Planar chiral palladacycle precatalysts for asymmetric synthesis

Chiral non-racemic palladacycles were employed as precatalysts for Pd(0) mediated asymmetric synthesis. Addition of HPAr2/base to a ferrocenyloxazoline planar chiral palladacycle resulted in ligand synthesis and palladium capture to give a bidentate Phosferrox/Pd(0) complex. A series of these complexes were generated in situ and applied successfully as catalysts for asymmetric allylic alkylation

Deuterium as a Stereochemically Invisible Blocking Group for Chiral Ligand Synthesis

Highly diastereoselective lithiation (s-BuLi/TMEDA ix Et2O, -78 degrees C, 2 h) of (5)-2-ferroceny1-4-(substituted)-oxazolines followed by addition of MeOH-d(4) gave up to 95% D incorporation. Subsequent application of alternative lithiation conditions (n-BuLi in THF, -78 degrees C, 2 h), followed by addition of an electrophile, resulted in a reversal of diastereoselectivity controlled primarily by the high k(H)/k(D) value for lithiation (isomer ratio typically between 10:1 and 20:1)

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

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

Application of a ferrocene-based palladacycle precatalyst to enantioselective aryl-aryl Kumada coupling

The palladium catalysed reaction of 1-iodo-2-methylnaphthalene and 2-methyl-1-naphthylmagnesium bromide gave quantitatively an ( S a )-configured cross-coupled product in 80% e.e. using ( R , S p )-PPFA as a ligand. N , N -Dimethylaminomethylferrocene was cyclopalladated (Na 2 PdCl 4 , ( S )-Ac-Phe-OH, 93% e.e., as determined by 1 H NMR as a result of self-induced non-equivalence), and the resulting ( S p )-configured dimeric palladacycle was employed as a precatalyst for this cross-coupling reaction (5 mol%). Addition to the palladacycle of diphenylphosphine and subsequent base-promoted bidentate ligand synthesis and palladium capture gave an in situ generated catalyst resulting in an ( S p )-configured product in up to 71% e.e

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

Reinvestigation of the palladation of (S)-2-ferrocenyl-4-(methylethyl)oxazoline with Pd(OAc)2 in CH2Cl2 was found to proceed with a dr of 3.6:1 in favor of the resulting S,Sp palladacycle. A similar 4:1 dr was obtained using Na2PdCl4 in MeOH. As an alternative approach, highly diastereoselective lithiation (dr >100:1) and transmetalation were investigated. Addition of PdX2(COD) (X = Cl, Br) to (S,Rp)-2-lithio-1-(2′-(4′-methylethyl)oxazolinyl)ferrocene resulted in double halide substitution and formation of cis-(S,S,Sp,Sp)-bis[2-(2′-(4′-methylethyl)oxazolinyl)ferrocene-1-C,3′-N]palladium(II) (42% from X = Cl, 50% from X = Br). Selective monoprotodepalladation with HCl gave an S,Sp palladacycle containing a removable ferrocenyloxazoline ligand. Addition of PdCl2(MeCN)2 to mercuracycles in acetonitrile, themselves generated from Li–Hg transmetalation, followed by a brine wash gave (S,Sp)-di-μ-chlorobis[2-(2′-(4′-methylethyl)oxazolinyl)ferrocene-1-C,3′-N]dipalladium(II) as a single diastereoisomer in high yield. The alternative S,Rp diastereoisomer was obtained in the same way by use of a deuterium blocking group to reverse lithiation diastereoselectivity

Copper(I) complexes of P-stereogenic Josiphos and related ligands

Starting from (R)-Ugi's amine, diastereoselective lithiation followed by Ar'PCl 2 and then Ar’’MgBr led to the generation, as single diastereoisomers, of (R,S p,S phos) [Ar’=Ph, Ar’’=o-Tol] and (R,S p,R phos) [Ar’=o-Tol, Ar’’=Ph] PPFA ligand derivatives. Amine substitution of both with HPCy 2 gave P-stereogenic Josiphos ligands, and then addition of CuCl, the corresponding copper(I) complexes. The latter were also generated by using borane P and N protecting groups and in situ Cu(I) complexation, avoiding the isolation of air-sensitive phosphine intermediates. This protection methodology was also applied to the synthesis of Josiphos/CuCl complexes derived from PCl 3. In addition, related bulky cobalt-sandwich complex-based derivatives were also obtained. Preliminary investigation revealed isolated CuCl complexes as competent catalyst precursors for enantioselective conjugate addition reactions

Metallocene to metallocene conversion. Synthesis of an oxazoline-substituted pentamethyliridocenium cation from a ferrocenyloxazoline

Reaction of (S)-2-ferrocenyl-4-(1-methylethyl)oxazoline with [(CpIrCl2)-Ir-star](2) in benzonitrile with KPF6 and NaOH gave (eta(5)-(S)-2-(4-(1-methylethyl))oxazolinylcyclopentadienyl)(eta(5)-pentamethylcyclopentadienyl)-iridium(III) hexafluorophosphate (68%). This transformation of an iron-based into an iridium-based metallocene proceeds via the rearrangement, with loss of cyclopentadienyliron, of an intermediate cationic ferrocenyliridacycle