Combined α,α-dialkylprolinol ether/Brønsted acid promotes Mannich reactions of aldehydes with unactivated imines. An entry to anti-configured propargylic amino alcohols
Gómez-Bengoa, Enrique; Jiménez, Jacqueline; Lapuerta, Irati; Mielgo, Antonia; Oiarbide, Mikel; Otazo, Itziar; Velilla, Irene; Vera, Silvia; Palomo, Claudio; Chemical Science 3 (2012) 2949–; doi:10.1039/c2sc20590d

data_1515082
_publ_section_title
;
 Combined \a,\a-dialkylprolinol ether/Br\/onsted acid promotes Mannich
 reactions of aldehydes with unactivated imines. An entry to
 anti-configured propargylic amino alcohols
;
_journal_issue                   10
_journal_name_full               'Chemical Science'
_journal_page_first              2949
_journal_paper_doi               10.1039/c2sc20590d
_journal_volume                  3
_journal_year                    2012
_chemical_absolute_configuration ad
_chemical_compound_source        'synthesis as described'
_chemical_formula_moiety         '2(C25 H19 N O3), 3(C H2 Cl2)'
_chemical_formula_sum            'C26.5 H22 Cl3 N O3'
_chemical_formula_weight         508.8
_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   difmap
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2012-01-19T09:45:12-00:00
_audit_creation_method           'WinGX routine CIF_UPDATE'
_cell_angle_alpha                90
_cell_angle_beta                 93.295(1)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.1490(1)
_cell_length_b                   11.5785(1)
_cell_length_c                   19.7361(1)
_cell_measurement_reflns_used    35762
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      74.04
_cell_measurement_theta_min      3.82
_cell_measurement_wavelength     1.54184
_cell_volume                     2315.36(3)
_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    'SIR92 (Altomare et al, 1993)'
_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 14.00 49.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 38.0000 120.0000 35

2 omega 30.00 79.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 77.0000 -150.0000 49

3 omega 12.00 114.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 57.0000 150.0000 102

4 omega 78.00 104.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 77.0000 -180.0000 26

5 omega 7.00 48.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 77.0000 -180.0000 41

6 omega -28.00 64.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 -57.0000 -120.0000 92

7 omega 3.00 89.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 -125.0000 60.0000 86

8 omega -76.00 -50.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -76.0000 93.0000 26

9 omega -77.00 -50.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -74.0000 108.0000 27

10 omega -75.00 -49.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -77.0000 150.0000 26

11 omega -78.00 -52.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -75.0000 171.0000 26

12 omega -78.00 -52.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -75.0000 160.0000 26

13 omega -75.00 -49.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -77.0000 -180.0000 26

14 omega -75.00 -49.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -77.0000 -150.0000 26

15 omega -76.00 -50.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -74.0000 123.0000 26

16 omega -76.00 -50.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -72.0000 -141.0000 26

17 omega -74.00 -49.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -77.0000 90.0000 25

18 omega -77.00 -51.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -71.0000 -177.0000 26

19 omega -78.00 -52.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -71.0000 178.0000 26

20 omega -77.00 -51.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -69.0000 123.0000 26

21 omega -77.00 -50.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -72.0000 67.0000 27

22 omega -76.00 -50.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -76.0000 71.0000 26

23 omega -75.00 -49.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -77.0000 120.0000 26

24 omega -76.00 -50.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -75.0000 161.0000 26

25 omega -79.00 -53.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -57.0000 65.0000 26

26 omega 75.00 150.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 77.0000 -180.0000 75

27 omega 75.00 101.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 77.0000 90.0000 26

28 omega 75.00 158.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 125.0000 -90.0000 83

29 omega 75.00 101.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 77.0000 -150.0000 26

30 omega 75.00 101.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 77.0000 120.0000 26

31 omega 31.00 67.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -30.0000 0.0000 36

32 omega 67.00 98.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -94.0000 150.0000 31

33 omega 84.00 153.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 61.0000 90.0000 69

34 omega 75.00 132.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 77.0000 150.0000 57

35 omega 83.00 110.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 61.0000 150.0000 27

36 omega 30.00 69.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -30.0000 -60.0000 39

37 omega 82.00 107.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 45.0000 -150.0000 25

38 omega 41.00 73.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -45.0000 -150.0000 32

39 omega 83.00 110.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 61.0000 120.0000 27

40 omega 82.00 109.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 61.0000 -150.0000 27

41 omega 46.00 77.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -45.0000 60.0000 31

42 omega 79.00 126.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 61.0000 -120.0000 47

43 omega 25.00 105.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -94.0000 -150.0000 80

44 omega 76.00 144.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 77.0000 60.0000 68

45 omega -119.00 -7.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- -40.7631 -77.0000 -90.0000 112

46 omega -98.00 -2.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- -40.7631 125.0000 -90.0000 96

47 omega -98.00 -2.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- -40.7631 125.0000 150.0000 96

48 omega -114.00 -63.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- -40.7631 -143.0000 179.0000 51

49 omega -115.00 -11.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- -40.7631 -57.0000 -30.0000 104

50 omega 63.00 114.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 143.0000 -179.0000 51

51 omega 11.00 115.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 57.0000 0.0000 104

52 omega 7.00 119.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 77.0000 90.0000 112

53 omega 63.00 114.00 1.0000 1.5000
omega____ theta____ kappa____ phi______ frames
- 40.7631 143.0000 -125.0000 51

54 omega -162.00 -91.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -77.0000 -90.0000 71

55 omega -162.00 -49.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -77.0000 30.0000 113

56 omega -162.00 -49.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- -83.0000 -77.0000 -30.0000 113

57 omega 30.00 69.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -30.0000 120.0000 39

58 omega 81.00 158.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 45.0000 -60.0000 77

59 omega 30.00 69.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -30.0000 -180.0000 39

60 omega 30.00 69.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -30.0000 30.0000 39

61 omega 24.00 109.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -94.0000 -30.0000 85

62 omega 78.00 158.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 30.0000 30.0000 80

63 omega 30.00 69.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -30.0000 -90.0000 39

64 omega 24.00 109.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -94.0000 30.0000 85

65 omega 64.00 101.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -94.0000 -90.0000 37

66 omega 91.00 118.00 1.0000 2.0000
omega____ theta____ kappa____ phi______ frames
- 108.3609 -125.0000 120.0000 27

;
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'Agilent SuperNova'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      0.0611004
_diffrn_orient_matrix_UB_12      -0.0116679
_diffrn_orient_matrix_UB_13      -0.069338
_diffrn_orient_matrix_UB_21      -0.1386736
_diffrn_orient_matrix_UB_22      0.0066192
_diffrn_orient_matrix_UB_23      -0.0358508
_diffrn_orient_matrix_UB_31      0.0122766
_diffrn_orient_matrix_UB_32      0.1324013
_diffrn_orient_matrix_UB_33      -0.0043223
_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  0.0274
_diffrn_reflns_av_unetI/netI     0.0176
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -24
_diffrn_reflns_number            45653
_diffrn_reflns_theta_full        70
_diffrn_reflns_theta_max         70
_diffrn_reflns_theta_min         4.36
_diffrn_source_current           0.8
_diffrn_source_power             0.04
_diffrn_source_voltage           50
_exptl_absorpt_coefficient_mu    3.836
_exptl_absorpt_correction_T_max  1
_exptl_absorpt_correction_T_min  0.68621
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.35.19 (release 27-10-2011 CrysAlis171 .NET)
(compiled Oct 27 2011,15:02:11)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.46
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             1052
_exptl_crystal_size_max          0.29
_exptl_crystal_size_mid          0.18
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.269
_refine_diff_density_min         -0.424
_refine_diff_density_rms         0.045
_refine_ls_abs_structure_details
;
The Friedel pair coverage of the experiment is almost complete (94%).
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 10-99. The absolute structure parameter y
(Hooft, Straver & Spek, 2008) was calculated using PLATON (Spek,
2010). The resulting value was y=-0.001(1), 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   0.008(7)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.976
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     604
_refine_ls_number_reflns         8536
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      0.976
_refine_ls_R_factor_all          0.0314
_refine_ls_R_factor_gt           0.0302
_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^)+(0.0577P)^2^+0.9962P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0805
_refine_ls_wR_factor_ref         0.0816
_reflns_number_gt                8368
_reflns_number_total             8536
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            c2sc20590d.txt
_cod_data_source_block           ito7150
_cod_original_cell_volume        2315.36(2)
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               1515082