Dynamic Kinetic Resolution of Carboxylic Esters Catalyzed by Chiral PPY N-Oxides: Synthesis of Nonsteroidal Anti-Inflammatory Drugs and Mechanistic Insights
Xie, Ming-Sheng; Li, Ning; Tian, Yin; Wu, Xiao-Xia; Deng, Yun; Qu, Gui-Rong; Guo, Hai-Ming; ACS Catalysis 11 (2021) 8183–8196; doi:10.1021/acscatal.1c01438

data_4518831
_publ_section_title
;
 Dynamic Kinetic Resolution of Carboxylic Esters Catalyzed by Chiral PPY
 N-Oxides: Synthesis of Nonsteroidal Anti-Inflammatory Drugs and
 Mechanistic Insights
;
_journal_issue                   13
_journal_name_full               'ACS Catalysis'
_journal_page_first              8183
_journal_page_last               8196
_journal_paper_doi               10.1021/acscatal.1c01438
_journal_volume                  11
_journal_year                    2021
_chemical_absolute_configuration ad
_chemical_formula_moiety
'Cl, C H2 Cl2, C27 H31 N4 O2, C27 H30 N4 O2, H2 O'
_chemical_formula_sum            'C55 H65 Cl3 N8 O5'
_chemical_formula_weight         1024.50
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2021-06-06
_audit_creation_method
;
Olex2 1.3
(compiled 2020.06.28 svn.raecde09e for OlexSys, GUI svn.r6132)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   14.6667(2)
_cell_length_b                   15.3682(2)
_cell_length_c                   23.1466(3)
_cell_measurement_reflns_used    34566
_cell_measurement_temperature    170.00(10)
_cell_measurement_theta_max      71.3160
_cell_measurement_theta_min      3.7630
_cell_volume                     5217.26(12)
_computing_cell_refinement       'CrysAlisPro 1.171.40.53 (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.53 (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.53 (Rigaku OD, 2019)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      170.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 8.0521
_diffrn_detector_type            EosS2
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.993
_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    -81.00  11.00   1.00    3.95    --  -35.62 110.00  -1.00   92
  2  \w     14.00 106.00   1.00    3.95    --   35.62  28.00 154.00   92
  3  \w     85.00 177.00   1.00   15.78    --  107.12  28.00 154.00   92
  4  \w     37.00 110.00   1.00   15.78    --  107.12-101.00 164.00   73
  5  \w    100.00 177.00   1.00   15.78    --  107.12 110.00  -1.00   77
  6  \w   -103.00 -19.00   1.00    3.95    --  -35.62 -57.00-180.00   84
  7  \w      4.00  76.00   1.00    3.95    --   35.62-101.00 164.00   72
  8  \w     55.00 108.00   1.00    3.95    --   35.62-178.00 -60.00   53
  9  \w     57.00 108.00   1.00    3.95    --   35.62 178.00 -30.00   51
 10  \w     39.00 125.00   1.00   15.78    --  107.12 -45.00-150.00   86
 11  \w     90.00 176.00   1.00   15.78    --  107.12  45.00  60.00   86
 12  \w     37.00 113.00   1.00   15.78    --  107.12-111.00-150.00   76
 13  \w     37.00 129.00   1.00   15.78    --  107.12 -30.00 -30.00   92
 14  \w     40.00 125.00   1.00   15.78    --  107.12 -61.00 -90.00   85
 15  \w     38.00 110.00   1.00   15.78    --  107.12 -95.00 120.00   72
 16  \w     37.00 129.00   1.00   15.78    --  107.12 -30.00 120.00   92
 17  \w   -103.00 -19.00   1.00    3.95    --  -35.62 -57.00  30.00   84
 18  \w   -103.00  -9.00   1.00    3.95    --  -35.62 -77.00 -60.00   94
 19  \w   -103.00  -9.00   1.00    3.95    --  -35.62 -77.00 150.00   94
 20  \w     57.00 108.00   1.00    3.95    --   35.62 178.00  30.00   51
 21  \w    -34.00 105.00   1.00    3.95    --   35.62   0.00  30.00  139
 22  \w     69.00 178.00   1.00   15.78    --  107.12  15.00-120.00  109
 23  \w     80.00 175.00   1.00   15.78    --  107.12  77.00   0.00   95
 24  \w     86.00 177.00   1.00   15.78    --  107.12  30.00 -60.00   91
 25  \w     80.00 175.00   1.00   15.78    --  107.12  77.00-120.00   95
 26  \w     89.00 174.00   1.00   15.78    --  107.12  61.00  90.00   85
 27  \w     38.00 110.00   1.00   15.78    --  107.12 -95.00  30.00   72
 28  \w     80.00 175.00   1.00   15.78    --  107.12  77.00 -60.00   95
 29  \w     38.00 110.00   1.00   15.78    --  107.12 -95.00 -90.00   72
 30  \w     80.00 175.00   1.00   15.78    --  107.12  77.00 150.00   95
 31  \w     86.00 177.00   1.00   15.78    --  107.12  30.00   0.00   91
 32  \w   -103.00  -9.00   1.00    3.95    --  -35.62 -77.00-120.00   94
 33  \w   -108.00 -35.00   1.00    3.95    --  -35.62-178.00-120.00   73
 34  \w   -103.00  -9.00   1.00    3.95    --  -35.62 -77.00  30.00   94
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, EosS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0096722000
_diffrn_orient_matrix_UB_12      -0.0769581000
_diffrn_orient_matrix_UB_13      0.0421843000
_diffrn_orient_matrix_UB_21      -0.0397659000
_diffrn_orient_matrix_UB_22      -0.0562776000
_diffrn_orient_matrix_UB_23      -0.0489871000
_diffrn_orient_matrix_UB_31      0.0967518000
_diffrn_orient_matrix_UB_32      -0.0308455000
_diffrn_orient_matrix_UB_33      -0.0158994000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0596
_diffrn_reflns_av_unetI/netI     0.0297
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       17
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       28
_diffrn_reflns_limit_l_min       -28
_diffrn_reflns_number            68685
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.990
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         71.809
_diffrn_reflns_theta_min         3.452
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.040
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.50010
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.53 (Rigaku Oxford Diffraction, 2019)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.304
_exptl_crystal_description       'rect. Prism'
_exptl_crystal_F_000             2168
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.07
_exptl_crystal_size_min          0.06
_refine_diff_density_max         0.816
_refine_diff_density_min         -0.791
_refine_diff_density_rms         0.058
_refine_ls_abs_structure_details
;
 Flack x determined using 4108 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.007(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.037
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     652
_refine_ls_number_reflns         10118
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.037
_refine_ls_R_factor_all          0.0519
_refine_ls_R_factor_gt           0.0503
_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^)+(0.0853P)^2^+2.3413P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1373
_refine_ls_wR_factor_ref         0.1391
_reflns_Friedel_coverage         0.805
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.986
_reflns_number_gt                9707
_reflns_number_total             10118
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            cs1c01438_si_002.cif
_cod_data_source_block           ln-20210605
_cod_depositor_comments
'Adding full bibliography for 4518829--4518831.cif.'
_cod_database_code               4518831
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C1 H1 O1 N1'
_shelx_estimated_absorpt_t_max   0.887
_shelx_estimated_absorpt_t_min   0.749
_reflns_odcompleteness_completeness 99.94
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_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 O(H) groups, All O(H,H) groups
2.a Free rotating group:
 O71(H71A,H71B)
2.b Ternary CH refined with riding coordinates:
 C19(H19), C23(H23), C49(H49), C56(H56)
2.c Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C12(H12A,H12B), C13(H13A,H13B), C14(H14A,H14B), C15(H15A,H15B),
 C16(H16A,H16B), C17(H17A,H17B), C18(H18A,H18B), C45(H45A,H45B), C46(H46A,H46B),
  C47(H47A,H47B), C48(H48A,H48B), C50(H50A,H50B), C51(H51A,H51B), C52(H52A,H52B)
2.d Aromatic/amide H refined with riding coordinates:
 C6(H6), C9(H9), C10(H10), C26(H26), C27(H27), C28(H28), C29(H29), C30(H30),
 C32(H32), C33(H33), C34(H34), C35(H35), C36(H36), C39(H39), C42(H42), C43(H43),
  C59(H59), C60(H60), C61(H61), C62(H62), C63(H63), C65(H65), C66(H66),
 C67(H67), C68(H68), C69(H69)
2.e Idealised tetrahedral OH refined as rotating group:
 O37(H37)
;
_shelx_res_checksum              29300
_shelx_hkl_checksum              93075
_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
;
_oxdiff_exptl_absorpt_empirical_full_max 1.663
_oxdiff_exptl_absorpt_empirical_full_min 0.565