Enantioselective Oxidative Homocoupling and Cross-Coupling of 2-Naphthols Catalyzed by Chiral Iron Phosphate Complexes

Abstract

Novel chiral iron phosphate complexes were prepared as catalysts for asymmetric oxidative coupling reactions. These catalysts were applied for the synthesis of enantio-enriched C- and C-symmetric BINOLs, in which the 3 and 3' positions are available for chemical modifications. It was proposed that the reaction takes place via an oxidative radical-anion coupling mechanism. A destructive BINOL racemization that competes with the enantioselective oxidative coupling of 2-naphthols was revealed, thereby offering new insights into this highly important reaction.

Lipase‐Catalyzed Dynamic Kinetic Resolution of C1‐ and C2‐Symmetric Racemic Axially Chiral 2,2′‐Dihydroxy‐1,1′‐biaryls

“…In addition, the enantioselective oxidative couplings of 2‐naphthol derivatives catalyzed by chiral, non‐racemic copper, iron, and vanadium complexes provides a more direct and atom‐economical route to C 2 ‐symmetric BINOLs . Unfortunately, the latter approach can suffer from product racemization leading to a drop in optical purity because this oxidative coupling proceeds through the formation of radical intermediates and similar coupling‐product radicals are also generated under the same reaction conditions, particularly in the case of BINOL itself and its 6,6′‐disubstituted derivatives –. Substrates are also limited when certain metal catalysts are used for oxidative coupling –.…”

“…Similarly, the practical asymmetric synthesis of optically active C 1 ‐symmetric, i.e., unsymmetrically substituted, BINOLs by oxidative coupling is still underdeveloped, which is, in part, due to the unavoidable formation of homocoupling products; in some cases, the preferred cross‐coupling specifically requires the coupling of 2‐naphthol partners of sufficiently different oxidation potential. Apart from Katsuki's report on the asymmetric synthesis of 3‐substituted C 1 ‐symmetric BINOLs through the iron(salen)‐mediated cross‐couplings of 3‐substituted 2‐naphthols with 6‐substituted 2‐naphthols, the group of Pappo reported an iron phosphate‐catalyzed cross‐coupling en route to enantio‐enriched 3‐unsubstituted C 1 ‐symmetric BINOLs . However, undesired racemization in the latter approach decreased the optical purity of the products.…”

Synthetic Applications of Oxidative Aromatic Coupling—From Biphenols to Nanographenes

“…Pappo and co‐workers developed a new chiral iron complex 99 bearing three BINOL‐phosphate ligands which turned out to be a very efficient catalyst for the enantioselective homo‐ and cross‐coupling of 2‐naphthols . Scheme presents selected examples of BINOLs ( 98 a – f ) prepared with good ee values using as little as 2.5 mol % of catalyst 99 in a mixture of DCE and HFIP as a solvent and with di‐ tert ‐butyl peroxide (1 equiv) as a terminal oxidant.…”

“…Reviews turned out to be av ery efficient catalyst for the enantioselective homo-and cross-coupling of 2-naphthols. [92] Scheme 14 presents selected examples of BINOLs (98 a-f) prepared with good ee values using as little as 2.5 mol %o f catalyst 99 in am ixture of DCE and HFIP as as olvent and with di-tert-butyl peroxide (1 equiv) as at erminal oxidant. Importantly,t he authors have also found that enantiopure BINOLs undergo racemization in the presence of Fe III and Cu II salts,w hich may reduce the enantiomeric excess of the products from the oxidative coupling.I nt he case of crosscoupling,t he reaction yields were significantly lower due to the formation of homocoupled side products.N evertheless, this is one of only af ew examples of enantioselective oxidative cross-coupling reactions to date.…”

Isothiourea‐Catalysed Regioselective Acylative Kinetic Resolution of Axially Chiral Biaryl Diols

“…[3] Enantiopure samples of these axially chiral biaryl compounds are typically prepared through classical stoichiometric resolution methods, and as such there is current interesti nt he development of alternative routes to these important compounds. [4] The catalytic enantioselective synthesis of BINOL derivatives can be achieved through the oxidative homocoupling of naphthols, [5] however somel imitations in substrates cope and enantioselectivity makes the development of alternative methods attractive. Recently an umber of catalytic methods have been reportedf or the kinetic resolution (KR) [6] of O-and/or N-protected BINOL and NOBIN derivatives [7] using enzymes, [8] transition metals, [9] and organocatalysts.…”