Gram-scale synthesis of (+)-elacestrant streamlined by iridium-catalyzed dynamic kinetic asymmetric hydrogenation of α-substituted tetralones.
Zong, Yan; Zou, Xiaomei; Zhang, Shaoke; Chen, Gen-Qiang; Zhang, Xumu; Chemical science 16 (2025) 20376–20381; doi:10.1039/d5sc05497d

data_1575894
_publ_section_title
;
 Gram-scale synthesis of (+)-elacestrant streamlined by iridium-catalyzed
 dynamic kinetic asymmetric hydrogenation of &#x3b1;-substituted
 tetralones.
;
_journal_issue                   43
_journal_name_full               'Chemical science'
_journal_page_first              20376
_journal_page_last               20381
_journal_paper_doi               10.1039/d5sc05497d
_journal_volume                  16
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C19 H17 N O'
_chemical_formula_sum            'C19 H17 N O'
_chemical_formula_weight         275.33
_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   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2025-06-16
_audit_creation_method
;
Olex2 1.5
(compiled 2025.05.31 svn.r86d253d1 for OlexSys, GUI svn.r7254)
;
_audit_update_record
;
2025-06-30 deposited with the CCDC.	2025-09-16 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.2953(7)
_cell_length_b                   12.2541(10)
_cell_length_c                   14.4762(12)
_cell_measurement_reflns_used    9953
_cell_measurement_temperature    100.0(2)
_cell_measurement_theta_max      56.92
_cell_measurement_theta_min      4.11
_cell_volume                     1471.5(2)
_computing_cell_refinement       'SAINT V8.40B (?, 2016)'
_computing_data_collection       'Apex3 (Bruker 2018)'
_computing_data_reduction        'SAINT V8.40B (?, 2016)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'ShelXT 2014'
_diffrn_ambient_temperature      100.0(2)
_diffrn_detector                 'Bruker PHOTON III area detector'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CMOS area detector'
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'Bruker D8 VENTURE'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  'mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           GaK\a
_diffrn_radiation_wavelength     1.34138
_diffrn_reflns_av_R_equivalents  0.0593
_diffrn_reflns_av_unetI/netI     0.0223
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            55679
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.998
_diffrn_reflns_theta_full        53.594
_diffrn_reflns_theta_max         56.947
_diffrn_reflns_theta_min         4.112
_diffrn_source                   'microfocus Metaljet'
_diffrn_source_current           2.0
_diffrn_source_power             0.1397
_diffrn_source_type              'Incoatec Metaljet'
_diffrn_source_voltage           69.85
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.396
_exptl_absorpt_correction_T_max  0.7512
_exptl_absorpt_correction_T_min  0.6950
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1339 before and 0.0713 after correction.
The Ratio of minimum to maximum transmission is 0.9252.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.243
_exptl_crystal_description       block
_exptl_crystal_F_000             584
_exptl_crystal_size_max          0.21
_exptl_crystal_size_mid          0.18
_exptl_crystal_size_min          0.15
_refine_diff_density_max         0.175
_refine_diff_density_min         -0.129
_refine_diff_density_rms         0.032
_refine_ls_abs_structure_details
;
 Flack x determined using 1211 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.02(8)
_refine_ls_extinction_coef       0.0156(19)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.044
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     192
_refine_ls_number_reflns         3011
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.044
_refine_ls_R_factor_all          0.0294
_refine_ls_R_factor_gt           0.0282
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0364P)^2^+0.2314P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0698
_refine_ls_wR_factor_ref         0.0707
_reflns_Friedel_coverage         0.731
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.998
_reflns_number_gt                2916
_reflns_number_total             3011
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5sc05497d2.cif
_cod_data_source_block           cxy6012_0m
_cod_depositor_comments
'Adding full bibliography for 1575893--1575894.cif.'
_cod_database_code               1575894
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.943
_shelx_estimated_absorpt_t_min   0.921
_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
2.a Ternary CH refined with riding coordinates:
 C6(H6), C7(H7)
2.b Secondary CH2 refined with riding coordinates:
 C16(H16A,H16B), C17(H17A,H17B)
2.c Aromatic/amide H refined with riding coordinates:
 C1(H1A), C3(H3), C4(H4), C9(H9), C10(H10), C11(H11), C12(H12), C13(H13),
 C15(H15), C19(H19)
2.d Idealised tetrahedral OH refined as rotating group:
 O1(H1)
;
_shelx_res_checksum              3636
_olex2_submission_special_instructions 'No special instructions were received'