2O2, BHT (>99%), TBAI (99%), NaI
(99%) and KI (99%) were purchased from commercial source and used as received. All reactions were
performed in pure water (>5 Mꢁ cm @ 25 °C, total organic content < 30 ppb). The reactions were
monitored by analytical TLC on silica gel G/GF 254 plates. The column chromatography was
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Page 14 of 37
performed with 60ꢀ120 mesh silica gel. NMR (1H and 13C) spectra were recorded on 600 and 400 MHz
spectrometers using CDCl3 as a solvent and TMS as an internal standard. The data are accounted as
follows: chemical shifts (δ ppm) (multiplicity, coupling constant (Hz), integration). The abbreviations
for multiplicity are as follows: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet and dd =
doublet of doublets. Melting points were determined with melting point apparatus and are uncorrected.
Optical rotation were determined using polarimeter with a 50 mm path length cell at 589 nm at 23 °C.
FTꢀIR spectra recorded on a IR spectrometer. HRMS were analyzed with QꢀTOF instrument. HPLC
analysis was carried out with Daicel Chiralcel OD and OJ column.
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4
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General Procedure for the Synthesis of Oxazolidines 2a-y. To a mixture of the substituted 1,2ꢀ
aminoalcohols 1a-y (0.5 mmol), TBAI (15 mol %) and water (1 mL) was added TꢀHydro (1.0 mmol) at
room temperature under air. The substrate 1a-y was floated on the surface of the water as an oil and the
resultant mixture was stirred at 60 °C for the appropriate time. The progress of the reaction was
monitored by TLC using hexane and ethyl acetate as an eluent. After completion, the reaction mixture
was cooled to room temperature, treated with saturated Na2S2O3 (500 ꢀL) and ethyl acetate (5 mL). The
organic layer was seperated, dried (Na2SO4) and evaporated to give a residue that was purified on a
silica gel column chromatography using hexane and ethyl acetate as an eluent.
General Procedure for the Synthesis of Imidazolidines 4a-ab. To a mixture of substituted 1,2ꢀ
diamines 3a-ab (0.5 mml) and 1,2ꢀdichloroethane (three drops, ~200 ꢀl), water (1 mL), TBAI (15 mol
%) and TꢀHydro (1.0 mmol) were added at room temperature under air. The substrate 3a-ab with DCE
was floated on the surface of the water, and the resultant mixture was stirred at 60 °C for the appropriate
time. Monitoring of the reaction, workꢀup and purification were performed as described for 2a-y.
3,4-Diphenyloxazolidine 2a′. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf = 0.61; pale
1
yellow liquid; yield 95% (107 mg); H NMR (600 MHz, CDCl3) δ 7.37ꢀ7.34 (m, 4H), 7.30ꢀ7.28 (m,
1H), 7.19 (t, J = 8.4 Hz, 2H), 6.75 (t, J = 7.2 Hz, 1H), 6.50 (d, J = 8.4 Hz, 2H) 5.33 (d, J = 1.8 Hz, 1H),
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5.04 (d, J = 1.8 Hz, 1H), 4.71 (dd, J = 6.6, 4.2 Hz, 1H), 4.41 (t, J = 7.8 Hz, 1H), 3.99 (dd, J = 8.4, 4.2
1
2
3
13
Hz, 1H); C NMR (150 MHz, CDCl3) δ 145.2, 141.6, 129.4, 129.0, 127.7, 126.4, 117.9, 112.9, 83.0,
4
5
6
75.9, 61.9; FTꢀIR (neat) 3061, 3028, 2928, 2864, 1600, 1508, 1495, 1346, 1166, 1090, 749, 692 cmꢀ1;
20
HRMS (ESI) m/z [M+H]+ calcd for C15H15NO 226.1226, found 226.1225; [α]D = +159.0 (c= 0.2,
7
8
9
CHCl3); HPLC analysis: 99% ee [Daicel Chiralcel OD column, hexane/iPrOH = 90:10, flow rate: 1
mL/min, λ = 254 nm, tR = 4.94 min (minor), 8.36 min (major)].
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3-(3-Ethylphenyl)-4-phenyloxazolidine 2c′. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf
= 0.62; pale yellow liquid; yield 86% (109 mg); 1H NMR (400 MHz, CDCl3) δ 7.37ꢀ7.32 (m, 4H), 7.29ꢀ
7.27 (m, 1H), 7.09 (t, J = 7.6 Hz, 1H), 6.62 (d, J = 7.6 Hz, 1H), 6.33ꢀ6.30 (m, 2H), 5.33 (d, J = 2 Hz,
1H), 5.03 (d, J = 2 Hz, 1H), 4.70 (dd, J = 6.8, 4.4 Hz, 1H), 3.39 (t, J = 7.6 Hz, 1H), 3.98 (dd, J = 8.4, 4.4
Hz, 1H), 2.56 (q, J = 7.6 Hz, 2H), 1.17 (t, J = 7.6 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 145.6, 145.3,
141.8, 129.3, 129.0, 127.7, 126.4, 117.6, 112.5, 110.5, 83.0, 75.9, 61.9, 29.3, 15.7; FTꢀIR (neat) 3030,
2963, 2929, 2869, 1603, 1493, 1453, 1356, 1166, 1090, 759, 697 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd
20
for C17H19NO 254.1539, found 254.1539; [α]D = +28.0 (c= 0.2, CHCl3); HPLC analysis: 98% ee
[Daicel Chiralcel OJ column, hexane/iPrOH = 85:15, flow rate: 1 mL /min, λ = 254 nm, tR = 6.31 min
(minor), 13.53 min (major)].
4-Phenyl-3-(m-tolyl)oxazolidine 2d. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf = 0.62;
1
pale yellow liquid; yield 84% (100 mg); H NMR (600 MHz, CDCl3) δ 7.36ꢀ7.33 (m, 4H), 7.29ꢀ7.27
(m, 1H), 7.06 (t, J = 7.8 Hz, 1H), 6.58 (d, J = 7.2 Hz, 1H), 6.32 (s, 1H), 6.30 (d, J = 8.4 Hz, 1H), 5.32
(d, J = 2.4 Hz, 1H), 5.02 (d, J = 1.8 Hz, 1H), 4.70 (dd, J = 6.6, 4.2 Hz, 1H), 4.38 (t, J = 8.4 Hz, 1H),
13
3.98 (dd, J = 7.8, 4.2 Hz, 1H), 2.26 (s, 3H); C NMR (150 MHz, CDCl3) δ 145.3, 141.8, 139.2, 129.3,
129.0, 127.7, 126.4, 118.8, 113.6, 110.2, 83.0, 75.9, 61.8, 22.0; FTꢀIR (neat) 3063, 3032, 2921, 2863,
1605, 1493, 1453, 1356, 1170, 1089, 945, 840 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C16H17NO
240.1383, found 240.1383.
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4-Phenyl-3-(3-(trifluoromethyl)phenyl)oxazolidine 2e. Analytical TLC on silica gel, 1:19 ethyl
1
2
3
1
acetate/hexane Rf = 0.60; colorless liquid; yield 55% (81 mg); H NMR (600 MHz, CDCl3) δ 7.37ꢀ7.32
4
5
6
7
8
(m, 4H), 7.31ꢀ7.28 (m, 1H), 7.23 (t, J = 8.4 Hz, 1H), 6.97 (d, J = 7.8 Hz, 1H), 6.66 (s, 1H), 6.59 (dd, J =
8.4, 2.4 Hz, 1H), 5.33 (d, J = 2.4 Hz, 1H), 5.05 (d, J = 2.4 Hz, 1H), 4.72 (dd, J = 6.6, 4.2 Hz, 1H), 4.43
9
13
(dd, J = 8.4, 7.2 Hz, 1H), 4.00 (dd, J = 8.4, 4.2 Hz, 1H); C NMR (150 MHz, CDCl3) δ 145.1, 140.7,
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131.8 (q, JCꢀF = 31.5 Hz), 129.8, 128.1, 126.3, 124.7 (q, JCꢀF = 93.0 Hz), 115.9, 114.3 (q, JCꢀF = 4.5 Hz),
109.1 (q, JCꢀF = 3.0 Hz), 82.7, 76.0, 61.8; FTꢀIR (neat) 3061, 3031, 2923, 2868, 1615, 1508, 1493, 1459,
1372, 1166, 1121, 782, 697 cmꢀ1; HRMS (APCI) m/z [M+H]+ calcd for C16H14F3NO 294.1100, found
294.1097.
3-(4-Bromophenyl)-4-phenyloxazolidine 2f. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf
1
= 0.59; pale yellow liquid; yield 77% (117 mg); H NMR (600 MHz, CDCl3) δ 7.36ꢀ7.27 (m, 5H), 7.24
(d, J = 8.4 Hz, 2H), 6.34 (d, J = 8.4 Hz, 2H), 5.27 (d, J = 2.4 Hz, 1H), 4.98 (d, J = 2.4 Hz, 1H), 4.66 (dd,
J = 7.2, 4.8 Hz, 1H), 4.41 (t, J = 6.0 Hz, 1H), 3.97 (dd, J = 8.4, 4.8 Hz, 1H); 13C NMR (150 MHz,
CDCl3) δ 144.0, 140.9, 132.1, 129.1, 128.0, 126.3, 144.5, 109.9, 82.8, 76.0, 61.9; FTꢀIR (neat) 3061,
3028, 2923, 2853, 1595, 1505, 1489, 1360, 1165, 1089, 944, 807, 757 cmꢀ1; HRMS (ESI) m/z [M+H]+
calcd for C15H14BrNO 304.0332, found 304.0328.
3-(4-Chlorophenyl)-4-phenyloxazolidine 2g. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane
1
Rf = 0.59; pale yellow liquid; yield 81% (105 mg); H NMR (600 MHz, CDCl3) δ 7.36ꢀ7.27 (m, 5H),
7.11 (d, J = 9.0 Hz, 2H), 6.38 (d, J = 9.0 Hz, 2H), 5.28 (d, J = 2.4 Hz, 1H), 4.99 (d, J = 2.4 Hz, 1H),
13
4.66 (dd, J = 6.6, 4.2 Hz, 1H), 4.41 (dd, J = 8.4, 6.6 Hz, 1H), 3.96 (dd, J = 8.4, 4.2 Hz, 1H); C NMR
(150 MHz, CDCl3) δ 143.7, 141.0, 129.3, 129.1, 128.0, 126.3, 122.8, 114.0, 82.9, 76.0, 62.0; FTꢀIR
(neat) 3063, 3028, 2924, 2854, 1601, 1504, 1493, 1358, 1166, 1095, 810 cmꢀ1; HRMS (ESI) m/z
[M+H]+ calcd for C15H14ClNO 260.0837, found 260.0836.
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3-(4-Isopropylphenyl)-4-phenyloxazolidine 2h. Analytical TLC on silica gel, 1:19 ethyl
1
2
3
1
acetate/hexane Rf = 0.63; pale yellow liquid; yield 88% (117 mg); H NMR (600 MHz, CDCl3) δ 7.37ꢀ
4
5
6
7
8
7.32 (m, 4H), 7.28 (d, J = 6.6, 1H), 7.05 (d, J = 7.8 Hz, 2H), 6.44 (d, J = 7.8 Hz, 2H), 5.31 (d, J = 2.4
Hz, 1H), 4.99 (d, J = 1.8 Hz, 1H), 4.66 (dd, J = 7.2, 4.8 Hz, 1H), 4.37 (t, J = 7.2 Hz, 1H), 3.95 (dd, J =
9
13
8.4, 4.8 Hz, 1H), 2.81ꢀ2.76 (m, 1H), 1.18 (d, J = 7.2 Hz, 6H); C NMR (150 MHz, CDCl3) δ 143.6,
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142.0, 138.4, 129.0, 127.7, 127.3, 126.5, 113.0, 83.3, 75.9, 62.3, 33.3, 24.4; FTꢀIR (neat) 3064, 3028,
2959, 2926, 2867, 1618, 1520, 1346, 1157, 1090, 816, 757, 704 cmꢀ1; HRMS (APCI) m/z [M+H]+ calcd
for C18H21NO 268.1696, found 268.1697.
4-Phenyl-3-(p-tolyl)oxazolidine 2i. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf = 0.62;
1
colorless liquid; yield 84% (100 mg); H NMR (600 MHz, CDCl3) δ 7.37ꢀ7.33 (m, 4H), 7.29ꢀ7.26 (m,
1H), 7.00 (d, J = 8.4 Hz, 2H), 6.42 (d, J = 8.4 Hz, 2H), 5.32 (d, J = 2.4 Hz, 1H), 5.00 (d, J = 2.4 Hz,
1H), 4.66 (dd, J = 6.6, 4.8 Hz, 1H), 4.40 (t, J = 8.4 Hz, 1H), 3.96 (dd, J = 8.4, 4.8 Hz, 1H), 2.23 (s, 3H);
13C NMR (150 MHz, CDCl3) δ 143.2, 141.7, 129.9, 129.0, 127.7, 127.1, 126.4, 113.1, 83.3, 75.9, 62.1,
20.5; FTꢀIR (neat) 3063, 3027, 2918, 2861, 1621, 1522, 1452, 1340, 1170, 1090, 804 cmꢀ1; HRMS
(ESI) m/z [M+H]+ calcd for C16H17NO 240.1383, found 240.1385.
3-(3,4-Dimethylphenyl)-4-phenyloxazolidine 2k. Analytical TLC on silica gel, 1:19 ethyl
1
acetate/hexane Rf = 0.63; brown liquid; yield 85% (108 mg); H NMR (600 MHz, CDCl3) δ 7.36ꢀ7.32
(m, 4H), 7.27ꢀ7.25 (m, 1H), 6.92 (d, J = 7.8 Hz, 1H), 6.31 (d, J = 1.8 Hz, 1H), 6.24 (dd, J = 7.8, 2.4 Hz,
1H), 5.30 (d, J = 1.8 Hz, 1H), 4.98 (d, J = 2.4 Hz, 1H), 4.65 (dd, J = 6.6, 4.8 Hz, 1H), 4.37 (t, J = 7.8
Hz, 1H), 3.94 (dd, J = 8.4, 4.2 Hz, 1H), 2.16 (s, 3H), 2.13 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 143.7,
141.9, 137.6, 130.5, 129.0, 127.6, 126.4, 126.0, 114.6, 110.6, 83.4, 75.9, 62.0, 20.4, 18.9; FTꢀIR (neat)
3060, 3025, 2921, 2859, 1617, 1513, 1452, 1354, 1274, 1089, 800, 717, 700 cmꢀ1; HRMS (ESI) m/z
[M+H]+ calcd for C17H19NO 254.1539, found 254.1539.
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3-(3,5-Dichlorophenyl)-4-phenyloxazolidine 2l. Analytical TLC on silica gel, 1:19 ethyl
acetate/hexane Rf = 0.59; pale yellow liquid; yield 70% (103 mg); 1H NMR (600 MHz, CDCl3) δ 7.36 (t,
J = 7.2 Hz, 2H), 7.32ꢀ7.28 (m, 3H), 6.70 (t, J = 1.8 Hz, 1H), 6.31 (d, J = 1.2 Hz, 2H), 5.24 (d, J = 2.4
Hz, 1H), 4.97 (d, J = 2.4 Hz, 1H), 4.66 (dd, J = 6.6 Hz, 4.2 Hz, 1H), 4.39 (dd, J = 8.4, 6.6 Hz, 1H), 3.98
(dd, J = 8.4, 3.6 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 146.3, 140.3, 135.7, 129.3, 128.2, 126.2,
117.6, 111.1, 82.4, 75.9, 61.6; FTꢀIR (neat) 3084, 3029, 2923, 2853, 1592, 1557, 1463, 1344, 1167,
1093, 820, 708 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C15H13Cl2NO 294.0447, found 294.0448.
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(E)-4-Phenyl-3-(4-(phenyldiazenyl)phenyl)oxazolidine 2m. Analytical TLC on silica gel, 1:19 ethyl
1
acetate/hexane Rf = 0.56; orange liquid; yield 47% (77 mg); H NMR (600 MHz, CDCl3) δ 7.82 (d, J =
9.0 Hz, 4H), 7.46 (t, J = 7.2 Hz, 2H), 7.39ꢀ7.29 (m, 6H), 6.54 (d, J = 9.0 Hz, 2H), 5.38 (d, J = 2.4 Hz,
1H), 5.14 (d, J = 2.4 Hz, 1H), 4.84 (dd, J = 6.6, 4.2 Hz, 1H), 4.45 (dd, J = 8.4, 6.6 Hz, 1H), 4.04 (dd, J =
8.4, 4.2 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 153.3, 147.0, 145.0, 140.8, 129.9, 129.2, 129.1, 128.1,
126.4, 125.2, 122.5, 112.7, 82.4, 76.0, 61.7; FTꢀIR (neat) 3061, 3025, 2959, 2922, 2851, 1602, 1515,
1497, 1389, 1373, 1140, 1088, 821, 766 cmꢀ1; HRMS (APCI) m/z [M+H]+ calcd for C21H19N3O
330.1601, found 330.1601.
4-(2-Chlorophenyl)-3-phenyloxazolidine 2n. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane
1
Rf = 0.58; pale yellow liquid; yield 75% (97 mg); H NMR (600 MHz, CDCl3) δ 7.43 (d, J = 7.2 Hz,
1H), 7.34 (d, J = 6.0 Hz, 1H), 7.25ꢀ7.20 (m, 4H), 6.78 (t, J = 7.2 Hz, 1H), 6.44 (d, J = 7.8 Hz, 2H), 5.35
(s, 1H), 5.11 (d, J = 4.2 Hz, 1H), 5.01 (s, 1H), 4.47 (t, J = 7.8 Hz, 1H), 4.06 (dd, J = 8.4 Hz, 2.4 Hz,
1H); 13C NMR (150 MHz, CDCl3) δ 144.7, 138.6, 132.4, 129.8, 129.6, 128.9, 127.9, 127.4, 118.1,
112.9, 82.6, 74.5, 59.2; FTꢀIR (neat) 3064, 3036, 2924, 2857, 1600, 1508, 1497, 1348, 1171, 1092, 744,
691 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C15H14ClNO 260.0837, found 260.0836.
4-(3-Methoxyphenyl)-3-phenyloxazolidine 2o. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane
1
Rf = 0.41; colorless liquid; yield 87% (111 mg); H NMR (600 MHz, CDCl3) δ 7.27 (t, J = 7.8 Hz, 1H),
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7.18 (t, J = 8.4 Hz, 2H), 6.96 (d, J =7.8 Hz, 1H), 6.91 (s, 1H), 6.83 (dd, J = 8.4, 2.4 Hz, 1H), 6.75 (t, J =
7.2 Hz, 1H), 6.50 (d, J = 8.4 Hz, 2H), 5.32 (d, J = 2.4 Hz, 1H), 5.02 (d, J = 2.4 Hz, 1H), 4.66 (dd, J =
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5
6
13
6.6, 4.2 Hz, 1H), 4.39 (t, J = 8.4 Hz, 1H), 3.98 (dd, J = 8.4, 4.2 Hz, 1H), 3.79 (s, 3H); C NMR (150
7
8
9
MHz, CDCl3) δ 160.3, 145.3, 143.5, 130.1, 129.4, 118.7, 117.9, 113.0, 112.9, 112.1, 83.0, 75.8, 61.9,
55.4; FTꢀIR (neat) 3040, 2997, 2935, 2866, 2835, 1600, 1508, 1495, 1346, 1284, 1146, 1091, 749, 692
cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C16H17NO2 256.1332, found 256.1337.
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3-Phenyl-4-(m-tolyl)oxazolidine 2p. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf = 0.62;
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pale yellow liquid; yield 81% (97 mg); H NMR (600 MHz, CDCl3) δ 7.24 (t, J = 7.2 Hz, 1H), 7.20ꢀ
7.15 (m, 4H), 7.10 (d, J = 7.2 Hz, 1H), 6.75 (t, J = 7.2 Hz, 1H), 6.50 (d, J = 7.8 Hz, 2H), 5.33 (d, J = 2.4
Hz, 1H), 5.02 (d, J = 2.4 Hz, 1H), 4.66 (dd, J = 6.6, 4.2 Hz, 1H), 4.39 (dd, J = 8.4, 7.2 Hz, 1H), 3.97
(dd, J = 8.4, 4.2 Hz, 1H), 2.35 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 145.3, 141.7, 138.7, 129.4, 128.9,
128.5, 127.0, 123.5, 117.8, 112.9, 83.0, 76.0, 62.0, 21.7; FTꢀIR (neat) 3051, 3025, 2922, 2853, 1600,
1506, 1384, 1343, 1277, 1087, 1033, 788 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C16H17NO
240.1383, found 240.1386.
4-(3-Nitrophenyl)-3-phenyloxazolidine 2q. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf
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= 0.53; yellow liquid; yield 65% (88 mg); H NMR (600 MHz, CDCl3) δ 8.23 (t, J = 1.8 Hz, 1H), 8.16
(dd, J = 8.4, 1.2 Hz, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.21 (dd, J = 9.0, 7.2 Hz, 2H
), 6.79 (t, J = 7.2 Hz, 1H), 6.46 (d, J = 7.8 Hz, 2H), 5.38 (d, J = 2.4 Hz, 1H), 5.01 (d, J = 2.4 Hz, 1H),
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4.79 (dd, J = 6.6, 3.6 Hz, 1H), 4.42 (dd, J = 8.4, 6.6 Hz, 1H), 4.00 (dd, J = 8.4, 3.6 Hz, 1H); C NMR
(150 MHz, CDCl3) δ 148.9, 144.6, 144.4, 132.6, 130.1, 129.7, 123.0, 121.5, 118.6, 113.0, 83.1, 75.5,
61.4; FTꢀIR (neat) 3031, 2964, 2928, 2867, 1603, 1494, 1454, 1355, 1172, 1091, 948, 848, 782 cmꢀ1;
HRMS (ESI) m/z [M+H]+ calcd for C15H14N2O3 271.1077, found: 271.1077.
4-(3-Phenyloxazolidin-4-yl)phenyl acetate 2r. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane
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Rf = 0.50; pale yellow liquid; yield 85% (120 mg); H NMR (600 MHz, CDCl3) δ 7.37 (d, J = 8.4 Hz,
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2H), 7.18 (t, J = 7.2 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.75 (t, J = 7.2 Hz, 1H), 6.47 (d, J = 9.0 Hz, 2H),
5.31 (d, J = 2.4 Hz, 1H), 5.00 (d, J = 2.4 Hz, 1H), 4.69 (dd, J = 7.2, 4.2 Hz, 1H), 4.37 (dd, J = 8.4, 6.6
Hz, 1H), 3.97 (dd, J = 8.4, 4.2 Hz, 1H), 2.29 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.7, 150.2,
145.1, 139.2, 129.5, 127.4, 122.1, 118.1, 113.0, 83.0, 75.8, 61.4, 21.4; FTꢀIR (neat) 3065, 3033, 2956,
2854, 1764, 1600, 1507, 1368, 1215, 1196, 1089, 749, 692 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for
C17H17NO3 284.1281, found 284.1287.
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4-(4-Bromophenyl)-3-phenyloxazolidine 2s. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf
= 0.58; pale yellow liquid; yield 79% (120 mg); 1H NMR (600 MHz, CDCl3) δ 7.48 (d, J = 7.8 Hz, 2H),
7.25 (d, J = 8.4 Hz, 2H), 7.19 (t, J = 7.8 Hz, 2H), 6.77 (t, J = 7.2 Hz, 1H), 6.46 (d, J = 7.8 Hz, 2H), 5.31
(s, 1H), 5.00 (s, 1H), 4.65 (t, J = 6.0 Hz, 1H), 4.38 (t, J = 7.8 Hz, 1H), 3.95 (dd, J = 8.4 Hz, 4.2 Hz, 1H);
13C NMR (150 MHz, CDCl3) δ 144.9, 140.8, 132.1, 129.5, 128.1, 121.5, 118.1, 112.9, 82.9, 75.7, 61.3;
FTꢀIR (neat) 3041, 2986, 2866, 2828, 1599, 1507, 1487, 1345, 1170, 1010, 823, 749, 692 cmꢀ1; HRMS
(ESI) m/z [M+H]+ calcd for C15H14BrNO 304.0332, found 304.0331.
4-(4-Chlorophenyl)-3-phenyloxazolidine 2t. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane Rf
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= 0.58; pale yellow liquid; yield 78% (101 mg); H NMR (600 MHz, CDCl3) δ 7.33ꢀ7.29 (m, 4H), 7.18
(t, J = 7.8 Hz, 2H), 6.76 (t, J = 7.2, Hz 1H), 6.46 (d, J = 8.4 Hz, 2H), 5.31 (s, 1H), 5.00 (s, 1H), 4.66 (t, J
= 5.4 Hz, 1H), 4.38 (t, J = 7.8 Hz, 1H), 3.94 (dd, J = 8.4 Hz, 3.6 Hz, 1H); 13C NMR (150 MHz, CDCl3)
δ 144.9, 140.3, 133.5, 129.5, 129.2, 127.8, 118.1, 112.9, 82.9, 75.7, 61.3; FTꢀIR (neat) 3063, 3040,
2924, 2854, 1600, 1508, 1495, 1346, 1167, 1090, 828, 747, 691 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd
for C15H14ClNO 260.0837, found 260.0840.
4-(4-Fluorophenyl)-3-phenyloxazolidine 2u. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane
Rf = 0.57; pale yellow liquid; yield 84% (102 mg); 1H NMR (600 MHz, CDCl3) 7.33 (t, J = 7.2 Hz, 2H),
7.20 (t, J = 7.2 Hz, 2H), 7.04 (t, J = 8.4 Hz, 2H), 6.77 (t, J = 7.2 Hz, 1H), 6.48 (d, J = 7.8 Hz, 2H), 5.33
(s, 1H), 5.01 (s, 1H), 4.68 (d, J = 3.6 Hz, 1H), 4.38 (t, J = 7.8 Hz, 1H), 3.96 (dd, J = 7.2, 3.0 Hz, 1H);
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13C NMR (150 MHz, CDCl3) δ 163.2 (d, JCꢀF = 244.5 Hz), 145.0, 137.4, 129.5, 128.0 (d, JCꢀF = 7.5 Hz),
118.0, 115.9 (d, JCꢀF = 21.0 Hz), 112.9, 82.9, 75.9, 61.2; FTꢀIR (neat) 3064, 3040, 2929, 2865, 1600,
1508, 1497, 1351, 1222, 1154, 1090, 836, 749, 692 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for
C15H14FNO 244.1132, found 244.1132.
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3-(3-Ethylphenyl)-4-(m-tolyl)oxazolidine 2v. Analytical TLC on silica gel, 1:19 ethyl acetate/hexane
Rf = 0.63; colorless liquid; yield 86% (115 mg); 1H NMR (600 MHz, CDCl3) δ 7.24 (t, J = 7.2 Hz, 1H),
7.19ꢀ7.16 (m, 2H), 7.11ꢀ7.09 (m, 2H), 6.62 (d, J = 7.2 Hz, 1H), 6.35ꢀ6.32 (m, 2H), 5.33 (s, 1H), 5.02 (s,
1H), 4.66 (t, J = 5.4 Hz, 1H), 4.37 (t, J = 7.8 Hz, 1H), 3.98 (dd, J = 7.8, 3.6 Hz, 1H), 2.57 (q, J = 7.2 Hz,
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2H), 2.35 (s, 3H), 1.19 (t, J = 7.8 Hz, 3H); C NMR (150 MHz, CDCl3) δ 145.6, 145.5, 141.9, 138.6,
129.3, 128.8, 128.5, 127.0, 123.5, 117.5, 112.5, 110.5, 83.0, 75.9, 62.0, 29.3, 21.7, 15.7; FTꢀIR (neat)
3030, 2963, 2928, 2868, 1604, 1494, 1454, 1355, 1172, 1092, 948, 783, 695 cmꢀ1; HRMS (ESI) m/z
[M+H]+ calcd for C18H21NO 268.1696, found 268.1709.
3-(4-Chlorophenyl)-4-(4-fluorophenyl)oxazolidine 2w. Analytical TLC on silica gel, 1:19 ethyl
acetate/hexane Rf = 0.57; colorless liquid; yield 82% (114 mg); 1H NMR (600 MHz, CDCl3) δ 7.30 (dd,
J = 8.4, 5.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 7.03 (t, J = 8.4 Hz 2H), 6.36 (d, J = 9.0 Hz, 2H), 5.28 (d,
J = 2.4 Hz, 1H), 4.96 (d, J = 1.8 Hz, 1H), 4.63 (dd, J = 6.6, 4.2 Hz, 1H), 4.39 (dd, J = 8.4, 7.2 Hz, 1H),
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3.93 (dd, J = 8.4, 4.2 Hz, 1H); C NMR (150 MHz, CDCl3) 163.3 (d, JCꢀF = 244.5 Hz), 143.5, 136.8,
129.3, 127.9 (d, JCꢀF = 7.5 Hz), 123.0, 116.1 (d, JCꢀF = 22.5 Hz), 114.0, 82.9, 75.9, 61.3; FTꢀIR (neat)
3045, 2987, 2926, 2867, 1604, 1509, 1493, 1357, 1168, 1095, 809, 767 cmꢀ1; HRMS (APCI) m/z
[M+H]+ calcd for C15H13ClFNO 278.0742, found 278.0738.
4-(3-(p-Tolyl)oxazolidin-4-yl)phenyl acetate 2x. Analytical TLC on silica gel, 1:19 ethyl
acetate/hexane Rf = 0.51; colorless liquid; yield 84% (125 mg); 1H NMR (600 MHz, CDCl3) δ 7.37 (d, J
= 8.4 Hz, 2H), 7.06 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 2H), 6.40 (d, J = 8.4 Hz, 2H), 5.30 (d, J =
2.4 Hz, 1H), 4.97 (d, J = 1.8 Hz, 1H), 4.65 (dd, J = 7.2, 5.4 Hz, 1H), 4.37 (dd, J = 8.4, 7.2 Hz, 1H), 3.95
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(dd, J = 8.4, 4.2 Hz, 1H), 2.29 (s, 3H), 2.23 (s, 3H) 13C NMR (150 MHz, CDCl3) δ 169.7, 150.1, 143.1,
139.3, 130.0, 127.4, 122.1, 113.1, 83.3, 75.8, 61.6, 21.4, 20.5; FTꢀIR (neat) 3032, 3007, 2983, 2921,
2862, 1764, 1619, 1523, 1505, 1368, 1215, 1197, 1162, 1089, 803 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd
for C18H19NO3 298.1438, found 298.1437.
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3-Phenyl-2,3,6,10b-tetrahydro-5H-oxazolo[2,3-a]isoquinoline 2y. Analytical TLC on silica gel, 1:19
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ethyl acetate/hexane Rf = 0.48; colorless liquid; yield 57% (72 mg); H NMR (400 MHz, CDCl3) δ 7.46
(d, J = 7.6 Hz, 2H), 7.42ꢀ7.40 (m, 1H), 7.37 (t, J = 7.6 Hz, 2H), 7.30ꢀ7.26 (m, 3H), 7.19ꢀ7.17 (m, 1H),
5.45 (s, 1H), 4.47 (t, J = 8.0 Hz, 1H), 4.32 (t, J = 10.2 Hz, 1H), 3.89 (dd, 8, 6.4, 1H), 3.08ꢀ2.98 (m, 3H),
2.85ꢀ2.80 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 141.9, 135.7, 132.9, 128.8, 128.7, 128.3, 128.2,
127.4, 126.8, 126.6, 90.3, 71.4, 68.8, 46.9, 29.4; FTꢀIR (neat) 3062, 3027, 2924, 2852, 1604, 1494,
1395, 1384, 1126, 1029, 937, 746, 700; HRMS (ESI) m/z [M+H]+ calcd for C17H17NO 252.1383, found
252.1384.
3,4-Diphenyl-1-tosylimidazolidine 4a′. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane Rf =
0.55; colorless solid; yield 81% (153 mg); mp 126ꢀ127 °C; 1H NMR (600 MHz, CDCl3) δ 7.68 (d, J =
8.4 Hz, 2H), 7.26ꢀ7.22 (m, 5H), 7.13ꢀ7.10 (m, 4H), 6.72 (t, J = 7.2 Hz, 1H), 6.37 (d, J = 8.4 Hz, 2H),
5.03 (d, J = 6.0 Hz, 1H), 4.76 (d, J = 6.0 Hz, 1H), 4.53 (t, J = 5.4 Hz, 1H), 3.92 (dd, J = 10.2, 7.2 Hz,
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1H), 3.46 (dd, J = 10.8, 5.4 Hz, 1H), 2.40 (s, 3H); C NMR (150 MHz, CDCl3) δ 145.0, 144.5, 140.6,
132.9, 130.1, 129.3, 129.1, 128.0, 127.9, 126.1, 118.4, 113.2, 66.2, 61.7, 55.7, 21.8; FTꢀIR (KBr) 3059,
3025, 2953, 2923, 2850, 1599, 1506, 1384, 1348, 1163, 1090, 1029, 814, 749 cmꢀ1; HRMS (ESI) m/z
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[M+H]+ calcd for C22H22N2O2S 379.1475, found 379.1473; [α]D = ꢀ26.0 (c= 0.2, CHCl3); HPLC
analysis: 97% ee [Daicel Chiralcel OD column, hexane/iPrOH = 85:15, flow rate: 1 mL/min, λ = 215
nm, tR = 9.49 min (major), 17.30 min (minor)].
4-Phenyl-3-(m-tolyl)-1-tosylimidazolidine 4c. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane
Rf = 0.56; colorless solid; yield 82% (161 mg); mp 133ꢀ134 °C; 1H NMR (600 MHz, CDCl3) δ 7.68 (d, J
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= 8.4 Hz, 2H), 7.25ꢀ7.22 (m, 4H), 7.11 (d, J = 6.0 Hz, 2H), 6.98 (t, J = 7.8 Hz, 1H), 6.56 (d, J = 7.8 Hz,
1H), 6.22 (s, 1H), 6.16 (d, J = 7.8 Hz, 2H), 5.06 (d, J = 5.4 Hz, 1H), 4.74 (d, J = 6.0 Hz, 1H), 4.54 (dd, J
= 7.2, 4.8 Hz, 1H), 3.89 (dd, J = 10.2, 7.8 Hz, 1H), 3.45 (dd, J = 10.2, 4.8 Hz, 1H), 2.40 (s, 3H), 2.22 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 145.0, 144.4, 140.7, 139.1, 133.0, 130.0, 129.1, 129.0, 128.0,
127.8, 126.1, 119.4, 113.9, 110.5, 66.3, 61.6, 55.7, 21.9, 21.8; FTꢀIR (KBr) 3064, 3025, 2961, 2921,
2850, 1604, 1493, 1384, 1350, 1163, 1091, 1030, 813, 764 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for
C23H24N2O2S 393.1631, found 393.1630.
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3-(3-Ethylphenyl)-4-phenyl-1-tosylimidazolidine 4d. Analytical TLC on silica gel, 1:9 ethyl
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acetate/hexane Rf = 0.56; pale yellow liquid; yield 82% (166 mg); H NMR (600 MHz, CDCl3) δ 7.69
(d, J = 8.4 Hz, 2H), 7.25ꢀ7.21 (m, 5H), 7.11 (d, J = 6.0 Hz, 2H), 7.01 (t, J = 7.8 Hz, 1H), 6.59 (d, J = 7.2
Hz, 1H), 6.23 (s, 1H), 6.18 (dd, J = 7.8, 1.8 Hz, 1H), 5.04 (d, J = 6.0 Hz, 1H), 4.75 (d, J = 5.4 Hz, 1H),
4.54 (dd, J = 7.2, 4.8 Hz, 1H), 3.91 (dd, J = 10.8, 7.8 Hz, 1H), 3.46 (dd, J = 10.2, 4.8 Hz, 1H), 2.52 (q, J
= 7.8 Hz, 2H), 2.40 (s, 3H), 1.12 (t, J = 7.8 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 145.5, 145.1,
144.4, 140.8, 133.0, 130.0, 129.2, 129.0, 128.0, 127.8, 126.1, 118.2, 112.9, 110.8, 66.3, 61.8, 55.7, 29.3,
21.8, 15.7; FTꢀIR (neat) 3059, 3025, 2925, 2848, 1599, 1504, 1354, 1163, 1091, 816, 746 cmꢀ1; HRMS
(ESI) m/z [M+H]+ calcd for C24H26N2O2S 407.1788, found 407.1791.
3-(4-Chlorophenyl)-4-phenyl-1-tosylimidazolidine 4e. Analytical TLC on silica gel, 1:9 ethyl
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acetate/hexane Rf = 0.54; pale yellow liquid; yield 75% (155 mg); H NMR (600 MHz, CDCl3) δ 7.68
(d, J = 8.4 Hz, 2H), 7.25ꢀ7.23 (m, 5H), 7.09 (d, J = 7.2 Hz, 2H), 7.05 (d, J = 9.0 Hz, 2H), 6.27 (d, J =
9.0 Hz, 2H), 4.98 (d, J = 6.0 Hz, 1H), 4.76 (d, J = 6.6 Hz, 1H), 4.45 (t, J = 6.6 Hz, 1H), 3.97 (dd, J =
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10.8, 7.8 Hz, 1H), 3.43 (dd, J = 10.8, 5.4 Hz, 1H), 2.40 (s, 3H); C NMR (150 MHz, CDCl3) δ 144.6,
140.0, 133.1, 130.1, 129.2, 129.1, 128.1, 128.0, 126.0, 123.4, 114.3, 66.3, 61.8, 55.8, 21.8; FTꢀIR (neat)
3067, 3025, 2925, 2889, 2820, 1601, 1507, 1346, 1162, 1024, 785, 748 cmꢀ1; HRMS (ESI) m/z [M+H]+
calcd for C22H21ClN2O2S 413.1085, found 413.1079.
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3-(4-Isopropylphenyl)-4-phenyl-1-tosylimidazolidine 4f. Analytical TLC on silica gel, 1:9 ethyl
acetate/hexane Rf = 0.56; colorless solid; yield 84% (176 mg); mp 140ꢀ141 °C; 1H NMR (600 MHz,
CDCl3) δ 7.71 (d, J = 7.8 Hz, 2H), 7.26ꢀ7.23 (m, 5H), 7.15 (d, J = 6.6 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H),
6.37 (d, J = 8.4 Hz, 2H), 5.07 (d, J = 6.0 Hz, 1H), 4.72 (d, J = 6.0 Hz, 1H), 4.53 (t, J = 6.6 Hz, 1H), 3.91
(t, J = 8.4 Hz, 1H), 3.46 (dd, J = 10.8, 5.4 Hz, 1H), 2.80ꢀ2.76 (m, 1H), 2.41 (s, 3H), 1.19 (d, J = 6.0 Hz,
6H); 13C NMR (150 MHz, CDCl3) δ 144.4, 143.2, 140.8, 138.9, 132.9, 130.0, 129.0, 127.8, 127.1,
126.1, 113.3, 66.5, 62.0, 55.7, 33.2, 24.3, 21.7; FTꢀIR (KBr) 3064, 3028, 2957, 2928, 2867, 1615, 1519,
1454, 1351, 1164, 1095, 814, 700 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C25H28N2O2S 421.1944,
found 421.1945.
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4-Phenyl-3-(p-tolyl)-1-tosylimidazolidine 4g′. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane
Rf = 0.55; colorless solid; yield 82% (161 mg); mp 141ꢀ142 °C; 1H NMR (600 MHz, CDCl3) δ 7.69 (d, J
= 8.4 Hz, 2H), 7.24ꢀ7.20 (m, 5H), 7.10 (d, J = 6.0 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 6.31 (d, J = 8.4 Hz,
2H), 5.03 (d, J = 6.0 Hz, 1H), 4.70 (d, J = 6.0 Hz, 1H), 4.51 (t, J = 6.6 Hz, 1H), 3.91 (dd, J = 10.2, 7.2
Hz, 1H), 3.42 (dd, J = 10.2, 5.4 Hz, 1H), 2.40 (s, 3H), 2.19 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
144.4, 142.9, 140.7, 133.0, 130.0, 129.8, 129.0, 128.0, 127.8, 126.1, 113.5, 66.6, 61.9, 55.7, 21.8, 20.5;
FTꢀIR (KBr) 3059, 3028, 2923, 2860, 1619, 1521, 1384, 1350, 1163, 1094, 1030, 804, 760 cmꢀ1; HRMS
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(ESI) m/z [M+H]+ calcd for C23H24N2O2S 393.1631, found 393.1633; [α]D = ꢀ8.0 (c= 0.2, CHCl3);
HPLC analysis: 97% ee [Daicel Chiralcel OD column, hexane/iPrOH = 85:15, flow rate: 1 mL/min, λ =
215 nm, tR = 8.25 min (major), 10.57 min (minor)].
3-(9H-Fluoren-2-yl)-4-phenyl-1-tosylimidazolidine 4h. Analytical TLC on silica gel, 1:9 ethyl
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acetate/hexane Rf = 0.52; colorless solid; yield 61% (142 mg); mp 232ꢀ233 °C; H NMR (600 MHz,
CDCl3) δ 7.70 (d, J = 7.8 Hz, 2H), 7.59 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.44 (d, J = 7.8
Hz, 1H), 7.30ꢀ7.22 (m, 6H), 7.19ꢀ7.13 (m, 3H), 6.58 (s, 1H), 6.38 (d, J = 8.4 Hz, 1H), 5.10 (d, J = 5.4
Hz, 1H), 4.84 (d, J = 6.0 Hz, 1H), 4.59 (t, J = 6.0 Hz, 1H), 3.95 (t, J = 8.4 Hz, 1H), 3.74 (s, 2H), 3.48
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(dd, J = 10.8, 5.4 Hz, 1H), 2.38 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 145.1, 144.5, 144.4, 142.4,
142.0, 140.6, 133.1, 132.8, 130.1, 129.1, 128.0, 127.9, 126.9, 126.1, 125.5, 124.9, 120.6, 118.9, 112.2,
110.0, 66.5, 61.8, 55.8, 37.2, 21.8; FTꢀIR (KBr) 3062, 3027, 2956, 2923, 2853, 1616, 1492, 1457, 1384,
1349, 1162, 1092, 1027, 812, 764 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C29H26N2O2S 467.1788,
found 467.1790.
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3,4-Diphenyl-1-(phenylsulfonyl)imidazolidine 4i. Analytical TLC on silica gel, 1:9 ethyl
acetate/hexane Rf = 0.54; colorless solid; yield 75% (137 mg); mp 125ꢀ126 °C; 1H NMR (600 MHz,
CDCl3) δ 7.81 (d, J = 7.8 Hz, 2H), 7.57 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.2 Hz, 2H), 7.24ꢀ7.20 (m, 3H),
7.12ꢀ7.10 (m, 4H), 6.72 (t, J = 7.2 Hz, 1H), 6.38 (d, J = 7.8 Hz, 2H), 5.05 (d, J = 6.0 Hz, 1H), 4.78 (d, J
= 6.0 Hz, 1H), 4.51 (t, J = 6.6 Hz, 1H), 3.92 (dd, J = 10.8, 7.8 Hz, 1H), 3.46 (dd, J = 10.2, 5.4 Hz, 1H);
13C NMR (150 MHz, CDCl3) δ 144.9, 140.5, 136.0, 133.5, 129.4, 129.3, 129.1, 128.0, 127.9, 126.0,
118.5, 113.3, 66.2, 61.7, 55.7; FTꢀIR (KBr) 3062, 3028, 2928, 2857, 1600, 1506, 1446, 1351, 1166,
1095, 1030, 749 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C21H20N2O2S 365.1318, found 365.1319.
3-Phenyl-1-tosyl-1,2,3,5,6,10b-hexahydroimidazo[2,1-a]isoquinoline 4j. Analytical TLC on silica
gel, 1:9 ethyl acetate/hexane Rf = 0.50; colorless solid; yield 63% (127 mg); mp 137ꢀ138 °C; 1H NMR
(600 MHz, CDCl3) δ 7.97 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 7.8 Hz, 2H), 7.41 (d, J = 7.8 Hz, 2H), 7.34 (t,
J = 7.8 Hz, 1H), 7.26ꢀ7.20 (m, 4H), 7.07 (d, J = 7.8 Hz, 1H), 6.88 (d, J = 7.2 Hz, 2H), 5.94 (s, 1H), 4.10
(t, J = 8.4 Hz, 1H), 3.70 (t, J = 8.4 Hz, 1H), 3.18 (t, J = 9.6 Hz, 1H), 3.16ꢀ3.08 (m, 1H), 2.94ꢀ2.88 (m,
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1H), 2.75ꢀ2.72 (m, 1H), 2.53 (s, 3H), 2.40 (d, J = 16.2 Hz, 1H); C NMR (150 MHz, CDCl3) δ 144.0,
138.8, 134.9, 134.1, 129.9, 129.2, 128.8, 128.6, 128.3, 127.7, 127.6, 127.2, 76.5, 60.9, 55.7, 41.5, 21.9,
21.4; FTꢀIR (KBr) 3056, 3028, 2950, 2924, 2861, 1598, 1453, 1344, 1157, 1090, 1005, 817, 759, 665
cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C24H24N2O2S 405.1631, found 405.1633.
3-(2-Chlorophenyl)-1-tosyl-1,2,3,5,6,10b-hexahydroimidazo[2,1-a]isoquinoline 4k. Analytical TLC
on silica gel, 1:9 ethyl acetate/hexane Rf = 0.49; colorless solid; yield 56% (123 mg); mp 145ꢀ146 °C; 1H
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NMR (600 MHz, CDCl3) δ 7.91 (d, J = 7.8 Hz, 1H), 7.76 (d, J = 7.8 Hz, 2H), 7.35ꢀ7.31 (m, 3H), 7.30ꢀ
7.24 (m, 2H), 7.13 (t, J = 7.8 Hz, 1H), 7.08 (d, J = 7.2 Hz, 1H), 6.99 (t, J = 7.8 Hz, 1H), 6.62 (d, J = 7.8
Hz, 1H), 6.01 (s, 1H), 4.59 (t, J = 7.8 Hz, 1H), 3.87 (t, J = 9.0 Hz, 1H), 3.17ꢀ3.13 (m, 2H), 2.99ꢀ2.92 (m,
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1H), 2.78ꢀ2.75 (m, 1H), 2.50 (s, 3H), 2.41 (d, J = 16.8 Hz, 1H); C NMR (150 MHz, CDCl3) δ 143.9,
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137.4, 134.6, 134.5, 134.4, 134.0, 129.9, 129.5, 128.9, 128.7, 128.4, 127.9, 127.8, 127.2, 127.1, 76.4,
56.8, 53.8, 41.9, 21.8, 21.5; FTꢀIR (KBr) 3061, 3022, 2953, 2923, 2850, 1597, 1453, 1347, 1159, 1090,
999, 814, 752, 664 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C24H23ClN2O2S 439.1242, found
439.1243.
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3-(m-Tolyl)-1-tosyl-1,2,3,5,6,10b-hexahydroimidazo[2,1-a]isoquinoline 4l. Analytical TLC on silica
gel, 1:9 ethyl acetate/hexane Rf = 0.51; colorless solid; yield 67% (140 mg); mp 151ꢀ152 °C; 1H NMR
(600 MHz, CDCl3) δ 7.95 (d, J = 7.8 Hz, 1H), 7.86 (d, J = 7.8 Hz, 2H), 7.41 (d, J = 7.8 Hz, 2H), 7.33 (t,
J = 7.2 Hz, 1H) 7.25 (d, J = 7.2 Hz, 1H), 7.11ꢀ7.04 (m, 3H), 6.70 (d, J = 7.2 Hz, 1H), 6.60 (s, 1H), 5.94
(s, 1H), 4.06 (t, J = 8.4 Hz, 1H), 3.68 (t, J = 8.4 Hz, 1H), 3.16 (t, J = 9.6 Hz, 1H), 3.12ꢀ3.07 (m, 1H),
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2.94ꢀ2.88 (m, 1H), 2.75ꢀ2.72 (m, 1H), 2.53 (s, 3H), 2.39 (d, J = 16.8 Hz, 1H), 2.23 (s, 3H); C NMR
(150 MHz, CDCl3) δ 144.0, 138.9, 138.5, 134.9, 134.2, 134.1, 129.9, 129.2, 129.1, 128.7, 128.6, 128.5,
128.1, 127.7, 127.2, 125.0, 76.6, 60.8, 55.7, 41.5, 21.9, 21.5, 21.4; FTꢀIR (KBr) 3056, 3025, 2959,
2923, 2851, 1598, 1492, 1453, 1345, 1159, 1091, 1004, 815, 751, 666 cmꢀ1; HRMS (ESI) m/z [M+H]+
calcd for C25H26N2O2S 419.1788, found 419.1789.
3-(4-Fluorophenyl)-1-tosyl-1,2,3,5,6,10b-hexahydroimidazo[2,1-a]isoquinoline 4m. Analytical TLC
on silica gel, 1:9 ethyl acetate/hexane Rf = 0.48; colorless solid; yield 59% (124 mg); mp 150ꢀ151 °C; 1H
NMR (600 MHz, CDCl3) δ 7.95 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 7.2 Hz, 2H), 7.41 (d, J = 7.8 Hz, 2H),
7.33 (t, J = 7.8 Hz, 1H), 7.25 (d, J = 7.2 Hz, 1H), 7.07 (d, J = 7.8 Hz, 1H), 6.89 (t, J = 7.2 Hz, 2H),
6.82ꢀ6.80 (m, 2H), 5.93 (s, 1H), 4.08 (t, J = 7.2 Hz, 1H), 3.68 (t, J = 7.8 Hz, 1H), 3.13ꢀ3.08 (m, 2H),
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2.92ꢀ2.86 (m, 1H), 2.72ꢀ2.68 (m, 1H), 2.53 (s, 3H), 2.41 (d, J = 16.8 Hz, 1H); C NMR (150 MHz,
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CDCl3) δ 163.5 (d, JCꢀF = 244.5 Hz), 144.1, 134.8, 134.6, 134.2, 134.0, 129.9, 129.2 (d, JCꢀF = 9.0 Hz),
128.6, 128.5, 127.8, 127.3, 115.7 (d, JCꢀF = 21.0 Hz), 76.5, 60.2, 55.6, 41.5, 21.9, 21.4; FTꢀIR (KBr)
3062, 3024, 2928, 2901, 1601, 1509, 1453, 1344, 1224, 1159, 1013, 838, 816, 754, 673 cmꢀ1; HRMS
(ESI) m/z [M+H]+ calcd for C24H23FN2O2S 423.1537, found 423.1538.
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3-(4-Bromophenyl)-1-tosyl-1,2,3,5,6,10b-hexahydroimidazo[2,1-a]isoquinoline 4n. Analytical TLC
on silica gel, 1:9 ethyl acetate/hexane Rf = 0.48; colorless solid; yield 57% (137 mg); mp 148ꢀ149 °C; 1H
NMR (600 MHz, CDCl3) δ 7.93 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 7.8 Hz, 2H), 7.40 (d, J = 7.8 Hz, 2H),
7.34ꢀ7.31 (m, 3H), 7.25 (d, J = 7.8 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 6.72 (d, J = 8.4 Hz, 2H), 5.93 (s,
1H), 4.06 (t, J = 7.8 Hz, 1H), 3.68 (t, J = 9.6 Hz, 1H), 3.12ꢀ3.09 (m, 2H), 2.89ꢀ2.86 (m, 1H), 2.71ꢀ2.68
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(m, 1H), 2.53 (s, 3H), 2.41 (d, J = 16.8 Hz, 1H); C NMR (150 MHz, CDCl3) δ 144.2, 138.1, 134.7,
134.1, 131.9, 129.9, 129.3, 129.2, 128.6, 128.5, 127.9, 127.3, 122.0, 76.5, 60.3, 55.4, 41.6, 21.9, 21.4;
FTꢀIR (KBr) 3054, 3021, 2923, 2852, 1597, 1486, 1345, 1158, 1010, 818, 749, 667 cmꢀ1; HRMS (ESI)
m/z [M+H]+ calcd for C24H23BrN2O2S 483.0736, found: 483.0737.
3-(2,4-Dimethylphenyl)-1-tosyl-1,2,3,5,6,10b-hexahydroimidazo[2,1-a]isoquinoline 4o. Analytical
TLC on silica gel, 1:9 ethyl acetate/hexane Rf = 0.54; colorless solid; yield 62% (134 mg); mp 161ꢀ162
°C; 1H NMR (600 MHz, CDCl3) δ 8.00 (d, J = 7.8 Hz, 1H), 7.83 (d, J = 7.8 Hz, 2H), 7.39ꢀ7.35 (m, 3H),
7.28 (d, J = 7.2 Hz, 1H), 7.09 (d, J = 7.8 Hz, 1H), 6.92 (s, 1H), 6.84 (d, J = 8.4 Hz, 1H), 6.61 (d, J = 7.8
Hz, 1H), 5.96 (s, 1H), 4.35 (t, J = 7.8 Hz, 1H), 3.75 (dd, J = 10.8, 8.4 Hz, 1H), 3.15ꢀ3.06 (m, 2H), 2.87ꢀ
2.79 (m, 2H), 2.54 (s, 3H), 2.41 (d, J = 13.8, 1H), 2.29 (s, 3H), 2.15 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 144.0, 137.1, 136.3, 135.0, 134.2, 133.8, 131.3, 129.9, 129.2, 128.6, 128.5, 127.7, 127.3,
127.2, 126.5, 76.2, 56.5, 54.5, 41.6, 21.9, 21.8, 21.1, 19.4; FTꢀIR (KBr) 3062, 3021, 2922, 2853, 1598,
1452, 1347, 1159, 1010, 816, 748, 664 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C26H28N2O2S
433.1944, found 433.1941.
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3-Phenyl-1-(phenylsulfonyl)-1,2,3,5,6,10b-hexahydroimidazo[2,1-a]isoquinoline 4p. Analytical TLC
on silica gel, 1:9 ethyl acetate/hexane Rf = 0.50; colorless solid; yield 60% (117 mg); mp 140ꢀ141 °C;
1H NMR (600 MHz, CDCl3) δ 7.97ꢀ7.95 (m, 3H), 7.24 (t, J = 7.2 Hz, 1H), 7.61 (t, J = 7.2 Hz, 2H), 7.34
(t, J = 7.2 Hz, 1H), 7.26ꢀ7.20 (m, 4H), 7.07 (d, J = 7.2 Hz, 1H), 6.86 (d, J = 7.2 Hz, 2H), 5.96 (s, 1H),
4.11 (t, J = 7.8 Hz, 1H), 3.71 (t, J = 7.8 Hz, 1H), 3.17 (t, J = 9.0 Hz, 1H), 3.12ꢀ3.08 (m, 1H), 2.93ꢀ2.88
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(m, 1H), 2.75ꢀ2.71 (m, 1H), 2.40 (d, J = 16.8 Hz, 1H); C NMR (150 MHz, CDCl3) δ 138.7, 137.0,
134.8, 134.1, 133.3, 129.3, 129.2, 128.8, 128.6, 128.5, 128.3, 127.8, 127.6, 127.3, 76.6, 60.8, 55.7, 41.5,
21.4; FTꢀIR (KBr) 3061, 3027, 2953, 2923, 1606, 1446, 1349, 1161, 1011, 754, 721, 603 cmꢀ1; HRMS
(ESI) m/z [M+H]+ calcd for C23 H22N2O2S 391.1475, found 391.1486.
4-(2-Chlorophenyl)-3-phenyl-1-tosylimidazolidine 4q. Analytical TLC on silica gel, 1:9 ethyl
acetate/hexane Rf = 0.54; colorless solid; yield 76% (157 mg); mp 120ꢀ121 °C; 1H NMR (600 MHz,
CDCl3) δ 7.67 (d, J = 7.8 Hz, 2H), 7.37 (d, J = 8.4 Hz, 1H), 7.20ꢀ7.16 (m, 3H), 7.13 (t, J = 7.2 Hz, 2H),
7.03 (t, J = 7.8 Hz, 1H), 7.00 (d, J = 9.0 Hz, 1H), 6.74 (t, J = 7.2 Hz, 1H), 6.28 (d, J = 8.4 Hz, 2H), 5.09
(d, J = 6.0 Hz, 1H), 4.84 (dd, J = 7.8, 4.2 Hz, 1H), 4.74 (d, J = 6.0 Hz, 1H), 4.00 (dd, J = 10.8, 7.2 Hz,
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1H), 3.54 (dd, J = 10.8, 4.8 Hz, 1H), 2.38 (s, 3H); C NMR (150 MHz, CDCl3) δ 144.5, 144.4, 137.6,
132.9, 132.3, 130.1, 129.9, 129.4, 129.0, 128.0, 127.5, 127.4, 118.6, 112.9, 66.0, 59.0, 54.1, 21.7; FTꢀIR
(KBr) 3061, 2956, 2923, 2848, 1600, 1506, 1384, 1352, 1164, 1092, 1032, 814, 750, 664 cmꢀ1; HRMS
(ESI) m/z [M+H]+ calcd for C22H21ClN2O2S 413.1085, found 413.1083.
3-Phenyl-4-(o-tolyl)-1-tosylimidazolidine 4r. Analytical TLC on silica gel, 1:9 ethyl acetate/hexane Rf
= 0.56; colorless solid; yield 73% (143 mg); mp 144ꢀ145 °C; 1H NMR (600 MHz, CDCl3) δ 7.70 (dd, J
= 8.4, 1.8 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.17ꢀ7.11 (m, 4H), 7.00ꢀ6.96 (m, 2H), 6.73 (t, J = 7.2 Hz,
1H), 6.29 (d, J = 8.4 Hz, 2H), 5.07 (d, J = 6.0 Hz, 1H), 4.62 (d, J = 6.0 Hz, 1H), 4.61 (t, J = 7.2 Hz, 1H),
4.01 (t, J = 9.6 Hz, 1H), 3.39 (dd, J = 10.2, 5.4 Hz, 1H), 2.40 (s, 3H), 2.36 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 144.9, 144.5, 137.9, 134.2, 133.0, 130.9, 130.0, 129.2, 127.9, 127.5, 126.8, 125.4, 118.3,
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113.0, 66.2, 58.8, 54.3, 21.7, 19.4; FTꢀIR (KBr) 3061, 3025, 2925, 2856, 1599, 1506, 1384, 1350, 1164,
1094, 1032, 814, 750 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C23H24N2O2S 393.1631, found
393.1631.
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4-(3-Bromophenyl)-3-phenyl-1-tosylimidazolidine 4s. Analytical TLC on silica gel, 1:9 ethyl
acetate/hexane Rf = 0.53; colorless solid; yield 78% (178 mg); mp 130ꢀ131 °C; 1H NMR (600 MHz,
CDCl3) δ 7.68 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 7.8 Hz, 1H), 7.24ꢀ7.23 (m, 3H), 7.15ꢀ7.11 (m, 3H), 7.07
(d, J = 7.8 Hz, 1H), 6.76 (t, J = 7.2 Hz, 1H), 6.37 (d, J = 8.4 Hz, 2H), 5.05 (d, J = 6.0 Hz, 1H), 4.75 (d, J
= 6.0 Hz, 1H), 4.49 (t, J = 6.0 Hz, 1H), 3.90 (t, J = 9.6 Hz, 1H), 3.47 (dd, J = 10.8, 4.8 Hz, 1H), 2.40 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 144.7, 144.6, 143.2, 132.9, 131.1, 130.7, 130.1, 129.4, 129.1,
127.9, 124.8, 123.2, 118.8, 113.2, 66.2, 61.2, 55.5, 21.8; FTꢀIR (KBr) 3070, 3022, 2920, 2817, 1600,
1507, 1385, 1346, 1161, 1088, 1024, 847, 747, 665 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for
C22H21BrN2O2S 457.0580, found 457.0584.
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4-(3-Chlorophenyl)-3-phenyl-1-tosylimidazolidine 4t. Analytical TLC on silica gel, 1:9 ethyl
acetate/hexane Rf = 0.54; colorless solid; yield 80% (165 mg); mp 140ꢀ141 °C; 1H NMR (600 MHz,
CDCl3) δ 7.69 (d, J = 7.8 Hz, 2H), 7.24ꢀ7.17 (m, 4H), 7.16ꢀ7.13 (m, 2H), 7.07 (s, 1H), 7.04 (d, J = 7.2
Hz, 1H), 6.77 (t, J = 7.2 Hz, 1H), 6.38 (d, J = 8.4 Hz, 2H), 5.07 (d, J = 6.0 Hz, 1H), 4.75 (d, J = 6.0 Hz,
1H), 4.51 (t, J = 6.6 Hz, 1H), 3.93 (t, J = 10.2 Hz, 1H), 3.48 (dd, J = 10.8, 4.8 Hz, 1H), 2.40 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 144.7, 144.6, 142.9, 134.9, 132.9, 130.3, 130.0, 129.3, 128.0, 127.9, 126.1,
124.3, 118.7, 113.2, 66.1, 61.2, 55.4, 21.7; FTꢀIR (KBr) 3061, 3028, 2925, 2889, 2820, 1601, 1508,
1346, 1162, 1027, 849, 758, 667 cmꢀ1; HRMS (ESI) m/z [M+H]+ calcd for C22H21ClN2O2S 413.1085,
found 413.1084.
4-(3-Phenyl-1-tosylimidazolidin-4-yl)phenyl acetate 4u. Analytical TLC on silica gel, 1:9 ethyl
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acetate/hexane Rf = 0.41; pale yellow liquid; yield 77% (168 mg); H NMR (600 MHz, CDCl3) δ 7.67
(d, J = 7.2 Hz, 2H), 7.24 (d, J = 7.8 Hz, 2H), 7.13ꢀ7.11 (m, 4H), 6.97 (d, J = 7.2 Hz, 2H), 6.74 (t, J = 6.6
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