Chiral Dirhodium Research Articles

Rhodium-Catalyzed B-H Bond Insertion Reactions of Unstabilized Diazo Compounds Generated in Situ from Tosylhydrazones.

Although transition-metal-catalyzed B-H bond insertion of carbenes into stable borane adducts has emerged as a promising method for organoborane synthesis, all the diazo compounds used to date as carbene precursors have had an electron-withdrawing group to stabilize them. Herein, we report a protocol for rhodium-catalyzed B-H bond insertion reactions of unstabilized diazo compounds generated in situ from tosylhydrazones. In addition, by using chiral dirhodium catalysts, we also achieved an asymmetric version of the reaction with good to excellent enantioselectivities (up to 98:2 e.r.). This is the first enantioselective heteroatom-hydrogen bond insertion reaction to use unstabilized diazo compounds as carbene precursors. The protocol exhibited good functional group tolerance and could be carried out on a gram scale. It also enabled one-pot transformation of a carbonyl group to a boryl group enantioselectively. The B-H bond insertion products could be easily transformed into chiral alcohols and other widely used organoboron reagents with enantiomeric fidelity.

Chiral Dirhodium(II) Carboxylates: New Insights into the Effect of Ligand Stereo-Purity on Catalyst Structure and Enantioselectivity

The current report contributes to the understanding of the stereoselectivity of chiral dirhodium(II) carboxylate catalysts carrying N-protected tert-leucine ligands. Investigating the possible effect of ligand stereo-purity on catalyst structure and enantioselectivity was carried out. This was justified through a new X-ray crystal structure for Rh2(S,S,S,R-PTTL)4 diastereomer.

Construction of All‐Carbon Quaternary Stereocenters via Asymmetric Cyclopropanations: Synthesis of Chiral Carbocyclic Pyrimidine Nucleosides

AbstractAn efficient route to synthesize chiral carbocyclic pyrimidine nucleoside analogues containing all‐carbon quaternary stereocenters has been established via the asymmetric intermolecular cyclopropanation of N1‐vinylpyrimidines and α‐aryl diazoesters. With 2 mol% of chiral dirhodium (II) carboxylate complex as the catalyst, a variety of chiral carbocyclic cytosine or uracil nucleoside analogues were obtained in good yields (up to 96% yield), high diastereoselectivities (>20:1 dr), and excellent enantioselectivities (up to 99% ee).magnified image

On the Structure of Chiral Dirhodium(II) Carboxylate Catalysts: Stereoselectivity Relevance and Insights

Modern experiments have offered alternative interpretations on the symmetry of chiral dirhodium(II) carboxylate complexes and its relationship to their level of enantioselectivity. So, this contribution is to provide an insight on how the knowledge around the structure of these catalysts has evolved with a particular emphasis on the impact of this knowledge on enantioselectivity prediction and catalyst design.

A Binaphthyl-Based Scaffold for a Chiral Dirhodium(II) Biscarboxylate Ligand with α-Quaternary Carbon Centers

A chiral dirhodium(II) paddlewheel complex has been synthesized from biscarboxylate ligands derived from BINOL, and the resulting complex has been used in enantioselective carbene/alkyne cascade reactions. The ligand design was guided by requirements of α,α-dimethyl substituted carboxylates and bidentate ligands to ensure high levels of catalytic activity. Previously disclosed chiral complexes lack these features, resulting in low product yields. The design successfully replicated or exceeded the yields of the unusually effective achiral catalyst for the cascade reaction, Rh2(esp)2, which often shows unique reactivity. Promising enantioselectivity was observed for aldehyde-derived hydrazone substrates (29–96% ee), showing that the new scaffold has significant potential.

Highly Regio-, Diastereo-, and Enantioselective Rhodium-Catalyzed Intramolecular Cyclopropanation of (Z)-1,3-Dienyl Aryldiazoacetates.

Chiral cyclopenta[2,3]cyclopropa[1,2-c]pyran-4-ones have been synthesized via dirhodium(II)-catalyzed intramolecular cyclopropanation of (Z)-1,3-dienyl aryldiazoacetates. High regio-, diastereo-, and enantiocontrol were achieved using chiral dirhodium 2-phthalimide carboxylates. Preferential addition occurs at the 3,4- rather than the 1,2-double bond with the chiral dirhodium catalysts, although both outcomes occur with other transition-metal catalysts.

Catalytic B-H Bond Insertion Reactions Using Alkynes as Carbene Precursors.

Herein, we report transition-metal-catalyzed B-H bond insertion reactions between borane adducts and alkynes to afford organoboron compounds in excellent yields under mild reaction conditions. This successful use of alkynes as carbene precursors in these reactions constitutes a new route to organoboron compounds. The starting materials are safe and readily available, and the reaction exhibits 100% atom-economy. Moreover, an asymmetric version catalyzed by chiral dirhodium complexes produced chiral boranes with excellent enantioselectivity (up to 96% ee). This is the first report of highly enantioselective heteroatom-hydrogen bond insertion reactions of metal carbenes generated in situ from alkynes. The chiral products of the reaction could be easily transformed to widely used borates and diaryl methanol compounds without loss of optical purity, which demonstrates its potential utility in organic synthesis. A kinetics study indicated that the Cu-catalyzed B-H bond insertion reaction is first order with respect to the catalyst and the alkyne and zero order with respect to the borane adduct, and no kinetic isotopic effect was observed in the reaction of the adduct. These results, along with density functional theory calculations, suggest that the formation of the Cu carbene is the rate-limiting step and that the B-H bond insertion is a fast, concerted process.

Stabilization of a Chiral Dirhodium Carbene by Encapsulation and a Discussion of the Stereochemical Implications.

For the first time, the stereochemical course of an asymmetric cyclopropanation can be discussed on the basis of experimental structural information on a pertinent chiral dirhodium carbene intermediate. Key to success was the formation of racemic single crystals of a heterochiral [Rh2 {(S*)-PTTL}4 {=C(Ar)COOMe}][Rh2 {(R*)-PTTL}4 ] (Ar=MeOC6 H4 ; PTTL=N-phthaloyl-tert-leucinate) capsule, which has been characterized by X-ray diffraction. NMR spectroscopic data confirm that the obtained structural portrait is also relevant in solution and provide additional information about the dynamics of this species. The chiral binding pocket is primarily defined by the conformational preferences of the N-phthaloyl-protected amino acid ligands and reinforced by a network of weak interligand interactions that get stronger when chlorinated phthalimide residues are used.

Stabilization of a Chiral Dirhodium Carbene by Encapsulation and a Discussion of the Stereochemical Implications

AbstractFor the first time, the stereochemical course of an asymmetric cyclopropanation can be discussed on the basis of experimental structural information on a pertinent chiral dirhodium carbene intermediate. Key to success was the formation of racemic single crystals of a heterochiral [Rh2{(S*)‐PTTL}4{=C(Ar)COOMe}][Rh2{(R*)‐PTTL}4] (Ar=MeOC6H4; PTTL=N‐phthaloyl‐tert‐leucinate) capsule, which has been characterized by X‐ray diffraction. NMR spectroscopic data confirm that the obtained structural portrait is also relevant in solution and provide additional information about the dynamics of this species. The chiral binding pocket is primarily defined by the conformational preferences of the N‐phthaloyl‐protected amino acid ligands and reinforced by a network of weak interligand interactions that get stronger when chlorinated phthalimide residues are used.

Catalytic Asymmetric Synthesis of Cyclopentyl β‐Amino Esters by [3+2] Cycloaddition of Enecarbamates with Electrophilic Metalloenolcarbene Intermediates

AbstractChiral cyclopentyl β‐amino esters are formed catalytically by [3+2] cycloaddition reactions of enecarbamates with electrophilic metalloenolcarbenes in high yield with up to 98 % ee and excellent diastereocontrol. Use of β‐silyl‐substituted enoldiazoacetates with a chiral dirhodium catalyst and trans‐β‐arylvinylcarbamates are optimal for this transformation, which occurs with hydrogen‐bond association between the vinylcarbamate and the intermediate metalloenolcarbene. Reductive conversion of the protected amino esters forms highly functionalized cyclopentyl β‐amino acids and 3‐aminocyclopentanones.

Catalytic Asymmetric Synthesis of Cyclopentyl β‐Amino Esters by [3+2] Cycloaddition of Enecarbamates with Electrophilic Metalloenolcarbene Intermediates

Chiral cyclopentyl β-amino esters are formed catalytically by [3+2] cycloaddition reactions of enecarbamates with electrophilic metalloenolcarbenes in high yield with up to 98 % ee and excellent diastereocontrol. Use of β-silyl-substituted enoldiazoacetates with a chiral dirhodium catalyst and trans-β-arylvinylcarbamates are optimal for this transformation, which occurs with hydrogen-bond association between the vinylcarbamate and the intermediate metalloenolcarbene. Reductive conversion of the protected amino esters forms highly functionalized cyclopentyl β-amino acids and 3-aminocyclopentanones.

ChemInform Abstract: Design and Synthesis of Novel Chiral Dirhodium(II) Carboxylate Complexes for Asymmetric Cyclopropanation Reactions.

AbstractA novel approach to the design of dirhodium(II) tetracarboxylates derived from (S)‐amino acid ligands is reported.

Design and Synthesis of Novel Chiral Dirhodium(II) Carboxylate Complexes for Asymmetric Cyclopropanation Reactions.

A novel approach to the design of dirhodium(II) tetracarboxylates derived from (S)-amino acid ligands is reported. The approach is founded on tailoring the steric influences of the overall catalyst structure by reducing the local symmetry of the ligand's N-heterocyclic tether. The application of the new approach has led to the uncovering of [Rh2 (S-tert PTTL)4 ] as a new member of the dirhodium(II) family with extraordinary selectivity in cyclopropanation reactions. The stereoselectivity of [Rh2 (S-tert PTTL)4 ] was found to be comparable to that of [Rh2 (S-PTAD)4 ] (up to >99 % ee), with the extra benefit of being more synthetically accessible. Correlations based on X-ray structures to justify the observed enantioinduction are also discussed.

ChemInform Abstract: Chiral Dirhodium Catalysts Derived from L‐Serine, L‐Threonine and L‐Cysteine: Design, Synthesis and Application.

A series of dirhodium tetrakis((4S)-3-(arylsulfonyl)oxazolidine-4-carboxylate), dirhodium tetrakis((4S,5R)-5-methyl-3-(arylsulfonyl)oxazolidine-4-carboxylate) and dirhodium tetrakis((4R)-3-(arylsulfonyl)thiazolidine-4-carboxylate 1,1-dioxide) complexes with different para-substituted arylsulfonyl groups (e.g. –NO2, –F, –CF3, –Me, –tBu, –OMe and –nC12H25) derived from L-serine, L-threonine and L-cysteine, respectively, were prepared with yields in the range of 40–87% through refluxing ligands in water with Na4Rh2(CO3)4. These chiral Rh(II) complexes have been fully characterized by EA, IR, UV-vis, NMR and specific rotation measurements. They are found to be effective chiral catalysts for asymmetric aziridination and cyclopropanation reactions in terms of reactivity and enantioselectivity. They are extremely stable and can be stored for a long period (at least 18 months) on the bench without adversely affecting their reactivity and selectivity. The heterocyclic rings as well as the substituents on the arylsulfonyl groups have critical effects on the degree of asymmetric induction. In general, a higher enantioselectivity was observed in the reactions catalyzed by the oxazolidine-4-carboxylate-derived catalysts than the thiazolidine-4-carboxylate 1,1-dioxide-based catalysts. Among these 21 new Rh(II) catalysts, the uses of dirhodium tetrakis((4S)-3-((4-dodecylphenyl)sulfonyl)oxazolidine-4-carboxylate) (Rh2(4S-DOSO)4) and dirhodium tetrakis((4S,5R)-5-methyl-3-((4-nitrophenyl)sulfonyl)oxazolidine-4-carboxylate) (Rh2(4S,5R-MNOSO)4) resulted in the highest levels of enantioselectivity in aziridination (94% ee) and cyclopropanation (98% ee) of styrene, respectively. The successful design and syntheses of these novel Rh(II) complexes enlarged the scope of accessible chiral dirhodium(II) catalysts.

Chiral Dirhodium(II) Catalysts for Selective Metal Carbene Reactions

Dirhodium(II) catalysts have proven effectiveness in controlling selectivity in metal carbene reactions of diazocarbonyl compounds. Over the years many dirhodium(II) paddlewheel derivatives with chiral ligands have been advanced, but three structural classes have emerged as being most effective for inducing high stereocontrol: chiral dirhodium carboxamidates derived from cyclic chiral carboxamides and chiral dirhodium carboxylic acids derived from sybstituted chiral prolinates or from phthalimide-protected α-amino acids. This review focuses on describing which of these classes of chiral dirhodium(II) catalysts have provided the highest levels of stereocontrol in intramolecular and intermolecular reactions of diazoacetates, diazoacetoacetates and diazomalonates, vinyl- and aryldiazoacetates, and enoldiazoacetates. Assessment is taken from published results that compare catalyst results for cyclopropanation, cyclopropenation, C-H insertion, ylide formation and reactions, as well as cycloaddition reactions, especially [3+3]- and [4+3]-cycloaddition. Keywords: Chiral durhodium(II) catalysts, acceptor-acceptor metal carbenes, donor-acceptor metal carbenes, enoldiazoacetates, enantioselectivity, cycloaddition, insertion, cyclopropanation.

ChemInform Abstract: Diastereo‐ and Enantioselective Cyclopropanation of Alkyenyl Fluorides with Benzyl Diazoarylacetates.

AbstractThe cyclopropanation reaction is conducted in the presence of a chiral dirhodium catalyst and allows the synthesis of cis‐β‐fluorocyclopropane carboxylates with high diastereoselectivities and enantioselectivities.

ChemInform Abstract: Enantioselective cis‐β‐Lactam Synthesis by Intramolecular C—H Functionalization from Enoldiazoacetamides and Derivative Donor—Acceptor Cyclopropenes.

β-Lactam derivatives are produced through intermediate donor–acceptor cyclopropene intermediates in high yield, exclusive cis-diastereoselectivity, and high enantiocontrol in a chiral dirhodium carboxylate catalyzed intramolecular C–H functionalization reaction of enoldiazoacetamides.

ChemInform Abstract: Diastereo‐ and Enantioselective Intramolecular 1,6‐C—H Insertion Reactions of α‐Diazo Esters Catalyzed by Chiral Dirhodium(II) Carboxylates.

AbstractThe first catalytic asymmetric 1,6‐C—H insertion reaction of α‐diazo esters catalyzed by 1 mol % of a chiral Rh‐complex is developed which provides facile access to optically active oxygen‐containing six‐membered cyclic core structures of biologically active natural products and pharmaceutical agents.

Enantioselective dirhodium(II)-catalyzed cyclopropanations with trimethylsilylethyl and trichloroethyl aryldiazoacetates

Highly functionalized cyclopropanecarboxylates were readily prepared by rhodium-catalyzed cyclopropanation of alkenes with aryldiazoacetates and styryldiazoaceates, in which the ester functionality is either trimethylsilylethyl (TMSE) or trichloroethyl (TCE). By having labile protecting groups on the ester, chiral triarylcyclopropane carboxylate ligands were conveniently prepared. The asymmetric induction during cyclopropanation is dependent on the nature of the ester group and the chiral dirhodium tetracarboxylate catalyst. The prolinate catalyst Rh2(S-DOSP)4 was the optimum catalyst for asymmetric intermolecular cyclopropanation of TMSE diazoesters with styrene, while Rh2(R-BPCP)4 was the optimum catalyst for TCE diazoesters.

ChemInform Abstract: An Efficient Route to Highly Enantioenriched Tetrahydroazulenes and β‐Tetralones by Desymmetrization Reactions of δ,δ‐Diaryldiazoaceto‐acetates.

A highly stereoselective desymmetrization reaction of δ,δ-diaryl-α-diazo-β-ketoesters catalyzed by chiral dirhodium carboxylates forms aromatic cycloaddition products in up to 97% ee.