Synthesis of ferrocene-based amido-phosphine ligands via highly diastereoselective ortho-lithiation and their application in Pd-catalyzed asymmetric allylic alkylations

An efficient synthesis of novel planar chiral ferrocene-based amido-phosphine ligands was accomplished via highly diastereoselective ortho-lithiation and subsequent in situ trapping with chlorodiphenylphosphine. The palladium complexes of mono-phosphino ferrocenecarboxamide, bis-phosphino ferrocenedicarboxamide ligands, and analogues with a ferrocenophane framework were applied in the allylic alkylation of (E)-1,3-diphenyl-2-propenyl acetate. The reactions proceeded with excellent conversions and ee’s of up to 82%, the most efficient being the camphane based mono-phosphino ferrocenecarboxamide 2.

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(Sp)-2-(Diphenylphosphino)-N-((1R,2S,3R,5R)-2-ethoxy-6,6-dimethylbicyclo[3.1.1]heptan-3-yl)-N-ethylethylferrocenecarboxamideC36H42FeNO2PDe >99% (NMR)[α]D20=-103.3 (c 0.12, CHCl3)Source of chirality: (−)-β-pineneAbsolute configuration: (1R,2S,3R,5R,Sp)

2-(Diphenylphosphino)-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)ferrocenecarboxamideC33H36FeNOPDe = 92% (NMR)[α]D20=-154.8 (с 0.16, CНCl3)Source of chirality: (+)-camphorAbsolute configuration: (1R,2R,4R)

(Sp,Sp)-2,2′-bis-(Diphenylphosphino)-N,N′-bis((1S,2R,3S,4R)-3-ethoxy-4,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)N,N′-diethyl-1,1′-ferrocenedicarboxmideC64H78FeNO2P2De >99% (NMR)[α]D20=-147.2 (c 0.16, CHCl3)Source of chirality: (+)-camphorAbsolute configuration: (1S,2R,3S,4R,Sp,Sp)

(R,R,Sp)-1,1′-[N,N′-(1,2-Cyclohexane-1,2-diyl)bis(N-methylcarboxamide)]2-(diphenylphosphino)-ferroceneC32H33FeN2O2PDe >99% (NMR)[α]D20=-115.2 (c 0.11, CHCl3)Source of chirality: (R,R)-1,2-diaminocyclohexaneAbsolute configuration: (R,R,Sp)

(R,R,Sp,Sp)-1,1′-[N,N′-(1,2-Cyclohexane-1,2-diyl)bis(N-methylcarboxamide)]2,2′-bis-(diphenylphosphino)-ferroceneC44H42FeN2O2P2De >99% (NMR)[α]D20=-375.9 (c 0.17, CHCl3)Source of chirality: (R,R)-1,2-diaminocyclohexaneAbsolute configuration: (R,R,Sp,Sp)