Atropselective synthesis of N-aryl pyridones via dynamic kinetic resolution enabled by non-covalent interactions
Sweet, Jamie S.; Wang, Ruichen; Manesiotis, Panagiotis; Dingwall, Paul; Knipe, Peter C.; Organic & Biomolecular Chemistry  (2022) –; doi:10.1039/D2OB00177B

data_7158559
_publ_section_title
;
 Atropselective synthesis of N-aryl pyridones via dynamic kinetic
 resolution enabled by non-covalent interactions
;
_journal_name_full               'Organic &amp; Biomolecular Chemistry'
_journal_paper_doi               10.1039/D2OB00177B
_journal_year                    2022
_chemical_absolute_configuration ad
_chemical_formula_moiety
'C23 H16 F N O2, C23 H15 F N O2, C35 H35 N2 O2'
_chemical_formula_sum            'C81 H66 F2 N4 O6'
_chemical_formula_weight         1229.37
_chemical_melting_point          ?
_chemical_name_systematic        6
_space_group_crystal_system      trigonal
_space_group_IT_number           146
_space_group_name_Hall           'R 3'
_space_group_name_H-M_alt        'R 3 :H'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2021-08-04
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6272)
;
_audit_update_record
;
2021-11-24 deposited with the CCDC.	2022-02-08 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            9
_cell_length_a                   28.7071(4)
_cell_length_b                   28.7071(4)
_cell_length_c                   25.9528(4)
_cell_measurement_reflns_used    18183
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      58.9970
_cell_measurement_theta_min      2.4790
_cell_volume                     18522.2(5)
_computing_cell_refinement       'CrysAlisPro 1.171.41.113a (Rigaku OD, 2021)'
_computing_data_collection       'CrysAlisPro 1.171.41.113a (Rigaku OD, 2021)'
_computing_data_reduction        'CrysAlisPro 1.171.41.113a (Rigaku OD, 2021)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2014/7 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10
_diffrn_detector_dtime           0.000
_diffrn_detector_type            'Rigaku, HyPix 6000'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w    -89.00  89.00   0.50    5.00    --    0.00  30.00  90.00  356
  2  \w    -84.00  58.00   0.50   20.00    --    5.00  49.00-180.00  284
  3  \w    -82.00 -19.00   0.50   20.00    --    5.00  30.00 -90.00  126
  4  \w    -27.00  -1.00   0.50   20.00    --  -90.00  57.00 -70.63   52
  5  \w   -147.00-115.00   0.50   20.00    --  -90.00  59.00 -24.92   64
  6  \w    -35.00  -1.00   0.50   20.00    --  -90.00  52.00 -32.25   68
  7  \w    -27.00  -1.00   0.50   20.00    --  -90.00  58.00 -48.41   52
  8  \w    -27.00  -1.00   0.50   20.00    --  -90.00  52.00 -53.47   52
  9  \w   -167.00-140.00   0.50   20.00    --  -90.00  59.00 -57.37   54
 10  \w    -26.00  -1.00   0.50   20.00    --  -90.00  59.00 -57.37   50
 11  \w   -118.00 -87.00   0.50   20.00    --  -90.00  59.00 -88.73   62
 12  \w    -27.00  -1.00   0.50   20.00    --  -90.00  59.00 -88.73   52
 13  \w   -103.00 -58.00   0.50   20.00    --  -90.00  30.00 -90.00   90
 14  \w    -41.00  -1.00   0.50   20.00    --  -90.00  43.00-100.61   80
 15  \w    -27.00  -1.00   0.50   20.00    --  -90.00  59.00 -24.92   52
 16  \w    -77.00 -51.00   0.50   20.00    --  -90.00  43.00-100.61   52
 17  \w   -163.00-106.00   0.50   20.00    --  -90.00  58.00-115.46  114
 18  \w    -99.00 -54.00   0.50   20.00    --  -90.00  58.00-115.46   90
 19  \w    -26.00  -1.00   0.50   20.00    --  -90.00  58.00-115.46   50
 20  \w    -27.00  -1.00   0.50   20.00    --  -90.00  59.00 -72.99   52
 21  \w    -26.00  -1.00   0.50   20.00    --  -90.00  55.00 -40.15   50
 22  \w    -28.00  -1.00   0.50   20.00    --  -90.00  59.00-101.42   54
 23  \w   -127.00-101.00   0.50   20.00    --  -90.00  43.00-100.61   52
 24  \w   -110.00 -73.00   0.50   20.00    --  -90.00  59.00 -24.92   74
 25  \w    -27.00  -1.00   0.50   20.00    --  -90.00  39.00 -90.00   52
 26  \w   -179.00 -47.00   0.50   20.00    --  -90.00  58.00-147.29  264
 27  \w    -91.00 -65.00   0.50   20.00    --  -90.00  52.00 -53.47   52
 28  \w   -159.00 -83.00   0.50   20.00    --  -90.00  52.00 -32.25  152
 29  \w    -53.00  -2.00   0.50   20.00    --  -90.00  30.00 -90.00  102
 30  \w    -48.00  -2.00   0.50   20.00    --  -90.00  39.00 -30.00   92
 31  \w    -29.00  -2.00   0.50   20.00    --  -90.00  49.00 -60.00   54
 32  \w    -28.00  -1.00   0.50   20.00    --  -90.00  58.00 -79.27   54
 33  \w   -179.00  -2.00   0.50   20.00    --  -90.00  45.00 -47.70  354
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_details 'Rigaku, AFC11 quarter \c goniometer'
_diffrn_measurement_device_type
'Rigaku 007HF diffractometer equipped with Varimax confocal mirrors, an AFC11 goniometer and HyPix 6000 detector'
_diffrn_measurement_method       'profile data from \w-scans'
_diffrn_measurement_specimen_support 'MiTeGen loops'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0493847000
_diffrn_orient_matrix_UB_12      0.0563129000
_diffrn_orient_matrix_UB_13      0.0078189000
_diffrn_orient_matrix_UB_21      0.0374682000
_diffrn_orient_matrix_UB_22      -0.0229017000
_diffrn_orient_matrix_UB_23      -0.0111858000
_diffrn_orient_matrix_UB_31      -0.0006010000
_diffrn_orient_matrix_UB_32      0.0120409000
_diffrn_orient_matrix_UB_33      -0.0576837000
_diffrn_radiation_collimation    'Varimax focusing mirrors'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0510
_diffrn_reflns_av_unetI/netI     0.0348
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       29
_diffrn_reflns_limit_h_min       -34
_diffrn_reflns_limit_k_max       34
_diffrn_reflns_limit_k_min       -21
_diffrn_reflns_limit_l_max       30
_diffrn_reflns_limit_l_min       -30
_diffrn_reflns_number            72024
_diffrn_reflns_point_group_measured_fraction_full 0.973
_diffrn_reflns_point_group_measured_fraction_max 0.973
_diffrn_reflns_theta_full        66.595
_diffrn_reflns_theta_max         66.595
_diffrn_reflns_theta_min         2.461
_diffrn_source                   'Rotating anode'
_diffrn_source_current           30.0
_diffrn_source_power             1.2
_diffrn_source_target            Cu
_diffrn_source_type              'Rigaku 007 HF'
_diffrn_source_voltage           40.0
_exptl_absorpt_coefficient_mu    0.527
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.39254
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.113a (Rigaku Oxford Diffraction, 2021)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    0.992
_exptl_crystal_description       lath
_exptl_crystal_F_000             5814
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: chloroform, hexane'
_exptl_crystal_size_max          0.22
_exptl_crystal_size_mid          0.04
_exptl_crystal_size_min          0.04
_refine_diff_density_max         0.152
_refine_diff_density_min         -0.110
_refine_diff_density_rms         0.021
_refine_ls_abs_structure_details
;
 Flack x determined using 3880 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.01(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.025
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     896
_refine_ls_number_reflns         14182
_refine_ls_number_restraints     841
_refine_ls_restrained_S_all      1.017
_refine_ls_R_factor_all          0.0641
_refine_ls_R_factor_gt           0.0402
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0592P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0987
_refine_ls_wR_factor_ref         0.1101
_reflns_Friedel_coverage         0.947
_reflns_Friedel_fraction_full    0.947
_reflns_Friedel_fraction_max     0.947
_reflns_number_gt                10313
_reflns_number_total             14182
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2ob00177b2.cif
_cod_data_source_block           2021ncs0303r1z
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_chemical_melting_point' value 'not measured' was changed
to '?' -- the value is undefined or not given.

Automatic conversion script
Id: cif_fix_values 7556 2019-12-06 15:28:31Z antanas 
;
_cod_original_cell_volume        18522.2(6)
_cod_original_sg_symbol_H-M      'R 3'
_cod_database_code               7158559
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C58 H50 F N3 O4'
_chemical_oxdiff_usercomment     JS-5-311
_shelx_estimated_absorpt_t_max   0.979
_shelx_estimated_absorpt_t_min   0.893
_reflns_odcompleteness_completeness 100.00
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.49
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Restrained distances
 C68A-C72B \\sim C68B-C72A
 with sigma of 0.04
 C67-C73A \\sim C67-C73B
 with sigma of 0.04
 C73A-C72B \\sim C73B-C72A
 with sigma of 0.02
 C67-C68A \\sim C67-C68B
 with sigma of 0.02
 C68A-C69A \\sim C68B-C69B
 with sigma of 0.02
 C70A-C72B \\sim C70B-C72A
 with sigma of 0.04
 C72B-C71A \\sim C72A-C71B
 with sigma of 0.02
 C69A-C71A \\sim C69B-C71B
 with sigma of 0.04
 C68A-C73A \\sim C68B-C73B
 with sigma of 0.02
 C69A-C70A \\sim C69B-C70B
 with sigma of 0.02
 C68A-C70A \\sim C68B-C70B
 with sigma of 0.04
 C73A-C71A \\sim C73B-C71B
 with sigma of 0.04
 C69A-C73A \\sim C69B-C73B
 with sigma of 0.04
 C70A-C71A \\sim C70B-C71B
 with sigma of 0.02
 C67-C69A \\sim C67-C69B
 with sigma of 0.04
3. Restrained planarity
 C68A, C69A, C70A, C71A, C72A, C73A
 with sigma of 0.1
 C68B, C69B, C70B, C71B, C72B, C73B
 with sigma of 0.1
4. Rigid body (RIGU) restrains
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 Sof(C68B)=Sof(C69B)=Sof(H69B)=Sof(C70B)=Sof(H70B)=Sof(C71B)=Sof(H71B)=
 Sof(C72B)=Sof(H72B)=Sof(C73B)=Sof(H73B)=1-FVAR(1)
 Sof(C68A)=Sof(C69A)=Sof(H69A)=Sof(C70A)=Sof(H70A)=Sof(C71A)=Sof(H71A)=
 Sof(C72A)=Sof(H72A)=Sof(C73A)=Sof(H73A)=FVAR(1)
6.a Ternary CH refined with riding coordinates:
 C11(H11), C12(H12), C14(H14), C15(H15)
6.b Secondary CH2 refined with riding coordinates:
 C13(H13A,H13B), C18(H18A,H18B), C19(H19A,H19B), C20(H20A,H20B), C21(H21A,H21B)
6.c Aromatic/amide H refined with riding coordinates:
 C37(H37), C38(H38), C39(H39), C40(H40), C43(H43), C46(H46), C47(H47),
 C48(H48), C49(H49), C50(H50), C51(H51), C54(H54), C55(H55), C57(H57), C58(H58),
  C60(H60), C61(H61), C62(H62), C63(H63), C66(H66), C69A(H69A), C69B(H69B),
 C70A(H70A), C70B(H70B), C71A(H71A), C71B(H71B), C72A(H72A), C72B(H72B),
 C73A(H73A), C73B(H73B), C74(H74), C77(H77), C78(H78), C80(H80), C81(H81),
 C3(H3), C4(H4), C6(H6), C7(H7), C10(H10), C16(H16), C24(H24), C25(H25),
 C26(H26), C27(H27), C29(H29), C31(H31), C32(H32), C33(H33), C34(H34)
6.d X=CH2 refined with riding coordinates:
 C17(H17A,H17B)
6.e Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C)
6.f Idealised tetrahedral OH refined as rotating group:
 O3(H3A), O2(H2)
;
_smtbx_masks_special_details
;
A solvent mask was calculated and 1559 electrons were 
found in a volume of 5917\%A^3^ in 1 void per unit cell. 
This is consistent with the presence of 
3[CHCl3] per Asymmetric Unit 
which account for 1566 electrons 
per unit cell.
;
_smtbx_masks_void_probe_radius   1.2
_smtbx_masks_void_truncation_radius 1.2
_shelx_res_checksum              46021
_shelx_hkl_checksum              17405
_shelx_fab_checksum              96896
_olex2_diffrn_ambient_temperature_device 'Oxford Cryosystems'
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a MITIGEN holder in perfluoroether oil'
_olex2_submission_original_sample_id JS-5-311
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 2.491
_oxdiff_exptl_absorpt_empirical_full_min 0.474