New Phenylglycine‐Derived Primary Amine Organocatalysts for the Preparation of Optically Active Warfarin

Abstract

In this work we present new, fully synthetic phenylglycine‐derived primary amine organocatalysts useful for the one‐step preparation of optically active warfarin, an important anticoagulant. Both enantiomeric forms of the catalysts are equally available and can be prepared by robust procedures without recourse to chromatographic purification. Together with a co‐catalyst, particularly acetic acid or 2,4‐dinitrophenol, they can furnish warfarin in approximately 80 % ee and represent inexpensive alternatives to other primary amine organocatalysts such as the chiral diamines and Cinchona‐derived primary amines.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Asymmetric Synthesis with Silicon‐Based Bulky Amino Organocatalysts

“…Very recently, Hansen and co-workers [50] found that diphenylphenylglycinol (77) was an effective catalyst in the Michael addition of 4-hydroxycoumarin (75) to benzylideneacetone albeit with only moderate enantioselectivity and yield. Further exploration showed that the TMS-protected diphenylphenylglycinol (21b) gave a promising higher enantioselectivity (Scheme 24).…”

Nitrogen-functionalized Isohexides in Asymmetric Induction

“…Following this strategy, simple bulky aminoalcohols derived from phenylglycine represent an alternative to other chiral diamines. [58] For a combined mechanism based on covalent/ non-covalent activation, bifunctional catalysts have been developed from previously described vicinal diamines. [ based access to this skeleton, in accordance with the twelve fundamental principles of green chemistry.…”

Amino Acid Functional Polymers: Biomimetic Polymer Design Enabling Catalysis, Chiral Materials, and Drug Delivery

“…The same group also derived primary amine organocatalysts from amino acid derivatives, such as phenylglycine, to catalyze asymmetric Michael additions. [72] The immobilization of organocatalysts onto polymer supports has been reviewed nicely by Kristensen and Hansen, but the review seems to be focussed primarily on proline and MacMillan-based organocatalysts, leaving room for the attachment of other amino acid-based organocatalysts to polymer supports. [73] A slightly different approach was also taken by Moore et al, using a tyrosinefunctionalized polymer, using the tyrosine as a functional handle on which to attach a MacMillan catalyst.…”