Direct Synthesis of Phosphine‐Phosphite Ligand and Its Implication in Asymmetric Hydrogenation of Functionalized Olefins

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPractical Syntheses of β-Amino Alcohols via Asymmetric Catalytic HydrogenationGuoxin Zhu, Albert L. Casalnuovo, and Xumu ZhangView Author Information Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, and DuPont Agricultural Products, Stine-Haskell Research Center, P.O. Box 30, Building 300, Newark, Delaware 19714 Cite this: J. Org. Chem. 1998, 63, 23, 8100–8101Publication Date (Web):October 29, 1998Publication History Received7 August 1998Published online29 October 1998Published inissue 1 November 1998https://pubs.acs.org/doi/10.1021/jo981590ahttps://doi.org/10.1021/jo981590arapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1302Altmetric-Citations76LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Alcohols,Catalysts,Hydrogenation,Ligands,Stereoselectivity Get e-Alerts

Photoredox/nickel‐cocatalyzed cross‐couplings have emerged as powerful methods for constructing carbon–heteroatom bonds under mild conditions. Despite their rapid development, catalytic asymmetric C(sp2)–heteroatom couplings remain largely underexplored and challenging. Herein, we established photoredox/nickel‐cocatalyzed asymmetric C–O and C–S couplings of racemic heterobiaryl triflates with diverse oxygen and sulfur nucleophiles. This straightforward protocol enables highly enantioselective C(sp2)–O and C(sp2)–S bond formation under mild reaction conditions, providing diverse axially chiral N‐heterobiaryls (>100 examples) with excellent atroposelectivity and functional group tolerance. These axially chiral N‐heterobiaryls can be further transformed into valuable chiral compounds, including commonly used chiral ligands and organocatalysts, while the resultant C–S coupling products can serve directly as chiral ligands in asymmetric catalysis. This study represents the first highly enantioselective photoredox/Ni‐cocatalyzed asymmetric C(sp2)–heteroatom bond coupling and introduces a new strategy for atroposelective synthesis of N‐heterobiaryl atropisomers with wide applicability. Mechanistic investigations reveal that both C–O and C–S couplings proceed via an energy‐transfer pathway: the C–O coupling follows a kinetic resolution mechanism, while the C–S coupling proceeds via dynamic kinetic asymmetric transformation, thus providing valuable insights into this class of C(sp2)–heteroatom couplings and advancing this field.

Photoredox/nickel-cocatalyzed cross-couplings have emerged as powerful methods for constructing carbon-heteroatom bonds under mild conditions. Despite their rapid development, catalytic asymmetric C(sp2)-heteroatom couplings remain largely underexplored and challenging. Herein, we established photoredox/nickel-cocatalyzed asymmetric C-O and C-S couplings of racemic heterobiaryl triflates with diverse oxygen and sulfur nucleophiles. This straightforward protocol enables highly enantioselective C(sp2)-O and C(sp2)-S bond formation under mild reaction conditions, providing diverse axially chiral N-heterobiaryls (>100 examples) with excellent atroposelectivity and functional group tolerance. These axially chiral N-heterobiaryls can be further transformed into valuable chiral compounds, including commonly used chiral ligands and organocatalysts, while the resultant C-S coupling products can serve directly as chiral ligands in asymmetric catalysis. This study represents the first highly enantioselective photoredox/Ni-cocatalyzed asymmetric C(sp2)-heteroatom bond coupling and introduces a new strategy for atroposelective synthesis of N-heterobiaryl atropisomers with wide applicability. Mechanistic investigations reveal that both C-O and C-S couplings proceed via an energy-transfer pathway: the C-O coupling follows a kinetic resolution mechanism, while the C-S coupling proceeds via dynamic kinetic asymmetric transformation, thus providing valuable insights into this class of C(sp2)-heteroatom couplings and advancing this field.

1,2-Bisphosphines have been identified as one class of important and powerful chiral ligands in asymmetric catalysis with transition metals. Herein, a copper(I)-catalyzed asymmetric hydrophosphination of α,β-unsaturated phosphine sulfides was developed with the assistance of "soft-soft" interaction between copper(I)-catalyst and the phosphine sulfide moiety, which afforded 1,2-bisphosphine derivatives with diversified electronic nature and steric hindrance in high to excellent yields with high to excellent enantioselectivity. Moreover, the challenging catalytic asymmetric hydrophosphination/protonation reaction was achieved with excellent enantioselectivity. Strikingly, the dynamic kinetic resolution of racemic diarylphosphines was also successfully carried out with high to excellent diastereo- and enantioselectivities. Interestingly, the nucleophilic copper(I)-diphenylphosphide species was characterized by 31 P NMR spectrum and mass spectrum. At last, three products were transformed to chiral 1,2-bisphosphines, which were employed as ligands in Rh-catalyzed asymmetric hydrogenation of α-amino-α,β-unsaturated ester. The α-amino acid derivative was produced in high enantioselectivity, which demonstrated the utility of the present methodology.

Abstract1,2‐Bisphosphines have been identified as one class of important and powerful chiral ligands in asymmetric catalysis with transition metals. Herein, a copper(I)‐catalyzed asymmetric hydrophosphination of α,β‐unsaturated phosphine sulfides was developed with the assistance of “soft–soft” interaction between copper(I)‐catalyst and the phosphine sulfide moiety, which afforded 1,2‐bisphosphine derivatives with diversified electronic nature and steric hindrance in high to excellent yields with high to excellent enantioselectivity. Moreover, the challenging catalytic asymmetric hydrophosphination/protonation reaction was achieved with excellent enantioselectivity. Strikingly, the dynamic kinetic resolution of racemic diarylphosphines was also successfully carried out with high to excellent diastereo‐ and enantioselectivities. Interestingly, the nucleophilic copper(I)‐diphenylphosphide species was characterized by 31P NMR spectrum and mass spectrum. At last, three products were transformed to chiral 1,2‐bisphosphines, which were employed as ligands in Rh‐catalyzed asymmetric hydrogenation of α‐amino‐α,β‐unsaturated ester. The α‐amino acid derivative was produced in high enantioselectivity, which demonstrated the utility of the present methodology.

Mesoporous silica MCM-41-supported norephedrine and ephedrine as heterogeneous chiral ligands in asymmetric catalysis

The N‐oxide (II), obtained by MCPBA oxidation of the pyridocamphor (I), is consecutively methylated with dimethyl sulfate (III) and treated with potassium cyanide (IV), producing a mixture of the cyanides (V) and (VI).

The title compound, a new chiral alkyl 2,2′‐ bipyridine containing a rigid alkyl framework, can be prepared through a six‐step reaction sequence from (+)‐camphor. Coordination of the new ligand to rhodium(I) procatalysts occurs with difficulty and the resulting species display a very low stereoselectivity in the catalytic transfer hydrogenation of acetophenone.

Axially chiral allenes are valuable motifs in natural products and chiral ligands in asymmetric catalysis, yet methods to access enantioenriched difluoromethylated analogues remain undeveloped. Here we report the efficient copper-catalyzed SN2'-type substitution of propargylic alcohol derivatives with Zn(CF2H)2(DMPU)2, to deliver enantioenriched difluoromethylated allenes under mild conditions. This transformation proceeds with high regioselectivity, a broad substrate scope, and operational simplicity, providing a general strategy to construct CF2H-substituted chiral allenes of potential relevance to drug discovery.

The efficient functionalization of planar chiral ruthenium naphthalene—and ruthenium indenyl—scaffolds is reported. Mild reaction conditions employing microwave heating have been developed for the derivatization of sensitive cationic naphthalene ruthenium complexes. In particular, a series of novel planar chiral monodentate phosphines and their gold(I) complexes have been synthesized and fully characterized by NMR spectroscopy and X-ray crystallography. Furthermore, the electronic properties of these phosphines (L) have been evaluated via the infrared CO stretching frequencies of the corresponding Ni(CO)3(L) complexes, providing valuable insight for the design and application of these chiral ligands in asymmetric catalysis.

The chiral borate counteranion bis[(R)-1,1′-bi-2-naphtholato]borate (1–) has been found to be a competent chiral 1H NMR shift reagent for cationic copper(I) complexes. This has been demonstrated by the addition of the Cu(NCMe)4+ salt of 1– to two classes of common chiral ligands in asymmetric catalysis: 2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl (tol-BINAP) (2) and 2,2′-isopropylidenebis(4-phenyl-2-oxazoline) (3). In the case of ligand 2, the addition of 1 equiv. of either (R,R)-2 or (S,S)-2 to Cu(NCMe)4+1– results in well-resolved 1H NMR resonances for the two enantiomers. Examination of standard solutions of non-enantiopure 2 shows that the copper complex can be an effective NMR shift reagent of a wide range of enantiomeric compositions. Cu(NCMe)4+1– also generates distinct 1H NMR resonances for the two separate enantiomers of 2,2′-isopropylidenebis(4-phenyl-2-oxazoline) (3). However, attempts to employ this copper salt as a chiral NMR shift reagent for rac-3 led to the discovery of a new and unexpected equilibrium: [(R,R)-3]Cu+ + [(S,S)-3]Cu+ [Formula: see text] [(R,R)-3][(S,S)-3]Cu+ + Cu+. Key words: chiral counteranion, copper, chiral NMR shift reagent, ion pairing.

Axially chiral arylpyrroles are key components of pharmaceuticals and natural products as well as chiral catalysts and ligands for asymmetric transformations. However, the catalytic enantioselective construction of optically active arylpyrroles remains a formidable challenge. Here we disclose a highly efficient strategy to access enantioenriched axially chiral arylpyrroles by means of organocatalytic atroposelective desymmetrization and kinetic resolution. Depending on the remote control of chiral catalyst, the arylpyrroles were obtained in high yields and excellent enantioselectivities under mild reaction conditions. This strategy tolerates a wide range of functional groups, providing a facile avenue to approach axially chiral arylpyrroles from simple and readily available starting materials. Selected arylpyrrole products proved to be efficient chiral ligands in asymmetric catalysis and also important precursors for further synthetic transformations into highly functionalized pyrroles with potential bioactivity, especially the axially chiral fully substituted arylpyrroles.

Axially chiral compounds have received much attention from chemists because of their widespread appearance in natural products, biologically active compounds, and useful chiral ligands in asymmetric catalysis. Because of the importance of this structural motif, the catalytic enantioselective construction of axially chiral scaffolds has been intensively investigated, and great progress has been accomplished. However, the majority of methodologies in this field focus on the use of metal catalysis, whereas approaches involving organocatalysis have started to emerge only recently. This Account describes certain advances in the organocatalytic asymmetric synthesis of axially chiral compounds involving the following strategies: kinetic resolution, desymmetrization, cyclization/addition, direct arylation, and so on. We began our investigation by developing a highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid-catalyzed imine formation and transfer hydrogenation cascade process, thereby providing a convenient route to generate chiral BINAM derivatives in high yields with excellent enantioselectivities. The desymmetrization of 1-aryltriazodiones (ATADs) through an organocatalyzed tyrosine clicklike reaction wherein a nucleophile was added to the ATAD afforded an interesting type of axially chiral N-arylurazole in an excellent remote enantiocontrolled manner. We then focused on a direct construction strategy involving cyclization and the addition strategy given the inherent limitations of the kinetic resolution in terms of the chemical yield and the desymmetrization in terms of the substrate scope. By utilizing the catalytic enantioselective Paal-Knorr reaction, we disclosed a general and efficient cyclization method to access enantiomerically pure arylpyrroles. The direct heterocycle formation and the stepwise method, which was executed in a one-pot fashion containing enantioselective cyclization and subsequent aromatization, were successfully applied for the construction of diverse axially chiral arylquinazolinones catalyzed by chiral Brønsted acids. We discovered the asymmetric organocatalytic approach to construct axially chiral styrenes through the 1,4-addition of arylalkynals in good chemical yields and enantioselectivities. Such structural motifs are important precursors for further transformations into biologically active compounds and useful synthetic intermediates and may have potential applications in asymmetric syntheses as olefin ligands or organocatalysts. To further tackle this challenge, we accomplished the phosphoric acid-catalyzed enantioselective direct arylative reactions of 2-naphthol and 2-naphthamine with quinone derivatives to deliver efficient access to a class of axially chiral BINOL and NOBIN derivatives in good yields with excellent enantioselectivities under mild reaction conditions. Most importantly, we discovered that the azo group can effectively perform as a directing and activating group for organocatalytic formal aryl C-H functionalization via formal nucleophilic aromatic substitution of azobenzene derivatives. Thus, a wide range of axially chiral arylindoles were synthesized in good yields with excellent enantioselectivities. We anticipate that this strategy will foster the development of many other transformations and motivate a new enthusiasm for organocatalytic enantioselective aryl functionalization. Moreover, SPINOLs are fundamental synthetic precursors in the construction of other chiral organocatalysts and ligands. We have successfully developed a phosphoric acid-catalyzed enantioselective approach for SPINOLs. This approach is highly convergent and functional-group-tolerant for the efficient generation of SPINOLs with good results, thus delivering practical access to this privileged structure.

Despite the rapid progress in the field of asymmetric catalysis, the search for new, efficient, and practical asymmetric catalytic transformations to facilitate the green synthesis of chiral natural products and drugs will continue to be a major ongoing effort in organic chemistry. Chiral phosphorus ligands have played a significant role in recent advances in transition-metal-catalyzed asymmetric transformations. However, there remain numerous challenging issues of reactivity and selectivity in catalysis. The development of new and efficient chiral phosphorus ligands with new structural motifs remains highly desirable. P-Chiral phosphorus ligands have been overlooked and are underdeveloped, except for the early success of DIPAMP, introduced first by Knowles in the early 1970s. It was not until the late 1990s that the development of P-chiral phosphorus ligands regained attention with the advent of bisP*, TangPhos, etc. Nonetheless, most P-chiral phosphorus ligands were either difficult to prepare or operationally inconvenient. The development of efficient, practical, and operationally convenient P-chiral phosphorus ligands with new structural motifs remains an important subject of research. This Account introduces the design and development of a series of practical and efficient P-chiral bis- and monophosphorus ligands based on a 2,3-dihydrobenzo[ d][1,3]oxaphosphole motif. Their unique structural and physical properties include conformational unambiguousness, high tunability of electronic and steric properties, and operational simplicity as air-stable solids, which make them practical and exceptional ligands for asymmetric catalysis. Chiral bisphosphorus ligands such as MeO-BIBOP (L3), WingPhos (L4), and iPr-BABIBOP (L7) have demonstrated excellent enantioselectivities and unprecedented turnover numbers (TONs) in various asymmetric hydrogenations and other transformations, providing practical and efficient solutions leading to chiral amines, alcohols, carboxylic acids, and α- and β-amino acids. Chiral biaryl monophosphorus ligands, including BI-DIME (L9), AntPhos (L15), iPr-BI-DIME (L11), etc., have proven to be a class of versatile and powerful ligands for a number of catalytic asymmetric transformations, including asymmetric Suzuki-Miyaura coupling, asymmetric palladium-catalyzed dearomative cyclization, asymmetric hydroboration/diboration, asymmetric nickel-catalyzed reductive coupling, asymmetric palladium-catalyzed intramolecular arylation, asymmetric alkene aryloxyarylation, asymmetric α-arylation, asymmetric Heck reaction, and asymmetric nucleophilic addition, providing efficient solutions leading to various synthetically challenging chiral structures such as chiral biaryls, chiral tertiary alcohols, chiral α-amino tertiary boronic esters, and chiral all-carbon quaternary stereocenters. The high enantioselectivities and TONs obtained with these ligands have resulted in the syntheses of several chiral natural products and therapeutic agents in concise and highly efficient manners. While our efforts on the development of P-chiral phosphorus ligands are ongoing, it should be emphasized that the development of ligands and catalysts with new structural motifs should continue in the search for new reactivity and selectivity to tackle current synthetic challenges. Such effort is destined to promote the advances of asymmetric catalysis as well as synthetic organic chemistry.

The pentafluorophenyl group as a module for the direct modification of chiral diamines for asymmetric catalysis