Tuning the Reactivity of Ketones through Unsaturation: Construction of Cyclic and Acyclic Quaternary Stereocenters via Zn-ProPhenol Catalyzed Mannich Reactions
Trost, Barry M.; Hung, Chao-I Joey; Gnanamani, Elumalai; ACS Catalysis 9 (2019) 1549–; doi:10.1021/acscatal.8b04685

data_4514762
_publ_section_title
;
 Tuning the Reactivity of Ketones through Unsaturation: Construction of
 Cyclic and Acyclic Quaternary Stereocenters via Zn-ProPhenol Catalyzed
 Mannich Reactions
;
_journal_issue                   2
_journal_name_full               'ACS Catalysis'
_journal_page_first              1549
_journal_paper_doi               10.1021/acscatal.8b04685
_journal_volume                  9
_journal_year                    2019
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C29 H29 N O3, 0.31(C H Cl3), 0.17(C H2 Cl2)'
_chemical_formula_sum            'C29.48 H29.66 Cl1.27 N O3'
_chemical_formula_weight         491.19
_space_group_crystal_system      monoclinic
_space_group_IT_number           5
_space_group_name_Hall           'C 2y'
_space_group_name_H-M_alt        'C 1 2 1'
_symmetry_space_group_name_Hall  'C 2y'
_symmetry_space_group_name_H-M   'C 1 2 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2018-07-03
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 99.524(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   25.1281(9)
_cell_length_b                   6.2680(2)
_cell_length_c                   15.9870(6)
_cell_measurement_reflns_used    9871
_cell_measurement_temperature    90
_cell_measurement_theta_max      77.459
_cell_measurement_theta_min      2.803
_cell_volume                     2483.29(15)
_computing_cell_refinement       'SAINT V8.38A (?, 2016)'
_computing_data_reduction        'SAINT V8.38A (?, 2016)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'XT (Sheldrick, 2015)'
_diffrn_ambient_temperature      90.0
_diffrn_detector                 'Bruker Photon100'
_diffrn_detector_area_resol_mean 10.4
_diffrn_detector_type            'CMOS area detector'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.994
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'D8 Venture'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_collimation    'focusing mirrors'
_diffrn_radiation_monochromator  'mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0542
_diffrn_reflns_av_unetI/netI     0.0294
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       31
_diffrn_reflns_limit_h_min       -31
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            38087
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.990
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         78.164
_diffrn_reflns_theta_min         2.803
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_type              'Incoatec I\ms'
_exptl_absorpt_coefficient_mu    1.886
_exptl_absorpt_correction_T_max  0.7541
_exptl_absorpt_correction_T_min  0.6148
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1327 before and 0.0756 after correction. The Ratio of minimum to maximum transmission is 0.8153. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.314
_exptl_crystal_description       needle
_exptl_crystal_F_000             1037
_exptl_crystal_size_max          0.252
_exptl_crystal_size_mid          0.04
_exptl_crystal_size_min          0.03
_refine_diff_density_max         0.396
_refine_diff_density_min         -0.328
_refine_diff_density_rms         0.050
_refine_ls_abs_structure_details
;
 Flack x determined using 2179 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.02(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.054
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     368
_refine_ls_number_reflns         5265
_refine_ls_number_restraints     80
_refine_ls_restrained_S_all      1.062
_refine_ls_R_factor_all          0.0430
_refine_ls_R_factor_gt           0.0406
_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^)+(0.0497P)^2^+2.4357P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0989
_refine_ls_wR_factor_ref         0.1012
_reflns_Friedel_coverage         0.820
_reflns_Friedel_fraction_full    0.994
_reflns_Friedel_fraction_max     0.984
_reflns_number_gt                5052
_reflns_number_total             5265
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            cs8b04685_si_003.cif
_cod_data_source_block           joey_eg_crystal_2
_cod_database_code               4514762
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_max   0.946
_shelx_estimated_absorpt_t_min   0.648
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C1S-Cl1S \\sim C1S-Cl2S \\sim C1S-Cl3S \\sim C2S-Cl1T \\sim C2S-Cl2T \\sim
C3S_$1-Cl1U_$1 ~
 C3S_$1-Cl3U_$1
 with sigma of 0.02
 Cl1S-Cl2S \\sim Cl1S-Cl3S \\sim Cl2S-Cl3S \\sim Cl1T-Cl2T \\sim Cl1U_$1-Cl3U_$1
 with sigma of 0.02
 Cl3U-Cl1U \\sim Cl2T-Cl1T
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(Cl3U) \\sim Ueq: with sigma of 0.1 and sigma for terminal atoms of 0.2
Uanis(C1S) = Uanis(C2S) = Uanis(C3S)
Uanis(Cl1S) = Uanis(Cl1T) = Uanis(Cl1U)
4. Rigid body (RIGU) restrains
 C3S, Cl1U, Cl3U, H3SA, H3SB
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
 Cl2T, C2S, H2SA, H2SB, Cl1T, C1S, Cl1S, Cl2S, Cl3S, H1S
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 1*[Sof(Cl1S)+Sof(Cl2S)+Sof(Cl3S)+Sof(C1S)+Sof(H1S)]+1*[Sof(C2S)+Sof(H2SA)+
 Sof(H2SB)+Sof(Cl1T)+Sof(Cl2T)]+1*[Sof(Cl1U)+Sof(Cl3U)+Sof(C3S)+Sof(H3SA)+
 Sof(H3SB)]=1 with esd of 0.01
 Sof(Cl1S)=Sof(Cl2S)=Sof(Cl3S)=Sof(C1S)=Sof(H1S)=0.5*FVAR(2)
 Sof(C2S)=Sof(H2SA)=Sof(H2SB)=Sof(Cl1T)=Sof(Cl2T)=0.5*FVAR(3)
 Sof(Cl1U)=Sof(Cl3U)=Sof(C3S)=Sof(H3SA)=Sof(H3SB)=0.5*FVAR(4)
6.a Ternary CH refined with riding coordinates:
 C9(H9), C1S(H1S)
6.b Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), C14(H14A,H14B), C15(H15A,H15B), C16(H16A,H16B), C2S(H2SA,H2SB),
 C3S(H3SA,H3SB)
6.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C1(H1A), C2(H2), C3(H3), C4(H4), C5(H5), C17(H17), C19(H19), C20(H20),
  C21(H21), C22(H22), C23(H23), C25(H25), C26(H26), C27(H27), C28(H28), C29(H29)
6.d Idealised Me refined as rotating group:
 C11(H11A,H11B,H11C)
;
_shelx_res_checksum              30879
_shelx_hkl_checksum              63777
_olex2_submission_special_instructions 'No special instructions were received'