Asymmetric Synthesis of 3,4-Disubstituted 2-(Trifluoromethyl)pyrrolidines through Rearrangement of Chiral 2-(2,2,2-Trifluoro-1-hydroxyethyl)azetidines.
Dolfen, Jeroen; Boydas, Esma Birsen; Van Speybroeck, Veronique; Catak, Saron; Van Hecke, Kristof; D'hooghe, Matthias; The Journal of organic chemistry 82 (2017) 10092–10109; doi:10.1021/acs.joc.7b01241

data_4032852
_publ_section_title
;
 Asymmetric Synthesis of 3,4-Disubstituted 2-(Trifluoromethyl)pyrrolidines
 through Rearrangement of Chiral
 2-(2,2,2-Trifluoro-1-hydroxyethyl)azetidines.
;
_journal_issue                   19
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              10092
_journal_page_last               10109
_journal_paper_doi               10.1021/acs.joc.7b01241
_journal_volume                  82
_journal_year                    2017
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C15 H18 F3 N O3'
_chemical_formula_sum            'C15 H18 F3 N O3'
_chemical_formula_weight         317.30
_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
_audit_creation_date             2016-12-14
_audit_creation_method
;
Olex2 1.2
(compiled Nov 22 2016 11:51:51 for OlexSys, GUI svn.r5269)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   5.73470(7)
_cell_length_b                   12.45975(15)
_cell_length_c                   20.4676(3)
_cell_measurement_reflns_used    16759
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      75.3180
_cell_measurement_theta_min      4.1240
_cell_volume                     1462.47(3)
_computing_cell_refinement       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.0(1)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.4839
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.9994
_diffrn_measured_fraction_theta_max 0.9925
_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    -70.00  30.00   1.00    1.00    --  -41.80  55.00 125.00  100
  2  \w     98.00 178.00   1.00    2.00    --  109.13  84.00 -13.00   80
  3  \w     81.00 178.00   1.00    2.00    --  109.13  55.00 125.00   97
  4  \w    -96.00  -2.00   1.00    1.00    --  -41.80 125.00-180.00   94
  5  \w     23.00  98.00   1.00    1.00    --   41.80-125.00 -30.00   75
  6  \w     23.00  98.00   1.00    1.00    --   41.80-125.00  90.00   75
  7  \w     80.00 178.00   1.00    2.00    --  109.13  61.00  90.00   98
  8  \w     83.00 178.00   1.00    2.00    --  109.13  45.00  30.00   95
  9  \w     28.00 144.00   1.00    2.00    --  109.13 -85.00 120.00  116
 10  \w   -114.00 -14.00   1.00    1.00    --  -41.80 -57.00  90.00  100
 11  \w   -114.00 -14.00   1.00    1.00    --  -41.80 -57.00-180.00  100
 12  \w   -118.00  -9.00   1.00    1.00    --  -41.80 -77.00   0.00  109
 13  \w     94.00 178.00   1.00    2.00    --  109.13 125.00 150.00   84
 14  \w     83.00 178.00   1.00    2.00    --  109.13  45.00 -60.00   95
 15  \w     26.00 109.00   1.00    2.00    --  109.13 -94.00 -60.00   83
 16  \w     80.00 178.00   1.00    2.00    --  109.13  61.00 -30.00   98
 17  \w     83.00 178.00   1.00    2.00    --  109.13  45.00-180.00   95
 18  \w     81.00 178.00   1.00    2.00    --  109.13  30.00-120.00   97
 19  \w    -66.00  32.00   1.00    1.00    --  -41.80  38.00  30.00   98
 20  \w   -118.00  -9.00   1.00    1.00    --  -41.80 -77.00  90.00  109
 21  \w   -114.00 -14.00   1.00    1.00    --  -41.80 -57.00-120.00  100
 22  \w     77.00 178.00   1.00    2.00    --  109.13  77.00-120.00  101
 23  \w     83.00 178.00   1.00    2.00    --  109.13  45.00  60.00   95
 24  \w     77.00 178.00   1.00    2.00    --  109.13  77.00 120.00  101
 25  \w     80.00 178.00   1.00    2.00    --  109.13  61.00-180.00   98
 26  \w     80.00 178.00   1.00    2.00    --  109.13  61.00 -60.00   98
 27  \w     26.00 109.00   1.00    2.00    --  109.13 -94.00  90.00   83
 28  \w   -118.00  -9.00   1.00    1.00    --  -41.80 -77.00-150.00  109
 29  \w     17.00  58.00   1.00    1.00    --   41.80  38.00 -60.00   41
 30  \w      9.00 118.00   1.00    1.00    --   41.80  77.00   0.00  109
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0658324000
_diffrn_orient_matrix_UB_12      -0.1098382000
_diffrn_orient_matrix_UB_13      0.0292250000
_diffrn_orient_matrix_UB_21      -0.2267855000
_diffrn_orient_matrix_UB_22      0.0000801000
_diffrn_orient_matrix_UB_23      0.0403698000
_diffrn_orient_matrix_UB_31      -0.1280017000
_diffrn_orient_matrix_UB_32      -0.0567692000
_diffrn_orient_matrix_UB_33      -0.0564179000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0502
_diffrn_reflns_av_unetI/netI     0.0200
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -25
_diffrn_reflns_number            25106
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.991
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.590
_diffrn_reflns_theta_min         4.154
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.077
_exptl_absorpt_correction_T_max  0.968
_exptl_absorpt_correction_T_min  0.914
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
Numerical absorption correction based on gaussian integration over
            a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.441
_exptl_crystal_description       block
_exptl_crystal_F_000             664
_exptl_crystal_size_max          0.259
_exptl_crystal_size_mid          0.161
_exptl_crystal_size_min          0.106
_refine_diff_density_max         0.189
_refine_diff_density_min         -0.270
_refine_diff_density_rms         0.053
_refine_ls_abs_structure_details
;
 Flack x determined using 1185 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.03(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.063
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     202
_refine_ls_number_reflns         3009
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.063
_refine_ls_R_factor_all          0.0376
_refine_ls_R_factor_gt           0.0369
_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^)+(0.0695P)^2^+0.2394P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0979
_refine_ls_wR_factor_ref         0.0989
_reflns_Friedel_coverage         0.699
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.987
_reflns_number_gt                2920
_reflns_number_total             3009
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo7b01241_si_001.cif
_cod_data_source_block           mdh034b
_cod_depositor_comments
'Adding full bibliography for 4032851--4032855.cif.'
_cod_database_code               4032852
_shelxl_version_number           2013-4
_chemical_oxdiff_formula         'C15 H18 F3 N O3'
_reflns_odcompleteness_completeness 99.94
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C1(H1), C3(H3A), C4(H4), C6(H6)
2.b Secondary CH2 refined with riding coordinates:
 C9(H9A,H9B)
2.c Aromatic/amide H refined with riding coordinates:
 C11(H11), C12(H12), C13(H13), C14(H14), C15(H15)
2.d Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C), C8(H8A,H8B,H8C)
2.e Idealised tetrahedral OH refined as rotating group:
 O3(H3)
;
_shelx_res_checksum              36122
_shelx_hkl_checksum              51068
_olex2_exptl_crystal_mounting_method 'mounted on a nylon loop'
_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
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.442
_oxdiff_exptl_absorpt_empirical_full_min 0.736