Regio- and Enantioselective Bromocyclization of Difluoroalkenes as a Strategy to Access Tetrasubstituted Difluoromethylene-Containing Stereocenters.
Miller, Edward; Kim, Suhong; Gibson, Katarina; Derrick, Jeffrey S.; Toste, F. Dean; Journal of the American Chemical Society  (2020) –; doi:10.1021/jacs.0c02331

data_4134874
_publ_section_title
;
 Regio- and Enantioselective Bromocyclization of Difluoroalkenes as a
 Strategy to Access Tetrasubstituted Difluoromethylene-Containing
 Stereocenters.
;
_journal_name_full               'Journal of the American Chemical Society'
_journal_paper_doi               10.1021/jacs.0c02331
_journal_year                    2020
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C14 H8 Br Cl F2 N O1.77, C6 H12'
_chemical_formula_sum            'C14 H12 Br Cl F2 N4 O3'
_chemical_formula_weight         456.04
_space_group_crystal_system      hexagonal
_space_group_IT_number           171
_space_group_name_Hall           'P 62'
_space_group_name_H-M_alt        'P 62'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2020-02-28
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            6
_cell_length_a                   18.0955(2)
_cell_length_b                   18.0955(2)
_cell_length_c                   10.63070(10)
_cell_measurement_reflns_used    89123
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      78.9320
_cell_measurement_theta_min      4.1890
_cell_volume                     3014.63(5)
_computing_cell_refinement       'CrysAlisPro 1.171.40.54a (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.54a (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.54a (Rigaku OD, 2019)'
_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_temperature      100(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.8140
_diffrn_detector_type            'Pilatus 200K'
_diffrn_measured_fraction_theta_full 0.993
_diffrn_measured_fraction_theta_max 0.981
_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     80.00 127.00   0.50    1.00    --   53.13 165.00-104.00   94
  2  \w     89.00 115.00   0.50    2.00    --  106.00 165.00-104.00   52
  3  \w     46.00  72.00   0.50    1.00    --   64.00  71.00  -7.89   52
  4  \w     42.00  68.00   0.50    1.00    --   60.00  72.00  15.79   52
  5  \w     38.00  64.00   0.50    1.00    --   56.00  72.00 -11.43   52
  6  \w     34.00  60.00   0.50    1.00    --   52.00  71.00 -58.15   52
  7  \w     42.00  72.00   0.50    1.00    --   60.00  71.00 -37.81   60
  8  \w     38.00  81.00   0.50    1.00    --   52.00  70.00-114.58   86
  9  \w     38.00  64.00   0.50    1.00    --   56.00  71.00-171.30   52
 10  \w     39.00  64.00   0.50    1.00    --   56.00  71.00-147.12   50
 11  \w     38.00  78.00   0.50    1.00    --   56.00  72.00 -88.12   80
 12  \w     42.00  74.00   0.50    1.00    --   60.00  70.00-140.30   64
 13  \w     19.00  44.00   0.50    1.00    --   36.00  74.00 -81.47   50
 14  \w      7.00  32.00   0.50    1.00    --   32.00  86.00-136.81   50
 15  \w     16.00  41.00   0.50    1.00    --   36.00  76.00-178.94   50
 16  \w     39.00  64.00   0.50    2.00    --  106.00 -61.00-150.00   50
 17  \w     36.00 102.00   0.50    2.00    --  106.00 -77.00-150.00  132
 18  \w     47.00  99.00   0.50    2.00    --  106.00 -94.00 -60.00  104
 19  \w     64.00 105.00   0.50    2.00    --  106.00-116.00  19.00   82
 20  \w     55.00 109.00   0.50    2.00    --  106.00-111.00 -30.00  108
 21  \w     55.00  80.00   0.50    1.00    --   53.13-165.00-127.00   50
 22  \w     87.00 132.00   0.50    2.00    --  106.00-165.00-127.00   90
 23  \w     37.00 105.00   0.50    2.00    --  106.00-111.00-150.00  136
 24  \w     36.00 106.00   0.50    2.00    --  106.00-111.00 -90.00  140
 25  \w     40.00 101.00   0.50    2.00    --  106.00-111.00  30.00  122
 26  \w     68.00 109.00   0.50    2.00    --  106.00-111.00 120.00   82
 27  \w     28.00  53.00   0.50    1.00    --   53.13-116.00  19.00   50
 28  \w     36.00 106.00   0.50    2.00    --  106.00 -94.00 120.00  140
 29  \w     36.00  68.00   0.50    2.00    --  106.00 -61.00 120.00   64
 30  \w     34.00 102.00   0.50    2.00    --  106.00 -77.00  60.00  136
 31  \w     34.00  93.00   0.50    2.00    --  106.00 -77.00  30.00  118
 32  \w     36.00  67.00   0.50    2.00    --  106.00 -61.00  30.00   62
 33  \w     39.00  65.00   0.50    1.00    --   56.00  72.00  91.14   52
 34  \w     48.00  74.00   0.50    1.00    --   64.00  71.00 118.96   52
 35  \w     81.00 106.00   0.50    1.00    --   53.13 116.00 108.00   50
 36  \w    114.00 140.00   0.50    2.00    --  106.00 116.00 108.00   52
 37  \w     39.00  65.00   0.50    1.00    --   56.00  72.00 153.59   52
 38  \w     42.00  68.00   0.50    1.00    --   60.00  72.00 159.92   52
 39  \w     15.00  44.00   0.50    1.00    --   36.00  78.00 103.72   58
 40  \w     42.00  68.00   0.50    1.00    --   60.00  72.00  41.26   52
 41  \w     42.00  67.00   0.50    1.00    --   60.00  72.00  61.44   50
 42  \w      9.00  34.00   0.50    1.00    --   32.00  83.00  61.15   50
 43  \w     -8.00  17.00   0.50    1.00    --   20.00  94.00 168.40   50
 44  \w    -66.00 -40.00   0.50    1.00    --    4.00 164.00  65.98   52
 45  \w    -71.00 -39.00   0.50    1.00    --   -4.00 160.00  17.78   64
 46  \w    -71.00 -23.00   0.50    1.00    --  -53.26 116.00 108.00   96
 47  \w    -91.00 -66.00   0.50    2.00    -- -100.00 116.00 108.00   50
 48  \w   -109.00 -63.00   0.50    2.00    -- -100.00 109.00  18.27   92
 49  \w    -63.00 -24.00   0.50    2.00    -- -100.00 104.00 -29.46   78
 50  \w    -66.00 -27.00   0.50    2.00    -- -100.00 109.00-138.52   78
 51  \w    -73.00 -30.00   0.50    2.00    -- -100.00  61.00 -30.00   86
 52  \w    -99.00 -22.00   0.50    1.00    --  -53.26 125.00 -90.00  154
 53  \w    -76.00 -45.00   0.50    1.00    --    0.00 171.00-160.70   62
 54  \w    -72.00 -41.00   0.50    1.00    --    0.00 167.00 -99.36   62
 55  \w   -106.00 -81.00   0.50    1.00    --  -53.26 165.00-104.00   50
 56  \w   -114.00 -89.00   0.50    2.00    -- -100.00 165.00-104.00   50
 57  \w   -108.00 -82.00   0.50    2.00    -- -100.00 104.00 -29.46   52
 58  \w   -109.00 -80.00   0.50    2.00    -- -100.00 109.00-138.52   58
 59  \w    -68.00 -38.00   0.50    1.00    --  -53.26 -70.00  76.16   60
 60  \w    -77.00 -52.00   0.50    1.00    --  -68.00 -66.00  11.84   50
 61  \w    -79.00 -53.00   0.50    1.00    --  -68.00 -66.00  50.22   52
 62  \w    -76.00 -50.00   0.50    1.00    --  -68.00 -70.00 113.30   52
 63  \w    -82.00 -56.00   0.50    1.00    --  -72.00 -65.00 166.79   52
 64  \w    -85.00 -57.00   0.50    1.00    --  -72.00 -65.00 134.49   56
 65  \w    -86.00 -56.00   0.50    1.00    --  -72.00 -66.00 149.42   60
 66  \w    -86.00 -60.00   0.50    1.00    --  -76.00 -65.00  94.97   52
 67  \w    -85.00 -59.00   0.50    1.00    --  -76.00 -69.00  76.04   52
 68  \w    -87.00 -61.00   0.50    1.00    --  -76.00 -64.00 125.87   52
 69  \w    -88.00 -63.00   0.50    2.00    --  -80.00 -69.00 113.93   50
 70  \w    -91.00 -66.00   0.50    2.00    --  -84.00 -70.00 164.82   50
 71  \w   -102.00 -72.00   0.50    2.00    --  -88.00 -66.00 132.42   60
 72  \w    -95.00 -69.00   0.50    2.00    --  -84.00 -65.00  69.96   52
 73  \w    -84.00 -59.00   0.50    1.00    --  -76.00 -68.00  37.40   50
 74  \w    -89.00 -63.00   0.50    2.00    --  -80.00 -68.00 -17.42   52
 75  \w    -90.00 -54.00   0.50    1.00    --  -72.00 -70.00 -74.90   72
 76  \w    -78.00 -52.00   0.50    1.00    --  -68.00 -69.00-106.94   52
 77  \w    -75.00 -50.00   0.50    1.00    --  -68.00 -70.00-152.21   50
 78  \w    -44.00 -19.00   0.50    1.00    --  -36.00 -78.00 -87.91   50
 79  \w    -79.00 -54.00   0.50    1.00    --  -53.26-165.00-127.00   50
 80  \w   -106.00 -58.00   0.50    1.00    --  -76.00 -70.00-115.52   96
 81  \w    -88.00 -63.00   0.50    2.00    --  -80.00 -68.00 -78.82   50
 82  \w    -87.00 -62.00   0.50    2.00    --  -80.00 -70.00 -40.87   50
 83  \w    -89.00 -63.00   0.50    2.00    --  -80.00 -68.00  -6.48   52
 84  \w    -91.00 -66.00   0.50    2.00    --  -84.00 -70.00  13.46   50
 85  \w   -106.00 -70.00   0.50    2.00    --  -84.00 -63.00  30.42   72
 86  \w    -98.00 -72.00   0.50    2.00    --  -88.00 -67.00  -3.37   52
 87  \w    -98.00 -72.00   0.50    2.00    --  -88.00 -67.00  49.24   52
 88  \w   -101.00 -75.00   0.50    2.00    --  -88.00 -63.00  65.15   52
 89  \w    -99.00 -73.00   0.50    2.00    --  -88.00 -64.00  93.17   52
 90  \w   -103.00 -77.00   0.50    2.00    --  -96.00 -74.00  38.25   52
 91  \w   -107.00 -80.00   0.50    2.00    -- -100.00 -77.00  36.88   54
 92  \w   -108.00 -82.00   0.50    2.00    -- -100.00 -71.00 -23.20   52
 93  \w   -113.00 -86.00   0.50    2.00    -- -100.00 -65.00   0.22   54
 94  \w   -116.00 -67.00   0.50    2.00    --  -84.00 -69.00 -21.03   98
 95  \w    -94.00 -68.00   0.50    2.00    --  -84.00 -66.00 -93.89   52
 96  \w    -99.00 -60.00   0.50    1.00    --  -76.00 -67.00-136.36   78
 97  \w    -90.00 -64.00   0.50    2.00    --  -80.00 -66.00-167.28   52
 98  \w    -97.00 -71.00   0.50    2.00    --  -88.00 -70.00-177.45   52
 99  \w   -101.00 -75.00   0.50    2.00    --  -92.00 -68.00-162.25   52
100  \w   -107.00 -81.00   0.50    2.00    -- -100.00 -76.00-104.91   52
101  \w   -108.00 -81.00   0.50    2.00    -- -100.00 -77.00-120.00   54
102  \w   -109.00 -81.00   0.50    2.00    -- -100.00 -77.00-180.00   56
103  \w   -114.00 -80.00   0.50    2.00    -- -100.00 -76.00-130.53   68
104  \w   -124.00 -81.00   0.50    2.00    -- -100.00 -76.00 -69.88   86
105  \w   -108.00 -82.00   0.50    2.00    -- -100.00 -71.00 -59.30   52
106  \w   -133.00-106.00   0.50    2.00    --  -80.00 -70.00 -40.87   54
107  \w   -129.00 -82.00   0.50    2.00    -- -100.00 -70.00 -65.52   94
108  \w   -132.00 -83.00   0.50    2.00    -- -100.00 -70.00-167.94   98
109  \w   -140.00 -84.00   0.50    2.00    -- -100.00 -69.00-147.00  112
110  \w   -129.00-104.00   0.50    2.00    -- -100.00-165.00-127.00   50
111  \w   -166.00-115.00   0.50    2.00    -- -100.00 -77.00-120.00  102
112  \w   -145.00 -81.00   0.50    2.00    -- -100.00 -74.00 -96.42  128
113  \w   -147.00 -84.00   0.50    2.00    -- -100.00 -65.00 -20.65  126
114  \w   -133.00 -83.00   0.50    2.00    -- -100.00 -68.00  92.44  100
115  \w   -111.00 -80.00   0.50    2.00    -- -100.00 -77.00  93.88   62
116  \w   -110.00 -83.00   0.50    2.00    -- -100.00 -69.00 102.78   54
117  \w   -110.00 -80.00   0.50    2.00    -- -100.00 -76.00 157.17   60
118  \w   -108.00 -82.00   0.50    2.00    -- -100.00 -73.00 117.56   52
119  \w   -126.00 -84.00   0.50    2.00    -- -100.00 -65.00 116.83   84
120  \w   -140.00 -82.00   0.50    2.00    -- -100.00 -71.00  78.72  116
121  \w   -152.00 -80.00   0.50    2.00    -- -100.00 -77.00  60.00  144
122  \w   -143.00 -83.00   0.50    2.00    -- -100.00 -68.00  -5.55  120
123  \w   -153.00-127.00   0.50    2.00    -- -100.00 -71.00 -59.30   52
124  \w   -155.00-129.00   0.50    2.00    -- -100.00-116.00  19.00   52
125  \w   -159.00-122.00   0.50    2.00    -- -100.00 -77.00  36.88   74
126  \w   -168.00-121.00   0.50    2.00    -- -100.00 -65.00   0.22   94
127  \w   -164.00-138.00   0.50    2.00    -- -100.00 -76.00 -69.88   52
128  \w   -161.00 -82.00   0.50    2.00    --  -96.00 -62.00-109.77  158
129  \w   -160.00 -80.00   0.50    2.00    -- -100.00 -76.00-116.80  160
130  \w   -163.00 -80.00   0.50    2.00    -- -100.00 -75.00 -78.98  166
131  \w   -171.00 -82.00   0.50    2.00    -- -100.00 -71.00-178.38  178
132  \w   -172.00 -81.00   0.50    2.00    -- -100.00 -77.00-150.00  182
133  \w   -171.00 -80.00   0.50    2.00    -- -100.00 -75.00 -40.55  182
134  \w   -167.00-130.00   0.50    2.00    -- -100.00 -65.00 116.83   74
135  \w   -158.00-123.00   0.50    2.00    -- -100.00 -76.00 157.17   70
136  \w   -167.00 -80.00   0.50    2.00    -- -100.00 -75.00 168.14  174
137  \w   -168.00 -80.00   0.50    2.00    -- -100.00 -77.00 153.79  176
138  \w   -172.00 -81.00   0.50    2.00    -- -100.00 -77.00  30.00  182
139  \w   -171.00-137.00   0.50    2.00    -- -100.00 -71.00 -23.20   68
140  \w   -171.00-104.00   0.50    2.00    -- -100.00 -73.00 -32.19  134
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'ROD, Synergy Custom DW system, Pilatus 200K'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0429757000
_diffrn_orient_matrix_UB_12      -0.0938559000
_diffrn_orient_matrix_UB_13      -0.0425769000
_diffrn_orient_matrix_UB_21      -0.0874601000
_diffrn_orient_matrix_UB_22      -0.0047730000
_diffrn_orient_matrix_UB_23      0.0000837000
_diffrn_orient_matrix_UB_31      0.0131069000
_diffrn_orient_matrix_UB_32      0.0288319000
_diffrn_orient_matrix_UB_33      -0.1384577000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.1232
_diffrn_reflns_av_unetI/netI     0.0282
_diffrn_reflns_Laue_measured_fraction_full 0.993
_diffrn_reflns_Laue_measured_fraction_max 0.981
_diffrn_reflns_limit_h_max       22
_diffrn_reflns_limit_h_min       -22
_diffrn_reflns_limit_k_max       23
_diffrn_reflns_limit_k_min       -22
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            129069
_diffrn_reflns_point_group_measured_fraction_full 0.989
_diffrn_reflns_point_group_measured_fraction_max 0.962
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         79.375
_diffrn_reflns_theta_min         2.820
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    4.360
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.58334
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.54a (Rigaku Oxford Diffraction, 2019)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.446
_exptl_crystal_description       plate
_exptl_crystal_F_000             1308
_exptl_crystal_size_max          0.5
_exptl_crystal_size_mid          0.16
_exptl_crystal_size_min          0.15
_refine_diff_density_max         1.036
_refine_diff_density_min         -1.255
_refine_diff_density_rms         0.166
_refine_ls_abs_structure_details
;
 Flack x determined using 1758 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.04(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.850
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     203
_refine_ls_number_reflns         4219
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.849
_refine_ls_R_factor_all          0.1111
_refine_ls_R_factor_gt           0.1093
_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^)+(0.2000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.3560
_refine_ls_wR_factor_ref         0.3658
_reflns_Friedel_coverage         0.859
_reflns_Friedel_fraction_full    0.984
_reflns_Friedel_fraction_max     0.941
_reflns_number_gt                4064
_reflns_number_total             4219
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ja0c02331_si_002.cif
_cod_data_source_block           BDF_Efavirenz
_cod_original_cell_volume        3014.63(7)
_cod_database_code               4134874
_shelx_shelxl_version_number     2016/6
_chemical_oxdiff_formula         'C H Cl F Br N O'
_diffrn_oxdiff_digest_frames
;
010a71860775297321de4532aba0d8fee210668e359
;
_diffrn_oxdiff_digest_hkl
;
01a092b971c020a665e93e03d4a4d77fc28135
;
_reflns_odcompleteness_completeness 100.00
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     74.33
_olex2_refinement_description
;
1. Others
 Fixed Uiso: H2(0.116) H6(0.104) H5(0.093) H12(0.095) H20A(0.116) H20B(0.116)
 H19A(0.116) H19B(0.116) H14A(0.116) H14B(0.116) H13A(0.121) H13B(0.121)
 H15A(0.116) H15B(0.116) H16A(0.116) H16B(0.116) H17A(0.116) H17B(0.116)
 H18A(0.116) H18B(0.116)
 Fixed X: H2(0.400762) H6(0.227334) H5(0.119113) H12(0.573682) H20A(0.398207)
 H20B(0.379364) H19A(0.43774) H19B(0.485921) H14A(0.466702) H14B(0.571002)
 H13A(0.574594) H13B(0.471074) H15A(0.497944) H15B(0.453038) H16A(0.551461)
 H16B(0.600819) H17A(0.629559) H17B(0.66389) H18A(0.586333) H18B(0.542057)
 Fixed Y: H2(0.12038) H6(-0.015642) H5(-0.037885) H12(0.334868) H20A(0.30796)
 H20B(0.213546) H19A(0.282814) H19B(0.239582) H14A(0.401785) H14B(0.453513)
 H13A(0.45453) H13B(0.403188) H15A(0.251192) H15B(0.297884) H16A(0.424682)
 H16B(0.386628) H17A(0.340681) H17B(0.439347) H18A(0.372794) H18B(0.415325)
 Fixed Z: H2(0.513573) H6(0.774643) H5(0.638498) H12(0.297514) H20A(0.80822)
 H20B(0.801278) H19A(1.000003) H19B(0.940023) H14A(0.408137) H14B(0.412601)
 H13A(0.2102) H13B(0.205769) H15A(0.6729) H15B(0.613739) H16A(0.698278)
 H16B(0.62703) H17A(0.818701) H17B(0.826227) H18A(1.008896) H18B(0.935836)
;
_shelx_res_checksum              20177
_shelx_hkl_checksum              86680
_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
;
_oxdiff_exptl_absorpt_empirical_full_max 4.459
_oxdiff_exptl_absorpt_empirical_full_min 0.291