Enantioselective Rhodium‐Catalyzed Addition of Arylboronic Acids to α‐Ketoesters

Abstract

The transition-metal-catalyzed asymmetric addition of organometallic reagents to carbonyl compounds to produce enantiomer-enriched secondary or tertiary alcohols is a powerful tool for the construction of carbon-carbon bonds. Many organometallic reagents have been successfully used in this addition reaction.[1] However, a drawback for most organometallic reagents is their sensitivity to moisture and air, both of which impede the practical applications of these asymmetric carbon-carbon bond-forming reactions. As an exception, arylboronic acids are very stable to air and moisture. The catalytic enantioselective addition of arylboronic acids to carbonyl compounds has became a current focus for research, [1d] and a number of efficient chiral catalysts have been developed for the catalytic asymmetric addition of arylboronic acids to aldehydes [2] and aldimines.[3] However, the catalytic asymmetric addition of arylboronic acids to ketones, which are less active relative to aldehydes and aldimines, is more difficult, and only limited progress has been achieved. In 2006, Hayashi et al. reported the asymmetric addition of arylboronic acids to isatins, cyclic aketoamides, catalyzed by a rhodium/MeO-Mop (MeO-Mop = 2-methoxy-2'-diphenylphosphino-1,1'-binaphthyl) complex in high enantioselectivities (72-91 % ee).[4] By using a chiral phosphoramidite ligand derived from H 8 -binol (binol = 2,2'-dihydroxy-1,1'-binaphthyl), de Vries, Minnard, Feringa and et al. obtained 55 % ee in the same reaction.[5] The chiral phosphoramidite ligand was also used in the asymmetric addition of arylboronic acids to trifluoromethyl ketones with good enantioselectivities (50-83 % ee).[6] The intramolecular asymmetric addition of arylboronic acids to ketones catalyzed by a cationic palladium complex of binap (binap = 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl) to give cyclic tertiary alcohols in high enantioselectivities (53-96 % ee) was reported by Lu et al. [7] To the best of our knowledge, the catalytic enantioselective addition of arylboronic acids to aketoesters to provide tertiary a-hydroxyesters has not yet been reported. [8] In the search for highly efficient methods to construct chiral 2-hydroxydiarylacetates, desirable chiral intermediates for the synthesis of antagonists of muscarinic receptors, [9] we became interested in the enantioselective addition of arylboronic acids to the a-aryl-and a-alkenyl-a-ketoesters. The Rh I /ShiP (ShiP = aryl(1,1'-spirobiindane-7,7'-diyl)phosphite) catalysts (1) recently developed by us [2c, 3b] were found to be highly efficient for this addition reaction to provide chiral tertiary a-hydroxyesters [10] in good yields and high enantiomeric excesses (up to 93 % ee).Preliminary experiments were carried out in H 2 O with catalyst generated in situ from 1.5 mol % [{RhCl-(CH 2 CH 2 ) 2 } 2 ][11] and 6 mol % (S)-1 a in the presence of two equivalents of LiF.[12] The addition of phenylboronic acid to ethyl 2-(4-chlorophenyl)-2-oxoacetate (2 a) at room temperature for 48 hours afforded tertiary a-hydroxyeste...

Access to enantioenriched compounds bearing challenging tetrasubstituted stereocenters via kinetic resolution of auxiliary adjacent alcohols

“…Actually, the method shows no limitation with respect to the steric and electronic difference of the two aryl substituents, and furthermore, through simply changing the synthesis route of the racemic substrates, both enantiopure diastereomeric diols can be obtained, as witnessed by 1b and 1j (the absolute configurations are opposite at the tertiary alcohol units). In literature reports, Rh-catalyzed asymmetric addition of aryl boric acids to ketones has been developed to make diaryl tertiary alcohols, but the system is usually compatible with activated ketones such as trifluoromethyl ketones and α-ketocarbonyls 21 , 54 , 55 . Titanium-catalyzed asymmetric Grignard addition to aryl ketones has also been developed, but in most cases, methyl aryl ketones were tested to give moderate ee, and ethyl aryl ketone proved inert to the reaction 20 .…”

Rhodium‐Catalyzed Asymmetric Arylation of β,γ‐Unsaturated α‐Ketoamides for the Construction of Nonracemic γ,γ‐Diarylcarbonyl Compounds

“…However, these substrates are particularly challenging for rhodium‐catalyzed asymmetric conjugate additions, owing to the high reactivity of the α‐keto moiety, which promotes 1,2‐addition 9. For instance, Zhou and co‐workers demonstrated a rhodium‐catalyzed asymmetric addition of arylboronic acids to ( E )‐benzyl‐2‐oxo‐4‐phenylbut‐3‐enoate using a spirophosphine ligand, to furnish the 1,2‐addition products with excellent yields and enantioselectivities (Scheme , Equation 1) 9c. Another challenge with these substrates is their ability to undergo sequential 1,4‐ and 1,2‐addition, which might complicate the reaction system.…”

Synthesis of Chiral Olefin Ligands and their Application in Asymmetric Catalysis

“…[44,45] In 2012, Xu and co-workers reported the Rh-catalyzed asymmetric addition of arylboronic acids 25 to a-ketoesters or a-diketones 90 with the use of ligand 71 and a 3 mol % catalyst loading to afford a series of tertiary a-hydroxy carbonyl compounds 91 in 45-99 % yields with 63-99 % ee (Scheme 26). The adducts can be transformed into chiral 1,3-dihydroisobenzofuran compounds, which have antidepressant activity, without loss of optical purity (Scheme 26).…”