The Synthesis of Methyl-Substituted Spirocyclic Piperidine-Azetidine (2,7-Diazaspiro[3.5]nonane) and Spirocyclic Piperidine-Pyrrolidine (2,8-Diazaspiro[4.5]decane) Ring Systems.
Smith, Aaron C.; Cabral, Shawn; Kung, Daniel W.; Rose, Colin R.; Southers, James A.; García-Irizarry, Carmen N; Damon, David B.; Bagley, Scott W.; Griffith, David A.; The Journal of organic chemistry 81 (2016) 3509–3519; doi:10.1021/acs.joc.5b02890

data_4036593
_publ_section_title
;
 The Synthesis of Methyl-Substituted Spirocyclic Piperidine-Azetidine
 (2,7-Diazaspiro[3.5]nonane) and Spirocyclic Piperidine-Pyrrolidine
 (2,8-Diazaspiro[4.5]decane) Ring Systems.
;
_journal_issue                   9
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              3509
_journal_page_last               3519
_journal_paper_doi               10.1021/acs.joc.5b02890
_journal_volume                  81
_journal_year                    2016
_chemical_formula_sum            'C139 H188 N8 O43'
_chemical_formula_weight         2658.96
_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   mixed
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            1
_cell_length_a                   19.8195(7)
_cell_length_b                   22.8286(8)
_cell_length_c                   7.8633(3)
_cell_measurement_reflns_used    9981
_cell_measurement_temperature    296(2)
_cell_measurement_theta_max      66.05
_cell_measurement_theta_min      2.97
_cell_volume                     3557.8(2)
_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      296(2)
_diffrn_measured_fraction_theta_full 0.961
_diffrn_measured_fraction_theta_max 0.958
_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  0.0548
_diffrn_reflns_av_unetI/netI     0.0305
_diffrn_reflns_Laue_measured_fraction_full 0.961
_diffrn_reflns_Laue_measured_fraction_max 0.958
_diffrn_reflns_limit_h_max       23
_diffrn_reflns_limit_h_min       -23
_diffrn_reflns_limit_k_max       27
_diffrn_reflns_limit_k_min       -27
_diffrn_reflns_limit_l_max       7
_diffrn_reflns_limit_l_min       -8
_diffrn_reflns_number            41080
_diffrn_reflns_point_group_measured_fraction_full 0.958
_diffrn_reflns_point_group_measured_fraction_max 0.955
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         67.810
_diffrn_reflns_theta_min         2.953
_diffrn_source                   'rotating anode'
_exptl_absorpt_coefficient_mu    0.761
_exptl_absorpt_correction_T_max  1
_exptl_absorpt_correction_T_min  0.8303
_exptl_absorpt_correction_type   empirical
_exptl_absorpt_process_details   sadabs
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.241
_exptl_crystal_description       FLAT
_exptl_crystal_F_000             1422
_exptl_crystal_size_max          0.320
_exptl_crystal_size_mid          0.040
_exptl_crystal_size_min          0.020
_refine_diff_density_max         0.415
_refine_diff_density_min         -0.242
_refine_diff_density_rms         0.039
_refine_ls_abs_structure_details
; 
 Flack x determined using 2254 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259). 
;
_refine_ls_abs_structure_Flack   -0.03(9)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.040
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     463
_refine_ls_number_reflns         6184
_refine_ls_number_restraints     17
_refine_ls_restrained_S_all      1.044
_refine_ls_R_factor_all          0.0530
_refine_ls_R_factor_gt           0.0475
_refine_ls_shift/su_max          1.473
_refine_ls_shift/su_mean         0.032
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0750P)^2^+0.9722P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1245
_refine_ls_wR_factor_ref         0.1292
_reflns_Friedel_coverage         0.759
_reflns_Friedel_fraction_full    0.955
_reflns_Friedel_fraction_max     0.951
_reflns_number_gt                5617
_reflns_number_total             6184
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo5b02890_si_002.cif
_cod_data_source_block           Z625
_cod_database_code               4036593
_shelx_estimated_absorpt_t_min   0.793
_shelx_estimated_absorpt_t_max   0.985
_shelx_res_checksum              99195
_shelx_hkl_checksum              5939