Catalytic enantioselective intramolecular Tishchenko reaction of meso-dialdehyde: synthesis of (S)-cedarmycins

The first successful example of a catalytic enantioselective intramolecular Tishchenko reaction of a meso-dialdehyde in the presence of a chiral iridium complex is described. Chiral lactones were obtained in good yields with up to 91% ee. The obtained enantioenriched lactones were utilized for the first synthesis of (S)-cedarmycins A and B.


Synthesis of meso-Dialdehyde 10
To a vigorously stirred suspension of silica gel-supported NaIO4 [4] (666 mg, 0.448mmol, 2 equiv) was added a solution of the diol 9 (70 mg, 0.224 mmol) in CH2Cl2 (2.24 mL, 0.1 M). The reaction was monitored by TLC until disappearance of the starting material (generally 10-30 min). The mixture was filtered through a sintered glass funnel, and the silica gel was thoroughly washed with CH2Cl2 to total volume 10 mL. The chemical yield (72%) was determined by 1 H-NMR using tetrachloroethane as an internal standard. For Tishchenko reaction in the table 2, the residue obtained by evaporation of the CH2Cl2 solution was used quickly by addition of CH2Cl2 or CH3CN. The sample for the NMR measurement was prepared in the same manner except for using CD2Cl2 instead of CH2Cl2.

Preparation of meso-Diol 12
To a CH2Cl2 solution of meso-dialdehyde 10 (99.3 mg, 0.320 mmol) was added MeOH (1.4 mL), then NaBH4 (16mg, 0.422 mmol) was added and stirred at the 30 °C for 24 h. The mixture was quenched by sat. NH4Cl and extracted with AcOEt, then the organic layer was washed with sat. NaHCO3 and brine, dried over Na2SO4. The organic layer was evaporated under reduced pressure to give the desired product 12 as a colorless liquid (88.6 mg, 88% yield).

Determination of the structure by X-ray Crystallography
The CS Analysis of diol 9 Diol 3 (in dichloromethane and hexane) was treated with a single crystal of [(ZnI2)3(tpt)2] complex [CS crystal; tpt = 2,4,6-tris(4pyridyl)triazine], 9 and the guest-absorbed CS crystal was subjected to a diffraction study. ORTEP diagram of the asymmetric unit is shown in Figure S1. CCDC 2019330 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif Figure S1. Asymmetric unit of the 9•[(ZnI2)3(tpt)2] inclusion complex. Solvent (dichloromethane) and hydrogens have been removed for clarify. Figure S2. Diol 9; ellipsoids are at 50% probability Experimental. A Single colourless rod-shaped crystals was attached to a capton film on an Rigaku XtaLAB PRO diffractometer. The crystal was kept at a steady T = 100.15 K during data collection. The structure was solved with the ShelXT (Sheldrick, 2015) structure solution program using the Intrinsic Phasing solution method and by using Olex2 (Dolomanov et al., 2009)

S9
A colorless rod-shaped crystal with dimensions 0.15×0.08×0.06 mm 3 was attached to a Kapton film. Data were collected using a Rigaku XtaLAB PRO diffractometer operating at T = 100.15 K.
Data were measured using ω scans using CuKα radiation. The total number of runs and images was based on the strategy calculation from the program CrysAlisPro (Rigaku, V1.171.40.35a, 2018) The maximum resolution that was achieved was θ = 80.472° (0.78 Å). The diffraction pattern was indexed. The total number of runs and images was based on the strategy calculation from the program CrysAlisPro (Rigaku, V1.171.40.35a, 2018) , 2015). All nonhydrogen atoms were refined anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model. Hydrogen atom positions were calculated geometrically and refined using the riding model. _exptl_absorpt_process_details: CrysAlisPro 1.171.40.35a (Rigaku Oxford Diffraction, 2018)Numerical absorption correction based on gaussian integration over a multifaceted crystal modelEmpirical absorption correction using spherical harmonicsas implemented in SCALE3 ABSPACK. The value of Z' is 2. This means that there are two independent molecules in the asymmetric unit. Crystal structure of (5aS,8aR)-11 Lattice Parameters a = 8.91118(16) Å b = 11.0174 (2)