Chemo- and Atroposelective Boc Protection for Asymmetric Synthesis of NH2-Free Axially Chiral Biaryl Amino Phenols
Wang, Yangyang; Wang, Yike; Xu, Zhe; Chen, Kexin; Liu, Ying-Guo; Chen, Xingkuan; Zhou, Hongwei; Xu, Jianfeng; Chemical Science  (2025) –; doi:10.1039/D5SC06233K

data_1576087
_publ_section_title
;
 Chemo- and Atroposelective Boc Protection for Asymmetric Synthesis of
 NH2-Free Axially Chiral Biaryl Amino Phenols
;
_journal_name_full               'Chemical Science'
_journal_paper_doi               10.1039/D5SC06233K
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C21 H21 N O4'
_chemical_formula_sum            'C21 H21 N O4'
_chemical_formula_weight         351.39
_chemical_name_systematic        0
_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     dual
_audit_creation_date             2025-03-12
_audit_creation_method
;
Olex2 1.5
(compiled 2025.03.04 svn.red2d20d0 for OlexSys, GUI svn.r7188)
;
_audit_update_record
;
2025-03-21 deposited with the CCDC.	2025-10-27 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.3684(7)
_cell_length_b                   14.5095(11)
_cell_length_c                   17.8628(14)
_cell_measurement_reflns_used    8209
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      73.5340
_cell_measurement_theta_min      3.9460
_cell_volume                     1909.7(3)
_computing_cell_refinement       'CrysAlisPro 1.171.40.84a (Rigaku OD, 2020)'
_computing_data_collection       'CrysAlisPro 1.171.40.84a (Rigaku OD, 2020)'
_computing_data_reduction        'CrysAlisPro 1.171.40.84a (Rigaku OD, 2020)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      293(2)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.989
_diffrn_measured_fraction_theta_max 0.928
_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   -115.00 -13.00   0.50    0.10    --  -39.95 -57.00-180.00  204
  2  \w   -125.00  31.00   0.50    0.10    --  -39.95   0.00 150.00  312
  3  \w    -42.00  -9.00   0.50    0.10    --  -39.95  37.00-180.00   66
  4  \w     15.00  46.00   0.50    0.10    --  -39.95  19.00 150.00   62
  5  \w    -27.00   0.00   0.50    0.10    --  -39.95  19.00 150.00   54
  6  \w     71.00 123.00   0.50    0.10    --   39.95 178.00 120.00  104
  7  \w     78.00 117.00   0.50    0.10    --   39.95 178.00  60.00   78
  8  \w    -18.00  27.00   0.50    0.10    --   39.95 -19.00-180.00   90
  9  \w     92.00 123.00   0.50    0.10    --   39.95-178.00 -60.00   62
 10  \w    -47.00 -21.00   0.50    0.40    --  -94.50  45.00  60.00   52
 11  \w    -86.00 -39.00   0.50    0.40    --  -94.50 125.00  60.00   94
 12  \w   -112.00 -61.00   0.50    0.40    --  -94.50 -30.00-180.00  102
 13  \w   -177.00-131.00   0.50    0.40    --  -94.50 -30.00-180.00   92
 14  \w    -51.00 -16.00   0.50    0.40    --  -94.50  45.00 -30.00   70
 15  \w    -84.00 -57.00   0.50    0.40    --  -94.50 125.00 120.00   54
 16  \w    147.00 175.00   0.50    0.40    --  108.87  15.00-120.00   56
 17  \w     23.00 177.00   0.50    0.40    --  108.87   0.00  60.00  308
 18  \w     29.00 116.00   0.50    0.40    --  108.87  15.00-120.00  174
 19  \w     40.00  69.00   0.50    0.40    --  108.87 -61.00 -60.00   58
 20  \w     40.00  89.00   0.50    0.40    --  108.87 -77.00  60.00   98
 21  \w     34.00  71.00   0.50    0.40    --  108.87 -61.00 -90.00   74
 22  \w     74.00 107.00   0.50    0.40    --  108.87-105.00 -56.87   66
 23  \w     44.00  92.00   0.50    0.40    --  108.87-125.00  30.00   96
 24  \w     77.00 103.00   0.50    0.40    --  108.87 -94.00 -90.00   52
 25  \w     52.00 109.00   0.50    0.40    --  108.87-125.00 -60.00  114
 26  \w     88.00 170.00   0.50    0.40    --  108.87  30.00 -90.00  164
 27  \w     68.00  94.00   0.50    0.40    --  108.87 -94.00 120.00   52
 28  \w     52.00  78.00   0.50    0.40    --  108.87-125.00-150.00   52
 29  \w     85.00 111.00   0.50    0.40    --  108.87-125.00-150.00   52
 30  \w     34.00  59.00   0.50    0.40    --  108.87 -61.00  30.00   50
 31  \w     45.00  71.00   0.50    0.40    --  108.87 -77.00 -30.00   52
 32  \w     53.00  97.00   0.50    0.40    --  108.87 -94.00-120.00   88
 33  \w     34.00  69.00   0.50    0.40    --  108.87 -61.00   0.00   70
 34  \w     40.00  70.50   0.50    0.40    --  108.87 -77.00-180.00   61
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0221200000
_diffrn_orient_matrix_UB_12      -0.0811131000
_diffrn_orient_matrix_UB_13      -0.0549900000
_diffrn_orient_matrix_UB_21      -0.0515537000
_diffrn_orient_matrix_UB_22      -0.0638132000
_diffrn_orient_matrix_UB_23      0.0656059000
_diffrn_orient_matrix_UB_31      -0.2010430000
_diffrn_orient_matrix_UB_32      0.0252416000
_diffrn_orient_matrix_UB_33      -0.0107077000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0708
_diffrn_reflns_av_unetI/netI     0.0445
_diffrn_reflns_Laue_measured_fraction_full 0.989
_diffrn_reflns_Laue_measured_fraction_max 0.928
_diffrn_reflns_limit_h_max       4
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            11533
_diffrn_reflns_point_group_measured_fraction_full 0.972
_diffrn_reflns_point_group_measured_fraction_max 0.891
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.251
_diffrn_reflns_theta_min         3.925
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.689
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.61824
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.84a (Rigaku Oxford Diffraction, 2020)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light white'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    white
_exptl_crystal_density_diffrn    1.222
_exptl_crystal_description       block
_exptl_crystal_F_000             744
_exptl_crystal_preparation       0
_exptl_crystal_recrystallization_method 0
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.315
_refine_diff_density_min         -0.355
_refine_diff_density_rms         0.074
_refine_ls_abs_structure_details
;
 Flack x determined using 987 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.2(4)
_refine_ls_extinction_coef       0.0140(15)
_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   1.057
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     217
_refine_ls_number_reflns         3619
_refine_ls_number_restraints     37
_refine_ls_restrained_S_all      1.057
_refine_ls_R_factor_all          0.1127
_refine_ls_R_factor_gt           0.0933
_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^)+(0.0508P)^2^+5.4725P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2227
_refine_ls_wR_factor_ref         0.2402
_reflns_Friedel_coverage         0.671
_reflns_Friedel_fraction_full    0.947
_reflns_Friedel_fraction_max     0.840
_reflns_number_gt                3128
_reflns_number_total             3619
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5sc06233k2.cif
_cod_data_source_block           b1
_cod_database_code               1576087
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C N H O F'
_shelx_estimated_absorpt_t_max   0.934
_shelx_estimated_absorpt_t_min   0.874
_reflns_odcompleteness_completeness 99.35
_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 N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Restrained distances
 C20-C18
 1.508 with sigma of 0.01
3. Uiso/Uaniso restraints and constraints
Uanis(O2) \\sim Ueq, Uanis(C16) \\sim Ueq: with sigma of 0.01 and sigma for
terminal atoms of 0.02
Uanis(C20) \\sim Ueq, Uanis(C18) \\sim Ueq, Uanis(C19) \\sim Ueq, Uanis(C17)
\\sim Ueq: with sigma of 0.001 and sigma for terminal atoms of 0.002
Uanis(C19) \\sim Ueq, Uanis(C20) \\sim Ueq, Uanis(C18) \\sim Ueq, Uanis(C17)
\\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
4.a Rotating group:
 N1(H1A,H1B)
4.b Aromatic/amide H refined with riding coordinates:
 C9(H9), C8(H8), C14(H14), C12(H12), C13(H13), C6(H6), C3(H3), C2(H2), C1(H1C)
4.c Fitted hexagon refined as free rotating group:
 C14(C15,C21,C11,C12,C13), C6(C5,C4,C3,C2,C1)
4.d Idealised Me refined as rotating group:
 C17(H17A,H17B,H17C), C20(H20A,H20B,H20C), C19(H19A,H19B,H19C)
4.e Idealised tetrahedral OH refined as rotating group:
 O1(H1)
;
_shelx_res_checksum              45687
_olex2_exptl_crystal_mounting_method 0
_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
;
_oxdiff_exptl_absorpt_empirical_full_max 5.036
_oxdiff_exptl_absorpt_empirical_full_min 0.668