A stereodivergent multicomponent approach for the synthesis of C-N atropisomeric peptide analogues.
Roper, Natalie J.; Campbell, Aaron D. G.; Waddell, Paul G.; Brown, Alistair K.; Ermanis, Kristaps; Armstrong, Roly J.; Chemical science 15 (2024) 16743–16751; doi:10.1039/d4sc04700a

data_1573031
_publ_section_title
;
 A stereodivergent multicomponent approach for the synthesis of C-N
 atropisomeric peptide analogues.
;
_journal_issue                   40
_journal_name_full               'Chemical science'
_journal_page_first              16743
_journal_page_last               16751
_journal_paper_doi               10.1039/d4sc04700a
_journal_volume                  15
_journal_year                    2024
_chemical_formula_moiety         'C27 H29 I N2 O2'
_chemical_formula_sum            'C27 H29 I N2 O2'
_chemical_formula_weight         540.42
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2023-08-22
_audit_creation_method
;
Olex2 1.5-ac5-023
(compiled 2022.04.12 svn.rca3783a0 for Rigaku Oxford Diffraction, GUI svn.r6498)
;
_audit_update_record
;
2024-05-15 deposited with the CCDC.	2024-09-16 downloaded from the CCDC.
;
_cell_angle_alpha                108.9080(10)
_cell_angle_beta                 102.9090(10)
_cell_angle_gamma                97.8830(10)
_cell_formula_units_Z            8
_cell_length_a                   13.4362(2)
_cell_length_b                   20.4573(3)
_cell_length_c                   20.6327(3)
_cell_measurement_reflns_used    45671
_cell_measurement_temperature    150.0(2)
_cell_measurement_theta_max      77.2310
_cell_measurement_theta_min      2.3190
_cell_volume                     5092.84(14)
_computing_cell_refinement       'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.5-ac5-023 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-ac5-023 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2019/1 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      150.0(2)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 100'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.949
_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    -51.00 -11.00   0.50    0.23    --  -92.45  45.00-120.00   80
  2  \w    -87.00 -19.00   0.50    0.23    --  -92.45  70.00-106.00  136
  3  \w    -75.00  26.00   0.50    0.23    --  -47.35  70.00-106.00  202
  4  \w    -51.00 -11.00   0.50    0.23    --  -92.45  45.00 -30.00   80
  5  \w    -51.00 -11.00   0.50    0.23    --  -92.45  45.00   0.00   80
  6  \w    -71.00 -15.00   0.50    0.23    --  -92.45  61.00  60.00  112
  7  \w    -51.00 -11.00   0.50    0.23    --  -92.45  45.00  90.00   80
  8  \w     17.00  43.00   0.50    0.23    --   50.00  81.00  -9.28   52
  9  \w     17.00  43.00   0.50    0.23    --   54.00  88.00 148.01   52
 10  \w     14.00  41.00   0.50    0.23    --   54.00  92.00  36.66   54
 11  \w     16.00  43.00   0.50    0.23    --   54.00  89.00 -60.48   54
 12  \w     15.00  42.00   0.50    0.23    --   54.00  91.00-149.70   54
 13  \w     74.00 122.00   0.50    0.23    --   46.35 125.00-150.00   96
 14  \w     19.00 120.00   0.50    0.23    --   46.35  70.00-106.00  202
 15  \w     77.00 178.00   0.50    0.23    --   97.10  45.00-180.00  202
 16  \w     70.00 171.00   0.50    0.23    --   97.10  70.00-106.00  202
 17  \w     81.00 178.00   0.50    0.23    --  108.07  70.00-106.00  194
 18  \w     88.00 178.00   0.50    0.23    --  108.07  45.00 -60.00  180
 19  \w     16.00  51.00   0.50    0.23    --   97.10 -45.00-150.00   70
 20  \w     20.00  71.00   0.50    0.23    --   97.10 -61.00-120.00  102
 21  \w     31.00  71.00   0.50    0.23    --  108.07 -61.00 -60.00   80
 22  \w     35.00  87.00   0.50    0.23    --  108.07 -70.00 121.00  104
 23  \w     24.00  87.00   0.50    0.23    --   97.10 -70.00 121.00  126
 24  \w    -27.00  74.00   0.50    0.23    --   46.35 -70.00 121.00  202
 25  \w     21.00 112.00   0.50    0.23    --   97.10-125.00 120.00  182
 26  \w     35.00 105.00   0.50    0.23    --  108.07 -95.00 120.00  140
 27  \w     33.00 112.00   0.50    0.23    --  108.07-125.00  60.00  158
 28  \w     35.00 105.00   0.50    0.23    --  108.07 -95.00 -60.00  140
 29  \w     35.00 105.00   0.50    0.23    --  108.07 -95.00-150.00  140
 30  \w   -133.00 -31.00   0.50    0.23    --  -62.00 -77.00  61.60  204
 31  \w   -166.00 -65.00   0.50    0.23    --  -92.45 -70.00 121.00  202
 32  \w   -121.00 -20.00   0.50    0.23    --  -47.35 -70.00 121.00  202
 33  \w   -164.00 -63.00   0.50    0.23    --  -90.00 -69.00   0.68  202
 34  \w   -166.00 -83.00   0.50    0.23    --  -92.45 -95.00-150.00  166
 35  \w   -123.00 -73.00   0.50    0.23    --  -47.35-125.00-150.00  100
 36  \w   -125.00 -24.00   0.50    0.23    --  -99.00 143.00  75.37  202
 37  \w   -109.00 -24.00   0.50    0.23    --  -99.00 116.00  17.47  170
 38  \w   -127.00 -25.00   0.50    0.23    --  -99.00 146.00-147.73  204
 39  \w   -112.00 -16.00   0.50    0.23    --  -92.45 125.00-180.00  192
;
_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      0.0895073000
_diffrn_orient_matrix_UB_12      0.0640940000
_diffrn_orient_matrix_UB_13      0.0167319000
_diffrn_orient_matrix_UB_21      -0.0528117000
_diffrn_orient_matrix_UB_22      0.0076999000
_diffrn_orient_matrix_UB_23      -0.0707001000
_diffrn_orient_matrix_UB_31      -0.0615603000
_diffrn_orient_matrix_UB_32      0.0501399000
_diffrn_orient_matrix_UB_33      0.0387914000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0315
_diffrn_reflns_av_unetI/netI     0.0235
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.949
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       25
_diffrn_reflns_limit_k_min       -24
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -26
_diffrn_reflns_number            95246
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.949
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.387
_diffrn_reflns_theta_min         2.344
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    10.069
_exptl_absorpt_correction_T_max  0.583
_exptl_absorpt_correction_T_min  0.282
_exptl_absorpt_correction_type   analytical
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.90a (Rigaku Oxford Diffraction, 2023)
Analytical numeric absorption correction using a multifaceted crystal
model based on expressions derived by R.C. Clark & J.S. Reid.
(Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897)
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    1.410
_exptl_crystal_description       rhombohedral
_exptl_crystal_F_000             2192
_exptl_crystal_size_max          0.26
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.07
_refine_diff_density_max         0.387
_refine_diff_density_min         -0.561
_refine_diff_density_rms         0.056
_refine_ls_extinction_coef       0.000073(8)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2019/1 (Sheldrick 2019)'
_refine_ls_goodness_of_fit_ref   1.075
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1276
_refine_ls_number_reflns         20504
_refine_ls_number_restraints     1342
_refine_ls_restrained_S_all      1.048
_refine_ls_R_factor_all          0.0300
_refine_ls_R_factor_gt           0.0246
_refine_ls_shift/su_max          0.004
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0336P)^2^+0.9407P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0673
_refine_ls_wR_factor_ref         0.0701
_reflns_Friedel_coverage         0.000
_reflns_number_gt                17317
_reflns_number_total             20504
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc04700a3.cif
_cod_data_source_block           rja230022_fa
_cod_original_cell_volume        5092.84(13)
_cod_database_code               1573031
_chemical_oxdiff_formula         'C27 H29 I1 N2 O2'
_shelx_estimated_absorpt_t_max   0.539
_shelx_estimated_absorpt_t_min   0.179
_diffrn_oxdiff_digest_frames
;
014285aae852a8b25b88e9ba2c24fcef22054000a12
;
_diffrn_oxdiff_digest_hkl
;
013ace93c24822779af227cd17943e67c6616b
;
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C71-C76B \\sim C71-C76A
 with sigma of 0.02
 C71-C72B \\sim C71-C72A
 with sigma of 0.02
 C73B-C74B \\sim C73A-C74A
 with sigma of 0.02
 C73B-C72B \\sim C73A-C72A
 with sigma of 0.02
 C73B-C75B \\sim C73A-C75A
 with sigma of 0.04
 C76B-C75B \\sim C76A-C75A
 with sigma of 0.02
 C74B-C72B \\sim C74A-C72A
 with sigma of 0.04
 C74B-C75B \\sim C74A-C75A
 with sigma of 0.02
 C76B-C74B \\sim C76A-C74A
 with sigma of 0.04
 C71-C73B \\sim C71-C73A
 with sigma of 0.04
 C71-C75B \\sim C71-C75A
 with sigma of 0.04
 C98-C12A \\sim C98-C12B
 with sigma of 0.04
 C99A-C11A \\sim C99B-C11B
 with sigma of 0.04
 C98-C13A \\sim C98-C13B
 with sigma of 0.02
 C98-C99A \\sim C98-C99B
 with sigma of 0.02
 C99A-C10A \\sim C99B-C10B
 with sigma of 0.02
 C98-C10A \\sim C98-C10B
 with sigma of 0.04
 C12A-C10A \\sim C12B-C10B
 with sigma of 0.04
 C11A-C12A \\sim C11B-C12B
 with sigma of 0.02
 C11A-C10A \\sim C11B-C10B
 with sigma of 0.02
 C12A-C13A \\sim C12B-C13B
 with sigma of 0.02
 C11A-C13A \\sim C11B-C13B
 with sigma of 0.04
3. Uiso/Uaniso restraints and constraints
C72B \\sim C73B \\sim C74B \\sim C75B \\sim C76B \\sim C72A \\sim C73A \\sim
C74A \\sim C75A \\sim C76A: within 2A with sigma of 0.04 and sigma for terminal
atoms of 0.08 within 2A
C10A \\sim C11A \\sim C12A \\sim C13A \\sim C99A \\sim C10B \\sim C11B \\sim
C12B \\sim C13B \\sim C99B: within 2A with sigma of 0.04 and sigma for terminal
atoms of 0.08 within 2A
4. Rigid body (RIGU) restrains
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 Fixed Sof: C10A(0.69693) H10J(0.69693) C11A(0.69693) H11A(0.69693)
 C12A(0.69693) H12A(0.69693) C13A(0.69693) H13A(0.69693) C72B(0.4422)
 H72B(0.4422) C73B(0.4422) H73B(0.4422) C74B(0.4422) H74B(0.4422) C75B(0.4422)
 H75B(0.4422) C76B(0.4422) H76B(0.4422) C99A(0.69693) H99A(0.69693)
 C10B(0.30307) H10K(0.30307) C11B(0.30307) H11B(0.30307) C12B(0.30307)
 H12B(0.30307) C13B(0.30307) H13B(0.30307) C72A(0.5578) H72A(0.5578)
 C73A(0.5578) H73A(0.5578) C74A(0.5578) H74A(0.5578) C75A(0.5578) H75A(0.5578)
 C76A(0.5578) H76A(0.5578) C99B(0.30307) H99B(0.30307)
6.a Ternary CH refined with riding coordinates:
 C16(H16), C43(H43), C70(H70), C97(H97)
6.b Aromatic/amide H refined with riding coordinates:
 C3(H3), C4(H4), C5(H5), C6(H6A), C7(H7), C10(H10), C12(H12), C18(H18),
 C19(H19), C20(H20), C21(H21), C22(H22), C30(H30), C31(H31), C32(H32), C33(H33),
  C34(H34), C37(H37), C39(H39), C45(H45), C46(H46), C47(H47), C48(H48),
 C49(H49), C57(H57), C58(H58), C59(H59), C60(H60), C61(H61), C64(H64), C66(H66),
  C84(H84), C85(H85), C86(H86), C87(H87), C88(H88), C91(H91), C93(H93),
 C10A(H10J), C11A(H11A), C12A(H12A), C13A(H13A), C72B(H72B), C73B(H73B),
 C74B(H74B), C75B(H75B), C76B(H76B), C99A(H99A), C10B(H10K), C11B(H11B),
 C12B(H12B), C13B(H13B), C72A(H72A), C73A(H73A), C74A(H74A), C75A(H75A),
 C76A(H76A), C99B(H99B)
6.c Idealised Me refined as rotating group:
 C14(H14A,H14B,H14C), C15(H15A,H15B,H15C), C25(H25A,H25B,H25C), C26(H26A,H26B,
 H26C), C27(H27A,H27B,H27C), C41(H41A,H41B,H41C), C42(H42A,H42B,H42C), C52(H52A,
 H52B,H52C), C53(H53A,H53B,H53C), C54(H54A,H54B,H54C), C68(H68A,H68B,H68C),
 C69(H69A,H69B,H69C), C79(H79A,H79B,H79C), C80(H80A,H80B,H80C), C81(H81A,H81B,
 H81C), C95(H95A,H95B,H95C), C96(H96A,H96B,H96C), C106(H10A,H10B,H10C),
 C107(H10D,H10E,H10F), C108(H10G,H10H,H10I)
;
_shelx_res_checksum              84261
_shelx_hkl_checksum              65363
_shelx_shelxl_version_number     2019/1
_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 1.308
_oxdiff_exptl_absorpt_empirical_full_min 0.747