page_title: Ugi's amine
section_title: Reactions of Ugi's Amine
hierarchical_section_title: Ugi's amine / Reactions of Ugi's Amine
caption_attribution_description: English: Rationale for the stereochemical outcome of directed lithiation of Ugi's Amine.
context_page_description: Ugi’s amine is a chemical compound named for the chemist who first reported its synthesis in 1970, Ivar Ugi. It is a ferrocene derivative. Since its first report, Ugi’s amine has found extensive use as the synthetic precursor to a large number of metal ligands that bear planar chirality. These ligands have since found extensive use in a variety of catalytic reactions. The compound may exist in either the 1S or 1R isomer, both of which have synthetic utility and are commercially available. Most notably, it is the synthetic precursor to the Josiphos class of ligands.
context_section_description: Ugi’s amine is capable of promoting directed ortho lithiation diastereoselctively (with respect to planar chirality). [(1S)-(dimethylamino)ethyl]-ferrocene treated with n-BuLi, then quenched with TMSCl produces a planar chirality of (Rₚ). Treatment of [(1R)-(dimethylamino)ethyl]-ferrocene under these conditions produces a planar chirality of (Sₚ). This selectivity is dictated by the orientation of the methyl substituent on the starting material in the conformation necessary for the nitrogen to be chelated to the lithiate. In one case this methyl substituent suffers from steric interactions with the other Cp ring, and in the other it points away from all other atoms. The high diastereoselectivity is independent of the electrophile used to trap the metalate, providing evidence for the stereoinductive step being lithiation and allowing broad synthetic utility of Ugi’s amine. If the (S,Sₚ) or (R,Rₚ) diastereomers are desired, the first metalate can be trapped with TMSCl to block the more favored lithiation position. Subsequent lithiation occurs at the only available, less favored site. Trapping with the desired electrophile and TBAF deprotection of the TMS group will provide the (S,Sₚ) or (R,Rₚ) diastereomer.
  Further functionalization can take place at the carbon alpha to the ferrocene by substituting the dimethylamine with various nucleophiles. This is usually accomplished by quaternization of the amine with methyl iodide or acetic acid, which upon heating eliminates, resulting in a stable α-ferrocenylethyl cation intermediate. Addition of nucleophiles results substitution that is usually completely stereoretentive. Amines, carboxylates, alcohols, thiols, and posphines are all competent nucleophiles. This is a common phenomenon for α-substituted ferrocenes.
caption: Rationale for the stereochemical outcome of directed lithiation of Ugi's Amine.
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