Base‐Free Conditions for Rhodium‐Catalyzed Asymmetric Arylation To Produce Stereochemically Labile α‐Aryl Ketones

The asymmetric arylation of 2,2‐dialkyl cyclopent‐4‐ene‐1,3‐diones with aryl boronic acids was found to be efficiently catalyzed by a chiral diene–rhodium μ‐chloro dimer, [{RhCl((R)‐diene*)}₂], in the absence of bases in toluene/H₂O to give 2,2‐dialkyl 4‐aryl cyclopentane‐1,3‐diones in high yields with high enantioselectivity. Such compounds can not be obtained with high enantiomeric purity under the standard basic conditions used for rhodium‐catalyzed asymmetric arylation because the α‐aryl ketone products undergo racemization under the basic conditions.     

Traceless Chelation‐Controlled Rhodium‐Catalyzed Intermolecular Alkene and Alkyne Hydroacylation

A new functional‐group tolerant, rhodium‐catalyzed, sulfide‐reduction process is combined with rhodium‐catalyzed chelation‐controlled hydroacylation reactions to give a traceless hydroacylation protocol. Aryl‐ and alkenyl aldehydes can be combined with both alkenes, alkynes and allenes to give traceless products in high yields. A preliminary mechanistic proposal is also presented.     

Rhodium‐Catalyzed Arylative Cyclization for the Enantioselective Synthesis of (Trifluoromethyl)cyclobutanols

A rhodium‐catalyzed cyclization of 1‐(trifluoromethyl)‐4‐alkyn‐1‐ones with arylboronic acids is described to yield a novel class of small rings: (trifluoromethyl)cyclobutanols bearing an exocyclic double bond. The use of a rhodium/chiral diene complex allowed the reaction to proceed under mild conditions, often with high enantioselectivity. An X‐ray crystal structure was obtained confirming the formation of the four‐membered ring products.     

Rhodium‐catalyzed Asymmetric Hydrogenation of α‐Dehydroamino Ketones: A General Approach to Chiral α‐amino Ketones

Rhodium/DuanPhos‐catalyzed asymmetric hydrogenation of aliphatic α‐dehydroamino ketones has been achieved and afforded chiral α‐amino ketones in high yields and excellent enantioselectives (up to 99 % ee), which could be reduced further to chiral β‐amino alcohols by LiAlH(tBuO)₃ with good yields_. This protocol provides a readily accessible route for the synthesis of chiral α‐amino ketones and chiral β‐amino alcohols.     

Highly Enantioselective Rhodium‐Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram

Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)‐WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)‐WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram.     

Rhodium(I)/Chiral Diene‐Catalyzed Enantioselective Addition of Boronic Acids to N‐Unsubstituted Isatin‐Derived Ketimines

Enantioselective addition of boronic acids to N‐unsubstituted isatin‐derived ketimines was realized using rhodium(I)/chiral diene catalysts. The reactions can be performed in the presence of catalytic amounts of a base to give adducts in high yield with high enantioselectivity. Preliminary mechanistic information including a computational model to explain the observed enantioselectivity is also provided.     

Substrate‐Directed Hydroacylation: Rhodium‐Catalyzed Coupling of Vinylphenols and Nonchelating Aldehydes

We report a protocol for the hydroacylation of vinylphenols with aryl, alkenyl, and alkyl aldehydes to form branched products with high selectivity. This cross‐coupling yields α‐aryl ketones that can be cyclized to benzofurans, and it enables access to eupomatenoid natural products in four steps or less from eugenol. Excellent reactivity and high levels of regioselectivity for the formation of the branched products were observed. We propose that aldehyde decarbonylation is avoided by the use of an anionic directing group on the alkene and a diphosphine ligand with a small bite angle.     

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

A highly regio‐ and enantioselective rhodium‐catalyzed 1,4‐addition of arylboronic acids to β,γ‐unsaturated α‐ketoamides using a simple new chiral sulfinylphosphine ligand is described. This transformation provides an attractive approach to construct chiral nonracemic γ,γ‐diarylsubstituted carbonyl compounds, as exemplified in the concise syntheses of sertraline and tetrahydroquinoline‐2‐carboxylamide.     

Asymmetric Synthesis of Axially Chiral 2‐Aminobiaryls by Rhodium‐Catalyzed Benzannulation of 1‐Arylalkynes with 2‐(Cyanomethyl)phenylboronates

Asymmetric benzannulation of 1‐arylalkynes, where the aryl group is an ortho‐substituted aromatic group, with 2‐(cyanomethyl)phenylboronate was catalyzed by a rhodium complex coordinated with a chiral diene ligand to give high yields of axially chiral 2‐aminobiaryls with greater than 90 % ee.     

Rhodium‐Catalyzed Sequential Allylic Amination and Olefin Hydroacylation Reactions: Enantioselective Synthesis of Seven‐Membered Nitrogen Heterocycles

Dynamic kinetic asymmetric amination of branched allylic acetimidates has been applied to the synthesis of 2‐alkyl‐dihydrobenzoazepin‐5‐ones. These seven‐membered‐ring aza ketones are prepared in good yield with high enantiomeric excess by rhodium‐catalyzed allylic substitution with 2‐amino aryl aldehydes followed by intramolecular olefin hydroacylation of the resulting alkenals. This two‐step procedure is amenable to varied functionality and proves useful for the enantioselective preparation of these ring systems.