Enantioselective synthesis of spiro[indoline-3,1′-pyrazolo[1,2-b]phthalazine] derivatives via an organocatalytic three-component cascade reaction
Song, Luying; Sun, Yuhong; An, Renbo; Wang, Liming; Jin, Ying; RSC Advances 15 (2025) 17031–17035; doi:10.1039/D5RA01633A

data_7250427
_publ_section_title
;
 Enantioselective synthesis of
 spiro[indoline-3,1&#x2032;-pyrazolo[1,2-b]phthalazine] derivatives via an
 organocatalytic three-component cascade reaction
;
_journal_issue                   21
_journal_name_full               'RSC Advances'
_journal_page_first              17031
_journal_page_last               17035
_journal_paper_doi               10.1039/D5RA01633A
_journal_volume                  15
_journal_year                    2025
_chemical_absolute_configuration syn
_chemical_formula_moiety
'C19 H10 F N5 O3, 0.833[H2O], 0.5[CH2Cl2], 0.5[C6H12]'
_chemical_formula_sum            'C19.92 H11.83 Cl1.83 F N5 O3'
_chemical_formula_weight         453.20
_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             2025-05-05
_audit_creation_method
;
Olex2 1.5
(compiled 2021.08.20 svn.r13c46975 for OlexSys, GUI svn.r6396)
;
_audit_update_record
;
2025-05-05 deposited with the CCDC.	2025-05-14 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            24
_cell_length_a                   16.7979(6)
_cell_length_b                   22.4214(9)
_cell_length_c                   35.2924(11)
_cell_measurement_reflns_used    9665
_cell_measurement_temperature    173.00
_cell_measurement_theta_max      63.579
_cell_measurement_theta_min      2.913
_cell_volume                     13292.3(8)
_computing_cell_refinement       'SAINT V8.40B (?, 2016)'
_computing_data_reduction        'SAINT V8.40B (?, 2016)'
_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 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      173.00
_diffrn_measured_fraction_theta_full 0.978
_diffrn_measured_fraction_theta_max 0.978
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0419
_diffrn_reflns_av_unetI/netI     0.0553
_diffrn_reflns_Laue_measured_fraction_full 0.978
_diffrn_reflns_Laue_measured_fraction_max 0.978
_diffrn_reflns_limit_h_max       19
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       25
_diffrn_reflns_limit_k_min       -22
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_limit_l_min       -40
_diffrn_reflns_number            51175
_diffrn_reflns_point_group_measured_fraction_full 0.953
_diffrn_reflns_point_group_measured_fraction_max 0.953
_diffrn_reflns_theta_full        63.769
_diffrn_reflns_theta_max         63.769
_diffrn_reflns_theta_min         3.187
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    2.802
_exptl_absorpt_correction_T_max  0.7524
_exptl_absorpt_correction_T_min  0.5634
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1418 before and 0.0588 after correction.
The Ratio of minimum to maximum transmission is 0.7488.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.359
_exptl_crystal_description       plate
_exptl_crystal_F_000             5532
_exptl_crystal_size_max          0.13
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.08
_refine_diff_density_max         0.862
_refine_diff_density_min         -0.673
_refine_diff_density_rms         0.164
_refine_ls_abs_structure_details
;
 Refined as an inversion twin.
;
_refine_ls_abs_structure_Flack   0.05(3)
_refine_ls_extinction_coef       0.00084(9)
_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   1.045
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1927
_refine_ls_number_reflns         20901
_refine_ls_number_restraints     477
_refine_ls_restrained_S_all      1.124
_refine_ls_R_factor_all          0.0725
_refine_ls_R_factor_gt           0.0649
_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^)+(0.1289P)^2^+2.7028P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1716
_refine_ls_wR_factor_ref         0.1803
_reflns_Friedel_coverage         0.798
_reflns_Friedel_fraction_full    0.923
_reflns_Friedel_fraction_max     0.923
_reflns_number_gt                18370
_reflns_number_total             20901
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ra01633a2.cif
_cod_data_source_block           1
_cod_database_code               7250427
_shelx_shelxl_version_number     2018/3
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.95(3)
 0.05(3)
2. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups, All N(H,H) groups
3. Restrained distances
 O17-O12
 3 with sigma of 0.01
 Cl27-C127 = Cl13-C127 = Cl9-C123 = Cl2-C61 = Cl19-C123 = Cl7-C2 = Cl29-C2 =
 Cl17-C61 = Cl5-C31 = Cl11-C125 = Cl3-C63 = Cl25-C63
 1.77 with sigma of 0.02
 Cl27-Cl13 = Cl9-Cl19 = Cl7-Cl29 = Cl5-Cl21 = Cl5-Cl21 = Cl3-Cl25 = Cl1-Cl8 =
 Cl11-Cl23
 2.92 with sigma of 0.02
 Cl15-Cl30
 2.92 with sigma of 0.01
 Cl9-Cl19
 2.916 with sigma of 0.03
 Cl30-C121 = Cl15-C121 = Cl9-C123 = Cl19-C123 = Cl5-C31 = Cl21-C31 = Cl11-C125
 = Cl23-C125
 1.77 with sigma of 0.01
 C115-Cl8
 1.77 with sigma of 0.02
 Cl1-C115
 1.77 with sigma of 0.02
 Cl2-Cl17
 2.92 with sigma of 0.02
 Cl23-C125
 1.77 with sigma of 0.02
 Cl26-C15
 1.78 with sigma of 0.02
 Cl26-C15 = Cl28-C15
 1.771 with sigma of 0.01
 Cl21-C31
 1.77 with sigma of 0.02
 Cl26-Cl28
 2.916 with sigma of 0.03
 Cl28-C15
 1.77 with sigma of 0.02
 O14-O7_$1
 3 with sigma of 0.01
 O14-C74 = O7-C66 = O17-C37 = O12-C48
 1.2 with sigma of 0.01
 Cl20-Cl18
 2.8 with sigma of 0.02
 Cl10-Cl12
 2.8 with sigma of 0.02
 Cl22-Cl24
 2.916 with sigma of 0.03
 Cl22-C119
 1.78 with sigma of 0.02
 Cl24-C119
 1.77 with sigma of 0.02
 Cl22-C119 = Cl24-C119
 1.771 with sigma of 0.01
 Cl11-Cl23
 2.92 with sigma of 0.04
 Cl26-Cl28
 2.92 with sigma of 0.04
 Cl22-Cl24
 2.92 with sigma of 0.04
 Cl10-C57 \\sim Cl20-C59 \\sim Cl12-C57 \\sim Cl18-C59
 with sigma of 0.02
4. Uiso/Uaniso restraints and constraints
Cl28 \\sim Cl26 \\sim Cl15 \\sim Cl30 \\sim Cl21 \\sim Cl5 \\sim C15 \\sim C31
\\sim Cl11 \\sim C125 \\sim Cl23 \\sim Cl19 \\sim Cl20 \\sim C59 \\sim Cl18
\\sim Cl9 \\sim Cl8 \\sim Cl3 \\sim Cl1 \\sim Cl22: within 2A with sigma of
0.04 and sigma for terminal atoms of 0.08 within 2A
Cl19 \\sim Cl9 \\sim Cl13 \\sim Cl8 \\sim Cl1 \\sim Cl3 \\sim Cl2: within 2A
with sigma of 0.003 and sigma for terminal atoms of 0.006 within 2A
Cl9 \\sim Cl19 \\sim C123: within 2A with sigma of 0.04 and sigma for terminal
atoms of 0.08 within 2A
Cl5 \\sim Cl21 \\sim C31: within 2A with sigma of 0.04 and sigma for terminal
atoms of 0.08 within 2A
Cl11 \\sim Cl23 \\sim C125: within 2A with sigma of 0.04 and sigma for terminal
atoms of 0.08 within 2A
Cl26 \\sim Cl28 \\sim C15: within 2A with sigma of 0.01 and sigma for terminal
atoms of 0.02 within 2A
Cl22 \\sim Cl24 \\sim C119: within 2A with sigma of 0.04 and sigma for terminal
atoms of 0.08 within 2A
C61 \\sim C127: within 2A with sigma of 0.01 and sigma for terminal atoms of
0.02 within 2A
Cl15 \\sim Cl22 \\sim C121 \\sim C119 \\sim Cl24: within 2A with sigma of 0.01
and sigma for terminal atoms of 0.02 within 2A
Uanis(Cl9) \\sim Ueq, Uanis(Cl19) \\sim Ueq: with sigma of 0.1 and sigma for
terminal atoms of 0.2
Uanis(Cl2) \\sim Ueq, Uanis(Cl11) \\sim Ueq, Uanis(Cl9) \\sim Ueq, Uanis(Cl26)
\\sim Ueq, Uanis(Cl5) \\sim Ueq, Uanis(Cl27) \\sim Ueq, Uanis(C57) \\sim Ueq,
Uanis(Cl15) \\sim Ueq, Uanis(Cl19) \\sim Ueq, Uanis(Cl30) \\sim Ueq,
Uanis(Cl21) \\sim Ueq, Uanis(Cl5) \\sim Ueq: with sigma of 0.01 and sigma for
terminal atoms of 0.02
Uanis(C127) \\sim Ueq, Uanis(C61) \\sim Ueq: with sigma of 0.05 and sigma for
terminal atoms of 0.1
Uanis(Cl11) \\sim Ueq, Uanis(Cl23) \\sim Ueq, Uanis(C125) \\sim Ueq: with sigma
of 0.1 and sigma for terminal atoms of 0.2
Uanis(C2) \\sim Ueq, Uanis(Cl29) \\sim Ueq, Uanis(Cl7) \\sim Ueq: with sigma of
0.01 and sigma for terminal atoms of 0.02
Uanis(Cl25) \\sim Ueq, Uanis(C63) \\sim Ueq, Uanis(C115) \\sim Ueq, Uanis(Cl3)
\\sim Ueq, Uanis(Cl8) \\sim Ueq, Uanis(Cl21) \\sim Ueq, Uanis(Cl10) \\sim Ueq:
with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(Cl20) \\sim Ueq, Uanis(Cl18) \\sim Ueq, Uanis(C117) \\sim Ueq: with sigma
of 0.01 and sigma for terminal atoms of 0.02
Uanis(Cl2) \\sim Ueq, Uanis(Cl17) \\sim Ueq: with sigma of 0.01 and sigma for
terminal atoms of 0.02
Uanis(C121) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(N29) \\sim Ueq: with sigma of 0.005 and sigma for terminal atoms of 0.01
Uanis(C123) \\sim Ueq: with sigma of 0.1 and sigma for terminal atoms of 0.2
Uanis(C31) \\sim Ueq, Uanis(C125) \\sim Ueq, Uanis(Cl13) \\sim Ueq: with sigma
of 0.05 and sigma for terminal atoms of 0.1
Uanis(Cl6) \\sim Ueq, Uanis(C29) \\sim Ueq, Uanis(Cl4) \\sim Ueq, Uanis(Cl23)
\\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C59) \\sim Ueq, Uanis(C119) \\sim Ueq, Uanis(C125) \\sim Ueq: with sigma
of 0.01 and sigma for terminal atoms of 0.02
5. Rigid body (RIGU) restrains
 Cl9, Cl19, C123
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 Cl5, Cl21, C31
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 Cl11, Cl23, C125
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 C61, Cl2, Cl17
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.02
 Cl26, Cl28, C15
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 Cl22, Cl24, C119
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
6. Others
 1*[Sof(Cl5)+Sof(Cl21)+Sof(C31)+Sof(H31A)+Sof(H31B)]+1*[Sof(Cl9)+Sof(Cl19)+
 Sof(C123)+Sof(H12C)+Sof(H12D)]+1*[Sof(Cl11)+Sof(Cl23)+Sof(C125)+Sof(H12E)+
 Sof(H12F)]=0.5 with esd of 0.001
 Sof(Cl30)=Sof(C121)=Sof(H12A)=Sof(H12B)=Sof(Cl15)=1-FVAR(1)
 Sof(Cl22)=Sof(Cl24)=Sof(C119)=Sof(H11F)=Sof(H11G)=FVAR(1)
 Sof(C63)=Sof(H63A)=Sof(H63B)=Sof(Cl3)=Sof(Cl25)=0.5*(1-FVAR(3))
 Sof(Cl1)=Sof(Cl8)=Sof(C115)=Sof(H11B)=Sof(H11C)=0.5*FVAR(3)
 Sof(Cl5)=Sof(Cl21)=Sof(C31)=Sof(H31A)=Sof(H31B)=FVAR(3)
 Sof(Cl9)=Sof(Cl19)=Sof(C123)=Sof(H12C)=Sof(H12D)=FVAR(4)
 Sof(Cl11)=Sof(Cl23)=Sof(C125)=Sof(H12E)=Sof(H12F)=FVAR(5)
 Sof(C127)=Sof(H12G)=Sof(H12H)=Sof(Cl13)=Sof(Cl27)=0.5*(1-FVAR(7))
 Sof(Cl2)=Sof(C61)=Sof(H61A)=Sof(H61B)=Sof(Cl17)=0.5*FVAR(7)
 Sof(Cl14)=Sof(Cl16)=Sof(C117)=Sof(H11D)=Sof(H11E)=0.5*(1-FVAR(8))
 Sof(Cl7)=Sof(Cl29)=Sof(C2)=Sof(H2A)=Sof(H2B)=0.5*FVAR(8)
 Fixed Sof: Cl10(0.5) Cl12(0.5) C57(0.5) H57A(0.5) H57B(0.5) Cl18(0.5)
 C59(0.5) H59A(0.5) H59B(0.5) Cl20(0.5) Cl26(0.5) Cl28(0.5) C15(0.5) H15C(0.5)
 H15D(0.5)
7.a Secondary CH2 refined with riding coordinates:
 C57(H57A,H57B), C115(H11B,H11C), C29(H29A,H29B), C117(H11D,H11E), C59(H59A,
 H59B), C119(H11F,H11G), C15(H15C,H15D), C121(H12A,H12B), C61(H61A,H61B),
 C123(H12C,H12D), C31(H31A,H31B), C125(H12E,H12F), C63(H63A,H63B), C127(H12G,
 H12H), C2(H2A,H2B)
7.b Aromatic/amide H refined with riding coordinates:
 N12(H12), N16(H16), N17(H17A), N19(H19), N5(H5A), N11(H11A), C64(H64),
 C80(H80), C108(H108), C114(H114), C124(H124), C128(H128), C33(H33), C67(H67),
 C17(H17), C71(H71), C9(H9), C75(H75), C77(H77), C79(H79), C5(H5), C41(H41),
 C83(H83), C21(H21), C87(H87), C11(H11), C89(H89), C45(H45), C91(H91), C23(H23),
  C93(H93), C47(H47), C95(H95), C3(H3), C97(H97), C49(H49), C99(H99), C25(H25),
 C101(H101), C51(H51), C13(H13), C53(H53), C27(H27), C109(H109), C55(H55),
 C111(H111), C7(H7), C113(H113)
7.c X=CH2 refined with riding coordinates:
 N26(H26A,H26B), N28(H28A,H28B), N15(H15A,H15B), N9(H9A,H9B), N21(H21A,H21B),
 N3(H3A,H3B)
;
_shelx_res_checksum              81731
_olex2_submission_special_instructions 'No special instructions were received'