Enamine-mediated Mannich reaction of cyclic N,O-acetals and amido acetals: the multigram synthesis of pyrrolidine alkaloid precursors
Turmanov, Rakhymzhan A.; Smolobochkin, Andrey V.; Gazizov, Almir S.; Rizbayeva, Tanzilya S.; Zapylkin, Danil D.; Voronina, Julia K.; Voloshina, Alexandra D.; Syakaev, Victor V.; Kurenkov, Alexey V.; Burilov, Alexander R.; Pudovik, Michail A.; Organic & Biomolecular Chemistry  (2022) –; doi:10.1039/D2OB01276F

data_7158857
_publ_section_title
;
 Enamine-mediated Mannich reaction of cyclic N,O-acetals and amido
 acetals: the multigram synthesis of pyrrolidine alkaloid precursors
;
_journal_name_full               'Organic &amp; Biomolecular Chemistry'
_journal_paper_doi               10.1039/D2OB01276F
_journal_year                    2022
_chemical_formula_moiety         '8(C20 H22 N2 O4 S), 4(C2 H6 O S), 0.5(H4 O2)'
_chemical_formula_sum            'C168 H202 N16 O37 S12'
_chemical_formula_weight         3422.16
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-C 2yc'
_space_group_name_H-M_alt        'C 1 2/c 1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_date             2022-05-25
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6408)
;
_audit_update_record
;
2022-05-26 deposited with the CCDC.	2022-08-25 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 121.812(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   60.154(7)
_cell_length_b                   7.6235(12)
_cell_length_c                   41.742(6)
_cell_measurement_reflns_used    2393
_cell_measurement_temperature    100.0
_cell_measurement_theta_max      22.60
_cell_measurement_theta_min      2.41
_cell_volume                     16267(4)
_computing_cell_refinement       'SAINT V8.40A (Bruker, 2019)'
_computing_data_reduction        'SAINT V8.40A (Bruker, 2019)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      100.0
_diffrn_measured_fraction_theta_full 0.995
_diffrn_measured_fraction_theta_max 0.995
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.2148
_diffrn_reflns_av_unetI/netI     0.2371
_diffrn_reflns_Laue_measured_fraction_full 0.995
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       71
_diffrn_reflns_limit_h_min       -67
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       49
_diffrn_reflns_limit_l_min       -49
_diffrn_reflns_number            46657
_diffrn_reflns_point_group_measured_fraction_full 0.995
_diffrn_reflns_point_group_measured_fraction_max 0.995
_diffrn_reflns_theta_full        25.000
_diffrn_reflns_theta_max         25.000
_diffrn_reflns_theta_min         1.989
_diffrn_source_current           1.4
_diffrn_source_power             0.07
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.245
_exptl_absorpt_correction_T_max  0.7461
_exptl_absorpt_correction_T_min  0.5478
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1140 before and 0.0540 after correction.
The Ratio of minimum to maximum transmission is 0.7342.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.397
_exptl_crystal_description       prizm
_exptl_crystal_F_000             7240
_exptl_crystal_size_max          0.1
_exptl_crystal_size_mid          0.06
_exptl_crystal_size_min          0.01
_refine_diff_density_max         0.925
_refine_diff_density_min         -1.072
_refine_diff_density_rms         0.105
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.006
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1054
_refine_ls_number_reflns         14232
_refine_ls_number_restraints     18
_refine_ls_restrained_S_all      1.006
_refine_ls_R_factor_all          0.2177
_refine_ls_R_factor_gt           0.0993
_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^)+(0.1071P)^2^+11.0576P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2245
_refine_ls_wR_factor_ref         0.2912
_reflns_Friedel_coverage         0.000
_reflns_number_gt                6325
_reflns_number_total             14232
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2ob01276f2.cif
_cod_data_source_block           n
_cod_database_code               7158857
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_max   0.998
_shelx_estimated_absorpt_t_min   0.976
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H,H) groups
2. Uiso/Uaniso restraints and constraints
Uanis(C2S) \\sim Ueq: with sigma of 0.005 and sigma for terminal atoms of 0.02
Uanis(C17C) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C3B) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C2S) = Uanis(C1S)
3. Others
 Fixed Sof: H3SD(0.5) H3SE(0.5)
4.a Free rotating group:
 O3S(H3SD,H3SE)
4.b Ternary CH refined with riding coordinates:
 C2A(H2A), C2D(H2D), C2B(H2B), C2C(H2C)
4.c Secondary CH2 refined with riding coordinates:
 C3A(H3AA,H3AB), C4A(H4AA,H4AB), C5A(H5AA,H5AB), C15A(H15A,H15B), C3D(H3DA,
 H3DB), C4D(H4DA,H4DB), C5D(H5DA,H5DB), C15D(H15C,H15D), C3B(H3BA,H3BB),
 C4B(H4BA,H4BB), C5B(H5BA,H5BB), C15B(H15E,H15F), C3C(H3CA,H3CB), C4C(H4CA,
 H4CB), C5C(H5CA,H5CB), C15C(H15G,H15H)
4.d Me refined with riding coordinates:
 C2S(H2SA,H2SB,H2SC)
4.e Aromatic/amide H refined with riding coordinates:
 N12A(H12A), C7A(H7A), C8A(H8A), C10A(H10A), C11A(H11A), C18A(H18A),
 C19A(H19A), C20A(H20A), C21A(H21A), C22A(H22A), N12D(H12D), C7D(H7D), C8D(H8D),
  C10D(H10D), C11D(H11D), C18D(H18D), C19D(H19D), C20D(H20D), C21D(H21D),
 C22D(H22D), N12B(H12B), C7B(H7B), C8B(H8B), C10B(H10B), C11B(H11B), C18B(H18B),
  C19B(H19B), C20B(H20B), C21B(H21B), C22B(H22B), N12C(H12C), C7C(H7C),
 C8C(H8C), C10C(H10C), C11C(H11C), C18C(H18C), C19C(H19C), C20C(H20C),
 C21C(H21C), C22C(H22C)
4.f Idealised Me refined as rotating group:
 C14A(H14A,H14B,H14C), C14D(H14D,H14E,H14F), C14B(H14G,H14H,H14I), C14C(H14J,
 H14K,H14L), C1S(H1SA,H1SB,H1SC), C4S(H4SA,H4SB,H4SC), C3S(H3SA,H3SB,H3SC)
;
_shelx_res_checksum              82186
_shelx_hkl_checksum              3846
_olex2_submission_special_instructions 'No special instructions were received'