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_4032853
_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         'C14 H18 F3 N O2'
_chemical_formula_sum            'C14 H18 F3 N O2'
_chemical_formula_weight         289.29
_space_group_crystal_system      trigonal
_space_group_IT_number           146
_space_group_name_Hall           'R 3'
_space_group_name_H-M_alt        'R 3'
_symmetry_space_group_name_Hall  'R 3'
_symmetry_space_group_name_H-M   'R 3 :H'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2016-05-26
_audit_creation_method
;
Olex2 1.2
(compiled Feb 16 2016 13:09:46 for OlexSys, GUI svn.r5155)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            18
_cell_length_a                   27.2782(5)
_cell_length_b                   27.2782(5)
_cell_length_c                   10.61163(18)
_cell_measurement_reflns_used    8501
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      75.1780
_cell_measurement_theta_min      4.5240
_cell_volume                     6838.2(2)
_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)'
_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 0.999
_diffrn_measured_fraction_theta_max 0.986
_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    -82.00  22.00   1.00    1.00    --  -41.80  97.00  15.00  104
  2  \w     -1.00  82.00   1.00    1.00    --   41.80 -97.00 -92.00   83
  3  \w    101.00 178.00   1.00    5.00    --  109.13  97.00  15.00   77
  4  \w     28.00 110.00   1.00    5.00    --  109.13 -97.00 -92.00   82
  5  \w    -96.00  -2.00   1.00    1.00    --  -41.80 125.00 150.00   94
  6  \w    -66.00  32.00   1.00    1.00    --  -41.80  38.00 150.00   98
  7  \w    -32.00  66.00   1.00    1.00    --   41.80 -38.00-180.00   98
  8  \w     94.00 178.00   1.00    5.00    --  109.13 125.00 -30.00   84
  9  \w     94.00 178.00   1.00    5.00    --  109.13 125.00-120.00   84
 10  \w     26.00 109.00   1.00    5.00    --  109.13 -94.00 150.00   83
 11  \w     26.00 109.00   1.00    5.00    --  109.13 -94.00 -30.00   83
 12  \w     81.00 178.00   1.00    5.00    --  109.13  30.00-180.00   97
 13  \w     26.00 109.00   1.00    5.00    --  109.13 -94.00  60.00   83
 14  \w     14.00 115.00   1.00    1.00    --   41.80  57.00 120.00  101
 15  \w      9.00 118.00   1.00    1.00    --   41.80  77.00-150.00  109
 16  \w     14.00 115.00   1.00    1.00    --   41.80  57.00  60.00  101
 17  \w     14.00 115.00   1.00    1.00    --   41.80  57.00 -30.00  101
 18  \w     81.00 178.00   1.00    5.00    --  109.13  30.00  90.00   97
;
_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      -0.0342960000
_diffrn_orient_matrix_UB_12      0.0245138000
_diffrn_orient_matrix_UB_13      0.0615807000
_diffrn_orient_matrix_UB_21      -0.0529486333
_diffrn_orient_matrix_UB_22      -0.0594257667
_diffrn_orient_matrix_UB_23      0.0010993333
_diffrn_orient_matrix_UB_31      0.0165057000
_diffrn_orient_matrix_UB_32      -0.0109761000
_diffrn_orient_matrix_UB_33      0.1314279000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0707
_diffrn_reflns_av_unetI/netI     0.0495
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.986
_diffrn_reflns_limit_h_max       34
_diffrn_reflns_limit_h_min       -32
_diffrn_reflns_limit_k_max       34
_diffrn_reflns_limit_k_min       -33
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -10
_diffrn_reflns_number            21663
_diffrn_reflns_point_group_measured_fraction_full 0.847
_diffrn_reflns_point_group_measured_fraction_max 0.822
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.595
_diffrn_reflns_theta_min         3.240
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.933
_exptl_absorpt_correction_T_max  0.994
_exptl_absorpt_correction_T_min  0.982
_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    1.264
_exptl_crystal_description       'rect. Prism'
_exptl_crystal_F_000             2736
_exptl_crystal_size_max          0.324
_exptl_crystal_size_mid          0.151
_exptl_crystal_size_min          0.084
_refine_diff_density_max         0.572
_refine_diff_density_min         -0.346
_refine_diff_density_rms         0.072
_refine_ls_abs_structure_details
;
 Flack x determined using 1491 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.15(15)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.064
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     386
_refine_ls_number_reflns         5209
_refine_ls_number_restraints     330
_refine_ls_restrained_S_all      1.088
_refine_ls_R_factor_all          0.0911
_refine_ls_R_factor_gt           0.0826
_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^)+(0.1298P)^2^+18.1884P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2245
_refine_ls_wR_factor_ref         0.2364
_reflns_Friedel_coverage         0.667
_reflns_Friedel_fraction_full    0.695
_reflns_Friedel_fraction_max     0.658
_reflns_number_gt                4449
_reflns_number_total             5209
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo7b01241_si_001.cif
_cod_data_source_block           mdh023_sqd
_cod_depositor_comments
'Adding full bibliography for 4032851--4032855.cif.'
_cod_original_cell_volume        6838.2(3)
_cod_database_code               4032853
_shelxl_version_number           2013-4
_chemical_oxdiff_formula         'C14 H18 F3 N O2'
_chemical_oxdiff_usercomment     JD530
_reflns_odcompleteness_completeness 100.00
_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. Restrained distances
 C23A-C24A
 1.39 with sigma of 0.01
 C24A-C25A
 1.39 with sigma of 0.01
 C25A-C26A
 1.39 with sigma of 0.01
 C26A-C27A
 1.39 with sigma of 0.01
 C27A-C28A
 1.39 with sigma of 0.01
 C28A-C23A
 1.39 with sigma of 0.01
 C23B-C24B
 1.39 with sigma of 0.01
 C24B-C25B
 1.39 with sigma of 0.01
 C25B-C26B
 1.39 with sigma of 0.01
 C26B-C27B
 1.39 with sigma of 0.01
 C27B-C28B
 1.39 with sigma of 0.01
 C28B-C23B
 1.39 with sigma of 0.01
 O4-C23A
 1.388 with sigma of 0.01
 O4-C23B
 1.388 with sigma of 0.01
 C9-C10
 1.39 with sigma of 0.01
 C10-C11
 1.39 with sigma of 0.01
 C11-C12
 1.39 with sigma of 0.01
 C12-C13
 1.39 with sigma of 0.01
 C13-C14
 1.39 with sigma of 0.01
 C14-C9
 1.39 with sigma of 0.01
 C23A-C25A
 2.38 with sigma of 0.02
 C24A-C26A
 2.4 with sigma of 0.02
 C25A-C27A
 2.38 with sigma of 0.02
 C26A-C28A
 2.4 with sigma of 0.02
 C27A-C23A
 2.38 with sigma of 0.02
 C28A-C24A
 2.4 with sigma of 0.02
 C23B-C25B
 2.38 with sigma of 0.02
 C24B-C26B
 2.4 with sigma of 0.02
 C25B-C27B
 2.38 with sigma of 0.02
 C26B-C28B
 2.4 with sigma of 0.02
 C27B-C23B
 2.38 with sigma of 0.02
 C28B-C24B
 2.4 with sigma of 0.02
 C9-C11
 2.38 with sigma of 0.02
 C10-C12
 2.4 with sigma of 0.02
 C11-C13
 2.38 with sigma of 0.02
 C12-C14
 2.4 with sigma of 0.02
 C13-C9
 2.38 with sigma of 0.02
 C14-C10
 2.4 with sigma of 0.02
 O4-C28A
 2.395 with sigma of 0.02
 O4-C28B
 2.395 with sigma of 0.02
 O4-C24A
 2.393 with sigma of 0.02
 O4-C24B
 2.393 with sigma of 0.02
 C17-C23A = C17-C23B
 2.39 with sigma of 0.02
3. Restrained planarity
 C23A, C24A, C25A, C26A, C27A, C28A
 with sigma of 0.01
 C23B, C24B, C25B, C26B, C27B, C28B
 with sigma of 0.01
 C9, C10, C11, C12, C13, C14
 with sigma of 0.01
4. Uiso/Uaniso restraints and constraints
All non-hydrogen atoms restrained to be isotropic: with sigma of 0.01 and sigma
for terminal atoms of 0.02
Uanis(C23A) = Uanis(C23B)
Uanis(C24A) = Uanis(C24B)
Uanis(C25A) = Uanis(C25B)
Uanis(C26A) = Uanis(C26B)
Uanis(C27A) = Uanis(C27B)
Uanis(C28A) = Uanis(C28B)
5. Others
 Sof(C24B)=Sof(H24B)=Sof(C25B)=Sof(H25B)=Sof(C26B)=Sof(H26B)=Sof(C27B)=
 Sof(H27B)=Sof(C28B)=Sof(H28B)=Sof(C23B)=1-FVAR(1)
 Sof(C23A)=Sof(C24A)=Sof(H24A)=Sof(C25A)=Sof(H25A)=Sof(C26A)=Sof(H26A)=
 Sof(C27A)=Sof(H27A)=Sof(C28A)=Sof(H28A)=FVAR(1)
6.a Ternary CH refined with riding coordinates:
 C1(H1), C3(H3A), C4(H4), C6(H6), C15(H15), C17(H17), C18(H18), C20(H20)
6.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C16(H16A,H16B)
6.c Aromatic/amide H refined with riding coordinates:
 C10(H10), C11(H11), C12(H12), C13(H13), C14(H14), C24A(H24A), C25A(H25A),
 C26A(H26A), C27A(H27A), C28A(H28A), C24B(H24B), C25B(H25B), C26B(H26B),
 C27B(H27B), C28B(H28B)
6.d Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C), C8(H8A,H8B,H8C), C21(H21A,H21B,H21C), C22(H22A,H22B,H22C)
6.e Idealised tetrahedral OH refined as rotating group:
 O1(H1A), O3(H3)
;
_shelx_res_checksum              49293
_shelx_hkl_checksum              64271
_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 1.474
_oxdiff_exptl_absorpt_empirical_full_min 0.649