Synthesis of enantiomerically enriched β-N-amino substituted analogs of the (S)-α-alanine via sequential nucleophilic Michael addition, cross-coupling and [3+2]-cycloaddition reactions on the coordination sphere of a chiral Ni(II) complex of amino acid Schiff bases
Khachatryan, Emma A.; Stepanyan, Lala A.; Gevorgyan, Hasmik; Sargsyan, Armen; Hovhannisyan, Anahit; Mkrtchyan, Anna; Malkov, Andrei; Saghyan, Ashot S.; Organic & Biomolecular Chemistry  (2025) –; doi:10.1039/D5OB01593F

data_7160922
_publ_section_title
;
 Synthesis of enantiomerically enriched \b-N-amino substituted analogs of
 the (S)-\a-alanine via sequential nucleophilic Michael addition,
 cross-coupling and [3+2]-cycloaddition reactions on the coordination
 sphere of a chiral Ni(II) complex of amino acid Schiff bases
;
_journal_name_full               'Organic &amp; Biomolecular Chemistry'
_journal_paper_doi               10.1039/D5OB01593F
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C34 H36 N4 Ni O3'
_chemical_formula_sum            'C34 H36 N4 Ni O3'
_chemical_formula_weight         607.38
_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             2025-08-29
_audit_creation_method
;
Olex2 1.5-ac7-018
(compiled 2025.08.06 svn.rb7424aed for Rigaku Oxford Diffraction, GUI svn.r7314)
;
_audit_update_record
;
2025-09-10 deposited with the CCDC.	2025-12-09 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.54522(7)
_cell_length_b                   16.10301(15)
_cell_length_c                   24.9287(2)
_cell_measurement_reflns_used    74191
_cell_measurement_temperature    100.01(14)
_cell_measurement_theta_max      32.3100
_cell_measurement_theta_min      2.6650
_cell_volume                     3028.86(5)
_computing_cell_refinement       'CrysAlisPro 1.171.44.119a (Rigaku OD, 2025)'
_computing_data_collection       'CrysAlisPro 1.171.44.119a (Rigaku OD, 2025)'
_computing_data_reduction        'CrysAlisPro 1.171.44.119a (Rigaku OD, 2025)'
_computing_molecular_graphics    'Olex2 1.5-ac7-018 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-ac7-018 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.01(14)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.927
_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    -22.00  44.00   0.50   20.62    --    9.02 -99.00 -90.00  132
  2  \w    -18.00  13.00   0.50   20.62    --    9.02 -99.00  60.00   62
  3  \w    -62.00 -12.00   0.50   20.62    --    9.02 -77.00-180.00  100
  4  \w    -63.00   5.00   0.50   20.62    --    9.02 -19.00-180.00  136
  5  \w      4.00  69.00   0.50   20.62    --    9.02  77.00 -60.00  130
  6  \w     19.00  44.00   0.50   20.62    --    9.02 -99.00  60.00   50
  7  \w    -38.00  22.00   0.50   20.62    --    9.02 -38.00 120.00  120
  8  \w      7.00  33.00   0.50   20.62    --    9.02 -77.00-180.00   52
  9  \w     36.00  81.00   0.50   20.62    --    9.02  77.00 150.00   90
 10  \w     -9.00  23.00   0.50   20.62    --    9.02  77.00 150.00   64
 11  \w    -85.00   1.00   0.50   20.62    --   -9.80 -19.00  60.00  172
 12  \w    -26.00  62.00   0.50   20.62    --   -9.80  57.00  30.00  176
 13  \w    -23.00  25.00   0.50   20.62    --   -9.80 -99.00   0.00   96
 14  \w    -51.00 -26.00   0.50   20.62    --   -9.80 111.00-102.57   50
 15  \w    -24.00  40.00   0.50   20.62    --   -9.80  38.00 -90.00  128
 16  \w    -10.00  25.00   0.50   20.62    --   -9.80 -99.00-180.00   70
 17  \w    -50.00 -22.00   0.50   20.62    --   -9.80 109.00 -71.26   56
 18  \w    -50.00 -25.00   0.50   20.62    --   -9.80 109.00  19.45   50
 19  \w    -18.00  18.00   0.50   20.62    --   -9.80 -99.00-120.00   72
 20  \w    -49.00 -24.00   0.50   20.62    --   -9.80 107.00 132.08   50
 21  \w    -49.00 -24.00   0.50   20.62    --   -9.80 107.00  56.41   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0060601000
_diffrn_orient_matrix_UB_12      -0.0262479000
_diffrn_orient_matrix_UB_13      0.0227690000
_diffrn_orient_matrix_UB_21      0.0147911000
_diffrn_orient_matrix_UB_22      -0.0346265000
_diffrn_orient_matrix_UB_23      -0.0170200000
_diffrn_orient_matrix_UB_31      0.0926354000
_diffrn_orient_matrix_UB_32      0.0072365000
_diffrn_orient_matrix_UB_33      0.0012206000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0283
_diffrn_reflns_av_unetI/netI     0.0139
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.927
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       22
_diffrn_reflns_limit_k_min       -23
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_limit_l_min       -34
_diffrn_reflns_number            98490
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.905
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         32.210
_diffrn_reflns_theta_min         2.066
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.681
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.77675
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.44.119a (Rigaku Oxford Diffraction, 2025)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'dark red'
_exptl_crystal_colour_modifier   dark
_exptl_crystal_colour_primary    red
_exptl_crystal_density_diffrn    1.332
_exptl_crystal_description       prism
_exptl_crystal_F_000             1280
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.347
_refine_diff_density_min         -0.234
_refine_diff_density_rms         0.043
_refine_ls_abs_structure_details
;
 Flack x determined using 3944 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.0096(18)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.042
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     380
_refine_ls_number_reflns         9681
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.042
_refine_ls_R_factor_all          0.0236
_refine_ls_R_factor_gt           0.0222
_refine_ls_shift/su_max          0.002
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0334P)^2^+0.5394P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0564
_refine_ls_wR_factor_ref         0.0571
_reflns_Friedel_coverage         0.752
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.877
_reflns_number_gt                9354
_reflns_number_total             9681
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ob01593f2.cif
_cod_data_source_block           ag061_100k
_cod_original_cell_volume        3028.85(5)
_cod_database_code               7160922
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         CHNONi
_shelx_estimated_absorpt_t_max   0.935
_shelx_estimated_absorpt_t_min   0.822
_diffrn_oxdiff_digest_hkl
;
43c27a59ba3c1a0ed57cd92dff73b6c6c07a86
;
_diffrn_oxdiff_digest_od_ed
;

;
_diffrn_oxdiff_measurement_exp_name AG061_100K.par
_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
2.a Ternary CH refined with riding coordinates:
 C13(H13), C33(H33)
2.b Secondary CH2 refined with riding coordinates:
 C14(H14A,H14B), C16(H16A,H16B), C17(H17A,H17B), C19(H19A,H19B), C31(H31A,
 H31B), C34(H34A,H34B), C35(H35A,H35B), C36(H36A,H36B)
2.c Aromatic/amide H refined with riding coordinates:
 C4(H4), C5(H5), C6(H6), C7(H7), C26(H26), C27(H27), C28(H28), C29(H29),
 C30(H30), C38(H38), C39(H39), C40(H40), C41(H41), C42(H42)
2.d Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C)
2.e :
 C21(H21)
;
_shelx_res_checksum              26160
_shelx_hkl_checksum              68998
_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 1.245
_oxdiff_exptl_absorpt_empirical_full_min 0.571