Application of Transmetalation to the Synthesis of Planar Chiral and Chiral-at-Metal Iridacycles

Abstract

Diastereoselective lithiation of (S)-2-ferrocenyl-4-(1-methylethyl)oxazoline followed by addition of HgCl2 resulted in the formation by transmetallation of an (S,Sp)-configured mercury substituted complex. Addition to this of [Cp*IrCl2]2 and tetrabutylammonium chloride resulted in a second transmetallation reaction and formation of an (S,Sp,RIr)-configured chloride-substituted half-sandwich iridacycle as exclusively a single diastereoisomer. By reversing the lithiation diastereoselectivity by use of a deuterium blocking group an alternative (S,Rp,SIr)-configured iridacycle was synthesised similarly. Use of (R)-Ugi's amine as substrate in the lithiation/double transmetallation sequence gave a (R,Sp,SIr)-configured half-sandwich iridacycle, complexes of this type being previously unavailable by direct cycloiridation. Lithium to gold transmetallation was also demonstrated with the synthesis of an (S,Sp)-configured Au(I) ferrocenyloxazoline derivative. Use of the (S,Rp,SIr)-iridacycle as a catalyst for the formation of a chiral product by reductive amination with azeotropic HCO2H/NEt3 resulted in a racemate.

Ferrocenyloxazoline-Derived Planar Chiral Palladacycles: C–H Activation, Transmetalation, and Reversal of Diastereoselectivity

“…( S , S p )- 9 (0.022 g, 0.04 mmol) and bis­(acetonitrile)palladium dichloride (0.021 g, 0.08 mmol) were placed in a flame-dried Schlenk tube and dissolved in acetonitrile (2.2 mL). The reaction mixture was stirred for 1 h and then loaded onto a plug of silica; the product was collected with 20% EtOAc in hexane and the solvent removed in vacuo to give a dark red-brown solid (0.02 g, 95%).…”

Recent Development in the Synthesis and Catalytic Application of Iridacycles

“…More recently, Richards et al. reported the synthesis of ferrocene‐based planar chiral iridacycles by using transmetallation as an alternative approach to cycloiridation (Scheme 12) [34] . This has made possible previously unavailable iridacycles by direct introduction of iridium via C−H activation.…”

“…Iridacycle 49 was investigated as a catalyst for reductive amination of acetophenone with benzylamine. However, the catalyst showed no asymmetric induction (Scheme 25) [34] …”

“…More recently, Richards et al reported the synthesis of ferrocene-based planar chiral iridacycles by using transmetallation as an alternative approach to cycloiridation (Scheme 12). [34] This has made possible previously unavailable iridacycles by direct introduction of iridium via CÀ H activation. In the presence of tetramethylethylenediamine (TMEDA) and sec-butyllithium (s-BuLi), diastereoselective lithiation of ferrocenyloxazoline followed by the addition of HgCl 2 resulted in mercury-substituted ferrocenyloxazoline 45 with d.r.…”

“…However, the catalyst showed no asymmetric induction (Scheme 25). [34] More recently, Leung et al [40] explored the iridacycle below, an isomer of 10, for the catalytic asymmetric 1,2dihydrophosphination of acrylonitrile, obtaining a remarkably high ee of 99 %. However, the conversion was low under the conditions employed even after three days of reaction (30 %), as shown in Scheme 26.…”