Synthesis of a Bicyclic Azetidine with In Vivo Antimalarial Activity Enabled by Stereospecific, Directed C(sp<sup>3</sup>)-H Arylation.
Maetani, Micah; Zoller, Jochen; Melillo, Bruno; Verho, Oscar; Kato, Nobutaka; Pu, Jun; Comer, Eamon; Schreiber, Stuart L.; Journal of the American Chemical Society 139 (2017) 11300–11306; doi:10.1021/jacs.7b06994

data_4131575
_publ_section_title
;
 Synthesis of a Bicyclic Azetidine with In Vivo Antimalarial Activity
 Enabled by Stereospecific, Directed C(sp<sup>3</sup>)-H Arylation.
;
_journal_issue                   32
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              11300
_journal_page_last               11306
_journal_paper_doi               10.1021/jacs.7b06994
_journal_volume                  139
_journal_year                    2017
_chemical_absolute_configuration ad
_chemical_formula_sum            'C15 H19 Br Cl2 N2 O'
_chemical_formula_weight         394.13
_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     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.071(2)
_cell_length_b                   10.749(3)
_cell_length_c                   19.914(5)
_cell_measurement_reflns_used    9785
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      23.63
_cell_measurement_theta_min      2.72
_cell_volume                     1727.6(8)
_computing_cell_refinement       'SAINT 7.46A (Bruker-AXS, 2015)'
_computing_data_collection       'APEX2 v2011.4.0 (Bruker-AXS, 2015)'
_computing_data_reduction        'SAINT 7.46A (Bruker-AXS, 2015)'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_structure_solution    'SHELXT-2015 (Sheldrick, 2015)'
_diffrn_ambient_temperature      100(2)
_diffrn_detector_area_resol_mean 8.3
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_diffrn_measurement_device_type  'Bruker Smart APEX2 CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0554
_diffrn_reflns_av_unetI/netI     0.0269
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       28
_diffrn_reflns_limit_l_min       -28
_diffrn_reflns_number            83926
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         30.027
_diffrn_reflns_theta_min         2.045
_diffrn_source
'I\mS micro-focus sealed tube, multilayer optics'
_exptl_absorpt_coefficient_mu    2.688
_exptl_absorpt_correction_T_max  0.7461
_exptl_absorpt_correction_T_min  0.5360
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Sheldrick, 2009)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.515
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       needle
_exptl_crystal_F_000             800
_exptl_crystal_size_max          0.508
_exptl_crystal_size_mid          0.224
_exptl_crystal_size_min          0.138
_refine_diff_density_max         0.280
_refine_diff_density_min         -0.603
_refine_diff_density_rms         0.046
_refine_ls_abs_structure_details
; 
 Flack x determined using 1522 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259). 
;
_refine_ls_abs_structure_Flack   0.028(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.025
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     221
_refine_ls_number_reflns         5053
_refine_ls_number_restraints     92
_refine_ls_restrained_S_all      1.033
_refine_ls_R_factor_all          0.0447
_refine_ls_R_factor_gt           0.0321
_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^)+(0.0288P)^2^+0.5795P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0748
_refine_ls_wR_factor_ref         0.0808
_reflns_Friedel_coverage         0.758
_reflns_Friedel_fraction_full    0.997
_reflns_Friedel_fraction_max     0.998
_reflns_number_gt                4125
_reflns_number_total             5053
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ja7b06994_si_002.cif
_cod_data_source_block           X17072
_cod_original_cell_volume        1727.7(8)
_cod_database_code               4131575
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_min   0.342
_shelx_estimated_absorpt_t_max   0.708
_shelx_res_checksum              46733
_shelx_hkl_checksum              10483