Enantioselective <i>de novo</i> synthesis of 14-hydroxy-6-oxomorphinans.
Moore, Jonathan C.; Modell, Louis; Glenn, Jacqueline R.; Jones, Kieran D.; Argent, Stephen P.; Lane, J. Robert; Canals, Meritxell; Lam, Hon Wai; Chemical communications (Cambridge, England) 60 (2024) 6007–6010; doi:10.1039/d4cc01788a

data_7133039
_publ_section_title
;
 Enantioselective <i>de novo</i> synthesis of 14-hydroxy-6-oxomorphinans.
;
_journal_issue                   47
_journal_name_full               'Chemical communications (Cambridge, England)'
_journal_page_first              6007
_journal_page_last               6010
_journal_paper_doi               10.1039/d4cc01788a
_journal_volume                  60
_journal_year                    2024
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C19 H23 N O3'
_chemical_formula_sum            'C19 H23 N O3'
_chemical_formula_weight         313.38
_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'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   difmap
_audit_creation_date             2024-03-12
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-03-19 deposited with the CCDC.	2024-05-10 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 92.8890(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.16300(10)
_cell_length_b                   13.6943(2)
_cell_length_c                   11.41840(10)
_cell_measurement_reflns_used    20442
_cell_measurement_temperature    120(2)
_cell_measurement_theta_max      72.3680
_cell_measurement_theta_min      3.8210
_cell_volume                     1587.14(3)
_computing_cell_refinement       'CrysAlisPro 1.171.43.63a (Rigaku OD, 2023)'
_computing_data_collection
'CrysAlisPro system (CCD 41.123a (release 20-01-2022))'
_computing_data_reduction        'CrysAlisPro 1.171.43.63a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      120(2)
_diffrn_crystal_treatment        'flash frozen in gaseous N2'
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 4.2207
_diffrn_detector_type            'Agilent Diffraction Titan S2 detector'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.994
_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     -4.00  29.00   1.00    3.00    --   30.00  89.00 159.58   33
  2  \w     -7.00  21.00   1.00    3.00    --   30.00  93.00   9.01   28
  3  \w     -6.00  20.00   1.00    3.00    --   30.00  93.00 112.60   26
  4  \w    -43.00  26.00   1.00    3.00    --  -42.25  57.00 -30.00   69
  5  \w    -73.00  25.00   1.00    3.00    --  -42.25  77.00  90.00   98
  6  \w     53.00 112.00   1.00    3.00    --   42.25  38.00   0.00   59
  7  \w     18.00  49.00   1.00    3.00    --   42.25  38.00   0.00   31
  8  \w     28.00  74.00   1.00    3.00    --   42.25-125.00 -90.00   46
  9  \w     13.00  38.00   1.00    3.00    --   46.00  82.00 -15.86   25
 10  \w     13.00  41.00   1.00    3.00    --   46.00  82.00  68.99   28
 11  \w     14.00  42.00   1.00    3.00    --   46.00  78.00 175.18   28
 12  \w     14.00  39.00   1.00    3.00    --   46.00  80.00 -77.14   25
 13  \w     29.00  54.00   1.00    3.00    --   58.00  70.00   4.17   25
 14  \w     73.00  99.00   1.00    3.00    --   58.00  71.00-135.67   26
 15  \w     90.00 126.00   1.00    3.00    --   58.00  70.00   4.17   36
 16  \w     30.00  56.00   1.00    3.00    --   58.00  69.00 117.98   26
 17  \w     28.00  56.00   1.00    3.00    --   58.00  71.00-135.67   28
 18  \w     35.00  72.00   1.00    3.00    --   62.00  71.00 -95.50   37
 19  \w     34.00 102.00   1.00    3.00    --   62.00  70.00 155.58   68
 20  \w     37.00  67.00   1.00    3.00    --   66.00  70.00  22.68   30
 21  \w     40.00  65.00   1.00    3.00    --   66.00  71.00 -51.01   25
 22  \w    112.00 137.00   1.00    3.00    --   66.00  70.00  22.68   25
 23  \w     41.00  84.00   1.00    3.00    --   70.00  70.00 -72.78   43
 24  \w     40.00  66.00   1.00    3.00    --   70.00  71.00  63.25   26
 25  \w     45.00 114.00   1.00   12.00    --   74.00  70.00 165.01   69
 26  \w     49.00  85.00   1.00   12.00    --   78.00  67.00  89.85   36
 27  \w     48.00  87.00   1.00   12.00    --   78.00  71.00-137.29   39
 28  \w     54.00  91.00   1.00   12.00    --   82.00  64.00   6.14   37
 29  \w     60.00  86.00   1.00   12.00    --   86.00  59.00 133.03   26
 30  \w     57.00  92.00   1.00   12.00    --   86.00  70.00 -42.34   35
 31  \w     31.00  77.00   1.00   12.00    --  101.13 -94.00  90.00   46
 32  \w     81.00 111.00   1.00   12.00    --  101.13-125.00   0.00   30
 33  \w     43.00 113.00   1.00   12.00    --  101.13-125.00  90.00   70
 34  \w    132.00 171.00   1.00   12.00    --  101.13 125.00 -60.00   39
 35  \w    125.00 163.00   1.00   12.00    --  101.13  61.00 120.00   38
 36  \w     76.00 119.00   1.00   12.00    --  101.13  61.00 120.00   43
 37  \w     74.00 136.00   1.00   12.00    --  101.13  61.00   0.00   62
 38  \w     76.00 166.00   1.00   12.00    --  101.13  61.00 150.00   90
 39  \w    114.00 164.00   1.00   12.00    --  101.13  61.00 -60.00   50
 40  \w     76.00 103.00   1.00   12.00    --  101.13  61.00 -60.00   27
 41  \w     33.00  91.00   1.00   12.00    --  101.13 -61.00-120.00   58
 42  \w     75.00 104.00   1.00   12.00    --  101.13  61.00  60.00   29
 43  \w     32.00  87.00   1.00   12.00    --  101.13 -61.00  90.00   55
 44  \w    123.00 170.00   1.00   12.00    --  101.13  61.00-180.00   47
 45  \w    118.00 170.00   1.00   12.00    --  101.13  61.00  60.00   52
 46  \w     74.00 124.00   1.00   12.00    --  101.13  61.00-150.00   50
 47  \w     75.00 112.00   1.00   12.00    --  101.13  61.00-180.00   37
 48  \w     31.00  93.00   1.00   12.00    --  101.13 -61.00 -60.00   62
 49  \w    116.00 163.00   1.00   12.00    --  101.13  61.00  30.00   47
 50  \w     75.00 112.00   1.00   12.00    --  101.13  61.00  30.00   37
 51  \w     36.00 113.00   1.00   12.00    --  101.13-125.00 -90.00   77
 52  \w    124.00 160.00   1.00   12.00    --  101.13  61.00  90.00   36
 53  \w     76.00 105.00   1.00   12.00    --  101.13  61.00  90.00   29
 54  \w     74.00 171.00   1.00   12.00    --  101.13  61.00 -90.00   97
 55  \w    112.00 171.00   1.00   12.00    --  101.13  61.00 -30.00   59
 56  \w    105.00 165.00   1.00   12.00    --  101.13  71.00-132.69   60
 57  \w     79.00 104.00   1.00   12.00    --  101.13  61.00 -30.00   25
 58  \w     80.00 106.00   1.00   12.00    --  101.13 -94.00  90.00   26
 59  \w     71.00  97.00   1.00   12.00    --  101.13  71.00-132.69   26
;
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'SuperNova, Titan S2'
_diffrn_measurement_method       '\w scans'
_diffrn_measurement_specimen_support 'MiTeGen micromount'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.1154148000
_diffrn_orient_matrix_UB_12      0.0678623000
_diffrn_orient_matrix_UB_13      -0.0376574000
_diffrn_orient_matrix_UB_21      -0.0849756000
_diffrn_orient_matrix_UB_22      -0.0472719000
_diffrn_orient_matrix_UB_23      0.0925094000
_diffrn_orient_matrix_UB_31      0.0499850000
_diffrn_orient_matrix_UB_32      0.0762680000
_diffrn_orient_matrix_UB_33      0.0909338000
_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  0.0206
_diffrn_reflns_av_unetI/netI     0.0148
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            27269
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.985
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.331
_diffrn_reflns_theta_min         3.876
_diffrn_source                   'microfocus sealed tube'
_diffrn_source_type              'Agilent Diffraction microfocus tube'
_exptl_absorpt_coefficient_mu    0.708
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.826
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.63a (Rigaku Oxford Diffraction, 2023)
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            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.312
_exptl_crystal_description       block
_exptl_crystal_F_000             672
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: EtOAc and pentane'
_exptl_crystal_size_max          0.201
_exptl_crystal_size_mid          0.136
_exptl_crystal_size_min          0.096
_refine_diff_density_max         0.670
_refine_diff_density_min         -0.167
_refine_diff_density_rms         0.035
_refine_ls_abs_structure_details
;
 Flack x determined using 2838 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.05(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.024
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     455
_refine_ls_number_reflns         6170
_refine_ls_number_restraints     21
_refine_ls_restrained_S_all      1.035
_refine_ls_R_factor_all          0.0326
_refine_ls_R_factor_gt           0.0322
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0502P)^2^+0.4191P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0859
_refine_ls_wR_factor_ref         0.0863
_reflns_Friedel_coverage         0.897
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.975
_reflns_number_gt                6103
_reflns_number_total             6170
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4cc01788a2.cif
_cod_data_source_block           jmhwld
_cod_depositor_comments
'Adding full bibliography for 7133037--7133039.cif.'
_cod_database_code               7133039
_nottingham_internal_coll_name   JMHWLD
_nottingham_internal_coll_number 19555
_nottingham_internal_coll_client JM/HWL
_nottingham_internal_coll_type   custom
_nottingham_internal_coll_frame_method '\w scans'
_nottingham_internal_coll_frame_time '12.00, 3.00'
_nottingham_internal_coll_frame_width 1.00
_nottingham_internal_coll_user   pczspa
_nottingham_internal_coll_date   11/10/2023
_nottingham_internal_coll_location NOTTS
_nottingham_internal_coll_instrument 'GVA, PL13110002'
_nottingham_internal_process_date 17/10/2023
_nottingham_internal_process_user pczspa
_nottingham_internal_solution_date 17/10/2023
_nottingham_internal_solution_user pczspa
_nottingham_internal_refinement_date 12/03/2024
_nottingham_internal_refinement_user pczspa
_nottingham_internal_validation_date 12/03/2024
_nottingham_internal_validation_user pczspa
_nottingham_internal_archive_date 12/03/2024
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C19H23NO3
_chemical_oxdiff_usercomment
'JMHWLD #19555 GVA-2085 JM/HWL fomblin oil on micromount'
_shelx_estimated_absorpt_t_max   0.935
_shelx_estimated_absorpt_t_min   0.871
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H,H) groups, H22A of C22A, H7A of C7A, H14A of C14A, H15A of C15A,
  H7B of C7B, H11B of C11B, H11A of C11A, H14B of C14B, H15B of C15B, H22B of
  C22B, H22C of C22C
 At 1.5 times of:
  All O(H) groups, H13B of C23C
2. Restrained distances
 O6B-H6B = O6A-H6A = O13A-H13A
 0.84 with sigma of 0.02
 C5B-H6B
 1.85 with sigma of 0.02
 N1B-C21B \\sim N1B-C21C
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
O18B: within 2A with sigma of 0.04 and sigma for terminal atoms of 0.08 within
2A
C17B \\sim O18B: within 2A with sigma of 0.01 and sigma for terminal atoms of
0.02 within 2A
4. Same fragment restrains
{C21A, C22A, C23A} sigma for 1-2: 0.02, 1-3: 0.04
as in
{C21C, C22C, C23C}
{C21A, C22A, C23A} sigma for 1-2: 0.02, 1-3: 0.04
as in
{C21B, C22B, C23B}
5. Others
 Sof(C21C)=Sof(H21C)=Sof(H21D)=Sof(C22C)=Sof(H22C)=Sof(C23C)=Sof(H23C)=
 Sof(H23D)=1-FVAR(1)
 Sof(C21B)=Sof(H21A)=Sof(H21B)=Sof(C22B)=Sof(H22B)=Sof(C23B)=Sof(H23A)=
 Sof(H23B)=FVAR(1)
6.a Ternary CH refined with riding coordinates:
 C7A(H7A), C7B(H7B)
6.b Secondary CH2 refined with riding coordinates:
 C2A(H2AA,H2AB), C3A(H3AA,H3AB), C8A(H8AA,H8AB), C16A(H16C,H16D), C19A(H19C,
 H19D), C20A(H20C,H20D), C21A(H21E,H21F), C2B(H2BA,H2BB), C3B(H3BA,H3BB),
 C8B(H8BA,H8BB), C16B(H16A,H16B), C19B(H19A,H19B), C20B(H20A,H20B), C21B(H21A,
 H21B), C21C(H21C,H21D)
6.c Aromatic/amide H refined with riding coordinates:
 C11A(H11A), C14A(H14A), C15A(H15A), C22A(H22A), C11B(H11B), C14B(H14B),
 C15B(H15B), C22B(H22B), C22C(H22C)
6.d X=CH2 refined with riding coordinates:
 C23A(H23E,H23F), C23B(H23A,H23B), C23C(H23C,H23D)
;
_shelx_res_checksum              995
_olex2_exptl_crystal_mounting_method 'in fomblin film on a micromount'
_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 1.151
_oxdiff_exptl_absorpt_empirical_full_min 0.854