Asymmetric Rh Research Articles

Systematic Parameter Determination Aimed at a Catalyst-Controlled Asymmetric Rh(I)-Catalyzed Pauson–Khand Reaction

Systematic Parameter Determination Aimed at a Catalyst-Controlled Asymmetric Rh(I)-Catalyzed Pauson–Khand Reaction

Concave P-Stereogenic Phosphorodiamidite Ligands for Enantioselective Rh(I) Catalysis.

The development of a new class of concave P-stereogenic phosphorodiamidite ligands, derived from Tröger's bases (TBs), is explored. These ligands, characterized by their remarkable stability and unique structural geometry around the P atom, are used in asymmetric Rh(I)-catalyzed additions of boronic acids to NH-isatins resulting in excellent reactivities and reasonable enantioselectivity (er up to 92:8).

Cooperative Rh(II)/Pd(0) Dual‐Catalyzed gem‐Difunctionalization of α‐Diazo Carbonyl Compounds: Construction of Quaternary Carbon Centers

AbstractThe efficient construction of quaternary carbon centers is a challenging task due to their enhanced structural complexity. Although the catalytic gem‐difunctionalization of α‐diazo carbonyl compounds via metal‐carbenoids is well‐documented, developing new methods to access quaternary carbon centers which are difficult or unattainable in monocatalysis is highly desirable. Dual catalysis where two different catalysts work concurrently has emerged as a powerful strategy to achieve new reactivity and selectivity. In this review, we highlight the recent advances in cooperative Rh(II)/Pd(0) dual catalysis for the construction of quaternary carbon centers, focusing on the synthetic utility of stable α‐diazo‐β‐keto‐esters and allylic carboxylates. Additionally, several challenging asymmetric Rh(II)/Pd(0) dual‐catalyzed transformations generating chiral quaternary carbon centers are also discussed.

Mechanistic investigation of Rh(i)-catalysed asymmetric Suzuki–Miyaura coupling with racemic allyl halides

Understanding how catalytic asymmetric reactions with racemic starting materials can operate would enable new enantioselective cross-coupling reactions that give chiral products. Here we propose a catalytic cycle for the highly enantioselective Rh(i)-catalysed Suzuki–Miyaura coupling of boronic acids and racemic allyl halides. Natural abundance 13C kinetic isotope effects provide quantitative information about the transition-state structures of two key elementary steps in the catalytic cycle, transmetallation and oxidative addition. Experiments with configurationally stable, deuterium-labelled substrates revealed that oxidative addition can happen via syn- or anti-pathways, which control diastereoselectivity. Density functional theory calculations attribute the extremely high enantioselectivity to reductive elimination from a common Rh complex formed from both allyl halide enantiomers. Our conclusions are supported by analysis of the reaction kinetics. These insights into the sequence of bond-forming steps and their transition-state structures will contribute to our understanding of asymmetric Rh–allyl chemistry and enable the discovery and application of asymmetric reactions with racemic substrates. A major drive in current chemistry research is to develop asymmetric versions of widely used carbon–carbon bond-forming reactions, such as Suzuki-Miyaura cross-couplings. Now, the origins of diastereo- and enantioselectivity in a Rh-catalysed cross-coupling of boronic acid and racemic allyl halides have been established.

Asymmetric Catalysis in Liquid Confinement: Probing the Performance of Novel Chiral Rhodium-Diene Complexes in Microemulsions and Conventional Solvents.

The role of liquid confinement on the asymmetric Rh catalysis was studied using the 1,2-addition of phenylboroxine (2) to N-tosylimine 1 in the presence of [RhCl(C2 H4 )2 ]2 and chiral diene ligands as benchmark reaction. To get access to Rh complexes of different polarity, enantiomerically pure C2 -symmetric p-substituted 3,6-diphenylbicyclo[3.3.0]octadienes 4 and diastereomerically enriched unsymmetric norbornadienes 5 and 6 carrying either the Evans or the SuperQuat auxiliary were synthesized. A microemulsion containing the equal amounts of H2 O/KOH and toluene/reactants was formulated using the hydrophilic sugar surfactant n-octyl β-d-glucopyranoside (C8 G1 ) to mediate the miscibility between the nonpolar reactants and KOH, needed to activate the Rh-diene complex. Prominent features of this organized reaction medium are its temperature insensitivity as well as the presence of water and toluene-rich compartments with a domain size of 55 Å confirmed by small-angle X-ray scattering (SAXS). Although bicyclooctadiene ligands 4 a,b,e performed equally well under homogeneous and microemulsion conditions, ligands 4 c,d gave a different chemoselectivity. For norbornadienes 5, 6, however, microemulsions markedly improved conversion and enantioselectivity as well as reaction rate, as was confirmed by kinetic studies using ligand 5 b.

Asymmetric Rh(I)-Catalyzed Functionalization of the 3-C( sp3)-H Bond of Benzofuranones with α-Diazoesters.

An asymmetric Rh(I)-catalyzed functionalization of the 3-C( sp3)-H bond of benzofuranones with α-diazoesters has been developed, providing a new strategy for the stereoselective 3-alkylation of benzofuranones. With low catalyst loadings (low to 0.02 mol % Rh), a number of benzofuranones bearing consecutive quaternary and tertiary stereogenic centers have been synthesized (up to 94% yield, 95:5 dr, and >99% ee). The synthetic utilities of this methodology have been demonstrated by elaborating the model product 3aa to a series of enantiopure compounds with similarities to natural products and drug candidates.

Asymmetric Rh(II)/Pd(0) Relay Catalysis: Synthesis of α-Quaternary Chiral β-Lactams through Enantioselective C–H Insertion/Diastereoselective Allylation of Diazoamides

A straightforward route toward construction of α-quaternary chiral β-lactam moiety via Rh(II)/Pd(0)-catalyzed stereoselective relay catalytic reaction is reported. This asymmetric dual relay catalysis involves Rh(II)-catalyzed enantioselective intramoluecular C–H insertions of α-diazoamides, and sequential Pd(0)-catalyzed diastereoselective intermolecular allylic alkylation. Under mild reaction conditions, a broad range of α-quaternary allylated chiral β-lactams have been synthesized in high yields (up to 99%) with excellent stereoselectivities [up to diastereomeric ratio (dr) >99:1, up to 98% enantiomeric excess (ee)].

Designing P-Chirogenic 1,2-Diphosphinobenzenes at Both P-Centers Using P(III)-Phosphinites.

A new enantiodivergent synthesis of P-chirogenic 1,2-diphosphinobenzenes (DP*B) bearing the chirality on one or both phosphorus centers is reported using aryne chemistry. The principle is based on successive reactions of 1,2-dibromobenzene with sec-phosphide boranes, then DABCO to remove the borane, and finally with chlorophosphines or P(III)-chirogenic phosphinites. The efficiency of this synthesis was demonstrated by the stereoselective preparation of (S,S)-1,2-bis(o-anisylphenylphosphino)benzene. A comparison of DIPAMP and homochiral DP*B ligands in asymmetric Rh- or Pd-catalyzed reactions was reported.

Chiral Cyclopentadienyls: Enabling Ligands for Asymmetric Rh(III)-Catalyzed C-H Functionalizations.

Transition-metal catalyzed C-H functionalizations became a complementary and efficient bond-forming strategy over the past decade. In this respect, Cp*Rh(III) complexes have emerged as powerful catalysts for a broad spectrum of reactions giving access to synthetically versatile building blocks. Despite their high potential, the corresponding catalytic enantioselective transformations largely lag behind. The targeted transformations require all the remaining three coordination sites of the central rhodium atom of the catalyst. In consequence, the chiral information on a competent catalyst can only by stored in the cyclopentadienyl unit. The lack of suitable enabling chiral cyclopentadienyl (Cp(x)) ligands is the key hurdle preventing the development of such asymmetric versions. In this respect, an efficient set of chiral Cp(x) ligands useable with a broad variety of different transition-metals can unlock substantial application potential. This Account provides a description of our developments of two complementary classes of C2-symmetric Cp(x) derivatives. We have introduced a side- and back-wall concept to enforce chirality transfer onto the central metal atom. The first generation consists of a fused cyclohexane unit having pseudo axial methyl groups as chiral selectors and a rigidifying acetal moiety. The second ligand generation derives from an atrop-chiral biaryl-backbone and which possesses adjustable substituents at its 3,3'-positions. Both ligand families can be modulated in their respective steric bulk to adjust for the specific needs of the targeted application. The cyclopentadienes can be metalated under standard conditions. The corresponding chiral rhodium(I) ethylene complexes are relatively air and moisture and represent storable stable precatalysts for the targeted asymmetric Rh(III)-catalyzed C-H functionalizations. These complexes are then conveniently oxidized in situ by dibenzoyl peroxide to give the reactive Cp(x)Rh(III)(OBz)2 species. For instance, this catalyst is used for directed C-H activations of aryl hydroxamates and the subsequent enantioselective trapping with olefins, providing dihydroisoquinolones in very high enantioselectivities. In addition, we have established highly selective intramolecular trapping reactions with tethered higher substituted alkenes giving dihydrobenzofurans with quaternary stereogenic centers. Concerning intermolecular reactions, allene coupling partners allow for an enantioselective hydroarylation yielding substituted allylated compounds. A trapping process of the cyclometalated intermediate with diazo reactants enables the enantioselective construction of isoindolinones. Moreover, the catalysts can be used for the construction of atropchiral biaryl motives using a dehydrogenative Heck-type reaction. The development of flexibly adjustable chiral Cp(x) ligands is described in this Account showcasing their applicability for a variety of Rh(III) catalyzed C-H functionalization reactions. These Cp(x) derivatives hold promise as powerful steering ligands for further transition-metals used in asymmetric catalysis.

A tripodal peptide ligand for asymmetric Rh(ii) catalysis highlights unique features of on-bead catalyst development

A tridentate eq-eq-ax peptide ligand for rhodium(ii) complexes, discovered by high-throughput on-bead screening, is an efficient and selective catalyst for asymmetric cyclopropanation reactions.

ChemInform Abstract: Rhodium(I)‐Catalyzed Enantioselective Hydrogenation of Substituted Acrylic Acids with Sterically Similar β,β‐Diaryls.

AbstractAn efficient asymmetric Rh(I)‐catalyzed hydrogenation of β,β‐disubstituted acrylic acids is developed using a BINOL‐derived phosphine oxide as monodentate chiral ligand.

Isolation and X-ray structures of four Rh(PCP) complexes including a Rh(I) dioxygen complex with a short O–O bond

The reaction of RhCl3·H2O with tBu2P(CH2)5PtBu2 afforded several complexes including [RhIII(H)Cl{tBu2P(CH2)2CH(CH2)2PtBu2}] (1), [RhIIIHCl2{tBu2P(CH2)5PtBu2}]2 (2), [RhICl{tBu2P(CH2)2CHCHCH2PtBu2}] (3) and [RhICl{tBu2PCH2C(O)CHCHCH2PtBu2}] (4). X-ray crystal structures of 3 and 4 showed that the CC bond on the C5 unit of tBu2P(CH2)5PtBu2 is bound to Rh(I) in a η2 configuration. In 4, the Rh atom has a trigonal pyramidal coordination geometry. The X-ray crystal structure of 2 consists of two rhodium(III) centers bridged by two tBu2P(CH2)5PtBu2 ligands with two phosphorus atoms, one from each ligand, trans to one another. The crystal structure of the rhodium oxygen adduct with 1,3-bis(di-t-butylphosphinomethyl)benzene [RhO2{tBu2PCH2(C6H3)CH2PtBu2}] (5) was also investigated. In this species the O2 is η2 coordinated to the Rh(I) center with asymmetric Rh–O bond lengths (2.087(7) and 1.998(8)Å). The O–O bond distance is short (1.337(11)Å) with νO–O of 990.5cm−1. DFT calculations on complex 5 yielded two η2–O2 structures that differed in energy by only 0.76kcal/mol. The lower energy one (5a) had near C2 symmetry, and had nearly equal Rh–O bond lengths, while the higher energy structure (5b) had near Cs symmetry and generally good agreement with the experimental structure. The calculated UV–Vis and IR spectra of complex 5 are in excellent agreement with experiment.

ChemInform Abstract: Asymmetric Rh(I)‐Catalyzed Intramolecular [3 + 2] Cycloaddition of 1‐Yne‐vinylcyclopropanes for Bicyclo[3.3.0] Compounds with a Chiral Quaternary Carbon Stereocenter and Density Functional Theory Study of the Origins of Enantioselectivity.

A highly enantioselective Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of 1-yne-VCPs to bicyclo[3.3.0] compounds with an all-carbon chiral quaternary stereocenter at the bridgehead carbon was developed. DFT calculations of the energy surface of the catalytic cycle (complexation, cyclopropane cleavage, alkyne insertion, and reductive elimination) of the asymmetric [3 + 2] cycloaddition reaction indicated that the rate- and stereo-determining step is the alkyne-insertion step. Analysis of the alkyne-insertion transition states revealed that the serious steric repulsion between the substituents in the alkyne moiety of the substrates and the rigid H(8)-BINAP backbone is responsible for not generating the disfavored [3 + 2] cycloadducts.

Asymmetric Rh(I)-Catalyzed Intramolecular [3 + 2] Cycloaddition of 1-Yne-vinylcyclopropanes for Bicyclo[3.3.0] Compounds with a Chiral Quaternary Carbon Stereocenter and Density Functional Theory Study of the Origins of Enantioselectivity

A highly enantioselective Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of 1-yne-VCPs to bicyclo[3.3.0] compounds with an all-carbon chiral quaternary stereocenter at the bridgehead carbon was developed. DFT calculations of the energy surface of the catalytic cycle (complexation, cyclopropane cleavage, alkyne insertion, and reductive elimination) of the asymmetric [3 + 2] cycloaddition reaction indicated that the rate- and stereo-determining step is the alkyne-insertion step. Analysis of the alkyne-insertion transition states revealed that the serious steric repulsion between the substituents in the alkyne moiety of the substrates and the rigid H(8)-BINAP backbone is responsible for not generating the disfavored [3 + 2] cycloadducts.

ChemInform Abstract: Asymmetric Rh(II)‐Catalyzed Cyclopropanation of Alkenes with Diacceptor Diazo Compounds: p‐Methoxyphenyl Ketone as a General Stereoselectivity Controlling Group.

AbstractThe reaction features the use of p‐methoxyphenyl ketone as a diastereo‐ and enantioselective controlling group for the synthesis of a series of cyclopropanes.

Asymmetric Rh(II)-Catalyzed Cyclopropanation of Alkenes with Diacceptor Diazo Compounds: p-Methoxyphenyl Ketone as a General Stereoselectivity Controlling Group

Different diacceptor diazo compounds bearing an α-PMP-ketone group were found to be effective carbene precursors for the highly stereoselective Rh(2)(S-TCPTTL)(4)-catalyzed cyclopropanation of alkenes (EWG = NO(2), CN, CO(2)Me). The resulting products were readily transformed into a variety of biologically relevant enantiopure molecules, such as cyclopropane α- and β-amino acid derivatives. Different mechanistic studies carried out led to a rationale for the high diastereo- and enantioselectivity obtained, where the PMP-ketone moiety was found to play a critical role in the stereoinduction process. Additionally, the use of catalytic amounts of achiral Lewis bases to influence the enantioinduction of the reactions developed is documented.

ChemInform Abstract: Asymmetric Rh(I)‐Catalyzed Addition of MIDA Boronates to N‐tert‐Butanesulfinyl Aldimines: Development and Comparison to Trifluoroborates.

AbstractThe MIDA boronates are efficient coupling partners which allow formation of α‐branched amines in good yields with excellent enantioselectivity.

Asymmetric Rh(I)-Catalyzed Addition of MIDA Boronates to N-tert-Butanesulfinyl Aldimines: Development and Comparison to Trifluoroborates

The Rh(I)-catalyzed addition of alkenyl and aryl MIDA boronates to N-tert-butanesulfinyl aromatic and aliphatic imines proceeds in good yields (up to 99%) and with very high selectivity (98:2 to >99:1). In comparison to trifluoroborates, higher yields and selectivities are observed for the addition to N-tert-butanesulfinyl aromatic imines. This new method expands upon the versatility of the Rh(I)-catalyzed addition of boron reagents to imines, thereby further enabling the synthesis of chiral alpha-branched amines.

Rh-Catalyzed [2+2+2] Cycloaddition of 1,6-Diynes

In previous studies, Shibata and others have described asymmetric Rh(I)-catalyzed [2+2+2] cycloadditions of 1,6-diynes with mono­alkenes containing an alkoxycarbonyl functionality (J. Am. Chem. Soc. 2006, 128, 13686). In the present work, the authors utilize a Rh(I)/BINAP complex to effect the cycloaddition of various 1,6-diynes with a protected dehydroamino acid. Strong bidentate coordination through the alkene and amide carbonyl moieties with rhodium should provide a tight chelate, leading to high levels of asymmetric induction.

Rhodium-Catalyzed Enantioselective Cycloaddition Route to Indolizidines

Described herein is a synthesis of indolizidines by an asymmetric Rh(I)-catalyzed [2+2+2] cycloaddition of 1,1-disubstituted alkenyl isocyanates to terminal alkynes. The reaction proceeds in moderate to high yields with a high level of enantio- and regioselectivity in the presence of the phosphoramidite ligands. Aliphatic alkynes gave lactams A as major products whereas vinylogous amides B predominated with aryl alkynes. The formation of 2-pyridones E as the major byproduct was suppressed under high dilution reaction conditions (typically 0.04 M). The isolated yields were low with sterically demanding substituents (e.g., R1 = i-Pr, Cy) and in such reactions an increase in the 2-pyridone byproduct was observed, presumably due to a slow rate of coordination-insertion of the alkene with Rh.