A General Approach to the Aza-Diketomorpholine Scaffold
Berthet, Mathéo; Legrand, Baptiste; Martinez, Jean; Parrot, Isabelle; Organic Letters  (2017) –; doi:10.1021/acs.orglett.6b03656

data_1545055
_publ_section_title
;
 A General Approach to the Aza-Diketomorpholine Scaffold
;
_journal_name_full               'Organic Letters'
_journal_paper_doi               10.1021/acs.orglett.6b03656
_journal_year                    2017
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C18 H18 N2 O4'
_chemical_formula_sum            'C18 H18 N2 O4'
_chemical_formula_weight         326.34
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   difmap
_atom_sites_solution_primary     direct
_cell_angle_alpha                90
_cell_angle_beta                 97.578(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   15.1202(7)
_cell_length_b                   5.6812(3)
_cell_length_c                   19.0459(8)
_cell_measurement_reflns_used    5539
_cell_measurement_temperature    175
_cell_measurement_theta_max      68.0610
_cell_measurement_theta_min      2.3240
_cell_volume                     1621.77(13)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_molecular_graphics    'CAMERON (Watkin et al., 1996)'
_computing_publication_material  'CRYSTALS (Betteridge et al., 2003)'
_computing_structure_refinement  'CRYSTALS (Betteridge et al., 2003)'
_computing_structure_solution    'SHELXS 86 (Sheldrick, 1986)'
_diffrn_ambient_temperature      175
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.0143
_diffrn_detector_type            Sapphire3
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.989
_diffrn_measurement_details
;
  1 omega  -50.00   37.00   1.0000   10.4900
omega____ theta____ kappa____ phi______ frames
    -      -33.5000   38.0000  -60.0000 87

  2 omega -104.00  -12.00   1.0000   10.4900
omega____ theta____ kappa____ phi______ frames
    -      -33.5000  -42.0000  139.0000 92

  3 omega  -62.00   36.00   1.0000   10.4900
omega____ theta____ kappa____ phi______ frames
    -      -33.5000   77.0000  -60.0000 98

  4 omega   19.00   90.00   1.0000   10.4900
omega____ theta____ kappa____ phi______ frames
    -       34.7565 -126.0000 -180.0000 71

  5 omega   16.00  103.00   1.0000   10.4900
omega____ theta____ kappa____ phi______ frames
    -       34.7565   57.0000   60.0000 87

  6 omega   12.00  105.00   1.0000   10.4900
omega____ theta____ kappa____ phi______ frames
    -       34.7565   38.0000   30.0000 93

  7 omega   29.00   65.00   1.0000   10.4900
omega____ theta____ kappa____ phi______ frames
    -       34.7565   57.0000    0.0000 36

  8 omega   72.00   99.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000   30.0000 27

  9 omega   48.00   74.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -30.0000   60.0000 26

 10 omega   71.00   97.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000  -30.0000 26

 11 omega   32.00  116.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -77.0000 -180.0000 84

 12 omega  120.00  146.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000  -30.0000 26

 13 omega  144.00  169.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000   30.0000 25

 14 omega   90.00  115.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000 -110.0000  -79.3527 25

 15 omega   71.00   97.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000    0.0000 26

 16 omega   33.00   72.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -45.0000  -90.0000 39

 17 omega  128.00  167.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000   60.0000 39

 18 omega   36.00   73.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -61.0000   60.0000 37

 19 omega   80.00  111.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000   30.0000 31

 20 omega   81.00  112.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   45.0000   30.0000 31

 21 omega   80.00  107.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000    0.0000 27

 22 omega  128.00  154.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000    0.0000 26

 23 omega   81.00  111.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000   60.0000 30

 24 omega   33.00   84.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -61.0000   30.0000 51

 25 omega   81.00  106.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000  -30.0000 25

 26 omega   38.00   64.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -95.0000 -180.0000 26

 27 omega   29.00   62.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000 -112.0000 -180.0000 33

 28 omega   78.00  113.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000 -112.0000 -180.0000 35

 29 omega   81.00  107.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -61.0000 -150.0000 26

 30 omega   74.00  144.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   30.0000   90.0000 70

 31 omega   71.00   97.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000   60.0000 26

 32 omega   80.00  112.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000   90.0000 32

 33 omega   80.00  120.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   30.0000   60.0000 40

 34 omega  104.00  146.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000  -60.0000 42

 35 omega   76.00  168.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   30.0000   30.0000 92

 36 omega   29.00   68.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -30.0000  -60.0000 39

 37 omega   73.00   99.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -95.0000 -180.0000 26

 38 omega   47.00   95.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -95.0000  -90.0000 48

 39 omega  102.00  136.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  112.0000  -60.0000 34

 40 omega  125.00  151.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  112.0000   60.0000 26

 41 omega  112.00  152.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000  150.0000 40

 42 omega   72.00   97.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000  -60.0000 25

 43 omega  111.00  136.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  112.0000   30.0000 25

 44 omega   30.00   90.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -30.0000 -180.0000 60

 45 omega   53.00   92.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -42.0000  139.0000 39

 46 omega   70.00   97.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000  -45.0000  -60.0000 27

 47 omega   52.00   78.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000 -112.0000   60.0000 26

 48 omega  132.00  169.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   -7.0000  129.9703 37

 49 omega  103.00  129.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   61.0000 -120.0000 26

 50 omega   80.00  108.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   45.0000    0.0000 28

 51 omega   80.00  108.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   45.0000   60.0000 28

 52 omega   90.00  115.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   45.0000   90.0000 25

 53 omega   71.00   97.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   77.0000   90.0000 26

 54 omega   30.00   71.00   1.0000   41.9500
omega____ theta____ kappa____ phi______ frames
    -      100.0000   -7.0000  129.9703 41

;
_diffrn_measurement_device       Area
_diffrn_measurement_device_type  'Xcalibur, Sapphire3, Gemini'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.0772956000
_diffrn_orient_matrix_UB_12      0.1157227000
_diffrn_orient_matrix_UB_13      0.0325827000
_diffrn_orient_matrix_UB_21      0.0661867000
_diffrn_orient_matrix_UB_22      0.0852459000
_diffrn_orient_matrix_UB_23      0.0633005000
_diffrn_orient_matrix_UB_31      0.0143409000
_diffrn_orient_matrix_UB_32      0.2297988000
_diffrn_orient_matrix_UB_33      -0.0399548000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.044
_diffrn_reflns_av_unetI/netI     0.0504
_diffrn_reflns_limit_h_max       18
_diffrn_reflns_limit_h_min       -18
_diffrn_reflns_limit_k_max       6
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            17075
_diffrn_reflns_theta_full        66.000
_diffrn_reflns_theta_max         68.574
_diffrn_reflns_theta_min         2.340
_exptl_absorpt_coefficient_mu    0.787
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.91440
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.337
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             687.996
_exptl_crystal_size_max          0.350
_exptl_crystal_size_mid          0.150
_exptl_crystal_size_min          0.050
_refine_diff_density_max         0.25
_refine_diff_density_min         -0.19
_refine_ls_abs_structure_details
;
Flack (1983), 2475 Friedel-pairs
6a3a-1_1_175_01_b.res in P2(1)

           Notification of SPECIAL conditions
 Initialising Special positions
 Floating origin in  y direction
                 molecular weight,  calculated density, absorption coefficient
                                        (gm/cm**3)                (cm-1)
  From LIST    5        652.703              1.337                 7.873
  From LIST   29        602.723              1.234                 6.355
  Friedif =     31.2   Estimated Friedel difference =     3.2034
 f computed from scattering factors, including f-prime

 Friedif =      31.17      Acta A63, (2007), 257-265
 Flack & Shmueli (2007) recommend a value >200 for
 general structures and >80 for enantiopure crystals

 No of Reflections processed =   4615         No of Friedel Pairs =   1896
 No of Friedel Pairs found =     1896 No of Friedel Pairs used  =        0
 No of Unpaired Reflections  =    374
 No of Centric Reflections   =    449
     Friedel Coverage        =     83 %
 Too few useful Friedel Pairs

 Excluded reflections - A reflection may fail more than one test

 /Ds/ < 0.50  sig(Do)                 1896
 As < 1.00  sig(Ao)                      1
 /Do/ > 2.00  2Ds(max)                   0
 Weight < 0.00100                        0
 Ratio > 2.50000                         2

6a3a-1_1_175_01_b.res in P2(1)

           Notification of SPECIAL conditions
 Initialising Special positions
 Floating origin in  y direction
                 molecular weight,  calculated density, absorption coefficient
                                        (gm/cm**3)                (cm-1)
  From LIST    5        652.703              1.337                 7.873
  From LIST   29        602.723              1.234                 6.355
  Friedif =     31.2   Estimated Friedel difference =     3.2034
 f computed from scattering factors, including f-prime

 Friedif =      31.17      Acta A63, (2007), 257-265
 Flack & Shmueli (2007) recommend a value >200 for
 general structures and >80 for enantiopure crystals

 No of Reflections processed =   4615         No of Friedel Pairs =   1896
 No of Friedel Pairs found =     1896 No of Friedel Pairs used  =      246
 No of Unpaired Reflections  =    374
 No of Centric Reflections   =    449
     Friedel Coverage        =     83 %
 Flack parameter obtained from original refinement
 Hooft parameter obtained with Flack x set to zero
   RA   RD    wRA2  wRD2   Friedif for all data and x=zero
   6.5  99.8   8.3 100.0     31.17

 Do-Dm R-factor(%) with Flack(x) of  -0.03(0.28) =   99.84%

 Continuing Calculations with     246 reflections
 Normal Probability Plot for    246 reflections
 Gradient for zero intercept =               1.896
  Slope, intercept and Cc (R) of NPP Plot =  1.896  0.242  0.623

 The slope should be unity and the intercept zero

No of reflections for which delta(Io) has same sign as delta(Ic)
Same sign   Opposite sign
     137           109

           Histogram distributions (deciles, octiles, quartiles)
      1/10      1/8       1/4       mean     3/4        7/8       9/10
     -5.92     -4.73     -2.64     -0.28      2.41      4.83      5.19

 Initial mean Flack(x) =     -0.0466
   Final mean Flack(x) =     -0.0753 and LSQ Flack(x)      -0.0753
           Internal su =      3.1323
           External su =      2.9945
 Number of refections with probability greater than  0.0010 =    230

       Flack Parameter & su   -0.0296    0.2803   @
      Difference Flack & su   -0.0528    0.2547   !
       Hooft Parameter & su    0.3110    0.3707   $
    Histogram mean (x) & SD   -0.0753    0.1975   &
    (Using   230 refelctions.  19.1% within -.5 to 1.5)
          Least Sq (x) & SD   -0.0753    0.2915

@  Flack,1983, Acta Cryst A39, 876-881
!  Thompson & Watkin, 2011, J Appl Cryst, 44, 1077-1022
$  Hooft et al, 2008, J Appl Cryst, 41, 96-103
&  Cooper & Watkin, to be published

              Probabilities
 Hooft probability analysis
 For an enantiopure material, there are 2 choices, P2
 P2(correct)     0.7982   i.e. 0.798211E+00

 If 50:50 twinning is possible, there are 3 choices, P3
 P3(correct)     0.3998   i.e. 0.399802E+00
 P3(rac-twin)    0.4991   i.e. 0.499128E+00
 P3(inverse)     0.1011   i.e. 0.101070E+00
 G              0.3781
 G S.U.         0.7415

 Excluded reflections - A reflection may fail more than one test

 /Ds/ < 0.10  sig(Do)                 1650
 As < 1.00  sig(Ao)                      1
 /Do/ > 2.00  2Ds(max)                  16
 Weight < 0.00100                        0
 Ratio > 2.50000                         2

;
_refine_ls_abs_structure_Flack   0.0(3)
_refine_ls_extinction_method     None
_refine_ls_goodness_of_fit_ref   1.0953
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     440
_refine_ls_number_reflns         4615
_refine_ls_number_restraints     7
_refine_ls_R_factor_all          0.0635
_refine_ls_R_factor_gt           0.0508
_refine_ls_shift/su_max          0.0029076
_refine_ls_shift/su_mean         0.0002599
_refine_ls_structure_factor_coef F
_refine_ls_weighting_details
;
 Method, part 1, Chebychev polynomial, (Watkin, 1994, Prince, 1982) 
 [weight] = 1.0/[A~0~*T~0~(x)+A~1~*T~1~(x) ... +A~n-1~]*T~n-1~(x)] 
 where A~i~ are the Chebychev coefficients listed below and x= Fcalc/Fmax 
 Method = Robust Weighting (Prince, 1982) 
 W = [weight] * [1-(deltaF/6*sigmaF)^2^]^2^ 
 A~i~ are: 
 1.98 3.05 2.00 0.938 0.303 
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_all         0.0792
_refine_ls_wR_factor_gt          0.0570
_refine_ls_wR_factor_ref         0.0570
_reflns_limit_h_max              18
_reflns_limit_h_min              -18
_reflns_limit_k_max              6
_reflns_limit_k_min              -6
_reflns_limit_l_max              22
_reflns_limit_l_min              0
_reflns_number_gt                4615
_reflns_number_total             5750
_reflns_threshold_expression     I>2.0\s(I)
_oxford_diffrn_Wilson_B_factor   0.00
_oxford_diffrn_Wilson_scale      0.00
_oxford_refine_ls_r_factor_ref   0.0508
_oxford_refine_ls_scale          0.5409(10)
_oxford_reflns_number_all        5750
_oxford_reflns_threshold_expression_ref I>2.0\s(I)
_cod_data_source_file            ol6b03656_si_002.cif
_cod_data_source_block           1
_cod_original_cell_volume        1621.77(7)
_cod_original_sg_symbol_H-M      'P 1 21 1 '
_cod_database_code               1545055
_cell_oxdiff_length_a            15.1210(8)
_cell_oxdiff_length_b            5.6836(3)
_cell_oxdiff_length_c            19.0342(8)
_cell_oxdiff_angle_alpha         89.963(4)
_cell_oxdiff_angle_beta          97.520(4)
_cell_oxdiff_angle_gamma         89.988(4)
_cell_oxdiff_volume              1621.76(13)
_montpellier_reflns_maxres       0.83
_montpellier_reflns_completeness_maxres 98.88
_montpellier_reflns_redundancy_maxres 5.21