Synthesis of enantioenriched spirocyclic 2-arylpiperidines via kinetic resolution
Choi, Anthony; Das, Anjan; Meijer, Anthony J. H. M.; Proietti Silvestri, Ilaria; Coldham, Iain; Organic & Biomolecular Chemistry 22 (2024) 1602–1607; doi:10.1039/D4OB00011K

data_7159836
_publ_section_title
;
 Synthesis of enantioenriched spirocyclic 2-arylpiperidines via kinetic
 resolution
;
_journal_issue                   8
_journal_name_full               'Organic &amp; Biomolecular Chemistry'
_journal_page_first              1602
_journal_page_last               1607
_journal_paper_doi               10.1039/D4OB00011K
_journal_volume                  22
_journal_year                    2024
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C20 H24 Cl F2 N O4'
_chemical_formula_sum            'C20 H24 Cl F2 N O4'
_chemical_formula_weight         415.85
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2022-04-11
_audit_creation_method
;
Olex2 1.5
(compiled 2021.12.09 svn.r5202d8cf for OlexSys, GUI svn.r6439)
;
_audit_update_record
;
2023-12-07 deposited with the CCDC.	2024-01-23 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 100.816(10)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   8.252(7)
_cell_length_b                   10.441(11)
_cell_length_c                   12.226(10)
_cell_measurement_reflns_used    4917
_cell_measurement_temperature    100.00
_cell_measurement_theta_max      25.64
_cell_measurement_theta_min      2.59
_cell_volume                     1034.7(16)
_computing_cell_refinement       'SAINT V8.40A (Bruker, 2019)'
_computing_data_reduction        'SAINT V8.40A (Bruker, 2019)'
_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  (Sheldrick, 2015)'
_diffrn_ambient_temperature      100.00
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.994
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0481
_diffrn_reflns_av_unetI/netI     0.0477
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            19144
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.993
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         28.712
_diffrn_reflns_theta_min         1.696
_diffrn_source_current           30.0
_diffrn_source_power             1.5
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.227
_exptl_absorpt_correction_T_max  0.7458
_exptl_absorpt_correction_T_min  0.6877
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.0587 before and 0.0545 after correction.
The Ratio of minimum to maximum transmission is 0.9221.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.335
_exptl_crystal_description       block
_exptl_crystal_F_000             436
_exptl_crystal_size_max          0.334
_exptl_crystal_size_mid          0.254
_exptl_crystal_size_min          0.177
_refine_diff_density_max         0.212
_refine_diff_density_min         -0.219
_refine_diff_density_rms         0.043
_refine_ls_abs_structure_details
;
 Flack x determined using 2040 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.02(3)
_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     257
_refine_ls_number_reflns         5317
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.025
_refine_ls_R_factor_all          0.0416
_refine_ls_R_factor_gt           0.0347
_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^)+(0.0352P)^2^+0.0911P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0751
_refine_ls_wR_factor_ref         0.0794
_reflns_Friedel_coverage         0.897
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.992
_reflns_number_gt                4760
_reflns_number_total             5317
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ob00011k2.cif
_cod_data_source_block           oic326s_0m
_cod_database_code               7159836
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.961
_shelx_estimated_absorpt_t_min   0.928
_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
2.a Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C4(H4A,H4B), C5(H5A,H5B), C14(H14A,H14B)
2.b Aromatic/amide H refined with riding coordinates:
 C7(H7), C8(H8), C10(H10), C11(H11)
2.c Idealised Me refined as rotating group:
 C13(H13A,H13B,H13C), C18(H18A,H18B,H18C), C19(H19A,H19B,H19C), C20(H20A,H20B,
 H20C)
;
_shelx_res_checksum              10444
_olex2_date_sample_data_collection 2022-03-30
_olex2_date_sample_submission    2022-03-29
_olex2_exptl_crystal_mounting_method 'Mitigen microloop in fomblin oil'
_olex2_submission_original_sample_id AC-14-87-P1
_olex2_submission_special_instructions 'No special instructions were received'