Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin.
Saavedra, Diana I.; Rencher, Benjamin D.; Kwon, Doo-Hyun; Smith, Stacey J.; Ess, Daniel H.; Andrus, Merritt B.; The Journal of organic chemistry 83 (2018) 2018–2026; doi:10.1021/acs.joc.7b02957

data_4033465
_publ_section_title
;
 Synthesis and Computational Studies Demonstrate the Utility of an
 Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene
 Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin.
;
_journal_issue                   4
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              2018
_journal_page_last               2026
_journal_paper_doi               10.1021/acs.joc.7b02957
_journal_volume                  83
_journal_year                    2018
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C22 H20 O7, C H Cl3'
_chemical_formula_sum            'C23 H21 Cl3 O7'
_chemical_formula_weight         515.75
_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'
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.0365(7)
_cell_length_b                   15.2618(16)
_cell_length_c                   20.961(2)
_cell_measurement_reflns_used    5612
_cell_measurement_temperature    119(2)
_cell_measurement_theta_max      68.11
_cell_measurement_theta_min      3.58
_cell_volume                     2251.0(4)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_structure_solution    'SHELXS-97 (Sheldrick 2008)'
_diffrn_ambient_temperature      119(2)
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.990
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0783
_diffrn_reflns_av_unetI/netI     0.0570
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.990
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -24
_diffrn_reflns_number            21020
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         68.874
_diffrn_reflns_theta_min         3.582
_diffrn_source                   'Bruker-Nonius FR591 Cu rotating anode'
_exptl_absorpt_coefficient_mu    4.075
_exptl_absorpt_correction_T_max  0.7531
_exptl_absorpt_correction_T_min  0.5580
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Sheldrick, 2009)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.522
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             1064
_exptl_crystal_size_max          0.200
_exptl_crystal_size_mid          0.140
_exptl_crystal_size_min          0.060
_refine_diff_density_max         0.208
_refine_diff_density_min         -0.232
_refine_diff_density_rms         0.046
_refine_ls_abs_structure_details
; 
 Flack x determined using 1493 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259). 
;
_refine_ls_abs_structure_Flack   -0.005(9)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.008
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     314
_refine_ls_number_reflns         4145
_refine_ls_number_restraints     312
_refine_ls_restrained_S_all      0.985
_refine_ls_R_factor_all          0.0358
_refine_ls_R_factor_gt           0.0316
_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^)+(0.0248P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0704
_refine_ls_wR_factor_ref         0.0720
_reflns_Friedel_coverage         0.733
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.985
_reflns_number_gt                3791
_reflns_number_total             4145
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo7b02957_si_002.cif
_cod_data_source_block           17003
_cod_depositor_comments
'Adding full bibliography for 4033464--4033465.cif.'
_cod_database_code               4033465
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_min   0.496
_shelx_estimated_absorpt_t_max   0.792
_shelx_res_checksum              16522
_shelx_hkl_checksum              6996