Stereoselective synthesis of atropisomeric amides enabled by intramolecular acyl transfer.
Wootton, Jack M.; Roper, Natalie J.; Morris, Catrin E.; Maguire, Victoria E.; Duff, Lee C.; Waddell, Paul G.; Whitwood, Adrian C.; Gammons, Richard J.; Miah, Afjal H.; Lynam, Jason M.; Armstrong, Roly J.; Unsworth, William P.; Chemical science 16 (2025) 3938–3945; doi:10.1039/d4sc05760k

data_1573763
_publ_section_title
;
 Stereoselective synthesis of atropisomeric amides enabled by
 intramolecular acyl transfer.
;
_journal_issue                   9
_journal_name_full               'Chemical science'
_journal_page_first              3938
_journal_page_last               3945
_journal_paper_doi               10.1039/d4sc05760k
_journal_volume                  16
_journal_year                    2025
_chemical_absolute_configuration unk
_chemical_formula_moiety         'C29 H36 N2 O'
_chemical_formula_sum            'C29 H36 N2 O'
_chemical_formula_weight         428.60
_chemical_name_systematic
N-(4-(benzyl(methyl)amino)butan-2-yl)-N-(2-(tert-butyl)phenyl)benzamide
_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             2024-06-17
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-06-17 deposited with the CCDC.	2025-01-23 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 93.6280(10)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   8.78770(10)
_cell_length_b                   13.2804(2)
_cell_length_c                   10.49030(10)
_cell_measurement_reflns_used    6777
_cell_measurement_temperature    110.00(10)
_cell_measurement_theta_max      77.7050
_cell_measurement_theta_min      4.2310
_cell_volume                     1221.81(3)
_computing_cell_refinement       'CrysAlisPro 1.171.43.94a (Rigaku OD, 2023)'
_computing_data_collection
'CrysAlisPro system (CCD 43.118a 64-bit (release 27-03-2024))'
_computing_data_reduction        'CrysAlisPro 1.171.43.94a (Rigaku OD, 2023)'
_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 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      110
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 100'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_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    -57.00 -27.00   0.50    1.00    --  -92.27  77.00 150.00   60
  2  \w   -105.00 -66.00   0.50    1.00    --  -92.27  77.00 150.00   78
  3  \w    -51.00 -25.00   0.50    1.00    --  -92.27  45.00   0.00   52
  4  \w    -66.00 -19.00   0.50    1.00    --  -92.27  61.00 -60.00   94
  5  \w    -71.00 -30.00   0.50    1.00    --  -92.27  61.00 -90.00   82
  6  \w    -27.00  28.00   0.50    1.00    --  -49.95  19.00-120.00  110
  7  \w    -47.00 -18.00   0.50    1.00    --  -92.27  45.00  30.00   58
  8  \w    -46.00 -20.00   0.50    1.00    --  -92.27  45.00 120.00   52
  9  \w    -51.00 -15.00   0.50    1.00    --  -92.27  45.00  90.00   72
 10  \w    -51.00 -26.00   0.50    1.00    --  -92.27  45.00 150.00   50
 11  \w    -48.00 -22.00   0.50    1.00    --  -49.95  97.00 156.00   52
 12  \w   -133.00-107.00   0.50    1.00    --  -92.27 -97.00  48.00   52
 13  \w   -122.00 -77.00   0.50    1.00    --  -49.95-125.00-180.00   90
 14  \w   -105.00 -23.00   0.50    1.00    --  -92.27  97.00 156.00  164
 15  \w    -87.00 -49.00   0.50    1.00    --  -49.95  97.00 156.00   76
 16  \w     79.00 121.00   0.50    1.00    --  103.47  77.00 120.00   84
 17  \w     74.00  99.00   0.50    1.00    --   48.70 125.00   0.00   50
 18  \w     82.00 119.00   0.50    1.00    --   48.70 125.00  30.00   74
 19  \w     86.00 152.00   0.50    1.00    --  111.41  97.00 156.00  132
 20  \w    104.00 129.00   0.50    1.00    --  103.47  97.00 156.00   50
 21  \w    127.00 172.00   0.50    1.00    --  103.47  77.00 120.00   90
 22  \w     39.00  70.00   0.50    1.00    --  103.47 -61.00  60.00   62
 23  \w     42.00  69.00   0.50    1.00    --  111.41 -61.00-180.00   54
 24  \w     39.00  64.00   0.50    1.00    --  111.41 -61.00 -90.00   50
 25  \w     38.00  64.00   0.50    1.00    --  111.41 -61.00 -60.00   52
 26  \w     44.00  91.00   0.50    1.00    --  111.41 -97.00  48.00   94
 27  \w     39.00  65.00   0.50    1.00    --  103.47 -97.00  48.00   52
 28  \w     -1.00  25.00   0.50    1.00    --   48.70 -97.00  48.00   52
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type
'XtaLAB Synergy, Single source at home/near, HyPix-Arc 100'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.1535147000
_diffrn_orient_matrix_UB_12      -0.0237876000
_diffrn_orient_matrix_UB_13      -0.0565668000
_diffrn_orient_matrix_UB_21      0.0577801000
_diffrn_orient_matrix_UB_22      0.1064637000
_diffrn_orient_matrix_UB_23      0.0358911000
_diffrn_orient_matrix_UB_31      0.0627792000
_diffrn_orient_matrix_UB_32      -0.0395070000
_diffrn_orient_matrix_UB_33      0.1310081000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0199
_diffrn_reflns_av_unetI/netI     0.0230
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            8334
_diffrn_reflns_point_group_measured_fraction_full 0.796
_diffrn_reflns_point_group_measured_fraction_max 0.794
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         68.247
_diffrn_reflns_theta_min         4.223
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.537
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.790
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.94a (Rigaku Oxford Diffraction, 2023)
Numerical absorption correction based on gaussian integration over
a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            Colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.165
_exptl_crystal_description       Blocks
_exptl_crystal_F_000             464
_exptl_crystal_recrystallization_method
'dichloromethane and hexane slow evaporation'
_exptl_crystal_size_max          0.254
_exptl_crystal_size_mid          0.142
_exptl_crystal_size_min          0.085
_refine_diff_density_max         0.149
_refine_diff_density_min         -0.158
_refine_diff_density_rms         0.026
_refine_ls_abs_structure_details
;
 Flack x determined using 1156 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.09(13)
_refine_ls_extinction_coef       0.0028(5)
_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     295
_refine_ls_number_reflns         3553
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.057
_refine_ls_R_factor_all          0.0262
_refine_ls_R_factor_gt           0.0253
_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^)+(0.0355P)^2^+0.1366P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0651
_refine_ls_wR_factor_ref         0.0658
_reflns_Friedel_coverage         0.519
_reflns_Friedel_fraction_full    0.572
_reflns_Friedel_fraction_max     0.569
_reflns_number_gt                3450
_reflns_number_total             3553
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc05760k2.cif
_cod_data_source_block           wpu24016
_cod_depositor_comments
'Adding full bibliography for 1573760--1573765.cif.'
_cod_original_sg_symbol_H-M      P21
_cod_database_code               1573763
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C29 H36 N2 O1'
_chemical_oxdiff_usercomment     'Jack Wootton jmw-cat'
_shelx_estimated_absorpt_t_max   0.956
_shelx_estimated_absorpt_t_min   0.876
_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:
 C11(H11)
2.b Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), C9(H9A,H9B), C10(H10A,H10B)
2.c Aromatic/amide H refined with riding coordinates:
 C1(H1), C2(H2), C3(H3), C4(H4), C5(H5), C15(H15), C16(H16), C17(H17),
 C18(H18), C19(H19), C21(H21), C22(H22), C23(H23), C24(H24)
2.d Idealised Me refined as rotating group:
 C8(H8A,H8B,H8C), C12(H12A,H12B,H12C), C27(H27A,H27B,H27C), C28(H28A,H28B,
 H28C), C29(H29A,H29B,H29C)
;
_shelx_res_checksum              54726
_shelx_hkl_checksum              92791
_olex2_date_sample_submission    2024-06-13
_olex2_exptl_crystal_mounting_method '200 micrometer micromount'
_olex2_submission_original_sample_id 'Jack Wootton jmw-cat'
_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 1.304
_oxdiff_exptl_absorpt_empirical_full_min 0.620