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_1576088
_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_formula_moiety         'C25 H23 N O4 S'
_chemical_formula_sum            'C25 H23 N O4 S'
_chemical_formula_weight         433.50
_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     iterative
_audit_creation_date             2025-03-27
_audit_creation_method
;
Olex2 1.5
(compiled 2022.04.07 svn.rca3783a0 for OlexSys, GUI svn.r6498)
;
_audit_update_record
;
2025-03-27 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                   7.54430(10)
_cell_length_b                   11.81730(10)
_cell_length_c                   24.0589(3)
_cell_measurement_reflns_used    13396
_cell_measurement_temperature    293
_cell_measurement_theta_max      73.4940
_cell_measurement_theta_min      3.6240
_cell_volume                     2144.93(4)
_computing_cell_refinement       'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_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    'olex2.solve 1.5 (Bourhis et al., 2015)'
_diffrn_ambient_temperature      293
_diffrn_detector_area_resol_mean 5.2684
_diffrn_detector_type            AtlasS2
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.993
_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    -73.00  35.00   1.00    1.00    --  -40.73  77.00 -30.00  108
  2  \w   -115.00 -16.00   1.00    1.00    --  -40.73 -38.00-180.00   99
  3  \w     34.00 121.00   1.00    2.15    --  106.95-125.00  90.00   87
  4  \w     24.00 109.00   1.00    2.15    --  106.95 -94.00-120.00   85
  5  \w     34.00 133.00   1.00    2.15    --  106.95 -45.00-120.00   99
  6  \w     19.00 178.00   1.00    2.15    --  106.95   0.00-150.00  159
  7  \w   -121.00   0.00   1.00    1.00    --  -40.73 -19.00 -60.00  121
  8  \w   -117.00  -8.00   1.00    1.00    --  -40.73 -77.00  90.00  109
  9  \w     29.00 139.00   1.00    2.15    --  106.95 -26.00  37.00  110
 10  \w     74.00 178.00   1.00    2.15    --  106.95  77.00-120.00  104
 11  \w     74.00 178.00   1.00    2.15    --  106.95  77.00 -60.00  104
 12  \w     81.00 178.00   1.00    2.15    --  106.95  45.00  30.00   97
 13  \w   -117.00  -8.00   1.00    1.00    --  -40.73 -77.00 -60.00  109
 14  \w    -69.00  32.00   1.00    1.00    --  -40.73  57.00 120.00  101
 15  \w     74.00 178.00   1.00    2.15    --  106.95  77.00  60.00  104
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, AtlasS2'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0426
_diffrn_reflns_av_unetI/netI     0.0264
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       29
_diffrn_reflns_limit_l_min       -29
_diffrn_reflns_number            20388
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.620
_diffrn_reflns_theta_min         3.674
_exptl_absorpt_coefficient_mu    1.608
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.72970
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.43f (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light yellow'
_exptl_crystal_density_diffrn    1.342
_exptl_crystal_description       block
_exptl_crystal_F_000             912
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.709
_refine_diff_density_min         -0.709
_refine_diff_density_rms         0.076
_refine_ls_abs_structure_details
;
 Flack x determined using 1706 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.004(10)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.082
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     321
_refine_ls_number_reflns         4281
_refine_ls_number_restraints     712
_refine_ls_restrained_S_all      1.079
_refine_ls_R_factor_all          0.0509
_refine_ls_R_factor_gt           0.0498
_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^)+(0.1000P)^2^+0.6154P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1408
_refine_ls_wR_factor_ref         0.1434
_reflns_Friedel_coverage         0.730
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.980
_reflns_number_gt                4162
_reflns_number_total             4281
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5sc06233k2.cif
_cod_data_source_block           6_sf
_cod_database_code               1576088
_shelx_shelxl_version_number     2018/3
_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
 H5C-H9B
 2.5 with sigma of 0.01
 C21-S1 \\sim C21-S2
 with sigma of 0.02
 S1-C23 \\sim S2-C13
 with sigma of 0.04
 S1-C3 \\sim S2-C27
 with sigma of 0.02
 C21-C3 \\sim C21-C27
 with sigma of 0.04
 C21-C11 \\sim C21-C25
 with sigma of 0.02
 C11-C3 \\sim C25-C27
 with sigma of 0.04
 C11-C23 \\sim C25-C13
 with sigma of 0.02
 C23-C3 \\sim C13-C27
 with sigma of 0.02
 C21-C23 \\sim C21-C13
 with sigma of 0.04
3. Uiso/Uaniso restraints and constraints
C21: within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02 within 2A
C1 \\sim C4 \\sim C6 \\sim C8 \\sim C10 \\sim C12 \\sim C14 \\sim C16 \\sim C18
\\sim C20 \\sim C22 \\sim C24 \\sim C26 \\sim C28 \\sim C7 \\sim C15 \\sim C2
\\sim C17 \\sim C9 \\sim C19 \\sim C5 \\sim C21: within 3.8A with sigma of 0.01
and sigma for terminal atoms of 0.02 within 3.8A
C21 \\sim S1 \\sim C11 \\sim C23 \\sim C3 \\sim S2 \\sim C25 \\sim C13 \\sim
C27: within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02 within 2A
Uanis(C21) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C21) \\sim Ueq, Uanis(S1) \\sim Ueq, Uanis(C11) \\sim Ueq, Uanis(C23)
\\sim Ueq, Uanis(C3) \\sim Ueq, Uanis(S2) \\sim Ueq, Uanis(C25) \\sim Ueq,
Uanis(C13) \\sim Ueq, Uanis(C27) \\sim Ueq: with sigma of 0.001 and sigma for
terminal atoms of 0.002
Uanis(C25) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
4. Others
 Fixed Sof: S1(0.5) C11(0.75) H11(0.75) C23(0.75) H23(0.75) C3(0.75) H3(0.75)
 S2(0.5) C25(0.25) H25(0.25) C13(0.25) H13(0.25) C27(0.25) H27(0.25)
5.a Rotating group:
 N1(H1A,H1B)
5.b Aromatic/amide H refined with riding coordinates:
 C16(H16), C18(H18), C20(H20), C24(H24), C28(H28), C7(H7), C15(H15), C2(H2),
 C11(H11), C23(H23), C3(H3), C25(H25), C13(H13), C27(H27)
5.c Idealised Me refined as rotating group:
 C9(H9A,H9B,H9C), C19(H19A,H19B,H19C), C5(H5A,H5B,H5C)
5.d Idealised tetrahedral OH refined as rotating group:
 O4(H4)
;
_shelx_res_checksum              69771
_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
- Detector area scaling
;