Enantioselective Synthesis of Biphenols from 1,4-Diketones by Traceless Central-to-axial Chirality Exchange Research By: F Guo, LC Konokol, and RJ Thomson; Northwestern University Summary by: Sonja Gamby; UMCP

Some terms “Axial Chirality” Axial chirality results from a hindered axis of rotation as opposed to a chiral center “Traceless” Denotes transition from sp 3 to sp 2 and the exchange between typical “central” chirality and axial chirality

Common molecule exhibiting axial chirality - BINOL The original synthesis of BINOL was reported by Pummerer et al. in Original syntheses involved oxidative coupling of the two naphthol units induced by FeCl3. There are two methods for the preparation of chiral binaphthol ligands: (a) through coupling reactions of substituted naphthol units and (b) through regioselective modification of the binaphthol scaffold.

Derivatives of BINOL: Why and How? Subject to racemization in acidic or basic media Limited control over electronics and sterics of metal center Useful in a variety of transformations Electrophilic aromatic substitutions in conjunction with protection of the hydroxyl moieties are a quick route to a vast library of derivatives

…Some derivatives Kelly et al. Diels-Alder reactions of naphthoquinone derivatives Kobayashi et al. Mannich Reaction involving silyl enolates I. II.

BINAP for use in asymmetric catalysis … To discover high-performance asymmetric catalysts, developing an excellent chiral ligand is crucial. Attracted by its molecular beauty [Chemica Scripta 1985, 25, 83], we initiated the synthesis of BINAP (2,2’-bis(diphenylphosphino)-1,1’- binaphthyl) [J. Am. Chem. Soc. 1980, 102, 1932] in 1974 at Nagoya with the help of H. Takaya, my respected long-term collaborator. BINAP was a new fully aromatic, axially dissymmetric C2 chiral diphosphine that would exert strong steric and electronic influences on transition metal complexes. Its properties could be fine-tuned by substitutions on the aromatic rings. … Ryoji Noyori, Nobel Lecture, December 8, 2001

2,2'-bis(diphenylphosphino)-1,1'- binaphthyl Synthesis from BINOL

Asymmetric Hydrogenation (Noyori et al.) …in the Isomerization of allylic amines..to reduce B-keto esters

Limited routes to axially chiral biphenyls I.Direct asymmetric Coupling Fusion of two naphthol rings using transition metals II. Atropselective transformation of preformed biaryls

Is there a better way??.... Yes!

Spectroscopic Confirmation

Scope of Methodology

(-)allocolchicine(-)steganacin Some Natural Products

Acknowledgements Dr. Davis Ben Roembke