Rhodium-catalyzed Asymmetric Conjugate Addition Research Articles

Rhodium-Catalyzed Asymmetric Conjugate Addition to γ-Substituted α,β-Unsaturated γ-Lactams through Dynamic Kinetic Resolution: Asymmetric Synthesis of trans-β,γ-Disubstituted γ-Lactams

The reaction of racemic γ-substituted α,β-unsaturated γ-lactams rac-1 with arylboron reagents 2 in the presence of a chiral diene L1a–rhodium catalyst under basic conditions (3.0 equiv of NEt3) gave high yields of β,γ-disubstituted trans-γ-lactams 3 with both high diastereo- and enantioselectivity. Fast racemization of 1 by way of a dienolate generated with the base followed by kinetic resolution of 1 with the chiral rhodium catalyst realized this highly efficient dynamic kinetic resolution. The synthetic utility of the present method is demonstrated by the synthesis of key intermediates to biologically active compounds.

C1-Symmetric Binap Derivative Featuring Single Diferrocenylphosphino-Donor Moiety

A C1-symmetric chiral bisphosphine, FcPh-Binap (1), which possesses a single diferrocenylphosphino moiety together with a conventional Ph2P-substituent, was prepared in enantiomerically pure forms. Ligand 1 is sterically less demanding than Fc-Segphos (A), which has two diferrocenylphosphino groups, and showed higher activity than A in the rhodium-catalyzed asymmetric conjugate addition of phenylboronic acid to 2-cyclohexenone. Ligand 1 was applied in the two palladium-catalyzed asymmetric reactions, namely the synthesis of axially chiral allenes and the intermolecular Heck reaction, and displayed higher enantioselectivity than parent Binap. The Pd/(R)-1 species showed up to 47% ee enhancement over the Pd/(R)-Binap catalyst in the former reaction and up to 39% ee enhancement in the latter.

Stereochemical Insights into the Anaerobic Degradation of 4-Isopropylbenzoyl-CoA in the Denitrifying Bacterium Strain pCyN1.

The constitutions and absolute configurations of two previously unknown intermediates, (1S,2S,4S)-2-hydroxy-4-isopropylcyclohexane-1-carboxylate and (S)-3-isopropylpimelate, of anaerobic degradation of p-cymene in the bacterium Aromatoleum aromaticum pCyN1 are reported. These intermediates (as CoA esters) are involved in the further degradation of 4-isopropylbenzoyl-CoA formed by methyl group hydroxylation and subsequent oxidation of p-cymene. Proteogenomics indicated 4-isopropylbenzoyl-CoA degradation involves (i) a novel member of class I benzoyl-CoA reductase (BCR) as known from Thauera aromatica K172 and (ii) a modified β-oxidation pathway yielding 3-isopropylpimeloyl-CoA analogously to benzoyl-CoA degradation in Rhodopseudomonas palustris. Reference standards of all four diastereoisomers of 2-hydroxy-4-isopropylcyclohexane-1-carboxylate as well as both enantiomers of 3-isopropylpimelate were obtained by stereoselective syntheses via methyl 4-isopropyl-2-oxocyclohexane-1-carboxylate. The stereogenic center carrying the isopropyl group was established using a rhodium-catalyzed asymmetric conjugate addition. X-ray crystallography revealed that the thermodynamically most stable stereoisomer of 2-hydroxy-4-isopropylcyclohexane-1-carboxylate is formed during p-cymene degradation. Our findings imply that the reductive dearomatization of 4-isopropylbenzoyl-CoA by the BCR of A. aromaticum pCyN1 stereospecifically forms (S)-4-isopropyl-1,5-cyclohexadiene-1-carbonyl-CoA.

Rhodium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Enones

Key words rhodium catalysis - arylboronic acids - oxazoline ligands - conjugate addition

Construction of axial chirality by rhodium-catalyzed asymmetric dehydrogenative Heck coupling of biaryl compounds with alkenes.

Enantioselective construction of axially chiral biaryls by direct C-H bond functionalization reactions has been realized. Novel axially chiral biaryls were synthesized by the direct C-H bond olefination of biaryl compounds, using a chiral [Cp*Rh(III)] catalyst, in good to excellent yields and enantioselectivities. The obtained axially chiral biaryls were found as suitable ligands for rhodium-catalyzed asymmetric conjugate additions.

二座ホスホロアミダイト配位子を用いる有機ホウ素化合物の不斉付加反応

The transition metal catalyzed addition reactions of organic electrophiles to activated alkenes, imines and carbonyl compounds are powerful tools for new carbon-carbon bonds with high enantioselectivity. Chiral bidentate phosphoramidite ligands (Me-BIPAM and N-Me-BIPAM) were synthesized from linked-BINOL as new ligands for asymmetric addition reactions of arylboronic acids. These bidentate phosphoramidite ligands appear to be highly effective for rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to α,β-unsaturated ketones. In the course of our study on bidentate phosphoramidites as a chiral ligand for enantioselective bond-forming reactions, we found that N-Me-BIPAM is effective for arylation of N-sulfonyl arylimines with arylboronic acids. Me-BIPAM was found to be highly efficient for ruthenium-catalyzed enantioselective arylation of aldehydes, α-ketoesters, glyoxylate, and isatins. In this review, we focus on chiral bidentate phosphoramidite ligands (Me-BIPAM and N-Me-BIPAM) for asymmetric carbon-carbon bond-forming reactions of arylboronic acids.

Chiral olefin–sulfoxide as ligands for rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to unsaturated esters

An efficient rhodium/olefin-sulfoxide catalyzed asymmetric conjugate addition of organoboronic acids to various unsaturated esters has been developed, where 2-methoxy-1-naphthyl sulfinyl functionalized olefin ligands have been shown to be highly effective, and are especially applicable to unsaturated methyl esters with up to 99% yield and 91% ee.

Correction to Rhodium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Nitroalkenes Using Olefin–Sulfoxide Ligands

Correction to Rhodium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Nitroalkenes Using Olefin–Sulfoxide Ligands

Rhodium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Nitroalkenes Using Olefin–Sulfoxide Ligands

An efficient rhodium/olefin-sulfoxide catalyzed asymmetric conjugate addition of organoboronic acids to a variety of nitroalkenes has been developed, where 2-methoxy-1-naphthyl sulfinyl functionalized olefin ligands have shown to be highly effective and are applicable to a broad scope of aryl, alkyl, and heteroaryl nitroalkenes.

Rhodium-Catalyzed Asymmetric Conjugate Addition withN-Sulfinyl Ligands

Rhodium-Catalyzed Asymmetric Conjugate Addition with<i>N</i>-Sulfinyl Ligands

A Class of Benzene Backbone-Based Olefin–Sulfoxide Ligands for Rh-Catalyzed Enantioselective Addition of Arylboronic Acids to Enones

A class of readily available and easily tunable benzene backbone-based olefin-sulfoxide ligands was developed for the rhodium-catalyzed asymmetric conjugate addition reaction of arylboronic acids to enones with up to 97% yield and 97% ee.

Rh-Catalyzed Asymmetric 1,4-Addition of Arylboronic Acids to α,β-Unsaturated Ketones with DIFLUORPHOS and SYNPHOS Analogues

Applications of electron-deficient DIFLUORPHOS and SYNPHOS analogues in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to α,β-unsaturated ketones afford the 1,4-addition adducts in yields up to 92% and with 99% ee. Particularly, a Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to nonsubstituted maleimide substrates using the (R)-3,5-diCF(3)-SYNPHOS ligand is also reported. This protocol provides access to various enantioenriched 3-substituted succinimide units of biological interest, in high yields and good to excellent ee up to 93%, which could be upgraded up to 99% ee, after a single crystallization.

Rhodium‐Catalyzed Asymmetric 1,4‐Addition of Aryl Alanes to Trisubstituted Enones: Binap as an Effective Ligand in the Formation of Quaternary Stereocenters

All for one and 1,4-all: Readily available aryl alanes are used in the rhodium-catalyzed asymmetric conjugate addition reaction with a variety of cyclic and acyclic enones. The enhanced reactivity of the system allows the use of the common binap ligand for the generation of quaternary benzylic stereocenters in excellent enantioselectivity (see scheme).

Rhodium-Catalyzed Asymmetric Conjugate Addition of Organoboronic Acids to Nitroalkenes Using Chiral Bicyclo[3.3.0] Diene Ligands

Rhodium-Catalyzed Asymmetric Conjugate Addition of Organoboronic Acids to Nitroalkenes Using Chiral Bicyclo[3.3.0] Diene Ligands

Rhodium-Catalyzed Asymmetric Conjugate Addition of Alkenylstannanes

The use of alkenylstannes as nucleophiles in metal-catalyzed asymmetric conjugate additions can provide several advantages over other pronucleophiles in terms of functional group tolerance and ease of preparation. The authors report the first examples of enantioselective conjugate additions of alkenylstannanes.

Synthesis of S1P1Receptor Agonists

The target molecule is a potential immunosuppressant that modulates lymphocyte trafficking by interacting with the sphingosine-1-phosphate receptor S1P1 in mice. An asymmetric synthesis of all four diastereoisomers required for an SAR study features an efficient Hayashi-Miyaura rhodium-catalyzed asymmetric conjugate addition as the first step.

Simple Chiral Diene Ligands Provide High Enantioselectivities in Transition-Metal-Catalyzed Conjugate Addition Reactions

Chiral dienes possessing the bicyclo[2.2.2]octadiene framework were prepared readily through the [4 + 2] cycloaddition of ( R)-alpha-phellandrene with methyl propiolate as the key step. Diene 9, substituted with a tertiary alcohol on one of the two double bonds, is prepared in just one step from the cycloadduct and is highly effective as a chiral ligand for rhodium-catalyzed asymmetric conjugate addition reactions, giving the corresponding addition products with higher enantioselectivity than other chiral dienes.

Rh‐Catalyzed Enantioselective Conjugate Addition of Arylboronic Acids with a Dynamic Library of Chiral tropos Phosphorus Ligands

A library of 19 chiral tropos phosphorus ligands, based on a free-to-rotate (tropos) biphenol unit and a chiral P-bonded alcohol (11 phosphites, 1-P(O)(2)O to 11-P(O)(2)O) or secondary amine (8 phosphoramidites, 12-P(O)(2)N to 19-P(O)(2)N), were screened, individually and in combinations of two, in the rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to enones and enoates. High enantioselectivities (up to 99 % ee) and excellent yields were obtained in the addition to either cyclic or acyclic substrates. The flexible biphenolic P ligands outperformed the analogous rigid binaphtholic P ligands. Variable-temperature (31)P NMR studies revealed that the biphenolic ligands are tropos even at low temperature. Only below 190 K was a coalescence observed; upon further cooling, two atropisomers were detected. The Rh homocomplexes ([Rh(L(a))(2)](+)) were also studied: in general, a single doublet (P-Rh coupling) was observed in the case of the biphenolic phosphite ligands, over the temperature range 380-230 K, demonstrating their tropos nature in the rhodium complexes even at low temperatures. On the other hand, the phosphoramidites showed different behaviors depending on the structure of the ligand and on the nature of the rhodium source. The spectrum at 230 K of the mixture of [Rh(acac)(eth)(2)] (eth=C(2)H(4)) with phosphite 6-P(O)(2)O and phosphoramidite 19-P(O)(2)N (the most enantioselective ligand combination in the conjugate addition reaction) revealed the presence of four homocomplexes (total approximately 40 %: [Rh{6-P(O)(2)O}(2)], [Rh{(aR)-19-P(O)(2)N}(2)], [Rh{(aS)-19-P(O)(2)N}(2)], [Rh{(aR)-19-P(O)(2)N}{(aS)-19-P(O)(2)N}]) and one heterocomplex, [Rh{6-P(O)(2)O}{(aR)-19-P(O)(2)N}] (approximately 60 %) In the heterocomplex, the biphenol-derived phosphite is free to rotate (tropos) while the biphenol-derived phosphoramidite shows a temperature-dependent tropos/atropos behavior (coalescence temperature=310 K).

Rhodium-Catalyzed Asymmetric Conjugate Additions of Boronic Acids to Enones Using DIPHONANE: A Novel Chiral Bisphosphine Ligand

[reaction: see text] The synthesis of a novel enantiopure C2-symmetric bisphosphine, DIPHONANE, was accomplished starting from 2,5-norbornadione, utilizing (R,R)- and/or (S,S)-(2,3-O-di[(phenylamino)carbonyl]tartaric acid for the resolution of an intermediate phosphineoxide. The application of this ligand in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to cyclic enones provides the 1,4-addition products in good yields (69-98%) and high ee's (78-95% ee). A byproduct arising from a consecutive 1,4-addition and 1,2-addition was also observed.

Highly Enantioselective Conjugate Additions of Potassium Organotrifluoroborates to Enones by Use of Monodentate Phosphoramidite Ligands

The use of phosphoramidite ligands in the rhodium-catalyzed asymmetric conjugate addition of potassium organotrifluoroborates to various enones in the absence of water is described. A systematic search for effective catalysts has been performed by use of high-throughput screening methods. Initially, we have screened reaction conditions, catalyst precursors, and focused ligand libraries. In the next stage we have used the monodentate ligand combination approach, and finally we have made a library of 96 different phosphoramidites by parallel synthesis in the robot (instant ligand libraries) and have tested these in the vinylation of cyclohexenone (up to 88% enantiomeric excess, ee) and 4-phenyl-3-buten-2-one (up to 42% ee). Arylation of cyclohexenone by use of potassium phenyltrifluoroborate gave 3-phenylcyclohexanone with 99% ee.