Synthesis of chiral α-alkynyl-α-hydroxyamides by enantioselective alkynylation of α-keto amides.
Prieto, Elena; Andrés, Celia; Nieto, Javier; Organic & biomolecular chemistry 23 (2025) 10596–10605; doi:10.1039/d5ob01546d

data_7160839
_publ_section_title
;
 Synthesis of chiral &#x3b1;-alkynyl-&#x3b1;-hydroxyamides by
 enantioselective alkynylation of &#x3b1;-keto amides.
;
_journal_issue                   46
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              10596
_journal_page_last               10605
_journal_paper_doi               10.1039/d5ob01546d
_journal_volume                  23
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C20 H19 N O2'
_chemical_formula_sum            'C20 H19 N O2'
_chemical_formula_weight         305.36
_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'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2021-12-17
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6408)
;
_audit_update_record
;
2024-10-17 deposited with the CCDC.	2025-10-31 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.2975(2)
_cell_length_b                   11.8780(3)
_cell_length_c                   16.8853(3)
_cell_measurement_reflns_used    6702
_cell_measurement_temperature    298.15
_cell_measurement_theta_max      74.5650
_cell_measurement_theta_min      5.2030
_cell_volume                     1664.18(7)
_computing_cell_refinement       'CrysAlisPro 1.171.40.67a (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.67a (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.67a (Rigaku OD, 2019)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      298.15
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.4757
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.995
_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   -129.00  47.00   1.00    1.00    --  -40.93   0.00 -60.00  176
  2  \w     57.00 130.00   1.00    1.00    --   40.93 178.00 -90.00   73
  3  \w     82.00 178.00   1.00    1.70    --  110.01  30.00  30.00   96
  4  \w     37.00 136.00   1.00    1.70    --  110.01 -45.00  60.00   99
  5  \w     77.00 178.00   1.00    1.70    --  110.01  77.00 -30.00  101
  6  \w     82.00 178.00   1.00    1.70    --  110.01  30.00 -60.00   96
  7  \w     94.00 178.00   1.00    1.70    --  110.01 125.00-150.00   84
  8  \w   -115.00 -17.00   1.00    1.00    --  -40.93 -37.00-180.00   98
  9  \w     57.00 130.00   1.00    1.00    --   40.93 178.00  90.00   73
 10  \w     84.00 178.00   1.00    1.70    --  110.01  45.00 120.00   94
 11  \w     81.00 178.00   1.00    1.70    --  110.01  61.00-180.00   97
 12  \w     27.00 110.00   1.00    1.70    --  110.01 -94.00   0.00   83
 13  \w     37.00 118.00   1.00    1.70    --  110.01-125.00 -30.00   81
 14  \w   -117.00  -8.00   1.00    1.00    --  -40.93 -77.00 -60.00  109
 15  \w   -117.00  -8.00   1.00    1.00    --  -40.93 -77.00 120.00  109
 16  \w     81.00 178.00   1.00    1.70    --  110.01  61.00  60.00   97
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0255578000
_diffrn_orient_matrix_UB_12      0.0541243000
_diffrn_orient_matrix_UB_13      0.0820017000
_diffrn_orient_matrix_UB_21      -0.1660419000
_diffrn_orient_matrix_UB_22      -0.0574052000
_diffrn_orient_matrix_UB_23      0.0061962000
_diffrn_orient_matrix_UB_31      0.0789424000
_diffrn_orient_matrix_UB_32      -0.1028870000
_diffrn_orient_matrix_UB_33      0.0396394000
_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  0.0360
_diffrn_reflns_av_unetI/netI     0.0220
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            15839
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.987
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.965
_diffrn_reflns_theta_min         4.551
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.623
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.188
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.67a (Rigaku Oxford Diffraction, 2019)
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    1.219
_exptl_crystal_description       block
_exptl_crystal_F_000             648
_exptl_crystal_size_max          0.566
_exptl_crystal_size_mid          0.403
_exptl_crystal_size_min          0.148
_refine_diff_density_max         0.129
_refine_diff_density_min         -0.109
_refine_diff_density_rms         0.024
_refine_ls_abs_structure_details
;
 Flack x determined using 1156 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.14(10)
_refine_ls_extinction_coef       0.0143(11)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.074
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     210
_refine_ls_number_reflns         3385
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.074
_refine_ls_R_factor_all          0.0416
_refine_ls_R_factor_gt           0.0363
_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^)+(0.0553P)^2^+0.0873P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0986
_refine_ls_wR_factor_ref         0.1043
_reflns_Friedel_coverage         0.723
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.976
_reflns_number_gt                3040
_reflns_number_total             3385
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ob01546d2.cif
_cod_data_source_block           ep_addpirrola
_cod_depositor_comments          'Adding full bibliography for 7160839.cif.'
_cod_database_code               7160839
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C20 H19 N O2'
_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 O(H) groups
2.a Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C4(H4A,H4B), C5(H5A,H5B), C6(H6A,H6B)
2.b Aromatic/amide H refined with riding coordinates:
 C12(H12), C13(H13), C14(H14), C15(H15), C16(H16), C24(H24), C25(H25),
 C26(H26), C27(H27), C28(H28)
2.c Idealised tetrahedral OH refined as rotating group:
 O1(H1)
;
_shelx_res_checksum              7924
_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 3.305
_oxdiff_exptl_absorpt_empirical_full_min 0.641