Alternatives to Phosphinooxazoline (t‐BuPHOX) Ligands in the Metal‐Catalyzed Hydrogenation of Minimally Functionalized Olefins and Cyclic β‐Enamides

Abstract

This studyp resents an ew serieso fr eadily accessible iridium-and rhodium-phosphite/oxazoline catalytic systems that can efficiently hydrogenate,f or the first time,b othm inimally functionalized olefins and functionalized olefins (62 examples in total) in high enantioselectivities( eesu pt o> 99%) and conversions. Thep hosphite-oxazoline ligands,w hich are readily available in only two synthetic steps,a re derived from previous privileged 4-alkyl-2-[2-(diphenylphosphino)phenyl]-2-oxazoline (PHOX) ligands by replacing the phosphinemoiety by ab iaryl phosphite group and/or the introductiono famethylene spacer between the oxazoline and the phenylr ing. The modular design of the ligands hasgiven us the opportunity not only to overcome the limitations of the iridium-PHOX catalytic systems in the hydrogenation of minimally functionalized Z-olefins and 1,1-disubstitutedo lefins, but also to expand theiru se to unfunctionalized olefins containing other challenging scaffolds (e.g.,e xocyclic benzofused andt riaryl-substitutedo lefins) anda lso to olefinsw ith poorly coor-dinativeg roups (e.g., a,b-unsaturated lactams,l actones,a lkenylboronic esters, etc.) with enantioselectivities typically > 95% ee. Moreover, both enantiomers of the hydrogenation product could be obtained by simply changing the configuration of the biaryl phosphite moiety.R emarkably, the new catalytic systems also provided excellent enantioselectivities (up to 99% ee)i nt he asymmetric hydrogenation of another challengingc lass of olefins -t he functionalized cyclic b-enamides.A gain, both enantiomers of the reduceda midesc ould be obtained by changing the metal from Ir to Rh. We also demonstrated that environmentally friendly propylene carbonate can be used with no loss of enantioselectivity.A nothera dvantage of the new ligands over the PHOX ligands is that the best ligands are derived from the affordable (S)-phenylglycinolr ather than from the expensive (S)-tert-leucinol.

Enantioselective Pd‐Catalyzed Allylic Substitution using Phosphite‐Oxazoline PHOX‐Based Ligands containing a Methylene Linker

“…The referenced 31 P{ 1 H} spectra in the Supporting Information are displayed without the internal standard. Racemic substrates S1 ‐ S9 [22] and ligands L1 – L3a – c [12a,b] were prepared as previously reported.…”

Self-Adaptable Tropos Catalysts

“…Interestingly, ligand 17 was also successfully applied in other asymmetric reactions such as hydrogenations, 39 hydroborations, 40 and intermolecular Heck reactions. 41 By changing the backbone of ligands 17 (ligands 18 – 22 ; Figure 8 ), the substrate scope was even further improved, with results comparable to or surpassing those for the best catalysts reported to date.…”

Recent Developments in Transition-Metal-Catalyzed Asymmetric Hydrogenation of Enamides

“…A new series of readily accessible catalytic systems based on rhodium-phosphite/oxazoline PHOX (CAT 1) has been used by Pàmies, Diéguez and co-workers to efficiently hydrogenate functionalized cyclic -enamides with enantioselectivities of up to 96% and yields of 81-89% (Scheme 15). 20 The new ligands were synthesized in two steps from affordable (S)-phenylglycinol and were air-stable solids. Interestingly, both enantiomers of the reduced amides could be obtained by changing the metal from rhodium to iridium.…”