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_4032854
_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      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2016-05-17
_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                 109.932(7)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.9857(6)
_cell_length_b                   14.0575(7)
_cell_length_c                   11.0980(6)
_cell_measurement_reflns_used    5850
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      75.2480
_cell_measurement_theta_min      4.2130
_cell_volume                     1464.55(15)
_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    'ShelXT (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 0.976
_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    -73.00  32.00   1.00    1.00    --  -41.68  72.00 -97.00  105
  2  \w   -116.00 -10.00   1.00    1.00    --  -41.68 -72.00 132.00  106
  3  \w     35.00 141.00   1.00    4.00    --  109.13 -72.00 132.00  106
  4  \w     78.00 178.00   1.00    4.00    --  109.13  72.00 -97.00  100
  5  \w      1.00  83.00   1.00    1.00    --   41.68 -99.00 -30.00   82
  6  \w     23.00  98.00   1.00    1.00    --   41.68-125.00  60.00   75
  7  \w     10.00 116.00   1.00    1.00    --   41.68  72.00 -97.00  106
  8  \w     36.00 121.00   1.00    4.00    --  109.13-125.00   0.00   85
  9  \w     36.00 135.00   1.00    4.00    --  109.13 -45.00 -30.00   99
 10  \w     36.00 121.00   1.00    4.00    --  109.13-125.00 150.00   85
 11  \w     36.00 121.00   1.00    4.00    --  109.13-125.00 -60.00   85
 12  \w     26.00 109.00   1.00    4.00    --  109.13 -94.00 -60.00   83
 13  \w     94.00 178.00   1.00    4.00    --  109.13 125.00-180.00   84
 14  \w   -116.00 -17.00   1.00    1.00    --  -41.68 -38.00-180.00   99
 15  \w   -118.00  -9.00   1.00    1.00    --  -41.68 -77.00  60.00  109
 16  \w    -70.00  31.00   1.00    1.00    --  -41.68  57.00 150.00  101
 17  \w     17.00 116.00   1.00    1.00    --   41.68  38.00  30.00   99
 18  \w     56.00 162.00   1.00    4.00    --  109.13  15.00 150.00  106
;
_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      -0.0863956000
_diffrn_orient_matrix_UB_12      0.0826457000
_diffrn_orient_matrix_UB_13      -0.0812408000
_diffrn_orient_matrix_UB_21      -0.0538132000
_diffrn_orient_matrix_UB_22      0.0272139000
_diffrn_orient_matrix_UB_23      0.1100018000
_diffrn_orient_matrix_UB_31      0.1287187000
_diffrn_orient_matrix_UB_32      0.0666976000
_diffrn_orient_matrix_UB_33      0.0555159000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0569
_diffrn_reflns_av_unetI/netI     0.0520
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.976
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            14048
_diffrn_reflns_point_group_measured_fraction_full 0.834
_diffrn_reflns_point_group_measured_fraction_max 0.799
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.517
_diffrn_reflns_theta_min         4.238
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.968
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.61935
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
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    1.312
_exptl_crystal_description       block
_exptl_crystal_F_000             608
_exptl_crystal_size_max          0.294
_exptl_crystal_size_mid          0.177
_exptl_crystal_size_min          0.109
_refine_diff_density_max         0.276
_refine_diff_density_min         -0.282
_refine_diff_density_rms         0.058
_refine_ls_abs_structure_details
;
 Flack x determined using 1338 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.08(12)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.050
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     365
_refine_ls_number_reflns         4861
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.050
_refine_ls_R_factor_all          0.0619
_refine_ls_R_factor_gt           0.0524
_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^)+(0.0980P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1372
_refine_ls_wR_factor_ref         0.1522
_reflns_Friedel_coverage         0.571
_reflns_Friedel_fraction_full    0.654
_reflns_Friedel_fraction_max     0.607
_reflns_number_gt                4221
_reflns_number_total             4861
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo7b01241_si_001.cif
_cod_data_source_block           mdh022
_cod_depositor_comments
'Adding full bibliography for 4032851--4032855.cif.'
_cod_database_code               4032854
_shelxl_version_number           2013-4
_chemical_oxdiff_formula         'C14 H18 F3 N O2'
_reflns_odcompleteness_completeness 99.93
_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(H1A), C3(H3A), C4(H4), C15(H15), C17(H17), C18(H18)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C6(H6A,H6B), C7(H7A,H7B), C16(H16A,H16B), C20(H20A,H20B),
 C21(H21A,H21B)
2.c Aromatic/amide H refined with riding coordinates:
 C10(H10), C11(H11), C12(H12), C13(H13), C14(H14), C24(H24), C25(H25),
 C26(H26), C27(H27), C28(H28)
2.d Idealised Me refined as rotating group:
 C8(H8A,H8B,H8C), C22(H22A,H22B,H22C)
2.e Idealised tetrahedral OH refined as rotating group:
 O1(H1), O3(H3)
;
_shelx_res_checksum              41766
_shelx_hkl_checksum              51594
_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 1.736
_oxdiff_exptl_absorpt_empirical_full_min 0.650