1. Effects of catalyst activation and ligand steric properties on the enantioselective allylation of amines and phenoxides
Andreas Leitner, Chutian Shu, John F Hartwig Org Lett. 2005 Mar 17;7(6):1093-6. doi: 10.1021/ol050029d.
[reaction: see text] The yields, enantioselectivities, and regioselectivities of the reactions of amines and phenoxides with allylic carbonates in the presence of a metallacyclic iridium catalyst were compared. These data show that both preactivation of the catalyst and the size of the ligand affect the yield, enantioselectivity, and regioselectivity. With the activated catalyst containing a bis-naphthethylamino group, the allylic amination and etherification of a broad range of allylic carbonates occurred in high yields and with high regioselectivities and enantioselectivities.
2. Identification of an activated catalyst in the iridium-catalyzed allylic amination and etherification. Increased rates, scope, and selectivity
Christoph A Kiener, Chutian Shu, Christopher Incarvito, John F Hartwig J Am Chem Soc. 2003 Nov 26;125(47):14272-3. doi: 10.1021/ja038319h.
Studies were conducted to determine possible intermediates in the highly enantioselective, iridium-catalyzed amination and etherification of allylic carbonates, and these studies revealed that cyclometalation of the phosphoramidite ligand is likely to generate the active catalyst. The square-planar [Ir(COD)(L1)Cl] (L1 = P(BINOL)(bisphenethylamine)) did not react with cinnamyl carbonate, but did react with amine to generate an Ir(I) trigonal bipyramidal complex coordinated by COD, a cyclometalated kappa2-phosphoramidite, and a kappa1-phosphoramidite. This complex reacted with phosphines to generate products from replacement of the kappa1-phosphoramidite. These cyclometalated complexes were highly active catalysts for allylic amination and etherification and retained the high selectivity of the original catalyst system. In addition, these complexes combined with [Ir(cod)Cl]2 catalyzed reactions of amines with lower loadings, catalyzed reactions of alkylamines and aromatic amines that did not react with the original catalyst system, and catalyzed reactions of phenoxides under milder conditions.
3. A simple iridium catalyst with a single resolved stereocenter for enantioselective allylic amination. Catalyst selection from mechanistic analysis
Andreas Leitner, Shashank Shekhar, Mark J Pouy, John F Hartwig J Am Chem Soc. 2005 Nov 9;127(44):15506-14. doi: 10.1021/ja054331t.
A study of the relationship between the stereochemical elements of a phosphoramidite ligand and the stereoselectivity of iridium-catalyzed amination of allylic carbonates is reported. During catalyst activation, a complex of a phosphoramidite ligand possessing one axial chiral binaphtholate group and two resolved phenethyl substituents converts to a more reactive cyclometalated complex containing one distal chiral substituent at nitrogen, one substituent that becomes part of the metalacycle, and one unperturbed binaphtholate group. Systematic changes were made to the different stereochemical elements. Replacement of the distal chiral phenethyl substituent with a large achiral cycloalkyl group led to a catalyst that reacts with rates and enantioselectivities that are similar to those of the original catalyst with the phenethyl group. Studies of the reactions of diastereomeric ligands containing (R) or (S) binaphtholate groups on phosphorus, along with one (R)-phenethyl and one achiral cyclododecyl group on nitrogen, show that the complexes of the two diastereomeric ligands undergo cyclometalation at much different rates. To access both diastereomeric catalysts and to determine if the reaction can occur selectively with an even simpler ligand containing a phenethyl substituent at nitrogen as the only resolved stereochemical element, the catalyst derived from a phosphoramidite containing a biphenolate group was studied. Catalysts generated from this ligand were shown to react in all cases examined with nearly the same rates, regioselectivities, and enantioselectivities as catalysts derived from the original more elaborate ligand. The absolute stereochemistry of the product implies that the major enantiomer is formed from the (R(a),R(c))-atropisomer of the catalyst containing the biphenolate group.
