Phosphinooxazolines, asymmetric Heck

A series of new phosphinooxazoline ligands have been recently prepared and tested in the asymmetric Heck reaction. Synthesis of the ligands involved the aromatic nucleophilic substitution of aryl fluorides with phosphide nucleophile generated from the corresponding phosphine and KHMDS (eq 49). The reaction proceeded in good yields, but proved to be more sluggish with electron-rich aryl fluorides and failed completely when the addition of electron-deficient phosphines was attempted. 

Compared to very extensive studies on Heck reactions, examples of successful asymmetric Heck reactions (abbreviated to AHR in this section) are rather limited, showing that AHRs are not easy to carry out, and careful tuning of conditions is crucial. Most of the HRs proceed by using monodentate ligands. On the other hand, chiral bidentate ligands are mainly required for AHRs. This may be a reason for the difficulty in achieving efficient AHRs. The ligands most extensively used are BINAP, its derivatives, and phosphinooxazolines [116]. 

Shibasaki (Equation 19.36) and Overman first reported the enantioselective Heck reaction. A few substrate combinations react intermolecularly with high enantiose-lectivity (Equation 19.37),but most enantioselective Heck reactions used in S)mthetic applications have been conducted intramolecularly. The asymmetric Heck reaction in Equation 19.37 has begun to be a test-bed for new chiral ligands. Although most Heck reactions that occur with high enantioselectivity have been conducted with BINAP as ligand, a phosphinooxazoline ligand has been used successfully (vide infra). Overman has applied an intramolecular version of the Heck reaction to form oxindoles (Equation 19.38) in the synthesis of a variety of natural products. ... 

Scheme 11.17 Asymmetric intermolecular Mizoroki Heck reaaion of 2,3-dihydrofuran (1) with phosphinooxazoline ferrocene ligands.

To date, the large majority of asymmetric Mizoroki-Heck reactions reported have utilized palladium complexes of BINAP (5). However, since their first application to the asymmetric Mizoroki-Heck reaction, P,N ligands have proven successful and have thus received a greater amount of attention recently [30], The phosphinooxazoline PJSl ligands 41-45 developed independently by the groups of Pfaltz [31], Williams [32] and Hehnchen [33] have shown dramatic improvement in enantioselectivity in a number of asymmetric transformations, including the intermolecular asymmetric Mizoroki-Heck reaction [34]. 

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