Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4-addition/Michael reaction through dynamic kinetic resolution under iminium catalysis. Development and mechanistic insights.
Orue, Ane; Uria, Uxue; Roca-López, David; Delso, Ignacio; Reyes, Efraím; Carrillo, Luisa; Merino, Pedro; Vicario, Jose L.; Chemical science 8 (2017) 2904–2913; doi:10.1039/c7sc00009j

data_1545175
_publ_section_title
;
 Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade
 1,4-addition/Michael reaction through dynamic kinetic resolution under
 iminium catalysis. Development and mechanistic insights.
;
_journal_issue                   4
_journal_name_full               'Chemical science'
_journal_page_first              2904
_journal_page_last               2913
_journal_paper_doi               10.1039/c7sc00009j
_journal_volume                  8
_journal_year                    2017
_chemical_absolute_configuration 2S,3R,3aR,7aS
_chemical_compound_source        'synthesis as described'
_chemical_formula_moiety         'C14 H14 O4'
_chemical_formula_sum            'C14 H14 O4'
_chemical_formula_weight         246.25
_chemical_name_systematic
;
 (2S,3R,3aR,7aS)-5-Oxo-2-phenylhexahydro-4H-furo[2,3-b]pyran-3-carbaldehyde
;
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_symmetry_Int_Tables_number      4
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2014-06-10T12:47:24-00:00
_audit_creation_method           'WinGX routine CIF_UPDATE'
_audit_update_record
;
2017-01-02 deposited with the CCDC.
2017-01-30 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 92.0730(10)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   9.16074(6)
_cell_length_b                   6.01447(4)
_cell_length_c                   10.6243(1)
_cell_measurement_reflns_used    18931
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      74.045
_cell_measurement_theta_min      4.142
_cell_measurement_wavelength     1.54184
_cell_volume                     584.984(8)
_computing_cell_refinement       'CrysAlis Pro (Oxford Diffraction Ltd., 2011)'
_computing_data_collection       'CrysAlis Pro (Oxford Diffraction Ltd., 2011)'
_computing_data_reduction        'CrysAlis Pro (Oxford Diffraction Ltd., 2011)'
_computing_molecular_graphics    'Diamond v.3.2f (Crystal Impact GbR, 2008)'
_computing_publication_material  'WinGX publication routines (Farrugia, 1999)'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 2008)'
_computing_structure_solution    'OLEX2 (Dolomanov et al, 2009)'
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.2012
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_details
;
  1 omega   10.00   43.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -40.5756    0.0000  120.0000 33

  2 omega -128.00    8.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -40.5756    0.0000  120.0000 136

  3 omega -115.00  -15.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -40.5756  -38.0000  -60.0000 100

  4 omega  -73.00  -39.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  125.0000 -120.0000 34

  5 omega  -39.00   -9.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000   45.0000  -30.0000 30

  6 omega  -75.00  -43.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000   45.0000  -30.0000 32

  7 omega  107.00  133.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   30.0000  -60.0000 26

  8 omega   45.00   89.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -94.0000  -90.0000 44

  9 omega   89.00  157.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   45.0000  120.0000 68

 10 omega   83.00  155.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000   60.0000 72

 11 omega   36.00   72.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -45.0000  -90.0000 36

 12 omega   96.00  156.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   45.0000 -150.0000 60

 13 omega   49.00   77.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -45.0000    0.0000 28

 14 omega   30.00   64.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -30.0000   60.0000 34

 15 omega   44.00   93.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -94.0000   30.0000 49

 16 omega   35.00  122.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609 -125.0000 -120.0000 87

 17 omega   39.00   76.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -45.0000 -180.0000 37

 18 omega   41.00   67.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -94.0000  -60.0000 26

 19 omega   71.00  103.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -94.0000  -60.0000 32

 20 omega   31.00   62.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -30.0000  -60.0000 31

 21 omega   35.00   62.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -30.0000  -30.0000 27

 22 omega   89.00  155.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000  -60.0000 66

 23 omega   35.00   60.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -45.0000  -60.0000 25

 24 omega  -94.00   -2.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -40.5756  125.0000   60.0000 92

 25 omega  -40.00  -15.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000   30.0000 -120.0000 25

 26 omega   48.00   88.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609 -125.0000 -180.0000 40

 27 omega   30.00   55.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -30.0000 -150.0000 25

 28 omega   92.00  134.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   45.0000 -180.0000 42

 29 omega   94.00  120.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609 -125.0000 -180.0000 26

 30 omega   97.00  124.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -77.0000    0.0000 27

 31 omega -115.00  -11.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -40.5756  -57.0000   60.0000 104

 32 omega -119.00   -7.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -40.5756  -77.0000 -150.0000 112

 33 omega -115.00  -11.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -40.5756  -57.0000 -120.0000 104

 34 omega    7.00  119.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       40.5756   77.0000    0.0000 112

 35 omega    7.00  119.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       40.5756   77.0000 -180.0000 112

 36 omega    2.00   98.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       40.5756 -125.0000  -90.0000 96

 37 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000 -120.0000 113

 38 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000  -90.0000 113

 39 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000 -150.0000 113

 40 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000   60.0000 113

 41 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000  -30.0000 113

 42 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000   90.0000 113

 43 omega -157.00  -53.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -61.0000   90.0000 104

 44 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000   30.0000 113

 45 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000 -180.0000 113

 46 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000  150.0000 113

 47 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000    0.0000 113

 48 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000  -60.0000 113

 49 omega   78.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   30.0000   30.0000 80

 50 omega   30.00   69.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -30.0000  120.0000 39

 51 omega   78.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   61.0000  120.0000 80

 52 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000   30.0000 83

 53 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000  -90.0000 83

 54 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000 -120.0000 83

 55 omega -115.00  -11.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -      -40.5756  -57.0000  -60.0000 104

 56 omega  -49.00  130.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       40.5756    0.0000 -120.0000 179

 57 omega    7.00  119.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       40.5756   77.0000   90.0000 112

 58 omega  -49.00  130.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       40.5756    0.0000  -90.0000 179

 59 omega  -49.00  130.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       40.5756    0.0000 -180.0000 179

 60 omega  -49.00  130.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       40.5756    0.0000 -150.0000 179

 61 omega -162.00  -49.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      -83.0000  -77.0000  120.0000 113

 62 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000 -150.0000 83

 63 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000  150.0000 83

 64 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000   60.0000 83

 65 omega   78.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   61.0000  -60.0000 80

 66 omega   78.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   61.0000   30.0000 80

 67 omega   81.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   45.0000   30.0000 77

 68 omega   31.00   69.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -34.0000   20.0000 38

 69 omega   78.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   61.0000 -180.0000 80

 70 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000 -180.0000 83

 71 omega   34.00   77.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609  -45.0000  120.0000 43

 72 omega   78.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   61.0000  -30.0000 80

 73 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000   90.0000 83

 74 omega   78.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   61.0000   60.0000 80

 75 omega   78.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   61.0000  150.0000 80

 76 omega   75.00  146.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000  -60.0000 71

 77 omega   75.00  158.00   1.0000    1.5000
omega____ theta____ kappa____ phi______ frames
    -      108.3609   77.0000  -30.0000 83

;
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'Agilent SuperNova'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.13996
_diffrn_orient_matrix_UB_12      0.1397636
_diffrn_orient_matrix_UB_13      0.0103515
_diffrn_orient_matrix_UB_21      -0.0898937
_diffrn_orient_matrix_UB_22      -0.1888079
_diffrn_orient_matrix_UB_23      -0.0627991
_diffrn_orient_matrix_UB_31      -0.0254241
_diffrn_orient_matrix_UB_32      -0.1021553
_diffrn_orient_matrix_UB_33      0.1303888
_diffrn_radiation_monochromator  'Multilayer optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_source         'Nova (Cu) X-ray micro-source'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0556
_diffrn_reflns_av_unetI/netI     0.0187
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            21603
_diffrn_reflns_theta_full        71.98
_diffrn_reflns_theta_max         71.98
_diffrn_reflns_theta_min         4.16
_diffrn_source_current           0.8
_diffrn_source_power             0.04
_diffrn_source_voltage           50
_exptl_absorpt_coefficient_mu    0.849
_exptl_absorpt_correction_T_max  0.958
_exptl_absorpt_correction_T_min  0.882
_exptl_absorpt_correction_type   analytical
_exptl_absorpt_process_details
;
        CrysAlisPro, Agilent Technologies,
        Version 1.171.36.24 (release 03-12-2012 CrysAlis171 .NET)
        (compiled Dec  3 2012,18:21:49)
Analytical numeric absorption correction using a multifaceted crystal
                        model based on expressions derived by R.C. Clark & J.S.
        (Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897)
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.398
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             260
_exptl_crystal_size_max          0.234
_exptl_crystal_size_mid          0.1168
_exptl_crystal_size_min          0.0601
_refine_diff_density_max         0.21
_refine_diff_density_min         -0.168
_refine_diff_density_rms         0.035
_refine_ls_abs_structure_details
;
The Friedel pair coverage of the experiment is almost complete (99%).
Analysis of the absolute structure using likelihood methods
(Hooft, Straver & Spek, 2008) was performed using PLATON (Spek, 2011).
 The results indicated that the absolute structure had been correctly
 assigned. The method calculated that the probability that the structure 
is inverted is smaller than 10-73. The absolute structure parameter y 
(Hooft, Straver & Spek, 2008) was calculated using PLATON (Spek,
2010). The resulting value was y=0.10(5), which together with Flack parameter 
value, indicate that the absolute structure has sureley been determined 
correctly.

Flack, H. D. (1983), Acta Cryst. A39, 876-881
Flack & G. Bernardinelli, Acta Cryst. 1999, A55, 908-915; 
H. D. Flack & G. Bernardinelli, J. Appl. Cryst. 2000, 33, 1143-1148.

R. W. W. Hooft, L. H. Straver & A. L. Spek, J. Appl. Cryst. 2008, 41, 96-103
A. L. Spek (2010) PLATON, Utrecht, The Netherlands; 
A. L. Spek, J. Appl. Cryst. 2003, 36, 7-13
A. L. Thompson & D. J. Watkin, Tetrahedron: Asymmetry 2009, 20, 712--717

;
_refine_ls_abs_structure_Flack   -0.03(13)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.073
_refine_ls_hydrogen_treatment    noref
_refine_ls_matrix_type           full
_refine_ls_number_parameters     163
_refine_ls_number_reflns         2281
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.073
_refine_ls_R_factor_all          0.0267
_refine_ls_R_factor_gt           0.0266
_refine_ls_shift/su_max          0
_refine_ls_shift/su_mean         0
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0481P)^2^+0.0651P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0714
_refine_ls_wR_factor_ref         0.0716
_reflns_number_gt                2269
_reflns_number_total             2281
_reflns_threshold_expression     >2\s(I)
_cod_data_source_file            c7sc00009j2.cif
_cod_data_source_block           424cf1
_cod_depositor_comments
;Adding full bibliography for 1545175--1545177.cif.

 Adding full bibliography for 1545175--1545177.cif.
;
_cod_database_code               1545175