Mechanistic Studies of a Pd-Catalyzed Direct Arylation En Route to Beclabuvir: Dual Role of a Tetramethylammonium Cation and an Unusual Turnover-Limiting Step
Hang, Chao; Ramirez, Antonio; Chan, Collin; Hsiao, Yi; DelMonte, Albert J.; Simmons, Eric M.; ACS Catalysis  (2021) 2460–2472; doi:10.1021/acscatal.0c05533

data_4518493
_publ_section_title
;
 Mechanistic Studies of a Pd-Catalyzed Direct Arylation En Route to
 Beclabuvir: Dual Role of a Tetramethylammonium Cation and an Unusual
 Turnover-Limiting Step
;
_journal_name_full               'ACS Catalysis'
_journal_page_first              2460
_journal_page_last               2472
_journal_paper_doi               10.1021/acscatal.0c05533
_journal_year                    2021
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C98 H140 N6 O12 P2 Pd2 S2'
_chemical_formula_sum            'C98 H140 N6 O12 P2 Pd2 S2'
_chemical_formula_weight         1933.01
_space_group_crystal_system      orthorhombic
_space_group_IT_number           18
_space_group_name_Hall           'P 2 2ab'
_space_group_name_H-M_alt        'P 21 21 2'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2020-10-20
_audit_creation_method
;
Olex2 1.3
(compiled 2020.07.31 svn.rc2a77460 for OlexSys, GUI svn.r6145)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   27.2621(9)
_cell_length_b                   33.0868(11)
_cell_length_c                   13.1605(4)
_cell_measurement_temperature    296.15
_cell_volume                     11871.0(7)
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_diffrn_ambient_temperature      296.15
_diffrn_detector                 'Bruker APEX2 II'
_diffrn_detector_area_resol_mean 8.33
_diffrn_detector_type            'CCD area detector'
_diffrn_measured_fraction_theta_full 0.989
_diffrn_measured_fraction_theta_max 0.989
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_collimation    'focusing mirror'
_diffrn_radiation_monochromator  'multilayer mirror'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0447
_diffrn_reflns_av_unetI/netI     0.0347
_diffrn_reflns_Laue_measured_fraction_full 0.989
_diffrn_reflns_Laue_measured_fraction_max 0.989
_diffrn_reflns_limit_h_max       29
_diffrn_reflns_limit_h_min       -29
_diffrn_reflns_limit_k_max       36
_diffrn_reflns_limit_k_min       -36
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -7
_diffrn_reflns_number            94561
_diffrn_reflns_point_group_measured_fraction_full 0.990
_diffrn_reflns_point_group_measured_fraction_max 0.990
_diffrn_reflns_theta_full        58.194
_diffrn_reflns_theta_max         58.194
_diffrn_reflns_theta_min         3.125
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_type              'Incoatec I\mS'
_exptl_absorpt_coefficient_mu    3.426
_exptl_crystal_density_diffrn    1.082
_exptl_crystal_F_000             4080
_exptl_crystal_size_max          0.12
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.593
_refine_diff_density_min         -0.851
_refine_diff_density_rms         0.110
_refine_ls_abs_structure_details
;
 Refined as an inversion twin.
;
_refine_ls_abs_structure_Flack   0.124(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.092
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1166
_refine_ls_number_reflns         16278
_refine_ls_number_restraints     1218
_refine_ls_restrained_S_all      1.061
_refine_ls_R_factor_all          0.0447
_refine_ls_R_factor_gt           0.0433
_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^)+(0.0737P)^2^+9.5383P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1233
_refine_ls_wR_factor_ref         0.1259
_reflns_Friedel_coverage         0.827
_reflns_Friedel_fraction_full    0.991
_reflns_Friedel_fraction_max     0.991
_reflns_number_gt                15860
_reflns_number_total             16278
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            cs0c05533_si_002.cif
_cod_data_source_block           L1Pd(Ar)dimer
_cod_database_code               4518493
_shelx_shelxl_version_number     2017/1
_shelx_estimated_absorpt_t_max   0.726
_shelx_estimated_absorpt_t_min   0.684
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.876(8)
 0.124(8)
2. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All C(H,H,H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
3. Restrained distances
 C51A-C52A = C51B-C52B
 1.54 with sigma of 0.02
 C51A-C48A = C51B-C48B
 1.54 with sigma of 0.02
 C52A-C53A = C52B-C53B
 1.54 with sigma of 0.02
 C50A-C53A = C50B-C53B
 1.54 with sigma of 0.02
 C48A-C51A \\sim C48B-C51B \\sim C53A-C50A \\sim C53B-C50B
 with sigma of 0.02
 C51A-C52A \\sim C51B-C52B \\sim C52A-C53A \\sim C52B-C53B
 with sigma of 0.02
 C35-C38 \\sim C35-C38A
 with sigma of 0.02
 C37-C39 \\sim C37A-C39A
 with sigma of 0.04
 C35-C39 \\sim C35-C39A
 with sigma of 0.04
 C38-C40 \\sim C38A-C40A
 with sigma of 0.04
 C35-C37 \\sim C35-C37A
 with sigma of 0.04
 C36-C40 \\sim C36A-C40A
 with sigma of 0.04
 C38-C39 \\sim C38A-C39A
 with sigma of 0.02
 C35-C36 \\sim C35-C36A
 with sigma of 0.02
 C39-C40 \\sim C39A-C40A
 with sigma of 0.02
 C36-C37 \\sim C36A-C37A
 with sigma of 0.02
 C37-C40 \\sim C37A-C40A
 with sigma of 0.02
 C10-C13 \\sim C10-C13A
 with sigma of 0.02
 C13-C14 \\sim C13A-C14A
 with sigma of 0.04
 C12-C14 \\sim C12A-C14A
 with sigma of 0.02
 C11-C12 \\sim C11A-C12A
 with sigma of 0.02
 C12-C15 \\sim C12A-C15A
 with sigma of 0.04
 C13-C15 \\sim C13A-C15A
 with sigma of 0.02
 C10-C11 \\sim C10-C11A
 with sigma of 0.02
 C14-C15 \\sim C14A-C15A
 with sigma of 0.02
 C10-C12 \\sim C10-C12A
 with sigma of 0.04
 C10-C15 \\sim C10-C15A
 with sigma of 0.04
 C11-C14 \\sim C11A-C14A
 with sigma of 0.04
4. Uiso/Uaniso restraints and constraints
Uanis(C38A) = Uanis(C38)
Uanis(C40) = Uanis(C40A)
Uanis(C37) = Uanis(C37A)
Uanis(C39A) = Uanis(C39)
Uanis(C51B) = Uanis(C51A)
Uanis(C50A) = Uanis(C50B)
Uanis(C48A) = Uanis(C48B)
Uanis(C12A) = Uanis(C12)
Uanis(C15) = Uanis(C15A)
Uanis(C11) = Uanis(C11A)
Uanis(C14A) = Uanis(C14)
Uanis(C13) = Uanis(C13A)
5. 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
6. Others
 Sof(H49C)=Sof(H49D)=Sof(C48B)=Sof(H48B)=Sof(C50B)=Sof(H50C)=Sof(H50D)=
 Sof(C51B)=Sof(H51C)=Sof(H51D)=Sof(C52B)=Sof(H52C)=Sof(H52D)=Sof(C53B)=
 Sof(H53C)=Sof(H53D)=1-FVAR(1)
 Sof(H49A)=Sof(H49B)=Sof(C48A)=Sof(H48A)=Sof(C50A)=Sof(H50A)=Sof(H50B)=
 Sof(C51A)=Sof(H51A)=Sof(H51B)=Sof(C52A)=Sof(H52A)=Sof(H52B)=Sof(C53A)=
 Sof(H53A)=Sof(H53B)=FVAR(1)
 Sof(H35A)=Sof(C36A)=Sof(H36C)=Sof(H36D)=Sof(C37A)=Sof(H37C)=Sof(H37D)=
 Sof(C40A)=Sof(H40C)=Sof(H40D)=Sof(C39A)=Sof(H39C)=Sof(H39D)=Sof(C38A)=
 Sof(H38C)=Sof(H38D)=1-FVAR(2)
 Sof(H35)=Sof(C36)=Sof(H36A)=Sof(H36B)=Sof(C37)=Sof(H37A)=Sof(H37B)=Sof(C38)=
 Sof(H38A)=Sof(H38B)=Sof(C39)=Sof(H39A)=Sof(H39B)=Sof(C40)=Sof(H40A)=Sof(H40B)=
 FVAR(2)
 Sof(H10A)=Sof(C11A)=Sof(H11C)=Sof(H11D)=Sof(C12A)=Sof(H12C)=Sof(H12D)=
 Sof(C14A)=Sof(H14C)=Sof(H14D)=Sof(C15A)=Sof(H15C)=Sof(H15D)=Sof(C13A)=
 Sof(H13C)=Sof(H13D)=1-FVAR(3)
 Sof(H10)=Sof(C11)=Sof(H11A)=Sof(H11B)=Sof(C12)=Sof(H12A)=Sof(H12B)=Sof(C13)=
 Sof(H13A)=Sof(H13B)=Sof(C14)=Sof(H14A)=Sof(H14B)=Sof(C15)=Sof(H15A)=Sof(H15B)=
 FVAR(3)
7.a Ternary CH refined with riding coordinates:
 C10(H10A), C10(H10), C19(H19), C23(H23), C29(H29), C35(H35), C35(H35A),
 C48A(H48A), C48B(H48B), C62(H62), C81(H81), C87(H87), C93(H93)
7.b Secondary CH2 refined with riding coordinates:
 C11(H11A,H11B), C12(H12A,H12B), C13(H13A,H13B), C14(H14A,H14B), C15(H15A,
 H15B), C17(H17A,H17B), C20(H20A,H20B), C24(H24A,H24B), C25(H25A,H25B),
 C26(H26A,H26B), C27(H27A,H27B), C28(H28A,H28B), C30(H30A,H30B), C31(H31A,H31B),
  C32(H32A,H32B), C33(H33A,H33B), C34(H34A,H34B), C36(H36A,H36B), C37(H37A,
 H37B), C38(H38A,H38B), C39(H39A,H39B), C40(H40A,H40B), C49(H49C,H49D),
 C49(H49A,H49B), C50A(H50A,H50B), C51A(H51A,H51B), C52A(H52A,H52B), C53A(H53A,
 H53B), C50B(H50C,H50D), C51B(H51C,H51D), C52B(H52C,H52D), C53B(H53C,H53D),
 C57(H57A,H57B), C60(H60A,H60B), C70(H70A,H70B), C77(H77A,H77B), C82(H82A,H82B),
  C83(H83A,H83B), C84(H84A,H84B), C85(H85A,H85B), C86(H86A,H86B), C88(H88A,
 H88B), C89(H89A,H89B), C90(H90A,H90B), C91(H91A,H91B), C92(H92A,H92B),
 C94(H94A,H94B), C95(H95A,H95B), C96(H96A,H96B), C97(H97A,H97B), C98(H98A,H98B),
  C36A(H36C,H36D), C37A(H37C,H37D), C40A(H40C,H40D), C39A(H39C,H39D), C38A(H38C,
 H38D), C11A(H11C,H11D), C12A(H12C,H12D), C14A(H14C,H14D), C15A(H15C,H15D),
 C13A(H13C,H13D)
7.c Me refined with riding coordinates:
 C2(H2A,H2B,H2C), C3(H3A,H3B,H3C), C41(H41A,H41B,H41C), C42(H42A,H42B,H42C),
 C61(H61A,H61B,H61C), C69(H69A,H69B,H69C), C75(H75A,H75B,H75C), C78(H78A,H78B,
 H78C)
7.d Aromatic/amide H refined with riding coordinates:
 C6(H6), C7(H7), C16(H16), C44(H44), C46(H46), C55(H55), C56(H56), C64(H64),
 C66(H66), C67(H67), C71(H71), C72(H72), C74(H74), C80(H80)
;
_smtbx_masks_void_probe_radius   1.2
_smtbx_masks_void_truncation_radius 1.2
_shelx_res_checksum              3898
_shelx_hkl_checksum              33786
_shelx_fab_checksum              47794
_olex2_submission_special_instructions 'No special instructions were received'