Synthesis of nine-membered azlactones by palladium-catalyzed ring-expansion of γ-methylidene-δ-valerolactones with aziridines

Article abstract of DOI:10.1021/jo2006158

A palladium-catalyzed formal [6 + 3] cyclization of γ-methylidene- δ-valerolactones with aziridines has been developed to produce 1,4-oxazonan-9-ones, a class of nine-membered azlactones that are not easily accessible by existing methods. The products thus obtained can also be further functionalized with ease.

Full text of DOI:10.1021/jo2006158

Synthesis of Nine-membered Heterocycles by Palladium-Catalyzed Ring-Expansion of
γ-Methylidene-δ-valerolactones
Ryo Shintani,* Keiichi Ikehata, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University,
Sakyo, Kyoto 606-8502, Japan
Supporting Information
I. X-ray Crystal Structure of 3aa•0.5Cl(CH2)2Cl
S2–S7
1
II. H and 13C Spectra
S8–S41
S1

I. X-ray Crystal Structure of 3aa•0.5Cl(CH2)2Cl
Data Collection
A colorless 1,2-dichloroethane solution of 3aa was prepared. Crystals suitable for X-ray
analysis were obtained by diffusion of pentane at room temperature.
A yellow prism crystal of C28H29NO4SCl having approximate dimensions of 0.50 x 0.20
x 0.20 mm was mounted on a glass fiber. All measurements were made on a Rigaku RAXIS
RAPID imaging plate area detector with graphite monochromated Cu-Kα radiation.
Indexing was performed from 3 oscillations that were exposed for 9 seconds. The crystal-
to-detector distance was 127.40 mm.
Cell constants and an orientation matrix for data collection corresponded to a C-centered
monoclinic cell with dimensions:
a = 32.1162(6) Å
b = 15.8781(3) Å
β = 105.4052(8)°
c = 10.14064(18) Å
V = 4985.36(16) Å3
For Z = 8 and F.W. = 511.05, the calculated density is 1.362 g/cm3. Based on the
systematic absences of:
hkl: h + k ± 2n
h0l: l ± 2n
packing considerations, a statistical analysis of intensity distribution, and the successful
solution and refinement of the structure, the space group was determined to be:
C2/c (#15)
The data were collected at a temperature of –180 ± 1 °C to a maximum 2θ value of
136.5°. A total of 30 oscillation images were collected. A sweep of data was done using ω
scans from 80.0 to 260.0° in 30.0° step, at χ = 54.0° and φ = 0.0°. The exposure rate was 5.0
[sec./°]. A second sweep was performed using ω scans from 80.0 to 260.0° in 30.0° step, at χ
= 54.0° and φ = 90.0°. The exposure rate was 5.0 [sec./°]. Another sweep was performed
using ω scans from 80.0 to 260.0° in 30.0° step, at χ = 54.0° and φ = 180.0°. The exposure
rate was 5.0 [sec./°]. Another sweep was performed using ω scans from 80.0 to 260.0° in
30.0° step, at χ = 54.0° and φ = 270.0°. The exposure rate was 5.0 [sec./°]. Another sweep
was performed using ω scans from 80.0 to 260.0° in 30.0° step, at χ = 0.0° and φ = 0.0°. The
S2

exposure rate was 5.0 [sec./°]. The crystal-to-detector distance was 127.40 mm. Readout was
performed in the 0.100 mm pixel mode.
Data Reduction
Of the 24014 reflections that were collected, 4554 were unique (R = 0.046).
int
The linear absorption coefficient, µ, for Cu-Kα radiation is 24.293 cm–1. An empirical
absorption correction was applied which resulted in transmission factors ranging from 0.499
to 0.615. The data were corrected for Lorentz and polarization effects.
Structure Solution and Refinement
The structure was solved by direct methods1 and expanded using Fourier techniques.2 The
non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the
riding model. The final cycle of full-matrix least-squares refinement3 on F was based on
20181 observed reflections (I > 2.00σ(I)) and 345 variable parameters and converged (largest
parameter shift was 0.00 times its esd) with unweighted and weighted agreement factors of:
R = Σ ||Fo| – |Fc|| / Σ |Fo| = 0.0483
R = [Σ w (|Fo| – |Fc|)2 / Σ w Fo2]1/2 = 0.0616
w
The standard deviation of an observation of unit weight4 was 1.01. A Chebychev
polynomial weighting scheme was used.5 Plots of Σ w (|Fo|–|Fc|)2 versus |Fo|, reflection order
in data collection, sin θ/λ and various classes of indices showed no unusual trends. The
maximum and minimum peaks on the final difference Fourier map corresponded to 3.66 and
–3.93 e–/Å3, respectively.
Neutral atom scattering factors were taken from Cromer and Waber.6 Anomalous
dispersion effects were included in Fcalc;7 the values for Δf' and Δf" were those of Creagh
and McAuley.8 The values for the mass attenuation coefficients are those of Creagh and
1 SIR92: Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.; Burla, M.; Polidori,
G.; Camalli, M. J. Appl. Cryst. 1994, 27, 435.
2 DIRDIF99: Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.; de Gelder, R.;
Israel, R.; Smits, J. M. M. The DIRDIF-99 program system, Technical Report of the
Crystallography Laboratory, University of Nijmegen, The Netherlands (1999).
3 Least Squares function minimized:
Σw(|F |–|F |)2 where w = Least Squares weights.
o
c
4 Standard deviation of an observation of unit weight:
[Σw(|F |–|F |)2/(N –N )]1/2
o
where: N = number of observations, N = number of variables
c
o
v
o
v
5 Carruthers, J. R.; Watkin, D. J. Acta Crystallogr. 1979, A35, 698.
6 Cromer, D. T.; Waber, J. T. "International Tables for X-ray Crystallography", Vol. IV, The
Kynoch Press, Birmingham, England, Table 2.2 A (1974).
7 Ibers, J. A.; Hamilton, W. C. Acta Crystallogr. 1964, 17, 781.
8 Creagh, D. C.; McAuley, W. J. "International Tables for Crystallography", Vol C, (A. J. C.
Wilson, ed.), Kluwer Academic Publishers, Boston, Table 4.2.6.8, pages 219–222 (1992).
S3

Hubbell.9 All calculations were performed using the CrystalStructure10,11 crystallographic
software package.
The crystal structure has been deposited at the Cambridge Crystallographic Data Centre
(deposition number: CCDC 818301). The data can be obtained free of charge via the Internet
at www.ccdc.cam.ac.uk/conts/retrieving.html.
9 Creagh, D. C.; Hubbell, J. H. "International Tables for Crystallography", Vol C, (A. J. C.
Wilson, ed.), Kluwer Academic Publishers, Boston, Table 4.2.4.3, pages 200–206 (1992).
10 CrystalStructure 3.8: Crystal Structure Analysis Package, Rigaku and Rigaku Americas
(2000-2007). 9009 New Trails Dr. The Woodlands TX 77381 USA.
11 CRYSTALS Issue 11: Carruthers, J. R.; Rollett, J. S.; Betteridge, P. W.; Kinna, D.; Pearce,
L.; Larsen, A.; Gabe, E. Chemical Crystallography Laboratory, Oxford, UK (1999).
S4

Experimental Details
A. Crystal Data
Empirical Formula
Formula Weight
Crystal Color, Habit
Crystal Dimensions
Crystal System
Lattice Type
C28H29NO4SCl
511.05
colorless, prism
0.50 X 0.20 X 0.20 mm
monoclinic
C-centered
Indexing Images
Detector Position
Pixel Size
3 oscillations @ 9.0 seconds
127.40 mm
0.100 mm
Lattice Parameters
a = 32.1162(6) Å
b = 15.8781(3) Å
c = 10.14064(18) Å
β = 105.4052(8)°
V = 4985.36(16) Å3
Space Group
Z value
C2/c (#15)
8
D
1.362 g/cm3
2152.00
calc
F
000
µ(CuKα)
24.293 cm–1
S5

B. Intensity Measurements
Diffractometer
Radiation
Rigaku RAXIS-RAPID
CuKα (λ = 1.54187 Å)
graphite monochromated
Detector Aperture
460 mm x 256 mm
30 exposures
80.0 - 260.0°
5.0 sec./°
Data Images
ω oscillation Range (χ=54.0, φ=0.0)
Exposure Rate
ω oscillation Range (χ=54.0, φ=90.0)
Exposure Rate
80.0 - 260.0°
5.0 sec./°
ω oscillation Range (χ=54.0, φ=18.0)
Exposure Rate
80.0 - 260.0°
5.0 sec./°
ω oscillation Range (χ=54.0, φ=270.0)
Exposure Rate
80.0 - 260.0°
5.0 sec./°
ω oscillation Range (χ=0.0, φ=0.0)
Exposure Rate
80.0 - 260.0°
5.0 sec./°
Detector Position
127.40 mm
0.100 mm
Pixel Size
2θ
max
136.5°
No. of Reflections Measured
Total: 24014
Unique: 4554 (R = 0.046)
int
Corrections
Lorentz-polarization
Absorption
(trans. factors: 0.499 - 0.615)
S6

C. Structure Solution and Refinement
Structure Solution
Refinement
Direct Methods (SIR92)
Full-matrix least-squares on F
Function Minimized
Σ w (|Fo| –|Fc|)2
Least Squares Weights
Chebychev polynomial with 3 parameters
63.6603, 83.2032, 25.2623
2θ
max
cutoff
136.5°
Anomalous Dispersion
All non-hydrogen atoms
No. Observations (I>2.00σ(I))
No. Variables
20181
345
Reflection/Parameter Ratio
Residuals: R (I>2.00σ(I))
Residuals: Rw (I>2.00σ(I))
Goodness of Fit Indicator
Max Shift/Error in Final Cycle
58.50
0.0483
0.0616
1.013
0.000
3
-
3.66 e /Å
Maximum peak in Final Diff. Map
Minimum peak in Final Diff. Map
3
-
–3.93 e /Å
S7

1
II. H and 13C Spectra
compound 1b
S8

compound 1b
S9

compound 1c
S10

compound 1c
S11

compound 1d
S12

compound 1d
S13

compound 1e
S14

compound 1e
S15

compound 1g
S16

compound 1g
S17

compound 3aa
S18

compound 3aa
S19

compound 3ba
S20

compound 3ba
S21

compound 3ca
S22

compound 3ca
S23

compound 3da
S24

compound 3da
S25

compound 3ea
S26

compound 3ea
S27

compound 3fa
S28

compound 3fa
S29

compound 3ga
S30