Pd-Catalysed Arylation of Secondary Phosphines

The last examples demonstrate that secondary phosphines and derivatives are versatile precursors for the synthesis of tertiary phosphines. However, their preparation in optically pure form requires stoichiometric quantities of chiral reagents. For this reason more recently the work has shifted towards racemic secondary phosphines and derivatives and chiral enantiopure metal catalysts. 

Secondary phosphines 49 were chosen with the hope that steric dissymmetry between the aromatic and methyl groups would provide better enantioselec-tivity in 51. Me-DuPhos palladium complex 50 was selected for the first set of experiments. The rather unusual sodium trimethylsilanoate was chosen based 

Entry Phi equiv. Cat. loading (%) NaSiOMe equiv. Solvent T rc) Yieltf (%) ee (%) 

Firstly, they looked at the precursor with the isityf group in 49, screening the influence of several parameters (Table 6.6) in order to find the optimal conditions. 

It was found that an excess of base or phenyl iodide is not required (entries 1 and 2 and 10-14) and that the catalyst loading can be lowered to 2.5% without significant loss of enantioselectivity. Apolar solvents (toluene and pentane) are preferred, as more polar ones slightly reduce enantioselectivity (entries 5-7). As expected, lower temperatures increase enantioselectivities (compare entries 1, 8 and 9). 

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More recently, Livinghouse and co-workers studied the effect of Cu(I) on Pd-catalysed arylation of secondary phosphine boranes. Apart from a marked beneficial effect on the coupling elSciency, they discovered that Cu(I) is able to suppress the base-mediated racemisation of the phosphide borane intermediate, to generate a configurationally stable metallophosphide 47 (Scheme 6.22). Consequently, tertiary phosphine boranes 48 were obtained with retention of configuration, in good yields and excellent enantioselectivities. 

Scheme 6.24 Proposed mechanism for Pd-catalysed arylation of secondary phosphines.

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