Application of organocatalysis in bioorganometallic chemistry: asymmetric synthesis of multifunctionalized spirocyclic pyrazolone‒ferrocene hybrids as novel RalA inhibitors
Zhang, Yuehua; Wang, Chunting; Huang, Wei; Haruehanroengra, Phensinee; Peng, Cheng; Sheng, Jia; Han, Bo; He, Gu; Organic Chemistry Frontiers 5 (2018) 2229–; doi:10.1039/C8QO00422F

data_1554335
_publ_section_title
;
 Application of organocatalysis in bioorganometallic chemistry: asymmetric
 synthesis of multifunctionalized spirocyclic pyrazolone--ferrocene
 hybrids as novel RalA inhibitors
;
_journal_issue                   14
_journal_name_full               'Organic Chemistry Frontiers'
_journal_page_first              2229
_journal_paper_doi               10.1039/C8QO00422F
_journal_volume                  5
_journal_year                    2018
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C33 H33 Fe N3 O4, C H2 Cl2'
_chemical_formula_sum            'C34 H35 Cl2 Fe N3 O4'
_chemical_formula_weight         676.40
_space_group_crystal_system      tetragonal
_space_group_IT_number           92
_space_group_name_Hall           'P 4abw 2nw'
_space_group_name_H-M_alt        'P 41 21 2'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2018-01-23
_audit_creation_method
;
Olex2 1.2
(compiled 2017.08.10 svn.r3458 for OlexSys, GUI svn.r5381)
;
_audit_update_record
;
2018-01-29 deposited with the CCDC.
2018-06-11 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   12.0535(3)
_cell_length_b                   12.0535(3)
_cell_length_c                   43.8649(13)
_cell_measurement_reflns_used    12308
_cell_measurement_temperature    139.05(10)
_cell_measurement_theta_max      72.9330
_cell_measurement_theta_min      4.1050
_cell_volume                     6373.0(3)
_computing_cell_refinement       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      139.05(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 15.9595
_diffrn_detector_type            EosS2
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.995
_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   -104.00 -20.00   1.00    3.19    --  -36.29 -57.00 -90.00   84
  2  \w    -55.00  33.00   1.00    3.19    --  -36.29  38.00-120.00   88
  3  \w    -31.00  53.00   1.00    3.19    --   36.29 -57.00 -60.00   84
  4  \w     20.00 104.00   1.00    3.19    --   36.29  57.00 150.00   84
  5  \w     23.00  90.00   1.00    3.19    --   36.29-125.00  30.00   67
  6  \w     91.00 177.00   1.00   12.75    --  108.71  45.00-180.00   86
  7  \w     39.00 109.00   1.00   12.75    --  108.71 -94.00 -30.00   70
  8  \w     39.00 130.00   1.00   12.75    --  108.71 -30.00   0.00   91
  9  \w    101.00 178.00   1.00   12.75    --  108.71  91.00 -52.00   77
 10  \w     37.00 147.00   1.00   12.75    --  108.71 -15.00-180.00  110
 11  \w    100.00 178.00   1.00   12.75    --  108.71 111.00 120.00   78
 12  \w     91.00 176.00   1.00   12.75    --  108.71  61.00 150.00   85
 13  \w     42.00 127.00   1.00   12.75    --  108.71 -61.00-180.00   85
 14  \w     20.00 104.00   1.00    3.19    --   36.29  57.00  60.00   84
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'New Gemini, Dual, Cu at zero, EosS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0327008000
_diffrn_orient_matrix_UB_12      0.0385516000
_diffrn_orient_matrix_UB_13      0.0322526000
_diffrn_orient_matrix_UB_21      0.0616981000
_diffrn_orient_matrix_UB_22      0.1104412000
_diffrn_orient_matrix_UB_23      -0.0052427000
_diffrn_orient_matrix_UB_31      -0.1070341000
_diffrn_orient_matrix_UB_32      0.0515848000
_diffrn_orient_matrix_UB_33      -0.0128804000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0790
_diffrn_reflns_av_unetI/netI     0.0521
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       54
_diffrn_reflns_limit_l_min       -54
_diffrn_reflns_number            34873
_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         73.202
_diffrn_reflns_theta_min         3.803
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    5.686
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.22709
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.46 (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear reddish red'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   reddish
_exptl_crystal_colour_primary    red
_exptl_crystal_density_diffrn    1.410
_exptl_crystal_description       block
_exptl_crystal_F_000             2816
_exptl_crystal_size_max          0.7
_exptl_crystal_size_mid          0.55
_exptl_crystal_size_min          0.35
_refine_diff_density_max         0.668
_refine_diff_density_min         -0.529
_refine_diff_density_rms         0.093
_refine_ls_abs_structure_details
;
 Flack x determined using 1827 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.001(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.070
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     401
_refine_ls_number_reflns         6315
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.070
_refine_ls_R_factor_all          0.0745
_refine_ls_R_factor_gt           0.0630
_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^)+(0.0760P)^2^+12.3423P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1467
_refine_ls_wR_factor_ref         0.1552
_reflns_Friedel_coverage         0.691
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.983
_reflns_number_gt                5512
_reflns_number_total             6315
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c8qo00422f2.cif
_cod_data_source_block           lq-p23-139k
_cod_database_code               1554335
_shelx_shelxl_version_number     2014/7
_reflns_odcompleteness_completeness 99.91
_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 C(H,H,H) groups, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C7(H7), C10(H10), C11(H11), C8(H8), C9(H9)
2.b Secondary CH2 refined with riding coordinates:
 C34(H34A,H34B)
2.c Aromatic/amide H refined with riding coordinates:
 C27(H27), C19(H19), C3(H3), C30(H30), C16(H16), C1(H1A), C33(H33), C5(H5),
 C17(H17), C20(H20), C28(H28), C32(H32), C31(H31), C25(H25), C29(H29), C4(H4),
 C2(H2), C26(H26)
2.d Idealised Me refined as rotating group:
 C22(H22A,H22B,H22C), C23(H23A,H23B,H23C), C21(H21A,H21B,H21C)
2.e Idealised tetrahedral OH refined as rotating group:
 O1(H1)
;
_shelx_res_checksum              60649
_shelx_hkl_checksum              20637
_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 2.837
_oxdiff_exptl_absorpt_empirical_full_min 0.551