Synthesis of Bis-pyrrolizidine-Fused Dispiro-oxindole Analogues of Curcumin via One-Pot Azomethine Ylide Cycloaddition: Experimental and Computational Approach toward Regio- and Diastereoselection.
Bharitkar, Yogesh P.; Das, Mohua; Kumari, Neha; Kumari, M. Padma; Hazra, Abhijit; Bhayye, Sagar S.; Natarajan, Ramalingam; Shah, Siddharth; Chatterjee, Sourav; Mondal, Nirup B.; Organic letters 17 (2015) 4440–4443; doi:10.1021/acs.orglett.5b02085

data_1534124
_publ_section_title
;
 Synthesis of Bis-pyrrolizidine-Fused Dispiro-oxindole Analogues of
 Curcumin via One-Pot Azomethine Ylide Cycloaddition: Experimental and
 Computational Approach toward Regio- and Diastereoselection.
;
_journal_issue                   18
_journal_name_full               'Organic letters'
_journal_page_first              4440
_journal_page_last               4443
_journal_paper_doi               10.1021/acs.orglett.5b02085
_journal_volume                  17
_journal_year                    2015
_chemical_formula_moiety         'C47 H48 N4 O8, 2(C H Cl3)'
_chemical_formula_sum            'C49 H50 Cl6 N4 O8'
_chemical_formula_weight         1035.63
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2014-12-26
_audit_creation_method
;
Olex2 1.2
(compiled 2014.07.22 svn.r2960 for OlexSys, GUI svn.r4862)
;
_cell_angle_alpha                90.494(13)
_cell_angle_beta                 100.476(13)
_cell_angle_gamma                113.249(13)
_cell_formula_units_Z            2
_cell_length_a                   13.203(3)
_cell_length_b                   13.977(3)
_cell_length_c                   14.658(3)
_cell_measurement_reflns_used    1767
_cell_measurement_temperature    296(2)
_cell_measurement_theta_max      17.75
_cell_measurement_theta_min      2.88
_cell_volume                     2434.2(10)
_computing_cell_refinement       'SAINT v8.34A (Bruker, 2013)'
_computing_data_reduction        'SAINT v8.34A (Bruker, 2013)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2008)'
_computing_structure_solution    'ShelXT (Sheldrick, 2008)'
_diffrn_ambient_temperature      296.15
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.978
_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  0.1631
_diffrn_reflns_av_unetI/netI     0.2559
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.978
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -17
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            46496
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.978
_diffrn_reflns_theta_full        26.000
_diffrn_reflns_theta_max         27.715
_diffrn_reflns_theta_min         1.592
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.411
_exptl_absorpt_correction_T_max  0.7456
_exptl_absorpt_correction_T_min  0.6268
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2014/4 (Bruker,2014) was used for absorption correction.
wR2(int) was 0.1336 before and 0.0705 after correction.
The Ratio of minimum to maximum transmission is 0.8407.
The \l/2 correction factor is 0.00150.
;
_exptl_crystal_density_diffrn    1.413
_exptl_crystal_description       needle
_exptl_crystal_F_000             1076
_exptl_crystal_size_max          0.24
_exptl_crystal_size_mid          0.21
_exptl_crystal_size_min          0.16
_refine_diff_density_max         0.329
_refine_diff_density_min         -0.552
_refine_diff_density_rms         0.077
_refine_ls_extinction_coef       0.015(3)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2014/7 (Sheldrick 2014'
_refine_ls_goodness_of_fit_ref   0.934
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     650
_refine_ls_number_reflns         11178
_refine_ls_number_restraints     98
_refine_ls_restrained_S_all      0.937
_refine_ls_R_factor_all          0.2899
_refine_ls_R_factor_gt           0.0974
_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^)+(0.1612P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2499
_refine_ls_wR_factor_ref         0.3544
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3347
_reflns_number_total             11178
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ol5b02085_si_003.cif
_cod_data_source_block           CL_cy_4Ea_0m_a
_cod_original_cell_volume        2434.2(8)
_cod_database_code               1534124
_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) groups
2. Restrained distances
 Cl6B-C48 \\sim Cl6A-C48 \\sim Cl5B-C48 \\sim Cl5A-C48 \\sim Cl4A-C48 \\sim
Cl4B-C48
 with sigma of 0.02
 Cl1A-C49 \\sim Cl1B-C49
 with sigma of 0.02
3. Rigid bond restraints
 Cl4B, Cl5B, Cl6B, Cl4A, Cl5A, Cl6A
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
 Cl1B, Cl1A, Cl2, Cl3
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
4. Uiso/Uaniso restraints and constraints
Cl4B \\sim Cl5B \\sim Cl6B \\sim Cl4A \\sim Cl5A \\sim Cl6A: within 1.7A with
sigma of 0.04 and sigma for terminal atoms of 0.08
Cl1B \\sim Cl1A \\sim Cl2 \\sim Cl3: within 1.7A with sigma of 0.04 and sigma
for terminal atoms of 0.08
Uanis(Cl5B) \\sim Ueq, Uanis(Cl6A) \\sim Ueq, Uanis(Cl5A) \\sim Ueq,
Uanis(Cl6B) \\sim Ueq, Uanis(Cl4B) \\sim Ueq, Uanis(Cl4A) \\sim Ueq: with sigma
of 0.1 and sigma for terminal atoms of 0.2
Uanis(Cl1A) \\sim Ueq, Uanis(Cl1B) \\sim Ueq: with sigma of 0.1 and sigma for
terminal atoms of 0.2
5. Rigid body (RIGU) restrains
 Cl4B, Cl4A, Cl6B, Cl6A, Cl5A, Cl5B, Cl1A, Cl1B
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
6. Others
 Sof(Cl1B)=Sof(H49A)=1-FVAR(1)
 Sof(Cl1A)=Sof(H49)=FVAR(1)
 Sof(Cl4B)=Sof(Cl5B)=Sof(Cl6B)=Sof(H48A)=1-FVAR(2)
 Sof(Cl4A)=Sof(Cl5A)=Sof(Cl6A)=Sof(H48)=FVAR(2)
7.a Ternary CH refined with riding coordinates:
 C3(H3A), C4(H4A), C5(H5A), C25(H25), C26(H26), C27(H27), C49(H49), C49(H49A),
 C48(H48), C48(H48A)
7.b Secondary CH2 refined with riding coordinates:
 C6(H6A,H6B), C7(H7A,H7B), C8(H8A,H8B), C29(H29A,H29B), C30(H30A,H30B),
 C31(H31A,H31B)
7.c Aromatic/amide H refined with riding coordinates:
 N1(H1), N4(H4), C1(H1A), C12(H12), C13(H13), C15(H15), C18(H18), C19(H19),
 C22(H22), C35(H35), C37(H37), C38(H38), C41(H41), C42(H42), C47(H47)
7.d Idealised Me refined as rotating group:
 C16(H16A,H16B,H16C), C23(H23A,H23B,H23C), C39(H39A,H39B,H39C), C45(H45A,H45B,
 H45C)
7.e Idealised tetrahedral OH refined as rotating group:
 O3(H3), O5(H5), O6(H6)
;
_shelx_res_checksum              51641
_shelx_hkl_checksum              92438
_shelx_shelxl_version_number     2014/7
_olex2_submission_special_instructions 'No special instructions were received'