Lanthanides-pybox: An Excellent Combination for Highly Enantioselective Electrophilic α-Amination of Acyclic β-Keto Esters. Isolation of Ternary Pybox/Ln/β-Keto Ester Complexes

Abstract

High enantioselection is obtained in α‐amination of acyclic β‐keto esters in the presence of lanthanide triflates and pybox ligands. The Eu3+ complexes proved more active than those with Yb3+ and La3+ and high dependence of ee on the type and steric bulk of the ester group was observed. Excellent results were achieved using a combination of europium triflate with ligand L4 (diphenyl‐pybox). Preparation of ternary complexes (8) [(L4)(β‐keto ester enolate)Ln (OTf)2] was accomplished. Complexes 8 and [(L4)(β‐keto ester)Ln (OTf)2]+, identified by ESI‐MS, are proposed as key intermediates of the α‐amination reaction.

Lanthanum‐Catalyzed Enantioselective Trifluoromethylation by Using an Electrophilic Hypervalent Iodine Reagent

“…[24][25][26][27] The versatility offered by lanthanides and their increased coordination numbers suggested us that we should test their combinationw ith cheap commercially available PyBOX chiral ligands in the a-trifluoromethylation reaction. [24][25][26][27] The versatility offered by lanthanides and their increased coordination numbers suggested us that we should test their combinationw ith cheap commercially available PyBOX chiral ligands in the a-trifluoromethylation reaction.…”

“…As af irst stage,w ed ecided to test the efficiency of the catalytic system in the model reactiono fb-keto ester 1a (Scheme 1). [25][26][27] Initially,b yu sing 5-(trifluoromethyl)dibenzothiophenium tetrafluoroborate 3a (Umemoto reagent) as the trifluoromethylation reagent,L a(OTf) 3 and L1,t he corresponding product 2a was obtainedi n1 0% yield and 50 % ee (Table 1, entry 1). [25,26] Keto ester 1a was achieved by treatment of methyl analogue 1b with the correspondinga lcohol using catalytic amounts of ZnO in refluxing toluenei n8 9% yield.…”

“…In our own research, we have extensively used PyBOX ligandsa nd lanthanides for the enantioselective a-amination of b-keto esters. [24][25][26][27] The versatility offered by lanthanides and their increased coordination numbers suggested us that we should test their combinationw ith cheap commercially available PyBOX chiral ligands in the a-trifluoromethylation reaction. As af irst stage,w ed ecided to test the efficiency of the catalytic system in the model reactiono fb-keto ester 1a (Scheme 1).…”

“…The selection of pentan-3-yl derivative 1a was done based in our previousf indings; normally increasing the size of the ester group the enantio-differentiation is enhanced. [25,26] Keto ester 1a was achieved by treatment of methyl analogue 1b with the correspondinga lcohol using catalytic amounts of ZnO in refluxing toluenei n8 9% yield. [28] The pre-catalyst was prepared mixing 10 %o fL a(OTf) 3 and 15 %o f PyBOXl igand (L)i nd ry acetonitrile in the presence of molecular sieves overnight.…”

“…The reactionc onditions had been previously optimized for a-amination reactions. [25][26][27] Initially,b yu sing 5-(trifluoromethyl)dibenzothiophenium tetrafluoroborate 3a (Umemoto reagent) as the trifluoromethylation reagent,L a(OTf) 3 and L1,t he corresponding product 2a was obtainedi n1 0% yield and 50 % ee (Table 1, entry 1). Changing to the To gni reagent (3b), product 2b was afforded in high yield (85 %), although the enantioselectivity did not increase( entry 3).…”