Enantioselective Synthesis of (-)-Tetrabenazine Via Continuous Crystallization-Induced Diastereomer Transformation
Kukor, Andrew J.; Depner, Noah; Cai, Isabelle; Tucker, John; Culhane, Jeffrey C.; Hein, Jason E.; Chemical Science  (2022) –; doi:10.1039/D2SC01825J

data_1567525
_publ_section_title
;
 Enantioselective Synthesis of (-)-Tetrabenazine Via Continuous
 Crystallization-Induced Diastereomer Transformation
;
_journal_name_full               'Chemical Science'
_journal_paper_doi               10.1039/D2SC01825J
_journal_year                    2022
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C10 H15 O4 S, C19 H28 N O3, H2 O'
_chemical_formula_sum            'C29 H45 N O8 S'
_chemical_formula_weight         567.72
_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   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2021-07-28
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6272)
;
_audit_update_record
;
2022-03-24 deposited with the CCDC.	2022-08-24 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90.936(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.8124(7)
_cell_length_b                   10.5313(7)
_cell_length_c                   27.852(2)
_cell_measurement_reflns_used    9082
_cell_measurement_temperature    90(2)
_cell_measurement_theta_max      30.50
_cell_measurement_theta_min      2.84
_cell_volume                     2877.8(3)
_computing_cell_refinement       'SAINT V8.40B (Bruker, 2016)'
_computing_data_reduction        'SAINT V8.40B (Bruker, 2016)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      90(2)
_diffrn_detector                 'Bruker APEX2 area detector'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD area detector'
_diffrn_measured_fraction_theta_full 0.992
_diffrn_measured_fraction_theta_max 0.977
_diffrn_measurement_device       'Bruker D8 Kappa diffractometer'
_diffrn_measurement_device_type  'Bruker APEX II area detector'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  'TRIUMPH curved-crystal'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.042
_diffrn_reflns_av_unetI/netI     0.0335
_diffrn_reflns_Laue_measured_fraction_full 0.992
_diffrn_reflns_Laue_measured_fraction_max 0.977
_diffrn_reflns_number            16775
_diffrn_reflns_point_group_measured_fraction_full 0.980
_diffrn_reflns_point_group_measured_fraction_max 0.951
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         30.571
_diffrn_reflns_theta_min         1.462
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_current           30.0
_diffrn_source_power             1.35
_diffrn_source_type              'Incoatec I\ms'
_diffrn_source_voltage           45.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.163
_exptl_absorpt_correction_T_max  0.994
_exptl_absorpt_correction_T_min  0.908
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
 TWINABS-2012/1 (Bruker,2012) was used for absorption correction.

Final HKLF 4 output contains 114408 reflections, Rint = 0.0417
 (68615 with I > 3sig(I), Rint = 0.0341)
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.310
_exptl_crystal_description       plate
_exptl_crystal_F_000             1224
_exptl_crystal_recrystallization_method
'The material was recrystallised from acetone by slow evaporation'
_exptl_crystal_size_max          0.21
_exptl_crystal_size_mid          0.18
_exptl_crystal_size_min          0.04
_refine_diff_density_max         0.495
_refine_diff_density_min         -0.354
_refine_diff_density_rms         0.050
_refine_ls_abs_structure_details
;
 Flack x determined using 6553 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.02(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.042
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     739
_refine_ls_number_reflns         16775
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.042
_refine_ls_R_factor_all          0.0424
_refine_ls_R_factor_gt           0.0369
_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^)+(0.0553P)^2^+0.3455P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0889
_refine_ls_wR_factor_ref         0.0911
_reflns_Friedel_coverage         0.854
_reflns_Friedel_fraction_full    0.967
_reflns_Friedel_fraction_max     0.922
_reflns_number_gt                15382
_reflns_number_total             16775
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2sc01825j2.cif
_cod_data_source_block           jh036
_cod_database_code               1567525
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.994
_shelx_estimated_absorpt_t_min   0.967
_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 Ternary CH refined with riding coordinates:
 C43(H43), C53(H53), C7(H7), C10(H10), C17(H17), C26(H26), C29(H29), C36(H36)
2.b Secondary CH2 refined with riding coordinates:
 C39(H39A,H39B), C41(H41A,H41B), C42(H42A,H42B), C44(H44A,H44B), C49(H49A,
 H49B), C51(H51A,H51B), C52(H52A,H52B), C54(H54A,H54B), C4(H4A,H4B), C5(H5A,
 H5B), C6(H6A,H6B), C9(H9A,H9B), C16(H16A,H16B), C23(H23A,H23B), C24(H24A,H24B),
  C25(H25A,H25B), C28(H28A,H28B), C35(H35A,H35B)
2.c Aromatic/amide H refined with riding coordinates:
 C2(H2), C12(H12), C21(H21), C31(H31)
2.d Idealised Me refined as rotating group:
 C47(H47A,H47B,H47C), C48(H48A,H48B,H48C), C57(H57A,H57B,H57C), C58(H58A,H58B,
 H58C), C14(H14A,H14B,H14C), C15(H15A,H15B,H15C), C18(H18A,H18B,H18C), C19(H19A,
 H19B,H19C), C33(H33A,H33B,H33C), C34(H34A,H34B,H34C), C37(H37A,H37B,H37C),
 C38(H38A,H38B,H38C)
;
_shelx_res_checksum              78409
_shelx_hkl_checksum              55814
_olex2_diffrn_ambient_temperature_device 'Oxford Cryosystems'
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a MITIGEN holder in oil'
_olex2_submission_original_sample_id AJK-2-114
_olex2_submission_special_instructions 'No special instructions were received'