Readily Accessible, Modular, and Tuneable BINOL 3,3'-Perfluoroalkylsulfones: Highly Efficient Catalysts for Enantioselective In-Mediated Imine Allylat

Link: http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/asap/abs/ja070742t.html

From Prof. Gregory R. Cook's and Guy C. Lloyd-Jones' groups at North Dakota State University, USA and University of Bristol, UK, respectively

A collaborative effort of the groups at ND State Univ and Univ of Bristol resulted in a new method for the allylation of imine N-acyl hydrazones mediated by indium, which was reported in JACS ASAP this month. The method was capable to produce indium-mediated allylated products in high yield and enantioselectively. In fact, this is the highest ee-yielding method to date in indium-mediated allylation.

Following their initial report of indium-mediated allylation of imine hydrazones using ligand 3a and 3b, they have found that the yield and enantioselectivity could be markedly improved using new BINOL ligands which were even more electron-deficient.

Therefore, new ligands were synthesized employing thia-Fries rearragement of BINOL to give fluoro- and perfluorosulfone derivatives. This also represendted the first examples of the rearrangement of higher perfluoralkylsulfonates. The syntheses of these BINOL are illustrated in Scheme 2.

Comparing to ligands 3a-b, ligands 4a-c were found to be supeior as shown in Table 1.

The presence of two SO2R(F) [R(F) = fluoroalkyl or perfluoroalkyl group)] in the new ligands was found to be crucial in term of selectivity. As a result, BINOL 4d and 4e were inferior to 4a-c, whereas ligands 5a and 5b (with one SO2R(F) group) were least effective.

Scope of ligand bis-SO2R(F) BINOL 4a was established in Table 2. The ligand was found to be very effective with aryl imine. Ligand 4a was even more effective when the aryl ring is substituted at the 6-position (compare entries 6-11), so much so that the loading of the ligand could be reduced to 2-3 mol%.

The only cases where this method did not work as well was when the R group is aliphatic. This is probably because when R is aliphatic, the substrate becomes more reactive. Even with this problem, substrate 1l (entry 17) still gave product 2l with up to 74% ee using ligand 4a, which compares favorably with lignad 3a, which afforded 2l in only 34% ee. This catalyst system is the highest ee-yielding to date. The ligand is easily recovered by silica gel chromatography and can be recycled up to 3 times without loss of reactivity or selectivity.