Synthesis of Chiral Acyclic Nucleosides by Sharpless Asymmetric Dihydroxylation: Access to Cidofovir and Buciclovir.
Qin, Tao; Li, Jian-Ping; Xie, Ming-Sheng; Qu, Gui-Rong; Guo, Hai-Ming; The Journal of organic chemistry 83 (2018) 15512–15523; doi:10.1021/acs.joc.8b02442

data_4034715
_publ_section_title
;
 Synthesis of Chiral Acyclic Nucleosides by Sharpless Asymmetric
 Dihydroxylation: Access to Cidofovir and Buciclovir.
;
_journal_issue                   24
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              15512
_journal_page_last               15523
_journal_paper_doi               10.1021/acs.joc.8b02442
_journal_volume                  83
_journal_year                    2018
_chemical_absolute_configuration ad
_chemical_formula_moiety
'0.25(C21 H28 N5 O3 Si), 0.5(C22 H31 N5 O3 Si), 0.25(C21 H24 N5 O3 Si)'
_chemical_formula_sum            'C22 H31 N5 O3 Si'
_chemical_formula_weight         441.61
_space_group_crystal_system      monoclinic
_space_group_IT_number           5
_space_group_name_Hall           'I 2y'
_space_group_name_H-M_alt        'I 1 2 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2018-07-18
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 102.714(2)
_cell_angle_gamma                90
_cell_formula_units_Z            16
_cell_length_a                   23.3389(3)
_cell_length_b                   15.1799(2)
_cell_length_c                   42.3532(6)
_cell_measurement_reflns_used    44887
_cell_measurement_temperature    298.3(10)
_cell_measurement_theta_max      71.2340
_cell_measurement_theta_min      3.9860
_cell_volume                     14637.1(4)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      air
_diffrn_ambient_temperature      298.3(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.1057
_diffrn_detector_type            EosS2
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.992
_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      6.00 107.00   1.00    5.50    --   35.50  19.00-120.00  101
  2  \w     17.00 105.00   1.00    5.50    --   35.50  38.00  30.00   88
  3  \w    -34.00  54.00   1.00    5.50    --   35.50 -38.00 150.00   88
  4  \w     23.00  89.00   1.00    5.50    --   35.50-125.00  30.00   66
  5  \w      1.00  74.00   1.00    5.50    --   35.50 -99.00   0.00   73
  6  \w    -34.00  54.00   1.00    5.50    --   35.50 -38.00-150.00   88
  7  \w    -32.00  62.00   1.00    5.50    --   35.50 -77.00   0.00   94
  8  \w      9.00 103.00   1.00    5.50    --   35.50  77.00 -30.00   94
  9  \w     19.00 103.00   1.00    5.50    --   35.50  57.00 -60.00   84
 10  \w     19.00 103.00   1.00    5.50    --   35.50  57.00  60.00   84
 11  \w    -32.00  52.00   1.00    5.50    --   35.50 -57.00 -90.00   84
 12  \w    -36.00  65.00   1.00    5.50    --   35.50 -19.00-150.00  101
 13  \w    -32.00  52.00   1.00    5.50    --   35.50 -57.00  90.00   84
 14  \w     39.00 112.00   1.00   30.00    --  108.69-111.00-120.00   73
 15  \w     91.00 177.00   1.00   30.00    --  108.69  45.00 120.00   86
 16  \w    100.00 178.00   1.00   30.00    --  108.69 111.00 -60.00   78
 17  \w     39.00 112.00   1.00   30.00    --  108.69-111.00 -30.00   73
 18  \w     39.00 112.00   1.00   30.00    --  108.69-111.00-180.00   73
 19  \w     39.00 130.00   1.00   30.00    --  108.69 -30.00-180.00   91
 20  \w     70.00 178.00   1.00   30.00    --  108.69  15.00-150.00  108
 21  \w     91.00 177.00   1.00   30.00    --  108.69  45.00  90.00   86
 22  \w     39.00 112.00   1.00   30.00    --  108.69-111.00  90.00   73
 23  \w    100.00 178.00   1.00   30.00    --  108.69 111.00 120.00   78
 24  \w     39.00 130.00   1.00   30.00    --  108.69 -30.00   0.00   91
 25  \w     39.00 130.00   1.00   30.00    --  108.69 -30.00  90.00   91
 26  \w     40.00 126.00   1.00   30.00    --  108.69 -45.00 -90.00   86
 27  \w     41.00 138.00   1.00   30.00    --  108.69 -82.00  -3.00   97
 28  \w     41.00 135.00   1.00   30.00    --  108.69 -77.00-180.00   94
 29  \w     17.00 105.00   1.00    5.50    --   35.50  38.00  90.00   88
 30  \w    -32.00  52.00   1.00    5.50    --   35.50 -57.00  60.00   84
 31  \w      9.00 103.00   1.00    5.50    --   35.50  77.00-120.00   94
 32  \w      9.00 103.00   1.00    5.50    --   35.50  77.00  30.00   94
 33  \w      9.00 103.00   1.00    5.50    --   35.50  77.00 -60.00   94
 34  \w      1.00  74.00   1.00    5.50    --   35.50 -99.00  60.00   73
 35  \w      9.00 103.00   1.00    5.50    --   35.50  77.00-150.00   94
 36  \w     19.00 103.00   1.00    5.50    --   35.50  57.00  30.00   84
 37  \w      9.00 103.00   1.00    5.50    --   35.50  77.00  90.00   94
 38  \w    -34.00  54.00   1.00    5.50    --   35.50 -38.00  90.00   88
 39  \w     23.00  89.00   1.00    5.50    --   35.50-125.00-120.00   66
 40  \w      9.00 103.00   1.00    5.50    --   35.50  77.00 120.00   94
 41  \w     17.00 105.00   1.00    5.50    --   35.50  38.00 -60.00   88
 42  \w     19.00 103.00   1.00    5.50    --   35.50  57.00  90.00   84
 43  \w     19.00 103.00   1.00    5.50    --   35.50  57.00-150.00   84
 44  \w     82.00 131.00   1.00   30.00    --  108.69  77.00 150.00   49
 45  \w     87.00 178.00   1.00   30.00    --  108.69  30.00  90.00   91
 46  \w     87.00 178.00   1.00   30.00    --  108.69  30.00 -30.00   91
 47  \w     82.00 176.00   1.00   30.00    --  108.69  77.00 120.00   94
 48  \w     82.00 176.00   1.00   30.00    --  108.69  77.00-180.00   94
 49  \w     87.00 178.00   1.00   30.00    --  108.69  30.00   0.00   91
 50  \w     82.00 176.00   1.00   30.00    --  108.69  77.00-120.00   94
 51  \w     87.00 178.00   1.00   30.00    --  108.69  30.00  60.00   91
 52  \w     91.00 177.00   1.00   30.00    --  108.69  45.00-120.00   86
 53  \w     87.00 178.00   1.00   30.00    --  108.69  30.00  30.00   91
 54  \w     70.00 178.00   1.00   30.00    --  108.69  15.00 -30.00  108
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, EosS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0279201000
_diffrn_orient_matrix_UB_12      -0.0714084000
_diffrn_orient_matrix_UB_13      -0.0176737000
_diffrn_orient_matrix_UB_21      0.0033035000
_diffrn_orient_matrix_UB_22      0.0661613000
_diffrn_orient_matrix_UB_23      -0.0271993000
_diffrn_orient_matrix_UB_31      0.0615253000
_diffrn_orient_matrix_UB_32      0.0288409000
_diffrn_orient_matrix_UB_33      0.0184646000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0332
_diffrn_reflns_av_unetI/netI     0.0200
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.992
_diffrn_reflns_limit_h_max       28
_diffrn_reflns_limit_h_min       -25
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       52
_diffrn_reflns_limit_l_min       -52
_diffrn_reflns_number            150046
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.984
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.799
_diffrn_reflns_theta_min         3.873
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.737
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.72586
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    0.802
_exptl_crystal_description       block
_exptl_crystal_F_000             3776
_exptl_crystal_size_max          0.13
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.558
_refine_diff_density_min         -0.342
_refine_diff_density_rms         0.065
_refine_ls_abs_structure_details
;
 Flack x determined using 8627 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.023(12)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.004
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1107
_refine_ls_number_reflns         28692
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.004
_refine_ls_R_factor_all          0.1005
_refine_ls_R_factor_gt           0.0872
_refine_ls_shift/su_max          0.030
_refine_ls_shift/su_mean         0.010
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.2000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2750
_refine_ls_wR_factor_ref         0.3009
_reflns_Friedel_coverage         0.907
_reflns_Friedel_fraction_full    0.996
_reflns_Friedel_fraction_max     0.974
_reflns_number_gt                21950
_reflns_number_total             28692
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo8b02442_si_003.cif
_cod_data_source_block           qt-20180612
_cod_database_code               4034715
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C1 H1 O1 N1 Si1'
_reflns_odcompleteness_completeness 99.96
_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, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Rigid bond restraints
 C7AA
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
3. Uiso/Uaniso restraints and constraints
C7AA: within 2A with sigma of 0.002 and sigma for terminal atoms of 0.004
Uanis(C3AA) = Uanis(C6AA)
Uanis(C046) = Uanis(C3BA)
4.a Rotating group:
 N011(H01A,H01B), N012(H01C,H01D), N01I(H01I,H01J)
4.b Secondary CH2 refined with riding coordinates:
 C13(H13A,H13B), C01R(H01E,H01F), C01S(H01G,H01H), C01W(H01K,H01M), C024(H02A,
 H02B), C028(H02G,H02H), C16(H16A,H16B), C14(H14A,H14B), C02G(H02E,H02F),
 C02I(H02C,H02D), C17(H17A,H17B), C03B(H03F,H03G), C21(H21A,H21B), C03I(H03H,
 H03I), C03K(H03J,H03K), C03U(H03A,H03B), C03X(H03D,H03E), C7(H7A,H7B),
 C045(H04A,H04B), C04F(H04I,H04J), C19(H19A,H19B), C3AA(H3AA,H3AB)
4.c Aromatic/amide H refined with riding coordinates:
 C01U(H01U), C01X(H01X), C02L(H02L), C12(H12), C02V(H02V), C02W(H02W),
 C031(H031), C1(H1), C034(H034), C035(H035), C036(H036), C037(H037), C039(H039),
  C03C(H03C), C03D(H03Q), C2(H2), C03M(H03M), C03N(H03N), C6(H6), C3(H3),
 C03R(H03R), C03S(H03S), C03V(H03V), C03W(H03W), C046(H046), C047(H047), C4(H4)
4.d X=CH2 refined with riding coordinates:
 N5(H5A,H5B)
4.e Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C), C03Y(H03L,H03O,H03P), C22(H22A,H22B,H22C), C04E(H04F,
 H04G,H04H), C04G(H04C,H04D,H04E), C2AA(H2AA,H2AB,H2AC), C6AA(H6AA,H6AB,H6AC),
 C20(H20A,H20B,H20C), C8AA(H8AA,H8AB,H8AC), C3BA(H3BA,H3BB,H3BC)
4.f Idealised tetrahedral OH refined as rotating group:
 O009(H009), O00K(H00K), O00N(H00N), O010(H010)
;
_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 1.448
_oxdiff_exptl_absorpt_empirical_full_min 0.474