Synthesis and crystal structure of 6-Trichloromethyl-9-oxa-5-azatricyclo[6. 2.1.01,5]undecan-10-one

Article abstract of DOI:10.3184/174751911X12984610068847

6-Trichloromethyl-9-oxa-5-azatricyclo[6.2.1.0^1,5]undecan-10-one was prepared and its structure clearly established from spectroscopic data and X-ray crystallography. The crystal structure belongs to the orthorhombic system, space group P2₁2₁2₁ with a = 8.4494(17), b = 9.3505(19), c = 15.315(3) A , α = β = γ = 90 °, V = 01210.0(4) A ³, Z = 4, Flack = 0.00(10). The absolute configuration of the title compound was determined as (1R,6R).

Full text of DOI:10.3184/174751911X12984610068847

JOURNAL OF CHEMICAL RESEARCH 2011
MARCH, 167–168
RESEARCH PAPER 167
Synthesis and crystal structure of
1
,5
6
-trichloromethyl-9-oxa-5-azatricyclo[6.2.1.0 ]undecan-10-one
Hua Yang*, Mo Ran Sun and Ming Zhu
School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, P. R. China
1
,5
6
-Trichloromethyl-9-oxa-5-azatricyclo[6.2.1.0 ]undecan-10-one was prepared and its structure clearly established
from spectroscopic data and X-ray crystallography. The crystal structure belongs to the orthorhombic system, space
3
group P2 2 2 with a = 8.4494(17), b = 9.3505(19), c = 15.315(3) Å, α = β = γ = 90 °, V = 01210.0(4) Å , Z = 4, Flack =
1
1 1,
0
.00(10). The absolute configuration of the title compound was determined as (1R,6R).
Keywords: oxazolidinone, pyrrolidine, butyrolactone, piperidine, indolizidine
The oxazolidinone 2 was the starting material for synthesis of
(1R,6R)-, the absolute structure Flack parameter of 0.00(10)
1
,2
15
α-substituted proline in some reported procedures. Alkyl-
ation of the enolate of oxazolidinone can be achieved in a dia-
stereoselective manner to afford alkyl oxazolidinone, which
was converted cleanly to the α-alkyl proline in 6N HCl at room
temperature. In our effort to obtain the allyl proline in differ-
ent ways, an unexpected reaction ensued when allyl oxazolid-
inone 3 was treated with 1.5-fold excess of CF SO H in CH Cl
or PPA to afford the title compound 4 in almost quantitative
yield (Scheme 1).
From a structural point of view, the most conspicuous
feature of 4 is an azatricyclic ring system consisting of the
combination of the butyrolactone and pyrrolidine sharing
the piperidine ring, namely 5-azatricyclo[6.2.1.0 ]undecane.
The piperidine and pyrrolidine moieties are found as core
structures or as sub-features in many structurally diverse and
stereochemically interesting alkaloids isolated from marine
confirmed this stereochemistry. Judging from its crystal
structure, a tentative mechanism for the formation of
compound 4 have been proposed (Scheme 2).
3
Experimental
4
All solvents were purified and dried by standard techniques, and dis-
tilled prior to use. All organic extracts were dried over MgSO , unless
3
3
2
2
4
otherwise noted. IR spectra were recorded on Nicolet IR200 instru-
ment using KBr disks in the 400–4000 cm region. HRMS were
obtained on a Waters Micromass Q-Tof Micro instrument using the
−1
1
,5
5
–7
and terrestrial plants and animals. Many of the indolizidine
alkaloids possess diverse and potent biological activities,
which has led to their use as drug candidates or as lead com-
8
–10
pounds in new drug designs.
A variety of methods have
been reported for the stereoselective construction of function-
1
1–13
alised indolizidine skeleton.
The title compound was
sought as a potent precursor for synthesis of indoliziline class
of marine alkaloids.
Our syntheses commenced with 2-trichloromethyl oxa-
zolidinone (2), which was obtained through condensation of
commercially available (S)-proline (1) with trichloroacetalde-
3
hyde (Scheme 1). The crystalline, air-stable compound was
produced as a single diastereomer, whose stereochemistry was
1
4
established by X-ray crystallography. Exposure of the allyl
lactone 3 to excess CF SO H (or PPA) readily produce the
3
3
compound 4. In order to confirm the structure and absolute
configuration of 4, its single crystal was cultivated and abso-
lute configuration was confirmed by X-ray crystallographic
analysis (Figs 1 and 2). The title compound have a chirality of
Fig. 1 Crystal structure of compound 4, showing 30% pro-
bability displacement ellipsoids.
Scheme 1 Synthesis of compound 4.
Correspondent. E-mail: yanghua001974@yahoo.com.cn
*

1
68 JOURNAL OF CHEMICAL RESEARCH 2011
(
CH ), 52.10 (CH ), 67.44, 71.87 (CH), 74.77 (CH), 102.84, 174.92;
2 2
+
HRMS: [M+H] 284.0010 (Calcd 284.0012). The crystal is of ortho-
rhombic, space group P2 2 2 , with a = 8.4494(17), b = 9.3505(19),
1
1 1
3
c = 15.315(3)Å, α = β = γ = 90 °, V = 1210.0(4) Å , Z = 4, Mr =
−
3
2
0
84.56, D = 1.562 g cm , λ = 0.71073 Å, F(000) = 584, µ =
c
1
−
−3
.741 mm , R = 0.0436 g cm and wR = 0.0975 for 1190 observed
reflection (I >2σ(I)).
A colourless prismatic crystal of compound 4 with dimensions
of 0.18×0.18×0.16 mm was selected for data collection performed on
a Rigaku RAXIS-IV imaging plate area detector equipped with a
graphite-monochromatic MoKa radiation (λ = 0.71073 Å). A total of
4
109 reflections together with 1265 independent ones(Rint = 0.0447)
were collected in the range of 2.55<θ<25.49 ° by using “Oscillation
frames” scan techniques at 291(2)K, of which 1190 were observed
with I>2σ(I).The correction for Lp factors were applied.
The structure was solved by direct methods and refined by
16
full-matrix least-squares refinement (SHELX97). All non-hydrogen
atoms were refined anisotropically, and hydrogen atoms were located
from difference Fourier map and added geometrically. The final cycle
2
2
of refinement gave R = 0.0436 and wR = 0.0975(w = 1/[σ (Fo ) +
2
2
2
(
0.0412P) + 0.6443P where P = (Fo +2Fc )/3). (∆/σ)max = 0.002,
3
S = 1.096, (∆ρ)max = 0.273 and (∆ρ)min = −0.263e/Å .
Full crystallographic details, excluding structure factors, have been
deposited at the Cambridge Crystallographic Data Center (CCDC).
Any request to the CCDC for this material should quote the full
literature citation and the reference number 805928.
Fig. 2 Crystal packing diagram of the title compound.
We thank the National Natural Science Foundation (20502023)
for the financial support.
Received 5 January 2011; accepted 18 February 2011
Paper 1100507 doi: 10.3184/174751911X12984610068847
Published online: 23 March 2011
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13
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3
procedure.
8
9
C H C1 NO 4: To a solution of compound 3 (1.9 g, 7 mmol) in
10
12
3
2
8
0, 149.
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2
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3
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4
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chromatography over a silica gel using petroleum ether-ethyl acetate
(
1
(
5:1) as eluant to give 4 (2.68 g, 96%) as a colourless crystal, m.p.
−
1
1
13.1–113.5 °C; IR(KBr): 1792 cm ; HNMR (CDCl ): δ1.78–1.99
3
1
1
5
6
m, 4H), 2.06–2.15 (m, 2H), 2.39 (dd, 1H, J = 2.0 Hz, 6.0 Hz, 11.6 Hz,
O–CH), 2.63–2.73 (m, 2H), 3.47 (dd, 1H, J = 6.0Hz, 10Hz, CH –Hα),
2
3
.77 (t, 1H, J = 8.4 Hz, CH –Hβ), 4.84 (t, 1H, J = 4.8 Hz, N–CH);
2
13
CNMR (CDCl ): δ21.48 (CH ), 27.57 (CH ), 33.53 (CH ), 39.52
3
2
2
2

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