Copper–cobalt double metal cyanides as green catalysts for phosphoramidate synthesis

Phosphoramidates are common and widespread backbones of a great variety of fine chemicals, pharmaceuticals, additives and natural products. Conventional approaches to their synthesis make use of toxic chlorinated reagents and intermediates, which are sought to be avoided at an industrial scale. Here we report the coupling of phosphites and amines promoted by a Cu3[Co(CN)6]2-based double metal cyanide heterogeneous catalyst using I2 as additive for the synthesis of phosphoramidates. This strategy successfully provides an efficient, environmentally friendly alternative to the synthesis of these valuable compounds in high yields and it is, to the best of our knowledge, the first heterogeneous approach to this protocol. While the detailed study of the catalyst structure and of the metal centers by PXRD, FTIR, EXAFS and XANES revealed changes in their coordination environment, the catalyst maintained its high activity for at least 5 consecutive iterations of the reaction. Preliminary mechanism studies suggest that the reaction proceeds by a continuous change in the oxidation state of the Cu metal, induced by a O2/I− redox cycle.


Supplementary notes, figures and tables:
X-ray diffraction:

0.044
Inductively coupled plasma atomic emission spectroscopy: Table S3. Elemental analysis of Cu and Co ions in the Cu-Co DMC catalyst.

Sample
Cu:Co ratio Cu-Co DMC 1.7 Table S4. Elemental analysis of Cu ions remaining in solution after reaction.

Sample
Cu mol% a Cu-BTC > 99% Cu-Co DMC 1.6% a Total amount of Cu that leached from the solid catalyst.     Supplementary Note 1: Detection of I2 in solution was achieved by measurement of the UV-Vis spectral signal of I3at 360 nm. This was done by diluting the desired I2 containing sample (to 5x10 -3 mM -1x10 -2 mM) in a 100mM NaI solution, transforming all I2 into I3 -. Extrapolation of the concentration of I2 was done using a previously constructed calibration curve. Fig. S11 I2 yield in the iodide oxidation by Cu-Co DMC in methanolic solution vs HCl concentration after 2.5 h reaction time. 2 mmol of NaI, room temperature and exposed to air. Yields were determined by measuring I3via UV-Vis measurements (λ = 360 nm)

Supplementary Discussion 1:
The overall low rate of oxidation of Ito I2, compared to the rate observed in the model reaction for the coupling of amines and phosphites could be explained by the use of the more polar solvent MeOH, instead of DCM. As in the case of ACN, a polar solvent such as methanol is presumably able to interact with the Lewis acid catalytic sites of the Cu-Co DMC, hindering the reaction. It is also worth noting that while the changes in oxidation-reduction potential due to the addition of HCl to the reaction are not the same when using different solvents, it helps us discern any underlying trend in the transformation.

XANES and EXAFS analyses:
Supplementary Note 2: In the following, theoretical XANES spectra were calculated in FDMNES code within the finite difference method. The convolution of theoretical spectra was performed using PyFitIt code. Optimization of structural parameters (interatomic distances) was also performed in PyFitIt code using machine learning approach.
Supplementary Note 3: EXAFS fitting was performed in the Artemis program of Demeter package. For the data presented in Figure 2c,d of the main text, the crystallographic model of Co-Cu cyanide was taken and the fitting was performed for the first three coordination shells (up to metal-metal contribution) including also the multiple scattering contributions. Due to limited Nipd given by the limited k-range, the following assumptions were made for the 3-shell fitting: all coordination numbers were fixed to 6, zero energy shift parameter was common for all contributions, and Debye-Waller parameter of multiple scattering paths were equal to that of the corresponding single scattering path. For accurate analysis of the first-shell coordination numbers, the fitting range was limited to 1..2 Å, and the fitting was performed varying 4 parameters for the first shell contribution: coordination number (N), interatomic distance (R), Debye-Waller parameter (σ 2 ), and zero energy shift (ΔE0), and then fixing ΔE0.   Cu-N 4.0 ± 1.1 2.00 ± 0.01 0.007 ± 0.004 0 Figure S15. Experimental Cu K-edge XANES spectra of the spent catalyst after reaction (solid purple lines), and theoretical spectra (dashed black) for square planar Cu sites coordinated by -OH (a) and -NC (b) ligands. The interatomic distances were optimized to obtain the best agreement with the experimental data. The first model gives slightly better agreement with the experimental spectrum. However, due to a big variety of hypothetical structures and possibility for their mixtures, Cu local structure in the spent catalyst was characterized as square planar Cu-X (X = N, O).
Product identification:  141.6, 136.6, 136.4, 133.9, 132.8, 129.0, 128.5, 127.7, 126.8, 125.0, 121.9, 121.2, 119.9, 43. A typical 1 H-NMR spectrum of product mixture (i.e. oxidative coupling of dibutyl phosphite and propylamine) is shown in figure S19. To determine the concentration of the desired product (i.e. dibutyl propylphosphoramidate) a characteristic peaks of the compound was integrated using the Bruker TopSpin 4.1.3 software. With the use of an external standard (i.e. trimethoxybenzene) the final yield could be determined as follow: Where . = purity of the internal standard, = purity of the limiting reagent, . = number of protons corresponding to the selected standard peak, = number of protons corresponding to the selected product peak, = area of the selected product peak, . = area of the selected standard peak, . = mols of standard and = mols of limiting reagent. Figure S16: Typical 1 H-NMR spectrum of a product mixture. Signals corresponding to product and